Room-temperature multicomponent synthesis of 3,4-dihydroquinoxalin-2-amine derivatives using highly ordered 3D nanoporous aluminosilicate catalyst

Article abstract of DOI:10.1055/s-0030-1260957

Here we demonstrate on the synthesis of multifunctional 3,4-dihydroquinoxalin-2-amine derivatives through a three-component condensation of substituted o-phenylenediamines (OPDA), diverse ketones, and various isocyanides in the presence of AlKIT-5 catalys

Full text of DOI:10.1055/s-0030-1260957

LETTER
1923
Room-Temperature Multicomponent Synthesis of 3,4-Dihydroquinoxalin-2-
amine Derivatives Using Highly Ordered 3D Nanoporous Aluminosilicate
Catalyst
S
ubstituted 3,4-D
i
.
hydroquinox
S
alin-2-amine
D
h
erivatives obha,a,b M. Adharvana Chari,*b L.-C. Sang,b Salem S. Aldeyab,c K. Mukkanti,a A. Vinu*b
a
Centre for Chemical Sciences & Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University,
Kukatpally, Hyderabad 500085, Andhra Pradesh, India
International Center for Materials Nanoarchitectonics,WPI Research Center, National Institute for Materials Science,
1-1 Namiki, Tsukuba, 305-0044, Japan
b
Fax +81(29)8604706; E-mail: vinu.ajayan@nims.go.jp
Department of Chemistry, Petrochemicals Research Chair, Faculty of Science, King Saud University,
P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia
c
Received 10 April 2011
densation of an aryl 1,2-diamine with a 1,2-dicarbonyl
compound in refluxing ethanol or acetic acid which offers
high yield. Iodine and iodoxybenzoic acid have also been
used as catalysts for the synthesis of quinoxaline deriva-
Abstract: Here we demonstrate on the synthesis of multifunctional
3,4-dihydroquinoxalin-2-amine derivatives through a three-compo-
nent condensation of substituted o-phenylenediamines (OPDA), di-
verse ketones, and various isocyanides in the presence of AlKIT-5
catalyst which was found to be highly active and selective, afford- tives. Among the quinoxaline derivatives, dihydroquinox-
ing excellent yields (85–98%) in ethanol at room temperature (2–4
alines are quite attractive as they possess biological
h).
activity mainly as inhibitors of cholesteryl ester transfer
Key words: three-component condensation, o-phenylenediamines,
ketones, isocyanides, AlKIT-5, 3,4-dihydroquinoxalin-2-amine de-
rivatives
proteins. However, the reports on the synthesis of these
compounds are quite limited. Recently, Shaabani et al. re-
ported the preparation of 3,4-dihydroquinoxaline-2-amine
through a simple three-component condensation reaction
of o-phenylenediamines, diverse carbonyl compounds,
and isocyanides in the presence of a catalytic amount of p-
toluenesulfonic acid (PTSA).11 Unfortunately, PTSA is a
homogenous catalyst and cannot be recyclable which
makes the process costly.
Multicomponent reactions1 have been receiving much at-
tention in recent years because of their wide range of ap-
plications in the industries dealing with the synthesis of
fine chemicals and drugs. Multicomponent reactions offer
significant benefits like saving energy, time, money, and
raw materials over conventional linear-step syntheses. In
addition, multicomponent reactions help to avoid the us-
age of expensive, toxic, and hazardous solvents as the
multistep synthesis involves various steps which produce
considerable amount of wastes due to isolation and sepa-
ration of the products after each step which makes these
reactions eco- and energy-friendly. Among the various
multicomponent reactions, the synthesis of isocyanide-
based heterocycles2,3 is particularly attractive which ex-
hibit a wide range of biological activities. Moreover, they
have been extensively used in the pharmaceutical indus-
try.4–6 Among these isocyanide-based derivatives, quin-
oxalinone and its derivatives are very interesting nitrogen-
containing heterocylic compounds and have been widely
used in dyes, pharmaceuticals, and electrical/photochem-
ical materials. They also exhibit a wide variety of biolog-
ical activities, including, antibacterial, antidiabetic,7 and
antiviral.8
Recently, in organic synthesis, the use of heterogeneous
catalysts13,14 especially nanoporous materials15–22 which
can offer high specific surface area, large pore volume,
and uniform pore diameter has received considerable im-
portance because of their ease of handling, recoverability,
enhanced reaction rates, greater selectivity, and simple
workup. Among the various heterogeneous nanoporous
silica catalysts, nanoporous catalysts with 3D structures
are more advantageous than the catalysts with 1D nanop-
orous structures. We have recently demonstrated the syn-
thesis of AlKIT-5 material, which is highly acidic and
possesses a 3D mesostructure with Fm3m symmetry and
large cage-type pores.15 In continuation of our earlier
work16–22 on the synthesis of various organic fine chemi-
cals, we have used AlKIT-5 as an efficient acidic catalyst
instead of PTSA for the synthesis of 3,4-dihydroquinoxa-
lin-2-amine derivatives. To the best of our knowledge,
there has been no report available on the synthesis of 3,4-
dihydroquinoxalin-2-amine derivatives using nanoporous
materials as catalysts until now. Here, we demonstrate a
simple, convenient, and efficient method for the
synthesis23 of 3,4-dihydroquinoxalin-2-amine derivatives
under ethanol solvent using AlKIT-5 catalyst through
one-pot condensation reaction of substituted o-phenylene-
diamines, diverse ketones, and various isocyanides.
