Nickel-catalysed dehydrogenative coupling of aromatic diamines with alcohols: Selective synthesis of substituted benzimidazoles and quinoxalines

Article abstract of DOI:10.1039/c9cc02319d

The first nickel-catalysed dehydrogenative coupling of primary alcohols and ethylene glycol with aromatic diamines for selective synthesis of mono- and di-substituted benzimidazoles and quinoxalines is reported. The earth-abundant, non-precious and simple NiCl₂/L1 system enables the synthesis of N-heterocycles releasing water and hydrogen gas as byproducts. Mechanistic studies involving deuterium labeling experiments and quantitative determination of hydrogen gas evaluation were performed.

Full text of DOI:10.1039/c9cc02319d

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DOI: 10.1039/C9CC02319D
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Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Nickel-Catalysed Dehydrogenative Coupling of Aromatic Diamines
with Alcohols: Selective Synthesis of Substituted Benzimidazoles
and Quinoxalines
www.rsc.org/
Atanu Bera, Motahar Sk, Khushboo Singh and Debasis Banerjee*
The first nickel-catalysed dehydrogenative coupling of primary based on Ru-phosphine or Ru-NNN pincer complexes required
o
alcohols and ethylene glycol with aromatic diamines for 165-200 C reaction temperature.6a-b Thereafter, an improved
selective synthesis of mono- and di-substituted acceptorless
de-hydrogenative
coupling
(ADC)
for
benzimidazoles and quinoxalines is reported. Earth-abundant, benzimidazole synthesis using defined Ir-catalysts were
non-precious and simple NiCl2/L1 system enables the established.6c-d Furthermore, Ru- and Ir-based heterogeneous
synthesis of N-heterocycles releasing water and hydrogen gas catalysts have been developed for benzimidazole synthesis
as byproducts. Mechanistic studies involving deuterium (Scheme 1a).6e-f
labeling experiments and quantitative determination of
a) Previous report
H
hydrogen gas evaluation were performed
.
Pincer-catalysts
N
NH2
M
Air-sensetive ligands
Multi-step ligand synthesis
Expensive PNP ligands
R
HO
R
+
N
NH2
Substituted benzimidazoles and quinoxalines motifs are
ubiquitous in bioactive natural products and significantly utilize
for anticancer, antiviral, antitumor, antibacterial and anti-HIV
related drugs.1 These N-heterocycles have found broad
applications in material research, pharmaceuticals as well as in
dyes industries.2 Traditionally, benzimidazoles are synthesized
involving condensation of 1,2-diaminobenzene with carboxylic
acid derivatives under harsh reaction conditions.3 Furthermore,
coupling of 1,2-di-aminobenzene with concentrated formic acid
is another extensively used procedure for benzimidazoles
synthesis.3 However, these processes often required strong
acidic or basic conditions as well as over stoichiometric oxidants
and limited to the formation of stoichiometric salt waste, low
atom-efficiency and functional group compatibility.4 Therefore,
development of efficient and environmentally benign
technologies which could minimize the waste generation and
avoids multi-step protocols is still a demand goal.4
M = Ir, Ru, Co, Cu and Mn
Ni-catalysed dehydrogenation to N-heterocycles
N
b) Present Work:
N
R2
OH
R2
R2
R1
R1
or
N
H
N
-H2, -H2O
NH2
24 examples, up to 91% yield
R2
R1
Ni
Bench-stable Nitrogen ligands
Inexpensive Ni-catalyst
Deuterium labelling experiments
Mechanistic studies
R1
OH
N
NH2
HO
-H2, -H2O
N
Phosphine free catalysis
Scheme 1: a) Pincer complex catalysed benzimidazole synthesis. b) Nickel-catalysed
dehydrogenative couplings for the synthesis of N-heteroaromatics.
Notably, replacement of noble-metal catalysts using base-
metals (Fe, Co, Mn and Ni) with equal efficiency for such key
organic transformations is a challenging task. Due to their high
abundance, low toxicity and inexpensive nature, base-metal
catalysts attract significant attention in homogeneous catalysis
(Scheme 1a).7 Recently, de-hydrogenative condensation of
alcohols with 1,2-diaminobenzene to benzimidazoles were
established using Cu, Co, and Mn-based homogeneous
catalysts. Nevertheless, most of these metal-complexes utilized
pincer ligands, such as, tridentate NNS-ligands, PNN-ligands,
NNN-core ligands as well as triazole-core phosphine ligands or
expensive phosphine ligands to achieve higher product yields.6,8
However, multi-step synthesis and expensive nature of pincer
ligands are often major concern in comparison to the base-
metal catalysts.8 Further, handling and storing of these pincer-
complexes required special attention under standard
laboratory conditions.
