Solvent-free preparation of N, N ′-dialkylbenzenediamines

Article abstract of DOI:10.1055/s-0032-1317936

A diiridium complex, stabilized by a bis(N-heterocyclic carbene) ligand, was found to be an effective precatalyst for the N,N′-dialkylation of o-, m-, and p-benzenediamine in excellent yields. Benzyl and primary aliphatic alcohols were used as alkylating reagents. Furthermore, the reactions were carried out without using any organic solvent, offering an environmentally benign process.

Full text of DOI:10.1055/s-0032-1317936

PAPER
▌189
paper
Solvent-Free Preparation of N,N′-Dialkylbenzenediamines
Iridium(I)-Catalyzed N,N′-Dialkylation of Benzenediamines
Hsin-Ya Kuo, Bei-Sih Liao, Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, ROC
Fax +886(2)33668671; E-mail: stliu@ntu.edu.tw
Received: 04.10.2012; Accepted after revision: 03.12.2012
work, we have prepared a diiridium–bis(NHC) complex 1
(Figure 1) and established its catalytic activity for the di-
alkylation of amines.8 Here, we explore the general appli-
cability of this diiridium complex catalyzed N,N′-
Abstract: A diiridium complex, stabilized by a bis(N-heterocyclic
carbene) ligand, was found to be an effective precatalyst for the
N,N′-dialkylation of o-, m-, and p-benzenediamine in excellent
yields. Benzyl and primary aliphatic alcohols were used as alkylat-
ing reagents. Furthermore, the reactions were carried out without dialkylation of benzenediamines.
using any organic solvent, offering an environmentally benign pro-
cess.
N
N
Key words: alkylation, amination, iridium, catalysis, carbene com-
plex
PhCH2
CH2Ph
N
N
Ir(CO)2Cl
Cl(CO)2Ir
1
N,N′-Dialkylbenzenediamines are useful chemicals for
many aspects such as their application as synthetic inter-
mediates, pharmaceuticals, chelating agents, and addi-
tives for antioxidant and dispersant viscosity modifiers.1–3
Many synthetic approaches leading to the desired amines
are known and the direct N-alkylation of amines ought to
be the most useful methodology.1,4 Transition-metal-cata-
lyzed amination of alcohols with amines has proven to be
an efficient method for the preparation of N-substituted
amines.5 The first step in this approach involves the dehy-
drogenation of the alcohol to give the corresponding alde-
hyde, accompanied by the generation of metal hydride
(Scheme 1). Subsequently, the carbonyl compound reacts
with an amine to form an imine, which is reduced to the
corresponding amine by the pregenerated hydride. In-
deed, numerous monoamine derivatives have been pre-
pared by this approach; however, the selective N,N′-
dialkylation of diamine compounds has been a challenge
until the recent development of the iridium-catalyzed am-
ination of alcohols using benzenediamines.6
Figure 1
As a starting point, we selected the reaction of o-benzene-
diamine with benzyl alcohol as a model to examine the ef-
fectiveness of this reaction (Scheme 2). In order to meet
an environmentally benign process, we carried out the re-
actions without using any organic solvent. Thus, a mixture
of o-benzenediamine (0.5 mmol), benzyl alcohol (3
mmol), complex 1 (3 μmol), base (0.15 mmol), and mo-
lecular sieves (0.3 g) was heated at 120 °C for 24 hours.
Instead of the desired dialkylation product 2, 2-phenyl-
1H-benzimidazole (3) was obtained as the exclusive prod-
uct from this reaction. Apparently, intramolecular attack
of the amino group toward the imine functionality occurs
prior to the reduction of imine (Scheme 2, path b). With
this disappointing result, we further modified the condi-
tions to avoid the production of 3. It has been disclosed
that the reduction of imines in transition-metal-catalyzed
amination can be facilitated in the presence of a hydrogen
atmosphere.9 Indeed, running the reaction of o-benzenedi-
amine with benzyl alcohol under an atmospheric pressure
of hydrogen readily afforded the desired dialkylation
product 2 in 90% isolated yield (Scheme 2, path a).
