Supported Palladium Nanoparticles Catalyzed Reductive Carbonylation of Nitroarenes to N-Arylformamides

Article abstract of DOI:10.1002/adsc.201700944

A facile reductive carbonylation reaction of nitroarenes to N-arylformamide synthesis was investigated under polymer supported palladium (Pd@PS) nanoparticles catalyzed conditions. Dual role of oxalic acid dihydrate ((CO₂H)₂ ? 2H₂O) as H₂ source for hydrogenation and CO source for carbonylation reaction for desired products synthesis was critically investigated under favorable DMF solvent conditions. Several cross experiments were performed to establish the best possible hypothesis for the proposed mechanism and understanding about the involvement of CO in the reaction pathway. Further, ortho-substituted nitroarenes were found to be highly specific for facile para-hydroxylation to give corresponding para-hydroxy N-aryl formamides. (Figure presented.).

Full text of DOI:10.1002/adsc.201700944

Title: Supported Palladium Nanoparticles Catalyzed Reductive
Carbonylation of Nitroarenes to N-Arylformamides
Authors: Vandna Thakur, Ajay Kumar, Nishtha Sharma, Arun Shil, and
Pralay Das
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700944
Link to VoR: http://dx.doi.org/10.1002/adsc.201700944

10.1002/adsc.201700944
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Supported Palladium Nanoparticles Catalyzed Reductive
Carbonylation of Nitroarenes to N-Arylformamides
Vandna Thakura,b , Ajay Kumara, Nishtha Sharmaa, Arun K. Shila and Pralay Dasa,b*
a
Natural Product Chemistry & Process Development Division, CSIR-Institute of Himalayan Bioresource Technology,
Palampur-176061, H.P., India, Fax: +91-1894-230433, E-mail: pdas@ihbt.res.in, pdas_nbu@yahoo.com
Academy of Scientific and Innovative Research, New Delhi, India
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
nitroarenes using CO gas as C1 source to synthesize
nitroarenes to N-arylformamide synthesis was investigated various amide moieties.[10] Moreover, DMF has also
Abstract. A facile reductive carbonylation reaction of
under polymer supported palladium (Pd@PS) nanoparticles
catalyzed conditions. Dual role of oxalic acid dihydrate
((CO2H)2.2H2O) as H2 source for hydrogenation and CO
source for carbonylation reaction for desire products
synthesis was critically investigated under favorable DMF
solvent conditions. Several cross experiments were
performed to establish the best possible hypothesis for the
proposed mechanism and understanding about the
involvement of CO in the reaction pathway. Further, ortho-
substituted nitroarenes were found to be highly specific for
facile para-hydroxylation to give corresponding para-
hydroxy N-aryl formamides.
served as alternative CO source in various transition
metal catalyzed reactions.[11]
In our continuous thrust to facilitate the use of
heterogeneous transition metal NPs as catalyst to
utilize in situ generated small molecules, we have
successfully demonstrated the use of oxalic acid as C1
source for carboxylation, carbonylative cyclization
reaction and pyrrolone-fused benzosuberenes
syntehsis.[12]
Herein, Pd@PS NPs was used as efficient catalyst to
synthesize N-arylformamides from nitroarenes using
bench stable oxalic acid in DMF as H2 and C1 source.
Moreover, DMF tends to decompose under acidic
conditions at high temperature giving CO or as a
formylating agent and hence may play crucial role in
N-arylformamide synthesis.[9, 11] Also, in our previous
report, we have established the role of oxalic acid as
CO source with 13C labelled experiment in presence
of DMF as solvent.[12b] Moreover, we have discussed
the effect of substrate at the ortho-position of
nitroarenes facilitating the nucleophilic attack of
hydroxy ion (OH- generated from water) on the
aromatic ring to give corresponding p-hydroxy-N-
arylformamides. To the best of our knowledge, this is
also the first such report for p-hydroxylation and is
controlled by the functional group at the ortho-
position of nitroarenes.
