Mechanisms of solvolyses of acid chlorides and chloroformates. Chloroacetyl and phenylacetyl chloride as similarity models

Article abstract of DOI:10.1021/jo0514366

Rate constants and product selectivities (S = ([ester product]/[acid product]) × ([water]/[alcohol solvent]) are reported for solvolyses of chloroacetyl chloride (3) at -10 °C and phenylacetyl chloride (4) at O °C in ethanol/and methanol/water mixtures. Additional kinetic data are reported for solvolyses in acetone/water, 2,2,2-trifluoroethanol(TFE)/water, and TFE/ethanol mixtures. Selectivities and solvent effects for 3, including the kinetic solvent isotope effect (KSIE) of 2.18 for methanol, are similar to those for solvolyses of p-nitrobenzoyl chloride (1, Z = NO₂); rate constants in acetone/water are consistent with a third-order mechanism, and rates and products in ethanol/and methanol/water mixtures can be explained quantitatively by competing third-order mechanisms in which one molecule of solvent (alcohol or water) acts as a nucleophile and another acts as a general base (an addition/elimination reaction channel). Selectivities increase for 3 as water is added to alcohol. Solvent effects on rate constants for solvolyses of 3 are very similar to those of methyl chloroformate, but acetyl chloride shows a lower KSIE, and a higher sensitivity to solvent-ionizing power, explained by a change to an S_N2/S_N1 (ionization) reaction channel. Solvolyses of 4 undergo a change from the addition/elimination channel in ethanol to the ionization channel in aqueous ethanol (<80% v/v alcohol). The reasons for change in reaction channels are discussed in terms of the gas-phase stabilities of acylium ions, calculated using Gaussian 03 (HF/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-311G(d,p) MO theory).

Full text of DOI:10.1021/jo0514366

Mechanisms of Solvolyses of Acid Chlorides and Chloroformates.
Chloroacetyl and Phenylacetyl Chloride as Similarity Models
,†
†
‡
‡
§
T. William Bentley,* H. Carl Harris, Zoon Ha Ryu, Gui Taek Lim, Dae Dong Sung, and
†
Stanley R. Szajda
Departments of Chemistry, University of Wales, Swansea, Singleton Park,
Swansea, SA2 8PP, Wales, U.K., Dong-Eui University, Busan 614-714, Korea, and Dong-A University,
Busan 604-714, Korea
cmsolvol@swansea.ac.uk
Received July 12, 2005
Rate constants and product selectivities (S ) ([ester product]/[acid product]) × ([water]/[alcohol
solvent]) are reported for solvolyses of chloroacetyl chloride (3) at -10 °C and phenylacetyl chloride
(
4) at 0 °C in ethanol/ and methanol/water mixtures. Additional kinetic data are reported for
solvolyses in acetone/water, 2,2,2-trifluoroethanol(TFE)/water, and TFE/ethanol mixtures. Selectivi-
ties and solvent effects for 3, including the kinetic solvent isotope effect (KSIE) of 2.18 for methanol,
are similar to those for solvolyses of p-nitrobenzoyl chloride (1, Z ) NO ); rate constants in acetone/
2
water are consistent with a third-order mechanism, and rates and products in ethanol/ and
methanol/water mixtures can be explained quantitatively by competing third-order mechanisms
in which one molecule of solvent (alcohol or water) acts as a nucleophile and another acts as a
general base (an addition/elimination reaction channel). Selectivities increase for 3 as water is
added to alcohol. Solvent effects on rate constants for solvolyses of 3 are very similar to those of
methyl chloroformate, but acetyl chloride shows a lower KSIE, and a higher sensitivity to solvent-
N N
ionizing power, explained by a change to an S 2/S 1 (ionization) reaction channel. Solvolyses of 4
undergo a change from the addition/elimination channel in ethanol to the ionization channel in
aqueous ethanol (<80% v/v alcohol). The reasons for change in reaction channels are discussed in
terms of the gas-phase stabilities of acylium ions, calculated using Gaussian 03 (HF/6-31G(d),
B3LYP/6-31G(d), and B3LYP/6-311G(d,p) MO theory).
Introduction
methoxybenzoyl chloride (1, Z ) OMe).3
S ) ([ester product]/[acid product]) ×
Solvolyses of acid halides in mixtures of aqueous
alcohol are nucleophilic substitutions leading to mix-
tures of acid and ester products. For aroyl chlorides,
substituent effects, solvent effects, and product selectivi-
ties (S, eq 1) can be explained by competing reaction
([water]/[alcohol]) (1)
As Y decreases (e.g., adding alcohol to water) and/or as
the substituent become less strongly electron-donating,
another reaction channel becomes competitive, a third-
order addition/elimination mechanism, much less sensi-
tive to changes in Y: e.g., solvolyses of p-nitrobenzoyl
1
,2
channels. Rate constants for one of the reaction chan-
nels (ionization or S 2/S 1) are strongly dependent on
N
N
the solvent ionizing power (Y): e.g., solvolyses of p-
4
a,b
chloride (1, Z ) NO
2
),
for which rate constants show
†
4
University of Wales.
an unusual shallow maximum, and the kinetic solvent
isotope effect (KSIE) in water or methanol is relatively
‡
Dong-Eui University, Korea.
§
Dong-A University, Korea.
(
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1
0.1021/jo0514366 CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/27/2005
J. Org. Chem. 2005, 70, 8963-8970
8963

Bentley et al.
large (ca. 2).4b The results can be explained by competing
third-order addition/elimination mechanisms in which
one molecule of solvent acts as a nucleophile assisted by
a second molecule of solvent acting as a general base
many previous studies of solvolyses acyl halides have
been made in solvents of low polarity, and relatively
complex kinetics have been observed.9
,12
Unlike the
systematic studies of electronic effects of para-substitu-
ents in aroyl chlorides (1), substituent effects for acyl
chlorides are a combination of electronic and steric
effects, with the strong possibility of additional complica-
tions from mechanistic changes. Although stereochemical
studies provided mechanistic insights into other substi-
4
catalyst.
Mechanistic changes due to structural effects (e.g.,
3,4
solvolyses of 1, Z ) OMe and NO
2
)
are well established.
