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Synlett 2006(7): 1009-1014  
DOI: 10.1055/s-2006-939066
LETTER
© Georg Thieme Verlag Stuttgart · New York

Ceric Ammonium Nitrate (CAN) Promoted Efficient Synthesis of 1,5-Benzodiazepine Derivatives [1]

Ravi Varala, Ramu Enugala, Sreelatha Nuvula, Srinivas R. Adapa*
Indian Institute of Chemical Technology, Hyderabad - 500 007, India
Fax: +91(40)27160921; e-Mail: rvarala_iict@yahoo.co.in;
Further Information

Publication History

Received 17 January 2006
Publication Date:
24 April 2006 (online)

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Abstract

Ceric ammonium nitrate was found to be an efficient ­reagent for the preparation of 1,5-benzodiazepine derivatives of a wide range of substituted o-phenylenediamines and electronically divergent ketones in moderate to excellent isolated yields (60-98%) under mild conditions using methanol as solvent at ambient temperature.

Key words

1,5-benzodiazepines - ceric ammonium nitrate - o-phen­ylenediamines

1

IICT communication no: 050809.

1

IICT communication no: 050809.

10

Representative Procedure.
A mixture of o-phenylenediamine (1.0 mmol), ketone (2.2 mmol) and CAN (0.055 g, 10 mol%) in MeOH (2 mL) was stirred at r.t. for the time specified in Table [1] . After the reaction was over, the reaction mixture was diluted with H2O and extracted with Et2O (3 ¥ 10 mL). The combined organic layers were dried over Na2SO4, concentrated in vacuo and purified by column chromatography on silica gel with EtOAc and n-hexane (2:8) as eluent to afford the corresponding pure 1,5-benzodiazapine. Previously reported materials were characterized by comparison of their NMR and mass spectra with those of authentic samples. All novel compounds gave satisfactory spectroscopic data in accordance to their proposed structures.
Spectral Data for Selected Compounds:
Compound 2: pale yellow crystalline solid, mp 98-99 °C. IR (KBr): 3318, 1630, 1598 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.72 (s, 3 H), 2.26 (s, 3 H), 2.32 (s, 3 H), 2.98 (d, J = 13.38 Hz, 1 H), 3.05 (d, J = 13.38 Hz, 1 H), 3.43 (br s, NH), 6.76 (m, 1 H), 7.01 (m, 6 H), 7.23 (m, 1 H), 7.49 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ = 20.75, 21.16, 29.85, 42.97, 73.06, 121.28, 121.38, 125.18, 126.03, 127.15, 128.50, 128.67, 128.92, 129.22, 136.45, 137.0, 138.18, 139.76, 140.32, 144.98, 166.82. MS (EI): m/z = 340 [M+]. [7i]
Compound 3: yellowish solid, mp 114-116 °C. IR (neat): 3325, 1135, 1640, 1594 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.71 (s, 3 H), 2.85 (d, J = 12.84 Hz, 1 H), 2.98 (d, J = 13.60 Hz, 1 H), 3.73 (s, 3 H), 3.77 (s, 3 H), 6.65-6.78 (m, 4 H), 6.95-7.02 (m, 2 H), 7.18-7.25 (m, 2 H), 7.42-7.55 (m, 4 H). MS (EI): m/z = 372 [M+].
Compound 4: yellow crystalline solid, mp 219-220 °C. IR (KBr): 3339, 1636, 1599 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.65 (s, 3 H), 2.77 (d, J = 12.63 Hz, 1 H), 2.89 (d, J = 7.43 Hz, 1 H), 4.18 (br s, NH), 6.57-6.64 (m, 4 H), 6.81-7.00 (m, 1 H), 7.10-7.18 (m, 1 H), 7.28-7.55 (m, 4 H).
MS (EI): m/z = 344 [M+].
