Hydroxy acids Esters

In addition to the above, Grignaid s leagent has been utilised m preparing olefines, etheis, ketonic esters, hydroxy-acids, quinols, amides, hydroxylammes, c., for details of wliicti books of reference must be consulted ... 

Lactone. A cyclic ester. Hydroxy acids may exist as lactones if the hydroxyl groups are situated so that the lactone formed has a five- or six-membered ring ch. 

N-Benzylamides are recommended when the corresponding acid is liquid and/or water-soluble so that it cannot itself serve as a derivative. Phe benzylamides derived from the simple fatty acids or their esters are not altogether satisfactory (see Table below) those derived from most hydroxy-acids and from poly basic acids or their esters are formed in good yield and are easily purified. The esters of aromatic acids yield satisfactory derivatives but the method must compete with the equally simple process of hydrolysis and precipitation of the free acid, an obvious derivative when the acid is a solid. The procedure fails with esters of keto, sul phonic, inorganic and some halogenated aliphatic esters. 

Preliminary indication of the presence of a phenol ester may be obtained by heating the compound with soda-lime esters of phenols and also aromatic hydroxy-acids usually give the phenol. (Likewise amides, Imides, nitriles, substituted hydrazines, uretheines, etc. eifiord ammonia.)... 

Hydroxy acids compounds that contain both a hydroxyl and a carboxylic acid function have the capacity to form cyclic esters called lactones This intramolecular esterification takes place spontaneously when the ring that is formed is five or six membered Lac tones that contain a five membered cyclic ester are referred to as 7 lactones, their six membered analogs are known as 8 lactones... 

A variety of a-amino acid derivatives, including the acids themselves, haUdes, esters, and amides can be transformed iato hydantoias by coadeasatioa with urea (67). a-Hydroxy acids and thek nitriles give a similar reaction (68) ... 

Apart from lactic and hydroxyacetic acids, other a- and P-hydroxy acids have been small-volume specialty products produced in a variety of methods for specialized uses. y-Butyrolactone [96 8-0] which is the monomeric inner ester of y-hydroxybutyric acid [591-81-17, is a large-volume chemical derived from 1,4-butanediol (see Acetylene-derived chemicals). 

Reactions and Uses. The common reactions that a-hydroxy acids undergo such as self- or bimolecular esterification to oligomers or cycHc esters, hydrogenation, oxidation, etc, have been discussed in connection with lactic and hydroxyacetic acid. A reaction that is of value for the synthesis of higher aldehydes is decarbonylation under boiling sulfuric acid with loss of water. Since one carbon atom is lost in the process, the series of reactions may be used for stepwise degradation of a carbon chain. 

Chemical Composition. Wool wax is a complex mixture of esters of water-soluble alcohols (168) and higher fatty acids (169) with a small proportion (ca 0.5%) of hydrocarbons (170). A substantial effort has been made to identify the various components, but results are compHcated by the fact that different workers use wool waxes from different sources and employ different analytical techniques. Nevertheless, significant progress has been made, and it is possible to give approximate percentages of the various components. The wool-wax acids (Table 9) are predominantiy alkanoic, a-hydroxy, and CO-hydroxy acids. Each group contains normal, iso, and anteiso series of various chain length, and nearly all the acids are saturated. 

Castor oil sulfation results largely in a sulfuric acid ester in which the hydroxyl group of ricinoleic acid has been esterified. However, other reactions can also take place. For example, the double bond can be attacked to produce an ester or the hydroxysulfonic acid (33). Hydrolysis of the sulfuric acid esters occurs during the reaction and subsequent treatment forming hydroxy acids and sulfuric acid. These hydroxy acids can be further sulfated. 

The acetyl content of cellulose acetate may be calculated by difference from the hydroxyl content, which is usually determined by carbanilation of the ester hydroxy groups in pyridine solvent with phenyl isocyanate [103-71-9J, followed by measurement of uv absorption of the combined carbanilate. Methods for determining cellulose ester hydroxyl content by near-infrared spectroscopy (111) and acid content by nmr spectroscopy (112) and pyrolysis gas chromatography (113) have been reported. 

