JPS6361955B2 - - Google Patents

Description

[Detailed description of the invention] The present invention relates to improved trimethylsilylation of organic compounds.
Regarding the method. In the field of manufacturing organic chemistry, for the protection of reactive groups
as well as physical properties such as volatility and solubility
of the use of trimethylsilyl group to change
Interest is increasing [for example, B.E. Cooper (B.E.
Cooper), Chem.and Ind.,1978, 794). Silylated products used on a large scale are e.g.
Methylchlorosilane and dimethyldichlorosilane
It is. The silylation reaction is said to be an equilibrium reaction.
Due to the fact that to shift the reaction towards the product side
The hydrogen chloride produced during the reaction is removed as quickly as possible.
It is necessary to remove the This is appropriate
By adding a tertiary amine to the reaction mixture
It can be carried out. Tertiary amines react with hydrogen chloride
The corresponding ammonia is usually sparingly soluble in the reaction mixture.
Produces um salt. Requires the use of large quantities of suitable solvents.
This step is usually carried out before purification of the desired product.
Removal of ammonium salts is necessary. However, Shiba
Traces of ammonium salts are often unavoidable in the product.
remains in Other frequently used silylating agents, e.g.
N,O (bis-trimethylsilyl)acetamide,
N,N'-bis(trimethylsilyl)urea, N-
trimethylsilyl-N,N'-diphenylurea,
N-trimethylsilylimidazole, trimethyl
Silyldiethylamine is often trimethylchloro
produced starting from rosilanes and silylated products
from the rest and put the rest into this series.
The disadvantage is that it must be isolated from the lubrication agent.
Ru. Another silicating agent used on a large scale is
1,1,1-trimethyl-N-(trimethylsili
) Silanamine (commonly known as hexamethyldisilazane,
HMDS) and this one
The only by-product is a gas, so it is easy to remove.
It is ammonium. Moreover, HMDS is relatively
Cheap silylation agent makes it attractive for industrial processes
It is. However, a significant drawback of HMDS is that in many cases
This means that the response is slow, and in some cases not at all.
Sometimes they don't even respond (e.g. S.H. Ranjiya)
- (S.H.Langer) c.s., J.Org.Chem.twenty three, 50
(1958)]. As a result, in order to complete the silylation,
higher reaction temperatures and/or longer reaction times
This makes this method less attractive.
unsuitable for heat-sensitive compounds. So
Additionally, large excesses of HMDS are often required. Therefore, the catalysis of silylation reaction by HMDS
For applications, lower reaction temperatures and/or
Much attention has been paid to reducing response times.
came. Examples of catalysts are amine salts (see DOS 2507882).
), trimethylchlorosilane [e.g.
S.H.Langer c.s., J.Org.Chem.twenty three,50
(1958)], sulfuric acid [e.g. D.A. Almitage]
(D.A.Armitage) c.s., Inorg.Synth.15, 207
(1974)], hydrogen chloride, inorganic acids such as phosphoric acid,
and their ammonium salts (e.g.
(see NL7613342), boron trifluoride and aluminum trichloride
Lewis acids like minium (also NL 7613342)
), bis(trialkylsilyl) sulfates (e.g.
See GE 2649536, (Fluoroalkyl) Sulfone
Acids (see e.g. GE 2557936) and imidazoles
[For example, D.N. Harpp c.s.J.
Amer.Chem.Soc.100, 1222 (1978).
However, even with these catalysts, the desired silyl
High reaction temperatures are required to obtain sufficient conversion to derivatives.
degree, excess HMDS and sometimes up to 48 hours
Very long reaction times are still required. This time, the present inventors investigated the use of certain nitrogen-containing compounds.
Many organic compounds can be prepared by using them as catalysts.
HMDS can greatly promote silylation of groups.
I realized something surprising: I was able to do this. The improved method of the present invention provides that the general formula X-NH-Y (In the above general formula, (a) X and Y are the same or different;
Rikao's one is formula [formula] and [expression] and [expression] (In the above formula, R₁and R₂are the same
Each bonito has one or more
Alkyl optionally substituted with halogen atom
group, or one or more halogen atoms or atom(s)
Alkyl group or alkoxy group or nitro group
an optionally substituted aryl group, or an aryl group that may be substituted;
Rukoxy group, or hydrogen atom or alkyl
Optionally substituted with a group or a nitro group
group, or R₃R_FourN group (In the above group, R₃and R_Fourare the same
Each bonito has a hydrogen atom or
or trialkylsilyl group or alkyl group
represents an electron-withdrawing group selected from (b) X is an electron-withdrawing group as defined in (a);
, Y is a hydrogen atom or a trialkylsilyl group
represents, or (c) X and Y together with the nitrogen atom form a cyclic system.
electron-withdrawing group, -A-Z-B- (In the above formula, A represents a [formula] group, and B represents [Formula] Group or -SO₂- group or -S- group or is [Formula] group or [Formula] represents a group, Z is any The group also has one or more halogen atoms or an alkyl group.
an optionally substituted alkylene group or alkyl group;
represents a nylene group or an arylene group). ) characterized by the presence of 0.001-10 mol% of the catalyst
organic compound containing one or more active hydrogen atoms
Trimethyl by compound hexamethyldisilazane
Concerning silylation. A suitable electron-withdrawing group for the melting medium of the above general formula is acyl
group, sulfonyl group, and phosphoryl group. electronic absorption
For more information about subscripts, see L.P. Hammett (L.P.
Hammet) Physical Organic Chemistry
Story (Physical Organic Chemistry), mug
McGraw-Hill Book
Company), New York, 1970, p347ff and
J.D. Roberts and M.C. Casse.
Co-authored by M.C. Caserio, Modern Organiz.
Ku Chemistry (Modern Organic
Chemistry), W.A. Benziyamin Co. (W.A.
See Benjamin Inc., New York, 1967, p.553ff.
I want to be illuminated. Examples of more specific electron-withdrawing groups are the following formulas (),
(), () [In the above formula (), R_Fiveis one or more halogens
Alkyl group optionally substituted with atoms, or
is substituted with one or more alkoxy or nitro groups
[indicates an optionally substituted aryl group], [In the above formula (), R₆is a methyl group, or
Substituted with one or more halogen atoms or methyl groups
is an aryl group which may be
R₆is R₇R₈N- group (among the above groups, R₇and R₈are the same
Each bonito is hydrogen.
atom or trialkylsilyl group or alkyl
(indicates a group)], [In the above formula (), R₉and R_Tenare the same
or different types of bonito, each with alkoxy
group, or substituted with a halogen atom or a nitro group.
Indicates an optionally substituted aryloxy group] It is shown by. Particularly suitable electrons that form a cyclic system with the nitrogen atom
The child attracting group is the following formula (), () [In the above formula (), Z is one or more halogen atoms
an alkyl group which may be substituted with a child or an alkyl group;
substituted with a kenyl group or one or more halogen atoms
[indicates an optionally substituted arylene group], [In the above formula (), x is 0 or 2, and Z
indicates an alkylene group or an arylene group] It is indicated by. Particularly preferred catalysts include electron-withdrawing groups having the following formula:
(), (), () [In the above formula (), R_Fiveis a dihalomethyl group,
or trihalomethyl group, or
Phenyl group optionally substituted with toxy group or
represents a nahityl group], [In the above formula (), R₆is a methyl group, or
May be substituted with methyl group or chlorine atom
phenyl group, amino group, or dial
Kylamino group or trialkylsilylamide
], [In the above formula (), R₉and R_Tenis methoxy
group, or ethoxy group, or propoxy
or substituted with a nitro group or a chlorine atom
[Indicates a phenyl group that may be substituted] It is indicated by. Similarly, especially those forming a cyclic system with the nitrogen atom
Examples of preferable electron-withdrawing groups are the following formulas (), (), [Z in the above formula () can be changed to a bell at will.
halo-substituted ethenylene group or phenyle
], [In the above formula (), x is 0 or 2, and Z
indicates a phenylene group] It is indicated by. In this specification, alkyl group, alkylene group, alkyl group, alkylene group,
Kenylene group, alkoxy group has 1 to 6 carbon atoms
including. A group of compounds according to the above definition having the desired catalytic properties
Examples are amides, sulfonamides, cyclic or
Chain imides, cyclic or chain sulfonimides
sulfamides, disulfonamides, acid
sulfonyl phosphoramidates, sulfonyl phosphoramids
midates and imidodiphosphates.
Ru. Suitable catalysts include, for example, trichloroacetamide,
Trifluoroacetamide, phthalimide, 3,
4,5,6-tetrachlorophthalimide, 3,
4,5,6-tetrabromophthalimide, 1,8
- naphthalimide, maleimide, barbituric acid,
Satucalin, N-benzoyl-4-toluenesul
Honamide, N-(2-methoxybenzoyl)-4
-Toluenesulfonamide, N-(1-naphthoi
)-4-Toluenesulfonamide, N-benzo
ylbenzenesulfonamide, N-(2-methoxy
C-1-naphthoyl)-4-toluenesulfona
Mido, N-(2-methoxy-1-naphthoyl)methane
Tansulfonamide, di(4-toluenesulfony)
) amine, dimethyl N-(trichloroacetyl)
Phosphoramidate, di-4-nitrophenyl N
-(trichloroacetyl)phosphoramidate,
Di-4-nitrophenyl N-(p-toluenesulfur)
Honyl) phosphoramidate, diisopropyl N
-(dichloroacetyl)phosphoramidate, dichloroacetyl
-o-chlorophenyl N-(4-chlorophenyl
sulfonyl) phosphoramidate, imidodiphosphoric acid
Tetraphenyl, sulfamide, N,N-dimethy
Rusulfamide, N,N'-bis(trimethylsilyl)
lyl) sulfamide, 1,2-benzisothiazo
ru-3(2H)-one and 4-benzoyloxi
C-1,2-dihydro-1-oxo-phthalazine
It is. Particularly preferred catalysts are saccharin, di-4-nito
Lofenyl N-(trichloroacetyl)phosphor
Imidate, di-4-nitrophenyl N-(4-
toluenesulfonyl) phosphoramidate and
Tetraphenyl imidodiphosphate. Reactions can be performed with or without organic solvents.
The process is carried out at temperatures ranging from 0 to 150°C. If melted
If a solvent is used, the solvent will separate the reaction components and products.
It must be inert to
For example, high ammonia concentrations reduce the reaction rate.
Therefore, at the temperature at which the reaction takes place, the amperage produced during the reaction is
Preferably it dissolves little or no monia.
Delicious. A suitable solvent has one or more halogen atoms.
Straight chain or branched chain or ring that may be substituted
Formula hydrocarbons, e.g. hexane, dichlorohexane,
dichloromethane, chloroform, or aromatics
Hydrocarbons such as benzene, toluene, xylene
or alkyl esters of carboxylic acids, e.g.
For example, ethyl acetate, butyl acetate, or nitric
such as acetonitrile, benzonitrile, etc.
or dimethylformamide, or dimethyl
sulfoxide or a mixture thereof. One or more -OH or NH groups or -NH₂
Organic compounds containing a group or a -SH group are included in the present invention.
It can be silylated by the following method. Such a compound
Examples of substances are alcohols, amines, and phenols.
, thiophenols, acids, amides, sulfonate
phosphoramides, thioamides, phosphoramides,
Amino acids, heterocyclic compounds, penicillanic acid and
and cephalosporanic acid derivatives, hydrolazine
N-hydroxy-succinimides, hydro
Xylamines, thiols and enolization possible
It is a highly functional ketone. one or more -OH groups or
NH group or -NH₂group or -SH group
There are many groups of organic compounds, so the ones listed above are
should not be considered limiting the general scope of the invention.
do not have. By using the catalyst of the present invention, the silyl of HMDS
Inherent disadvantage of use as a oxidizing agent: long reaction
time and/or high reaction temperature and/or
) The use of large excess of silylating agent was overcome. now
, silylation reaction in a short time, and/or
Can be carried out at lower reaction temperatures and usually with a small excess
silylating agent is sufficient. Furthermore, these anti-
under different conditions, a cleaner reaction mixture can be obtained;
This results in a purer product and in many cases
High yields are obtained. Another improved method of the present invention
One benefit is known to not react with HMDS
With the use of the catalyst of the present invention, compounds with
It became possible to silylate with
be. Examples of such compounds are tertiary alcohols [S.
H. Langer (S.H.Langer) c.s., J.Org.Chem.
23, 50 (1958)], phthalimide (D.N. Herr)
D.N.Harpp c.s., J.Amer.Chem.Soc.100,
1222 (1978)] and thiols. Furthermore, by applying the method of the present invention,
of penicillanic acid and cephalosporanic acid derivatives
Production of N,O-bis(trimethylsilyl) derivatives
can be carried out in a simple manner and with quantitative yields.
Wear. Production of these derivatives is difficult by other methods
[For example, F. voltesi]
(F.Bortesi) c.s., J.Pharm.Sci.66, 1767 (1977)
reference〕. Another method for producing a silylated compound of the present invention
Benefits include, for example, N-trimethylsilylimidazo
N,N'-bis(trimethylsilyl)urea
What kind of compound can be used as a silylating agent to perform silylation?
These silyl compounds can be
When using oxidizing agents, there are
silylated compounds with ammonium salts during their formation.
The reason lies in the fact that it is not contaminated. An example disclosing this invention is the silylation of urea.
Ru. The silylation of urea without catalyst is described in NL7613342.
As shown, it takes 36 hours at about 125℃. salt
6 at 118℃ using ammonium chloride as a catalyst.
It takes time (example of the above patent). but,
In the present invention, saccharin is used as a catalyst.
Therefore, a reaction time of 20 minutes is sufficient for the reaction to complete.
I found out something. Another example is phenylhydrazine and HMDS
This is the reaction. After 12 hours at 130℃ without catalyst
A yield of 12% was obtained. [R. Huetsenden (R.
Fessenden) c.s.J.Org.Chem.26, 4638 (1961)].
Using ammonium chloride as a catalyst, the same
A yield of 89% was obtained using the reaction conditions. Satsuka
When phosphorus is used as a catalyst, the silicification product is
It took only 2.5 hours to obtain the same yield. Trimethylchlorosilane is present as a catalyst
Tertiary alcohol compounds and HMDS will react even if
Although it is known that it does not [S.H.Ranjiyar]
(S.H.Langer) c.s.J.Org.Chem.twenty three, 50 (1958)
[See] The reaction between this tertiary alcohol and HMDS is now
Proceeds rapidly to extremely rapidly under the influence of
do. For example, t-amyl alcohol is
Reacts with HMDS in 3 hours using chlorine as a catalyst
It becomes trimethylsilyl ether, and di-
4-Nitrophenyl N (4-toluenesulfonyl)
2-Methylation using phosphoramidate as a catalyst
-2-hexanol reacts in just 15 minutes
Becomes a methylsilyl derivative. Phthalimide and
Reactions with HMDS also benefit from the use of the catalysts of the present invention.
show. Phthalimide hexamethyldisilazane
The silylation with imidazole and imidazole as a catalyst is
Requires reflux for 2 days [D.N. Harp (D.N.
