Amberlyst-15: An efficient and reusable catalyst for multi-component synthesis of 3,4-dihydroquinoxalin-2-amine derivatives at room temperature

Article abstract of DOI:10.1016/j.tetlet.2011.09.015

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 an efficient and re

Full text of DOI:10.1016/j.tetlet.2011.09.015

Tetrahedron Letters 52 (2011) 6108–6112
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journal homepage: www.elsevier.com/locate/tetlet
Amberlyst-15: an efficient and reusable catalyst for multi-component
synthesis of 3,4-dihydroquinoxalin-2-amine derivatives at room temperature
⇑
Murugulla Adharvana Chari
Dr. MACS Bio-Pharma Pvt. Ltd., Plot-32/A, Westren Hills, Kukatpally, Hyderabad 85, A.P., India
Department of Complexity Science and Engineering, School of Frontier Sciences, 5-1-5, Kashiwanoha, Kashiwa, University of Tokyo, Chiba 277-8561, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
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 var-
ious isocyanides in the presence of an efficient and reusable amberlyst-15 catalyst which was found to be
highly active and afforded excellent yields (85–99%) in ethanol at room temperature (2–3 h).
Ó 2011 Elsevier Ltd. All rights reserved.
Received 3 August 2011
Revised 31 August 2011
Accepted 4 September 2011
Available online 8 September 2011
Keywords:
Three component condensation
o-Phenylenediamines
Diverse ketones
Various isocyanides
Amberlyst-15
3,4-Dihydroquinoxalin-2-amine derivatives
Due to the wide range of industrial applications, multi compo-
nent reactions (MCRs)1 have been receiving much attention in re-
cent years. Among the various MCRs, the synthesis of isocyanide
based heterocycles2,3 is particularly attractive which exhibit a wide
range of biological activities. Moreover, they have been extensively
used in the pharmaceutical industry.4–6 Among these isocyanide
based derivatives, quinoxalinone and its derivatives are very inter-
esting nitrogen containing heterocycles with wide applications in
the pharmaceutical field,7,8 and several synthetic strategies have
been followed for the preparation of quinoxaline derivatives.9–11
One of the most important methods is the simple condensation of
an aryl 1,2-diamine with a 1,2-dicarbonyl compound in refluxing
ethanol or acetic acid which offers high yield. Among the quinoxa-
line derivatives, dihydroquinoxalines are quite attractive, as they
act as inhibitors of cholesteryl ester transfer proteins. However,
the reports on the synthesis of these compounds are quite limited.
Recently, Shaabani et al.11e first reported the synthesis of 3,4-dihy-
droquinoxaline-2-amines through a simple three-component con-
densation reaction of o-phenylenediamines, diverse carbonyl
compounds, and isocyanides in the presence of a catalytic amount
of p-toluenesulfonic acid (PTSA). A few other reports have also ap-
peared on the synthesis of various 3,4-dihydroquinoxaline-2-
amines using Fe(ClO4)3,12 ceric ammonium nitrate (CAN),13 and
EDTA.14 Unfortunately, these are homogenous catalysts and are
not recyclable which makes the process expensive. Recently, in or-
ganic synthesis the use of heterogeneous catalysts15 especially
amberlyst-1516–20 has received considerable importance because
of their ease of handling, recoverability, enhanced reaction rates,
greater selectivity, and simple work-up. In continuation of our ear-
lier work15b–e on the synthesis of various organic compounds, using
different heterogeneous catalysts, herein we wish to report a simple,
convenient, and efficient method for the synthesis of 3,4-dihydro-
quinoxalin-2-amine derivatives using ethanol as solvent and
amberlyst-15 as the recyclable catalyst involving a one pot conden-
sation of substituted o-phenylenediamines, diverse ketones and,
various isocyanides. To the best of our knowledge, there has been
no report on the synthesis of 3,4-dihydroquinoxalin-2-amine deriv-
atives using amberlyst-15 as heterogeneous catalyst till now.
