JPS6327699B2 - - Google Patents

Description

[Detailed description of the invention] The present invention has particular applications for photography and more particularly for photographic products.
Relating to the use of realylmethane compounds. Photographic film, and especially multicolor film, is
Despite efforts to “repeat” the film,
It may change from one to the next, but generally it does not change.
Waru. Manufacturers of multicolor photographic film should avoid manufacturing operations.
Minimize the influence of difficult fluctuations on the final polychromatic image
Many processes have been developed for this purpose. These variations are individual
Due to the misfit of the D log E curves for red, green and blue exposures of
Mainly in color balance as reflected
reflected in the movement. To coat multicolor film
Although the equipment used for this purpose is extremely precise, it
Anticipated applications of silveride and/or dye imaging materials
Variations occur between ranges. Anti-silver halide emulsion
Return batches may vary in their photo responses and
Normally different. Each layer is slightly different
dried. As the film ages
After coating, it is stored for a certain period of time so that it can be
Changes in sensitometry following coating are observed before sales.
has a chance of reaching a certain value. film is photo
Designed to be developed by a finisher or in a darkroom
When processing exposed multicolor film, the film
Minimizes sensitometric variation from film to film
within a very narrow range, typically indicated
The temperature is adjusted to within ±0.5 degrees of the ambient temperature. this multicolor
If the film is a negative format, the sensor
Opportunity to adjust tometry to achieve desired final positive image
Occurs when printing and prints during this operation.
Exposure is appropriately color filtered. The basic causes of the sensitometric variations mentioned above are many.
Also available on color diffusion transfer film, once the film is released.
When loaded, the sensitometric properties are essentially
There is additional complexity that is determined. given by darkroom processing
The opportunity for adjustment is, in practical terms, self-developing.
It is unavailable to film users. Occupation
and color balance for high-end amateur photographers.
color correction to at least partially “rebalance” the
Be skilled enough to use positive filters
However, ordinary film users will not be able to handle this extra operation.
It just confuses you. Using optical screening dyes on photographic elements
It is well known. This dye is used as a filter dye.
in one or more light-sensitive emulsion layers
or two layers coated on top of the light-sensitive emulsion layer.
Mixed between different color sensitized emulsion layers and recorded in the emulsion layer
corrects the light that is transmitted or the light that enters the underlying photosensitive layer.
to adjust the spectral composition or prevent halation.
What kind of support holds the photosensitive layer(s) as a stopping layer?
It can be added to the insensitive layer placed on either side.
can. Provides the necessary spectral absorption characteristics for the anticipated application.
In addition to having, the dyes used for these purposes are
have no adverse effect on the properties of the light-sensitive emulsion layer(s);
Should not be processed, and also stains on photographic elements
photo prints by dissolving them without leaving any residue.
may be bleached or removed during processing.
Must be able to do it. Can be dissolved in processing solution.
Photographic methods that remove dyes by
To avoid contamination of processing solution and processed photosensitive
To prevent staining from residual dyes on the elements
It is preferred that the dye also bleaches. Used for anti-halation and color correction filter layer.
Various types of dyes have been proposed for use in
The dyes used so far are not entirely satisfactory.
Nakatsuta. Some dyes reduce photosensitivity and cause fogging.
or have a tendency to adversely affect photosensitive materials.
show. However, the main dyes used in the past
Defects are due to incomplete bleaching or bleaching to the original colored form.
Due to the tendency to cause stains due to the reversal of colored objects.
be. For example, some dyes are "bleached" or removed.
Depends on the presence of reagents like sulfites for color;
This dye is then removed from the light-sensitive material during or after processing.
If you don't remove it, the color will eventually reappear.
Ru. Types of conventionally used optical screening dyes
It contains triarylmethane. For example,
Permit No. 1879537, No. 1994876, No. 2350090 and
No. 3005711 has a fuchson type in the anti-halation layer.
Discloses the use of dyes and U.S. Patent No. 3,406,069
No. 3615548 is a halation dye.
Concerning metal chelates of chthonic dyes. these species
and other types of triarylmethane dyes as mentioned above.
If you are troubled by one or more of the defects in
However, conventional dyes of this type require no treatment during the treatment following bleaching.
maintain bleaching at pH values normally encountered in the final product and final product.
was difficult. Stanley M.Bloom
Bloom), Alan L.
Borror) and James D'Avrille Fouorii
(James W. Foley) U.S. Patent No. 4,139,381
As a true optical filter agent and filter agent precursor
Certain 3,3-disubstituted sulfur(na)phthalenes
Direct the use of in. as stated there
, one of the 3-substituents is 4'-hydroxy-1'-
enyl moiety or 4'-hydroxy-1'-naphthyl
and the other 3-substituents are phenyl moieties.
or naphthyl moiety, and sulfam(na)phthyl moiety.
The N atom of the thalein ring is substituted with a carbonyl moiety.
It undergoes an irreversible cleavage reaction in alkaline solution.
Let's go. These compounds are initially colorless, i.e.
Do not absorb visible radiation intended to be exposed to photosensitive materials.
When it comes in contact with a base, it can absorb this radiation.
Produces colored compounds, which can be caused by ambient light
Preventing further exposure of the photosensitive material and for a certain period of time
This colored compound after remaining in contact with the base for
The compound becomes free as a result of irreversible cleavage of the carbonyl moiety.
Produces color compounds. U.S. Pat. No. 4,186,001 and U.S. Pat. No. 4,195,180 are
Rubonyl-3,3-disubstituted sulfam(na)sta
Regarding rain. Monkeys disclosed in these applications
Fuam(na)phthalene is first colored and then
When in contact with bases these have a different color
This is converted into a form that is in contact with the base for a certain period of time.
It undergoes an irreversible cleavage reaction after being left in contact with the
This produces a bleached form. U.S. Patent No. 4,316,950
and No. 4304834, which is produced by irreversible cleavage with a base.
disclosed a decolorizing xanthene dye, and the first
Like sulfur(na)phthalein colored in
a completely and irreversibly virtually inert colorless raw material.
Due to its ability to decolorize products, traditional optical screening
offers advantages over bleaching dyes. The present invention is used as a photographic optical screening dye.
heading and also traditionally used for this purpose
to another type of compound that does not contain the defects associated with dyes.
related. The topics of this application are very specifically defined below.
Reallyl methane dyes have a visible range of 400 to 700 mm.
effective absorption of radiation within a predetermined area within the
Absorbent and gelatin or other processing composition
Can be incorporated into material-permeable colloidal binders and
Decolorization with caustic PH yields a colorless product.
Extra reagents, e.g. sulfite for “bleach” reactions
completely and irreversibly with bases without the need for acid salts
Due to its ability to reversely bleach and irreversibly cleave
A new colorless product is produced in the PH range of 1 to 14.
This is why it remains colorless in aqueous solution.
Cleavage products have no possibility of color reappearance over time
Can be retained on photosensitive elements. Since it is non-contaminating,
In addition, this compound is usually not practical for photosensitive materials.
Qualitatively inert and therefore adjacent to the silver halide layer
can be placed in the layer or have an adverse effect on the properties of the emulsion.
It can be directly blended into the emulsion layer without any process. Therefore, the main purpose of the present invention is to use alkaline photographic processing.
Forms a novel ring closure compound upon contact with the composition
Certain colors are irreversibly bleached by
Photographic products using colored triarylmethane compounds
The goal is to provide Another object of the present invention is to improve the multicolor appearance of the film unit.
Asymmetry in color sensitometry of photogenic elements
Exposure is done through it to correct the balance.
The above triarylimethane dye arranged as
Photographic for multicolor diffusion transfer imaging containing (multiple) layers
The purpose is to offer goods. Other objects of the invention are partly obvious and include:
Some of them are shown below. Accordingly, the present invention resides in the features illustrated in the detailed description below.
products and compositions with their own characteristics, properties and relationships;
and including the scope of application indicated in the claims.
nothing. For a fuller understanding of the nature and purpose of the invention
See detailed description below regarding attached drawings.
Should. In particular, the compounds used according to the invention have the formula: [In the formula, A is a phenyl moiety or a naphthyl moiety]
the law of nature, B is 4'-oxo-1'-phenyl moiety or 4'-oxo-1'-phenyl moiety
is a xo-1′-naphthyl moiety, X is (a) {wherein R is unsubstituted or solubilized
an alkyl group or a phenyl group substituted with a group
and R′ is (However, R″ is not replaced or only one
or substituted with two halo groups, or
Substituted with phenyl, alkoxy or phenoxy groups
methyl) and (However, Y is an electron-withdrawing group)
or R and R′ together with the above -N- in the formula
hand }, (b) (wherein R is unsubstituted or solubilized
an alkyl group or a phenyl group substituted with a group
and Y is an electron-withdrawing group), (c) (In the formula, R^ois hydrogen; or unsubstituted
Squid or halo, alkoxy, carboxy group
by substituted alkoxy, phenoxy or phenyl
an alkyl group substituted with
not in the m- or p-position
halo, alkoxy, nitro, dimethyla
substituted with amino or alkyl), or
Taha (d) (In the formula, R is unsubstituted or substituted.
is an alkyl substituted with a solubilizing group and Y is
is an electron-withdrawing group)
I can do it. A portion of the compound represented by the above formula and/or
Part B contains one or more parts in addition to those specified.
The above substituents may also be included in the compound.
I understand that I should not interfere with the intended use of
It will be. Typical substituents are branched or straight chain alkyl, e.g.
For example, methyl, ethyl, n-propyl, isopropyl
n-butyl, t-butyl, hexyl, octyl
dodecyl, hexadecyl, octadecyl and
oicosanyl; aryl such as phenyl and sodium
Phthyl; alkaryl and aralkyl, preferably
or alkyl-substituted phenyl and phenyl-substituted alkyl
p-ethyl phenyl, p-octyl
Phenyl, p-dodecyl phenyl, benzyl, phenyl
enethyl, phenylhexyl and phenyldodecyl
Alkoxy, such as methoxy, ethoxy, butyl;
Toxy, octadecyloxy, 1-ethoxy-2
-(β-ethoxyethoxy); aryloxy, e.g.
For example, phenoxy, benzyloxy and naphthyloxy
C; alkoxyalkyl, such as methoxyethyl
, ethoxymethyl and dodecyloxyethyl;
Halo, such as fluoro, bromo and chloro; tri
halomethyl; e.g. trifluoromethyl and trifluoromethyl;
Chloromethyl; sulfonamide (-NH-
S.O.₂R₀, where R₀is alkyl, aryl, al
quaaryl or aryl); sulfur
Moyle (−SO₂−NH−R₀, where R₀is shown above.
); sulfonyl (-SO₂
−R₀, where R₀has the same meaning as indicated above.
); sulfo; hydroxy; mono- and di-substituted atom
Amino including mino (-NR₁R₂, where R₁and R₂
are hydrogen, alkyl, aryl, and alkary, respectively.
or aralkyl; R₁and R₂be together
to represent the atoms necessary to complete the heterocyclic ring.
For example, piperidino, pyrrolidino, N-lower
Alkylpiperazino, morpholino, thiomorpholino
and tetrahydro-2H,4H-1,3,6-
Contains dioxazosino. Examples of useful X groups are [Formula] (wherein R is unsubstituted or substituted with a solubilizing group,
Kyl group or phenyl group; R¹is [formula] (wherein R″ is unsubstituted, or e.g. one or two
substituted with two halo groups, or phenyl, alkoxy
Methyl substituted with xy or phenoxy group
) and [formula] (where Y is electron attraction and R and R¹is before
Together with the following [formula] Represents [formula]); [Formula] (in the formula, R and Y are as above) have the same meaning as given);
[Formula] (In the formula, R is substituted with an alkyl group substituted with a solubilizing group.
and Y has the same meaning as given above.
); and [formula] (where R^ois hydrogen; unsubstituted or e.g. halo, alkoxy, carboxyl
Boxy-substituted alkoxy, phenoxy or phenyl
alkyl substituted with; or unsubstituted or
For example, halo, alkoxy, nitro, dimethylamino
or alkyl, usually metanu is in the para position
phenyl). As mentioned above, the compounds of the present application are first colored.
i.e. can absorb visible radiation, and
undergoes an irreversible cleavage reaction with bases at alkaline pH.
It is converted to a colorless product by heating. shape
The colorless product formed is different from colored compounds and has a pH
A new change that is irreversible to the colored compound due to changes in
It is a compound. In particular, with a scheduled alkaline PH
An alkaline solution completes within a specified time.
The central carbon atom undergoes a reversible cleavage reaction.
with an X group substituted with a phenyl moiety in the ortho position
Yes, the A moiety is likely to be 4'-hydroxyphenyl.
and the B moiety is 4'-oxo-phenylidene
This results in new closed ring compounds such as those exemplified below. The by-products produced upon cleavage of the X group are colorless.
That can be acknowledged. The cleavage reaction is higher
Since it progresses at a faster rate at the PH value, the compound of the present application
at least the necessary amount for decolorization to the corresponding ring-closure product.
Especially for photographic methods where the PH is kept above about 10 for an hour.
Are suitable. Triarylmethane optical screening of the present invention
Examples of dyes are those represented by the formula below.
Ru: (R in the formula₁is hydrogen, alkyl, alkoxy or hydrogen
Droxy and R²and R^Fourare hydrogen and alkyl, respectively.
selected from chloro, alkoxy, chloro and fluoro.
R;R¹and R²together complete the fused benzene ring.
represents the carbon atoms necessary to form; R³is water
element, alkyl, alkoxy, hydroxy, -N,
N-(dialkyl)amino, -N,N-(ω-R⁸a
Lukiru)₂Amino (where R⁸is halo or hydroxide
), piperidino, pyrrolidino, N-methy
Lupiperazino, morpholino, thiomorpholino or
Tetrahydro-2H,4H-1,3,6-dioxa
It's Zoshino ;R²,R³and R^Fourare melting together
combination [ij] necessary to complete the quinolizidene ring.
Represents an atom; R^Fiveis hydrogen, phenyl, alkyl,
alkoxy, chloro, fluoro or perhalomethi
Lucarbinol; R⁶is hydrogen, alkyl,
Alkoxy, chloro or fluoro; R⁷teeth
Hydrogen, alkyl, alkoxy or hydroxy
ri；R⁶and R⁷together complete the fused benzene ring.
represents the carbon atom necessary to form the
both are unsubstituted or substituted with a solubilizing group
is an alkyl group or a phenyl group; R₁teeth
[Formula] (In the formula, R″ is not substituted or is substituted with two halo groups or phenyl, alkyl
Methyl group substituted with koxy or phenoxy group
) and [Formula] (where Y is an electron is an attractive group); R and R' are selected from
Together with the [formula] of ). “Solubilizing groups” are used in alkaline photographic processing solutions.
Refers to a group that increases the solubility of a compound. preferably
, this solubilizing group is −SO₃H, -COOH or -OH
and said R has 1 to 4 carbon atoms.
It is an alkyl group. If R″ is replaced
, the halo group(s) are preferably chlorine, odor
selected from elemental, fluorine, and two halo elements.
When substituted with groups, these are preferably identical
It is. When substituted with alkoxy, this atom
Lukoxy preferably has 1 to 4 carbon atoms
Ru. Electron-withdrawing group Y is preferably larger than 0.6
Positive sigma value (σ^-). suitable electronic suction
Characteristic groups are nitro; cyano; -SO₂CH₃;
[Formula] [Formula] COCH₃and −SO₂N(CH₂Ph)₂including. these
groups and other groups, such as -CHO, -COOH, -
COOC₂H_Fiveand −CONH₂The sigma value for
Eugen Mu¨ller〓“Methodeu”
der Organische Chemie” Georg Suime
Verlag, Stuttgart, 1970, p. 78
Based on the ionization of p-substituted phenols to σ^-
reported in terms of value. Usually, R¹,R²,R³,R^Four,R^Five,R⁶and R⁷of
Contains 1 to 4 alkyl and alkoxy substituents
lower alkyl having a carbon atom, such as methyl,
Ethyl, n-propyl, isopropyl and n-butyl
chill, and lower alkyls having 1 to 4 carbon atoms.
Koxy, e.g. methoxy, ethoxy, propoxy
and butoxy. Also -N,N-(dialkyl
) amino and -N,N-(ω-R⁸alkyl)₂−
The alkyl group of the amino substituent has 1 to 4 carbon atoms.
and R⁸halo
When it is, preferably chlorine is used. R^Fiveis perhalo
This is preferred when methylcarbinol
[Formula] (In the formula, R〓 is perhalomethyl, For example, trifluoromethyl, difluoromethyl,
Difluorochloromethyl, dichlorofluoromethi
, dichloromethyl and trichloromethyl.
and R〓 is hydrogen or the above-mentioned perhalomethyl, commonly
is always the same as R〓). (In the formula, R, R¹,R²,R³,R^Four,R^Five,R⁶,R⁷as well as
Y has the same meaning as given above). (R in the formula¹¹is hydrogen, alkyl, alkoxy or hydrogen
Droxy and R¹²and R¹⁴are hydrogen and alkyl, respectively.
selected from chloro, alkoxy, chloro and fluoro.
