Efficient catalytic activity of transition metal ions in Vilsmeier-Haack reactions with acetophenones

Article abstract of DOI:10.1002/kin.20807

Vilsmeier-Haack (VH) formylation reactions with acetophenones are sluggish in acetonitrile medium even at elevated temperatures. However, millimolar concentrations of transition metal ions such as Cu(II), Ni(II), Co(II), and Cd(II) were found to exhibit efficient catalytic activity in Vilsmeier-Haack Reactions with acetophenones. Reactions are accelerated remarkably in the presence of transition metal ions. The VH reactions followed second order kinetics and afforded acetyl derivatives under kinetic conditions also irrespective of the nature of oxychloride (POCl₃ or SOCl₂) used for the preparation of VH reagent along with DMF. On the basis of UV-vis spectroscopic studies and kinetic observations, participation of a ternary precursor [M(II) S (VHR)] in the rate-limiting step has been proposed to explain the mechanism of the metal ion-catalyzed VH reaction.

Full text of DOI:10.1002/kin.20807

Efficient Catalytic Activity
of Transition Metal Ions in
Vilsmeier–Haack Reactions
with Acetophenones
1
2
2
2
1
F. ANEESA, K. C. RAJANNA, M. VENKATESWARLU, K. RAJENDAR REDDY, Y. ARUN KUMAR
1Department of Chemistry, M. J. C. E. T., Hyderabad, India
2Department of Chemistry, Osmania University, Hyderabad 500 007, India
Received 24 January 2013; revised 9 May 2013; 31 May 2013; accepted 2 June 2013
DOI 10.1002/kin.20807
Published online 3 August 2013 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Vilsmeier–Haack (VH) formylation reactions with acetophenones are sluggish in
acetonitrile medium even at elevated temperatures. However, millimolar concentrations of
transition metal ions such as Cu(II), Ni(II), Co(II), and Cd(II) were found to exhibit efficient
catalytic activity in Vilsmeier–Haack Reactions with acetophenones. Reactions are accelerated
remarkably in the presence of transition metal ions. The VH reactions followed second order
kinetics and afforded acetyl derivatives under kinetic conditions also irrespective of the nature
of oxychloride (POCl3 or SOCl2) used for the preparation of VH reagent along with DMF. On
the basis of UV–vis spectroscopic studies and kinetic observations, participation of a ternary
precursor [M(II) S (VHR)] in the rate-limiting step has been proposed to explain the mechanism
of the metal ion–catalyzed VH reaction. ꢀC 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 721–
733, 2013
INTRODUCTION
therapeutically interesting biological activities [5].
More specifically, 3-formylchromones have been ex-
tensively used as versatile building blocks for the syn-
thesis of a large number of heterocyclic systems [6–10].
Inspired by the versatility of the Vilsmeier–Haack
(VH) reagent, there has been an upsurge in the past
several years to explore its use for formylation, acety-
lation, cyclization, benzylation, bromination, nitration,
and sulfonation reactions [8–17]. One-pot synthesis of
Chromone derivatives have been the subject of con-
siderable pharmaceutical and chemical interest in the
recent past, because of their broad spectrum of bio-
logical activities such as antifungal, antiviral, antimi-
crobial, antiallergenic, antitubulin, and antitumor ac-
tivity [1–5]. Besides, many flavonoids are based on the
chromone structure and have been shown to exhibit
3-formylchromones has also been achieved smoothly
from o-hydroxy acetophenones under VH conditions
from our laboratories and elsewhere [18–22]. How-
ever, an insight into the reaction times of VH reactions
for 3-formylchromones indicates that the reactions are
very slow under conventional conditions [18–22]. This
Correspondence to: K. C. Rajanna; e-mail: kcrajannaou@
yahoo.com.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
ꢀ
C
2013 Wiley Periodicals, Inc.

7
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ANEESA ET AL.
prompted the author to use an ecofriendly additive as a
catalyst to enhance the synthesis. Transition metals and
their compounds function as catalysts either because of
their ability to change the oxidation state or, in the case
of the metals, to adsorb other substances onto their sur-
face and activate them in the process. Transition metals
are good metal catalysts because they easily lend and
take electrons from other molecules [23,24]. Recently,
Hegedus has published a review on the use of transi-
tion metals as catalysts in organic synthesis. It offered
a fairly comprehensive coverage of the literature, with
extensive citations, unusual and significant transfor-
mations in organic synthesis [25]. The present study
is one such exercise in which transition metal ions
such as Cu(II), Ni(II), Co(II), and Cd(II) are used as
catalysts to explore the synthesis, kinetics, and mecha-
nism of VH reactions with acetophenones and hydroxy
acetophenones.
