Thiophenes methoxylation

The electrochemical oxidation of 2,5-dimethylthiophene in various electrolytes has been investigated (71JOC3673). In non-halide electrolytes such as ammonium nitrate or sodium acetate, the primary anodic process is the oxidation of the thiophene to the cation-radical (159). Loss of a proton, followed by another oxidation and reaction with solvent methanol, leads to the product (160) (Scheme 31). When the electrolyte is methanolic NaCN, however, nuclear cyanation is observed in addition to side-chain methoxylation. Attack by cyanide ion on the cation-radical (159) can take place at either the 2- or the 3-position, leading to the products (161)-(163) (Scheme 32). 

When benzothiophene and its derivatives are oxidized in methanol/KOH at a Pt anode, 2,3- and 4,7-methoxylated products are obtained [212, 213], and it was shown that their formation is temperature dependent [213]. The electrooxidation of benzothiophene and 2-methyl- and 3-methyl-benzo[Z ]thiophene in methanol containing NaCN leads to heterocyclic ring-substitution products [214]. 

Anodic oxidation in methanol of thiophene and substituted thiophenes at low temperatures (—20 to — 30°C) results in methoxylation and ring opening with loss of sulfur as SO2 [190]. From thiophene is isolated butenedialdehyde tetramethylacetal, some methoxysuc-cinic dialdehyde tetramethylacetal, and a small amount of methyl y6-formylpropionate. In general, oxidation of thiophenes results in the formation of derivatives of a, -unsaturated y-dicarbonyl compounds or y-keto esters. Cyanomethoxylation of 2,5-dimethyl thiophene yields mainly cis- and rm/i5-2-cyano-5-methoxy-2,5-dimethyldihydrothiophene and 3-cyano-2,5-dimethylthiophene [191]. 

The anodic methoxylation of aromatic compounds such as naphthalene [41], anthracene [42], alkylbenzenes [31,43], phenols [44-46], anisoles [33,47-54] and other alkoxyben-zenes [53], methoxynaphthalenes [33], methoxyanthracenes [50,54], inden-l-ones [55], / a/r/-substituted anilides [56] and heterocyclic compounds, such as furans [57], thiophenes [58], and pyrroles [59], has received considerable attention. 

The reactions between 2-alkyl-quinolines and dimethyl acetylenedicarboxy-late have been further investigated, and a mechanism for the formation of the cyclobutapyrroloquinoline (143) from 2-methylquinoline has been proposed. The reaction of the 2-(benzylsulphonyl)quinoline (144) with sodium methoxide unexpectedly gives the 2-methoxylated benzyl ketone (145) via the intermediate formation of a thiophen SS-dioxide. " ort/io-Lithiation of 2-,3-,5-,6-, and 7-fluoroquinolines has been achieved by the reaction at a low temperature (—60°C) with lithium di-isopropylamide in THF, this system obviating the problem of addition reactions.A variety of... 

Thiazole does not have a relative diene character possessed by other heterocycles, unlike other heterocyclic structures such as 1,3-oxazole and furan. So 1,3-thiazoIe does not undergo Diels-AIder reactions very easily due to the its low reactivity on accoimt of greater aromaticity than oxazoles as well as due to highly nucleophilic thiazole. However, there are exceptions where an intramolecular Diels-AIder reaction of thiazole with alkyne activated by a methoxyl group is facilitated to produce a thiophene, albeit in a rather low yield of 48%, after three days at reflux in degassed mesitylene. This happens through the extrusion of acetonitrile. 

Direct etherification via C—H activation is rarely documented, especially on heterocycles. Shi used an N-(pyridinyl-2-yl)isopropylcarboxamide as directing group for the direct methoxylation of heteroarenes including pyridines, pyridazines, and thiophenes (137 138) (Scheme 69)... 

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