R;R¹¹and R¹²When considered together, completes a fused ring
represents the carbon atoms necessary for R¹³is water
element, alkyl, alkoxy, hydroxy, -N,
N-(dialkyl)amino, -N,N-(ω-R⁸a
(rukyl) amino (R in the formula⁸is halo or hydroxy
); piperidino, pyrrolidino, N-methyl
piperazino, morpholino, thiomorpholino or te
Trahydro-2H,4H-1,3,6-dioxazo
It's Shino ;R¹⁵is hydrogen, phenyl, alkyl,
Alkoxy, chloro or fluoro; R¹⁶teeth
Hydrogen, alkyl, alkoxy, chloro or fluoro
R¹⁷is hydrogen, alkyl, alkoxy or
is hydroxy and R¹⁶and R¹⁷Summary
Considering this, it is necessary to complete the fused benzene ring.
represents a carbon atom; and R⁰is hydrogen; substituted
or halo, alkoxy, or carboxy substituted a
substituted with phenoxy, phenoxy or phenyl
Alkyl; unsubstituted or in m or p position
halo, alkoxy, alkyl, nitro or dimethyl
Phenyl substituted with thylamino. ) R¹¹,R¹²,R¹³,R¹⁴,R¹⁵,R¹⁶and R¹⁷including
Mi, and R⁰and R⁰Alkyl containing substituents above
and the alkoxy substituent has 1 to 4 carbon atoms.
lower alkyl groups such as methyl, ethyl, n
-propyl, isopropyl and n-butyl and 1
lower alkoxy having from to 4 carbon atoms, e.g.
methoxy, ethoxy, propoxy and butoxy
It is. Also, -N,N-(dialkyl)amino and
and -N,N-(ω-R⁸alkyl)amino substituent
Alkyl groups usually have 1 to 4 carbon atoms
lower alkyl, and R⁸is a halo
Sometimes preferred is chlorine. (In the formula, R is unsubstituted or substituted with a solubilizing group.
is the alkyl and R¹¹,R¹²,R¹³,R¹⁴,
R¹⁵,R¹⁶,R¹⁷and Y are the same as shown above
). Preferably R is 1 to
It is an alkyl having 4 carbon atoms. Scope of the invention
Specific examples of compounds within the brackets are as follows: When preparing a compound of the formula: [In the formula, A is a phenyl moiety or a naphthyl moiety]
B′ is a 4′-hydroxy-1′-phenyl moiety or
4′-hydroxy-1′-naphthyl moiety;
Then, R′′′′ is [formula] and R′, i.e. [Formula] (in the formula, R″ is unsubstituted methyl, or is substituted with one or two halo groups or phenyl
substituted with alkyl, alkoxy, or phenoxy groups
methyl), and [formula] (wherein Y is an electron-withdrawing group)
3,3-disubstituted-2,3-dihydrobenz[d]
isothiazole-1,1-dioxide, R is
When [expression] or [expression], The substance of this [formula] or [formula] group The above 2,3-dihydrobenz without cleavage
[d] Opening isothiazole 1,1-dioxide
Reacts with the alkylating agent in the presence of a base in sufficient concentration to
Accordingly, the formula: (In the formula, B is an oxo-1'-phenylidene moiety or
4'-oxo-1'-naphthylidene moiety; A is
has the same meaning as above: D is replaced
or is an alkyl group substituted with a solubilizing group.
R′ is from [formula] and [formula] selected, and Y has the same meaning as above.
), and R is
When [expression] is this [Formula] said compound with a base sufficient to yield the compound described above.
Process (a) of: When carrying out the above method, 2-R'-3,3
-disubstituted 2,3-dihydrobenz[d]isothia
Sol-1,1-dioxide starting material was selected
The alkylating agent is dissolved in an inert organic solvent, e.g.
Hydrofuran, acetone, dimethyl sulfoxide
or reacted in N,N-dimethylformamide.
quaternary ammonia as aqueous phase and phase transfer catalyst.
of dichloromethane, preferably using nium salts.
This is done in a two-phase system containing an organic phase of a polar organic solvent such as
react. Use equal amounts of reactants or
in excess up to about 10 equivalents per equivalent of sothiazole.
This alkylating agent can be used. Isothiazole starting material 2 [Formula] 2 [Formula] and 2 [Formula] substitution The groups, and especially the substituents of the product, are Extremely fast in alkaline solutions, especially with higher PH values
It undergoes irreversible cleavage, so it cannot be used in the method of the present application.
The concentration of base is such that the isothiazole ring allows for N substitution.
The above two substitutions should be sufficient to open
starting material by initiating substantial cleavage of the group.
high enough to destroy (or desired product)
must not. The N-alkylation reaction is carried out in a two-phase system.
If the desired result is obtained, the pH is
Usually around 10. The reaction is carried out in an inert organic solvent.
If carried out, approximately 1 equivalent of the base is added to the isothiazole
Use with 1 equivalent of 1. The specific amount is slightly
Depends on the source and the appropriate concentration of base
It is admitted that this can be easily determined empirically. The order in which the reactants are added is not critical, but
If a batch is included or the addition is interrupted.
The starting material is damaged due to irreversible cleavage reaction when left standing.
The base should be added last to prevent loss.
Ru. If the reaction product is photosensitive, in the dark
It is desirable to carry out the reaction. Although not required,
The reaction may also be carried out under an inert atmosphere, e.g. nitrogen.
This is desirable. The reaction temperature ranges over a relatively wide range from about 0 to 50℃.
can be changed over time and usually favors the reaction
Perform at room temperature. When using a two-phase system, quaternary ammonium
What salts are commonly used as phase transfer catalysts?
and usually about 20 on each alkyl group.
Tetraalkylammocontaining carbon atoms up to
nium bromide or chloride, e.g. n-tetra bromide
Butylammonium, tetrahexylammonium chloride
Ethylhexadecyldimethylammonium bromide
benzyltriethylammonium chloride,
Dodecyltrimethylammonium bromide and trichloride
It is lyoctylpropylammonium. The base can be a hydroxide, hydride or carbonate, e.g.
For example, potassium or sodium hydroxide, hydroxide
Trabutylammonium, sodium or potassium
Muum carbonate or sodium hydride may be used. The alkylating agent used has the formula MD, where M is
halo and D is an unsubstituted or solubilizing group
is an alkyl substituted with ).
Because of their great reactivity, halo substituents are usually
Iodine, but it could also be chlorine or bromine.
Other alkylating agents may also be used to specify the specific N-position desired.
It can be used depending on the reaction product. For example, an alkyl group
is the solubilizing group -SO₃N-al substituted with H
1,3-propanesulfate for the synthesis of kylated products
or 1,4-butanesultone can be used;
The alkyl group is substituted with −OH as a solubilizing group.
Ethylene oxide is used for the synthesis of N-alkylated products.
You can use Sid. -N where COOH is a solubilizing group
- For the synthesis of alkylated products, the alkylation of this acid is
esters, such as I(CH₂)₂COOCH₃Through
The ester of the N-alkylated compound is then converted to the free acid.
These can be manufactured by converting to In addition to these “external” alkylating agents,
Brightness also includes internal alkylation. For example, sulfo
The amide moiety is [formula] In the production of N-alkylated compounds, 2-
[Formula]-3,3-disubstituted-2,3- dihydrobenz[d]isothiazole-1,1-
These can be removed by treating the dioxide with a base.
Manufacture. In this case, 2-
[Formula] root −CH₂The Z substituent is an “internal” alkylating agent
acts as a ring-closing product. chosen
If appropriate to obtain N-substituted products, those skilled in the art
Replacement of the above with other alkylating agents known to those skilled in the art.
It is recognized that it can be done. on the 3,3-substituent, two or more free
2-R′-3,3-disubstituted-2 containing hydroxyl group,
3-dihydrobenz[d]isothiazole-1,
Synthesis of N-alkylated compounds from 1-dioxide
In the presence of potassium hydroxide base, dimethyl
Sulfoxide or N,N-dimethylformamide
Alkylation in an aprotic solvent selected from
Performing the reaction results in a significant increase in yield
There was found. 3-(4′-OP-1′-phenylene) where P is a protecting group
/4'-OP-1'-naphthyl)-2,3-dihydro
Benz[d]isothiazole-1,1-dioxy
1 mole of hydrogen is selected in pyridine at about 0 to 100°C.
selected carboxylic acid halides, e.g.
ClCOR″, ClCO₂(CH₂)₂Y or
[Formula] React with about 1 to 2 moles to give the corresponding 2-carbonyl derivative, followed by
Has a pH of about 0.1 to 5.0 at about 20 to 100℃
The protecting group is removed with acid to form the corresponding 2-carbonyl-
3-(4'-OH-1'-phenyl/4'-OH-1'-naph
thyl)-3-(phenyl/naphthyl)-2,3-di
Hydrobenz[d]isothiazole-1,1-di
The 3,3-substituents are identical by forming an oxide.
one or different 2-substituted-3,3-disubstituted-
2,3-dihydrobenz[d]isothiazole-
A 1,1-dioxide starting material can be synthesized. departure
3-(Phenyl) which ultimately forms part A of the substance
hydroxyl group with a protected substituent (naphthyl/naphthyl), e.g.
-OR or -N(CH₂CH₂OP)₂if you have
, it is necessary to remove this protecting group,
Free -OH or -N as desired
(CH₂CH₂OH)₂Unblock this to play
can be converted into The protecting group used was 3-(4′-OP-phenylene).
Nyl/4′-OP-naphthyl) substituent
The protecting group may be the same as or different from the protecting group. example
For example, 3-(4'-OP-1-naphthyl/4'-OP-1'-
Naphthyl) substituents can be unblocked.
Protecting groups such as trimethylsilyl protecting groups can be selected.
On the other hand, the hydrogen of the 3-(phenyl/naphthyl) substituent
Protecting groups on droxy, e.g. methoxymethyl protection
Leave the foundation. 3,3-disubstituted-2,3-dihydrobe
Lens[d]isothiazole-1,1-dioxide
before N-acylation and subsequent removal of protecting groups.
The method described forms the subject of Canadian Patent No. 1110237
do. The acid used for this deblocking step is
Protic acid solvents such as water, alkanols, etc.
methanol or ethanol; or aqueous alkano
an inorganic acid such as hydrochloric acid or sulfuric acid, or
Organic acids, alone or in protic solvents, e.g. vinegar
acid or trifluoroacetic acid. Carboxylic acid halides can be prepared by conventional methods, e.g.
Trisalt of selected carboxylic acid, e.g. R″COOH
By reacting with phosphorus chloride or phosphorus pentachloride or thionyl chloride
yielding the corresponding R″COCl or the selected
HO(CH₂)₂Respond by reacting Y with phosgene
ClCO₂(CH₂)₂It can be manufactured by producing Y. 3-(4′-OP-1′-phenyl/4′-OP-1′-na
phthyl)-3-(phenyl/naphthyl)-2,3-
dihydrobenz[d]isothiazole-1,1-
To produce dioxide, 3-(4'-OP-1'-
Phenyl/4′-OP-1′-naphthyl)benz[d]
-isothiazole-1,1-dioxide
Zen, diethyl ether, dioxane, hexa
toluene, petroleum ether or tetrahydrofuran
at least 1 mol in an inert organic solvent such as oran
Equivalent amount of phenyllithium or naphthyllithium sample
React with the drug. The reaction temperature depends on the specific reactants.
Although it can be easily determined by
They vary over a wide range of purposes. get maximum yield
Therefore, the reaction is generally carried out at temperatures below about 0°C, and preferably
The test is carried out at a temperature of about -65 to -25°C. child
3-(4′-OP-1′-phenyl/4′-OP-1′-na)
phthyl)-3-(phenyl/naphthyl)-2,3-
dihydrobenz[d]isothiazole-1,1-
This method of producing dioxide has been awarded Canadian Patent No.
Forms the subject matter of No. 1110039. selected 4-halofenols or 4-halo-
1-Naphthol, as appropriate, a functional hydroxyl
Blocking groups and optional substituents
And this blocked phenol or 1-na
Phthol with corresponding Grignard or lithium
converted into a drug, which is then reacted with the saccharin reagent
This 3−(4′−OP−1′−Phenyl)
/4'-OP-1'-naphthyl)-bendi[d]-iso
Produce thiazole-1,1-dioxide. Li
phenol or block where the tium reagent is blocked.
1-naphthol is reacted with lithium metal.
4-halo substitution when produced by
The radicals are chlorine, bromine or iodine, and for example
Lithium exchange reaction using n-butyllithium
When making lithium reagent via bromine or iodine
Any of the elements. Blocked phenol
reacts 1-naphthol with magnesium metal
When producing Grignard reagent by
The 4-halo substituent is chlorine, bromine or iodine.
Ru. Grignard or Lichi produced in this way
um reagent to saccharin, saccharin N-lithium
Corresponds by reacting with mu salt or saccharine pseudochloride
3-(4′-OP-1′-phenyl/4′-OP-1′-
naphthyl)benz[d]isothiazole-1,1
-Produces dioxide. In general, the Grignard test
React the drug with pseudochloride and lithium reagent
is reacted with N-lithium salt. Functionality present in phenol or 1-naphthol
Phenolic or naphtholic hydroxyl groups and other water
The group chosen to protect the acid group is an organolithium
stable and compatible with and Grignard reagents
and the synthesis of said compound followed by a
hydroxyl group for reaction under the conditions encountered in the silation step.
(plural) should be protected. Further selected protection
The protecting group is the N-carbonyl moiety or other substituent that is present.
Contained under mildly acidic conditions to regenerate hydroxyl groups without removal of groups.
Must be easily removable. N-carbonyl
Methyl and
Alkyl groups such as ethyl can be used. these
without interfering with the N-substituent or other substituents.
Since it is easily removed, phenol or 1-naph
Toll is preferably methoxymethyl, 2'-tetra
Hydropyranyl or dimethyl-t-butylsilyl
protected by For example, Kaoru Fujii et al.Synthesis, 4th
methoxy as described on pages 276-277 (1975)
By methylation, e.g.
William E. Parham et al.J.Am.Chem.
Soc. , 70, pp. 4187-4189 (1948).
or by tetrahydropyranylation as
- Ray (E.J.Corey) etc.J.Am.Chem.Soc．． ,94,
Imitation as described on pages 6190-6191 (1972)
By silylation in the presence of dazole, e.g.
Using t-butylsilyl chloride, these
Blocked phenols and
and 1-naphthol. As above, phenol and 1-naphthol
The hydroxyl group outside the functional −OH is, for example, tetrahydro
Functional hydroxyl by pyranylation or methoxymethylation
It is blocked at the same time as the original. Hydroxylic acid to be protected
Groups other than the group may be added before blocking the functional -OH or
It is subsequently blocked. For example carboxy
The groups are carboxy-substituted 4-halophenol
(or 4-halo-1-naphthol) to 2-amino
- react with 2-dimethyl-1-propanol,
It is then protected by blocking the functional −OH.
Ru. Sulfonmamide (-NH-SO₂−R₀) and sa
Luhuamoil (−SO₂−NH−R₀) Substituent is t-
Protected by a butyl group. 3-(4'-OP-phenyl/4'-OP-naphthyl)
Benz[d]isothiazole-1,1-dioxy
Finally, part A of the starting material is formed by reacting with
phenyl and naphthyllithium reagents are substituted
may be substituted or unsubstituted, the corresponding halo substitution
Manufactured from compounds. For example, N,N-dimethy
Halogenating luaniline to produce 4-halo compounds
This is then treated with lithium metal or n-butyl lithium.
reacts with 4-lithium to produce 4-lithium compounds.
Either chlorine or bromine, with or without catalyst
or using N-bromosuccinimide or
Halogenate in the usual manner using iodine monochloride.
Perform rogenization. 4-For the production of lithium compounds
When using lithium metal, the halo substituent is a salt
chlorine, bromine or iodine, and lithium exchange
When using the reaction, either bromine or iodine
be. When a substituent such as a hydroxyl group is present
are blocked with a suitable protecting group to form 4-
Compatibility with organometallic reagents prior to conversion of lithium compounds
should be made. 2-substituted-3,3-disubstituted-2,3-dihydro
Benz[d]isothiazole-1,1-dioxy
When the 3,3-substituents of the starting materials are different,
3-(phenyl/naphthyl)benz[d]isothi
Azole-1,1-dioxide, i.e. 4'-OP-
3-(phenyl/naphthyl) base containing substituents
Lens[d]isothiazole-1,1-dioxide
Preferably below about 0°C, inert organic
At least 1 equivalent of 4-OP-phenylated in the solvent
Reaction with lithium/4-OP-naphthyllithium reagent
to give the corresponding 3,3-disubstituted-2,3-dihyde
Robenz[d]isothiazole-1,1-dioxy
sid, followed by N-acylation and as described above.
These can also be produced by deblocking the sea urchin.
Ru. halo-benzene or halo- as appropriate
Blocking substituents of naphthalene compounds
and convert this halo compound into the corresponding Grignard or
converting it into a lithium reagent, which is then converted into a lithium reagent.
3-(Phenyl) by reacting with phosphorus reagent
/naphthyl)benz[d]isothiazole-
1,1-dioxide can be produced. 3-(Fueni
/naphthyl)-3-(4'-OP-1'-phenyl/
4′-OP-1′-naphthyl)-2,3-dihydroben
[d]isothiazole-1,1-dioxide
The above method of synthesis is the subject of US Pat. No. 4,178,447.
form a topic. 2-substituted-3,3-disubstituted-2,3-dihydro
Benz[d]isothiazole-1,1-dioxy
When the 3,3-substituents of the starting materials are the same
is preferably dissolved in a small amount in an inert organic solvent at below 0°C.
At least 2 equivalents of 4-OP-phenyllithium/4
-OP- naphthyllithium reagent in 1 equivalent
By reacting with phosphorus pseudochloride, the corresponding 3,3-bi
Su-(4′-OR-1′-phenyl/4′OP-1′-naphthyl)
)-2,3-dihydrobenz[d]isothiazo
by producing alcohol-1,1-dioxide
These can also be synthesized. Next, add this bis compound to
reacted with acid chloride, and as discussed earlier
Unblock using the same method. 3,3-bis-
(4′-OP-1′-phenyl/4′-OP-1′-naphthyl)
-2,3-dihydrobenz[d]isothiazole
The above synthesis of -1,1-dioxide is described in U.S. Pat.
Forms the subject of issue No. 4191689. One of the 3,3-substituents is perhalomethyl carbide.
4′-OH-1′-phenyl/4′- with a nol moiety
OH-1′-naphthyl substituent 2-substituted-3,
3-Disubstituted-2,3-dihydrobenz[d]iso
Synthesis of thiazole-1,1-dioxide starting material
The preferred method of
4-OLi- substituted with [formula] moiety in medium Phenyllithium/4-OLi-naphthyllithium
At least 2 equivalents of reagent and 3-substituted-benz[d]i
By reacting sothiazole-1,1-dioxide
The corresponding reaction product is produced, followed by addition with acid at pH 6.
After water decomposition, the above 3-(4'-OH-1'-phenyl/
4′-OH-1′-naphthyl substituent is [formula] moiety 3-(4'-OH-1'-phenyl/4'-OH
-1'-naphthyl)-3-(substituted)-2,3-dihyde
Robenz[d]isothiazole-1,1-dioxy
Including producing sid. “Lithiumization
(Iithiated) “Perhalomethylcarbinol-substituted
from enol (or 1-naphthol) to the above-mentioned pel
Production of halomethyl carbinol substituted compounds
The method of forms the subject of US Pat. No. 4,283,537. Perhalomethylcarbino prepared as described above
acidic alumina or zeolite
in pyridine at 0 to 100°C in the presence of small sieves.
