untitled European Journal of Chemistry 2 (4) (2011) 544‐551 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2011 EURJCHEM DOI:10.5155/eurjchem.2.4.544‐551.478 European Journal of Chemistry Journal homepage: www.eurjchem.com Reactions with hydrazonoyl halides 66: Synthesis of some new 1,3,4‐thiadiazoles, triazolino[4,3‐a]pyrimidines and isoxazolo[3,4‐d]pyridazines containing coumarin moiety Abdou Osman Abdelhamid*, Abdelgawad Ali Fahmi and Abeer Bahlol Ali Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt *Corresponding author at: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. Tel.: +202.35676573; fax: +202.35727556. E‐mail address: abdelhamid45@gmail.com (A.O. Abdelhamid). ARTICLE INFORMATION ABSTRACT Received: 10 June 2011 Received in revised form: 21 July 2011 Accepted: 22 July 2011 Online: 31 December 2011 KEYWORDS 2,3‐Dihydro‐1,3,4‐thiadiazoles, triazolino[4,3‐a]pyrimidines, isoxazoles and isoxazolo[3,4‐ d]pyridazines containing coumarin moities were synthesized from the reactions of methyl (or benzyl) carbodithioate, pyrimidine‐2‐thione and 3‐(3‐(dimethylamino)acryloyl)‐2H‐chromen‐ 2‐one derivatives with C‐coumarinoyl‐N‐phenylhydrazonoyl bromide. The structures of all the newly synthesized compounds were confirmed by elemental analyses and spectral data. Coumarins Nitrilimines 1,3,4‐Thiadiazoles Pyrimidine‐2‐thione Isoxazolo[3,4‐d]prymidines Triazolino[4,3‐a]pyrimidines 1. Introduction Coumarin derivatives constitute an important class of heterocyclic compounds with anticoagulant [1,2], anticoagulant rodenticide [3], insecticide [4] and antibacterial [5,6] pharmacolgical activities. On the other hand, 1,3,4‐thiadiazole derivatives have become very useful compound in medicine, agriculture and in many fields of technology [7]. As an extension of our study [8,9‐15] and a part of our program aiming at the synthesis of different heterocyclic derivatives, herein we report the convenient synthesis of 2,3‐dihydro‐1,3,4‐ thiadiazoles, triazolino[4,3‐a]pyrimidines and isoxazolo[3,4‐ d]pyridazines containing coumarins moities. 2. Experimental 2.1. Instrumentation All melting points were determined on an electrothermal apparatus and are uncorrected. IR spectra were recorded (KBr disc) on a Shimadzu FT‐IR 8201 PC spectrophotometer. 1H NMR spectra were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini 300 MHz spectrometer and chemical shifts are expressed in  ppm units using TMS as an internal reference. Mass spectra were recorded on a GC‐MS QP1000 EX Shimadzu. Electronic absorption was recorded on Shimadzo 3101 PC spectrophotometer. Elemental analyses were carried out at the Microanalytical Center of Cairo University. Hydrazonoyl halides [16,17‐19], 2‐acetylbenzo[f]2H‐chromen‐ 3‐one [20], 3‐(2‐bromoacetyl)‐2H‐chromen‐2‐one [21] and alkyl carbodi‐thioates [22] were prepared as previously reported. 2.2. Synthesis of 3‐{5‐[(arylidene)‐hydrazono]‐4‐phenyl‐4,5‐ dihydro‐[1,3,4]thiadiazole‐2‐carbonyl}‐chromen‐2‐one (7a‐ j) A mixture of the appropriate methyl (or benzyl) carbodithioate 3a‐j or 4a‐j (5 mmol), C‐coumarin‐3‐oyl‐N‐ phenylhydrazonoyl bromide, 1 (1.86 g, 5 mmoles), and triethylamine (0.75 mL, 5 mmol) in ethanol (20 mL) was stirred for 2 hrs at room temperature. The resulting solid was collected and recrystallized to give 2,3‐dihydro‐1,3,4‐thiadiazoles, 7a‐j (Scheme 1). Benzaldehyde [5‐(2‐oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐1,3,4‐ thiadiazol‐2(3H)‐ylidene]hydrazone (7a): Yellow crystals from AcOH. Yield: 77%. M.p.: 192‐194 °C. FT‐IR (KBr, cm‐1): 3055 (CH), 1732, 1654 (CO's), 1624 (C=N), 1612 (C=N),1589 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.42‐7.46 (m, 7H, ArH's), 7.47‐7.55 (m, 4H, ArH's), 7.76‐7.94 (m, 3H, ArH's), 8.52 (s, 1H, ArH), 8.85 (s, 1H, CH=). MS (EI, m/z (%)): 453 (M+1, 17.84), 335 (11.45), 173 (38.35), 135 (12.08), 101 (14.50), 89 (100), 77 (28.84), 69 (10.08), 63 (14.38), 63 (14.38). UV (EtOH, max, nm): 320, 419.5. Anal. calcd. for C25H16N4O3S (452.48): C, 66.36; H, 3.56; N, 12.38. Found: C, 66.48; H, 3.67; N, 12.41%. 4‐Methylbenzaldehyde [5‐(2‐oxo‐2H‐chromen‐3‐yl)‐3‐ phenyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene]hydrazone (7b): Orange crystals from dioxane. Yield: 78 %. M.p.: 244‐248 °C. FT‐IR (KBr, cm‐1): 3051, 2981 (CH), 1735, 1647 (CO's), 1604 (C=N), 1565 (C=C), 1365 (CH3). 