1,1-Dicarboxylic acids, decarboxylation reaction, with esters

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Only the 1-benzyl-vic-triazole, crysts(from eth at 20°), mp 61°, appears to have been prepd and reported in the literature. Curtius Raschig(Ref 2) prepd 1-benzyl-vic-triazole by the reaction of benzyl azide with the methyl ester of acetylene-dicarboxylic acid, followed by sapon and decarboxylation. Wiley et al(Ref 3) prepd the compd directly and in better yield from acetylenedicar-boxylic acid, followed by decarboxylation to 1 -benzyl-vic-triaZole(77% yield)... 

The C8 aldehyde ester may be produced by cleavage of the 9-hydroperoxide of ethyl llnoleate followed by terminal hydroperoxidation. Further oxidation would produce the corresponding dicarboxylic acid which upon decarboxylation would give rise to ethyl heptanoate. The 8-alkoxy radical may also decompose to give the C7 alkyl radical, which would yield ethyl heptanoate or form a terminal hydroperoxide, and so on. Polymerization, both intra- and intermolecular, is also a major reaction in high temperature oxidation. Combination of alkyl, alkoxy, and peroxy radicals yields a variety of dimeric and polymeric compounds with C-O-C or C-O-O-C crosslinks. 

The reaction of isatins 9 with halogen-substituted acids or their esters 61 takes place even at room temperature. The obtained dicarboxylic acids 62 are decarboxylated in situ, and the final products are derivatives of 3-hydroxy-4-quinolinecarboxylic acid 63 [48, 49],... 

Cyclizative condensations based on aldol-type reactions which conform to the IIbd pattern have also been developed. Condensation of bis(alkoxycarbonylmethyl)amines or bis(cyanomethyl)amines with benzil affords 3,4-diarylpyrrole-2,5-dicarboxylic acid esters or nitriles. These reactions frequently lead to partial hydrolysis of at least one of the alkoxycarbonyl substituents and if the 3,4-diarylpyrrole is the ultimate objective, work-up involving complete hydrolytic decarboxylation is appropriate (equation 119) (61LA(639)102, 65JOC859). 

The oxidation of 1,4-dicarboxylic acids with LTA in benzene results in double decarboxylation with the formation of a double bond (equation 16). Similarly, the pyrolysis of the di-r-butyl peroxy esters of 1,4-dicarboxylic acids in high boiling solvents leads to the formation of double bonds (equation 17). The method is especially useful in so far as 1,4-diacids are readily available from Diels-Alder reactions using derivatives of mtdeic and fumaric acid as the dienophile. Apparently, application of the 0-acyl thiohydroxamate method to 1,4-diacids does not result in the formation of double bonds but rather in the product of double decarboxylative rearrangement (Section S.4.6.1). ... 

Preparation. Imidazole can be prepared by a remarkable method discovered by Maquenne D-tartaric acid is converted into the dinitrate, and the ester on reaction with ammonium hydroxide and formaldehyde affords imidazole-4,5-dicarboxylic acid, which is decarboxylated to the parent heterocycle. Diketosuccinic... 

There are two classical reaction sequences in organic chemistry that rely on enolate alkylation. One is the malonic ester synthesis.61 jjj synthetic example taken from the Clive and Hisaindee synthesis of brevioxime,62 diethyl malonate was treated with a base such as sodium ethoxide, under thermodynamic control conditions. The resulting enolate anion is treated with the indicated alkyl halide to give the alkylated product 81 (in 72% yield).Saponification of 81 to the dicarboxylic acid (82, in 99% yield), was followed by decarboxylation (sec. 2.9.D) and formation of the substituted acid 83, in 94% yield. ... 

This reaction was initially reported by Franchimont in 1872. It is a condensation of two a-bromocarboxylic acids in absolute alcohol in the presence of sodium cyanide to give 1,2-dicarboxylic acids after hydrolysis and decarboxylation. In the case of a-bromoketones, 1,4-diketones are produced similarly after hydrolysis with phosphoric acid. It was found that the bulky group at the ester end prevents condensation, as in the case of phenyl and naphthyl esters. Although the substituent at j0-position does not prevent such condensation, it reduces the overall yield. In addition, a compound with two ester groups at proper position will form cyclic diacid under such reaction conditions and cyclobutane, " cyclopentane and cyclohexane dicarboxylic acid have been prepared in such a way. In the case of l,4-dibromo-l,4-dibenzoylbutane, a derivative of cyclopentanone is produced after acidic hydrolysis. It should be pointed out that other common solvents—including acetone, ether, and acetonitrile- are not good for this reaction. ... 

Poly(benzimidazoles) are produced from dicarboxylic acids and aromatic tetramines. Commercially, 3,3 -diaminobenzidine tetrahydrochloride and diphenyl isophthalate are preferentially used. The diphenyl ester is used because (a) the free acids decarboxylate under the high reaction temperatures of 250-400 C (b) the acyl chlorides react too fast, making ring closure difficult and (c) the amino groups are partially methylated if the methyl esters are used. The hydrochloride is used because it is more stable to oxidation than the free amine itself. The polycondensation is carried out in two stages. A prepolymer. A, is formed in the first stage with foaming and phenol elimination ... 