Examples of solvent-induced mechanistic changes are
rarer, and more difficult to establish. Solvolyses of
p-dimethylaminobenzoyl fluoride (2) in ethanol/water
provide a clear example of mechanistic changes induced
simply by adding water to alcohol solvent.1a In more polar
solvent compositions, the rates depend strongly on sol-
vent polarity, and the ionization reaction channel is
favored. As the solvent polarity decreases, the dominant
process is an addition/elimination reaction channel,
almost insensitive to solvent polarity. The above inter-
pretation is supported by a recent comparison with
solvolyses of benzoyl fluoride, which reacts by an addi-
tion/elimination mechanism.5a
2
13
tutions at sp carbon (e.g., oximoyl halides ), they are
uninformative for substitutions at carbonyl carbon. Leav-
ing group effects (especially fluoride/chloride ratios) are
7b,c,12
useful broad indicators of mechanistic changes,
and
kinetic isotope effects provide detailed specific informa-
tion about individual reactions.14
Data for solvent effects on rates and products allow
us to detect mechanistic changes for solvolyses of acyl
chlorides. Solvolyses of acetyl chloride in methanol and
in more polar mixtures proceed via the ionization reaction
channel; they show a low KSIE (1.3), a low S, a high
sensitivity to Y, and a relatively high sensitivity to
10
solvent nucleophilicity N. Except for the latter, these
mechanistic features are “similar”15 to those for solvolyses
of 1, Z ) OMe. The high sensitivity to N can be explained
N
by S 2 character or by nucleophilic solvation of a cationic
10
transition state, a proposal recently supported by
density functional theory (DFT) calculations of acetyl
chloride solvated by up to six methanol molecules.
1
-6
17
Kinetic data for many acid chlorides
and chlorofor-
mates (both aryl7a and alkyl
7b-e
) are consistent with
We now report rate and product data for solvolyses of
chloroacetyl chloride (3) and phenylacetyl chloride (4).
The solvolyses data for 3 are shown to be very similar to
reactions via one or both of these two competing reaction
channels (ionization and/or addition/elimination). Clear
differences due to mechanism-related charge effects are
also observed when rate constants in aqueous anionic and
cationic micelles are compared. However, the mecha-
nistic changes for chlorides are not as clear as those for
fluorides, and additional supporting data from S values
eq 1) in alcohol/water have been useful in characterizing
the two reaction channels, and the region of mechanistic
2
that of 1, Z ) NO , and of methyl chloroformate (MeO-
COCl). The data for 4 link solvolyses of 3 with those of
acetyl chloride and reveal mechanistic changes not previ-
ously apparent. Mechanistic interpretations are com-
pared with cation stabilities, obtained by DFT and other
MO calculations using Gaussian 03.18
8
(
change. For solvolyses of 1, Z ) OMe, S values are low
3
and close to constant. For solvolyses of 1, Z ) NO
2
, S
increases as water is added to alcohol.4 In contrast,
solvolyses of 1, Z ) H and Cl, show clear maxima in S as
water is added to alcohol, consistent with a change in
reaction channel.
Solvolyses of acyl chlorides have not yet yielded clear-
(
11) (a) Ryu, Z. H.; Lim, G. T.; Bentley, T. W. Bull. Korean Chem.
cut mechanistic conclusions. The scope of kinetic data is
Soc. 2003, 24, 1293-1302. (b) An S. K.; Yang, J. S.; Cho, J. M.; Yang,
K.; Pal, J. P.; Bentley T. W.; Lee, I.; Koo, I. S. Bull. Korean Chem. Soc.
limited by the high reactivity of acyl chlorides,9
-11
so
2
002, 23, 1445-1450. (c) Ryu, Z. H.; Shin, S. H.; Lee, J. P.; Lim, G. T.;
Bentley, T. W. J. Chem. Soc., Perkin Trans. 2 2002, 1283-1287. (d)
Oh, Y. H.; Jang, G. G.; Lim, G. T.; Ryu, Z. H. Bull. Korean Chem. Soc.
2002, 23, 1089-1096.
(5) (a) Kevill D. N.; D’Souza, M. J. J. Org. Chem. 2004, 69, 7044-
7
2
3
7
050. (b) Kevill, D. N.; Carver, J. S. Org. Biomol. Chem. 2004, 2, 2040-
043. (c) Kyong, J. B.; Yoo, J.-S.; Kevill, D. N. J. Org. Chem. 2003, 68,
425-3432. (d) Kevill, D. N.; Miller, B. J. Org. Chem. 2002, 67, 7399-
406.
(12) Kevill, D. N.; Wang, W. F. K. J. Chem. Soc., Perkin Trans. 2
1998, 2631-2637.
(13) Johnson, J. E.; Dolliver, D. D.; Yu, L.; Canseco, D. C.; McAl-
lister, M. A.; Rowe, J. E. J. Org. Chem. 2004, 69, 2741-2749.
(14) (a) Hess, R. A.; Hengge, A. C.; Clelland, W. W. J. Am. Chem.
Soc. 1998, 120, 2703-2709. (b) Hengge, A. C. Acc. Chem. Res. 2002,
35, 105-112.
(
(
6) Liu, K.-T.; Hou, I.-J. Tetrahedron, 2001, 57, 3343-3347.
7) (a) Kevill, D. N.; Bond, M. W.; D’Souza M. J. J. Org. Chem. 1997,
6
6
2, 7869-7871. (b) Kevill, D. N.; D’Souza, M. J. J. Org. Chem. 1998,
3, 2120-2124. (c) Kevill, D. N.; D’Souza, M. J. J. Chem. Soc., Perkin
Trans. 2 2002, 240-243. (d) Kyong, J. B.; Kim, Y.-G.; Kim, D. K.;
Kevill, D. N. Bull Korean Chem. Soc. 2000, 21, 662-664. (e) Kyong, J.
B.; Won, H.; Kevill, D. N. Int. J. Mol. Sci. 2005, 6, 87-96.
(15) For discussion of “similarity” and “similarity models”, see ref
16.
(16) (a) Sj o¨ str o¨ m, M.; Wold, S. W. Acta Chem. Scand. 1981, B35,
537-554. (b) Kamlet, M. J.; Doherty, R. M.; Famini, G. R.; Taft, R. W.
