Kinetics and mechanism of the pyridinolysis of phenyl chloroformates in acetonitrile

Article abstract of DOI:10.1021/jo9814905

Kinetic studies on the reactions of Y-phenyl chloroformates with X- pyridines in acetonitrile are carried out at 25.0 °C. Both the Hammett and Bronsted plots are linear with enhanced substituent constants, σ(p)^-, and basicities, pK(a)^-, for strong para π-acceptor X-substituents, p-CN and p- CH₃CO. This indicates that the electron-rich formate (O-C-O) moiety overlaps with the pyridine ring π-system enabling, through conjugation with the para π-acceptors, the rate-limiting formation of a tetrahedral intermediate. The difference in the aminolysis mechanism between methyl, II, and phenyl chloroformate, III, is attributed to the much stronger electron-donating polarizability effect of C₆H₅ than of CH₃. The proposed mechanism is supported by a relatively small β(X) (? 0.3) and by the lower δH(+) (6.7 kcal mol^-1) and δS(+) (-44 eu) values for a stronger donor Y (Y = p- CH₃O) coupled with a stronger para π-acceptor (X = p-CN) in pyridine.

Full text of DOI:10.1021/jo9814905

9834
J . Org. Chem. 1998, 63, 9834-9839
Kin etics a n d Mech a n ism of th e P yr id in olysis of P h en yl
Ch lor ofor m a tes in Aceton itr ile
Han J oong Koh, Kwang Lae Han,† Hai Whang Lee,‡ and Ikchoon Lee*,‡
Department of Science Education, Chonju National University of Education, Chonju, 560-757 Korea
Received J uly 27, 1998
Kinetic studies on the reactions of Y-phenyl chloroformates with X-pyridines in acetonitrile are
carried out at 25.0 °C. Both the Hammett and Bro¨nsted plots are linear with enhanced substituent
constants, σp-, and basicities, pKa-, for strong para π-acceptor X-substituents, p-CN and p-CH3CO.
This indicates that the electron-rich formate (O-C-O) moiety overlaps with the pyridine ring
π-system enabling, through conjugation with the para π-acceptors, the rate-limiting formation of
a tetrahedral intermediate. The difference in the aminolysis mechanism between methyl, II, and
phenyl chloroformate, III, is attributed to the much stronger electron-donating polarizability effect
of C6H5 than of CH3. The proposed mechanism is supported by a relatively small âX (=0.3) and by
the lower ∆Hq (6.7 kcal mol-1) and ∆Sq (-44 eu) values for a stronger donor Y (Y ) p-CH3O) coupled
with a stronger para π-acceptor (X ) p-CN) in pyridine.
In tr od u ction
In this paper, we report the kinetics of reaction of
substituted pyridines with phenyl chloroformates, III, in
acetonitrile at 25.0 °C, eq 1. The object of this work is to
investigate the mechanism more closely, (i) confirm our
The aminolysis rates of carbonyl compounds with good
leaving groups usually exhibit a biphasic dependence on
amine basicity. The Bro¨nsted plots for these nucleophilic
reactions show a change in slope from a large (ânuc = 0.8-
1.0) to a small (ânuc = 0.1-0.3) value, which can be
attributed to a change in the rate-determining step from
breakdown to formation of a tetrahedral intermediate in
the reaction path as the basicity of the amine nucleophile
increases.1 For acetyl chloride,1g I, and methyl chloro-
formate,1d II, such a change in the slope of the Bronsted
plots were found to occur at relatively low amine basicity,
previously proposed mechanism of the rate-limiting at-
tack, and (ii) predict which of the two possibilities, a
stepwise reaction with rate-limiting formation of a tet-
rahedral intermediate or a concerted process, are more
likely. We chose 12 pyridines for this purpose including
two strong π-acceptors, p-CH3CO and p-CN. It turned out
that these two pyridines with strong π-acceptors are
crucial to substantiate the transition-state structure in
the rate-limiting formation of the tetrahedral intermedi-
ate.
pKa = 3.6, in aqueous solution. In contrast, however,
structurally similar phenyl chloroformate,2 III, was found
to react with aniline nucleophiles in acetonitrile by rate-
limiting attack in the formation of a tetrahedral inter-
mediate or by an associative SN2 process. Since the
aniline nucleophiles used there have a relatively narrow
range of low basicity (five anilines of pKa ranging from
4.60 to 1.00 in water at 20 °C), the evidence presented
was considered not very convincing to decide whether the
mechanism is stepwise (formation of a tetrahedral in-
termediate) or concerted (SN2).
