An Insight into Nitromethane as an Organic Nitrile Alternative Source towards the Synthesis of Aryl Nitriles

Article abstract of DOI:10.1002/ejoc.201900909

Directed by an unusual in situ reduction of Cu^II, our protocol is a simple Cu^I-mediated synthesis of aryl nitriles, with inexpensive and readily available nitromethane as the cyanating source, in moderate to good yields. Exhibiting a wide substrate scope, the method involves simple reaction conditions, is additive free with low catalyst loading. The plausible mechanism of cyanation of aryl halides is elucidated by a congregation of three cycles, namely the in situ reduction of Cu^II species by nitromethane, generation of HCN species from nitromethane and a regular organometallic pathway which releases the nitrile derivative. The detail of the mechanism of generation of CN^– from nitromethane is computationally validated. Our protocol holds the distinction of involving a rarely encountered Cu^I catalytic species as well as facile in situ generation of nucleophilic CN^– to yield synthetically useful aromatic nitriles.

Full text of DOI:10.1002/ejoc.201900909

A Journal of
Accepted Article
Title: An insight into nitromethane as an organic nitrile alternative
source towards the synthesis of aryl nitriles
Authors: Rakhee Saikia, Satyajit Dey Baruah, Ramesh Ch Deka,
Ashim J Thakur, and Utpal Bora
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900909
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900909
Supported by

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
An insight into nitromethane as an organic nitrile alternative
source towards the synthesis of aryl nitriles
Rakhee Saikia,[b] Satyajit Dey Baruah,[b] Ramesh C. Deka,[b] Ashim J. Thakur*[a] and Utpal Bora*[a]
Abstract: Directed by an unusual in situ reduction of Cu(II), our
protocol is a simple Cu(I)-mediated synthesis of aryl nitriles, with
inexpensive and readily available nitromethane as the cyanating
source, in moderate to good yields. Exhibiting a wide substrate
scope, the method involves simple reaction conditions, is additive
free with low catalyst loading. The mechanism of cyanation of aryl
halides is elucidated by a congregation of three cycles, namely the in
situ reduction of Cu(II) species by nitromethane, generation of HCN
species from nitromethane and a regular organometallic pathway
which releases the nitrile derivative. The detail of the mechanism of
generation of CNˉ from nitromethane is computationally validated.
Our protocol holds the distinction of involving a rarely encountered
Cu(I) catalytic species as well as facile in situ generation of
nucleophilic CNˉ to yield synthetically useful aromatic nitriles.
The pioneers of employing the inexpensive, less-toxic and
readily available indirect organic nitrile source CH3NO2, Yu and
his group, successfully cyanated aryl C-H bonds with
nitromethane, the mechanism of which was rationalized through
a radical-cation pathway.[19] Henceforth, nitromethane was
utilized to cyanate organic scaffolds with operational simplicity
and economic viability.
Although, a variety of atypical transition metals, such as Pd,[20]
Ni,[21] Co,[22] Zn,[14] and Rh[23] have been identified to assist the
process of cyanation without the need of pre-functionalised
substrates,[24] the role of Cu as an inexpensive and readily
available transition metal in cyanation, cannot be overlooked.[25]
Moreover, efficient and sustainable processes of cyanation of
common functionalized substrates, such as aryl halides, needs
further exploration.[26] The abundance of aryl halides in nature
and their affinity towards a metal in a metal-catalyzed reaction,
prompted us to employ them as substrates in our reaction. To
the best of our knowledge, Cu-catalyzed cyanation of aryl
Introduction
[27]
iodides with nitromethane has been reported only once,
The exploration of novel methodologies for the introduction of a
nitrile group into an aromatic framework is a much desired
endeavour, considering the broad synthetic utility of the nitrile
mechanistic aspects of which, is unexplored in detail.
Herein, we report a Cu(I)-catalyzed cyanation of aryl halides
(iodides/bromides) with nitromethane. Our protocol highlights an
unprecedented, dual role played by nitromethane in the reaction.
