JPS6059906B2 - α-thio-α-aryl group-substituted alkanonitrile - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula Al-, -N-O゛ [wherein is a phenyl group or a thienyl group, R is hydrogen or an alkyl group, and R゛ is an alkyl group or an aryl group,
Y is oxygen or carbonyl group.

] This relates to an α-thio α-aryl group-substituted alkanonitrile represented by the following. The α-thio α-aryl group-substituted alkanonitrile represented by the above general formula (I) is a new compound unknown in the literature, and the compound represented by the above general formula (I) in which R is hydrogen can be reacted in the presence of a base. By reacting with an alkylating agent, a compound represented by general formula (I) and in which R is an alkyl group can be easily obtained.

By subjecting these compounds to a reduction deflow reaction and a hydrolysis reaction, the general formula Ar, , Y HCOOH-(
n) [In the formula, Ar) R and Y are the same as above.

] (See Reference Examples below). The general formula (
Many of the compounds represented by (2) have anti-inflammatory, medicinal, analgesic, or antipyretic effects. For example, a compound in which R is a methyl group, Ar is a phenyl group, Y is oxygen, and Ar-Y- is substituted at the meta position, that is, α-1(m-phenoxyphenyl)propionic acid, It is fenoprofen (so-called anti-inflammatory analgesic). Also, a compound in which R is a methyl group, Ni is a phenyl group, Y is a carbonyl group, and Ar-Y- is substituted at the meta position, that is, α-(m-benzoylphenyl)propionic acid. is the anti-inflammatory analgesic ketoprofen7. Further, a compound in which R is a methyl group, Ar is a 2-thienyl group, Y is a carbonyl group, and Ar-Y- is substituted at the para position, that is, α-[p-(2-thienylcarbonyl )
Phenyl]propionic acid is known as the anti-inflammatory analgesic sprophene. Conventionally, many methods for producing α-aryl group-substituted alkane carboxylic acids or derivatives thereof have been proposed, and a representative process for fenoprofen and ketoprofen is as follows.

The following two methods are known for producing fenoprofen. Method (1) m-phenoxyacetophenone is reduced with sodium boron hydride to give m-phenoxy α-monophenethyl alcohol, and then reacted with phosphorus tribromide to give m-phenoxy α-phenerbromide.

This product is further reacted with sodium cyanide in dimethyl sulfoxide under heating, and then hydrolyzed with sodium hydroxide to obtain the desired α-(m-phenoxyphenyl)propionic acid (U.S. P.36
(See OO437). Method (2) m-methyldiphenyl ether is brominated with N-bromosuccinimide to produce m
-(bromomethyl)diphenyl ether is obtained. This is reacted with sodium cyanide in dimethyl sulfoxide to synthesize m-(cyanomethyl)diphenyl ether, which is hydrolyzed and esterified to obtain ethyl α-(m-phenoxyphenyl)acetate. This was further reacted with diethyl carbonate in the presence of metallic sodium, and once 2
Diethyl -(m-phenoxyphenyl)malonate is formed, and diethyl 2-methyl-2-(m-phenoxyphenyl)malonate is synthesized by reaction with this and iodination. Sara 6
This is hydrolyzed to produce 2-methyl-2-(m-phenoxyphenyl)malonic acid, and then heated and decarboxylated to produce α-(m-phenoxyphenyl)propionic acid (Japanese Patent Publication No. 51-197). 45586).
, In addition, there are the following methods for producing ketoprofen. Method (1)m
-(Bromomethyl)benzophenone and sodium cyanide are reacted to synthesize (m-benzoylphenyl)acetonitrile, which is then reacted with diethyl carbonate in the presence of sodium ethoxide to form ethyl α-cyano(m-benzoylphenyl)acetate. Use as sodium salt.

