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E-mail: hwlee@inha.ac.krReceived March 24, 2014, Accepted March 31, 2014Key Words : Biphasic free energy correlation, Phosphoryl transfer reaction, Pyridinolysis, Aryl N,N-Dimethylphosphoroamidochloridate The kinetic studies on the reactions of Y-aryl N,N-di-methyl phosphoroamidochloridates (1) with X-anilines anddeuterated anilines in acetonitrile (MeCN) were reported bythis lab.

concave upwards with a break point at X = 3-Ph and Y = H, respectively. The sign of cross-interaction constants (CICs; ρXY) is positive with all X and Y. Proposed mechanism is a stepwise process with a rate-limiting leaving group departure from the intermediate with all X and Y. The kinetic results of 1 are compared with those of Yaryl phenyl chlorothiophosphates (2). In the case of Y = electron-withdrawing groups, the cross-interaction between Y and Y, due to additional substituent Y, is significant enough to change the sign of ρXY from negative with 2 to positive with 1, indicative of the change of mechanism from a rate-limiting bond formation to bond breaking.

The substituent effects on the pyridinolysis (XC5H4N) of Y-aryl ethyl chlorophosphates are investigated in acetonitrile at 35.0 C. The two strong π-acceptor substituents, X = 4-Ac and 4-CN in the X-pyridines, exhibit large positive deviations from the Hammett plots but little positive deviations from the Bronsted plots. The substituent Y effects on the rates are really significant and the Hammett plots for substituent Y variations in the substrates invariably change from biphasic concave downwards via isokinetic at X = H to biphasic concave upwards with a break point at Y = 3-Me as the pyridine becomes less basic. These are interpreted to indicate a mechanistic change at the break point from a stepwise mechanism with a rate-limiting bond formation (ρXY = –6.26) for Y = (4-MeO, 4-Me, 3-Me) to with a rate-limiting leaving group expulsion from the intermediate (ρXY = +5.47) for Y = (4-Me, H, 3-MeO). The exceptionally large magnitudes of ρXY values imply frontside nucleophilic attack transition state.

E-mail: hwlee@inha.ac.krReceived December 16, 2013, Accepted January 6, 2014The kinetic studies on the reactions of O,O-diethyl Z-S-aryl phosphorothioates with X-pyridines have beencarried out in dimethyl sulfoxide. The free energy correlations with X in the nucleophiles are biphasic concaveupwards with a break point at X = H, while those for substituent Z variations in the leaving groups are linear.The negative sign of ρ

E-mail: hwlee@inha.ac.krReceived November 22, 2013, Accepted December 5, 2013The kinetic studies on the reactions of O-methyl N,N-diisopropylamino phosphonochloridothioate with X-anilines and X-pyridines have been carried out in acetonitrile. The free energy relationship with X in theanilines exhibits biphasic concave upwards with a break region between X = (H and 4-F), giving unusualnegative β

The nucleophilic substitution reactions of Y-aryl N,N-dimethyl phosphoroamidochloridates with substituted anilines and deuterated anilines are kinetically investigated in acetonitrile at 65.0 C. A stepwise mechanism with a rate-limiting leaving group departure from the intermediate is proposed based on the positive ρXY value. The deuterium kinetic isotope effects involving deuterated anilines show secondary inverse with all the nucleophiles, rationalized by a dominant backside nucleophilic attack.

Summary of the Second-Order Rate Constants ( k 2 × 10 3 /M –1 s –1 ) at 35.0 o C, NBO Charges at the Reaction Center P Atom,Summations of the Steric Constants and Selectivity Parameters ( X and  XY ) for the Reactions of 1 - 11 with X-Pyridines in MeCNno R 1 OR 2 O k 2 × 10 3 a charge at P – E S  X e  XY 1 MeO MeO 1.54 c 1.687 0 1.09/0.20 – 2 MeO EtO 0.620 1.693 0.07 1.50/0.43 – 3 EtO EtO 1.19 c 1.701 0.14 1.02/0.29 – 4 EtO PrO 0.609 1.700 0.43 1.44/0.36 – 5 PrO PrO 1.16 1.702 0.72 1.08/0.31 – 6 BuO BuO 1.01 1.703 0.78 1.26/0.31 – 7 i -PrO i -PrO 0.460 1.723 0.94 0.99/0.15 – 8 MeO YC 6 H 4 O 0.835 b 1.686 2.48 0.89-0.98/0.29-0.32 –0.71/–0.36 e 9 EtO YC 6 H 4 O0.137 b,d 1.687 2.55 2.31-2.33/0.45-0.47 0/0/0/0 f 10 PrO YC 6 H 4 O 0.781 b 1.687 2.84 0.74-0.93/0.30-0.39 1.59/0.94 e 11 PhO YC 6 H 4 O 0.333 b 1.661 4.96 1.36-1.50/ 0.23-0.48 2.42/5.14/–1.02/–0.04 fa Value with X = H at 35.0 o C. b Value with Y = H. c Extrapolated value. d Empirical kinetic data. e Strongly/weakly basic pyridines.