Resu lts
The pseudo-first-order rate constants observed (kobs) for
all the reactions obeyed eq 2 with negligible ko () 0) in
acetonitrile. The second-order rate constants, k2/dm3
mol-1 s-1, summarized in Table 1, were determined using
eq 2 with at least five pyridine concentrations, [Py]. No
third-order or higher-order terms were detected, and no
† Department of Science Education, Kwangju National University
of Education, Kwangju, 500-703 Korea.
kobs ) ko + k2[Py]
(2)
‡ Department of Chemistry, Inha University, Inchon, 402-751 Korea.
(1) (a) J encks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90, 2622.
(b) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963. (c)
Fersht, A. R.; J encks, W. P. J . Am. Chem. Soc. 1970, 92, 5442. (d) Bond,
P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1976,
68. (e) Castro, E. A.; Gil, F. J . Am. Chem. Soc. 1977, 99, 7611. (f) Castro,
E. A.; Freudenberg, M. J . Org. Chem. 1980, 45, 906. (g) Palling, D. J .;
J encks, W. P. J . Am. Chem. Soc. 1984, 106, 4869. (h) Castro, E. A.;
Ibanez, F.; Salas, M.; Santos, J . G.; Sepulveda, P. J . Org. Chem. 1993,
58, 459.
complications were found in the determination of kobs and
also in the linear plots of eq 2. This suggests that there
is no base-catalysis or noticeable side reactions, and the
overall reaction follows the route given by eq 1. The
Hammett FX (Fnuc) and FY, (Figures 1 and 2), and the
Bro¨nsted âX (ânuc) values (Figure 3), are also shown in
Table 1. For the two strong π-acceptors, p-CH3CO and
p-CN, enhanced substituent constants, σp-, and basici-
(2) Yew, K. H.; Koh, H. J .; Lee, H. W.; Lee, I. J . Chem. Soc., Perkins
Trans. 2 1995, 2263.
10.1021/jo9814905 CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/04/1998

Pyridinolysis of Phenyl Chloroformates
J . Org. Chem., Vol. 63, No. 26, 1998 9835
Ta ble 1. Ra te Con sta n ts, k2 (M-1 s-1), for th e Rea ction s of Y-P h en yl Ch lor ofor m a tes w ith X-P yr id in es in Aceton itr ile a t
25.0 °C
a
g
X or Y
p-CH3
pKa
6.03
5.67
5.59
p-CH3O
11.5
6.76
6.76
6.46
5.50
2.63
1.09
0.603
0.589
0.575
0.159
0.0575
0.0201
-2.35 ( 0.05
(0.996)
0.33 ( 0.01
(0.996)
p-CH3
17.4
10.7
11.0
10.2
5.90
4.37
1.78
0.991
0.989
0.871
0.263
0.0832
0.0309
-2.28 ( 0.06
(0.996)
0.33 ( 0.01
(0.995)
H
p-Cl
p-NO2
FY
19.1
15.1
15.5
15.1
9.55
6.03
2.51
1.66
1.58
1.55
0.339
0.141
39.8
28.2
26.9
26.3
18.2
12.9
5.13
3.02
2.82
2.69
1.01
-
-
-
-
0.98 ( 0.04
1.02 ( 0.05
1.01 ( 0.04
1.01 ( 0.05
1.03 ( 0.05
1.17 ( 0.03
1.18 ( 0.03
1.19 ( 0.05
1.16 ( 0.05
1.18 ( 0.07
1.33 ( 0.04
1.39 ( 0.03
1.39 ( 0.03
m-CH3
p-C6H5CH2
m-C6H5CH2
H
m-C6H5
m-CONH2
m-CH3CO
m-Cl
(5.62)c
