Hydrogen, reaction with bromine nitrous oxide

These agents would be used as adjuncts to beta lactams since they have no antibacterial activity in their own right. A key reaction in the synthesis of each compound involves the replacement of the amine at 6 and the protection of that position as a mono- or di-halide. Thus reaction of 6-APA (2-4) with nitrous acid gives the diazonium salt (9-1) this is converted to the dibromide (9-2) on treatment with bromine. The ring sulfur is then oxidized with permanganate to the sulfone (9-3). Hydrogenolysis of the product replaces the two bromine atoms by hydrogen to afford sulbactam (9-4) [13]. 

Rice, Fryling, and Weselowski (J. Amer. Chem. Soc., 1924, 46, 2405) make all reaction rates proportional to the concentration of what they call residual molecules, which have to be formed endothermically from one of the reactants. The proportion of these increases with temperature and accounts for the increase in reaction rate. Something of this kind may be true in special cases, for example, in the formation of HBr the residual molecule would be the bromine atom. But this resolution into atoms is only the limiting case of ordinary activation, and it is difficult indeed to see what the residual molecule could be, or what tautomeric change could occur in the simple decomposition of hydrogen iodide or nitrous oxide. 

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