Consequently, several synthesis strategies have been fol-
lowed for the preparation of quinoxaline derivatives.9–12
One of the most important methods being the simple con-
SYNLETT 2011, No. 13, pp 1923–1929
x
x
.x
x
.2
0
1
1
Advanced online publication: 14.07.2011
DOI: 10.1055/s-0030-1260957; Art ID: U03211ST
© Georg Thieme Verlag Stuttgart · New York

1924
D. Shobha et al.
LETTER
R2
R3
H
N
R1
NH2
NH2
R1
O
AlKIT-5
R4
N
CH
+
+
R2
R3
EtOH, r.t., 2–4 h
N
N
R4
H
1
2
3
4
R1 = H, Cl
R2 = alkyl
R4 = cyclohexyl, benzyl
R
3 = alkyl, Ph
Scheme 1 Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives using AlKIT-5 catalyst at r.t.
Initially to optimize the reaction conditions, o-phenylene- ity of the catalyst increased with increasing the amount of
diamine 1 (108 mg, 1 mmol), butanone 2 (72 mg, 1 the catalyst in the reaction mixture which is mainly due to
mmol), and cyclohexyl isocyanide 3 (109.7 mg, 1 mmol) the availability of more number of active adsorption sites
were employed for the synthesis of novel 3,4-dihydro- in the reaction mixture. The yield of the final product in-
quinoxalin-2-amine derivative 4a (Table 3, entry 1) using creased from 70 to 94% with increasing the catalyst
AlKIT-5 catalyst with different Al contents in ethanol at weight from 50 to 200 mg. The effect of the amount of Al-
room temperature (Scheme 1).
KIT-5 catalyst on the synthesis of dihydroquinoxalines is
presented in the Table 1. Among the catalyst studied, the
AlKIT-5 with nSi/nAl ratio of 10 was found to be highly ac-
tive which is mainly due to its high acidity and large sur-
face area. The catalyst afforded the yield of product 4a
almost 94% within three hours reaction time.
The reaction was also carried out in the absence of AlKIT-
5 catalyst. Unfortunately, no product was formed under
such conditions. However, as expected, a significant dif-
ference in the activity of the catalyst was observed upon
increasing the Al content in the sample. The catalyst with
a high Al content registers a high activity with a high We surmise that AlKIT-5 catalyst acts as a Brønsted acid
product yield. A similar result was also obtained in our catalyst and the possible mechanism for the formation of
previous work on various acid-catalyzed transformations 3,4-dihydroquinoxalin-2-amine derivatives 4, as pro-
using AlKIT-5 as the catalyst.16–22 Interestingly, the activ- posed by Shaabani et al. is shown in Scheme 2.11 During
the reaction, firstly the intermediate A is formed in the
Table 1 Effect of the Weight on the Catalytic Activity of the AlKIT-
pore channel of the AlKIT-5 by the reaction with the di-
5 Catalysts and Comparison with Other Catalysts for the Synthesis of
amine 1 and the ketone which are adsorbed on the Brønst-
ed acid sites of the catalyst. The intermediate A was
converted into another intermediate B with the help of the
nucleophilic attack of isocyanide 3, which was further
converted into intermediate C through an intramolecular
nucleophilic attack of NH2 group to the activated nitrile
moiety. Finally, the intermediate undergoes the imine–
enamine tautomerization to yield the final product 4. It is
Novel 3,4-Dihydroquinoxalin-2-amine Derivativesa
Entry Catalyst
Weight of
catalyst (mg) (nm)
Dpads, BJH Acidity Yield
(mmol/g) (%)
1
2
3
4
5
6
7
8
AlKIT-5 (10)
50
100
150
200
150
150
100
6.0
6.0
6.0
6.0
5.6
5.2
–
0.50
0.50
0.50
0.50
0.32
0.14
–
70
94
94
94
84
75
92
85
AlKIT-5 (10)
AlKIT-5 (10)
AlKIT-5 (10)
AlKIT-5 (28)
AlKIT-5 (44)
Amberlyst
Table 2 The Effect of Solvent on the Synthesis of 3,4-Dihydro-
quinoxalin-2-amine Derivatives
Entry
Solvent
CH2Cl2
THF
Yield (%)
1
2
3
4
78
80
84
94
Montmorillonite 100
–
–
MeCN
EtOH
a Reaction conditions: substrate: o-phenylenediamine, butanone, and
cyclohexyl isocyanide; reaction time: 3 h, reaction temperature: r.t.,
solvent: EtOH, Dp: pore diameter.
