JPS6014024B2 - Method for producing optically active N-halosulfilimines - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing novel optically active N-halosulfimines having optical activity on the sulfur atom. More specifically, the present invention relates to a method for producing corresponding optically active N-halosulfimines by halogenating sulfilimines [1] having optical activity on the sulfur atom. Generally, it is difficult to predict whether an optically active substance is stable or unstable;
Optically unstable active substances will racemize even if left at room temperature, but such racemization can be caused by heat, light,
It is caused by physical causes such as dissolving in a solvent, or chemical causes such as alkalis and acids. For this reason, with the exception of carbon compounds, it is generally extremely difficult to predict whether a chemical reaction involving a certain optically active substance will proceed with steric retention, inversion, or racemization. That's true. Particularly in the case of organic sulfur compounds, empty square orbitals of sulfur may be involved in the reaction, which is even more difficult to predict than in the case of carbon. On the other hand, organic compounds with an S→N skeleton are used as additives for pharmaceuticals, surfactants, and resins due to their unique chemical structures.
Although it is a useful compound as a solvent, paint, agricultural chemical, intermediate for organic synthesis, etc., sufficient knowledge has not yet been obtained regarding its optically active form. However, in addition to the various uses mentioned above, an optically active compound with an S→N skeleton can also be used as an optical resolution agent, selectively or exclusively having medicinal properties, due to its specific property of being an optically active entity. They have additive or synergistic uses as pharmaceuticals, reagents for asymmetric synthesis, model compounds for various enzymes, etc., and therefore there is a need for a production method that provides these useful optically active compounds. That is, N-halosulfuimines

[0] is in the air,
When kept at room temperature, it gives the corresponding sulfonium salt; at room temperature it reacts with sulfide, phosphine, amine, etc. to give the corresponding sulfonium salt, and at room temperature it acylates to give the corresponding N
- acyl form, treated with alkali at 4500 to give corresponding sulfoximines, treated with alkali cyanide at room temperature to give N-cyanosulfilimines, and reacted with an alkylating agent and an arylating agent, It is a highly reactive compound that provides various useful organic sulfilimine compounds under mild conditions, such as N-alkyl sulfilimine, N-arylsulfilimine, etc., and its optically active form. To date, there are no examples of manufacturing [D]. In view of these facts, the present inventors conducted extensive research and discovered optically active sulfilimines [1] and c. The present invention was completed based on the discovery that the reaction with a genifying agent proceeds without racemization. *That is, the present invention is based on the formula: [In the formula, R1 and R2 optionally represent a phenyl group or a lower alkoxy-substituted phenyl group. ] A sulfuilimine having optical activity on a sulfur atom represented by the formula: [wherein R1, R2 is the same as above. X represents a halogen atom. ] This is a method for producing N-halosulfimines having optical activity on the sulfur atom. Although the mechanism of the reaction between the optically active sulfilimines [1] and the halogenating agent is not clear, as shown in the following formula m, for example, it can be obtained by the halogenation reaction of [1]a.

