Transition Metal Ions as Efficient Catalysts for Vilsmeier-Haack Formylation of Hydrocarbons with Reagents: Kinetics and Mechanism

Article abstract of DOI:10.1007/s10953-016-0442-5

The Vilsmeier-Haack formylation reactions with hydrocarbons are sluggish in acetonitrile medium. The VH reactions follows second-order kinetics and affords formyl derivatives under kinetic conditions that are also irrespective of the nature of the oxychloride (POCl₃ or SOCl₂) used for the preparation of VH reagent along with DMF. However, the reactions undergo significant rate accelerations in the presence of transition metal ions such as Cu(II), Ni(II), Co(II) and Cd(II). Transition metal ion catalyzed VH formylation is explained through the formation of a mixed ligand complex of the [M(II)S(VHR)] type prior to the rate determining rearrangement step, before yielding formyl derivatives of hydrocarbons.

Full text of DOI:10.1007/s10953-016-0442-5

J Solution Chem (2016) 45:371–394
DOI 10.1007/s10953-016-0442-5
Transition Metal Ions as Efficient Catalysts
for Vilsmeier–Haack Formylation of Hydrocarbons
with Reagents: Kinetics and Mechanism
1
2
2
1
•
K. C. Rajanna
3
M. Arifuddin
•
Aneesa Ferdose
M. Moazzam Ali
•
K. Rajendar Reddy
•
Received: 20 August 2015 / Accepted: 3 December 2015 / Published online: 17 February 2016
Ó Springer Science+Business Media New York 2016
Abstract The Vilsmeier–Haack formylation reactions with hydrocarbons are sluggish in
acetonitrile medium. The VH reactions follows second-order kinetics and affords formyl
derivatives under kinetic conditions that are also irrespective of the nature of the oxy-
chloride (POCl or SOCl ) used for the preparation of VH reagent along with DMF.
3
2
However, the reactions undergo significant rate accelerations in the presence of transition
metal ions such as Cu(II), Ni(II), Co(II) and Cd(II). Transition metal ion catalyzed VH
formylation is explained through the formation of a mixed ligand complex of the
[M(II)S(VHR)] type prior to the rate determining rearrangement step, before yielding
formyl derivatives of hydrocarbons.
Keywords Vilsmeier–Haack formylation Á Hydrocarbons Á Transition metal ions Á
Catalysts Á Kinetics Á Mechanism
1
Introduction
The Vilsmeier–Haack reagent is a versatile reagent in organic synthesis [1–14]. Formy-
lation of organic compounds is an important reaction in organic synthesis, which can be
achieved more conveniently under Vilsmeier–Haack conditions than with other procedures
[
15–17] such as the Reimer–Tiemann [15], Gattermann–Koch [16], and Duff methods [17].
Earlier publications from our laboratory reported certain kinetic and mechanistic aspects of
formylation, cyclization, acetylation and benzylation under VH conditions in various
&
K. C. Rajanna
kcrajannaou@yahoo.com
1
2
3
Department of Chemistry, Osmania University, Hyderabad 500007, India
Department of Chemistry, M. J. C. E. T., Hyderabad 500034, India
National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India
123

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J Solution Chem (2016) 45:371–394
solvent media [11–14]. Over the years, transition metal ions have received enormous
attention by synthetic, inorganic and physical organic chemists all over the world because
of their proven ability as efficient homogeneous catalysts in organic synthesis dealing with
different redox [18–32], photochemical [29], and substitution reactions such as hydro-
genation [30], nitration [31] and formylation reactions [32]. Even though many results
have been published in the literature showing the catalytic effects of transition metal based
species in a variety of chemical reactions. not much work has reported on transition metal
ion catalyzed kinetic studies of VH reactions [29]. In continuation of our ongoing research
on synthesis, kinetics and mechanism of VH reactions, the authors performed a detailed
kinetic study of transition metal ion catalyzed Vilsmeier–Haack formylation of aromatic
hydrocarbons.
2
Experimental Details
2
.1 Materials
Solvents such as acetonitrile and dichloroethane were of highest purity HPLC grade.
Deionized water was further purified over acid dichromate and alkaline permanganate
solutions before use. All the other chemicals used in this study (organic substrates such as
hydrocarbons, phenols, and their substituted compounds) were procured from Sigma
Aldrich Chemicals (Hyderabad, India) with highest purity (99 %). A carbonate-free
sodium hydroxide stock solution was prepared according to standard procedures and the
concentration was systematically checked by titration against potassium hydrogen phtha-
late. All the metal nitrates used in the present work were of Analytical Reagent (AR) grade
of 99 % purity (S.D. Fine Chemicals Ltd., India). Stock solutions of metal nitrates (Cu(II),
Co(II), Ni(II) and Cd(II) nitrates) were prepared in acetonitrile solvent and standardized by
EDTA titrations according to literature procedures [33].
