Palladium-Catalyzed Deformylation Reactions with Detailed Experimental and in Silico Mechanistic Studies

Article abstract of DOI:10.1002/ejoc.201700451

A facile, efficient, and general deformylation reaction with a wide-ranging functional group compatibility has been developed with palladium acetate as a precatalyst under exogenous ligand-free conditions. The mechanistic details of the palladium-catalyzed deformylation reaction have been outlined on the basis of a combination of experimental and computational studies. The heterogeneous pathway is predominant for the deformylation, and homogeneous catalysis occurs to a lesser extent. This ligand-free catalytic cycle is proposed to undergo oxidative addition, migratory extrusion, and reductive elimination as the key steps. Kinetic studies reveal a first-order rate dependency with respect to the aldehyde. Furthermore, kinetic isotope effects, competition experiments, and Hammett studies suggest that the migratory extrusion step is the rate-determining step. For the homogeneous pathway, the experimental findings are also supported by DFT studies.

Full text of DOI:10.1002/ejoc.201700451

A Journal of
Accepted Article
Title: Palladium catalyzed deformylation reaction with detailed
experimental and in-silico mechanistic studies
Authors: Debabrata Maiti, Atanu Modak, Sujoy Rana, and Ashwini K.
Phukan
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700451
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700451
Supported by

European Journal of Organic Chemistry
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Palladium catalyzed deformylation reaction with detailed
experimental and in-silico mechanistic studies
a
a
b
a
Atanu Modak , Sujoy Rana , Ashwini K. Phukan *, Debabrata Maiti *
Abstract: A facile, efficient and general deformylation reaction has
been developed using palladium acetate as precatalyst under
exogenous ligand-free conditions with a wide range of functional
group compatibility. Mechanistic details of the palladium catalyzed
deformylation reaction have been outlined based on the combination
of experimental and computational studies. The heterogeneous
pathway is predominant for the deformylation along with the existence
of lesser extent of homogeneous catalysis. This ligand-free catalytic
cycle is proposed to undergo oxidative addition, migratory extrusion
workers reported the palladium catalyzed decarbonylation of
acyl chlorides and aldehydes, but this protocol also required
high temperature.9
In 2012, our group communicated a simple and
efficient methodology for the deformylation of aldehyde with
Pd(OAc)
2
as catalyst under exogenous ligand-free
conditions.10 A broad range of substrates were studied using
the reaction protocol. Moreover, this reaction was utilized as
11a
a key step of one pot dehydroxymethylation reaction.
,
Recently we addressed decarbonylation reaction using catalytic
st
and reductive elimination as key steps. Kinetic studies reveal the 1
amount of silica supported palladium nanoparticles with broad
substrate scope.1
1b
Amongst other metals, expensive
order rate dependency with respect to aldehyde. Furthermore, kinetic
isotope effect, competition experiment and Hammett study suggest
that the migratory extrusion step is the rate determining step. In case
of homogenous pathway, the experimental findings have also been
supported by DFT studies.
rhodium,12 iridium metal salts are known for deformylation
13
reaction. A stoichiometric amount of Wilkinson’s complex,
1
2a,12b
RhCl(PPh
3
)
3
or
phosphine
chelated
Rh-
complexes1
2c,12d
were utilized for desired deformylation
reaction. Using the catalytic amount of Wilkinson’s catalyst,
deformylation was achieved only at elevated reaction
1
2e,12f
temperatures (>160 °C)
or in the presence of a CO
scavenger.1 A ruthenium(II)porphyrin complex catalyzing
2g
Introduction
deformylation reaction is also known in the literature.14
Development
of
a
transition
metal
mediated
Fristrup et al have extensively demonstrated the
combined experimental and computational studies for
rhodium catalyzed deformylation in 2008, where oxidative
addition, migratory extrusion, and reductive elimination were
established as key steps for the catalytic cycle.1 However,
the mechanism of palladium catalyzed deformylation is yet to
be analyzed. Herein, we describe a combined experimental
defunctionalization reaction has immense significance in
metal catalysed coupling reactions for their similarity in
reaction pathways. Since,
intermediate is responsible for both the reaction, the
mechanistic understanding of the defunctionalization
reaction can give rise to the discovery of new synthetic
a
common metal-organic
2f
1
15
transformations. In this context, the metal mediated
and in silico studies with the goal of gaining insights into the
deformylation reaction, involving the extrusion of carbonyl
group as carbon monoxide has played an important role in
the development of novel strategies. An effective
deformylation reaction can also act as an in situ carbon
monoxide source in CO insertion reactions (eg. Pauson
Khand reaction) as metal–CO intermediate is the key
species in both transformations.2 On the other hand, the
removal of aldehyde moiety has direct implication in
synthetic chemistry viz. the production of fuel grade organic
materials via deformylation of biomass degraded materials.3
Deformylation also enables the aldehyde moiety to act as a
palladium catalyzed deformylation reaction.