In addition to being the cyanating source, nitromethane also
helps in the in situ generation of active Cu(I) species by
reduction of the parent Cu(II) salt. The mechanistic aspect of our
protocol is explained in detail, by experimental as well as
computational methods. Moreover, it involves mild reaction
conditions, low catalyst loading and requires no additives.
functionality.[1] Its appearance in
a
number of natural
heterocyclic products and easy transformation into a plethora of
useful functionalities such as aromatic acids, esters, amines,
amides, aldehydes and nitrogen heterocycles accounts for its
popularity and applications.[2-3] Since the first nitrile synthesis,
with Rosenmund-von Braun[4] and Sandmeyer[5] reactions being
the breakthrough protocols, all the traditional methods of nitrile
synthesis suffered from the use of stoichiometric amounts of
toxic metal cyanides (M-CN; M = alkali metal, Cu, Zn, Ag), which
generated a significant amount of waste. Requirement of
elevated temperatures (150-250 °C) being another shortcoming
of those processes. One of the practical solutions that has
emerged to reduce the risk of hazardous metal cyanides, is to
employ, either non-metallic cyanide sources, such as aryl(cyano)-
iodonium triflates,[6] acetone cyanohydrin,[7] malononitrile,[8]
AIBN,[9] benzyl cyanide,[10] acetonitrile,[11] butyronitrile,[12] ethyl
(ethoxymethylene)cyanoacetate,[13] etc., or sources which can
generate CN− group in situ (indirect sources). Recent examples
of such „indirect sources‟ are nitromethane,[14] the combination of
NH4I-DMF,[15] NH4HCO3-DMSO or NH4HCO3-DMF,[16] DMF[17]
and t-BuNC.[18]
Results and Discussion
At first, a mixture of 4-Iodoanisole (1a), nitromethane (2) and a
catalytic amount of CuCl2 were made to react with each other in
DMF. After 16 hours under reflux condition, the reaction offered
an unexpected cyanated product in 71% yield. Allowing the
reaction to proceed beyond 16 hours, however, did not increase
the yield of the cyanated product.
With 4-Iodoanisole (1a) as the model substrate, we optimized
the reaction conditions suitable for cyanation (Table 1). It was
found that although both Cu(I) and Cu(II) salts (Table 1, entries
11-14) could easily facilitate cyanation, the reaction proceeded
.
best with 5 mol% of Cu(NO3)2 3H2O. Its complexation with 10
mol% of 1,10-Phen in situ, among other ligands, provided a
better yield in less time (Table 1, entries 15 and 16). Among all
the organic and inorganic bases screened (Table 1, entries 7-
10), K2CO3 showed the best activity under the given conditions.
Further study revealed a crucial role of the solvent and best
results were obtained in DMSO (Table 1, entries 1-6) at 100 °C.
A decrease in temperature results in a significant decrease in
product yield (Table 1, entry 17), while further increase in
temperature from 100 °C did not bring about any change in the
yield of the desired product (Table 1, entry 18).
[a]
Dr. A. J. Thakur, Dr. Utpal Bora
Department of Chemical Sciences
Tezpur University
Napaam, Tezpur-784028, Assam, India.
E-mail:utbora@yahoo.co.in
http://www.tezu.ernet.in/dcs/ub.html
https://nanocathetero.wixsite.com/website
[b]
Rakhee Saikia, Satyajit Dey Baruah, Prof. R. C. Deka
Department of Chemical Sciences
Tezpur University
Napaam, Tezpur-784028, Assam, India.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
.
Table 1. Initial investigation of reaction conditions for the Cu(I)-catalyzed
cyanation of 4-Iodoanisole (1a) with nitromethane (2).[a]
Table 2. Scope exploration of the Cu(I)-catalyzed cyanation of aryl iodides
and bromides with nitromethane as the cyanating source [a]
Entry
1
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
(C2H5)3N
DABCO
NaHCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cu-salt
Solvent
CH3NO2
CH3OH
CH3CN
DMF
Yield[b] (%)
Entry
1
Substrate [1]
Product [3]
Yield[b] [%]
50
.
Cu(NO3)2 3H2O
-
.
2
Cu(NO3)2 3H2O
67
73
83
85
62
70
57
59
61
62
83
67
64
65
77
62
85
.
2
3
4
3
Cu(NO3)2 3H2O
72
80
.
4
Cu(NO3)2 3H2O
.
5
Cu(NO3)2 3H2O
DMSO
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
.
6
Cu(NO3)2 3H2O
.
52
7
Cu(NO3)2 3H2O
.
8
Cu(NO3)2 3H2O
5
6
7
8
9
.
68
65
78
70
9
Cu(NO3)2 3H2O
.
10
11
12
13
14
15[c]
16[d]
17[e]
18[f]
Cu(NO3)2 3H2O
.
