Page 226 - Tandem Techniques

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with an alcohol in the presence of hydrochloric acid. A few milligrams of the material is heated with
100-200 µl of the alcohol containing 3 M HCl, for about 30 minutes at 70°C. The alcohol is removed by
evaporation in a stream of nitrogen (assuming the derivative is considerable less volatile than the
alcohol). Boron trifluoride and boron trichloride are also useful esterifying reagents. BF3 catalyzed
reactions are fairly rapid, and after heating in a boiling water bath are complete in a few minutes. A few
milligrams of the sample are added to 1 ml of the reagent, heated in boiling water for about 2 minutes
and the esters extracted into n-heptane. Diazomethane is another reagent used to produce methyl esters
but, unfortunately, it is extremely carcinogenic and must be handled with great care. N-methyl-N-nitro-
N-nitrosoguanidine is sometimes used as the starting material for generating diazomethane, but it too is
exceedingly carcinogenic. The De Boer and Backer reagent (Diazald) (N-methyl-Nnitroso-p-
toluenesulphonamide) [31] is to be preferred. Diazomethane is a yellow gas, sometimes employed as a
solution in diethyl ether in the presence of methanol. It is usually prepared as required, employing the
simple generating apparatus described by Schlenk and Gellerman [32].

A few milligrams of the acid are dissolved in 2 ml of ether containing 10% of methanol, and the gas
generated from 2 mmol of Diazald is bubbled into the solution by a stream of nitrogen. When the
yellow color in the sample solution persists, the ether/methanol is removed in a stream of nitrogen,
providing a residue of the ester. The trimethyl silyl reagents, e.g. trimethylsilyl chloride, readily
produce trimethyl silyl esters, although there are a number of other silicone compounds that can be used
to produce similar esters. A few milligrams of the acid are dissolved in 600 µl of pyridine, and 200 µl
of di(chloromethyl)tetramethyldisilazane are added, together with 100 µl of chloromethyldimethylsilyl
chloride. The mixture is then allowed to stand for 30 minutes at room temperature to react. Another
reagent that works well, and is frequently used for esterification using a similar procedure, is
hexamethyldisilazane.

Acylation

Acylation can greatly reduce the polarity of amino, hydroxy, and thiol groups attached to small
molecular weight substances. As a result, their