Acta Chem. Scand. 1987, B41, 589-598. (c) Zalewski, R. I.; Krygowski,
T. M.; Shorter, J. Similarity Models in Organic Chemistry, Biochem-
istry and Related Fields; Elsevier: New York, 1991. (d) Williams, A.
Free Energy Relationships in Organic and Bio-organic Chemistry; Royal
Society of Chemistry: Cambridge, UK, 2003, Chapter 1.
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2004, 69, 7317-7328.
(
8) Bunton, C. A. J. Phys. Org. Chem. 2005, 18, 115-120; see also:
Garcia-Rio, L.; Leis, J. R.; Moreira, J. A. J. Am. Chem. Soc. 2000, 122,
0325-10334.
1
(
9) (a) Kevill, D. N.; Daum, P. H.; Sapre, R. J. Chem. Soc., Perkin
Trans. 2 1975, 963-965. (b) Kevill, D. N.; Kim, C.-B. J. Chem. Soc.,
Perkin Trans. 2 1988, 1353-1358.
(10) Bentley, T. W.; Llewellyn, G.; McAlister, J. A. J. Org. Chem.
1
996, 61, 7927-7932.
8964 J. Org. Chem., Vol. 70, No. 22, 2005

Solvolyses of Acid Chlorides and Chloroformates
TABLE 1. Rate Constants (k/10- s-1) for Solvolyses of
Chloroacetyl Chloride (3) in Acetone/, Ethanol/ and
Methanol/Water at -10.0 °Ca
3
TABLE 3. Rate Constants (k/10-3 s-1) for Solvolyses of
Chloroacetyl Chloride (3) at - 10.0 °C in
a
Trifluoroethanol (TFE)/Water and TFE/Ethanol
solvent
%
TFE/waterb
0.070d
1.03 ( 0.07
7.54 ( 0.05
12.5 ( 0.1
35.1 ( 0.7
81.5 ( 0.1
87.1 ( 2.3
TFE/EtOHc
%
v/v
acetone
ethanol
methanol
97
1
00
101 ( 2b
33.9 ( 0.3
73.2 ( 0.5
103 ( 1
260 ( 4c
256 ( 4
327 ( 4
341 ( 3
366 ( 6
378 ( 6
391 ( 8
385 ( 2
361 ( 4
90
80
70
60
50
30
1.40 ( 0.01
6.60 ( 0.04
12.7 ( 0.3
23.9 ( 0.3
43.6 ( 0.1
9
8
7
6
5
4
3
2
0
0
0
0
0
0
0
0
551 ( 22
765 ( 32
149 ( 1
1230 ( 110
965 ( 46
755 ( 7
183 ( 1
228 ( 1
a
As for Table 1. b Wt %. Vol %. Calculated by extrapolation
c
d
254 ( 4d
3
-1
of the following data: 10 k/s (T/°C) 0.660 ( 0.001 (20.0); 0.327
303 ( 2
q
q
(
0.005 (10.0); 0.157 ( 0.006 (0.0); ∆H ) 10.9 kcal/mol and ∆S
a
Determined conductometrically at least in duplicate; errors
) -36 eu.
b
shown are average deviations. In agreement with data from ref
3
-1
c
9
a: 10 k ) 101.6 ( 8.9 s at -9.8 °C. Additional data for MeOD:
TABLE 4. Product (% Ester) and Selectivities (S, Eq 1)
d
k ) 119 ( 5, so KSIE is 2.18. Extrapolation of the correlation
for Solvolyses of Chloroacetyl Chloride (3) at -10.0 °C
-
1
line in Figure 1 gives a value of 0.35 s for the rate constant in
water.
and for Phenylacetyl Chloride (4) at 0.0 °Ca in Ethanol/
and Methanol/Water
3
4
TABLE 2. Rate Constants (k/10- s-1) for Solvolyses of
Phenylacetyl Chloride (4) in Acetone/, Ethanol/ and
Methanol/Water at 0.0 °Ca
3
solventa
% esterb
Sc
% esterd
Sc
9
5EtOH
90EtOH
80EtOH
90.3
84.9
79.8
65.9
1.6
2.0
3.2
4.2
4.3
93.0
89.3
81.6
2.3
3.0
3.6
4.1
2.9
2.4
solvent
%
v/v
acetone
ethanol
methanol
e
60EtOH
40EtOH
20EtOH
90MeOH
80MeOH
70MeOH
60MeOH
50MeOH
40MeOH
65.4
1
00
20.4 ( 1b,c
44.5 ( 4
54.7 ( 2
77.6 ( 2
96.2 ( 1
144 ( 5
264 ( 24
82.7 ( 1.4d
126 ( 3
f
e
46.8
37.6
9
8
7
6
5
4
3
0
0
0
0
0
0
0
2.45 ( 0.01
4.62 ( 0.12
9.38 ( 0.40
16.5 ( 0.7
59.2 ( 1
f,g
15.7
b
188 ( 1
f
97.5
91.0
94.6
273 ( 14
435 ( 77
5.7
9.2
93.3
7.8
7.1
6.1
f
e,h
91.5
88
e
86.0
80.4
139 ( 1
h
83
11
432 ( 20
59.9i
5.0
a
As for Table 1. Ref 11a. c Data calculated from ref 9a: 103k
b
a
Solvents are % v/v. b Determined by HPLC from at least
-
1 d
)
17.0 s
.
At 10 °C, the KSIE (MeOH/MeOD) ) (1.44 ( 0.05) ×
duplicate analyses of duplicate samples, using an appropriate ester
as internal standard; injected 100 µL of 4% solution of acid chloride
in acetonitrile into 5.0 mL of solvolysis medium; typical average
-
1
-1
1
0
/(1.03 ( 0.02) × 10 ) 1.40.
c
deviations (1%. Calculated from eq 1, and the molarities of the
Results
Rate constants for solvolyses of 3 and 4 in acetone/,
ethanol/, and methanol/water are shown in Tables 1 and
, respectively, and constants in TFE/water and TFE/
ethanol are shown in Table 3. Product selectivities (S,
eq 1) for ethanol/ and methanol/water are shown in
Table 4.