Nucleophilic substitution reactions of ethyl methyl (2), ethyl propyl (4) and diisopropyl (7) chlorothiophosphates with substituted anilines and deuterated anilines are investigated kinetically in acetonitrile at . A concerted mechanism is proposed based on the selectivity parameters. The deuterium kinetic isotope effects (DKIEs; ) are secondary inverse () with 2, primary normal and secondary inverse () with 4, and primary normal () with 7. The primary normal and secondary inverse DKIEs are rationalized by frontside attack involving hydrogen bonded, four-center-type transition state, and backside attack involving in-line-type transition state, respectively. The anilinolyses of ten chlorothiophosphates are examined based on the reactivity, steric effect of the two ligands, thio effect, reaction mechanism, DKIE and activation parameter.

)are positive for both electron-donating and electron-withdrawing Y substituents. The kinetic results of 1 arecompared with those of Y-aryl phenyl chlorothiophosphates (2). The cross-interaction between Y and Y, dueto additional substituent Y, is significant enough to result in the change of the sign of ρ

) invariably increase from secondaryinverse to primary normal as the aniline becomes more basic, rationalized by the transition state variation froma backside to a frontside attack. For the pyridinolysis of 1, the authors propose a stepwise mechanism with arate-limiting step change from bond breaking for more basic pyridines to bond formation for less basicpyridines based on the selectivity parameters and activation parameters. Biphasic concave upward free energyrelationship with X is ascribed to a change in the attacking direction of the nucleophile from a frontside attackwith more basic pyridines to a backside attack with less basic pyridines.Key Words : Phosphoryl transfer reaction, Anilinolysis, Pyridinolysis, Bis(2-oxo-3-oxazolidinyl) phosphinicchloride, Deuterium kinetic isotope effectIntroductionContinuing the kinetic studies on the aminolyses of(Lig

concave upwards with a break point at X = H (2) and 3-Ph (4), respectively. A stepwise mechanism with a ratelimiting leaving group expulsion from the intermediate is proposed based on the magnitudes of selectivity parameters for both substrates. The considerably large values of βX = 1.50(2) and 1.44(4) with strongly basic pyridines and relatively small values of βX = 0.43(2) and 0.36(4) with weakly basic pyridines are interpreted as a change of the attacking direction of the X-pyridines from a frontside to a backside attack toward the chloride leaving group.

E-mail: hwlee@inha.ac.krReceived June 5, 2013, Accepted June 14, 2013Key Words : Thiophosphoryl transfer reaction, Biphasic free energy correlation, Pyridinolysis, O-Propyl andO-isopropyl phenyl phosphonochloridothioatesContinuing the kinetic studies on the pyridinolyses of thephosphonochloridothioates, the nucleophilic substitutionreactions of O-propyl (4) and O-isopropyl (5) phenylphosphonochloridothioates with X-pyridines have beencarried out kinetically in acetonitrile (MeCN) at 35.0 ± 0.1oC (Scheme 1). The kinetic results of the present work arecompared with those of the pydidinolyses of Y-O-arylmethyl [1; Me(YC

N2 mechanism is proposed for the anilinolyses of 1, 3 and 4. The anilinolysis rates of the phosphonochloridothioates are predominantly dependent upon the steric effects over the inductive effects of the two ligands. The deuterium kinetic isotope effects (DKIEs; kH/kD) are primary normal with 1 and 3, while secondary inverse with 4. Primary normal and secondary inverse DKIEs are rationalized by frontside and backside nucleophilic attack transition state, respectively. The DKIEs of the phosphonochloridothioates do not have any consistent correlations with the two ligands.