The Pd@PS catalyst was developed through
reduction and deposition approach using Amberlite
IRA 900 Cl‾ resin as polymer support (PS) and
Pd(OAc)2 salt as metal precursor (supporting
information, ESI). The prepared catalyst was washed
and dried under vacuum and well characterized by
SEM, EDS, HRTEM, SAED and XRD studies as
discussed in our earlier reports.[12a, d]
Keywords: Oxalic acid; hydrogenation, carbonylation; N-
arylformamide; heterogeneous catalyst; hydroxylation
N-Arylformamides have drawn great interest
because of their application in the synthesis of
biologically active scaffolds.[1] These have been
widely used as precursor in pharmaceuticals as
antibacterials and cancer chemotherapeutic agents and
agrochemical industry as fungicides, herbicides etc.[2,
3]
Moreover, N-formyl compounds also behave as
Lewis bases catalyzing allylation reactions.[4]
Typical route to synthesize N-arylformamides
comprise one pot reductive formylation of nitroarenes
to N-arylformamides using HCO2H or its derivatives.
The different reaction approaches involving
Fe/HCO2NH4, Pd/C-HCO2H, Zn-HCO2NH4 and
Au/TiO2-HCO2NH4 have been well established,[5]
replacing the hazardous reagents or harsh reaction
conditions.[6] The hydrogenation of nitroarenes to
amines[7] and their subsequent formylation using
formic
acid
or
its
derivatives,
CO2-
Initially, to assess the optimal reaction conditions,
a detailed investigation into screening of different
solvents, catalyst loading, suitable quantity of oxalic
acid ((CO2H)2.2H2O), reaction time and temperature
was carried out. The effect of solvents on the reaction
is highly profound as the reaction is favoured by polar
solvents while DMF providing best results (Table 1,
H2/hydrosilanes/boranes and paraformaldehyde has
also been employed to give N-arylformamides.[8]
Recently, DMF has also been used as formylating
source in trans-amidation reactions using various
catalysts.[9] Another critical transformation is the
transition metal catalyzed reductive carbonylation of
1
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10.1002/adsc.201700944
Advanced Synthesis & Catalysis
entries 1-6). Further, we estimated the suitable with different heterogeneous Pd catalysts to determine
quantity of (CO2H)2.2H2O and Pd@PS catalyst the efficiency for 2a formation by describing yield,
loading with best reaction conditions corresponding conversion, selectivity, TON and TOF (ESI, Table
to reaction of 4-nitrotoluene with (CO2H)2.2H2O (15 S1). The reaction was also performed using malonic
equiv.) and Pd@PS (8 mol%) in distilled DMF (3 acid and succinic acid but no product formation was
mL) at 135 oC for 20 h (Table 1, entry 10). The course observed (Table 1, entries 21-22). Using acetic acid in
of reaction was also monitored at different reaction DMF also gave the corresponding product in poor
temperatures, while elevated temperatures (135-145 yield (30%) (Table 1, Entry 23), which clearly
oC) facilitated the reaction (Table 1, entries 13). This indicated that the combination of (CO2H)2.2H2O and
may be attributed to the decomposition of DMF serve as the best reagent for the N-aryl
(CO2H)2.2H2O to its constituents at ≥ 130 oC.[13]
formamide synthesis (86%) (Table 1, entry 10).
After the detailed optimization studies, the scope of
Table1. Optimization studies for Pd@PS catalyzed the reaction was further expanded to other nitroarenes.
synthesis of N-arylformamidesa
Table 2. Pd@PS catalyzed synthesis of N-arylformamides
using oxalic acid as C1 sourcea
a]Reaction conditions: 4-Nitrotoluene 1a (0.73 mmol),
oxalic acid dihydrate, Pd@PS (0.94 wt%) in 3 mL of
solvent as stated above. All yields are isolated yields, nr =
no reaction, [b]Malonic acid, [c]succinic acid and [d] acetic
acid used instead of oxalic acid.
[a]Reaction conditions: nitroarenes 1b-o (1 equiv.), oxalic
acid dihydrate (15 equiv.), Pd@PS (8 mol% of Pd) in N,N-
dimethylformamide (3 mL) in closed vessel at 135 C, 20
o
The reaction was not feasible at all in the absence of h; all yields are isolated yields; c4-aminoacetophenone
catalyst (Pd@PS), thus affirming the role of catalyst isolated in 15% yield.
