Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-05-22
1997-03-04
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D23356
Patent
active
056080808
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 PCT/JP94/01578 Aug. 26, 1994.
1. Technical Field
The present invention relates to a process for industrially producing a 2-substituted benzo[b]thiophene which is useful, for example, as an intermediate for drug synthesis.
2. Background Art
For the production of 2-substituted benzo[b]thiophene, there is proposed a process which comprises reacting benzo[b]thiophene with a strong base such as butyl lithium or the like and reacting the reaction mixture with an acid chloride such as acetyl chloride or the like to obtain a 2-acylbenzo[b]thiophene [J. Chem. Soc., Chem. Comun., 3447 (1971)].
The above process, however, has problems in that the use of butyl lithium (which is difficult to handle) in the reaction makes the industrial operation difficult and moreover benzo[b]thiophene and butyl lithium both used as raw materials are expensive.
A process is also known which comprises reacting 2-mercaptobenzaldehyde with an .alpha.-haloketone such a s chloroacetone or the like to obtain a 2-acylbenzo[b]thiophene (Comptes rendus, Vol. 234,736).
This process, however, has problems in that the industrial synthesis of 2-mercaptobenzaldehyde used as a raw material is difficult and moreover this compound is unstable and needs careful handling.
The task of the present invention is to provide a process for industrially producing a 2-substituted benzo[b]thiophene inexpensively.
DISCLOSURE OF THE INVENTION
The present inventors made a study on the process for industrial production of 2-substituted benzo[b]thiophene. As a result, the present inventors unexpectedly found out that the conventional problems could be solved and a 2-substituted benzo[b]thiophene could easily be produced by reacting a 2-halogenobenzaldehyde of high commercial availability with a particular inorganic sulfur compound and reacting the reaction mixture with a compound represented by general formula (2) (shown below) to give rise to intramolecular ring closure. The present invention has been completed based on the above finding.
The present invention provides a process for producing a 2-substituted benzo[b]thiophene, which is characterized by reacting a substituted or unsubstituted 2-halogenobenzaldehyde with sulfur and a compound represented by general formula (1) represents an integer of 1 or more; and k represents an integer of 1-2 with a proviso that i+k=2), or with a compound of general formula (1) wherein j is 2 or more, in the presence of an aprotic polar solvent, and then reacting the reaction mixture with a compound represented by general formula (2) substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted arylcarbonyl group or a cyano group) to give rise to intramolecular ring closure.
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is described in detail below.
The present invention comprises a first reaction of reacting a substituted or unsubstituted 2-halogenobenzaldehyde (which may hereinafter be referred to simply as 2-halogenobenzaldehydes) with sulfur and a compound represented by general formula (1), or with a compound of general formula (1) wherein j is 2 or more, in the presence of an aprotic polar solvent to obtain a reaction mixture, and a second reaction of reacting the reaction mixture obtained in the first reaction, with a compound represented by general formula (2) to give rise to intramolecular ring closure to obtain a 2-substituted benzo [b]thiophene.
Description is made firstly on the aprotic polar solvent used throughout the first and second reactions of the present invention.
Specific examples of the aprotic polar solvent used throughout the first and second reactions of the present invention are N-methylpyrrolidone, N-octylpyrrolidone, 1,3-dimethylimidazolidinone, diethylacetamide, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, sulfolane, tetramethylurea, hexamethylphosphoric triamide and N-methyl-N-phenylformamide. These aprotic polar solvents can be used in any combination of two or more of them.
In the present process there may be used, as th
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Hiyoshi Hidetaka
Saito Yoshinori
Yazawa Naoto
Ihara Chemical Industry Co. Ltd.
Lambkin Deborah
Raymond Richard L.
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