Dicarboxylic acids formation

Broadway NM, EM Dickinson, C Ratledge (1993) The enzymology of dicarboxylic acid formation by Cory-nebacterium sp. strain 7E1C grown on n-alkanes. J Gen Microbiol 139 1337-1344. 

Fatty acid w-hydroxylation is involved in the.metabolism of prostaglandins and leukotrienes, and is the first step of dicarboxylic acid formation in the cell. In this assay, lauric acid is hydroxylated to form 12-hydroxylauric acid, which is then fluorescence-labeled on the carboxyl group with 3-bromomethyl-7-methoxy-l,4-benzoxazin-2-one. 

HOaQCHjlfiCOiH, CSH14O4. Important dicarboxylic acid obtained by oxidizing ricino-leic acid (from castor oil) also obtained by oxidation of cyclo-octene or cyclo-octadiene formerly obtained from cork. Used in the formation of alkyd resins and polyamides. Esters are used as plasticizers and heavy duty lubricants and oils. 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Polyesters are a second class of condensation polymers and the principles behind their synthesis parallel those of polyamides Ester formation between the functional groups of a dicarboxylic acid and a diol... 

Chroman-6-carboxylic acid, 8-hydroxy-2-methyl-4-0X0—see Rosellinic acid, 718 Chroman-2,7-dicarboxylic acid, 2,4,4-trimethyl-formation, 3, 733... 

Similar compounds to those described above have been prepared by the same group using the bis-cesium salts of pyridine-3,5-dicarboxylic acids. In a number of experiments Piepers and Kellogg showed that Cs plays an irreplacable role as compared with Na", K and Rb for the formation of [the macrocycle shown below] . 

The reaction of cyclohexane-cw-1,2-dicarboxylic acid with sulfur tetrafluoride affords the correspoding cyclic ether in a 70% yield with very limited formation of the bis(trifluoromethyl) derivative [2IJ] (equation 107)... 

The crystal structure of many compounds is dominated by the effect of H bonds, and numerous examples will emerge in ensuing chapters. Ice (p. 624) is perhaps the classic example, but the layer lattice structure of B(OH)3 (p. 203) and the striking difference between the a- and 6-forms of oxalic and other dicarboxylic acids is notable (Fig. 3.9). The more subtle distortions that lead to ferroelectric phenomena in KH2PO4 and other crystals have already been noted (p. 57). Hydrogen bonds between fluorine atoms result in the formation of infinite zigzag chains in crystalline hydrogen fluoride... 

The electron-deficient nature of the s-tetrazine ring-carbons is indicated by formation of a dipotassium salt (C2N4K2) of tetrazine in liquid ammonia, by easy decarboxylation of the 3,6-dicarboxylic acid (335), and by the very weak basicity of the 3,6-diamine (336). 

With a mixed anhydride two different arylketones may be formed. Reaction of a cyclic anhydride of a dicarboxylic acid, e.g. succinic anhydride, leads to formation of an arylketo acid. ... 

In a modified procedure the free carboxylic acid is treated with a mixture of mercuric oxide and bromine in carbon tetrachloride the otherwise necessary purification of the silver salt is thereby avoided. This procedure has been used in the first synthesis of [1.1.1 ]propellane 10. Bicyclo[l.l.l]pentane-l,3-dicarboxylic acid 8 has been converted to the dibromide 9 by the modified Hunsdiecker reaction. Treatment of 9 with t-butyllithium then resulted in a debromination and formation of the central carbon-carbon bond thus generating the propellane 10." ... 

C,4H2204, melting at 182 5. The formation of this cedrene-dicarboxylic acid serves for the detection of cedrene in essential oils. It is sufficient if the fraction to be examined be oxidised by permanganate or ozone, and the acid obtained (boiling-point at 10 mm. = 200° to 220° C.) be then oxidised further, either by an alkaline solution of bromine or by nitric acid. Even very small proportions of cedrene have definitely led to the obtaining of this acid melting at 182 5° C. 

The first synthesis of a 3//-3-benzazepine, e.g. 65 (R1 = R2 = Me), was achieved by the condensation of phthalaldehyde with a bis[(alkoxycarbonyl)methyl]methylamine.24"25 With sodium methoxide as the base, A%V-bis[(methoxycarbonyl)methyl]pheiiylaniine condenses with the dialdehyde in a similar manner to give dimethyl 3-phenyl-3//-3-benzazepine-2,4-dicar-boxy late (65, Rl — Ph R2 — Me).99 However, replacement of methoxide by potassium tert-butoxide results in formation of 3-phenyl-3//-3-benzazepine-2,4-dicarboxylic acid (65, R1 = Ph R2 = H).25... 