Kinetic studies on the reactions of O-methyl (2) and O-ethyl (3) phenyl phosphonochloridothioates with X-pyridines have been carried out in acetonitrile at 35.0°C. The pyridinolysis rates of 2 are slightly faster than those of 3. The substituent effects of X on the pyridinolysis rates of 2 and 3 are similar. The Hammett and Bronsted plots with X in the nucleophiles are biphasic concave upward with a break point at X = 3-Ph for both substrates. The stepwise mechanism with rate-limiting leaving group departure from the intermediate is proposed based on the βX values and biphasic concave upward free energy relationship for both substrates. The biphasic concave upward free energy relationships are rationalized by a frontside nucleophilic attack TSf with more basic pyridines and backside attack TSb with less basic pyridines for both substrates.

Kinetic studies on the reactions of Y-aryl phenyl isothiocyanophosphates with substituted X-anilines and deuterated X-anilines were carried out in acetonitrile at 55.0 °C. The free-energy relationships with X in the nucleophiles were biphasic concave upwards with a break region between X = H and 4-Cl, giving unusual positive ρX and negative βX values with less basic anilines (X = 4-Cl and 3-Cl). A stepwise mechanism with rate-limiting bond breaking for more basic anilines and with rate-limiting bond formation for less basic anilines is proposed based on the positive and negative ρXY values, respectively. The deuterium kinetic isotope effects involving deuterated anilines (XC6H4ND2) showed primary normal and secondary inverse DKIEs for more basic and less basic anilines, rationalized by frontside attack involving hydrogen-bonded four-center-type TSf and backside attack TSb, respectively. The positive ρX values with less basic anilines are substantiated by the tight TS, in which the extent of the bond formation is great and the degree of the bond breaking is considerably small.

2 mechanism is proposed involving achange of the attacking direction of the X-pyridines from a frontside attack with the strongly basic pyridines toa backside attack with the weakly basic pyridines.Key Words : Thiophosphoryl transfer reaction, Diisopropyl chlorothiophosphate, Pyridinolysis, Biphasic con-cave upward free energy relationshipIntroductionThis lab previously reported the kinetics and mechanismof the pyridinolyses of the chlorothiophosphates in aceto-nitrile (MeCN): dimethyl [1: (MeO)

E-mail: hwlee@inha.ac.krReceived December 8, 2011, Accepted December 12, 2011Key Words : Phosphoryl transfer reaction, Pyridinolysis, Dibutyl chlorophosphate, Steric effectKinetics and mechanism of the phosphoryl and thiophosphoryltransfer reactions have been studied extensively by this lab:pyridinolyses

The kinetic studies on the reactions of phenyl N-phenyl phosphoramidochloridate (8) with substituted anilines () and deuterated anilines () have been carried out in acetonitrile at . The obtained deuterium kinetic isotope effects (DKIEs; ) are huge secondary inverse ( = 0.52-0.69). A concerted mechanism is proposed with a backside attack transition state (TS) on the basis of the secondary inverse DKIEs and the variation trends of the values with X. The degree of bond formation in the TS is really extensive taking into account the very small values of the DKIEs. The steric effects of the two ligands on the rates are extensively discussed for the aminolyses of the chlorophosphate-type substrates on the basis of the Taft equation.

The nucleophilic substitution reactions of O-ethyl phenyl phosphonochloridothioate with substituted anilines () and deuterated anilines () are kinetically investigated in acetonitrile at . The deuterium kinetic isotope effects (DKIEs) invariably increase from a secondary inverse DKIE ( = 0.93) to a primary normal DKIE ( = 1.28) as the substituent of nucleophile (X) changes from electron-donating to electron-withdrawing. These can be rationalized by the gradual transition state (TS) variation from a backside to frontside attack. A concerted mechanism is proposed. A trigonal bipyramidal TS is proposed for a backside attack while a hydrogen-bonded, four-center-type TS is proposed for a frontside attack.

The kinetics and mechanism of the pyridinolysis () of dimethyl isothiocyanophosphate are investigated in acetonitrile at . The Hammett and Brnsted plots for substituent X variations in the nucleophiles exhibit two discrete slopes with a break region between X = 3-Ac and 4-Ac. These are interpreted to indicate a mechanistic change at the break region from a concerted to a stepwise mechanism with a rate-limiting expulsion of the isothiocyanate leaving group from the intermediate. The relatively large values imply much greater fraction of frontside nucleophilic attack TSf than that of backside attack TSb. The steric effects of the two ligands play an important role to determine the pyridinolysis rates of isothiocyanophosphates.