5.21
58.9
43.7
20.0
11.5
10.7
10.2
3.89
1.66
(4.87)c
3.33b
(3.10)c
2.81
m-CH3C(O)O
m-CN
3.26b
1.35
p-CH3CO
p-CN
(0.46)d 2.83
(-0.57)d 1.86
0.263
0.0977
-2.23 ( 0.03
(0.999)
0.31 ( 0.01
(0.994)
0.0537
-2.25 ( 0.06
(0.996)
0.31 ( 0.01
(0.997)
0.548
- e
FX
-2.50 ( 0.21
(0.976)
0.28 ( 0.02
(0.991)
- f
âX
a
b
pKa values in water at 25.0 °C taken from ref 3. Taken from Dean, J . A. Handbook of Organic Chemistry; McGraw-Hill: New York,
1987; Table 8. c Calculated values using eq 3. Calculated values with σp- constants. e The σ and σp- values were taken from Hansch, C.;
d
Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165. Correlation coefficients are shown in parenthesis. f Based on the pKa values in acetonitrile
g
at 25.0 °C calculated by eq 4. The source of σ is the same as in e. Correlation coefficients are better than 0.990 in all cases.
F igu r e 2. The Hammett plots (σY) for the X-pyridinolysis of
phenyl chloroformates (for X ) H, m-CH3CO and p-CN) in
F igu r e 1. The Hammett plots (FX-) for the pyridinolysis of
MeCN at 25.0 °C.
phenyl chloroformates (for Y ) p-CH3O and Y ) p-Cl) in MeCN
at 25.0 °C.
by Charton4 (slope, intercept: -5.70, 5.39), Clark and
Perrin5 (-5.90, -5.25), and Leffek6a (-5.24, 5.34). These
pKa values for pyridinium ions in water can be converted
to those in acetonitrile using a relationship given by eq
4.6 The âX values shown in Table 1 are those based on
pKa’s in acetonitrile.
ties, pKa- (vide infra), were required for the linear plots,
indicating operation of through-conjugation between the
reaction site, the N atom of pyridine, and the strong
-
π-acceptor substituents. The pKa values for p-CH3CO
-
-
-
-
(σp ) 0.82, pKa ) 0.46) and p-CN (σp ) 1.00, pKa
)
-0.57) were determined by extrapolation using σp- values
in eq 3, which was obtained with 30 pKa values in water
at 25 °C.3
pKa(acetonitrile) ) (1.23 ( 0.03)pKa(water) + (6.2 ( 0.2)
(4)
The activation parameters, ∆Hq and ∆Sq (Table 2),
were determined based on the k2 values at three tem-
pKa ) -5.73((0.12)σ + 5.16((0.05)
r ) 0.994, n ) 30
(3)
(4) Charton, M. J . Am. Chem. Soc. 1964, 86, 2033.
Similar correlations between pKa and σ were reported
(5) Clark, J .; Perrin, D. D. Quart. Rev. Chem. Soc. 1964, 18, 295.
(6) (a) Foroughifar, N.; Leffek, K. T.; Lee, Y. G. Can. J . Chem. 1992,
70, 2856. (b) Spillane, W. J .; Hogan, G.; McGrath, P.; King, J .; Brack,
C. J . Chem. Soc., Perkin Trans. 2 1996, 2099.
(3) The 30 pKa values used to derive this correlation were taken
from Fisher, A.; Galloway, W. J .; Vaughan, J . J . Chem. Soc. 1964, 3591.

9836 J . Org. Chem., Vol. 63, No. 26, 1998
Koh et al.