Results and Discussion
During our initial investigation,10 it was found that 3-8 mol%
palladium acetate afforded good to excellent yields of the
deformylated product in cyclohexane at 110-140 ºC.
Interestingly, the yield of the deformylated product
decreased in the presence of an exogenous ligand.10
Although the addition of molecular sieves (MS, 4 Å) improved
the yield, later it was found that molecular sieves have no
effect while using dry solvents.
transient directing group in
a
particular organic
4
transformation (Diels-Alder reaction , domino oxa-Michael-
aldol reaction etc.) for better reactivity and selectivity.6
Applying these strategies, deformylation reaction has been
carried out as a vital step in a number of natural product
5
With the optimized conditions, a variety of aryl aldehydes
(1a
-1i), heterocyclic aldehydes (1j-1p), aliphatic(1s, 1t) and
7
syntheses. In 1960, Wilt first reported the Pd/charcoal
alkenyl aldehydes (1q
,
1r) were deformylated successfully in
catalyzed removal of aldehydes albeit at elevated
10
good to excellent yields. The optimized deformylation
protocol showed its compatibility towards a sterically
demanding ortho-disubstituted aldehyde (table 1, entry 1c).
Aldehydes with electron donating as well as electron
withdrawing groups were successfully deformylated with
8
temperature (more than 180 ˚C). Later, in 1965 Tsuji and co-
[
a] Atanu Modak, Sujoy Rana and Prof. Debabrata Maiti; Department of
Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai-400
satisfactory yields (entries 1d-1i). Interestingly, the
0
76,
http://www.chem.iitb.ac.in/~dmaiti/
b] Prof. Ashwini K. Phukan; Department of Chemical Sciences, Tezpur
India.
E-mail:
dmaiti@chem.iitb.ac.in;
Homepage:
carboxylic acid moiety remained intact under the present
reaction conditions (entry 1g). Also five- and six- membered
[
heterocyclic
deformylation (entries 1j
carboxaldehydes
1p).
were
amenable
to
University,
ashwini@tezu.ernet.in;
http://www.tezu.ernet.in/dcs/people/faculty/~ashwini/
Supporting information for this article is given via a link at the end of
the document
Napaam-784028,
Assam,
India.
E-mail:
-
Nitrogen containing
Homepage:
heterocyclic aldehydes, even with unprotected nitrogen
a.
centre (NH) were successfully deformylated (entries 1k and
2
1
p
). Despite bearing activated olefinic sp C–H bond, alkenyl
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European Journal of Organic Chemistry
10.1002/ejoc.201700451
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aldehydes yielded anticipated deformylated product with
good yields (entries 1q and 1r). Moreover, aliphatic
naphthaldehyde. Furthermore, the controlled experiments
with corresponding acids, with or without a base, did not
produce the decarboxylated product under experimental
condition. These experimental observations suggest that
deformylation did not undergo oxidation-decaboxylation
pathway. Moreover, CO was detected from the Pd-catalyzed
deformylation reaction by UV-vis spectroscopic study.16
When the gas mixture from reaction was injected to a
myoglobin-Fe2 aqueous solution (soret peak at 434 nm in
aldehydes (entries 1s
,
1t
)
resulted in the desired
deformylated products overriding the competitive β–H
elimination reaction after carbon monoxide elimination (entry
1t).