The kinetics and mechanism of the pyridinolysis () of diethyl isothiocyanophosphate are investigated in acetonitrile at . The Hammett and Bronsted plots for substituent X variations in the nucleophiles exhibit the two discrete slopes with a break region between X = 3-Ac and 4-Ac. These are interpreted to indicate a mechanistic change at the break region from a concerted to a stepwise mechanism with rate-limiting expulsion of the isothiocyanate leaving group from a trigonal bipyramidal pentacoordinated intermediate. The relatively large values with more basic and less basic pyridines imply much greater fraction of frontside nucleophilic attack TSf than that of backside attack TSb.

E-mail: hwlee@inha.ac.krReceived January 2, 2012, Accepted January 31, 2012Key Words : Thiophosphoryl transfer reaction, Pyridinolysis, Dibutyl chlorothiophosphate, Biphasic concaveupward free energy relationshipIn previous work, the kinetic studies of the pyridinolysesof chlorothiophosphates (dimethyl [1: (MeO)

< 1. Key Words : Phosphoryl transfer reaction, Anilinolysis, (2R,4R,5S)-(+)-2-Chloro-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine 2-sulfide, Deuterium kinetic isotope effect IntroductionThe anilinolysis rates of cyclic five-membered ring phos-phate esters are much faster than their acyclic counterparts inacetonitrile (MeCN).

The kH and kD values with X-anilines and deuterated Xanilines, respectively, are summarized in Table 1, together with the DKIEs (kH/kD) and Hammett ρX(H and D) and Bronsted βX(H and D) coefficients. The pKa(X) values of the X-anilines in water were used to obtain the Bronsted βX values in MeCN, and this procedure was justified experimentally and theoretically. 3 The values of pKa(X) and σX of the deuterated X-anilines are assumed to be identical to those of the Xanilines. Perrin and coworkers reported that the basicities of β-deuterated analogs of benzylamine, N,N-dimethylaniline and methylamine increase roughly by 0.02 pKa units per deuterium, and that these effects are additive. 4 Thus, the pKa(X) values of deuterated X-anilines may be slightly greater than those of X-anilines, however, the difference is too small to be taken into account. The anilinolysis rate increases with a more electrondonating substituent X in the nucleophile which is consistent with a typical nucleophilic substitution reaction with positive charge development at the nucleophilic reaction center N atom in the transition state (TS). The Hammett (Fig. 1; log kH(D) vs σX) and Bronsted [Fig. 2; log kH(D) vs pKa(X)] plots for substituent X variations in the nucleophiles give considerably large magnitudes of ρX(H) = –4.83 (ρX(D) = –5.24) and βX(H) = 1.71 (βX(D) = 1.85). The magnitudes of selectivity parameters with the deuterated anilines are slightly greater than those with the anilines. The DKIEs are primary normal (kH/kD > 1) and the values of DKIEs invariably increase as the nucleophile becomes weaker. The remarkably large value of kH/kD = 2.19 with X = 3-Cl is the largest one, observed for the phosphoryl transfer reactions in this lab. 8

= 1.10-1.35). A concertedmechanism involving predominant frontside nucleophilic attack is proposed on the basis of the primary normalDKIEs and selectivity parameters. Hydrogen bonded, four-center-type transition state is proposed. The stericeffects of the two ligands on the anilinolysis rates of the chlorothiophosphates are discussed. The anilinolysesof P=S systems are compared with those of their P=O counterparts on the basis of the reactivities, thio effects,selectivity parameters, and DKIEs.Key Words : Thiophosphoryl transfer reaction, Anilinolysis, Dibutyl chlorothiophosphate, Deuterium kineticisotope effectIntroductionThe kinetics and mechanism of the phosphoryl and thio-phosphoryl transfer reactions involving tetracoordinatedphosphorus atom have been studied extensively by this lab.Continuing the kinetic studies on the thiophosphoryl transferreactions, the nucleophilic substitution reactions of dibutylchlorothiophosphate (4S) with substituted anilines (XC

