Complex metal hydrides, reductions with

When ethyl 4-methyl-2-methylthiopyrimidine-5-carboxylate or ethyl 2,4-dimethylpyrimidine-5-carboxylate was treated with lithium aluminum hydride at — 70°C, preferential reduction of the ester group occurred, yielding the 5-hydroxymethyl derivative rather than ring reduction.181 

Shadbolt and Ulbricht reported182 reduction of a number of 2-methyl-thiopyrimidines by LiAlH4 in tetrahydrofuran and by NaBH4 in ethanol to form the corresponding 1,6-dihydro derivatives (105) [Eq. (39)]. 

Mamaev and Gracheva suggested183 that a yellow by-product, which was isolated from the reduction of 4,6-diphenylpyrimidin-2-one, is 1,2-dihydropy-rimidine 21a. Although attempts to prepare an analytically pure sample of this material failed. Reinvestigation and consequent optimization of this reaction enabled the preparation of 21a in 78% yield.184 The material was stable, could 

This reaction was extended to other derivatives. Thus 2-phenyl-1,6-dihydropyrimidine was prepared by LiAlH4 reduction of 2-phenylpyrimidin-4-one or 2-phenylpyrimidine. Undoubtedly, there is great potential in the reduction of pyrimidines with complex hydrides, and this approach should attract wide attention in the future. 

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Gaylord, N. G, 1956, Reduction with Complex Metal Hydrides, Interscience New York... 

Oxygen-containing azoles are readily reduced, usually with ring scission. Only acyclic products have been reported from the reductions with complex metal hydrides of oxazoles (e.g. 209 210), isoxazoles (e.g. 211 212), benzoxazoles (e.g. 213 214) and benzoxazolinones (e.g. 215, 216->214). Reductions of 1,2,4-oxadiazoles always involve ring scission. Lithium aluminum hydride breaks the C—O bond in the ring Scheme 19) 76AHC(20)65>. 

N. G. Gaylord, Reduction with Complex Metal Hydrides, Interscience, New York, 1956, KM6 pp. J. S. Pizey, Lithium Aluminium Hydride, Ellis Horwood, Ltd., Chichester, 1977,... 

For a review, sec Gaylord Reduction with Complex Metal Hydrides. Wiley New York. 1956. pp. 322-373. SJ1For a lisl of reagents, with references, see Ref. 21, pp. 548-549. 

The reactions of complex metal hydrides occur by an attack of the nucleophilic hydride ion on an electrophilic center.1 Aromatic nitrogen heterocycles in which the nitrogen has contributed only one electron to the -system (1) are electrophilic as compared with benzene, and have been shown to undergo reduction by the active reducing agent, lithium aluminum hydride. The nitrogen heterocycles in which the heteroatom has contributed two electrons to the 77-system (2) are electron-rich as compared with benzene and usually do not undergo reaction by reduction with complex metal hydrides.2 A combination of these two structural features, as in oxazoles (3), usually induces sufficient electrophilicity to allow attack by the hydride ion and reduction. 

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