Harpp) c.s.J.Amer.Chem.soc.100, 1222
(1978)]. Nowadays, phthalate using satsucalin as a catalyst
Silylation of imide with HMDS within 1.5 hours
Proceeds completely and gives substantially higher yields
I found out. Furthermore, the modification of silylation by HMDS of the present invention
A good method is one that has been previously described in the literature.
of organic compounds that could not be silylated
Enables the production of trimethylsilyl derivatives. child
This is especially true for certain organic thiols.
Ru. Therefore, another feature of the present invention is that the general formula R-S-SiMe₃ (In the above general formula, R is one or more hetero atoms.
5-membered nitrogen or sulfur atom or
6-membered heterocyclic group with one or more alkyl groups
or phenyl group or trimethylsilyl group or
is an alkylamino group or trimethylsilyloxy
compound optionally substituted with a cyclocarbonylmethyl group
(represents a bare cyclic group) This is the production of trimethylsilyl-substituted compounds. Up
Examples of the R group include 1,3,4-thiadiazolyl group or
is 1,2,3,4-tetrazolyl group or 1,
2,3-triazolyl group or 1,2,4-tri
Azolyl group or imidazolyl group or pyrimidine
These groups are methyl or phenyl groups.
group or methylamino group or trimethylsilyl group
or trimethylsilyloxycarbonyl group.
It may be substituted with a thyl group. According to the general formula above
The compound is, for example, (5-methyl-1,3,4-
thiadiazole-2-thio)trimethylsilane,
1-Methyl-5-trimethylsilylthiotetrazo
silyl, 1-trimethylsilyl-5-trimethylsilyl
Lylthio-1,2,3-triazole, 1-methy
-2-(trimethylsilylthio)imidazole,
1-trimethylsilyl-3-trimethylsilyl
O-1H-1,2,4-triazole, 1-phene
Nyl-5-trimethylsilylthio-1H-tetra
sol, 4,6-dimethyl-2-(trimethylsil)
(lylthio)pyrimidine, 2-methylamino-5-
Trimethylsilylthio-1,3,4-thiadiazole
5-trimethylsilylthio-1H-tetra
Zolyl-1-acetate trimethylsilyl, 5-trimethyl
Tyrsilylthio-1,3,4-thiadiazolyl-
2-trimethylsilyl acetate. These birds
Methylsilylated thiols have been shown to be useful by novel methods.
It is a useful intermediate in the production of compounds. Kaka
Examples of beneficial compounds include therapeutically effective 3'-thio substituted
Cephalosporins or intermediates thereof. child
These compounds pair trimethylsilylated thiols.
reacts with the corresponding 3′-halo-substituted cephalosporins.
Manufactured by These cephalos
This new method for producing sporins is patented in the Netherlands.
Described in Application No. 8005041. trimethyl
Other applications of silylthio compounds are e.g.
(Mukaiyama) c.s. (Chem. Lett., 187, 1974 and
and Chem.Lett., 1013, 1974) and Evans
(Evans) c.s. [J.Am.Chem.Soc.,99, 5009 (1977)
It is described by. Therefore, the compounds produced by the method of the present invention
is a general formula R-S-SiMe₃ In the above general formula, R is one or more hetero atoms
5- or 6-membered nitrogen or sulfur atom
a membered heterocyclic group with one or more alkyl groups
or phenyl group or trimethylsilyl group or
is an alkylamino group or trimethylsilyloxy
compound optionally substituted with a cyclocarbonylmethyl group
(represents an elementary cyclic group) This is a new compound. An example of the above R group is 1,3,4-thiazoazolyl group
or 1,2,3,4-tetrazolyl group or
1,2,3-triazolyl group or 1,2,4-
Triazolyl group or imidazolyl group or pyri
midyl groups, these groups are methyl groups or fluoride groups.
enyl group or methylamino group or trimethyl
Silyl group or trimethylsilyloxycarbonyl group
may be substituted with a methyl group. General formula above
Compounds according to (5-methyl-1,3,
4-thiadiazole-2-thio)trimethylsila
1-methyl-5-trimethylsilylthiotetate
Razol, 1-trimethylsilyl-5-trimethy
Lucilylthio-1,2,3-triazole, 1-
Methyl-2-(trimethylsilylthio)imidazo
1-trimethylsilyl-3-trimethylsilyl
Lylthio-1H-1,2,4-triazole, 1
-Phenyl-5-trimethylsilylthio-1H-
Tetrazole, 4,6-dimethyl-2-(trimethyl)
tylsilylthio)pyrimidine, 2-methylamino
-5-trimethylsilylthio-1,3,4-thia
Diazole, 5-trimethylsilylthio-1H-
Tetrazolyl-1-trimethylsilyl acetate, 5-
Trimethylsilylthio-1,3,4-thiadiazole
It is trimethylsilyl lyl-2-acetate. Yet another produced by the method of the invention
The new compound is 7-phenylacetamide-3
-(1-methyl-1H-tetrazolyl-1-thio)
Methyl-3-cephem-4-carboxylic acid trimethylate
Lucilyl 1-oxide, N,O-bis(trimethylate)
Lucilyl)-7-phenylacetamide-3-
(1H-1,2,3-triazolyl-5-thio)methane
Chil-3-cephem-4-carboxylic acid 1-oxy
7-trimethylsilylamino-3-(5-methane)
Thyl-1,3,4-thiadiazolyl-2)-thio
Methyl-3-cephem-4-carboxylic acid trimethylate
Lucilyl, 7-trimethylsilylamino-3-
(1-trimethylsilyl-1H-1,2,3-tri
Azole-5)-thiomethyl-3-cephem-4
-trimethylsilyl carboxylate, 7-trimethyl
silylamino-3-(1-methyl-1H-tetrazo
Lyle-5)-thiomethyl-3-cephem-4-ka
Trimethylsilyl rubonate, 7-phenylaceto
Amido-3-(1-methyl-1H-tetrazolyl-
5-thio)methyl-3-cephem-4-carvone
trimethylsilyl acid, 7-phenylacetamide
-3-(1-trimethylsilyl-1H-1,2,3
-triazolyl-5-thio)methyl-3-cefe
Trimethylsilyl mu-4-carboxylate. child
These compounds are therapeutically effective cephalosporins.
is a useful compound for the production of The catalyst may be added to the reaction mixture in its pure form.
can be added, but it can also be added in masked form.
can be used, for example silylated derivatives of catalysts or
sodium salt or by decomposition in the reaction mixture.
It may also be added as another derivative that becomes the catalytic compound described below.
It is clear to those skilled in the art that
Dew. The present invention will be further explained below with reference to Examples.
However, the present invention is limited to application to the compounds in the examples.
It's not something you can do. Example 1 Production of 1-trimethylsilyloxide dodecane A: 18.6g (0.1mol) of 1-dodecanol
Add tucarin (90 mg; 0.5 mmol) and mix.
The mixture was heated to 130°C. hexamethyldisila
Zan (15.6 ml; 0.075 mol) was added during 8 minutes.
did. The ammonia produced in the reaction is treated with dry nitrogen.
It was poured into water and titrated with 1NHCl. hexamethi
of the calculated amount during 15 minutes after starting the addition of rudisilazane.
It was discovered that ammonia was present. Reflux
Continue for 10 minutes and remove excess hexamethyldisilazane.
evaporate under reduced pressure and vacuum distill the residue, b.
p.120℃/0.5mmHg;n^{twenty five} _D1-trimethy of 1.4268
25.42g (98.5%) of lucilyl oxide dodecane
Obtained. B 9.3 g (50 mmol) in 50 ml dichloromethane
1-dodecanol and 51 mg (0.27 mmol) of 1-dodecanol.
A refluxing solution containing saccharin
and hexamethyldisilazane (7.8 ml; 38 mmol)
) was added. By the method described in Example 1A,
A calculated amount of ammonia was generated after 1 hour of reflux.
I found out. C 9.30 g (50 mmol) in 50 ml dichloromethane
70 mg (0.25 mmol) of 1-dodecanol
dimethyl N-trichloroacetyl phosphor
heating a solution containing Ruamidate to reflux,
Hexamethyldisilazane (7.8ml; 37.5mmol
) was added rapidly with a pressure equalizing addition funnel.
After refluxing for 75 minutes, the calculated amount of ammonia was generated.
I found out. D This preparation was carried out as described in Example 1C.
Ivy. However, 121 mg (0.25 mmol) of Di-4
-Nitrophenyl N-trichloroacetylphos
Foramidate was used as a catalyst. The reaction is
It was completed in 40 minutes. E 121 mg (0.25 mmol) of di-4-nitroph
enyl N-toluenesulfonylphosphoramide
The reaction time was 60
It was hot in minutes. Example 2 Production of trimethylsilyloxycyclohexane By the method described in Example 1A, cyclohexane
Nol (15.0 g; 0.15 mol) in 5 minutes at 23.4
ml (0.112 mol) of hexamethyldisilazane.
silylation by adding This silylation
The reaction was catalyzed with 137 mg (0.75 mmol) of saccharin.
Mediated. A calculated amount of ammonia is generated in 18 minutes.
Ta. Then continue refluxing for 10 minutes and remove excess hexafluoride under reduced pressure.
Distill off the hexamethyldisilazane and vacuum evaporate the residue.
boiling point 53-55℃/12mmHg, n^{twenty five} _D1.4281
Trimethylsilyloxycyclohexane 22.01g
I got it. Example 3 2-trimethylsilyloxy-2-methylbuta
manufacturing 17.6g (0.20mol) 2-methyl-2-butano
alcohol (t-amyl alcohol) and 0.18g (1ml
A refluxing mixture consisting of mol) of saccharin
Hexamethyldisilazane (21.9ml; 0.105
mol) was added. The silylation process is Example 1A
I did it as described. 50% of calculation amount
It was found that a near event occurs in 18 minutes. Reflux
After continuing for 3.25 hours, 98% of the calculated amount of ammonia is
Occurred. Boiling point 129-130℃ by atmospheric distillation; n^{twenty two} _D
1.3980 pure 2-trimethylsilyloxy-2
-22.75 g (71%) of methylbutane were obtained. boiling point 125
−129℃, n^{twenty two} _D1.3974 pre-distillate is 88% by NMR analysis
It contained the title compound. Example 4 17-β-trimethylsilyloxy-4-and
Production of Rosten-3-one 577 mg (2.0 mmol) in 10 ml dichloromethane
17-β-hydroxy-4-androstene
-3-one and 1.8 mg (0.01 mmol) of Satsukari
Hexamethyl is added to a refluxing suspension containing
Disilazane (246 mg, 1.5 mmol) was added.
The reaction process is shown on Kieselgel.
60F₂₅₄Toluene and acetic acid on [Merk]
A thin-layer film using a 9+1 mixture of
It was tracked by romatography. 2 hours later
The starting material no longer exists and one new
It was found that a product was formed. solvent under vacuum
The product obtained in quantitative yield after evaporation of
However, by NMR spectroscopy, pure 17-β-tri
Methylsilyloxy-4-androstene-3-
It was confirmed that it was on. Melting point of this product
The temperature was 126-128°C (decomposition). Example 5 1-trimethylsilyloxy-2-propene
manufacturing Allyl alcohol (24.28g; 0.418mol) and salt
Tukarin (0.36g; 2mmol) and 50ml pen
The mixture was heated to reflux.
Add hexamethyldisilazane to this mixture for 7 minutes.
(51 ml; 0.25 mol) was added. occurs during the reaction
The calculated amount of ammonia is determined by titration of ammonia.
It was found that this occurs in 1.5 hours. atmospheric distillation
, boiling point 97−100℃, n^{twenty five} _D1-trimethyl of 1.3943
Obtained 46.1 g (85%) of silyloxy-2-propene.
Ta. Example 6 Made of penta(trimethylsilyl)fructose
Construction 7.20 g (40 mmol) fructose and 0.07 g
(0.4 mmol) of satsucalin and 24 ml of chloroform
and 8 ml of pyridine at refluxing mixture.
Hexamethyldisilazane (42ml; 0.20mol) in 8 minutes.
) was added dropwise. The generated ammonia is absorbed into the water.
1NH₂S.O._FourTitrated with 0.10 after refluxing for 1 hour.
It was found that moles of ammonia were generated. 30
After continuing refluxing for a minute and distilling off the solvent at normal pressure, the remaining
Distillate the distillate under vacuum to obtain a boiling point of 138-142℃/0.5mmH.
g;n^{twenty five} _D1.4306 penta(trimethylsilyl) fluoride
19.63g (90.9%) of lactose was obtained. Example 7 Production of 1-trimethylsilyloxyhexane A: 5.10g (50mmol) of 1-hexanol
Mixed with 0.37 g (2.5 mmol) phthalimide
and heated to 130°C in an oil bath. hexamethyl
Disilazane (7.8 ml; 37.5 mmol) was added;
Absorbs ammonia into water to eliminate ammonia generation
Let me 1NH₂S.O._FourFollow up by titrating with
did. Ammonia with a calculated amount of 25 mmol is 130
It was found that this occurred within minutes. B 2.5 mmol of 3,4,5,6-tetrachlor
Repeat the above experiment using loftalimide as a catalyst.
Ta. The calculated amount of ammonia was generated in 70 minutes. C 2.5 mmol of 3,4,5,6-tetrabro
Repeat the above experiment using mophtalimide as a catalyst.
Ta. Calculated amount of ammonia is generated in 20 minutes
I understood. D Experiments were also conducted without the addition of catalyst. in this case
calculated amount of ammonia after 205 minutes of reflux.
There has occurred. E 5.10 g (50 mmol) of 1-hexanol
Mix with the catalyst listed in the table below and heat to 130℃ in an oil bath.