1 to 6 equivalents of acid halide, ClCO₂(CH₂)
The above 3-(4'-OH-1'-phenylene)
/4′-OH-1′-naphthyl) substituent
[Formula] has the corresponding 2-(- C.O.₂(CH₂)₂Y-3-(4'-OH-1'-phenyl/
4′-OH-1′-naphthyl)-3-(substituted)-2,3-
dihydrobenz[d]isothiazole-1,1-
Produces dioxide. The above 2-(-CO₂
(CH₂)₂Y) This method of manufacturing the compound is a US patent.
Forms the subject of Grant No. 4210752. This “lithiated” perhalomethyl carbino
Made from 1-substituted phenols (or 1-naphthol)
The perhalomethyl carbinol-substituted compound prepared by
Also, 3 to 6 units of pyridine at 0 to 100℃
of the acid halide ClCOR''
(4′-O-COR″-1′-phenyl/naphthyl) substitution
The corresponding tris in which the group has the [formula] moiety Acyl compound 2-(-COR″)-3(4′-O-
COR″-1′-phenyl/4′-O-COR″-1′-naph
(chill)-2,3-dihydrobenz[d]isothia
sol-1,1-dioxide followed by zero
Treated with 0.01 to 2.0N base at 40°C.
Therefore, phenolic (or naphtholic) hydroxyl group
and select acyl group only from carbinol hydroxyl group
to remove. This base is, for example, methylamine.
but preferably ionic hydroxide bases, e.g.
water and/or lower alkanols such as methanol
tetrahydroxide in a solvent such as alcohol or ethanol
Butylammonium, sodium hydroxide or hydroxide
potassium. The above 2-(-COR″) compound
This method of synthesizing the product is described in U.S. Pat. No. 4,255,578.
Form a theme. The foregoing method for producing starting materials useful in the foregoing method.
Certain 2-substitutions useful as starting materials outside of the process
-3,3-disubstituted-2,3-dihydrobenz
[d] Isothiazole-1,1-dioxide is rice
National Patent No. 4178446, National Patent No. 4204061, National Patent No.
No. 4195180, No. 4231929 and No. 4259493
disclosed and claimed, and these patents
Inserted here for convenience by reference. The R group in the above [Formula] moiety is substituted phenyl without or substituted with a solubilizing group
() Compounds can exist functionalities -OH and other -
If the OH group is a bromine such as 2'-tetrahydropyranyl,
Phenol/1-naphthol protected by a tsuku group
It can be produced from sulfonephthalein. For example -
After “blocking” the OH group, the protected chain is
Enol/1-naphtholsulfonephthalein
Corresponding by reaction with thionyl chloride or phosphorus pentachloride
sulfonyl chloride, which can be converted into an alkyl or alkyl chloride.
Reel Amine RNH₂(In the formula, R is as shown above.
) has the same meaning as
produces sulfonamide. Next, this sulfonamide
with a suitable acylating agent, e.g. ClR' (wherein R' is
have the same meaning as shown in ).
This produces a leuco dye precursor, which we will now use as an example.
Remove protecting groups before oxidation with O-chloranil
to produce a dye product. Phenolsulfonf blocked with protecting group
Thalein is used to illustrate this reaction sequence. Here, R and R' in the above order are as shown above.
has the same meaning as To further illustrate the preparation of compounds of formula (),
A synthesis example is shown below. Synthesis example 1 formula: Manufacture of a compound having Potassium carbonate (K) in 50ml of water₂C.O.₃)0.23g and 2
−(−CO₂CH₂CH₂S.O.₂CH₃)-3(3',5'-dimethy
-4′-hydroxy-1′-phenyl)-3-(4″-
N-morpholinyl-1″-phenyl)-2,3-di
Hydrobenz[d]isothiazole-1,1-di
1.0 g of oxide was added. Iodide this red solution
Add 50 ml of dichloromethane containing 2 ml of methyl
A two-phase system was created. Tetrabutyl ammonium chloride
4% solution (21 mg) and this mixture
Stir thoroughly for 48 hours, at which time the aqueous phase will be colorless.
and the dichloromethane layer was red.
Separate this dichloromethane and K₂C.O.₃Wash with dilute solution
then rinse with water and dry with sodium sulfate.
It was dry. Evaporate this dichloromethane to form a red solid.
Yield 1.02g. This solid is dissolved in isopropanol.
Recrystallization from 30 ml yielded 0.75 g of red crystals.
Add 9.5ml of ether/0.5ml of methanol to silica gel.
The TLC used is traces of benz[d]isothiazo.
ole-1,1-dioxide starting material is still present.
It was shown that The remaining red crystals (~0.65g)
Medium pressure liquid chromatography (silica gel/acetic acid
(ethyl) to yield 0.5 g of the title compound.
It was. Synthesis example 2 formula: Manufacture of a compound having K in 50ml of water₂C.O.₃0.16g and 2-(-
C.O.₂CH₂CH₂CN)-3-(3',5'-dimethyl-4'-
hydroxy-1′-phenyl)-3-(4″-N,N-
dimethylamino-2″-methyl-1″-phenyl)-
2,3-dihydrobenz[d]isothiazole-
0.6 g of 1,1-dioxide was added. Then iodide
Add 50 ml of dichloromethane containing 3 ml of methyl
As a result, a two-phase system is formed, and the aqueous layer is intensely red.
Ta. Add 4% tetyl chloride to this well-stirred mixture.
Add Butylammonium and reaction mixture
was stirred for 16 hours. After stirring, the water layer is light yellow.
color and the dichloromethane layer is red.
Ta. Separate this dichloromethane layer and wash with water
dried with sodium sulfate and evaporated to red
A colored solid remained. Chloroform 9.5 on silica gel
TLC using ml/0.5ml methanol has three steps.
It showed the pot. Remove remaining red solid with silica gel
Place on a packed column and add chloroform
Elution is indicated in the solvent system: methanol/methanol (9.5:0.5).
yielded a compound. Synthesis example 3 formula: Manufacture of a compound having K₂C.O.₃2- in 25 ml of water containing 0.027 g
(COCH₃)-3-(4'-hydroxy-1'-naphthyl)
-3-(4″-N,N-diethylamino-1″-phene
nil)-2,3-dihydrobenz[d]isothia
0.100 g of sol-1,1-dioxide was added.
2 ml of methyl iodide and tetrabutylammonium chloride
25 ml of dichloromethane with spatula tips
added. As you stir, the color changes to magenta.
formation occurred and the aqueous layer became colorless. (Jik
The lolomethane layer contained dye). This reaction mixture
I stirred things all night. 7/3 ether/petroleum
TLC on silica gel using ether shows that the reaction is complete.
indicated that it was completed. Separate the dichloromethane layer
, dried and evaporated to dryness to appear as a red solid.
This yielded 0.100 g of the following compound. Synthesis example 4 formula: Manufacture of a compound having K in 20 ml of water at room temperature₂C.O.₃0.0205g, 2-
(COCH₃)-3(3',5'-dimethoxy-4'-hydro
xy-1′-phenyl)-3-(4″-N,N-diethyl
Ruamino-1″-phenyl)-2,3-dihydrobe
Lens[d]isothiazole-1,1-dioxide
0.076g, dichloromethane 20ml, methyl iodide 2
ml and spatch of tetrabutylammonium hydroxide
Added Yurachip. The blue water layer quickly becomes colorless.
and the dichloromethane layer turns magenta.
Ta. Stir the reaction mixture overnight until dry.
evaporate to produce the compound shown as a magenta solid.
left. Dichloromethane 9.7ml/methanol 0.3ml
TLC on silica gel shows that the product is homogeneous.
It showed that there is. Synthesis example 5 formula: Manufacture of a compound having 2-(-COCH dissolved in methanol₃)-3-
(4′-hydroxy-1′-naphthyl)-3-(4″-N
，
N-diethylamino-1″-phenyl)-2,3-
dihydrobenz[d]isothiazole-1,1-
Add tetrabutyl hydroxide to a solution of 0.10 g of dioxide.
0.2 g of a 25% methanol solution of ammonium was added.
The resulting solution is evaporated to dryness and the residue is converted into tetrahydride.
Dissolved in 20 ml of Lofuran and 1,3-propantha.
Added 0.5 g of Luton. This reaction mixture was heated overnight.
Reflux and remove tetrahydrofuran under reduced pressure.
did. Dissolve the residue in 2 ml of chloroform and
and silica gel and 9/1 ether/methanol.
Separate the products using preparative TLC techniques using
Ta. The indicated compound is obtained as a pure hygroscopic solid.
It was. Synthesis example 6 formula: Manufacture of a compound having K in 20ml of water₂C.O.₃0.071g, dichloromethane 20ml,
2 ml of methyl iodide and tetrabutylammonium chloride
2-(-
COCH₃)-3-(3',5'-dichloro-4'-hydroxy
C-1′-phenyl)-3-(4″-N,N-diethyl
Amino-1″-phenyl)-2,3-dihydroben
[d]isothiazole-1,1-dioxide
Added 0.266g. A blue aqueous solution tends to become colorless.
The dichloromethane layer turned purple. This reaction mixture
Stir the mixture well overnight and remove the dichloromethane layer.
Separate, dry with sodium sulfate and evaporate
It left behind a purple residue that crystallized on standing. child
The crystals were washed with ethanol and filtered. workman
Evaporation of the tanol filtrate yields the indicated compound.
Ta. Synthesis example 7 formula: Manufacture of a compound having 2-(-COCH₃)-3-(3'-chloro-4'-hydro
Roxy-1′-naphthyl)-3-(4″-N,N-die
thylamino-1″-phenyl)-2,3-dihydro
Benz[d]isothiazole-1,1-dioxy
0.158g, water 10ml, K₂C.O.₃0.041g, dichloromethane
Stir together 20 ml of tan and 2 ml of methyl iodide.
Ta. Tetrabutylammonium chloride is added to this blue mixture.
Added Umu's Spatuyula Chip. This blue water soluble
The liquid immediately becomes colorless and the dichloromethane layer is
It turned purple. Stir this reaction mixture overnight.
Ta. TLC on silicage in ether completes the reaction.
showed that. Separate the dichloromethane layer and add sodium sulfate
dried over 100 ml and evaporated to a dark purple solid.
0.162 g of the indicated compound remained. Synthesis example 8 formula: Manufacture of a compound having 2-(-COCH₃)-3-[(3'-α-hydroxy
-α-trifluoromethyl-β,β,β-trif
(fluoroethyl)-4′-hydroxy-1′-naphthyl]
-3-(4″-diethylamino-1″-phenyl)-
2,3-dihydrobenz[d]isothiazole-
1,1-dioxide 0.584g, K₂C.O.₃0.12g, water
25ml, dichloromethane 25ml, methyl iodide 2ml and
and one splice of tetrabutylammonium chloride.
They stirred the yura chips together. This blue aqueous solution
It becomes colorless immediately and dichloromethane is blue.
It was hot. The reaction mixture was stirred for 16 hours. workman
TLC is a very small amount of silica gel using
This indicated that the desired reaction product had formed. chloride
One more spatula of trabutylammonium
Further K₂C.O.₃Added with. This reaction mixture was heated overnight.
After stirring through, TLC shows approximately 50% conversion.
did. Purify the indicated compound using preparative TLC
and obtained as a blue solid. Synthesis example 9 formula: Manufacture of a compound having 2-(-COCH₃)-3-[3'-α-hydroxy-
α-Trifluoromethyl-β,β,β-triflu
(oroethyl)-4'-hydroxy-1'-naphthyl]-
3-(9'-diulolidinyl)-2,3-dihydrobe
Lens[d]isothiazole-1,1-dioxide
0.30g in dichloromethane 25ml, water 25ml,
K₂C.O.₃0.07g (10% excess), 2ml methyl iodide and
Tetrabutylammonium chloride spatula
I put it in the flask with Tsupu. dichloromethane layer
is colored cyan. The reaction mixture was stirred overnight.
Stir quickly. Separate the dichloromethane layer and dry
Dry and evaporate. TLC prepared with residual sample
Separate the appropriate bands using
The acetone is then evaporated to form a cyanide solid.
to give the title compound. Synthesis example 10 2-(-CO₂CH₂CH₂CN)-3-(3',5'-dime
thyl-4'-hydroxy-1'-phenyl)-3-
(4″-methoxy-1″-phenyl)-2,3-dihyde
Robenz[d]isothiazole-1,1-dioxy
0.9 g of cid, 20 ml of water, 20 ml of dichloromethane,
K₂C.O.₃0.252g, 2ml methyl iodide and tetyl chloride
With labylammonium spatula tips
I put it in a flask. Stir this reaction mixture well overnight.
Stirred. Using 8/2 ether/chloroform
TLC on silica gel showed that the reaction was almost complete.
and showed. Then separate this chloroform layer and
Dry with sodium sulfate and evaporate to yellow
A solid remained. Dissolve this yellow solid in chloroform.
diluted and silicaed with 8/2 ether/chloroform.
Put chloroform into a column packed with Kagel.
It was eluted with Collect and evaporate appropriate fractions
yielded the title compound as a yellow solid. Synthesis example 11 formula: Manufacture of a compound having 2-(-COCH₂CH₂CN)-3-[(3'-α-hydro
Roxy-α-trifluoromethyl-β,β,β-
trifluoroethyl)-4'-hydroxy-1'-na
phthyl]-3-(9'-diulolidinyl)-2,3-
dihydrobenz[d]isothiazole-1,1-
Dissolve 0.068g of dioxide in 20ml of dichloromethane
and add K to this solution₂C.O.₃0.013g, water 20ml,
1 ml of methyl uride and tetrabutylammonium chloride
Added the spatula chips. Cyan color of water layer
was transferred to the dichloromethane layer. This reaction mixture
Stir at room temperature for 4 hours. Silica with ether
TLC on gel showed the reaction was complete. Ji
Separate the chloromethane layer, wash with water and sulfuric acid
Drying with sodium yields a blue solid upon drying
Ta. Using TLC prepared with silica gel and ether
The cyan band was separated by elution with an acetate solution.
Processed with Filter and remove this acetone
The title compound was obtained as a cyan solid. Synthesis example 12 formula: Manufacture of a compound having K dissolved in 50ml of water₂C.O.₃2−(−
C.O.₂CH₂CH₂S.O.₂CH₃)-3-(3',5'-dimethoxy
-4′-hydroxy-1′-phenyl)-3-(4″-N
-morpholinyl-1″-phenyl)-2,3-dihy
Dorobenz[d]isothiazole-1,1-dio
731 mg of oxide was added resulting in a strong red solution.
Add 50 ml of dichloromethane and 3 ml of methyl iodide to this solution.
ml, followed by several mg of tetrabutylammonium chloride.
added. The reaction mixture was incubated quickly under nitrogen for 16 h.
I mixed it up. The aqueous phase becomes virtually colorless and
The lolomethane layer was colored. Separate dichloromethane
and rinse with two 100ml portions of water and sodium sulfate.
and filtered. Evaporate the filtrate to dryness
and reconsolidate the remaining sample from 45 ml of boiling propanol.
Crystallize and dry at 50-55 °C in vacuum overnight.
This yielded 460 mg of the title compound. Synthesis example 13 formula: Manufacture of a compound having 2-(-) in 35 ml of dry tetrahydrofuran
C.O.₂CH₂CH₂S.O.₂CH₃)-3-(3',5'-dimethoxy
-4'-hydroxy-1'-phenyl)-3-(9'-di
eurolidinyl)-2,3-dihydrobenz[d]
2.82 g of isothiazole-1,1-dioxide, continued
and added 304.3 mg of 85% potassium hydroxide (powdered).
I got it. After stirring for 15 minutes, add 5.6 ml of methyl iodide.
was added all at once and the reaction mixture was allowed to stand at room temperature for 5 hours.
Stir and pour into 350 ml of water containing 10 drops of 6NHCl.
I entered. Mix this mixture with three 100 g of chloroform
Chloroform extract extracted and combined in ml portions
Three 100ml portions of water, saturated sodium chloride solution
Wash with solution and dry with sodium sulfate overnight.
did. This solvent was removed leaving a purple residue, which
was recrystallized from about 25 ml of ethanol to give a slight departure.
This yielded 1.8 g of crude product containing material. This coarse
Pass the product through a medium pressure liquid chromatography column.
filtered and eluted with 40/1 chloroform/methanol.
Ta. The residue from the column was recrystallized from ethanol.
This yielded 1.4 g of the title compound. Synthesis example 14 formula: Manufacture of a compound having 2-(-
C.O.₂CH₂CH₂S.O.₂CH₃)-3-(3',5'-dimethoxy
-4′-hydroxy-1′-phenyl)-3(2″,4″-
dimethoxy-1″-phenyl)-2,3-dihydro
Benz[d]isothiazole-1,1-dioxy
Added 1.0 g. Then K in 15ml of water₂C.O.₃115mg
solution, followed by 937 mg of methyl iodide and tetyl chloride.
278mg of butylammonium was added. reaction mixture
Stir the mixture at room temperature for about 24 hours and transfer to a separatory funnel.
did. Separate the dichloromethane layer and add water (3 x 25
ml), washed with saturated sodium chloride solution (1 x 25 ml).
and then dried over sodium sulfate. Dissolution under reduced pressure
The medium was removed leaving 1.2 g of a red-orange oil. this oil
Add to about 50ml of isopropanol and heat until dissolved.
and allowed to cool to room temperature. orange yellow
A solid precipitated. TLC showed a small amount of impurity.
Add the remaining solid (780 mg) to isopropylene while stirring.
Redissolved in panol. Cool this solution to room temperature
Collect the yellow crystalline precipitate and convert it into the notation.
600 g of compound were obtained (melting range 145-6°C). Synthesis example 15 formula: Manufacture of a compound having 2-(-
COCH₃)-3-(3',5'-dimethyl-4'-hydroxy
-1′-phenyl)-3-[4″-N,N-di(β-
hydroxyethyl)amino-1″-phenyl]-2,
3-dihydrobenz[d]isothiazole-1,
K in 0.500g of 1-dioxide₂C.O.₃Contains 0.131g
10-12 ml of water was added. strong violet maze
A tan color developed in the aqueous phase. Next, 2 ml of methyl iodide
and a catalytic amount of n-tetrabutylammonium chloride.
(spatiula chips) and the reaction mixture
was stirred overnight at room temperature. 60/40 ethyl acetate/
Silica gel using petroleum ether with little TLC
showed traces of newly colored spots. room temperature
Continue stirring and then add another 4ml of methyl iodide.
and a small amount of catalyst was added. The reaction mixture was incubated again overnight.
Stir, and 60/40 ethyl acetate/petroleum acetate.