The formation of porphyrins from 1,19-dideoxybi)enes-/r can be achieved starting either from the 1-methyl derivatives or from l,19-dideoxybilene-Z>-l,19-dicarboxylic acid esters. In the first case the desired methine bridge of the porphyrin stems from the 1-methyl group whereas in the latter case orthoformates have to be added in the condensation step as a precursor for the methine unit. The 1-methyl- and also 1,19-dimethyl-l,19-dideoxybilene- > salts can be cy-clized to the corresponding porphyrins with copper(II) acetate in methanol.56 However, when the bilenes contain /i-acceptor substituents, the yields of porphyrins obtained by this method are very low.57... 

The epoxidation method developed by Noyori was subsequently applied to the direct formation of dicarboxylic acids from olefins [55], Cyclohexene was oxidized to adipic acid in 93% yield with the tungstate/ammonium bisulfate system and 4 equivalents of hydrogen peroxide. The selectivity problem associated with the Noyori method was circumvented to a certain degree by the improvements introduced by Jacobs and coworkers [56]. Additional amounts of (aminomethyl)phos-phonic acid and Na2W04 were introduced into the standard catalytic mixture, and the pH of the reaction media was adjusted to 4.2-5 with aqueous NaOH. These changes allowed for the formation of epoxides from ot-pinene, 1 -phenyl- 1-cyclohex-ene, and indene, with high levels of conversion and good selectivity (Scheme 6.3). 

Sulfur compounds have also been widely studied as activating agents for polyesterification reactions. p-Toluenesulfonyl chloride (tosyl chloride) reacts with DMF in pyridine to form a Vilsmeir adduct which easily reacts with carboxylic acids at 100-120° C, giving highly reactive mixed carboxylic-sulfonic anhydrides.312 The reaction is efficient both for aromatic dicarboxylic acid-bisphenol312 and hydroxybenzoic acid314 polyesterifications (Scheme 2.31). The formation of phenyl tosylates as significant side products of this reaction has been reported.315... 

Faraday, in 1834, was the first to encounter Kolbe-electrolysis, when he studied the electrolysis of an aqueous acetate solution [1], However, it was Kolbe, in 1849, who recognized the reaction and applied it to the synthesis of a number of hydrocarbons [2]. Thereby the name of the reaction originated. Later on Wurtz demonstrated that unsymmetrical coupling products could be prepared by coelectrolysis of two different alkanoates [3]. Difficulties in the coupling of dicarboxylic acids were overcome by Crum-Brown and Walker, when they electrolysed the half esters of the diacids instead [4]. This way a simple route to useful long chain l,n-dicarboxylic acids was developed. In some cases the Kolbe dimerization failed and alkenes, alcohols or esters became the main products. The formation of alcohols by anodic oxidation of carboxylates in water was called the Hofer-Moest reaction [5]. Further applications and limitations were afterwards foimd by Fichter [6]. Weedon extensively applied the Kolbe reaction to the synthesis of rare fatty acids and similar natural products [7]. Later on key features of the mechanism were worked out by Eberson [8] and Utley [9] from the point of view of organic chemists and by Conway [10] from the point of view of a physical chemist. In Germany [11], Russia [12], and Japan [13] Kolbe electrolysis of adipic halfesters has been scaled up to a technical process. 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

Esters of dicarboxylic acids having hydrogen on the 8 or e carbon atcans undergo intramolecular cyclisation when heated with sodium or with sodium ethoxide. This cyclisation is known as the Dieckmaim reaction. It is essentially an application of the Claiseu (or acetoacetic ester) condensation to the formation of a ring system the condensation occurs internally to produce s... 

Another approach to improve the color formation properties of Malachite Green lactone has been the introduction of nitrogen atoms into the phthalide ring. Thus, condensation of pyridine-2,3-dicarboxylic acid anhydride with dimethylaniline in the presence of zinc chloride has been shown54 to yield a mixture of the 4- and 7-azaphthalides 11 and 12. 

Stepwise addition of the aniline moieties in analogy to Scheme 7 (Route A) allows the preparation of asymmetrically substituted derivatives.55,56 The use of pyridine-3,4-dicarboxylic acid anhydride similarly results in the formation of mixtures of 5- and 6-azaphthalides.57 Quinoline-2,3-dicarbo-xylic anhydride has also been converted into the corresponding azaphthal-ides in a similar manner.58 Pyrazine-2,3-dicarboxylic acid anhydride yields... 

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