(Table 1, entry 15). Also, the reaction did not occur
by removing (CO2H)2.2H2O from the reaction mixture
which established the need of oxalic acid in the The set reaction conditions were applied for the
reaction (Table 1, entry 16). To determine the role of transformation of nitroarenes containing various
support and the catalyst in the reaction, we screened functional groups to their respective formamides
Pd(OAc)2 and different heterogeneous Pd catalysts synthesis (Table 2). The nitrobenzene afforded the
such as Pd/C (10 wt%), Pd/Al2O3 (5 wt%), Pd/SiO2 corresponding N-phenylformamide 2b in 87% yield
(0.94 wt%) and results have been summarized in under the set reaction conditions. The nitroarenes with
Table 1 (entries 17-20). The Pd@PS was found most electron releasing functional group like p-OCH3 gave
efficient for the selective synthesis of 2a. The variety corresponding product 2c in 85% yield. The p- and m-
of CO/H2 sources such as HCOOH, (CH2O)n, N- chloro nitroarenes were successfully transformed to
formylsaccharin/Et3SiH have also been used along corresponding products 2d-e in 89% and 83% yields
2
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10.1002/adsc.201700944
Advanced Synthesis & Catalysis
respectively and no dehalogenation was observed in 72% yield while corresponding fomamide 2r was
any case. The nitroarenes with electron withdrawing formed as minor product in 12% (Table 3, entry 3).
functionalities chemo-selectively participated in the The molecular structure of 3r was also characterized
reaction to give formamide analogues 2f-h up to 86% by X-ray single crystallography (Figure 1). The
yields. Both the nitro groups of 1,4-dinitrobenzene reaction of aryl substituted nitrobenzene 1s also gave
participated in the reaction to give 2i in 82% yield. 2s and 3s in 14 and 71% yields respectively (Table 3).
The hydroxyl group did not influence the reaction The synthesis of p-hydroxy substituted formamides
much and gave the corresponding products 2j-l in was assisted by ortho-substrates and majorly aryl
good yields. Formamide analogues, 2m-o were groups at the ortho position of nitroarenes as evident
efficiently prepared from their respective nitro from the results (Table 3). To elaborate the
derivatives in 82-85% yields. All the functional nucleophilic attack of hydroxyl ion on the aromatic
groups were well tolerated under the standardized ring, we subjected 2r to standard reaction conditions
reaction conditions and no profound effect was but formation of 3r was not observed and traces of
observed.
respective amine was formed (Scheme 1, ‘a’). To
Interestingly, the reaction of o-substituted further decipher the nucleophilic attack of hydroxy
nitroarenes under the optimized reaction conditions ion and the role of catalyst in the rection, 1p was
gave p-hydroxy substituted formamides along with treated with oxalic acid dihydrate in absence of
the conventional formamide products (Table 3). The catalyst, but there was no reaction and the reactant
reaction of o-nitrotoluene gave corresponding was recovered (Scheme 1‚ ‘b’). This implied that the
formamide 2p in 40% and p-hydroxy N- hydroxylation reaction may require the presence of
arylformamide 3p in 43% yields respectively. catalyst.
Similarly,
1-chloro-2-nitrobenzene
also
gave
corresponding fomamide 2q and p-hydroxy
substituted formamide 3q in 42 and 36% yields
respectively.
Table 3. Pd@PS catalyzed reaction of o-substituted
nitroarenes.
Figure 1. Molecular structure of 3r determined by X-ray
crystallography (CCDC 1563564)
Moreover, the product distribution of 2p and 3p was
examined at 10 and 30 h reaction times which was
found almost unaltered. This led to the conclusion
that formyl group does not direct the nucleophilic
attack at para-position and the substrate at ortho-
position of nitroarenes in its intermediate steps may
be promoting in situ hydroxylation reaction.
A set of control experiments was also carried out to
establish the role of (CO2H)2.2H2O as C1 and H2
source (Scheme 1). We have also attempted the
reaction in two-vial system where oxalic acid
dihydrate in DMF was placed in one vial and 1a,
Pd@PS and DMF in another vial to afford 2a in 38%
yield (Scheme 1, ‘c’). Similarly, using (CO2H)2.2H2O
in PEG-400:1,4-dioxane (1:1) in a two-vial reaction
system gave 2a in 36% yield which clearly
[a]Reaction conditions: 1p-s (1 equiv.), oxalic acid
dihydrate (15 equiv.), 8 mol% of Pd (Pd@PS) in DMF (3
o
mL) at 135 C for 24 h; Yields in parentheses refer to
isolated yields.