TLC on silica gel to remove some starting material and place
Indicate the following spots that correspond to the desired product.
Ta. Remove the solvent to leave a dark maroon-magenta colored solid.
left. 80/20 ethyl acetate/petroleum ether solvent
Prepare the indicated compound using TLC technique using
separated. Synthesis example 16 formula: Manufacture of a compound having 2-(-
C.O.₂CH₂CH₂CN)-3-(3',5'-dimethyl-4'-
Hydroxy-1′-phenyl)-3-[4″-N,N-
Di(β-hydroxyethyl)amino-1″-phenylated
]-2,3-dihydrobenz[d]isothiazo
0.691 g of alcohol-1,1-dioxide was added. Next
niK₂C.O.₃50ml of water containing 0.168g was added. dark
A deep magenta-violet color developed in the aqueous layer.
Stir this mixture vigorously and add the tetrabromide
6 ml of methyl iodide with 45 mg of butylammonium
added. Stir the reaction mixture vigorously overnight.
Zeta. The aqueous phase has a deep magenta-violet color.
Most of the liquid was lost and the organic phase became orange-yellow.
Silica gel with 85/15 ethyl acetate/acetone
TLC has one major red-magenta spot and
and other small spots of trace starting material.
Ta. Decant this organic dichloromethane phase and
Wash the aqueous phase with several portions of dichloromethane and
were combined with the organic phase. Add the blended organic phase to 3 ml of water.
The shrimp can be washed in portions and then removed the solvent under reduced pressure.
A brown-bronze tar is produced which is dried under vacuum.
This produced bright maroon-bronze solid particles.
This solid was purified via medium pressure column chromatography.
(85/15 ethyl acetate/acetone solvent)
silica gel used). Implied - maroon eluent
When collected and the solvent is removed, 0.6g of the indicated compound is obtained.
occured. Synthesis example 17 formula: Manufacture of a compound having (a) Dissolved in 25-30 ml of N,N-dimethylformamide.
2−(−CO₂CH₂CH₂S.O.₂CH₃)-3-
[(3′-α-hydroxy-α-trifluoromethyl
-β,β,β-trifluoroethyl)-4′-
Hydroxy-1′-naphthyl]-3[4″-N,N-
di(β-2″-tetrahydropyranyloxyethyl
)-1″-phenyl]-2,3-dihydrobenz
[d] Isothiazole-1,1-dioxide 1.9
g to 1.5 ml of methyl iodide and powdered 85% hydroxide
0.15g of potassium was added. This reaction mixture is
Stir vigorously for 3 to 4 hours at warm temperature. 80/20
Ethyl acetate/acetone (or pure ethyl acetate)
Silica gel TLC was performed using
There was no indication that he was present. The reaction mixture is then mixed with a small amount of
Inject into cold water containing HCl and acetic acid
Top layer with ethyl. Decant the water and add ethyl acetate.
The chill was washed several times with water. Then remove the solvent
Dissolve the blue solid in 20ml of ethyl acetate.
and 80/20 ethyl acetate/hexane as solvent.
Low pressure liquid chromatography using
I put it on top of the screen. Collect the blue part and remove the solvent
and the residue was dried under vacuum to obtain 0.340 g of solid.
occured. (b) Mix the product of step (a) (0.340 g) with methanol 35
Dissolved in ~40ml and then added 4 drops of concentrated HCl. child
Gently heat the solution in a steam bath for about 15 minutes, slightly
Injected into cold water containing sodium chloride
and extracted with ethyl acetate. This ethyl acetate is
Anhydrous sodium sulfate in the presence of dried activated carbon
and filtered. remove the solvent and
Dry the residue under vacuum to obtain 0.214g of the indicated compound.
occured. Synthesis example 18 formula: Manufacture of a compound having 2-(-
COCH₃)-3-(3',5'-dimethyl-4'-hydroxy
C-1′phenyl)-3-(4″-N-morpholinyl-
1″-phenyl)-2,3-dihydrobenz[d]
Approximately 2.0 g of isothiazole-1,1-dioxide
The solution is K dissolved in 200 ml of water.₂C.O.₃0.28g solution
added to. Tetrabutylammonium chloride is added to this mixture.
0.22 g of sodium and 17.2 ml of methyl iodide were added. child
The two-phase reaction mixture was stirred for 18 hours. TLC is
It showed that some starting material was still present. The rest
Minute K₂C.O.₃Methiodide (complete small spatula)
was added along with an additional 2 ml. Then the reaction mixture was
I stirred for hours, but there was no apparent change in TLC.
Ta. Separate the organic dichloromethane layer from the aqueous layer and add water
Wash with 300ml and dichloromethane under reduced pressure.
Removal yielded 1.06 g of a dark orange solid. Chlorinate solids
Dissolve in 10ml of Roform and perform medium pressure liquid chromatography.
Charge it to e-column (silica gel) and add 8/2 vinegar.
0.50 of the indicated compound eluted with ethyl acid/hexane
g. Synthesis example 19 formula: Manufacture of a compound having (a) 2-(-COCH dissolved in 50 ml of methanol₃)
-3-(3',5'-dimethyl-4'-methoxymethoxy
C-1'-phenyl)-3-(9'-diyloliginy)
)-2,3-dihydrobenz[d]isothia
In a solution of 0.67 g of sol-1,1-dioxide,
Added 2 drops of HCl. Put this solution in a steam bath for half an hour.
Refluxed. TLC shows no starting material present.
Katta. The methanol was removed leaving an oil. child
of oil in dichloromethane and three times with water.
Washed. (b) Dissolve the dichloromethane solution from step (a) in 40ml of water.
K did₂C.O.₃0.3g and tetrabutyl ammonium chloride
was added to a solution of 0.2 g of um. This two-phase system
Add 0.5 ml of methyl chloride, and reduce the reaction mixture to 16
I stirred the time. TLC indicates reaction is complete
showed that. Separate the organic phase, wash three times with water,
Dry and evaporate the dichloromethane.
A dark brown oil was produced. Add this oil to silica gel (100~
200 mesh) and 7/3
Expressed as eluted with acetic acid ether/hexane solution
yielded a pure sample of the compound. Synthesis example 20 formula: Manufacture of a compound having 2-(-
C.O.₂CH₂CH₂CN)-3-(3',5'-dimethyl-4'-
hydroxy-1′-phenyl)-3-(3″,5″-dime
Chil-4″-methoxymethoxy-1″-phenyl)-
2,3-dihydrobenz[d]isothiazole-
Add a small amount of (catalyst) to a solution of 0.55 g of 1,1-dioxide.
Amount) Tetrabutylammonium chloride and methioiodide
K in 60 ml of water with 2 ml of₂C.O.₃Add 0.2g of solution
I got it. The reaction mixture was stirred at room temperature for 4 hours,
Then wash several times with water and separate the organic dichloromethane layer.
Separation and evaporation yielded 0.68 g of a yellow solid.
Dissolve this solid in methanol containing 1 drop of concentrated HCl.
and the solution was heated at reflux for 20 minutes.
The methanol was removed leaving an orange-red solid. preparation
Using TLC technique, 0.12g of the indicated compound remained
was recovered from. Synthesis example 21 formula: Manufacture of a compound having Dissolved in 50ml of dry N,N-dimethylformamide.
2−(−CO₂CH₂CH₂S.O.₂CH₃)−3−(3′,
5′-dimethoxy-4′-hydroxy-1′-phenyl)
-3-(3″,5″-dimethoxy-4″-hydroxy-
1″-phenyl)-2,3-dihydrobenz[d]
85 in 5.7g of isothiazole-1,1-dioxide
0.66 g of powdered potassium hydroxide was added. Next
Gradually add 10 ml of methyl uride at room temperature, and dark green
The yellow reaction mixture was stirred for 4 hours. (After 2 hours,
The reaction mixture was orange in color and had a small amount of suspended
Contains KOH. ) Add 0.5ml of methyl iodide separately.
Well, after another 2 hours the TLC looked the same. next
Water containing 1 drop of concentrated HCl and about 5 g of sodium chloride
Injected into 400ml. Decant the water from the oil and add this
Dissolve the oil in dichloromethane and add sodium sulfate to
dried in a vacuum. This solution was evaporated under vacuum to an orange color.
Yielded 6.6 g of oil. Add this oil to 200ml of methanol.
A solid formed upon heating. This solid is dichloro
The indicated compound was recrystallized from methane/hexane.
(melting point range 184-186°C) yielding 3.50g. Synthesis example 22 formula: Manufacture of a compound having 2-(-
COCH₃)-3-(3',5'-dimethoxy-4'-hydro
xy-1′-phenyl)-3-(4″-N-morpholini
-1″-phenyl)-2,3-dihydrobenz
[d] Isothiazole-1,1-dioxide 0.3
K in 10 ml of water in solution₂C.O.₃0.1g of solution and a few crystals
Tetrabutylammonium chloride was added. This mixture
Stir the mixture at room temperature and add 1 ml of methyl iodide.
added. Stir the reaction mixture for a total of 24 hours.
After 8 hours, an additional 0.5 ml of methyl iodide was added.
(No changes in TLC were observed). Jiku
Separate the lolomethane layer, wash with water, and remove sodium sulfate.
and evaporated. 3% methanol
- Prepared in dichloromethane solvent using TLC technique
The residue yielded 0.07 g of the title compound. Synthesis example 23 formula: Manufacture of a compound having Dissolved in 30ml of dry N,N-dimethylformamide.
2−(−COCH₃)-3-(3',5'-dimethoxy
cy-4′-hydroxy-1′-phenyl)-3-(3″,
5″-dimethoxy-4″-dihydroxy-1″-phenylene
)-2,3-dihydrobenz[d]isothiazo
Powdered into a solution of 2.82 g of alcohol-1,1-dioxide
0.36g of 85% potassium hydroxide and 4ml of methyl iodide
added. Stir the reaction mixture for 2 hours at room temperature.
When washed, the color changed from very dark green to pale orange-yellow.
(TLC showed the presence of large amounts of starting material). You
Add another 3 ml of methyl chloride and a small amount of potassium hydroxide.
and stir the reaction mixture for another 16 h.
Ta. The reaction mixture was then acidified with 3 drops of concentrated hydrochloric acid.
Pour into 200ml of water, extract with chloroform,
Drying and evaporation yielded a yellow oil. this yellow
The colored oil was placed in a medium pressure column of silica and 1:1
Elution with hexane-acetone gives the indicated compound 0.43
g. Synthesis example 24 formula: Manufacture of a compound having 2-(-COCH₂CH₂S.O.₂CH₃)−3−(3′,5′−
Dimethyl-4'-hydroxy-1'-phenyl)-3
−(3″,5″-dimethyl-4″-hydroxy-1″-ph)
enyl)-2,3-dihydrobenz[d]isothi
Powdered 1.73g of azole-1,1-dioxide85
% Potassium hydroxide 0.23g and methyl iodide 4ml
was dissolved in 25 ml of dry N,N-dimethylformamide.
I understand. Stir the reaction mixture at room temperature for 3 hours.
Next, inject one drop of concentrated HCl into the water and
and extracted with dichloromethane. dichloromethane
was dried and evaporated to give an orange oil. this oil
When dissolved in hot ethanol and cooled,
A pale yellow impurity precipitated. This mother liquor is evaporated
When this happens, oil remains and this is placed in a medium pressure column (silica).
and eluted with dichloromethane to obtain the indicated compound.
Yielded 0.94 g. Synthesis example 25 2 dissolved in 100 ml of dry tetrahydrofuran
-[Formula]-3[(3'-α -hydroxy-α-trifluoromethyl-β,
β,β-trifluoroethyl)-4′-hydroxy
-1'-naphthyl]-3-(9'-dicololidinyl)-
2,3-dihydrobenz[d]isothiazole-
Add sodium hydride to a solution of 3.8 g of 1,1-dioxide.
Add 0.21 g of 50% oil dispersion of Umium and 5 ml of methyl iodide.
I got it. The reaction mixture was kept in the dark at room temperature under nitrogen for 48 h.
I stirred it up. Silica gel using ether
TLC showed the reaction was complete. Concentrated HCl 5ml
Pour this reaction mixture into 1 part of water containing
Extract with ether and dry the ether with sodium sulfate.
Dry and evaporate. Dichloromethane 20% of the residue
ml, place in a medium pressure column, and add a suitable
Elute with ether until the band is removed. this
Evaporation of the solvent yielded 1.135 g of the title compound. Synthesis example 26 formula: Production of compounds with 2-(-
C.O.₂CH₂CH₂S.O.₂CH₃)-3-[(3'-α-hydroxy
C-α-trifluoromethyl-β,β,β-tri
(fluoroethyl)-4'-hydroxy-1'-naphthi
]-3(9′-diulolidinyl)-2,3-dihydro
Robenz[d]isothiazole-1,1-dioxy
3.25 g of hydride in 50% sodium hydride under nitrogen at room temperature
0.2 g of oil dispersion was added. Add methioiodide to this mixture.
Add 5 ml of water and leave the reaction mixture in the dark for 48 hours.
Stirred. Silica gel using ether
TLC produces many spots other than one main product.
Indicated. React into water 1 containing 5 ml of concentrated HCl.
The mixture was poured and extracted with ether. this
Dry the ether with sodium sulfate and evaporate
I set it. Dissolve the blue residue in 15ml of dichloromethane,
Place on medium pressure column and elute with ether, then
1%, 2%, 3%, 4% methanol in
Eluted with 100ml. The rest of the elution is done after the product has been removed.
using 4% methanol in ether until
Ta. 0.537 g of the obtained product was placed in a medium pressure column.
and elute as above to obtain the pure designated compound.
Yielded 0.48g. The compound of Synthesis Example 26 was also prepared as follows.
: Three-stage system equipped with mechanical stirrer and nitrogen inlet pipe
Dry dimethyl sulfoxide in a 250ml neck flask
2-(-CO in 80ml₂CH₂CH₂S.O.₂CH₃)−3[3′−
α-hydroxy-α-trifluoromethyl-β,
β, β-trifluoroethyl)-1′-naphthyl]-
3-(9'-diulolidinyl)-2,3-dihydrobe
Lens[d]isothiazole-1,1-dioxide
18g was added in the dark. mechanically into this solution at room temperature.
While stirring, 12 ml of methyl iodide was added. last
Add 1.9 g of powdered 85% potassium hydroxide pellets to
added. After stirring the mixture for 1 hour in the dark,
Silica gel using 1/9 methanol/ether
TLC showed the reaction was complete. Concentrated HCl6
Pour this reaction mixture into water containing 5 ml
did. Remove the blue precipitate by vacuum filtration in a Buchner funnel.
Collected and washed thoroughly with water. Pressure to dry the precipitate
Squeeze, dissolve in 600ml of hot methanol, and filter.
It was then cooled to room temperature. The product is as green crystals
separated. Filter these and vacuum dry them.
yielded 7.1 g of product giving a single spot on TLC.
Ta. This mother liquor was concentrated to almost dryness in a rotary evaporator.
Ta. Dissolve the residue in 50 ml of acetone and then add
500ml of chill ether was added. Celite pad
Remove precipitated impurities by filtering through
I left. The ether solution was evaporated to dryness. this
The residue was crystallized again from methanol (75 ml) and completely
9.8 g (53% yield) of the second compound of the title.
Yield (2.7g) resulted. Synthesis example 27 formula: Manufacture of a compound having 2-(-
C.O.₂CH₂CH₂CN)-3-(3',5'-dimethoxy-
4′-hydroxy-1′-phenyl)-3-(3″, 5″-
dimethoxy-4″-hydroxy-1″-phenyl)-
2,3-dihydrobenz[d]isothiazole-
Powdered 85% hydroxide to 0.057g of 1,1-dioxide
0.014 g of potassium and 0.01 ml of methyl iodide were added.
The air was removed and the reaction mixture was refluxed for 3 hours. 15%
with silica gel using methanol/ether
TLC detects several spots containing small amounts of starting material.
showed that. Pour the reaction mixture into acidic water and ether
and the ether was evaporated under vacuum.
An orange residue was produced. Dissolve the residue in dichloromethane.
The indicated compound was recovered by preparative TLC.
did. Synthesis example 28 formula: Manufacture of a compound having 2-(- in 2 ml dimethylformamide
COCH₃)-3-(3',5'-dimethoxy-4'-hydro
xy-1′-phenyl)-3-(4″-N-morpholini
-1″-phenyl)-2,3-dihydrobenz
[d] Isothiazole-1,1-dioxide test
Add 200mg (0.38mM) of powdered hydroxide under nitrogen atmosphere.
20 mg (0.38 mM) of potassium oxide was added. hydroxide
After the lium has dissolved, propane sultone 0.66ml
(7.63mM) was added to the maroon solution at room temperature.
TLC analysis showed that the reaction was approximately half complete 2 hours after stirring.
indicated that it was completed. Heat this reaction mixture under vacuum.
The mixture was concentrated to give a maroon solid. This material
Dissolve in ethanol and add to ethyl ether
and this caused the product to precipitate.
Preparative TLC (silica gel/methanol ethyl acetate-
1:5), the indicated compound forms a dark solid (green color).
It was obtained as Synthesis example 29 (a) 2-(-
COCH₃)-3-(3',5'-dimethyl-4'-hydro
xy-1′-phenyl)-3-(3″,5″-dimethyl
−4″-methoxy-methoxy-1″-phenyl)−
2,3-dihydrobenz[d]isothiazole
-In a solution of 0.40g of 1,1-dioxide
K₂C.O.₃Added 0.11 g and 20 ml of water. Next, the amount of catalyst
Tetrabutylammonium chloride (spatium chloride)
was added along with 2 ml of methyl iodide. water layer
Violet color and organic dichloromethane layer
was yellow. After stirring for several hours, the aqueous layer is
It becomes colorless and the dichloromethane layer is dark yellow.
It was hot. Then separate this dichloromethane layer and
Wash with an equal volume of water and dry briefly with sodium sulfate.
filtered and evaporated under reduced pressure to give an orange syrup.
530 mg of the liquid was left. Preparative TLC (eluted with ether)
This syrup is made using silica gel
Separated. N-methylated as orange-yellow syrup
180 mg of the compound was obtained, which was oxidized with methanol.
Crystallized when barred. (b) The compound (0.18g) produced in step (a) is
Dissolve in 50 ml of alcohol and heat at reflux in an oil bath.
Ta. After all solids have dissolved and about 15 minutes 2
A drop of concentrated HCl was added. of wine red produced
Refluxing of the solution was continued for approximately 1 hour, and then the solution was evaporated under reduced pressure.