When [0]a is dehalogenated and reduced, the initial [1
The fact that [1]a having an optical rotation comparable to that of [1]a is obtained indicates that the halogenation reaction according to the present invention proceeds with good optical yield without racemization. The present invention can be implemented, for example, as follows. The raw material optically active sulfilimines can be obtained, for example, by a method of treating with an alkali a sulfonic acid salt of optically active sulfilimines obtained by acid-treating optically active N-sulfonylsulfilimines. Optically active sulfilimines thus obtained [
1] is mixed with a halogenating agent, if necessary in the presence of a solvent, and reacted. After the reaction, it is optional to separate and, if necessary, purify according to a conventional method. Usually, optically active sulfilimines used as raw materials or optically active N produced
- Considering the optical stability of halosulfimines, reaction conditions such as reaction temperature are appropriately selected, and the reaction molar ratio of optically active sulfilimines and halogenating agent is usually about 1:1. selected. The reaction is usually carried out at around room temperature, but may be cooled if necessary. Further, in order to prevent racemization, it is preferable to handle the entire reaction system at a temperature of 60 oo or less. The halogenating agent according to the present invention is preferably a halogen-based oxidizing agent, and ordinary halogen-based oxidizing agents can be used without any problem. sodium chlorite,
Hypohalites such as potassium hypobromite and calcium hypochlorite, ethyl hypochlorite, isopropyl hypobromite, alkyl hypohalites such as rt-butyl hypochlorous acid, N-chloro Examples include succinimide, N-halosuccinimide such as N-bromosuccinimide, chloramine T, and these halogen-based oxidizing agents may be used alone or in combination. Examples of the alkyl group according to the present invention include saturated alkyl groups such as methyl group, ethyl group, propyl group, butyl group, rt-butyl group, hexyl group, 2-ethylhexyl group, dodecyl group, cyclopropyl group, Examples include saturated cycloalkyl groups such as cyclohexyl group, unsaturated alkyl groups such as vinyl group, 1-probenyl group, 4-hexenyl group, and 9-pentadecenyl group, and unsaturated cycloalkyl groups such as cyclohexenyl group. Examples include phenyl group, naphthyl group, etc. Examples of the skeleton of the sulfur-containing cyclic compound in which RI and R2 form a ring include thiolane, thian, oxathian, 1,2-dihydrothionaphthene, benzothian, thiabicycloheptane, phenoxatin, phenothiazine, thioxanthene, penicillin, and cephalosporin. It's coming. Examples of substituents for the substituted sulfur-containing cyclic compounds, substituted alkyl groups, and substituted aryl groups of the present invention include, in addition to hydrocarbon groups, halogens, alkoxy groups, aryloxy groups, alkylthio groups, arylthio groups, nitro basis,
Examples include sia/group, acyl group, and sulfonyl group. More specifically, examples of optically active N-halosulfilimines obtained according to the present invention include N-chloroS-methyl-S-isopropylsulfylimine, N-bromoS-methyl-S-phenylsulfimine, Rufilimine, N-iodo-S-methyl-S-phenylsulfuimine, N-chloro-S-methyl-S-phenylsulfuimine, N-bromo-S-cyclobropyru-S
-Phenylsulfuimine, N-chloro-S-ethyl-S-cyclohexylsulfuimine, N-promo-
S-methoxyphenyl-S-ethylsulfuilimine, N-chloroS-ethyl-S-p-ethoxyphenylsulfuimine, N-iodo-S-tolyl-S
-Phenylsulfyl imine, N-chloro-S-methylthiophenyl-S-phenylsulfyl imine, N
-bromoS-o-nitrophenyl-S-phenylsulfuimine, N-iodo-S-o-methoxyphenyl-S-p-tolylsulfuimine, N-chloro-S-o-chlorophenylsulfuimine , N-bromo S
-Phenyl-S-2,6-dichlorophenylsulfuilimine, N-chloro-S-phenyl-S-p-cyanophenylsulfuimine, N-bromo-S-tolyl-S-p-tolylsulfuimine , S-chloroimino-2-cyanothiolane, S-bromoimino-2-methoxythiane, S-chloroimino-2-methyl-1,2-dihydrothionaphthene, S-iodoimino-4,4-dimethylbenzo[b]thiane, S-bromoimino-2-chloro-7 -thiabicyclo[2.2.1]hebutane, S-chloroimino-4-methylphenoxatin, S-chloroimino-1-chlorophenothiazine, S-iodoimino-
Examples include optically active substances such as 4-toxythioxanthene, S-bromoiminobenicillin, and S-bromoiminocephalosporin. In the present invention, examples of solvents that may be used if necessary include acetone, benzene, and chlorine. Examples include loform and dichloromethane. Ha. Examples of genes include chlorine, bromine, iodine, and the like.
The present invention provides highly reactive optically active N-halosulfimines that are useful as optical resolution reagents, reagents for asymmetric synthesis, pharmaceuticals having selective or exclusive medicinal effects, etc. There is a lot to contribute to this industry. EXAMPLES The present invention will be explained in more detail by referring to Examples and Reference Examples below. Example 1 (1)-(S)-S-methoxyphenyl-S-phenylsulfoylimine ([Q] deprivation: -194o (C; 1
．． 0.00, CHC13)) 0.37% was dissolved in 5 parts of acetone, cooled with ice and water, and N-chlorosuccinimide 0.
．． 21 Add immediately and dissolve, remove the scale and continue to stir for 1 powder at room temperature. After the reaction, pour the reaction solution into ice water to remove the precipitated solid (pal).
(e-yellow color) was collected in a furnace, dried, and recrystallized from benzene/n-hexane to obtain (1)-(S)-S
-o-methoxyphenyl-S-phenyl-N-chlorosulfuimine (paleyellowc) 0.
Get 28 evenings. [Q] Color 5: -790 (C; 0.29,
CHC13). m-p. 79-80°C (decomp.
). Yield: 67%. m (KBr);〃SN: Spot 6
Hypochemistry-1 Example 2 (1)-(S)-S1o-Methoxyphenyl-S-phenylsulfuilimine ([Q] Color 5-73.9o(C;
1.44, CHC13)) was treated in the same manner as in Example 1 to obtain 0.28 g of (1)-(S)-S-o-methoxyphenyl-S-phenyl-N-chlorosulfilimine.

Claims (1)

[Claims] 1 Formula: ▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 and R^2 optionally represent a phenyl group or a lower alkoxy-substituted phenyl group. Formula: ▲Mathematical formula, chemical formula, table etc. ▼ [In the formula, R^1 and R^2 are the same as above. X represents a halogen atom. ] A method for producing N-halosulfuimines having optical activity on the sulfur atom.