Ta ble 3. Ra te Con sta n ts, k2 (x103 M-1 s-1), for th e
Rea ction s of Meth yl Ch lor ofor m a te w ith X-P yr id in es in
Aceton itr ile a t 25.0 °C
X
p-CH3Oa p-CH3 m-CH3
309 280 244
H
m-CONH2 m-Cl p-CN m-CN
31.5 11.8 2.67 1.23
k2
158
a
The pKa value in water at 25.0 °C for X ) p-CH3O in 6.58.3
F igu r e 4. Lone pair and π-orbitals in pyridine with
π-acceptor para substituent, X.
a
no directly comparable rate data available for the reac-
tion of acetyl chloride,1g I, the rate of phenyl chlorofor-
mate, III, is much lower than that of I. This lower rate
is attributed to initial-state stabilization by π-electron
resonance IVa , which is smaller than that of carboxylate
anion, IVb,9 due to charge separation. The negative
charge delocalization over the two oxygen atoms forms
nevertheless a π-electron-rich O-C-O moiety in IVa as
well as in IVb.
F igu r e 3. Bro¨nsted plots (âX) for the pyridinolysis of phenyl
chloroformates (for Y ) p-CH3O and p-Cl) in MeCN at 25.0
°C.
Ta ble 2. Activa tion P a r a m eter sa for th e Rea ction s of
Y-P h en yl Ch lor ofor m a tes w ith X-P yr id in es in
Aceton itr ile
-
The magnitudes of FX (-2.23- -2.50) and FY (0.98-
k2
∆Hq
-∆Sq
X
Y
T/°C (M-1 s-1
)
(kcal mol-1
)
(cal mol-1 K-1
)
1.39) for the reactions with pyridines are quite similar
again with those corresponding reactions with anilines
p-CH3 p-CH3O
5.0
15.0
4.55
7.23
25.0 11.5
7.1 ( 0.1
6.7 ( 0.1
6.9 ( 0.1
7.2 ( 0.1
30 ( 1
44 ( 2
32 ( 1
26 ( 1
-
(FX ) -2.21- -2.30, FY ) 1.16-1.26).2 For the strong
π-acceptor para substituents, p-NO2 in aniline2 and
p-CH3CO and p-CN in pyridine, the enhanced para
p-CN p-CH3O
5.0
15.0
25.0
5.0
15.0
25.0
0.00837
0.0130
0.0201
2.23
3.50
5.50
-
substituent constants of σp are required for linear
correlations, Figure 1. This suggests that the π-acceptor
para substituents interact directly through the ring
π-system with the reaction site, the N atom on the
pyridine, in the rate-determining step. This state of
affairs is, however, rather surprising in view of the fact
that the σ-lone pair on N is orthogonal to the ring
π-system, Figure 4; the reaction, no doubt, takes place
with the σ-lone pair while the interaction with the
π-acceptor para substituent occurs through the ring
π-system, and the two are orthogonal so that the two,
reaction site (σ-lone pair) and ring π-system, are com-
pletely independent and do not mix together. In this
H
H
p-CH3O
p-NO2
5.0 23.0
15.0 36.8
25.0 58.9
a
Calculated by the Eyring equation. Errors shown are standard
deviations.
peratures, 5.0, 15.0, and 25.0 °C. These are comparable
to those corresponding values for the reactions of phenyl
chloroformate with anilines in acetonitrile.2 The second-
order rate constants, k2, for the pyridinolysis of methyl
chloroformate in acetonitrile at 25.0 °C are summarized
in Table 3.
-
respect, the linear correlation with σp for p-NO2 in
aniline is quite normal.2 In aniline the reaction site is
again the lone pair on the amino nitrogen, which is,
however, nearly a π-type, Figure 5. The nucleophilic
reaction takes place at the lone-pair on N which, unlike
the σ-lone pair on the N atom of pyridine, can interact
directly through the ring π-system with a π-acceptor para
substituent.
Discu ssion
Comparison of k2 under the same reaction conditions,
in MeCN at 25.0 °C, shows that the two nucleophiles,
aniline2 (pKa ) 4.60, k2 ) 6.37) and pyridine (pKa ) 5.17,
k2 ) 9.55 dm3 mol-1 s-1) react with phenyl chloroformate
at approximately the same rate. This rate is, however,
(7) Lee, I.; Koh, H. J .; Lee, B. C. J . Phys. Org. Chem. 1994, 7, 50.