E-mail: hwlee@inha.ac.krReceived October 27, 2011, Accepted November 7, 2011Key Words : Phosphoryl transfer reaction, Pyridinolysis, Bis(N,N-dimethylamino) phosphinic chloride, Bi-phasic concave upward free energy relationshipThe kinetic studies of the pyridinolyses of tetracoordi-nated phosphorus have been studied extensively by this lab.

correlations for substituent X variations in the nucleophiles exhibit biphasic concave upwards with a breakpoint at a X = 3-Cl. Unusual positive ρX (= +5.40) and negative βX (= –0.83) values are obtained with the weakly basic pyridines. The pyridinolysis rate of 5 is hundreds times slower compared to that of bis(phenyl) chlorophosphate because of the steric hindrance of the four ortho-methyl substituents in the two phenyl rings. Ion-pair mechanism is proposed and positive ρX and negative βX values are substantiated by an imbalance of the transition state.

The kinetic studies on the reactions of dipropyl chlorophosphate (3O) with substituted anilines () and deuterated anilines () have been carried out in acetonitrile at . The obtained deuterium kinetic isotope effects (DKIEs; ) are primary normal ( = 1.09-1.01) with the strongly basic anilines while secondary inverse ( = 0.74-0.82) with the weakly basic anilines. The steric effects of the two ligands on the rates are extensively discussed for the anilinolyses of the ()()P(=O or S)Cl-type chlorophosphates and chlorothiophosphates. A concerted mechanism is proposed with a frontside nucleophilic attack involving a hydrogen-bonded four-center-type transition state for the strongly basic anilines and with a backside attack transition state for the weakly basic anilines on the basis of the DKIEs, primary normal and secondary inverse with the strongly and weakly basic anilines, respectively.

The nucleophilic substitution reactions of ethylene phosphorochloridate (1c) with substituted anilines () and deuterated anilines () are investigated kinetically in acetonitrile at . The anilinolysis rate of 1c involving a cyclic five-membered ring is four thousand times faster than its acyclic counterpart (1a: diethyl chlorophosphate) because of great positive value of the entropy of activation of 1c ( compared to negative value of 1a () over considerably unfavorable enthalpy of activation of 1c () compared to 1a (). Great enthalpy and positive entropy of activation are ascribed to sterically congested transition state (TS) and solvent structure breaking in the TS. The free energy correlations exhibit biphasic concave upwards for substituent X variations in the X-anilines with a break point at X = 3-Me. The deuterium kinetic isotope effects are secondary inverse ( > 1) with the weakly basic anilines and rationalized by the TS variation from a dominant backside attack to a dominant frontside attack, respectively. A concerted mechanism is proposed and the primary normal deuterium kinetic isotope effects are substantiated by a hydrogen bonded, four-center-type TS.

= 0.91 with the strongly basic nucleophiles. Proposed reaction mechanism is a stepwise process with a rate-limiting leaving group expulsion from the intermediate involving a backside nucleophilic attack with thestrongly basic nucleophiles and a frontside attack with the weakly basic nucleophiles. The kinetic results arecompared with those of the benzylaminolysis of O,O-diphenyl Z-S-aryl phosphorothioates.Key Words : Phosphoryl transfer reaction, Benzylaminolysis, O,O-Diethyl Z- S-aryl phosphorothioate, Cross-interaction constant, Concave downward free energy correlationIntroductionThe various phosphoryl and thiophosphoryl transfer reac-tions have been studied kinetically by this lab: anilinolysis

The nucleophilic substitution reactions of bis(N,N-dimethylamino) phosphinic chloride (3) with substituted anilines () and deuterated anilines () are investigated kinetically in acetonitrile at . The anilinolysis rate of 3 is rather slow to be rationalized by the conventional stereoelectronic effects. The magnitudes of (= -6.42) and (= 2.27) values are exceptionally great. The deuterium kinetic isotope effects (DKIEs; ) are secondary inverse ( = 0.69-0.96). A concerted mechanism involving a backside attack is proposed on the basis of secondary inverse DKIEs and the variation trend of the values with X. The anilinolyses of six phosphinic chlorides in MeCN are briefly reviewed by means of DKIEs, steric effects of the two ligands, positive charge of the reaction center phosphorus atom, and selectivity parameters to obtain systematic information on phosphoryl transfer reaction mechanism.

