JP3404714B2 - Thiouracil derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] [0001] The present invention relates to a radically polymerizable polymer.
The present invention relates to a thiouracil derivative having a saturated bond. This switch
The uracil derivative is used as a precious metal adhesive component on metals.
Medical, electronic materials, precision machinery and jewelry bonding gin
It can be used in many fields, especially in the dental field.
And useful. [0002] 2. Description of the Related Art Iron, nickel, chromium, cobalt, silver
As an adhesive for base metals such as aluminum, copper, titanium, etc.
Phthalic anhydride, phthalic, malonic,
Acrylic or methacrylic acid having various functional groups such as acid groups
Adhesives containing ril-based polymerizable monomers have been proposed and
ing. However, gold, platinum, palladium, silver, etc.
Adhesives with sufficient adhesion to precious metals have been developed
Not. Therefore, adhesion to precious metal
It is common to tin-plate or oxidize metal surfaces
Met. These methods are cumbersome and have sufficient adhesion
No precious metal adhesive or precious metal
Development of a surface treatment agent has been desired. In recent years, in response to the above demand, thiophosphoric acid groups (specifically,
Kaihei 1-138282), thiophosphoric acid chloride group (JP-A
Hei 5-117595) and triazinedithione derivatives (particularly
Adhesive weight having a functional group such as
Compatible monomers have been proposed. These adhesive polymerizable monomers
The surface treatment agent containing the body is applied to the precious metal surface in advance,
By curing the compatible resin, the contact with precious metals
It is possible to wear. [0004] However, the above table
Adhesive strength for precious metal bonding using surface treatment agent
Or water resistance and durability are still not enough,
Instable polymerizable monomers and poor storage stability of surface treatment agents
In addition, there are problems such as the adhesive strength being affected by the amount of application. So
Here, in the present invention, a sufficient initial
Has adhesive strength, adhesive durability, water resistance and storage stability
New compound as a metal surface treatment agent component with good
The purpose was to provide. [0005] [MEANS FOR SOLVING THE PROBLEMS]
As a result of intensive studies, radically polymerizable unsaturated bonds
Thiouracil derivative has storage stability and noble metal
Have an effect on adhesive strength, water resistance, durability, etc.
And completed the present invention. That is, the present invention provides the following general formula (1):
(2) [0007] Embedded imageIn the formula, R¹, R^TwoIs a hydrogen atom or
Is an alkyl group;¹And R^TwoAt least one is hydrogen
An atom, R^ThreeIs a hydrogen atom, alkyl group or phenyl
R^FourIs a divalent saturated hydrocarbon having 2 to 12 carbon atoms
Element group, or the following general formula (3), (4) or (5) [0009] Embedded image Wherein n is an integer of 1 to 5, and o and
p is an integer of 1 to 10, and q is an integer of 1 to 5
And r and s are each an integer of 1 to 5
You. And Z is -COO.
-Group, -CH_TwoO-group or -C₆H_Four-CH_TwoO-group
R^FiveIs a hydrogen atom or a methyl group. Indicated by｝
Thiouracil Derivatives Having a Polymerizable Unsaturation Bond
You. In the above general formulas (1) and (2),
R¹, R^TwoRepresents a hydrogen atom or an alkyl group, respectively.
R¹And R^TwoAt least one is a hydrogen atom. Suitable a
Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, and a butyl group.
An alkyl group having 1 to 4 carbon atoms such as a tyl group is exemplified. Further, in the above general formulas (1) and (2),
And R^ThreeRepresents a hydrogen atom, an alkyl group or a phenyl group
Represent. R^ThreeIs an alkyl group, the alkyl group is methyl
Group, ethyl group, propyl group, butyl group, etc.
Is preferably an alkyl group. Further, the above general formulas (1) and (2)
Where R^FourIs a divalent saturated hydrocarbon having 2 to 12 carbon atoms
Or a group represented by the above general formula (3), (4) or (5)
Represents any group represented by R^FourIs divalent having 2 to 12 carbon atoms
In the case of a saturated hydrocarbon group, the saturated hydrocarbon group has a branch.
You may. Specific examples of such groups include ethylene
Group, propylene group, isopropene group, hexylene group,
Examples include a silene group and a dodecylene group.
Those having an alkylene group having 5 to 10 elementary atoms have adhesive strength and synthesis
This is preferred in terms of ease of operation. Represented by the above general formula (3)
In the group, n is an integer from 1 to 5. The above general formula
In the group represented by (4), o and p are each 1 to
It is an integer of 10, and each is different in terms of adhesive strength and ease of synthesis.
It is preferably an integer of 3 to 6. Also, the general
In the group represented by the formula (4), q is an integer of 1 to 5.
And an integer of 1 to 3 in terms of adhesive strength and ease of synthesis.
Is preferred. Further, the group represented by the general formula (5)
Where r and s are each an integer of 1 to 5,
Are each an integer of 1 to 3 in terms of power and ease of synthesis.
Is preferred. In the above general formulas (1) and (2),
R^FiveRepresents a hydrogen atom or a methyl group. In the above general formulas (1) and (2),
Z represents a -COO- group, -CH_TwoO-group or -C₆H_Four−
CH_TwoRepresents an O- group. Among them, those which are -COO- groups
It is suitable in terms of polymerizability, ease of handling, and the like. Formulas (1) and (2)
Among the thiouracil derivatives, the above general formula (1) and
In (2), R¹And R^TwoIs a hydrogen atom or carbon, respectively
An alkyl group of Formulas 1 to 4 (provided that R¹, R^TwoAt least one of
Is a hydrogen atom. ) And R^ThreeIs hydrogen atom, carbon
An alkyl group or a phenyl group represented by the following formulas^FourBut charcoal
An alkylene group having a prime number of 5 to 10 or the general formula (3),
Any group represented by (4) or (5) (however,
In these formulas, n is an integer of 1 to 5, and o and p are each
Is an integer of 3 to 6, q is an integer of 1 to 3, r and
And s are integers of 1 to 3, respectively. ) And R^FiveBut
A hydrogen atom or a methyl group, and Z is a -COO- group
The thing is, in terms of adhesive strength, ease of synthesis and ease of handling
Particularly preferred. Specific examples of the thiouracil derivative of the present invention
It is as follows if shown. [0018] Embedded image [0019] Embedded image[0020] Embedded image[0021] Embedded image[0022] Embedded image[0023] Embedded image[0024] Embedded image[0025] Embedded imageThe compounds represented by the general formulas (1) and (2)
The method for producing the thiouracil derivative is particularly limited.
However, any method may be adopted. Industrially suitable
The following is a specific example of such a method. First, the thiourasi represented by the general formula (1)
The method for producing the derivative will be described. That is, the following general formula
(6) [0028] Embedded image Where R¹, R^TwoIs a hydrogen atom or
Is an alkyl group;¹And R^TwoAt least one is hydrogen
Is an atom. ) And a thiourea derivative represented by the following general formula:
Equation (7) [0030] Embedded image Where R^ThreeRepresents a hydrogen atom, an alkyl group or
Is a phenyl group. )
After the reaction, the following general formula (8) [0032] Embedded image Ｒ where R¹, R^TwoAnd R^ThreeIs the above general formula
It is the same as the definition in (6) and (7). Indicated by｝
Carboethoxythiouracil derivative, followed by
By the deesterification reaction, the following general formula (9) [0034] Embedded image In the formula, R¹, R^TwoAnd R^ThreeIs the above general formula
It is the same as the definition in (6) and (7). Indicated by｝
After obtaining the carboxythiouracil derivative,
The general formula (10) [0036] Embedded image In the formula, R^FourIs a divalent saturated compound having 2 to 12 carbon atoms.
