Reduction water-soluble azides

Scheme 4.13 Reduction of water-soluble azides in water and reaction mechanism for the transformation in question.

The synthesis of MZP is shown in Scheme 3.1. Nitration of the readily available antimalarial diaminopyrimidine pyrimethamine (PYM) (113) yielded w-nitropyrimethamine (MNP) (114) exclusively, and reduction to the corresponding amine w-aminopyrimethamine (MAP) (115), followed by diazotisation and azidation afforded the azide (111) in excellent overall yield [135, 136]. The extremely poor aqueous solubility of MZP (22 4/water-soluble salt for biological evaluation, and m-azidopyrimethamine ethanesulphonate MZPES (112), with an aqueous solubility of 17.60 0.45 mg/ml at 20°C, was the most appropriate for this purpose. A series of derivatives (116)-(123), differing... 

Carbamates are one of the most widely used protecting groups for amines and the development of one-pot conversions of azides to carbamates such as Boc, Cbz, and allyl further expanded the scope of utility of the Staudinger reduction. Treatment of the Staudinger reaction iminophosphorane intermediate 26 with 1.05 equivalents of 2-t-(butoxycarbonyloximino)-2-phenylacetonitrile (Boc-on) led to Boc-protected amines 28 thru 32 in 87-100% overall yield.19 This process utilizes trimethylphosphine, which is more reactive than triphenylphosphine and provides an easier work-up because trimethylphosphine oxide is water soluble. It should be noted that the use of di-f-butyldicarbonate (B0C2O) has been investigated but leads to lower yields in comparison.20... 

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