Kinetic studies for the reactions of Y-aryl phenyl chlorothiophosphates with X-pyridines have been carried out in acetonitrile at 35.0 oC. The Hammett and Bronsted plots for substituent X variations in the nucleophiles are biphasic concave upwards with a break point at X = 3-Ph, while the Hammett plots for substituent Y variations in the substrates are biphasic concave downwards (and partially upwards) with a break point at Y = H. The signs and magnitudes of the cross-interaction constant (ρ XY) are strongly dependent upon the nature of substituents, X and Y. The proposed mechanism is a stepwise process with a rate-limiting step change from bond breaking with the weaker electrophiles to bond formation with the stronger eletrophiles. The nonlinear free energy correlations of biphasic concave upward plots for substituent X variations in the nucleophiles are rationalized by a change in the attacking direction of the nucleophile from a backside with less basic pyridines to a frontside attack with more basic pyridines.

= 0.80-0.96). The anilinolyses often P=S systems in MeCN are reviewed on the basis of DKIEs and selectivity parameters to obtain systematicinformation on the DKIEs and mechanism for thiophosphoryl transfer reactions. The steric effects of the twoligands on reactivity, DKIEs, mechanism, and substituent effects of the nucleophile (X) on the DKIEs arediscussed.Key Words : Phosphoryl transfer reaction, Anilinolysis, Diisopropyl thiophosphinic chloride, Deuterium ki-netic isotope effect IntroductionA considerable amount of work has been focused on thetwo types of phosphoryl and thiophosphoryl transfer reac-tion mechanisms; stepwise through a trigonal bipyramidalpentacoordinate (TBP-5C) intermediate, and concertedthrough a single pentacoordinate transition state (TS). Theattacking direction of the nucleophile can be backside and/orfrontside, depending on the substrate, nucleophile, leavinggroup, and reaction condition. In previous work, this labreported upon various types of phosphoryl and thiopho-sphoryl transfer reactions: anilinolysis

pKa values for the anilinium ions determined in DMSO, an approximate straight line is obtained when they are plotted against those determined in water. 4 Spillane and coworkers reported that the βX value for the reactions of N-phenyl sulfamoyl chloride (PhNHSO2Cl) with X-anilines in DMSO is similar when determined using the pKa values of anilines measured in water (βX = 0.69) and DMSO (βX = 0.62). 5 Accordingly, it may be inferred that the βX values in Table 1 are reasonably positive. The pKa and σ values of deuterated anilines are assumed to be the same as those of anilines. The pKa(X) values of deuterated X-anilines may be slightly greater than those of X-anilines, however, the difference is too small to be taken into account. 6 Figures 1 and 2 show the Hammett (log kH(D) vs σX) and Bronsted [log kH(D) vs pKa(X)] plots, respectively, for substituent X variations in the nucleophiles. The rate consistently increases with a more electrondonating substituent X in the nucleophile, which is consistent with a typical nucleophilic substitution reaction with positive charge development at the nucleophilic N atom in the transition state (TS). The magnitudes of the ρX and βX values with the deuterated anilines are slightly greater than those with the anilines, suggesting more sensitive to substituent effects of the deuterated anilines compared to the

Kinetic studies on the reactions of Y-S-aryl phenyl phosphonochloridothioates with X-pyridines have been carried out in MeCN at . The Hammett and Bronsted 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 is changed from unusual negative ( > 0) with the stronger electrophiles. The stepwise mechanism is proposed on the basis of the , , and 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 (=S)Cl-type substrates are discussed.

The nucleophilic substitution reactions of diisopropyl chlorophosphate (3) with substituted anilines () and deuterated anilines () are investigated kinetically in acetonitrile at . The anilinolysis rate of 3 is rather slow to be rationalized by the conventional stereoelectronic effects. The obtained deuterium kinetic isotope effects (DKIEs; ) are secondary inverse ( = 0.71-0.95) with maximum magnitude at X = H.A concerted mechanism involving predominant backside nucleophilic attack is proposed on the basis of the secondary inverse DKIEs.