Japanese hydrocarbon group, or the following general formulas (3), (4) or
(5) [0038] Embedded imageWherein n is an integer of 1 to 5, and o and
p is an integer of 1 to 10, and q is an integer of 1 to 5
And r and s are each an integer of 1 to 5
You. ), Wherein Z is -COO-
Group, -CH_TwoO-group or -C₆H_Four-CH_TwoO-group
R^FiveIs a hydrogen atom or a methyl group. Indicated by｝
Alcohol having a polymerizable unsaturated bond
Has a polymerizable unsaturated bond of the general formula (1)
Thiouracil derivative is obtained. The thiourea derivative represented by the general formula (6)
Any known materials can be used without limitation. For example,
Urea, methylthiourea, ethylthiourea, propylthio
Orea, butylthiourea and the like are preferably used. Malonic acid derivative represented by the above general formula (7)
Is due to the reaction between diethyl malonate and triethyl orthoate.
Synthesized. As triethyl orthoate, orthoformic acid
Triethyl, triethyl orthoacetate, orthopropion
And triethyl orthobenzoate.
You. More specifically, it is represented by the general formula (7).
Malonic acid derivative is composed of 1 mole of diethyl malonate and
2 to 3 moles of um ethoxide are charged in the presence of a solvent,
The reaction is carried out by gradually dropping 1 mol of triethyl tomate
Is obtained by The polymerizable unsaturated compound represented by the general formula (10)
As the alcohol having a bond, Z is a group represented by -COO- group.
In case, esterification of (meth) acrylic acid and glycol
Reaction of (meth) acrylic acid chloride with glycol
Obtained by a sterilization reaction or the like. Z is -CH_TwoO-group
In such cases, the reaction between allyl chloride and glycol
Can be obtained. Z is -C₆H_Four-CH_TwoO-group
Is the reaction between 4-vinylbenzyl chloride and glycol
Obtained by equivalent. As the glycol, ethylene glycol,
Propylene glycol, pentamethylene glycol, f
Xamethylene glycol, octamethylene glycol,
Decamethylene glycol, dodecamethylene glycol,
Neopentyl glycol, 1,2-propanediol,
1,2-butanediol, 1,5-hexanediol,
Para-xylene glycol, diethylene glycol, 1,
3-bis (3-hydroxypropyl) -1,1,3,3
-Tetramethyldisiloxane, 1,3-bis (4-hydr
Roxybutyl) -1,1,3,3-tetramethyldisilo
An example is xan. More specifically, in general formula (10)
When Z is a —COO— group, the corresponding alcohol (1
0) is glycol (meth) acrylic acid per mole,
Charge 1 to 4 mol and 0.01 to 0.1 mol of acid catalyst
And obtained by reacting. As an acid catalyst, p
-Toluenesulfonic acid, benzenesulfonic acid, etc. are preferred
Commonly used. Alternatively, 1 to 4 moles of glycol and dehalo
1 mole of tertiary amine or molecular as hydrogenating agent
-Sheave 3A in the presence of solvent, and (meth) acrylic
1 mol of acid chloride is slowly added dropwise to carry out the esterification reaction.
It can also be obtained by doing Pyridine, tertiary amine
Liethylamine and the like are preferably used. In the general formula (10), Z is -CH
_TwoIn the case of an O-group, the corresponding alcohol (10) is
Dissolve 1 to 4 mol of coal and 1 to 1.2 mol of basic catalyst
Charge in the presence of a medium and slowly add 1 mol of allyl chloride
It is obtained by reacting it. As a basic catalyst
For example, sodium hydride or the like is preferably used. Further, in the general formula (10), Z is -C
₆H_Four-CH_TwoIn the case of an O-group, the corresponding alcohol (1
0) is 1 to 2 moles of glycol and 1 to 2 basic catalysts.
1.2 mol was charged in the presence of a solvent, and 4-vinylbenzyl was added.
The reaction is carried out by gradually dropping 1 mol of chloride.
Can be obtained. Sodium hydride etc. as basic catalyst
It is preferably used. In these cases, the product is a monosubstituted product
(10) and a di-substituted product are obtained. Distillation or column chromatography
The monosubstituted product (10) is separated and purified by chromatography.
Can be The thiourea derivative represented by the general formula (6)
In the condensation reaction with the malonic acid derivative of the formula (7),
Malo of the general formula (7) for the thiourea derivative of the formula (6)
The reaction molar ratio of the acid derivative is preferably 0.5 to 1.5 mol.
No. The reaction catalyst used at this time is a known one.
Can be used, such as sodium ethoxide
And the amount added is based on the thiourea derivative of the general formula (6).
The molar ratio is preferably 0.5 to 1.5 times. The solvent used in this reaction is ethanol.
And the like. Reaction temperature ranges from 40 to 80 ° C
And preferably in the range of 60 to 80 ° C.
It is an enclosure. Reaction time is not particularly limited and is generally
Can be selected from a range of about 1 to 10 hours.
It may be determined in relation to the degree. After the reaction, the precipitated salt is dissolved in water, and the acid is removed.
In addition, by making the solution acidic, it is represented by the general formula (8).
To give a carbethoxythiouracil derivative. However, the thiourea represented by the general formula (6)
And R¹, R^TwoWhen any of is an alkyl group, the general formula
The carboethoxythiouracil derivative (8) is an alkyl
As a mixture of isomers depending on the position of substitution on the N atom of the group.
Can be These are separated by column chromatography
It can be purified. The thiourea derivative of the general formula (6)
General formula obtained by reaction with a malonic acid derivative of formula (7)
De-esterification of the carboethoxythiouracil derivative of (8)
The deesterification agent used in the
Known ones can be used, but potassium tertiary butter
It is preferable to use a solution of oxide in dimethyl sulfoxide.
No. In addition, the amount of the deesterifying agent
The range of 6 to 20 moles per mole of the thiothiouracil derivative is
Although preferred, a range of 12 to 16 times is more preferred. The reaction temperature is selected from the range of room temperature to 80 ° C.
But preferably at room temperature to 40 ° C.
is there. The reaction time is not particularly limited, and is generally
The reaction temperature can be selected from the range of about 1 to 24 hours.
May be determined in relation to After the reaction, water was added to the reaction mixture to
By adding an acid to the solution to make the solution acidic, the general formula
A carboxythiouracil derivative represented by (9) is obtained.
It is. The carboxythiouracil of the above formula (9)
Having a polymerizable unsaturated bond represented by the general formula (10):
In the reaction with alcohol, the carboxylic acid represented by the general formula (9)
Polymerizability of general formula (10) for cythiouracil derivatives
The reaction molar ratio of the alcohol having an unsaturated bond is from 1 to 5.
The reaction can be performed in a range, but the range of 1-3 is more preferable.
preferable. The esterification reaction used at this time
P-toluenesulfonic acid, benzene
Sulfonic acid, N, N'-dicyclohexylcarbodiimid
And the like. The amount of these reaction catalysts added is
0.1 to 1 times the carboxythiouracil derivative
A molar range is preferred. The solvent used in this reaction is tetra
Hydrofuran, acetone, toluene and the like can be mentioned. Ma
Hydroquinone, hydroquinone monomethyl ether
And a small amount of a polymerization inhibitor such as butylhydroxytoluene.
It is also preferred to add. The reaction temperature is selected from the range of room temperature to 80 ° C.
But preferably at room temperature to 70 ° C.
is there. The reaction time is not particularly limited, and is generally
The reaction temperature can be selected from a range of about 1 to 50 hours.
It may be determined within the range in which the reactant does not polymerize. After the reaction, the precipitate was filtered and the solvent was distilled off under reduced pressure.
After removal, the concentrate is dissolved in an inert solvent such as ethyl acetate.
Separation and purification by passing through a silica gel column as a medium
This gives a highly pure product. Next, the thiourasi represented by the general formula (2)
The method for producing the derivative will be described. That is, the following general formula (6) [0066] Embedded image (Wherein R¹, R^TwoIs the same as above. )
And a thiourea derivative represented by the following general formula (11) [0068] Embedded image (Wherein R^ThreeRepresents a hydrogen atom, an alkyl group or
Is a phenyl group. )
And the following general formula (12) [0070] Embedded image(Where R¹, R^TwoAnd R^ThreeIs the above general formula
Is the same as the definition in )
Obtain the thiothiouracil derivative, followed by deesterification
By the following general formula (13) [0072] Embedded image (Wherein R¹, R^TwoAnd R^ThreeIs the above general formula
Is the same as the definition in Carboxy represented by)
After obtaining an uracil derivative, this is combined with the following general formula (10) [0074] Embedded image In the formula, R^FourIs a divalent saturated compound having 2 to 12 carbon atoms.
