Aqueous reactions dicarboxylic acids

In 1910, Hinsberg described the reaction between benzil and diethylthiodiacetate, resulting in the preparation of the thiophene ring system. The reaction was run under Claisen condensation conditions, and after hydrolysis with aqueous acid at reflux, the free dicarboxylic acid 1 was produced. 

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). 

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. 

Alternatively, treat a solution of 3 9 g. of the 6is-diazo ketone in 50 ml. of warm dioxan with 15 ml. of 20 per cent, aqueous ammonia and 3 ml. of 10 per cent, aqueous silver nitrate under reflux in a 250 or 500 ml. flask on a water bath. Nitrogen is gently evolved for a few minutes, followed by a violent reaction and the production of a dark brown and op>aque mixture. Continue the heating for 30 minutes on the water bath and filter hot the diamide of decane-1 10-dicarboxylic acid is deposited on cooling. Filter this off and dry the yield is 3 -1 g., m.p. 182-184°, raised to 184-185° after recrystallisation from 25 per cent, aqueous acetic add. Hydrolyse the diamide (1 mol) by refluxing for 2-5 hours with ZN potassium hydroxide (4 mols) acidify and recrystallise the acid from 20 per cent, acetic acid. The yield of decane-1 10-dicarboxylic acid, m.p. 127-128°, is almost quantitative. 

The kinetic solvent-isotope effects on these reactions are made up of primary and secondary kinetic isotope effects as well as a medium effect, and for either scheme it is difficult to estimate the size of these individual contributions. This means that the value of the isotope effect does not provide evidence for a choice between the two schemes (Kresge, 1973). The effect of gradual changes in solvent from an aqueous medium to 80% (v/v) Me2SO—H20 on the rate coefficient for hydroxide ion catalysed proton removal from the monoanions of several dicarboxylic acids was interpreted in terms of Scheme 6 (Jensen et al., 1966) but an equally reasonable explanation is provided by Scheme 5. 

The addition product of ethyl acetoacetate and methyl a-methoxyacrylate was hydrolyzed, and the resulting dicarboxylic acid was treated with dimethylamine hydrochloride and aqueous formaldehyde. The product of the Mannich reaction was decarboxylated, reesterifed, and finally treated with methyl iodide to supply quaternary salt 469 as the main product. During the above one-pot process, elimination also took place, yielding unsaturated ketone 470, which was later utilized as its hydrogen bromide adduct 471. Reaction of 3,4-dihydro- 3-car-boline either with 469 or 471 furnished the desired indolo[2,3-a]quinolizine derivative 467 as a mixture of two diastereomeric racemates. 

The BASF route started from hydroquinone, which was converted to 2,5-dihydroterephthalic acid by a Kolbe-Schmitt reaction. One mole of this acid was treated with two moles of an arylamine, both components being in the form of a suspension in aqueous methanol. This was added to a small amount of a solution of vanadium(III) chloride and sodium chlorate. Gentle heating gave a 95% yield of 2,5-bis(arylamino)benzo-l,4-quinone-3,6-dicarboxylic acid. Ring closure to the trans-quinacridonequinone took place in the presence of concentrated sulphuric acid at 60-80 °C. This was then reduced to the required crude pigment by zinc or aluminium powder in caustic soda under pressure,in an aluminium chloride/urea melt or by the use of a sulphuric acid/polyphosphoric acid mixture. 

Aqueous NaOCl (10%, 400 ml) is added with stirring to the cycloalkanone (0.1 mol) and Aliquat (4 g, 10 mmol) at 10°C. The mixture is stirred and the pH is maintained at 12.0 by the addition of aqueous NaOH (0.5 M). On completion of the reaction, the aqueous phase is separated, washed with CH2C12 (200 ml), and acidified to pH 2.0 with HC1 (2M). The acidic solution is cooled to 0°C to cause precipitation of the dicarboxylic acids (e.g. cyclohexanone yields a mixture of adipic acid 63%, succinic acid 9%, glutaric acid 17%, and a,a-dichloroadipic acid 5%). 

