Download PDF
Synlett 2009(18): 2992-2996  
DOI: 10.1055/s-0029-1218006
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Expeditious Concise Synthesis of Benzo[b]pyrano[2,3-d]oxepines and Dibenzo[b,d]oxepines

Vishnu K. Tandon*a, Hardesh K. Mauryaa, Balendu Kumara, Brijesh Kumarb, Vishnu Ji Ram*a
a Department of Chemistry, Lucknow University, Lucknow 226007, U.P., India
Fax: +91(522)2623405; e-Mail: vjiram@yahoo.com;
b Division of SAIF, Central Drug Research Institute, Lucknow, 226001, India
Further Information

Publication History

Received 15 July 2009
Publication Date:
08 October 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient concise synthesis of 4-methylthio-2-oxo-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepine-3-carbonitriles has been delineated through condensation-cyclization of 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones and methyl 2-cyano-3,3-dimethylthioacrylate in DMF using powdered KOH as a base. A base-­induced reaction of 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones and 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitrile in the presence of powdered KOH in DMF gave an isomeric mixture of (E)- and (Z)-2-(4-phenyl-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepin-2-ylidene)acetonitriles. However, the ring transformation of 6-aryl-4-(sec-amino)-2H-pyran-2-one-3-carbonitriles from 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones under analogous reaction conditions exclusively gave 8-phenyl-10-(sec-amino)-6,7-dihydrodibenzo[b,d]oxepine-11-carbonitriles.

Keywords

2-pyranone - benzo[b]pyrano[2,3-d]oxepine - dibenzo[b,d]oxepine - ring-transformation reaction

20

Data for Compounds
General Procedure for the Synthesis of 4-Methylthio-2-oxo-5,6-dihydro-2 H -benzo[ b ]pyrano[2,3- d ]oxepine-3-carbonitriles (5)
A mixture of 3,4-dihydro-2H-benzo[b]oxepin-5 (2H)-one (1 mmol) and methyl 2-cyano-3,3-dimethylthioacrylate (1, 1 mmol) in DMF (8 mL) in the presence of powdered KOH (2 mmol) for 5 h. Excess of DMF was removed under reduced pressure and the residue poured onto crushed ice with vigorous stirring. The aqueous suspension was neutralized with 10% HCl (5 mL) and the precipitate obtained was filtered, washed with H2O, and purified on silica gel column, using 40% hexane in CH2Cl2 as eluent.
Compound 5c: yellow solid; yield 65%; mp 178 ˚C; IR (KBr): 2956, 2361, 2216 (CN), 1722 (C=O), 1585, 1489, 1271, 1212, 1037, 840, 761, 668, 502 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 2.87 (t, J = 6 Hz, 2 H), 3.01 (s, 3 H, SCH3), 3.83 (s, 3 H, OCH3), 4.47 (t, 2 H, J = 6.0 Hz, OCH2), 7.03 (s, 1 H, ArH), 7.28 (d, J = 9 Hz, 2 H, ArH). ¹³C NMR (300 MHz, CDCl3): δ = 18, 27, 55, 75, 93, 112 (2 C), 114, 115, 120, 123, 124, 150, 155, 158, 168. MS: m/z = 315 [M+]. ESI-HRMS: m/z calcd for C16H14NO4S: 316.0626 [M+ + 1]; found: 316.0643.
General Procedure for the Synthesis of 8-Phenyl-10-( sec -amino)-6,7-dihydrodibenzo[ b , d ]oxepine-11-carbonitriles (6) A mixture of 3,4-dihydrobenzo[b]oxepine-5 (2H)-ones 4 (1 mmol) and 6-phenyl-4-(sec-amino)-2H-pyran-2-one-3-carbonitriles 3 (1 mmol) in DMF (6 mL) was stirred for
3 h in the presence of powdered KOH (2 mmol). After completion of the reaction, content was poured onto crushed ice with vigorous stirring and neutralized with 10% HCl. The precipitate obtained was filtered, washed with H2O, and dried. The crude product was purified through silica gel column using a mixture of hexane-CH2Cl2 (7:3) as eluent and repurified by abs. MeOH.
Compound 6a: white solid; yield 44%; mp 144 ˚C. IR (KBr): 3069, 2934, 2850, 2804, 2370, 2218 (CN), 1573, 1496, 1439 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.52-1.69 (m, 6 H), 3.06 (m, 2 H), 3.20 (m, 4 H), 3.79 (s, 3 H), 4.24 (m, 2 H), 6.97-7.03 (m, 2 H), 7.08 (s, 1 H), 7.24 (d, 1 H, J = 3.0 Hz), 7.38-7.48 (m, 5 H). ¹³C NMR (300 MHz, CDCl3): δ = 24, 26 (2 C), 28, 53 (2 C), 55, 78, 105, 115, 116, 118, 119, 122, 127 (2 C), 128 (3 C), 132 (2 C), 140, 143, 146, 148, 155, 156. MS: m/z = 411 [M+ + 1], 412 [M+ + 2]. ESI-HRMS: m/z calcd for C27H27N2O2: 411.20725 [M+ + 1]; found: 411.20728.
General Procedure for the Synthesis of 2-{4-Phenyl-5,6-dihydro-2 H -benzo[ b ]pyrano[2,3-d]oxepin-2-ylidene}-acetonitriles (7)
A mixture of 3,4-dihydrobenzo[b]oxepine-5 (2H)-ones 4 (1 mmol), 6-(4-phenyl-4-methylthio)-2-oxo-2H-pyran-3-carbonitriles 2 (1 mmol) and powdered KOH (2 mmol) in DMF (8 mL) was stirred for 3 h.The reaction mixture was poured onto crushed ice with vigorous stirring. The aqueous phase was neutralized with 10% HCl, and the precipitate obtained was filtered, washed with H2O, and purified on silica gel column using hexane-CH2Cl2 mixture (7:3) as eluent.
Compound 7b: red colored solid; yield 55%; mp 200 ˚C; IR (KBr): 3077, 2927, 2834, 2368, 2189 (CN), 1639, 1570, 1490, 1404 cm-¹. ¹H NMR (300 MHz, CDCl3): δ (Z-isomer, 70%) = 2.50 (s, 2 H, CH2), 3.89 (s, 3 H, OCH3), 4.26 (s, 2 H, OCH2), 6.18 (s, 1 H, CH), 6.65-7.43 (m, 8 H, ArH); δ (E-isomer, 30%) = 2.41 (s, 2 H, CH2), 3.83 (s, 3 H, OCH3), 4.35 (s, 2 H, OCH2), 6.65 (s, 1 H, CH), 6.65-7.43 (m, 8 H, ArH). ¹³C NMR (300 MHz, CDCl3): δ = 31, 55, 65, 72, 110, 112, 115, 116, 117, 118, 119, 122 (2 C), 129 (2 C), 135 (2 C), 146, 150, 151, 155, 164. MS: m/z = 378 [M+], 380 [M+ + 2]. ESI-HRMS: m/z calcd for C22H17ClNO3: 378.0897 [M+ + 1]; found: 378.0889.