2
.2 VH Reagents
Flasks containing DMF dissolved in a suitable solvent {generally dichloroethane (DCE), or
acetonitrile (ACN)}, along with SOCl and POCl , were cooled and thermally equilibrated
2
3
for about 30 min at -5 °C by keeping them in a benzene trough chilled from outside with
ice and NaCl. Requisite amounts of solvent and amide were transferred into a 100 mL flask
and POCl or SOCl was added drop wise, at -5 °C, with constant stirring. The resultant
3
2
reagent mixture was kept aside for about an hour to ensure complete formation of the VH
adduct. Its concentration was checked by acid–base titration to the bromocresol green end
point according to literature reports [9–14].
2
.3 Kinetic Method
Organic substrates such as hydrocarbons, phenols, and their substituted derivatives were
used for kinetic studies of VH reactions in ACN and DCE. The thermostat (Toshniwal,
India) was adjusted to the desired reaction temperature (with a precision of ± 0.1 °C). Two
different flasks, one containing known amount of Vilsmeier–Haack reagent (DMF/SOCl2
or DMF/POCl ) in a suitable solvent, and the other with the substrate solution, were taken
3
and clamped in the thermostatic bath for about 30 min. The reaction was initiated by
1
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J Solution Chem (2016) 45:371–394
373
adding the requisite amount of substrate solution to the reaction vessel containing the other
contents of the reaction mixture. The entire reaction mixture was stirred until the end of the
reaction. A kinetic method was adopted to monitor progress of the VH reaction, which is
similar to that reported in our earlier papers [11–14]. Aliquots of the reaction mixture were
withdrawn into a conical flask, containing considerable (and known) amount of hot dis-
tilled water, at different time intervals. The unreacted VH adduct underwent hydrolysis and
gave a mixture of acids (hydrochloric and sulfuric acids for DMF/SOCl and hydrochloric
2
and phosphoric acids for DMF/POCl ). The acid content was estimated against standard
3
NaOH solution to the bromocresol green end point. Reproducibility of the results was
crosschecked by conducting kinetic runs three to four times. The results were reproducible
within ± 3 % error.
2
.4 Product Analysis Under Kinetic Conditions
After completing the kinetic study of the reaction, excess (remaining part of the reaction
mixture) was refluxed further and left aside overnight. The solution was then poured into ice-
cold water with vigorous stirring and kept aside for about 2 h. The resultant solution was
neutralized with sodium hydrogen carbonate. The organic phase was extracted with DCE,
dried over MgSO and the solvent evaporated. Products of the reaction were isolated and
4
1
found to be formyl derivatives of the substrates (Scheme 1) as characterized by H-NMR and
mass spectra with comparison to authentic samples and found to be satisfactory (Table 1).
3
Results and Discussion
.1 Order of the VH Reaction
Plots of ln V versus time were linear with negative slope and intercept as shown in Figs. 1 and
3
t
2
, when [substrate] ꢀ [VHR] the reaction shows first-order kinetics in [substrate]. Rep-
o
o
resentative data are presented in Table 2. However, under the condition [VHR] =
o
[substrate] , the plots of [1/(a – x)] or [1/V ] versus time are linear with positive slope and
o t
intercept at the ordinate indicating that the VH reaction follows overall second-order kinetics
Figs. 3 and 4). From the slopes of these plots, second-order rate constant were evaluated.
(
3
.1.1 Reactive Species of VH Adduct and Mechanism of Formylation Reactions
Involving the DMF–Oxychloride [POCl or SOCl ] Adduct
3
2
In spite of different opinions prevailing on the formulae of the reactive VH adduct species,
3
1
infrared spectroscopic studies of Arnold and Holy, electronic spectroscopic and P NMR
spectroscopic study results of Marino, Martin and several others [3–10], together with the
O
Y
Y
VHR = DMF / Oxychloride
H
X
X
(
i) ACN/DCE
(
ii)ACN/M(II) Nitrate
Scheme 1 VHR = DMF ? (SOCl
2
3
or POCl ); Y = OH; X = ED or EWD groups
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J Solution Chem (2016) 45:371–394
375
t 3
Fig. 1 Plots of ln V versus time for the formylation of phenol using (POCl ? DMF) at 333 K
t 2
Fig. 2 Plots of ln V versus time for the formylation of naphthol using (SOCl ? DMF) at 333 K
Chart 1 H reactive species with DMF POCl
3
kinetic studies reported from our laboratory [11, 12] on VH adducts, revealed that a
number of covalent, ionic and ion-pair species of VH-adduct (I to VI) can exist in solution
as shown in Chart 1, taking DMF and POCl as a specific example (Chart 1).
