No abstract

Nitrile oxides (3) are rapidly generated in situ on dissolution of the corresponding hydroxamoyl chlorides (1) in aqueous solution a t pH > 4; reaction of (3) with the solvent is slow at pH < 10. Primary and secondary amines react stereospecifically t o give only theZ-amidoximes (1 1 ), in which the nucleophile and OH groups are cis. With primary amines and ammonia the Z-isomer is also thermodynamically favoured but with the more bulky secondary amines subsequent isomerisation to the more stable €-isomer (1 2) occurs. Several criteria (p +0.53 for substituent variation in the nitrile oxide ; Pnllc 0.48 for primary amine variation ; small enhancement shown b y ' a-effect ' amines ; small steric effect of ortho-substituents in nitrile oxide) are consistent with a transition state for amidoxime formation in which there is little bond formation between the amine and the carbon of the nitrile oxide.

A new group of reactive N-amidinohydrazonyl halides is described. These materials may be isolated as stable hydrobromide salts but undergo rapid halide displacement on dissolution in ionizing solvents. Their solvolytic behaviour was investigated in detail in aqueous dioxan ; because of the rapidity of the reaction, measurements were possible (at 25") only in solutions of high acidity and low aqueous content. The initial product formed at all pH values was the corresponding hydrazide (formed by water attack on an intermediate azocarbonium ion) rather than the expected 3-amin0-5-aryl-l.2.4-triazoles.The latter is obtained a t higher temperatures from the hydrazide in basic solution (tt ca. 1 h for cyclization at pH 9 at 900). The mechanism of formation of the N-amidinohydrazonyl bromides by direct bromination of the corresponding hydrazones was also investigated and the rate-determining step for this process was shown to be a slow geometric isomerisation (E-Z) about the azomethine bond.

No abstract

Conformationally defined enantiomeric local anesthetics and fluorescent dyes were synthesized. Neither the local anesthetics nor the fluorescent probes showed stereospecificity in interacting with nerve membranes. The fluorescence signals generated by the dyes showed excellent correlation with the time course and shape of the nerve action potential.