1H NMR (300 MHz, DMSO‐ d6, δ, ppm): 2.34 (s, 3H, 4‐CH3C6H4), 7.28 (d, 2H, J = 8 Hz, ArH's), 7.44‐7.94 (m, 11H, ArH's), 8.48 (s, 1H, ArH), 8.85 (s, 1H, CH=). MS (EI, m/z (%)): 465 (M‐1, 43.3), 335 (33.3), 334 (13.3), 302 (20), 185 (20), 184 (16.7), 173 (53.3), 172 (46.7), 162 (26.7), 161 (13.3), 145 (20), 135 (30), 131 (26.7), 117 (13.3), 102 Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 545 NNHC(S)SR''' R' R'' N NH SR''' Ph SR NN R' R'' N N SR Ph NHN SR''' R'' R' N N SR Ph N N R' R'' 1 2 5 6 7 (3-7)a, R' = C6H5, R'' = H (3-7)b, R' = 4-CH3C6H4, R'' = H (3-7)c, R' = 4-CH3OC6H4, R'' = H (3-7)d, R' = 4-ClC6H4, R'' = H (3-7)e, R' = 4-O2NC6H4, R'' = H (3-7)f, R' = 2-C4H3O, R'' = H (3-7)g, R' = 2-C4H3S, R'' = H (3-7)h, R' = C6H5,, R'' = CH3 (3-7)i, R' = 4-CH3C6H4, R'' = CH3 (3-7)j, R' = 2-C4H3O, R'' = CH3 RC:NNPh O O O N Br NH Ph R = 3, R''' = CH3 4, R''' = CH2C6H5 + + Scheme 1 (33.3), 101 (66.7), 100 (13.01), 99 (10.0), 91 (20), 90 (33.3), 89 (50), 78 (43.3), 77 (66.7), 75 (23.3), 74 (16.7), 73 (26.7), 72 (16.7), 83 (16.7). UV (EtOH, max, nm): 322, 417. Anal. calcd. for C26H18N4O3S (466.51): C, 66.94; H, 3.89; N, 12.01; S, 6.87. Found: C, 67.12; H, 3.98; N, 12.22; S, 6.78%. 4‐Methoxylenzaldehyde [5‐(2‐oxo‐2H‐chromen‐3‐yl)‐3‐ phenyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene]hydrazone (7c): Red crystals from dioxane. Yield: 78.8 %. M.p.: 228‐230 °C. FT‐IR (KBr, cm‐1): 3042, 2981 (CH), 1736, 1652 (C=O), 1614 (C=N), 1589 (C=C), 1365 (CH3). 1H NMR (300 MHz, DMSO‐ d6, δ, ppm): 3.82 (s, 3H, 4‐CH3OC6H4), 7.14‐7.77 (m, 13H, ArH's), 8.48 (s, 1H, ArH), 8.85 (s, 1H, CH=). MS (EI, m/z (%)): 484 (M+2, 9.76), 483 (M+1, 16.70), 482 (M+, 30.50), 336 (10.34), 335 (4.49), 310 (3.92), 174 (13.64), 173 (91.22), 145 (18.93), 135 (21.06), 134 (18.13), 120 (97.75), 119 (15.68), 105 (21.26), 104 (19.38), 101 (36.26), 96 (32.41), 95 (20.85), 91 (100), 89 (63.94), 77 (75.45), 70 (10.65), 65 (16.29), 63 (33.03), 62 (18.08), 35 (25.86). UV (EtOH, max, nm): 328, 423. Anal. calcd. for C26H18N4O4S (482.51): C, 64.72; H, 3.76; N, 11.61; S, 6.65. Found: C, 64.64; H, 3.68; N, 11.51; S, 6.53%. 4‐Chlorobenzaldehyde [5‐(2‐oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐ 1,3,4‐thiadiazol‐2(3H)‐ylidene]hydrazone (7d): Yellow crystals from dioxane. Yield: 79 %. M.p.: 226‐228 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1739, 1658 (CO's), 1616 (C=N), 1569 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.39‐7.57 (m, 7H, ArH's), 7.63‐7.49 (m, 6H, ArH's), 8.52 (s, 1H, ArH), 8.85 (s, 1H, CH=). MS (EI, m/z (%)): 191 (9.8), 189 (43.9), 173 (43.9), 172 (26.8), 171 (12.2), 170 (8.5), 160 (13.9), 147 (13.4), 133 (8.5), 132 (18.3), 130 (36.6), 129 (18.3), 119 (13.4), 117 (17.1), 105 (31.7), 104 (26.8), 103 (13.4), 102 (24.4), 99 (12.2), 93 (11), 91 (24.4), 87 (40.2), 86 (24.4), 77 (100), 65 (23.2), 61 (51.2). UV (EtOH, max, nm): 333.5, 417.5. Anal. calcd. for C25H15ClN4O3S (486.93): C, 61.67; H, 3.10; N, 11.51; S, 6.59. Found: C, 61.81; H, 3.22; N, 11.74; S, 6.70%. 4‐Nitrobenzaldehyde [5‐(2‐oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐ 1,3,4‐thiadiazol‐2(3H)‐ylidene]hydrazone (7e): Orange crystals from AcOH. Yield: 79 %. M.p.: 248‐250 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1732, 1654 (CO's), 1624 (C=N), 1589 (C=C), 1531, 1338 (NO2). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.41‐ 7.58 (m, 5H, ArH's), 7.76‐7.94 (m, 5H, ArH's), 9.03 (d, 1H, J = 8Hz, ArH), 8.29 (d, 2H, J = 8 Hz, ArH's), 8.636 (s, 1H, ArH), 8.867 (s, 1H, CH=). MS (EI, m/z (%)): 499 (M+2, 1.5), 498 (M+1, 9.4), 497 (M+, 26), 496 (M‐1, 25), 335 (12.1), 334 (11.6), 173 (82), 135 (30.6), 134 (21.8), 101 (26), 90 (12.13), 89 (100), 88 (22.8), 77 (39.6), 76 (25.5), 65 (7.7), 63 (40.6), 62 (11.9). UV (EtOH, max, nm): 276.5, 364.5, 422.5. Anal. calcd. for C25H15N5O5S (497.48): C, 60.36; H, 3.04; N, 14.08; S, 6.45. Found: C, 60.42; H, 2.89; N, 14.14; S, 6.35%. 2‐Furaldehyde [5‐(2‐furyl)‐3‐phenyl‐1,3,4‐thiadiazol‐2(3H)‐ ylidene]hydrazone (7f): Red crystals from AcOH. Yield: 77 %. M.p.: 176‐180 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1732, 1654 (CO's), 1624 (C=N), 1589 (C=C). 1H NMR (300 MHz, DMSO‐ d6, δ, ppm): 6.66 (s, 1H, furan H3), 6.99 (s, 1H, ArH), 7.31‐8.82 (m, 10H, ArH's and furan protons), 8.83 (s, 1H, ArH), 8.84 (s, 1H, CH=). MS (EI, m/z (%)): 443 (M+1, 70.12), 335 (66.23), 173 (100), 145 (13.11), 135 (22.33), 108 (42.06), 101 (33.83), 89 (33.20), 80 (66.92), 77 (39.17), 65 (27.7), 62 (13.60). UV (EtOH, max, nm): 331.5, 418.5. Anal. calcd. for C23H14N4O4S (442.45): C, 62.44; H, 3.19; N, 12.66; S, 7.25. Found: C, 62.35; H, 3.22; N, 12.79; S, 7.32%. Thiophene‐2‐carbaldehyde [5‐(2‐furyl)‐3‐phenyl‐1,3,4‐ thiadiazol‐2(3H)‐ylidene]‐hydrazone (7g): Red crystals from AcOH. Yield: 78 %. M.p.: 196‐198 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1734, 1653 (CO's), 1614 (C=N), 1589 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.39‐8.00 (m, 13H, ArH's and thiophene protons), 8.84 (s, 1H, CH=). MS (EI, m/z (%)): 459 (30.13), 335 (18.12), 256 (12.36), 220 (10.48), 206 (12.44), 174 (42.64), 173 (55.84), 145 (15.55), 135 (32.31), 110 (38.39), 109 (27.32), 101 (23.22), 96 (100), 89 (62.23), 77 (55.15), 69 (61.86), 65 (22.43). UV (EtOH, max, nm): 341, 424.5. Anal. calcd. for C23H14N4O3S2 (458.5): C, 60.25; H, 3.08; N, 12.22; S, 13.99. Found: C, 60.32; H, 3.14; N, 12.45; S, 14.12%. 