Synergistic effect in the catalysis by pyridine N-oxide-triethylamine mixture of acyl transfer processes with participation of benzoyl, diethoxyphosphinoyl, and p-toluenesulfonyl chlorides

Article abstract of DOI:10.1023/A:1015319228542

The kinetics of benzoylation of substituted phenols with benzoyl chloride in the presence of pyridine N-oxide-triethylamine was analyzed with regard to previously reported data on benzoylation, phosphorylation, and sulfonylation of phenols and carboxylic acids. A common mechanism of the synergistic effect was established. The synergistic effect decreases in the series PhCOCl (EtO)₂POCl > TsCl.

Full text of DOI:10.1023/A:1015319228542

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 111 114. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 118 121.
Original Russian Text Copyright
2002 by Belousova, Savelova, Simanenko, Panchenko.
Synergistic Effect in the Catalysis
by Pyridine N-Oxide Triethylamine Mixture of Acyl Transfer
Processes with Participation of Benzoyl, Diethoxyphosphinoyl,
and p-Toluenesulfonyl Chlorides
I. A. Belousova, V. A. Savelova, Yu. S. Simanenko, and B. V. Panchenko
Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine,
ul. R. Luxemburg 70, Donetsk, 83114 Ukraine
e-mail: savelova@infou.donetsk.ua
Received August 2, 2000
Abstract The kinetics of benzoylation of substituted phenols with benzoyl chloride in the presence of
pyridine N-oxide triethylamine was analyzed with regard to previously reported data on benzoylation, phos-
phorylation, and sulfonylation of phenols and carboxylic acids. A common mechanism of the synergistic effect
was established. The synergistic effect decreases in the series PhCOCl >> (EtO)2POCl > TsCl.
The synergistic effect of a pyridine N-oxide tri-
ethylamine mixture in the catalytic acyl transfer
processes was studied by us in [1 6]. We examined in
detail the kinetic features of phosphorylation [5] and
sulfonylation [6] of substituted phenols (4-nitroso-
phenol, 4-nitrophenol, 2,4-, 2,5-, and 2,6-dinitro-
phenols, and 2,4,6-trinitrophenol) and 2-(4-dimethyl-
aminophenylazo)benzoic acid (RCOOH) with diethyl
chlorophosphate (EtO)2POCl and p-toluenesulfonyl
chloride (TsCl), respectively. Available published
data for related reactions with benzoyl chloride as
a representative of carboxylic acid derivatives include
only the reaction with 4-phenylazophenol [2] and
2-(4-dimethylaminophenylazo)benzoic acid [3]. There-
fore, it is difficult to compare with a sufficient
reliability synergistic effects in reactions of various
compounds, namely carboxylic, phosphoric, and sul-
fonic acid derivatives. In the present work we studied
the kinetics of acylation of 4-nitro- and 4-nitroso-
phenols with benzoyl chloride in the presence of
pyridine N-oxide (I) triethylamine (II) as catalytic
system in dioxane at 25 C. The rates of benzoylation
of more acidic dinitrophenols and trinitrophenol were
too high to include these compounds into the set of
substrates for the present study.
A and B are intermediates formed by nucleophilic
activation of the acylating agent AcX and general base
activation of the nucleophile YH; Keq = k1/k and
1
KB are the equilibrium constants for formation of
intermediates A and B; kB is the rate constant of the
reaction of A with B, leading to final products and
regenerating the catalyst.
(1)
(2)
(3)
(4)
(5)
A combination of nucleophilic and general base
catalysis was proposed previously [2 6] to rationalize
synergistic effect in systems containing pyridine
N-oxide and triethylamine [reactions (1) (3)]. Here,
The synergistic effect produced by a mixture of
bases I and II is reflected in the fact that the rate
of reaction (3) is considerably higher than the overall
rate of the reactions of complex A with nucleophilic
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112
BELOUSOVA et al.
reagent YH [nucleophilic catalysis, reaction (4)] and
of complex B with substrate AcX [general base
catalysis, reaction (5)] under the same conditions. The