R2
R3
••
H
R1
NH2
R1
N
O
AlKIT-5
R4
N
C
+
+
R2
R3
NH2
NH2
1
2
A
3
R2
R3
H
N
R2
R3
R2
R3
H
N
H
N
R1
R1
R1
– H+
R4
R4
••
••
H
N
N
N
NH2
N
N
R4
H
B
C
4
Scheme 2 Proposed mechanism for the synthesis of 3,4-dihydroquinoxalin-2-amine derivatives 4 using diamines 1, ketones 2, and iso-
cyanides 3
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York

LETTER
Substituted 3,4-Dihydroquinoxalin-2-amine Derivatives
1925
amazing to note that all the reaction processes are taken (CH2Cl2), tetrahydrofuran (THF), acetonitrile (MeCN),
place inside the nanochannels of AlKIT-5 where pores and ethanol (EtOH) studied, ethanol was found to be the
with large cages are available. These results reveal that excellent solvent for this transformation, and the results
AlKIT-5 is the best catalyst to synthesize dihydroquinox- are shown in Table 2 (using substrates as shown in
alines via a multicomponent reaction pathway.
Table 3, entry 1).
The effect of solvents was also investigated for this syn-
thesis. Among the various solvents like dichloromethane
Table 3 Synthesis of 3,4-Dihydroquinoxalin-2-amine Derivatives 4 Using Diamines 1, ketones 2, and Isocyanides 3
Entry
1
Diamine 1
Ketone 2
Isocyanide 3
Product 4a
Time (h) Yield (%)b
H
N
CH3
CH2CH3
N
N
N
C
C
C
NH2
O
3
3
3
94
91
93
N
N
H
H3C
CH2CH3
NH2
4a
H
N
O
NH2
NH2
2
3
N
N
H
4b
CH3
H
N
O
NH2
NH2
N
H
CH3
N
4c
H2N
CH3
H
N
O
N
C
NH2
NH2
4
3
90
CH3
N
N
H
NH2
4d
H
N
CH3
O
Br
N
N
C
C
NH2
NH2
5
6
4
2
90
98
CH3
N
N
H
Br
4e
H
N
CH3
O
CH3
NH2
NH2
CH3
N
N
H
H3C
4f
H2N
H
N
O
NH2
N
C
NH2
NH2
7
8
3
3
92
91
N
N
H
4g
H
N
CH3
O
N
C
NH2
NH2
CH3
N
NH
4h
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York

1926
D. Shobha et al.
LETTER
Table 3 Synthesis of 3,4-Dihydroquinoxalin-2-amine Derivatives 4 Using Diamines 1, ketones 2, and Isocyanides 3 (continued)
Entry
9
Diamine 1
Ketone 2
Isocyanide 3
Product 4a
Time (h) Yield (%)b
H
N
CH3
O
CH3
N
N
N
C
C
C
NH2
3
3
3
92
90
88
CH3
N
NH
NH2
H3C
4i
H
N
CH3
CH2CH3
Cl
Cl
Cl
NH2
NH2
O
10
11
N
N
H
H3C
CH2CH3
4j
H
N
Cl
O
NH2
NH2
N
N
H
4k
H
N
CH3
Cl
O
N
C
Cl
NH2
NH2
12
13
3
3
91
88
CH3
N
N
H
4l
H2N
H
N
CH3
O
Cl
N
C
Cl
NH2
NH2
CH3
NH2
N
N
H
4m
CH3
H
N
Cl
O
Br
N
N
C
C
Cl
Cl
NH2
NH2
14
15
4
3
85
92
CH3
N
N
H
Br
4n
H
N
CH3
Cl
O
CH3
NH2
NH2
CH3
N
N
H
H3C
4o
H2N
O
NH2
N
C
H
N
Cl
NH2
NH2
Cl
16
3
87
N
N
H
4p
a The products were characterized by 1H NMR and IR spectroscopy, and mass spectrometry.
b Yield refers to pure products after crystallization.