R1CH2OH
R1CHO
R2NH2
H2O
MLn
LmM H
R1CH2
R2
N
H
R1CH=NR2
H
N CH2Ph
NH2
H2
Scheme 1 Pathway of the N-alkylation of amines with alcohols
N CH2Ph
2
H
NH2
PhCH2OH
(a)
(b)
1 (1 mol%), CsOH
+
molecular sieves
N-Heterocyclic carbenes (NHCs) have become an impor-
tant class of ligands for transition metal complex cataly-
sis. It is known that the introduction of an NHC ligand to
the metal center enhances its catalytic activity compared
to the transition metal–phosphine counterpart.7 In recent
H
N
Ph
N
3
Scheme 2 Alkylation of o-benzenediamine with benzyl alcohol
SYNTHESIS 2013, 45, 0189–0192
Advanced online publication: 19.12.2012
DOI: 10.1055/s-0032-1317936; Art ID: SS-2012-H0776-OP
© Georg Thieme Verlag Stuttgart · New York
To obtain information on the catalytic system, we also ex-
amined this dialkylation with the use of various other irid-
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

190
H.-Y. Kuo et al.
PAPER
ium complexes as the catalyst for comparison (Table 1), cohols such as 1-octanol and ethyl alcohol can also be
given that iridium complexes are frequently used as prec- employed as the alkylating agent. Thus, reaction of m- and
atalysts for C–N bond formation. Based on the 100% con- p-benzenediamine with 1-octanol yielded N,N′-dioctyl-m-
version and product analysis, all of the tested iridium benzenediamine and -p-benzenediamine in 85% and 90%
complexes have excellent activity for the oxidation of yield, respectively (Table 2, entries 7 and 11). In contrast,
benzyl alcohol into benzaldehyde; however, we found that the nitro-substituted benzyl alcohol is not suitable as the
the catalytic systems based on mononuclear iridium com- alkylating agent, as the reaction gave a mixture of uniden-
plexes associated with various ligands gave benzimid- tified products (Table 2, entry 12). Presumably, partial re-
azole 3 as the major product, not dialkylation product 2, duction of the nitro group resulted in complication of the
even though the reactions were carried out under hydro- reaction.
gen atmosphere (Table 1). From this screening, it clearly
shows that complex 1 is the most promising catalyst for
the N,N′-dialkylation of benzenediamines with alcohols.
In summary, we have described an efficient diiridium cat-
alytic process for the dialkylation of benzenediamines
with various alcohols. This catalytic system offers several
Presumably, the cooperative effect between the two metal
advantages for the preparation of such benzenediamines,
centers in complex 1 plays an important role in facilitating
such as low loading of catalyst, no required organic sol-
the reduction of imine, an effect which is absent in a
vent, high selectivity, and high yields, which make it a
mononuclear system.
useful and attractive methodology for organic synthesis.
In this study, we have established that the dimetallic cata-
Table 1 N,N′-Dialkylation of o-Benzenediamine Catalyzed by
lyst affects the catalytic selectivity dramatically, presum-
ably due to a synergistic effect. Detailed mechanistic
studies and further applications are currently under inves-
tigation.
Various Iridium Complexesa
Entry
Iridium catalyst
Conv.b (%) Yieldc (%)
3
2
1H and 13C NMR spectra were recorded in CDCl3 on a Bruker AM-
300 or Avance 400 spectrometer. Chemical shifts are given in parts
per million relative to TMS. HRMS data were recorded by using
ESI-TOF (Waters Micromass LCT Premier XE) and FABMS
(JEOL JMS-700) techniques. Chemicals and solvents were of ana-
lytical grade and were used as received, unless otherwise stated.
Complex 1 was prepared according to the method previously report-
ed.8
1
2
3
4
5
6
complex 1
100
100
100
98
–
90
–
Ir(IBn)(CO)2Cld
[Ir(cod)2Cl]2
78
80
50
70
38
–
[Ir(cod)2Cl]2/Ph3P
[Ir(cod)2Cl]2/dpppe
47
20
50
100
IrCl3/Me2N(CH2)2NMe2 97
Iridium-Catalyzed N,N′-Dialkylation of Benzenediamines;
General Procedure
a Reaction conditions: diamine (0.5 mmol), alcohol (3 mmol), iridium
complex (3 μmol), CsOH·H2O (0.15 mmol), molecular sieves (0.3 g),
120 °C, 48 h, under H2 atmosphere.
