Highly efficient synthesis of quinoxaline derivatives catalized by iridium complex

Article abstract of DOI:10.1134/S1070363216120562

A novel iridium complex was used to catalyze a mild reaction of phenylenediamine with propanediol that led to formation of quinoxaline derivatives with moderate to high yields. The reaction diemonstrated strong compatibility with substrates bearing various functional groups.

Full text of DOI:10.1134/S1070363216120562

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 12, pp. 2887–2890. © Pleiades Publishing, Ltd., 2016.
Highly Efficient Synthesis of Quinoxaline Derivatives Catalized
1
by Iridium Complex
a
a
a
b
a
D. Lv *, Z. Xie , B. Gu , H. Wu **, and H. Wan
a
School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu Province, 214122 China
b
Huzhou Entry-Exit Inspection and Quarantine Bureau, Huzhou, 313000 China
e-mail: *lvdongyunjnu.chemistry@yahoo.com; **whp@hz.ziq.gov.cn
Received January 5, 2016
Abstract—A novel iridium complex was used to catalyze a mild reaction of phenylenediamine with
propanediol that led to formation of quinoxaline derivatives with moderate to high yields. The reaction
diemonstrated strong compatibility with substrates bearing various functional groups.
Keywords: phenylenediamine, propanediol, quinoxaline derivatives, iridium complex
DOI: 10.1134/S1070363216120562
Quinoxaline derivatives attracted close attention of
pharmaceutical industry due to their antibacterial [1],
antiviral [2], kinase inhibition [3, 4] and anticancer [5]
activity. Quinoxalines have been tested as dyes [6, 7],
organic semiconductors [8, 9] and building blocks for
the synthesis of cavitands [10].
media and Cs CO as most efficient base for the
process (Table 1).
2
3
a
Table 1. Screening of optimized reaction conditions for 3a
HO
NH2
N
Various strategies have been developed for the
synthesis of quinoxalines. The use of θ-phenylene
diamine and 1,2-dicarbonyl compounds as starting
materials is considered as the conventional method
A
+
solvent
HO
Me
NH2
N
1
2
3a
b
[11]. Later higher yields of the products were achieved
Entry
Base
Solvent
Toluene
Yield , %
24
by using various catalysts [13–15] and synthetic
methods[16–18] that still had some disadvantages.
Recently Goldberg and co-workers [19] reported a new
type of iridium compound A (Scheme 1) which proved
to be an efficient catalyst for hydrogenation of
carboxylic acids under relatively mild conditions.
Herein, we report the iridium catalyzed condensation of
phenylenediamines and propanediols that gave
quinoxaline derivatives with moderate to high yields.
1
2
3
4
5
6
7
8
9
Na
Na
Na
Na
2
2
2
2
CO
CO
CO
CO
3
3
3
3
CH
2
Cl
2
<5
Benzene
DMF
24
<10
<10
14
Na CO3
2
THF
Na
2
2
CO
CO
3
3
Dioxane
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Na
31
RESULTS AND DISCUSSION
NaHCO
KOH
3
41
Initially we targeted development of a new method
of synthesis of quinoxaline derivatives from phenylene-
diamines and propanediols with iridium complex A
16
1
1
1
0
1
2
t-BuOK
44
(
Scheme 1). 1,2-Phenylenediamine and 1,2-propane-
Cs
CO
t-BuONa
2
CO
3
73
diol were selected as the model substrates for testing
the reaction. The corresponding product was isolated
with 24% yield. (Table 1, entry 1). Following tests of
various solvents and bases indicated xylene as the best
K
2
3
39
13
51
a
Conditions: 1 (0.5 mmol, 1.0 equiv), 2 (1.0 equiv), Cat. [Ir]
5 mmol %), base (3.0 equiv), solvent (4 mL), 48 h, reflux.
Isolated yields base on 1.
(
1
b
The text was submitted by the authors in English.
2
887

