The present invention is concerned with a novel process for the manufacture of 5-cyano-4-lower alkyl-oxazoles. These oxazoles form an important group of substances. For example, 5-cyano-4-methyl-oxazole is an important intermediate in the synthesis of pyridoxine (vitamin B.sub.6).
A number of processes for the manufacture of 5-cyano-4-methyl-oxazole by dehydrating 5-carbamoyl-4-methyl-oxazole have already been described. This dehydration takes place, for example, in the presence of phosphorus pentoxide. The disadvantage of this process is, however, the low product yield, which is attributed to the carbonization which occurs very readily in this reaction.
An improvement in this process comprises reacting 5-carbamoyl-4-methyl-oxazole with phosphorus pentoxide in the presence of quinoline as a solvent U.S. Pat. No. 3,222,374!. This process is also associated with disadvantages which arise from the toxicity of the quinoline, its unpleasant odor and its thermal instability. Moreover, quinoline is a relatively expensive solvent. Furthermore, the regeneration of the quinoline, the use of stoichiometric amounts of phosphorus pentoxide, the working-up of the phosphorus pentoxide by-products and their disposal according to environmental regulations, give rise to problems.
Another known process for the manufacture of 5-cyano-4-methyl-oxazole comprises reacting 5-carbamoyl-4-methyl-oxazole with a lower alkanecarboxylic acid anhydride and subjecting the reaction mixture, or the 4-methyl-5-(N-lower alkanoyl-carbonyl)-oxazole isolated therefrom, to a pyrolysis European Patent Application EP 0 010 607!. The final pyrolytic step has, however, certain disadvantages; in particular, corrosion problems occur with the materials from which the reactor is constructed and by-products which are difficult to recyclize from.
A further process U.S. Pat. No. 4,026,902! comprises catalytically dehydrating 5-carbamoyl-4-methyl-oxazole to 5-cyano-4-methyl-oxazole while heating in the presence of phosphorus pentoxide on a solid carrier. Disadvantages in this process are the handling of 5-carbamoyl-4-methyl-oxazole, especially the sublimation which is uppermost and therewith the solid dosing of the difficultly volatile starting material.
Furthermore, the one-stage conversion of 5-carboxylic acid ethyl ester-4-methyl-oxazole into 5-cyano-4-methyl-oxazole is described in U.S. Pat. No. 4,772,718. In this process, the corresponding oxazole ester is converted into 5-cyano-4-methyl-oxazole in the presence of ammonia and a zirconium oxide or hafnium oxide catalyst in the gas phase. Here, however, the use of a relatively expensive catalyst and, in order to achieve an optimal reaction course, the maintenance of very narrow reaction conditions, are disadvantageous.
Finally, the gas phase dehydration of 5-carbamoyl-4-methyl-oxazole to 5-cyano-4-methyl-oxazole described in European Patent Application EP 0 492 233 has the disadvantage of a reaction temperature of 400.degree. C.-500.degree. C. and must be carried out at a pressure of 50 to about 300 kPa.
Olah et al., Synthesis, 1980:657-658, (August 1980), describe a general method of preparing nitriles from amides by dehydration. The procedure describes adding cyanuric chloride to a solution of the amide in dimethylformamide. The method described by Olah is not practicable for the object of the present invention because of the exothermic reaction (Handbook of Reactive Chemical Hazards, fourth edition, Butterworth 1990, page 331-333). For Olah et al. the exothermic reaction presented no problem as they were only interested in preparing very small amounts of nitrile. Using cyanuric chloride and 5-carbamoyl-4-methyl-oxazole without dimethylformamide led to very low yields (.apprxeq.1%) of the corresponding nitrile.
USPTO Backgrounds
USPTO Backgrounds