3
Thionyl chloride, being a good Lewis acid like POCl , can easily interact with a Lewis
3
base (DMF) to form VH adducts analogous to DMF/POCl . In view of this, the reaction
3
mechanism with DMF/SOCl does not differ much from that with DMF/POCl . It is
2
3
therefore reasonable to consider similar type of reactive species (VII to X) in the present
work. Accordingly, the species can be written as:
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J Solution Chem (2016) 45:371–394
Â
Ã
ðCH3Þ N ¼ CHCl þ½OSOClŠÀ
ðVIIÞ
ðVIIIÞ
ðIXÞ
2
Â
Ã
þ
À
ðCH3Þ N ¼ CH-OSOCl Cl
2
Â
Ãþ
ðCH3Þ N ¼ CHClOSOCl
2
Â
Ã
þ
ðCH3Þ N ¼ CHCl
This aspect, coupled with the observed linearity of the plot of log k (POCl ) versus log
ðXÞ
2
1
0
3
10
k (SOCl ), indicates that a similar type of mechanism is operative in both the POCl and
3
2
SOCl systems. Earlier studies from our laboratory also revealed that the reaction rates
2
were relatively higher in DCE media (solvent of low dielectric constant) than those of
MeCN media (solvent of high dielectric constant). Ingold’s rule states that, for ion–ion and
ion–dipole type species participating in the slow step, reaction rates should be faster in the
solvent of low dielectric constant. This statement lends support for considering the par-
?
ticipation of cationic species of VH adduct (Me N-CHCl) in the rate limiting step. In
2
?
addition to this, the cationic species of VH adduct (Me N-CHCl) is electrophilically more
2
reactive than non-ionic or ion-pair intermediates of the VH adduct (Scheme 2).
For the above scheme the rate law is,
Table 2 First-order rate constants for VH formylation with hydrocarbons
0
-5 -1
VH Reagent
Substrate
First order rate constant (k 9 10 )/s
Native
Cu(II)
Ni(II)
Co(II)
Cd(II)
DMF/POCl
3
Naphthalene
Phenol
13.3
11.7
5.00
3.33
8.33
8.33
16.7
20.0
13.3
13.3
3.33
3.33
1.67
1.67
5.00
6.70
5.00
5.00
5.00
5.00
18.3
16.7
6.67
8.33
15.0
13.3
21.7
23.3
18.3
23.3
5.00
5.00
3.33
1.67
6.67
8.33
6.67
6.67
5.00
6.67
20.0
18.3
6.67
8.33
16.7
15.0
23.3
23.3
20.0
23.3
5.00
5.00
1.67
1.67
6.66
8.33
6.66
6.66
6.66
6.66
17.0
15.0
6.70
6.70
13.0
12.0
22.0
23.0
18.0
23.0
3.33
5.00
1.67
1.67
6.67
8.33
5.00
6.67
5.00
6.67
15.0
15.0
12.0
6.70
12.0
12.0
22.0
23.0
18.0
22.0
3.33
5.00
1.67
1.67
6.67
8.33
5.00
6.67
5.00
6.67
4
2
-Nitrophenol
-Chlorophenol
o-Cresol
p-Cresol
Toluene
Anisole
1
2
-Naphthol
-naphthol
DMF/SOCl
2
Naphthalene
Phenol
4
2
-Nitrophenol
-Chlorophenol
o-Cresol
p-Cresol
Toluene
Anisole
1
2
-Naphthol
-Naphthol
-
3
-3
[
subs] = 0.09 molÁdm ; [VHR] = 0.005 molÁdm
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377
t 3
Fig. 3 Plots of (1/V ) versus time for the formylation of phenol using (POCl ? DMF) at 333 K
Fig. 4 Plots of (1/V
t
) versus time for the formylation of naphthol using (SOCl
2
? DMF) at 333 K
Path - B
Path - A
2
DCE medium
Me CN medium
+
-
+
[
Me N-C(H)SOCl] [Cl]
Me N - COH + SOCl2
[Me N - C(H) Cl]
2
2
2
Ar-H = Aromatic Hydrocarbon
Ar-H
Ar-H
(Formyl Derivative)
Scheme 2 General mechanism of VH formylation reactions
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J Solution Chem (2016) 45:371–394
Àd ½substrateŠ
dt
¼
k½substrateŠ ½VH adductŠ
This rate law explains second-order kinetics with first-order dependences on [substrate]
and [VH adduct], showing the consistency of the proposed mechanism.
3
.1.2 Mechanism of VH Reactions in Transition Metal Ion Catalyzed Reactions
In order to have a closer look into the transition metal ion catalyzed reactions, a detailed
spectrophotometric study dealing with M(II) binding with the substrate and VHR under
different conditions has been undertaken. Electronic absorption spectra of Cu(II), Ni(II)
and Co(II) showed bands at 756, 490 and 512 nm, respectively. These bands underwent
either hypsochromic or bathochromic shifts in the presence of aromatic hydrocarbon, with
or without VHR. Observed shifts are shown in Figs. 5, 6, 7, 8 and the data are presented in
Table 3. These observations indicate binary and ternary complex formation due to the
interaction of substrate with metal ion M(II) in the absence and/or presence of VHR.
