Nitrothiophenes synthesis

Sodium thenoate is bromodecarboxylated in low yield, slower than sodium anisate, but more rapidly than sodium benzoate. However, the Hunsdiecker reaction with silver salts has been used preparatively for the synthesis of 2,3-dibromo-4-nitrothiophene from 3-bromo-4-nitro-2-thiophenecarboxylic acid. ... 

Raney nickel desulfurization has been applied especially to the synthesis of different kinds of amino acids. a-Amino acids have been prepared by the Strecker synthesis of substituted thiophenealdehydes, followed by desulfurization of the thiophene a-amino acids. a-Amino-n-enantic acid, a-amino-n-caprylic acid, and norleucin have been obtained in about 50% yield from the appropriate thiophene aldehydes. From the desulfurization of thiophene -amino acids, obtained from the reaction of thiophenealdehydes with malonic acid in ammonia, aliphatic j8-amino acids, isolated as acetates, have been obtained in high yields. The desulfurization of 3-nitrothiophenes, such as (232), in ammonia leads to y-substituted amino acids (233). ... 

As part of the synthesis of reverse transcriptase inhibitors, the tctrahydropyrrolo[l,2- thieno[3,2-f ]pyrazin-5-onc 193 was made by the reduction/cyclization of the 3-nitrothiophene 192 (Equation 48) <2002H(57)97>. 

Both 2- and 3-nitrothiophenes have been synthesized by direct cyclization. While the former have been prepared with the help of type 1 reagents alone (nitromethane, bromonitromethane), the preparation of the latter has involved reagents of types 2 and 3. A synthesis in which both reactants carry nitro groups has led to 2,4-dinitrothiophenes. 

In an extension of their synthesis of 2-nitrothiophenes, Cagniant and co-workers have prepared 2-nitroselenophenes and -tellurophenes by similar procedures.32,33 Thus, the / -chloro-a,/ -unsaturated aldehyde 38 (R = Ph R = H) reacts with bromonitromethane and sodium selenide to form the 2-nitroselenophene 39. Similarly, with sodium telluride and bromonitromethane, chlorovinylaldehydes yield 2-nitrotellurophenes (40). 

The reaction of 3,4-dinitrothiophenene 89 with Grignard reagents has been shown to give thienylphenols, as exemplified by the formation of 90. A mechanistic rationale was provided to account for this unusual transformation <04EJO3566>. Synthesis of a number of 2-thienylphosphonates has been achieved by treatment of 2-chloro-3-nitrothiophenes with triethyl phosphite via a Michaelis-Arbuzov type reaction <04S668>. 

Benzylic Reactivity. 2,5-Dimethyl-3,4-dinitrothiophen has been condensed with aromatic aldehydes to give 3,4-dinitro-2,5-distyryl-thiophens. " An improved synthesis of 3-nitro-2-styryl-thiophens involves bromination of 3-methyl-2-nitrothiophen with A-bromosuccinimide, followed by a modified Wit-tig reaction. From 2,5-di(chloromethyl)thiophen, the phosphonate was prepared by the Arbusov reaction, which was used for the preparation of 2,5-distyryl-thiophens. Trichloromethyl(thienyl)carbinols have been converted into the corresponding fluoro-derivatives through the reaction with phenyl-tetrafluorophosphorane. The liquid-phase catalytic oxidation of phenyl-(2-thienyl)methane in acetic acid in the presence of cobalt(ll) acetate and sodium bromide has been investigated. ... 

Substituted nitrothiophenes serve as precursors for a variety of condensed thiophenes. The synthesis of thienopyrroles has been reviewed <85S143>. Treatment of (2-nitro-3-thienyl)methyl phenyl sulfone (497) with diethyl maleate in the presence of K2CO3 and 18-crown-6 gave the thienopyridine A -oxide (498) in 38% yield <92acs689>. The reaction apparently proceeds by Michael addition, followed by elimination of phenylsulfinate and cyclization. The starting material can be prepared by vicarious nucleophilic substitution discussed earlier. 

SCHEME 11.14 Synthesis of thieno[2,3-b]pyridine via reaction of 2-nitrothiophene with carbanion of allyl tolyl sulfone [29]. 

Scheme 109 Synthesis of 5,5-fused thiophene yl ctams initiated by 3-cyanoalkylation of 2-nitrothiophene [169]...

---