SCHEME 5
SCHEME 6
FIGURE 5. Influence of total buffer concentration, ClCH2COOH/
ClCH2COONa, on kobs for AcAc nitrosation in acidic media. Ionic
strength 1.00 M (NaClO4); [AcAc] ) 5.3 × 10-4 M; T ) 25.0 °C. (9)
pH ) 2.23; Intercept ) (4.69 ( 0.15) × 10-3 M-1 s-1; Slope ) (8.26
( 0.46) × 10-3 M-2 s-1; (O) pH ) 2.69; Intercept ) (4.84 ( 0.37) ×
10-3 M-1 s-1; Slope ) (1.33 ( 0.12) × 10-2 M-2 s-1; (b) pH ) 3.15;
Intercept ) (5.00 ( 0.41) × 10-3 M-1 s-1; Slope ) (1.73 ( 0.18) ×
known among the potential nitroso group donors. Likewise,
many reactions described in the literature involve intramolecular
transfer of the nitroso group. Typical examples are the O-NOfN-
NO migrations observed in the nitrosation of amides and ureas,23
amino acids24 in acidic media, and hydroxylamines;25 the
C-NOfN-NO migrations found in the nitrosation of indoles26
in acidic media, and the N-NOfC-NO migrations observed in
the Fischer-Hepp27 rearrangement. Also, S-NOfN-NO migra-
tions are common when studying nitrosation of cysteine in
acidic28 and basic or neutral29 media, thioureas,30 and thioproline
or thiomorpholine.31
10-2 M-2 s-1
.
O-
k
[enolate][NO+] will be considered. From this expression,
NO
after the corresponding mass balances, the following equation
is obtained
[H+]2
O-
NO
kobs ) k KAa cAcKNO
[AcAc]T
(1)
(KaAcAc + [H+])(KHa NO + [H ])
+
2
O-
Taking into account the keto-enol isomerization of acety-
lacetone, there are different pathways which can be considered
as an explanation for a base-catalyzed nitrosation (Scheme 6).
where k is the nitrosation rate constant through the enolate
NO
form; KNO is the equilibrium constant for NO+ formation (KNO
) 3.5 × 10-7 M-1); and KaHNO and KAa cAc are the acidity
2
constant for nitrous acid and AcAc, respectively (KHa NO ) 3.80
2
× 10-4 M and KaAcAc ) 1.62 × 10-9 M).
(20) (a) Garc´ıa-R´ıo, L.; Iglesias, E.; Leis, J. R.; Pen˜a, M. E.; R´ıos, A. J. Chem.
Soc., Perkin Trans. 2 1993, 29–37. (b) Garc´ıa-R´ıo, L.; Leis, J. R.; Iglesias, E. J.
Org. Chem. 1997, 62, 4701–4711. (c) Garc´ıa-R´ıo, L.; Leis, J. R.; Iglesias, E. J.
Org. Chem. 1997, 62, 4712–4720.
(21) Garc´ıa-R´ıo, L.; Leis, J. R.; Moreira, J. A.; Norberto, F. J. Org. Chem.
2001, 66, 381–390.
(22) (a) Oae, S.; Shinhama, K. Org. Prep. Proc. Int. 1983, 15, 165–198. (b)
Al-Kaabi, S. S.; Williams, D. L. H.; Bonnett, R.; Ooi, S. L. J. Chem. Soc., Perkin
Trans. 2 1982, 227–230. (c) Barnett, D. J.; R´ıos, A.; Williams, D. L. H. J. Chem.
Soc., Perkin Trans. 2 1995, 1279–1282. (d) Barnett, D. J.; McAninly, J.; Williams,
D. L. H. J. Chem. Soc., Perkin Trans. 2 1994, 1131–1133. (e) Munro, A. P.;
Williams, D. L. H. J. Chem. Soc., Perkin Trans. 2 1999, 1989–1993. (f) Munro,
A. P.; Williams, D. L. H. J. Chem. Soc., Perkin Trans. 2 2000, 1794–1797.
(23) (a) Castro, A.; Iglesias, E.; Leis, J. R.; Pen˜a, M. E.; Va´zquez-Tato, J.