Importantly, till date, most of these homogeneous and
heterogeneous based catalytic protocols are often limited with
2-substituted benzimidazoles. However, a general catalytic
protocol for 2-susbtituted as well as 1,2-disubstituted
benzimidazoles is highly desirable. More specifically, herein we
demonstrated the first nickel-catalysed a general protocol for
selective synthesis of substituted benzimidazoles using
renewable alcohols with 1,2-diaminobenzene.9 A number of
In this context, transition metal-catalysed de-hydrogenative
coupling of renewable alcohols with 1,2-diaminobenzene would
be an alternative synthetic approach for benzimidazoles, since
water and hydrogen gas are only valuable byproducts.5 Since
last two decades, considerable progress have been directed for
acceptorless de-hydrogenation of alcohols with diamines for
benzimidazoles
synthesis
involving
sustainable
transformations, however, often limited with noble-metal
catalysts and harsh reaction conditions. For instance, studies
Department of Chemistry, Laboratory of Catalysis and Organic Synthesis, Indian
Institute of Technology Roorkee, Roorkee-247667, Uttarakhand, India.
E-mail: dbane.fcy@iitr.ac.in
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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bonds activation and formation selectively occurred in one-pot
operation using inexpensive nickel-catalyst releasing water and
hydrogen gas as by-products. Again, this Ni-catalysed route was
employed for quinoxalines synthesis. Preliminary catalytic and
mechanisctic studies were also performed (Scheme 1b).
Recently, we started a program to establish Ni-catalysed
(de)hydrogenative transformations using renewable alcohols or
diols and a couple of novel protocols were demonstrated for the
synthesis of indoles, substituted pyrroles, pyridines and
quinolines.10 Herein, we explored a nickel-catalysed tandem
one-pot constructions of substituted benzimidazoles and
quinoxalines. Remarkably, coupling of 1,2-benzenediamines
with alcohols comprises one pot multiple step operations; de-
hydrogenation of alcohol to aldehyde followed by condensation
to imine and thereafter intramolecular cyclisation and de-
hydrogenation resulted the formation of benzimidazoles
(Scheme 3e).
formamide (DMF), N,N-dimethyl acetamide (DMA), and p-
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xylene, proof inefficient (SI Table S4). WDhOeIr:e1a0s.1,0i3n9/cCa9sCeCo02f311,94D-
dioxane we observed moderate product conversion (SI Table
S4). As expected, product conversion suppress significantly
when the reaction was performed at a lower reaction
temperature (SI, Table S6). Control experiments in absence of
catalyst, ligand and base proof their significant role to achieve
higher product yield and selectivity (Table 1, entries 10-11 and
SI Table S1-S6).
Table 2: Ni-catalysed selective synthesis of 1,2-disubstituted benzimidazolesa
N
Het/Ar
NiCl2 (2.5 mol%)
Ar
NH2
NH2
OH
N
1,10-Phen (3 mol%)
Het/Ar
2a-h
Ar
t-BuOK (1.0 equiv.)