(8) Kim, T. H., Huh, C.; Lee, B. S.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 1995, 2257.
(9) Ruff, F.; Csizmadia, I. G. Organic Reactions. Equilibria, Kinetics
and Mechanism; Elsevier: Amsterdam, 1994; p 330.
1
lower (ca. /2) than those for the corresponding reactions
of benzoyl7 and cinnamoyl chlorides.8 Although there is

Pyridinolysis of Phenyl Chloroformates
J . Org. Chem., Vol. 63, No. 26, 1998 9837
F igu r e 5. Lone pair and π-orbitals in aniline with a π-accep-
tor para substituent, X.
The similiarity and difference between the role of the
lone pair on N in the nucleophilic reactions of aniline and
that of pyridine are quite intriguing and in fact provide
a useful mechanistic criterion. Although the linear Ham-
mett plots for the aminolysis of phenyl chloroformate in
acetonitrile required the enhanced constants, σp-, for the
π-acceptor para substituents in both aniline (p-NO2)2 and
pyridine nucleophiles (p-CH3CO and p-CN), the Bro¨nsted
plots using the experimental pKa values (pKa for p-NO2
) 1.00) were linear for anilines but were nonlinear for
pyridines (e.g., pKa value for p-CN ) 1.86 in H2O at 25
°C) and required enhanced pKa values (an extrapolated
F igu r e 6. The proposed transition-state structure.
in the pKa measurements so that the para π-acceptors
exhibit abnormally higher pKa values in contrast to the
substituent constants, σp, which represent the inductive
and π-electron-withdrawing effects only.
However, whenever an anionic center or an electron-
rich moiety, such as IVa and IVb, overlaps with the
π-orbital on the N atom of pyridine and hence with the
ring π-system, through-conjugation with the π-acceptor
para substituent becomes viable and an elevated para
constant, σp-, is required to correlate the effect of the
anionic center as evidenced by the Hammett plots, Figure
1. This causes, however, a nonlinear Bro¨nsted plot if the
-
-
pKa of -0.57 for p-CN) corresponding to σp (say pKa
)
to obtain linear correlations. Rationalization of this
dichotomy is as follows.
The protonation/deprotonation of aniline in water
involves the lone pair on the amino nitrogen, which can
overlap with the ring π-system, i.e., the lone pair on N
in aniline is practically a π-lone pair, Figure 5. Thus a
strong π-electron acceptor para substituent can interact
directly through the ring π-system with the lone pair in
aniline. For such substituents, the Hammett correlation
requires σp- constants. On the other hand, the pKa values
of anilines represent protonation/deprotonation at the
lone-pair so that the experimentally determined pKa
values correspond to basicities under through-conjugative
condition, e.g., for p-NO2 in aniline, σ- ) 1.24 and pKa )
1.00 in water at 25 °C represent the same substituent
effect.
In contrast for pyridine, the protonation/deprotonation
takes place at the σ lone pair on N which is orthogonal
to the ring π-system (Figure 4) so that the protonation/
deprotonation (pKa measurement) does not disturb the
ring π-system, but the positive charge center in the
conjugate acid, of course, attracts π-electrons inductively
and there is no through-conjugation between the σ-lone
pair and the π-acceptor para substituent. Thus the
experimental pKa value represents the inductive effect
experimentally determined pKa value is used to correlate
the effect. In such cases an elevated pKa value (pKa
-
)
corresponding to σp- is required. Experimental determi-
nation of such an elevated basicity, pKa-, is, however,
impossible, since experimentally protonation/deprotona-
tion (pKa measurement) involves a σ lone pair on the
pyridine nitrogen atom which is orthogonal to the ring
π-system. A linear correlation between the pKa and σm,
-
eq 3, can be used to extrapolate the pKa value corre-
-
sponding to the σp value. For example, p-CN has σp )
-
-
0.66 and σp ) 1.00 so that substitution of σp ) 1.00
-
into eq 3 leads to pKa ) -0.57, which is much more
negative than the experimentally determined pKa ) 1.86
corresponding to σp () 0.66).
