Anhydrides, alcoholysis acids

Table 11.1-23. Lipase-catalyzed enantiomer- and enantiotopos-differentiating alcoholysis of carboxylic acid esters and anhydrides, alcoholysis or hydrolysis of oxazolin-2-ones, and esterification of carboxylic acids (PPL pig pancreas lipase, PCL Pseudomonas cepacia lipase, ANL Aspergillus niger lipase, CSL Candida sp. lipase, Candida cylindracea lipase, CAL-B Candida antarctica B lipase, CRL Candida rugosa lipase).

Acidic contaminants are poisonous to the alcoholysis catalysts and must be avoided. If the oil has a high acid number, or there are high acidity residues left in the reactor from the previous batch, such as sublimed phthaUc anhydride condensed under the dome of the reactor, the reaction can be severely retarded. A longer batch time or additional amount of catalyst is then required. Both are undesirable. 

The acid chlorides are generally more reactive than the corresponding acid anhydrides. In fact, the alcoholysis of acid chlorides is probably the best laboratory method for preparing esters. Frequentiy, basic materials are added during the course of the reaction to neutralize by-product hydrochloric acid. When the basic material is aqueous caustic, the procedure is referred to as the Schotten-Baumann procedure (73). Esterification of tertiary alcohols by acid chlorides is described in Reference 74. Esters of tertiary alcohols can also be formed through an intermediate /-butyl thioate group (75) ... 

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). 

A mixture of ethanol and acetic anhydride detonated and the compounds combusted causing a fire when sodium hydrogensulphate was introduced into the mixture by mistake. The acid nature of this salt obviously catalysed this alcoholysis. 

The compounds referred to as azolides are heterocyclic amides in which the amide nitrogen is part of an azole ring, such as imidazole, pyrazole, triazole, tetrazole, benzimidazole, benzotriazole, and their substituted derivatives. In contrast to normal amides, most of which show particularly low reactivities in such nucleophilic reactions as hydrolysis, alcoholysis, aminolysis, etc., the azolides are characterized by high reactivities in reactions with nucleophiles within the carbonyl group placing these compounds at about the same reactivity level as the corresponding acid chlorides or anhydrides. 11... 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

Esters are less reactive than acid chlorides and acid anhydrides. They are converted to carboxylic acid hy acid or base hydrolysis, and to another ester by acid or base alcoholysis (transesterification). The 1°, 2° or 3° amides are obtained from esters by treatment with ammonia or 1° or 2° amines, respectively. 

Mannitol hexanitrate is obtained by nitration of mannitol with mixed nitric and sulfuric acids. Similarly, nitration of sorbitol using mixed acid produces the hexanitrate when the reaction is conducted at 0—3°C and at —10 to —75°C, the main product is sorbitol pentanitrate (117). Xylitol, ribitol, and L-arabinitol are converted to the pentanitrates by fuming nitric acid and acetic anhydride (118). Phosphate esters of sugar alcohols are obtained by the action of phosphorus oxychloride (119) and by alcoholysis of organic phosphates (120). The 1,6-dibenzene sulfonate of D-mannitol is obtained by the action of benzene sulfonyl chloride in pyridine at 0°C (121). To obtain 1,6-dimethanesulfonyl-D-mannitol free from anhydrides and other by-products, after similar sulfonation with methane sulfonyl chloride and pyridine the remaining hydroxyl groups are acetylated with acetic anhydride and the insoluble acetyl derivative is separated, followed by deacetylation with hydrogen chloride in methanol (122). Alkyl sulfate esters of polyhydric alcohols result from the action of sulfur trioxide—trialkyl phosphates as in the reaction of sorbitol at 34—40°C with sulfur trioxide—triethyl phosphate to form sorbitol hexa(ethylsulfate) (123). 

Alcoholysis of trihalides 0-6 Hydrolysis of ortho esters 0-20 Alcoholysis of acyl halides 0-21 Alcoholysis of anhydrides 0-22 Esterification of carboxylic acids 0-23 Transesterification 0-24 Alkylation of carboxylic acid salts 0-25 Cleavage of ethers with anhydrides 0-26 Alkylation of carboxylic acids with diazo compounds... 