3a-l
Het/Ar
toluene, 140 °C, 24 h
1a-c
N
N
N
N
N
iPr
Et
N
3c, 70%
3a, 91%
3b, 72%
Table 1: Optimisation of the reaction conditionsa,b
iPr
Et
OMe
N
N
N
N
N
N
H
NH2
NH2
N
N
N
Cl
Ni-Cat./L
Ph
+
Ph
HO
Ph
+
t-BuOK,
toluene
140 ºC, 24 h
N
3a
4a
1a
2a
3e + 3e', 69% (3:1)
Cl
Ph
3d, 64%
3f + 3f', 56% (3:1)
entry
catalyst (mol%)
ligand
(mol%)
L1 (3)
L1 (3)
L1 (3)
L1 (3)
L2 (3)
L3 (3)
L4 (3)
L5 (3)
L1 (3)
-
base
conv (%)
3a
MeO
N
N
N
N
N
4a
Et
iPr
1
2
NiCl2 (2.5)
NiBr2 (2.5)
Ni(acac)2 (2.5)
NiCl2(DME) (2.5)
NiCl2 (2.5)
NiCl2 (2.5)
NiCl2 (2.5)
NiCl2 (2.5)
NiCl2 (2.5)
-
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuONa
t-BuOK
t-BuOK
98(91)
65
2
5
N
Cl
Cl
Cl
3
56
11
6
3g, 59%
3h, 67%
3i, 71%
Et
iPr
4
54
N
N
N
N
N
5
57
20
12
6
S
6
O
76
N
N
7
55
S
O
3j, 78%
3l, 34%
3k, 32%
8
33
75
21
35
5
9
0
0
N
Reaction Conditions: a1 (0.5 mmol), benzyl alcohol 2 (1.0 mmol), NiCl2 (0.0125 mmol),
1,10-phen. (0.015 mmol), t-BuOK (0.5 mmol), toluene (2.0 mL), Schlenk tube under N2
atmosphere at 140 ⁰C in an oil bath for 24 h.
9
10c
11c
NiCl2 (2.5)
-
Reaction conditions: a1a (0.5 mmol), benzyl alcohol 2a (1.0 mmol), Ni-cat (0.0125 mmol),
L (0.015 mmol), t-BuOK (0.5 mmol), toluene (2.0 mL) in a Schlenk tube under nitrogen
atmosphere at 140 °C in an oil bath for 24 h reaction time. bConversion was determined
by GC-MS (isolated yield in parentheses, average yield of two runs). ct-BuOK (0.5 mmol)
was used. L1 = 1,10-phenanthroline. L2 = 2,9-dimethyl-1,10-phenanthroline. L3 =
bipyridine. L4 = 4,4’- dimethylbipyridine. L5 = 2,2'-biquinoline.
Next, a series of 1-benzyl-2-aryl-1H-benzo[d]imidazole derivatives
were synthesized using 1,2-benzenediamines with substituted
benzyl alcohols involving standard catalytic conditions of Table 1
(Table 2). For instance, benzyl alcohol substituted with alkyl or
methoxy group resulted in up to 72% isolated yield of 3b-3d (Table
2). Importantly, 2-pyridinemethanol 2f efficiently transformed to
1,2-disubstituted benzimidazole 3j in 78% yield. However,
application of other heterocyclic alcohols, such as, 2-thiophene-
methanol 2g and 2-furfuralmethanol 2h gave moderate yield of 3k-
3l (Table 2). Moreover, 4-methyl-1,2-phenylenediamine 1b and 4-
chloro-1,2-phenylenediamine 1c efficiently participated with
substituted benzyl alcohols and furnished the desired
benzimidazoles derivatives 3e-3i in 56-71% yield respectively (Table
2). Notably, in case of 4-methyl-1,2-phenylenediamine 1b an
isomeric mixture of products were obtained.
Initially, we studied the model reaction using 1,2-benzene-
diamines 1a with benzyl alcohols 2a to establish the efficient
catalytic system for benzimidazole synthesis. Primarily, four
different nickel pre-catalysts were employed involving 1,10-
phenanthroline L1 as ligand of our choice (Table 1, entries 1-4).
Pleasingly, we observed 91% isolated yield of 1,2-disubstituted
benzimidazole 3a with >49:1 selectivity involving a combination
of 2.5 mol% NiCl2, 3 mol% 1,10-phenthroline L1 with 0.5 mmol
of t-BuOK at 140 °C in toluene (Table 1, entry 1). Next, influence
of different nitrogen ligands L2-L5 further did not improve the
product yield and the selectivity of 3a (Table 1, entries 5-8 and
Supporting Information Table S2). Further, we examined the
efficacy of different bases, such as, t-BuONa, K3PO4, K2CO3 and
Cs2CO3 and observed moderate product conversion to 3a (Table
Further, we explored the synthesis of 2-substituted benzimidazoles
using the optimized conditions of Table 1. To our delight, a series of
benzyl as well as alkyl alcohols were utilized to the desired products
1, entry 9 and SI Table S3). When using different polar as well as in moderate to acceptable yields (Table 3). Notably, reaction of 1a
with benzyl alcohols decorated with bromide or trifluoromethyl
non-polar solvents, such as, n-butanol, N,N-dimethyl
2 | J. Name., 2012, 00, 1-3
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group gave moderate yield of 4b-4c. However, when benzyl alcohol bearing functional groups, such as, nitro, cyano, hydroxyl, esters,
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2a and 2-naphthylmethanol 2k were employed, desired 2-aryl imine, amine, aldehyde, alkyne as well as alkene moieties were not
DOI: 10.1039/C9CC02319D
substituted benzimidazoles 4a and 4d were obtained in 52-56% yield successful and we observed only poor or no product conversion to
respectively (Table 3). Next, we studied the reactivity of more the desired benzimidazoles (SI, Table S11).
