NHC-assisted Ni(II)-catalyzed acceptorless dehydronation of amines and secondary alcohols

Article abstract of DOI:10.1002/aoc.5379

A novel catalytic system including NiCl₂-NHC ligand precursor has been developed for the preparation of imines from amines and ketones from alcohols. Owing to the acceptorless dehydrogenation pathway for this reaction, the hydrogen gas is liberated as a by-product. The active catalyst is generated in situ by the reaction of nickel (II) chloride, bis (imidazolium) chlorides and potassium tert-butoxide. The products were obtained in good to excellent yields and a wide variety of amines and ketones were applied successfully in this protocol.

Full text of DOI:10.1002/aoc.5379

Received: 24 August 2019
DOI: 10.1002/aoc.5379
Revised: 21 October 2019
Accepted: 24 October 2019
C O M M U N I C A T I O N
NHC-assisted Ni(II)-catalyzed acceptorless dehydronation
of amines and secondary alcohols
1
1
1
Ahmad Takallou | Azizollah Habibi
| Azim Ziyaei Halimehjan
|
2
Saeed Balalaie
1
Faculty of Chemistry, Kharazmi
A novel catalytic system including NiCl -NHC ligand precursor has been
University, No. 43. Mofatteh Street,
2
Enghelab Ave, 15719-14911 Tehran, Iran
developed for the preparation of imines from amines and ketones from alco-
hols. Owing to the acceptorless dehydrogenation pathway for this reaction, the
hydrogen gas is liberated as a by-product. The active catalyst is generated in
situ by the reaction of nickel (II) chloride, bis (imidazolium) chlorides and
potassium tert-butoxide. The products were obtained in good to excellent yields
and a wide variety of amines and ketones were applied successfully in this
protocol.
2
Department of Chemistry, K.N.Toosi
University of Technology, P.O.Box 15875
–
4416 Tehran, Iran
Correspondence
Azizollah Habibi, Faculty of Chemistry,
Kharazmi University, No. 43. Mofatteh
Street, Enghelab Ave, 15719-14911
Tehran, Iran.
Email: habibi@khu.ac.ir
K E Y W O R D S
acceptorless dehydrogenation, imines, ketones, Ni catalysis, secondary alcohols
1
| INTRODUCTION
diversification of reactions that can be catalyzed by Ni
Complexes. Nickel catalysts were applied extensively for
In the past two decades, acceptorless dehydrogenation of
amines and alcohols has been emerged as an immensely
strong tool for the synthesis of a wide range of organic
hydrogenation reactions, C-H bond activation reactions,
and cross-coupling reactions to make carbon–carbon or
carbon-heteroatom bonds in the complex organic
[1]
[4]
compounds.
In this type of reaction, the primary
molecules.
amines and alcohols are converted to imines and car-
bonyl species that are very efficient intermediates for fur-
ther transformations. Considering the mechanism of the
reaction, the hydrogen gas is liberated as a by-product. In
spite of the common oxidation reactions, this reaction
does not require a stoichiometric amount of an oxidant
In the case of the Ni-catalyzed acceptorless dehydro-
genation reactions, Dai and co-workers developed three
Ni (II) complexes with N'NN type pincer ligands for the
0
dehydrogenation of primary alcohols to the carboxylic
[
5]
acids with the liberation of hydrogen gas. In addition,
Parua and co-workers reported the mono- and double-
dehydrogenative synthesis of quinolones derivatives
starting from o-aminobenzylalcohols with ketones and
secondary alcohols using [Ni (tetramethyltetraaza[14]
[2]
or additive for completion.
In order to develop these kinds of transformations,
some of the costly metals such as Ir and Ru have been
successfully applied for a variety of organic reactions.
Nowadays, the Earth-Abundant Metals (EAMs) including
Mn, Zn, Fe, Co and nickel have been examined in the
acceptorless dehydrogenative reactions as inexpensive
[
6]
annulene)] complex as active catalyst. Very recently,
Liu et al. applied Raney-Ni as commercial Ni source for
the synthesis of primary benzyl amines from pimary
benzylalcohols and ammonia passing through from
[3]
[7]
alternatives for the expensive rare metals. Compare to
other EAMs, there are some advantages in the use of Ni
such as low cost, electronic properties of platinum group,
diversity of ligands which can be employed, and
hydrogen borrowing pathway.
Recently, we reported a series of bis (imidazolium)
chloride based on 1,2-phenylenediamine as efficient
ligand precursor for the Mizoroki-Heck cross-coupling
Appl Organometal Chem. 2020;e5379.
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© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5379