The reaction of this sodium salt with methyl iodide yields ethyl α-cyano α-(m-benzoylphenyl)propionate, which is hydrolyzed and then subjected to a decarboxylation reaction to produce α-cyano α-(m-benzoylphenyl)ethyl propionate.
Synthesize (m-benzoylphenyl)probionitrile. α-(m-benzoylphenyl)propionic acid is produced by alkaline hydrolysis of this α-(m-benzoylphenyl)probionitrile [British Patent No. 1164]
585 (1969)]. Method (2) α-(m-carboxyphenyl) is produced by the reaction of benzyne and probionitrile generated from 2-chlorobenzoic acid in the presence of a stronger base.
Producing probionitrile [R. Biehletal
．． , J. Org. Chem. ,? , 602 (1966)
]. This α-(m-carboxyphenyl)probionitrile is converted to α-(m-chlorocarbonylphenyl)propionitrile with thionyl chloride. α-(m-
Friedel-Crafts reaction of chlorocarbonylphenyl)probionitrile with benzene using aluminum chloride gives α-(m-benzoylphenyl)probionitrile. This α-(m-benzoyl phenyl)
Probionitrile is hydrolyzed with methanol-sodium hydroxide to produce α-(m-benzoylphenyl)propionic acid (see Japanese Patent Publication No. 8301/1983). The conventional production methods for fenoprofen and ketoprofen shown here are difficult to obtain industrially in some cases, such as m-phenoxyacetophenone, which is the starting material in method (1) for fenoprofen. many. On the other hand, aryl aldehydes are treated by oxidation of the methyl group of the corresponding compound, reduction of the corresponding nitrile compound, ester compound, acid chloride, etc.
reaction (for example, see Chemistry, Vol. 15, p. 384), Gattermann method (0rg. Reacti)
0ns Vol. 19, top 3) or the Gatternlann-KOch method (0r'G.
Many of them can be easily manufactured industrially by methods such as ReactiOnsl Vol. 5, p. 290). In fact, an industrial manufacturing method for m-phenoxybenzaldehyde, which is the raw material for fenoprofen, has already been established (for example, in JP-A-52-9
No. 5623, JP-A No. 53-4073). Therefore, the development of a method for converting aryl aldehyde into an α-aryl group-substituted alkane carboxylic acid using aryl aldehyde as a starting material has been eagerly awaited in the art. The present inventors have already invented an α-aryl group-substituted alkane carboxylic acid derivative having a thio group at the α position (JP-A-53-82750;
4-61159), and by utilizing this new substance, a new method for producing α-aryl group-substituted alkanecarboxylic acids using aryl aldehyde as a raw material was established (see JP-A-53-50134). After that, as a result of further intensive research, the present inventors utilized the novel α-thio α-aryl group-substituted alkanonitrile represented by the general formula (1), and found that the general formula (■ ) We have achieved a new manufacturing technology for α-aryl group-substituted alkanecarboxylic acids. New technology utilizing the new substance of the present invention and prior technology by the inventors (
When compared with JP-A-53-8275-1 and JP-A-54-61159), the technique of the present invention has the following advantages.

That is, from the aryl aldehyde represented by the general formula (■) described later, an α-aryl group-substituted alkane represented by the general formula (■) and in which R is an alkyl group can be obtained by a method utilizing the novel substance of the present invention. Whereas carboxylic acid can be produced in five steps, in the technique of the previous invention, the same aryl aldehyde (■) is represented by the above general formula (■), and R
Six steps are required to produce the α-aryl group-substituted alkane carboxylic acid in which is an alkyl group. That is, by utilizing the compound of the present invention, it is possible to shorten the number of steps. Furthermore, although both the technology of the present invention and the technology of the prior invention include an alkylation step, the method for activating the compound of the present invention in this alkylation step uses an industrially advantageous solvent such as methanol and sodium methoxide. It is possible to use industrially advantageous bases such as. The compound of the present invention represented by general formula (1) can be produced based on the following formula using aryl aldehyde (■) as a starting material.

[In the formula, N, . Y and R1 are the same as above, R2 is a lower alkyl group or an aryl group, and R3 is an alkyl group.

] First step (■ → ■) In this step, aryl aldehyde (■) is treated with an alkali cyanide such as potassium cyanide or sodium cyanide and a sulfonic acid chloride (R2SO2Cl) such as p-toluenesulfonyl chloride or methanesulfonyl chloride. O-sulfonyl-substituted mandelnitrile (■
) is the process of manufacturing.