J. Chem. Soc., Perkin Trans. 2 1986, 1725–1729. (b) Meijide, F.; Va´zquez-
Tato, J.; Casado, J.; Castro, A.; Mosquera, M. J. Chem. Soc., Perkin Trans. 2
1987, 159–165. (c) Castro, A.; Gonza´lez, M.; Meijide, F.; Mosquera, M. J. Chem.
Soc., Perkin Trans. 2 1988, 2021–2027.
(24) Casado, J.; Castro, A.; Leis, J. R.; Mosquera, M.; Pen˜a, M. E. J. Chem.
Soc., Perkin Trans. 2 1985, 1859–1864.
(25) Dal-Magro, J.; Meijide, F.; Provost, S.; Va´zquez-Tato, J.; Yunes, R. A.
J. Chem. Soc., Perkin Trans. 2 2001, 1192–1194.
(26) (a) Bravo, C.; Herve´s, P.; Leis, J. R.; Pen˜a, M. E. J. Chem. Soc., Perkin
Trans. 2 1992, 185–189. (b) Castro, A.; Herve´s, P.; Iglesias, E.; Leis, J. R.;
Pen˜a, M. E. J. Chem. Res. 1988, 76–77.
(27) Williams, D. L. H. J. Chem. Soc., Perkin Trans. 2 1982, 801–804, and
references therein.
(28) (a) Meyer, T. A.; Williams, D. L. H. J. Chem. Soc., Chem. Commun.
1983, 1067–1068. (b) Jorgensen, K. A. J. Org. Chem. 1985, 50, 4758–4762.
(29) Adam, C.; Garc´ıa-R´ıo, L.; Leis, J. R.; Ribeiro, L. J. Org. Chem. 2005,
70, 6353–6361.
(30) (a) Meijide, F.; Stedman, G. J. Chem. Res. 1989, 232–233. (b) Meijide,
F.; Stedman, G. J. Chem. Soc., Perkin Trans. 2 1988, 1087–1090. (c) Lown,
J. W.; Chauhan, S. M. S. J. Chem. Soc., Chem. Commun. 1981, 675–676. (d)
Williams, D. L. H. J. Chem. Soc., Perkin Trans. 2 1977, 128–132. (e) Collings,
P.; Al-Mallah, K.; Stedman, G. J. Chem. Soc., Dalton Trans. 1974, 2469–2472.
(31) (a) Coello, A.; Meijide, G.; Va´zquez-Tato, J. J. Chem. Soc., Perkin Trans.
2 1989, 1677–1680. (b) Castro, A.; Iglesias, E.; Leis, J. R.; Va´zquez-Tato, J.;
Meijide, F.; Pen˜a, M. E. J. Chem. Soc., Perkin Trans. 2 1987, 651–656.
Assuming diffusion-controlled kinetics for nitrosation through
O-
the enolate form (k ∼ 1010 M-1 s-1), it is possible to estimate
NO
a value for the observed rate constant as a function of pH and
AcAc concentration. Thus, at pH ) 1 and [AcAc] ) 5.3 ×
10-4 M, kobs ) 2.58 × 10-9 s-1 is obtained. On the other hand,
the experimental kobs under the same conditions (see Figure 2)
is found to be 2 × 105 times larger than the previously calculated
one, which completely confirms that nitrosation reaction of
AcAc proceeds entirely through the enol form.
To investigate a simultaneous O-nitrosation mechanism,
experiments were conducted in ClCH2COOH, Cl2CHCOOH,
and Cl3CCOOH buffer solutions. Figure 5 shows the observed
catalytic effect.
As in the case of acetone, the catalytic efficacy of the buffer
increases with the pH, which is indicative of a general base
catalysis. The observed buffer catalysis is compatible with the
kinetic behavior found in O-nitrosation reactions.13 Therefore,
a mechanism through an equilibrium process where proton
transfer is rate limiting can be proposed (Scheme 5). This
mechanism and the nature of the electrophilic attack will be
discussed in detail.
Intermolecular transfer of the nitroso group is the basis of
the widely studied transnitrosation reactions. O-Nitroso com-
pounds (alkyl nitrites20), N-nitroso compounds (N-nitrososul-
fonamides21), and S-nitroso compounds (thionitrites22) are well-
(19) Williams, D. L. H. Nitrosation Reactions and the Chemistry of Nitric
Oxide; Elsevier: Amsterdam, 2004.
J. Org. Chem. Vol. 73, No. 21, 2008 8201