Cu(OAc)2 H2O
CuCl2
CuCl
CuI
.
Cu(NO3)2 3H2O
.
61
73
Cu(NO3)2 3H2O
.
Cu(NO3)2 3H2O
10
.
Cu(NO3)2 3H2O
[a] Reaction conditions: 4-Iodoanisole 1a (1 mmol), nitromethane 2 (1.5
equiv.), Cu-salt (5 mol%), Ligand (10 mol%), base (1 equiv.), solvent (3 mL),
100 °C, 16 h; 1,10-Phen = 1,10-Phenanthroline monohydrate [b] Isolated yield
based on 4-Iodoanisole 1a [c] N,N Dimethylurea was used as a ligand [d]
a ligand [e], [f] Reaction temperature was
maintained at 80 °C and 120 °C respectively.
11
12
54
72
65
75
2,2‟•Bipyridyl was used as
Post optimization, the results of scope exploration of the Cu(I)
catalyzed cyanation of aryl iodides and bromides is presented in
Table 2. Various o-, m- and p-substituted aryl iodides and
bromides (Table 2, entries 1-15) have reacted with nitromethane
2 under the optimized condition (Table 1, entry 4) to give the
respective cyanated product in moderate to good yields. A
decent range of electron withdrawing and electron donating
groups have reacted to afford the desired product, 3a1-p, in 52-
85% yields. Nitromethane (2) cyanated all the substituted aryl
iodides and bromides selectively at the aryl C-X (X = I/Br) bond.
Electron releasing groups have shown a higher reaction yield in
comparison to electron withdrawing groups. This can be
attributed to the positive inductive effect of the electron-releasing
substituents. The optimized reaction conditions tended to favour
13[b]
14
15
63
[a] Reaction conditions: Aryl halide (1 mmol), nitromethane (1.5 equiv.),
Cu(NO3)2 3H2O (5 mol%), 1,10-Phen (10 mol%), K2CO3 (1 equiv.), DMSO (3
mL), 100 °C, 16 h (the reaction time was not optimized for each substrate),
[b] 4-Iodobenzonitrile was obtained as a minor product (GC yield = 31%).
.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
p-substituted aryl halides more than the o- and m-substitutes.
We are yet to establish a plausible reason for this inconsistency.
Interestingly, 1-Iodo-2-nitrobenzene underwent cyanation, with
simultaneous reduction of the nitro group in 73% yield (Table 2,
entry 10).When nitrobenzene was made to react under the same
reaction conditions; aniline was obtained. This may be due to
the reducing tendency of DMSO.[28] However, no such
transformation was observed for the m- and p- analogues.
(Table 2, entries 7, 9 and 12).
(Figure 1c).[31] The UV-Vis, CV, and EPR data confirms the
change in oxidation state of Cu from +2 to +1 during the reaction.
The reaction mechanism can be divided into three stages, viz.,
(A) the reduction of [Cu(phen)2]2+ to [Cu(phen)2]+ by
nitromethane; (B) generation of HCN from nitromethane and (C)
the general organometallic cycle involving oxidative addition,
ligand exchange and reductive elimination to yield the desired
nitrile derivative (Scheme 1).
The mechanistic study of the reaction began with the isolation of
a [Cu(phen)2]2+ complex (ESI-S21).The obtained [Cu(phen)2]2+
complex was then reacted with 4-Iodoanisole (1a) and
nitromethane (2) to give the cyanated product (3a). Interestingly,
we found that the active catalyzing species of the reaction is its
cuprous analogue formed through an unusual in situ reduction of
[Cu(phen)2]2+ in the presence of nitromethane.
The formation of Cu(I) in the reaction medium was confirmed by
UV-Vis spectroscopy, cyclic voltammetry and EPR spectroscopy.
The broad absorption band at 420 nm is a characteristic of the
MLCT
electronic
transition
in
[Cu(phen)2]+
complex
corresponding to the transfer of an electron from a 3d orbital of
Cu to antibonding π* orbital of 1,10-Phen ligand (Figure 1a).[29]
X-band EPR spectra before the start of reaction, shows a sharp
band with g|| = 2.26 and g⊥ = 2.17 which is characteristic of Cu(II)
ion (Figure 1b).[30] The decrease in intensity of the EPR signal
recorded for the reaction mixture after 16 hours confirms the
irreversible reduction of Cu(II) to Cu(I) during the reaction. Cu(I)
being a d10 ion, is diamagnetic.