ous stirring and kept aside for about 2 h. The resultant
solution was neutralized by sodium hydrogen carbon-
ate. The organic phase was extracted with DCE and
dried MgSO4, and the solvent evaporated. Products of
the reaction were isolated under kinetic conditions and
found to be acetyl derivatives of the substrates. The
1
products were characterized by H NMR and mass
spectra with authentic samples and found to be satis-
factory. It is interesting to note that orthohydroxy ace-
tophenone (OHAP) underwent cyclization followed by
formylation and afforded 3-formyl chromone and 2,5–
dihydroxy acetophenone (DHAP) afforded 3-formyl-
6-hydroxy-chromone without affecting the second hy-
droxyl group as described in our earlier work [16,17],
while acetophenone and 4-nitroacetophenone did not
undergo cyclization but afforded the corresponding
formyl derivatives (Table I):
EXPERIMENTAL
VH Reagents
where VHR = DMF + (SOCl2 or POCl3), Y =
−COCH , and X = electron donating or electron-
3
withdrawing groups
Flasks containing DMF dissolved in a suitable sol-
vent (generally DCE, or MeCN) along with SOCl2
and POCl3 were cooled and thermally equilibrated
RESULTS AND DISCUSSION
◦
for about 30 min at –5 C by keeping in a benzene
trough chilled from outside with ice and NaCl. Req-
uisite amounts of solvent and amide were transferred
into a 100-mL flask, and POCl3 or SOCl2 was added
Kinetic Features of the Present Study
The kinetic and mechanistic features of transition metal
ion–mediated VH reactions with hydroxyacetophe-
nones are by and large similar to those observed in
earlier studies. Reaction kinetics indicated first order
in [VHR] as could be seen from the linear plots of ln
Vt versus time (Fig. 1), when [substrate]0 ꢁ [VHR]0.
However, under the conditions [VHR]0 = [substrate]0,
plots of [1/ (a – x)] or [1/Vt] versus time were linear with
a positive slope and an intercept on the ordinate, indi-
cating that VH reaction follows over all second-order
kinetics. Certain second-order plots are presented in
Fig. 2. Rate constant data pertaining to first-order and
second-order kinetics are presented in Tables II and III.
Effect of [M(II)]: Reactions underwent significant
rate accelerations in the presence of transition metal
ions such as Cu(II), Ni(II), Co(II), and Cd(II), which
can be seen from the data presented in Table III.
◦
dropwise at –5 C with constant stirring. The resultant
reagent mixture was kept aside for about 1 h to ensure
complete formation of the VH adduct. Its concentration
was checked by acid–base titrations at Bromocresol
Green end point according to literature reports [7–9].
Kinetics of the Study
It is alsoproposed to study thekinetics of the reactionas
reported in the papers published from our laboratories
[7,8]. Aliquots of the reaction mixture were quenched
in hot water at different intervals of time and kept a side
for at least 2 h to allow the hydrolysis of the unreacted
[VH adduct]. Upon hydrolysis, the VH adduct liberates
a mixture of phosphoric and hydrochloric acids. The
acid content thus liberated is titrated against standard
NaOH using Bromocresol Green as an indicator.
Reactive Species and Mechanistic Features
Product Analysis under Kinetic Conditions
The kinetic features observed in the present work are by
and large similar to those reported earlier from our lab-
oratory using DMF/POCl3 as a VH reagent [14,15]. A
perusal of the publications from our laboratory [14,15]
coupled with other literature reports [2–5] suggests that
After completing the kinetic study of the reaction, ex-
cess (remaining part) of the reaction mixture was re-
fluxed further for 4–5 h and left aside overnight. The
solution was poured into ice-cold water with vigor-
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
723
Figure 1 First-order kinetic plots for VH formylation of
orthohydroxy acetophenone at 333 K and MeCN solvent.
