# US 5,708,185 A · Process for producing 1-hydroxythienoimidazole carboxylic acid and thienoimidazole carboxylic acid > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,708,185 A - Document ID: US5708185A - Status: Granted - Kind: A - Application number: 08/773,354 - Filed: 1996-12-26 - Granted: 1998-01-13 - Earliest claimed: 1995-12-26 - Assignees: Sumitomo Chemical Company, Limited - Inventors: Norihiko Hirata; Yasunobu Miyamoto; Masahiko Mizuno; Toshiya Takahashi - Web page: https://patentgrep.com/patent/US5708185A ## CPC - C07D 495/04: Ortho-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract A process for producing 1-hydroxythienoimidazole carboxylic acid represented by formula (2): ##STR1## wherein R.sup.1 and R.sup.2 are as defined in the specification; wherein said process comprises the steps of: (a) reacting thienoimidazole represented by formula (1) with 1,4-dihalogenodimagnesium butane, in the presence of tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent to produce a reaction mixture: ##STR2## wherein R.sup.1 and R.sup.2 are as defined above; (b) adding the reaction mixture obtained in said step (a) and, optionally, carbon dioxide, to: (i) a solution comprising carbon dioxide and tetrahydrofuran, or (ii) a solution comprising carbon dioxide, tetrahydrofuran and an dramatic solvent to give a reaction liquid; and (c) hydrolyzing said reaction liquid. ## Claims ### Claim 1 A process for producing 1-hydroxythienoimidazole carboxylic acid represented by formula (2): ##STR8## wherein R.sup.1 and R.sup.2 are each selected from the group consisting of an aralkyl group and allyl group, wherein said aralkyl group and allyl group are unsubstituted or substituted by one member selected from the group consisting of an alkyl group, alkoxyl group, nitro group, and halogen atom; wherein said process comprises the steps of: (a) reacting thienoimidazole represented by formula (1) with 1,4-dihalogenodimagnesium butane, in the presence of tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent to produce a reaction mixture: ##STR9## wherein R.sup.1 and R.sup.2 are as defined above; (b) adding the reaction mixture obtained in said step (a) and, optionally, carbon dioxide, to: (i) a solution comprising carbon dioxide and tetrahydrofuran, or (ii) a solution comprising carbon dioxide, tetrahydrofuran and an aromatic solvent to give a reaction liquid; and (c) hydrolyzing said reaction liquid. ### Claim 2 (depends on 1) The process according to claim 1, wherein the step (a) is carried out further in the presence of a tertiary amine. ### Claim 3 (depends on 1) The process according to claim 1, wherein said aromatic solvent in step (a) and said aromatic solvent in step (b) are selected from the group consisting of benzene, toluene, o-xylene, m-xylene, p-xylene and mixed xylene. ### Claim 4 (depends on 2) The process according to claim 2, wherein said tertiary amine is N,N,N',N'-tetramethylethylenediamine. ### Claim 5 (depends on 1) The process according to claim 1, wherein said solution comprising carbon dioxide and tetrahydrofuran and said solution comprising carbon dioxide, tetrahydrofuran and aromatic solvent are saturated with carbon dioxide. ### Claim 6 (depends on 1) The process according to claim 1, wherein thienoimidazole represented by formula (1) is added to the reaction in step (a) either directly or in a cake state or slurry state, wherein said cake state and slurry state are made by adding a small amount of either tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent. ### Claim 7 A process for producing 1-hydroxythieno carboxylic acid represented by formula (2): ##STR10## wherein R.sup.1 and R.sup.2 are each selected from the group consisting of an aralkyl group and allyl group, wherein said aralkyl group and allyl group are unsubstituted or substituted by one member selected from the group consisting of an alkyl group, alkoxyl group, nitro group, and halogen atom; wherein said process comprises the steps of: (a) reacting a thienoimidazole represented by formula (1) with 1,4-dihalogenodimagnesium butane, in the presence of tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent to produce a reaction mixture: ##STR11## wherein R.sup.1 and R.sup.2 are as defined above; and wherein said thienoimidazole represented by formula (1) is added to said 1,4-dihalogenodimagnesium butane either directly or in a cake state or slurry state, wherein said cake state and slurry state are made by adding a small amount of either tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent; (b) reacting said reaction mixture obtained in step (a) with carbon dioxide to produce a reaction liquid; and (c) hydrolyzing said reaction liquid. ### Claim 8 (depends on 7) The process according to claim 7, wherein said step (a) is carried out in the presence of a tertiary amine. ### Claim 9 (depends on 7) The process according to claim 7, wherein said aromatic solvent in said step (a) between said thienoimidazole represented by formula (1) and 1,4-dihalogenodimagnesium butane and used in the mixed solvent to form said thienoimidazole represented by formula (1) in the cake or slurry state, is selected from the group consisting of benzene, toluene, o-xylene, m-xylene, p-xylene and mixed xylene. ### Claim 10 (depends on 8) The process according to claim 8, wherein said tertiary amine is N,N,N',N'-tetramethylethylenediamine. ### Claim 11 A process for producing thienoimidazole carboxylic acid represented by formula (3): ##STR12## wherein R.sup.1 and R.sup.2 are each selected from the group consisting of an aralkyl group and allyl group, wherein said aralkyl group and allyl group are unsubstituted or substituted by one member selected from the group consisting of an alkyl group, alkoxyl group, nitro group, and halogen atom; wherein said process comprises the steps of: (a) reacting thienoimidazole represented by formula (1) with 1,4-dihalogenodimagnesium butane, in the presence of tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent to produce a reaction mixture: ##STR13## wherein R.sup.1 and R.sup.2 are as defined above; (b) adding the reaction mixture obtained in said step (a) and, optionally, carbon dioxide, to: (i) a solution comprising carbon dioxide and tetrahydrofuran, or (ii) a solution comprising carbon dioxide, tetrahydrofuran and an aromatic solvent to give a reaction liquid; and (c) hydrolyzing and dehydrating said reaction liquid. ### Claim 12 A process for producing thienoimidazole carboxylic acid represented by formula (3): ##STR14## wherein R.sup.1 and R.sup.2 are each selected from the group consisting of an aralkyl group and allyl group, wherein said aralkyl group and allyl group are unsubstituted or substituted by one member selected from the group consisting of an alkyl group, alkoxyl group, nitro group, and halogen atom; wherein said process comprises the steps of: (a) reacting a thienoimidazole represented by formula (1) with 1,4-dihalogenodimagnesium butane, in the presence of tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent to produce a reaction mixture: ##STR15## wherein R.sup.1 and R.sup.2 are as defined above; and wherein said thienoimidazole represented by formula (1) is added to said 1,4-dihalogenodimagnesium butane either directly or in a cake state or slurry state, wherein said cake state and slurry state are made by adding a small amount of either tetrahydrofuran or a mixed solvent comprising tetrahydrofuran and an aromatic solvent; (b) reacting said reaction mixture obtained in step (a) with carbon dioxide to produce a reaction liquid; and (c) followed by hydrolyzing and dehydrating the reaction liquid. ### Claim 13 (depends on 1) The process according to claim 1, wherein at least one of said R.sup.1 and R.sup.2, in formula (1) and formula (2), is a benzyl group. ### Claim 14 (depends on 7) The process according to claim 7, wherein at least one of said R.sup.1 and R.sup.2, in formula (1) and formula (2), is a benzyl group. ### Claim 15 (depends on 11) The process according to claim 11, wherein at least one of said R.sup.1 and R.sup.2, in formula (1) and formula (3), is a benzyl group. ### Claim 16 (depends on 12) The process according to claim 12, wherein at least one of said R.sup.1 and R.sup.2, in formula (1) and formula (3), is a benzyl group.