scheme including reactions (1) (3) was kinetically
proved by experimentally observed change of the rate-
determining stage depending on the phenol acidity
and concentration [5, 6]. This is typical of both phos-
phorylation [5] and sulfonation processes [6]. For
phenols with pKa(H2O) > 5 the rate-determining stage
is reaction (3), whereas for more acidic phenols
with pKa(H2O) < 5 the rate-determining stage is
activation of the substrate, characterized by the rate
constant k1. As the reaction progresses (and the phenol
concentration decreases), the rate-determining stage
changes from reaction (1) (k1) to reaction (3) (kB).
We also found previously that the kinetics of
benzoylation of 4-phenylazophenol [pKa(H2O) 8.20]
and 2-(4-dimethylaminophenylazo)benzoic acid
[pKa(H2O) 5.22] in the presence of catalyst mixture
I/II conform to the above scheme; i.e., these processes
are described by reactions (1) (3), the latter being
the rate-determining stage. Therefore, the kinetics of
benzoylation of 4-nitrosophenol [pKa(H2O) 6.48] and
4-nitrophenol [pKa(H2O) 7.15] were analyzed in terms
of the same scheme.
The equilibrium concentration of complex B was
calculated by Eq. (8) [5, 6]:
KB [II]0 [YH]0
[B] =
=
II [YH]0 , (8)
1 + KB [II]0 + KB [I]0
where
complex B:
is the fraction of phenol bound into
II
KB [II]0
=
.
(9)
II
1 + KB [II]0 + KB [I]0
The equilibrium constants KB for 4-nitrosophenol
[5] and 4-nitrophenol [6] in dioxane were measured
previously by UV spectroscopy; the KB value for
4-nitrosophenol was also measured in the present
work by the same method (see table). The
values
II
calculated therefrom range from 0.002 to 0.009.
Taking into account that the fraction of phenol bound
into complex B (at given [I]0 and [II]0) is very small
( 1%), the equilibrium concentration [B] could be
calculated by simplified formula (10), as it was done
in [2, 3] for 4-phenylazophenol and 2-(4-dimethyl-
aminophenylazo)benzoic acid:
The reaction rate was measured following the dis-
appearance of phenols by UV spectroscopy at 335
(4-nitrosophenol) and 342 nm (4-nitrophenol). The
initial reactant concentration ratio was [YH]0 <<
[AcX]0 [I]0 + [II]0. The apparent pseudofirst-order
[B] = KB [II]0 [YH]0.
(10)
Insofar as treatment of the kinetic data by Eqs. (8)
and (10) gives the same results, we used Eq. (8) as
more accurate.
In keeping with the scheme including reactions
(1) (3), the latter being the rate-determining stage,
and taking into account Eqs. (7) (9), the gain in the
apparent rate constant kap is expressed by the follow-
ing equation [5, 6]:
1
rate constants kap (s ) did not change during the reac-
tion. Their averaged values at [AcX]0 = 0.35 5.15,
[I]0 = 0.33 2.94, and [II]0 = 0.32 2.87 M are col-
lected in a summary table which is available from
the authors.
In order to calculate the equilibrium concentrations
of complexes A and B it was necessary to know the
constants of equilibria (1), (2), and (6).
kap = Keq kB II [AcX]0 [I]0
= kB II [AcX]0 [I]0 ,
(11)
(6)
II
ap
II
where kB = Keq kB and kap = kap
k
(here, k is
ap
the apparent pseudofirst-order rate constant in the
presence of triethylamine alone). At the given reactant
II
Indirect estimation of the constant Keq for forma-
tion of complex A from benzoyl chloride and pyridine
N-oxide gives a value less than 1 mol/l [2]. Then, at
[AcX]0 = 0.35 5.15 and [I]0 = 0.33 2.94 mM, the
equilibrium concentration of intermediate A can be
calculated by the formula
concentrations, the value of k which reflects the
ap
contribution of reaction (5) to kap was calculated
using the data of [7]. However, this contribution is
insignificant: it does not exceed 2%. The contribution
of reaction (4) was not taken into account at all while
calculating kap; in keeping with the data of [2], it
is much smaller than the contribution of reaction (5).
Thus reaction (3) appears to be the only path leading
[A] = Keq [AcX]0 [I]0.
(7)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