The reaction was carried out using approximately equimolar amounts of aryl aldehyde (■), alkali cyanide, and sulfonic acid chloride, and using water as a solvent.
This is achieved by mixing at 15° C. to room temperature, but excess amounts of alkali cyanide, sulfonic acid chloride, or both may be used. - It is also possible to add organic solvents that do not participate in the reaction, such as methanol, ethanol, tetrahydrofuran, 1●2-dimethoxyethane, benzene, and methylene chloride. In addition, a small amount of a so-called surfactant such as tetrabutylammonium chloride or trimethylbenzylalmonium chloride may be added to make the reaction proceed smoothly. Second step (■ → 1a) In this step, thiol (R
α-thio α-aryl group-substituted acetonitrile (1a) is obtained by reacting with α-thio α-aryl group (1a).

Examples of the base used include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal alkoxides such as sodium methoxide and sodium ethoxide, and metal hydrides such as potassium hydride and sodium hydride. However, it is preferable to use alkali metal alkoxides or alkali metal hydroxides because they are inexpensive and easy to handle. As the thiol, alkyl mercaptans such as methyl mercaptan and ethyl mercaptan, and aryl mercaptans such as benzenethiol and p-toluenethiol can be widely used, and the amount used is approximately equimolar to O-sulfonyl-substituted mandelnitrile (■). That's enough. Alternatively, a thiolate anion may be prepared in advance from a base and a thiol and allowed to act on the O-sulfonyl-substituted mandenitrile (■). As a solvent, a compound relatively inert to the reaction, such as water, methanol, ethanol, tetrahydrofuran, benzene, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), can be used. The reaction proceeds smoothly at -20°C to room temperature. Moreover, it is preferable to carry out the reaction under an inert gas atmosphere such as argon or nitrogen. Third step (
1a+Ib) In this step, the α-thio α-aryl group-substituted acetonitrile (1a) obtained in the second step is reacted with an alkylating agent in the presence of a base to obtain a compound represented by the general formula (1b). .

base. Examples include metal hydrides such as sodium hydride and potassium hydride, organic thio compounds such as methyllithium and butyllithium, alkali metal amides such as lithium diethylamide and sodium amide, and alkali metals such as sodium methoxide and sodium ethoxide. Alkoxides, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, etc. can be used. Alkylating agents include alkyl halides such as alkyl iodides and alkyl bromides, dialkyl sulfates, and trialkyl phosphates.
Active alkyl esters such as alkyl methanesulfonate, alkyl fluorosulfonate, and the like can be used. It is sufficient to use the base and the alkylating agent in approximately equimolar amounts based on the starting compound. Solvents include protic solvents such as ethanol and methanol, and DMF. ．． Aprotic solvents such as DMSO can be widely used. The reaction is-
Although the process proceeds smoothly at 20°C to room temperature, it is preferably carried out at 0°C to room temperature for ease of operation. Further, in order to suppress side reactions, it is desirable to carry out the reaction under an inert gas atmosphere such as argon or nitrogen. As described above, the compound of the present invention can be easily produced using aryl aldehyde (■) as a starting material via O-sulfonyl-substituted mandelnitrile (■), but various other production methods are also possible. .

For example, the general formula [where N, . R. ．． Rl and Y are the same as described above, and x is a halogen or a functional group having a similar function as a halogen as a leaving group, such as a sulfonyloxy group.

] A method can be mentioned in which ECN is made to act on a compound represented by Further, the general formula [wherein Ar and Y are the same as above]. ] In the presence of a base, sulfenyl chloride, sulfenyl cyanide, disulfide,
Compounds of the invention can also be prepared by reaction with thiolating agents such as sulfonic acid thiol esters or mixtures of sulfur and alkyl halides. Furthermore, the general formula [wherein Ar. Y. ．． R and X are the same as above.

However, only in this formula, when R is hydrogen, a sulfonyl group is excluded as X. ] It is also possible to lead to the compound of the present invention by reacting a thiol with the compound represented by the above formula in the presence of a base. As described above, by subjecting the α-thio α-aryl group-substituted alkanonitrile represented by the general formula (1), which can be produced by various methods, to the reductive desulfurization reaction and the hydrolysis reaction, the α-aryl group can be easily converted to the α-aryl group. This can lead to substituted alkane carboxylic acids. Hereinafter, the present invention will be explained in more detail with reference to Examples and Reference Examples. Example 1 m-phenoxybenzaldehyde 3.96f and p-chloride
A mixture with 3.97 f of toluenesulfonyl was stirred under ice cooling, and an aqueous solution of 1.47 f of sodium cyanide (1
0wL1) was added dropwise in 3 drops.