3
(
(
a) Uncatalyzed reaction, [Sub] = 0.09 mol/dm ; [VHR]
3
POCl3+DMF) = 0.005 mol/dm . (b) Cu(II)-catalyzed VH
reaction using (POCl3+DMF). (c) Uncatalyzed VH formy-
lation of orthohydroxy acetophenone using (SOCl2+DMF).
(
d) Cu(II)-catalyzed formylation using (SOCl2+DMF).
Figure 2 Second-order kinetic plots for VH formylation of
orthohydroxy acetophenone at 333 K and MeCN solvent. (a)
Uncatalyzed reaction using (POCl3+DMF) as VH reagent.
(
b) Cu(II)-catalyzed reaction using (POCl3+DMF) as VH
reagent. (c) Uncatalyzed VH formylation of orthohydroxy
acetophenone using (SOCl2+DMF). (d) Cu(II)-catalyzed
formylation using (SOCl2+DMF).
the VH reagent, in solution, is present in a number of
covalent, ion-pair, and cationic forms [DMF/SOCl2]
reagent in the lines of [DMF/POCl3] reagent. Isolated
products of the reaction are also similar to those of
earlier work. On the basis of these similar experimen-
tal observations, it is reasonable to consider a simi-
lar type of reactive species in both (DMF/POCl3) and
(
DMF/SOCl2) systems. Accordingly, species could be
written as (I) to (IV) in the (DMF/POCl3) system and
V) to (VIII) in the (DMF/SOCl2) system:
(
+
−
[
(CH3)2 N=CHCl] [OPOCl2]
(I)
+
−
[
(CH3)2 N=CH − OPOCl2] Cl
(II)
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

7
24
ANEESA ET AL.
3
Table II VH Formylation First-Order Reactions with Acetophenones [Subs] = 0.09 mol/dm ;
3
3
[
VHR] = 0.005 mol/dm ; M(II) = 0.001 mol/dm
5
First-Order Rate Constant (10 k’ /s)
VHR
Substrate
Acetophenone
Native
Cu(II)
Ni(II)
Co(II)
Cd(II)
DMF/POCl3
3.33
15.0
13.3
11.6
5.00
6.60
3.33
3.33
5.00
20.0
20.0
15.0
6.67
8.33
3.33
5.00
5.00
18.0
18.0
13.0
6.67
8.33
3.33
5.00
5.0
18.0
18.0
13.0
6.67
8.33
3.33
5.00
5.0
17.0
15.0
12.0
6.67
8.33
3.33
5.00
Orthohydroxy acetophenone
2
4
,5-Dihydroxyacetophenone
-Nitroacetophenone
DMF/SOCl2
Acetophenone
Orthohydroxy acetophenone
2
4
,5-Dihydroxyacetophenone
-Nitroacetophenone
Table III Temperature-Dependent Second-Order Rate Constants and Activation Parameters for VH Formylation
Reactions with Acetophenones in MeCN Medium
4
3
Second-Order Rate Constant (×10 k dm /mol/s)
System
Substrate
Acetophenone
Temperature (K)
313
Uncatalyzed
Cu(II)
Ni(II)
Co(II)
Cd(II)
DMF/POCl3
6.16
15.7
38.6
7.28
19.0
47.6
7.28
20.7
55.4
6.72
17.3
45.9
5.60
14.0
33.0
3.36
8.96
22.9
2.24
6.16
16.8
3.36
11.7
33.0
11.3
28.1
59.4
14.6
27.5
72.3
13.5
39.9
103.0
9.72
22.7
74.5
10.08
25.76
60.5
6.70
17.9
46.4
4.40
12.3
38.6
8.40
22.4
51.5
10.8
25.4
53.46
12.96
27.5
59.9
11.9
34.0
89.1
8.64
21.1
66.9
9.50
24.64
57.1
6.16
16.8
42.0
3.92
10.6
27.4
8.40
20.7
48.1
10.1
25.7
60.48
10.64
25.8
63.3
11.2
33.0
82.3
8.40
20.7
63.3
8.40
21.84
57.1
5.04
13.4
36.9
3.36
8.90
21.8
7.84
20.1
47.6
7.20
20.1
47.6
10.0
26.3
61.0
10.1
28.5
73.3
7.20
19.0
58.8
7.30
17.9
43.7
4.50
11.8
31.9
2.20
7.30
20.2
3.40
13.4
41.4
3
3
313
23
33
OHAP
3
3
23
33
2,5-Dihydroxyacetophenone
313
3
3
23
33
p-Nitroacetophenone
Acetophenone
OHAP
313
3
3
23
33
DMF/SOCl2
313
3
3
23
33
313
3
3
23
33
2,5-Dihydroxyacetophenone
313
3
3
23
33
p-Nitroacetophenone
313
3
3
23
33
(CH3)2 N=CHClOPOCl2]+ (III)
In our earlier publications on VH reactions [16–18],
we reported second-order kinetics with first order in
[substrate] and first order in [VH] reagent, and the reac-
tion rates were faster at a low dielectric dichloroethane
[
[
(CH3)2 H2N=CHCl]+ (IV)
+
[
(CH3)2 N=CHCl] [OSOCl]− (V)
(DCE) solvent as compared to a high dielectric acetoni-
trile (MeCN) medium with the trend: DEC > MeCN.