Initially to optimize the reaction conditions, o-phenylenedi-
amine 1 (1 mmol), butanone 2 (1 mmol), and cyclohexyl isocyanide
3 (1 mmol) were employed for the synthesis of 3,4-dihydroquinox-
alin-2-amine derivative 4a (Table 3, entry a) using 150 mg of
amberlyst-15 catalyst at room temperature (Scheme 1).
No product was formed in the absence of the amberlyst-15 cat-
alyst. The effect of the amount of amberlyst-15 catalyst on the syn-
thesis of dihydroquinoxalin-2-amines is presented in Table 1. The
results obtained here indicate that the efficiency of the reaction
(higher yield) increased when a higher amount of the catalyst is
used. The yield of the final product increases from 77% to 98% with
increasing the amount of the catalyst from 50 to 150 mg. Among
the various amounts of the catalyst studied, 150 mg amberlyst-15
was found to be highly active. The catalyst afforded 98% yield of
the product 4a in 2 h time at rt.
⇑
Fax: +91 40 40206647.
E-mail address: drmac_s@yahoo.com
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doi:10.1016/j.tetlet.2011.09.015

M. Adharvana Chari / Tetrahedron Letters 52 (2011) 6108–6112
6109
H
N
R2
R3
R1
NH2
+
NH2
R1
O
Amberlyst-15
+ R4 N C
R2
R3
N R4
H
EtOH, R.T., 2-3h
R4 = Cyclohexyl, Benzyl
R3 = Alkyl, Phenyl
N
4(a-t)
1
3
2
R2 = Alkyl
R1= H, Cl
Scheme 1. Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives using amberlyst-15 catalyst at rt.
Table 1
Table 2
Effect of the amount of the amberlyst-15 and montmorillonite-K10 catalysts on
reaction yield for the synthesis of 3,4-dihydroquinoxalin-2-amine derivative (4a)
The effect of solvent on the synthesis of 3,4-dihydroquinoxalin-2-amine derivative
(4a)
S. No. Catalyst
Wt of the catalyst (mg) Time
(h)
Yield
(%)
S. No.
Solvent
Yield (%)
1
2
3
4
Methylene chloride
Tetrahydrofuran
Acetonitrile
78
84
86
98
1
2
3
4
Amberlyst-15
50
2
2
2
2
77
92
98
85
Amberlyst-15
Amberlyst-15
Montmorillonite-
K10
100
150
150
Ethanol
Reaction conditions: substrates: o-phenylenediamine, butanone and cyclohexyl
isocyanide; reaction time: 2 h, reaction temperature: room temperature, solvent:
ethanol.
and cyclic ketones and afforded good yields. Diamine or chloro
substituted diamine 1, aliphatic, aromatic or cyclic ketones 2,
and cyclohexyl or benzyl isocyanides 3 gave good yields of prod-
ucts (Table 3, entry 4a–t). As shown in Table 3, the catalyst also
gave good yield when aliphatic ketones were used (Table 3, entry
a, j, and n). Furthermore, cyclic ketones were then introduced to
prepare structurally interesting spirocyclic compounds (Table 3,
entry b, c, d, k, and o). Chloro substituted diamines and various
electrophilic and nucleophilic substituted aromatic ketones were
used to synthesize multifunctionalized 3,4-dihydroquinoxalin-2-
amine derivatives. In addition, aminobenzophenone also under-
went smooth conversion to afford the corresponding product with
reasonable yields (Table 3, entry i and t). It was also found that the
presence of electron-donating methyl group (Table 3, entry h and
m) in the ketone significantly enhanced the rate of the reaction
and afforded high yield. The recyclability of the catalyst was also
checked to prove the heterogeneous nature and its repeated use.
We found that the catalyst showed 95%, 92%, and 90% of yields
(Table 3, entry a) in 2nd, 3rd, and 4th cycles, respectively. All the
synthesized products (4a–t) were stable and characterized by
using IR, 1H NMR, and MALDI-mass spectral analysis. Amberlyst-
15 is an inexpensive and non-hazardous solid acid catalyst. It can
be easily handled and separated from the reaction mixtures by
simple filtration. The recovered catalyst was reused three times
with a minimum variation in the yields of the products.