Table 1. Representative substrate scope for palladium catalyzed
deformylation of aldehydes10
+
2
+
UV-vis), myoglobin-Fe –CO complex was formed and
showed characteristic peaks at 423 nm in soret region and
also at 542 nm and 578 nm.1 All these observations indeed
suggested that carbon monoxide was released from the aldehyde
group in course of the reaction.
6a
4
23 nm
A
402 nm
3+
myoglobin (Fe )
0.5
0.4
0.3
0.2
0.1
0.0
2+
myoglobin (Fe )
2+
4
34 nm
myoglobin (Fe )-CO
5
55 nm
5
42 nm
578 nm
a
aldehyde (0.5 mmol), MS (150 mg), and Pd(OAc)
2
(8 mol%), cyclohexane
, 140 °C; 16 mol% Pd(OAc) , 140 °C;
, 120 °C;
b
c
(
1.3 mL), 140 °C; 3 mol% Pd(OAc)
yield was calculated by gas chromatography; 8 mol% Pd(OAc)
2
2
350
400
450
500
550
600
650
700
750
800
d
f
e
2
h
1
2 mol% Pd(OAc)
, 120 °C.
2
, 110 °C; g5 mol% Pd(OAc)
2
, 140 °C; 12 mol%
Wave length (nm)
Fig 1 Absorbance spectra in soret and visible regions for met-myoglobin
Pd(OAc)
2
3
+
2+
(
Fe
) (black), deoxygenated myoglobin (Fe ) (blue) and carbon
Mechanistic studies
monoxide-myoglobin (Fe2+) adduct (red).
The kinetic studies with 4-methyl benzaldehyde revealed a
2
well fitted (R = 0.99) exponential decay with time. By plotting
the initial rate vs substrate concentration, a straight line was
obtained with slope 0.95 (Figure 3) which suggested that the
st
deformylation reaction follows a 1 order kinetics with
respect to the aldehyde.
0.14
0.12
0.10
0.08
0.06
0.04
0.02
Equation
Adj. R-Square
y = A1*exp(-x/t1) + y0
0.99772
Scheme
1
Labelling experiment, control experiment and carbon
0.00
0
2
4
6
8
10
12
14
monoxide detection experiment in palladium catalyzed deformylation
reaction.
time (h)
In order to gain mechanistic insights into the transformation,
at first, we performed deuterium labelling experiment where
Fig 2 Decay of 4-methyl benzaldehyde with respect to time. (reaction was
done with 0.25 mmol aldehyde, 10 mol% Pd(OAc) in 2 mL cyclohexane)
2
1
1
1
-naphthaldehyde-α-d resulted 1-naphthalene-d . Notably,
The comparative kinetic studies revealed that the
we failed to detect CO from the deformylation of 1-
2
1
deformylation reaction of 4-methylbenzaldehyde-α-d is
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European Journal of Organic Chemistry
10.1002/ejoc.201700451
FULL PAPER
relatively slower than that of 4-methylbenzaldehyde.
A
concentration of aldehydes at time = 0 and time = t
respectively). An excellent linear fitting also re-established
the reaction first order with respect to the aldehyde (figure 5).
deuterium isotope effect k
H D
/k of 1.63 is observed which is
12f
similar to the rhodium catalyzed deformylation reaction.
The relatively small value of kinetic isotope effect (KIE)
indicates that C–H bond breaking may not be involved in the
transition state related to the rate determining step.