On the basis of these observations, the possibility
of a change in the reactive species was suggested,
passing from higher dielectric acetonitrile to low
dielectric dichloroethane medium according to the
+
[
(CH3)2 N=CH − OSOCl] Cl (VI)
(CH3)2 N=CHClOSOCl]+ (VII)
(CH3)2 H2N=CHCl]+ (VIII)
[
[
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
725
Scheme 1 Reaction mechanism for the uncatalyzed VH reaction with OHAP.
+
Ingold rule. Cationic [(CH3)2 H2N = CHCl] species
(electronic absorption spectra of Cu(II), Ni(II), and
Co (II) indicated bands at 756, 490, and 512 nm,
respectively). These bands underwent hypsochromic
or bathochromic shifts in the presence of acetophe-
nones with or without VHR as shown in Figs. 3–5
and Table IV. These observations indicate binary and
ternary complex formation in the presence of VHR.
In the presence of OHAP, Cu(II) and Ni(II) under-
went a hypsochromic shift, whereas Co(II) indicated a
bathochromic shift. These shifts establish the forma-
tion of binary complexes with OHAP. However, in the
presence of VHR and OHAP, the metal ions under-
went hypsochromic shifts, depicting the formation of
ternary precursors prior to rate-limiting steps, as shown
in Schemes 2 and 3. [M(II)-S] and [M(II)-VHR] bind-
ing constants were determined by using the Benesi–
Hildebrand method [25] according to the following
equilibria and relationships:
were suggested in DCE medium, whereas ion-pair
+
−
species [(CH3)2 N = CHCl] [OPOCl2] /[(CH3)2 N =
+
−
CHCl] [OSOCl] were considered in MeCN medium
as shown in Scheme 1.
Products of the reaction were separated by TLC
according to literature procedures. Products of the re-
action were also analyzed by spectroscopy according
to literature procedures. Acetyl derivatives have been
found to be the products irrespective of the nature of
the VH reagent used, as was depicted by similar IR
spectra of the isolated product. For the above scheme,
the rate law comes out as
−
d[Substrate]
=
k [Substrate] [VH adduct]
dt
This rate-law explains second-order kinetics with
a first-order dependence on [substrate] and also on
[VH adduct], showing the consistency of the proposed
mechanism. It is of interest to note that OHAP un-
derwent cyclization followed by formylation to afford
formyl chromone.
Metal Ion–Substrate Interactions.
K1
M(II) + S ꢀ M(II)S
K1[M(II)]CS
+ K1[M(II)]
Mechanism of VH Reactions in Metal
Ion–Catalyzed Reactions
⇒
[M(II)S] =1
(1)
To observe one-to-one binding between a single
substrate (S) and metal ion (M) using UV–vis ab-
sorbance, the Benesi–Hildebrand method can be now
employed. Using the Beer–Lambert law, the concen-
tration of [M(II) S] can be rewritten as
The mechanistic path in metal ion–catalyzed VH re-
actions depends on several factors such as metal ion
interactions with the substrate, VH reagent to give bi-
nary/ ternary precursor(s) prior to the rate-limiting step.