A possible mechanism for the formation of 3,4-dihydroquinox-
alin-2-amine derivatives 4, as proposed by Shaabani et al. is shown
in Scheme 211e and that amberlyst-15 catalyst acts as a Brönsted
acid. During the reaction, firstly the intermediate A is formed in
the pore channel of the amberlyst by the reaction of the diamine
1 and ketone which are adsorbed on the Brönsted acid sites of
the catalyst. The intermediate A is converted into another interme-
diate B with nucleophilic attack of isocyanide 3, which is further
converted into intermediate C through an intramolecular nucleo-
philic attack of –NH2 group to the activated nitrile moiety. Finally,
the intermediate C undergoes, tautomerization to the more stable
imine-enamine (due to conjugation with the aromatic ring) to
yield the final product 4. These results reveal that amberlyst-15
is the best catalyst to synthesize dihydroquinoxalin-2-amines via
MCR pathway.
The effect of solvents was also investigated for this synthesis.
Among the various solvents, such as methylene chloride, tetrahy-
drofuran (THF), acetonitrile, and ethanol studied, ethanol was
found to be the excellent solvent for this transformation and the
results are shown in Table 2.
The reaction21 was also carried out using optimized conditions
with chloro substituted o-phenylenediamine and its unsubstituted
precursor 1, ketones 2, and isocyanides 3 using amberlyst-15 cat-
alyst at room temperature for 2–3 h (Table 3). Various structurally
diverse isocyanides 3 including cyclohexyl and benzyl substituted
ones were used to get products 4 in excellent yields. It was found
that the catalyst also worked well with aliphatic, substituted aryl
In conclusion, we have synthesized a polysubstituted 3,4-dihy-
droquinoxalin-2-amine derivatives using various aromatic dia-
mines, carbonyl compounds, and diverse isocyanides in the
presence of amberlyst-15 as a heterogeneous solid acid. 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-dihydroquinoxa-
R2
H
R1
NH2
NH2
R1
N
O
Amberlyst-15
R3
R3
R4
N
C
+
R2
+
NH2
1
2
A
C
3
R2
H
N
H
N
R2
R3
H
N
R2
N
R3
R1
R1
R1
R3
-H
R4
R4
N
N
H
N
N
H
NH2
R4
B
4
Scheme 2. Proposed mechanism for the synthesis of 3,4-dihydroquinoxalin-2-amine derivatives 4 using diamines 1, ketones 2, and isocyanides 3.

6110
M. Adharvana Chari / Tetrahedron Letters 52 (2011) 6108–6112
Table 3
Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives 4(a–t) using diamines 1, ketones 2, and isocyanides 3
Entry
Diamine(1)
Ketone(2)
Isocyanide(3)
Producta 4(a–t)
Time(h)
2
Yieldb (%)
H
NH2
O
CH
CH -CH
C
N
3
N
2
3
a
98,95c,92c,90c
H3C
CH2-CH3
NH2
N
H
N
H
NH2
NH2
O
O
C
C
N
N
N
b
c
3
3
92
95
N
N
H
H
N
NH2
NH2
N
N
H
NH2
NH2
O
H
N
C
C
N
N
d
e
3
3
85
97
N
N
H
CH
NH2
NH2
O
O
H
N
3
CH3
CH3
N
H
N
H2N
NH2
NH2
C
N
CH
H
N
3
f
3
94
NH2
N
N
H
CH
NH2
NH2
O
H
N
3
C
C
N
N
Br
CH3
g
3
2
90
99
N
H
N
Br
H
N
NH2
NH2
O
CH3
CH3
CH3
h
N
H
N
H3C
NH2
NH2
NH2
H2N
O
C
N
H
N
i
j
3
3
92
96
N
N
H
H
N
NH2
NH2
O
CH3
C
N
CH3
CH3
H3C
O
N
H
N
H
N
NH2
NH2
C
N
k
l
3
3
3
92
91
92
N
N
H
H
N
NH2
NH2
NH2
NH2
O
CH3
C
N
N
H
N
CH3
N
O
H
N
CH3
HN
C
CH3
CH3
m
N
H3C

M. Adharvana Chari / Tetrahedron Letters 52 (2011) 6108–6112
6111
Table 3 (continued)
Entry
Diamine(1)
Ketone(2)
Isocyanide(3)
Producta 4(a–t)
Time(h)
3
Yieldb (%)
Cl
NH2
NH2
O
H
CH3
CH2-CH3
C
N
N
N
Cl
H3C
O
CH -CH3
2
n
90
N
H
Cl
Cl
NH2
NH2
H
N
N
N
C
C
C
Cl
Cl
o
p
3
3
88
92
N
H
N
NH2
NH2
O
O
H
N
CH3
CH3
N
H
N
Cl
NH2
NH2
H2N
CH3
N
H
N
Cl
Cl
Cl
CH3
NH2
q
3
88
N
N
H
NH2
NH2
O
H
N
C
Cl
Cl
N
N
N
CH3
Br
CH3
CH3
r
3
3
85
93
N
N
H
Br
NH2
NH2
O
H
N
CH3
C
CH3
s
N
N
H
H3C
Cl
NH2
NH2
O
NH2
C
H2N
H
N
Cl
t
3
87
N
H
N
a
b
c
The products were characterized by 1H NMR, IR and Maldi-Mass spectroscopy.