3
.1.3 Metal Ion–Substrate Interactions
K1
MðIIÞ þ S ꢀ MðIIÞS
According to this model, a metal ion–substrate complex [M(II)S] is formed in the pre-
equilibrium step due to the interaction of metal ion (M) with substrate (S). The equilibrium
constant K or (K ) is the binding constant, which can be determined using an approach of
1
Benesi and Hildebrand [34–41]:
Fig. 5 UV–Visible spectra of Cu(II) with naphthalene and VHR
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J Solution Chem (2016) 45:371–394
379
Fig. 6 UV–Visible spectra of Cu(II) with phenol and VHR
K1½MðIIފCS
þ K1½MðIIފ
where the total concentration of substrate is C , which is also considered as the algebraic
)
½MðIIÞSŠ ¼ 1
ð1Þ
S
sum of free substrate species (S) and metal ion bound substrate species (M(II)S). To
observe one-to-one binding between a single substrate (S) and metal ion (M) using UV–V
is absorbance, the Benesi–Hildebrand method [34–36] can be now employed. Using the
Beer–Lambert law, the concentration of [M(II)S] can be rewritten as,
A ¼ e½MðIIÞSŠb ðwhere b ¼ path lengthÞ
where [M(II)S] = A/eb; when b = 1 cm, [M(II)S] = A/e.
Substituting for [M(II)S] in the binding isotherm Eq. 1, the equilibrium constant K can
now be correlated to the change in absorbance due to the formation of the M(II)S complex.
A
K½MðIIފCS
! e ¼ ½MðIIÞSŠ ¼
1 þ K½MðIIފ
A
DeK½MðIIފ
)
¼ ½MðIIÞSŠ ¼
CS
1 þ K½MðIIފ
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J Solution Chem (2016) 45:371–394
Fig. 7 UV–Visible spectra of Cu(II) with 2-naphthol and VHR
Fig. 8 UV–Visible spectra of Ni(II) with naphthalene and VHR
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381
Table 3 UV spectroscopic observations of transition metal species in VH reactions
S. N.
Substrate
Metal
ion
M(II) ion
peak (nm)
M(II) ? substrate
peak(nm)
M(II) ? substrate
?VHR peak (nm)
1.
2.
3.
4.
Naphthalene
Cu(II)
Ni(II)
Co(II)
Cu(II)
Ni(II)
Co(II)
Cu(II)
Ni(II)
Co(II)
Cu(II)
Ni(II)
Co(II)
756
490
520
756
490
520
756
490
520
756
490
520
757
479
(hypsochromic)
(
slight bathochromic)
462
hypsochromic)
510
hypsochromic)
415
hypsochromic)
470
hypsochromic)
517
hypsochromic)
453
hypsochromic)
464
hypsochromic)
510
hypsochromic)
748
hypsochromic)
463
hypsochromic)
517
499
(bathochromic)
(
588, 684
(bathochromic)
(
Phenol
470
(hypsochromic)
(
499
(bathochromic)
(
589,685
(bathochromic)
(
2-Naphthol
489
(hypsochromic)
(
498
(bathochromic)
(
587,654
(bathochromic)
(
Toluene
470
(hypsochromic)
(
497
(bathochromic)
(
589, 685
(bathochromic)
(
hypsochromic)
CS
1
1
) A
¼
þ e
eK½MðIIފ
Further modifications result in an equation where a double reciprocal plot can be made
with (C /A) as a function of 1/[M(II)], and the value of e can be derived from the intercept
S
while K can be calculated from the slope. Such reciprocal plots have been made in this
study and can be seen in Fig. 9. The values of K and e are presented in Table 4.