Japanese hydrocarbon group, or the following general formula (3), (4) or
(5) [0076] Embedded image (Where n is an integer of 1 to 5, and o and
p is an integer of 1 to 10, and q is an integer of 1 to 5
And r and s are each an integer of 1 to 5
You. And Z is -COO.
-Group, -CH_TwoO-group or -C₆H_Four-CH_TwoO-group
R^FiveIs a hydrogen atom or a methyl group. Indicated by｝
Reacting the alcohol with the general formula
(2) a thiouracil derivative having a polymerizable unsaturated bond
Is obtained. The thiourea derivative represented by the general formula (6)
As in the case of the production of the general formula (1).
Things are used without restriction. The succinic acid derivative represented by the above general formula (11)
Any known body can be used without limitation. For example, 2-O
Diethyl succinate, 2-methyl-2'-oxo succinate
Diethyl succinate, 2-ethyl-2'-oxosuccinic acid die
Butyl, diethyl 2-butyl-2'-oxosuccinate and the like.
It is preferably used. The polymerizable unsaturated compound represented by the general formula (10)
Examples of the alcohol having a bond include those represented by the above general formula (1)
The same one as in the case of manufacturing is used. The thiourea derivative of the general formula (6)
In the condensation reaction with the succinic acid derivative of the formula (11),
The thiourea derivative of the general formula (6)
The reaction molar ratio of the succinic acid derivative is preferably 0.5 to 1.5 mol.
Good. The reaction catalyst used at this time is a known one.
Can be used, such as sodium ethoxide
And the amount added is based on the thiourea derivative of the general formula (6).
Thus, the molar ratio is preferably 0.5 to 1.0 times. The solvent used in this reaction is ethanol.
And the like. Reaction temperature ranges from 40 to 80 ° C
And preferably in the range of 60 to 80 ° C.
It is an enclosure. Reaction time is not particularly limited and is generally
Can be selected from a range of about 1 to 10 hours.
It may be determined in relation to the degree. After the reaction, the precipitated salt is dissolved in water to remove the acid.
In addition, by making the solution acidic, the general formula (12)
The carboethoxythiouracil derivative shown is obtained
You. However, the thiourea represented by the general formula (6)
And R¹, R^TwoWhen any of is an alkyl group, the general formula
The carboethoxythiouracil derivative (12) is an alkyl
As a mixture of isomers depending on the substitution position on the N atom of the
can get. These are separated by column chromatography.
It can be purified. The thiourea derivative represented by the general formula (6)
General formula obtained by reaction with a succinic acid derivative of formula (11)
Removal of carboethoxythiouracil derivative of (12)
The tellurization reaction is carried out by a carbohydrate represented by the general formula (8).
It can be carried out in the same manner as in the case of the xythiouracil derivative.
You. The carboxythio represented by the general formula (13)
A uracil derivative and a polymerizable unsaturated bond of the general formula (10)
The reaction with an alcohol having a carboxylic acid represented by the general formula (9)
Xythiouracil derivative and polymerizability of the above general formula (10)
Perform the same procedure as for the reaction with alcohol having an unsaturated bond.
Can be. In the general formula (1) or (2) of the present invention,
Thiouracil derivatives with polymerizable unsaturated bonds shown
Glues resin with precious metals, such as dental precious metal alloys
It is preferably used as a component of an adhesive.
In this case, the above thiouracil derivative is dissolved in an organic solvent before use.
It is preferred to use Organic solvents that are preferably used include
As long as it can dissolve thiouracil derivatives,
Solvent or polymerizable monomer used without any restrictions
You. However, when the organic solvent is non-volatile,
Unless the concentration of the racil derivative is increased, the effect of the present invention is exhibited
It is difficult to use volatile organic solvents
It is suitable. The above-mentioned organic solvents that can be suitably used are specifically
For example, methanol, ethanol, isopropyl alcohol
Alcohols such as alcohol and butanol; acetone,
Ketones such as tyl ethyl ketone; ethyl ether;
Ethers such as 4-dioxane and tetrahydrofuran;
Esters such as ethyl acetate and ethyl formate; toluene,
Aromatic solvents such as silene and benzene; pentane, hexa
Hydrocarbon solvents such as benzene, heptane and octane;
Methylene chloride, chloroform, 1,2-dichloroethane
And other chlorinated solvents; trifluoroethanol and other fluorinated solvents
And the like. Among these, solubility and storage
For reasons such as stability, acetone, toluene, ethanol, etc.
Is particularly preferably used. Further, it is preferably used as an organic solvent in the present invention.
Possible polymerizable monomers, for example, show radical polymerizability
It is. Specific examples of polymerizable monomers that can be suitably used
If shown, methyl (meth) acrylate, ethyl (meth)
TA) Acrylate, isopropyl (meth) acrylate
G, butyl (meth) acrylate, hydroxyethyl
Highly polymerizable acrylic such as (meth) acrylate or
Examples include methacrylic polymerizable monomers and styrene.
You. The above-mentioned organic solvents may be used alone or in combination of two or more.
They can also be used together. [0092] The present invention is represented by the general formula (1) or (2) of the present invention.
The thiouracil derivative is a novel compound,
Ouracil derivatives have excellent adhesion to precious metals
It is useful as an adhesive component of a metal surface treatment agent. Sa
In addition, since it contains a polymerizable unsaturated bond and sulfur,
It can be used as an intermediate for products, dyes, etc. [0093] Next, the present invention will be described in more detail by way of examples.
Although described, the present invention is limited to such an embodiment.
There is no. Embodiment 1 Potassium tert-butoxide (43.7 g, 389
mmol) and dimethyl sulfoxide (400 ml).
Dissolve in a liter eggplant-shaped flask and add
Tyl 2-thiouracil-5-carboxylate (5.
0 g, 25.0 mmol) was slowly added dropwise and left for 1 hour.
The reaction was carried out at warm. After completion of the reaction, add methanol to the reaction mixture.
(500 ml) was added, and the deposited precipitate was filtered.
The obtained precipitate is dissolved in water, and hydrochloric acid is added to the aqueous solution.
, Light yellow solid 5-carboxy-2-thiouracil
(2.54 g) was obtained. 2-hydroxyethyl methacrylate
(3.90 g, 30 mmol), N, N'-dicyclohexane
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-2-thiouracil (1.72 g, 10
mmol) and tetrahydrofuran (50 ml).
Dissolve in a 00 ml three-necked flask and leave at room temperature for 3 days
Stirring was continued. A white precipitate forms as it reacts
After completion of the reaction, the white precipitate was filtered. The filter obtained
The tetrahydrofuran is distilled off from the liquid under reduced pressure, and the residue is
Added to gel column chromatography. Ethyl acetate
Using a mixed solvent of toluene and hexane as the developing solvent
The 2-methacryloyl oxy represented by the following formula 25
Ciethyl 2-thiouracil-5-carboxylate
[A] (0.91 g, 3.2 mmol) was obtained. NMR
(D6DMSO), MASS and elemental analysis results
Shown below. [0096] Embedded image[0097] NMR (δ, ppm); 1.88 (3H, −CH ₃ )                       4.36 (4H, -COO-CH ₂ CH ₂ -OCO-)                       5.68, 6.03 (2H,CH ₂ = C-)                       7.97 (1H, -N-CH= C-)                       12.6 (2H,-NH-) MASS (M + 1)⁺= 285 Elemental analysis; C₁₁H₁₂N_TwoO_FiveS                            CHN             Calculated value 46.47 4.25 9.85             Found 46.45 4.26 9.83 Example 2 Under a nitrogen atmosphere, 1,6-hexanediol (47.3)
g, 0.40 mol) and molecular sieve 3A powder (4
0 g) and acetonitrile (470 ml)
Methacrylic acid chloride in a 3 liter three-necked flask
(20.9 g, 0.2 mol) in acetonitrile
(30 ml) was slowly dropped at room temperature using a dropping funnel.
did. After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. Then room temperature
The mixture is allowed to cool down, and the molecular sieve 3A powder
Was filtered, and acetonitrile was distilled off from the filtrate under reduced pressure. Remaining
300 ml of methylene chloride was added to the
The solution was washed with water. Dry methylene chloride layer with anhydrous sodium sulfate
And the solvent was distilled off under reduced pressure. Silica gel from this residue
Colorless and transparent liquid by column chromatography
Xyhexyl methacrylate (33.3g) was separated and purified
did. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-2-thiouracil (1.72 g, 10
mmol) and tetrahydrofuran (50 ml).
