Methyl thioglycolate

The synthesis of benzo[6]thiophenes from o-nitrobenzaldehydes or o-nitrobenzonitriles and methyl thioglycollate can be viewed as an extension of the foregoing approach (Scheme 64) (72JOC3224). 

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

Halogenated- ,/S-unsaturated ketones or aldehydes are reacted with methyl thioglycolate and cyclized with alkali alcoholate/ Thus jS-bromobenzalacetone (75) gives methyl 3-methyl-5-phenyl-2-thio-phenecarboxylate (76) and from a-methyl-j5-chlorocrotonaldehyde (77), 4,5-dimethyl-2-thiophenecarboxylate (78) is obtained. 

Using a,jS-dihalogenonitriles instead of carbonyl derivatives in the reaction with methyl thioglycolate leads to methyl 3-amino-2-thio-phenecarboxylates. Thus, a, -dichlorobutyronitrile (79) gave methyl 3-amino-5-methyl-2-thiophenecarboxylate (80)... 

The pyrimido[6,l-F][l,4]oxazine-6,8-diones 164 (Y = O) and pyrimido[6,l-c][l,4]thiazine-6,8-diones 164 (Y = S) were synthesized by treating 6-chloromethyl-uracil with methyl glycolate 162 (Y = O) or methyl thioglycolate 162 (Y = S), respectively, and reacting the resulting 163 with DMF-dimethyl acetal (Scheme 20) <2004W02004/014354>. 

Methyl thienyl ketone, a57 Methyl thioglycolate, m298... 

Dichloropyridine-4-carboxaldehyde reacts with thiophenol to produce a diaryl sulfide. The diaryl compound and methyl thioglycolate undergo an aldol-type cyclization reaction in the presence of a weak base to afford 4-substituted thieno[2,3-f]pyridine derivative 121 (Scheme 38) <2002JOC943>. 

If the sulfur atom has been introduced in another way in order to form, for example, 485, oxidation of the sulfur atom by treatment with sodium borate leads to a mixture of the corresponding sulfoxides and sulfones (major product) in a total yield of 95%. Now treatment with methyl thioglycolate in basic medium gives 486 (Equation 182) <2001SC725>. 

Heating the thiazolo[5,4-d]pyrimidine obtained by triethylamine catalysed condensation of 6-chloro-l,3-dimethyl-5-nitrouracil with methyl thioglycolate with an equimolar amount of DMAD in 5% aqueous methanol gives the pyrrolo[3,2-d]pyrimidine 1 in 71% yield. 

Scheme 34 a Methyl thioglycolate, reflux, 16 h b ammonia, methanol, sealed tube, 80 °C, 6 days c 2-sulfanyl acetamide, methanol, reflux, 16 h [44]... 

Methods based on the pyridine to thieno[3,2-c]pyridine transformation are less well developed. Most of the above-described procedures are based on the nucleophilic displacement of the substituent at position 4 of the pyridine ring with a sulfur-containing fragment followed by cyclization of the resulting product. For example, the reaction of 4-chloropyridines 286 with methyl thioglycolate produced 287 and 288 in one step as a result of the replacement of the chlorine atom and Thorpe or Thorpe Dieckmann cyclization (1987JHC85). 

The regiospecific nucleophilic displacement of 1,2-cyclic sulfamidates 130 with methyl thioglycolate or a-amino esters 130 can be accompanied by lactamization (thermal, base mediated, or cyanide catalyzed) to give thiomorpho-lin-3-ones and piperazin-2-ones 131 (Scheme 19) <20030L811>. If malonate esters, phosphonate-stabilized esters, or aryl-substituted enolates were used as nucleophiles in this reaction, trisubstituted pyrrolidines were obtained in high yield <2004OL4727>. 

Trifluoromethyl-a-(p-toluenesulfonyloxyimino)benzylcyanide Methyl thioglycolate Triethylamine Potassium hydroxide... 

To a stirred solution of 3-trifluoromethyl-a-(p-toluenesulfonyloxyimino) benzylcyanide in methanol containing methyl thioglycolate was added dropwise over a 30 min period triethylamine. The reaction mixture was stirred at room temperature for 4 h following complete addition, and then was cooled to 0°C and filtered. The precipitate which was collected was recrystallized from hexane and ethyl acetate to provide methyl 3-(3-trifluoromethylphenyl)-4-amino-5-isothiazolecarboxylate, melting point 94°-95°C. 

Tetrahydrothiophenone 130 was prepared in 52% yield by addition of sodium salt of methyl thioglycolate 129 and methyl-4-terf.-butoxybut-2-enoate 128. 

Electrospray ionization mass spectrometry (ESI-MS) of the reactions between methyl thioglycolate and bismuth(m) chloride in absolute ethanol, 95% ethanol, or methanol revealed the presence of mono-, bis-, and tris-ester complexes 95-97 as well as ligand-bridged dibismuth species 98 and 99 <2003IC3136>. 

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