Naphthalene with Cu(II)
Naphthalene with Ni(II)
0
.012
0
.008
0
0
0
0
.0118
.0116
.0114
.0112
0.007
0.006
0.005
0.004
0.003
0.002
0.001
0
y = 4E-06x + 0.002
R² = 0.976
0
.011
y = 1E-06x + 0.010
R² = 0.993
0
0
0
.0108
.0106
.0104
0
500
1000
1500
0
500
1000
1500
1
/[Cu(II)]
1/[Ni(II)]
Fig. 9 Benesi–Hildebrand plots for K
1
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J Solution Chem (2016) 45:371–394
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J Solution Chem (2016) 45:371–394
383
3
.1.4 Interaction of Metal ion with Substrate in the Presence of VHR
The model for ternary complex formation in micellar media is represented in the following
equilibria:
K1
MðIIÞ þ S ꢀ MðIIÞS
K2
MðIIÞS þ VHR ꢀ ½MðIIÞSÀVHRŠ
The terms M, S and VHR represent metal ion, substrate, brominating reagent in these
equations while [M(II)S] and [M(II)S–VHR] refer to binary and ternary complexes formed
due to the interaction of metal ion, substrate, and VHR respectively:
½MðIIÞSÀVHRŠ ¼ K2½MðIIÞSŠ½VHRŠ
½
MðIIÞSŠ ¼ K1½MðIIފ½SŠ ) ½SŠ ¼ ½MðIIÞSŠ=K1½MðIIފ
However, the total substrate concentration ([S] ) is the sum of free substrate (S) and metal
t
ion bound substrate (M(II)S) concentrations, respectively:
½
SŠ ¼ ½SŠ þ ½MðIIÞSŠ ) ½SŠ ¼ ½SŠ À ½MðIIÞSŠ
t
t
Application of the equilibrium concept finally leads to an expression for [M(II)S-VHR]:
K1K2½MðIIފ½SŠ ½VHRŠ
t
t
½
MðIIÞS À VHRŠ ¼ À
Á
ð2Þ
1
þ K1½MðIIފ þ K1K2½MðIIފ½SŠ
t
Using the Beer–Lambert law, this equation can be rewritten with the absorption coeffi-
cients and concentrations of each component:
A ¼ e½ðMðIIÞS À VHRފb ðwhere b ¼ path lengthÞ
where [(M(II)S-VHR)] = A/eb; when b = 1 cm, [M(II)S] = A/e. Substituting for
[(M(II)S-VHR)] in the binding isotherm Eq. 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:
À
Á
À
Á
e K1K2½MðIIފ½SŠ ½VHRŠ
e K1K2½MðIIފ½SŠ ½VHRŠ
t
t
t
t
A ¼ À
Á ¼
À
Á
1
þ K1½MðIIފ þ K1K2½MðIIފ½SŠ
1 þ K1½MðIIފ 1 þ K2½SŠ
t
t
Taking reciprocals to the above equation affords a reciprocal plot with (1/A) as a function
of 1/[M(II)], and e can be derived from the intercept while K can be calculated from the
slope:
1
1 þ K1½MðIIފð1 þ K2½SŠ Þ
t
¼
À
Á
A
e K K ½MðIIފ½SŠ ½VHRŠ
1
2
t
t
À
Á
Á
1
1
1 þ K2½SŠ
t
¼
À
Á ¼ À
Á
A
e K K ½MðIIފ½SŠ ½VHRŠ
e K ½SŠ ½VHRŠ
1
2
t
t
2
t
t
À
½
SŠ ½VHRŠ
1
1 þ K2½SŠ
eK2
t
t
t
¼
¼
A
eðK1K2½MðIIފÞ
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Now, from the reciprocal plot with ([S] [VHR] /DA) as a function of 1/[M(II)], a straight
t
t
line with intercept (1 ? K [S] )/eK and slope = (1/eK K ) should be obtained, which is
2
t
2
1 2
observed in the present study (Fig. 10). From the intercept, the value e can be computed
with the assumption that 1 ꢁ K [S] , which ultimately leads to intercept = [S] /e, while K
2
t
t
2
can be calculated from the slope with proper substitution of K evaluated earlier for the
1
binary system. Gibbs energy values (DG) involving the formation constants (K and K ) are
1
2
evaluated according to van’t Hoff’s isotherm, and related data are presented in Table 4:
DG ¼ ÀRTlnKi:
3
.1.5 Metal Ion Catalyzed Mechanism of Formylation Reactions Involving a DMF–
Oxychloride [POCl or SOCl ] Adduct
3
2
UV spectroscopic studies (Figs. 5, 6, 7 and 8) of metal ion interactions with aromatic
hydrocarbons and in the absence and presence of VH reagents clearly indicate that aro-
matic hydrocarbons form binary [M(II)S] complexes as well as ternary complexes of the
type [M(II)–S–VHR]. These findings, coupled with the observed second-order kinetics
with first-order rate dependences on [substrate] as well as [VHR] and rate enhancements in
metal ion catalyzed reactions, substantiate the formation of a binary [M(II)S] complex in
the first step giving rise to a ternary complex in the second step. The ternary complex thus
formed rearranges to give products in the slow step, as is shown in Schemes 3 and 4.
In Schemes 3 and 4, [M(II)S] and [M(II)S–VHR] refer to binary and ternary complexes
formed due to the interaction of metal ion, substrate, and VHR, respectively. The products
are obtained from the decomposition of [M(II)S–VHR] in the slow step in the metal ion
catalyzed reactions. For the above schemes the rate law is given by:
kcK1K2½MðIIފ½SŠ ½VHRŠ
t
t
)
V ¼ À
Á
1
þ K1½MðIIފ þ K1K2½MðIIފ½SŠ
t
According to this rate law, the reaction kinetics should indicate first-order kinetics with
respect to [VHR] and fractional order in both [substrate] as well as [M(II)]. But, the
kinetics of the study indicate first order in both the reactants [VHR] and [substrate]. This
change may be explained due to the small contribution of the product of (K K [M(II)][S] ).