Heat 7.8 ml (37.5 mmol) hexamethylene
Ludisilazane was added. half of the theoretical amount
The time (t) for generation of monia was measured. detail
is shown in the table below. 【table】 Example 8 (2-methyl-2-hexoxy)trimethylsil
Orchid production 5.80 g (50 mmol) of 2-methyl-2-hex
Sanol and 25 mg (0.05 mmol) di-4-nit
Lofenyl N-4-toluenesulfonylphosphor
Place the mixture with amidate in an oil bath at 140°C,
7.8 ml (37.5 mmol) hexamethyldisilaza
was added. Calculated amount of ammonia after refluxing for 15 minutes
It turned out that near had occurred. boiling point in vacuum distillation
54-60℃/18mmHg;n^{twenty five} _D1.4074 (2-methyl
-2-hexoxy)trimethylsilane 8.66g (92
%)was gotten. Example 9 Reaction of hexamethylenedisilazane with water 740mg (41ml) in 15ml dry acetonitrile
mol) of water and 21.4 mg (0.12 mmol) of Satsukari
reflux and boiling solution for 5 minutes.
12.5 ml (60 mmol) hexamethyldisilazane
was added dropwise. The generated ammonia is poured into the water using a nitrogen stream.
and titrated with 1N sulfuric acid. 4 from the start of addition
After 50 minutes, 50% of the calculated amount of ammonia has already been collected.
Ta. After 35 minutes, no more ammonia is produced.
The amount of calculation was collected. Example 10 Production of N-trimethylsilyl-p-toluidine 17.25 g (0.16 mol) p-toluidine and 0.15
(0.8 mmol) in an oil bath mixture with saccharin
Heat to 130℃ and add hexamethyldisilazane to this.
(25 ml; 0.12 mol) was added over 5 minutes. reaction
By titrating the ammonia generated in the
A calculated amount of ammonia was generated after 2 hours of reflux.
I found out. Continue refluxing for 30 minutes and mix the reaction.
Distill the substance under vacuum to obtain a boiling point of 98-102℃/12-13mmH
g of N-trimethylsilyl-p-triidine 24.0
g (83%). Example 11 Production of phenoxy(trimethyl)silane 19 g (0.2 mol) in 15 ml dichloromethane
80 mg (0.4 mmol) of phenol Satucalin
Hexame into a solution boiling under reflux containing
Tildisilazane (31 ml; 0.15 mol) was added dropwise.
Before 25 minutes, a calculated amount of ammonia was generated.
This could be confirmed by titration using the method described above.
By fractional distillation, boiling point 62-63℃/12mmHg;n²⁶ _D
1.4731 phenoxy(trimethyl)silane 31.6g
(95%). Example 12 Production of o-trimethylsilyloxytoluene 10.80g (0.1 mol) in 30ml dichloromethane
o-cresol was dissolved. Satucalin (90mg;
0.5 mmol) and heat the mixture to reflux.
Hexamethyldisilazane (15.6ml; 0.075ml)
) was added. Theoretical amount of ammonia in 30 minutes
I found out that it had happened. Solvent and excess hexa
After evaporating the samethyldisilazane, remove the residue
Vacuum distillation, boiling point 46-53℃/0.5-0.7mmHg; n^{twenty five} _D
1.4756 o-trimethylsilyloxytoluene
16.91g (93.9%) was obtained. Parallel experiments without saccharin require an enormous amount of calculation.
Requires 3.75 hours of reflux for near
Ta. Example 13 (2,6-di-sec-butylphenoxy)tri
Production of methylsilane 10.4 g (50 mmol) of 2,6-di-secbutylene
luphenol and 23 mg (0.05 mmol) of di-4-
Nitrophenyl N-trichloroacetylphosphor
Refluxing of amidate and 20 ml of chloroform
Hexamethyldisilazane (7.8ml;
37.5 mmol) was added. After refluxing for 3 1/2 hours
Ammonia production has stopped. Chloroform under reduced pressure
The residue was distilled off to a boiling point of 86-90℃.
/0.4mmHg;n^{twenty five} _D12.64g of the title compound of 1.4812
(90%). Example 14 Production of trimethyl(phenylthio)silane A 16.0 g (0.145 mol) in 25 ml of chloroform
of Thiophenol and 135 mg (0.75 mmol)
The refluxing solution containing saccharin is
Add samethyldisilazane (23.4 ml; 0.11 mol).
added. Titrate the ammonia generated during the reaction
By refluxing for 2.66 hours, the silylation was
I found out it was completed. Solvent and excess
After distilling off the hexamethyldisilazane under reduced pressure,
The residue was fractionated to a boiling point of 92-95℃/12-13mmH.
g,n^{twenty five} _D1.5270 trimethyl (phenylthio)
24.4 g (92.1%) of silane was obtained. B 17.4 g (0.158 mol) of thiophenol and 135
mg (0.75 mmol) of Satucalin and 24.7 ml
(0.12 mol) of hexamethyldisilazane
The mixture was refluxed for 2 hours and distilled to a boiling point of 88-90
°C/12mmHg, n^{twenty five} _D1.5308 Trimethyl (Fue)
23.9 g (83%) of nilthio)silane were obtained. Example 15 (5-methyl-1,3,4-thiadiazolyl
-Production of 2-thio)trimethylsilane 13.2 g (0.1 mol) of 2- in 25 ml of toluene
Mercapto-5-methyl-1,3,4-thiadias
zol and 92 mg (0.5 mmol) of satsucalin.
Hexamethyldisilazane is added to the refluxing solution containing
(15.6 ml; 0.075 mol) was added. Occur
By titrating ammonia, the reaction is carried out for 30 min.
It was found that the process was completed after refluxing. Torr at normal pressure
The ene is distilled off, the residue is vacuum distilled, and the boiling point is 150 ~
(5-methyl-1,3,4-
Thiadiazolyl-2-thio)trimethylsilane
18.63g (91.3%) was obtained. The distillate has a melting point of 67-69
It became a solid with a temperature of ℃. NMR (60MHz; internal
with tetramethylsilane (δ=0) as standard
CCl_Fourmiddle): two singlets at 0.56 and 2.42, product
The ratio is 3:1. Example 16 1-Methyl-5-trimethylsilylthiotetra
Manufacture of sol 0.582 g (5.0 mmol) of 5-mercapto-1
- methyltetrazole and 5.0 mg (0.03 mmol)
12ml of ethyl acetate and 25ml of dichloromethane.
Dissolve in a mixture with chloromethane. This mixture
Reflux the mixture and add hexamethyldisilazane (1.26 ml;
5.5 mmol) was added. After refluxing for 1 hour,
The occurrence of Monia has stopped. Volatile substances under vacuum
Evaporated to 0.94 g 1-methyl-5-trimethyl
Silylthiotetrazole was obtained. NMR spectrum
(CCl_Four): two singlets at 0.61 and 3.79ppm,
Integral ratio 3:1. Example 17 1-trimethylsilyl 5-trimethylsilyl
Production of o-1,2,3-triazole 0.49 g (4.86 mmol) of 5-mercapto-
1,2,3-(1H) triazole and 5 mg (0.027
mmol) of saccharin and 10 ml of ethyl acetate and 15
ml of dichloromethane to the refluxing mixture.
Hexamethyldisilazane (1.52ml; 7.3mmol)
was added. The generated ammonia was recorded in Example 1A.
1NH using the method described₂S.O._FourTitrated with 2 equivalents (4.9 mm
mol) of ammonia generated after 30 minutes of reflux.
I understood. Evaporate volatile substances under vacuum,
From the residue (1.19g: 96%) in carbon tetrachloride solution
NMR spectrum taken: δ0.31 (9H); 0.48 (9H); 7.46 (1H). Example 18 1-Methyl-2-(trimethylsilylthio)i
Manufacture of midazole 1.14 g (10 mmol) of 1-methyl-2-mel
Captoimidazole and 18 mg (0.1 mmol)
Boil under reflux consisting of Tukarin and 20 ml of toluene.
A stream of nitrogen is passed through the rising mixture.
xamethyldisilazane (1.5 ml; 7.2 mmol)
Added. The generated ammonia is released into the water using a nitrogen stream.
Introduced. 40 min by titration with 1N sulfuric acid
It was found that a calculated amount of ammonia was generated within
Ivy. The mixture was evaporated to dryness under reduced pressure and the residue
was dried under vacuum at room temperature to give a 1-metal solution with a melting point of 49-52°C.
Thyl-2-(trimethylsilylthio)imidazo
1.78 g (95%) of the product was obtained. ¹HNMR (CCl_Four): 0.55 (s, 9H); 3.49 (s,
3H); 6.48 (d, 1H, J2Hz); 6, 69
(d, 1H, J2Hz). Example 19 1-trimethylsilyl-3-trimethylsilyl
Production of thio-1H-1,2,4-triazole 9.70g (96ml) in 200ml dichloromethane
mole) of 3-mercapto-1H-1,2,4-t
Riazole and 100 mg (0.25 mmol) of di-4-
Nitrophenyl N-(4-toluenesulfonyl)
Boil under reflux, including phosphoramidates
While passing a stream of dry nitrogen through the suspension,
29.2 ml (0.14 mol) of hexamethyldisilazane
Added quickly. The generated ammonia is removed with a nitrogen stream.
By introducing it into water and titrating it with 1N sulfuric acid,
The calculated amount of ammonia (96 mmol) was
I found out that it happened inside. Boil for another 0.5 hours
After continuing to boil, pour the colorless and transparent solution onto a rotating film.
Evaporate to dryness using a rotating film evaporator
and 1-trimethyl-3-trimethane with a melting point of 90-94°C.
Tyrsilylthio-1H-1,2,4-triazo
23.1 g (98%) of the product was obtained. ¹HNMR (CCl_Four): 0.52 (s, 9H); 0.55 (s,
9H); 7.52 (s, 1H). Example 20 1-phenyl-5-trimethylsilylthio-
Production of 1H-tetrazole In the same manner as described in Example 19, 50 ml of 1,
1.78 g (10 mmol) in 2-dichloroethane
1-phenyl-5-mercapto-1H-tetrazo
5 mg (0.03 mmol) of saccharin.
2.60 ml (12.4 mmol) of hexa
It was silylated with methyldisilazane. Total within 20 minutes
A large amount of ammonia was collected. Boil for another 10 minutes
After continued boiling, evaporate the mixture to dryness and remove the residue.
Dry to give 1-phenyl-5-t, melting point 67-68°C.
Limethylsilylthio-1H-tetrazole 2.58g
(103%). ¹HNMR (CCl_Four): 0.68 (s, 9H); 7.38−7.64
(m, 3H); 7.91-8.17 (m, 2H). Example 21 Trimethylsilyl (4-chlorophenylthio)
Manufacture of silane 14.50 g (0.10 mol) of 4 in a Claisen container
-chlorothiophenol and 45 mg (0.25 mmol)
of saccharin and dry nitrogen over the mixture.
It was heated to 120° C. in an oil bath while running a stream of water.
To this mixture hexamethyldisilazane (20.8 ml,
0.10 mol) was rapidly added dropwise. thereby precipitating
was formed, but the precipitate disappeared after heating for 10 minutes. Departure
The produced ammonia is introduced into the water with a nitrogen flow, and 1N
Monitor reaction progress by titration with sulfuric acid
However, the calculated amount of ammonia will be generated within 40 minutes.
I understood. The product was isolated by vacuum fractionation and the melting point
Trimethylsilyl (4-k) at 82-84℃/20mmHg
19.81g (91.5%) of lolophenylthio)silane
Obtained. Example 22 Trimethyl(4-methylphenylthio)silane
Manufacturing of A. 40 mg (0.08 mg) according to the method described in Example 21.
catalyzed tetraphenyl imidodiphosphate (remol)
14.70 g (118 mmol) of 4-methane
Add 25 ml (12 mmol) of tilthiophenol to
It was silylated with hexamethyldisilazane. Cyril
It was found that the process was completed within one hour. Living
The product was isolated by vacuum distillation and had a boiling point of 80.5-82.0℃/
Trimethyl (4-methylphenylthi) at 2.5 mmHg
e) 22.16g (95.4%) of silane was obtained. B In the second experiment, 11.35 g (91.5 mmol) of
4-methylthiophenol and 20.8ml (100ml
mol) of hexamethyldisilazane,
200 mg (0.42 mmol) imidodiphosphate tetra
Phenyl was used as a catalyst. This amount of catalyst
Now we know that the reaction is already complete within 30 minutes.
It was. By distillation, boiling point 79-81℃/2.5mmHg
trimethyl(4-methylphenylthio)sila
was obtained with a yield of 84%. Example 23 4,6-dimethyl-2-(trimethylsilylthi)
e) Production of pyrimidine 0.70 g (5.0 mmol) of 4,6-dimethyl-
2-mercaptopyrimidine and 10 mg (0.02 mmol)
of tetraphenyl imidodiphosphate and 25 ml of
A mixture boiling under reflux consisting of
to 1.0 ml (4.8 mmol) of hexamethyldisil
Zan was added. Following the method described in Example 19,
A calculated amount of ammonia is generated after 1.5 hours of boiling.
I found out that This mixture was evaporated to dryness and the remaining
The distillate was dried to yield 1.08 g (102%) of 4,6-dimethane.
Thyl-2-(trimethylsilylthio)pyrimidine
I got it. ¹HNMR (CCl_Four): 0.43 (s, 9H); 2.32 (s,
6H); 6.63 (s, 1H). Example 24 2-methylamino-5-trimethylsilylthio
-Production of 1,3,4-thiadiazole 298 mg (2.03 mmol) in 10 ml ethyl acetate
2-methylamino-5-mercapto-1,3,
4-thiadiazole and 2 mg (0.004 mmol)
containing tetraphenyl imidodiphosphate under reflux.
0.42 ml (2.0 mmol) of
Hexamethyldisilazane was added. Example 19
After boiling for 0.5 hours, add ammonia according to the method described above.
It was found that the outbreak ended. At that point 1
Millimoles of ammonia were collected. 0.5 more
After continuing boiling for an hour, remove the solvent and other volatiles.
The substance was removed in a rotary film evaporator to reduce the melting point to 80−
2-methylamino-5-trimethylsilyl at 82℃
Thio-1,3,4-thiadiazole 434 mg (97%)
I got it. ¹HNMR (CCl_Four): 0.60 (s, 9H); 2.90 (d, 3H,
J5.5Hz); 5.85 (q, 1H, J5.5Hz). Example 25 Trimethyl(4-bromophenylthio)silane
Manufacturing of 25 mg (0.05 mm) according to the method described in Example 21.
mol) of di-4-nitrophenyl N-(4-tolu
Ensulfonyl) phosphoramidate as a catalyst
10.82 g (57.2 mmol) of 4-bromo
8.9 ml (42.6 mmol) of thiophenol
It was silylated with samethyldisilazane. Reflux for 15 minutes
After boiling to the bottom, a calculated amount of ammonia is collected.