Scheme 1. Plausible mechanism of cyanation
Studies on the thermochemistry of nitromethane show that its
decomposition at high temperatures can be subdivided into
many phases with different products in each stage. Two of such
important decomposition products are CO and NO[32] i.e.
oxidation of the carbon atom of CH3NO2 to CO with subsequent
reduction of the nitrogen atom to N2 via the formation of NO.[33]
The released NO interacts with Cu(II) in the reaction medium,
causing the reduction of [Cu(phen)2]2+ to [Cu(phen)2]+ (A).[34]
Control experiments suggest that reduction of Cu(II) to Cu(I)
takes place only in the presence of nitromethane.
From previous literature, the process of generation of HCN from
nitromethane (B) can be rationalized through proton abstraction
(i) (The reaction does not proceed in the absence of a base),
followed by dehydration of (ii) to form a nitrile oxide (iii). The
generated nitrile oxide, HCNO, undergoes addition of a water
molecule, to form a hydroxyformaldoxime species (iv). The in
situ generated Cu+ species preferentially coordinates to the N-
donor atom of (iv) causing labilization of the C-O and N-O bonds
(v). Thereafter, the HCN species (vi) is generated, releasing a
molecule of hydrogen peroxide.[35] Controlled experiment
supports the involvement of Cu in the facile release of CN−
(Scheme 2).
Figure 1. (a) UV-Vis spectra of [black: in situ generated Cu(I) complex; blue:
1,10-Phen; red: Cu(NO3)2 3H2O] in DMSO;(b) X-band EPR spectra of [blue:
reaction mixture before the start of reaction; red: reaction mixture at the end of
reaction i.e. 16 hours] in DMSO at 100 K; (c) Cyclic Voltammogram of the
reaction mixture in DMSO.
.
In 0.1 M KCl, the reaction mixture showed an anodic peak
potential at 0.936 V vs Ag/AgCl suggesting oxidation of Cu(I) to
Cu(II) and a cathodic peak potential at −0.173 V vs Ag/AgCl
suggesting reduction of Cu(II) to Cu(I), at a scan rate of 50 mV/s
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
Scheme 2. No cyanation of benzyl bromide in the absence of Cu.
Since the formation of benzyl cyanide from benzyl bromide does
not involve the usual organometallic cycle, failure to yield the
cyanated product in absence of Cu, suggests that Cu plays an
important role in the evolution of CN− from nitromethane. The in
situ generation of CN− is further supported by the picrate paper
test (ESI-S20).[36] The generated HCN species then enters the
organometallic cycle (C) at the stage of ligand exchange. The
representative 4-Iodoanisole oxidatively adds to the active Cu(I)
complex, forming an arylCu(III) species (D). It undergoes ligand
exchange with HCN to form (E), which on reductive elimination
yields 4-Methoxybenzonitrile with simultaneous regeneration of
[Cu(phen)2]+ complex.
Along with the experimental analysis, to look into the heart of the
electronic structure at an atomistic level, DFT calculations have
been performed to gain an in-depth mechanistic insight for the in
situ generation of HCN (Figure 2). A potential energy surface
(PES) is constructed to investigate the detailed mechanism with
energetics (Figure 3).
The potential energy surface was built by considering the ground
state energies of initial reactants as zero. The absolute energies
and relative energies are presented in Table S1, ESI-S23.
The formation of species (i) proceeds via a transition state, TS1
(imaginary frequency = 1146i cm-1) where, one of the C-H bonds
of nitromethane interacts with K2CO3 and undergoes an
elongation from 1.09 Å to 1.35 Å to release HCO32-. This step
has an activation barrier of 11.27 kcal/mol and is spontaneous,
with Gibbs free energy change (G) of -0.9 kcal/mol. TS2 marks
the elongation of the O-H bond of HCO32- from 0.976 Å to 1.35 Å
resulting in the formation of (ii), a new O-H bond with a bond
distance of 1.12 Å. Only one imaginary frequency (680i cm-1) is
obtained with an activation barrier of 11.35 kcal/mol and G
value of 13.53 kcal/mol. Species (ii) then undergoes dehydration
to generate HCNO (iii). This step is a barrierless transition
(barrier of activation is -0.5 kcal/mol, imaginary frequency = 278i
cm-1) which may be due to the presence of a good leaving group
(H2O) in the transition state (TS3). The resultant HCNO species
(iii) is quite stable, as represented in the PES (Figure 3a). The
process is spontaneous with G = -14.07 kcal/mol. The addition
of
a
molecule of H2O to HCNO species to form
hydroxyformaldoxime (iv) passes through TS4 (imaginary
frequency of 105i cm-1) with a very low barrier of 1.01 kcal/mol;
the process is spontaneous with G = -0.20 kcal/mol. TD-DFT
spectrum of [Cu(phen)2]+ confirms formation of the Cu(I)complex
with λmax obtained at 417 nm (ESI-S22) in correlation to the
experimental absorption intensity (λmax) at 420 nm. The metal to
ligand charge transfer (MLCT) is depicted by the metal-centered
HOMO and the ligand-centered LUMO of [Cu(phen)2]+ complex
(ESI-S22). [Cu(phen)2]+ complex interacts with species (iv) to
form (v) (pre-reaction complex).