-
-
-
-
-
-
3.6
3.8
4.0
4.2
4.4
4.6
Equation
Adj. R-Squar
y = a + b*x
0.99827
Value
Standard Error
0.0 51 29 79 52
B
ISn l toe pr ec ept - 01 . 95 56 89 27 91
Fig 5 Relative kinetic plot of decarbonylation of para-substituted
benzaldehydes (cH0 implies the concentration of benzaldehyde at time =
0
H
; c implies the concentration of benzaldehyde at time = t; cx0 implies the
-
3.2
-3.0
-2.8
-2.6
-2.4
-2.2
concentration of para-substituted benzaldehyde at time = 0; c
concentration of para-substituted benzaldehyde at time = t).
H
implies the
ln [aldehyde]
Fig 3 Plot for ln(rate) vs ln[aldehyde] for 4-methyl benzaldehyde.
With the slope (k
X H
/k ) of these first order kinetic curves (figure
5
), Hammett plot (figure 6) has been obtained by correlating
–
.
18
0.14
0.12
0.10
0.08
0.06
0.04
0.02
p p p
the different sets of σ (σ , σ , σ ) values from literature.
Equation
Adj. R-Square 0.98881
-tolyl-CHO
-tolyl-CDO Equation
Adj. R-Square
y = A1*exp(-x/t1) + y0
The best linear fit (R2 = 0.99) has been obtained by
4
4
–
considering σ
–
p
values of –Cl, –Me, –NMe
2
and σ
p
values of
y = A1*exp(-x/t1) + y0
0.99772
NO , –CN, –CO
2
2
Me for their extended (–ve) mesomeric
effect (figure 6). The generation of a small negative charge
at the transition state (TS) of the rate determining step (RDS)
is established from the observed positive slope of +0.59 from
the Hammett plot. All these informations indeed suggested
that an oxidative addition at the C–H bond of aldehyde and
the migratory extrusion of CO to the palladium centre were
involved in the catalytic cycle as both of these steps can lead
to the complex with more negative charge.
0
2
4
6
8
time (h)
1
Fig 4 Comparative kinetic study of 4-methylbenzaldehyde-α-d (blue line)
and 4-methylbenzaldehyde (red line). (reaction was done with 0.25 mmol
aldehyde, 10 mol% Pd(OAc) in 2 mL cyclohexane)
2
Scheme
2 Competition studies for the decarbonylation of para-
substituted benzaldehydes vs benzaldehyde
Fig 6 Hammett plot for decarbonylation of para-substituted benzaldehyde.
Furthermore, to investigate electronic dependence, we have
studied relative kinetics of a set of para–substituted
Furthermore, to find out any metal contamination in the
deformylation reaction, we carried out the atomic absorption
spectroscopy on Pd-catalyst, which failed to detect any Ni-,
benzaldehydes (–NO
2 2 2
, –CN, –CO Me, –Cl, –Me, –NMe )
versus benzaldehyde through competition experiments
12f,17
Co-, Ru-, Rh- and Ir.
optimization, we have seen that Pd
In the course of palladium salt
(dba) , a palldium (0) salt
(scheme 2).
Electron deficient aldehydes underwent a
2
3
faster rate in deformylation reaction compared to the electron
rich ones. Considering the first order kinetics of this reaction
shows the same reactivity with a little decrease in yield with
respect to palladium acetate in the absence of an oxidant.10
This experiment implies the probability of Pd(0)-Pd(II) cycle
for the catalytic activity. We conceive that palladium acetate
with respect to the aldehyde, we have plotted ln(c
substituted benzaldehydes against the same values of
benzaldehyde at different reaction times (c and c are the
0
/c) of para
0
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European Journal of Organic Chemistry
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undergoes reduction to palladium (0) under prolonged
heating at 130 ˚C in cyclohexane solvent and takes part in
catalytic cycle. In order to test the heterogeneity of the
reaction we performed the mercury poison test, filtration test
and collected TEM images of the aliquots.19 In the presence
of mercury metal, the reaction was completely quenched and
resulted the full recovery of starting material. But, from the
mercury poison test it is sometimes skeptical to judge the
heterogeneity of the reaction.20 TEM images of the reaction
mixture showed the formation of palladium nano particles
migratory extrusion of carbon monoxide from the acyl-Pd(II)
takes place followed by a successful reductive elimination
which yields the deformylated product and Pd(0)–CO
complex.
monoxide is replaced by aldehyde molecule. Reactions with
deuterated solvents (d -DMSO, CDCl , C andCD COOD)
To regenerate the catalytic cycle, carbon
6
3
6
D
6
3
have not resulted any deuterium incorporation in the starting
material or final product. Such an experiment also indirectly
supported the reaction pathway depicted in Figure 9.