It was. Boiling point 87-88℃/0.8mm by vacuum fractional distillation
Hg,n^{twenty five} _D1.5652 trimethyl (4-bromophenyl)
Lucio) silane was obtained. Example 26 Trimethyl (3,4-dichlorophenylthio)
Manufacture of silane 22 mg (0.045 mg) according to the method described in Example 21.
Tetraphenyl imidodiphosphate (Limol) as a catalyst
8.45 mg (47.2 mmol) of 3,4-di
7.40 ml (35.4 mmol) of chlorothiophenol
silylated with hexamethyldisilazane. 35 minutes
A calculated amount of ammonia was generated within vacuum fractional distillation
The boiling point is 96-97℃/0.8mmHg, n^{twenty five} _D1.5600 to
Limethyl(3,4-dichlorophenylthio)sila
I got this. Example 27 5-trimethylsilylthio-1H-tetrazoly
Production of trimethylsilyl-1-acetate 318 mg (2.0 mmol) of 5-mercapto-1H
-tetrazolyl-1-acetic acid and 5.5 mg (0.03 mmol)
25 ml of toluene and 25 ml of toluene.
Add hexamethyldi to the mixture boiling under reflux.
Silazane (0.6 ml; 2.9 mmol) was added. 2
After boiling for an hour, ammonia evolution ceased. the
At that point 2 mmol of ammonia had been collected. Mixed
The mixture was evaporated to dryness under reduced pressure and 5-trimethylsilyl
ruthio-1H-tetrazolyl-1-acetic acid trimethy
0.60 g (100%) of Lucilyl was obtained as a viscous oil. ¹HNMR (CCl_Four): 0.29 (s, 9H); 0.65 (s,
9H); 4.87 (s, 2H). Example 28 5-trimethylsilylthio-1,3,4-thia
Production of trimethylsilyl diazolyl-2-acetate 0.44 g (2.5 mmol) of 5-mercapto-1,
3,4-thiadiazolyl-2-acetic acid and 5.0mg
(0.025 mmol) of Satucalin and 30 ml of dichloro
A mixture boiling under reflux consisting of methane
0.9 ml (4.3 mmol) of hexamethyldisilate
Zan was added. After boiling for 1.5 hours, the amount of calculation
Mmmonia (2.5 mmol) was generated. Then this
The mixture was evaporated to dryness and the residue was dried under reduced pressure.
5-trimethylsilylthio- with a melting point of 45-49°C
1,3,4-thiadiazolyl-2-acetic acid trimethy
0.80 g (100%) of Lucilyl was obtained. ¹HNMR (CCl_Four): 0.33 (s, 9H); 0.60 (s,
9H); 3.73 (s, 2H). Example 29 Production of trimethylsilyl benzoate A 12.2 g (0.1 mol) in 30 ml dichloromethane
of benzoic acid and 90 mg (0.5 mmol) of Satsukari
Hexamethyl is added to a refluxing solution containing
disilazane (15.6 ml; 0.075 mol) for 5 minutes.
Added. By titration of the ammonia generated,
40 minutes after starting the addition of hexamethyldisilazane
It is found that a large amount of ammonia is generated in
Ta. The solvent was distilled off at normal pressure, and the residue was vacuum distilled.
boiling point 102-104℃/13mmHg, n^{twenty five} _D1.4837 low
Trimethylsilyl zoate 17.80g (91.7%)
Obtained. In a catalyst-free implementation, the calculated amount of ammonia is
Reflux must be continued for 2.25 hours to generate
It was impossible. In both cases, hexamethylene
Although a thick precipitate formed after the addition of rudisilazane,
This precipitate disappeared as the silylation proceeded. B. 117 mg (0.5 mmol) instead of Satucalin
Satucalin Sodium 2H₂above using O
The experiment was repeated. After refluxing for 40 minutes, the amount of calculation
Monia occurred. Fractional distillation boiling point 56-57℃/0.5
mmHg, n^{twenty five} _D1.4843 trimethylsilyl benzoate
18.85g (97.2%) was obtained. Example 30 Production of trimethylsilyl trichloroacetate 34 mg (0.18 mmol) of satsucalin and 31.3 ml
(150 mmol) of hexamethyldisilazane
The mixture is placed in a chamber while a stream of dry nitrogen is passed over the mixture.
30 ml of 1,2-dichloroethane at room temperature within 10 minutes.
A drop of was added. A precipitate was thereby formed. Next
The mixture was boiled under reflux for 1.5 hours.
As a result, the two-layer system that originally existed disappeared.
The solution becomes homogeneous and the calculated amount of ammonia is collected.
It was done. Dichloroethane is then removed by atmospheric distillation.
This causes a small amount of solids to separate in the cooler.
Ta. The residue was vacuum distilled to a boiling point of 63-64℃/11mm.
Hg；n^{twenty five} _D1.4360 trichloroacetic acid trimethylsilicate
14.94 g (84.9%) of the product was obtained. Example 31 Trimethylene 2-trimethylsilyloxybenzoate
Manufacture of Luciril 13.80 g (0.10 mol) salicylic acid and 50 mg (0.1
mmol) of di-4-nitrophenyl N(4-t
Mixture with (ruenesulfonyl) phosphoramidate
Heat the substance to 130℃ and add 41.7ml (0.20mol) to it.
of hexamethyldisilazane was added dropwise over 5 minutes.
The ammonia evolved is passed onto the reaction mixture by a dry
A stream of dry nitrogen was introduced into the water. Titrate with 1N sulfuric acid
As a result, the calculated amount of ammonia is released within 45 minutes.
I found out that it will survive. By vacuum fractional distillation, the boiling point
104−105℃/1.5mmHg;n^{twenty five} _D1.4746 2-trimethy
Obtain trimethylsilyl lucilyloxybenzoate
Ta. Example 32 Production of ethyltrimethylsilyl malonate 22.9 g (0.173 mol) in 25 ml dichloromethane
of ethyl hydrogen malonate and 30 mg (0.17 mmol) of
A solution containing saccharine and boiling under reflux.
Add 20.8 ml of the solution to the solution while passing a stream of dry nitrogen over the solution.
(0.10 mol) of hexamethyldisilazane quickly
Added dropwise. A two-layer system is thereby obtained, which two
As the reaction progresses, the layer system gradually disappears and becomes uniform.
It became a solution. By titration of ammonia, ammonia
It was found that the generation of Nia was completed after 1.5 hours.
Ta. After continuing boiling for another 0.5 hours, the mixture
Fractional distillation under reduced pressure, boiling point 49.0-50.5℃/0.4mm
Hg；n²⁶ _D1.4135 Ethyltrimethylsilisil Malonate
34.1 g (96.6%) of the product was obtained. Example 33 5-Mercapto-1H-tetrazolyl-1-vinegar
Production of trimethylsilyl acid 0.30g in 25ml 1,2-dichloroethane
(1.86 mmol) of 5-mercapto-1H-tetra
6.0 mg (0.012 mmol) of ionic acid in zolyl-1-acetic acid
After adding tetraphenyl midodiphosphate, under reflux
0.5 ml (2.4 mmol) of hexane while boiling to
Methyldisilazane was added. Boil under reflux for 1 hour
After boiling, 1 equivalent of ammonia was evolved. Next
Next, the mixture was evaporated to dryness under reduced pressure and the residue was
When dried, 5-mercapto has a melting point of 130-133°C.
1H-tetrazolyl-1-trimethylsilyl acetate
0.45g (105%) was obtained. ¹HNMR (CDCl₃): 0.30 (s, 9H); 4.99 (s,
2H); 14.28 (s, 1H). Example 34 Production of N,N'-bis(trimethylsilyl)urea
Construction Dissolved in 15 ml of refluxing ethyl acetate.
2.4 g (40 mmol) of urea and 73 mg (0.4 mmol) of urea
hexamethyldisilazane to saccharin (mol)
(10 ml; 48 mmol) was added. Anmo immediately
Nia begins to develop and completes after 20 minutes of reflux.
This was determined by titration with 1NHCl. volatile matter
The substance was evaporated under vacuum and the residue was dried under vacuum.
N,N'-bis(trimethylsilyl) with melting point 219-222℃
8.06 g (99%) of urea was obtained. Without adding saccharin (as a catalyst)
In order for the generation of ammonia to be slow and complete,
The reaction must be carried out for at least 24 hours. Example 35 N-trimethylsilyl-trichloroacetamide
Manufacture of de 16.24g (0.10mol) trichloroacetamide
and 15 mg (0.08 mmol) of saccharin and 25 ml of
Toluene and 15 ml (0.07 mol) hexamethyldis
Mixture with lazan in a preheated oil bath (120 °C)
and reflux for 30 minutes, after which it will no longer be hot.
No generation of ammonia could be detected. Volatile under vacuum
After evaporation of the evolving substances, the residue was dried under vacuum at 50 °C.
It was dry. This crude N-trimethylsilyl-tric
Loroacetamide has a melting point of 75-85℃ and is
Clearly dissolved in ether. Yield: 22.58g
(96.3%) Example 36 Production of N-trimethylsilylbenzamide Satucalin (40mg; 0.22ml) in 15ml toluene
mol) and benzamide (5.0 g; 41.3 mmol)
and the resulting mixture was heated to reflux. F
xamethyldisilazane (6.4 ml; 31 mmol)
and the generated ammonia is passed onto the reaction mixture.
was introduced into the water with a stream of nitrogen. 1NH₂S.O._Fourby
Titration generates calculated amount of ammonia in 15 minutes
I found out what to do. Solvent and excess hexame
Tyldisilazane is evaporated under vacuum and has a melting point of 111−
N-trimethylsilylbenzamide at 114.5℃
A residue of 8.04 g (101%) was obtained. The above experiment was repeated without the addition of sacculin.
In this case, 82% of the theoretical amount occurs in 15 minutes,
88% occurred within 50 minutes. Example 37 N-trimethylsilyl-4-nitrobenzami
Manufacture of de A Satucalin (50
mg; 0.27 mmol)
lobenzamide (5.0 g; 30.1 mmol) at 20
Hexamethyl in ml of refluxing butyl acetate
Ludisilazane (4.7ml of 93% purity; 21ml)
mol). Theoretical amount of ammonia in 15 minutes
A has occurred. Evaporate volatile substances under vacuum
A light brown residue with a melting point of 130.5-134.5°C
Limethylsilyl-4-nitrobenzamide
(7.2g; 100%) was obtained. B 5.0 g (30.1 mmol) of 4-nitrobenz
amide and 100 mg (0.5 mmol) of 1,8-naf
talimide and 20 ml of butyl acetate under reflux.
Hexamethyldisilazane (4.5
ml; 22 mmol) was added. After refluxing for 35 minutes,
A theoretical amount of ammonia was generated. The same experiment as above was carried out without catalyst. In that case
After refluxing for 15 minutes, the ammonia content is only 16% of the theoretical amount.
only occurred. After refluxing for 1 hour, the theoretical amount of
Only 83% ammonia was generated. Example 38 N-trimethylsilyl-α,α-dimethylpro
Production of pionamide 5.0 g in 15 ml of toluene at reflux
(49.5 mmol) of α,α-dimethylpropion
Amide and 10mg (0.05mmol) of Satucalin
7.7 ml (37 mmol) of hexamethyldisilaza in
was added over 15 minutes. After refluxing for 45 minutes, ammonia
The outbreak has completely stopped. Evaporate to dryness in vacuum
N-trimethylsilyl with a melting point of 101-105.5°C
α,α-Dimethylpropionamide 8.04g (98
%) was obtained. According to NMR analysis, the purity of this product is 92%
It was hot. Example 39 Production of N-trimethylsilylacetamide 5.90 g (0.1 mol) of acetamide and 55 mg (0.3
(mmol) of saccharin was heated to 130°C.
Heat and add 15.6 ml (0.075 mol) of hexamethyldis
Lasan was added over 3 minutes. Those described in Example 1A
After starting the addition of hexamethyldisilazane according to the
Calculated amount of ammonia will be generated in 35 minutes from
I understood. Continue refluxing for 10 min and remove excess hexa
Evaporate methyldisilazane under reduced pressure to a solid residue
was vacuum dried. As a result, the purity was 95% by NMR analysis.
% or more of N-trimethylsilylacetamide
12.80g (97.7%) was obtained. Example 40 Production of N-trimethylsilyl urethane 8.9 g (0.1 mol) of urethane and 183 mg (1 mol) of urethane
mol) of saccharin and 10 ml of toluene.
Hexamethyldisilazane to the refluxing mixture
(15.6 ml; 0.075 mol) was added over 2 minutes. theory
of ammonia was generated in 30 minutes. Reflux for 15 minutes
Continue with solvent and excess hexamethyldisilazane
The chlorine was removed under reduced pressure and the residue was distilled under vacuum.
Point 73℃/12mmHg;n^{twenty five} _D1.4268 N-trimethylsilane
15.6 g (96.9%) of rillurethane was obtained. Example 41 N,N'-bis(trimethylsilyl)malona
Manufacture of Mido A: 3.06g (0.03mol) of malonic acid diamide and
18.3 mg (0.1 mmol) of satsucalin and 50 ml of
Reflux consisting of ethyl acetate and 5 ml of pyridine
Add 7.5 ml (36 mmol) of hexafluoride to the bubbling mixture.
Samethyldisilazane was added. The ann that occurred
By titrating Monia with 1N sulfuric acid,
After refluxing, 30 mmol of ammonia was removed.
I found out that Volatile substances are evaporated in vacuum
Vacuum dry the residue that crystallizes when left standing.
and N,N'-bis(trimethylene) with a melting point of 72-76℃.
Obtained 7.32 g (99%) of malondiamide
Ta. NMR spectrum (CDCl₃: δ0.24(s, 18H);
3.20 (s, 2H); 6.5 (broad, 2H) B Similar procedure using 30 ml of butyl acetate as solvent
In the experiment, we generated a calculated amount of ammonia.
This required 15 minutes of reflux. The melting point of the residue is 71−
At 80°C, the yield was 6.72g (91%). Example 42 Production of N-trimethylsilylcaprolactam 22.6g (0.2mol) caprolactam and 0.73g
(4 mmol) of saccharin and 40 ml (0.19 mole)
mixture with hexamethyldisilazane for 3.5 hours
After refluxing, ammonia generation can no longer be detected.
Kinakatsuta. The dark brown reaction mixture was distilled under vacuum.
