B. Basappa, B. H. Doreswamy, M. Mahendra
May 10, 2005
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0
Influential Citations
3
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ChemInform
Abstract
The reduction of aldehydes such as 2-butyl-5-chloro-3H-imidazole-5-carbaldehyde and veratraldehyde, which are pharmaceutical key intermediates, have been reduced to alcohols by catalytic hydrogenation method in the presence of magnesium and also oximes are reduced to primary amines successively by magnesium/ammonium formate system, is a large scale feasible and cheaper method. The crystal structure of the product, (2-butyl-5-chloro-3H-imidazole-4-yl)methanol 1 is reported. IPC: Int.Cl. 7 C 07 D 233/54 The reduction of aldehydes and oximes with catalytic hydrogenation method in the presence of Raneynickel provides a convenient method for the preparation of alcohols and primary amines. Reduction of alkenes by catalytic hydrogenation method usually proceeds rapidly and cleanly 1 . Most reduction of carbonyl compounds are done with reagents that transfer a hydride from boron or aluminium such as sodium borohydride, lithium borohydride. There are a few reports on the use of these reducing agents since almost all of them are volatile unstable material, hazardous and not feasible for large-scale synthesis 2 . The development of a process for large-scale synthesis and effective reduction of aldehydes, which are pharmaceutical intermediates, is still an area of considerable synthetic interest, particularly when a product has to be obtained in a good yield 3 . Microwave assisted synthesis and X-ray crystallographic studies of 2-butyl- 4-chloro-5-imidazolaldehyde was reported. 2-Butyl-4-chloro-5-imidazolaldoxime was prepared and used for the discovery of new antifungal agents. Also initially we report a detailed study leading to the synthesis of novel γlactams from 3-biphenyl isoxazolidines via catalytic hydrogenation method 4 . As part of our continuing interest towards the method development for the transformation of functional groups such as aldehydes and oximes to their corresponding alcohols and amines, which are key intermediates in biosynthesis of many pharmacological important compounds, we report herein an efficient and high yield method for the preparation of alcohols like imidazolyl methanol and veratryl alcohol. Among aldehydes, 2-butyl-5chloro-3H-imidazole-5-carbaldehyde was reduced to its corresponding alcohol by catalytic transfer hydrogen method in the presence of magnesium as a catalyst was found to be good in yield and well feasible for large-scale synthesis. The product (2butyl-5-chloro-3H-imidazol-4-yl)-methanol was a key intermediate of DuP 753 (losartan), a non-peptide angiotensin II antagonist that is an orally active antihypertensive agent. Also we have successfully converted veratraldehyde to its corresponding alcohol, which is a key intermediate for the preparation of pinaverium bromide, an antiplasmodic agent and some other biological molecules 5 . The results and physical data of the reduced compounds are shown in the Scheme I and Table I.