(figure 7). The recovered nanoparticles exihibited the
catalytic property in the next batch of deformylation reaction.
However, in filtration test it has been observed that the
palladium also exist in solution state. But the majority of the
reaction goes through heterogeneous pathway as, the
reaction rate of the homogeneous state is ~11 times slower
than the heterogeneous state (figure 8).19
Fig 9 Catalytic cycle for decarbonylation of aldehyde.
DFT Calculation for the reaction in homogenous pathway
In order to support the experimental findings, we studied the
catalytic cycle using Density Functional Theory.20 The first
step of the catalytic cycle (Figure 10) involves oxidative
Fig 7 TEM image of the deformylation reaction residue (after reaction time
t=24 h).
addition of one of the C–H bonds of (PhCHO)
2
Pd, 1 to the
Pd atom yielding via a three-center transition state, TSOA
2
.
reaction profile with unfiltered part
reaction profile with filtered part
This step is slightly endergonic by 2.2 kcal/mol (4.0 kcal/mol
in the gas phase). The product obtained after oxidative
addition is destabilized by only 1.6 kcal/mol relative to the
100
starting compound. The minimum energy structure of
2
exhibits a T- shape geometry while a pseudo trigonal planar
structure is obtained for TSOA (Figure S1, Supporting
Information). The next step in the catalytic cycle is migratory
extrusion of CO leading to the formation of a four coordinate
80
60
40
20
0
square planar complex
TSME. The barrier height for the formation of
to be 29.2 kcal/mol (31.3 kcal/mol in the gas phase).
Complex has a relative Gibbs free energy of 2.1 kcal/mol
3
via a high energy transition state,
3
is calculated
Equation
y = A1*exp(-x/t1) + y0
3
Adj. R-Squar 0.958 0.9660
Value Standard Error
B
B
B
(3.8 kcal/mol in the gas phase). The transition state for
migratory extrusion of CO (TSME) has a planar geometry with
a three-membered metallacycle consisting of the carbonyl
carbon, Pd and the ipso carbon atom of the phenyl ring
y0
A1
t1
96.161
-101.4
222.06
5.33641
7.88608
39.03055
0
200
400
600
800
1000
1200
1400
1600
(Figure S1). After the formation of 3, reductive elimination of
time (min)
benzene takes place through another three-center transition
state, TSRE. Similar to the formation of the oxidative addition
product 2, the formation of 4 is also marginally endergonic
Fig 8 Deformylation reaction profile of unfiltered and filtered reaction
mixtures (reaction was done with 1.0 mmol naphthaldehyde, 10 mol%
involving a barrier of 2.3 kcal/mol (0.4 kcal/mol in the gas
phase) indicating very facile elimination of benzene. The
DFT computational study suggests that the migratory
extrusion step is the rate determining step which is re-
established by the experimental findings of Hammett study
and the kinetic isotope effect.
2
Pd(OAc) , molecular sieves (4 Å) in 6 mL cyclohexane, filtration was done
at the time = 75 min)
In homogeneous condition, substrate is considered to
coordinate with palladium (0). Palladium (0) then undergoes
oxidative addition at the aldehydic C–H bond forming the
palladium (II) acyl hydride complex (figure 9). In next step,
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European Journal of Organic Chemistry
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(c) Following general procedure A, 1-naphthoic acid (0.5 mmol, 86 mg), 8
2 3
mol% palladium acetate (0.04 mmol, 9 mg), K CO (0.75 mmol, 104 mg)
and 1.3 mL cyclohexane were used. After reaction, mixture was
characterized by GC-MS. No trace of naphthalene was found by GC-MS.