challenging acyclic and cyclic alkyl alcohols. We were pleased to Next, to gain more insight for such dehydrogenative couplings
observe that long chain C6-C10 alkyl alcohols can be incorporated into we explored the initial mechanistic studies for the process. To
the benzimidazole core with good to moderate isolated yield (Table understand the involvement of the putative key Ni-
3, 4e-4h). Notably, renewable terpenoid alcohol, citronellol 2o and intermediate species, Cat. A was independently prepared,10
1-cyclohexylmethanol 2p resulted the 2-alkylbenzimidazoles 4i-4j in and used for the model reaction of Table 1 in catalytic (2.5 mol
acceptable yield (Table 3). This remarkable chemo-selective %) and stoichiometric (100 mol %) amount. As expected, 3a was
transformation of citronellol highlights the potential of the present obtained in 64-90% yield along with a small amount of 4a
protocol. Nevertheless, in all these cases unreacted alcohols were (Scheme 3a).
recovered and often small amount of di-substituted benzimidazoles
3a. Stoichiometric and catalytic studies using defined catalyst
was observed as side products. At this point, it is to be note that,
NH2
Cat. A
(2.5 mol%)
Cat. A
(100 mol%)
3a + 4a
10%
3a + 4a
N
variations of alcohol equivalency control the product selectivity to
mono- or di-substituted benzimidazoles. More specifically, under the
optimised conditions of Table 1, used of two equivalent of alcohols
gave di-substituted benzimidazoles, whereas, one equivalent of
alcohol is required for 2-substituted benzimidazoles.
Ph
OH
64%
90% 7%
N
NH2
Ni
Cl
Cl
standard Conditions
2a
standard Conditions
1a
Cat. A
3b. Deuterium labeling experiments
NH2
N
N
standard Conditions
Ph
+
Ph
Ph
OD
+
N
H
N
NH2
2a-d1 (98% D)
1a
Ph
3a,77%
4a,10%
(0%)
H/D
Table 3: Ni-catalysed selective synthesis of 2-substituted benzimidazolesa
NH2
N
N
N
D
D
R'
R'
NH2
NiCi2 (2.5 mol%)
N
standard Conditions
Ph
Ph
+
+
1,10- Phen (3 mol%)
R
R
OH
Ph
OH
N
H
NH2
N
H
t-BuOK
toluene, 140 °C, 24 h
NH2
2a, 2i-2p
2a-d2 (92% D)
Ph
1a
3a-d1, 10%
4a, 90%
4a-j
H/D (90%)
1a-b
3c. Control experiments
NH2
N
N
N
Catalyst
Base
3a
4a
CF3
Br
standard Conditions
On
On
98% 2%
21% 0%
Ph
+
OH
N
H
N
H
N
H
On
Off
Off
On
NH2
2a
1a
4c, 38%
4a, 52%
4d, 56%
4b, 35%
5%
0%
standard Conditions
NH2
NH2
O
Catalyst
Base
3d
4k
N
N
N
N
+
On
Off
5% 95%
Off
On
Ar
H
Ar
N
N
H
N
2d'
n
90% 10%
N
1a
H
H
n = 1 4f, 30%b
n = 4 4g, 41%b
Ar= 4-OMePh
4e, 56%b
4k
H
3d. N-alkylation of imidazole
N
N
N
N
N
N
OMe
standard Conditions
+
OMe
Ph
OH
2a
N
H
N
N
H
N
H
4k
Not formed
H
Ph
4i, 37%b
4h, 45%b
4j, 39%b
3e. Possible mechanistic pathway
Ni-Cat.