5‐(2‐Oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐1,3,4‐thiadiazol‐2(3H)‐ one[(1‐phenylethyl‐idene]‐hydrazone (7h): Orange crystals from AcOH. Yield: 78 %. M.p.: 192‐194 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1731, 1654 (CO's), 1614 (C=N), 1589 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 2.34 (s, 3H, CH3), 7.20‐8.01 (m, 14H, ArH's), 8.35 (s, 1H, ArH). MS (EI, m/z (%)): 467 (10.0), 335 (11.68), 234 (9.62), 173 (6.76), 135 (16.24), 117 (10.51), 10 (90.24), 111 (15.55), 135 (32.31), 110 (38.39), 109 (27.32), 101 (23.22), 96 (100), 89 (25.46), 91 (13.77), 89 (20.36), 77 (61.46). UV (EtOH, max, nm): 328.5, 421.5. 546 Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 Scheme 2 Anal. calcd. for C26H18N4O3S (466.51): C, 66.94; H, 3.89; N, 12.01; S, 6.87. Found: C, 67.15; H, 3.92; N, 12.14; S, 6.75%. 5‐(2‐Oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐1,3,4‐thiadiazol‐2(3H)‐ one[(1‐4‐methyl‐phenylethylidene]hydrazone (7i): Red crystals from AcOH. Yield: 79 %. M.p.: 208‐210 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1733, 1655 (CO's), 1604 (C=N), 1589 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 2.36 (s, 3H, CH3), 2.43 (s, 3H, CH3) 7.27‐8.00 (m, 13H, ArH's), 8.84 (s, 1H, ArH). MS (EI, m/z (%)): 481 (14.47), 173 (100), 145 (11.19), 135 (23.53), 118 (44.98), 115 (38.07), 101 (33.87), 94 (41.65), 77 (46.96), 65 (84.59), 55 (18.35). UV (EtOH, max, nm): 321, 425.5. Anal. calcd. for C27H20N4O3S (480.54): C, 67.48; H, 4.20; N, 11.66; S, 6.67. Found: C, 67.54; H, 4.31; N, 11.75; S, 6.72%. 5‐(2‐Oxo‐2H‐chromen‐3‐yl)‐3‐phenyl‐1,3,4‐thiadiazol‐2(3H)‐ one[1‐(2‐furyl)‐ethylidene]hydrazone (7j): Red crystals from AcOH. Yield: 79 %. M.p.: 180‐182 °C. FT‐IR (KBr, cm‐1): 3074 (CH), 1735, 1654 (CO's), 1612 (C=N), 1579 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 2.35 (s, 3H, CH3), 6.35 (s, 1H, furan H‐3), 7.20‐7.79 (m, 11H, ArH's), 8.44 (s, 1H, ArH). MS (EI, m/z (%)): 457 (1.0), 173 (5.72), 144 (6.09), 135 (11.89), 101 (12.61), 94 (62.93), 88 (13.20), 77 (15.14), 65 (42.36). UV (EtOH, max, nm): 332, 429. Anal. calcd. for C24H16N4O4S (456.47): C, 63.15; H, 3.53; N, 12.27; S, 7.02. Found: C, 63.23; H, 3.71; N, 12.15; S, 6.89%. 2.3. Synthesis of triazolino[4,3‐a]pyrimidines (11a‐f), [1,2,4]triazolo[3,4‐b]quinazolin‐5‐one (15) 1H‐benzo[4,5] imidazo[2,1‐c][1,2,4]triazol‐3‐yl)‐methanone (16) and 1,2,3a,10‐tetraaza‐cyclopenta[b]fluoren‐4‐one (17) Method A: A mixture of the hydrazonoyl bromide, 1, (1.86 g, 5 mmol) and the appropriate of pyrimidine‐2‐thione derivatives [23] 8a‐f, 2‐thioxo‐2,3‐dihydro‐1H‐quinazolin‐4‐ one, 2‐thioxo‐2,3,5,6,7,8‐hexahydro‐1H‐benzo[4,5]thieno[2,3‐ d]‐pyrimidin‐4‐one, or 2‐mercaptobenzimidazole (5 mmol) in chloroform (20 mL) containing triethylamine (0.5 g (0.75 mL), 5 mmol) was refluxed for 20 h. Chloroform was evaporated under reduced pressure and the remaining solid was crystallized from the proper solvent to givel 11a‐f, and 15‐17, respectively (Scheme 2 and 3). Method B: A mixture of the appropriate hydrazonoyl bromide, 1 (1.68 g, 5 mmol), the appropriate of 14a‐e [22] (5 mmol), and sodium ethoxide (0.34 g, 5 mmol) in ethanol (20 mL) was refluxed for 3 hrs. The reaction mixture was cooled and the resulting solid was collected and crystallized from the proper solvent gave products identical in all aspects (m.p., mixed m.p., and spectra) with corresponding products obtained by Method A. Ethyl 7‐methyl‐3‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐1,5‐ diphenyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrimidine‐6‐ carboxylate (11a): Brown crystals from AcOH. Yield: 82 %. M.p.: 250‐252 °C. FT‐IR (KBr, cm‐1): 3062, 2977 (CH), 1720 (CO), 1608 (C=N), 1550 (C=C), 1450 (CH2), 1373 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.01 (t, J = 7.5 Hz, 3H, CH2CH3), 2.09 (s, 3H, CH3), 4.11 (q, J = 7.5 Hz, 2H, CH2CH3), 5.4 (s, 1H, pyrimidine H‐4), 6.91‐7.73 (m, 15H, ArH). MS (EI, m/z (%)): 532 (0.37), 152 (5.71), 150 (15.39), 139 (12.68), 104 (18.11), 97 (27.38), 95 (17.47), 93 (16.42), 91 (19.60), 89 (14.97), 85 (23.06), 83 (36.06), 81 (34.82), 79 (27.56), 76 (93.30), 71 (57.99), 69 (57.88), 67 (36.52), 65 (24.19). UV (EtOH, max, nm): 285.5, 591. Anal. calcd. for C31H24N4O5 (532.55): C, 69.92; H, 4.54; N, 10.52. Found: C, 70.08; H, 4.45; N, 10.72%. Ethyl 7‐methyl‐3‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐5‐ phenyl‐1‐p‐tolyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrimidine‐ 6‐carboxylate (11b): Brown crystals from dioxane. Yield: 83 %. M.p.: 226‐230 °C. FT‐IR (KBr, cm‐1): 3062, 2974 (CH), 1739 (CO), 1624 (C=N), 1558 (C=C), 1473 (CH2), 1392 (CH3). Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 547 Scheme 3 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.24 (t, 3H, J = 7.5 Hz, CH2CH3), 2.18 (s, 3H, CH3), 2.27 (s, 3H, CH3), 4.11 (q, J = 7.5 Hz, 2H, CH2CH3), 5.4 (s, 1H, pyrimidine H‐4), 7.27‐7.73 (m, 11H, ArH), 8.16 (d, 2H, J = 8 Hz, ArH's), 8.38 (s, 1H, ArH). MS (EI, m/z (%)): 547 (M+1, 0.42), 546 (M+, 0.85), 349 (30.49), 378 (29.28), 323 (32.21), 318 (34.14), 321 (22.04), 302 (15.88), 276 (27.92), 258 (31.48), 217 (14.90), 202 (8.15), 199 (12.47), 184 (14.37), 173 (13.22), 158 (23.38), 156 (17.00), 144 (33.18), 143 (61.35), 135 (11.99), 127 (35.70), 118 (74.32), 115 (63.66), 102 (10.23), 101 (24.67), 91 (100), 86 (59.45), 77 (95.66), 65 (62.31). UV (EtOH, max, nm): 285.5, 606. Anal. calcd. for C32H26N4O5 (546.57): C, 70.32; H, 4.79; N, 10.25. Found: C, 70.21; H, 4.95; N, 10.41%. Ethyl 5‐(4‐isopropyl‐phenyl)‐7‐methyl‐3‐(2‐oxo‐2H‐ chromene‐3‐carbonyl)‐1‐phenyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐ a]pyrimidine‐6‐carboxylate (11c): Brown crystals from DMF. Yield: 83 %. M.p.: 292‐294 °C. FT‐IR (KBr, cm‐1): 3070, 2958 (CH), 1720 (CO), 1612 (C=N), 1550 (C=C), 1446 (CH2), 1369 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.16 (t, J = 7.5 Hz, 3H, CH2CH3), 1.17 (d, 6H, (CH3)2CH), 2.18 (s, 3H, CH3), 2.77 (sept., 1H, (CH3)2CH, 4.07 (q, J = 7.5 Hz, 2H, CH2CH3), 5.35 (s, 1H, pyrimidine H‐4), 7.27‐7.78 (m, 13H, ArH's), 8.10 (s, 1H, ArH). MS (EI, m/z (%)): 575 (0.44), 505 (11.06), 431 (13.85), 378 (24.96), 377 (38.97), 347 (66.21), 332 (31.61), 330 (71.78), 304 (100), 289 (68.99), 287 (12.07), 260 (12.14), 257 (52.73), 244 (24.82), 229 (26.91), 217 (15.89), 211 (18.07), 199 (12.42), 184 (24.28), 179 (16.04), 143 (59.71), 135 (19.86), 128 (55.56), 118 (40.82), 114 (24.23), 102 (31.85), 91 (43.57), 85 (11.20), 76 (33.72). UV (EtOH, max, nm): 286.5, 622. Anal. calcd. for C35H30N4O5 (574.22): C, 71.07; H, 5.26; N, 9.75. Found: C, 71.15; H, 5.34; N, 9.89%. Ethyl 5‐benzo[1,3]dioxol‐4‐yl‐7‐methyl‐3‐(2‐oxo‐2H‐ chromene‐3‐carbonyl)‐1‐phenyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐ a]pyrimidine‐6‐carboxylate (11d): Brown crystals from DMF. Yield: 83 %. M.p.: 190‐192 °C. FT‐IR (KBr, cm‐1): 3070, 2900 (CH), 1712 (CO), 1608 (C=N), 1566 (C=C), 1442 (CH2), 1373 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.12 (t, J = 7.5 Hz, 3H, CH2CH3), 2.25 (s, 3H, CH3), 4.07 (q, J = 7.5 Hz, 2H, CH2CH3), 5.35 (s, 1H, pyrimidine H‐4), 5.96 (s, 2H, OCH2O), 7.15‐7.37 (m, 13H, ArH). MS (EI, m/z (%)): 576 (M+, 0.35), 377 (5.71), 146 (5.07), 145 (6.52), 144 (5.41), 143 (6.22), 118 (25.56), 115 (29.93), 101 (21.92), 92 (15.70), 91 (36.58), 88 (41.63), 86 (16.65), 76 (100), 69 (16.67), 66 (14.44), 65 (26.24), 63 (62.04). UV (EtOH, max, nm): 286.5, 510, 621.5. Anal. calcd. for C32H24N4O7 (576.56): C, 66.66; H, 4.20; N, 9.72. Found: C, 66.75; H, 4.18; N, 9.89%. Ethyl 5‐(2,3‐dimethoxy‐phenyl)‐7‐methyl‐3‐(2‐oxo‐2H‐ chromene‐3‐carbonyl)‐1‐phenyl‐1,5‐dihydro‐[1,2,4]triazolo[4,3‐ a]pyrimidine‐6‐carboxylate (11e): Brown crystals from DMF. Yield: 83 %. M.p.: 160‐162 °C. FT‐IR (KBr, cm‐1): 3070, 2935 (CH), 1712 (CO), 1608 (C=N), 1566 (C=C), 1485 (CH2), 1369 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.16 (t, J = 7.5 Hz, 3H, CH2CH3), 2.09 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 4.13 (q, J = 7.5 Hz, 2H, CH2CH3), 5.35 (s, 1H, pyrimidine H‐4), 7.15‐7.37 (m, 13H, ArH's). MS (EI, m/z (%)): 593 (M+, 0.87), 396 (37.70), 394 (17.31), 380 (9.92), 364 (21.94), 362 (40.49), 322 (16.86), 321 (100), 304 (20.39), 302 (25.91), 261 (17.30), 258 (29.58), 233 (14.37), 184 (18.65), 150 (13.17), 144 (21.83), 134 (10.04), 117 (26.85), 102 (18.78), 91 (30.79), 76 (22.79). UV (EtOH, max, nm): 281.5, 598.5. Anal. calcd. for C33H28N4O7 (592.6): C, 66.88; H, 4.76; N, 9.45. Found: C, 66.98; H, 4.57; N, 9.61%. Ethyl 5‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐7‐methyl‐3‐(2‐oxo‐ 2H‐chromene‐3‐carbonyl)‐1‐phenyl‐1,5‐dihydro‐[1,2,4]triazolo [4,3‐a]pyrimidine‐6‐carboxylate (11f): Brown crystals from AcOH. Yield: 85 %. M.p.: 160‐162 °C. FT‐IR (KBr, cm‐1): 3070, 2935 (CH), 1712 (CO), 1608 (C=N), 1566 (C=C), 1485 (CH2), 1369 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.16 (t, J = 7.5 Hz, 3H, CH2CH3), 2.09 (s, 3H, CH3), 4.13 (q, J = 7.5 Hz, 2H, CH2CH3), 5.35 (s, 1H, pyrimidine H‐4), 7.15‐7.37 (m, 21H, ArH's and pyrazole H‐5). MS (EI, m/z (%)): 674 (M‐1, 3.03), 478 (11.05), 478 (25.23), 476 (19.05), 403 (20.79), 402 (11.20), 119 (11.07), 104 (14.13), 103 (7.67), 102 (5.99), 78 (10.28), 77 (100). UV (EtOH, max, nm): 283. Anal. calcd. for C40H30N6O5 (674.7): C, 71.21; H, 4.48; N, 12.46. Found: C, 71.34; H, 4.51; N, 12.64%. 3‐(2‐Oxo‐2H‐chromene‐3‐carbonyl)‐1‐phenyl‐1H‐[1,2,4] triazolo[3,4‐b]quinazolin‐5‐one (15): Brown crystals from AcOH. Yield: 79 %. M.p.: 150‐152 °C. FT‐IR (KBr, cm‐1): 3070 (CH), 1701, 1666 (CO's), 1608 (C=N), 1566 (C=C), 1485 (CH2), 1369 (CH3). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.90‐7.83 (m, 10H, ArH), 8.10‐8.14 (m, 2H, ArH's), 8.30‐8.35 (m, 2H, ArH’s). MS (EI, m/z (%)): 435 (M+1, 1.09), 254 (10.98), 237 (100), 120 (19.54), 119 (28.44), 92 (25.40), 90 (27.49), 77 (20.04), 63 (40.77). UV (EtOH, max, nm): 289.5, 467.5. Anal. calcd. for C25H14N4O4 (434.4): C, 69.12; H, 3.25; N, 12.90. Found: C, 69.23; H, 3.41; N, 13.11%. 3‐(2‐Oxo‐2H‐chromene‐3‐carbonyl)‐1‐phenyl‐5,6,7,8‐tetra hydro‐1H‐9‐thia‐1,2,3a,10‐tetraaza‐cyclopenta[b]fluoren‐4‐one (16): Brown crystals from EtOH. Yield: 75 %. M.p.: 156‐158 °C. FT‐IR (KBr, cm‐1): 3070, 2935 (CH), 1712 (CO), 1608 (C=N), 1566 (C=C), 1485 (CH2), 1369 (CH3). 1H NMR (300 MHz, CDCl3, δ, ppm): 1.61‐1.64 (m, 4H, 2CH2), 2.80‐2.98 (m, 4H, 2CH2), 7.17‐7.24 (m, 2H, ArH's), 7.37‐7.43 (m, 3H, ArH's), 7.54 (d, 1H, J = 8 Hz, ArH), 7.73‐7.77 (m, 1H, ArH's), 8.10‐8.14 (m, 548 Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 Scheme 4 2H, ArH's), 8.39 (d, 1H, J = 8 Hz, ArH). MS (EI, m/z (%)): 491 (M‐2, 0.15), 225 (38.17), 287 (3.88), 267 (21.68), 179 (100), 151 (67.92), 135 (23.01), 125 (22.52), 123 (25.74), 120 (33.78), 115 (23.92), 108 (10.40), 104 (10.83), 100 (25.17), 96 (29.64), 93 (11.35), 90 (51.03), 85 (31.84), 83 (11.15), 80.60 (14.36), 78 (34.29), 76 (89.18), 71 (10.96), 65 (53.62). UV (EtOH, max, nm): 320.5, 468. Anal. calcd. for C27H18N4O4S (494.52): C, 65.58; H, 3.67; N, 11.33; S, 6.48. Found: C, 65.73; H, 3.71; N, 11.45; S, 6.60%. 3‐(1‐Phenyl‐1H‐benzo[4,5]imidazo[2,1‐c][1,2,4]triazole‐3‐ carbonyl)‐chromen‐2‐one (17): Dark brown crystals from AcOH. Yield: 77 %. M.p.: 242‐244 °C. FT‐IR (KBr, cm‐1): 3055, 2923 (CH), 1747 (CO), 1604 (C=N), 1566 (C=C), 1438 (CH2), 1373 (CH3). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.31‐8.34 (m, 11 H, ArH's), 8.10‐8.14 (m, 2H, ArH's), 8.39 (d, 1H, J = 8 Hz, ArH). MS (EI, m/z (%)): 408 (M+2, 11.02), 357 (13.32), 301 (8.31), 227 (17.58), 177 (12.20), 174 (11.13), 151 (10.19), 142 (13.83), 139 (14.59), 137 (10.60), 120 (15.27), 117 (12.60), 116 (16.61), 115 (10.18), 105 (15.34), 103 (13.38), 102 (13.81), 101 (13.85), 99 (10.92), 94 (10.95), 92 (14.19), 91 (26.22), 88 (25.19), 82 (29.89), 78 (30.40), 77 (45.78), 76 (98.26), 75 (37.03), 74 (20.66), 73 (15.95), 69 (39.71), 65 (57.38), 63 (80.72). UV (EtOH, max, nm): 236.5, 302, 464. Anal. calcd. for C24H14N4O3 (406.39): C, 70.93; H, 3.47; N, 13.79. Found: C, 71.12; H, 3.53; N, 13.97%. 2.4. Synthesis of isoxazoles (23a‐d) and (25a‐d) Method A: Triethylamine (0.5 g (0.75 mL), 5 mmol) was added dropwise to equimolar a mount of 18a (or 18b) and the appropriate hydroximoyl chloride [25,26‐28] 19a‐d (5 mmol, each) in dry toluene (20 mL) while stirring. The reaction mixture was stirred for 6 hrs.; evaporate the solvent and then triturated with petroleum ether (40‐60 oC). The resulting solid was collected and crystallized gave 23a‐d and 25a‐d, respectively (Scheme 4). Method B: Equimolar a mount of 18a (or 18b) and the appropriate hydroximoyl chloride 19a‐d (5 mmol, each) in dry toluene (20 mL) were heated under reflux for 18 h. The reaction mixture was filtered off and the filtrate was evaporated and triturated with petroleum ether (40‐60 oC). The resulting solid was collected and crystallized to give products identical in all aspects (mp. mixed mp. and spectra) with 23a‐d. 3‐(3‐Benzoylisoxazole‐4‐carbonyl)‐chromen‐2‐one (23a): Brown crystals from AcOH. Yield: 81 %. M.p.: 170‐172 °C. FT‐IR (KBr, cm‐1): 3070 (CH), 1724, 1678 (CO's), 1608 (C=N), 1562 (C=C). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.33‐8.64 (m, 7H, ArH's), 8.60‐8.62 (d, 3H, J = 8 Hz, ArH's), 8.97 (s, 1H, isoxazole H5). MS (EI, m/z (%)): 345 (M+, 4.45), 344 (M‐1, 76.57), 340 (58.62), 173 (12.88), 163 (8.30), 150 (7.89), 142 (6.24), 115 (11.04), 105 (58.81), 102 (10.80), 101 (15.22), 100 (5.78), 92 (12.16), 88.60 (34.60), 87 (19.94), 77 (85.96), 74 (40.64), 62 (64.76). UV (EtOH, max, nm): 278.5, 296.5, 349.5. Anal. calcd. for C20H11NO5 (345.31): C, 69.57; H, 3.21; N, 4.06. Found: C, 69.74; H, 3.32; N, 4.11%. 3‐[3‐(Naphtha‐2‐oyl)‐isoxazole‐4‐carbonyl]‐chromen‐2‐one (23b): Deep brown crystals from AcOH. Yield: 83 %. M.p.: 184‐ 186 °C. IR (KBr): 3058 (CH), 1724, 1678 (CO's), 1608 (C=N), 1570 (C=C). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.33‐8.79 (m, 12H, ArH's), 8.97 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 395 (M+, 0.22), 356 (51.65), 329 (33.91), 271 (5.00), 243 (5.11), 155 (29.45), 127 (100), 113 (15.27), 75 (10.19). UV (EtOH, max, nm): 288.5, 351.5. Anal. calcd. for C24H13NO5 (395.36): C, 72.91; H, 3.31; N, 3.54. Found: C, 73.12; H, 3.54; N, 3.33%. 3‐[3‐(Thieno‐2‐oyll)‐isoxazole‐4‐carbonyl]‐chromen‐2‐one (23c): Deep brown crystals from AcOH. Yield: 83 %. M.p.: 164‐ 166 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1724, 1678 (CO's), 1608 (C=N), 1570 (C=C). 