S
N
2 Mechanism for Solvolyses of Acetyl Chloride
J . Org. Chem., Vol. 61, No. 22, 1996 7931
Acetyl chloride solvolyses about 10-fold faster than
An additional explanation of the high reactivity of
acetyl chloride is nucleophilic solvent assistance to car-
bocation formation. Solvolyses in acetic acid and tri-
fluoroethanol (Table 5) are 50- and 300-fold slower,
respectively, than solvolyses in more nucleophilic aqueous
media having the same ionizing power, and from these
data we estimate a large l value (ca. 0.8) for the
1
5
trimethylacetyl chloride (1) and 150-fold faster than 2,
Z ) OMe,2 but all are highly reactive. One possible
explanation of the high reactivity is that reaction occurs
via prior addition of solvent to the carbonyl group;1
a
38
3a,31
8
a
fast addition followed by slow heterolysis seems unlikely,
and alternatively the hydrated acid chloride (5, R ) Me)
may be formed in a slow step and may then dissociate
rapidly to the highly stabilized cation (6),31 but counter-
arguments are given below.
sensitivity of solvolyses of acetyl chloride to solvent
39-42
nucleophilicity.
An l value of 0.8 is similar to that
for solvolyses of ethyl tosylate (solvolyses of methyl
tosylate have l ) 1.0 by definition).4
0b
Solvolyses of
dimethylcarbamoyl chloride are also strongly sensitive
T
to both solvent nucleophilicity (l ) 0.6 using the N scale)
and solvent-ionizing power.1 A preliminary hydration
mechanism via 5 would also be expected to show a high
sensitivity to solvent nucleophilicity, but would not be
so sensitive to solvent-ionizing power (Table 6).
3b
We have calculated5a from the enthalpy of chloride ion
exchange in the gas phase (R ) Ph, eq 2) that direct
heterolysis of benzoyl chloride to give the benzoyl cation
is more favorable by 13 ( 7 kcal/mol than heterolysis of
tert-butyl chloride to give the tert-butyl cation (a recent
Third-order kinetics has been observed for solvolyses
1
5b
of acetyl chloride in 95-99% acetone/water, and the
mechanism may involve the second reaction channel with
one solvent molecule acting as a general base catalyst to
substantially revised value for ∆H
f
of the tert-butyl
deprotonate the attacking nucleophile.1
7a,22,43
Such ca-
cation32 would increase this to 20 kcal/mol.). Hence, the
talysis can be detected from the increased solvent isotope
1
00-fold greater solvolytic reactivity of benzoyl chloride
effects;1
8,19
the low MeOH/MeOD value of 1.29 for acetyl
5
a,23b
compared with tert-butyl chloride
parallels the sta-
chloride (Table 5) is consistent with our proposal that
solvolyses of acetyl chloride in alcohol/water mixtures
involve only the dissociative reaction channel. As solvent-
ionizing power is decreased, it would be expected that
bilities of the corresponding carbocations, and a hydration
mechanism via 5 is not necessary to explain the results.
A similar calculation for chloride ion exchange between
acetyl chloride and tert-butyl chloride (R ) Me, eq 2) gave
H ) -3.5 ( 3 kcal/mol,33 so heterolysis to give the acetyl
contributions from the second reaction channel would
∆
increase (e.g., in 95-99% acetone/water1
5b,19c
).
Am in olyses. The mechanism of aminolysis will de-
pend on substrate, solvent, and amine, and it is known
that mechanistic changes can occur as the amine is varied
cation is probably more favorable than heterolysis of tert-
butyl chloride (or the same, considering experimental
uncertainties). As solvolyses of acetyl chloride (e.g., in
because of changes in the the stabilities of tetrahedral
intermediates.9
,44
However, aminolyses of benzoyl fluo-
5
ride in water appear to be mechanistically very similar
to solvolyses,45 so there is a strong mechanistic link
between solvolyses and aminolyses. The results dis-
cussed here refer primarily to mechanisms for m-nitro-
aniline (a relatively weak nucleophile) in relatively polar
solvolysis media.
water at 0 °C) are over 10 -fold faster than corresponding
solvolyses of tert-butyl chloride,4,23b gas phase cation
stabilities also parallel solvolysis rates in this case.
Because the acetyl cation has fewer atoms over which to
delocalize and stabilize charge,37 solvolyses of acetyl
chloride would probably benefit more than tert-butyl
chloride from general solvation.