A mixture of the benzenediamine (54 mg, 0.5 mmol), an alcohol (3
mmol), iridium complex 1 (3 mg, 3 μmol), CsOH·H2O (25.2 mg,
0.15 mmol), and 4 Å molecular sieves (0.3 g) in a reaction tube was
flushed with nitrogen gas. The reaction mixture was heated at
120 °C for 48 h under hydrogen atmosphere. After the reaction
completion, H2O (5 mL) and EtOAc (3 × 5 mL) were added. The or-
ganic extract was separated, dried (MgSO4), and concentrated. The
desired product was purified by chromatography (CH2Cl2–EtOAc,
30:1 to 10:1). The structures of the products were confirmed from
their spectroscopic (1H and 13C NMR, and MS) data, which were
similar to those reported in the literature. Spectroscopic data of new
compounds are summarized below.
b Based on the consumption of diamine.
c NMR yields.
d IBn = 1,3-dibenzylimidazol-2-ylidene.
e dppp = Ph2P(CH2)3PPh2.
With this promising result, the scope and generality of the
N,N′-dialkylation reaction was investigated (Table 2). As
expected, all of the reactions proceeded smoothly and
some functional groups were tolerated, including methyl,
methoxy, bromo, and trifluoromethyl groups, but not the
nitro group. Thus, reaction of o-benzenediamine with var-
ious benzyl alcohols afforded the corresponding N,N′-
dibenzyl-o-benzenediamines in good to excellent yields
(Table 2, entries 1–4). The yield decreased slightly with
the use of the ortho-substituted benzyl alcohol presum-
ably due to steric hindrance (Table 2, entry 5).
N,N′-Bis(p-bromobenzyl)-o-benzenediamine10
Yield: 0.168 g (75%); yellow solid; mp 120–122 °C.
1H NMR (400 MHz, CDCl3): δ = 4.28 (s, 4 H, -ArCH2N-), 6.66–
6.68 (m, 2 H), 6.81–6.83 (m, 2 H), 7.26 (d, J = 6.4 Hz, 4 H), 7.47
(d, J = 6.4 Hz, 4 H).
13C NMR (100 MHz, CDCl3): δ = 138.2, 136.6, 131.5, 129.2, 120.8,
119.6, 112.2, 48.2.
HRMS–FAB: m/z [M]+ calcd for C20H18N2Br2: 443.9837; found:
443.9830.
Next, we explored the isomeric benzenediamines. Dial-
kylations of m- and p-benzenediamine with various alco-
hols, including aliphatic alcohols, proceeded smoothly to
yield the corresponding amines in good yields (Table 2,
entries 6–11). It should be noted that these reactions can
be carried out under nitrogen atmosphere, i.e. the hydro-
gen atmosphere is not required. Furthermore, aliphatic al-
N,N′-Bis[p-(trifluoromethyl)benzyl]-o-benzenediamine
Yield: 0.149 g (70%); yellow solid; mp 118–120 °C.
1H NMR (400 MHz, CDCl3): δ = 4.41 (s, 4 H, -ArCH2N-), 6.64–
6.67 (m, 2 H), 6.78–6.80 (m, 2 H), 7.49 (d, J = 8.0 Hz, 4 H), 7.59
(d, J = 8.0 Hz, 4 H).