N
R
Reaction conditions: a1 (0.5 mmol), alcohol 2 (0.5mmol), NiCl2 (0.0125 mmol), 1,10-phen
(0.015 mmol), t-BuOK (0.5 mmol), toluene (2.0 mL), Schlenk tube under N2 atmosphere,
140 ⁰C in an oil bath for 24 h. b2 (1.0 mmol) was used.
1a
Quantitative evalution
of H2 gas was
performed for the
overall process
R
OH
A
R
O
2
NH2
-H2O
H2
2'
Detected using GC-MS
Detected using GC-MS
Finally, we explored the de-hydrogenative coupling of 1,2-di-
aminobenzenes with ethylene glycol for the synthesis of quinoxaline
derivatives. Though, long chain vicinal diols are effective partner for
quinoxaline synthesis, application of ethylene glycol is still a
challenging task and rarely explored.11 Gratifyingly, using our nickel-
catalyzed protocol, ethylene glycol efficiently coupled with 1a as well
as 4-methoxy-1,2-diaminobenzene 1d and resulted up to 40% yield
of 5a-5b (Scheme 2). Further, screening of reaction conditions, such
as, variation of pre-catalysts and bases, effect of solvents including
variable reaction temperatures did not improve the product yield
further (SI, Table S7-S10).
N
N
H
N
N
R
N
R
O
R
Ni-Cat.
2'
R
R
N
N
H2
N
R
3
H
H
C
4
B
R
Detected using GC-MS
Scheme 3: Preliminary mechanistic studies and control experiments. Deuterium labelling
experiments were performed using 1a (0.10 mmol) and 2a-d1/2a-d2 (0.20 mmol)
following standard conditions of Table 1. (See. SI, Schemes S1-S2)
Further, deuterium labeling experiments using 1a with 2a-d1
(98% D), resulted 3a in 77% yield and we did not observe any
deuterium incorporation at the imidazole core (Scheme 3b).
However, dehydrogenative couplings of 1a with 2a-d2 (92% D)
exhibited 90% deuterium incorporatoion in 3a-d1 along with 4a
in 90% product yield (Scheme 3b and SI Scheme S1). These
deuterium labeling experiments evident the participation of
benzylic C-H bond of alcohols for imidazole synthesis.
Moreover, control experiments in absence of base and catalyst
highlights their potential role for the dehydrogenative
condensation to imidazole synthesis (Scheme 3c). In addition,
we also performed catalytic condensation of 1a with
4-methoxybenzaldehyde 2d’ under standard conditions. These
experiments resulted the formation of 3d and 4k at variable
amounts, which strongly support that, the first step is the
metal-catalyzed dehydrogenation of alcohol to aldehyde and
thereby, base mediated condensation/cyclisation facilitate the
product formation. Notably, it also provides the evidences for
NiCl2 (6 mol%)
1,10- Phen (12 mol%)
R
N
R
NH2
NH2
HO
t-BuOK
toluene, 140 °C, 36 h
N
HO
2q
R = H 5a, 25%
1a,d
R = OMe, 5b, 40%
Scheme 2: Synthesis of quinoxalines: Reaction conditions: a1 (0.5 mmol), ethylene glycol
2q (2.5 mmol), NiCl2 (0.03 mmol), 1,10-phen (0.06 mmol), t-BuOK (1.0 mmol), toluene
(2.0 mL) in Schlenk tube under a nitrogen atmosphere, 140 ⁰C in oil bath, 36 h.
The catalytic protocol is tolerant to aryl, alkyl, methoxy, halides (Cl
and Br), trifluoromethyl as well as pyridine, thiophene and furfural
moieties. Importantly, chemo-selective transformations in the
presence of reducible alkene highlight the synthetic potential of the
established protocol. Notably, applications of benzyl alcohols
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4. (a) B. M. Trost, Science, 1991, 254, 147; (b) K. Barta and P. C.
the potential role of the metal catalyst for bond activation,
condensation followed by construction of new bonds for
imidazole synthesis (Scheme 3c).
View Article Online
Ford, Acc. Chem. Res., 2014, 47, 1503.
