Salicylic acids, decarboxylation

Pimelic Acid (Heptanedioic Acid or 1,5-Pentane-dicarboxytlc Acid). HOOC.(CH2)s.COOH mw 160.17 white prisms mp 106° bp 272° at 100mm (subl), and 212° at 10mm d 1.329 g/cc at 15°. Sol in w, ethanol, eth and hot benz. Prepn is by oxidn of cycloheptanone, capric acid or oleic acid treatment of salicylic acid with Na in amyl ale, or by decarboxylating 1,1,5,5-pentanetetracarboxylic acid with heat Pimelic acid has been combined with cis and trans-, 4-cyclohexanediol to give polyesters, and with m-xylene-ce,ol -diamine or poly-methylenediamines to form polyamides. With diperoxides, the acid forms resins. It is also used as the parent compd to form the expls presented below... 

Decarboxylation of salicylic acid takes place with slow heating because of the presence of the electronic configuration of the carboxyl group ortho to the hydroxyl group, but does not occur in the other isomers of hydroxybenzoic acid. On rapid heating, salicylic acid sublimes because of its low vapor pressure. This property allows commercial separation from the other isomers as a means of purification analogous to distillation. The differences in the vapor pressures are shown in Table 4. 

Since OH is strongly electrophilic, the OH group directs OH into its ortho- and para-positions [reactions (51)—(53)]. One of the ortho-positions is occupied by the somewhat bulky carboxylate group which renders reaction (51) less likely than reaction (52). An addition to the meta-position can be largely neglected. Upon oxidation of the OH-adduct radicals, cyclohexadienones are formed [reactions (54)-(56)] which either decarboxylate [reaction (57)] or rearrange into the corresponding phenols [reactions (58) and (59) e.g., Bausch et al. 1976]. Product yields from hydroxybenzoic acids are compiled in Table 3.5 from salicylic acid in Table 3.6. 

Unsubstituted indoxazenes cannot be prepared in this way instead of the expected product one obtains the corresponding isomeric salicylonitrile (9) or its hydrolysis products.20 With o-bromophenyl-glyoxylic acid oxime (10) in alkaline solution the reaction proceeds similarly, with decarboxylation, ring opening, and hydrolysis to salicylic acid.21... 

However, if the slow step of the reaction involves proton transfer from the positive ion H30+ to an anionic substrate, AS is close to zero or even positive [53] (see the examples in the bottom part of Table 4). The data for these examples do not obey the Matesich relationship. Within the series of the 4-substituted salicylic acids, AS for the decarboxylation reaction increases with decreasing reactivity [53]. A positive contribution... 

The magnitude of the solvent isotope effect and the absence of a carbon isotope effect confirm that proton transfer is rate-determining in the reactions referring to s. As far as the reactions referring to are concerned, the experimental values of these rate coefficients for the decarboxylation of 2- and 4-aminobenzoic acids, as well as the Arrhenius parameters, are comparable to those of the substituted salicylic acids if expected substituent effects are taken into account (Table 21) there is a correlation between log A and Ea. Therefore, it is reasonable to expect that the mechanism is the same. The observed general catalysis supplies additional evidence for rate-determining proton transfer from H30+ to S (sigma complex formation) in the decarboxylation of 4-aminobenzoic acid. 

The formation of the phenoxide anion enhances the reactivity of the ortho and para positions of the aromatic ring towards electrophilic reagents. The reaction of the phenoxide anion with carbon dioxide at 130 °C leads to ortho carboxylation (the Kolbe reactior. Thus phenol gives salicylic acid (4.4), the acetate of which is aspirin. The reaction is reversible and ortho phenolic acids undergo decarboxylation on heating. 

Sublimation pressures down to 0.001 bar are considered feasible. At lower pressures and in some instances at higher ones, entrainer gas is used, usually air or nitrogen or steam. By such means, for instance, salicyclic acid is purified by sublimation at 150°C with an entrainer of air with sufficient CO2 to prevent decarboxylation of the acid. At the operating temperature, the vapor pressure is only 0.0144 bar. Operating conditions corresponding to equilibrium in a salicylic acid sublimer appear in Figure 20.13. Equilibrium may be approached in equipment where contact between phases is intimate, as in fluidized beds, but in tray types percent saturation may be as low as 10%. 

The purification of salicylic acid provides a good example of the use industrially of entrainer sublimation. Air may be used as the carrier gas but as salicylic acid can be decarboxylated in hot air, a mixture of air and CO2 is often preferred. The process shown in Figure 8.30 is carried out batchwise. A 5-10 per cent mixture of CO2 in air is recycled through the plant, passing over heater coils before over the containers, e.g. bins or trays, holding the impure salicylic acid in the vaporizer. The vapours then pass to a series of air-cooled... 