1
2
t
If (1 ? K [M(II)]) ꢀ K K [M(II)][S] in the denominator of the above rate equation, then
1
1
2
t
the contribution of (K K [M(II)][S] ) can be neglected. The rate equation now takes the
t
1
2
form,
Ni(II) with Napthalene and VHR
0
0
0
0
0
0
0
0
.0038
.0037
.0036
.0035
.0034
.0033
.0032
.0031
y = 6E-07x + 0.003
R² = 0.969
0
.003
0
500
1000
1500
1/[Ni(II)
Fig. 10 Benesi–Hildbrand plots for K
2
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J Solution Chem (2016) 45:371–394
385
Scheme 3 Metal ion catalyzed
VH reaction with hydrocarbons
K1
M(II) + S
M(II)S
K2
VHR
kc
[M(II) S - VHR]
Products
OH
OM(II)
K1
H+
M(II) +
O
P
H Cl
-
Cl
O
H C
3
Cl
N
K2
H C
3
(
VHR)
-
[PO Cl ]
2
2
OM(II)
H
OM(II)
OM(II)
NMe2
NMe
NMe2
k
-H+
Slow
2
H
Cl
O
Cl
H
H
H
H
OH
OM(II)
NMe2
CHO
+
-H
-
M(II)
O
H
H
+
H +
PO Cl2
HPO Cl
2 2
2
Scheme 4 Metal ion catalyzed VH mechanism with phenol
kcK1K2½MðIIފ½SŠ ½VHRŠ
t
t
V ¼
Rearranging the rate law gives:
1
þ K1½MðIIފ
V
kcK1K2½MðIIފÞ
1 þ K1½MðIIފ
0
0
¼
k ¼
½
SŠ ½VHRŠt
t
123

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J Solution Chem (2016) 45:371–394
3
Fig. 11 Gibbs–Helmholtz plots for VH formylation of phenol using (POCl ? DMF)
2
Fig. 12 Gibbs–Helmholtz plots for VH formylation of 1-naphthol using (SOCl ? DMF)
-
1
Since very low concentrations ([M(II) \ 0.001 molÁL ) are used in this study, the con-
tribution due to (K [M(II)]) can be neglected in the denominator. The above equation then
1
takes the form,
00
k
¼ kcK1K2½MðIIފ
00
Second-order rate constants (k ) are reported in Table 4 and related activation parameters
were computed from Eyring’s equation using the theory of reaction rates [37, 38].
According to Eyring’s theory of reaction rates, the rate constant (k) can be given as
#
k ¼ ðktÞ ðRT=NhÞexpðÀDG =RTÞ
ð3Þ
In the above equation, the transmission coefficient (k ) is assumed to be unity; R, N, h
t
and T represent the gas constant, Avogadro number, Planck’s constant and reaction
1
23

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387
123

388
J Solution Chem (2016) 45:371–394
1
23

J Solution Chem (2016) 45:371–394
389
123

390
J Solution Chem (2016) 45:371–394
1
23

J Solution Chem (2016) 45:371–394
391
123

392
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#
temperature, and DG the Gibbs energy of activation. Rearrangement of the above equation
gives:
À
Á
#
exp DG =RT ¼ ðRT=NhkÞ
Taking the natural logarithm for the above equation then gives:
ð4Þ
#
DG ¼ RT1n ðRT=NhkÞ
ð5Þ
#
The Gibbs energy of activation (DG ) has been evaluated at various temperatures by
#
using the above equation. But, the Gibbs energy of activation (DG ) is related to the
#
#
enthalpy (DH ) and entropy of activation (DS ) by the Gibbs–Helmholtz equation:
#
#
#
DG ¼ DH À TDS
ð6Þ
#
Now, the plots of DG as a function of temperature (T) should be linear with negative
#
#
slopes (DS ) and definite intercepts on the ordinate which are equal to (DH ). Such plots
were realized in the present study (Figs. 11 and 12). From the slopes and intercepts of these
plots, the enthalpies and entropies of activation were evaluated. Activation parameters
have been evaluated for all the substrates studied in this reaction and the data are presented
#
in Tables 5, 6 and 7. It is of interest to note that Gibbs energies of activation (DG ) for all
the substrates are by and large of the same magnitude, indicating a similar type of
#
mechanism is operative. The small entropies of activation (DS ) presented in these
tables show that the transition state is tending towards decomposition to afford
stable products. Obtained negative Gibbs energy values (DG) for binding constants K and
1
K indicate the favorable nature of complex formation during the course of the reaction.
2
4
Conclusions
In summary, the authors have successfully demonstrated transition metal ion catalyzed
Vilsmeier–Haack formylation reactions with hydrocarbons in acetonitrile medium. The
VH reactions followed second-order kinetics and afford formyl derivatives under kinetic
conditions, also irrespective of the nature of oxychloride used for the preparation of VH
#
reagent along with DMF. The calculated Gibbs energies of activation (DG ) for all the
substrates are, by and large, of the same magnitude, indicating a similar type of mechanism
#
is operative. Small positive entropies of activation (DS ) observed in this study probably
indicate that the transition state is tending towards decomposition to afford stable products.