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TAKALLOU ET AL.
[
8]
reaction. Although it is well documented that the Pd-
NHC and Ni-NHC complexes are efficient catalysts in
cross-coupling reactions, but developing the chemistry of
metal-NHC complexes especially Ni-NHC catalytic sys-
tems in new organic transformations has remained very
interesting. For this purpose, the acceptorless dehydroge-
nation of benzylamines and secondary alcohols has been
2.3 | General procedure for
dehydrogenative synthesis of imines
Benzylamines (1 mmol), amine (2 mmol), Potassium tert-
butoxide (0.25 mmol, 28 mg), anhydrous NiCl2
(0.04 mmol, 5 mg) and 1d (0.04 mmol, 15 mg) were
charged in a tube which was closed with a septum rub-
ber. The tube was degassed by vacuum and perched with
investigated in the presence of NiCl and NHC ligands
2
toward synthesis of imines and ketones. The traditional
methods for the synthesis of imines include using alde-
hydes and amines or oxidative condensation of alcohols
and amines. The main disadvantages of these
approaches are using toxic and costly reagents and pro-
ducing wastes in the reaction media. Direct synthesis
of imines via dehydrogenative homo (hetero)-coupling of
amines and dehydrogenative coupling of alcohols with
amines are new and instructive methods accompanied
N gas and finally degassed mesitylene (4 ml) was added
2
via a syringe into the mixture. Afterward, resulting mix-
ꢀ
ture was heated at 155 C in a silicon bath for 48 hr
under N atmosphere. Then, the mixture was cooled to
2
room temperature and the solvent was evaporated under
reduced pressure. The resulted crude products was puri-
fied by silica gel flash chromatography (98/2 n-
[9]
hexane/Et N as eluent).
3
by advantages such as liberating of H gas as a useful
2
by-product and using a minimum amounts of catalysts
and additives in the reaction medium. In addition, the
catalytic acceptorless dehydrogenation of alcohols has
been emerged as a powerful tool for the synthesis of car-
2.4 | General procedure for catalytic
ketones synthesis
Alcohol (1 mmol), potassium tert-butoxide (0.30 mmol,
[
10]
bonyl compounds starting from inexpensive alcohols.
34 mg), anhydrous NiCl (0.04 mmol, 5 mg) and 1d
2
Alcohols are also well known as potent liquid hydrogen
carriers and can be transformed to other invaluable
organic materials.
(0.04 mmol, 15 mg) were charged in a tube which was
closed with a septum rubber. The tube was degasses by
vacuum and perched with N gas and then degassed
2
mesitylene (4 ml) was added via a syringe into the mix-
ꢀ
ture. Afterward, the mixture was heated at 155 C in a sil-
2
2
| EXPERIMENTAL
.1 | General
icon bath for 60 hr under N atmosphere. Then, the
2
mixture was cooled to room temperature and the solvent
was evaporated under reduced pressure. The resulted
crude products were purified by silica gel flash chroma-
tography using ethyl acetate/hexane (1:9) as eluent.
All materials were purchased from Merck, Aldrich, and
Fluka, and used as received. Melting points were mea-
sured by an Electrothermal 9100 apparatus and are
uncorrected. FT-IR spectra was recorded on a Perkin-
3 | RESULTS AND DISCUSSION
1
Elmer 843 spectrophotometer using KBr disc. HNMR
spectra were recorded on Bruker 300 MHz, Bruker DMX-
The NHC precursors 1a-d were prepared according to the
previously reported procedure (Scheme 1).
4
00 and Bruker 500 MHz using CDCl and DMSO-d as
3 6
solvent and Me Si (TMS) as internal standard at 298 K.
After synthesis of the NHC ligand, the model reaction
4
The chemical shifts (δ) are reported in parts per million
between p-anisidine (2 mmol) and benzylamine (1 mmol)
ꢀ
(
ppm) and coupling constants (J) are given in Hz. Low
resolution mass was carried out on a Hewlett-Packard
973 mass spectrometer operating at 70 eV. Elemental
analyses were carried out on a Perkin-Elmer 2004 series
II] CHN elemental analyzer.
in the presence of 4 mol % of NiCl and 1d at 150 C for
2
5
[
2.2 | General procedure for the
preparation of 1a–d
These compound were prepared according to pervious
report.
SCHEME 1 Structure of NHC precursors employed in this
study
[8]

