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The nucleophilic substitution reactions of Y-O-aryl phenyl phosphonochloridothioates with substituted anilines (XC 6 H 4 NH 2 ) and deuterated anilines (XC 6 H 4 ND 2 ) are kinetically investigated in acetonitrile at 55.0 o C. The deuterium kinetic isotope effects (DKIEs) invariably increase from an extremely large secondary inverse (k H /k D = 0.439; min) to a primary normal (k H /k D = 1.34; max) as both substituents of nucleophile (X) and substrate (Y) change from electron-donating to electron-withdrawing. These results are opposite to the DKIEs on Y-O-aryl methyl phosphonochloridothioates, and can be rationalized by the gradual transition state (TS) variation from backside to frontside attack. The trigonal bipyramidal pentacoordinate TS is proposed for a backside attack, while the hydrogen-bonded, four-center-type TS is proposed for a frontside attack. The negative values of the cross-interaction constants (ρ XY(H) = −0.38 for XC 6 H 4 NH 2 and ρ XY(D) = −0.29 for XC 6 H 4 ND 2 ) indicate that the reactions proceed by a concerted S N 2 mechanism.

Flavonoids, polyphenolic heteronuclear compounds which are naturally occurring antioxidants are widely used as antiaging substances. Synthesis of new naturally occuring organic compounds with basic skeleton of chalcones, flavones and oxygenated flavones and their antimicrobial activity were reported by this research group for long. Presently comparative molecular field analysis (CoMFA) implemented in Sybyl 7.3 was conducted on a series of substituted flavones. CoMFA is an effective computer implemented 3D QSAR technique deriving a correlation between set of the biologically active molecules and their 3D shape, electrostatic and hydrogen bonding characteristics employing both interactive graphics and statistical techniques. Evaluation of 38 compounds were served to establish the models with grid spacing (2.0 Å).

Kinetic studies on the reactions of Y-S-aryl phenyl phosphonochloridothioates with X-pyridines have been carried out in MeCN at 55.0 ºC. The Hammett and Brönsted plots for substituent X variations in the nucleophiles are biphasic concave upwards with a break point at X = H. The Hammett plots for substituent Y variations in the substrates are biphasic concave upwards with a break point at Y = H, and the sign of ρ Y is changed from unusual negative (ρ Y < 0) with the weaker electrophiles to positive (ρ Y > 0) with the stronger electrophiles. The stepwise mechanism is proposed on the basis of the ρ X , β X , and ρ XY values as follows: a ratelimiting leaving group departure from the intermediate involving a frontside attack and product-like TS for the stronger nucleophiles and weaker electrophiles; a rate-limiting leaving group departure from the intermediate involving a backside attack and product-like TS for the weaker nucleophiles and electrophiles; a rate-limiting bond formation involving a frontside attack for the stronger nucleophiles and electrophiles; a rate-limiting bond formation involving a backside attack for the weaker nucleophiles and stronger electrophiles. The substituent effects of X and Y on the pyridinolysis mechanisms of R 1 R 2 P(=S)Cl-type substrates are discussed.

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