The Bro¨nsted plots in Figure 3 clearly show that the
two strong π-acceptor para substituents require enhanced
-
basicities (pKa values) which give excellent linear cor-
relations (correlation coefficients > 0.992; standard de-
viations of the slopes < 0.03). The âX (ânuc) values in Table
1 range from 0.28 to 0.33, which agree with the similar
range of values for the aminolysis of acyl compounds
when nucleophilic attack is rate limiting.1 The linear
correlation over the whole range of pKa values (pKa )
-0.45-+6.03) with low âX (=0.3) and and the require-
only and corresponds to the basicity of the normal σ
-
constant (for p-NO2, σp ) 0.78), not σp- (for p-NO2, σp
)
1.24). This is evident from a comparison of the effects of
a substituent in meta and para positions on the pyridine
basicities. Normally a stronger inductive acceptor (δσ >
0), meta substituent, leads to a weaker basicity (δpKa <
0) than does a weaker inductive acceptor, para substitu-
ent, as expected from a consideration of inductive electron
depletion of the N atom of pyridine. Thus the pKa and σ
are inversely correlated, δpKa/δσ ) (pKa(meta) -
pKa(para))/σm - σp) < 0. However, for substituents which
have strong para π-acceptor ability, e.g., CN, NO2, etc.,
the sign reverses to δpKa/δσ >0. For example, the ratios
for substituents CH3, CH3O, Br, and Cl are ca. -4, -5,
-6, and -73 respectively, whereas for NO2 and CN they
are ca. +3 and +5,3 respectively. This simply shows that
the experimental values of pyridine reflect the weak
π-electron-donating effects under a cationic charge on N
-
ment of the pKa values for the strong π-acceptor para
substituents in the Bro¨nsted plots strongly support that
the aminolysis (with pyridines as well as with anilines)
of phenyl chloroformates in acetonitrile at 25.0 °C
proceeds by a rate-limiting attack of the nucleophile.
The transition state (TS) structure can be envisaged
as shown in Figure 6, where the through-conjugative
π-overlap is explicitly shown. A similar TS structure can
be constructed for the reactions with anilines. The
requirement of pKa-, i.e., the possibility of through-
conjugation between N and π-acceptors, in the linear
Bro¨nsted plots for the reactions of phenyl chloroformate
with pyridines (and also with anilines) rules out a

9838 J . Org. Chem., Vol. 63, No. 26, 1998
Koh et al.
than for the methyl group (σR ) -0.03).10 Thus in the
charge-separated resonance form of the phenyl chloro-
formate, IVa , the positive charge on the ester oxygen can
be much more stabilized by strong electron donation from
the phenyl group in III than by the relatively weak
electron donation from CH3 in II. As a result, the formate
moiety becomes strongly electron-rich in III, and direct
conjugation with the para π-acceptor substituents is
possible in the rate-limiting attack; for II this is not
possible due to insufficient electron supply from the CH3
group to provide an electron-rich formate moiety. There-
fore, the key to the mechanistic changeover to rate-
limiting formation of the intermediate for III is the
sufficiently strong electron supply from the C6H5 group
to provide the electron-rich O-C-O moiety which can
donate π-electrons through the ring π-system to a para
acceptor in pyridine.
+
Since electrons will be partially depleted from the
formate moiety by the leaving group, Cl-, in a concerted
(SN2) mechanism, through-conjugation will not be viable,
and hence the enhanced basicity (pKa-) will not be
required for the linear Bro¨nsted correlation. We therefore
conclude that the aminolysis of phenyl chloroformate
with pyridines as well as with anilines proceeds by a
stepwise mechanism in which the formation of a tetra-
hedral intermediate is rate limiting. Our recent results
are in line with the proposed mechanism. (i) In the
pyridinolysis of benzenesulfonyl chlorides in methanol,
log k vs pKa plots were normal but log k vs σ plots showed
positive deviations for the para π-acceptors, p-CN and
p-CH3CO, indicating positive charge development on N
of pyridines in the TS as required from an SN2 mecha-
nism. (ii) In the correlation of solvolysis rate constants
of phenyl chloroformate, incorporation of aromatic-ring
parameter, hI, gave excellent linearity in contract to
scattered plots without the hI term. This indicates that
in the solvolysis of phenyl chloroformate, the phenyl ring
participates to stabilize the TS as proposed in the present
work.