To ascertain the [M(II)-S], [M(II)-VHR], and [M(II)-
S-VHR] interaction, spectrophotometric studies have
been performed. As a typical case, Cu(II), Ni(II), and
Co(II) interactions were studied with OHAP in the
presence and absence of VHR. All the three metal
ions indicated absorption bands in the visible region
A = ε [M(II)S] b (where b = path length)
⇒
⇒
[M(II)S] = A/ε b; and when b = 1 cm
[M(II)S] = A/ε
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

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ANEESA ET AL.
Figure 3 UV–vis spectra of Cu(II) with OHAP and VHR.
Figure 4 UV–vis spectra of Ni(II) with OHAP and VHR.
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
727
Figure 5 UV–vis spectra of Co(II) with OHAP and VHR.
K1
Substituting for [M(II)S] in the binding isotherm
equation (1), the equilibrium constant K can now be
correlated to the change in absorbance due to the for-
mation of the M(II)S complex:
M(II)S + VHR ꢀ [M(II)S − VHR]
Intheabovescheme, M, S, andVHRrepresentmetal
ion, substrate, brominating reagent, whereas [M (II) S]
and [M (II) S-VHR] refer to binary and ternary com-
plexes formed due to the interaction of metal ion, sub-
strate, and VHR, respectively:
A
K1 [M (II)] CS
1 + K1 [M (II)]
⇒ ε = [M(II)S] =
Rearranging the above equation,
[
M(II)S − VHR] = K2 [M(II)S] [VHR]
A
CS
ꢀεK1 [M (II)]
1 + K1 [M (II)]
⇒
⇒
= [M(II)S] =
[M(II)S] = K1 [M(II)] [S] ⇒ [S]
ꢀ
CS
A
1
1
=
[M(II)S] K1 [M (II)]
=
+
ꢀεK1 [M (II)] ꢀε
But the total substrate concentration ([S]t) is the
sum of free substrate (S) and metal ion bound substrate
A double reciprocal plot can be made with (CS /A)
as a function of 1/[M(II)], and ε can be derived from
the intercept, whereas K1 can be calculated from the
slope. Such reciprocal plots have been realized in this
study (Fig. 6). The values of K1 and ε are presented in
Table IV.
(
M (II) S) concentrations, respectively:
[
S] = [S] + [M(II)S] ⇒ [S] = [S] − [M(II)S]
t
t
Application of equilibrium concept finally leads to
an expression for [M (II) S –VHR]:
Interaction of Metal Ion with the Substrate in the
Presence of VHR. The model for ternary complex for-
mation in micellar media is represented in the follow-
ing equilibria:
⇒
[M(II)S − VHR]
K1K2 [M(II)] [S]t [VHR]t
1 + K [M(II)] + K K [M(II)] [S] )
= (
1
1
2
t
K1
(
2)
M(II) + S ꢀ M(II)S
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ANEESA ET AL.
Using the Beer–Lambert law, the equation can be
rewritten with the absorption coefficients and concen-
trations of each component:
A = ε [M(II)S − VHR] b
(
where b = path length)
⇒
[M(II)S − VHR] = A/ε b;
and when b = 1 cm
[M(II)S] = A/ε
⇒
Substituting [(M(II)S –VHR)] in the binding
isotherm equation (2), the equilibrium constant K can
now be correlated to the change in absorbance due to
the formation of the [(M(II)S–VHR)] complex:
(
K K [M(II)] [S] [VHR] )
1 2
t
t
⇒
A = (
1 + K [M(II)] + K K [M(II)] [S] )
1
1
2
t
ε (K1K2 [M(II)] [S]t [VHR]t )
= 1
+ K1 [M(II)] + (1 + K2 [S]t )
Reciprocals of the above equation with proper rear-
rangement afford
[
S]t [VHR]t
1
(1 + K2 [S] )
t
=
+
A
ε (K1K2 [M(II)])
ε K2
Now from the reciprocal plot with ([S]t [VHR]t/ꢀA)
as a function of 1/[M(II)], a straight line withan inter-
cept = (1 + K2[S]t)/ εK2 and slope = 1/ε(K1K2) should
be obtained. From the intercept value, ε can be com-
puted with the assumption that (1 ꢂ K2[S]t), which
ultimately leads to the intercept = [S]t /ε, whereas K2
can be calculated from the slope with proper substi-
tution of K1 evaluated earlier for the binary system.
