JPS6141905B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for producing optically active organic isocyanates. More specifically, pharmaceuticals, agricultural chemicals, which are characterized by photodegrading N-acylsulfilimine having optical activity on the carbon α-position with respect to the carbonyl group.
This field relates to a safe method for producing various optically active organic isocyanates useful as synthetic intermediates for dyes, polymer raw materials, etc. Conventionally, organic isocyanates have been obtained through reactions such as alkyl calcium sulfate and potassium cyanate, alkyl iodide and silver cyanate, arylamine hydrochloride and phosgene, and the thermal decomposition of acid azides, but all of them are extremely difficult to obtain. It is necessary to use isocyanates, phosgene, sodium azide, etc., which are toxic or dangerous to handle, and it is difficult to obtain starting materials.
Only a limited number of isocyanates can be synthesized in limited locations, and a safe and general method for synthesizing isocyanates has been desired. As a result of extensive research in search of a safe and general method for producing optically active organic isocyanates, the present inventors discovered that optically active N-acylsulfilimine was added to the carbon α-position relative to the carbonyl group. By photolysis, optically active organic isocyanates with extremely high optical purity, which have optical activity on the carbon α-position relative to the isocyanate group while retaining their steric properties, can be easily obtained in high yield. They discovered this and completed the present invention. That is, the present invention has the following formula: (In the formula, R represents a phenyl-substituted lower alkyl group and a lower alkyl group having optical activity on the carbon at the α-position with respect to the carbonyl group.) This is a method for producing optically active organic isocyanates of the formula R-NCO (wherein R is the same as above), which is characterized by photolyzing enylsulfilimines. In general, it is difficult to predict whether an optically active form is stable or unstable, and optically unstable active forms will racemize even if left at room temperature. It is caused by physical causes such as dissolving in water, or chemical causes such as alkalis and acids. Therefore, it is generally extremely difficult to predict whether a photolysis reaction involving an optically active substance like the one of the present invention will proceed with steric retention, or will proceed with inversion or racemization. That's true. The functional groups that can be substituted on the hydrocarbon group of R in the above formula are as described above, but are not limited to these as long as they do not react with the isocyanate group to be produced. The solvent used in the present invention is preferably one that dissolves the optically active N-acyl-S,S-diphenylsulfyl imine, but any solvent may be used as long as it does not react with the isocyanates produced. -Acyl-S,S-diphenylsulfuilimines and optically active isocyanates are appropriately selected depending on the type thereof, and may be used alone or in combination. Isocyanates are generally very active and can be used as solvents with polymerizable double bonds or active hydrogen.
For example, water, alcohol, amines, organic acids, acrylonitrile, etc. are not preferred. Examples of the solvent used in the present invention include benzene, toluene, xylene, ethylbenzene, anisole, n
-Hexane, cyclohexane, methylene chloride, chloroform, ethylene chloride, chlorobenzene, ether, isopropyl ether, n-hexyl ether, 1,4-dioxane, furan, tetrahydrofuran, ethylene glycol diethyl ether, diethylene glycol diethyl ether, acetonitrile, etc. . As a light source for photolysis, one having a wavelength of 200 to 400 mμ is usually used, and examples thereof include a carbon arc lamp, a xenon arc lamp, a mercury lamp, and the like. The reaction is carried out, for example, with optically active N-acyl-S,S