1H NMR (300 MHz, CDCl3, δ, ppm): Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 549 7.18‐8.17 (m, 7H, ArH's and thiophene protons), 8.56 (s, 1H, ArH), 8.99 (s, 1H, isoxazole H5). MS (EI, m/z (%)): 351 (M+, 15.60), 128 (10.99), 113 (33.91), 111 (100), 101 (11.85), 88 (25.40), 82 (25.76), 62 (15.70). UV (EtOH, max, nm): 304. Anal. calcd. for C18H9NO5S (351.33): C, 61.53; H, 2.58; N, 3.99; S, 9.13. Found: C, 61.53; H, 2.58; N, 3.99; S, 9.13%. 3‐[3‐(Furan‐2‐carbonyl)‐isoxazole‐4‐carbonyl]‐chromen‐2‐ one (23d): Brown crystals from AcOH. Yield: 80 %. M.p.: 208‐ 210 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1715, 1651 (CO's), 1604 (C=N), 1570 (C=C). 1H NMR (300 MHz, CDCl3, δ, ppm): 6.62 (s, 1H, furan H‐3), 7.18‐8.17 (m, 6H, ArH's and furan protons), 8.56 (s, 1H, ArH), 8.99 (s, 1H, isoxazole H‐5). UV (EtOH, max, nm): 299. Anal. calcd. for C18H9NO6 (335.27): C, 64.48; H, 2.71; N, 4.18. Found: C, 64.57; H, 2.68; N, 4.35%. 2‐(3‐Benzoyl‐isoxazole‐4‐carbonyl)‐benzo[f]chromen‐3‐one (24a): Yellow crystals from AcOH. Yield: 83 %. M.p.: 140‐142 °C. FT‐IR (KBr, cm‐1): 3093 (CH), 1720, 1662 (CO's), 1643 (C=N), 1596 (C=C). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.28‐ 8.00 (m, 8H, ArH's), 8.51‐8.62 (m, 4H, ArH's), 8.99 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 396 (M+1, 12.41), 177 (5.79), 151 (16.03), 139 (34.28), 105 (100), 77 (78.02). UV (EtOH, max, nm): 259.5, 391. Anal. calcd. for C24H13NO5 (395.36): C, 72.91; H, 3.31; N, 3.54. Found: C, 73.11; H, 3.42; N, 3.31%. 2‐[3‐(Naphthalene‐2‐carbonyl)‐isoxazole‐4‐carbonyl]‐ benzo[f]chromen‐3‐one (24b): Dark brown crystals from AcOH. Yield: 87 %. M.p.: 204‐206 °C. FT‐IR (KBr, cm‐1): 3020 (CH), 1724, 1685 (CO's), 1624 (C=N), 1596 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.38‐8.42 (m, 13H, ArH's), 8.65 (s, 1H, ArH), 9.04 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 445 (M+, 0.12), 155 (26.57), 139 (10.42), 127 (100), 101 (10.28), 87 (5.47), 77 (14.33), 75 (15.32), 62 (12.68), 50 (12.55). UV (EtOH, max, nm): 255, 296. Anal. calcd. for C28H15NO5 (445.1): C, 75.50; H, 3.39; N, 3.14. Found: C, 75.37; H, 3.45; N, 3.28%. 2‐{[3‐(2‐thienylcarbonyl)isoxazol‐4‐yl]carbonyl}‐3H‐ benzo[f]chromen‐3‐one (24c): Yellow crystals from AcOH. Yield: 87 %. M.p.: 222‐224 °C. FT‐IR (KBr, cm‐1): 3089 (CH), 1716, 1647 (CO's), 1593 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.13‐7.94 (m, 8H, ArH's), 8.51 (d, 1H, ArH), 8.65 (s, 1H, ArH), 9.04 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 404 (M+, 100), 223 (18.33), 189 (22.07), 176 (23.51), 163 (10.97), 151 (53.98), 89 (17.09), 86 (18.93), 82 (52.65), 74 (12.16), 62 (13.35). UV (EtOH, max, nm): 266, 392. Anal. calcd. for C22H11NO5S (401.04): C, 65.83; H, 2.76; N, 3.49; S, 7.99. Found: C, 65.75; H, 2.62; N, 3.51; S, 8.14%. 2‐{[3‐(2‐furoyl)isoxazol‐4‐yl]carbonyl}‐3H‐benzo[f]chromen‐ 3‐one (24d): Yellow crystals from AcOH. Yield: 82 %. M.p.: 240‐ 242 °C. FT‐IR (KBr, cm‐1): 3097 (CH), 1716, 1654 (CO's), 1593 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.64 (s, 1H, furan H‐3), 7.13‐7.33 (m, 4H, ArH's), 7.94‐7.97 (m, 3H, ArH's), 8.32 (d, 2H, J = 8 Hz), ArH), 9.04 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 385 (M+, 5.7), 223 (13.0), 222 (9.1), 139 (10.6), 112 (15.2), 95 (100), 94 (20.8), 89 (17.09), 86 (18.93), 82 (52.65), 74 (12.16), 62 (13.35). UV (EtOH, max, nm): 281.5, 291, 390.5. Anal. calcd. for C22H11NO6 (385.33): C, 68.57; H, 2.88; N, 3.64. Found: C, 68.66; H, 3.10; N, 3.48%. 2.5. Synthesis of isoxazolo[3,4‐d]pyridazines (25a‐d) and (26a‐d) Equimolar a mount of each of the appropriate isoxazoles (23a‐d, 24a‐d) (5 mmol) and hydrazine hydrate (1 mL, 99%) in ethanol (20 mL) was boiled under reflux for 2h. The resulting solid was collected and crystallized to give isoxazolo[3,4‐d]pyridazines, 25a‐d, 26a‐d (Scheme 4). 3‐(7‐Phenyl‐isoxazolo[3,4‐d]pyridazin‐4‐yl)‐chromen‐2‐one (25a): Beige crystals from EtOH. Yield: 85 %. M.p.: >300 °C. FT‐ IR (KBr, cm‐1): 3058 (CH), 1685 (CO), 1612 (C=N), 1566 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.27‐7.56 (m, 7H, ArH's), 7.94 (d, 2H, J = 8 Hz, ArH's), 8.55 (s, 1H, isoxazole H‐5), 875 (s, 1H, pyran H‐4). MS (EI, m/z (%)): 342 (M+1, 0.12), 284 (23.73), 225 (22.25), 197 (48.30), 168 (24.92), 141 (37.45), 115 (100), 101 (24.34), 89 (21.91), 86 (20.97), 77 (13.59), 75 (30.23), 62 (29.28). UV (EtOH, max, nm): 302, 335, 349. Anal. calcd. for C20H11N3O3 (341.32): C, 70.38; H, 3.25; N, 12.31. Found: C, 70.50; H, 3.42; N, 12.48%. 