Figure 2. Optimized geometries of all the species involved in the generation of
HCN from nitromethane at RPBE/DNP level of theory (ball and stick model).
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
the unusual mechanism of generation of a CN− species from
nitromethane, with simultaneous in situ reduction of Cu(II) to
Cu(I). We believe our study will lead to newer avenues on
nitromethane and its extensive utilization in synthetic organic
chemistry.
Experimental Section
General Information
All the chemicals used for the reactions were procured commercially and
used without further purification. The progress of the reaction was
monitored through thin layer chromatography on Merck Kieselgel Silica
gel 60 F254 plates using short wave UV light (λ=254 nm). The products
were purified by column chromatography using Silica gel (60-120 mesh
and 100-200 mesh). The identification of the purified products was done
by NMR spectroscopy. The 1H and 13C NMR spectra were recorded on a
400 MHz JEOL NMR spectrometer (400 MHz for 1H and 100 MHz for 13
C
spectroscopy). Chemical shifts for both 1H (δH) and 13C (δC) NMR are
assigned in parts per million (ppm) using TMS (0 ppm) as the internal
reference and CDCl3 and DMSO-d6 as solvent (CDCl3: δH = 7.25 ppm
and δC = 77.1 ppm; DMSO-d6: δH = 2.5 ppm, DMSO-d6 absorbed water =
3.3 ppm and δC = 40.0 ppm). The multiplicities of the signals are
assigned as: s = singlet, d = doublet, t = triplet, br = broad and m =
multiplet. HRMS data were recorded in Q-TQF mass analyzer by electron
spray ionization technique.
All the computation was performed as in Dmol3 program package.[37-38]
Generalized gradient approximation (GGA) using revised Perdew-Burke-
Ernzerhof exchange-correlation functional has been used to optimize the
electronic structures of the reactants, pre-reactive complexes (RCs),
transition states (TSs) and products with double numerical with
polarization (DNP) basis set for our calculations.[39] DNP basis set used
for our calculations is comparable to Gaussian 6-31G**, but DNP is more
accurate than a Gaussian basis set of the same size.[40-41] For the
vibrational frequency calculations, same level of theory was used. We
have obtained stable minima which correspond to the real and positive
values and the first order saddle points (transition states) are
characterized by imaginary frequency. To improve computational
performance, a global orbital cutoff of 4.5 Å was employed. Self-
consistent field (SCF) procedures are done with tolerances of the energy,
gradient, and displacement convergences: 1.0*10-5 Ha, 2*10-3 Ha Å and
5*10-3 Å respectively. RPBE functional has been preferred for the
calculations as it displays better results with good accuracy
comprehensive for improved adsorption energies of small molecules on
transition metal complexes, which is the ultimate goal of this study. The
effect of solvent continuum, in DMSO is incorporated using conductor-
like screening model (COSMO) in Dmol3 module. Temperature ranging
from 25 K to 1000 K at an interval of 25 has been carried out. Analysis of
373 K in correlation to the experimental run to simulate the same
environment has been performed.
Figure 3. Potential energy surface depicting the generation of HCN from
nitromethane at RPBE/DNP level of theory.
In (v), two Cu-N bonds of [Cu(phen)2]+ elongates from 2.08 Å to
2.30 Å and 2.44 Å respectively. Moreover, the bond distances of
O-H groups from each other in (iv) changes from 2.65 Å to 2.13
Å in (v). Thus, transition (TS5) takes place with an activation
barrier of 10.68 kcal/mol, (imaginary frequency = 499i cm-1) and
Gibbs free energy change (G) of -6.36 kcal/mol to form IM5.