The activation parameters in Table 2 are also consist-
ent with the proposed mechanism. Since a bond is being
formed and there is no bond cleavage in the TS, the
energy requirement will be small, a low ∆Hq, and the
entropy loss will be large, a large negative ∆Sq. Albeit
the differences in activation parameters are small and
may not warrant a close examination, there is a correct
trend of the lowest ∆Hq and ∆Sq values for X ) p-CN
with Y ) p-CH3O; a π-donor on the phenyl ring will
increase the electron density of the formate moiety and
should lead to a strongest through-conjugation with a
strongest π-acceptor, p-CN, rendering the TS the greatest
degree of bond formation, i.e., the lowest activation
enthalpy coupled with the largest negative entropy of
activation.
F igu r e 7. Bronsted plot (âX) for the pyridinolysis of methyl
chloroformate in MeCN at 25.0 °C.
stepwise mechanism with rate-limiting breakdown of a
tetrahedral intermediate; in the tetrahedral intermedi-
ate, and/or in the TS for rate-limiting expulsion of the
leaving group, Cl-, the π-orbital in the formate moiety
is orthogonal to, and hence cannot overlap with, the ring
π-system, precluding the possibility of through-conjuga-
tion. If the reactions were proceeding by rate-limiting
breakdown of the intermediate, the normal pKa values
for p-CN (pKa ) 1.86) would have been required in a more
steeper linear Bro¨nsted plot (âX = 0.8-0.9), as has been
reported for the pyridinolysis of methyl chloroformate in
water.1d,g This provides a novel way of distinguishing
between the two rate-limiting steps, formation and
breakdown of the intermediate, T(. That this mechanistic
difference of the pyridinolysis between methyl (biphasic
Bro¨nsted plots in water)1d and phenyl chloroformate
(monophasic Bro¨nsted plots with rate-limiting attack in
acetonitrile) is not due to the solvent effect has been
tested by conducting the pyridinolysis of methyl chloro-
formate in acetonitrile (Table 3). The results show that
the same biphasic Bro¨nsted plot with a break at pKa =
3.61d is also applicable in acetonitrile, Figure 7. The
Hammett plot is also biphasic with a lower slope (FX )
-0.48 ( 0.02) for electron-donating X-substituents and
a greater slope (FX ) -3.10 ( 0.25) for electron acceptor
X-substituents, clearly indicating a mechanistic changeover
at ∼σX ) 0.0. This mechanistic change from biphasic for
methyl, II, to monophasic with rate-limiting formation
of the intermediate for phenyl, III, may be attributed to
the strong electron-donating polarizability effect of C6H5,
which has a much greater negative polarizability sub-
stituent constant (σR ) -0.81) than CH3 (σR ) -0.35).10
The resonance electron-donating ability expressed by the
Finally the 63 rate constants (k2 ) kXY) in Table 1 are
subjected to multiple regression analysis using eq 5, and
the result is presented in eq 6.14 We note that the
correlation is quite satisfactory with the cross-interaction
(10) Taft, R. W.; Koppel, I. A.; Topsom, R. D.; Anvia, F. J . Am. Chem.
Soc. 1990, 112, 2047.
(11) Hong, S. W.; Koh, H. J .; Lee, I. J . Phys. Org. Chem., in press.
(12) Kevill, D. N.; D’Souza, M. J . J . Chem. Soc., Perkin Trans 2 1995,
973.
(13) Koo, I. S.; Yang, K.; Kang, D. H.; Park, H. J .; Kang, K.; Lee, I.
Unpublished.