3‐(7‐Naphthalen‐2‐yl‐isoxazolo[3,4‐d]pyridazin‐4‐yl)‐ chromen‐2‐one (25b): Brown crystals from AcOH. Yield: 87 %. M.p.: 224‐226 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1685 (CO), 1612 (C=N), 1566 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.27‐7.32 (m, 2H, ArH's), 7.45‐7.61 (m, 4H, ArH's), 7.65‐ 8.74 (m, 5H, ArH's), 8.12 (s, 1H, isoxazole H‐5), 8.65 (s, 1H, pyran H‐4). MS (EI, m/z (%)): 391 (M+, 0.62), 253 (56.02), 225 (26.88), 197 (40.04), 168 (15.27), 141 (34.75), 115 (84.29), 100 (11.01), 98 (18.90), 91 (27.20), 89 (47.44), 87 (38.86), 83 (12.73), 77 (64.68), 65 (24.13), 62 (100). UV (EtOH, max, nm): 286, 330, 353.5. Anal. calcd. for C24H13N3O3 (391.38): C, 73.65; H, 3.35; N, 10.74. Found: C, 73.51; H, 3.48; N, 10.68%. 3‐[7‐(2‐thienyl)isoxazolo[3,4‐d]pyridazin‐4‐yl]‐2H‐chromen‐ 2‐one (25c): Brown crystals from EtOH. Yield: 86 %. M.p.: 240‐ 242 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1681 (CO), 1612 (C=N), 1566 (C=C). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.27‐7.32 (m, 3H, ArH's), 7.55‐7.62 (m, 2H, ArH's), 7.71‐7.73 (d, 1H, J = 8 Hz, ArH's), 8.38 (s, 1H, thiophene H‐3), 8.65 (s, 1H, isoxazole H‐5), 8.78 (s, 1H, pyran H‐4). MS (EI, m/z (%)): 347 (M+, 0.89), 330 (11.55), 284 (24.53), 269 (13.53), 253 (71.95), 225 (63.57), 213 (10.26), 197 (33.75), 168 (14.73), 152 (40.57), 146 (14.99), 141 (30.43), 140 (44.78), 127 (32.00), 118 (18.96), 111 (49.49), 109 (18.92), 107 (21.97), 101 (34.64), 97 (35.83), 93 (34.62), 91 (32.52), 89 (39.72), 87 (37.03), 81 (34.84), 76 (42.42), 69 (28.07), 62 (89.59). UV (EtOH, max, nm): 261, 335, 351. Anal. calcd. for C18H9N3O3S (347.35): C, 62.24; H, 2.61; N, 12.10; S, 9.23. Found: C, 62.41; H, 2.74; N, 12.25; S, 9.18%. 3‐[7‐(2‐furyl)isoxazolo[3,4‐d]pyridazin‐4‐yl]‐2H‐chromen‐ 2‐one (25d): Beige crystals from EtOH. Yield: 85 %. M.p.: >300 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1695 (CO), 1616 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.91 (s, 1H, furan H‐3), 7.27‐ 7.71 (m, 5H, ArH's), 8.92 (s, 1H, ArH), 9.12 (s, 1H, isoxazole H‐ 5), 8.78 (s, 1H, pyran H‐4). UV (EtOH, max, nm): 280.5. Anal. calcd. for C18H9N3O4 (331.28): C, 65.26; H, 2.74; N, 12.68. Found: C, 65.42; H, 2.84; N, 12.75%. 2‐(7‐Phenylisoxazolo[3,4‐d]pyridazin‐4‐yl)‐7,10‐dihydro‐3H‐ benzo[f]chromen‐3‐one (26a): Yellowish green crystals from DMF. Yield: 87 %. M.p.: 292‐294 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1685 (CO), 1620 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.41‐7.94 (m, 11H, ArH's), 8.25 (d, 1H, J = 8Hz, ArH), 8.55 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 392 (M+, 0.11), 323 (7.66), 170 (47.61), 152 (7.25), 143 (13.51), 141 (17.94), 127 (29.56), 115 (100), 101 (6.85), 88 (21.20), 77 (6.16). UV (EtOH, max, nm): 314, 357, 407. Anal. calcd. for C24H13N3O3 (391.38): C, 73.65; H, 3.35; N, 10.74. Found: C, 73.55; H, 3.52; N, 10.89%. 2‐(7‐Naphthylisoxazolo[3,4‐d]pyridazin‐4‐yl)‐7,10‐dihydro‐ 3H‐benzo[f]chromen‐3‐one (26b): Brown crystals from DMF. Yield: 89 %. M.p.: 276‐278 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1628 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.41‐8.35 (m, 13H, ArH's), 8.55 (s, 1H, isoxazole H‐5), 8.78 (s, 1H, ArH). MS (EI, m/z (%)): 442 (M+, 20.16), 380 (19.95), 168 (28.36), 140 (22.52), 127 (34.50), 119 (24.52), 114 (34.52), 111 (23.96), 89 (27.04), 82 (20.08), 79 (21.48), 77 (47.82), 76 (31.32), 75 (19.95), 74 (24.52), 63 (61.89), 62 (34.08), 57 (42.31). UV (EtOH, max, nm): 273, 330, 404. Anal. calcd. for C28H15N3O3 (441.44): C, 76.18; H, 3.42; N, 9.52. Found: C, 76.23; H, 3.52; N, 9.78%. 2‐[7‐(2‐thienyl)isoxazolo[3,4‐d]pyridazin‐4‐yl]‐7,10‐dihydro‐ 3H‐benzo[f]chromen‐3‐one (26c): Beige crystals from DMF. Yield: 88 %. M.p.: 304‐306 °C. FT‐IR (KBr, cm‐1): 3058 (CH), 1628 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.32‐7.85 (m, 8H, ArH's), 8.12 (d, 1H, J = 8Hz, ArH), 8.39 (s, 1H, thiophene H‐3), 8.62 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 397 (M+, 550 Abdelhamid et al. / European Journal of Chemistry 2 (4) (2011) 544‐551 0.01), 183 (5.29), 170 (100), 154 (11.30), 152 (19.21), 127 (81.44), 101 (18.41), 88 (41.71), 77 (9.26), 75 (8.37), 65 (9.55), 63 (17.59). UV (EtOH, max, nm): 327, 411. Anal. calcd. for C22H11N3O3S (397.41): C, 66.49; H, 2.79; N, 10.57; S, 8.07. Found: C, 66.62; H, 2.85; N, 10.75; S, 7.85%. 2‐[7‐(2‐furyl)isoxazolo[3,4‐d]pyridazin‐4‐yl]‐7,10‐dihydro‐ 3H‐benzo[f]chromen‐3‐one (26d): Yellow crystals from DMF. Yield: 87 %. M.p.: > 300 °C; IR (KBr): 3058 (CH), 1628 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.85 (s, 1H, furan H‐3), 7.32‐7.85 (m, 8H, ArH's), 8.12 (d, 1H, J = 8Hz, ArH), 8.62 (s, 1H, isoxazole H‐5). MS (EI, m/z (%)): 381 (M+, 0.01), 183 (5.29), 170 (100), 154 (11.30), 152 (19.21), 127 (81.44), 101 (18.41), 88 (41.71), 77 (9.26), 75 (8.37), 65 (9.55), 63 (17.59). UV (EtOH, max, nm): 302, 313, 344, 356. Anal. calcd. for C22H11N3O4 (381.34): C, 69.29; H, 2.91; N, 11.02. Found: C, 69.42; H, 3.15; N, 10.89%. 