Yield refers to pure products after crystallization.
Yields in 2nd, 3rd, and 4th cycles, respectively.
6. Cheeseman, G. W. H.; Cookson, R. F. In The Chemistry of Heterocyclic Compounds;
Weissberger, A., Taylor, E. C., Eds., 2nd ed.; Wiley: New York, 1979; p 1.
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Riess, G.; Winkler, I. U.S. Patent, 5723461, 1998.
9. More, S. V.; Sastry, M. N. V.; Wang, C. C.; Yao, C.-F. Tetrahedron Lett. 2005, 46,
6345.
10. More, S. V.; Sastry, M. N. V.; Wang, C. C.; Yao, C. F. Tetrahedron Lett. 2005, 46,
6345.
lin-2-amine using substituted ketones and the diamines. The cata-
lyst being heterogeneous and reusable catalyst makes this method
simple, clean, practical, and economically viable for the synthesis
of various 3,4-dihydroquinoxalin-2-amine derivatives.
Acknowledgment
11. (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, Kh.; Bamoharram, F. F. Catal. Commun. 2006, 7, 373; (e)
Shaabani, A.; Maleki, A.; Mofakham, H.; Khavasi, H. R. J. Comb. Chem. 2008, 10,
323.
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13. Li, J.; Liu, Y.; Li, C.; Jia, X. Tetrahedron Lett. 2009, 50, 6502.
14. Srinivasa Rao, K.; Lee, Y. R. Tetrahedron 2010, 66, 8938.
15. (a) Breton, G. W. J. Org. Chem. 1997, 62, 8952; (b) Chari, M. A.; Syamasundar, K.
Catal. Commun. 2005, 6, 67; (c) Shobha, D.; Chari, M. A.; Tamil Selvan, S.; Oveisi,
H.; Mano, A.; Mukkanti, K.; Vinu, A. Micropor. Mesopor. Mater. 2010, 129, 112;
(d) Adharvana Chari, M.; Karthikeyan, G.; Pandurangan, A.; Naidu, T. S.;
Sathyaseelan, B.; Javaid Zaidi, S. M.; Vinu, A. Tetrahedron Lett. 2010, 51, 2629;
(e) Shobha, D.; Chari, M. A.; Mano, A.; Selvan, S. T.; Mukkanti, K.; Vinu, A.
Tetrahedron 2009, 65, 10608.
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Khaksar, S. Synlett 2007, 2347.
The author is thankful to Dr. MACS Bio-Pharma Pvt. Ltd for
financial support.
References and notes
1. For reviews, see: (a) Kappe, C. O. Tetrahedron 1993, 49, 6937; Kappe, C. O. In
Multicomponent Reactions; Zhu, J., Bienayme´, H., Eds.; Wiley-VCH: Weinheim
Germany, 2005; p 95.
2. For reviews on isocyanides based MCRs, see: (a) Dömling, A.; Ugi, I. Angew.
Chem., Int. Ed. 2000, 39, 3168; (b) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.;
Sreekanth, A. R.; Mathen, J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36, 899; (c)
Dömling, A. Chem. Rev. 2006, 106, 17.
