Kinetics and Mechanism of the Pyridinolysis of Aryl Phenyl Isothiocyanophosphate Bull. Korean Chem. Soc. 2003, Vol. 24, No. 8 1135 Kinetics and Mechanism of the Pyridinolysis of Aryl Phenyl Isothiocyanophosphate in Acetonitrile Keshab Kumar Adhikary, Hai Whang Lee, * and Ikchoon Lee * Department of Chemistry, Inha University, Inchon 402-751, Korea Received April 4, 2003 The kinetics and mechanism of the pyridinolysis (XC5H4N) of Y-aryl phenyl isothiocyanophosphates (1; (YC6H4O)(C6H5O)P(=O)NCS) are investigated in acetonitrile at 55.0 o C. The Hammett plots for substituent (Y) variations in the substrate (log k2 vs σ Y) exhibit a convex upward biphasic type with breaks at Y = H. For electron-donating Y groups the Hammett coefficients, ρ Y, are positive and cross-interaction constant ρ XY is negative, while those for electron-withdrawing Y groups ρ Y values are negative with a positive ρ XY. These results are interpreted to indicate mechanistic change at the breakpoint ( σ Y = 0) from a concerted to a stepwise mechanism with rate-limiting expulsion of the - NCS group from a trigonal bipyramidal pentacoordinated (TBP-5C) intermediate. Biphasic plots of log k2 vs σ X or pKa(X) with steeper slopes for the more basic nucleophiles are obtained suggesting an equatorial nucleophilic attack in contrast to an apical attack for the less basic nucleophiles with smaller magnitude of ρ X or β X. Key Words : Pyridinolysis, Aryl phenyl isothiocyanophosphates, Cross-interaction constant Introduction Phosphoryl transfers from phosphate monoesters and diesters are an important class of reaction that is involved in many aspects of chemistry and biochemistry ranging from organic synthesis through enzyme catalyzed reactions such as DNA replication and repair. 1 A considerable amount of work has been carried out to clarify the problem whether the phosphoryl transfer reactions proceed concertedly with a single transition state (TS) or stepwise with a pentacoordi- nated phosphorane intermediate. 1,2 In our previous works 3 the aminolyses of diphenyl chlorophosphate and 4-chlorophenyl Y-substituted phenyl chlorophosphates have been studied in acetonitrile. The anilinolysis of diphenyl chlorophosphate 3a proceeds through a concerted pathway but unexpectedly with a late TS. The anilinolysis of 4-chlorophenyl Y-phenyl chlorophosphates 3c proceeds through a concerted pathway with a relatively larger magnitude of ρ X and β X values indicating a larger degree of bond formation than diphenyl chlorophosphate in the TS. The pyridinolysis of diphenyl chlorophosphate 3b proceeds concertedly with an early TS in which the extent of both bond formation and leaving group departure is small. A dramatic result was found recently in the investigation of the reactions of Z-aryl bis(4-methoxyphenyl) phosphates, (4-MeOC6H4O)2P(=O)OC6H4Z, with X-pyridines, (XC5H4N), in acetonitrile. 4 In the case of the more basic phenolate leaving groups, the mechanism changes from a concerted process for the less basic pyridines to a stepwise process with rate-limiting formation of a trigonal bipyramidal pentacoordinated (TBP-5C) intermediate for the more basic pyridines. In the case of the less basic phenolate leaving groups, the reaction proceeds through a direct backside attack TBP-5C. In this work we extend our studies of the mechanism of phosphoryl transfer reactions to the pyridinolysis of Y-aryl phenyl isothiocyanophosphate (1) in acetonitrile at 55 o C, eq. 1. X = 4-OCH3, 4-CH3, 3-CH3, H, 3-C6H5, 3-COCH3, 3-Cl, 4-COCH3, 4-CN Y = 4-OCH3, 4-CH3, H, 3-OCH3, 4-Cl Isothiocyanophosphates are used in various organic syn- thesis. Liang and coworkers 5 reported new derivatizing reagents for C-terminal peptide sequencing at low nanomole levels and they showed that diphenyl isothiocyanophosphate is one of the superior reagents due to its double function of activation and derivatization. Diphenyl isothiocyanophosphate is also used as an automated carboxy-terminal sequence analysis of peptides and proteins. 6 Kristian and coworkers 7 have developed a new simple method for preparation of α- isothiocyanatoethers from P(=O)(NCS)3 or (PhO)2P(=O)NCS with an equimolar mixture of aldehydes and alcohols. Our interest in the present work is centered in the mechanistic change and / or TS structure variation associated with the substituent changes in the substrate (Y) and nucleophile (X) in the phosphoryl transfer involving isothio- cyanate leaving group, - NCS , by determining the Hammett ( ρ X, ρ Y) and Brönsted coefficients ( β X), and cross-interaction constants 8 ( ρ XY) in eqs. 2 where X and Y denote the sub- stituents in the nucleophile and the substrate, respectively. log (kXY/kHH) = ρ X σ X + ρ Y σ Y + ρ XY σ X σ Y (2a) ρ XY = ∂ρ Y/ ∂σ X = ∂ρ X/ ∂σ Y (2b) (1)