Oppenauer-type oxidation of secondary alcohols can be a convenient procedure for obtaining the corresponding carbonyl compounds. It was found recently [19], that Ir(I)- and Rh(I)-complexes of 2,2 -biquinoline-4,4 -dicarboxylic acid dipotassium salt (BQC) efficiently catalyze the oxidation of secondary alcohols with acetone in water/acetone 2/1 mixtures (Scheme 8.5). The reaction proceeds in the presence of Na2C03 and affords medium to excellent yields of the isolated ketones. The process is much faster in largely aqueous solutions, such as above, than in wet organic solvents in acetone, containing only 0.5 % water, low yields were observed (15 % vs. 76 % in case of cyclohexanol). 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

Reaction of 1,2 -dicarboxylic acids has been used for the formation of a number of strained alkenes and also applied to the Diels-Alder addition products from maleic anhydride (Table 9.5). Both cis- and tr s-diacids take part in the process. Aqueous pyridine containing, triethylamine as a strong base, is considered the best solvent and higher yields are obtained at temperatures of around 80 "C [130]. Use of a divided cell avoids a possibility of electrocatalytic hydrogenation of the product at the cathode. The addition of /a/-butylhydroquinone as a radical scavenger prevents polymerization of the product [127], An alternative chemical decarboxylation process is available which uses lead tetraacetate [131] but problems can arise because of reaction between the alkene and lead tetraacetate. 

However, reactions of PAHs in ambient air to form more polar species (e.g., nitro-PAHs, ketones, quinones, lactones, and dicarboxylic acids) greatly enhance their solubilities in aqueous systems. This has major implications when one considers the distribution of PAHs, and their atmospherically formed PAC derivatives, through the air, water, and soil environments. These increases in solubility upon reaction are important not only from an environmental chemistry perspective but also in terms of possible impacts on public health and ecosystems, e.g., in both the exposure and the health effect... 

Protons present in aqueous acid also act as reasonably efficient electron acceptors. If the reduced hydrogen atoms are formed on metallized suspensions, catalytic hydrogenation can result. For example, in contrast to the oxidative chemistry reported earlier for cyclohexene-4,5-bis-dicarboxylic acid (Eq. 28), if the reaction is conducted in the absence of oxygen in aqueous nitric acid, catalytic hydrogenation of the double bond becomes a major pathway, Eq. (34). ... 

Another approach attempts to explain the different effect of the ester structure in different reaction media simply by the changing ability of the esters to be absorbed by the resin. Qualitatively, this approach was used [476] to interpret the results for water and aqueous acetone and a similar idea was suggested for the hydrolysis of dicarboxylic acid esters in water—dioxan mixtures [482,483]. Quantitative interpretation was based [481,489] on Helfferich s model [427]. It follows from eqn. (30) and from the relation... 

Aqueous alkali hydrolyzes lactones and the products, e.g. (287), are frequently unstable or recyclize, depending on other substituents present. Coumarin is hydrolyzed by dilute alkali first to the yellow cis acid (coumarinic acid) salt (288) which recyclizes to coumarin on acidification but when heated with alkali isomerizes to the trans acid (coumaric acid) salt (289). When it is desirable to identify the hydrolytic product of such a reaction it is better to incorporate a methylating agent so that the reverse reaction cannot then occur. Hot aqueous alkali converts methyl 3-bromocoumalate (290) into furan-2,4-dicarboxylic acid (73JCS(Pl)ll30). 

Dehydrohalogenation sometimes leads to cyclization which gives cycloalkanes or heterocycles. The fluorinated diester 1 has proved to be a convenient source of polyfluoroalkylated cyclopropanes. Reaction of 1 with aqueous potassium hydroxide gives 2- HA //-hepta-fluorobutyl)cyclopropane-l, 1 -dicarboxylic acid (2) in quantitative yield.120 The diethyl ester 3 ot this acid is obtained in a yield of 87% by the reaction of 1 with sodium ethoxide in anhydrous ethanol.120... 

As expected easily from analogy with Lys, photocatalytic reaction in deaerated aqueous suspensions of semiconductor particles produces piperidine-2,6-dicarboxylic acid (PDC) from 2,6-diaminopimelic acid (DAP). The product PDC was optically inactive when an optically inactive 1 1 2 mixture of L, D, and meso isomers of DAP was used. However, two diastereomers, trans and cw-PDC s were obtained and their molar ratio strongly depended on the kind of photocatalyst used (Fig. 11.4). 

Dicarboxylic Acid Monoesters. Enzymatic synthesis of monoesters of dicarboxyUc acids by hydrolysis of the corresponding diesters is a widely used and thoroughly studied reaction. It is catalyzed by a number of esterases, Upases, and proteases and is usually carried out in an aqueous buffer, pH 6—8 at room temperature. Organic cosolvents may be added to increase solubiUty of the substrates. The pH is maintained at a constant level by the addition of aqueous hydroxide. After one equivalent of base is consumed the monoesters are isolated by conventional means. 

Oxidation reactions included the use of alkaline permanganate, alkaline copper(II)oxide, and aqueous chlorine (Schnitzer and Khan, 1972 Christman et al., 1989).The degradation products consisted of aromatic and aliphatic acids. Aliphatic dicarboxylic acids ranging from ethanedioic to decanedioic acids were identified. Methylation prior to oxidation prevented phenolic groups from degradation and allowed gas chromatography (GC) analysis. 

---