Kinetic resolution of chiral, racemic anhydrides In this process the racemic mixture of a chiral anhydride is exposed to the alcohol nucleophile in the presence of a chiral catalyst such as A (Scheme 13.2, middle). Under these conditions, one substrate enantiomer is converted to a mono-ester whereas the other remains unchanged. Application of catalyst B (usually the enantiomer or a pseudo-enantiomer of A) results in transformation/non-transformation of the enantiomeric starting anhydride ). As usual for kinetic resolution, substrate conversion/product yield(s) are intrinsically limited to a maximum of 50%. For normal anhydrides (X = CR2), both carbonyl groups can engage in ester formation, and the product formulas in Scheme 13.1 are drawn arbitrarily. This section also covers the catalytic asymmetric alcoholysis of a-hydroxy acid O-carboxy anhydrides (X = O) and of a-amino acid N-carboxy anhydrides (X = NR). In these reactions the electrophilicity of the carbonyl groups flanking X is reduced and regioselective attack of the alcohol nucleophile on the other carbonyl function results. 

No examples of simple organocatalytic kinetic resolution of dicarboxylic acid anhydrides, e.g. by alcoholysis (Scheme 13.1, middle, X = CR2) seem to have been reported. This type of transformation requires that one anhydride enantiomer remains unchanged while the other is transformed to a mono-ester. Nucleophilic catalysts such as cinchona alkaloids have been shown to effect parallel kinetic resolution, that is, the two enantiomers of the anhydride are converted to regioiso-meric esters. This type of transformation is therefore discussed in Section 13.1.3. 

No examples of organocatalytic dynamic kinetic resolution of dicarboxylic acid anhydrides, e.g. by alcoholysis (Scheme 13.1, bottom right, X = CR2), seem to have been reported. 

Quite remarkable progress has also been achieved in enantioselective transformation of cyclic anhydrides derived from a-hydroxy and a-amino carboxylic acids. By careful choice of the reaction conditions, dynamic kinetic resolution by alcoholysis has become reality for a broad range of substrates. Again, the above mentioned dimeric cinchona alkaloids were the catalysts of choice. In other words, organoca-talytic methods are now available for high-yielding conversion of racemic a-hydroxy and a-amino acids to their enantiomerically pure esters. If desired, the latter esters can be converted back to the parent - but enantiomerically pure - acids by subsequent ester cleavage. 

Each structural assignment of signals 1-7 in the spectrum of Figure 4 is based on the addition of the authentic compound to the crude ozonolysis mixture, and—aside from peak 1—is also based on additional analytical evidence 2,2,3,3-tetrabromobutane (peak 2), 3,3-dibromobu-tanone (peak 4), and acetic acid were actually isolated while acetyl bromide (peak 3) as well as acetic anhydride (peak 5) were further identified by their sensitivity to solvolysis reactions, particularly hydrolysis and alcoholysis to form the corresponding esters. Diacetylperoxide (peak 6) was identified by the disappearance of peak 6 from the NMR spectrum as well as the disappearance of the typical infrared bands at 1810 and 1835 cm"1 when the reaction mixture was treated with sodium iodide. 

The arsonons esters are easily synthesized by the reaction of the dihaloarsines with alcohols or alkoxides. With alcohols, CaCl2 mnst be present because the esters are very sensitive toward hydrolysis, which leads to the reformation of the anhydride (equation 129). The reaction of an alcohol with a bisaminoarsine leads to an arsonous ester (equation 130), as does the alcoholysis of the anhydride. Reaction of diols with bis(drmethylamino)alkylarsines leads to esters of macrocycUc arsinous acid. ... 

The various ways in which esters of cellulose and phosphorous adds can be synthesized are esterification cellulose with free acids alcoholysis, with cellulose, of the esters and amides of phosphoric adds and esterification with mixed anhydrides df phosphoric adds and carboxylic adds. 

Polymers with pendant groups that are derivatives of carboxylic acid can he hydrolyzed to yield poly(acrylic acid). This includes polymers like polyacrylamide, polyacrylonitrile, and polyacrylates. When heated, poly(acrylic acid) form polymeric anhydrides, which undergo typical reactions of anhydrides, such as hydrolysis, alcoholysis, and amidation. 

Alcoholysis of amides is possible, although it is usually difficult. It has been most common with the imidazolide type of amides (e.g., 100). For other amides, an activating agent is usually necessary before the alcohol will replace the NR2 unit. Dimethylformamide, however, reacted with primary alcohols in the presence of 2,4,6-trichloro-l,3,5-pyrazine (cyanuric acid) to give the corresponding formate ester. Treatment of an amide with triflic anhydride (CF3SO2OSO2CF3) in the... 

Nucleophilic attack by a primary alcohol on the gamma phosphate of ATP (alcoholysis of an acid anhydride). This is a very favourable reaction. 

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