The energetics of reactions of a wide range of acid
chlorides (ZCOCl) in the absence of solvent was outlined
using Gaussian 03,18 by comparing the energies of various
acylium ions with the acetyl cation in chloride transfer
reactions (eq 2, Table 5). Contributions from the stabi-
lization energies of neutral ground states were calculated
bulk solvent concentrations; see Table 1, footnote a of ref 4a.
d
Calculated from the observed ester/acid area ratios, determined
by HPLC from at least duplicate analyses of duplicate samples;
injected 40 µL of 10% solution of acid chloride in acetonitrile into
5.0 mL of solvolysis medium; typical average deviations (1%.
2
e
First sample was from 10% solution, but duplicate sample was
f
an injection of 100 µL of 4% solution of acid chloride. Determined
g
from a single sample. Precipitate formed at 0 °Csanalyzed after
h
i
warming. Average deviation (2%. Injected 100 µL of 4% solu-
tion as first sample and 100 µL of 2% solution as “duplicate”
sample.
from isodesmic reactions (eq 3, Table 6).
+
+
MeCO + ZCOCl f MeCOCl + ZCO
(2)
(3)
(
18) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
ZCOCl + C H f ZMe + MeCOCl
2
6
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson,
G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai,
H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P.
Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas,
O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.;
Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.;
Gonzalez, C.; Pople, J. A. Gaussian 03, revision C.02; Gaussian, Inc.:
Wallingford, CT, 2004.
Discussion
Solvolysis Rate Constants and Selectivities. A plot
of logarithms of rate constants for solvolyses of p-
nitrobenzoyl chloride (1, Z ) NO ) at 25 °C vs solvolyses
2
of chloroacetyl chloride (3) at -10 °C is linear with a slope
of 0.96 for solvents from 90% to 20% acetone/water,
including ethanol/ and methanol/water mixtures (Figure
1
); inclusion of data for the much slower solvolyses in
TFE/water and TFE/ethanol gives a similar slope (1.09)
and shows the high sensitivity of the solvolyses to solvent
J. Org. Chem, Vol. 70, No. 22, 2005 8965

Bentley et al.
TABLE 5. Calculated Energies (kcal/mol) for Chloride
+
Ion Transfer between Acylium Ions (ZCO ) and Acetyl
Chloride (eq 2) at Three Levels of MO Theorya
Z
HF/6-31G(d)b B3LYP/6-31G(d)c B3LYP/6-311G(d,p)d
H
27.5
0.0
31.0
0.0
30.1
0.0
e
e
e
Me
Et
-4.4
12.3
-4.7
11.1
4.0
-4.3
11.5
3.9
CH2Cl
CH2OMe
CH2SMe
CH2Ph
1.5
-0.5
-10.0
-15.5
-6.4
-12.5
-17.7
25.7
-5.9
-11.5
-16.4
24.5
f
Ph
HO
MeO
EtO
MeS
30.0 g
(10.6)
(9.1)g
0.4
(7.9)g
0.9
g
(-0.6)
3.4
a
Calculated from the total energies obtained using Gaussian
b
0
3, with fully optimized geometries for each level of theory. Total
FIGURE 1. Logarithms of rate constants for solvolyses of
energies (Hartrees) for HF/6-31G(d) calculations of individual
c
p-nitrobenzoyl chloride (1, Z ) NO ) at 25 °C and of methyl
species are in Table S1. Total energies (Hartrees) for B3LYP/6-
2
d
3
1G(d) calculations of individual species are in Table S2. Total
chloroformate (MeOCOCl) at 40 °C vs solvolyses of chloroacetyl
energies (Hartrees) for B3LYP/6-311G(d,p) calculations of indi-
vidual species are in Table S3. By definition. f Experimental
thermochemical data give ∆H ) -15.5 ( 4.2 kcal/mol (but see
2
chloride (3) at -10 °C. For 1, Z ) NO , slope of the correlation
e
line shown: 1.09 ( 0.05; R ) 0.98, n ) 18. Excluding the three
TFE-containing solvent mixtures: slope ) 0.96 ( 0.06; R )
0.98, n ) 15; data from Tables 1 and 3 and refs 4b and 19. For
methyl chloroformate (data from ref 20): slope ) 0.98 ( 0.06,
R ) 0.98, n ) 12.
g
discussion). Bond between the CH2 and the oxygen atom in the
cation is unusually long, so the O-alkyl bond is beginning to
break.
TABLE 6. Calculated Ground-State Stabilization
Energies (kcal/mol) from Methyl Transfer between Acid
Chlorides (ZCOCl) and Ethane (Eq 3) at Two Levels of
SCHEME 1. Competing Third-Order Rate
Constants for Solvolyses of Chloroacetyl Chloride
(3) in Alcohol/Water Mixturesa
a
Theory
Z
HF/6-31G(d)b
B3LYP/6-31G(d)c
H
-10.0d
-10.6d
Me
0.0
0.0
Ph
0.7
1.8
HO
MeO
MeS
16.1
15.5
-0.7
15.7
14.7
3.3
a
Calculated using Gaussian 03. b Total energies (Hartees) for
c
individual species are in Tables S1 and S4. Total energies
d
(
Hartees) for individual species are in Tables S2 and S4. By
a
The first letter of the subscript to the rate constant (k) refers
definition.
to water (w) or alcohol (a) acting as a nucleophile and the second
letter refers to the role of solvent as a general base.
nucleophilicity (N).20,21 On the same plot (Figure 1),
logarithms of rate constants for solvolyses of methyl
chloroformate at 40 °C also give a good linear correlation
that of the bulk solvent composition, then the true S
would be lower (e.g., 4-fold). In contrast, solvolyses of
(
slope ) 0.98) for solvents including TFE mixtures. These
10
3
acetyl chloride and 1, Z ) OMe, show much lower S
values in ethanol/ and methanol/water (<2), almost
independent of solvent composition for each binary
alcohol/water mixture. Consequently, we will now further
explore the possibility that variations in S values arise
from mechanistic changes.
results provide a link between rate constants for solvoly-
ses of aroyl and acyl chlorides (containing electron-
withdrawing substituents) and solvolyses of methyl
chloroformates, known to react similarly to other chloro-
7
c
formates.