The possibility that solvolyses of acetyl chloride pro-
ceed via a hydrate 5 can be excluded because the kinetic
solvent isotope effect (e.g., MeOH/MeOD of 1.29, Table
Aminolyses by m-nitroaniline (3) in methanol gave
second-order rate constants, kam, from the rate enhance-
(38) Howald, R. A. J . Org. Chem. 1962, 27, 2043.
(
39) The l value may be estimated by assuming that major devia-
tions from the mY equation are caused by solvent nucleophilicity
see the appendix and Table 5 of ref 40a). If YCl is chosen as the
5
) is small and is similar to the value of 1.22 observed
for solvolyses of p-methoxybenzoyl chloride (2, Z )
(
OMe).1 Both S
8a
1 and S
2 solvolyses give low solvent
16d
N
N
most appropriate Y scale, the deviation for 97% trifluoroethanol is
isotope effects,1
8a,d,19b
320-fold (by comparison with data for 40% ethanol, Table 5). For
but reactions involving hydration
3
8
-3 -1
acetic acid, the observed rate constant at 25 °C of 8.5 × 10
s
is
of a carbonyl group would be expected to show larger
isotope effects (as observed for hydrolyses of chloro-
first corrected to 0 °C by dividing by 10; the YCl value of acetic acid is
1
6d
-1.6,
constant for solvolysis of acetyl chloride is ca. 4 × 10
polated from data in Table 1); hence, the deviation for acetic acid is
corresponding to ca. 95% ethanol/water, in which the rate
-
2
-1
formates3
e,31a
s
(inter-
).
4
0b
5
0-fold. If solvent nucleophilicity is represented by the NOTs scale,
l
(
31) (a) Queen, A. Can . J . Chem. 1967, 45, 1619. (b) Minato, H.
Bull. Chem. Soc., J pn. 1964, 37, 316.
32) Szulejko, J . E.; McMahon, T. B. J . Am. Chem. Soc. 1993, 115,
839.
values of 0.89 and 0.72 are then obtained from the deviations of 320
and 50, respectively, i.e. the average l value of 0.8 would slightly
underestimate the deviation for trifluoroethanol, as occurs for other
(
4
0b
7
solvolyses.
(
33) Gas phase thermochemical data, ∆Hf/kcal/mol: CH
3
COCl, -58.0
(40) (a) Bentley, T. W.; Roberts, K. J . Chem. Soc., Perkin Trans. 2
1989, 1055. (b) Schadt, F. L.; Bentley, T. W.; Schleyer, P. v. R. J . Am.
Chem. Soc. 1976, 98, 7667.
+
+
+
3 3 3
0.2 (ref 34); (CH ) C , 170 ( 1 (refs 32 and 35), CH CO 152 ( 1
(
ref 36); (CH
3
)
3
CCl, -43.5 ( 0.6 (ref 34).
34) Pedley, J . B.; Naylor, R. D.; Kirby, S. P. Thermochemical Data
of Organic Compounds; Chapman and Hall: London, 1986.
35) (a) Keister, J . W.; Riley, J . S.; Baer, T. J . Am. Chem. Soc. 1993,
(
(41) Alternatively, for solvolyses in acetic acid, 97% trifluoroethanol
and six other aqueous and/or alcoholic solvents, using the mYCl + lN
T
4
2
(
eq, m ) 0.68 ( 0.03 and l ) 0.86 ( 0.04 (we thank M. J . D’Souza for
this result).
1
1
(
15, 12613. (b) Traeger, J . C. Rapid Commun. Mass Spectrom. 1996,
0, 119. (c) Smith, B. J .; Radom, L. J . Am. Chem. Soc. 1993, 115, 4885.
d) Smith, B. J .; Radom, L. Chem. Phys. Lett. 1994, 231, 345.
(42) Kevill, D. N.; Anderson, S. W. J . Org. Chem. 1991, 56, 1845.
(43) (a) Kevill, D. N.; Foss, F. D. J . Am. Chem. Soc. 1969, 91, 5054.
(b) Kevill, D. N.; Knauss, D. C. J . Chem. Soc., Perkin Trans. 2 1993,
307.
(44) (a) Castro, E. A. Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
63. (b) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6970.
(45) Song, B. D.; J encks, W. P. J . Am. Chem. Soc. 1989, 111, 8479.
(36) (a) Traeger, J . C.; McLoughlin, R. G.; Nicholson, A. J . C. J . Am.
Chem. Soc. 1982, 104, 5318. (b) Smith, B. J .; Radom, L. Int J . Mass
Spectrom. Ion Processes, 1990, 101, 209.
(
37) Lossing, F. P.; Holmes, J . L. J . Am. Chem. Soc. 1984, 106,
6
917.