3. For some recently reported examples with isocyanide, see: (a) Fujiwara, S. I.;
Asanuma, Y.; Shin-Ike, T.; Kambe, N. J. Org. Chem. 2007, 72, 8087; (b) Silva, R. A.
D.; Santra, S.; Andreana, P. R. Org. Lett. 2008, 10, 4541; (c) Shaabani, A.;
Rezayan, A. H.; Ghasemi, S.; Sarvary, A. Tetrahedron Lett. 2009, 50, 1456; (d)
Haravi, M. M.; Baghernejad, B.; Oskooie, H. A. Tetrahedron Lett. 2009, 50, 767.
4. (a) Shaabani, A.; Teimouri, M. B.; Arab Ameri, S. Tetrahedron Lett. 2004, 45,
8409; (b) Shaabani, A.; Soleimani, E.; Maleki, A. Tetrahedron Lett. 2006, 47,
3031; (c) Shaabani, A.; Maleki, A.; Moghimi-Rad, J. J. Org. Chem. 2007, 72, 6309.
5. Porter, A. E. A. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C.
W., Eds.; Pergamon Press: NewYork, 1984; Vol.3, p 191.

6112
M. Adharvana Chari / Tetrahedron Letters 52 (2011) 6108–6112
1606, 1568, 1528, 1486, 1212, 910, 749 cmÀ1 1H NMR (300 MHz, DMSO-d6): d
;
21. Experimental:
General procedure for synthesis of 3,4-dihydro-quinoxalin-2-amine derivatives: To
1.32 (s, 6H), 3.53 (br s, 1H), 4.64 (br s, 3H), 6.57 (dd, 1H, J = 7.2 and 1.5 Hz),
6.67–6.84 (m, 2H), 7.09 (d, 1H, J = 6.0 Hz), 7.28–7.36 (m, 5H); MALDI-MS: m/z
[M+] = 266; Anal. Calcd for C17H19N3: C, 76.98; H, 7.17; N, 15.85%. Found: C,
76.95, H, 7.15; N, 15.80%. Compound 4k: Off white solid; mp 166–168 °C; IR
a solution of diamine (1 mmol), ketone (1 mmol) and isocyanide (1 mmol) in
3 mL of ethanol was added amberlyst-15(150 mg). The resulting mixture was
stirred for 2–3 h at room temperature. After completion of the reaction, as
indicated by TLC (ethyl acetate/n-hexane 2/1), the catalyst was filtered off and
the product in filtrate was precipitated by the addition of 10 mL of cold water.
The residue was crystallized from ethanol to give 4a–t as solids. All products
were characterized by spectral (IR, NMR & Mass) data and also by the melting
points of the samples. The spectral data of all compounds are given below.
Compound 4a: White solid; mp 218–220 °C; IR (KBr): mmax 3293, 2935, 2861,
(KBr):
m
max 3449, 3397, 3017, 2935, 2856, 1610, 1573, 1525, 1486, 1296, 1242,
;
745 cmÀ1
1H NMR (300 MHz, DMSO-d6): d 1.17–1.25 (m, 1H), 1.36–1.47 (m,
3H), 1.55–1.74 (m, 4H), 1.87(d, 2H, J = 9.0 Hz), 4.19 (s,1H), 4.63 (s, 2H), 4.75(br
s, 1H), 6.64 (dd, 1H, J = 7.2 and 1.8 Hz), 6.75–6.87 (m, 2H), 7.08 (d, 1H,
J = 7.5 Hz), 7.26–7.35 (m, 5H); MALDI-MS: m/z [M+] = 306; Anal. Calcd for
C
20H23N3: C, 78.69; H, 7.54; N, 13.77%. Found: C, 78.65, H, 7.50; N, 13.70%.
