Sodium thiophene-2-carboxylate

Silver oxide, easily prepared from silver nitrate and sodium hydroxide, is probably the best reagent for the preparation of pure acids from aldehydes. An additional advantage is that it does not attack other easily oxidizable groups in the molecule. Typical examples are 3-thiophene-carboxylic acid (97%), palmitic acid (98%), and anthracene-9 carboxyIic acid (72%). Its use in the preparation ol olefinic acids from olefinic aldehydes is illustrated by the preparation of 2-methyI-2-pentenoic acid (60%). Organic peracids have also been used in the oxidation of aldehydes to carboxylic acids. ... 

Sodium trifluoroacetate, in the presence of copper(l) iodide, was also used as trifluoromethyl source to replace halogen by trifluoromelhyl group in the thiophene system. Sodium trifluoroacetate was decarboxylated, forming fluoroform, when heated alone in aqueous N-methylpyrrolidin-2-one. The addition of copper(l) iodide increased the rate of decarboxylation dramatically. The mechanism of this process was explored and an intermediate [CFsCul] was proposed. Introduction of higher perfluoroalkyl groups from their corresponding sodium perfluoroalkane carboxyl-ates was also shown to be possible [58],... 

Benzoic acid and naphthoic acid are formed by the oxidative carbonylation by use of Pd(OAc)2 in AcOH. t-Bu02H and allyl chloride are used as reoxidants. Addition of phenanthroline gives a favorable effect[360], Furan and thiophene are also carbonylated selectively at the 2-position[361,362]. fndole-3-carboxylic acid is prepared by the carboxylation of 1-acetylindole using Pd(OAc)2 and peroxodisulfate (Na2S208)[362aj. Benzoic acid derivatives are obtained by the reaction of benzene derivatives with sodium palladium mal-onate in refluxing AcOH[363]. 

Rates of debromination of bromonitro-thiophenes and -selenophenes with sodium thio-phenoxide and sodium selenophenoxide have been studied. Selenophene compounds were about four times more reactive than the corresponding thiophene derivatives. The rate ratio was not significantly different whether attack was occurring at the a- or /3-position. As in benzenoid chemistry, numerous nucleophilic displacement reactions are found to 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 77) (75JCS(P1)1390). 

The synthesis of the four monocarboxylic acids of dibenzothiophene has been recorded in the previous review. However, several modified preparations have since been described. Ethyl 1-dibenzothiophene-carboxylate has been synthesized from 2-allylbenzo[6]thiophene (Section IV,B, 1) hydrolysis afforded the 1-acid (57% overall). In a similar manner, 3-methyl-1-dibenzothiophenecarboxylic acid was obtained from the appropriately substituted allyl compound. This method is now the preferred way of introducing a carbon-containing substituent into the 1-position of dibenzothiophene. 2-Dibenzothiophenecarboxylic acid has been prepared by oxidation of the corresponding aldehyde or by sodium hypoiodite oxidation of the corresponding acetyl compound. Reaction of 2-acetyldibenzothiophene with anhydrous pyridine and iodine yields the acetyl pyridinium salt (132) (92%), hydrolysis of which yields the 2-acid (85%). The same sequence has been carried out on 2-acetyldibenzothiophene 5,5-dioxide. The most efficient method of preparing the 2-acid is via carbonation of 2-lithio-... 

Thus, methyl (5-acetyl-2-thienyIthio)acetate (62) was prepared by acetylation of 61. Addition of a second acetyl group in the presence of excess AlClj led to methyl (3,5-diacetyl-2-thienylthio)acetate (63), which, on heating in ethanolic sodium ethoxide yielded about 95% of 5-acetyl-3-methylthieno[2,3-6]thiophene-2-carboxylic acid (64) reduction of acid 64 resulted in 5-ethyl-3-methylthieno[2,3-6] ophene 2-carboxylic add (65), identical with the acid obtained by cyclization of methyl (3-acetyl-5-ethyl-2-thienylthio)acetate. Decarboxylation of acid 64 gave 5-acetyl-3-methylthieno[2,3-6]thiophene (66) [Eq. (25)1. 

Dihydrothieno[3,4-Z ]thiophene (131) was prepared by two methods. In the first (Scheme 8), chloromethylation of methyl thiophene-2-carboxylate (132) forms methyl 2,3-bischloromethyl-thiophene-5-carboxylate (133) (85%) cyclization of 133 with sodium sulfide in methanol yields (66%) methyl 4,6-dihydrothieno[3,4-i]-thiophene-2-carboxylate (134). Peroxide oxidation of 134 gives 2-methoxycarbonyl-4,6-dihydrothieno[3,4-h]thiophene 5,5-dioxide (135) and hydrolysis of 134 followed by metaperiodate oxidation furnishes the sulfoxide (91). Thienothiophene (131) was produced by hydrolysis and decarboxylation of 134. As indicated above, the sulfoxide (91) was used for the synthesis of thieno[3,4-6]thiophene (3). 

Analogous oxidation of methyl 4,6-dihydrothieno[3,4-i]thiophene-2-carboxylate (134) leads to the 5,5-dioxide (135) (70%) hydrolysis and subsequent oxidation with sodium metaperiodate at 0° (cf. Leonard and Johnson ) results in 2-carboxy-4,6-dihydrothieno[3,4-i]thiophene-5-oxide (91) (74%). ... 

The insertion of carbon monoxide into azolylpalladium complexes proceeds readily and in most cases leads to the formation of carboxylic acid derivatives or ketones. In a modified version of the carbonylation 3-bromothiophene was reacted with carbon monoxide in the presence of sodium formate. This reagents converts the intermediate acylpalladium formate complex, through the release of carbon dioxide into the acylpalladium hydride (c.f 7.47.), which in turn releases thiophene carboxaldehyde as the sole product (6.62.),92 If sodium formate was replaced... 

Thienylsodium has been prepared from thiophene by treatment with bromobenzene and sodium amalgam (63AHC(l)l). 2-Methylthiophene has also been metallated at position 5 with n-butylpotassium and n-butylcaesium subsequent reaction with C02 gave the carboxylic acid (75BSF1302). 

Hinsburg first reported that various a-dicarbonyl compounds (256) condensed with thiodiglycolic esters in the presence of alcoholic sodium ethoxide to give various substituted thiophene-2,5-dicarboxylic esters (257). R1 and R2 in (256) could be H, OH, alkyl, OR, aryl or carboxyl groups o-quinones will also condense. If the condensation is carried out in aqueous alcohol, as is the case when glyoxal (256 R1 = R2 = H) is used, the thiophene-2,5-dicarboxylic acid is isolated directly. Pyruvic acid gives the half-ester of (257 R1 = Me, R2 = OH). The earlier work has been reviewed (52HC(3)l). 

The (aminomethyl)thiophene-2-carboxylic acid isomers were prepared from the corresponding methylthiophene-2-carboxylic acid esters, as exemplified for the 3-(aminomethyl) isomer 79 (Scheme 22))66 The 4-(aminomethyl) isomer was prepared in the same way, but with a low yield for the bromination step (7%))66,111 For the 5-(aminomethyl) isomer the bromomethyl compound was reacted with sodium azide, followed by catalytic reduction)74 The corresponding furan and pyridine analogues were prepared similarly. 

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