1,2:5,6-Di-0-isopropylidene-o-mannitol
(1) is the most important source of o-glyceraldehyde derivatives which are usedIe widely in synthesis. The formation of 1 from o-mannitol (2) has been studied severally"5. All of the syntheses require the separation of 1 from the accompanying 1,2:3,4:5,6_triacetal3 by crystallisation. Recent studieP6 of the acetonation of 2 have shown that complex mixtures of products are formed under most of the reaction conditions.
An unusual synthesis of 1, conducted in pyridine solution, resulted during studies of the development of alternative catalysts for the acetalation of acid-sensitive substrates. An effective, alternative procedure for the isolation and purification of 1 was also developed and applied to some known alternative syntheses of 1. The results of these studies are described below.
A solution of o-mannitol (2) in pyridine containing a catalytic amount of p-toluenesulfonic acid was treated at reflux temperature with 2,2_dimethoxypropane for 3.5-4 h. T.1.c. then demonstrated the absence of 2 and the presence of 1 and 3as the main components. Treatment of the neutralised mixture with acetic anhydride-pyridine and then with ice-water precipitated only the pure crystalline 3,4-diacetate (4) of 1. The yield of 4 (5 l-54%), although modest, represents an approximate average for many of the various acetonation reactions of 2.
The material in the aqueous phase was deacetylated and column chromatography then gave 3 (18%) 1 (9"/), and syrupy mixtures of other acetals which were not investigated further. Deacetylation of the diacetate 4 in methanolic potassium cyanide17 yielded pure 1 in almost quantitative yield (9698O/,). No reaction occurred when 2 in pyridine was treated with 2,2_dimethoxypropane in the absence of p-toluenesulfonic acid.
The catalytic effect of p-toluenesulfonic acid in pyridine solution has been employed" for the esterification of phenols and alcohols in the presence of dicyclohexylcarbodi-imide. In the absence of the catalyst, the yields were poor due to the formation of N-acylurea. The relative acidities of several organic acids have been compared'9*20 in * Acetalation Studies, Part VIII. For Part VII, see ref. 25.