2 -Methoxythiophene

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. 

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

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... 

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). 

However, Mannich reactions on the thiophene nucleus are rare 2- and 3-methoxythiophenes underwent this reaction in good yield to produce the Mannich bases (88) and (89) respectively (75SC59). 

As in benzenoid chemistry, some nucleophilic displacement reactions can be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g., AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 136). Analogously, 2-methoxythiophene can be prepared in 83% yield by refluxing 2-bromothiophene in methanol containing excess sodium methoxide, along with copper(I) bromide as catalyst. For the analogous preparation of 3-methoxythiophene, addition of a polar cosolvent (e.g., l-methyl-2-pyrrolidone) is beneficial. In the case of halothiophenes, an SrnI mechanism is involved. 

Methoxide addition in basic methanolic solutions has been reported for various mononitro- and dinitrothiophenes and -selenophenes. The presence of C-2 adducts (177) has been established for each of the thiophenes and selenophenes in Table VIII.330-336 2-Nitro-3-methoxythiophene adds methoxide at C-5 in dimethyl sulfoxide to give 178.330 No adduct could be observed for 2-methyl-5-nitrothiophene under the same conditions.330... 

This is prepared by UAIH4 reduction of methyl 3-methoxythiophene-2-carboxylate, followed by workup under neutral conditions (R. A. Aitken and A. N. Garnett, unpublished data). All contact with acids must be avoided. 

Methoxy-5-(177-pyrrol-2-yl)-2-thienyl]-177-pyrrole 621 was also prepared by a cross-coupling reaction, Stille reaction in this case, between A -SEM-2-(trimethylstannyl)-l/7-pyrrole 620 and 2,5-dibromo-3-methoxythiophene in the presence of a Pd catalyst, followed by nitrogen deprotection (Scheme 126) <1997CM2876>. If Negishi coupling is applied, the main reaction product is, in this case, A -SEM-2,2 -dipyrrole, and the desired compound can be isolated only in trace amount. 

Thiophene itself undergoes Mannich reactions more sluggishly than furan or pyrrole. The Mannich reaction of 3-alkoxythiophenes and 3,4-dialkoxythiophenes has been investigated in detail <2001J(P1)2595>. The reaction of 3-methoxythiophene with secondary amines and formaldehyde in acetic acid at room temperature led to the... 

DNBF 205 is a powerful electrophile - even more powerful than the proton or/)-nitrobenzenediazonium cation. The reaction of 3-methoxythiophene with DNBF has been investigated <1997J(P2)2667>. The reaction leads to the formation of the formal product of SeAt substitution 206 in quantitative yield (Equation 96). The product could be isolated as a crystalline sodium salt. The kinetic data from this reaction provide strong support to the view that 3-methoxythiophene exhibits behavior characteristic of a vinyl ether. 

The regioselectivity observed with many nucleophilic arenes is moderate to excellent, and generally follows the pattern expected for aromatic electrophilic substitution (e.g., nitration, bromination, etc.) of the arenes. 3-Methoxythiophene reacts first at the 2-position but double arylation at the 2- and 5-positions is achieved in the absence of DME additive. 2-Ethylthiophene, 2,3-dimethylfuran, and 2,2 -bithiophene react at the expected 5-position and, similarly, thiophene reacts at the 2-position. 1,3-Dimethoxybenzene reacts exclusively at the 4-position while... 

---