Reaction with thiophenecarboxylic acids

The dianions of methylated thiophenecarboxylic acids e.g. 155) are also readily generated by reaction with LDA they undergo preparatively useful reactions with a range of carbon electrophiles (80JOC4528). 

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. ... 

Condensation reaction of thioglycolic acid derivatives with a,P-acetylenic esters, which upon treatment with base result in the formation of 3-hydroxy-2-thiophenecarboxylic acid derivatives. 

Oxidation of 2-acetyldibenzothiophene with peracetic acid yields the corresponding sulfone (86%) and with sodium hypoidite, 2-dibenzo-thiophenecarboxylic acid. A color reaction for 2-acetyldibenzothiophene has been reported. ... 

Reaction of pyrocatechol dichloromethylene acetaP (133) with dibenzothiophene in the presence of titanium tetrachloride yields o-hydroxjrphenyl-2-dibenzothiophenecarboxylate (134) (100%). This reaction is closely related to the Rieche formylation of dibenzothiophene (Section VI,F, 1) in which a mixture of 2- and 4-dibenzothiophene-carboxaldehyde was obtained. The complete absence of the 4-isomer in this reaction may be due to steric effects at the 4-position between the sulfur atom and the bulky reagent. Hydrolysis of 134 yields 2-dibenzo-thiophenecarboxylic acid (70%). 4-Methyl-3-dibenzothiophenecar-... 

Hi) Carboxylic acids and derivatives. The haloform reaction on thienyl methyl ketones leads to thiophenecarboxylic acids, which can be treated with Raney nickel to produce the open-chain acids. This method has been used for the five-carbon homologation of carboxylic acids and to produce dicarboxylic acids (Scheme 51). Long-chain carboxylic acids may also be prepared by using dicarboxylic acid derivatives for the acylation of thiophenes (Scheme 52). In the synthesis of Queen substance, the precursor (213) has been generated by Raney nickel desulfurization of the appropriate thiophene-2-acetic acid derivative (79T329). 

Reaction of thienyllithium with C02 leads to thiophenecarboxylic acid. Other electrophiles which provide derivatives of carboxylic acids include ethyl chloroformate and phenyl isocyanate (Scheme 176) <790R(26)1>. 

Reaction between 3-amino-2-thiophenecarboxylic acid and R2GeCl2 with a deficiency of the L1NH2 gives the monoamino compounds 158 while an excess of lithium amide leads to formation of the diamino derivatives 159513 515-516 p(le authors suggest that intermolecular O — Ge coordination increases the lability of chlorine substituent in the intermediate 158 and favors the formation of the diamino derivatives 159510 513-515... 

The mixture described just above is cooled to 5-10° and carbonated with freshly crushed Dry Ice. A temperature rise usually accompanies carbonation. Completion of the carbonation reaction is indicated by a decrease of the temperatuie to 0-5°. Alcohol (100 ml.) is cautiously added to the mixture, accompanied by vigorous stirring, to consume any unrcacted sodium. Water (350 ml.) is then added and the aqueous phase is separated, filtered, and acidulated with 230 ml. of concentrated hydrochloric acid, and cooled. The 2-thiophenecarboxylic acid is filtered off, and after one recrystallization from water melts at 126-128°. 

Procedure. The sodium amalgam is prepared as described above (see Preparation of Sodium Amalgam Sand of 2-thiophenccarboxylic acid), blanketed with 200 ml. of ether, and the 3-methylthiophene is added. Ethyl chloride is condensed from a cylinder into a tared flask cooled in an ice bath, poured into 4(X) ml. of ice cold ether, and added rapidly to the reaction flask maintained at 10-20°. The mixture is stirred for two hours at room temperature. Carbonation is then carried out as described above under 2-thiophenecarboxylic acid and the product is purified in the same manner (one-half the amount of water and acid being required). The white crystalline needles melt at 119-121°. 

Interestingly, N-phenyl-2-thiophenecarboxamides undergo 2,3,5-triarylation accompanied by a formal decarbamoylation upon treatment with excess bromo-benzenes (Equation 10.50) [74]. The reaction involves an initial coordination-assisted 3-arylation and successive decarbamoylation which is promoted by a Pd(II) species and the stoichiometric base. A related decarboxylative arylation of 2-thiophenecarboxylic acids at the ipso-position has been reported (Equation 10.51) [75]. The introduction of an electron-withdrawing group at the 3-position of thiophene makes the 4-arylation possible, while the reaction at 2- and 5-positions precedes. Thus, the reaction of 3-cyanothiophene affords the corresponding 2,4,5-triarylated products (Equation 10.52) [74]. Whilst the mechanism for the 4-... 

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

A numerous series of compounds containing a N,O-chelating ligand, namely the derivatives of anthranilic (157) and 3-amino-2-thiophenecarboxylic (158 and 159) acids, were prepared by the reactions of organohalogermanes with esters, amides or lithium derivatives of acids510-516. 

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