Processes for producing isothiazole derivatives

Details Processes for producing isothiazole derivatives Processes for producing isothiazole derivatives

1997-05-19

1999-01-05

Lambkin, Deborah C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

544368, C07D27504

Patent

active

058565043

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP95/02484 filed Dec. 4, 1995.


TECHNICAL FIELD

The present invention relates to a novel method for producing 1,2-benzisothiazoles and 3-halo-1,2-benzisothiazoles using 2-(alkylthio)benzaldehyde oximes as starting materials. The present invention further relates to a novel method for producing 1-(1,2-benzisothiazol-3-yl)piperazines using 3-halo-1,2-benzisothiazoles as starting materials. 1-(1,2-benzisothiazol-3-yl)piperazines are useful compounds as therapeutic agents for the central nervous system disorders (antipsychotic agents) and neural relaxants, or intermediates for the production of these agents.


BACKGROUND ART

Conventionally, the known methods for producing 1,2-benzisothiazoles and 3-halo-1,2-benzisothiazoles include the following: ##STR1##
However, the above known methods have the following drawbacks:
In (A) and (B), examples of methods for producing 1,2-benzisothiazoles are disclosed. Since there are no disclosures concerning a method by which 2-substituted benzaldehyde oximes, the starting materials, can be obtained on an industrial scale, details are unknown. Also, the yields by these methods are not high.
In (C) and (D), examples of methods for producing 3-chloro-1,2-benzisothiazoles are disclosed. The method of (C) uses expensive 1,2-benzisothiazol-3-ones as the starting materials, and gives a poor yield. The method of (D) cannot be said to be industrially advantageous because this method requires the use of expensive thiosalicylic acid as the starting material and achieves an unsatisfactory yield.
As mentioned above, with any known methods, it has been difficult to advantageously produce 1,2-benzisothiazoles and 3-halo-1,2-benzisothiazoles on an industrial scale.


DISCLOSURE OF THE INVENTION

In view of the above situation, the present inventors have made intensive studies to provide a simple and economically advantageous method for producing 1,2-benzisothiazoles and 3-halo-1,2-benzisothiazoles on an industrial scale without using expensive materials. As a result, the inventors have found that a 1,2-benzisothiazole represented by the general formula (II) can be obtained by treating a 2-(alkylthio)benzaldehyde oxime represented by the general formula (I) with a halogen compound. ##STR2## wherein R.sup.1 represents an alkyl group having 1 to 4 carbon atoms; and R.sup.2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom.
The present inventors have further found that a 3-halo-1,2-benzisothiazole represented by the general formula (III) can be obtained by the reaction between a 1,2-benzisothiazole represented by the general formula (II) and a halogenating agent. ##STR3## wherein X represents a chlorine atom or a bromine atom; and R.sup.2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom.
Also, the present inventors have found that even when the above two reactions are successively carried out, the remainder of a halogen compound which is used for the cyclization of the 2-(alkylthio)benzaldehyde oxime does not affect the subsequent halogenation process and, therefore, the above two reactions can be carried out in a one-pot process. Specifically, the present inventors have found that a 3-halo-1,2-benzisothiazole represented by the general formula (III) can be obtained from a 2-(alkylthio)benzaldehyde oxime represented by general formula (I) in a one-pot process. The present inventors have completed the present invention after they have further found that a 1-(1,2-benzisothiazol-3-yl)piperazine represented by the general formula (V) can be obtained by the reaction between a 3-halo-1,2-benzisothiazole represented by the general formula (III) obtained by the production method of the present invention, and a piperazine represented by the general formula (IV). ##STR4## wherein X represents a chlori

REFERENCES:
patent: 4590196 (1986-05-01), Smith et al.
Becke et al., Liebigs Annalen Der Chemie, 729: 146-151 (1969).
Ricci et al., Ann. Chim. (Rome), 53(5), 577-587 (1963).
Meth-Cohn et al., Synthesis (1), 58-60 (1978).
McKinnon et al., Can. J. Chem. 66, 1405-9 (1988).
Rahman et al., J. Chem. Soc. Perkin Trans. I, 385-90 (1984).

Affiliated with

Also associated with

Rating

Processes for producing isothiazole derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Processes for producing isothiazole derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Processes for producing isothiazole derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-863815