Nitro acids, decarboxylation preparation

Aminobenzo[6]thiophene-2-carhoxylic acids are conveniently obtained by reduction of the corresponding nitro compound.152,185,333, 334,33c, 338,497 Djazotization of these, followed by the usual replacement reactions of the diazonium group, provides many substituted benzo[6]thiophene-2-carboxylic acids, decarboxylation of which leads to some otherwise rather inaccessible benzo[6]thiophenes. 5-Hydroxy-benzo[6]thiophene-2-carboxylic acid is most conveniently prepared from the corresponding amino compound by means of the Bucherer reaction,338,497 in which the dicarboxylic acid (303) is formed as a by-product.152... 

Other decarboxylations are noteworthy. Thermal decomposition of 2,4,6-trinitrobenzoic acid furnishes 1,3,5-trinitrobenzene in 46% yield. In an adaptation of a procedure for the decarboxylation of halogenated furoic acids with boiling quinoline and powdered copper, 2- and 3-nitro-benzofuran are prepared from nitro acids and 5-nitrothionaphthene is formed from the corresponding 2-carboxylic acid. ... 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

The quindoline 224 may be prepared by the condensation of indoxyl-2-carboxylic acid with 6-aminopiperonaldehyde in the presence of hydrochloric acid, when decarboxylation and cyclization take place. Nitric acid oxidation of 224 gave an unstable nitrodicarboxylic acid which decarboxylated readily to a nitromonocarboxylic acid formulated as 8-nitro-8-carboline-3-carboxylic acid (225). ... 

Castro and Stephens16 developed a method for the preparation of unsymmetrical disubstituted acetylenes, which involves the reaction of copper(I) acetylides with aromatic iodo compounds. Bond and Hooper7 extended this route to the preparation of 2-arylisatogens (22). 2-Nitro-phenylpropiolic acid (19a) is readily decarboxylated to the acetylene (19b), which on treatment with copper(I) chloride gives 19c. The reaction of 19c with substituted aromatic iodo compounds (20) gives the corresponding acetylenes (21), which subsequently cyclize to the isatogens (22). The alternative route (23 + 24 - 21) has been little used.17... 

Mononitration of benzo[6]thiophene gives a complex mixture in which the 3-isomer predominates (73% in acetic anhydride at 25 °C) and can be separated from other isomers, which may include 4-, 5-, 6- and 7-nitro derivatives. However, benzo[6]thiophenes with electron-donating groups at the 3-position, e.g. 3-methyl-, 3-acetamido- or 3-bromo-benzo[6]thiophene, are nitrated almost exclusively in the 2-position. 2-Nitro-benzo[6] thiophene may be prepared by debromination of 3-bromo-2-nitro-benzo[6 ]thiophene, or by decarboxylation of 2-nitrobenzo[6]thiophene-3-carboxylic acid (70AHC(11)177). 

Nitrobenzo[6]thiophene is obtained in 10% yield by the cycliza-tion of (p-nitrophenylthio)acetaldehyde dimethyl acetal (Section IV,B) 7-nitrobenzo[6]thiophene cannot be prepared by this method.488 5-Nitrobenzo[6]thiophene84,218,338,422,538,543-545 and its 3-phenyl,333 3-methyl,298 3,6-dimethyl,330 and 7-nitro-3-phenyl334 derivatives may be obtained most conveniently by decarboxylation of the readily available (Section IV, D) 2-carboxylic acids. 5- 4 J4.54e 0. 494,548 an(j 7.494 nitro-3-acetoxybenzo[6]thiophene may be prepared almost quantitatively by cyclization reactions (Section IV, D). 

As a preparative method the direct decarboxylation of olefinic acids is almost limited to the formation of styrenes and stilbenes from substituted cinnamic acids. Thermal decomposition of cinnamic acid gives styrene (41%). The yield is nearly quantitative if the reaction is carried out in quinoline at 220° in the presence of a copper catalyst. The yields of substituted styrenes where the aryl radical contains halo, methoxyl, aldehyde, cyano, and nitro groups are in the range of 30-76%. cis-Stilbene and cis-p-nitrostilbene are prepared in this way from the corresponding a-phenylcinnamic acids (65%). One aliphatic compound worthy of mention is 2-ethoxypropene, prepared by heating -ethoxycro-tonic acid at 165° (91% yield). The mechanism of acid-catalyzed decarboxylations of this type has been studied. Isomerization of the double bond from the a,/5- to the /5, y-position before decarboxylation very likely occurs in many instances. ... 

A number of a-nitro carboxylic acids are easily dicarboxylated to furnish nitro compounds. The synthesis of nitromethane in this manner is a classical example (38%). Nitroethane and higher homologs have been similarly prepared from the a-bromo acids and sodium nitrite. Another example is found in the synthesis of phenylnitromethane. Treatment of benzyl cyanide with methyl nitrate in the presence of sodium ethoxide gives the sodium salt of the aci-niao compound, which is then hydrolyzed and decarboxylated. ... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

E. Other Electrophiles - Amino acids can be prepared either by direct introduction ot the amino function,85 or by elaborating hippuric acid by alkylation.66 A nitro group can be introduced directly, and, after decarboxylation, nitroalkanes are obtained.49 In addition to decomposition... 

Acetamidobenzo[b] thiophene is obtained by reductive acetylation of the 3-nitro compound with Fe-Ac0H-Ac20.393 Unstable 3-aminobenzo-[b] thiophene is best prepared in situ by decarboxylation of the corresponding 2-carboxyIic acid.389... 

Similar to Cr(CO)3 complexes, less stabilized carbon nucleophiles such as MeLi and acetone enolate add irreversibly at the position ortho to chloride in (chlo-robenzene)FeCp [84]. Nucleophiles stabilized by a nitro, p-dicarbonyl, or related groups add reversibly with ultimate formation of a substitution product [66, 85]. Ketoarene complexes 35 can be prepared by addition of a malonate derivative followed by acid-induced decarboxylation [86]. 

Nitro- and 6-nitroveratric acids, prepared from vanillin by the method of R. Pschorr and C. Sumuleanu (29), were separately subjected to the Bischoff synthesis (27), their chlorides being condensed with diethyl malonate, and the products reduced, cyclized and decarboxylated by treatment with tin and aqueous-alcoholic hydrochloric acid. 

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