4.3. General procedure for the formation of 6a-d
The first step of HKA formation was performed similarly to the synthesis method of 5 [27]. In another 50 mL round-bottomed flask, the mixtures of 1,3-indandion (2 mmol), malononitrile (1 mmol), p-TSA (20%mol) and 5 mL EtOH were added and the reaction mixture was stirred for 1 h at room temperature. Next, two round-bottomed flasks were added and the solution was refluxed for the time given in Table 3. The progress of the reaction was monitored by TLC using ethyl acetate/n-hexane (1:1). After completion of the reaction, the precipitated product was filtered off and washed on the filter funnel with a small amount of EtOH to give pure products 6a-d.
4-Nitro-2,3-dihydro-1H,6H-spiro[imidazo[1,2-a]indeno[2,1-e]pyridine-5,1'-indene]-3',6(2'H)-dione (5a): Red solid; yield: 0.293 g (76%); mp 308–310 oC; IR (KBr) (ῡmax): 3419 (NH), 2922 (C-H), 1723 (C = O), 1640 (C = O), 1456, 1377 (NO2), 1214 (C-N), 772 cm− 1; 1H NMR (300 MHz, DMSO-d6): δ = 2.88 (1H, d, 2JHH = 18.6 Hz, CH2), 3.09 (1H, d, 2JHH = 18.3 Hz, CH2), 3.98 (2H, t, 3JHH = 8.7 Hz, CH2), 4.60 (2H, t, 3JHH = 8.7 Hz, CH2N), 7.17–7.72 (8H, m, ArH), 9.97 (1H, s, NH, D2O exchange); 13C NMR (75 MHz, DMSO- d6): δ = 43.4 (CH2), 44.7 (Cspiro), 46.3 (CH2NH), 49.6 (CH2N), 109.5 (C-NO2), 112.1 (CO-C = C), 121.8, 121.9, 125.1, 128.0, 131.3, 132.9, 133.4, 135.2, 137.3, 152.4 (Ar), 153.2 (CO-C = C), 158.2 (C = C-NO2), 189.4 (CO), 204.6 (CO); MS (EI, 70 eV): m/z (%) = 385 (1) [M]+, 338 (57), 294 (73), 216 (100), 91 (42).
2-Methyl-4-nitro-2,3-dihydro-1H,6H-spiro[imidazo[1,2-a]indeno[2,1-e]pyridine-5,1'-indene]-3',6(2'H)-dione (5b): Red solid; yield: 0.287 g (72%); mp 301–304 oC; 1H NMR (300 MHz, DMSO- d6): δ = 1.47 (3H, d, 3JHH = 6.8 Hz, CH3), 2.70 (1H, d, 2JHH = 18.0 Hz, CH2), 2.87 (1H, d, 2JHH = 18.0 Hz, CH2), 4.12–4.19 (1H, m, CH), 4.31–4.48 (1H, m, CH2N), 4.60–4.76 (1H, m, CH2N), 7.17–7.94 (8H, m, ArH), 10.09 (1H, br s, NH); 13C NMR (75 MHz, DMSO- d6): δ = 21.1 (CH3), 43.4 (CH2), 49.7 (Cspiro), 52.9 (CH2NH), 53.0 (CH2N), 109.1 (C-NO2), 112.2 (CO-C = C), 121.7, 121.9, 125.1, 125.2, 127.9, 131.2, 132.8, 134.9, 135.3, 137.3, 152.3 (Ar), 152.4 (CO-C = C), 158.3 (C = C-NO2), 189.4 (CO), 204.4 (CO).
