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2.2. Bacisity of Pyridine vs PyrimidinePart-IAim of Present WorkAs suggested above, one of the options that has not been tried is the 3-aza analog ofpyridine i.e. pyrimidine, which is it’s logical bioisoster.NNPyridinepKa : 5.2NPyrimidinepKa : 1.31A review of a basic literature on organic & the heterocyclic chemistry reveals that indeedpyrimidine ring is the ring of choice. This is because1. Pyrimidine is weakly basic or rather acidic than pyridine (lower pKa)2. Electronegativity of the additional N 3 Nitrogen depletes electrons on N 1 .3. Depletion of the π-electrons is caused by an insertion of the second electronattracting nitrogen.The weakly basic nature of pyrimidine (pKa-1.31) is striking in relation to pyridine (pKa-5.2). 8 It is understandable as an inductive effect (depletion of π-electrons), caused byinsertion of the avidity electron-attracting second nitrogen atom at N 3 . Pyrimidine maytherefore be likened more to β-nitropyridine (pKa-0.8), which contains the equally strongelectron-attracting nitro group, than to the parent pyridine.A cursory review of the literature does reveal only one successful use of this logic 9(structure-6).NONSNONH6(Roussel Morishita Co. Ltd., under clinical trials)NO60