studied substrate of 1,2-phenylene phosphorochloridate is cyclic five-membered ring of phosphorus ester, and the anilinolysis rate of 1 is much faster than its acyclic analogue (4: ethyl phenyl chlorophosphate) because of extremely small magnitude of the entropy of activation of 1 compared to 4. The Hammett and Bronsted plots exhibit biphasic concave upwards for substituent X variations in the nucleophiles with a break point at X = 3Me. The values of deuterium kinetic isotope effects (DKIEs; kH/kD) change from secondary inverse (kH/kD 1) with the weakly basic anilines. The secondary inverse with the strongly basic anilines and primary normal DKIEs with the weakly basic anilines are rationalized by the transition state (TS) variation from a predominant backside attack to a predominant frontside attack, in which the reaction mechanism is a concerted SN2 pathway. The primary normal DKIEs are substantiated by a hydrogen bonded, four-center-type TS.

inverse (kH/kD = 0.439; min) to a primary normal (kH/kD = 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 (ρXY(H) = �0.38 for XC6H4NH2 and ρXY(D) = �0.29 for XC6H4ND2) indicate that the reactions proceed by a concerted SN2 mechanism.

2806 Bull. Korean Chem. Soc. 2011, Vol. 32, No. 8 Notescenter P atom or with the steric hindrance (size) of the twoligands. This means that the magnitude of the positivecharge on the reaction center P atom and the size (or thesteric effect) of the two ligands do not play any role todetermine the reactivity of the pyridinolysis of R

to expectations for the electronic influence of the two ligands and exhibits exceptionally great negative deviation from the Taft’s eq. The deuterium kinetic isotope effects (DKIEs) involving deuterated anilines invariably change from primary normal (kH/kD > 1; max kH/kD = 1.10 with X = 4-MeO) with the strongly basic anilines (X = 4-MeO, 4-Me, 3-Me) to secondary inverse (kH/kD < 1; min kH/kD = 0.673 with X = 3-Cl) with the weakly basic anilines (X = H, 4-F, 4-Cl, 3-Cl). A concerted SN2 mechanism is proposed on the basis of both secondary inverse and primary normal DKIEs. The obtained DKIEs imply that the fraction of a frontside attack increases as the aniline becomes more basic. A hydrogen-bonded, four-center-type transition state is suggested for a frontside attack, while the trigonal bipyramidal pentacoordinate transition state is suggested for a backside attack.

C. The kinetic results of 1 are comparedwith those of Y-aryl phenyl chlorophosphates (2). The substrate 1 has one more identical substituent Ycompared to substrate 2. The cross-interaction between Y and Y, due to additional substituent Y, is significantenough to result in the change of the sign of cross-interaction constant (CIC) from negative ρ

The second-order rate constants [k2 (M –1 s –1 )] are summarized in Table 1. The Bronsted βX values were calculated by correlating log k2(MeCN) with pKa(H2O), 5 which was justified theoretically and experimentally. 6 The substituent effects of the nucleophiles upon the pyridinolysis rates correlate with those for a typical nucleophilic substitution reaction where the stronger nucleophile leads to a faster rate. However, both the Hammett (log k2 vs σX; Fig. 1) and Bronsted [log k2 vs pKa(X); Fig. 2] plots are biphasic concave upwards with a break point at X = 3-Ph. The magnitudes of ρX (= –6.02) and βX (= 1.23) values with the strongly basic pyridines (X = 4-MeO, 4-Me, 3-Me, H, 3-Ph) are much greater than those (ρX = –0.85 and βX = 0.14) with the weakly basic pyridines (X = 3-Ph, 3-MeO, 3-Cl, 3-Ac, 4Ac, 3-CN, 4-CN). Table 2 shows the natural bond order (NBO) charges at the reaction center P atom in the gas phase [B3LYP/6311+G(d,p) level of theory], 7 summations of the Taft’s steric Table 1. Second-order rate constants (k × 10 /M s ) of the reactions of 3 [cHex P(=O)Cl] with XC H N in MeCN at 55.0 oC X 4-MeO 4-Me 3-Me H 3-Ph 3-MeO 3-Cl 3-Ac 4-Ac 3-CN 4-CN k × 10 180 ± 2 53.0