ACCEPTORLESS DEHYDRONATION OF AMINES AND SECONDARY ALCOHOLS
3 of 8
4
8 hr was performed under base-free condition. The
the model reaction in refluxing toluene and p-xylene
(Table 1, entries 8, 9). While lower yields of imine were
obtained by decreasing the reaction temperature to 140
imine adduct was obtained in 53% isolated yield (Table 1,
entry 1). To prevent the formation of homo-coupling
adduct, 2 equivalents of p-anisidine was used for an
equivalent of benzylamine. To improve the reaction yield,
the model reaction was performed in the presence of vari-
able amounts of different bases such as KOtBu, K CO ,
ꢀ
and 150 C in the presence of 25 mol% of KOtBu, similar
ꢀ
yield was observed at 160 C (Table 1, entries 10–12). In
addition, lower yields were achieved by shortening the
reaction time to 24 hr and 36 hr (Table 1, entries 13–14).
Furthermore, while by decreasing the metal and ligand
loading to 3 mol%, the corresponding imine was obtained
in 81% yield, increasing the catalyst loading to 5 mol%
doesn't improve the yield (Table 1, entries 15–16).
2
3
KOH and LiOH. The results revealed that the best yield
89%) was obtained when 25 mol% of KOtBu was applied
(
in the model reaction (Table 1, entries 2–7). No improve-
ment in the reaction yield was observed by performing
a
TABLE 1 Optimization of the reaction conditions
ꢀ
b
Entry
Solvent
Base (mol%)
-
T ( C)/t (h)
Ligand, NiCl
2
(x mol %)
Yield
53
73
84
89
83
68
72
64
62
66
85
89
64
82
81
89
84
84
83
60
60
c
1
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
p-Xylene
155/48
155/48
155/48
155/48
155/48
155/48
155/48
140/48
110/48
140/48
150/48
160/48
155/24
155/36
155/48
155/48
155/48
155/48
155/48
155/48
155/48
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
5
4
4
4
4
4
c
2
KOtBu (10%)
KOtBu (20%)
KOtBu (25%)
c
3
c
4
c
5
2 3
K CO (25%)
c
6
KOH (25%)
LiOH (25%)
c
7
c
8
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
KOtBu (25%)
c
9
Toluene
c
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
Mesitylene
c
c
c
c
c
c
d
e
f
g
c,h
a
Reaction conditions: benzylamine (1 mmol), p-anisidine (2 mmol), solvent (4 ml).
b
Isolated yields.
c
Ligand precursor (1d).
d
ligand precursor (1a).
Ligand precursor (1b).
e
f
Ligand precursor (1c).
g
Under ligand free condition.
h
1
mmol of p-anisidine was employed.

4
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TAKALLOU ET AL.
a
TABLE 2 Synthesis of imines from different benzylic amines and amines
b
Entry
Benzylic amines
Product
Yield
1
68
2
78
3
4
91
73
5
6
7
80
88
54
(
Continues)