Product selectivies (S, eq 1) for solvolyses of 3 are even
The relatively high KSIE for 3 in MeOH of 2.18 (Table
higher than those for the much more hydrophobic sub-
1
, footnote c) is the same within experimental errors as
4
3b
strate 1, Z ) NO
2
. These results support other evidence
4b
2
the values of 1.8-2.3 for 1, Z ) NO , for which a third-
that preferential solvation of hydrophobic substrates by
alcohol in alcohol/water mixtures is not the cause of high
S valuessif the true mole ratio of alcohol to water at the
reaction site were significantly greater (e.g., 4-fold) than
order mechanism (second-order in solvent) has been
4
proposed. A very similar KSIE value in MeOH (2.17 (
7e
0
.03) was observed for n-propyl chloroformate. If one
molecule of solvent acts as a nucleophile, and the other
acts a general base, then there are four possible third-
order reactions in binary alcohol/water mixtures, with
rate constants kww, kaw, kwa, and kaa (Scheme 1).
Assuming kinetic control of product formation and
third-order rate laws for formation of each product, the
product ratio E/A ) [ester]/[acid] is then given by eq 4,
where square brackets refer to molar concentrations.
Rearrangement of eq 4 gives eq 5.
(
19) (a) Swain, C. G.; Mosely, R. B.; Bown, D. E. J. Am. Chem. Soc.
955, 77, 3531-3537. (b) Bentley, T. W.; Harris, H. C. J. Chem. Soc.,
Perkin Trans. 2 1986, 619-624.
20) Kevill, D. N.; Kim, J. C.; Kyong, J. B. J. Chem. Res. (S) 1999,
50-151.
21) Kinetic data for solvolyses of 1, Z ) NO
equation: log(k/k ) ) 0.54YCl + 1.78N + 0.1, for details, see ref 2b.
For methyl chloroformate: log(k/k ) ) 0.58YCl + 1.58N + 0.16 (ref
0). Data for 3 (Tables 1 and 3) are correlated by the equation: log-
k/k ) ) 0.45YCl + 1.54N + 0.16.
1
(
1
(
2
, are correlated by the
0
T
0
T
2
(
0
T
8966 J. Org. Chem., Vol. 70, No. 22, 2005

Solvolyses of Acid Chlorides and Chloroformates
2
E/A ) {k [alcohol][water] + k [alcohol] }/
aw
aa
2
{
kwa[alcohol][water] + kww[water] } (4)
2
2
f(rates) ) {(E/A)kww[water] - k [alcohol] }/
aa
[
alcohol][water] ) -(E/A)kwa + kaw (5)
Values of kaa and kww are obtained from the observed first-
order rate constants in a pure solvent divided by the
4
molar concentration of solvent. Plots of f(rates) vs E/A
(eq 5) for ethanolysis of 3 are linear (Figure 2); the slope
is -kwa and the intercept is kaw (see legend to Figure 2).
The sum of all four terms in eq 4 is the calculated first-
order rate constant: e.g. for 40% ethanol/water, in which
-
1
-1
the rate reaches a maximum, kcalc ) 3.91 × 10
s
in
-
1
FIGURE 2. Evaluation of k and kaw from eq 5, based on
good agreement with the observed value of 3.84 × 10
wa
-1
the mechanism shown in Scheme 1 for ethanolysis of chloro-
acetyl chloride (3) at -10 °C; solvent concentrations are
molarities from ref 4b. From data for pure solvents: kaa ) 1.01
s . The calculations indicate that contributions from kaw
and kwa are dominant, in part because the [alcohol] ×
[
water] term is large. The mechanism (Scheme 1) also
-2
2
-4
-2 -1
-1
×
10 /(17.14) ) 3.44 × 10
M
s
and kww ) 3.5 × 10
/
accounts for two unusual features of solvolyses of 3: as
water is added to alcohol, S increases as reactivity
increases, and a rate maximum is reached in ca. 50 vol
2
-4
-2 -1
(
55.5) ) 1.1 × 10
M
s . From the correlation line: slope
-
4
-2 -1
(k ) ) (2.8 ( 0.3) × 10
wa
M
s
and intercept (kaw) ) (8.0 (
-
4
-2 -1
1.3) × 10
M
s ; R ) 0.989.
%
alcohol.
The above results strongly support the third-order
mechanism (Scheme 1) for solvolyses of 3 in aqueous
alcohols. Adapting the same mechanism for solvolyses
in acetone/water, values of kww can be obtained by
dividing the observed first-order rate constants by [wa-
2
ter] ; for this calculation, we assume that acetone is a
relatively inert solvent and has no significant role as a
general base or as a nucleophile (however, it is possible
4c
that acetone could act as a weak general base catalyst ).
A plot of the logarithms of calculated third-order rate
constants for solvolyses of 3 in acetone/water vs Grun-
wald-Winstein Y values is linear (Figure 3), with the
same slope for the same range of solvents as for solvolyses
4
a
2
of 1, Z ) NO .
If solvolyses of 4 in acetone/water are also assumed
for comparison) to be second-order in water solvent, the
(
FIGURE 3. Plots of logarithms of calculated third-order rate
constants for solvolyses of 3 at -10 °C and 4 at 0 °C in acetone/
water vs Grunwald-Winstein Y values; kinetic data from
Tables 1 and 2; Y values from ref 22. For 3: slope ) m ) -0.18
( 0.01, intercept ) -3.35 ( 0.02, R ) 0.990, n ) 8.
calculated third-order rate constants (Figure 3) show a
shallow U-shaped curve or two linear regions, with a
minimum around Y ) 0. A very similar result was
observed for solvolyses of 1, Z ) Cl,1b for which competing
reaction channels were proposed. In addition to the third-
order mechanisms (Scheme 1), which are relatively
insensitive to changes in solvent ionizing power (Y), there
is a competing reaction channel more sensitive to Y.
Strong support for the competing mechanism is provided
made for differences in reactivity and the solvent effect
on relative rates is obtained. Such plots are particularly
useful if, as in the case of 4, a mechanistic change occurs
around Y ) 0.