The reaction was also carried out with various substituted ing AlKIT-5 catalyst at room temperature for two to four
o-phenylenediamines 1, ketones 2, and isocyanides 3 us- hours (Table 3). Several structurally diverse isocyanides 3
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York

LETTER
Substituted 3,4-Dihydroquinoxalin-2-amine Derivatives
1927
including cyclohexyl- and benzyl-substituted ones were
used to get the products 4 in excellent yields. It was found
that the catalyst also worked well with other substituted
aryl and cyclic diamines and afforded good yields. All
synthesized products (4a–p) were stable and character-
References and Notes
(1) For reviews, see: (a) Kappe, C. O. Tetrahedron 1993, 49,
6937. (b) Kappe, C. O. In Multicomponent Reactions; Zhu,
J.; Bienaymé, H., Eds.; Wiley-VCH: Weinheim, 2005, 95.
(2) For reviews on isocyanide-based multicomponent reactions,
see: (a) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39,
3168. (b) Dömling, A. Chem. Rev. 2006, 106, 17. (c) Nair,
V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.;
Mathen, J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36, 899.
(3) For some recently reported examples with isocyanide, see:
(a) Silva, R. A. D.; Santra, S.; Andreana, P. R. Org. Lett.
2008, 10, 4541. (b) Fujiwara, S.-I.; Asanuma, Y.; Shin-Ike,
T.; Kambe, N. J. Org. Chem. 2007, 72, 8087. (c) Shaabani,
A.; Rezayan, A. H.; Ghasemi, S.; Sarvary, A. Tetrahedron
Lett. 2009, 50, 1456. (d) Heravi, M. M.; Baghernejad, B.;
Oskooie, H. A. Tetrahedron Lett. 2009, 50, 767.
(4) (a) Shaabani, A.; Maleki, A.; Moghimi-Rad, J. J. Org.
Chem. 2007, 72, 6309. (b) Shaabani, A.; Soleimani, E.;
Maleki, A. Tetrahedron Lett. 2006, 47, 3031. (c) Shaabani,
A.; Teimouri, M. B.; Arab Ameri, S. Tetrahedron Lett.
2004, 45, 8409.
(5) Porter, A. E. A. In Comprehensive Heterocyclic Chemistry,
Vol. 3; Katritzky, A. R.; Rees, C. W., Eds.; Pergamon Press:
New York, 1984, 191.
(6) Cheeseman, G. W. H.; Cookson, R. F. In The Chemistry of
Heterocyclic Compounds, 2nd ed.; Weissberger, A.; Taylor,
E. C., Eds.; Wiley: New York, 1979, 1.
(7) Gupta, D.; Ghosh, N. N.; Chandra, R. Bioorg. Med. Chem.
Lett. 2005, 15, 1019.
(8) Rosner, M.; Billhardt-Troughton, U. M.; Kirsh, R.; Kleim, J.
P.; Meichsner, C.; Riess, G.; Winkler, I. .
1
ized by using IR, H NMR, and MALDI-mass spectral
analysis.23 In addition, elemental analysis and melting
point measurements were carried out in order to confirm
the purity of the products.
The reactions were very clean and no other side products
were observed. Diamines and chloro-substituted diamines
1, aliphatic, aromatic, and cyclic ketones 2 and cyclohexyl
and benzyl isocyanides 3 gave satisfactory results
(Table 3, entries 1–16). As shown in Table 3, the catalyst
also gave good yield when aliphatic ketones were used
(Table 3, entries 1 and 10). Furthermore, cyclic ketones
were then introduced to prepare structurally interesting
spirocyclic compounds (Table 3, entries 2 and 11). Chlo-
ro-substituted diamines and various electrophilic and nu-
cleophilic substituted aromatic ketones were used to
synthesize multifunctionalized 3,4-dihydroquinoxalin-2-
amine derivatives. In addition, benzophenone also under-
went smooth conversion to afford the corresponding prod-
uct with reasonable yields (Table 3, entries 7 and 16).
Particularly, the detection and isolation of these com-
pounds are very easy, since the colors of the compounds
were yellow and brown. It has been also found that the
presence of the electron-donating methyl group (Table 3,
entries 6, 9, and 15) in the ketone significantly enhances
the rate of the reaction and afforded a high yield. The re-
cyclability of the catalyst was also checked to prove the
heterogeneous nature and its repeated use. We found that
the catalyst showed 90%, 88%, and 85% of yields
(Table 3, entry 1) in 2nd, 3rd, and 4th cycles, respectively.