Dissolve in a 00 ml three-necked flask and leave at room temperature for 3 days
Stirring was continued. A white precipitate forms as it reacts
After completion of the reaction, the white precipitate was filtered. Then the actual
By performing the same separation and purification treatment as in Example 1,
6-methacryloyloxyhexyl represented by Formula 26
  2-thiouracil-5-carboxylate [B]
(1.13 g, 3.3 mmol) were obtained. NMR (d6
DMSO), MASS and elemental analysis results are shown below.
You. [0099] Embedded image [0100] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       1.87 (3H,-CH ₃ )                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       7.94 (1H, -N-CH= C-)                       12.7 (2H,-NH-) MASS (M + 1)⁺= 341 Elemental analysis; C_FifteenH₂₀N_TwoO_FiveS                             CHN             Calculated value 52.93 5.92 8.23             Found 52.96 5.92 8.25 Example 3 Under a nitrogen atmosphere, 1,10-decanediol (34.9)
g, 0.20 mol) and molecular sieve 3A powder (2
0g) and tetrahydrofuran (350ml)
Chlorinated methacrylate into a 1-liter three-necked flask.
(10.5 g, 0.1 mol) in tetrahydrofuran
The solution (30 ml) is slowly added at room temperature using a dropping funnel.
It was dropped. After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. afterwards
Allow to cool to room temperature and remove molecular sieve 3A from the reaction mixture.
The powder is filtered, and tetrahydrofuran is distilled off from the filtrate under reduced pressure.
did. 300 ml of methylene chloride was added to the residue,
The methylene solution was washed with water. The methylene chloride layer is
After drying with thorium, the solvent was distilled off under reduced pressure. From this residue
Colorless transparent liquid 1 by silica gel column chromatography
0-hydroxydecyl methacrylate (14.5 g)
Separated and purified. 10-hydroxydecyl methacrylate
(7.27 g, 30 mmol), N, N'-dicyclohexane
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-2-thiouracil (1.72 g, 10
mmol) and tetrahydrofuran (50 ml).
Dissolve in a 00 ml three-necked flask and leave at room temperature for 3 days
Stirring was continued. A white precipitate forms as it reacts
After completion of the reaction, the white precipitate was filtered. Then the actual
By performing the same separation and purification treatment as in Example 1,
10-methacryloyloxydecyl represented by Formula 27
  2-thiouracil-5-carboxylate [C]
(1.15 g, 2.9 mmol) were obtained. NMR (d6
DMSO), MASS and elemental analysis results are shown below.
You. [0102] Embedded image [0103] NMR ([delta], ppm); 1.3-1.8 (16H, -COO-CH₂ (CH ₂ )
₈ CH₂-OCO-)                       1.87 (3H,-CH ₃ ),                       4.08, 4.13 (4H, -COO-CH ₂ (CH_Two)₈ CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-),                       7.93 (1H, -N-CH= C-),                       12.8 (2H,-NH-) MASS (M + 1)⁺= 397 Elemental analysis; C₁₉H₂₈N_TwoO_FiveS                              CHN            Calculated value 57.56 7.12 7.07            Obtained 57.51 7.14 7.08 Example 4 Under a nitrogen atmosphere, 1,6-hexanediol (47.3)
g, 0.40 mol) and molecular sieve 3A powder (4
0g) in acetonitrile solution (470 ml)
In a 3-liter three-necked flask, add acrylic acid chloride (1
8.1 g, 0.2 mol) in acetonitrile solution (30
ml) was slowly added dropwise at room temperature using a dropping funnel.
After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. After the reaction, Example 2
The same treatment as described above is performed, and then a colorless transparent liquid 6-hydroxy
Separated and purified sihexyl acrylate (28.9 g)
Was. 6-hydroxyhexyl acrylate
(5.17 g, 30.0 mmol), N, N'-dicine
Rohexylcarbodiimide (2.27 g, 11 mmol
1), 5-carboxy-2-thiouracil (1.72)
g, 10 mmol) and tetrahydrofuran (50 m
l) into a 200 ml three-necked flask to dissolve
For 3 days. As the reaction proceeds, a white precipitate forms
After completion of the reaction, the white precipitate was filtered. That
Thereafter, the same separation and purification treatment as in Example 1 is performed.
Thus, 6-acryloyloxyhe represented by the following formula 28:
Xyl 2-thiouracil-5-carboxylate
[D] (1.01 g, 3.1 mmol) was obtained. NMR
(D6DMSO), MASS and elemental analysis results
Shown below. [0105] Embedded image[0106] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.82, 6.12, 6.45 (3H,CH ₂ =CH-),                       7.93 (1H, -N-CH= C-),                       12.7 (2H,-NH-) MASS (M + 1)⁺= 327 Elemental analysis; C₁₄H₁₈N_TwoO_FiveS                              CHN            Calculated value 51.52 5.56 8.58            Obtained value 51.56 5.57 8.57 Example 5 Under a nitrogen atmosphere, 60% sodium hydride (1.92 g,
48 mmol) in tetrahydrofuran (20 ml)
Into a 300 ml three-necked flask containing
Tetrahi of sundiol (4.72 g, 40 mmol)
Room temperature of drofuran solution (30 ml) using dropping funnel
And slowly dripped. Followed by chloromethylstyrene
(6.1 g, 40 mmol) in tetrahydrofuran
(30 ml) was slowly added dropwise. 4 hours after dropping
Heated to reflux. Then, let it cool to room temperature.
The reaction was stopped by adding dilute hydrochloric acid. Extract the aqueous layer with ether
And the combined organic layers are saturated aqueous sodium bicarbonate,
Washed with saturated saline. Dry over anhydrous magnesium sulfate
And the solvent is distilled off under reduced pressure.
In the fee, 1-hydroxy-6- (p-vinylbenzyl
Xy) hexane (7.97 g was separated and purified). 1-hydroxy-6- (p-vinyl benzyl)
Ruoxy) hexane (7.03 g, 30 mmol),
N, N'-dicyclohexylcarbodiimide (2.27
g, 11 mmol), 5-carboxy-2-thiouracil
(1.72 g, 10 mmol) and tetrahydrofuran
Put the run (50ml) in a 200ml three-necked flask
Dissolve and continue stirring at room temperature for 3 days. White as it reacts
A color precipitate is formed.After the reaction is completed, the white precipitate is filtered.
I have. Thereafter, the same separation and purification treatment as in Example 1 is performed.
Thus, 6- (p-vinyl) represented by the following formula 29
Rubenzyloxy) hexyl 2-thiouracil-5
Carboxylate [E] (1.17 g, 3.0 mmol
1) was obtained. NMR (d6DMSO), MASS and
The results of the elemental analysis are shown below. [0108] Embedded image [0109] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH₂ (CH ₂ ) ₄
CH₂-OCH₂−)                       3.49, 4.1 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCH_Two-)                       4.53 (2H, -OCH ₂ -C₆H_Four)                       5.27, 5.84, 6.71 (3H,CH ₂ =CH-),                       7.3 to 7.4 (4H,C ₆ H ₄ )                       7.93 (1H, -N-CH= C-),                       12.7 (2H,-NH-) MASS (M + 1)⁺= 389 Elemental analysis; C₂₀H_{twenty four}N_TwoO_FourS                              CHN            Calculated value 61.84 6.23 7.21            Found 61.81 6.27 7.24 Example 6 2,2-dimethyl-1,3-propanegio under nitrogen atmosphere
(20.8g, 0.2mol) and molecular sieve
3A powder (20 g) and tetrahydrofuran (350
ml) into a 1-liter three-necked flask containing
Tetrayl acid chloride (10.5 g, 0.1 mol)
Hydrofuran solution (30 ml) was added to the chamber using a dropping funnel.