5. (a) G. E. Dobereiner and R. H. CrabtDreOeI:,1C0h.1e0m39./CR9eCvC.,022301190D,
110, 681; (b) A. J. A. Watson and J. M. J. Williams, Science,
2010, 329, 635; (c) J. Moran and M. J. Krische, Pure Appl.
Chem., 2012, 84, 1729.
On the basis of the initial mechanistic studies and control
experiments, we hereby postulated a probable catalytic
pathway for the Ni-catalysed dehydrogenative condensation of
aromatic diamines with alcohols (Scheme 3e).8a Initially, Ni-
catalysed dehydrogenation of primary alcohol gave aldehyde 2’
followed by condensation with 1a to imine intermediate A,
which subsequently undergoes cyclisation and dehydro-
genation to product 4 via intermediate B. It is noteworthy to
mention that, in the GC-MS analysis of the crude reaction
mixture we detected intermediate 2’ as well as intermediate A.
Another possibility is that, intermediate B could couple with 2’
to intermediate C, which subsequently undergoes intra-
molecular cyclisation and rearrange to 1,2-disubstituted
imidazoles (Scheme 3e). Nevertheless, to exclude the possibility
of N-alkylation of 2-arylimidazoles, 4k was allowed to react with
benzyl alcohol under standard conditions and we did not
observed any desired product (Scheme 3d). Moreover, during
optimization studies we detected intermediate C in the GC-MS
analysis, which support our hypotheses for 1,2-disubstituted
imidazoles synthesis. Notably, the overall process released only
water and dihydrogen as side products, rendering it sustainable.
Thereafter, we measured the quantitative evaluation of
hydrogen gas for the process and confirmed through gas
chromatography (SI, Scheme S4-S5).
In conclusion, herein we demonstrated the first Ni-catalysed
selective dehydrogenative condensation of aromatic diamines
with a series of primary alcohols to substituted benzimi-dazoles.
A simple and inexpensive Ni-catalyst and 1,10-phenthroline
ligand enables to a vareity of functionalised benzimidazoles and
quinoxalines in up to 91% yield. The catalytic system is tollerant
to alkyl, alkoxy, halides, trifluoromethyl as well as heterocyclic
rings including unsaturated alcohols. Initial mechanistic
investigations involving defined Ni-catalyst, deuterium labeling
experiments as well as quantitative determination of hydrogen
gas were performed to establish the dehydrogenation process.
6. (a) T. Kondo, S. Yang, K. Huh, M. Kobayashi, S. Kotachi and Y.
Watanabe, Chem. Lett., 1991, 20, 1275; (b) L. Li, Q. Luo, H.
Cui, R. Li, J. Zhang and T. Peng, ChemCatChem, 2018, 10,
1607; (c) T. Hille, T. Irrgang and R. Kempe, Chem.-Eur. J.,
2014, 20, 5569; (d) A. K. Sharma, H. Joshi, R. Bhaskar and A.
K. Singh, Dalton Trans., 2017, 46, 2228; (e) K. Tateyama, K.
Wada, H. Miura, S. Hosokawa, R. Abe and M. Inoue, Catal.
Sci. Technol., 2016, 6, 1677; (f) K. J. Won, H. Jinling, Y.
Kazuya and M. Noritaka, Chem. Lett., 2009, 38, 920; (g) Z.
Xu, X. Yu, X. Sang, and D. Wang, Green Chem., 2018, 20,
2571; (h) K. Tateyama, K. Wada, H. Miura, S. Hosokawa, R.
Abe and M. Inoue, Catal. Sci. Technol., 2016, 6, 1677.
7. (a) R. M. Bullock, Catalysis Without Precious Metals, Eds.:
Wiley-VCH, Weinheim, 2010; (b) B. Su, Z.-C. Cao and Z.-J. Shi,
Acc. Chem. Res., 2015, 48, 886.
8. (a) Z. Xu, D.-S. Wang, X. Yu, Y. Yang and D. Wang, Adv. Synth.
Catal., 2017, 359, 3332; (b) P. Daw, Y. Ben-David and D.
Milstein, ACS Catal., 2017, 7, 7456; (c) K. Das, A. Mondal,
and D. Srimani, J. Org. Chem., 2018, 83, 9553; (d) A. J.
