Methoxythiophenes

Methoxythiophene and 3-cyanothiophene have been prepared from 3-bromothiophene by means of a cupric oxide-catalyzed Williamson synthesis and by reaction with cuprous cyanide in quinoline, respectively. 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

The methoxy group of methoxythiophenes shows a reactivity which, in many respects, differs appreciably from the reactivity of the corresponding anisoles. Thus, in an attempted Hoesch synthesis with 5-methoxy-2-thenylcyanide (167) and phloroglucinol, the methoxy group reacted instead and 5-(2, 4, 6 -trihydroxyphenyl)-2-thenyl cyanide (168) was obtained. 2-Thenyl cyanide reacts normally in the Hoesch synthesis, Likewise, upon acid hydrolysis of the reaction product of 5-methoxy-2-thienyllithium with benzophenone, (169) was obtained instead of the expected substituted methoxythiophene. No defined products could be isolated from the attempted Claisen rear-... 

Furthermore, the preparation and reactions of 2-methoxythiophene were studied by Sice (70). This compound was obtained by a copper catalysed Williamson synthesis. It was also found that iodothiophene reacted readily with sodium alkoxides, whereas bromothiophene reacted slowly and chlorothiophene did not react at all. Sodium iodide accelerated the reaction of bromothiophene. The ortho, para orienting alkoxy group on carbon atom 2 increased the directive influence of the sulphur atom to the 5 position but competed with it to induce some attack on the 3 position by electrophilic reagents (nitration, acylation). The acylation of 2-methoxythiophene with stannic chloride at low temperatures furnished a mixture of two isomers. The 5-methoxy-2-acetothienone was obtained in higher yield and was identified by its ultraviolet absorption spectrum. 

Scheme 3 First coupling steps after the oxidation of 3-methylthio- or 3-methoxythiophene (pyrrole) (2).

Treatment of 2-methoxy-5-methylthiophene with NBS gave a 4 1 mixture of 3- and 4-bromo products, with some 3,4-dibromination also evident. The dibromination became more significant when 2 mol of NBS were used. Similarly 2-methoxythiophene gave the 3,5-dibromo derivative (84BAU1447). Bromination of 2-(2 -thienyl)-thiophenes (21) and 2-(3 -thienyl)-thiophenes gave the 5- and 2-bromo products in high yield [79CS157 91H(32)1805]. With four molar equivalents of bromine in acetic acid the tetrabromo derivative (22) was obtained in 97% yield. Reduction removed the 5,5 -bromines preferentially [91H(32)1805] (Scheme 9). This... 

Problem 20.12 Write structures for the mononitration products of the following compounds and explain their formation (a) 3-nitropyrroIe, (b) 3-methoxythiophene, (c) 2-acetyIthiophene, (rf) 5-methyl-2-methoxy-thiophene, (e) 5-methylfuran-2-carboxylic acid. <... 

As expected, there is a general tendency for the nucleophile to attack the a position. This preference is preserved even when a methoxy group occupies a fi position (formation of 133 from 2-nitro-3-methoxythiophene). H-NMR evidence indicates that in methanol solution an adduct at C-2 of 2-methoxy-5-nitrothiophene (134) is formed as an intermediate in a decomposition sequence probably involving ring opening.176 However, in DMSO no evidence of such an adduct was recorded.17... 

Another electrophilic reagent which has been used to introduce an oxygen function is alkyl peroxybenzoate. Thus 5-methoxy-2-thienyllithium on reaction with r-butyl peroxy-benzoate gives 2-r-butoxy-5 -methoxythiophene in 72% yield (790R(26)1>. 

Perfluorothiophene and sodium methoxide yield trifluoro-5-methoxythiophene (l).115... 

There have been several studies utilizing the ability of 4,6-dinitrobenzofuroxan (DNBF) to act as a super-electrophile. It has been shown that the initial product of its reaction with phenoxide ions is the O-bonded adduct (29), although this rearranges to give die C-bonded adduct.117 The reaction of DNBF with ethyl vinyl ether yields a dihydrooxazine A -oxidc cycloadduct as a mixture of two diastereoisomers, and in the presence of excess ether a di-adduct (30) is formed.118 Rate constants have been reported for the reaction of DNBF with 3-methoxythiophene in DMSO-water mixtures. The reaction results in a er-adduct which is the product of Se-At substitution in the thiophene, and the results were used to probe the carbon basicity of the thiophene derivative.119... 

The electropolymerization of 3-methoxythiophene (MOT) was performed in an aqueous micellar medium containing sodium dodecylsulfate (SDS) as a surfactant. The electronic absorption spectra, the fluorescence excitation and emission spectra, and the quantum yields of 546, were measured in different solvents of various polarities and hydrogen bond abilities (89SM(28)C487 98SM(93)175 00JF107 00POLLDG4047 ... 

SA1391). Poly(3-methoxythiophene-polybithiophene composite film shows an absorption at 510 nm (99PCCP1731). 

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