A Three Part Research Report: The Synthesis of Potential Insecticides, N-(4-Heteroaryloxybenzoyl)-N\u27-(2,4-Dichlorobenzoyl) Hydrazines: A Reinvestigation of Hexamethylphosphoramide with Ketoximes; Regioselective Fluoralkoxylation and Polyfluoroalkoxylation of Activated Dihalobenzenes and Dihaloheterocycles

This report discusses research in three areas of organic synthesis: The synthesis of potential insecticides; the reinvestigation of the reaction of hexamethylphosphoramide with ketoximes; and the regioselective fluoroalkoxylation and polyfluoroalkoxylation of activated dihalobenzenes and dihaloheterocycles. In Part I, a series of N-(4-heteroaryloxybenzoyl)-N\u27-(2, 3-dichlorobenzoyl) hydrazines are synthesized, and attempts at cyclic dehydration to the corresponding 2, 5-disubstituted-1, 3, 4-oxadiazoles are discussed. In Part II, the synthesis of N, N-dimethyl-N\u27-aryl amidines by the reaction of aryl alkyl and diaryl ketoximes with HMPA is discussed. In Part III, a series of activated dihalobenzenes and dihaloheterocycles are reacted with sodium trifluoroethoxide to study the possibility of regioselective fluoroalkoxylation and polyfluoroalkoxylation of these activated substances

Alpha-Alkyl-alpha-amino-beta-sulphone Hydroxamates as Potent MMP Inhibitors that Spare MMP-1

A series of α-alkyl-α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from \u3e10 to \u3e1000. Selected compounds were orally bioavailable

MMP-13 Selective Isonipecotamide Alpha-sulfone Hydroxamates

A series of N-aryl isonipecotamide α-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13

α-Amino-β-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1

A series of α-amino-β-sulphone hydroxamates was prepared and evaluated for potency versus MMP-13 and selectivity versus MMP-1. Various substituents were employed on the α-amino group (P1 position), as well as different groups attached to the sulphone group extending into P1′. Low nanomolar potency was obtained for MMP-13 with selectivity versus MMP-1 of \u3e1000× for a number of analogues. α-Amino-β-sulphone hydroxamates were prepared, which are potent MMP-13 inhibitors with selectivity versus MMP-1 of \u3e1000× for a number of analogues. Selected compounds exhibited oral bioavailability

A Reinvestigation Of The Reaction Of Hmpa With Ketoximes

A series of ketoximes have been found to react with HMPA in the absence of acid catalysis to produce N,N-dimethyl-N′-arylamidines in reasonable yields

Regioselective Fluoroalkoxylation And Polyfluoroalkoxylation Of Activated Polyhalobenzenes

A series of activated polyhalobenzenes have been reacted with various amounts of sodium 2,2,2-trifluoroethoxide in DMF or HMPA. The nature of these monosubstitution and polysubstitution reactions are described