The formation of H2O2 in IM4 triggers the generation of HCN.
This transition (TS6) is barrierless with Gibbs free energy
change of G = - 8.7 kcal/mol. From the PES (Figure 3), it is
observed that the post reaction complex (L2Cu + HCN) is a
reasonably stable species. Only one imaginary frequency
provides testimony of the transition states connecting the
reactants and products.
Conclusions
General experimental procedure
To summarize our work, we have developed a simple Cu(I)
catalyzed methodology for the generation of synthetically and
pharmaceutically important aryl nitriles, with nitromethane as the
cyanating source. Easily synthesizable [Cu(phen)2]2+ catalyst
ensures homogeneity of the reaction medium, surpassing the
risk of catalyst deactivation. Operational simplicity of the method
overcomes most drawbacks associated with usual cyanation
processes. We have demonstrated the first detailed outlook on
An oven-dried 50 ml round-bottomed flask, with a magnetic stirring bar,
was charged with Cu(NO3)2.3H2O (5 mol%, 0.05 mmol, 0.0123 g), 1,10-
Phenanthroline monohydrate (10 mol%, 0.1 mmol, 0.0199 g), 2 (1.5
equiv., 1.5 mmol, 80 μL ) substrate 1a (1 mmol, 0.235 g), K2CO3 (1 equiv.,
0.138 g) in DMSO (3 mL). It was then fitted to a condenser and stirred at
100 °C under reflux conditions in an oil bath. After 16 h, the crude
mixture was extracted with EtOAc and washed with crushed ice. The
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
organic phase was dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The resulting reaction mixture was purified by
column chromatography using hexane-EtOAc mixture as eluent to afford
product 3a.
[16] a) X. Ren, J. Chen, F. Chen, J. Cheng, Chem. Commun. 2011, 47,
6725-6727; b) A. B Pawar, S. Chang, Chem. Commun. 2014, 50, 448-
450; c) G. Zhang, X. Ren, J. Chen, M. Hu, J. Cheng, Org. Lett. 2011, 13,
5004-5007.
[17] a) S. Ding and N. Jiao, J. Am. Chem. Soc. 2011, 133, 12374; b) Y. Yan,
Y. Yuan, N. Jiao, Org. Chem. Front., 2014, 1, 1176.
[18] a) S. Xu, X. Huang, X. Hong, B. Xu, Org. Lett. 2012, 14, 4614-4617; b) J.
Peng, J. Zhao, Z. Hu, D. Liang, J. Huang, Q. Zhu, Org. Lett. 2012, 14,
4966-4969.
Acknowledgments
Financial support from the Department of Science and
[19] X. Chen, X. S. Hao, C. E. Goodhue, J. Q. Yu, J. Am. Chem. Soc. 2006,
128, 6790-6791.
Technology,
New
Delhi
is
acknowledged
(No.
[20] a) . Maestri, . Ca eque, N. ella Ca‟, . erat, M. Catellani, G. P.
Chiusoli, M. Malacria, Org. Lett. 2016, 18, 6108-6111; b) X. Jia, D. Yang,
S. Zhang, J Cheng, Org. Lett. 2009, 11, 4716-4719; c) M. Sundermeier,
A. Zapf, S. Mutyala, W. Baumann, J. Sans, S. Weiss, M. Beller,. Chem.
Eur. J. 2013, 9, 1828-1836; d) S. Zhang, H. Neumann, M. Beller, Chem.
Eur. J. 2018, 24, 67-70.
EMR/2016/005944). R. S. acknowledges Tezpur University for
providing institutional fellowship and all departmental facilities.
S.D.B. is thankful to Department of Science and Technology,
New Delhi for providing DST INSPIRE fellowship. The authors
would also like to thank Dr. Sanjeev Pran Mahanta, Dr. Kiran
Mohan and Mr. Rajkumar Gogoi for their help during the
research work.
[21] a) P. Yu, B. Morandi, Angew. Chem. Int. Ed. 2017, 56, 15693-15697; b)
X. Zhang, A. Xia, H. Chen, Y. Liu, Org. Lett. 2017, 19, 2118-2121.
[22] a) J. Li, L. Ackermann, Angew. Chem. Int. Ed. 2015, 54, 3635−3638 b)
. . u, . ensch, . de zambuja, . V squez-C spedes, . lorius,
J. Am. Chem. Soc. 2014, 136, 17722−17725.
Keywords: aryl nitrile • copper • cyanation • in situ reduction •
nitromethane
[23] M. Chaitanya, D. Yadagiri, P. Anbarasan, Org. Lett. 2013, 15, 4960-
4963.
