Alternative procedure using diglyme

A mixture of the dicarboxylic acid (21.0 g, 0.12 mol) and acetic anhydride (600 ml, dried over 4 A sieves) is heated at 100°C (4h) with vigorous stirring. The mixture is evaporated in vacuo, and the residue is triturated with acetone, and azeotropically dried with toluene to afford the product (14.6g, 95%), m.p. 245-248°C (dec). 

A mixture of the dicarboxylic acid (0.850 g, 5 mmol) and NJ4-dimethylacetamide (25 ml) is heated at 180°C (3 h). The mixture is evaporated, and the residue is triturated with benzene, followed by recrystallization from ethanol to give the product (0.470 g, 75%), m.p. 245-246°C. A substantial amount of the other isomer is also formed. 

Specific preparation of each of the above isomers should theoretically be possible by methylation of imidazole-4-carboxylic acid in neutral and basic media. Methylation yields, however, are unlikely to be high, and the separation 

Ring-synthetic procedures which lead to carboxyl-substituted imidazoles are usually multistep and seldom give high yields. Nevertheless, they are frequently the only viable routes to products with a particular substitution pattern. A summary of the methods available follows. 

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The hydroboration amination sequence in diglyme is a general procedure for the conversion of olefins to primary amines without rearrangement and with predictable stereochemistry.5 An alternative procedure, using tetrahydrofuran as solvent and either hydroxylamine-O-sulfonic acid or chloramine, is applicable with terminal olefins and relatively unhindered internal and alicyclic olefins.6 O-Mesitylenesulfonylhydroxylamine also gave desired amines in comparable yield.7 Alternative procedures for the hydroboration of olefins use commercially available solutions of di-borane in tetrahydrofuran8 or dimethylsulfide.9... 

If the substrate is insoluble in ethanol or if it is sensitive to protic media another solvent must of course be used. Ethyl acetate, tetrahydrofuran or diglyme are suitable alternatives but not dimethylformamide or acetonitrile which poison the catalyst. If an alternative solvent is needed the catalyst is prepared in ethanol as in step 1 and 2, but the procedure thereafter is modified as follows. 

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