(d) Following general procedure B, 1-naphthoic acid (0.5 mmol, 86 mg), 8
mol% palladium acetate (0.04 mmol, 9 mg), K CO (0.75 mmol, 104 mg)
2
3
and 1.3 mL cyclohexane were used. After 24 h, reaction mixture was
characterized by GC-MS. No trace of naphthalene was found by GC-MS.
Carbon monoxide detection experiment.
A clean, oven-dried screw cap schlenk reaction tube with magnetic stir–
bar was charged with molecular sieves (4Å, 225 mg), palladium acetate (8
mol%, 27 mg). The tube was then evacuated and back-filled with nitrogen.
The evacuation/backfill sequence was repeated two additional times.
Under a counter flow of nitrogen, 1-naphthaldehyde (1.5 mmol, 234 mg,
2
04 µL) was added, followed by cyclohexane (3 mL) by syringe. The tube
was tightly closed by screw cap and placed in a preheated oil bath at 140
C. The reaction mixture was vigorously stirred for 24 h. The reaction
˚
mixture was cooled to room temperature then from the closed reaction
tube gas mixture was taken out using a Hamilton 5 mL gas syringes.
Preparation of deoxygenated myoglobin (Fe2+) solution. In a two–necked
3+
round bottom flask met–myoglobin (Fe ) was taken then 10 mL of distilled
water was added. Two necks were closed with septa. Then the solution
was degassed after cooling at –78 °C (dry ice/acetone) and backfilled with
nitrogen. This evacuation/backfill sequence was repeated two additional
times. Absorbance spectra of this solution in soret region showed peak at
Fig 10. Calculated free energy profile for the decarbonylation of
benzaldehyde using cyclohexane. The calculated Gibbs free energy
values in the gas phase are given within parenthesis.
4
2 2 4
09 nm. Aqueous solution of Na S O was added to this myoglobin
3+
2+
solution using syringe to reduce Fe to Fe . Absorbance spectra of this
solution in soret region showed peak at 434 nm. It is the characteristic
peak of Myoglobin (Fe ) complex.
Conclusions
2+
In summary, we have illustrated the mechanistic details of
palladium catalyzed deformylation reaction with the combination
of experimental and computational studies. An oxidative addition
at the C–H bond of aldehyde, followed by rate determining CO
transfer to the palladium center and reductive elimination to form
the final deformylated product have been proposed with the help
of rate kinetics, kinetic isotope effect, competition experiments,
Hammett study and DFT calculations. The heterogeniety test
revealed the existence of both the homogenous and
heterogenous pathway in the reaction condition.
2+
Preparation of myoglobin (Fe )–CO complex. Gas filled syringe was
2+
injected into this aqueous myoglobin (Fe ) solution. Absorbance spectra
of this solution showed peak at 423 nm soret region and also the peaks at
542 nm and 578 nm. These are the characteristic peaks of myoglobin
2+
(Fe )–CO complex.
Decay plot for deformylation of 4-methylbenzaldehyde. A clean, oven-
dried screw cap schlenk reaction tube with previously placed magnetic
stir–bar was charged with molecular sieves (4Å, 150 mg), 4-
methylbenzaldehyde (0.25 mmol, 30 mg), palladium acetate (10 mol%,
0.025 mmol, 5.6 mg. Cyclohexane (2 mL) was added to this mixture by
syringe. The tube was tightly closed by screw cap and placed in a
preheated oil bath at 130 ˚C. The reaction mixture was vigorously stirred
for different reaction times, putting the reactions at different times.
Conversion of aldehyde and yield of the deformylated product was
determined by gas chromatography using naphthalene as internal
standard.