Representative plots are shown in Fig. 7. Free energy
(
ꢀG) values for formation constants (K1 and K2) are
evaluated from the vant Hoff’s isotherm according to
standard procedures and compiled in Table IV:
ꢀ
G = −RT ln Ki
Mechanistic Scheme. On the basis of the kinetic
and spectroscopic features coupled with evidence for
ternary complex formation, the most plausible mech-
anism for metal ion–catalyzed VH reactions with ace-
tophenone and OHAP could be proposed with the par-
ticipation of the ternary precursor [M(II)-(S)(VHR)]
in the rate-limiting step as shown in Schemes 2 and 3,
respectively.
For Schemes 2 and 3, the rate law for the M(II)-
catalyzed reaction could be given as in Eq. (3)
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
729
Scheme 2 Reaction mechanism for metal ion–catalyzed VH reaction with acetophenone.
on the basis of discussion given in the Supporting
Information:
the rate law finally takes the following form:
=
k kcK1K2 [M(II)]
kcK1K2 [M(II)] [S]t [VHR]t
V = 1
(3)
+ K1 [M(II)] (1 + K2[S]t )
Activation parameters are computed from Eyring’s
equation using the theory of reaction rates [22]. Ac-
cording to Eyring’s theory of reaction rates, the rate
constant (k) can be given as
This rate law shows first-order kinetics with re-
spect to [VHR] and fractional order in both [substrate]
as well as [M(II)]. But experimental observations of
the present study revealed first-order kinetics in both
the reactants [VHR] and [substrate] associated with
highly significant rate enhancements and yields of the
products, which are clearly demonstrated in Tables I–
III. This change from theory to experiment could be
explained due to the small contribution of the term
#
k = (kt ) (RT /Nh) exp (−ꢀG /RT )
(4)
In the above equation, the transmission coefficient
(
kt) is assumed to be unity, R, N, h, and T represent the
gas constant, Avogadro’s number, Planck’s constant,
#
and reaction temperature, and ꢀG the free energy of
(
(
K1K2 [M(II)][S]t) in the derived rate equation. If
1+ K1[M(II)]) ꢁ K1K2 [M(II)][S]t in the denomi-
activation, respectively. Rearrangement of the above
equation gives the following equation:
nator of the above rate equation, the contribution of
(
K1K2[M(II)][S]t) could be neglected. The rate equa-
#
exp (ꢀG /RT ) = (RT /Nhk)
(5)
tion now takes the following form:
Natural logarithm for the above equation gives
kcK1K2 [M(II)] [S]t [VHR]t
V =
1
+ K1 [M(II)]
#
ꢀ
G = RT 1n (RT /Nhk)
(6)
Upon rearrangement, the rate law becomes
#
The free energy of activation (ꢀG ) has been ob-
tained at various temperatures by using the above equa-
tion. An almost similar magnitude of free energies of
V
(kcK1K2 [M(II)])
1 + K1 [M(II)]
=
=
t
k
[
S] [VHR]
t
#
activation (ꢀG presented in Table V) probably indi-
It is reasonable to neglect contribution of K1[M(II)]
cates that a similar type of mechanism is operative in
both the VH systems studied irrespective of the nature
of the oxychloride used for the VH reagent. Enthalpy
≪
1 in the denominator of the above equation, as
M(II)] is far less than either [S] or [VHR]. Therefore,
[
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ANEESA ET AL.
O
O
K1
M(II)
+
–H+
OM(II)
Cl
OH
O
O
H C
O
3
K2
N
O
P
C
–
HPO Cl
2 2
H C
H
Cl
H
3
Cl
(
VHR)
O
2
H+
O
O
H
O
+
H
C
CH2
H
Cl
H
C
O
O
+
M (II)
slow
+NMe2
NHMe2
OH
k
fast
.
.
2
O
O
H
H
C
H
H
C
NMe2
C
Cl
O
O
NMe2
+
M (II)
HCl
fast
H O
fast
2
MCl
O
O
H
C
H
H
C
Cl
H
O
NMe
2
C
+
NMe2
O
H
fast
fast
O
O
NHMe2
H
+
2
H
Me N = C
Cl
+
C
Cl
fast
NMe2
O
O
H
.
.
H O
2
HPO Cl
2
2
H PO4 + 2HCl
3
fast
Scheme 3 Reaction mechanism for the metal ion–catalyzed VH reaction with OHAP.