The pyridinolysis of methyl phenyl phosphinic chloride is investigated kinetically in acetonitrile at -20.0 . The Hammett and Brnsted plots for substituent X variations in the nucleophiles are biphasic concave downwards with a break point at X = H, and unusual positive (= 2.94) and negative (= -0.48) values are obtained for the strongly basic nucleophiles. A stepwise mechanism with a rate-limiting step change from bond breaking for the weakly basic pyridines to bond formation for the strongly basic pyridines is proposed on the basis of biphasic concave downward Hammett and Brnsted plots. Unusual positive and negative values are rationalized by the isokinetic relationship. The pyridinolyses and anilinolyses of four P(=O)Cl-type substrates, dimethyl, diethyl, methyl phenyl, and diphenyl phosphinic chlorides in acetonitrile are compared to obtain systematic information on phosphoryl transfer reaction mechanism. The combination of the two ligands, Me and Ph, shows unexpected kinetic results for both the anilinolysis and pyridinolysis: greatest magnitude of (= 2.10) involving deuterated anilines for the anilinolysis, and exceptionally fast rate and biphasic concave downward free energy correlation for the pyridinolysis.

(X)] plots for substituent Xvariations in the nucleophiles exhibit a break region betweenX = H and 3-Cl, resulting in discrete two parts with one partfor the strongly basic pyridines (X = 4-MeO, 4-Me, 3-Me,H) and the other part for the weakly basic pyridines (X = 3-Cl, 3-Ac, 4-Ac), respectively (Fig. 1). The Hammett plots(log k

The energetics and transition state (TS) structures of the reactions of six substrates, R1R2P(=O or S)Cl-type where R1 = R2 = Me and/or MeO, with ammonia in acetonitrile are theoretically investigated at the level of CPCM-MP2/6-31+G(d) and CPCM-MP2/6-311+G(3df,2p). The degrees of distortion of TS from the ideal trigonal bipyramidal pentacoordinate, Δδ≠b for a backside and Δδ≠f for a frontside attack, are calculated. The results of calculation suggest that the feasibility of a frontside attack for P=S is greater than that for P=O system when the two ligands, R1 and R2, becomes larger. The experimental and calculated results of anilinolyses of R1R2P(=O or S)Cl-type show the consistent tendencies.

< 1) for Y = electron-withdrawing substituent. The proposed mechanisms of the benzylaminolyses of N-methyl-Y-α-bromoacetani-lides are a concerted mechanism with a five membered ring TS involving hydrogen bonding between hydrogen(deuterium) atom in N-H(D) and oxygen atom in C = O for Y = electron-donating, while a concertedmechanism with an enolate-like TS in which the nucleophile attacks the α-carbon for Y = electron-withdrawing substituents.Key Words :Benzylaminolysis, N-Methyl-α-bromoacetanilides, Cross-interaction constant, Deuterium kineticisotope effect, Biphasic nonlinear free energy correlationIntroductionIn a series of the nucleophilic substitution reactions ofα-halocarbonyl compounds

o C to gain further information of mechanism. The pyridinolyses of eleven R1R2P(=O or S)Cl-type substrates in MeCN (eq 1) are reviewed to obtain systematic information on phosphoryl transfer reaction mechanism. The kinetic results are discussed on the bases of thio effect on reactivity, steric effect of R1 and R2 on reactivity of substrate, electrophilicity of substrate, comparison between anilinolysis and pyridinolysis, and pyridinolysis mechanism. Eleven R1R2P(=O or S)Cl-type substrates are as follows: dimethyl phosphinic chloride (1O); 1h

The reactions of Z-aryl dimethyl (1), methyl phenyl (2), and diphenyl (3) phosphinates with X-anilines in dimethyl sulfoxide at 60.0 °C are studied kinetically. Kinetic results yield the primary normal deuterium kinetic isotope effects (DKIEs) involving deuterated aniline (XC(6)H(4)ND(2)) nucleophiles, k(H)/k(D) = 1.03-1.17, 1.15-1.29, and 1.24-1.51, and the cross-interaction constants (CICs), ρ(XZ) = 0.37, 0.34, and 0.65 for 1, 2, and 3, respectively. The steric effects of the ligands (R(1) and R(2)) on reaction rates play a role, but are relatively much smaller compared to other phosphinate systems. A stepwise mechanism with a rate-limiting leaving group expulsion from the intermediate is proposed on the basis of the CICs positive signs. The dominant frontside nucleophilic attack through a hydrogen-bonded, four-center-type transition state is proposed on the basis of primary normal DKIEs and large magnitudes of the CICs for 2 and 3, while both frontside and backside attack are proposed on the basis of relatively small primary normal DKIEs for 1.