Compound 4l: Off white solid; mp 160–162 °C; IR (KBr): max 3276, 2947, 2780,
1656, 1624, 1490, 1455, 1211, 1192, 815, 682 cmÀ1 1HNMR (300 MHz, DMSO-
1642, 1619, 1508, 1455, 1211, 1178, 750, 681 cmÀ1
;
1H NMR (300 MHz, DMSO-
m
d6): d 0.88 (t, J = 3.0 Hz, 3H, –CH2CH3), 1.35 (q, J = 2.8 Hz, 2H, –CH2–), 1.49 (s,
3H, –CH3), 1.11–2.34 (m, 10H, 2 Â 5CH2 of cyclohexyl), 3.99 (br s, 1H, –CH–
NH), 6.31–6.41 (br s, 1H, –NH), 6.70–6.74 (br s, 1H, –NH), 6.78–7.65 (m, 4H, Ar-
H) 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 4b: Off white
;
d6): d 1.92 (s, 3H, –CH3), 2.32 (s, 2H, –CH2 of benzyl isocyanide), 4.03 (br s, 1H, –
NH), 4.93 (br s, 1H, –NH), 6.97–7.83 (m, 14H, Ar-H) 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 4m: Pale yellow solid; mp 140–142 °C; IR
(KBr): mmax 3250, 2996, 2850, 1654, 1624, 1489, 1450, 1190, 1160, 815,
solid; mp 148–150 °C; IR (KBr):
mmax 3430, 3265, 2931, 2855, 2354, 1568, 1511,
1311, 1200, 742 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 1.08–1.25 (m, 4H)
;
680 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 1.17 (s, 3H, –CH3), 2.34 (s, 3H, –CH3
;
1.38–1.50 (m, 2H), 1.61–1.78 (m, 10H), 2.02–2.06 (m, 2H), 3.64 (br s, 1H), 4.06
(m, 1H), 4.24 (m, 1H), 6.53 (m, 1H), 6.72–6.80 (m, 2H), 7.01–7.06 (m, 1H);
MALDI-MS: m/z [M+] = 284; Anal. Calcd for C18H25N3: C, 76.33; H, 8.83; N,
14.85%. Found: C, 76.28, H, 8.80; N, 14.83%. Compound 4c: Off white solid; mp
230–232 °C; IR (KBr): mmax 3351, 2935, 2851, 1622, 1541, 1508, 1448, 1314,
of 4-methylacetophenone), 3.56–3.61 (m, 2H, –CH2 of benzyl isocyanide), 4.03
(br s, 1H,–NH), 4.90 (br s, 1H,–NH), 7.12–7.79 (m, 13H, Ar-H) 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%. Compound 4n: Pure light gray ash color solid; mp
190–192 °C; IR (KBr): mmax 3261, 2933, 2860, 1640, 1620, 1502, 1455, 1200,
1190, 738, 685 cmÀ1
;
1H NMR (300 MHz, DMSO-d6): d 0.98–1.95 (m, 20H,
1191, 815, 682 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 0.87 (t, J =3.0 Hz, 3H, –
;
2 Â 5CH2 of cyclohexyl), 3.86 (br s, 1H, –CH–NH), 6.69 (br s, 1H, –NH), 6.77 (br
s, 1H, –NH), 7.02–7.46 (m, 4H, Ar-H) 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 4d: Semi solid; mp 44–46 °C; IR (Neat): mmax 3454, 3046,
CH2CH3), 1.22 (q, J = 2.8 Hz, 2H, –CH2–), 1.50 (s, 3H, –CH3), 1.30–2.33 (m, 10H,
2 Â 5CH2 of cyclohexyl), 3.93–4.04 (br s, 1H, –CH–NH), 6.45–6.56 (br s, 1H, –
NH), 6.72–6.84 (br s, 1H, –NH), 6.89–7.65 (m, 3H, 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%. Compound 4o: Brown solid; mp 148–150 °C; IR (KBr):
2922, 2855, 2347, 1578, 1506, 1189, 1096, 741 cmÀ1 1H NMR (300 MHz,
;
DMSO-d6): d 1.11–1.26 (m, 4H); 1.41–1.57 (m, 12H), 1.71–1.76 m, 4H), 2.01–
2.04 (m, 2H), 3.82 (br s, 1H), 4.03 (m, 1H), 4.34 (m, 1H), 6.55 (dd, 1H, J = 7.2 and
1.5), 6.70–6.81 (m, 2H), 7.02 (d, 1H, J = 7.2 Hz), MALDI-MS: m/z [M+] = 312;
Anal. Calcd for C20H29N3: C, 77.17; H, 9.32; N, 13.51%. Found: C, 77.15, H, 9.29;
N, 13.50%. Compound 4e: Pale yellow solid; mp 305–307 °C; IR (KBr): mmax
m ;
max 3338, 2929, 2890, 1636, 1619, 1500, 1450, 1198, 1186, 815, 684 cmÀ1 1H
NMR (300 MHz, DMSO-d6): d 0.81–2.32 (m, 20H, 2 Â 5CH2 of cyclohexyl), 3.86
(br s, 1H, –CH–NH), 6.69–6.76 (br s, 1H, –NH), 6.76–6.85 (br s, 1H, –NH), 7.01–
7.52 (m, 3H, Ar-H) ppm; MALDI-MS: m/z [M+] = 331; Anal. Calcd for
C
19H26ClN3: C, 68.76; H, 7.90; N,12.66%. Found: C, 68.69; H, 7.87; N, 12.64%.