The solution was slowly dropped at a warm temperature. After the completion of dropping, reflux for 4 hours.
I let you. After the reaction, the same treatment as in Example 3 was performed, and
Roxy-2,2-dimethylpropyl methacrylate (1
3.1 g) was separated and purified. 3-hydroxy-2,2-dimethylpropyl
Methacrylate (5.18 g, 30 mmol), N,
N'-dicyclohexylcarbodiimide (2.27 g,
11 mmol), 5-carboxy-2-thiouracil
(1.72 g, 10 mmol) and tetrahydrofura
(50 ml) into a 200 ml three-necked flask
Dissolve and continue stirring at room temperature for 3 days. White as it reacts
A precipitate is formed. After the reaction is completed, the white precipitate is filtered.
did. Thereafter, the same separation and purification treatment as in Example 1 is performed.
By the formula, 3-methacryloy represented by the following formula 30
Luoxy-2,2-dimethylpropyl 2-thiourasi
Le-5-carboxylate [F] (0.91 g, 2.8
mmol). NMR (d6DMSO), MASS
And the results of elemental analysis are shown below. [0111] Embedded image [0112] NMR (δ, ppm); 0.91 (6H, -CH_TwoC(CH ₃ ) ₂ CH_Two-)                       1.87 (3H, CH_Two= C-CH ₃ ),                       4.1, 4.18 (4H, -COO-CH ₂ C (CH_Three)_Two CH ₂ -OCO-)                       5.66, 6.02 (2H,CH ₂ = C-),                       7.93 (1H, -N-CH= C-),                       12.8 (2H,-NH-) MASS (M + 1)⁺= 327 Elemental analysis; C₁₄H₁₈N_TwoO_FiveS                              CHN            Calculated value 51.52 5.56 8.58            Obtained 51.54 5.55 8.57 Example 7 1-methyl-1,5-pentanediol under nitrogen atmosphere
(47.3 g, 0.40 mol) and molecular sieve 3
A powder (40 g) in acetonitrile solution (470 ml)
Methacrylic acid in a 1 liter three-necked flask containing
Acetonitrile of chloride (20.9g, 0.2mol)
Solution (30 ml) slowly at room temperature using a dropping funnel
Dripped. After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. reaction
Thereafter, the same treatment as in Example 2 is performed, and then a colorless transparent liquid
5-hydroxy-5-methylpentyl methacrylate
(29.4 g) was separated and purified. 5-hydroxy-5-methylpentyl meta
Acrylate (5.59 g, 30 mmol), N, N'-
Dicyclohexylcarbodiimide (2.27 g, 11 m
mol), 5-carboxy-2-thiouracil (1.7
2 g, 10 mmol) and tetrahydrofuran (50
ml) in a 200 ml three-necked flask to dissolve
Stirring was continued at warm for 3 days. As it reacts, a white precipitate forms
Although formed, after the reaction was completed, the white precipitate was filtered. So
Thereafter, the same separation and purification treatment as in Example 1 is performed.
And 5-methacryloyloxy represented by the following formula 31:
-1-methylpentyl 2-thiouracil-5-carbo
Xylate [G] (0.71 g, 2.1 mmol) was obtained.
Was. NMR (d6DMSO), MASS and elemental analysis
The results are shown below. [0114] Embedded image[0115] NMR (δ, ppm); 1.24 (3H, -OCH (CH ₃ ) CH_Two-)                       1.3-1.7 (6H, -COO-CH(CH ₂ ) ₃ CH_Two-OCO-)                       1.87 (3H, CH_Two= C-CH ₃ ),                       4.69, 4.13 (3H, -COO-CH(CH_Two)_Three CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-),                       7.94 (1H, -N-CH= C-),                       12.7 (2H,-NH-) MASS (M + 1)⁺= 341 Elemental analysis; C_FifteenH₂₀N_TwoO_FiveS                              CHN            Calculated value 52.93 5.92 8.23            Obtained 52.91 5.95 8.25 Example 8 Under a nitrogen atmosphere, para-xylene glycol (55.2)
g, 0.40 mol) and molecular sieve 3A powder (4
0 g) and acetonitrile (470 ml)
Methacrylic acid chloride in a 3 liter three-necked flask
(20.9 g, 0.2 mol) in acetonitrile
(30 ml) was slowly dropped at room temperature using a dropping funnel.
did. After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. Then room temperature
The mixture is allowed to cool down, and the molecular sieve 3A powder
Was filtered, and acetonitrile was distilled off from the filtrate under reduced pressure. Remaining
300 ml of methylene chloride was added to the
The solution was washed with water. Dry methylene chloride layer with anhydrous sodium sulfate
And the solvent was distilled off under reduced pressure. Silica gel from this residue
4- (hydroxy)
Cimethyl) benzyl methacrylate (34.8 g)
Separated and purified. 4- (hydroxymethyl) benzylmethac
Relate (6.48 g, 30 mmol), N, N'-di
Cyclohexylcarbodiimide (2.27 g, 11 mm
ol), 5-carboxy-2-thiouracil (1.72).
g, 10 mmol) and tetrahydrofuran (50 m
l) into a 200 ml three-necked flask to dissolve
For 3 days. As the reaction proceeds, a white precipitate forms
After completion of the reaction, the white precipitate was filtered. That
Thereafter, the same separation and purification treatment as in Production Example 1 was performed.
Thus, 4- (methacryloyloxy) represented by the following formula 32:
Cimethyl) benzyl 2-thiouracil-5-carboxy
Silate [H] (0.91 g, 2.5 mmol) was obtained.
Was. NMR (d6DMSO), MASS and elemental analysis
The results are shown below. [0117] Embedded image [0118] NMR (δ, ppm); 1.90 (3H, −CH ₃ ),                       5.17, 5.23 (4H, -COO-CH ₂ -C₆H_Four-CH ₂ -OCO-)                       5.70, 6.07 (2H,CH ₂ = C-),                       7.40 (4H,-C ₆ H ₄ -),                       8.00 (1H, -N-CH= C-),                       12.8 (2H,-NH-) MASS (M + 1)⁺= 361 Elemental analysis; C₁₇H₁₆N_TwoO_FiveS                              CHN            Calculated value 56.66 4.47 7.77            Obtained 56.42 4.31 7.82 Example 9 Under a nitrogen atmosphere, diethylene glycol (42.4 g,
0.40 mol) and molecular sieve 3A powder (40
g) and acetonitrile (470 ml)
In a three-necked flask of turtle, methacrylic acid chloride (2
0.9 g (0.2 mol) of acetonitrile solution (30
ml) was slowly added dropwise at room temperature using a dropping funnel.
After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. Then release to room temperature
Cool and filter molecular sieve 3A powder from reaction mixture
Then, acetonitrile was distilled off from the filtrate under reduced pressure. Salt to residue
300 ml of methylene chloride is added and the methylene chloride solution is added.
Washed with water. Dry the methylene chloride layer with anhydrous sodium sulfate
Then, the solvent was distilled off under reduced pressure. Silica gel color from this residue
Liquid diethylene glycol by chromatography
Monomethacrylate (59.2 g) was separated and purified. Diethylene glycol monomethacrylate
(5.22 g, 30 mmol), N, N'-dicyclohexane
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-2-thiouracil (1.72 g, 10
mmol) and tetrahydrofuran (50 ml).