N-trimethyl with a boiling point of 103-106℃/12mmHg
21.64 g (58.5%) of silyl caprolactam was obtained. Example 43 Production of trimethylsilylsacchulin 1.83g (10mmol) of saccharin and 10mg
(0.02 mmol) of di-4-nitrophenyl N-
(4-Toluenesulfonyl)phosphoramidate
and 20 ml of acetonitrile and boil under reflux.
Apply a stream of dry nitrogen over the mixture.
2 ml (9.6 mmol) of hexame while sending
Tildisilazane was added. Ammonia generated
was introduced into the water with a stream of nitrogen and titrated with 1N sulfuric acid.
The calculated amount of ammonia was generated within 0.5 hours.
Rotary film evaporation of solvents and other volatile substances
After evaporation in a vacuum chamber, the residue is dried in a vacuum.
Trimethylsilyl saccharide, dried, melting point 90-92℃
Obtained 2.50 g (98%). ¹HNMR (CCl_Four): 0.53 and 0.57 (two singlets,
Both 9H); 7.66-8.13 (m, 4H). ¹³CNMR (CDCl)₃, 20MHz, internal standard TMS):
1.2; −0.4; 1.8; 120.5; 121.4;
123.6; 124.8; 133.3; 133.8; 134.8. Example 44 N-trimethylsilylbenzenesulfonamide
Manufacturing of 15.72 g (0.1 mol) of base in 45 ml of ethyl acetate.
18 mg (0.1 mmol) of zenesulfonamide
Add to the refluxing suspension containing saccharin.
Add samethyldisilazane (15.6 ml; 75 mmol).
added. A stream of nitrogen is passed over the reaction mixture to emit it.
water to quantify the amount of ammonia produced.
Ta. 1NH₂S.O._FourBy titrating with
It was found that ammonia was generated in 25 minutes.
N residue obtained by evaporating volatile substances in vacuum
- Trimethylsilylbenzenesulfonamide is
The temperature was 62-63℃. Example 45 Production of N-methylsilylmethanesulfonamide 3.0 g (31.6 mmol) methanesulfonamide
and 20 mg (0.11 mmol) of saccharin and 15 ml of
Add hex to a refluxing mixture of toluene and
samethyldisilazane (5.1 ml; 24.5 mmol)
Added. generated by passing a stream of nitrogen over the reaction mixture.
removes ammonia and absorbs it into water,
1NH₂S.O._FourIt was titrated with refluxing for 20 minutes will reduce the calculated amount.
It was found that ammonia was generated. Solvent and
and excess hexamethyldisilazane by evaporation in vacuo.
The solid residue was dried under vacuum. Melting point 69−74.5
N-trimethylsilylmethanesulfonamide at °C
The yield was 5.22g (99.5%). The above experiment was repeated without adding saccalin. So
In the case of , the calculated amount of ammonia is generated in 35 minutes
did. N with a melting point of 68-72.5℃ treated as above
-Trimethylsilylmethanesulfonamide 5.25g
(100%) obtained. Example 46 Production of N-trimethylsilylthioacetamide 11.3 g (0.15 mol) of thioacetamide and 0.14
g (0.75 mmol) of saccharin and 50 ml of toluet
Hexamethylene is added to the refluxing mixture consisting of
Ludisilazane (17.2 ml; 82 mmol) in 10 minutes.
Added. The ammonia produced during the reaction is removed by dry nitrogen.
Passed through water in a neat stream and titrated with 1NHCl. Hexa
Calculated at reflux for 1.5 hours after addition of methyldisilazane
It was found that a large amount of ammonia was generated. Tor
ene and excess hexamethyldisilazane at normal pressure.
The residue was vacuum distilled to a boiling point of 97-99
N-trimethylsilylthioacetate at °C/0.7mmHg
13.12 g (59.2%) of amide was obtained. Example 47 N-trimethylsilyldiphenylphosphoramide
manufacture of dates 5.0 g in 35 ml of toluene at reflux
(20.1 mmol) of diphenylphosphoramide
and 36 mg (0.20 mmol) of saccharin.
Hexamethyldisilazane (3.2ml; 15.4mmol)
was added. A stream of nitrogen is sent over the reaction mixture to generate
Absorb the ammonia in water and make 1NH₂S.O._Fourin
titrated. The calculated amount of ammonia is generated in 15 minutes.
Ta. Continue refluxing for 10 min and evaporate the solvent in vacuo.
I set it. Obtained N-trimethylsilyldiphenyl
Phosphoramidate (6.69g) has a melting point of 83-86.5
There are ℃. The above experiment was repeated without the addition of sacculin.
After refluxing for 15 minutes, 26% of the calculated amount of ammonia was generated.
However, 69% was generated after 1 hour of reflux. Example 48 N,O,O-tris(trimethylsilyl)-DL
-Manufacture of serine 10.5 g (0.1 mol) DL− in 30 ml toluene
91 mg (0.5 mmol) of saline in a suspension containing serine.
Tucarin was added. Heat the mixture to reflux;
52.2 ml (0.25 mmol) hexamethyldisilaza
was added. A stream of nitrogen is passed over the reaction mixture and this
into the water to quantify the amount of ammonia that generated
got through. 1NH₂S.O._Four3 equivalents of ammonia by titration with
Near occurs in 3 hours (2 equivalent occurs after 1 hour)
I found out that this is true. toluene and excess
Evaporate the hexamethyldisilazane in vacuo and leave the remaining
Distillate the distillate under vacuum to obtain a boiling point of 87-89℃/05-06mm
Hg；N^{twenty five} _D1.4213 N,O,O-tris(trimethylene)
22.92g (76.2%) of DL-serine was obtained.
Ta. Example 49 d,l-α-trimethylsilylaminopropio
Production of trimethylsilyl phosphate 8.90 g (0.1 mol) of d,l-alanine and 50 mg
(0.1 mmol) of di-4-nitrophenyl N-4
- Mixture with toluenesulfonylphosphoramidate
Place the compound in a preheated (to 140 °C) oil bath at 41.6
Add ml (0.2 mol) of hexamethyldisilazane
did. After refluxing for 2 hours, the calculated amount (0.1 mol) of ammonium
Monia occurred. This means that the generated ammonia
A was introduced into the water, and 1NH₂S.O._Fourto titrate with
It turned out to be true. Vacuum distillation of the resulting colorless solution
and boiling point 78-81℃/18mmHg;n^{twenty five} _Dd of 1.4145,
l-α-trimethylsilylaminopropionic acid
20.72 g (88.9%) of remethylsilyl was obtained. Example 50 Production of N-trimethylsilylsuccinimide A: 50ml of toluene and 19.80g (0.20mol) of salt
The refluxing mixture consists of a mixture with succinimide.
Satucalin (458 mg; 2.5 mmol) in suspension
and hexamethyldisilazane (31.5ml; 0.15mol
and reflux was continued for 2 hours. Siri
15 minutes after adding the lubrication agent, a pale yellow clear solution appears.
is obtained, and this solution turns brown when it continues to reflux.
It changed to The reaction mixture was cooled, filtered and dissolved.
After evaporating the medium, the residue is vacuum distilled to a boiling point of 86
-88℃/1.3mmHg N-trimethylsilyl sulfate
31.04 g (90.8%) of cinimide was obtained. B 9.90 g (0.1 mol) in 50 ml dichloromethane
of succinimide and 0.24 g (0.5 mmol) of
Di-4-nitrophenyl N-4-toluenesul
under reflux containing Honylphosphoramidate
15.6 ml (0.075 mol) of hexame in a suspension
Tildisilazane was added dropwise over a few minutes. reaction mixture
Ammonia generated by a nitrogen stream sent over the material
Nia was introduced into the water. This generated ammonia
The progress of the reaction was checked by titration of a.
of ammonia after boiling under reflux for 1.5 h.
The generation was found to be complete. At this time, the theoretical quantity
90% ammonia was generated. Boil for another 2 hours
After continued boiling, the solvent was removed by atmospheric distillation.
Fractional distillation under reduced pressure, boiling point 118-119℃/18mm
Hg；n^{twenty five} _D1.4745 N-trimethylsilyl succinate
15.36 g (89.8%) of imide was obtained. Example 51 Production of N-trimethylsilyl phthalimide 36.8g (0.25mol) of phthalimide and 0.92g
(5 mmol) of saccharin and 75 ml (0.36 mole)
a mixture consisting of hexamethyldisilazane and
Place in an oil bath preheated to 120°C. Ammonium
Formation of A started immediately and a clear solution appeared after 30 minutes.
Obtained. This mixture was then refluxed for 60 minutes.
Ta. Evaporate volatile substances under vacuum and add 50 ml of petroleum
Add ether (boiling point 80-110℃) and convert the mixture to
Evaporated to dryness again. The almost colorless residue has a melting point
is 66-68℃, and N-trimethylphthalimide
It is in good agreement with the literature value. Nominal name for this compound
The structure was also confirmed by NMR spectra. The yield is
It was 54.89g (100%). Example 52 Production of N-trimethylsilylimidazole 13.62g (0.2mol) imidazole and 28mg
(0.15 mmol) of Satucalin was heated to 100℃,
Add 31.5 ml (0.15 mol) of hexamethyldisilate to this
Zan was added dropwise over 45 minutes. During this addition,
The bath temperature was increased from 100°C to 140°C. hexamethyldi
After adding the silazane, the mixture was kept at a bath temperature of 140°C for 30 minutes.
Stir and remove excess hexamethyldisilazane under reduced pressure.
The residue was vacuum distilled to a boiling point of 103−
105℃/22mmHg;n^23.5 _D1.4740 N-trimethyldi
22.25 g (79.5%) of limidazole was obtained. Example 53 1,3-bis(trimethylsilyl)-5,5-
Production of dimethylhydantoin 50ml toluene and 40mg (0.22mmol) satu
Quince and 38.45g (0.30mol) of 5,5-dimethy
A refluxing suspension consisting of ruhydantoin
Hexamethyldisilazane (80 ml; 0.38 mol) was added to
Added over 30 minutes. of ammonia immediately
The outbreak has begun. half of hexamethyldisilazane
All the solids dissolve in the solution when
Ta. After addition of hexamethyldisilazane, reflux was increased to 1
Continue for an hour, distill off the toluene, and store the residue at 45°C.
Vacuum dried, 1,3-bis(trifluoride) with a melting point of 46-49℃
methylsilyl)-5,5-dimethylhydantoin
79.0g (97%) was obtained. According to NMR analysis, this
The purity of the compound was 91%. Example 54 N-trimethylsilyl-2-oxazolidone
manufacturing Satucalin (10mg; 0.05ml) in 25ml toluene
moles) and 94% pure 2-oxazolidone (10.0
g; 108 mmol) and this mixture was
Heat to reflux. Hexamethyldisilazane (14.3
ml; 69 mmol) over 10 minutes and refluxed.
The flow was continued for 1 hour. After that time, ammonia
The outbreak has completely stopped. Evaporate the solvent in vacuo
The residue was vacuum distilled to a boiling point of 62℃/0.2mm.
Hg；n^{twenty three} _D1.4529 N-trimethylsilyl-2-o
14.6 g (85%) of xazolidone was obtained. Example 55 1-trimethylsilyl-1,2,4-triazo
Manufacture of rolls 10.35 g (0.15 mol) of 1,2,4-triazo
and 127 mg (0.75 mmol) of saccharin.
Heat a mixture of
23.4 ml (0.11 mol) of hexamethyldisilazane
Added. Ammonia production started immediately.
After refluxing for 30 minutes, it was measured as described in Example 1A.
A calculated amount of ammonia was generated. By vacuum distillation
boiling point 76.5-78.0℃/12mmHg;n^{twenty five} _D1 of 1.4592
-trimethylsilyl-1,2,4-triazole
19.37g (91.6%) was obtained. Example 56 Production of trimethylsilyl 6-aminopenicillanate
Construction A 1.08g (5.0ml) in 20ml dichloromethane
mol) of 6-aminopenicillanic acid and 20 mg (0.11
With reflux consisting of saccharin (mmol)
Hexamethyldisilazane (1.0
ml; 4.8 mmol) was added. Reflux for 0.5 hours
Afterwards, an almost clear solution was obtained. This is zicro
Lomethane-insoluble 6-aminopenicillanic acid is available.
Converted to soluble trimethylsilyl ester
and Without saccharin, the reaction time is
It was extended to 4 hours. B in 20 ml of refluxing dichloromethane
1.08 g (5.0 mmol) of 6-aminopenicilla
acid and 30 mg (0.11 mmol) of dimethyl N-t
Lichloroacetylphosphoramidate and Karana
Hexamethyldisilazane (1.0 ml;
4.8 mmol) was added. After refluxing for 40 minutes,
A bright solution was obtained, with dichloromethane insoluble 6-
Trimethylsilica in which aminopenicillanic acid is soluble
It was shown that it changed to a luester. C 1.08 g (5.0 mmol) of 6-aminopenicine
with lanic acid and 20 mg (0.11 mmol) of saccharin
15ml chloroform (without alcohol)
A suspension consisting of is heated to reflux, and this
Hexamethyldisilazane (0.75ml; 3.6mmol
) was added. After refluxing for 20 minutes, an almost clear solution appears.
A dichloromethane-insoluble 6-amino acid solution was obtained.
Nopenicillanic acid is soluble trimethylsilylene
It showed that it had changed to Stell. Satukarin
Without it, the reaction time was extended to 1.5 hours. D in 20 ml of refluxing dichloromethane
1.08 g (5.0 mmol) of 6-aminopenicilla
acid and 53 mg (0.11 mmol) of di-4-nitro
Phenyl N-trichloroacetylphosphoramide
Add 1.0 ml (4.8 mmol) of the suspension consisting of
Hexamethyldisilazane (1) was added. twenty five
After refluxing for a minute, a clear solution was obtained and dichloromethane
Solubility of tan-insoluble 6-aminopenicillanic acid
was changed to trimethylsilyl ester of
Indicated. Example 57 6-trimethylsilylaminopenicillanic acid tri
Production of methylsilyl 0.86 g (4 mmol) of 6-aminopenicillane
acid and 12 mg (0.07 mmol) saccharin and 2.5 ml
of chloroform and a refluxing suspension of
Hexamethyldisilazane (2.5 ml; 12 mmol)
was added. After refluxing for 20 minutes, a clear solution is obtained.
Ta. After refluxing for 2 hours, volatile substances were removed under vacuum at a bath temperature of 40°C.
evaporated under. Remove 4ml of the remaining colorless and transparent oil.