Logarithms of observed first-order rate constants for
by the maxima in S values observed for solvolyses of 1,
1
5
1
acetyl chloride (selected as a similarity model for the
ionization reaction channel for solvolyses of acyl chlo-
rides) give a precise linear plot vs Y (Figure 4), with slope
m ) 0.63 ( 0.02, showing a larger dependence on solvent-
ionizing power. In contrast, rate constants for solvolyses
of 3 (selected as a similarity model for the third-order
reaction channel for solvolyses of acyl chlorides) vary less
than 1.5-fold from 90% to 20% ethanol/water. The rate
profile for solvolyses of 4 is almost superimposable on
that of 3 from ethanol to 80% ethanol/water (Y ) 0), but
then it diverges and the slope gradually increases
until it is similar to that for solvolyses of acetyl chloride
2
Z ) Cl, NO , and H, in alcohol/water mixtures.
In contrast to the upward trend in S values for
solvolyses of 3, solvolyses of 4 show a maximum S in
ethanol/water and a downward trend in methanol/water
(
Table 4), consistent with a change in mechanism; a
similar but clearer maximum in S values was observed
for solvolyses of 1, Z ) Cl.1b Further support for mecha-
nistic change can be obtained by comparing rate profiles
for solvolyses of 3 and 4 in ethanol/water with those for
solvolyses of acetyl chloride. If log(k/k ) is plotted, where
o
k is the rate constant in 80% ethanol/water (Y ) 0) as
o
2
2
in typical Grunwald-Winstein plots, corrections are
(
Figure 4).
In the absence of the similarity model (3) for the third-
order reaction channel, it could appear that there was
(
22) Fainberg, A. H.; Winstein, S. J. Am. Chem. Soc. 1956, 78, 2770-
2
777.
J. Org. Chem, Vol. 70, No. 22, 2005 8967

Bentley et al.
TABLE 7. Comparisons of Calculated and Experimental
Energies (kcal/mol) for Chloride Ion Transfer from
tert-Butyl Chloride to the Acetyl Cation (Eq 6)
theory/method
calculated
experimentala
G3b
-0.3
-8.0
-10.7
-5.4
-1.2c
d
(3.5 ( 3)e
B3LYP/6-311G(d,p)
d
B3LYP/6-31G(d)
HF/6-31G(d)
d
a
Experimental values are calculated from enthalpies of forma-
b
c
tion of each of the four species in eq 6. Ref 17. Thermochemical
data from ref 10, except for a revised value for the acetyl cation;
the previous value of 152 ( 1 kcal/mol (ref 10) was reevaluated
(
ref 29) to give a new recommended value of 156.7 kcal/mol; this
was the value we chose, and it is in good agreement with a recent
value of 157.6 ( 0.3 kcal/mol, obtained by threshold photoelectron
FIGURE 4. Grunwald-Winstein plots for solvolyses of acetyl
chloride, chloroacetyl chloride (3) and phenylacetyl chloride
d
photoion coincidence (ref 30). This work, using total energies
(
Tables S1-S4), excluding small corrections for differences in ZPE.
(
4) in ethanol (Y ) -2) and in ethanol/water mixtures; 80E
e
Using pre-1996 data in ref 10.
refers to 80% v/v ethanol/water (Y ) 0); kinetic data from
Tables 2 and 3 and ref 10; Y values from ref 22. For acetyl
chloride: slope ) m ) 0.63 ( 0.02, intercept ) 0.02 ( 0.02,
R) 0.998, n ) 5.
6
-311G(d,p)26 DFT methods agreed well but showed
greater substituent effects than those observed from
appearance potentials; the difference in stability between
2a
only one reaction channel for solvolyses of 4. The plot
for 4 (Figure 4) is related linearly to Y over the whole
range of alcohol/water solvent compositions (m ) 0.27 (
p-OMe and p-NO
2
substituted benzoyl cations was 23.75
or 21.5926 kcal/mol from theory, but only ca. 15 kcal/mol
19b
from experiment. The discrepancy can be explained (at
least in part) by the greater ionization probabilities of
electron-rich aromatic compounds, one of the factors not
accounted for in the semilog method for measuring
appearance potentials.27
Appropriate experimental data were not available for
the chloroacetyl cation.28 Consequently, to try to over-
come the problems associated with the lack and/or
inadequacy of experimental data for acylium ions, theo-
retical results were obtained (Table 5). A minor difference
0
.02, R ) 0.98, n ) 8); only on closer inspection is the
shallow S-shape discernible. We previously reached the
conclusion, based on a linear mY plot, that solvolyses of
2
thiomethylacetyl chloride (MeSCH COCl) reacted by a
single reaction channel;1 however, the solvent effect is
almost identical to that for 4, except that the change in
slope beyond Y ) 0 is offset by about one unit of Y, and
so thiomethyl acetyl chloride probably solvolyses by
competing reaction channels in ethanol/water mixtures.
Theoretical Calculations and Gas-Phase Ion
Chemistry. Useful mechanistic insights have been
obtained by comparing experimental data for gas-phase
ion chemistry with solvolytic reactivity. Relative rates
of solvolyses of tert-butyl and 2-propyl halides are solvent
dependent, and in weakly nucleophilic media approach
1c
2a,26
between the two theoretical treatments
(discussed
above) is that only the later one26 included correction for
2
6
changes in zero-point energies (ZPE); published data
show that neglect of differences in ZPE introduces small
errors (up to 0.3 kcal/mol).
A recent G3 MO calculation17 giving -0.3 kcal/mol for
the enthalpy of chloride ion transfer from tert-butyl
chloride to the acetyl cation (eq 6) is in good agreement
with the latest experimental value of -1.2 kcal/mol
8
the value of 10 expected from the cation stabilities in
2
4
the gas phase. Relative rates of 1-adamantyl and tert-
butyl solvolyses increase in less nucleophic media, and
(
Table 7). These results provide an important reference
1-adamantyl becomes of comparable or greater reactivity
point for mechanistic discussions of acyl halides because
they confirm that the acetyl cation is of comparable
than tert-butyl (as expected from gas-phase ion chemis-
try; contrary to expectations based on “unfavorable”
bridgehead cations).25 Increases in relative rates in more
nucleophilic media can be explained by nucleophilic
stability to the tert-butyl cation; consequently, S 2/S 1
reaction channels could operate in corresponding solvoly-
ses.1
N
N
0,17
solvent assistance (S
and (to a smaller extent) tert-butyl solvolyses.