Dissolve in a 00 ml three-necked flask and leave at room temperature for 3 days
Stirring was continued. A white precipitate forms as it reacts
After completion of the reaction, the white precipitate was filtered. Then
By performing the same separation and purification treatment as in Example 1,
2- (2-methacryloyloxy) represented by Formula 33
Toxi) ethyl 2-thiouracil-5-carboxylate
[I] (1.05 g, 3.2 mmol) was obtained. NM
R (d6DMSO), MASS and elemental analysis results
It is shown below. [0120] Embedded image [0121] NMR (δ, ppm); 1.86 (3H, −CH ₃ ),                       3.70 (4H, -CH2CH ₂ -O-CH ₂ CH2-)                       4.21, 4.26 (2H, 2H,-CH ₂ CH_Two-O-CH_Two CH ₂ -)                       5.66, 6.01 (2H,CH ₂ = C-),                       7.95 (1H, -N-CH= C-),                       12.8 (2H,-NH-) MASS (M + 1)⁺= 329 Elemental analysis; C₁₃H₁₆N_TwoO₆S                              CHN            Calculated value 47.56 4.91 8.53            Obtained 47.37 4.84 8.41 Example 10 Under a nitrogen atmosphere, 1,3-bis (3-hydroxypropyl
) -1,1,3,3-tetramethyldisiloxane (1
00g, 0.40mol) and molecular sieve 3A powder
(40 g) and acetonitrile (470 ml)
Chlorinated methacrylate into a 1-liter three-necked flask.
(20.9 g, 0.2 mol) in acetonitrile
(30 ml) was slowly dropped at room temperature using a dropping funnel.
did. After the completion of the dropwise addition, the mixture was heated under reflux for 5 hours. Then room temperature
The mixture is allowed to cool down, and the molecular sieve 3A powder
Was filtered, and acetonitrile was distilled off from the filtrate under reduced pressure. Remaining
300 ml of methylene chloride was added to the
The solution was washed with water. Dry methylene chloride layer with anhydrous sodium sulfate
And the solvent was distilled off under reduced pressure. Silica gel from this residue
Colorless and transparent liquid 1- (3-
Methacryloyloxypropyl) -3- (3-hydroxy
(Cipropyl) -1,1,3,3-tetramethyldisiloxy
Sun (46.2 g) was separated and purified. 1- (3-methacryloyloxypropyl)
Ru) -3- (3-hydroxypropyl) -1,1,3,
3-tetramethyldisiloxane (9.54, 30 mmol
1), N, N'-dicyclohexylcarbodiimide
(2.27 g, 11 mmol), 5-carboxy-2-
Thiouracil (1.72 g, 10 mmol) and tet
Lahydrofuran (50ml) 200ml three-necked frus
Dissolved in a flask and continued stirring at room temperature for 3 days. React
As the reaction proceeds, a white precipitate is formed.
The precipitate was filtered. Then, the same separation and purification as in Production Example 1
By performing the processing, a compound represented by the following formula 34 is obtained.
The product [J] (1.13 g, 2.4 mmol) was obtained. NM
R (d6DMSO), MASS and elemental analysis results
It is shown below. [0123] Embedded image [0124] NMR (δ, ppm); 0.06 (12H, -Si-CH3),                       0.51 (4H, -Si-CH ₂ -CH_Two-CH_Two-OCO-),                       1.69 (4H, -Si-CH_Two-CH ₂ -CH_Two-OCO-),                       1.87 (3H,-CH ₃ ),                       4.23 (4H, -Si-CH_Two-CH_Two-CH ₂ -OCO-),                       5.67, 6.03 (2H,CH ₂ = C-),                       7.96 (1H, -N-CH= C-),                       12.8 (2H,-NH-) MASS (M + 1)⁺= 473 Elemental analysis; C₁₉H₃₂N_TwoO₆SSi_Two                              CHN            Calculated value 48.28 6.82 5.93            Obtained value 48.35 6.74 5.73 Example 11 Under a nitrogen atmosphere, sodium ethoxide (13.6 g,
0.20mol) ethanol solution (200ml)
Ethoxymethylene monomer in a 1 liter three-necked flask
Etano of diethyl lonate (43.2 g, 0.2 mol)
Solution (100 ml) at room temperature using a dropping funnel.
It dripped clearly. After the completion of the dropwise addition, the mixture was heated to reflux. Continue
Of methylthiourea (18.0 g, 0.2 mol)
Tunnel solution (100 ml) was slowly added using a dropping funnel.
It was dripped. After the completion of the dropwise addition, the mixture was heated under reflux for 3 hours. Room
Allowed to cool to room temperature and the reaction mixture was poured into water (500 ml)
Added to beaker. When concentrated hydrochloric acid was added to the resulting solution,
At this time, a pale yellow solid precipitated. The precipitated solid is filtered,
This is separated and purified by column chromatography.
From ethyl 3-methyl-2-thiouracil-5-ca
Ruboxylate (14.1 g) was obtained. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
Ethyl 3-methyl-2-thiouracil-5 was added to this solution.
-Carboxylate (5.35 g, 25.0 mmol)
Was slowly added dropwise and reacted for 1 hour at room temperature. End of reaction
Thereafter, methanol (500 ml) was added to the reaction mixture,
The deposited precipitate was filtered. Dissolve the resulting precipitate in water
Hydrochloric acid was added to the aqueous solution to give a light yellow solid 5-carbohydrate.
Xy-3-methyl-2-thiouracil (2.88 g)
Obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-3-methyl-2-thiouracil (1.
86 g, 10 mmol) and tetrahydrofuran (5
0 ml) in a 200 ml three-necked flask to dissolve,
Stirring was continued at room temperature for 3 days. White precipitate as it reacts
However, after completion of the reaction, the white precipitate was filtered.
Thereafter, the same separation and purification treatment as in Example 1 is performed.
Thus, 6-methacryloyl oxy represented by the following formula 35:
Cyhexyl 3-methyl-2-thiouracil-5-cal
Boxylate [K] (1.16 g, 3.28 mmol)
I got NMR (d6DMSO), MASS and elements
The results of the analysis are shown below. [0127] Embedded image [0128] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH₂ (CH ₂ ) ₄
CH₂-OCO-)                       1.87 (3H,-CH ₃ )                       3.78 (3H, N-CH_Three)                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       7.94 (1H, -N-CH= C-)                       12.4 (1H,-NH-) MASS (M + 1)⁺= 354 Elemental analysis; C₁₆H_{twenty two}N_TwoO_FiveS                             CHN             Calculated value 54.22 6.25 7.90             Obtained 54.20 6.23 7.93 Example 12 Ethyl 3-methyl-2-thioura obtained in Example 8
In the separation and purification of sil-5-carboxylate,
Certain ethyl 1-methyl-2-thiouracil-5-cal
Boxylate (15.3 g) was obtained. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
Ethyl 1-methyl-2-thiouracil-5 was added to this solution.
-Carboxylate (5.35 g, 25.0 mmol)
Was slowly added dropwise and reacted for 1 hour at room temperature. End of reaction
Thereafter, methanol (500 ml) was added to the reaction mixture,
The deposited precipitate was filtered. Dissolve the resulting precipitate in water
Hydrochloric acid was added to the aqueous solution to give a light yellow solid 5-carbohydrate.
Xy-1-methyl-2-thiouracil (2.65 g)
Obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-1-methyl-2-thiouracil (1.
86 g, 10 mmol) and tetrahydrofuran (5
0 ml) in a 200 ml three-necked flask to dissolve,
Stirring was continued at room temperature for 3 days. White precipitate as it reacts
However, after completion of the reaction, the white precipitate was filtered.
Thereafter, the same separation and purification treatment as in Example 1 is performed.
Thus, 6-methacryloyl oxy represented by the following formula 36:
Sihexyl 1-methyl-2-thiouracil-5-cal
Boxylate [L] (1.23 g, 3.56 mmol)
I got NMR (d6DMSO), MASS and elements
The results of the analysis are shown below. [0131] Embedded image [0132] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       1.87 (3H,-CH ₃ )                       3.61 (3H, N-CH_Three)                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       7.94 (1H, -N-CH= C-)                       12.4 (1H,-NH-) MASS (M + 1)⁺= 354 Elemental analysis; C₁₆H_{twenty two}N_TwoO_FiveS                             CHN             Calculated value 54.22 6.26 7.90             Obtained 54.21 6.24 7.90 Example 13 Under a nitrogen atmosphere, sodium ethoxide (13.6 g,
0.2mol) ethanol solution (200ml)
Into a 1-liter three-necked flask with diethyl malonate (1
6.0 g (0.1 mol) ethanol solution (50 m
l) was slowly dropped at room temperature using a dropping funnel. drop
After the lower end, the mixture was heated to reflux. Continue to ortho benzoate
Ethyl solution of ethyl (22.4 g, 0.1 mol)
The solution (100 ml) is slowly dropped using a dropping funnel.