(14) (a) Lee, I. Chem. Soc. Rev. 1990, 19, 317. (b) Lee, I. Adv. Phys.
Org. Chem. 1992, 27, 57.
+
+
σR scale is also much larger for phenyl (σR ) -0.22)

Pyridinolysis of Phenyl Chloroformates
J . Org. Chem., Vol. 63, No. 26, 1998 9839
were used after identification by GC-MS and TLC analysis
without further purification. Since they are corrosive and
moisture sensitive, they were treated in a glove box filled with
N2 gas.
log(kXY/kHH) ) FXσX + FYσY + FXYσXσY
(5)
log(kXY/kHH) ) (-2.25 ( 0.02)σX + (1.07 ( 0.03)σY +
(0.31 ( 0.06)σXσY
Ra te Con sta n ts. Rates were measured conductimetrically
at 25.0 ( 0.05 °C. The conductivity bridge used in this work
was a self-made computer automatic A/D converter conductiv-
ity bridge. Pseudo-first-order rate constants, kobs, were deter-
mined by the Guggenheim method13 with a large excess of
pyridine; [phenyl chloroformate] = 1 × 10-4 M and [Py] )
0.002-0.025 M. Second-order rate constants, k2, were obtained
from the slope of a plot of kobs vs [Py] with more than five
concentrations of pyridine, eq 2. The k2 values in Table 1 are
the averages of more than three runs and were reproducible
to within (3%.
P r od u ct An a lysis. p-Chlorophenyl chloroformate was re-
acted with an excess of p-methylpyridine with stirring for more
than 15 half-lives at 25.0 °C in acetonitrile, and the products
were isolated by evaporating the solvent under reduced
pressure. The product mixture was treated with column
chromatography (silica gel, 20% ethyl acetate/n-hexane). Analy-
sis of the product gave the following results. p-ClC6H4OC(d
O)N+C5H4-p-CH3. Mp 131-133 °C. δH, NMR (250 MHz,
CDCl3), 2.18 (3H, s, CH3), 7.19-7.48 (8H, m, C5H4N, C6H4),
νmax (KBr), 2900 (CH, aromatic), 1720 (CdO); mass, m/z 248
(M+) Anal. Calcd for C13H11NO2: C, 62.9; H, 4.44. Found: C,
63.0; H, 4.43.
r ) 0.998, n ) 63
(6)
constant, FXY, of +0.3. Previously we have shown that in
the SN2 process or in the rate-limiting formation of an
intermediate the FXY is negative, but in a stepwise
mechanism with a rate-limiting breakdown of the tetra-
hedral intermediate it is large positive.12 In the present
work, a small positive FXY value is obtained and this does
not conform to any of the two mechanisms, a negative
FXY for SN215a and a large positive FXY for rate-limiting
breakdown.12c The small positive FXY obtained in this
work15d and the small negative FXY obtained in the
reactions with aniline nucleophiles (FXY ) -0.04)2 thus
appear to be in line with rate-limiting formation of the
intermediate for the aminolysis of phenyl chloroformate
in acetonitrile.
Exp er im en ta l Section
Ma ter ia ls. Merck GR acetonitrile was used after three
distillations. The pyridine nucleophiles, Aldrich GR, were used
without further purification. Aldrich Y-phenyl chloroformates
Ack n ow led gm en t. We thank the Korea Science and
Engineering Foundation, Chonju National University
of Education, and Kwangju National University of
Education for support of this work.
(15) (a) Lee, I.; Park, Y. K.; Huh, C.; Lee, H. W. J . Phys. Org. Chem.
1994, 7, 555. (b) Lee, I. Bull. Korean Chem. Soc. 1994, 15, 985. (c) Oh,
H. K.; Shin, C. H.; Lee, I. J . Chem. Soc., Perkin Trans. 2 1995, 1169.
(d) Oh, H. K.; Shin, C. H.; Lee, I. Bull. Korean Chem. Soc. 1995, 16,
657.
(16) Guggenheim, E. A. Phil. Mag. 1926, 2, 538.
J O9814905