Compound 5: red crystalline solid, mp 156-158 °C. IR (KBr): 3325, 1642, 1597 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.83 (s, 3 H), 2.96 (d, J = 13.38 Hz, 1 H ), 3.27 (d, J = 13.38 Hz, 1 H), 3.52 (br s, NH), 6.98 (m, 1 H), 7.00 (m, 6 H), 7.22 (m, 1 H), 7.47 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ = 30.02, 42.92, 73.37, 121.29, 122.16, 123.53, 123.38, 126.78, 127.57, 127.75, 129.58, 137.23, 138.80, 144.65, 146.95, 148.40, 154.05, 163.82. MS (EI): m/z =
402 [M+].
Compound 6 (X = F): pale-yellow crystalline solid, mp 104-105 °C. IR (KBr): 3271, 1651, 1603, 1231 cm-1.
1H NMR (300 MHz, CDCl3): δ = 1.75 (s, 3 H), 2.87 (d, J = 13.60 Hz, 1 H), 3.04 (d, J = 12.84 Hz, 1 H), 3.30 (br s, NH), 6.75-6.79 (m, 1 H), 6.82-6.92 (m, 4 H), 7.00-7.05 (m, 2 H), 7.19-7.25 (m, 1 H), 7.48-7.62 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ = 29.72, 42.94, 73.38, 114.70, 114.79, 114.97, 115.06, 126.22, 127.0, 128.50, 129.20, 135.46, 137.44, 140.36, 143.2, 160.23, 162.22, 165.26, 165.53, 163.50. MS (EI): m/z = 348 [M+].
Compound 9: pale-yellow crystalline solid; mp 102-103 °C. IR (KBr): 3325, 1636, 1594 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.72 (s, 3 H), 2.26-2.36 (s, 6 H), 2.45 (s, 3 H), 2.58 (s, 3 H), 2.91 (d, J = 12.84 Hz, 1 H), 3.03 (d, J = 13.60 Hz, 1 H), 3.29 (br s, NH), 6.56 (s, 1 H), 7.02-7.07 (m, 1 H), 7.24-7.28 (m, 4 H), 7.47-7.53 (m, 2 H), 7.83-7.87 (d, 2 H). 13C NMR (75 MHz, CDCl3): δ = 19.12, 21.10, 29.88, 43.06, 72.88, 122.34, 125.24, 127.05, 128.44, 128.76, 128.94, 129.58, 129.60, 134.58, 136.56, 137.26, 137.96, 139.68, 166.76. MS (EI): m/z = 368 [M+].
Compound 10: yellow crystalline solid, mp 158-160 °C. IR (KBr): 3304, 1638, 1603, 761 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.75 (s, 3 H), 2.93 (d, J = 13.60 Hz, 1 H), 3.12 (d, J = 12.84 Hz, 1 H), 3.49 (br s, NH), 6.88 (s, 1 H), 7.13-7.30 (m, 5 H), 7.36 (s, 1 H), 7.50-7.53 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 29.97, 43.23, 72.97, 121.90, 124.14, 125.33, 127.30, 128.35, 128.76, 130.13, 137.84, 139.26, 146.83, 168.81. MS (EI): m/z = 381 [M+].
Compound 11: pale-yellow solid, mp 179-180 °C. IR (KBr): 3434, 1636, 1597, 817 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.75 (s, 3 H), 2.34 (s, 3 H), 2.37 (s, 3 H), 2.95 (d, J = 13.60 Hz, 1 H), 3.09 (d, J = 13.60 Hz, 1 H), 3.50 (br s, NH), 6.88 (s, 1 H), 7.05-7.09 (t, 3 H), 7.28 (s, 1 H), 7.38-7.44 (t, 3 H), 7.50-7.53 (d, 2 H). MS (EI): m/z = 409 [M+].
Compound 12: pale-yellow crystalline solid, mp 199-200 °C. IR (KBr): 3325, 1630, 1594 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.77 (s, 3 H), 2.88 (d, J = 13.60 Hz, 1 H), 3.11 (d, J = 13.60 Hz, 1 H), 3.48 (br s, NH), 6.92 (s, 1 H), 7.21-7.25 (m, 4 H), 7.38 (s, 1 H), 7.45-7.51 (m, 4 H). MS (FAB): m/z = 451 [M+ + 1].
Compound 13: reddish crystalline solid, mp 218-220 °C. IR (KBr): 3387, 1640, 1585 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.74 (s, 3 H), 2.69 (d, J = 9.82 Hz, 1 H), 2.82 (d, J = 11.33 Hz, 1 H), 2.93 (br s, NH), 6.92 (s, 1 H), 7.21-7.25 (m, 4 H), 7.38 (s, 1 H), 7.45-7.51 (m, 4 H). MS (FAB): m/z = 472 [M+ + 1].
Compound 15 (R = R1 = Cl): reddish crystalline solid, mp 92-94 °C. IR (KBr): 3325, 1636, 1590 cm-1. 1H NMR (200 MHz, CDCl3): δ = 1.35 (s, 6 H), 2.26 (s, 2 H), 2.34 (s, 1 H), 6.78 (s, 1 H), 7.18 (s, 1 H). MS (EI): m/z = 257 [M+].