Methyl 3-hydroxythiophene-2-carboxylates

Chlorination of methyl 3-hydroxythiophene-2-carboxylate by sulfuryl chloride gives the 2-chloro-thiophen-3-one (250). This reacts with a series of nucleophiles at position 5 by an addition-elimination process, giving 5-substituted-3-hydroxythiophene-2-carboxylates <86JCR(S)168, 87JHC1301,90JHC315>. 

Methyl 3-hydroxythieno[2,3-Zr)thiophene-2-carboxylates were also synthesized by cyclization of substituted methyl 3-hydroxythiophene-2-carboxylates (91MI1). 

The presence of alkyl, or other groups, both stabilise the oxy compounds and the double bond to which they are attached. In these more stable compounds alternative tautomers are found, thus 5-methyl-2-hydroxythiophene exists as a mixture (actually separable by fractional distillation ) of the two enone tautomers and ethyl 5-hydroxythiophene-2-carboxylate is in the hydroxy-form to the extent of 85%. ... 

Hydroxythiophenes from a-mercapto-carboxylic acid esters. 4-Methylpenta-2,3-dienenitrile added dropwise with stirring during 5 min. to a suspension of methyl sodium sulfidoacetate (prepared from mercaptoacetate and Na-ethoxide in abs. ethanol) in anhydrous ether, and stirred 1 hr. at room temp, after the mildly exothermic reaction has ceased -> 4-hydroxy-2-isopropylthiophene-3-carbonitrile. 

Synthesis of Thiophens by Ring-closure Reactions.— The Hinsberg reaction between a-diketones and dialkyl thiodiacetate has been used for the synthesis of a series of 3,4-disubstituted thiophen-2-carboxylates and -2,5-dicarboxylates. The corresponding condensation of ethyl phenyl glyox-ylate and methyl pyruvate with dialkyl thiodiacetate, which yields 3-phenyl-and 3-methyl-4-hydroxythiophen-2,5-dicarboxylates, proceeds through a... 

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