2-Acetyl-5-methylthiophene

Acetyl-5-methylthiophene (Methyl 5-methyl-2-thienyl ketone) COCHj CH3... 

Scope of the Reaction. The above procedure has lieen used to obtain 1168-1220 g. of 2-acetyl-5-methylthiophene from 2-methylthiophene, b.p. 84.5° at 2 mm., in.p. 27-28°. The reaction gives yields of the same high order If carried out with one or two moles of 2- or 3-niethylthiophene. 

J.20) Ethanone, l-(5-methyl-2-thienyl)-, 1-(5-methyl-2-thienyl)ethanone, 2-acetyl-5-methylthiophene 113679-74-8]... 

De-f-butylation during electrophilic substitution is a fairly common phenomenon in thiophene chemistry. The A1C13 catalyzed acylation of 2-methyl-5-f-butylthiophene with acetyl chloride gives 3,5-diacetyl-2-methylthiophene as the main product (69BSF991). Treatment of the acid (324) with PPA in toluene results in ring closure and de-r-butylation to form (325) (73BSF343). 

Irradiation of 3-methylthiophene in hexafluoropropan-2-ol with added methanesulfonic acid brings about single electron-transfer oxidation and this yields a species that has been identified as the Z>w-protonated radical-cation of (289). Irradiation of 2-acetyl-5-iodothiophene leads to cleavage of the C-I bond and the resultant radical adds to acrylonitrile to afford the adduct (290) in moderate yield. Reactions of this type have also been described for iodofuran and iodopyrrole derivatives and in the latter case 4,5-diiodo-l//-pyrrole-2-carboxaldehyde reacts photochemically with thiophene to give... 

Reactions at Benzylic Positions. - The catalytic oxidation, using a cobalt bromide catalyst, of 2,5-dimethylthiophen to the dialdehydeof 3-methyl-2-ethylthiophen to 2-acetyl-3-methylthiophen and l-(3-methyl-2-thienyl)-ethyl acetate, of the four isomeric methyl acetothienones to the corresponding acetylthiophencarboxylic acids, and of 2-acetoxymethylthio-phen to thiophen-2-carboxylic acid has been reported. The Wittig reaction between 2- and 3-thenyltriphenylphosphonium salts and crocetin dialdehyde has been used for the synthesis of carotenoid analogues with terminal thiophen rings. ... 

Nitration of thiophene needs to be conducted in the absence of nitrous acid which can lead to an explosive reaction the use of acetyl nitrate or nitronium tetrafluoroborate are satisfactory. Invariably the major 2-nitro-product is accompanied by approximately 10% of the 3-isomer. Further nitration of either 2- or 3-nitrothiophenes" also leads to mixtures - equal amounts of 2,4- and 2,5-dinitrothiophenes from the 2-isomer, and mainly the former from 3-nitrothiophene. Similar, predictable isomer mixtures are produced in other nitrations of substituted thiophenes, for example 2-methylthiophene gives rise to 2-methyl-5- and 2-methyl-3-nitrothiophenes, and 3-methylthiophene gives 4-methyl-2-nitro- and 3-methyl-2-nitrothiophenes, " in each case in ratios of 4 1. 

Electrophilic Substitution Reactions of Monocyclic Thiophens.— The reaction of thiophen with iV-(methylsulphonyl)hexafluoroacetoneimine gave (34) in 57% yield. Nitration of 3-(diacetoxymethyl)thiophen with acetyl nitrate or cupric nitrate in acetic anhydride gave the 5- and 2-isomers in the ratio 2.3 3.0. The product composition from the nitration of 3-methylthiophen was determined to be 3-methyl-2-nitrothiophen, 78% 3-methyl-4-nitrothiophen, 2.1% and 4-methyl-2-nitrothiophen, 20%. ... 

The reactivity of thiophen has also been compared with that of seleno-phen and the relative reactivities in five electrophilic substitutions have been determined by kinetic or competitive procedures. The results have been compared with those available in the literature for furan. In all the reactions examined, selenophen exhibited a reactivity intermediate between those of furan and thiophen. p-Constants for electrophilic substitution of substituted thiophens are usually smaller than in the benzene series. A comparison of the trifluoroacetylation of a series of substituted thiophens and furans yielded p-values of — 7.4 and — 10.7 respectively. The observed order of substrate selectivity in the trifluoroacetylation (furan > thiophen) thus parallels the positional selectivity in electrophilic substitution, the oi ratio always being larger in furans than in thiophens. The relative importance of primary steric effects in benzene and thiophen has been investigated by determination of the isomer distributions in the acetylations of 2- and 3-methylthiophen, 2- and 3-t-butylthiophen, and toluene and t-butylbenzene. Steric hindrance is less significant in the thiophen series owing to the more favourable geometry. - ... 

The AlCls-catalysed alkylation of 2-methylthiophen with t-butyl chloride in carbon disulphide yields a mixture of 80% 2-methyl-5-t-butylthiophen and 20% 2-methyl-4-t-butylthiophen in 40% yield, and about 30% of 3,5-di-t-butyl-2-methylthiophen. During the Aldg-catalysed acylation of 2-methyl-5-t-butylthiophen with acetyl chloride, cleavage of the t-butyl occurred, yielding 3,5-diacetyl-2-methylthiophen as the main product. However, when succinic acid monomethyl ester chloride was used, the acylation proceeded normally, yielding (58). A new method of synthesizing... 

Dihydrothiophene as a bridging unit was also investigated instead of cyclopentene [70]. In this case, acetylation of 2-chloro-5-methylthiophene in the presence of AICI3 gave C-4-acylated product in 78% yield (Scheme 52) [70]. 

Thiophenes are found in many foods and often contribute significantly to their organoleptic properties. They are important as aromatic components of meat, roasted coffee, roasted nuts, onions and other foods. For example, while unsubstituted thiophene has an odour reminiscent of benzene, 2-methyl substituted thiophenes positively affect the flavour of canned meat. 2-Methylthiophene odour is described as green, heated onion, sidfurous and sweet dimethylthiophenes are important components of fried onion aroma, 2-acetyl-3-methylthiophene is reminiscent of honey and roasted nuts and 3-acetyl-2,5-dimethylthiophene has a sidfurous odour. 

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