N
2 character) in 2-propyl solvolyses,
24,25
+
+
(
CH ) CCl + CH CO ) (CH ) C + CH COCl (6)
Rates of solvolyses of para-substituted acid chlorides
in TFE show about the same substituent effects as the
appearance potentials of acylium ions produced by gas-
3 3 3 3 3 3
Energies calculated for eq 6 from the three levels of
theory we used (Table 5) vary by 5 kcal/mol, and are at
least 4 kcal/mol more negative than the best available
values (Table 7). Differences in predicted energies be-
tween DFT and higher level methods (e.g. MP2) have
recently been noted in calculations for cationic intermedi-
phase fragmentation of acetophenones, so the solvolyses
9b
in TFE were thought then to be S
N
1 reactions.1 How-
ever, later independent theoretical investigations of para-
substituted acylium ions by HF/6-31G(d)2a and B3LYP/
(
23) Koo, I. S.; Yang, K.; Kang, K.; Lee, I.; Bentley, T. W. J. Chem.
Soc., Perkin Trans. 2 1998, 1179-1183.
(26) Krygowski, T. M.; Cyra n˜ ski, M. K.; Sung, D. D.; Stepie n˜ , B. T.
J. Phys. Org. Chem. 2004, 17, 699-706.
(
24) (a) Fry, J. L.; Harris, J. M.; Bingham, R. C.; Schleyer, P. v. R.
J. Am. Chem. Soc. 1970, 92, 2540-2542. (b) Bentley, T. W.; Bowen, C.
T.; Parker, W.; Watt, C. I. F. J. Chem. Soc., Perkin Trans. 2 1980,
(27) Bentley, T. W.; Johnstone, R. A. W. Adv. Phys. Org. Chem. 1970,
8, 177-180.
1
244-1252.
(28) (a) A low ionization energy of chloroacetyl chloride of 10.30 eV
has been reported (ref 28b), but the radical ion may not dissociate
immediately to the chloroacetyl cation. (b) Katsumata, S.; Kimura, K.
J. Electron Spectrosc. 1975, 6, 309-319.
(
25) (a) Bentley, T. W.; Carter, G. E. J. Am. Chem. Soc. 1982, 104,
5
2
741-5747. (b) Bentley, T. W.; Roberts, K. J. Chem. Soc., Perkin Trans.
1989, 1053-1060.
8968 J. Org. Chem., Vol. 70, No. 22, 2005

Solvolyses of Acid Chlorides and Chloroformates
increase in stability of incipient acylium ions. Nucleo-
philic attack at carbonyl carbon is favored when the
acylium ion is destabilized. The chloroacetyl cation is
calculated to be 12 kcal/mol less stable than the acetyl
cation (Table 5), and the p-nitrobenzoyl cation is 12-15
kcal/mol less stable the benzoyl cation.2 Consequently,
an ionization mechanism becomes substantially more
favorable in the absence of electron-withdrawing sub-
i.e. it is not homodesmotic).26,32 Consequently, caution
a,26
stituents (e.g. Cl or NO
2
), and experimental evidence
indicates that a change of reaction channel does occur
10
for solvolyses of acetyl (Figure 4) and benzoyl chlo-
1,2
+
rides. Acylium ions (ROCO ) from chloroformates (RO-
+
COCl) are susceptible to fragmentation to R and CO
so more electron-donating alkyl groups (R) favor mecha-
nistic change. As the S 2/S l reaction channel involves
2
,
N
N
direct heterolysis, it is more sensitive to solvent polarity,
and so mechanistic changes will also be favored in more
polar solvents.
As expected, smaller cations (e.g. H-substituted) are less
favorable, and larger cations (e.g. Ph-substituted) are
favored. The large substituent effect for chloroformates
Experimental Section
Materials. Chloroacetyl chloride (3, >98%) and pheny-
lacetyl chloride (4, >98%) were used as obtained. Solvents for
kinetic studies were dried and distilled by standard methods.
(
ROCOCl, e.g. Z ) OH, OMe, OEt in Table 5) appears to
+
be associated with fragmentation of the ROCO cation
to R and CO .
2
1
+
Solvents for product studies (ethanol and methanol) were AR
or HPLC grades respectively, containing 0.01% water. Aceto-
nitrile was a dried HPLC grade, containing 0.006% water.
Water was glass-distilled. Solvolysis media were prepared as
v/v solutions, mixed at room temperature, except for TFE/
water mixtures prepared as % w/w; the water content of 97%
w/w TFE/water was checked by Karl Fisher titration using
HYDRANAL (5) titrant.
33
The proposal that the low reactivity of chloroformates
ROCOCl) could be due in part to stabilization of the
(
ground state of neutral chloroformates (e.g. by resonance
interactions between RO and CO) is now supported by
calculationssa stabilization energy of ca. 15 kcal/mol is
calculated for Z ) OH and OMe (Table 6).
Replacement of the alkyl-oxygen by sulfur favors the
Kinetic Methods. Rate constants were determined using
a rapid-injection, conductometric method. A freshly prepared,
ionization channel,7b as the cation is more favorable
4b
(
Table 5). Ethyl thiochloroformate (EtSCOCl) is thought
dilute solution of the acid chloride in dry acetonitrile was
injected into a rapidly stirred solution of the solvolysis
medium. Increases in conductance were monitored automati-
cally, and rate constants were calculated with the Origin 6.0
program, using the Guggenheim equation. Traces of acid
impurities do not affect the accuracy of measurements of rate
constants, monitored from changes in conductance after a set
mixing time (additional acid is formed as the reaction pro-
ceeds).