(9) More, S. V.; Sastry, M. N. V.; Wang, C.-C.; Yao, C.-F.
Tetrahedron Lett. 2005, 46, 6345.
(10) (a) Heravi, M. M.; Keivanlo, A.; Rahimzadeh, M.; Bakavoli,
M.; Ghassemzadeh, M. Tetrahedron Lett. 2004, 45, 5747.
(b) Heravi, M. M.; Keivanlo, A.; Rahimzadeh, M.; Bakavoli,
M.; Ghassemzadeh, M. Tetrahedron Lett. 2005, 46, 1607.
(c) Heravi, M. M.; Derikvand, F. J. Mol. Catal. A. 2005, 242,
173. (d) Heravi, M. M.; Bakhtiari, K.; Bamoharram, F. F.
Catal. Commun. 2006, 7, 373.
In summary, we have synthesized novel polysubstituted
3,4-dihydroquinoxalin-2-amine derivatives using various
aromatic diamines, carbonyl compounds, and diverse iso-
cyanides in the presence of AlKIT-5 catalyst. The catalyst
was very active and afforded high yield in a short reaction
time and worked well for the synthesis of derivatives of
3,4-dihydroquinoxalin -2-amine using substituted ketones
and the diamines. The catalyst can also be recyclable and
truly heterogeneous. These excellent structural features of
the AlKIT-5 catalyst make this process simple and clean
which promote its use in various acid-catalyzed multi-
component reactions and create a platform for the devel-
opment of various pharmaceutical products.
(11) Shaabani, A.; Maleki, A.; Mofakham, H.; Khavasi, H. R.
J. Comb. Chem. 2008, 10, 323.
(12) (a) Kolla, S. R.; Lee, Y. R. Tetrahedron 2010, 66, 8938.
(b) Li, J.; Liu, Y.; Li, C.; Jia, X. Tetrahedron Lett. 2009, 50,
6502.
(13) Heravi, M. M.; Maryam, K. B.; Tehrani, H.; Javadi, N. M.;
Oskooie, H. A. ARKIVOC 2006, (xvi), 16.
(14) Chari, M. A.; Syamasundar, K. Catal. Commun. 2005, 6, 67.
(15) Srinivasu, P.; Alam, S.; Balasubramanian, V. V.; Velmathi,
S.; Sawant, D. P.; Bohlmann, W.; Mirajkar, S. P.; Ariga, K.;
Halligudi, S. B.; Vinu, A. Adv. Funct. Mater. 2008, 18, 640.
(16) Chakravarti, R.; Kalita, P.; Selvan, S. T.; Oveisi, H.;
Balasubramanian, V. V.; Kantam, M. L.; Vinu, A. Green
Chem. 2010, 12, 49.
(17) Shobha, D.; Chari, M. A.; Mano, A.; Selvan, S. T.;
Mukkanti, K.; Vinu, A. Tetrahedron 2009, 65, 10608.
(18) Vinu, A.; Kalita, P.; Balasubramanian, V. V.; Oveisi, H.;
Tamil Selvan, T.; Mano, A.; Chari, M. A.; Subba Reddy, B.
V. Tetrahedron Lett. 2009, 50, 7132.
(19) Chakravarti, R.; Kalita, P.; Pal, R. R.; Halligudi, S. B.;
Lakshmi Kantam, M.; Vinu, A. Microporous Mesoporous
Mater. 2009, 123, 338.
Acknowledgment
This work was financially supported by the Ministry of Education,
Culture, Sports, Science and Technology (MEXT) under the Strate-
gic Program for Building an Asian Science and Technology Com-
munity Scheme and World Premier International Research Center
(WPI) Initiative on Materials Nanoarchitectonics, MEXT, Japan.
(20) Balasubramanian, V. V.; Srinivasu, P.; Anand, C.; Pal, R. R.;
Ariga, K.; Velmathi, S.; Alam, S.; Vinu, A. Microporous
Mesoporous Mater. 2008, 114, 303.
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York

1928
D. Shobha et al.
LETTER
(21) Shobha, D.; Chari, M. A.; Tamil Selvan, S.; Oveisi, H.;
Mano, A.; Mukkanti, K.; Vinu, A. Microporous Mesoporous
Mater. 2010, 129, 112.
(22) Adharvana Chari, M.; Karthikeyan, G.; Pandurangan, A.;
Naidu, T. S.; Sathyaseelan, B.; Javaid Zaidi, S. M.; Vinu, A.
