Influence of ortho methyl and isopropyl substituents on the reactivity of N-t-butyl P-arylphosphonamidic chlorides with isopropylamine and t-butylamine: steric acceleration of metaphosphonimidate formation by an elimination addition mechanism; contrasting behaviour of N,N-dimethyl P-arylphosphonamidic chlorides

Abstract

The two types of phosphonamidic chloride ArP(O)(Cl)NMe₂(5) and ArP(O)(Cl)NHBu^t(7) have been prepared with Ar = Ph, o-MeC₆H₄, 2,4,6-Me₃C₆H₂, and 2,4,6-Prⁱ₃C₆H₂. Both types give the expected phosphonic diamide substitution products with PrⁱNH₂ and Bu^tNH₂ in MeCN, but the two types display contrasting reactivity. With Bu^tNH₂ the NMe₂ substrates (5) become progressively less reactive as the degree of steric crowding increases, and although the decrease is quite small (70-fold overall) it seems consistent with an associative [S_N2(P)] mechanism. These substrates react 100 times faster with PrⁱNH₂, than with Bu^tNH₂ and in PrⁱNH₂–Bu^tNH₂ competitive experiments they give almost exclusively (99%) the product derived from the less hindered PrⁱNH₂. For the NHBu^t substrates (7) with Bu^tNH₂, there is little difference in reactivity between the Ph and o-MeC₆H₄ compounds, and between the 2,4,6-Me₃C₆H₂ and 2,4,6-Prⁱ₃C₆H₂ compounds, but remarkably the more crowded pair of substrates is the more reactive, by a factor of ca. 100. Also, in competitive experiments these substrates display relatively little preference for reaction with PrⁱNH₂. Here a dissociative eliminationaddition mechanism, with a metaphosphonimidate intermediate, is seen to be important. A possible explanation of the steric acceleration is advanced. The ability of (7; Ar = Ph) to undergo substitution by elimination–addition makes possible the phosphonylation of unreactive nucleophiles such as Bu^tOH and Prⁱ₂NH under mild conditions.