The obtained negative Gibbs energy values (DG) for binding constants K and K indicate
1
2
the spontaneous nature of complex formation during the course of reaction. The present
finding is advantageous to understand the nature of reactive species as well as the
mechanism of formylation.
Acknowledgments The authors thank Prof. P. K. Saiprakash (Former Dean, Science Faculty, O.U.),
authorities of MJCET, and NIPER for constant encouragement.
References
1
2
. Vilsmeier, A., Haack, A.: Vilsmeier–Haack reaction. Ber. Bunsenges. Chem. Ges. 60, 119–122 (1927)
. Meth-Cohn, O.: The Vilsmeier-Haack reaction. Comp. Org. Syn. 2, 777–794 (1991)
1
23

J Solution Chem (2016) 45:371–394
393
3
4
5
6
. Arnold, Z., Holy, A.: Synthetic reactions of dimethylformamide. XIV. Some new findings on adducts of
the Vilsmeier-Haack type. Collect. Czech. Chem. Commun. 27, 2886–2897 (1962)
. Arnold, Z., Holy, A.: Synthetic reactions of dimethylformamide. XVIII. Reactivity of methyl groups in
polymethinium salts. Collect. Czech. Chem. Commun. 28, 2040–2046 (1963)
. Smith, T.D.: The reaction of NN-dimethylformamide with phosphorus trichloride. J. Chem. Soc. A 7,
841–842 (1966)
. Martin, G.J., Poignant, S.: Nuclear magnetic resonance investigations of carbonium ion intermediates.
Part I. Kinetics and mechanism of formation of the Vilsmeier-Haack reagent. J. Chem. Soc. Perkin 2
1964–1966 (1972)
7. Martin, G.J., Poignant, S.: Nuclear magnetic resonance investigations of carbonium ion intermediates.
Part II. Exchange reactions in chloro-iminium salts (Vilsmeier–Haack reagents). J. Chem. Soc. Perkin 2
642–646 (1974)
8
9
. Sethna, S.M., Shah, N.M.: The chemistry of coumarins. Chem. Rev. 36, 1–62 (1945)
. Alumi, S., Linda, P., Marino, G., Santine, S., Salvelli, G.: The mechanism of the Vilsmeier–Haack
reaction. Part II. A kinetic study of the formylation of thiophen derivatives with dimethylformamide and
phosphorus oxychloride or carbonyl chloride in 1,2-dichloroethane. J. Chem. Soc Perkin 2 2070–2073
(1972)
1
1
0. Linda, P., Lucccarelli, A., Marino, G., Savelli, G.: The mechanism of the Vilsmeier–Haack reaction.
Part III. Structural and solvent effects. J. Chem. Soc. Perkin 2 1610–1612 (1974)
1. Rajanna, K.C., Soloman, F., Moazzam Ali, M., Saiprakash, P.K.: Kinetics and mechanism of Vilsmeier-
Haack synthesis of 3-formyl chromones derived from o-hydroxy aryl alkyl ketones: a structure reac-
tivity study. Tetrahedron 52, 3669–3682 (1996)
1
2. Rajanna, K.C., Soloman, F., Moazzam Ali, M., Saiprakash, P.K.: Vilsmeier-Haack formylation of
coumarin derivatives. A solvent dependent kinetic study. Int. J. Chem. Kinet. 28, 865–872 (1996)
3. Rajanna, K.C., Venkateswarlu, M., Satish Kumar, M., Umesh Kumar, U., Ramgopal, S., Saiprakash,
P.K.: Kinetics and mechanism of certain acetylation reactions with acetamide/oxychloride in acetoni-
trile under Vilsmeier-Haack conditions. Helv. Chim. Acta 94, 2168–2187 (2011)
4. Rajanna, K.C., Venkateswarlu, M., Satish Kumar, M., Umesh Kumar, U., Venkateshwarlu, G., Sai-
prakash, P.K.: Kinetics and mechanism of certain benzoylation reactions under Vilsmeier-Haack con-
ditions using benzamide and oxychloride in acetonitrile medium. Int. J. Chem. Kinet. 45, 69–80 (2013)
5. Wynberg, H.: The Reimer-Tiemann reaction. Chem. Rev. 60, 169–184 (1960)
6. Jack, L.J.: Name Reactions: A Collection of Detailed Reaction Mechanisms, 2nd edn, p. 157. Springer,
New York (2003)
1
1
1
1
1
1
7. Ogata, Y., Sugiura, F.: Kinetics and mechanism of the Duff reaction. Tetrahedron 24, 5001–5010 (1968)
8. Wiberg, N., Holleman, A.F., Wiberg, N.: Holleman-Wiberg Inorganic Chemistry, 34th edn. Academic
Press, New York (2001)
1
2
9. Elschenbroich, Ch., Salzer, A.A.: Organometallics, 2nd edn. VCH, Weinheim (1992)
0. Thompson, D.T.: Some basic research in coordination chemistry and catalysis, related to applications
for industry. Coord. Chem. Rev. 154, 179–192 (1996)
2
2
1. Jagirdar, B.R.: Transition metal complexes and catalysis. Resonance 4, 63–65 (1999)
2. Lakshmi, P.J., Rajanna, K.C., Saiprakash, P.K.: Mechanism of oxidation of iron(II) chelates by hex-
avalent chromium and heptavalent manganese in aqueous sulfuric acid and micellar media—a kinetic
approach. Transit. Met. Chem. 21, 135–141 (1996)
2
2
2
3. Reddy, K.N., Ram Reddy, M.K., Rajanna, K.C., Saiprakash, P.K.: A kinetic study of the 1,10-
phenanthroline-catalysed iron(III) oxidation of epimeric aldo-, and D-, and L-ketohexoses. Transit. Met.