Tetrahedron Lett. 2010, 51, 2629.
680 cm–1. 1H NMR (300 MHz, DMSO-d6): d = 1.00–2.29
(m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.39 (s, 3 H, CH3), 3.97
(br s, 1 H, CHNH), 6.53 (br s, 1 H, NH), 6.77 (br s, 1 H, NH),
6.79–7.51 (m, 8 H, ArH) ppm. MALDI-MS: m/z [M+] = 398.
Anal. Calcd for C21H24BrN3: C, 63.32; H, 6.07; N, 10.55.
Found: C, 63.28; H, 6.01; N, 10.50.
(23) Experimental Procedure
Compound 4f: white solid; mp 202 °C. IR (KBr): nmax =
All chemicals and solvents were obtained from Aldrich and
used without further purification. The 1H NMR spectra of
samples were recorded on a JEOL 300-MHz NMR
spectrometer using TMS as an internal standard in DMSO-
d6. Mass spectra were recorded on a MALDI-MS. FT-IR
spectra of all the final products were recorded on a Perkin
Elmer 100 instrument by averaging 50 scans with a
resolution of 2 cm–1 measuring in absorbance mode by using
the KBr self-supported pellet technique. The melting points
of the novel products were determined by using melting
point apparatus.
3249, 2937, 2858, 1644, 1622, 1508, 1452, 1397, 1204,
1184, 754, 680 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.05–2.31 (m, 10 H, 2 × 5 CH2 of cyclohexyl) 1.37 (s, 3 H,
CH3), 1.38–1.50 (s, 3 H, CH3 of tolyl), 3.89 (br s, 1 H,
CHNH), 6.33–6.41 (br s, 1 H, NH), 6.69–6.73 (br s, 1 H,
NH), 6.73–7.57 (m, 8 H, ArH) ppm. MALDI-MS: m/z
[M+] = 333. Anal. Calcd for C22H27N3: C, 79.24; H, 8.16; N,
12.60. Found: C, 79.20; H, 8.12; N, 12.56.
Compound 4g: white solid; mp 250–252 °C. IR (KBr):
n
max = 3252, 2925, 2880, 1648, 1622, 1508, 1451, 1209,
1188, 753, 679 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.10–2.29 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 3.90 (br s, 1
H, CHNH), 6.50–6.58 (br s, 1 H, NH), 6.74–6.77 (br s, 1 H,
NH), 6.78–7.56 (m, 13 H, ArH) ppm. MALDI-MS: m/z
[M+] = 396. Anal. Calcd for C26H28N4: C, 78.75; H, 7.12; N,
14.13. Found: C, 78.70, H, 7.09; N, 14.10.
Typical Procedure for the Synthesis of 3,4-
Dihydroquinoxalin-2-amine Derivatives
To a solution of diamine (1 mmol), ketone (1 mmol), and
isocyanide (1 mmol) in EtOH (3 mL) was added AlKIT-5
(100 mg). The resulting mixture was stirred for 2–4 h at r.t.
After completion of the reaction, as indicated by TLC
(EtOAc–n-hexane, 2:1). The catalyst was filtered off, and
the product in filtrate was precipitated by addition of cold
H2O (10 mL). The residue was crystallized from EtOH to
give 4a–p as crystals. All products were characterized by
spectral (IR, NMR and MS) data and also by the melting
points of the samples. The spectral data of all novel
compounds are given below.
Compound 4h: off white solid; mp 160–162 °C. IR (KBr):
n
max = 3276, 2947, 2780, 1656, 1624, 1490, 1455, 1211,
1192, 815, 682 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.92 (s, 3 H, CH3), 2.32 (s, 2 H, CH2 of benzyl), 4.03 (br s, 1
H, NH), 4.93 (br s, 1 H, NH), 6.97–7.83 (m, 14 H, ArH) ppm.
MALDI-MS: m/z [M+] = 327. Anal. Calcd for C22H21N3: C,
80.70; H, 6.46; N, 12.38. Found: C, 80.66, H, 6.40, N, 12. 80.