Next, 10 ml of ethanol was added and the mixture was mixed with ice-cooling, stirred for 30 minutes at room temperature, and extracted with methylene chloride (30 ml).
x3 times). The extract was washed with water (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol to give O-(p-toluenesulfonyl)-
3.816y of m-phenoxymandelnitrile was obtained.
The recrystallized mother liquor was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane and benzene) to further obtain 1.846y. Total yield 5.662
V (yield 75%). Colorless crystal Mp: 56-57.5°C (
from ethanol), IR (KBr): 16001159
0, 1495, 149011450, 138\1260
11195, 1185, 1005, 1000, 990,
885, 850, 815, 795, 780, 68015
90156015(4)o-1.

NMR (CDCl3): δ2.41 (3H,.s), 5
．． 97 (1H1s), 6.8-7.4 (11H..m)
, 8.75 (2H,.d,.J=8Hz).

Calculated value as C2lHl7NO,S: Cl66.47; Hl4.52; Nl3.69
;Sl8.45%. Measured value: Cl66.44; H14.
55:Nl3.73:Sl8.58%. Example 2 5.00 y of p-toluenethiol was dissolved in 6 ml of methanol, and 1.60 ml of a methanol solution of sodium methoxide (2.5 M) was added at room temperature under an argon stream, followed by stirring under ice cooling.

To this was added 1.516 y of O-(p-toluenesulfonyl)-m-phenoxyandernitrile, and the mixture was stirred for three times under ice cooling and then for one time at room temperature. 20 ml of water was added and extracted with methylene chloride (30 ml x 3), the extract was washed with water (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, benzene) to obtain α-(p-tolylthio) (
m-phenoxyphenyl)acetonitrile 1.334f
was obtained as a colorless oil. Yield 100%. 1R(N
eat): 2250, 1595, 1500, 1450,
1280, 125C) Sl2l5s82 to 80 to 75 70 泗-1. NMR (CDCl3): δ2.30 (3H
．． ．． s), 4.78 (1H1s), 6.8-7.4 (1
3H. sm) MS (70eV): m/E33l (48,
M, 209 (21), 208 (68), 181 (10
0), 123 (39), 91 (14), 77 (24).
Example 3 1.245y of α-(p-tolylthio)(m-phenoxyphenyl)acetonitrile was dissolved in 5ml of anhydrous methanol, and a methanol solution (2.2M) of sodium methoxide was added and stirred under an argon atmosphere at room temperature. 0.35 ml of methyl chloride was added dropwise.

After stirring the powder three more times at room temperature, ammonium chloride aqueous solution (
3y/20m1) and ether extraction (20m1 x 3
times). The extract was washed with water (30ml x 3 times), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The oily residue was purified by column chromatography (silica gel, hexane and methylene chloride) to give α-(p-tolylthio)-α-
(m-phenoxyphenyl)probionitrile 1.12
I got 5y. Yield 86%. Pale yellow oily substance 1R (Neat): 1584, 149011256, 1
218, 811, 692 cm-1. NMR (CDCl3
): δ1.90(31(,s), 2.28(3H1s)
, 6.8-7.4 (13H,.m). MS(7(g)V)
): m/E345 (6, M+), 223 (27), 22
2 (75), 221 (50), 195 (38), 124
(100), 123 (27), 91 (39), 77 (5
1). Example 40-(p-toluenesulfonyl)-m-
Phenoxymandelnitrile 3.79f anhydrous Dr! I
The mixture was dissolved in 10 ml of F' and stirred under ice cooling under an argon atmosphere, and 4.35 ml of a methanol solution (2.3 M) of sodium methyl mercaptan was added dropwise thereto over 10 minutes.

After further stirring the powder three times under ice-cooling, 30 ml of water was added and the mixture was extracted with ether (30 ml x 3 times). Wash the extract with water (20
m1), dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and separated and purified the residue by column chromatography (silica gel, hexane and benzene) to obtain α-(methylthio).
(m-phenoxyphenyl)acetonitrile 1.007
y was obtained as a colorless oil. Yield 39%. IR(N
eat): 2230, 1590, 1490, 1445,
1270, 125 to 121 to 79 to 75 6% o-1.
NMR (CDCl,): δ2.18 (3H..s), 4
．． 64 (1H1s), 6.8-7.4 (9H..m).
MS (70eV): m/E255 (62, M, 209
(19), 208 (45), 181 (100), 149
(19), 77(26). Example 5α-(methylthio)
(m-phenoxyphenyl)acetonitrile 956m9
was dissolved in 5 ml of anhydrous methanol, and a methanol solution of sodium methoxide (2.5
Add 1.7 ml of M) and stir, and add 0.34 ml of methyl iodide.
ml was added dropwise.