Chem. 21, 112–116 (1996)
4. Reddy, J.N., Giridhar, S., Rajanna, K.C., Saiprakash, P.K.: Equilibrium and kinetic studies of electron
transfer reactions involving quinolinium dichromate and amino alcohols in aqueous acid media. Transit.
Met. Chem. 21, 105–111 (1996)
5. Somaiah, P.V., Bal Reddy, K., Sethuram, B., Navaneeth Rao, T.: Kinetics and mechanism of oxidation
of aryl b-styryl ketones by osmium tetroxide in sulphuric acid–acetic acid medium. A structure-reac-
tivity correlation study. Transit. Met. Chem. 18, 58–60 (1993)
2
2
6. Sondu, S., Sethuram, B., Rao, T.N.: Kinetics and mechanism of Rh(III)-catalysed oxidation of 1,2-
glycols by acid bromate. Transit. Met. Chem. 15, 78–80 (1990)
7. Sarala, G., Jayaprakash Rao, P., Sethuram, B., Navaneeth Rao, T.: Kinetics and mechanism of
osmium(VIII)-catalyzed oxidation of phosphite by diperiodatoargentate(III) in alkaline medium.
Transit. Met. Chem. 13, 113–115 (1988)
2
8. Laxmi Venkat Rao, K., Prasada Rao, M., Sethuram, B., Navaneeth Rao, T.: Oxidations by iron(VI).
Kinetic study of uncatalysed and osmium(VIII) catalysed oxidation of dimethyl sulphoxide in alkaline
medium. Transit. Met. Chem. 14, 165–168 (1989)
123

394
J Solution Chem (2016) 45:371–394
2
3
3
3
9. Lingamurthy, S., Sethuram, B., Navaneeth Rao, T.: Study of photoelectrochemical cells: micellar effect
2
?
on the [Ru(bpy)
1992)
3
]
-sensitized photoreduction of dyes by Na
2
EDTA. Transit. Met. Chem. 17, 506–508
(
0. Ramesh, B., Sadanand, D.T., Gopikanth Reddy, S., Venkata Swamy, K., Saiprakash, P.K.: Hydro-
genation of 1-alkenes catalysed by anchored montmorillonite palladium(II) complexes: a kinetic study.
Transit. Met. Chem. 25, 639–643 (2000)
1. Ramesh, K., Shylaja, S., Rajanna, K.C., Giridhar Reddy, P., Saiprakash, P.K.: Polyethylene glycol-
mediated kinetic study of nitrodecarboxylation of a, b-unsaturated acids by Blau’s Fe(III) bipy com-
plex. Int. J. Chem. Kinet. 46, 126–137 (2014)
2. Aneesa, F., Rajanna, K.C., Venkateswarlu, M., Rajendar Reddy, K., Arun Kumar, Y.: Efficient catalytic
activity of transition metal ions in Vilsmeier-Haack reactions with acetophenones. Int. J. Chem. Kinet.
4
5, 721–733 (2013)
3. Mendham, J., Denney, R.C., Barnes, J.D., Thomas, M.J.K.: Vogel’s Quantitative Chemical Analysis,
th edn. Prentice Hall, New York (2000)
4. Benesi, H., Hildebrand, J.: A spectrophotometric investigation of the interaction of iodine with aromatic
hydrocarbons. J. Am. Chem. Soc. 71, 2703–2707 (1949)
3
3
6
3
3
5. Rao, C.N.R.: Ultraviolet and Visible Spectroscopy. Butterworths, London (1961)
6. Ketelaar, J.A., von de Stolpe, C., Goud-Smit, A., Dzubas, W.: Spectrophotometric study of the solvation
of iodine in dioxan solution II. Rec. Trav. Chim 71, 1104–1114 (1952)
3
3
7. Laidler, K.J.: Chemical Kinetics, 3rd edn. Harper and Row, New York (1987)
8. Laidler, K.J., Meiser, J.H.: Physical Chemistry, 3rd edn. Houghton Mifflin, New York (1999)
1
23