Compound 4i: pale yellow solid; mp 140–142 °C. IR (KBr):
Compound 4a: white solid; mp 218–220 °C. IR (KBr):
nmax = 3250, 2996, 2850, 1654, 1624, 1489, 1450, 1190,
nmax = 3293, 2935, 2861, 1642, 1619, 1508, 1455, 1211,
1160, 815, 680 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.17 (s, 3 H, CH3), 2.34 (s, 3 H, CH3 of tolyl), 3.56–3.61 (m,
2 H, CH2 of benzyl), 4.03 (br s, 1 H, NH), 4.90 (br s, 1 H,
NH), 7.12–7.79 (m, 13 H, ArH) ppm. MALDI-MS: m/z
[M+] = 342. Anal. Calcd for C23H23N3: C, 80.90; H, 6.79; N,
12.31. Found: C, 80.86; H, 6.70; N, 12.28.
1178, 750, 681 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
0.88 (t, J = 3.0 Hz, 3 H, CH2CH3), 1.35 (q, J = 2.8 Hz, 2 H,
CH2), 1.49 (s, 3 H, CH3), 1.11–2.34 (m, 10 H, 2 × 5 CH2 of
cyclohexyl), 3.99 (br s, 1 H, CHNH), 6.31–6.41 (br s, 1 H,
NH), 6.70–6.74 (br s, 1 H, NH), 6.78–7.65 (m, 4 H, ArH)
ppm. MALDI-MS: m/z [M+] = 271. Anal. Calcd for
C17H25N3: C, 75.23; H,9.28; N,15.48. Found: C, 75.20; H,
9.24; N, 15.45.
Compound 4j: light grey solid; mp 190–192 °C. IR (KBr):
nmax = 3261, 2933, 2860, 1640, 1620, 1502, 1455, 1200,
1191, 815, 682 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
0.87 (t, J = 3.0 Hz, 3 H, CH2CH3), 1.22 (q, J = 2.8 Hz, 2 H,
CH2), 1.50 (s, 3 H, CH3), 1.30–2.33 (m, 10 H, 2 × 5 CH2 of
cyclohexyl), 3.93–4.04 (br s, 1 H, CHNH), 6.45–6.56 (br s,
1 H, NH), 6.72–6.84 (br s, 1 H, NH), 6.89–7.65 (m, 3 H, Ar-
H) ppm. MALDI-MS: m/z [M+] = 305. Anal. Calcd for
C17H24ClN3: C, 66.76; H, 7.91; N, 13.74. Found: C, 66.71;
H, 7.88, N, 13.70.11
Compound 4b: off white solid; mp 230–232 °C. IR (KBr):
n
max = 3351, 2935, 2851, 1622, 1541, 1508, 1448, 1314,
1190, 738, 685 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
0.98–1.95 (m, 20 H, 2 × 5 CH2 of cyclohexyl), 3.86 (br s, 1
H, CHNH), 6.69 (br s, 1 H, NH), 6.77 (br s, 1 H, NH), 7.02–
7.46 (m, 4 H, ArH) ppm. MALDI-MS: m/z [M+] = 297.
Anal. Calcd for C19H27N3: C, 76.72; H, 9.15; N, 14.13.
Found: C, 76.69; H, 9.10, N, 14.10.
Compound 4k: brown solid; mp 148–150 °C. IR (KBr):
Compound 4c: pale yellow solid; mp 305–307 °C. IR (KBr):
nmax = 3338, 2929, 2890, 1636, 1619, 1500, 1450, 1198,
n
max = 3300, 3252, 2938, 2863, 1649, 1621, 1512, 1462,
1186, 815, 684 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
0.81–2.32 (m, 20 H, 2 × 5 CH2 of cyclohexyl), 3.86 (br s, 1
H, CHNH), 6.69–6.76 (br s, 1 H, NH), 6.76–6.85 (br s, 1 H,
NH), 7.01–7.52 (m, 3 H, ArH) ppm. MALDI-MS: m/z
[M+] = 331. Anal. Calcd for C19H26ClN3: C, 68.76; H, 7.90;
N,12.66. Found: C, 68.69; H, 7.87; N, 12.64.11
1213, 1179, 752, 683 cm–1. 1H NMR (300 MHz, DMSO-d6):
d = 1.06–2.33 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.89 (s, 3
H, CH3), 4.05 (br s, 1 H, CHNH), 6.64–6.71 (br s, 1 H, NH),
6.95–6.99 (br s, 1 H, NH), 7.09–7.67 (m, 9 H, ArH) ppm.
MALDI-MS: m/z [M+] = 319. Anal. Calcd for C21H25N3: C,
78.96; H, 7.89; N, 13.15. Found: C, 78.93; H, 7.86; N, 13.10.
