Carboxylic acids dimerisation

Ruhlmann and co-workers found194-196 that carboxylic acid esters react under dimerisation to form acyloins if they are treated with sodium/TMS-Cl (142) in inert solvents. This Bouveault-Blanc-like synthesis has many parallels to the reductive silyl-ation (vide supra). 

Bromination of ketone 3.17 gives 3.18 which can be converted to azide 3.19. Hydrogenation of 3.19 in the presence of hydrochloric acid affords aminoketone hydrochloride salt 3.20. Such aminoketones are often isolated as the corresponding salts because the free aminoketones are prone to dimerisation, having both nucleophilic and electrophilic centres. (For a common alternative preparation of aminoketones, see the Knorr pyrrole synthesis, Chapter 2.) Liberation of the free base of 3.20 in the presence of the acid chloride affords amide 3.21 which is cyclised to oxazole 3.22. Ester hydrolysis then affords the biologically-active carboxylic acid 3.23. 

The dimerisation of larger calix[6]arenes bearing three carboxylic acid groups in alternate positions on the upper rim has been reported. In this case the cavity is of sufficient size to encapsulate simple pyridinium salts. ... 

Synthesis of trifluoromethylated compounds 152 has been achieved via ester-enolate [2,3]-Wittig and [3,3]-lreland-Claisen rearrangements. Perfluorocyclo-butane phosphonium ylides, e.g. 153, have been used as a masked fluoride anion source in their reactions with alcohols and carboxylic acids which lead to alkyl-and acyl-fluorides. Ylides 153 are also reported to cleave Si-C and Si-O bonds, cause dimerisation of fluoro-olefins, and also react with acid chlorides or other activated aromatic compounds under halogen exchange. ... 

Butadiene-1-carboxylic acid and styrene, Y. A. Titov and A. I. Kuznetsova, Izvest. Akad. Nauk SSSR, Otdel. Khim. Nauk, 1960, 1810 and 1815 Chem. Abs., 1961, 55, 15408c and 15408f) H. R. Snyder and G. I. Poos, J. Am. Chem. Soc., 1949, 71, 1057 2-cyanolbutadiene dimerising (which is also a Z-substituted dienophile), C. S. Marvel and... 

In connection with our studies on the dimerisation of aylethanals and arylacetones with boron tribromide, we first turn to the reaction of methoxylated arylpyruvic acids [38], Arylpyruvic acids that were obtained mainly in their Z-enol form, did not dimerise. When the ortho aromatic position is unsubstituted, only an isomerisation occurs that allowed us to isolate some 2-hydroxyarylpropenoic acids in their E-form. In the cases of (2-methoxyphenyl)arylpropenoic acids, cyclisations were also observed leading of mixtures of benzofuran-2-carboxylic acids and 3-hydroxycoumarins that are easily separated, Fig. (12). We observed a competition between cyclisation and isomerisation that have apparently similar kinetic parameters. 

A third route to rra 5-2,3-dibenzylbutyrolactones involves oxidative dimerisation of the dianion of a dihydrocirmamic acid (scheme 7) [51,52]. Reduction of the anhydride to the lactone completes the sequence. This approach, which is ideally suited to the preparation of symmetrically substituted lignans, has also been extended to the preparation of unsymmetrically substituted compounds [53]. This is achieved by reacting an a-iodocarboxylate anion with an appropriate carboxamide dianion or carboxylic acid dianion. 

There may be equilibria other than those expressed by eqn. 3.5.1 in concentrated solutions, but they can generally be ignored except in the most precise work. It is possible that some dimerisation of carboxylic acids occurs even in aqueous solution. Ion-pairing is negligible except in methanol, the solvent with the lowest dielectric constant (32-70 at 25°C) of this group. 