Red with a metallic green luster when the liquid evaporates
produced a film. This red film is
evaporate the methanol and warm
Dry the residue under reduced pressure in a hot water bath to form a red solid.
This yielded 140 mg of the title compound. Synthesis example 30 formula: Manufacture of a compound having (a) 2- suspended in 60 ml of methanol
【formula】 -3-(3',5'-dimethyl-4'-methoxymethoxy
-1′-phenyl)-3-(3″,5″-dimethyl-
4″-methoxy-methoxy-1″-phenyl)-2,
3-dihydrobenz[d]isothiazole-
Add 3 drops of concentrated HCl to 1.5 g of 1,1-dioxide.
and heat the resulting mixture at reflux for 20 min.
did. When the red solution is cooled and evaporated, the red
Isothiazole deblocked as a colored solid
1.5 g of -1,1-dioxide was produced. (b) Dissolve this red solid in 60 ml of methanol and
K in 10ml of water₂C.O.₃0.5g was added dropwise. child
The reaction mixture was stirred at room temperature for 1 hour, then mixed.
The pH of the compound was adjusted to 5 with 1NHCl. generated
Collect the solid and reflux ethanol for 40 min.
Washing for a period of time yields the listed compound as a yellow solid.
Ta. Synthesis example 31 formula: Manufacture of a compound having Dry N,N-dimethylformamide 17 under nitrogen
2-(-COCH dissolved in ml₃)-3-(3',5'-di
methoxy-4′-hydroxy)-3-(4″-morpholo
Linyl-1″-phenyl)-2,3-dihydroben
d[d]-isothiazole-1,1-dioxide
87.3% potassium hydroxide pellets in 3g solution 0.39
g was added. A deep maroon color developed. Add this solution to 3
Stir for a minute (a small amount of KOH remains undissolved).
) and 7.1 ml of ethyl iodide at once.
Ta. After stirring for about 25 hours at room temperature, 4 drops of 10%
Pour this reaction mixture into 250 ml of water containing HCl
did. Extract the mixture with 200 ml of chloroform and
Separate the chloroform layer and dry with sodium sulfate.
dried and concentrated in a dark maroon oil containing the listed compounds.
Shrunk. Selected 3,3-disubstituted phthalides
Converting the corresponding phthalin
This corresponds to forming the methyl ester of
to reduce to phthalols, then phthalols
acyl derivative, which is oxidized to give tria
formula by yielding the lyle methane dye product
The compound () can be produced. As a departure phthalide
In this case below using phenolphthalein.
Illustrate the composition. R^ohas the same meaning as given in Eq. Another method of producing these compounds is anhydrous tet
Lithium aluminum hydride in lahydrofuran
The 3,3-disubstituted phthalide starting material selected in
Including giving back. Substituents present in phthalide
Depending on the reduction product, the corresponding phthalol,
Talin, phthalane or a mixture thereof. centre
If talan is formed, this can be done with sulfuric acid or
A suitable acid, HOOCR, in the presence of boron fluoride catalyst^o
reacts with to form a triarylmethane dye product
Ru. Phenol phthalein as a phthalide starting material
This synthesis is illustrated below using a R^ohas the same meaning as shown in the formula. When phthalin is formed as a reduction product
is exemplified by the above reaction sequence for (A) to (D)
As mentioned above, this is converted to methyl ester etc.
Ru. Where phthalols are formed as reduction products
In this case, this is a suitable acid, HOOCR^ocan react with
to give the corresponding acyl derivatives, followed by (C) and (D)
As shown in the above reaction formula for triaryl
Oxidized to amine dye oxide. Alternatively, the file
Talol is e.g. O-chloranil or dicyanodi
Oxidation of chloroquinone to the corresponding phthalane
Yes, and this pthalane is as discussed above.
reacts with a suitable acid. 3,3- used as starting material in the above synthesis
Disubstituted phthalides can be prepared using a variety of methods known to those skilled in the art.
It can be manufactured using One of the more common processes involves
Phenols, such as thymol, O-cresol and
and phenols themselves, such as zinc chloride or sulfuric acid.
phthalic anhydride at elevated temperatures in the presence of a suitable catalyst.
React to obtain the corresponding symmetric 3,3-disubstituted lid
lido, i.e., the 3,3 substituents are identical.
Ru. 3,3-di-substituted where the 3,3 substituents are the same or different
Another method of synthesizing phthalides is by Alan L.
Bohler U.S. Pat. No. 3,931,228 and
Complained. In the latter method, phenol or
Reacting 1-naphthol with phthalaldehyde acid
The corresponding p-phthalidylphenol or phthalidylphenol
Dehydrogenation produces dillnaphthol, which is converted into acid by dehydrogenation.
water from the 3-position of the phthalidyl part of the adduct.
selectively removes phenolic or naphthyl
hydrogen is removed from the hydroxyl group. Then this oxidation
The resulting intermediate is phenolated, preferably in the presence of an acid catalyst.
3,3-di
yields substituted phthalides. 3,3-di-substituted phthalide to the corresponding 3,3-di-substituted phthalide
Rather than reducing to substituted phthalane, 1 equivalent
phthalide for example 2 equivalents of protected lithium
phenols, such as 2'-tetrahydropyranyl
Correspond by reacting with 4-Li-phenyl ether
yielding a symmetric 3,3-disubstituted phthalane, followed by
After removing the 2′-tetrahydropyranyl protecting group,
by regenerating the phenolic hydroxyl group as in
Phthalane can be synthesized directly: 1 equivalent of an organolithium reagent, e.g. 4-Li-
1 equivalent of N,N-(dialkyl)aniline
4-(2'-hydroxymethyl base) by reacting with
(Nzoyl)-N,N-(dialkyl)aniline
and then convert this intermediate into e.g.
reacts with phenyllithium (dropyranyloxy)
to produce the corresponding asymmetric 3,3-disubstituted phthalane.
The same is followed by deblocking the phenolic −OH,
i.e., removing the 2′-tetrahydropyranyl protecting group
As a result, asymmetric phthalanes can be produced. Functional phenolic or naphtholic present -
Usually used to protect OH and other −OH substituents
Suitable blocking groups to be used are as described above.
It is recognized that it can be used. Used when synthesizing phthalol acetyl derivatives
The method is explained by M.Hubacher.
J.Amer.Chem.Soc. , 74, p. 5216 (1952). The method involves reducing selected phthalenes with lithium aluminum hydride in anhydrous ether to the corresponding phthalols and then reacting the phthalols with the selected acids. The following examples further illustrate the preparation of compounds of formula (). Synthesis example 32 Formula: Manufacture of a compound having (a) A three-neck flask equipped with a mechanical stirrer, a condenser with a nitrogen inlet, and an addition funnel was charged with lithium aluminum hydride (3.0 g) and 100 ml of dry tetrahydrofuran. Phenolphthalein (6.4 g) dissolved in 300 ml of dry tetrahydrofuran was added dropwise to the stirred lithium aluminum hydride at a rate that maintained a slow reflux. When the addition was complete, the reaction mixture was heated to an oil bath at reflux for 6 hours and then left overnight. To the stirred solution was added excess ethyl acetate followed by 500 ml of water. dark
The PH was adjusted to approximately 2 with HCl and the solution was extracted with two 500 ml portions of ether. The ether layer was washed six times with 10% aqueous potassium carbonate (the base layer was magenta each time) and then evaporated to dryness to leave a slightly off-white solid (4.5 g crude yield). . This solid is crystallized from 440 ml of 20% ethanol and dried in vacuo at 60°C to yield the corresponding phthalane as very pale yellow crystals (yield 3.3 g, melting range 195-
197.5℃) using ether-silica gel
TLC showed one spot. Nmr is methine H
and was more consistent with the cyclic ether (phenolphthalein) than the open form (phenolphthalol). (b) A test tube was charged with the phthalane spatula chips produced in step (a) and about 0.5 ml of glacial acetic acid. 2
Add a drop of concentrated sulfuric acid (a bright orange color was observed),
The reaction mixture was then heated at about 80° C. for 10 minutes, poured into 10 ml of water and extracted with ether. TLC of the ether layer on silica gel showed the title compound as a yellow spot, which was identical to a sample of the title compound prepared as described below. (1) A test tube was charged with 0.2 g of phenolphthalol and 2 ml of glacial acetic acid. This reaction mixture was
Heated at reflux for 1/2 hour, poured into 50 ml of water and extracted twice with ethyl ether. The ether was washed with sodium bicarbonate solution, brine, dried over sodium sulfate and dried in vacuo to leave a colorless oil with a brownish hue. TLC on ether/silica gel showed a small amount of starting material and a major spot above this starting material, which was the monoacetyl ester of phenolphthalol. (2) The monoacetyl ester of phenolphthalol produced in step (1) without purification was dissolved in 10 ml of dry tetrahydrofuran in a test tube.
Dicyanodichloroquinone (0.2g) was added in one portion. The reaction mixture turned yellow-brown and was left stirring for 1 hour. silica gel/
TLC using ether showed one key spot. Preparative TLC on a portion of the tetrahydrofuran solution showed a small amount of the title compound as a yellow oil. (TLC showed the oil to be homogeneous). The phenolphthalol was prepared as follows: (i) 20 ml of sodium hydroxide dissolved in 400 ml of water.
Sodium dithionite (26.1
g) was added followed by phenolphthalein (15.92g) to yield a pink-red solution.
A fever of approximately 35°C was observed. The reaction mixture was then heated to 83°C for approximately 20 minutes. The hazy color solution was placed in an ice bath and 42 ml of concentrated HCl was slowly added as the solution cooled from 35°C to about 5°C.
After adding about 24 ml of HCl, a precipitate started to form. After all the HCl was added, the strongly acidic solution was filtered and the white solid was collected and washed with water. The wet filter cake was set aside overnight and then heated under reflux in approximately 1500 ml of water. When the refluxing solution started bubbling in the condenser at 100°C, the solution was hot filtered. (Substantial solids were unable to dissolve.) A small amount of solid in the filtrate turned a faint pink color with aqueous sodium hydroxide, but the "insolubles" recovered from the hot aqueous solution were dissolved in sodium hydroxide. It didn't turn pink. The white hot water "insoluble" solid was then dissolved in approximately 500 ml of methanol to yield a slightly hazy straw colored solution which was heated and filtered to yield a clear colorless filtrate. Evaporation of this filtrate leaves a white solid residue,
This was redissolved in approximately 200 ml of methanol and evaporated again to yield 12.5 g of a white solid residue. The filtrate containing hot water "insoluble" solids was filtered and the small white needles recovered remained quite wet when compressed. Both the white solid residue and the white needles were heated under vacuum for several hours and then kept under vacuum at room temperature. Repeated drying under vacuum gave a total yield of 15.03 g of phenolphthalin. (Hot water “insoluble matter” 12.11g plus hot water “soluble matter”)
2.92g, both of which melted at 237-239°C to yield a clear pale yellow melt. ) (ii) In a three-necked flask equipped with a magnetic stirrer, nitrogen inlet and condenser vented to the exhaust gas bubbler, 2.92 g of phenolphthalin was dissolved in 100 ml of methanol. Two drops of concentrated sulfuric acid were added to the solution and the reaction mixture was then heated in an oil bath under nitrogen. Furthermore, concentrated sulfuric acid (approx. 25 drops)
was added and refluxing under nitrogen was continued until the reaction was substantially complete. Next, add the reaction solution to 200ml of ice water.
The methanol is removed by injection, treatment with sodium bicarbonate to neutralize the sulfuric acid, and evaporation to remove the methanol. The white solid residue was collected, washed with water and dry pressed to yield 2.93 g of methyl ester of phenolphthalin. (iii) A solution of 0.5 g of the methyl ester of phenolphthalin prepared in step (ii) dissolved in 30 ml of dry tetrahydrofuran was slowly added to a suspension of 0.5 g of lithium aluminum hydride in 20 ml of dry tetrahydrofuran. The resulting reaction mixture was heated at reflux for 30 minutes and then excess ethyl acetate was added. The reaction mixture is poured into 1N HCl, extracted with two 200 ml portions of ethyl ether, and the ether is evaporated to leave a solid residue and some water. The residue was taken up with ethyl ether, the ether was decanted from the water, dried over sodium sulfate,
The solvent is then removed in vacuo to yield 0.42 g of phenolphthalol as a white solid. with silica gel using ether
TLC showed the title compound as one major spot and the nmr was consistent with the phthalol structure. Synthesis example 33−35 Formula: (a) Phenol phthalane was produced by the step shown in step (a) of Synthesis Example 32 above. (b) Approximately 100 mg of phenolphthalane and chloroacetic acid,
Each was dissolved in 0.5 ml of phenoxyacetic acid and methoxyacetic acid. Two drops of concentrated sulfuric acid were added to each reaction solution and each solution was heated to about 80° C. for 10 minutes. 10ml water
After addition, each solution was extracted with ether.
Preparation of yellow ether layer using silica gel/ether TLC showed each labeled compound. The compound of Synthesis Example 35 was also prepared as follows: (1) To a three-necked flask was added 250 ml of dry tetrahydrofuran under nitrogen followed by 4.61 g of lithium aluminum hydride (95%). Phenolphthalein (20.0 g) dissolved in 250 ml of dry tetrahydrofuran was added dropwise to the well-stirred lithium aluminum hydride suspension at a rate such as to prevent vigorous reaction. Addition was completed in 90 minutes. The reaction mixture was then refluxed for 30 minutes by applying external heat. TLC on silica gel in ether showed that some unreacted phenolphthalein was present. Reflux was continued for 2 1/2 hours. Silica gel TLC in ether showed no further changes. The heat source was removed and 60 ml of ethyl acetate was added to the reaction mixture to destroy unreacted lithium aluminum hydride. Then 200 ml of saturated ammonium chloride was added and the pH was adjusted to about 4-6 with 1N HCl. Decant the organic part;
The solvent was then removed under reduced pressure to leave a yellow oil. Dissolve this oil in 350 ml of ether and
The ether was extracted with a total of 4 doses of 10% sodium carbonate to remove unreacted phenolphthalein. The ether was then removed to leave a yellow oil, which was dissolved in a boiling 20% ethanol:80% water mixture to give a clear,
A pink-red solution resulted. Upon cooling, a slightly off-white crystalline product formed and the solution was left in the refrigerator for 3 days. The solid was filtered, washed with 20% ethanol at room temperature to remove the yellow-pink color, and collected to yield a very pale yellow crystalline product. 20% ethanol
Recrystallization from 750 ml yielded 11.8 g of the corresponding phthalane as a very pale yellow crystalline solid.
Silica gel TLC in ether showed only one spot corresponding to phthalane. (b) 5.0g of phenolphthalane and 30% of methoxyacetic acid
ml and stirred the mixture vigorously. All solids did not dissolve. The mixture was cooled in an ice water bath and 2.32 g of boron trifluoride etherate was added. A pink-yellow color developed. Stir the reaction mixture cold for 30 minutes;
Then, it was left to stand until it reached room temperature. All solids did not dissolve and the reaction mixture was heated slowly for 35 minutes. Silica gel TLC in ether showed unreacted phthalane. Another 2.32 g of poron trifluoride etherate was added and slow heating continued for 1 hour. unreacted phthalane again
Detected by TLC. After adding an additional 5.0 g of boron trifluoride etherate and continuing slow heating and stirring for 1 hour, silica gel TLC in ether showed almost no phthalane. The reaction mixture was diluted with ice water and extracted with ether. The yellow ether solution was washed with several portions of fresh water and dried over anhydrous sodium sulfate. The ether was removed leaving a dark yellow oil containing some water, which was dried under vacuum in the presence of sulfuric acid. This oil (4.4 g) was purified by high pressure chromatography using approximately 25% methanol in dichloromethane to yield 2.6 g of the title compound. Synthesis example 36 (a) Phthalane of thymolphthalein was prepared by the process shown in step (a) of Synthesis Example 32 above and the crude product was used without purification. (b) Crude product obtained in step (a) above (4.8 g)
was dissolved in 30 ml of acetic acid and 6.5 g of boron trifluoride etherate was added. The reaction mixture was heated near reflux for 2 1/2 hours. silica gel
TLC showed new yellow spots formed on the starting material. The reaction mixture was poured into water and extracted with dichloromethane. The organic solvent portion was washed with several portions of water and the solvent was removed leaving a yellow solid. Prepared in silica gel with 90%; 10% ether/petroleum ether
TLC: 0.116g of compound listed as orange-yellow solid
gave. Synthesis example 37 Formula: Manufacture of a compound having (a) 200 ml of dry tetrahydrofuran under nitrogen while cooling to −60 °C in a flame-dried three-necked flask equipped with a nitrogen inlet, magnetic stirrer, thermometer rubber septum, and dry ice-acetone bath.
2'-tetrahydropyranyl-4-bromo- in ml
2,6-dimethoxyphenyl ether 12.68g
was dissolved. To this solution was added 25 ml of n-butyllithium (1.6 M in hexane) via syringe over about 10 minutes at a rate that maintained a temperature of -50 to -60°C. After stirring for about 30 minutes at -50 to -60°C, 2.68 g of phthalide was added in one portion, resulting in a pale yellow solution. The reaction solution was allowed to stir while the reaction temperature reached room temperature over the weekend. A small sample (1/2 ml) of the reaction mixture was poured onto ice, diluted with HCl and extracted with ether. TLC of the ether using silica gel/petroleum ether-ether (2:1) showed major spots turning deep magenta when treated with sulfuric acid. Pour the remaining mixture onto 100 c.c. of crushed ice and bring the pH to 5-6 with dilute HCl while stirring.
and extracted with two 125 ml portions of ether. The ether extracts were combined, washed with water (three 50 ml portions), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was dried in vacuo at room temperature for 2 hours. Add about 13.0g of the residue to 50-75ml of methanol at room temperature.
and then 3 drops of concentrated HCl were added. After stirring overnight at room temperature, the slightly off-white crystals were filtered, washed with methanol and air dried to yield 4.64 g of 3',3'',5',5''-tetramethoxyphenolphthalane. . (b) 1.60 phthalane produced in step (a) with 20 drops of concentrated sulfuric acid
g and 10 g of iodoacetic acid at 75° C. were added to the stirred melt and stirring and heating continued for 45 minutes. The dark mass was then poured onto approximately 25 c.c. of crushed ice and extracted with four 25 ml portions of methylene chloride. The combined methylene chloride extracts were washed with water, filtered and the solvent was removed under reduced pressure at 35-40°C. 100 ml of ether was added to the dark residue and after stirring for about 1 hour the dark crystals were removed by filtration. This solid was dissolved in ethanol containing Norite: the solution was filtered and placed in the refrigerator for 2-5 hours to cause crystallization. The crystals were filtered, washed with ethanol and then two 10 ml portions of ether, and air dried to yield 645 mg of the title compound. Synthesis example 38 Formula: Manufacture of a compound having The title compound was produced by the steps shown in Synthesis Example 37, except that iodoacetic acid was replaced with chloroacetic acid in step (b). Synthesis example 39 Formula: Manufacture of a compound having (a) Dissolved in 400ml of dry tetrahydrofuran
2'-tetrahydropyranyl 4-bromo-2,6
-dimethoxyphenyl ether 25.36g, n-
Using 50 ml of butyl lithium (1.6 M in hexane) and 4.83 g of phthalide, but instead of dilute HCl, 7 g of ammonium chloride was added to the ice-cold reaction mixture.