Dissolved in dry carbon tetrachloride. NMR spectrum of this solution
6-trimethylsilylaminopenicin from the spectrum
When trimethylsilyl lanate is present at 90% purity
I was able to conclude. Example 58 6-D-(-)-α-aminophenyl acetamide
Production of trimethylsilyl dopenicillanate 6-D-(-)-α-aminophenyl acetamide
Dopenicillanic acid (3.49 g; 10 mmol) in 35 ml
Satucalin (92 mg; suspended in dichloromethane;
0.5 mmol) was added. Heat the mixture to reflux.
Flow, 1.55 ml (7.4 mmol) hexamethyl
Disilazane was added. Clear and colorless after refluxing for 25 minutes
A dichloromethane-insoluble penicillium is obtained.
Trimethylsiliester with soluble lanic acid derivatives
It was shown that there was a change in Do not add saccharin
In a parallel experiment, a clear solution was obtained after refluxing for 50 min.
Ta. Example 59 6-(D-(-)-α-amino-p-trimethyl
Silyloxyphenylacetamide) Penicilla
Production of trimethylsilyl phosphate 0.73 g (2 mmol) in 15 ml dichloromethane
6-(D-(-)-α-amino-p-hydro
xyphenylacetamide) penicillanic acid and 5mg
(0.027 mmol) of saccharin.
0.7 ml (3.4 mmol) of hexamethane in one suspension.
Tildisilazane was added. obtained after refluxing for 20 minutes.
The resulting clear solution was refluxed for an additional hour. solvent
was evaporated under vacuum and the residue was dried under vacuum. solid
The body residue (1.15 g) was determined by NMR spectroscopy.
and the starting material O,O-bis(trimethylsilyl)
It was a derivative. In parallel experiments without the addition of saccharin, a clear solution
It took 2.5 hours of reflux to obtain a liquid. Example 60 6-trimethylsilylaminopenicillanic acid tri
Production of methylsilyl 1-oxide 1.0 mg in the same manner as described in Example 72.
(0.002 mmol) of tetraphenyl imidodiphosphate
465 in 20 ml of chloroform using as catalyst
mg (2.0 mmol) of 6-aminopenicillanic acid 1
- 1.6 ml (7.7 mmol) of hexamethylene oxide
It was silylated with rudisilazane. Amount of calculation in 1.5 hours
of ammonia was generated. boiled for 1.75 hours
Then, the mixture was evaporated to dryness in a rotary film evaporator.
After adding 10 ml of dry carbon tetrachloride, evaporate to dryness.
repeated. Dissolve the residue (0.81g) in carbon tetrachloride
did. ¹HNMR: 0.11 (s, 9H); 0.33 (s, 9H); 1.17 (s, 3H); 1.65 (s, 3H); 2.36 (d,
1H, J12.8Hz); 4.45 (s, 1H); 4.45, 4.76
and 4.72 (dd and s, 2H, J4.5Hz). Example 61 6-trimethylsilylaminopenicillanic acid tri
Production of methylsilyl 1,1-dioxide In the same manner, 1.0 mg (0.002 mmol) of di-4
-Nitrophenyl N-trichloroacetylphospho
6-aminopenidate using Ruamidate as a catalyst.
Silanoic acid 1,1-dioxide (containing 6% water by weight)
1.9 ml (9.1 mm) of chloroform in 20 ml of chloroform.
silylated with hexamethyldisilazane
did. Calculated amount (3.6 mmol) in 3.25 hours
Monia occurred. The solvent was then removed under reduced pressure.
Ta. of residue (0.76g)¹to HNMR spectrum
It was confirmed that complete disilylation was carried out.
It was. ¹HNMR (CCl_Four): 0.14 (s, 9H); 0.34 (s,
9H) ;1.33(s,3H);1.53(s,3H);227(d,
1H, J14Hz); 4.28 (s, 1H); 4.47 (d,
1H, J4.5Hz); 4.60 and 4.85 (dd, 1H,
J4.5 and 14Hz). Example 62 7-amino-3-methyl-3-cephem-4-
Production of trimethylsilyl carboxylate A 20 ml of chloroform (stabilized with ethanol)
1.07 g (5.0 mmol) in (analytical quality)
7-amino-3-methyl-3-cephem-4
- into a refluxing suspension containing a carboxylic acid;
Hexamethyldisilazane (1.25ml; 6mmol)
and satsucalin (20 mg; 0.11 mmol)
A gentle stream of dry nitrogen was then passed over the reaction mixture.
It helps eliminate ammonia produced by
It was kept anhydrous. After refluxing for 25 minutes, the color becomes yellowish and transparent.
A solution is obtained of chloroform-insoluble carvone
Acid changes to soluble trimethylsilyl ester
I showed that I did it. When no saccharin is added to the reaction mixture
The reaction time was extended to 3.5 hours. B. Using the method described in Example 62A, add 20 ml of dichloromethane.
Tan (alcohol-free) and 1.07g (5.0
mmol) of 7-amino-3-methyl-3-se
fem-4-carboxylic acid and 1.05 ml (5 mmol)
20mg (0.11ml) of hexamethyldisilazane
10 minutes
After refluxing for a while, a clear solution was obtained. The same experiment was performed using only 6.1 mg (0.03 mmol) of saline.
When using tucarin, a clear solution was obtained.
It takes 20 minutes of reflux for
The reaction time was 2.5 hours when conducted without
Ivy. C 1.07g (5.0ml) in 20ml dichloromethane
mol) of 7-amino-3-methyl-3-cephene
Refluxing suspension containing mu-4-carboxylic acid
20 mg (0.11 mmol) of saccharin in liquid and 0.75
ml (3.6 mmol) hexamethyldisilazane
was added. After refluxing for 30 minutes, a clear solution is obtained.
It was done. In a parallel experiment without saccharin, the clear solution
It took 3.5 hours to get it. D 1.50g (7.0ml) in 20ml dichloromethane
mol) of 7-amino-3-methyl-3-cephene
Refluxing suspension containing mu-4-carboxylic acid
Add trichloroacetamide (82mg; 0.5ml) to the solution.
mol) and hexamethyldisilazane (1.05 ml;
5.0 mmol) was added. After refluxing for 50 minutes,
A bright solution was obtained. If trichloroacetamide is not added,
The time required to obtain a clear solution was 210 minutes.
Ta. E 1.07 g (5 mmol) in 20 ml dichloromethane
7-amino-3-methyl-3-cepheme
Refluxing suspension containing -4-carboxylic acid
was added with sulfamide (10 mg; 0.1 mmol).
added. After 2 hours of reflux, a clear solution was obtained.
Ta. Without sulfamide, a clear solution is obtained.
It took 210 minutes. F 25ml dichloromethane and 1.07g (5 mmol)
7-amino-3-methyl-3-cepheme
-4-carboxylic acid and 26 mg (0.11 mmol) of
N,N'-bis(trimethylsilyl)sulfur
Hex to a refluxing mixture consisting of
Methyldisilazane (0.75ml; 3.6mmol)
Added. After refluxing for 2 hours, a clear solution was obtained.
Ta. N,N'-bis(trimethylsilyl)sulfur
When the same experiment was performed without adding amide,
It took 210 minutes of reflux to obtain a clear solution. G By the method described in Example 62F, N-benzoi
Rubenzenesulfonamide (41.4mg; 0.15ml)
mol) as a catalyst, the reaction takes 35 minutes
It took. H By the method described in Example 62F, N-(2-methane)
Toxy-1-naphthoyl)-4-toluenesul
Honamide (54.8 mg; 0.15 mmol) as catalyst
The reaction required 135 minutes when used as I N-(2-mer) by the method described in Example 62F
Toxy-1-naphthoyl) methanesulfonamide
(42.8 mg; 0.16 mmol) was used as a catalyst.
In this case, the reaction took 150 minutes. J 1.08 g (5.0 mmol) of 7-amino-3-
Methyl-3-cephem-4-carboxylic acid and 10mg
(0.05 mmol) of Satucalin and 20 ml of Dichlor
into a refluxing suspension consisting of
Hexamethyldisilazane (528 mg; 3.28 mmol)
was added. Clear solution obtained after refluxing for 1 hour
was evaporated to dryness and the residue was dried under vacuum at room temperature.
Ta. The residue (1.48g) was determined using the internal standard method.
It was analyzed by quantitative NMR analysis. Thus, Torimeti
7- calculated for the lucilyl ester peak
Amino-3-methyl-3-cephem-4-cal
The yield of trimethylsilyl bonate was 93%.
Ta. In the NMR spectrum, 3-methyl-7-t
Limethylsilylamino-3-cephem-4-ka
Only trace amounts of trimethylsilyl rubonate were detected.
I couldn't. Example 63 7-trimethylsilylamino-3-methyl-3
-trimethylsilyl cefem-4-carboxylate
Manufacturing of A 40ml of chloroform (for analyzes containing ethanol)
di-4-nitrophenyl N-4-to
Luenesulfonylphosphoramidate (12 mg;
0.024 mmol) and leave at reflux for 30 minutes.
The active hydrogen atom-containing impurities present were destroyed. child
The ammonia generated during the period is transferred onto the mixture.
Killed by sending a gentle stream of dry nitrogen
did. Next, 1.07 g (5.0 mmol) of 7-amino
Nor-3-methyl-3-cephem-4-carvone
Acid was added and reflux continued under the same conditions. However
However, this time, we investigated the problems caused by introducing a nitrogen flow into the water.
Ammonia was absorbed and titrated with 0.1N sulfuric acid. Ten
After refluxing for a minute (at that time, 25 ml of 0.1N sulfuric acid solution has disappeared).
), a clear solution is obtained, and 35 min
After refluxing, 50 ml of sulfuric acid solution is consumed and complete dilution is achieved.
It was found that it shows silylation. B 0.80 g (3.7 mmol) of 7-amino-3-
Methyl-3-cephem-4-carboxylic acid and 1.87
ml (11.6 mmol) hexamethyldisilazane
and 8.8 mg (0.048 mmol) of satsucalin and 20 ml
of chloroform is heated to reflux.
I let it flow. A clear solution was obtained after 10 minutes. 2
After refluxing for an hour, the volatiles were evaporated under vacuum.
(Bath temperature 50℃). Dissolve the solid residue in carbon tetrachloride
Ta. From the NMR spectrum of this solution, (N-
Trimethylsilyl signal and O-trimethylsilyl signal
(by comparing the ratio with GNAR) N, O
-Conclude that 80% of disilylated derivatives are present
I was able to do that. Example 64 3-Methyl-7-phenylacetamide-3-
Cefem-4-carboxylic acid trimethylsilyl 1
- Manufacture of oxides A: 1.4g (4 mmol) in 25ml dichloromethane
3-methyl-7-phenylacetamide
-3-cephem-4-carboxylic acid 1-oxide
Hexamethyl dichloride was added to the refluxing suspension containing
Silazane (1.25 ml; 6.0 mmol) was added.
Clear after 30 minutes of reflux indicating complete silylation
A solution was obtained. B 13 mg (0.04 mmol) of ditosylamine was added to the
The experiment was repeated with addition as a medium. 8 minute return
A clear solution was obtained after running. C 74.8 mg (0.66 mmol) of 2,2,2-tri
15 minutes using fluoroacetamide as catalyst
A clear solution was obtained after refluxing for a while. D 1.083 g (3.1 mmol) of 3-methyl-7-
Phenylacetamido-3-cephem-4-ka
Rubonic acid 1-oxide and 42 mg (0.15 mmol)
N-benzoyl-4-toluenesulfonamide
and 25 ml of dichloromethane.
Heat to reflux. hexamethyldisilazane
(0.57 ml; 2.73 mmol) and refluxed for 5 minutes.
After continuing the flow, a slightly brown clear solution is obtained.
Ta. Reflux for 45 min for parallel experiments without catalyst addition
Afterwards a clear solution was obtained. E 1.04 g (3.0 mmol) of 3-methyl-7-
Phenylacetamido-3-cephem-4-ka
Rubonic acid 1-oxide and 14.5 mg (0.3 mmol)
of formamide and 30 ml of dichloromethane.
Hexamethyldisulfide is added to the refluxing mixture.
Lasan (0.5 ml; 2.4 mmol) was added. 45
A clear solution was obtained after refluxing for a minute. In a parallel experiment performed without the addition of formamide.
requires 75 minutes of reflux to obtain a clear solution.
Ta. Example 65 7-phenylacetamido-3-methyl-3-
Cefem-4-carboxylic acid trimethylsilyl 1
-Production of α-oxide 0.17 g (0.5 mmol) of 7-phenylaceto
Amido-3-methyl-3-cephem-4-carbo
1-α-oxide and 0.88 mg (0.005 mmol)
of Satucalin and 0.065 ml (0.31 mmol) of Hex
samethyldisilazane and 5 ml of deuterochlorophos
Boil the mixture consisting of rum under reflux for 30 minutes
The title compound was prepared by:¹HNMR
According to the spectrum, the product is quantitatively produced.
Ta. ¹HNMR (CDCl₃): 0.33 (s, 9H); 2.18 (s,
3H); 3, 33 and 3.98 (ABq, 2H, J16.5
Hz); 3.58 (s, 2H); 4.47 (d, 1H, J4.5
Hz); 5.29 and 5.42 (dd, 1H, J4.5 and
8Hz); 7.13 (d, 1H, J8Hz); 7.29 (s,
5H). Example 66 7-formamide-3-methyl-3-cephem
-4-carboxylic acid trimethylsilyl 1-oxy
Manufacture of de 1.34 g (5.0 mmol) of 7-formamide
3-Methyl-3-cephem-4-carboxylic acid 1-
oxide (96%) and 5 mg (0.01 mmol) of imi
Tetraphenyl dodiphosphate and 50ml dichloromethane
0.62 ml to a refluxing, boiling suspension consisting of
(3.0 mmol) of hexamethyldisilazane added
did. The calculated amount of ammonia was generated in 80 minutes.
Evaporate volatiles under reduced pressure and dry under vacuum at room temperature.
After drying, 1.63 g (99%) of 7-formamide
3-Methyl-3-cephem-4-carboxylic acid tri
Methylsilyl 1-oxide as a pale yellow solid
Obtained. The characterization of the product is as follows.