Poly(benzimidazoles) have become commercially important. Whereas polyimides contain two carboxyl groups per amine group, two amine groups are allowed to react with a carboxyl group in poly(benzimidazole) manufacture. Diphenyl esters are used as dicarboxyl compounds, since (a) the free acids decarboxylate under the reaction conditions (250°C at first, subsequently 400°C), (b) the acyl chlorides react too quickly, so that ring closure becomes difficult, and (c) with methyl esters, the amino groups become partially methylated. Moreover, eliminated phenol can easily be washed out. Typical materials are 3,3 -diaminobenzidine and diphenyl... 

Recall from Section 14.3C that the hydrolysis of an ester in aqueous sodium hydroxide (saponification), followed by acidification of the reaction mixture with HCl or other mineral acid, converts an ester to a carboxylic acid and an alcohol. Recall also from Section 13.8 that )3-ketoacids and )3-dicarboxylic acids readily undergo decarboxylation (lose CO2) when heated. The following equations illustrate the results of a Claisen condensation, followed by saponification, acidification, and decarboxylation ... 

Ester enolates undergo alkylation reactions. When ethyl 3-methylpentanoate (110) reacts with sodium ethoxide in ethanol and then with bromoethane, the product is 111. Alkylation of malonate derivatives leads to an interesting sequence of reactions that are useful in synthesis. The reaction of diethyl malonate (90) and NaOEt in ethanol, followed by reaction with benzyl bromide, gives 112. In a second reaction, 112 reacts with NaOEt in ethanol and then with iodomethane to give 113. Saponification of 113 (see Chapter 20, Section 20.2) gives the dicarboxylic acid, 114, and heating leads to decarboxylation (Section 22.8) and formation of acid 115. This overall sequence converted malonic acid via the diester to a substituted carboxylic acid, and it is known as the malonic ester synthesis. 

The details of carbon metabolism in the citric acid cycle are beyond the scope of this article. In brief, pyruvate is first oxidatively decarboxylated to yield CO2, NADH, and an acetyl group attached in an ester linkage to a thiol on a large molecule, known as coenzyme A, or CoA. (See Fig. 2.) Acetyl CoA condenses with a four-carbon dicar-boxy lie acid to form the tricarboxylic acid citrate. Free CoA is also a product (Fig. 6). A total of four oxidation-reduction reactions, two of which are oxidative decarboxylations, take place, which results in the generation of the three remaining NADH molecules and one molecule of FADH2. The citric acid cycle is a true cycle. For each two-carbon acetyl moiety oxidized in the cycle, two CO2 molecules are produced and the four-carbon dicarboxylic acid with which acetyl CoA condenses is regenerated. 

Reaction of malonic esters with 1,2-dibromoethane and 1,3-dibromopropane under liquiddiquid two-phase conditions produces the cyclopropane- and cyclobutane- 1,1 -dicarboxyl ic esters, which can be hydrolysed under the basic conditions (6.2.24.C) [e.g. 75, 109] and decarboxylated to give the monocarboxylic acid [e.g. 109]. 

A mixture of lupinine and epilupinine is obtainable by the following series of reactions. The betaine XXVI on cyclic hydrogenation and subsequent decarboxylation with 20 % hydrochloric acid gives a mixture of epimeric lupininic acids (XXIX). The dicarboxylic ester XXVIII is also obtained by the mercuric acetate dehydrogenation of the piperidine derivative XXX and by the alkylation of monomeric piperideine with a y-bromopropylmalonic ester. The last route is presumably a first Mannich condensation followed by an alkylation. Hydrolysis of the malonic esters, decarboxylation (XXIV), esterification, and reduction with lithium aluminum hydride complete the synthesis of a mixture which consists of 80% dZ-epilupinine and 20% dMupinine. Thermal... 

The total synthesis of (+ )-dehydroheliotridine (4), a toxic metabolite of the pyrrolizidine alkaloids (e.g. lasiocarpine and heliotrine), has also been described.2 The pyrrole ring was obtained by reaction of l,6-dihydroxy-2,5-dicyanohexa-l,3,5-triene-l,6-dicarboxylic ester (5) with j3-alanine, which afforded the N-substituted pyrrole ester (6), together with the appropriate amide of oxalic acid. Careful hydrolysis of (6) with dilute alkali afforded the related tricarboxylic acid, which was converted, by Dieckmann cyclization, hydrolysis and decarboxylation, into the keto-acid (7). Esterification of (7) with diazomethane, followed by reduction with lithium aluminium hydride, finally afforded ( )-dehydroheliotridine (4), identical, except in optical rotation, with dehydroheliotridine obtained earlier by Culvenor et al.3... 

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