The process of step (a) of Synthesis Example 37 was repeated by adding the solution of . After recrystallizing the air-dried solid from 100 ml of boiling ethanol, the yield of 3',3'',5',5''-tetramethoxyphenolphthalane was 9.02 g. (b) Phthalane (8.5g) produced in step (a)
Dissolved in 90g of methoxyacetic acid at 95°C. While stirring, 15 ml of boron fluoride etherate was added dropwise. Heating and stirring of the reaction mixture at 95° C. was continued for 1 1/4 hours, then a small sample was prepared for TLC using silica gel and 3% methanol/methylene chloride. After 15 minutes, the remaining reaction mixture was poured onto crushed ice and extracted with two 125 ml portions of ether. The combined ether extracts were washed with two 50 ml portions of water, and the combined aqueous phase was extracted with three 100 ml portions of methylene chloride. The combined methylene chloride extract was washed with 50 ml of water, dried over sodium sulfate, filtered, and the solvent removed leaving a residue of 18.7 g. Repeating the above steps and incorporating the residue from the methylene chloride extract
A total residue of 31.45g resulted. High pressure chromatography using methylene chloride/methanol (trace) yielded 14.5 g of product, which was dried in vacuo at room temperature overnight, then dissolved in methanol and the methanol solution was filtered through Celite. The solvent was removed and the solid was dried in vacuo to yield 12.5 g of the title compound. Synthesis example 40 Formula: Manufacture of a compound having (a) Lithium aluminum hydride (0.2 g) was added to approximately 40 ml of dry tetrahydrofuran at room temperature under nitrogen. 3-[4′-(dimethyl)amino-1′-phenyl)-3-(3″,5″-diisopropyl-4″-
Oxo-1″-phenyl)phthalide (1.0 g) was dissolved in 40 ml of dry tetrahydrofuran and this solution was added dropwise to the lithium aluminum hydride suspension. The temperature rose to approximately 30°C. On completion of the addition, A sample of the reaction mixture was poured into water and extracted with ether. TLC on silica gel using 1:1 ether/petroleum ether.
indicated that the reaction was complete and there was no unreacted phthalide. After neutralizing the lithium aluminum hydride with ethyl acetate, the reaction mixture was diluted with 200 ml of water.
ml, adjusted the pH to 3 with HCl and extracted with ether. The ether layer was washed with 200 ml of 5% aqueous sodium hydroxide, dried over sodium sulfate and the ether was evaporated leaving a pink-red residue. This residue was dissolved in about 20 ml of ether and petroleum ether was added to precipitate a white solid. After filtration, the solution was evaporated to yield the corresponding phthalane as a pink solid. (b) The phthalane prepared in step (a) was dissolved in about 20 ml of glacial acetic acid and about 2 ml of boron trifluoride etherate solution was added. The resulting orange-red solution was heated in a steam bath for 1 3/4 hours. TLC of the reaction solution on silica gel with 1:1 ether/petroleum ether showed no unreacted phthalane.
The reaction solution was then poured into 100 ml of water and extracted with ether, which was dried and evaporated leaving a tarry residue with an odor of acetic acid. Dissolve this residue in about 20ml of methanol, then water
Pour into 100ml and filter to give a red powder.
This powder is dried and then silica gel (100-200
1:1 ether/hexane and eluted with the same solvent. Appropriate fractions were collected and evaporated to give the compound described as a brick-red solid.
Yield 0.040g. (TLC showed one spot). Synthesis example 41 Formula: Manufacture of a compound having A small amount of boron trifluoride etherate was added to a stirred mixture of 3',3'',5',5''-tetramethoxyphenolphthalane (3.9g; 0.009M) and phenoxyacetic acid (20.0g; 0.13M). This was heated slowly until a melt formed. Furthermore
BF ₃ .Et ₂ O (6.0 ml) was added dropwise to the melt over 10 minutes. The resulting deep blue solution was heated to 95 °C for approximately 10
After stirring for a minute, it was diluted with 350 ml of ice water and extracted with ether. The ether was removed and the residue was dissolved in benzene. The solution was extracted repeatedly with hot water to remove excess phenoxyacetic acid. The benzene layer was dried over sodium sulfate and the solvent was removed to yield 5.7 g of crude product. High pressure preparation liquid chromatography (silica gel/3
% methanol/methylene chloride) to obtain a pure sample of the title compound. Synthesis example 42 Formula: Manufacture of a compound having (a) 9.52 g (0.0264 M) of 3′,3″,5′,5″-tetramethylphenolphthalane in two flasks equipped with a nitrogen inlet, mechanical stirrer, and thermometer;
41.2 g (0.63 M) of zinc dust and 300 ml of acetic acid were charged. Mild fever was observed (31°C).
The gray slurry was stirred at room temperature for 6 hours, filtered, and the filtrate was slowly added to water 2. The resulting white precipitate was collected by filtration, dissolved in hot methylene chloride, filtered through sodium sulfate and allowed to crystallize overnight. After separation and drying, 6.6 g of the corresponding 3',3'',5',5''-tetramethylphenolphthalol were obtained as slightly gray to white crystals. An extra amount of the phthalol was produced by the above process. (b) 500 ml of dry toluene in one flask equipped with a magnetic stir bar, nitrogen inlet and distillation head;
21.59 g (0.185 M) of diglycolic anhydride and a small amount of p-toluene sulfonic acid hydrate ("Spatula chips") were added. The mixture was heated to its boiling point. After removing approximately 50 ml of toluene-water azeotrope, 8.29 g of 3′,3″,5′,5″-tetramethylphenolphthalol
(0.018M) was added to the hot solution; heating was continued again and approximately 70ml of distillate was removed. After heating the solution under reflux conditions for 4 hours, the toluene was removed. The residue was removed with methylene chloride and the total
Extracted three times with 750 ml of water. The organic phase was dried over sodium sulfate, filtered and the solvent removed, giving the formula: This yielded 9 g of a substance consisting of the corresponding phthalolacyl derivative. This material was obtained as a pale yellow floss and was used without further purification. (c) Phthalolacyl derivative obtained in step (b) (7.4 g; 0.0155 M), sodium bicarbonate (6.51
4.44 g of iodine in 175 ml of methylene chloride to a stirred slurry of g; 0.078 M) and water (200 ml).
(0.018M) was added dropwise. After a total of 20 minutes of stirring at room temperature, the aqueous layer was separated and neutralized by adding 1 of water containing 15 ml of concentrated hydrochloric acid. The aqueous fraction was extracted with methylene chloride, the organic phase was dried over sodium sulfate and the solvent was removed in vacuo. The dark orange residue was purified via medium pressure column chromatography (silica gel, methanol-methylene chloride varying from 0.5 to 2%; methanol content). The title compound was isolated as an orange glass.
(λmax 424 nm, epsilon 22.500 measured in ethanol). 2'-tetrahydropyranyl-4-bromo-
The 3′,3″,5′,5″-tetramethylphenolphthalane used in the above synthesis example was produced by the step shown in step (a) of Synthesis Example 37 using 2,6-dimethylphenyl ether. Manufactured. Synthesis example 43 Formula: Manufacture of a compound having (a) Nitium aluminum hydride (0.2 g) was added to 35 ml of anhydrous tetrahydrofuran at room temperature under nitrogen. This stirred mixture was added to 3,3-bis-[4′-(2″-tetrahydropyranyloxy)-1′-naphthyl)]-phthalide in tetrahydrofuran.
30 ml of a 1.0 g solution was added dropwise. Once the addition is complete, TLC on silica gel using ether.
indicated that the reaction was complete. Ethyl acetate was added dropwise until the exotherm and hydrogen evolution ceased. The reaction mixture was poured into water, brought to pH 6 with HCl and extracted with ether. The ether was evaporated to give a yellow solid. A sample of this yellow solid was dissolved in methanol and concentrated.
Added 1 drop of HCl. A yellow-green color developed. The resulting solution was refluxed for 10 minutes and TLC on silica gel with 1:1 ether/petroleum ether showed complete deblocking of the 2''-tetrahydropyranyl protecting group from the naphtholic --OH group.
The methanol was then removed under vacuum to yield 1-naphtholphthalene. (b) Glacial acetic acid was added to the 1-naphtholphthalane prepared in step (a) along with a few drops of boron trifluoride etherate solution. A strong green color was formed. The reaction solution was heated in a steam bath until a yellow-green color developed (approximately 15 minutes), then poured into water and extracted with ether. The ether was evaporated and TLC on the residue using silica gel with 1:1 ether/petroleum ether showed many spots. The spot that was orange-brown when dry and turned blue with sodium hydroxide solution was the title compound, which was isolated and purified using preparative TLC techniques. Reaction of selected 3,3-disubstituted phthalides (phthaleins) with R″ _NH2 yields the corresponding phthalimidines, followed by reduction with diborane in tetrahydrofuran solution to the corresponding iso-indolines, which are converted to the appropriate Compounds of formula () can be prepared by reaction with chloroformate to yield a triarylmethane dye product. This synthesis is illustrated below using phenolphthalein as the phthalide starting material. R and Y have the same meaning as shown in the formula. The chloroformate and 3,3-disubstituted phthalide can be prepared as described above. The following synthetic examples are provided to further illustrate the preparation of compounds of formula (). Synthesis example 44 Formula: Manufacture of a compound having (a) Phenolphthalein (100g) for 5 days40
% methylamine solution at room temperature. (After stirring for 48 hours, the pink color will disappear and
A white flocculent solid then precipitated. ) The white solid was filtered, air dried and crystallized from isopropanol to yield 39.7 g of N-methyl-phenolphthalimidine. Place the filtrate in the refrigerator and give an additional 27.6 g of this phthalimidine.
A total yield of 67.3g resulted. (b) Diborane (200 ml) as a 1M solution in BH ₃ in tetrahydrofuran and 300 ml of dry tetrahydrofuran were charged to a three-necked flask equipped with a thermometer, condenser, addition funnel and overhead with stirring under an atmosphere of nitrogen. The flask was cooled in an ice bath to 0-5°C and 16.6 g of the compound of step (a) in 100 ml of dry tetrahydrofuran were added dropwise, keeping the temperature at 0-5°C. The reaction mixture became cloudy and then a white precipitate appeared.
After the addition was complete, the flask was allowed to warm to room temperature and then heated at reflux for 24 hours. A white precipitate gradually dissolves, but a small amount of gummy material remains.
It remained after hours. The reaction mixture was cooled in an ice bath, treated carefully with 120 ml of 6NHCl, and stirred until a clear pale pink solution formed. The solution was removed under vacuum leaving a pink solid. This solid was heated to boiling in 150 ml of water and 8.3 ml of concentrated HCl (color faded to a white solid) and left in the refrigerator over the weekend. Add this white solid to 100ml of water.
was suspended in 200 ml of ether and treated with 12.6 g of sodium bicarbonate. The solid dissolved in the ether layer. The ether layer was separated and the phase was re-extracted with 100 ml of ether. The combined ether extracts were dried over sodium sulfate and the solvent removed leaving a sticky solid that crystallized from the benzene to yield N-methyl-bis-(4'-hydroxy-1'-phenyl)-iso-indoline ( yielding 13.17 g (melting point range 186-8°C). (c) β-(methylsulfonyl) in 8 ml of toluene
Ethyl chloroformate (196 mg) was added dropwise over 20 minutes to a refluxing solution of 317.3 mg of the compound prepared in step (b) in 15 ml of toluene. The yellow mixture was left stirring under reflux for an additional hour after the addition was complete. The reaction mixture was deep yellow. TLC for samples using silica gel and 10% methanol/chloroform showed 3 major components and 2 minor components. When treated with 1N NaOH, the yellow spot representing the title compound developed a magenta color, which turned white in about 5 seconds. The solvent was removed from the remaining reaction mixture under vacuum to yield a yellow solid. Solid in 4 ml of tetrahydrofuran using 10% methanol/chloroform
Preparative TLC using 150 mg showed a yellow band which was separated and washed with acetone to yield approximately 5 mg of the title compound. Phenolphthalin is reacted with excess thionyl chloride to yield the corresponding carbonyl chloride; this carbonyl chloride is reacted with the selected amine _RNH2 to yield the corresponding monoamide and functional-
The OH and other -OH substituents are blocked with appropriate protecting groups and the protected compound is treated with butyllithium and reacted with the selected chloroformate, ClCO ₂ (CH ₂ ) ₂ Y to form the leuco dye. by forming a precursor; and after removing the protecting group with a weak acid, oxidizing the leuco dye with e.g. 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form the dye product. Compounds of formula can be prepared. This synthesis is illustrated below using phenolphthalin as the starting material. Here R and Y have the same meaning as given in the formula and P is a protecting group. The phthalin and chloroformate used as starting materials in preparing the compound of formula can be prepared as described above. It will also be appreciated that any suitable blocking group may be used to protect the functional phenolic or naphthol-OH and other -OH substituents present as described above. Synthesis example 45 Formula: Manufacture of a compound having (a) Formula: The acid chloride was prepared in quantitative yield by refluxing 10.0 g of phenolphthalin in excess thionyl chloride for 2 hours. Removal of the thionyl chloride by distillation at atmospheric pressure and then at reduced pressure provided a viscous yellow syrup that was used directly in the next step. (Theoretical yield of acid chloride = 10.2 g; 15.1 g of crude product was weighed) (b) A solution of 15.1 g of crude acid chloride prepared in step (a) dissolved in ether (preliminarily at 0 °C) saturated)
Added dropwise to a cold ethereal solution of methylamine. Neutralization with hydrochloric acid followed by aqueous ethanol
Corresponding amides by recrystallization twice, melting range
255-258°C, 5.68g was obtained. Infrared and
The nmr spectrum was consistent with and supported the desired structure. (c) 2.2 equivalents of t-butyldimethylsilyl chloride in 60 ml of dry N,N-dimethylformamide.
5.68 g of this amide with 4.4 equivalents of imidazole
The phenolic functionality of the amide prepared in step (b) was blocked by treatment with (0.017 mol) overnight at room temperature. The reaction solids were collected by filtration and washed with water. Recrystallization from ethanol produces a blocked product with a melting range of 175-178°C.
Yielded 5.0g. Infrared and nmr were consistent with and supported the desired structure. (d) Blocked compound prepared in step (c) 3.89
(0.007 mol) was treated with 1.2 equivalents of n-butyllithium in dry tetrahydrofuran at -65°C. This cold solution was also combined with 1.5 equivalents of chloroformate in dry tetrahydrofuran.
Added to a cold (-65<0>C) solution of _ClCO2 ( _CH2 ) _{2 - SO2CH3} . Work-up, including high-pressure column chromatography, produces compounds as straw-colored syrup. 1.23g (25% yield) was provided. infrared and nmr
The spectrum was consistent with and supported the desired structure. (e) The compound prepared in step (d) was reacted with methanolic hydrogen chloride overnight at room temperature to effect the desired cleavage of the silyloxy protecting group. The deblocked compound was obtained as a white solid, 0.41 g (50% yield). Infrared and nmr spectra were consistent with and supported the assigned structure. (f) 2,3-dichloro-5,6-dicyano-1,
Oxidation of the deblocked compound of step (e) with 4-benzoquinone followed by a workup involving medium pressure column chromatography yielded the title compound as an amorphous orange solid. This material was further purified using preparative TLC (silica gel/95: _5CH2Cl2 : _MeOH ). Infrared and nmr spectra were consistent with and supported the assigned structure. The title compound gave a yellow solution in methanol and ethanol. Addition of aqueous base (1N NaOH) immediately produced a magenta coloration, which rapidly and irreversibly became colorless. Add a sample of the purified dye compound solution in acetone to fresh PH=12 buffer and measure the first half-life (T 1/2) and second half-life (T 1/2) with the following results: where OD indicates optical density. T 1/2 means the time measured for half of the colored compound to be bleached. Experiment 1 1st T 1/2 = 10.0 seconds 2nd T 1/2 = 8.5 seconds Initial OD2.20 Initial OD extrapolated from OD = 2.00 at 1.5 seconds = 0.02 Experiment 2 1st T 1/2 = 9.5 seconds 2T 1/2 = 8.5 seconds Initial OD = 1.15 Final OD extrapolated from OD = 0.90 at 3.0 seconds = 0.01 λmax of the compound in pure notation is −PH in acetone
12 buffer at 560 nm and T 1/2 values were measured at this wavelength. A sample of the indicated compound dissolved in methanol was also treated with aqueous 1N NaOH and, after decolorization, the cleavage compound was compared with the known compound and was found to be identical. Compounds represented by formulas (), (), and () are disclosed in U.S. Pat.
4277406 form each subject matter. The compound represented by formula () is disclosed in U.S. Patent No.
