No abstract

Starting from protected a-hydroxy amides, cyanohydrins (a-hydroxy nitriles) are obtained through dehydration by cyanuric chloride/DMF in excellent yield. The advantages of the procedure are the extremely mild reaction conditions that prevent racemization.Cyanohydrins (a-hydroxy nitriles) are commonly synthesized by the addition of hydrocyanic acid to an aldehyde, as described in several standard textbooks of organic chemistry. 1 Naturally, this method yields racemic mixtures of a-hydroxy nitriles. Starting from an aldehyde, enantiomerically pure a-hydroxynitriles can be obtained using an enzyme (oxynitrilase) 2,3 or by the chiral Lewis acid-catalyzed addition of hydrocyanic acid (or cyanotrimethylsilane) (M = Ti, 4 B, 5 Sn, 6 Re 7 ). Cyanohydrins are of particular interest as intermediates since they can readily be converted into a variety of valuable starting materials for synthesis (b-amino alcohols, a-hydroxy ketones, ahydroxy carboxylic acids).An alternative method to prepare a-hydroxy nitriles is the dehydration of a-hydroxy amides. We became interested in alternative dehydration methods since all the established procedures give rise to insurmountable problems when conducted on an industrial scale, e.g. expensive reagents, large excess of the cyano component, painstaking workup, toxic solvents, waste problems, etc. The mixture cyanuric chloride/DMF was introduced by Olah and coworkers for the dehydration of aliphatic and aromatic amides to the corresponding nitriles. 8 The potential of this method has so far not been exploited with the notable exception of the synthesis of heterocyclic carbonitriles. 9,10 At around the same time, Rodrigues and Maetz described the preparation of N-protected chiral a-amino nitriles from N-protected a-amino acid amides using cyanuric chloride/DMF. 11Based on our experience with the synthesis of heterocyclic amides we decided to extend our methodology to the dehydration of functionalized amides. We chose cyanohydrins as target molecules for two reasons: on the one hand, there exists a vast experience with enantiomerically enriched cyanohydrines concerning synthesis and analytics, and on the other hand the hydroxy amide precursors are readily available as starting materials. In our model study, the enantiopure a-hydroxy amide was obtained by aminolysis of D-and L-pantolactone (1), respectively (Scheme 1). The hydroxy groups were protected with isopropenyl methyl ether (IPM). 12 Standard procedures for the introduction of a protecting group for the hydroxy functionalities did not yield satisfactory results. Protection with acetone/p-TsOH gave only a yield of 35% of the dioxane 3, while the alternative acetone/orthoester procedure led to only a slight increase of product yield (55%). Scheme 1The crucial step, the dehydration of the 1,3-dioxane-4-carboxamide 3 to the nitrile 4, could be conducted in excellent yields by means of the reaction conditions outlined in Scheme 1. Standard acid-catalyzed deprotection gives the desired cyanohydrin 5. The key question was whether or not the D...

Methanetrisulfonic acid had been prepared for the first time over 140 years ago, but it was used only scarcely in chemical transformations. In the course of our activities dealing with key-steps of industrial syntheses of vitamins, e.g. economically important vitamin E (acetate), we found that methanetrisulfonic acid is an extremely effective catalyst in a variety of reactions. Examples of its applications are Wagner-Meerwein rearrangements, Friedel-Crafts alkylations and ring closures, as well as acylation reactions. Use of this catalyst in truly catalytic amounts (0.04-1.0 mol%) resulted in highly selective transformations and yields over 95%. (Remark by the authors: We are describing only one example each for the various types of reactions. Therefore, it would be more appropriate to write (here and in the Introduction and in the Conclusion sections): "Wagner-Meerwein rearrangement, Friedel-Crafts alkylation and ring closure, as well as acylation reactions")

A new method for the preparation of an E/Z mixture of vitamin A acetate from hydroxenin monoacetate is described. This two-step reaction was studied by changing the reaction parameters (reaction temperature, ultrasound power, and reaction time) and the alcohol used. This approach consists of the dehydration reaction of hydroxenin monoacetate under ultrasound irradiation in CCl4 and an aliphatic alcohol under an inert atmosphere. The formation of small amounts of HCl from CCl4 and an aliphatic alcohol under ultrasound irradiation is followed by the dehydration reaction of hydroxenin monoacetate. An E/Z mixture of vitamin A acetate was obtained resulting in the desired pentaenes. Some ethers derivatives were also formed as by-products, isolated and characterized. Study of the reaction mechanism is also reported here.