#
#
#
(
ꢀH ) and entropy of activation (ꢀS ) are obtained
(ꢀH ) values. Activation parameters have been evalu-
ated for all the substrates studied in this reaction, and
the data are presented in Tables V and VI. It is of
#
from the plots of ꢀG as a function of temperature (T)
Fig. 8), using the Gibbs–Helmholtz equation:
(
#
interest to note that free energies of activation (ꢀG )
#
#
#
ꢀ
G = ꢀH − TꢀS
(7)
observed for DMF/SOCl2 versus (DMF/POCl3)VH re-
actions are by and large linear, indicating that a sim-
ilar type of mechanism is operative. Small entropies
#
According to this equation, ꢀG as a function of
temperature (T) should be linear with negative slopes
of the Gibbs–Helmholtz plots gave (ꢀS ), whereas
#
#
of activation (ꢀS ) presented in these tables probably
observed definite intercepts on the ordinate afforded
suggest that the transition state is tending toward de-
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
731
composition to yield stable products. Negative free en-
ergy values (ꢀG) calculated for binding constants K1
and K2 (Table IV) indicate spontaneous nature of com-
plex formation during the course of reaction.
To have a further insight into the activation param-
‡
eters, we have tried to correlate (ꢀH ) values with
(
‡
ꢀS ) obtained for both DMF/POCl3 and DMF/SOCl2
systems under uncatalyzed and metal ion–catalyzed
‡
‡
systems. The plots of (ꢀH ) values with (ꢀS ) were
linear with a positive slope and intercept. The correla-
2
tion coefficients (R values) obtained for these plots are
Figure 6 Benesi–Hildbrand plots for K1.
in the range of a well to fairly good linear relationship
(compiled in Table VII). These observations satisfy the
following Leffler’s equation:
‡
‡
‡
ꢀ
H = βꢀS + ꢀH
0
The slope of the Leffler’s plot represents the “isoki-
netic temperature” (“β,” the temperature (T)) at which
all members of a series obeying the isokinetic rela-
tionship react at the same rate. According to Leffler’s
theory [26], such linearity indicates compensation of
both enthalpy and entropy factors in controlling the
reactions in a series of structurally related substrates
Figure 7 Reciprocal plots for K2.
Table V Temperature-Dependent Free Energy of Activation Using Second-Order Rate Constants for VH Formylation
Reactions with Acetophenones in MeCN Medium
#
ꢀ
G (kJ/mol)
System
Substrate
Acetophenone
Temperature (K) Uncatalyzed Cu(II) Ni(II) Co(II) Cd(II)
313
DMF/POCl3
72.16
71.94
71.75
71.62
71.41
71.17
71.62
71.19
70.75
71.83
71.66
71.27
72.31
72.24
72.19
73.64
73.44
73.20
74.70
74.45
74.06
73.64
72.71
72.19
70.38
70.28
70.18
70.03
69.98
69.92
69.92
69.33
68.94
70.78
70.72
69.83
70.78
70.60
70.51
71.84
71.58
71.24
72.93
72.59
71.75
71.20
71.19
70.90
70.60
70.55
70.46
70.38
70.33
69.90
70.26
69.76
69.34
71.10
71.05
70.13
70.93
70.72
70.67
72.06
71.70
71.52
73.23
72.98
72.70
71.25
71.19
71.14
70.78
70.60
70.51
70.64
70.60
70.38
70.50
69.93
69.66
71.25
71.19
70.39
71.25
71.05
70.67
72.58
72.35
71.87
73.64
73.46
73.33
71.43
71.26
71.05
71.65
71.26
71.17
70.80
70.54
70.48
70.78
70.33
69.98
71.65
71.42
70.59
71.62
71.58
71.41
72.87
72.70
72.28
74.70
73.9
3
3
313
23
33
OHAP
3
3
23
33
2,5-Dihydroxyacetophenone
313
3
3
23
33
p-Nitroacetophenone
Acetophenone
OHAP
313
3
3
23
33
DMF/SOCl2
313
3
3
23
33
313
3
3
23
33
2,5-Dihydroxyacetophenone
313
3
3
23
33
73.50
73.60
72.36
71.56
p-Nitroacetophenone
313
3
3
23
33
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

7
32
ANEESA ET AL.
that undergo the same change or when the reaction
conditions for a single substrate are changed in a sys-
tematic way. However, the supposed isokinetic rela-
‡
tionships as established by a direct correlation of ꢀH
‡
with ꢀS are often spurious and has been criticized by
Exner, Peterson, Cornish-Bowden, and others [27,28].