Furthermore, aryl functionalized compound such as o-
phenylnitrobenzene primarily afforded p-hydroxy
substituted formamide product 3r as major product in
3
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10.1002/adsc.201700944
Advanced Synthesis & Catalysis
gave arylisocyanate (VIII) which may undergo
hydration and subsequent formylation or following
the transfer hydrogenation approach[15] to give final
product 2 and regenerating the Pd@PS catalyst (I) in
the process (Scheme 2). We were able to confirm the
formation of highly reactive and unstable isocyanate
intermediate in sterically hindered substrates like 2-
nitrotoluene and 2-chloro-nitrobenzene using GCMS
(ESI). Also, the H2 evolved from (CO2H)2.2H2O may
participate in the catalytic transfer hydrogenation to
give amines which can subsequently be formylated to
afford final product 2 (Scheme 2, pathway ‘b’).
The Hg poisoning test was carried out to establish
the heterogeneity of Pd in Pd@PS catalyst which
gave the low product yield of 23% (ESI). Besides, the
Pd@PS catalyst was recycled up to four cycles
without significant loss of catalytic activity. The TEM
analysis of recycled Pd@PS after 4th cycle revealed
the increase in the average particle size of Pd NPs
which could be the responsible factor for loss in the
catalytic activity (ESI). The ICP-AES analysis of the
reaction mixture confirmed less than 1 ppm leaching
of palladium metal into the solution which was
conducted after 2nd and 4th cycle (ESI).
The decomposition products of oxalic acid
dihydrate were efficiently utilized in presence of
heterogeneous Pd@PS catalyst to procure N-
arylformamide derivatives from their corresponding
nitroarenes with detailed mechanistic understanding.
Functional groups like chloro, ketone, ester, amide
and hydroxy were well tolerated in the reaction
conditions.
Scheme 1. Set of control experiments
established the role of oxalic acid as C1 and H2 source
(Scheme 1, ‘d’). In another experiment, formic acid
(15 equiv.) in PEG-400:1,4-dioxane (1:1) was used
instead of (CO2H)2.2H2O but the corresponding
product 2a was not formed, affirming oxalic acid
dihydrate as C1 and H2 source and further
establishing the existence of C1 insertion reaction
pathway (scheme 1, ‘e’). Further, the 3-
chlorophenylisocyanate in presence of (CO2H)2.2H2O
(15 equiv.) can be converted into corresponding
formamide 2d in good yields irrespective of the
solvent used (scheme 1, ‘f and g’).
An insight into the reaction mechanism was carried
out and a plausible pathway was outlined considering
earlier reports, control experiments and was validated
by detecting the associated intermediates (Scheme 2).
The nitroarene interacts with Pd@PS (I) catalyst to
give intermediate (II). The CO generated from the
decomposition of (CO2H)2.2H2O and may be partly
from DMF, participate in the reaction to give
intermediate (III). The removal of CO2 molecule and
further addition of CO transform intermediate (III)
into (IV) which subsequently gave rise to
intermediate (V) after the removal of CO2 molecule.
The addition of CO to (V) produced intermediate (VI)
and also (V) in presence of water and CO (which is
present in the reaction system) may procure
corresponding amine (VII).[14] The intermediate (VI)
Scheme 2. The plausible mechanism for the synthesis of N-
arylformamides
4
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10.1002/adsc.201700944
Advanced Synthesis & Catalysis
The effect of o-substituted nitroarenes for the [6] a) B. K. Banik, C. Mukhopadhyay, M. S. Venkatraman,
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CCDC
1563564
contain
the
supplementary
crystallographic data for the crystal structure 3r of this
manuscript. The data can be obtained free of charge from
the Cambridge crystallographic data centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Acknowledgements
Authors are grateful to Director CSIR-IHBT for providing
necessary facilities during the course of the work. The authors
thank DST Nano Mission Project (SR/NM/NS-1340/2014) for
financial support. VT thank UGC-New Delhi for awarding
fellowships.
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5
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Advanced Synthesis & Catalysis
COMMUNICATION
Supported Palladium(0) Nanoparticles
Catalyzed Reductive Carbonylation of
Nitroarenes to N-Arylformamides
Adv. Synth. Catal. Year, Volume, Page – Page
Vandna Thakura,b , Ajay Kumara, Nishtha Sharmaa,
Arun K. Shila and Pralay Dasa,b*
6
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