Reaction of cyanohydrins with absolute ethanol in the presence of HCl yields the ethyl esters of a-hydroxy acids (3). A/-substituted amides can be synthesized by heating a cyanohydrin and an amine in water. Thus formaldehyde cyanohydrin and P-hydroxyethylamine lead to A/- (P-hydroxyethyl)hydroxyacetamide (4). 

This can be achieved by an indirect method. The lithio derivative is first reacted with a borate ester. Sequential acid hydrolysis and oxidation yields the corresponding hydroxy derivative. This procedure is illustrated by the conversion of 2-lithiobenzo[6]thiophene to 2-hydroxybenzo[6]thiophene, which exists predominantly in the 2(3//)-one tautomeric form (200) <70JCS(C)1926). 

The lac resin is associated with two lac dyes, lac wax and an odiferous substance, and these materials may be present to a variable extent in shellac. The resin itself appears to be a polycondensate of aldehydic and hydroxy acids either as lactides or inter-esters. The resin constituents can be placed into two groups, an ether-soluble fraction (25% of the total) with an acid value of 100 and molecular weight of about 550, and an insoluble fraction with an acid value of 55 and a molecular weight of about 2000. 

The most common O- and N-acylation procedures use acylating agents that are more reactive than caiboxylic acids or their esters. Carboxylic acid chlorides and anhydrides react rapidly with most unhindered hydroxy and amino groups to give esters and amides, respectively ... 

Of more direct interest is the preparation of 3-ethylquinuclidine by this method (Prelog, Sogtaric and Gustak (1940)). Ethyl tetrahydropyranyl ketone (X R = tetrahydropyranyl in X to XIV) was condensed wiA ethyl brpmoacetate (XI) to give the hydroxy-acid ester (XII) which was dehydrated by potassium acid sulphate at 90° to ethyl 3-(tetrahydro-pyranyl-4)-pentenate (XIII) and this hydrogenated to tie corresponding... 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

Figure 15.7 Cliromatographic separation of cliiral hydroxy acids from Pseudomonas aeruginosa without (a) and with (h) co-injection of racemic standards. Peak identification is as follows 1, 3-hydroxy decanoic acid, methyl ester 2, 3-hydroxy dodecanoic acid, methyl ester 3, 2-hydroxy dodecanoic acid, methyl ester. Adapted from Journal of High Resolution Chromatography, 18, A. Kaunzinger et al., Stereo differentiation and simultaneous analysis of 2- and 3-hydroxyalkanoic acids from hiomemhranes hy multidimensional gas cliromatog-raphy , pp. 191 -193, 1995, with permission from Wiley-VCH. (continuedp. 419)...

Copper chromite 14) and barium-promoted copper chromite (75,/7) have been used for acid reductions but very high temperatures (300 C) are required. The necessary temperature is sufficiently higher than that required foresters to permit selective reduction of half-acid esters to the hydroxy acid 23). The reverse selectivity can be achieved by reduction over H Ru4 CO)a PBu3)4 at I00-200 C and 1500-3000 psig. This homogeneous catalyst will reduce acids and anhydrides, but not esters (2). 

Less important methods are the self condensation of w-hydroxy acid and the ring opening of lactones and cyclic esters. In self condensation of w-hydroxy acids, cyclization might compete seriously with linear polymerization, especially when the hydroxyl group is in a position to give five or six membered lactones. 

Methyl esters of unsaturated acids (loss of CH3OH + HzO) Methyl esters of straight-chain hydroxycarboxylic acids except 2-hydroxy acids... 

Polyesters have been obtained in organic medium by polyesterification of hydroxy acids,328,329 hydroxy esters,330 stoichiometric mixtures of diols and diacids,331-333 diols and diesters,334-339 and diols and cyclic anhydrides.340 Lipases have also been reported to catalyze ester-ester interchanges in solution or in die bulk at moderate temperature.341 Since lipases obviously catalyze the reverse reaction (i.e., hydrolysis or alcoholysis of polyester), lipase-catalyzed polyesterifications can be regarded as equilibrium polycondensations taking place in mild conditions (Scheme 2.35). 

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