SYNERGISTIC EFFECT IN THE CATALYSIS BY PYRIDINE N-OXIDE TRIETHYLAMINE
113
Kinetic parameters for acylation of phenols and 2-(4-dimethylaminophenylazo)benzoic acid with benzoyl chloride, diethyl
chlorophosphate, and p-toluenesulfonyl chloride in dioxane at 25 C; kB = Keq kB,
= Keq kB/(KB k0B)
PhCOCl
(EtO)2P(O)Cl
p-MeC6H4SO2Cl
R in
RC6H4OH l mol
KB,
KB,
l mol
1
1
6
kB 10 ,
k0B a
[7]
kB, l2
k0B a
[5]
kB, l2
k0B a
[8]
l2 mol 2 s
mol 2 s
mol 2 s
1
1
1
4-NO
4-N02
10.0 0.13 7.28 0.26 4.43 0.29
[5]
22.9 1.5 347 14 0.149
104
2.3
102
3.17 0.9
[5]
6.08 0.83 3.73 0.42
[6]
1.5
7.8 224 17 0.0652 1.1 40.2 5.7 0.0723 1.8
105 103 102
4-PhN N 1.3 0.5
[2]
4.42 0.07 0.031 0.0030 5.79 4.1
[2]
0.90 0.05 0.37 0.02
[3] [3]
[2]
103
RCOOHb
6.9 1.5
[3]
1.92 2.8 290 12 0.101
4.2 42.6 6.8 0.0763 8.1
102 101
104
a
1
l mol 1 s .
b
RCOOH is 2-(4-dimethylaminophenylazo)benzoic acid.
to the final products. This suggests a strong syn-
ergistic effect of catalysts I and II in the benzoylation
of phenols.
the Keq k0c in the denominator can be neglected. Table
gives the synergistic effects defined as the ratio
Keq kB/(KB k0B). It is seen that strongly depends on
the nature of the acylating agent. The greatest catalytic
effect of mixture I/II is observed for benzoyl chloride.
The corresponding effects for diethyl chlorophosphate
and p-toluenesulfonyl chloride are lower by about
2 and 3 orders of magnitude, respectively. While
analyzing these results, one should keep in mind that
KB does not depend on the acylating agent. Further-
more, the ratio kB/k0B which characterizes the reactivity
difference between the activated (A) and nonactivated
(AcX) acylating agent also should not depend strongly
on its nature. Moreover, we could expect a priori that
the above ratio should increase in going from PhCOCl
to (EtO)2POCl and then to TsCl (in keeping with the
reactivity selectivity principle) rather than decrease
as does the quantity . Hence the different synergistic
effects in the acylation of phenols and carboxylic acid
with PhCOCl, (EtO)2POCl, and TsCl should be
treated in terms of the difference in the equilibrium
constants Keq. For example, the ratio of Keq in the
formation of N-benzoyloxy- and N-(p-tolylsulfonyl)-
4-dimethylaminopyridinium chloride (CH2Cl2, 25 C)
[9, 10] is about two orders of magnitude.
As follows from the summary table, the kB value
calculated by Eq. (11) remains constants in experi-
ments with various concentrations [AcX]0, [I]0, and
[II]0 or [I]0 +[II]0 (30 runs for 4-nitrophenol and
22 runs for 4-nitrosophenol). This is in full agreement
with the proposed mechanism of synergistic effect for
phenols with pKa(H2O) > 5, indicating that the reac-
tions with PhCOCl, (EtO)2POCl, and TsCl follow the
same mechanism [scheme (1) (3)] where reaction (3)
is the rate-determining stage. The averaged kB values
for benzoylation of 4-nitrophenol and 4-nitrosophenol
are given in table together with the data reported
previously for acylation of phenols and 2-(4-dimethyl-
aminophenylazo)benzoic acid with benzoyl chloride
[2, 3], diethyl chlorophosphate [5], and p-toluene-
sulfonyl chloride [6].
To estimate the synergistic effect
in systems
where intermediates A and B do not accumulate in
appreciable amounts and the rate-determining stages
are reactions (3) (5), it is reasonable to use Eq. (12):
Keq kB
KB k0B + Keq k0c
=
.
(12)
EXPERIMENTAL
Here, Keq kB, KB k0B, and Keq k0c are the apparent
rate constants corresponding to a combination of
nucleophilic and general base catalysis, general base
catalysis, and nucleophilic catalysis, respectively.
Insofar as in all the examined systems the contribu-
tion of nucleophilic catalysis is negligible [2, 3, 5, 6],
Spectrophotometric measurements were performed
on a Specord UV-Vis instrument. The progress of
reactions was monitored following the disappearance
of nucleophile. The apparent pseudofirst-order rate
constants kap were calculated by standard procedure
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

114
BELOUSOVA et al.
[11]. Linear dependences were processed by the least-
squares procedure.
7. Belousova, I.A., Simanenko, Yu.S., Savelova, V.A.,
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no. 11, pp. 1656 1664.
Dioxane [12], pyridine N-oxide [13], and triethyl-
amine [14] were purified by known methods. Benzoyl
chloride was repeatedly distilled under reduced pres-
sure. p-Toluenesulfonyl chloride was twice recrystal-
lized from petroleum ether, mp 70 71 C [15]. Phenols
were purified as described in [5]; their melting points
coincided with those given in [15].
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Zh. Obshch. Khim., 1987, vol. 57, no. 7, pp. 1612
1616.
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