Pyridine 1-oxides nitration

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

Pyridine is nitrated in the /3 position only under vigorous conditions (see Problem 20.21(6)]. However, its N-oxide is nitrated readily in the y position the intermediate formed by such attack is very stable because all atoms have an octet of electrons. The N-oxide behaves like phenoxide ion, C HjO (Problem 19,18( )j. 

Pyridine 1-oxide is nitrated (H2SO4/HN03, 100°C) to give the 4-nitro derivative in good yield. Substituted pyridine oxides such as the 2- and 3-methyl, -halo and -methoxy derivatives also give... 

It has been shown recently by den Hertog and Overhoff [78] that N-pyridine oxide can readily be nitrated with a nitric and sulphuric acid mixture. 4-Nitro-pyridine is formed in good yield-about 81%. 

The transformation shown in equation (27) is impressive since DMSO had previously beat tried and shown to fail for this substrate. The reaction was so performed as a one-pot procedure, with pyridine -oxide and silver nitrate in acetonitrile followed by addition of triethylamine. This is the prrferred method of these authors for these substrates. 

Silver dichromate-pyridine complex (tetrapyridine silver dichromate), Ag2Cr207 4C5H5N, an orange-yellow solid prepared by adding a warm solution of potassium dichromate to a solution of silver nitrate in water and pyridine, oxidizes allylic and benzylic alcohols to aldehydes and acyl-tiins to a-diketones [659]. 

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