[24] Y. Ping, Q. Ding, Y. Peng, ACS Catal. 2016, 6, 5989-6005.
[25] Q. Wen, J. Jin, L. Zhang, Y. Luo, P. Lu, Y. Wang, Tetrahedron Lett.
2014, 55, 1271-1280.
[1]
P. Y. Yeung, C. M. So, C. P. Lau, F. Y. Kwong, Angew. Chem. 2010,
122, 9102-9106.
[2] a) E. Ciganek, W. J. Linn, O. W. Webster, H. Rappoport in The
Chemistry of the Cyano group. Z. Rappoport, Ed, 1970, pp. 423-638; b)
R. C. Larock in Comprehensive Organic Transformations, Wiley-VCH,
New York, 1989, p. 819.
[26] a) T. Schareina, A. Zapf, W. Mägerlein, N. Müller, M. Beller, Chem. Eur.
J. 2007, 13, 6249-6254; b) P. Anbarasan, H. Neumann, M. Beller, Chem.
Eur. J. 2011, 17, 4217-4222.
[27] Y. Ogiwara, H. Morishita, M. Sasaki, H. Imai, N. Sakai, Chem. Lett. 2017,
46, 1736-1739.
[3] a) M. H. Rock, A. Merhold, US Patent 6, 2000, 162, 942; b) D. Sriram, P.
Yogeeswari in Medicinal Chemistry, Pearson Education, München, 2007,
p. 35; c) A. Cagir, S. H. Jones, R. Gao, B. M. Eisenhauer, S. M. Hecht, J.
Am. Chem. Soc. 2003, 125, 13628-13629; d) J. X. Qiao, X. Cheng, D. P.
Modi, K. A. Rossi, J. M. Luettgen, R. M. Knabb, P. K. Jadhav, R. Wexler,
Bioorg. Med. Chem. Lett. 2005, 15, 29-35; e) Y. Ju, F. Liu, C. Li, Org.
Lett. 2009, 11, 3582-3585.
[28] C. L. Øpstad, T. B. Melø, H. R. Sliwka, V. Partali, Tetrahedron 2009, 65,
7616-7619.
[29] a) M. Sandroni, Y. Pellegrin, F. Odobel, C. R. Chimie 2016, 19, 79-93; b)
C. T. Cunningham, J. J. Moore, K. L. Cunningham, P. E. Fanwick, D. R.
McMillin, Inorg. Chem. 2000, 39, 3638-3644; c) N. Armaroli, Chem. Soc.
Rev. 2001, 30, 113-124 d) . Rawner, “Copper(I) Phenanthrolines in
Photocatalysis”,University of Regensburg, June 2016.
[4] a) K.W. Rosenmund and E. Struck, Ber. Chem. Dtsch. Chem. Ges. 1919,
52, 1749-1756; b) J. von Braun, G. Manz, Justus Liebigs Ann. Chem.
1931, 488, 111-126; c) G. Ellis and T. Romney-Alexander, Chem. Rev.
1987, 87, 779-794.
[30] R. Kumar, P. Mathur, RSC Adv. 2014, 4, 33190-33193.
[31] B. Yuan, Y. Zhu, K. Xu, Int. J. Electrochem. Sci. 2015, 10, 4138-4145.
[32] a) D. S. Y. Hsu, M. C. Lin, J. Energ. Mater. 1985, 3, 95-127; (b) Z.
Homayoon, J. M. Bowman, A. Dey, C. Abeysekera, R. Fernando, A. G.
Suits, Z. Phys. Chem. 2013 , 227, 1267-1280.
[5] H. H. Hodgson, Chem. Rev. 1947, 40, 251–277.
[6] D. Zhu, D. Chang, L. Shi, Chem. Commun. 2015, 51, 7180-7183.
[7] a) H. J. Cristau, A. Ouali, J. F. Spindler, M. Taillefer, Chem. Eur. J. 2005,
11, 2483-2492; b) M. Sundermeier, A. Zapf, M. Beller, Angew. Chem. Int.
Ed. 2003, 42, 1661-1664.