After stirring for another hour at room temperature, ammonium chloride aqueous solution (
3y/20m1) and ether extraction (20m1 x 3
times). The extract was diluted with water (25ml x 3 times), dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane and methylene chloride) to obtain α-(methylthio)-α- 817 mg of (m-phenoxyphenyl)probionitrile was obtained as a colorless oil. Yield 82%. 1R (Neat): 2
225, 1587, 1494, 1440, 1258, -
121λ9 mark d-1. NMR (CDCl3): δ1.9
0 (3H,.s), 2.06 (3H1s), 6.8-7
．． 4 (9H,.m). MS (7(g)V) m/E26
9 (40, M+), 222 (100), 196 (67)
, 77(38). Example 6 p-toluenethiol 372
Dissolve m9 in 2 ml of anhydrous methanol, and add a methanol solution of sodium methoxide (2 ml) at room temperature under an argon atmosphere.
．． 5r! 4) After adding 1.20 ml, the mixture was cooled to -15°C and stirred.

To this was added an anhydrous DMF solution of 1.170f of 30-(p-toluenesulfonyl)-m-benzoylmandelnitrile (
4ml of 1ml) was added dropwise to the mixture, and while stirring was continued, the temperature was gradually raised to 0°C after 3 hours. At this point, 30 ml of water was added to the reaction mixture and methylene chloride extraction 4 (20 ml) was added to the reaction mixture.
The extract was washed with water (20 ml), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, benzene) to obtain α-
(p-tolylthio)(m-benzoylphenyl)acetonitrile 837W! 9 was obtained as colorless crystals. Yield 82
%. Mp: 79-79.58C (from ethanol). 1
R (KBr): 2230, 1650, 1600, 149
5, 1450, 132\1315s130 to 810, 7
9 to 71-1 NMR (CDCl3): δ2.35 (3
H,. s), 4.98 (1H1s), 6.9-7.9 (
13H. ．． m). MS (7(g)V): m/E343(
21, M+), 221 (14), 220 (37), 16
5 (28), 123 (100), 105 (44), 91
(15), 77(45). Calculated value as C22Hl7NOS: Cl76.93: Hl4.99; Nl4. O8
;Sl9.34%. Measured value: Cl76.9l: Hl5.
Ol; Nl 3.97: Sl 9.37%. Example 7 2 ml of anhydrous methanol was added to 439 Tng of α-(p-tolylthio)(m-benzoylphenyl)acetonitrile, and the mixture was stirred under ice cooling.

Add to this a methanol solution of sodium methoxide (2.5
M) 0.55 ml then 0.12 methyl iodide
ml was added dropwise. After stirring for three more times at room temperature, ammonium chloride aqueous solution (0.5y/20ml) was added and extraction with methylene chloride (15ml x 3 times) was performed. Wash the extract with water (1
After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure to obtain an oily residue. This was purified by column chromatography (silica gel, benzene) to obtain 422m9 of α-(p-tolylthio)-α-(m-benzoylphenyl)probionitrile as a colorless substance. Yield 92%
. IR (Neat): 2230, 1665, 1600,
1495, 1450, 132 length 1285s122 length 81
＼71泗-1. NMR (CDCl3): δ1.96 (3
H. ．． s), 2.26 (3H1s), 6.9-7.9 (
13H,. m). MS (7(g)V): m/E357(
6, M+), 234 (74), 124 (100), 10
5 (72), 91 (23), 77 (58). Example 80
979 m9 of -(p-toluenesulfonyl)-m-benzoylmandenitrile was dissolved in 2 ml of DMF and stirred under ice cooling under an argon atmosphere.