Forms the subject matter of No. 4282160. The specifications of these patents are incorporated herein by reference for convenience. As mentioned above, the dyes of the present invention are completely and irreversibly decolorized with base by undergoing an irreversible cleavage reaction at a predetermined PH and within a predetermined time to yield a new colorless compound, which is “ During processing following "bleaching" it remains colorless at the PH values normally encountered, and thus this new compound will eventually have the ability to be retained in photographic film units, e.g. light-sensitive elements, without the possibility of color reappearance. has. Dyes are typically selected for use as antihalation dyes, eg, in non-light-sensitive layers disposed intermediate the light-sensitive silver halide emulsion layer and the support. Dyes are also selected for use as color correction filter dyes where absorption of light within a particular wavelength range during exposure is desirable to obtain proper color balance. Exemplary film units in which the dyes of the invention may be usefully used as antihalation dyes are described, for example, in GB 1,482,156. These film units consist of, in the order in which the incident light passes, an additive polychrome screen, a light-sensitive silver halide emulsion layer,
It includes an antihalation layer in which the selected compound is disposed, and preferably an image receiving layer. As described herein, the halide emulsion is passed through a screen having an optical filter element that selectively transmits a predetermined portion of the incident radiation, e.g., red, green, and blue light, to the underlying light-sensitive silver halide emulsion layer. Exposure of the silver layer is performed. During photographic processing with aqueous alkaline processing compositions, soluble silver complexes are transferred by diffusion and deposited in the stacked image-receiving layers as a function of the degree of exposure of the silver halide after each filter element. The silver image thus formed then serves to control the amount of light passing through the filter element in the opposite direction during projection through the transparent support. In a preferred embodiment, the image-receiving layer is between the light-sensitive silver halide emulsion layer and the additive polychrome screen;
It then remains in place as part of an integral film unit before, during and after image formation. The antihalation dye is disposed in the processing composition transparent layer adjacent to the photosensitive layer on the side opposite the screen and serves to prevent reflection or backscatter of incident light passing through the photosensitive layer, thereby preventing the intended exposure. Eliminating exposure of silver halide grains within the photosensitive layer other than those within the passageways. As mentioned above, the dyes of the invention are also useful in multilayered photographic film units containing multicolor light-sensitive elements using blue, green, and red sensitized silver halide layers, and in particular in image-receiving layers that carry color transfer images. It is useful as a color correcting filter dye in integral negative-positive diffusion transfer film units in which the dye is not separated from the developed photosensitive layer after processing and both components are held together as a permanent laminate. A layer of light reflective material, preferably titanium dioxide, disposed between the image bearing layer and the developed photosensitive layer(s) is included as part of the laminate. A light reflective layer separating the image-bearing and photosensitive components provides a white background for the transferred image and masks the developed photosensitive layer(s). Besides these layers, the laminate usually includes dimensionally stable outer layers or supports, at least one of which is transparent, so that the resulting transferred image is provided by the light-reflective layer. It can be seen by reflection against the background. An example of a patent describing this film unit is Howard G. Rogers.
U.S. Patent No. 2983606, issued March 9, 1961.
No., Edwin H.
U.S. Patent No. 10, issued October 10, 1968 to
3415644, 3415645 and 3415646, U.S. Patent Nos. 3594164 and 3594165, issued to Howard G. Rogers on July 20, 1971, and U.S. Pat. No. 3,647,437. U.S. Pat. No. 4,329,411 to Edwin Etsch Rand relates to a multicolor diffusion transfer film unit in which a layer of dye, preferably a dye releasable by a processing composition, is disposed such that exposure is effected therethrough; This makes the dye layer effective as a color correction filter. For convenience, the specification of this application is specifically incorporated herein. Whether used as antihalation dyes, color correction filters, or in other conventional photographic light screening applications, the dyes of the present invention convert into new, colorless, closed-ring compounds into colored dyes when placed in a processing composition permeable layer. The color is completely and irreversibly decolored by contacting with an aqueous alkaline processing composition for the time necessary to exchange the compounds. The time required for decolorization, i.e. the exchange of the colored compound to a colorless product via the irreversible cleavage reaction described above, is measured at a constant alkaline PH, and for the selected decolorization time, the colored filter is contacted with the dye. PH of the processed composition as it is applied and remains in contact
must be at least as high as expected to give the selected bleaching time. T
For 1/2, the preferred compound is about 1NaNaOH and about
Has a half-life (T 1/2) of 30 seconds or less.
T 1/2 means the time measured for half of the colored dye to be bleached. The dyes of this invention can be incorporated into the appropriate layers of a photographic film unit using any of the techniques known to those skilled in the art. For example, the selected compound can be dissolved in a suitable solvent and then dispersed, optionally in the presence of a wetting agent, in a coating solution containing a hydrophilic colloid binder, such as gelatin, and the resulting coating solution can be mixed with the desired It can be applied as a layer, for example coated over a transparent support to provide an antihalation layer, or coated over the outermost photosensitive layer of a multilayered, multicolor photosensitive element so that exposure can take place through. Provides a color correction filter layer. The concentration of compounds in this layer will vary depending on the product for which the filter layer is to be used and can be easily determined empirically to provide the necessary optical density for a particular application. It will be appreciated that the dyes of the present invention can be used in combination with each other and also with other types of dyes conventionally used in antihalation color correction and other filter layers. FIG. 1 of the accompanying drawings showing one embodiment of the invention is an enlarged cross-sectional view of an integral diffusion transfer film unit, which units are arranged in a geometrically repeating distribution in a sequentially aligned relationship on a substantially single plane. an additive multicolor screen 3 consisting of a plurality of red primary color filter elements, a plurality of green primary color filter elements, and a plurality of blue primary color filter elements, a light-insensitive layer 5 holding silver precipitation nuclei, and a silver halide crystal. It consists of a transparent film base or carrier 1 which carries on one surface a photosensitive layer 7 containing a photoscreening dye of the present invention and an antihalation layer 9 containing one or more photoscreening dyes of the invention. As discussed in the above-mentioned GB 1482156, the degree of light absorption of the antihalation layer in this film unit varies over a relatively wide range, but typically the antihalation layer will have a thickness of between about 0.4 and 1.4. It has a transmission density range. Preferably,
This transmission density is greater than 0.6, so that when multiple film units are used in stacked relationship during exposure, the antihalation layer has sufficient density, ie, to substantially prevent reflections, as well as to prevent exposure of the film units below. It will have blocking light absorption ability. Conventionally used on the front surface of a camera lens as a convenient way to approach the type and amount of filtration desired to be provided in determining the appropriate light absorption performance for cyan, magenta and yellow for color correction purposes. “Color compensation” filters can be used in the usual way. A layer containing suitable color correcting dye(s) at a corresponding density is then provided as the layer through which exposure is carried out. Multicolor diffusion transfer images can be obtained by various arrangements of the image-receiving layer and silver halide emulsion. The layers can thus be kept on a common support stacked together after exposure. A particularly useful film structure is U.S. Patent No.
No. 3,415,644, in which the required layers are in stacked relationship before and during exposure, and the layers are maintained in stacked relationship as a permanent laminate after processing and imaging. The film unit typically includes an outer transparent layer or support through which exposure takes place and the final multicolor image is viewed, and another outer layer or support that carries at least the photosensitive layer and is opaque. These supports or sheet-like elements are simply held in superimposed relation, ie around the edges, by binding tape, and in a preferred embodiment the elements are superimposed together before exposure. This pre-lamination offers many advantages in both manufacturing and exposure. After exposure, the elements are delaminated by dispensing a fluid processing composition which, when solidified, bonds the elements together to form the desired permanent laminate. The method of forming this prelaminated film, in which two elements are temporarily laminated together before exposure, was described, for example, by Albert J.
U.S. Patent No. 3,625,231, issued March 28, 1972 to Frederick J.
No. 3652282 and Edwin Etsuchi Land.
No. 3,793,023, issued February 19, 1974. A further explanation of this embodiment of the invention is readily provided with reference to FIG. 2 of the accompanying drawings, in which a diffusion transfer film unit suitable for providing an integral negative-positive reflection print and employing a dye developer as the image dye is shown. shows. FIG. 2 shows a diffusion transfer film unit consisting of a photosensitive element or component 2, a breakable container 30, and an image receiving element or component 4. The photosensitive element sequentially comprises a cyan dye developer layer 12, a red sensitive silver halide emulsion layer 14, an intermediate layer 16, a magenta dye developer layer 18, and a green sensitive silver halide emulsion layer 2.
0, intermediate layer 22, yellow dye developer layer 24, blue-sensitive silver halide emulsion layer 26 and auxiliary layer 28
an opaque support 10 holding a . The positive or image-receiving layer 4 sequentially comprises a transparent support 40 carrying a polymeric acid layer 42, a timing layer 44 and an image-receiving layer 46 having dispersed therein a bleachable dye of the invention as a color correcting filter dye. The two elements are held in superimposed, registered relationship, for example by bonding tape (not shown), so that exposure of the silver halide emulsion is through an image receiving layer 46 containing a bleachable dye. Destructible container 30
contains a treatment composition and is arranged such that upon rupture this treatment composition is distributed between the superposed elements 2 and 4. The inclusion of a light-reflective pigment, such as titanium dioxide, in the processing composition provides a light-reflective layer against which the transferred image formed on image-receiving layer 46 is viewed.
The developed photosensitive layer is masked from view by this light reflective layer and remains as part of the permanent laminate with image receiving layer 46. This destructible container 3
0 is of the type shown in U.S. Pat. No. 2,543,181 and is located adjacent the leading edge of the film unit. In processing this film unit, compressive pressure is applied to the breakable container 30 to release the liquid contents between the photosensitive element 2 and the image receiving element 4, and then the liquid mass is deposited between the sheets towards the trailing edge. The film unit is advanced against and between a pair of pressure applying members that distribute the film to form a substantially uniform layer of predetermined thickness that is at least coextensive with the image area. Excess processing liquid can be provided in the container 30 to ensure sufficient processing liquid to form a layer of the required area and thickness between the sheets, and excess processing overrun can be collected. A trapping device (not shown) may also be provided for holding. Details of this film unit and the various layers of the film unit of FIG. 1 can be found in the patent applications cited herein and need not be recited here. Processing of a film unit of the type shown in FIG. 2 begins by distributing a processing composition between the predetermined layers of the film unit. In the exposed and developed areas, the dye developer becomes immobilized as a result of development. In the unexposed and undeveloped areas, the dye developer is unreacted and diffusive;
This in turn provides an imagewise distribution of non-oxidizing dye developer that can be diffused in the processing composition as a function of point-to-point exposure of the silver halide layer. The desired transferred image is obtained by diffusion transfer of at least a portion of this imagewise distribution of non-oxidizing dye developer into the image-receiving layer. In an exemplary embodiment, in accordance with the teachings of the aforementioned U.S. Pat. and lowers alkalinity to a PH that is non-diffusive. As is easily recognized,
Details of this method do not form part of the invention, but
Well known; reference may be made to the aforementioned US patents for a more specific discussion of this method. Multicolor images are obtained by providing the requisite number of differentially exposeable silver halide emulsions, which are usually provided as individual layers coated in superimposed relationship. Film units intended to provide polychromatic images contain two or more selectively sensitized silver halide layers, each with a spectral absorption substantially complementary to the light to which the associated silver halide is exposed. A suitable image dye supply material is bonded thereto which provides an image dye with properties. The negative elements most commonly used to form polychromatic images are of the "tripack" construction and contain blue, green and red light-sensitive silver halide layers, each with the same layer or adjacent layers. Yellow, magenta and cyan image dye supply materials are each bonded thereto. If desired, intermediate or spacer layers may be provided between each silver halide layer and the associated image dye supply material or between other layers. This general type of monolithic polychromatic photosensitive element was manufactured by Edwin
To Etsuchi Rand and Howard G. Rogers
No. 3,345,163, issued October 3, 1967, as well as the aforementioned U.S. patents, e.g.
It is disclosed in FIG. 9 of No. 2983606. Many variations of the structure described with respect to FIG. 2 will readily suggest themselves to those skilled in the art. Thus, for example, a multicolor multilayer negative was published by Edwin Etsch Rand in 1961.
It can be replaced by a screen type negative as shown in U.S. Pat. Image dye supplies that can be used in this method are (1) initially soluble or diffusible in the processing composition but selectively rendered non-diffusible in the imagewise pattern as a function of development; or (2) the process It is generally characterized as being either initially insoluble or non-diffusible in the processing composition, but selectively rendered diffusive in an imagewise pattern as a function of development, or providing a diffusible product. These materials may be complete dyes or dye intermediates, such as color formers. The necessary differences in mobility or solubility can be obtained by chemical reactions such as redox reactions or coupling reactions. Examples of initially soluble or diffusible materials and their applications in color diffusion transfer include, for example, U.S. Pat.
No. 3087817; No. 3185567; No. 3230082; No.
Examples include those disclosed in No. 3345163 and No. 3443943. US Pat. No. 3,185,567 as the first example of its use in non-diffusible materials and color transfer systems;
No. 3719489; No. 3443939; No. 3443940;
3227550; 3227552 and 4076529. Many types of image dye-providing materials and film units useful herein are also discussed in the above-referenced US Pat. No. 3,647,437. It should also be understood that "direct positive" silver halide emulsions can be used, depending on the particular image dye supply material used and whether a positive or negative color transfer image is desired. Suitable opacifying systems to be included in the processing composition for off-camera processing are disclosed in the aforementioned U.S. Pat.
No. 3,647,437 and has an optical transmission density greater than about 6.0 optical density with respect to incident radiation and about 1.0 with respect to incident visible radiation which is active for photosensitive silver halide when the processing composition is applied. of an optical filtering agent at a concentration effective to provide a layer exhibiting an optical reflection density less than the optical density.
Includes a dispersion of an inorganic light-reflecting pigment that also contains at least one light absorber, ie, an optical filtering agent, at a pH greater than or equal to PKa. Instead of having a light-reflecting pigment in the processing composition, the light-reflecting pigment used to mask the photosensitive layer and provide a background for viewing the color transfer image formed in the image-receiving layer may be preformed in the film unit. It may be initially present in whole or in part as a layer. Examples of such prefabricated layers are those disclosed in Edwin Etsch Land, U.S. Pat. No. 3,615,421, issued October 26, 1971, and U.S. Pat. Can be mentioned. The reflector is a U.S. patent issued to Edwin Etsch Rand on March 7, 1972.
3647434 and 3647435. The dye developer (or other image dye supply material) is preferably useful in performing subtractive color photography.
The dyes are selected for their ability to provide the aforementioned cyan, magenta and yellow colors. These are incorporated into each silver halide emulsion or, in preferred embodiments, in a separate layer after each silver halide emulsion. Thus, the dye developer may be, for example, in a coating or layer after each silver halide emulsion and in a suitable film-forming natural or synthetic polymer, such as gelatin, polyvinyl alcohol, etc., to be penetrated by the processing composition. This layer of dye developer can be applied by use of a coating solution containing each dye developer distributed, at a concentration calculated to give the desired coverage of dye developer per unit area. Dye developers as described above are compounds containing a dye coloring system and also a silver halide developing function.
"Silver halide development functionality" means a group suitable for developing exposed silver halide. A preferred silver halide development functionality is a hydroquinonyl group. Other suitable development functionalities include ortho-dihydroxyphenyl and ortho- and para-amino substituted hydroxyphenyl groups. Generally, the development functionality includes a benzenoid development functionality, ie, an aromatic development group that forms a quinonoid or quinone material when oxidized. The image-receiving layer comprises one of the materials known to those skilled in the art, such as polyvinyl alcohol, gelatin, etc. It contains suitable reagents for mordanting or otherwise fixing the transferred image dye(s). Suitable materials are polyvinyl alcohol or gelatin containing dyes such as poly-4-vinylpyridine as disclosed in U.S. Pat. No. 3,148,061 and U.S. Pat. No. 3,756,814.
4-vinylpyridine-containing graft copolymers as disclosed in No. In various color diffusion transfer systems previously described and using aqueous-alkaline processing fluids, the image stability is increased and/or from a first PH where the image dye is diffusive to a second PH where the image dye is non-diffusive. PH of 2
It is well known to use acid-reactive reagents in the layers of the film unit to lower the PH of the surrounding area subsequent to the substantially transferred image to adjust the PH (to lower). For example, the aforementioned US Pat. No. 3,415,644 accomplishes this desired PH reduction by providing a polymeric acid layer adjacent to the dyeable layer. These polymeric acids are polymers containing acid groups, such as carboxylic and sulfonic acid groups, which can form salts with alkali metals or organic bases; or naturally acid-forming groups, such as anhydrides or lactones. Preferably the acid polymer contains free carboxyl groups. Alternatively, the acid-reactive reagent is in a layer adjacent to the silver halide furthest from the image receiving layer as disclosed in U.S. Pat. No. 3,573,043, issued March 30, 1971 to Edwin Etch. . Another system for providing acid-reactive reagents is disclosed in U.S. Pat. No. 3,576,625, issued April 27, 1971 to Edwin Etsch Rand. An inert intermediate layer or spacer layer is preferably placed between the polymeric acid layer and the dyeable layer to control the PH reduction or "time" adjustment without prematurely and without interfering with the development process. .
Spacer or "timing" layers suitable for this purpose are inter alia US Pat. No. 3,362,819;
No.; No. 3421893; No. 3455686; and No. 3575701
listed in the issue. The acid layer and the associated spacer layer may be included in positive components used in systems in which the dyeable layer and the photosensitive layer are contained on separate supports, e.g. between the support for the image-receiving element and the dyeable layer. or bonded to the dyeable layer in these integral film units, e.g. on the side of the dyeable layer opposite from the negative component, if desired, as described e.g. in U.S. Pat. It may be combined with a photosensitive layer as described in US Pat. No. 3,573,043. The aforementioned U.S. patent no.
In film units such as those described in US Pat. No. 3,594,164 and No. 3,594,165 these may be included on the spreader sheet used to facilitate the application of process fluids. As is now well known and exemplified, the liquid processing compositions mentioned for performing multicolor diffusion transfer processes, e.g. and preferably has a PH of 12 or higher, and most preferably constitutes a film-forming material of the type that forms a relatively stiff and relatively stable film when the composition is spread and dried. Contains enhancing compounds. Suitable film-forming materials include high molecular weight polymers, such as polymeric water-soluble ethers, which are inert to alkaline solutions, such as hydroxyethylcellulose or sodium carboxymethylcellulose. Other film-forming materials or thickening agents whose ability to increase viscosity is not substantially affected when left in solution for extended periods of time may also be utilized. This film-forming material is produced at temperatures of approximately 24°C.
above 100Cps, and preferably at this temperature
It may be included in the treatment composition in a suitable amount to impart a viscosity to the composition on the order of 100,000 to 200,000 cps. In a particularly useful embodiment, a transparent polymeric support is provided with fog due to light piping due to internal reflection within the transparent support and subsequent exit of the incident active light from the surface of the support carrying the photographic layer onto its edges. Contains small amounts of pigments, e.g. carbon black, to prevent formation; this element is described in Belgian patent no.
Described in No. 777407. This transparent support advantageously contains a UV absorber. EXAMPLES For the purpose of illustrating the invention, as cyan, dye developer, magenta dye developer and yellow dye developer. A multicolor photosensitive element was prepared by coating a gelatin-subbed ^thymil opaque polyethylene terephthalate film base with the following layers ^: A layer of cyan dye developer dispersed and coated, plus 4'-methylphenylhydroquinone coated at a coverage of 6.3 mg/ ^ft2 and ^2'- coated at a coverage of 25.1 mg/ft2.