Synthesis 2013, 45, 189–192
© Georg Thieme Verlag Stuttgart · New York

PAPER
Iridium(I)-Catalyzed N,N′-Dialkylation of Benzenediamines
191
Table 2 N,N′-Dialkylation of Benzenediamines with Various Alcoholsa
Entry
Diamine
Alcohol
Product
Yieldc (%)
1b
2b
3b
4b
5b
6
o-C6H4(NH2)2
BnOH
o-C6H4(NHBn)2
90
90
75
70
61
85
85
72
78
63
90
–
p-MeOC6H4CH2OH
p-BrC6H4CH2OH
p-F3CC6H4CH2OH
o-MeC6H4CH2OH
BnOH
o-C6H4(NHCH2C6H4-p-OMe)2
o-C6H4(NHCH2C6H4-p-Br)2
o-C6H4(NHCH2C6H4-p-CF3)2
o-C6H4(NHCH2C6H4-o-Me)2
m-C6H4(NHBn)2
m-C6H4(NH2)2
p-C6H4(NH2)2
7
Me(CH2)7OH
EtOHd
m-C6H4[NH(CH2)7Me]2
m-C6H4(NHEt)2
8
9
BnOH
p-C6H4(NHBn)2
10
11
12
p-F3CC6H4CH2OH
Me(CH2)7OH
p-O2NC6H4CH2OH
p-C6H4(NHCH2C6H4-p-CF3)2
p-C6H4[NH(CH2)7Me]2
unidentified mixture
a Reaction conditions: diamine (0.5 mmol), alcohol (3 mmol), iridium complex 1 (3 μmol), CsOH·H2O (0.15 mmol), molecular sieves (0.3 g),
120 °C, 48 h.
b Under H2 atmosphere.
c Isolated yields.
d Reaction was carried out in a sealed reactor.
13C NMR (100 MHz, CDCl3): δ = 143.3, 136.6, 129.6, 129.3 (JC–F
=
13C NMR (100 MHz, CDCl3): δ = 149.4, 129.7, 102.7, 96.9, 38.6,
3.8 Hz), 127.7, 125.4, 119.8, 112.3, 48.3.
15.1.
ESI-HRMS: m/z [M + H]+ calcd for C22H19N2F6: 425.1447; found:
ESI-HRMS: m/z [M + H]+ calcd for C10H17N2: 165.1386; found:
425.1455.
165.1390.
N,N′-Bis(o-methylbenzyl)-o-benzenediamine
Yield: 0.094 g (61%); yellow solid; mp 110–112 °C.
N,N′-Dibenzyl-p-benzenediamine6a
Yield: 0.112 g (78%); yellow solid; mp 107–109 °C.
1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 6 H, -CH3), 4.29 (s, 4 H,
-ArCH2N-), 6.77–6.79 (m, 2 H), 6.86–6.88 (m, 2 H), 7.19–7.23 (m,
6 H), 7.32 (d, J = 6.2 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ = 3.43 (br, 1 H, -NH-), 4.25 (s, 4 H,
-ArCH2N-), 6.57 (s, 4 H, Ar-H), 7.25–7.28 (m, 2 H, Ar-H), 7.31–
7.38 (m, 8 H, Ar-H).
13C NMR (100 MHz, CDCl3): δ = 136.8, 136.6, 136.1, 129.9, 128.1,
127.0, 125.7, 119.0, 111.5, 47.0, 19.3.
13C NMR (100 MHz, CDCl3): δ = 140.2, 139.4, 128.1, 127.2, 126.6,
114.3, 49.6.
ESI-HRMS: m/z [M + H]+ calcd for C22H25N2: 317.2012; found:
317.2017.
ESI-HRMS: m/z [M + H]+ calcd for C20H21N2: 289.1699; found:
289.1679.
N,N′-Dioctyl-m-benzenediamine11
Yield: 0.141 g (85%); white solid; mp 59–60 °C.
Acknowledgment
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 6 H, -CH3),
1.27–1.37 (m, 20 H, -CH2-), 1.55–1.62 (m, 4 H, -CH2-), 3.06 (t,
J = 6.8 Hz, 4 H, -CH2-), 3.49 (br, 2 H, -NH-), 5.85 (s, 1 H, Ar-H),
6.00 (dd, J = 8.0 Hz, 2.0 Hz, 2 H, Ar-H), 6.94 (t, J = 8.0 Hz, 1 H,
Ar-H).
We thank the National Science Council for financial support
(NSC100-2113-M-002-001-MY3).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
13C NMR (100 MHz, CDCl3): δ = 149.2, 129.5, 102.4, 96.8, 44.3,
m
tgioSrantnugIifoop
r
itmnatr
32.2, 30.0, 29.8, 29.6, 27.6, 23.1, 14.6.
ESI-HRMS: m/z [M + H]+ calcd for C22H41N2: 333.3264; found:
333.3249.
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© Georg Thieme Verlag Stuttgart · New York
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