Compound 4p: Pale pink solid; mp 245–247 °C; IR (KBr): max 3259, 2938, 2859,
1644, 1619, 1501, 1456, 1212, 1182, 816, 680 cmÀ1 1H NMR (300 MHz, DMSO-
3300, 3252, 2938, 2863, 1649, 1621, 1512, 1462, 1213, 1179, 752, 683 cmÀ1
;
m
1H NMR (300 MHz, DMSO-d6): d 1.06–2.33 (m, 10H, 2 Â 5CH2 of cyclohexyl),
1.89 (s, 3H, –CH3), 4.05 (br s, 1H, –CH–NH), 6.64–6.71 (br s, 1H, –NH), 6.95–
6.99 (br s, 1H, –NH), 7.09–7.67 (m, 9H, Ar-H) 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 4f: Pale yellow solid; mp 240 °C; IR (KBr): mmax 3249,
;
d6): d 1.04–2.28 (m, 10H, 2 Â 5CH2 of cyclohexyl), 1.40 (s, 3H, –CH3), 3.92–4.19
(br s, 1H, –CH–NH), 6.70–6.88 (br s, 1H, –NH), 6.88–7.07 (br s, 1H, –NH), 7.08–
7.88 (m, 8H, Ar-H) ppm; MALDI-MS: m/z [M+] = 353; Anal. Calcd for
C
21H24ClN3: C, 71.27; H, 6.84; N, 11.87%. Found: C, 71.23; H, 6.80; N, 11.80%.
Compound 4q: Pale pink solid; mp 258–260 °C; IR (KBr): max 3273, 2923, 2851,
1646, 1625, 1513, 1458, 1401, 1207, 1188, 810, 680 cmÀ1 1H NMR (300 MHz,
2925, 2864, 1647, 1620, 1508, 1397, 1451, 1187, 752, 679 cmÀ1
;
1H NMR
m
(300 MHz, DMSO-d6): d 1.01–2.28 (m, 10H, 2 Â 5CH2 of cyclohexyl), 1.39 (s, 3H,
–CH3), 3.90 (br s, 1H, –CH–NH), 6.52 (br s, 1H, –NH), 6.74 (br s, 1H, –NH), 6.77–
7.51 (m, 8H, Ar-H) 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 4g:
White solid; mp 262 °C; IR (KBr): mmax 3253, 2937, 2864, 1642, 1620, 1509,
;
DMSO-d6): d 1.04–2.28 (m, 10H, 2 Â 5CH2 of cyclohexyl), 1.40 (s, 3H, –CH3),
3.83–3.94 (br s, 1H, –CH–NH), 6.69–6.74 (br s, 1H, –NH), 6.75–6.78 (br s, 1H, –
NH), 6.78–7.50 (m, 7H, Ar-H) ppm; MALDI-MS: m/z [M+] = 369; Anal. Calcd for
C
21H25ClN4: C, 68.37; H, 6.83; N, 15.19%. Found: C, 68.31; H, 6.80; N, 15.12%.