[33] a) C. F. Melius, Le Journal de Physique IV, 1995, 5, C4-535-C4-538; b)
R. I. Kaiser, P. Maksyutenko, Chem. Phys. Lett. 2015, 631, 59-65.
[34] a) S. Itoh, N. Kishikawa, T. Suzuki, H. D. Takagi, Dalton Tran. 2005, 6,
1066-1078; b) M. D. Lim, K. B. Capps, T. B. Karpishin, P. C. Ford, Nitric
Oxide, 2005, 12, 244-251; c) D. Tran, B. W Skelton, A. H. White, L. E
Laverman, P. C Ford, Inorg. Chem. 1998, 37, 2505-2511; d) D. Tran, P.
C. Ford, Inorg. Chem. 1996, 35, 2411-2412.
[8] Z. Jiang, Q. Huang, S. Chen, L. Long, X. Zhou, Adv. Synth. Catal. 2012,
354, 589-592.
[9] H. Xu, P.T. Liu, Y.H. Li, F. S. Han, Org. Lett. 2013, 15, 3354-3357.
[10] Q. Wen, J. Jin, B. Hu, P. Lu, Y. Wang, RSC Adv. 2012, 2, 6167-6169.
[11] a) Y. Zhu, M. Zhao, W. Lu, L. Li, Z. Shen, Org. Lett., 2015, 17, 2602; b)
W. Xu, Q. Xu, J. Li, Org. Chem. Front. 2015, 2, 231; c) X. Kou, M. Zhao,
X. Qiao, Y. Zhu, X. Tong, Z. Shen, Chem. Eur. J. 2013, 19, 16880-16886.
[12] C. Qi, X. Hu and H. Jiang, Chem. Commun. 2017, 53, 7994-7997.
[13] P. Yu and B. Morandi, Angew. Chem. Int. Ed. 2017, 56, 15693-15697.
[14] a) J. S. Qiu, Y. F. Wang, G. R. Qi, P. G. Karmaker, H. Q. Yin, F. X. Chen,
Chem. Eur. J. 2017, 23, 1775-1778. b) Y. Nagase, T. Sugiyama, S.
Nomiyama, K. Yonekura, T. Tsuchimoto, Adv. Synth. Catal. 2014, 356,
347-352; c) Z. H. Wang, X. M. Ji, M. L. Hu, R. Y. Tang, Tetrahedron Lett.
2015, 56, 5067-5070.
[35] a) D. A. Pantazis, A. C. Tsipis, C. A. Tsipis, J. Phys. Chem. A. 2002, 106,
1425-1440; b) W. F. Hu, T. J. He, D. M. Chen, F. C. Liu, J. Phys. Chem.
A. 2002, 106, 7294-7303.
[36] (a) G. Zhang, X Ren, J. Chen, M. Hu, J. Cheng, Org. Lett. 2011, 13,
5004; (b) J. Kim, J. Choi, K. Shin, S. Chang, J. Am. Chem. Soc. 2012,
134, 2528-2531
[37] B. Delley, J. Chem. Phys. 1990, 92, 508–517.
[38] B. Hammer, L. B. Hansen, J. K. Norskov, Phys. Rev. B. 1999, 59, 7413.
[39] B. Delley, J. Chem. Phys. 2000, 113, 7756–7764.
[40] N. A. Benedek, I. K. Snook, K. Latham, I. Yarovsky, J. Chem. Phys.
2005, 122, 144102-144109.
[15] a) J. Kim, J. Choi, K. Shin, S. Chang, J. Am. Chem. Soc. 2012, 134,
2528–2531; b) J. Kim, H. Kim, S. Chang, Org. Lett. 2012, 14, 3924-3927.
[41] Y. Inada, H. Orita, J. Comput. Chem. 2008, 29, 225–232.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900909
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
Layout 1:
FULL PAPER
An experimental and computational
study into the synthesis of aryl nitriles
with nitromethane as an organic and
non-toxic alternative of traditional
cyanating sources is investigated. The
mechanistic pathway of cyanation is
the highlight of the current study.
cyanation • nitromethane *
Rakhee Saikia, Satyajit Dey Baruah,
*
Ramesh C. Deka, Ashim J. Thakur and
Utpal Bora*
Page No. 1– Page No. 7
An insight into nitromethane as an
organic nitrile alternative towards the
synthesis of aryl nitriles
This article is protected by copyright. All rights reserved.