To this was added 1.08 ml of a methanol solution (2.3 M) of sodium methyl mercaptan over 5 minutes, and the mixture was further stirred for 1 hour under ice cooling. Ammonium chloride aqueous solution (0.2
f/30mt) and extracted with methylene chloride, the extract was washed with water (10ml) and dried over anhydrous magnesium sulfate,
It was concentrated under reduced pressure. The oily residue was separated and purified by column chromatography (silica gel, methylene chloride) to obtain 533 m9 of α-(methylthio)(m-benzoylphenyl)acetonitrile as a pale orange oil. Yield 80%.
IR (Neat): 2230, 1665, 1605, 1
71\70h-1 to 455, 1325, 129. NMR
(CDCl3): δ2.23(31(,s), 4.82
(1H1s), 7.3-8.0 (9H.m). MS (7
0e ■): m/E267 (12, M two, 222 (15)
, 221(91), 220(81), 193(24),
165 (74), 115 (19), 105 (100),
77(93). Example 9 433 ml of α-(methylthio)(m-benzoylphenyl)acetonitrile was dissolved in 2 ml of anhydrous methanol and stirred under ice-cooling and argon atmosphere.

Add to this a methanol solution of sodium methoxide (2.5
M) 0.65 ml, then 0.15 ml of methyl iodide
ml was added dropwise. After further stirring for 1 hour under ice-cooling, ammonium chloride aqueous solution (a). 5V/30ml) and extracted with methylene chloride (20ml x 3 times). The extract was washed with water (10 ml), dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was subjected to column chromatography using silica gel.
(methylene chloride) to obtain α-(methylthio)-α-(
m-benzoylphenyl)probionitrile 334m9
was obtained as a pale yellow oil. Yield 73%. IR(Ne
at):2225, 1665, 16001145011
325, 1285s720, 70\6%d-1. NMR
(CDCl3): Sl. 97 (311..s), 2.1
0 (3H1s), 7.3-8.1 (9FI,.m). M
S (7 (g) ■): 281 (8, M two, 235 (32)
, 234 (100), 207 (12), 176 (16)
, 149(10), 105(47), 77(48). Example 100-(p-Toluenesulfonyl)-p-(2-thienylcarbonyl)mandelnitrile (795 m9) was dissolved in 3 ml of anhydrous DMF and heated to -15°C under an argon atmosphere.
It was stirred with

A solution prepared by adding 0.80 ml of a methanol solution of sodium methoxide (2.5 M) to a solution of 250 ml of p-toluenethiol in anhydrous methanol (2 ml) at room temperature was added dropwise over 10 minutes. After the dropwise addition, the temperature was gradually raised while stirring was continued, and after two drops, the temperature was brought to -5°C. At this point, ammonium chloride aqueous solution (1f1/30m
1) was added and extracted with methylene chloride (20 ml x 3 times). The extract was washed with water (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol to obtain 387 m9 of α-(p-tolylthio)[p-(2-thienylcarbonyl)phenyl]acetonitrile as colorless crystals. In addition, the mother liquor was concentrated under reduced pressure and the residue was subjected to column chromatography (silica gel, methylene chloride).
95 mg of α-(p-tolylthio)[p-(2-thienylcarbonyl)phenyl)acetonitrile]
I also got more. Total yield 482 mg, yield 69%. Mp:
124-126°C (from ethanol). 1R (KBr)
:223011635, 1610, 1420, 1355
,129＼1240s1050,88飄to817ao-
1. NMR (CDCl3): δ2.33 (3H..s)
, 4.95 (1H1s), 7.0-7.9 (11H, .
m). Calculated value as C2OHl5NOS2: C,. 68.74; Hl4.33; Nl4. O
l;Sll8.35%. Measured value: Cl68.95:Hl
4.27;Nl4. O2;Sll8.4l%. Example 1
1 3 ml of anhydrous methanol was added to 351 ml of α-(p-tolylthio)[p-(2-thienylcarbonyl)phenyl]acetonitrile, and the mixture was stirred under ice-cooling and an argon atmosphere.

Claims (1)

[Claims] 1 α-thio-α-aryl group-substituted alkanonitrile represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [wherein Ar is a phenyl group or thienyl group, R is hydrogen or The alkyl group, R_1, is an alkyl group or an aryl group, and Y is oxygen or a carbonyl group. ]. 2. The compound according to claim 1, wherein R is hydrogen or a methyl group.