ACCEPTORLESS DEHYDRONATION OF AMINES AND SECONDARY ALCOHOLS
5 of 8
TABLE 2 (Continued)
b
Entry
Benzylic amines
Product
Yield
8
92
9
79
1
0
83
1
1
1
2
43
38
c
a
ꢀ
Reaction conditions: Benzylic amine (1 mmol); amine (2 mmol); NiCl (4 mol%); 1d (4 mol%); KOtBu (25 mol%), Mesitylene (4 ml), 155 C, 48 hr.
2
b
Isolated yield.
c
ꢀ
The reaction was performed at 130 C.
Afterward, different ligand precursors containing
electron-releasing (ERG) and electron-withdrawing
groups were examined. Based on the results, the presence
of ERGs on the phenyl ring has a positive impact on the
reactivity of the catalytic system which may be due to
higher electron density on the nitrogen of the amide
group (Table 1, entries 17–19). It is notable that under
ligand-free condition, the imine was produced in 60%
yield (Table 1, entry 21). It shows that the presence of a
ligand in the reaction mixture has positive effect on the
reaction and improve the yield to 89%. Finally, by
employing 1 mmol of p-anisidine in the reaction with 1
equivalent of amine, the corresponding imine was pro-
duced in 60% (Table 1, entry 21).
employed in this protocol to explore the scope of the
reaction. In the first step, some benzylic amines were
selected for the homo-coupling and the desired imines
were synthesized in 83–92% (Table 2, entries 3, 8 and 10).
Considering the homo-coupling reaction yields, it is con-
ceivable that the presence of EWG on the phenyl ring
decreases the reaction yield. Additionally, reactivity dif-
ference between benzylic amines and aniline derivatives
allows us to perform hetero-coupling reactions as well
(Table 2). As shown in Table 2, the presence of ERGs in
both aniline derivatives and on the phenyl ring of the
benzylic amines can enhance the reactivity of reactants.
On the other hand, in the absence of ERGs in one of
reactants or both of them, the reactivities are decreased
(Table 2, entries 1, 2, 4, 7 and 9). Linear and cyclic pri-
mary aliphatic amines did not work as well as aromatic
Under optimized reaction conditions, various ben-
zylic amines and aromatic and aliphatic amines were

6
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TAKALLOU ET AL.
a
TABLE 3 Acceptorless synthesis of ketones starting from secondary alcohols
b
Entry
Alcohol
Product
Yield
1
81
2
3
4
5
6
83
87
47
84
73
51
c
7
a
ꢀ
Reaction conditions: alcohols (1 mmol); NiCl (4 mol%); 4a (4 mol%); KOtBu (30 mol%), Mesitylene (4 ml), 155 C, 60 hr.
2
b
Isolated yield.
c
ꢀ
The reaction was performed at 120 C.

ACCEPTORLESS DEHYDRONATION OF AMINES AND SECONDARY ALCOHOLS
7 of 8
intermediate can be formed. The resulting aldimine
undergoes condensation reaction with RNH to form the
2
corresponding imine. It is plausible that the secondary
alcohols proceed through from the same pathway to pro-
duce the corresponding ketones.
4
| CONCLUSION
In summary, we have developed a new in-situ generated
Ni-NHC catalytic system which has been employed in
the acceptorless dehydrogenation of benzylamines and
also secondary alcohols. Detection of the liberated H gas
2
SCHEME 2 Possible mechanism for benzylic amines
confirmed the dehydrogenative nature of these transfor-
mations. The performance of the mentioned catalyst had
been tested in order to synthesize a variety of imines and
ketones in moderate to excellent yields. The main advan-
tages of present study include using inexpensive earth-
abundant metal, oxidant free condition, applying the cat-
alytic amount of additive and developing a direct Ni
catalysed synthesis of imines starting from benzyl
amines.
dehydrogenation
amines in the optimized reaction conditions and gave
moderate yields (Table 2, entries 11–12).
Dehydrogenative transformation of secondary alco-
hols to ketones was also investigated under optimized
reaction conditions developed in the previous reaction.
We have confirmed that under this catalytic system, vari-
ous secondary alcohols including benzylic, linear and
cyclic alcohols can be converted to the corresponding
ketones in good to excellent yields. According to the
results, the nature of the substituent on the para position
of the benzene ring doesn't have significant effects on the
reaction yields (Table 3, entries 1–3, 5). When the -Cl was
used as substituent in the -ortho position of alcohol, the
reaction yield was dropped and the corresponding ketone
was produced in 47% yield (Table 3, entry 4).
Cyclohexanol was converted to cyclohexanone in 73%
yield (Table 3, entries 5). In order to examine the reactiv-
ity of linear aliphatic secondary alcohol in the optimized
reaction conditions, 4-methyl-2-pentanol was selected. It
was converted to the ketone in 51% yield (Table 3, entry
ACKNOWLEDGEMENT
We are grateful to the Ministry of Research of Kharazmi
University for supporting this work.
ORCID
Azizollah Habibi https://orcid.org/0000-0003-4320-1374
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catalyzed acceptorless dehydronation of amines
and secondary alcohols. Appl Organometal Chem.
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