Experimental Section
Kinetic isotope effect study. A clean, oven-dried screw cap schlenk
reaction tube with previously placed magnetic stir-bar was charged with
molecular sieves (4Å, 150 mg), 4-methylbenzaldehyde -α-d1 (0.25 mmol,
General Procedure A for deformylation of aldehydes with 3–16 mol%
palladium catalyst loading under air. A clean, oven-dried screw cap
reaction tube with magnetic stir-bar was charged with molecular sieves (4Å,
3
1 mg), palladium acetate (10 mol%, 0.025 mmol, 5.6 mg. Cyclohexane
(2 mL) was added to this mixture by syringe. The tube was tightly closed
1
50 mg), aldehyde (0.5 mmol) and palladium acetate (5–16 mol%).
by screw cap and placed in a preheated oil bath at 130 ˚C. The reaction
mixture was vigorously stirred for different reaction times, putting the
reactions at different times. Conversion of aldehyde and yield of the
deformylated product was determined by gas chromatography using
naphthalene as internal standard.
Cyclohexane (1.3 mL) was added to this mixture by syringe. The tube was
tightly closed by screw cap and placed in a preheated oil bath at required
temperature. The reaction mixture was vigorously stirred for 24 h.
General Procedure B for deformylation of aldehydes with 5–16 mol%
palladium catalyst loading under nitrogen. A clean, oven-dried screw
cap reaction tube with magnetic stir-bar was charged with molecular
sieves (4Å, 150 mg), aldehyde (0.5 mmol), palladium acetate (5–16 mol%).
The tube was then evacuated and back–filled with nitrogen. The
evacuation/backfill sequence was repeated two additional times. Under a
counter flow of nitrogen, remaining liquid reagents were added, followed
by cyclohexane (1.3 mL) by syringe. The tube was tightly closed by screw
cap and placed in a preheated oil bath at required temperature. The
reaction mixture was vigorously stirred for 24 h.
Reactions in deuterated solvents.
(
a) Following general procedure A, 4-nitrobenzaldehyde (0.025 mmol, 38
mg), 8 mol% palladium acetate (0.02 mmol, 5 mg), 0.5 mL cyclohexane,
.5 mL Benzene-d1 were used at 135 °C. After reaction, mixture was
0
1
1
characterized by GC-MS. No trace of nitrobenzene-d or -d -4-
nitrobenzaldehyde were found by GC-MS.
(
b) Following general procedure A, anthracene–9–carboxaldehyde (0.05
mmol, 104 mg), 8 mol% palladium acetate (0.04 mmol, 9 mg), 1.3 mL
cyclohexane, 100 µL DMSO-d were used at 135 °C. After reaction,
Reactions with corresponding acid.
6
1
1
(a) Following general procedure A, 1-naphthoic acid (0.5 mmol, 86 mg), 8
mixture was characterized by GC-MS. No trace of anthracene-d or -d
-anthracene-9-carboxaldehyde was found by GC-MS.
mol% palladium acetate (0.04 mmol, 9 mg) and 1.3 mL cyclohexane were
used. After reaction, mixture was characterized by GC-MS. No trace of
naphthalene was found by GC-MS.
(c) Following general procedure A, 1-naphtaldehyde (0.01 mmol, 16 mg),
10 mol% palladium acetate (0.001 mmol, 2.2 mg), 75 mg moleculer sieve
(
1
4Å), 0.5 mL cyclohexane, 100 µL CD
3
COOH were used at 130 °C. After
(b) Following general procedure B, 1-naphthoic acid (0.5 mmol, 86 mg), 8
1
2h, mixture was characterized by GC–MS. No trace of naphthalenee-d
mol% palladium acetate (0.04 mmol, 9 mg) and 1.3 mL cyclohexane were
used. After reaction, mixture was characterized by GC-MS. No trace of
naphthalene was found by GC-MS.
1
or -d -1- naphtaldehyde were found by GC–MS. Naphthalene yield 65%.