The copper catalyzed oxidation of benzoic acid to phenol proceeds through benzoyl salicylic acid (I), which undergoes hydrolysis and decarboxylation ... 

The predominant gaseous products of the decomposition [1108] of copper maleate at 443—613 K and copper fumarate at 443—653 K were C02 and ethylene. The very rapid temperature rise resulting from laser heating [1108] is thought to result in simultaneous decarboxylation to form acetylene via the intermediate —CH=CH—. Preliminary isothermal measurements [487] for both these solid reactants (and including also copper malonate) found the occurrence of an initial acceleratory process, ascribed to a nucleation and growth reaction. Thereafter, there was a discontinuous diminution in rate (a 0.4), ascribed to the deposition of carbon at the active surfaces of growing copper nuclei. Bassi and Kalsi [1282] report that the isothermal decomposition of copper(II) adipate at 483—503 K obeyed the Prout—Tompkins equation [eqn. (9)] with E = 191 kJ mole-1. Studies of the isothermal decompositions of the copper(II) salts of benzoic, salicylic and malonic acids are also cited in this article. 

An improved route to fluorinated 4-hydroxycoumarins has been reported, based on a facile decarboxylation-deacetylation of their 3-(3-oxopropanoic acid) derivatives <96TL15S1>. The reaction of methyl salicylates with triphenylphosphoranylidene ketene, Ph3P=C=C=0, affords 4-methoxycoumarins <96JCS(P1)2799> and the formation of coumarin 3-phosphonates from salicylaldehydes and phosphonoacetates, Et02CCH2P(0)(0R)2, has been investigated <96T12597>. 

Metal salicylates are occasionally incorporated into mixtures of unknowns for qualitative inorganic analysis. During the conventional group separation, organic radicals are removed by evaporation with nitric acid. When salicylates are present, this can lead to formation of trinitrophenol through nitration and decarboxylation. This may react with any heavy metal ions present to form unstable or explosive picrates, if the evaporation is taken to dryness. The MAQA alternative scheme of analysis obviates this danger. 

Similar azomethine ylides 48 are involved as key intermediates in the racemi-zation of optically active a-amino acids in the presence of a catalytic amount of aldehyde (83JOC843). Grigg confirmed this mechanism (83TL4457) and carried out the reactions of optically pure a-amino acids with salicyl- or o-methoxybenzaldehyde and maleic anhydride or N-phenylmaleimide in acetic acid. Cycloadducts of N-unsubstituted azomethine ylides 48 with dipolaropbiles were obtained only as racemates. These results indicate that the a-amino acids first produced the corresponding imine carboxylic acids with the retention of optical activity but these then undergo a tautomeric equilibration with N-protonated azomethine ylides 48 losing their optical purity. The ylides 48 were captured by several dipolaropbiles as racemic cycloadducts. As the imines of a-amino acids usually suffer spontaneous decarboxylation (as will be discussed later in Section (II,E), the formation of... 

A variant of this route to 2-unsubstituted chromones employs oxalic acid half-ester half-acid chloride, which gives a 2-ethoxycarbonyl-chromone, hydrolysis and decarboxylation of which achieves the required result. Diethyl carbonate as the ester gives rise to 2,4-dioxygenated heterocycles, which exist as 4-hydroxy-coumarins. The condensation of a salicylate with an ester, using three mole equivalents of base also leads through to 4-hydroxy-coumarins, as illustrated below. ... 

Decarboxylation usually occurs on hydrogenation of aromatic hydroxy acids their salts also can be only partly reduced without decarboxylation. On hydrogenation of 65 g of methyl salicylate in 65 g of methanol containing NiO, Ipatiev and Rasuwajev223 obtained 40 g of cyclohexanol. 

Condensation of 4,6-dimethoxy-2-hydroxyacetophenone with diethyl carbonate and an alkoxide ion has now been shown to give the coumarin-3-carboxylic ester (245), and not 4-hydroxy-5,7-dimethoxycoumarin (246), as originally reported. Heating the ester with aqueous alkali resulted in hydrolysis and decarboxylation to (246). The well-established acid cyclization of salicyl-aldehyde with ethyl cyanoacetate to give coumarin-3-carboxylic acids has been studied in alkaline media and found to give the ester (247 X = O) and the imino-ester (247 X = NH). When the proportion of the cyano-ester was increased, high yields of the latter were obtained. "... 

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