Communications
Kinetic data for the methanolysis of 5a–e were obtained by UV/
[13] A referee rightly points out that the ammonium ion in 6 does not
have the zwitterionic stabilization of ꢀSCH2CH2N+(H)Et2, so the
sspKa value will not be as high as 13.3; while true, we note that the
sspKa value of triethylamine is 10.78, thus indicating that the
nitrogen atom in 6 will still be substantially protonated at
sspH 9.1.
Vis methods, as described earlier for phosphates, phosphorothioates,
and phosphonates.[8,9,11] The reactions were run under pseudo first-
order conditions of excess catalyst in duplicate with a substrate
concentration of 0.2m m. Pseudo first-order rate constants were
evaluated by fitting traces of the absorbance versus time to a standard
exponential, and the second-order rate constants were evaluated as
the gradients of the plots of kobs versus [catalyst].
[14] The methoxide-promoted methanolysis of VX and O-ethyl S-
ethyl methylphosphonothioate at 228C and 0.25–0.3m concen-
trations of base have k2 values of 1.85 ꢁ 10ꢀ3 and 1.70 ꢁ
10ꢀ3 mꢀ1 sꢀ1[5], which is similar to that expected for 6 under
highly basic conditions; however, the methoxide reaction on 6 at
any sspH value at which the nitrogen atom is protonated is
computed by Equation (1) to be 1000-fold faster at 1.28 Æ
The turnover experiment was conducted with 3.62m m 5a in
0.6 mL of methanol buffered with 17 mm N-ethylmorpholine and
s
s
perchloric acid in a 4:1 ratio to achieve a pH value of 9.1. La(OTf)3
and tetrabutylammonium hydroxide were added to this reaction
mixture so that the final concentration of each was 0.36 mm and
0.09 mL of [D1]methanol. The reaction was followed using 31P NMR
spectroscopic analysis on a 400-MHz machine.
0.10mꢀ1 sꢀ1
.
[15] The predicted rate constants assume that the Brønsted relation-
ships of Equations (2) and (3), which are derived for aryl thiols,
are followed by a primary alkyl thiol. Previous studies indicate
that methanolysis and hydrolysis of carboxylate esters bearing
aryloxy groups are up to tenfold less reactive than those bearing
primary alkoxyl groups, presumably because of steric effects;
see: a) N. E. Sunderland, A. A. Neverov, R. S. Brown, Org.
Biomol. Chem. 2005, 3, 65; b) J. F. Kirsch, W. P. Jencks J. Am.
Chem. Soc. 1964, 86, 837.
Titrations were performed in duplicate on 2m m solutions of thiol
in methanol under nitrogen at 258C using standardized 20 mm
s
s
NaOCH3 as the titrant. The pKa values were obtained by fitting the
titration data using the program Hyperquad 2000 (version 2.1 NT).[16]
Received: September 7, 2005
Keywords: chemical warfare · lanthanum · methanolysis ·
phosphorus · zinc
.
[16] P. Gans, A. Sabatini, A. Vacca, Talanta 1996, 43, 1739.
[1] The content of the information discussed herein does not
necessarily reflect the position or the policy of the federal
government of the United States of America, and no official
endorsement should be inferred.
[2] a) Y.-C. Yang, J. A. Baker, J. R. Ward, Chem. Rev. 1992, 92, 1729;
b) Y.-C. Yang, Acc. Chem. Res. 1999, 32, 109; c) Y.-C. Yang,
Chem. Ind. 1995, 334.
[3] The Merck Index, 11th ed., Merck and Co., Rahway, NJ, 1989; the
toxicity of VX in rabbits is given as LD50s.c. = 15.4 mgkgꢀ1
.
[4] H. Morales-Rojas, R. A. Moss, Chem. Rev. 2002, 102, 2497, and
references therein.
[5] N. B. Munro, S. S. Talmage, G. D. Griffin, L. C. Waters, A. P.
Watson, J. F. King, V. Hauschild, Environ. Health Perspect. 1999,
107, 933.
[6] Y.-C. Yang, F. J. Berg, L. L. Szafraniec, W. T. Beaudry, C. A.
Bunton, A. Kumar, J. Chem. Soc. Perkin Trans. 2 1997, 607.
[7] Yang et al. also showed[5] that the HOOꢀ ion reacts with
phosphoniothioates to give exclusive P–S cleavage, although
these reactions are not catalytic and are carried out under
alkaline conditions.
[8] a) J. S. Tsang, A. A. Neverov, R. S. Brown, J. Am. Chem. Soc.
2003, 125, 7602; b) T. Liu, A. A. Neverov, J. S. W. Tsang, R. S.
Brown, Org. Biomol. Chem. 2005, 3, 1525; c) J. S. W. Tsang,
A. A. Neverov, R. S. Brown, Org. Biomol. Chem. 2004, 2, 3457;
d) W. Desloges, A. A. Neverov, R. S. Brown, Inorg. Chem. 2004,
43, 6752.
[9] R. E. Lewis, A. A. Neverov, R. S. Brown, Org. Biomol. Chem.
2005, 3, 4082.
[10] For the designation of “pH” in methanol and measurement
thereof, see: G. T. T. Gibson, A. A. Neverov, R. S. Brown, Can. J.
Chem. 2003, 81, 495; the autoprotolysis constant of methanol is
10ꢀ16.77 m2 so neutral sspH in methanol is 8.4; E. Bosch, F. Rived,
M. Rosꢀs, J. Sales, J. Chem. Soc. Perkin Trans. 1 1999, 2, 1953.
[11] C. Maxwell, A. A. Neverov, R. S. Brown, Org. Biomol. Chem.
2005, 3, 4329.
[12] In actuality, the turnover experiment for the La3+-catalyzed
methanolysis of 5a must be essentially complete early in the
NMR experiment because if it were not the summation of the
256 scans over five minutes would have revealed the presence of
starting material in the first few scans.
1770
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 1767 –1770