Product Studies. Acid chlorides were dissolved in dry
acetonitrile, and were stored as stock 10 or 20% solutions for
up to a few hours. Equimolar amounts of internal standards
were added to the stock solutions for solvolyses of chloroacetyl
chloride (methyl propionate for methanolysis and ethyl acetate
for ethanolysis). More dilute solutions (4% and 2%ssee
footnotes to Table 4) were prepared by diluting the stock
solutions, and were then used immediately. Experiments were
initiated by injecting acetonitrile solutions into the thermo-
to hydrolyze by the ionization reaction channel, and in
water at 25 °C is over 100 times more favorable
kinetically than the addition-elimination channel for
EtOCOCl. Although the ground-state effect is calculated
to be small for thiochloroformates (Table 6), EtOCOCl is
slightly more reactive than EtSCOCl in ethanol.7b
1
1a
7b
Conclusions
Rates and products of solvolyses of chloroacetyl chlo-
ride (3) are remarkably similar to those of p-nitrobenzoyl
2
chloride (1, Z ) NO ) in selectivity (S, eq 1), KSIE
(
MeOH/D), low sensitivity to solvent ionizing power, and
high sensitivity to solvent nucleophilicity. Solvolyses of
20
23
methyl and p-nitrophenyl chloroformates are also very
similar (Figure 1). All of the reactions fit a third-order
addition/elimination mechanism, involving attack by a
solvent nucleophile assisted by another molecule of
solvent acting as a general base (Scheme 1).
4b
stated solvolysis medium (5 mL) in a turbo-stirred apparatus;
usually multiple injections were made in rapid succession (e.g.,
2
× 20 µL, or 2 × 50 µL, or 5 × 20 µL).
Analyses of quenched alcoholysis products were carried out
Mechanistic changes from addition/elimination (Scheme
) to S 2/S 1 reaction channels can be explained by an
N N
to correct for acid impurities present in the chloroacetyl
chloride stock solutions, after manipulations (including storage
in dry acetonitrile). For each stock solution, yields of chloro-
acetyl esters were monitored by comparison of the area ratio
with an internal standard and set to 100% for solvolysis in
pure alcohols, so correcting for any acid impurities in the
solutions of acid chloride in acetonitrile. It was necessary to
check the calibrations (area ratios) about every 2 h, and to
make small corrections for the changes due to slow decomposi-
tion of the acid chloride.
For the phenylacetyl solvolyses, accurate 40 µL aliquots of
the 10% stock solutions in acetonitrile were injected into 5.00
mL of ethanol, methanol, or 40% acetonitrile/water to obtain
standard solutions of the two ester products and the acid.
1
(
29) Traeger, J. C.; Kompe, B. M. In Energetics of Organic Free
Radicals, Simeos, J. A. M., Greenburg, A., Liebman, J. F. Eds.;
Chapman and Hall: London, 1996; pp 59-109.
(
30) Fogleman E. A.; Koizumi, H.; Kercher, J. P.; Szt a´ ray, B.; Baer,
T. J. Phys. Chem. A 2004, 108, 5288-5294.
(
31) Chen, L.; Xiao, H.; Xiao, J. J. Phys. Org. Chem. 2005, 18, 62-
6
8.
(
32) George, P.; Trachtman, M.; Bock, C. W.; Brett, A. M. Theor.
Chim. Acta 1975, 38, 121-129.
(
33) (a) Kivinen, A. In The Chemistry of Acyl Halides; Patai, S., Ed.;
Interscience: New York, 1972; Chapter 6, p 182. (b) Kevill, D. N. In
The Chemistry of Acyl Halides; Patai, S., Ed.; Interscience: New York,
972; Chapter 12, p 409.
1
J. Org. Chem, Vol. 70, No. 22, 2005 8969

Bentley et al.
These samples were then analyzed immediately by HPLC at
least in triplicate to obtain the areas of acid and ester signals
Calculations. Gaussian 03 calculations18 were performed
at the Rutherford Appleton Laboratory (Columbus service),
using the EPSRC National Service for Computational Chem-
istry software (NSCCS). Linear regressions were performed
using Microsoft Excel; errors quoted in statistical analyses are
the standard errors. Graphs were plotted using KaleidaGraph
(
after injecting 10 µL of solution as accurately as possible).
Ester/acid area ratios were calculated after correcting for the
ca. 3% acid present after manipulations in the stock solutions.
Duplicate samples were analyzed several hours later, and it
was shown that no significant deterioration of the stock
acetonitrile solution occurred. UV responses of the two esters
and the acid were identical within ca. 2%.
(
Synergy Software, Reading, PA).
Product mixtures were analyzed by injecting 10 µL of
product solutions onto the HPLC column, as soon as possible
after completion of the reaction, because the acid products were
esterified in highly alcoholic, relatively acidic solutions. Ester
exchange was also minimized in the same way, and also (for
chloroacetyl solvolyses) by the choice of appropriate methyl
or ethyl ester as internal standard. Additional details are given
in the footnotes to Table 4.
Acknowledgment. We are grateful to EPSRC for
financial support. We thank Dr. S. Wilsey for assistance
in using NSCCS, and Dr. M. S. Garley for additional
assistance with computing. Helpful correspondence and
information from R. D. Bach, O. Dmitrenko, D. N.
Kevill, and J. Traeger are gratefully acknowledged.
The HPLC system comprised a 5 µm, 15 cm Apex Advantage
ODS column, a pump (flow rate 1 mL/min), a detector and an
integrator/plotter. Chloroacetyl solvolyses were monitored at
Supporting Information Available: Total energies (Har-
tees) calculated by HF/6-31G(d) for acid chlorides (ZCOCl) and
+
corresponding cations (ZCO ), Table S1. Total energies (Har-
2
10 nm with absorbance FSD ) 0.05 (eluents: 18% v/v
methanol/water for methanolysis and 30% v/v methanol/water
for ethanolysis). Under these conditions, the signal for chloride
ion overlapped with that for chloroacetic acid; addition to the
tees) calculated by B3LYP/6-31G(d) for acid chlorides (ZCOCl)
+
and corresponding cations (ZCO ), Table S2. Total energies
(Hartees) calculated by B3LYP/6-311G(d,p) for acid chlorides
-
2
+
eluent of 10
M ammonium chlorides, or triethylamine
(ZCOCl) and corresponding cations (ZCO ), Table S3. Other
hydrochloride was investigated, but did not lead to good
quantitative data. Phenylacetyl solvolyses were monitored at
total energies (Hartees) required to calculate stabilization
energies of neutral acid chlorides, Table S4. This material is
available free of charge via the Internet at http://pubs.acs.org.
2
60 nm with absorbance FSD ) 0.05 (eluent: 60% v/v
methanol/water to which 1% glacial acetic acid was then
added).
JO0514366
8970 J. Org. Chem., Vol. 70, No. 22, 2005