Compound 4r: Violet solid; mp 218–220 °C; IR (KBr): mmax 3270, 2938, 2864,
1648, 1620, 1503, 1456, 1205, 1185, 815, 680 cmÀ1 1H NMR (300 MHz, DMSO-
1455, 1202, 1190, 753, 680 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 1.00–2.29
;
(m, 10H, 2 Â 5CH2 of cyclohexyl), 1.39 (s, 3H, –CH3), 3.97 (br s, 1H, –CH–NH),
6.53 (br s, 1H, –NH), 6.77 (br s, 1H, –NH), 6.79–7.51 (m, 8H, Ar-H) 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%. Compound 4h: White solid; mp 202 °C; IR
(KBr): mmax 3249, 2937, 2858, 1644, 1622, 1508, 1452, 1397, 1204, 1184, 754,
;
d6): d 1.02–2.27 (m, 10H, 2 Â 5CH2 of cyclohexyl), 1.37 (s, 3H, –CH3), 4.01 (br s,
1H, –CH–NH), 6.68–6.74 (br s, 1H, –NH), 6.75–6.81 (br s, 1H, –NH), 6.89–7.57
(m, 7H, Ar-H) ppm; MALDI-MS: m/z [M+] = 432; Anal. Calcd for C21H23BrClN3:
C, 58.28; H, 5.36; N, 9.71%. Found: C, 58.22; H, 5.28; N, 9.65%. Compound 4s:
Brown solid; mp 235–237 °C; IR (KBr): mmax 3272, 2924, 2853, 1647, 1612,
680 cmÀ1
;
1H NMR (300 MHz, DMSO-d6): d 1.05–2.31 (m, 10H, 2 Â 5CH2 of
cyclohexyl) 1.37 (s, 3H, –CH3), 1.38–1.50 (s, 3H, –CH3 of 4-methyl-
acetophenone), 3.89 (br s, 1H, –CH–NH), 6.33–6.41 (br s, 1H, –NH), 6.69–
6.73 (br s, 1H, –NH), 6.73–7.57 (m, 8H, Ar-H) 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 4i: White solid; mp 250–252 °C; IR (KBr): mmax 3252,
1513, 1457, 1208, 1188, 810, 680 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 0.98–
;
2.20 (m, 10H, 2 Â 5CH2 of cyclohexyl), 1.37 (s, 3H, –CH3), 2.26 (s, 3H, –CH3 of 4-
methyl acetophenone), 4.00 (br s, 1H, –CH–NH), 6.58–6.74 (br s, 1H, –NH),
6.74–6.77 (br s, 1H, –NH), 6.77–7.49 (m, 7H, 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%. Compound 4t: Pale brown solid; mp 258–260 °C; IR
(KBr): mmax 3275, 2925, 2864, 1639, 1629, 1501, 1458, 1401, 1200, 1186, 810,
2925, 2880, 1648, 1622, 1508, 1451, 1209, 1188, 753, 679 cmÀ1 1H NMR
;
(300 MHz, DMSO-d6): d 1.10–2.29 (m, 10H, 2 Â 5CH2 of cyclohexyl), 3.90 (br s,
1H, –CH–NH), 6.50–6.58 (br s, 1H, –NH), 6.74–6.77 (br s, 1H, –NH), 6.78–7.56
(m, 13H, Ar-H) 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%. Compound 4j: Off
679 cmÀ1
;
1H NMR (DMSO-d6): d 1.14–2.29 (m, 10H, 2 Â 5CH2 of cyclohexyl);
3.87 (br s, 1H, –CH–NH), 6.71–6.74 (br s, 1H, –NH), 6.75–6.78 (br s, 1H, –NH),
6.79–7.52 (m, 12H, Ar-H) ppm; MALDI-MS: m/z = 430; Anal. Calcd for
white solid; mp 151–153 °C; IR (KBr):
mmax 3340, 3294, 3022, 2968, 2925, 2370,
C26H27ClN4: C, 72.46; H, 6.31; N, 13.00%. Found: C, 72.40, H, 6.29, N, 13.05%.