Crystalline derivatives preparation acid anhydrides

Maleic anhydride is commonly prepared by passing a mixture of benzene vapour and air over a catalyst (e.g. a vanadium derivative) at elevated temperatures (e.g. 450°C). It is a crystalline solid melting at 52.6°C (the acid melts at 130 C). 

The structure of difructose anhydride II has not yet been determined. McDonald and Jackson76 prepared its hexamethyl ether, which proved to be a crystalline compound melting at 73°. The behavior of the product from the acid hydrolysis of this hexamethyl derivative toward phenylhydrazine suggests that two different trimethyl-D-fructoses are present, the identification of which remains to be accomplished. Lately some evidence concerning the structure of this anhydride has been obtained by the use of per-iodic acid oxidation, as described on page 275. 

Anhydro-D-dulcitol (XXXV) has been prepared by a method which demonstrates its structure. Hockett and coworkers11 prepared it from methyl 3,6-anhydro-a-D-galactopyranoside but both the anhydride itself and its tetraacetate were liquid. Carr63 obtained another anhydro derivative of dulcitol by heating it with phosphoric acid. This also was a liquid but gave rise to a crystalline dibenzoate and a dicarbanilate and was a dianhydro derivative, but no constitutional studies have yet been carried out on this substance. 

Representatives of this new type of meso-ionic system (502) have been prepared by cyclodehydration of the acid derivatives 503 using trifluoroacetic anhydride. For example, the acid 503, R = p.ClCgH4, gave the red crystalline meso-ionic l,3-oxathiol-5-one (502, R =p.Cl.CgH4, R = CF3.CO) which is readily hydrolysed to the ketone (504, R = j3.Cl.CgH4). The trifluoroacetyl group in the 4-position appears to be essential for the stability of the meso-ionic system (502). 

The Pasteur method can also be applied to the resolution of neutral racemates, if these can be first converted into an acidic or basic derivative from which eventually a mixture of crystalline diastereoisomeric salts may be prepared by appropriate neutralisation. Thus, a racemic alcohol (e.g. ( )-octan-2-ol, Expt 5.220) may be converted into the corresponding racemic hydrogen phthalate ester by heating with phthalic anhydride, and the ester is then resolved by the Pasteur procedure using an optically active base. The resulting optically active hydrogen phthalate ester is then carefully hydrolysed with aqueous sodium hydroxide to regenerate one of the optically active forms of the alcohol. 

Besides the D-glucose derivative just described, three other crystalline dichlorides have been prepared from 2-hydroxyglycals, namely, the dichlorides from 2,3,4,6-tetra-0-benzoyl-(2-hydroxy-D-glucal)10 (yield, 22%), 2,3,6,2, 3, 4, 6,-hepta-0-acetyl-(2-hydroxycellobial)IS (yield, 30%), and 2,3,4-tri-0-benzoyl-(2-hydroxy-D-xylal)12 (yield, 17%). The 2,3,4,6-tetra-0-benzoyl-l,2-dichloro-l-deoxy-D-hexose prepared from the first of these by short chlorination in benzene reacted with sodium acetate in hot, glacial acetic acid. The crystalline product was assigned the structure of l-0-acetyl-3,4,6-tri-0-benzoyl-D-glucosone10 since it is not converted to kojic acid by pyridine-acetic anhydride (see below). A benzoyl group has been lost. 

Carboxylic, and arylsulfonic acid halides react rapidly with pyridines generating 1-acyl- and 1-arylsulfonylpyridinium salts in solution, and in suitable cases some of these can even be isolated as crystalline solids. The solutions, generally in excess pyridine, are commonly used for the preparation of esters and sulfonates from alcohols and of amides and sulfonamides from amines. 4-Dimethylaminopyridine (DMAP) is widely used (in catalytic quantities) to activate anhydrides in a similar manner. The salt derived from DMAP and t-butyl chloroformate is stable even in aqueous solution at room temperature. " ... 

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