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DOI: 10.1055/s-0030-1260957
Room-Temperature Multicomponent Synthesis of 3,4-Dihydroquinoxalin-2-amine Derivatives Using Highly Ordered 3D Nanoporous Aluminosilicate Catalyst
Publication History
Publication Date:
14 July 2011 (online)
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Abstract
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 catalyst which was found to be highly active and selective, affording excellent yields (85-98%) in ethanol at room temperature (2-4 h).
Key words
three-component condensation - o-phenylenediamines - ketones - isocyanides - AlKIT-5 - 3,4-dihydroquinoxalin-2-amine derivatives
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References and Notes
Experimental Procedure
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-d
6.
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.
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 4a: white solid; mp 218-220 ˚C.
IR (KBr):
νmax = 3293, 2935,
2861, 1642, 1619, 1508, 1455, 1211, 1178, 750, 681 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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 4b: off white solid; mp 230-232 ˚C.
IR (KBr): νmax = 3351, 2935, 2851,
1622, 1541, 1508, 1448, 1314, 1190, 738, 685 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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 4c: pale yellow solid; mp 305-307 ˚C.
IR (KBr): νmax = 3300, 3252, 2938,
2863, 1649, 1621, 1512, 1462, 1213, 1179, 752, 683 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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):
νmax = 3249, 2925,
2864, 1647, 1620, 1508, 1397, 1451, 1187, 752, 679 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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): νmax = 3253, 2937, 2864,
1642, 1620, 1509, 1455, 1202, 1190, 753, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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.
Compound 4f: white solid; mp 202 ˚C.
IR (KBr): νmax = 3249, 2937, 2858,
1644, 1622, 1508, 1452, 1397, 1204, 1184, 754, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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):
νmax = 3252, 2925,
2880, 1648, 1622, 1508, 1451, 1209, 1188, 753, 679 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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.
Compound 4h: off white solid; mp 160-162 ˚C.
IR (KBr): νmax = 3276, 2947, 2780,
1656, 1624, 1490, 1455, 1211, 1192, 815, 682 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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): νmax = 3250, 2996, 2850,
1654, 1624, 1489, 1450, 1190, 1160, 815, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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.
Compound 4j: light grey solid; mp 190-192 ˚C.
IR (KBr): νmax = 3261, 2933, 2860,
1640, 1620, 1502, 1455, 1200, 1191, 815, 682 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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 4k:
brown solid; mp 148-150 ˚C. IR (KBr):
νmax = 3338,
2929, 2890, 1636, 1619, 1500, 1450, 1198, 1186, 815, 684 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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
Compound 4l: pale pink solid; mp 245-247 ˚C.
IR (KBr): νmax = 3259, 2938, 2859,
1644, 1619, 1501, 1456, 1212, 1182, 816, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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
Compound 4m: pale pink solid; mp 258-260 ˚C.
IR (KBr): νmax = 3273, 2923, 2851,
1646, 1625, 1513, 1458, 1401, 1207, 1188, 810, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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
Compound 4n: violet solid; mp 218-220 ˚C.
IR (KBr):
νmax = 3270, 2938,
2864, 1648, 1620, 1503, 1456, 1205, 1185, 815, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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 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):
νmax = 3272, 2924,
2853, 1647, 1612, 1513, 1457, 1208, 1188, 810, 680 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 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 4p: pale brown solid; mp 258-260 ˚C.
IR (KBr): νmax = 3275, 2925, 2864,
1639, 1629, 1501, 1458, 1401, 1200, 1186, 810, 679 cm-¹. ¹H
NMR (DMSO-d
6): δ = 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