In view of this large criticism, we can at best say that
the linearity of Leffler’s plots coupled with almost a
‡
similar magnitude of free energies of activation (ꢀG )
presented in Table III indicates that a similar type of
mechanism is operative in the present study.
CONCLUSIONS
In summary, we have successfully demonstrated tran-
sition metal ion–catalyzed VH formylation reactions
with acetophenones in acetonitrile medium. The VH
reactions followed second-order kinetics and afforded
acetyl derivatives under kinetic conditions also irre-
spective of the nature of oxychloride used for the prepa-
ration of VH reagent along with DMF. Reactions are
accelerated remarkably in the presence of transition
metal ions. The present finding is advantageous for un-
Figure 8 Gibbs–Helmholtz plots for VH formylation of
orthohydroxy acetophenone at 333 K and MeCN solvent.
(
a) Uncatalyzed reaction using (POCl3+DMF) as VH
reagent. (b) Cu(II)-catalyzed reaction using (POCl3+DMF)
as VH reagent. (c) Uncatalyzed VH formylation of ortho-
hydroxy acetophenone using (SOCl2+DMF). (d) Cu(II)-
catalyzed formylation using (SOCl2+DMF).
Table VI Enthalpy and Entropy of Activation Parameters for VH Formylation Reactions with Acetophenones in MeCN
Medium
#
#
ꢀ
H (kJ/mol)
ꢀS (J/K/mol)
System
Substrate
Uncatalyzed Cu(II) Ni(II) Co(II) Cd(II) Uncatalyzed Cu(II) Ni(II) Co(II) Cd(II)
DMF/POCl3 Acetophenone
OHAP
76.9
79.4
84.9
80.6
74.3
81.4
84.0
97.0
73.4 73.3 73.8 79.4
71.9 78.1 76.0 77.0
85.5 84.3 84.5 83.2
85.8 86.9 85.4 87.5
75.0 75.6 80.3 74.7
81.2 79.8 83.7 82.1
91.5 81.0 78.3 93.4
75.1 73.0 75.5 106
15.0
25.0
42.0
28.0
10.0 10.0 10.0 25.0
6.00 24.0 17.0 20.0
50.0 45.0 45.0 40.0
47.0 50.0 45.0 50.0
13.0 15.0 29.0 10.0
30.0 25.0 35.0 20.0
59.0 25.0 15.0 60.0
2,5-Dihydroxyacetophenone
p-Nitroacetophenone
DMF/SOCl2 Acetophenone
OHAP
,5-Dihydroxyacetophenone
6.00
25.0
30.0
75.0
2
p-Nitroacetophenone
12.0
5.00 13.0 105.0
#
#
Table VII Leffler’s Plots (ꢀH vs. ꢀS )
System
System
Equation
β (K)
2
DMF/POCl3
Uncatalyzed
Cu(II)
Ni(II)
Co(II)
Cd(II)
Uncatalyzed
Cu(II)
Ni(II)
Co(II)
Cd(II)
y = 0.299x + 72.22; R = 0.995
299
320
328
318
331
323
353
380
304
312
2
y = 0.320x + 70.10; R = 0.995
2
y = 0.328x + 70.05; R = 0.995
2
y = 0.318x + 70.59; R = 0.996
2
y = 0.331x + 70.59; R = 0.986
2
DMF/SOCl2
y = 0.323x + 73.18; R = 0.992
2
y = 0.353x + 70.62; R = 0.999
2
y = 0.380x + 70.7; R = 0.961
2
y = 0.304x + 72.44; R = 0.954
2
y = 0.312x + 73.79; R = 0.981
International Journal of Chemical Kinetics DOI 10.1002/kin.20807

EFFICIENT CATALYTIC ACTIVITY OF TRANSITION METAL IONS
733
derstanding the nature of reactive species as well as the
mechanism of acetylation.
14. Ali, M. M.; Sana, S.; Tasneem Rajanna, K. C.;
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International Journal of Chemical Kinetics DOI 10.1002/kin.20807