- Dissolve diphenylsulfuimines in an appropriate solvent and irradiate with light with or without inert gas replacement. Although the irradiation time varies depending on the optically active N-acyl-S,S-diphenylsulfilimine, a period of several minutes to about 4.5 hours is sufficient. The reaction is usually carried out at around room temperature, but may be cooled or heated if necessary. After the reaction is completed, the product is separated by a conventional method such as distillation or extraction. In addition, the produced isocyanates are reacted with acidic sulfites, aromatic amines, alcohols, amides, phenols, lactams, heterocyclic compounds, hydrocyanic acid, sulfites, etc., to produce so-called isocyanate regenerants, or by decomposing the produced isocyanates to produce amines. It may be separated as a derivative, a urea derivative, etc. by dimerization. The diphenyl sulfide obtained by photolysis is recovered and converted into diphenyl sulfyl imine.
It can also be used in circulation. For example, N-acyl-S,S-diphenylsulfylimines that have optical activity on the carbon α-position to the carbonyl group can be mixed with an acylating agent that has optical activity on the carbon α-position of the carbonyl group. It can be synthesized easily and in high yield with high optical purity at room temperature by reaction with enylsulfoylimine. Organic isocyanates having optical activity on the α-position carbon of the isocyanate group obtained by the present invention can be obtained by a normal reaction of isocyanates.
It is extremely useful as a synthetic intermediate for pharmaceuticals, etc., as it can be easily derived into optically active isocyanate regenerants, amine derivatives, urea derivatives, etc. with high optical purity and high yield. In this way, by using the method of the present invention,
The isocyanate derivative of the optically active acylating agent used can be easily obtained in high yield. The method of the present invention does not use any toxic or dangerous chemicals to handle.
It makes a huge contribution to this industry, such as being able to produce a wide range of optically active organic isocyanates. Reference examples and examples will be described below. Parts in Reference Examples and Examples indicate parts by weight. Reference Example 1 α-phenylpropionic acid is optically resolved with strychnine to obtain (+)-α-phenylpropionic acid. (+)-α-phenylpropionic acid 52.6
parts/59.5 parts of thionyl chloride in 500 parts of methylene chloride
part/500 parts of methylene chloride was added dropwise, and the mixture was stirred at 30 to 50°C for 3 hours. After the reaction, 54.3 parts of (+)-α-phenylpropionyl chloride (yield 92
%). bp56℃/1mmHg, [α]+87.8° ((c=2.86, in benzene). 50 parts of diphenylsulfilimine/benzene
A solution of 42 parts of (+)-α-phenylpropionyl chloride/450 parts of benzene was added dropwise into the 450 parts solution, and the mixture was stirred at room temperature for 1 hour. After adding a dilute alkaline solution to the reaction solution, it was extracted with benzene, and after drying, the benzene was distilled off to obtain (-)-N-α-phenylpropionyl-S,S-diphenylsulfuimine.
77.74 parts (94% yield) are obtained. mp93~95℃.
[α] −36.5° (c=1.17, in benzene). Example 1 (-)-N-α-phenylpropionyl-S,
75 parts of S-diphenylsulfoylimine in benzene
Dissolve in 1300 parts and irradiate with a low-pressure mercury lamp for 3 hours at room temperature in a quartz glass container under argon gas substitution. The solvent was distilled off and 15.6 parts (yield 47%) of (-)-α-phenethyl isocyanate was obtained by gas chromatography (SE-30, 2m, 100°C).
[α] −17.4° (c=1.38, in benzene). The results of IR and elemental analysis are shown below. IR; ν _nax (film) = 2260cm ^-1 elemental analysis C ₉ H ₉ NO, MW147.18

[Table] Reference Example 2 15 parts of (-)-α-phenethyl isocyanate obtained in Example 1 was poured into 50 parts of concentrated hydrochloric acid, and the amount of -5~
Stir at -10°C for 3 hours. The reaction solution is neutralized with dilute alkali, extracted with benzene, dried, and then benzene is distilled off to obtain 9.2 parts of (-)-α-phenethylamine (75% yield). [α] −33.9° (c=2.64,
in benzene), optical yield 98.0%.

Claims (1)

[Claims] 1 formula (In the formula, R represents a phenyl-substituted lower alkyl group and a lower alkyl group having optical activity on the carbon at the α-position with respect to the carbonyl group.) A method for producing optically active organic isocyanates of the formula R-NCO (where R is the same as above), which comprises photolyzing enylsulfyl imines.