Blacker, M. M. Farah, M. I. Hall, S. P. Marsden, O. Saidi and
J. M. J. Williams, Org. Lett., 2009, 11, 2039.
9. For selected reviews, see: (a) S. Z. Tasker, E. A. Standley, T. F.
Jamison, Nature, 2014, 509, 299; (b) A. Valentine and P.
Ananikov, ACS Catal., 2015, 5, 1964; (c) J. E. Dander and N.
K. Garg, ACS Catal., 2017, 7, 1413 and references cited
therein; (d) F. Alonso, P. Riente and M. Yus, Acc. Chem. Res.,
2011, 44, 379.
10. (a) M. Vellakkaran, K. Singh and D. Banerjee, ACS Catal.,
2017, 7, 8152; (b) K. Singh, M. Vellakkaran and D. Banerjee,
Green Chem., 2018, 20, 2250; (c) J. Das, K. Singh, M.
Vellakkaran and D. Banerjee, Org. Lett., 2018, 20,
5587−5591; (d) K. Singh, L. M. Kabadwal, S. Bera, A.
Alanthadka and D. Banerjee, J. Org. Chem., 2018, 83,
15406.
11. For quinoxaline synthesis, see: (a) F. Xie, M. Zhang, H. Jiang,
M. Chen, W. Lv, A. Zheng and X. Jian, Green Chem., 2015,
17, 279; (b) M. J. Climent, A. Corma, J. C. Hernández, A. B.
Hungría, S. Iborra and S. Martínez-Silvestre, J. Catal., 2012,
292, 118; (c) C. S. Cho and S. G. Oh, Tetrahedron Lett., 2006,
47, 5633; (d) D.-Q. Shi and G.-L. Dou, Synth. Commun.,
2008, 38, 3329; (e) T. Hille, T. Irrgang and R. Kempe, Chem.-
Eur. J., 2014, 20, 5569; (f) P. Daw, A. Kumar, N. A. Espinosa-
Jalapa, Y. Diskin-Posner, Y. Ben-David and D. Milstein, ACS
Catal., 2018, 8, 7734; (g) M. Mastalir, M. Glatz, E.
Pittenauer, G. Allmaier, and K. Kirchner, Org. Lett., 2019,
21, 1116.
Conflicts of interest
There are no conflicts to declare.
The authors thank SERB, India (ECR/2015/000600) and IIT Roorkee
(SMILE-32). M. S. Thank. DST/2018/IF180079 for financial support. A.
B. and K. S. thank IIT-R for a fellowship.
Notes and references
1. (a) D. A. Horton, G. T. Bourne and M. L. Smythe, Chem. Rev.,
2003, 103, 893; (b) Z. Lixin and L. D. Arnold, Natural
Products: Drug Discovery and Therapeutic Medicine;
Humana Press: Totowa, NJ, 2005; p 341; (c) R. Sarges, H. R.
Howard, R. G. Browne, L. A. Lebel, P. A. Seymour and B. K.
Koe, J. Med. Chem., 1990, 33, 2240.
2. (a) H. M. Smith, High Performance Pigments; Wiley−VCH
Verlag GmbH & Co. KGaA: Weinheim, Germany, 2002; pp
135; (b) Scherer, G. G. Fuel Cells II; Springer-Verlag: Berlin,
2008; pp 65.
3. (a) E. C. Wagner and W. H. Millett, Org. Synth., 1939, 19, 12;
(b) J. B. Wright, Chem. Rev., 1951, 48, 397; (c) P. N. Preston,
Chem. Rev., 1974, 74, 279; (d) K. J. Lee and K. D. Janda, Can.
J. Chem., 2001, 79, 1556; (e) M. Curini, F. Epifano, F.
Montanari, O. Rosati and S. Taccone, Synlett, 2004, 1832; (f)
K. Bahrami, M. M. Khodaei and I. Kavianinia, Synthesis,
2007, 2007, 547.
4 | J. Name., 2012, 00, 1-3
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ChemComm
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DOI: 10.1039/C9CC02319D
Graphical Abstract:
Nickel-catalysed dehydrogenative coupling of 1,2-di-amino-
benzene with primary alcohols and diols for the synthesis of
N-heterocycles is reported. The catalytic protocol enables the
transformation in up to 91% yield and generates water and
hydrogen gas as by products.
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