Room-Temperature Multicomponent Synthesis of 3,4-Dihydroquinoxalin-2-amine Derivatives Using Highly Ordered 3D Nanoporous Aluminosilicate Catalyst

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

References and Notes

• For reviews, see:
• 1a Kappe CO. Tetrahedron  1993,  49:  6937 
• 1b Kappe CO. In Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005.  p.95 
• For reviews on isocyanide-based multicomponent reactions, see:
• 2a Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
• 2b Dömling A. Chem. Rev.  2006,  106:  17 
• 2c Nair V. Rajesh C. Vinod AU. Bindu S. Sreekanth AR. Mathen JS. Balagopal L. Acc. Chem. Res.  2003,  36:  899 
• For some recently reported examples with isocyanide, see:
• 3a Silva RAD. Santra S. Andreana PR. Org. Lett.  2008,  10:  4541 
• 3b Fujiwara S.-I. Asanuma Y. Shin-Ike T. Kambe N. J. Org. Chem.  2007,  72:  8087 
• 3c Shaabani A. Rezayan AH. Ghasemi S. Sarvary A. Tetrahedron Lett.  2009,  50:  1456 
• 3d Heravi MM. Baghernejad B. Oskooie HA. Tetrahedron Lett.  2009,  50:  767 
• 4a Shaabani A. Maleki A. Moghimi-Rad J. J. Org. Chem.  2007,  72:  6309 
• 4b Shaabani A. Soleimani E. Maleki A. Tetrahedron Lett.  2006,  47:  3031 
• 4c Shaabani A. Teimouri MB. Arab Ameri S. Tetrahedron Lett.  2004,  45:  8409 
• 5 Porter AEA. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon Press; New York: 1984.  p.191 
• 6 Cheeseman GWH. Cookson RF. In The Chemistry of Heterocyclic Compounds   2nd ed.:  Weissberger A. Taylor EC. Wiley; New York: 1979.  p.1 
• 7 Gupta D. Ghosh NN. Chandra R. Bioorg. Med. Chem. Lett.  2005,  15:  1019 
• 8 Rosner M. Billhardt-Troughton UM. Kirsh R. Kleim JP. Meichsner C. Riess G. Winkler I.   , 
• 9 More SV. Sastry MNV. Wang C.-C. Yao C.-F. Tetrahedron Lett.  2005,  46:  6345 
• 10a Heravi MM. Keivanlo A. Rahimzadeh M. Bakavoli M. Ghassemzadeh M. Tetrahedron Lett.  2004,  45:  5747 
• 10b Heravi MM. Keivanlo A. Rahimzadeh M. Bakavoli M. Ghassemzadeh M. Tetrahedron Lett.  2005,  46:  1607 
• 10c Heravi MM. Derikvand F. J. Mol. Catal. A.  2005,  242:  173 
• 10d Heravi MM. Bakhtiari K. Bamoharram FF. Catal. Commun.  2006,  7:  373 
• 11 Shaabani A. Maleki A. Mofakham H. Khavasi HR.
  J. Comb. Chem.  2008,  10:  323 
• 12a Kolla SR. Lee YR. Tetrahedron  2010,  66:  8938 
• 12b Li J. Liu Y. Li C. Jia X. Tetrahedron Lett.  2009,  50:  6502 
• 13 Heravi MM. Maryam KB. Tehrani H. Javadi NM. Oskooie HA. ARKIVOC  2006,  (xvi):  16 
• 14 Chari MA. Syamasundar K. Catal. Commun.  2005,  6:  67 
• 15 Srinivasu P. Alam S. Balasubramanian VV. Velmathi S. Sawant DP. Bohlmann W. Mirajkar SP. Ariga K. Halligudi SB. Vinu A. Adv. Funct. Mater.  2008,  18:  640 
• 16 Chakravarti R. Kalita P. Selvan ST. Oveisi H. Balasubramanian VV. Kantam ML. Vinu A. Green Chem.  2010,  12:  49 
• 17 Shobha D. Chari MA. Mano A. Selvan ST. Mukkanti K. Vinu A. Tetrahedron  2009,  65:  10608 
• 18 Vinu A. Kalita P. Balasubramanian VV. Oveisi H. Tamil Selvan T. Mano A. Chari MA. Subba Reddy BV. Tetrahedron Lett.  2009,  50:  7132 
• 19 Chakravarti R. Kalita P. Pal RR. Halligudi SB. Lakshmi Kantam M. Vinu A. Microporous Mesoporous Mater.  2009,  123:  338 
• 20 Balasubramanian VV. Srinivasu P. Anand C. Pal RR. Ariga K. Velmathi S. Alam S. Vinu A. Microporous Mesoporous Mater.  2008,  114:  303 
• 21 Shobha D. Chari MA. 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 TS. Sathyaseelan B. Javaid Zaidi SM. Vinu A. Tetrahedron Lett.  2010,  51:  2629 

23

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):
ν_max = 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): ν_max = 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): ν_max = 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):
ν_max = 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): ν_max = 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): ν_max = 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):
ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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):
ν_max = 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): ν_max = 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): ν_max = 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):
ν_max = 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):
ν_max = 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): ν_max = 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