Phenylbenzimidazole; 2. Red-sensitive gelatinoiodosilver bromide emulsion coated with a coverage of 120 mg/ft ² silver and 72 mg/ft ^{2 gelatin; 3. Copolymer 232.8 mg/ft 2 and} polyacrylamide 7.2 mg/ft ² A layer of butyl acrylate, diacetone acrylamide, 60-30-4-6 tetrapolymer of styrene and methacrylic acid and polyacrylamide coated with a coverage of 4 dyes 60mg/ft ² and gelatin 42mg/ft ² coverage a layer of magenta dye developer dispersed and coated in gelatin; and about 21 mg/ft ² of 2-
Phenylbenzimidazole; 5. Green-sensitive gelatinioodosilver bromide emulsion with a coverage of approximately 74 mg/ft ² of silver and 36 mg/ft ² of gelatin; 6. Application of tetrapolymer 126.9 mg/ft ² and polyacrylamide 8.1 mg/ft ² a layer containing the tetrapolymer shown above plus polyacrylamide; and also 6.6 mg/ft ²
7. A layer of yellow dye developer dispersed and coated in gelatin with a coverage of 90 mg/ft ² of dye and 42 mg/ft ² of gelatin; and also 19 mg/ft ² of 2-phenyl. Contains benzimidazole; 8 Blue-sensitive gelatinoiodosilver bromide emulsion coated with a coverage of 119 mg/ft ² of silver and 62 mg/ft ² of gelatin; and also contains 19 mg/ft ² of 4'-methylphenylhydroquinone and 9 contains a layer of gelatin coated with a coverage of 45 mg/ft ² of gelatin and also carbon black coated with a coverage of 4 mg/ft ² . The image-receiving element was formed by successively coating a transparent thymyl polyethylene terephthalate base with the following layers: 1. Partial butyl ester of polyethylene at a coverage of about 2500 mg/ft ² as a polymeric acid layer/about 9: A mixture of maleic anhydride copolymer and polyvinyl butyral in a ratio of 1:2; 60-30-4-6 tetra of butyl acrylate, diacetone acrylamide, styrene and methacrylic acid in a 14: ¹ ratio with a coverage of 500 mg/ft2. 3. a timing layer containing a polymer and polyvinyl alcohol; and 3. a timing layer containing polyvinyl alcohol and polyvinyl alcohol coated at a coverage of 300 mg/ ^ft2 to provide an image-receiving layer.
3 parts by weight of a 2:1 mixture by weight of 4-vinylpyridine and 1 part by weight of a graft copolymer of 4-vinylpyridine and vinylbenzyltrimethylammonium chloride grafted onto hydroxyethylcellulose in a weight ratio of 2.2/1/2.2. admixture. The aqueous alkaline processing composition contained the following in weight percent: Water 49.28 Potassium hydroxide 5.39 Carboxymethylhydroxyethyl cellulose
1.79 Benzotriazole 0.77 4-Aminopyrazolo-3,4-D-pyrimidine
0.20 6-methyluracil 0.21 N-2-hydroxyethyl-N,N,N-doscarboxymethyl-ethylenediamine 0.81 Bis(2-aminoethyl) sulfide 0.02 Polyethylene glycol (molecular weight 6000) 0.50 Titanium dioxide 38.10 Colloidal silica aqueous dispersion ( 30% SiO ₂ ) 1.68 N-phenethyl-α-picolinium bromide 1.25 100 g of the above composition was given the formula: 1.35g of PH-sensitive dye and formula: 0.30 g of PH-sensitive dye was added. The photosensitive element was exposed to a multicolor step wedge, an image-receiving layer was overlaid onto the exposed photosensitive element, and a breakable container of processing composition was attached. This assembly is passed between a pair of pressure rolls so that an approximately 0.003" thick layer of processing composition is distributed between the gelatin overcoat layer 9 of the photosensitive element and the image receiving layer 3 of the image receiving element. The blue, green, and red Dlog E curves of the resulting multicolor transfer image (control image) were constructed using the same processing composition, the same photosensitive element, and the same image-receiving element and in the same manner as above. I made a test multicolor transfer image, but the above synthesis example
The compounds prepared in 16, 26, 27, and 39 were blended into the image-receiving layer 3 in the application range (mg/ft ² ) indicated in the table. Create blue, green and red Dlog E curves of the test image,
and blue, green and red H and D at the 0.75 reflection density intercept (0.75Neut.Exp.) of the neutral density column for each pair of control and test multicolor transfer images.
Sensitivity was measured in log E units for the curve. Obtained with the above 0.75 reflection density-exposure intercept
The log E sensitivity measurements and the maximum and minimum reflection densities (Dman and Dmin) obtained for the blue (B), green (G) and red (R) H and D curves are listed in the table. In addition to the above, test multicolor transfer images were made in the same manner as above using the compounds of Synthesis Examples 26 and 36, but
However, prior to exposure, the photosensitive element and image receiving element were stacked and exposure was carried out through the image receiving element of the integral film unit to the multicolor step wedge. The log E sensitivity measurements and reflection densities determined for each pair of control and integral film unit test images are listed in the table below. [TABLE] [TABLE] The dyes of the present application are effective at absorbing radiation within a specific wavelength range in the visible region, thereby producing color as evidenced by the change in log E sensitivity at 0.75 density. It is clear with respect to the table that the balance is selectively shifted. This change in color balance was obtained without adversely affecting maximum or minimum density. This lack of change indicates depigmentation. Additionally, it was observed that decolorization of the filter dye in the test images occurred in about 10 seconds or less. The methods of the present invention can be prepared by incorporating certain of the compounds into the image-receiving layer 3 of the same image-receiving element as defined above and then contacting this image-receiving element with the aqueous alkaline processing composition as defined above. Decolorization of the dye was also observed. The specific compound tested, its concentration in the image-receiving layer, and the solvent used to incorporate the compound into the image-receiving layer are shown in the table below. TABLE All these compounds were visibly observed to "bleach" or decolorize in about 10 seconds or less upon contact with the aqueous alkaline processing composition described above. Samples of the compounds prepared in Synthesis Examples 24, 26, and 39 above were also dissolved in a small amount of methanol, and aqueous 1N sodium hydroxide was added to each solution to decolorize the compounds. After decolorization, add aqueous hydrochloric acid to each solution.
The PH was lowered to PH1 and all solutions were observed to remain colorless even at PH1. In addition, the solution of the compound produced in Synthesis Example 44 was prepared using aqueous 1N NaOH
It was completely decolorized within 5 seconds when treated with aqueous 1NaOH and remained colorless after acidification and treatment again with aqueous 1NaOH. The "bleaching" rates for the compounds of Synthesis Examples 21, 23, 24, 39 and 41 were measured at PH=12 with respect to T 1/2.
T 1/2 means the time measured for half of the colored compound to bleach. When making these measurements, a cell containing about 3 ml of PH=12 buffer (aqueous) was loaded into the visible spectrometer. A sample of each compound was dissolved in methanol and a small amount (0.1 cc or less) of each solution was injected into this buffer.
Then record the optical density at the selected wavelength value and
1/2 was measured. The results are shown below. [Table] Also, when added to aqueous 1N NaOH, the methanol solution of the compound of Synthesis Example 9 decolorizes in about 5 seconds, and when added to aqueous 1N NaOH, the methanol solution of the compound of Synthesis Example 26 decolorizes almost instantly. It was observed that Synthesis examples 12, 13, 24, 26 using appropriate solvents
Construct the following structures by mixing a solution of a sample of the dye compound prepared in steps 3 and 39 with a solution of the graft copolymer and coating this mixture on the timing layer to complete each of the image-receiving components. Each sample was blended into the image-receiving layer 3 of the image-receiving component. A clear 4 mil thick polyethylene terephthalate film base was subsequently coated with: 1 A polyethylene partial butyl ester/maleic anhydride copolymer coated with a coverage of approximately 2500 mg/ ^ft2 as a polymeric acid layer. A mixture of about 9 parts polyvinyl butyral and 1 part polyvinyl butyral; butyl acrylate, diacetone acrylamide, in a 14:1 ratio, with a coverage of 2500 mg/ ^ft2 ;
a timing layer containing a 60-30-4-6 tetrapolymer of styrene and methacrylic acid and polyvinyl alcohol; 3 weights of 2.2/1/2.2 ^each coated at a coverage of 300 mg/ft2 to provide an image-receiving layer; In ratio, 4
- a graft copolymer of vinylpyridine and vinylbenzyltrimethylammonium chloride grafted onto hydroxyethyl cellulose and contains a selected dye compound with a coverage of 22 mg/ft ² . Each of the image-receiving components containing each dye compound was placed on a piece of gelatin-coated Mylar; red (R);
The transmission density for green (G) and blue (B) was recorded using a transmission densitometer. A few drops of aqueous 1N NaOH were then added to each gelatin sheet and the receiver component was lightly pressed against the gelatin sheet to decolorize the dye compound. 15
After ~60 seconds, the transmission densities were again recorded for red (R), green (G), and blue (B) for each "sandwich." The results are shown below. [Table] The dye compound of Synthesis Example 45 was blended into the image-receiving layer 3 of the image-receiving component constituting the above structure, and an aqueous 1N
It is quickly decolorized with NaOH to produce a colorless (“to the
A clear yellow film was produced leaving behind a film ("eye"). It is important to note that a variety of solvents can be used to disperse this dye in the image-receiving layer or other suitable layer of the photographic product and that the compounds given the useful solvents It will be appreciated that additional -OH or other solubilizing groups, such as -
COOH or -SO ₃ H as a dye molecule, e.g.
and/or can be bonded via the B moiety or the X moiety. Depending on the mobility of the dye in a given substrate or binder, immobilizing groups or substrates may be added to avoid migration of the dye, especially if the photographic product is subjected to conditions of high temperature and humidity before use. It is desirable to use mordanting groups. It is also possible to utilize the dyes of the present application to correct color balance, e.g., by exposing the photosensitive element to a suitable multicolor step wedge and treating it with a processing composition and an image-receiving component to provide a diffusion transfer. It would be acceptable to use it in transfer photographic film units. Next, the blue, green, and red of the multicolor transfer image (sample image) generated
Create a Dlog E curve. These Dlog E curves are tested using color photographic sensitometry.
The manner and extent to which the E-curve deviates from the desired curve shape will be shown to those skilled in the art. From this test it can further be determined by routine analysis and experimentation how many three lights are required for any wavelength range to obtain the desired color balance. The photosensitive element of another film unit having the same photosensitive element, receiver element and processing composition as that used in obtaining the sample image is then subjected to the changes necessary to provide the desired change in the Dlog E curve of the sample image. Give the same exposure through normal color correction filter(s) of estimated color and density. Next, the test multicolor transfer images produced are blue, green and red.
Create a Dlog E curve and compare with the sample. While one or more "tests" are required to determine which color triad is most effective in providing the desired Dlog E curve shape change, this test is quick and easy to perform. When the appropriate color 3 light is determined, a layer containing a color correcting dye or dye(s) that absorbs light in the appropriate wavelength range(s) is applied to the transparent support with a coverage area calculated to provide the required density. Cover over the body. This "test" color correcting dye layer is placed in the exposure path and the previous exposure test is repeated. Analysis of the Dlog E curve of the resulting multicolor transfer image indicates what changes, if any, should be made in the spectral absorption range and density prior to incorporation of the corresponding color correcting dye layer into the diffusion transfer film unit. The dyes containing the dye(s) of the present application "filter", i.e. reduce the exposure given to the exposed silver halide layer(s) by the light absorbed by said color correcting dye(s). and that one or more of the dyes of the invention may vary in one, two or all three of the individual red, green and blue H and D curves to obtain the desired color balance. It will be appreciated that it can be used with other filter dyes to obtain. Although the dyes of the present application find particular use in diffusion transfer and photographic film units where it is desirable to decolorize the dye(s) during processing following exposure of the dye layer(s), the dyes of the present application may also be applied to the transfer or final image. It can be used in diffusion transfer and other film units where the dye is arranged so as not to contribute dye density. "Unbleached" if the filter dye layer through which the exposure was made is not part of the transferred image, or if the final image is masked from viewing as in certain integral negative-positive reflective print constructions. The filter dye must be non-diffusible to the image-receiving layer containing the transferred image.
This necessary non-diffusive property is obtained by the use of suitable mordants, the use of long chain "ballast" or "anchor" substituents, and/or other techniques known to those skilled in the art. As illustrated by the examples above, in an integral diffusion transfer film unit, color correcting dye(s) can be incorporated into the image receiving layer. color correcting dye(s)
The choice of location depends primarily on determining at what stage of the manufacturing process the color correcting dye is incorporated. As will be readily apparent, providing the color correcting dye(s) in separate layers has the advantage of allowing transformation after the components have sufficiently "aged" and also allowing different transformations of portions of the same lot of positive components. Supports for the various layers may be of any useful type known to those skilled in the art. In preferred embodiments in which integral negative-positive reflective prints are obtained, the support should be dimensionally stable and may be based on polyethylene terephthalate or other polymeric films as disclosed in the patents referenced above and below. It will be appreciated that the transferred image formed following exposure and processing of a film unit of the type shown in FIG. 2 is a geometrically inverted image of the object. Therefore, in order to provide a geometrically non-reversing transfer image, the exposure of this film unit is carried out through image reversing optics, such as that of Douglas B.
Tiffany), US Pat. No. 3,447,437, issued June 3, 1969. Where the expression "positive image" is used, this expression should not be construed in a restricted sense, since this refers to the image of the light-sensitive emulsion layer, in the positive-negative sense; It is used primarily for illustrative purposes in defining the image produced on the image-bearing layer. As an example of another meaning for "positive image," suppose a photosensitive element is exposed to actinic radiation through a negative transparency. In this case, the latent image in the light-sensitive emulsion layer is positive and the dye image produced on the image-bearing layer is negative. The expression "positive image" is intended to cover the image produced on the image bearing layer as well as the transferred image obtained by the use of a direct positive silver halide emulsion to provide a "positive" image of the imaged object. While the utility of the dyes of the present application is illustrated as applied to an integral diffusion transfer film unit in which the transferred image is retained with the developed photosensitive element as part of a permanent laminate, the use of either silver or dye In diffusion transfer film units where the transferred image is separated from the developed photosensitive layer(s) following processing, the dyes of the present invention may also be used to provide antihalation, color correction or other filtration layer(s). I agree that it can be used. Although the image dye-providing material is preferably a dye developer, it will be appreciated that other types of image dyes and dye intermediates can be used to provide dye transfer images. In addition to their utility in diffusion transfer photographic products and methods, the dyes of the present invention can also be used in filter layers of conventional photographic materials, such as antihalation or color correction layers of conventional negatives, or to provide desired filtration effects. They can be arranged in appropriate layers in sufficient quantities to serve the purpose. The selection and formulation of dyes for the desired filtration effect is carried out in a known manner using conventional techniques;
and is well within the skill of those skilled in the art. selected dye(s), e.g. for color correction purposes
is capable of absorbing light within a particular wavelength range, for example blue, green, or red light, or a combination of several wavelength ranges, and is placed in the layer in which the exposure takes place. In fact, it is desirable in certain cases to filter light of two different wavelength ranges in a certain proportion so that one silver halide emulsion receives more exposed light than the other. As in diffusion transfer film units, the dye selected for color correction ( It is beneficial to apply multiple). When the dyes of the present application are used for antihalation purposes, they can be attached to layers on one or both sides of a support carrying photosensitive layers, and when they are used as optical filtering agents, These are arranged to prevent post-exposure fog during processing in ambient light, without of course interfering with imagewise exposure of the photosensitive layers or viewing the final image. All materials included in the foregoing description are to be construed in an illustrative and limiting sense, as certain changes may be made in the subject matter defined herein without departing from the scope of the invention contained herein. isn't it.

[Brief explanation of the drawing]

1 is an enlarged cross-sectional view schematically showing a diffusion transfer film unit having a dye of the present invention bound thereto as a decolorizable antihalation dye layer, and FIG.
The figure is a schematic enlarged cross-sectional view of another diffusion transfer film unit having a dye of the invention bonded to the image receiving layer as a color correcting filter dye.

Claims (1)

[Scope of Claims] 1 Comprising a plurality of layers including at least one light-sensitive silver halide emulsion layer carried on a support, and at least one of the layers has the formula [In the formula, A is a phenyl moiety or a naphthyl moiety, B is a 4'-oxo-1'-phenyl moiety or a 4'-oxo-1'-naphthyl moiety, and X is (a) {where R is an alkyl or phenyl group, unsubstituted or substituted with a solubilizing group, and R′ is (wherein R″ is methyl, unsubstituted or substituted with one or two halo groups or substituted with phenyl, alkoxy or phenoxy groups) and (However, Y is an electron-withdrawing group), or R and R' together with -N- in the formula (b) (c) where R is an alkyl or phenyl group, unsubstituted or substituted with a solubilizing group, and Y is an electron-withdrawing group. (wherein R ^o is hydrogen; or an alkyl group which is unsubstituted or substituted by halo, alkoxy, carboxy-substituted alkoxy, phenoxy or phenyl; or which is unsubstituted or is substituted in the m- or p-position phenyl substituted with halo, alkoxy, nitro, dimethylamino or alkyl), or (d) wherein R is an alkyl unsubstituted or substituted with a solubilizing group and Y is an electron-withdrawing group. Photo products. 2. A red light-sensitive silver halide emulsion layer having a combination of a cyan image dye-providing substance, a green light-sensitive silver halide emulsion layer having a combination of a magenta image dye-providing substance, and a blue light-sensitive halogen having a combination of a yellow image dye-providing substance. a first sheet-like element comprising a first support carrying a silveride emulsion layer; a second sheet-like element comprising a second support (the first and second sheet-like elements being in a superimposed relationship or an aqueous alkali suitable for being brought into mating relationship; said supports being the outermost; at least one of said supports being transparent to permit exposure of said silver halide emulsion therethrough; A rupturable container releasably retaining a processing composition, the rupturable container being positioned between a pair of predetermined layers held by the support to release the processing composition. ); and an image-receiving layer carried by one of said supports; and a processing composition permeable layer carried by one of said supports.
A photographic product according to claim 1 for forming a multicolor diffusion transfer image comprising a colored triarylmethane compound according to claim 1.