Compound 4d: pale yellow solid; mp 240 °C. IR (KBr):
Compound 4l: pale pink solid; mp 245–247 °C. IR (KBr):
n
max = 3259, 2938, 2859, 1644, 1619, 1501, 1456, 1212,
n
max = 3249, 2925, 2864, 1647, 1620, 1508, 1397, 1451,
1182, 816, 680 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.04–2.28 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.40 (s, 3 H,
CH3), 3.92–4.19 (br s, 1 H, CHNH), 6.70–6.88 (br s, 1 H,
NH), 6.88–7.07 (br s, 1 H, NH), 7.08–7.88 (m, 8 H, ArH)
ppm. MALDI-MS: m/z [M+] = 353. Anal. Calcd for
C21H24ClN3: C, 71.27; H, 6.84; N, 11.87. Found: C, 71.23;
H, 6.80; N, 11.80.11
1187, 752, 679 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.01–2.28 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.39 (s, 3 H,
CH3), 3.90 (br s, 1 H, CHNH), 6.52 (br s, 1 H, NH), 6.74 (br
s, 1 H, NH), 6.77–7.51 (m, 8 H, ArH) ppm. MALDI-MS:
m/z [M+] = 334. Anal. Calcd for C21H26N4: C, 75.41; H, 7.84;
N, 16.75. Found: C, 75.37; H, 7.80; N, 16.70.
Compound 4e: white solid; mp 262 °C. IR (KBr): nmax
=
Compound 4m: pale pink solid; mp 258–260 °C. IR (KBr):
nmax = 3273, 2923, 2851, 1646, 1625, 1513, 1458, 1401,
3253, 2937, 2864, 1642, 1620, 1509, 1455, 1202, 1190, 753,
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York

LETTER
1207, 1188, 810, 680 cm–1. 1H NMR (300 MHz, DMSO-d6):
Substituted 3,4-Dihydroquinoxalin-2-amine Derivatives
1929
nmax = 3272, 2924, 2853, 1647, 1612, 1513, 1457, 1208,
d = 1.04–2.28 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.40 (s, 3
H, CH3), 3.83–3.94 (br s, 1 H, CHNH), 6.69–6.74 (br s, 1 H,
NH), 6.75–6.78 (br s, 1 H, NH), 6.78–7.50 (m, 7 H, ArH)
ppm. MALDI-MS: m/z [M+] = 369. Anal. Calcd for
C21H25ClN4: C, 68.37; H, 6.83; N, 15.19. Found: C, 68.31;
H, 6.80; N, 15.12.11
1188, 810, 680 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
0.98–2.20 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.37 (s, 3 H,
CH3), 2.26 (s, 3 H, CH3 of tolyl), 4.00 (br s, 1 H, CHNH),
6.58–6.74 (br s, 1 H, NH), 6.74–6.77 (br s, 1 H, NH), 6.77–
7.49 (m, 7 H, Ar) ppm. MALDI-MS: m/z [M+] = 367. Anal.
Calcd for C22H26ClN3: C, 71.82; H, 7.12; N, 11.42. Found:
C, 71.78; H, 7.08; N, 11.36.11
Compound 4n: violet solid; mp 218–220 °C. IR (KBr):
n
max = 3270, 2938, 2864, 1648, 1620, 1503, 1456, 1205,
Compound 4p: pale brown solid; mp 258–260 °C. IR (KBr):
1185, 815, 680 cm–1. 1H NMR (300 MHz, DMSO-d6): d =
1.02–2.27 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 1.37 (s, 3 H,
CH3), 4.01 (br s, 1 H, CHNH), 6.68–6.74 (br s, 1 H, NH),
6.75–6.81 (br s, 1 H, NH), 6.89–7.57 (m, 7 H, ArH) ppm.
MALDI-MS: m/z [M+] = 432. Anal. Calcd for
nmax = 3275, 2925, 2864, 1639, 1629, 1501, 1458, 1401,
1200, 1186, 810, 679 cm–1. 1H NMR (DMSO-d6): d = 1.14–
2.29 (m, 10 H, 2 × 5 CH2 of cyclohexyl), 3.87 (br s, 1 H,
CHNH), 6.71–6.74 (br s, 1 H, NH), 6.75–6.78 (br s, 1 H,
NH), 6.79–7.52 (m, 12 H, ArH) ppm. MALDI-MS:
m/z = 430. Anal. Calcd for C26H27ClN4: C, 72.46; H, 6.31; N,
13.00. Found: C, 72.40, H, 6.29, N, 13.05.11
C21H23BrClN3: C, 58.28; H, 5.36; N, 9.71. Found: C, 58.22;
H, 5.28; N, 9.65.11
Compound 4o: brown solid; mp 235–237 °C. IR (KBr):
Synlett 2011, No. 13, 1923–1929 © Thieme Stuttgart · New York