4'-Nitro-1',2'-dihydro-6'H-spiro[indene-1,5'-indeno[2,1-e]thiazolo[3,2-a]pyridine]-3,6'(2H)-dione (5c): Red solid; yield: 0.341 g (85%); mp 313–316 oC; IR (KBr) (ῡmax): 1700 (C = O), 1621 (C = O), 1520 (NO2), 1269 (C-N), 758 cm− 1; 1H NMR (300 MHz, DMSO-d6): δ = 2.62 (1H, d, 2JHH = 16.2 Hz, CH2), 3.08 (1H, d, 2JHH = 16.2 Hz, CH2), 3.46 (2H, t, 3JHH = 7.4 Hz, CH2), 4.74 (2H, t, 3JHH = 7.8 Hz, CH2N), 7.12–7.63 (8H, m, ArH); 13C NMR (75 MHz, DMSO- d6): δ = 29.3 (CH2S), 43.9 (CH2), 50.5 (Cspiro), 52.9 (CH2N), 114.8 (CO-C = C), 122.0 (C-NO2), 122.3, 123.0, 125.6, 126.1, 128.6, 131.2, 132.9, 133.3, 135.4, 135.7, 151.9 (Ar), 157.6 (C = C-NO2), 161.1 (CO-C = C), 190.0 (CO), 203.9 (CO); MS (EI, 70 eV): m/z (%) = 402 (6) [M]+, 384 (16), 356 (6), 322 (100), 294 (9), 267 (12), 238 (14), 105 (5), 76 (2).
6-Nitro-1,3,4,4a,5,13a-hexahydro-2H,8H-spiro[benzo[4, 5]imidazo[1,2-a]indeno[2,1-e]pyridine-7,1'-indene]-3',8(2'H)-dione (5d): Red solid; yield: 0.267 g (61%); mp 320–324 oC; 1H NMR (300 MHz, DMSO- d6): δ = 1.30–1.55 (2H, m, CH2), 1.56–1.78 (2H, m, CH2), 2.04–2.27 (4H, m, 2CH2), 2.64 (1H, d, 2JHH = 18.2 Hz, CH2), 2.89 (1H, d, 2JHH = 18.2 Hz, CH2), 4.29–4.37 (1H, m, CH), 5.03–5.14 (1H, m, CHN), 7.14–7.79 (8H, m, ArH), 9.86 (1H, br s, NH).
(Z)-5-Amino-8-nitro-3'-oxo-2'-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)-2,2',3,3'-tetrahydro-1H-spiro[imidazo[1,2-a]pyridine-7,1'-indene]-6-carbonitrile (6a): Brown solid; yield: 0.440 g (98%); mp 309 oC; IR (KBr) (ῡmax): 3415, 3277 (NH2, NH), 2924 (C-H), 2209 (CN), 1614 (C = O), 1527 (C = C), 1384, 1451 (NO2), 1257 (C-N), 756 cm− 1; 1H NMR (300 MHz, DMSO- d6): δ = 2.27 (2H, s, CH2), 3.08 (2H, t, 3JHH = 6.6 Hz, CH2), 3.69 (2H, t, 3JHH = 6.3 Hz, CH2N), 5.64 (1H, s, NH, D2O exchange), 7.10 (2H, d, 3JHH = 7.8 Hz, ArH), 7.46–7.51 (2H, m, ArH), 7.66–7.70 (2H, m, ArH), 7.85 (1H, br s, NH, D2O exchange), 7.93 (2H, d, 3JHH = 8.1 Hz, ArH), 9.34 (1H, br s, NH, D2O exchange); 13C NMR (75 MHz, DMSO-d6): δ = 21.2 (CH2), 38.5 (CH2NH), 42.9 (CH2N), 57.8 (Cspiro), C-CN (92.6), 116.8 (C-NO2), 121.2 (CN), 122.7, 125.9, 128.5, 128.6, 131.3, 131.4, 136.1, 136.6 (Ar), 138.3 (CO-C = C), 145.9 (CO-C = C), 162.8 (C = C-NO2), 165.0 (C-NH2), 192.0 (CO), 199.2 (CO); MS (EI, 70 eV): m/z (%) = 451 (0.5) [M]+, 236 (16), 207 (56), 172 (91), 91 (100), 65 (34).
