Synthesis of 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid

Christopher M. Hattan; Jalil Shojaie; Serrine S. Lau; M. W. Anders

doi:10.1080/00397911.2011.587078

Synthesis of 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid

Christopher M. Hattan, Jalil Shojaie, Serrine S. Lau, M. W. Anders

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.

Original language	English (US)
Pages (from-to)	1-8
Number of pages	8
Journal	Synthetic Communications
Volume	43
Issue number	1
DOIs	https://doi.org/10.1080/00397911.2011.587078
State	Published - Jan 1 2013
Externally published	Yes

Keywords

Alkyne activation
antioxidants
methimazole
thiols
β-oxidation

ASJC Scopus subject areas

Organic Chemistry

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10.1080/00397911.2011.587078

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@article{0c37004bf6b84cb0827d616ba9509fa4,

title = "Synthesis of 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid",

abstract = "The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.",

keywords = "Alkyne activation, antioxidants, methimazole, thiols, β-oxidation",

author = "Hattan, {Christopher M.} and Jalil Shojaie and Lau, {Serrine S.} and Anders, {M. W.}",

note = "Funding Information: This work was supported by the P30 ES006694 Southwest Environmental Health Sciences Center (SSL), T32 ES007091 and T32 ES016652 (both to C. M. H.), at the University of Arizona. We would like to acknowledge Dr. Richard T. Miller for critical review of the manuscript.",

year = "2013",

month = jan,

day = "1",

doi = "10.1080/00397911.2011.587078",

language = "English (US)",

volume = "43",

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journal = "Synthetic Communications",

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T1 - Synthesis of 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid

AU - Hattan, Christopher M.

AU - Shojaie, Jalil

AU - Lau, Serrine S.

AU - Anders, M. W.

N1 - Funding Information: This work was supported by the P30 ES006694 Southwest Environmental Health Sciences Center (SSL), T32 ES007091 and T32 ES016652 (both to C. M. H.), at the University of Arizona. We would like to acknowledge Dr. Richard T. Miller for critical review of the manuscript.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.

AB - The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2- ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.

KW - Alkyne activation

KW - antioxidants

KW - methimazole

KW - thiols

KW - β-oxidation

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DO - 10.1080/00397911.2011.587078

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JO - Synthetic Communications

JF - Synthetic Communications

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ER -

Synthesis of 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid

Abstract

Keywords

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