Useful exploratory studies of acid-base behaviour in solvents of low dielectric constant have been made by conductance " and potentio-metric " titrations. Association constants are usually obtained from spectrophotometric measurements. The strengths of various bases can be compared by means of their association with an indicator acid like 2,4-dinitrophenol. If both acid and base are colourless, a competition for the base can be established between the acid and an indicator acid like bromophthalein magenta In solvents like benzene, other reactions than simple 1 1 association between B and RX may occur. Self-association of the acid or base is one such auxiliary reaction. A classic example is the dimerisation of carboxylic acids in benzene. If allowance is not made for this, constant values of the quotient [BRX]j[B][RX] will not be obtained. (Variations in the quotient cannot be attributed to interionic forces or other nonideal behaviour BRX is scarcely dissociated into ions at all and in spectrophotometric work very low concentrations of B and RX can be used.) Evidence for association ratios other than 1 1 can be obtained from indicator studies. The method developed by Kolthoff and Bruckenstein for studying reactions in anhydrous acetic acid fails for reactions in benzene and similar solvents because more than one acid molecule reacts with the indicator to give complexes of the form/w J r"(HX)yi. In such studies it is generally a good approximation... 

A first example that illustrated this concept of directing a photochemical [2 + 2] dimerisation in the solid state was reported by Ito and Sheffer/ in which diamines were used to form salts from a,p unsaturated carboxylic acids. The transference of the acidic proton in carbo g lic acids by strong base leads to the molecular salts where photodimerisation occurs between two anionic moieties. For example, two cinnamate anions are positioned in parallel form suitable for a [2 -I- 2] photocycloaddition using ethylenediamine via charge-assisted hydrogen bonds 0 ). 

The addition of water to the carbonyl group in aqueous solutions can lead to the formation of hydrates. The reactions and stability of hydrates depend primarily on the inductive effect of substituents. Hydration of formaldehyde readily yields methylene glycol (methanediol), which polymerises to linear oligomers and also to polymers known as paraformaldehyde. Hydrates of a-dicarbonyl and a-hydroxycarbonyl compounds spontaneously dimerise into various cyclic 1,4-dioxanes (see Figure 4.62). These hydrates are intermediates of other a-dicarbonyl and a-hydroxycarbonyl compounds in the oxidation-reduction reactions and precursors of carboxylic acids. Dialkyl ketones do not form hydrates. 

The photochemistry of a phenyldiacrylic acid derivative has been studied in Langmuir-Blodgett films J The crystal structure of the major dimer formed on perdeuterioacetone-sensitized irradiation of f-butyl-2,5-dihydro-5,5-dimethyl-2-0X0-IH-pyrrole-l-carboxylate has been determined. Styryldicyanopyrazines undergo topochemical dimerisation when they are irradiated in the crystalline phase. ... 

Dimerisation of monounsaturated fatty acids has been exploited to prepare monomers bearing two carboxylic functions and, after reduction, the corresponding diols [2], i.e., potential monomers for the synthesis of polyesters, polyamides, polyethers and polyurethanes incorporating long aliphatic motifs. Scheme 2.7 shows two possible mechanisms associated with this reaction (i.e., ene- or carbonation coupling), which is inevitably accompanied by further additions to give trimers and oligomers, if not carried out under finely controlled conditions. 

The partial substitution of water in the solvent by propylene glycol favours the dimerisation process. This is reflected in an increase of the dimer formation constant and in the fact that the association of monomeric species containing unprotonated carboxylates and protonated amino groups is accompanied in water with the protonation of one carboxylate and in the solvent mixture with that of two. The dimer formation increases the protonation constants of these carboxylates showing that the dimerization of BPTI is due to the formation of intermolecular H-bonds in which these carboxylate-oxygens act as pillar atoms. Thus the pH dependence of the dimerization is determined by the protonation - deprotonation equilibria of these groups. The increased acidity of the other carboxyls in the solvent mixture may be due to the steric effect of the macro-molecular dimer. 

The radical -COOH (CAS 2564-86-5) has only a separate fleeting existence. The acid dissociation constant of-COOH has been measured using electron paramagnetic resonance spectrocopy. The carboxyl group tends to dimerise to form oxalic acid. 

The phrase not always seen in Table 23.9 indicates bands only observed in low molecular species (i.e. three to four amino acids). In larger molecules, these absorptions may either appear as shoulders on neighbouring bands or completely disappear if the Zwitter ion does not exist (or dimerisation of carboxyl groups takes place). 

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