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European Journal of Organic Chemistry
10.1002/ejoc.201700451
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(
1
(
d) Following general procedure A, 1-naphtaldehyde (0.01 mmol, 16 mg),
0 mol% palladium acetate (0.001 mmol, 2.2 mg), 75 mg moleculer sieve
4Å), 0.5 mL cyclohexane, 100 µL CDCl were used at 130 °C. After 12h,
mixture was characterized by GC-MS. No trace of naphthalene-d or d -
- naphtaldehyde were found by GC-MS. Naphthalene yield 51%.
We thank INSA-India (SP/YSP/98/2014) for funding.
Financial support received from CSIR-India (fellowship to
A.M. and S.R.) is gratefully acknowledged.
3
1
1
1
Mercury poison test:
An oven-dried screw-cap test tube containing a stirring bar was charged
with 1-naphthaldehyde (78 mg, 0.5 mmol), Pd(OAc) (11.2 mg, 0.05 mmol),
2
Keywords: deformylation • CO detection • Hammett Plot •
reaction kinetics • DFT calculation
molecular sieves (4 Å) (200 mg), and cyclohexane (2 mL). Then 200 mg
of Hg and 0.5 mmol of n-decane (as internal standard for gas
chromatography) were added to this reaction mixture and the mixture was
stirred in a pre-heated oil bath (130 ºC). The yield of the product was
checked by gas chromatography taking the reaction aliquot at a 4 hour
interval. Up to 24 hour no conversion of aldehyde was observed.
Filtration test.
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An oven-dried screw-cap test tube containing a stirring bar was charged
with 1-naphthaldehyde (156 mg, 1 mmol), Pd(OAc) (22.4 mg, 0.1 mmol),
2
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ºC). The reaction was stirred for 75 min and yield was measured. Then
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homogenous pathway also exist in lesser extent.
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[
TEM experiment.
An oven-dried screw-cap test tube containing a stirring bar was charged
with 1-naphthaldehyde (78 mg, 0.5 mmol), Pd(OAc) (11.2 mg, 0.05 mmol),
2
molecular sieves (4 Å) (200 mg), and cyclohexane (2 mL). Then the
reaction mixture was stirred at pre-heated oil bath. After 1.5 hour and 24 h
[
[
[
1
mL of aliquots were taken out. Another 10 mL of cyclohexane was added
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A clean, oven–dried screw cap schlenk
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molecular sieves (4Å, 150 mg), benzaldehyde (0.25 mmol, 26.6 mg), 4-X
benzaldehyde (0.25 mmol), palladium acetate (8 mol%, 0.04 mmol, 9 mg),
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2
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Computational Details. All the structures were completely optimized
using the hybrid DFT method, labeled as M06 without any symmetry
2
1
constraints.
We have used the relativistic small-core ECP of
2
2
Stuttgart/Dresden (SDD) for the palladium and 6-31+G* basis set for
other atoms as implemented in the Gaussian 09 suite of programs.23
Frequency calculations were performed at the same level of theory to
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structures were verified as minimum by confirming that their respective
Hessian (matrix of analytically determined second order derivative of
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stationary points with only one negative frequency. The polarized
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[19] see supporting information.
,
9
2
4
continuum model (PCM) had been employed for the solution phase
calculations using cyclohexane as the solvent. The discussion of the
catalytic cycle involves solvent corrected Gibbs free energies even though
they were also calculated in the gas phase.
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European Journal of Organic Chemistry
10.1002/ejoc.201700451
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European Journal of Organic Chemistry
10.1002/ejoc.201700451
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Entry for the Table of Contents
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Deformylation
a
a
Atanu Modak , Sujoy Rana , Ashwini K.
b
a
Phukan *, Debabrata Maiti *
Page No. – Page No.
Palladium
reaction with detailed experimental and
in-silico mechanistic studies
catalyzed
deformylation
A mechanistic details of the palladium acetate catalyzed deformylation reaction have been
outlined herein. Based on kinetic studies, competition experiments and Hammett study, a
plausible catalytic cycle have been proposed. From heterogeneity test, existence of both
the states have been suggested. DFT calculations also have been carried out to support
the catalytic pathway in homogenous condition.
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