3. Results and discussion Methyl N'‐(4‐Methyl‐benzylidene)‐hydrazine carbodi‐ thioate (3b) reacted with 3‐aza‐2‐bromo‐1‐(2‐oxo(2H‐ chromen‐3‐yl)‐3‐(phenylamino)prop‐2‐en‐1‐one (1) to afford 3‐{5‐[(4‐methyl‐benzylidene)‐hydrazono]‐4‐phenyl‐4,5‐ dihydro‐[1,3,4]‐thiadiazole‐2‐carbonyl}‐chromen‐2‐one (7b) (Scheme 1). Structure 7b was confirmed by elemental analysis, spectra and alternative synthetic route. Thus, treatment of benzyl N'‐(4‐Methyl‐benzylidene)‐hydrazine carbodithioate (4b) with 1 gave a product identical in all aspects (M.p., mixed m.p. and spectra) with 7b. The formation of 7b is assumed to proceed via 1,3‐addition of thiol tautomer of carbodithioate 3b (or 4b) to nitrilium imide 2 (generated in situ by treatment of 1 with triethylamine) can give 6a, nucleophilic cyclization to yield 5b. Alternatively, 1,3‐cycloaddition of nitrilium imide 2 to the C=S of carbodithioate 3b (or 4b) can give 6b directly, and then afforded 7b by loss of alkyl mercaptan (Scheme 1). Analogously, treatment of 1 with the appropriate 3a, c‐j in ethanolic triethylamine gave thiadiazoline derivatives 7a, c‐j, respectively. Also, treatment of 1 with the pyrimidine‐2‐thione 8b in boiling chloroform gave triazolino[4,3‐a]pyrimidines 11b in a good yields (Scheme 2). Structure of 11b was elucidated by elemental analysis, spectral data and alternative synthetic route. Thus, 1H NMR spectrum of 11b showed signals at : 2.24 (s, CH3, 4‐CH3C6H4), 5.05 (s, 1H, pyrimidine H‐4), 7.44‐8.24 (m, 19H, ArH's). Its IR spectrum revealed bands at 1702 (CO ester), 1650 (CO conjugated) and 1615 (C=N). Compound 11b was obtained from the reaction of ethyl 6‐methy‐2‐methylthio‐4‐ phenyl‐3,4‐dihydropyrimidine‐5‐carboxylate, 14b with 1 in boiling sodium ethoxide solution. The mechanism outlined in Scheme 2 seems to be the most plausible pathway for the formation of 11 from the reaction of 1 with 8 or 14. 1. 1,3‐addition of the thiol tautomer 8 to the nitrilium imide 2 to give the thiohydrazonate ester 9 which undergoes nucleophilic cyclization to yield spiro compounds 10. The latter ring open and cyclized to yield 11 by loss hydrogen sulfide; and 2. 1,3‐cycloaddition of nitrilium imide 2 to C=S double bond of 8 to give directly 10 (Scheme 2). Attempts to isolate the thiohydrazonate ester 9 or intermidate 10 did not succeed even under mild conditions as they readily undergo in situ cyclization followed by elimination of hydrogen sulfide to give the final product 11 in Scheme 2. Analogously, reactions of 2‐thioxo‐2,3‐dihydro‐1H‐quina‐ zolin‐4‐one [29], 2‐thioxo‐2,3,5,6,7,8‐hexahydro‐1H‐benzo[4,5] thieno[2,3‐d]pyrimidin‐4‐one [30], 2‐mercaptobenzimidazole or with hydrazonoyl bromide 1 were carried out in refluxing chloroform in presence of TEA gave 3‐(2‐oxo‐2H‐chromene‐3‐ carbonyl)‐1‐phenyl‐1H‐[1,2,4]triazolo[3,4‐b]quinazolin‐5‐one 15, 3‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐1‐phenyl‐5,6,7,8‐tetra‐ hydro‐1H‐9‐thia‐1,2,3a,10‐tetraaza‐cyclopenta[b]fluoren‐4‐ one, 16 and 3‐(1‐phenyl‐1H‐benzo[4,5]imidazo[2,1‐c][1,2,4] triazole‐3‐carbonyl)‐chromen‐2‐one, 17, respectively (Scheme 3). Finally, treatment of 3‐(3‐(dimethylamino)acryloyl)‐2H‐ chromen‐2‐one (18) with 2‐chloro‐2‐(hydroxyimino)‐1‐ phenylethanone (19a) in dry toluene and presence of triethylamine at 0 oC afforded one isolable product identified as 3‐(3‐benzoyl‐isoxazole‐5‐carbonyl)chromen‐2‐one (22a) or 3‐ (3‐benzoyl‐isoxazole‐4‐carbonyl)‐chromen‐2‐one (23a) Scheme 4. Structure 23a was elucidated by elemental analysis, spectra, alternative synthetic route and chemical transformation. Formation of 23 can be explained via reaction of nitrile oxide, which formed in situ from the appropriate hydroximoyl chlorides 19 and triethylamine, with the appropriate 18 to afford cyclo adduct intermediate 20 or 21, and then eliminate dimethylamine to give isoxazole as final product 22 or oxazole 23. The later was ruled out on the basis of the formation of isoxazolo[4,3‐d] pyridazine 25. Other isoxazolo[4,3‐d] pyridazines 25b‐e were obtained in a good yield from boiling the appropriate isoxazole 23a‐e with hydrazine in boiling ethanol. Structures 25b‐e were elucidated on the basis of elemental analysis and spectral data. Analogously, treatment of 2‐(3‐(dimethylamino)acryloyl)‐3H‐benzo[f]chromen‐3‐one (18b) with appropriate hydroximoyl chlorides 19a‐e gave isoazoles 24a‐e, which it converted to isoxazolo[3,4‐ d]pyridazines 26a‐e (Scheme 4). 4. Conclusion The 1,3,4‐thiadiazoline, triazolo[4,3‐a]pyrimidines, isoxazole and isoxazolo[3,4‐d]pyridazine derivatives containing the coumarin moiety in a good yields were synthesized by reaction of hydrazonoyl halides and hydroximoyl chlorides with alkyl carbodithioates, pyrimidine‐ 2‐thiones and enaminones. References [1]. Anderson, D. M.; Shelley, S.; Crick, N.; Buraglio, M. J. Clin. Pharmacol. 2002, 42, 1358‐1365. [2]. Tassies, D.; Freire, C.; Puoan, J.; Maragall, S.; Monteagudo, J.; Ordinas, A.; Reverter, J. C. 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