I went there. 106 mg of 7-formamide-3
-Methyl-3-cephem-4-carboxylic acid 1-o
Xide, 0.5 mg of saccharin, and 3 ml of deutero
Chloroform and 0.05ml hexamethyldisilazane
The mixture was boiled under reflux for 1 hour.
of the solution thus obtained.¹to HNMR spectrum
Therefore, trimethylsilyl signal and 7-proton
Silylation can be quantitatively determined from the integral ratio between the signal and
I found out that it was progressing. ¹HNMR (CDCl₃): 0.32 (s, 9H); 2.16 (s,
3H); 3.23 and 3.68 (ABq, 2H, J18
Hz); 4.53 (d, 1H, J4.5Hz); 5.97 and
6.11 (dd, 1H, J4.5 and 9.8Hz); 7.20
(d, 1H, J9.8Hz); 8.31 (s, 1H). Example 67 7-phenylacetamido-3-(1-methyl
-1H-tetrazolyl-1-thio)methyl-3
-trimethylsilyl cefem-4-carboxylate
Production of 1-oxide 2 ml of juice in the same manner as described in Example 75.
-115 mg (0.25 mmol) in telochloroform
7-phenylacetamido-3-(1-methyl
-1H-tetrazolyl-5-thio)methyl-3-
Cefem-4-carboxylic acid 1-oxide,
Catalyzed 0.048mg (0.00026mmol) of Satucalin
used as 0.10 ml (0.48 mmol) of hexame
Silylation was performed with tildisilazane for 1.5 hours. ¹HNMR (CDCl₃); 0.33 (s, 9H); 3.54 (s,
2H); 3.25, 3.58, 3.88, 4.21 (ABq, 2H,
J19Hz); 383 (s, 3H); 4.06, 4.29, 4.43,
4.66 (ABq, 2H, J13Hz); 4.44 (d, 1H,
J4.5Hz); 5.99 (dd, 1H, J4.5 and 10
Hz); 6.82 (d, 1H, J10Hz); 7.27 (s,
5H). Example 68 7-phenylacetamide-3-(1H-1,
2,3-triazolyl-5-thio)methyl-3
-Cefem-4-carboxylic acid 1-oxide
(trimethylsilyl) conversion 130 mg in the same manner as described in Example 76
(0.29 mmol) of 7-phenylacetamide-
3-(1H-1,2,3-triazolyl-5-thi
e) Methyl-3-cephem-4-carboxylic acid 1-
1.0 mg (0.002 mmol) of oxide as a catalyst
di-4-nitrophenyl N-trichloroacetyl
In the presence of ruphosphoramidate, 0.10 ml
(0.48 mmol) with hexamethyldisilazane,
Boil under reflux in 2 ml deuterochloroform
By making that bis(trimethylsilyl)
transformed into a derivative. From the NMR spectrum, this
The product is trimethylsilyl in the triazole ring.
Is it a mixture of two isomers that differ in the position of the group?
I was able to conclude that. ¹HNMR (CDCl₃); 0.25 and 0.28 (2s, both
9H); 0.49 and 0.53 (2s, both 9H); approximately 3.2
−4.7 (m, 7H); 5.95 (dd, 1H, J4.5 and
6.82 and 6.98 (2d, both 1H, both
J9Hz); 7.28 (s, 5H); 7.65 and 7.85
(2s, 1H together). Example 69 3-acetoxymethyl-7-amino-3-ceph
Production of trimethylsilyl em-4-carboxylate 0.82 g (3.0 mmol) in 15 ml dichloromethane
3-acetoxymethyl-7-amino-3-
Refluxing containing cefem-4-carboxylic acid
Satucalin in the suspension Satucalin in the suspension (11 mg;
0.06 mmol) and hexamethyldisilazane
(0.63 ml; 3.0 mmol) was added. Dichloromethane
The insoluble carboxylic acid is replaced by the soluble trimethylsilane.
A clear solution indicating that it has changed to lyle ester is 10
Obtained after refluxing for minutes. The same experiment as above without the addition of saccharin was also carried out.
Ivy. In that case, 50 min to obtain a clear solution.
The reflux had to continue. Example 70 7-trimethylsilylamino-3-acetoxy
Methyl-3-cephem-4-carboxylic acid trime
Production of tilsilyl 1.08 g (4 mmol) of 3-acetoxymethyl
-7-amino-3-cefem-4-carboxylic acid and
15 mg (0.08 mmol) of saccharin and 25 ml of crocodile
into a refluxing suspension consisting of
Add samethyldisilazane (2.5 ml; 12 mmol).
added. The mixture became clear after 10 minutes, but at 2 o'clock
Refluxed for a while. Remove the solvent and filtrate under vacuum at a bath temperature of 40°C.
After evaporating the excess hexamethyldisilazane, a brown
A colored oily residue was obtained. Dry this with 4ml of carbon tetrachloride.
After dissolving in and filtering, it was subjected to NMR analysis. 7
-trimethylsilylamino-3-acetoxymethythyl
Trimethylsilyl-3-cephem-4-carboxylic acid
It was found that at least 80% of the rills were present. Example 71 7-trimethylsilylamino-3-(5-methyl
Ru-1,3,4-thiadiazolyl-2)-thio
Methyl-3-cephem-4-carboxylic acid trime
Production of tilsilyl 0.85 g (2.5 mmol) of 7-amino-3-(5
-Methyl-1,3,4-thiadiazolyl-2)-
Thiomethyl-3-cephem-4-carboxylic acid and 12
mg (0.07 mmol) of satsucalin and 25 ml of chloro
A mixture of form and
Hexamethyldisilazane (1.6 ml; 7.7 mmol)
) was added. A clear solution was obtained instantaneously.
After refluxing for 2 hours, volatiles were evaporated under reduced pressure and
Dissolve the clear, viscous residue in 4 ml of dry carbon tetrachloride.
I understand. From the NMR spectrum of this solution, 7-
trimethylsilylamino-3-(5-methyl-1,
3,4-thiadiazolyl-2)-thiomethyl-3
-Cefem-4 carboxylic acid trimethylsilyl is low.
We were able to conclude that at least 80% was generated. Example 72 7-trimethylsilylamino-3-(1-tri
Methylsilyl-1H-1,2,3-triazoli
Ru-5) Thiomethyl-3-cephem-4-cal
Production of trimethylsilyl boronate 1.65 ml (80 mmol) in 20 ml chloroform
Hexamethyldisilazane and 1.0mg (0.002ml
mol) of di-4-nitrophenyl N-(4-tolu
(en-sulfonyl) phosphoramidate is added.
Ta. Then this mixture no longer produces ammonia
It was refluxed until it stopped. This means that the reaction mixture
Ammonia is introduced into the water by a stream of dry nitrogen sent over the object.
Verified by titration with IN sulfuric acid.
It was. 2.6 mmol of ammonia generated in 1.5 hours
did. Next, add 0.632 g (2 mmol) to this mixture.
7-Amino-3-(1H-1,2,3-triazo
Ryl-5)thiomethyl-3-cephem-4-cal
Adding bonic acid and no longer ammonia under the same conditions
Boiling was continued until no more was liberated. 1.75 hours
3 mmol of ammonia was collected. under reduced pressure
After evaporating to dryness, add 5 ml of carbon tetrachloride and then
The evaporation to dryness was repeated. Dry the residue (1.13g)
Dissolved in dry carbon tetrachloride. ¹HNMR: 0.11 (s, 9H); 0.28 (s, 9H);
0.52 (s, 9H); 1.41 (d, 1H, J12H₂)；3.40o
and 3.80 (ABq, ZH, J18Hz); 3.75 and 4.29
(ABq, 2H, J13.5Hz); 4.49 and 4.75, 4.73
(dd and s, 2H, J4.8Hz); 7.57 (s, 1H). IR (CCl_Four): 3400, 1795, 1720, 1380, 1270,
865cm^-1 Example 73 7-trimethylsilylamino-3-(1-methyl
Ru-1H-tetrazolyl-5)thiomethyl-3
-trimethylsilyl cefem-4-carboxylate
Manufacturing of In the same manner as described in Example 72, 30 ml of clone
1.64 g (4.6 mmol) of 7-amino in loform
No-3-(1-methyl-1H-tetrazolyl-5)
Thiomethyl-3-cephem-4-carboxylic acid (including
amount 91%) and 5.0 mg (0.01 mmol) as catalyst
di-4-nitrophenyl N-trichloroacetyl
Using 3.0ml (14.4ml)
mol) of hexamethyldisilazane for 2 hours.
It was made into a rill. The mixture is evaporated in a rotary film evaporator.
After being concentrated into a foam, it was vacuum dried to give 2.21g.
(103%) of the title compound was obtained. ¹HNMR (CCl_Four): 0.11 (s, 9H); 0.34 (s,
9H); 1.43 (d, 1H, J12Hz); 3.66 (s,
2H); 3.90 (s, 3H); 4.14 and 4.51
(ABq, 2H, J13.5Hz); 4.58, 4.83 and
4.82 (dd and s, 2H, J4.5Hz). Example 74 7-D-(0-trimethylsilyl)mandelua
Mido-3-(1-methyl-1H-tetrazolyl-
5) Thiomethyl-3-cephem-4-carvone
Production of trimethylsilyl acid 3.23 g (6.3 mmol) of 7-D-(-)mande
Ruamido-3-(1-methyl-1H-tetrazolyl
-5) Thiomethyl-3-cephem-4-carvone
Acid [90%; cefamandole]
and 10.0 mg (0.02 mmol) of di-4-nitrophe
Nyl N-(4-toluenesulfonyl)phosphor
midate and 1.90 ml (9.1 mmol) hexamethylene
consisting of ludisilazane and 30 ml of dichloromethane.
The suspension was boiled under reflux. onto the reaction mixture.
The generated ammonia is released into the water using a stream of dry nitrogen.
Introduced. IN 0.5 h by titration with sulfuric acid
The generation of ammonia is completed after boiling for a while.
I understand. This consumes 65 ml of IN sulfuric acid.
It was. The solid remaining after evaporation to dryness under reduced pressure was
A mixture of ml petroleum ether and 5 ml ethyl acetate
Washing with water gave 3.1 g (81%) of the title compound.
the ¹HNMR spectra are known from the literature
It was consistent with what was said. Example 75 7-phenylacetamido-3-(1-methyl
-1H-tetrazolyl-5-thio)methyl-3
-trimethylsilyl cefem-4-carboxylate
Manufacturing of 0.048mg (0.00026ml) in 1ml of dichloromethane
25 ml of saccharin solution containing mol) of saccharin
into a round bottom flask and then evaporate the solvent under reduced pressure.
I let it happen. Next, add 113mg (0.25mg) into this flask.
7-phenylacetamide-3-(1
-Methyl-1H-tetrazolyl-5-thio)methy
Weigh out Le-3-cephem-4-carboxylic acid,
Then 2 ml of deuterochloroform and 0.05
ml (0.25 mmol) of hexamethyldisilazane
Added. Pass a gentle stream of dry nitrogen through the mixture.
The mixture was stirred at room temperature while stirring. Almost transparent after 10 minutes
A solution was obtained. After stirring for 1 hour, a clear solution
Record an NMR spectrum and from this spectrum
It was found that silylation progressed quantitatively. ¹HNMR (CDCl₃): 0.31 (s, 9H); 3.58 (s,
2H); 3.64 (s, 2H); 3.86 (s, 3H); 4.33
(s, 2H); 4.88 (d, 1H, J4.5Hz); 5.78
(dd, 1H, J4.5 and 9Hz); 6.22 (d,
1H, J9Hz); 7.27 (s, 5H). Example 76 7-Phenylacetamide-3-(1-trimethane)
Tyrsilyl-1H-1,2,3-triazolyl
-5-thio)methyl-3-cephem-4-cal
Production of trimethylsilyl boronate 0.25 mg (0.0005 mmol) di-4-nitroph
enyl N-trichloroacetylphosphoramide
2 ml of the solution containing
Evaporated to dryness under vacuum. Then 103 in this flask
mg (0.25 mmol) of 7-phenylacetamide
-3-(1H-1,2,3-triazolyl-5-thi
e) Methyl-3-cephem-4-carboxylic acid was measured.
and add 2 ml of deuterochloroform.
Ta. Then, while boiling under reflux, 0.10ml
(0.48 mmol) of hexamethyldisilazane
added. Continue boiling for 45 minutes, then depressurize the mixture
Evaporation to dryness gave 144 mg of the title compound. ¹HNMR (CDCl₃): 0.28 (s, 9H); 0.53 (s,
9H); 3.23, 3.53, 3.64, 3.95 (ABq, 2H,
J18Hz); 3.61 (s, 2H); 3.68, 3.90, 4.15,
4.39 (ABq, 2H, J13Hz); 4.88 (d, 1H,
J4.5Hz); 5.78 (dd, 1H, J4.5 and 9
Hz); 6.53 (d, 1H, J9Hz); 7.33 (s,
5H); 7.66 (s, 1H). Example 77 3-Methyl-7-phenylacetamide-3-
Cefem-4-carboxylic acid trimethylsilyl 1
- Manufacture of oxides 142 mg (0.41 mmol) of 3-methyl-7-phenyl
enylacetamido-3-cephem-4-carbo
acid 1-oxide and 0.5 mg (0.003 mmol)
of Satucalin in 3 ml of deuterochloroform
suspended in. Internal standard for quantitative NMR analysis
9-methylanthracene (57 mg; 0.297
mmol) was added. hexamethyldisilazane
(0.05 ml; 0.24 mmol) and mix the mixture with 10
Reflux for minutes. The resulting pale yellow transparent solution was cooled to room temperature.
It was cooled to From the NMR spectrum of this solution,
3-methyl-7-phenylacetamide produced
-3-cephem-4-carboxylic acid trimethylsilicate
trimethylsilyl ester of 1-oxide
Methyl pipe of 9-methylanthracene added with
When calculated by comparing the integral ratio with
Ru-7-phenylacetamide-3-cephem-
4-carboxylic acid trimethylsilyl 1-oxide
The yield was 97%. Example 78 7-trimethylsilylamino-3-methyl-3
-trimethylsilyl cefem-4-carboxylate
Preparation of 1-β-oxide and 1-α-oxide
Construction A 122 mg (0.53 mmol) of 7-amino-3-
Methyl-3-cephem-4-carboxylic acid 1-β
-oxide and 0.5 mg (0.001 mmol) of di-4
-Nitrophenyl N-(4-toluenesulfony
) phosphoramidate and 2 ml dichloromethane
While stirring, add 0.2 ml to the suspension consisting of
(0.96 mmol) of hexamethyldisilazane
Added. While sending a stream of dry nitrogen over the mixture
After boiling for 6 minutes under reflux, a clear solution was obtained.