Was. After the completion of the dropwise addition, the mixture was heated under reflux for 6 hours. Allow to cool to room temperature
Then, ethanol was distilled off under reduced pressure, and 200 ml of water was added to the residue.
In addition, extract with ether (3 times). Saturate the ether layer
Wash with brine, dry over anhydrous magnesium sulfate and concentrate.
The residue was distilled under reduced pressure, and 1'-ethoxy-1'-phenyl
Diethyl tylenemalonate (18.2 g) was obtained. Under a nitrogen atmosphere, sodium ethoxide
(3.4 g, 0.05 mol) in ethanol solution (50
ml) into a 500 ml three-necked flask containing 1'-d.
Diethyl toxic-1'-phenylmethylenemalonate (1
4.6 g (0.05 mol) of an ethanol solution (50 m
l) was slowly dropped at room temperature using a dropping funnel. drop
After the lower end, the mixture was heated to reflux. Subsequently, thiourea (3.
8g, 0.05mol) ethanol solution (50ml)
Was slowly dropped at room temperature using a dropping funnel. End of dripping
After completion, the mixture was heated under reflux for 3 hours. Allow to cool to room temperature and mix
The mixture was added to a beaker containing water (200 ml).
When concentrated hydrochloric acid was added to the resulting solution, a pale yellow solid precipitated.
Issued. By filtering the precipitated solid, ethyl
6-phenyl-2-thiouracil-5-carboxyle
(7.6 g) was obtained. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
Ethyl 6-phenyl-2-thiouracil-
5-carboxylate (6.90 g, 25.0 mmol
l) was slowly added dropwise and reacted for 1 hour at room temperature. reaction
After completion, add methanol (500ml) to the reaction mixture
Then, the deposited precipitate was filtered. Put the resulting precipitate in water
Dissolve and add hydrochloric acid to this aqueous solution to give a pale yellow solid 5-ca.
Rubox-6-phenyl-2-thiouracil (3.10
g) was obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
5-carboxy-6-phenyl-2-thiouracil
(2.00 g, 10 mmol) and tetrahydrofura
(50 ml) into a 200 ml three-necked flask
Dissolve and continue stirring at room temperature for 3 days. White as it reacts
A precipitate is formed. After the reaction is completed, the white precipitate is filtered.
did. Thereafter, the same separation and purification treatment as in Example 1 is performed.
6-methacryloy represented by the following formula 37:
Luoxyhexyl 6-phenyl-2-thiouracil-
5-carboxylate [M] (1.29 g, 3.10 m
mol). NMR (d6DMSO), MASS
And the results of elemental analysis are shown below. [0136] Embedded image [0137] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       1.87 (3H, C = C-CH ₃ )                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       7.62 (5H,C ₆ H ₅ )                       12.5 (2H,-NH-) MASS (M + 1)⁺= 416 Elemental analysis; C_{twenty one}H_{twenty four}N_TwoO_FiveS                             CHN             Calculated value 60.56 5.81 6.73             Found 60.55 5.79 6.73 Example 14 Under a nitrogen atmosphere, sodium ethoxide (13.6 g,
0.20mol) ethanol solution (200ml)
2-oxosuccinic acid in a one liter three-necked flask
Diethyl (37.6 g, 0.2 mol) dissolved in ethanol
Liquid (100 ml) slowly using a dropping funnel at room temperature
It was dropped. After the completion of the dropwise addition, the mixture was heated to reflux. Continue
Eurea (15.2 g, 0.2 mol) in ethanol
(100 ml) slowly using a dropping funnel
Was. After the completion of the dropwise addition, the mixture was heated under reflux for 3 hours. Allow to cool to room temperature
And place the reaction mixture in a beaker containing water (500 ml).
Was added. When concentrated hydrochloric acid was added to the resulting solution,
A colored solid precipitated. By filtering the precipitated solid
, Ethyl 2-thiouracil-6-carboxylate
(28.4 g) was obtained. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
To this solution was added ethyl 2-thiouracil-6-carboxy.
Rate (5.00 g, 25.0 mmol) slowly drops
And allowed to react for 1 hour at room temperature. After the reaction is completed,
Methanol (500 ml) was added to the solution, and the precipitate
The material was filtered. The precipitate obtained is dissolved in water,
Hydrochloric acid was added to the solution to give a light yellow solid 6-carboxy-2-thio.
Ouracil (2.80 g) was obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
6-carboxy-2-thiouracil (1.72 g, 10
mmol) and tetrahydrofuran (50 ml).
Dissolve in a 00 ml three-necked flask and leave at room temperature for 3 days
Stirring was continued. A white precipitate forms as it reacts
After completion of the reaction, the white precipitate was filtered. Then the actual
By performing the same separation and purification treatment as in Example 1,
6-methacryloyloxyhexyl represented by Formula 38
  2-thiouracil-6-carboxylate [N]
(1.07 g, 3.15 mmol) were obtained. NMR (d
6DMSO), MASS and elemental analysis results
Show. [0140] Embedded image [0141] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       1.87 (3H,-CH ₃ )                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       6.87 (1H, -N-CH= C-)                       12.9 (2H,-NH-) MASS (M + 1)⁺= 340 Elemental analysis; C_FifteenH₂₀N_TwoO_FiveS                             CHN             Calculated value 52.93 5.92 8.23             Found 52.96 5.95 8.25 Example 15 Under a nitrogen atmosphere, sodium ethoxide (13.6 g,
0.20mol) ethanol solution (200ml)
2-methyl-2'-into a one liter three-necked flask
Diethyl succinate (40.4 g, 0.2 mol)
Ethanol solution (100 ml) using a dropping funnel
It was slowly added dropwise at room temperature. After dropping, heat to reflux
Was. Subsequently, thiourea (15.2 g, 0.2 mol)
Ethanol solution (100 ml) using a dropping funnel
It was dripped slowly. After completion of dropping, heat to reflux for 3 hours
Was. The reaction mixture was allowed to cool to room temperature, and water (500 ml) was added.
The beaker was added. Concentrated hydrochloric acid is added to the resulting solution.
As a result, a pale yellow solid precipitated. Filter the precipitated solid
To give ethyl 5-methyl-2-thioura
Sil-6-carboxylate (26.5 g) was obtained. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
Ethyl 5-methyl-2-thiouracil-6 was added to this solution.
-Carboxylate (5.35 g, 25.0 mmol)
Was slowly added dropwise and reacted for 1 hour at room temperature. End of reaction
Thereafter, methanol (500 ml) was added to the reaction mixture,
The deposited precipitate was filtered. Dissolve the resulting precipitate in water
Hydrochloric acid was added to this aqueous solution to give a pale yellow solid 6-carbohydrate.
Xy-5-methyl-2-thiouracil (2.93 g)
Obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
6-carboxy-5-methyl-2-thiouracil (1.
86 g, 10 mmol) and tetrahydrofuran (5
0 ml) in a 200 ml three-necked flask to dissolve,
Stirring was continued at room temperature for 3 days. White precipitate as it reacts
However, after completion of the reaction, the white precipitate was filtered.
Thereafter, the same separation and purification treatment as in Example 1 is performed.
