The di-Zn(II) complex of 1,3-bis[ N1, N1'-(1,5,9-triazacyclododecyl)]propane with an associated methoxide ( 3:Zn(II) 2: (-)OCH 3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters ( 6) was studied at s (s)pH 9.8 in methanol at 25.0 +/- 0.1 degrees C. Plots of k obs vs [ 3:Zn(II) 2: (-)OCH 3] free for all members of 6 show saturation behavior from which K(M) and kcat (max) were determined. The second order rate constants for the catalyzed reactions (kcat (max)/K(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k 2 (-OMe)) by 1.4 x 10(8) to 3 x 10 (9)-fold. The values of k cat (max) for all members of 6 are between 4 x 10(11) and 3 x 10(13) times larger than the solution reaction at s (s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO 2 or C(O)OCH 3 groups. Based on the linear Brønsted plots of k cat (max) vs s (s)pKa of the phenol, beta lg values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO 2 or C(O)OCH 3 groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH 3O (-): 6], giving a hypothetical [ 3:Zn(II) 2:CH 3O (-): 6] complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO 2 or C(O)OCH 3 groups.
As good as the original: Extremely effective methanolysis of phosphonothioates using metal‐containing systems (e.g., 1) was achieved. The catalytic methanolysis of a SCH2CH2NEt2 derivative, an analogue of the organophosphorus chemical warfare material VX, was predicted, and the catalyzed methanolysis of S‐(3,5‐dichlorophenyl) O‐ethyl methylphosphonothioate was shown to involve a concerted displacement of the aryl thioate (transition state 2).
The kinetics and cleavage products of 2-hydroxypropyl p-nitrophenyl phosphate were determined in methanol containing the di-Zn(II) complex of bis-1,3-N1,N1'-(1,5,9-triazacyclododecyl)propane (4). Time-dependent 1H NMR spectra of the reaction mixture at sspH 9.8 +/- 0.1 show that the catalytic reaction proceeds via a cyclic phosphate (4-methylethylene phosphate, 2) that is subsequently cleaved into a kinetic mixture of two isomeric products, 2-hydroxypropyl methyl phosphate (3) and 1-hydroxypropan-2-yl methyl phosphate (3a), in a 29/71 ratio. In the presence of 4, the kinetic mixture of 3/3a is transformed into a thermodynamic mixture of 72/28 3/3a. The time-dependent 1H NMR spectra of 4 and a 22/78 mixture of 3/3a in CD3OH show that the formation of the thermodynamic mixture occurs on the same time scale as replacement of the P-OCH3 group of the 3/3a starting materials with OCD3. Detailed kinetic studies indicate that the dominant process for loss of the OCH3 group and equilibration of 3/3a is via a 4-catalyzed process where each of the isomers cyclizes to methylethylene phosphate (2), which subsequently reforms the 3/3a thermodynamic mixture. The kcatmax for 4-catalyzed cyclization of 3 and three other 2-hydroxypropyl O-alkyl phosphates (alkyl = CF3CH2- (6a), CH2FCH2- (6b), and CH3CH2- (6c)) has been determined, and the Brønsted plot comprising the log kcatmax vs leaving group sspKa that includes several previously studied 2-hydroxypropyl aryl phosphates is linear, following the expression log kcatmax = (-0.85 +/- 0.02) sspKa + (12.8 +/- 0.4). The betalg value of -0.85 suggests that the catalyzed cleavage of the P-OAr/OR bond has progressed to about 45% in the transition state. The combined results are analyzed in terms of two possible processes involving either a concerted reaction leading to the cyclic phosphate 2 from which the thermodynamic mixture of 3/3a is formed or a stepwise one involving a transient phosphorane whose predominant fate is to eliminate methoxide and proceed to 2 rather than partitioning between 3, 3a, and 2.
So gut wie das Original: Mit metallhaltigen Systemen wie 1 gelang die sehr effektive Methanolyse von Phosphonothioaten. Die katalytische Methanolyse eines SCH2CH2NEt2‐Derivats, eines Analogons des Organophosphorkampfstoffs VX, wird vorhergesagt. Zudem wird gezeigt, dass bei der katalysierten Methanolyse von S‐(3,5‐Dichlorphenyl)‐O‐ethyl(methylphosphonothioat) das Arylthioat in einem konzertierten Schritt verdrängt wird (Übergangszustand 2).
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