2
888
LV et al.
Scheme 1. Some methods for preparation of quinoxalines derivatives.
NH2
O
N
CuPd
OH
[
Previsious work]
NH2
NH2
N
N
O
GdZn
+
+
[
Previsious work]
NH2
O
N
N
NH2
HO
R2
A
[This work]
NH2
HO
R1
N
(
OTf)2
Ir
N
OH2
N
MeOOC
COOMe
A
Scheme 2. Proposed mechanism of the reaction.
HO
HO
NH2
N
N
[
M]
+
−
2H , −2H O
2
2
NH2
[
M]
[
M]H2
[M]H2
[M]
OH
O
O
N
N
NH2
NH2
HO
NH2
NH2
The synthetic data are presented in Table 2.
EXPERIMENTAL
eluents. All yields are presented for pure products. The
reaction progress was commonly monitored by TLC
using SiO sheets and compounds were visualized
2
1
under UV light. The products were verified by H
All chemicals were commercially available and
NMR spectra recorded on a Bruker Advance 400 and
used without further purification unless otherwise
stated. All solvents were dried and freshly distilled
under the atmosphere of nitrogen. The products were
separated and purified by column chromatography on
silica gel (200–300 or 100–200 mesh) by using
petroleum ether (60–90°C) and ethyl acetate as the
300 in CDCl using TMS as the reference.
3
General procedure for the synthesis of 3a. The
catalyst A (5% mmol, 0.05 mmol), 1,2-phenylene
diamine (1 mmol, 1.0 equiv), 1,2-propanediol (1 mmol,
1.0 equiv), Cs CO (3.0 equiv) and xylene (4 mL) were
2
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 12 2016

HIGHLY EFFICIENT SYNTHESIS OF QUINOXALINE DERIVATIVES
2889
a
Table 2. Synthesis of quinoxalines derivatives
NH2
N
N
R2
R1
HO R2
Ir, 5%
R
+
R
NH2
HO R1
1
2
3
b
b
Comp.
no.
Yield , Comp.
Yield ,
%
Substrate
HO
Product
N
Substrate
Product
%
no.
NH2
3
a
73
3e
N
66
O
NH2
NH2
HO
HO
Me
Me
N
N
O
N
N
3
b
71
65
58
3f
3g
3h
56
62
43
HO
HO
Me
N
N
Cl
N
NH2 Cl
N
NH2
N
3
c
N
HO
HO
Ph
Ph
N
N
Ph
Ph
NH2
N
N
HO
3
d
HO
Ph
N
Ph
HO
N
a
Conditions: 1 (1 mmol, 1.0 equiv), 2 (1 equiv), Cat. [Ir] (5% mmol), Cs
Isolated yields based on 1.
2 3
CO (3.0 equiv), xylene (4 mL), 48 h, reflux.
b
1
added to a Schlenk tube under the atmosphere of
nitrogen. The mixture was heated for 48 h at 150°C
and then cooled down to room temperature. The volatile
solvent was evaporated. The residue was purified by
column chromatography to give the corresponding
product 3a.
6-Chloro-2,3-dimethylquinoxaline (3f). H NMR
spectrum, δ, ppm: 7.86 s (1H), 7.80 d (1H, J = 9.2 Hz),
7.50 d.d (1H, J = 8.8, 1.6 Hz), 2.63 s (6H).
1
2
,3-Dimethylpyrido[3,4-b]pyrazine (3g). H NMR
spectrum, δ, ppm: 9.33 s (1H), 8.66 d (1H, J = 5.6 Hz),
.74 d (1H, J = 5.6 Hz), 2.71 s (6H).
7
1
2
-Methylquinoxaline (3a). H NMR spectrum, δ,
1
1
,2,3,4-Tetrahydrophenazine (3h). H NMR spec-
trum, δ, ppm: 7.87 d.d (2H, J = 6.4, 3.2 Hz), 7.56 d.d
2H, J = 6.0, 3.2 Hz), 3.07 m (4H), 1.94 m (4H).
CONCLUSIONS
ppm: 8.66 s (1H), 7.99 d (1H, J = 8.0 Hz), 7.94 d (1H,
J = 8.0 Hz), 7.69–7.59 m (2H), 2.70 s (3H).
(
1
2
,3-Dimethylquinoxaline (3b). H NMR spectrum,
δ, ppm: 7.88 d.d (2H, J = 6.0, 3.6 Hz), 7.55 d.d (2H,
J = 6.0, 3.6 Hz), 2.62 s (6H).
A simple, convenient, mild conditions, and
moderate to high yields procedure for the synthesis of
quinoxalines has been developed using iridium
complex as the catalyst.
1
2
-Phenylquinoxaline (3c). H NMR spectrum, δ,
ppm: 9.22 s (1H), 8.22–7.92 m (4H), 7.67 m (2H),
.53–7.36 m (3H).
7
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