Thus, 6-methacryloyl oxy represented by the following formula 39:
Cyhexyl 5-methyl-2-thiouracil-6-cal
Boxylate [O] (1.13 g, 3.19 mmol)
I got NMR (d6DMSO), MASS and elements
The results of the analysis are shown below. [0144] Embedded image [0145] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH_Two (CH ₂ ) ₄ CH_Two-OCO-)                       1.87 (3H, CH_Two= C-CH ₃ )                       2.34 (3H, C = C-CH_Three)                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       12.6 (2H,-NH-) MASS (M + 1)⁺= 354 Elemental analysis; C₁₆H_{twenty two}N_TwoO_FiveS                             CHN             Calculated value 54.22 6.25 7.90             Obtained 54.19 6.23 7.90 Example 16 Under a nitrogen atmosphere, sodium ethoxide (13.6 g,
0.20mol) ethanol solution (200ml)
2-methyl-2'-into a one liter three-necked flask
Diethyl succinate (40.4 g, 0.2 mol)
Ethanol solution (100 ml) using a dropping funnel
It was slowly added dropwise at room temperature. After dropping, heat to reflux
Was. Subsequently, methylthiourea (18.0 g, 0.2 m
ol) in ethanol solution (100 ml).
And slowly dropped. After dropping, heat reflux for 3 hours
I let it. The mixture was allowed to cool to room temperature, and the reaction mixture was washed with water (500 m
1) was added to the beaker. Concentrated salt in the resulting solution
Upon addition of the acid, a pale yellow solid precipitated. Precipitated solid
The body is filtered and separated using column chromatography.
To produce ethyl 3,5-dimethyl-2-thio.
Ouracil-6-carboxylate (16.2 g) was obtained.
Was. Potassium tert-butoxide (43.
7 g, 389 mmol) and dimethyl sulfoxide (40
0 ml) in a 2 liter eggplant-shaped flask to dissolve,
To this solution was added ethyl 3,5-dimethyl-2-thiouracil.
Le-6-carboxylate (5.70 g, 25.0 mm
ol) was slowly added dropwise and reacted for 1 hour at room temperature. Anti
After the reaction, methanol (500 ml) was added to the reaction mixture.
Was added, and the deposited precipitate was filtered. The resulting precipitate is washed with water
, And hydrochloric acid was added to this aqueous solution to give a pale yellow solid 6-
Carboxy-3,5-dimethyl-2-thiouracil
(2.88 g) was obtained. 6-hydroxyhexyl methacrylate
(5.59 g, 30 mmol), N, N'-dicyclo
Xylcarbodiimide (2.27 g, 11 mmol),
6-carboxy-3,5-dimethyl-2-thiouracil
(2.00 g, 10 mmol) and tetrahydrofura
(50 ml) into a 200 ml three-necked flask
Dissolve and continue stirring at room temperature for 3 days. White as it reacts
A precipitate is formed. After the reaction is completed, the white precipitate is filtered.
did. Thereafter, the same separation and purification treatment as in Example 1 is performed.
6-methacryloy represented by the following formula 40:
Leoxyhexyl 3,5-dimethyl-2-thiouracil
-6-carboxylate [P] (1.13 g, 3.07
mmol). NMR (d6DMSO), MASS
And the results of elemental analysis are shown below. [0148] Embedded image[0149] NMR (δ, ppm); 1.3-1.7 (8H, -COO-CH₂ (CH ₂ ) ₄
CH₂-OCO-)                       1.87 (3H, CH_Two= C-CH ₃ )                       2.36 (3H, C = C-CH_Three)                       3.68 (3H, N-CH_Three)                       4.09, 4.13 (4H, -COO-CH ₂ (CH_Two)_Four CH ₂ -OCO-)                       5.65, 6.01 (2H,CH ₂ = C-)                       12.3 (1H,-NH-) MASS (M + 1)⁺= 368 Elemental analysis; C₁₇H_{twenty four}N_TwoO_FiveS                             CHN             Calculated value 55.42 6.57 7.60             Obtained 55.48 6.54 7.61 Application examples 1 to 16 The 16 thiouracil derivatives (AP) shown in Table 1 were
Investigating the adhesive effect on precious dental metals using
Was. The structure of the thiouracil derivative and its abbreviation are described first.
As shown. Each of these compounds was used at a concentration of 0.5% by weight.
An acetone solution was used as a metal surface treatment agent. On the adherend
Dental gold-silver-palladium alloy "Gold Para 12" (To
10 × 10 × 3 mm manufactured by Wagiken Co., Ltd., pure gold plate (10 × 10
× 3 mm) was polished with # 1500 water-resistant abrasive paper
After that, sand blasting is applied to fix the adhesive area
Adhesive tape with 4mmφ hole is attached to fix
I did. Apply the previously prepared metal surface treatment agent to this surface
It was applied with a brush and the acetone was air-dried. 1 minute later, metal surface
"Bistite resin" is a dental adhesive applied to the surface treated with a treatment agent.
Cement "(made by Tokuyama)
Was. Next, a sandblast treatment was performed in advance 8
Push a SUS304 round bar of mmφ × 18mm against the adhesive surface
They were attached and bonded. Remove excess resin cement,
One hour later, the adhesive test piece was immersed in water at 37 ° C. 24:00
After a while, Shimadzu Autograph (Crosshead Speed
(10 mm / min). each
The average of the measured values for each of the six test specimens is shown in Table 1.
did. [0151] [Table 1]Application Examples 17 to 32 Prepare a 0.5% acetone solution of Compound A used in Application Example 1.
Noble metal alloy for dental manufacture according to the methods of Application Examples 1 to 16
And apply it to the “Gold Para 12” and “Pure Gold Plate”
After drying, "Bistite resin cement" (made by Tokuyama)
A stainless steel rod is adhered using
7). Similarly, adhesion test pieces using compounds B to P
(Application Examples 18 to 32). These specimens are adhesive resistant
One hour after bonding, immersed in water at 37 ° C to evaluate durability
After 24 hours, place in a constant temperature water bath at 4 ° C and 60 ° C for 1 minute.
Thermal cycle test of immersion alternately 5000 times,
The tensile adhesive strength was measured. Table 2 shows the results. [0153] [Table 2]When any of the metal surface treating agents was used (see
Examples 17 to 32) also show various metals after the thermal cycle test.
The bond strength is the initial bond strength {the value in parentheses in Table 2}.
There was no significant decrease. Application Examples 33 to 48 Prepare a 0.5% acetone solution of Compound A used in Application Example 1.
After preparation, 3 primers were evaluated to evaluate the storage stability of the primers.
It was stored for 2 months in a constant temperature room at 7 ° C. Primer after storage
Is a dental precious metal alloy according to the methods of Application Examples 1 to 16.
Apply to “gold 12” and “pure gold plate”
Using "Bistite resin cement" (manufactured by Tokuyama)
A stainless steel rod is bonded to form an adhesive test piece (Application Example 33).
Was. Similarly, prepare a 0.5% acetone solution of compounds BP.
After that, it is stored at 37 ° C for 2 months, and adhesion is performed using them.
And an adhesion test piece (Application Examples 34 to 48). these
The test piece was immersed in water at 37 ° C one hour after bonding, and
After the elapse, the tensile adhesive strength was measured. The results are shown in Table 3.
You. [0156] [Table 3]Metal surface treating agent stored at 37 ° C. for 2 months
Is used (Application Examples 33 to 48),
The initial bond strength is the number in parentheses in Table 3.
There was no significant decrease compared to the value｝.

────────────────────────────────────────────────── ─── Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C07D 239/56 C07F 7/10 C09J 5/02 A61K 6/00 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] (Claim 1) The following general formula (1) or (2) In the formula, R ¹ and R ² are each a hydrogen atom or an alkyl group, and at least one of R ¹ and R ² is a hydrogen atom;
R ³ is a hydrogen atom, an alkyl group or a phenyl group;
R ⁴ is a divalent saturated hydrocarbon group having 2 to 12 carbon atoms, or the following general formula (3), (4) or (5): (In the formula, n is an integer of 1 to 5, o and p are each an integer of 1 to 10, q is an integer of 1 to 5, and r and s are each an integer of 1 to 5. ), And Z is a —COO— group, —CH ₂ O
— Or —C ₆ H ₄ —CH ₂ O—, and R ⁵ is a hydrogen atom or a methyl group. A thiouracil derivative represented by｝.