It was. After boiling for 40 minutes, pour the mixture into a rotary
It was evaporated to dryness using an illum evaporator. solid residue
Dry under vacuum at room temperature. 208 mg of 7-t
Limethylsilylamino-3-methyl-3-ceph
Trimethylsilyl 1-β em-4-carboxylate
-Oxide was obtained. ¹HNMR (CDCl₃): 0.14 (s, 9H); 0.36 (s,
9H); 1.99 (d, 1H, J14Hz); 2.16 (s,
3H); 3.19, 3.60 (Aq, 2H, J18Hz); 4.34
(d, 1H, J4.5Hz); 4.62, 4.86 (dd, 1H,
J4.5 and 14Hz). B In the same manner as above, 7-trimethylsilyla
Mino-3-methyl-3-cephem-4-carbo
Trimethylsilyl 1-α-oxide was obtained. ¹HNMR (CDCl₃): 0.17 (s, 9H); 0.34 (s,
9H); 1.54 (d, 1H, J13Hz); 2.13 (s,
3H); 3.37 and 3.97 (ABq, 2H, J17
Hz); 4.44 (d, 1H, H4.5Hz); 4.80 and
5.02 (dd, 1H, J4.5 and 13Hz). Example 79 1-trimethylsilyl-2-phenylhydrazi
manufacturing 90 to 10.8g (0.1mol) of phenylhydrazine
mg (0.5 mmol) of satsucalin was added to obtain
The mixture was heated to 130°C. hexamethyldi
Add silazane (15.6 ml; 0.075 mol) and reflux
continued for 2.5 hours. by the method described in Example 1A.
After 2 hours of reflux, the calculated amount of ammonia is generated.
I found out what happened. Vacuum distill the mixture and boil
Point 112-116℃/11mmHg; 2_D ^{twenty five}1-trimeter of 1.5241
Tyrsilyl-2-phenylhydrazine 16.15g
(89.7%). Example 80 Production of N-trimethyloxysuccinimide 5.60 g (47.2 mmol) N-Hydroxysc
Cinimide (97% purity) and 46 mg (0.25 mmol)
of saccharin was heated to 130°C and 7.8mg
(37.5 mmol) of hexamethyldisilazane
added. Immediately, intense ammonia production begins.
15 minutes after starting the addition of hexamethyldisilazane.
Ammonia generation has been completed. Cool the mixture;
Excess hexamethyldisilazane is distilled off under reduced pressure.
The residue was fractionally distilled to a boiling point of 109-110℃/0.4mm.
Hg, N-trimethylsilyloxane, melting point 55-57°C
7.70 g (87.2%) of cis-succinimide was obtained. Example 81 N-benzoyl-N,O-bis(trimethylsilyl)
Lili) and production of droxylamine 1.21 g (8.8 mmol) benzohydroxam
acid and 5 mg (0.01 mmol) di-4-nitrophe
Nyl N-(4-toluenesulfonyl)phosphor
Reflux consisting of midate and 10 ml dichloromethane
Add 4.2 ml (20.2 ml) to the mixture while it is boiling.
mol) of hexamethyldisilazane quickly added dropwise.
, thereby forming a precipitate. Reflux for 15 minutes
After boiling at the bottom, the generation of ammonia stops and the transparent
A bright solution was obtained. Volatile substances are evaporated under reduced pressure
2.35 g (95%) of N-
Benzoyl-N,O-bis(trimethylsilin)
Hydroxylamine was obtained. ¹HNMR (CCl_Four): 0.26 (s, 9H); 0.30 (s,
9H); 0.6-7.8 (m, 2H). Example 82 N-trimethylsilyloxy-4-toluene
Production of sulfonamide 0.94 g (5.0 mmol) N-hydroxy-4
- Toluenesulfonamide and 5 mg (0.01 mmol)
20 ml of tetraphenyl imidodiphosphate and
A boiling mixture under reflux consisting of
Add hexamethyldisilazane (1.0ml; 4.8ml) to the mixture.
mol) was added. 0.1N of generated ammonia
Annealing after boiling for 50 minutes by titration with sulfuric acid
It was found that the occurrence of monia stopped. at the time
2.5 mmol of ammonia was collected. reaction mixture
The mixture was evaporated to dryness to give N-trimethane with a melting point of 87-90°C.
Tyrsilyloxy-4-toluenesulfonamide
1.29g (100%) was obtained. ¹HNMR (CCl_Four): 0.17 (s, 9H); 2.43 (s,
3H); 7.20, 7.34, 7.69, 7.83 (q, 4H). Example 83 1-trimethylsilyloxycyclohexene-
Manufacture of 3-one 8.4 g (72 mmol) cyclohexanedione
-1,3- (96% purity) and 70 mg (0.38 mmol)
of Satucalin and 60 ml (288 mmol) of Hexa
Mixed with methyldisilazane. Preheat this mixture
The mixture was placed in an oil bath and brought to reflux. play during reaction
By titrating ammonia separated from
It was found that the amount of ammonia removed in 50 minutes.
Ta. Continue refluxing for an additional 10 min to remove excess hexane.
Evaporate the tildisilazane in vacuo and remove the residue under vacuum.
It was empty distilled. 1-t with boiling point 119-121℃/2.0mmHg
Limethylsilyloxycyclohexen-3-one
10.67g (80.5%) was obtained. Example 84 3-trimethylsilyloxy-2-butenoic acid ester
Chill manufacturing 9.75 g (75 mmol) of ethyl acetoacetate and 70
mg (0.38 mmol) of Satucalin
Heat the material to 130°C in an oil bath and add hexamethyldisulfide.
Add Lasan (60 ml; 288 mmol) and mix
was refluxed for 1.5 hours. excess hexamethyldis
The lasane was distilled off under reduced pressure and the residue was vacuum distilled.
3-trimethyl with a boiling point of 102-104℃/16mmHg
Ethyl silyloxy-2-butenoate 12.71g (84
%) was obtained. Example 85 Production of 1-trimethylsilyloxybutane 1 of the catalysts shown in the table below in 15 ml of dichloromethane
1.48 in 10 ml dichloromethane.
g (20.0 mmol) of butanol-1 solution
and heat the mixture to reflux to 2.50ml
(12.0 mmol) of hexamethyldisilazane
added. When half the amount of calculation amount of ammonia is generated
The distance (t) was measured. Further details are shown in the table below.
It is. 【table】 Luenesulfonamide
Example 86 N,N-dimethyl-N'-trimethylsilyls
Manufacture of Rufamide 2.48 g (20 mmol) N,N-dimethylsulfate
Fuamide and 9 mg (0.05 mmol) of saccharin
A refluxing mixture consisting of 30 ml of toluene
and hexamethyldisilazane (3 ml; 14.4 mmol)
) was added. After refluxing for 1 hour by the above method
It was found that a calculated amount of ammonia was generated in
Ivy. The volatiles are then evaporated under reduced pressure and the remaining
The distillate was dried at room temperature to give N,N-
Dimethyl-N'-trimethylsilylsulfamide
3.96g (101%) was obtained. Example 87 trimethylsilylthioacetate trimethylsilyl
manufacturing 1.20 g (13.0 mmol) in 10 ml of toluene
Mercaptoacetic acid and 18 mg (0.036 mmol) di-
4-Nitrophenyl N-(4-toluenesulfony
) Phosphoramidate. It's refluxing
Hexamethyldisilazane (4.0 ml; 19.2
mmol) was added. 25 minutes using the above method
After refluxing the calculated amount (13 mmol) of ammonia is
I found out that it was happening. Next, the rotary
After the volatile substances are evaporated in the lum evaporator, the residue
Keep under vacuum for 0.5 h to remove trimethylsilylthi
Obtained 2.87g (93.4%) of trimethylsilyl oleacetate.
Ta. ¹HNMR (CCl_Four): 0.28 (s, 9H); 0.32 (s,
9H); 3.01 (s, 2H).

Claims (1)

[Claims] 1 General formula: X-NH-Y [In the above general formula, (a) Formula] (In the above formula, R ₁ and R ₂ are the same or different, and each is an alkyl group optionally substituted with one or more halogen atoms, or one or more halogen atoms or alkyl or an aryl group which may be substituted with a group or an alkoxy group or a nitro group, or an alkoxy group, or an aryloxy group which may be substituted with a hydrogen atom, an alkyl group, or a nitro group, or an R ₃ R ₄ N group (the above ( _b ) X is ( _a ), Y represents a hydrogen atom or a trialkylsilyl group, or (c) X and Y form a cyclic system together with the nitrogen atom, -A-Z- B- (In the above formula, A represents a [formula] group, B represents a [formula] group or a -SO ₂ - group or a -S- group, a [formula] group or a [formula] group, and Z represents any The group also represents an alkylene group, an alkenylene group, or an arylene group which may be substituted with one or more halogen atoms or alkyl groups.] The catalyst represented by is present in the reaction mixture in an amount of 0.001 to 10 mol%. A method for trimethylsilylating an organic compound containing one or more active hydrogen atoms with hexamethyldisilazane, characterized in that the electron-withdrawing group has the following formula (), () () [In the above formula (), R ₅ represents an alkyl group optionally substituted with one or more halogen atoms, or an aryl group optionally substituted with one or more alkoxy groups or nitro groups], [In the above formula (), R ₆ represents a methyl group, or an aryl group optionally substituted with one or more halogen atoms or a methyl group, or
R ₇ R ₈ N- group, where R ₇ and R ₈ are the same or different and each represents a hydrogen atom or a trialkylsilyl group or an alkyl group], [In the above formula (), R ₉ and R ₁₀ are the same or different, and each represents an alkoxy group, or an aryloxy group optionally substituted with a halogen atom or a nitro group], Or, an electron-withdrawing group forming a cyclic system with a nitrogen atom has the following formula (), () [In the above formula (), Z represents an alkenylene group optionally substituted with one or more halogen atoms or an alkyl group, or an arylene group optionally substituted with one or more halogen atoms], [In the above formula (), x is 0 or 2, and Z
represents an alkylene group or an arylene group] The method according to claim 1. 3 The electron-withdrawing group has the following formula (), (), () [In the above formula (), R ₅ represents a dihalomethyl group, a trihalomethyl group, or a phenyl group or naphthyl group, each of which may be substituted with a methoxy group], [In the above formula (), R ₆ represents a methyl group, a phenyl group optionally substituted with a methyl group or a chlorine atom, an amino group, a dialkylamino group, or a trialkylsilylamino group], [In the above formula (), R ₉ and R ₁₀ represent a methoxy group, an ethoxy group, a propoxy group, or a phenyl group which may be substituted with a nitro group or a chlorine atom], or together with a nitrogen atom The electron-withdrawing group forming the cyclic system has the following formula (), () [In the above formula (), Z represents an ethenylene group, a phenylene group, or a naphthylene group, each of which is optionally substituted with perhalo], [In the above formula (), x is 0 or 2, and Z represents a phenylene group] The method according to claim 1, wherein x is 0 or 2, and Z represents a phenylene group. 4 The catalyst is an amide, a sulfonamide, a cyclic or chain imide, a cyclic or chain sulfonimide,
Sulfamide, disulfonamide, acylphosphoramidate, sulfonylphosphoramidate,
and imidodiphosphate esters,
A method according to claim 1. 5 The catalyst is trichloroacetamide, trifluoroacetamide, phthalimide, 3,4,5,
6-tetrachlorophthalimide, 3,4,5,6
-Tetrabromophthalimide, 1,8-naphthalimide, maleimide, barbituric acid, saccharin, N-benzoyl-4-toluenesulfonamide, N-(2-methoxybenzoyl)-4-toluenesulfonamide, N-(1-naphthoyl) )-4-
Toluenesulfonamide, N-benzoylbenzenesulfonamide, N-(2-methoxy-1-naphthoyl)-4-toluenesulfonamide, N-
(2-methoxy-1-naphthoyl)methanesulfonamide, di(4-toluenesulfonyl)amine, dimethyl N-(trichloroacetyl)phosphoramidate, di-4-nitrophenyl N-(trichloroacetyl)phosphoramidate, di -4
-Nitrophenyl N-(p-toluenesulfonyl)
Phosphoramidate, diisopropyl N-(dichloroacetyl)phosphoramidate, di-o-chlorophenyl N-(4-chlorophenylsulfonyl)phosphoramidate, tetraphenyl imidodiphosphate, sulfamide, N,N-dimethylsulfamide , N,N'-bis(trimethylsilyl)sulfamide, 1,2-benzisothiazole-3
(2H)-one and 4-benzoyloxy-1,
5. A method according to claim 4, selected from the group of 2-dihydro-1-oxo-phthalazines. 6. The patent in which the catalyst is selected from the group of saccharin, di-4-nitrophenyl N-(trichloroacetyl)phosphoramidate, di-4-nitrophenyl N-(4-toluenesulfonyl)phosphoramidate and tetraphenyl imidodiphosphate. The method according to claim 5. 7 General formula R-S-SiMe ₃ (in the general formula, R is a 5- or 6-membered heterocyclic group having one or more nitrogen or sulfur atoms as a hetero atom, and one or more alkyl groups, (a phenyl group, a heterocyclic group optionally substituted with a trimethylsilyl group, an alkylamino group, or a trimethylsilyloxycarbonylmethyl group bonded to a nitrogen atom constituting a ring) Claim No. The method described in Section 1. 8 The R group is a 1,3,4-thiadiazolyl group, a 1,2,3,4-tetrazolyl group, or a 1,
2,3-triazolyl group, 1,2,4-triazolyl group, imidazolyl group, or pyrimidyl group, each of which is a methyl group, phenyl group, methylamino group, or a trimethylsilyl group or trimethylsilyl group bonded to a nitrogen atom constituting a ring. The method according to claim 7, which may be substituted with an oxycarbonylmethyl group. 9 The compound is (5-methyl-1,3,4-thiadiazole-2-thio)-trimethylsilane, 1
-Methyl-5-trimethylsilylthio-1H-tetrazole, 1-trimethylsilyl-5-trimethylsilylthio-1H-1,2,3-triazole, 1-methyl-2-(trimethylsilylthio)
Imidazole, 1-trimethylsilyl-3-trimethylsilylthio-1H-1,2,4-triazole, 1-phenyl-5-trimethylsilylthio-1H-tetrazole, 4,6-dimethyl-2-
(trimethylsilylthio)pyrimidine, 2-methylamino-5-trimethylsilylthio-1,3,
Claim 7, which is selected from the group of 4-thiadiazole, 5-trimethylsilylthio-1H-tetrazolyl-1-trimethylsilyl acetate, and 5-trimethylsilylthio-1,3,4-thiadiazolyl-2-trimethylsilyl acetate. the method of. 10. The process of claim 1, wherein the catalyst is added in the form of a derivative thereof, which decomposes in the reaction mixture to yield the catalyst of claim 1. 11. The method according to claim 10, wherein the catalyst added is a silylated derivative.