(Z)-5-Amino-2-methyl-8-nitro-3'-oxo-2'-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)-2,2',3,3'-tetrahydro-1H-spiro[imidazo[1,2-a]pyridine-7,1'-indene]-6-carbonitrile (6b): Brown solid; yield: 0.455 g (98%); mp 282–286 oC; IR (KBr) (ῡmax): 3485, 3414 (NH, NH2), 2865 (C-H), 2202 (CN), 1623 (C = O), 1541 (C = O), 1467, 1380 (NO2), 1177 (C-N), 620 cm− 1; 1H NMR (300 MHz, DMSO-d6): δ = 1.20 (3H, d, 3JHH = 7.8 Hz, CH3), 2.28 (2H, s, CH2), 3.43–3.53 (1H, m, CH), 3.62 (2H, d, 3JHH = 6.6 Hz, CH2N), 5.69 (1H, s, NH), 7.05 (2H, d, 3JHH = 7.8 Hz, ArH), 7.46–7.51 (2H, m, ArH), 7.72 (2H, d, 3JHH = 6.9 Hz, CH2N), 7.91 (1H, br s, NH), 7.91–7.94 (2H, m, ArH), 9.31 (1H, br s, NH); 13C NMR (75 MHz, DMSO-d6): δ = 16.7 (CH3), 21.2 (CH2), 46.7 (CH), 48.3 (CH2N), 57.9 (Cspiro), 92.7 (C-CN), 116.87 (C-NO2), 121.3 (CN), 121.5, 122.6, 125.9, 128.7, 131.3, 131.4, 136.0, 136.6, 138.3 (Ar), 145.3 (CO-C = C), 162.1 (CO-C = C), 163.0 (C = C-NO2), 165.0 (C-NH2). MS (EI, 70 eV): m/z (%) = 465 (0.3) [M]+, 370 (4), 322 (12), 250 (24), 221 (42), 172 (58), 91 (69), 44 (100).
(Z)-1-Amino-4-nitro-3'-oxo-2'-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)-2',3',5a,6,7,8,9,9a-octahydro-5H-spiro[benzo[4, 5]imidazo[1,2-a]pyridine-3,1'-indene]-2-carbonitrile (6c): Brown solid; yield: 0.314 g (62%); mp 284–288 oC; IR (KBr) (ῡmax): 3432, 3265 (NH, NH2), 2925 (C-H), 2208 (CN), 1609 (C = O), 1509 (C = O), 1446, 1384 (NO2), 1202 (C-N), 755 (Ar) cm− 1; 1H NMR (300 MHz, DMSO-d6): δ = 1.28–1.51 (4H, m, 2CH2), 1.61–2.06 (4H, m, 2CH2), 2.27 (2H, s, CH2), 3.39–3.52 (1H, m, CH), 4.08–4.16 (1H, m, CHN), 5.76 (1H, d, 3JHH = 7.8 Hz, NH), 7.09 (1H, d, 3JHH = 7.8 Hz,, ArH), 7.37–7.89 (7H, m, ArH), 8.52 (1H, br s, NH), 9.13 (1H, br s, NH); 13C NMR (75 MHz, DMSO-d6): δ = 20.2 (2CH2), 26.0 (CH2), 27.5 (CH2), 50.4 (CH2), 54.0 (CH), 57.2 (CH), 58.3 (Cspiro), 92.7 (C-CN), 93.7 (C-NO2), 116.7 (CN), 122.5, 125.8, 125.9, 128.5, 128.6, 131.1, 131.3, 131.4, 136.9, 138.2 (Ar), 146.0 (CO-C = C), 162.4 (CO-C = C), 162.5 (C = C-NO2), 165.1 (C-NH2). MS (EI, 70 eV): m/z (%) = 505 (0.2) [M]+, 370 (14), 322 (24), 224 (81), 195 (46), 172 (83), 91 (100), 65 (38).
(Z)-6'-Amino-3',3'-dimethyl-9'-nitro-3-oxo-2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)-1',2,2',3,3',4'-hexahydrospiro[indene-1,8'-pyrido[1,2-a]pyrimidine]-7'-carbonitrile (6d): Brown solid; yield: 0.404 g (82%); mp 280–281 oC; IR (KBr) (ῡmax): 3434, 3349 (NH, NH2), 2927 (C-H), 2207 (CN), 1618 (C = O), 1574 (C = O), 1440, 1387 (NO2), 1174 (C-N), 749 (Ar) cm− 1; 1H NMR (300 MHz, DMSO-d6): δ = 0.97 (6H, s, 2CH3), 2.27 (2H, s, CH2), 2.78 (4H, s, 2CH2), 5.63 (1H, s, NH), 7.11 (2H, d, 3JHH = 7.5 Hz,, ArH), 7.58 (2H, d, 3JHH = 7.5 Hz,, ArH), 7.75–7.84 (4H, m, ArH), 7.87 (1H, br s, NH), 9.07 (1H, br s, NH).