p-nitrobenzoic acid promoted synthesis of 1,5-benzodiazepine derivatives

ARTICLE

p-nitrobenzoic acid promoted synthesis of 1,5-benzodiazepine derivatives

Ravi Varala^*; Ramu Enugala; Srinivas R. Adapa

Indian Institute of Chemical Technology, Hyderabad-500 007, India

ABSTRACT

p-Nitrobenzoic acid was found to be the versatile Bronsted organic acid promoter among the carboxylic acids tested for the preparation of 1,5-benzodiazepine derivatives from a wide range of substituted o-phenylenediamines and ketones. The corresponding products were obtained in good isolated yields (62-92%) under mild conditions using acetonitrile as solvent at ambient temperature. Further, the reagent could be easily recovered and reused.

Keywords: 1,5-benzodiazepines, bronsted acid, o-phenylenediamines and ketones, p-nitrobenzoic acid

RESUMO

Entre vários ácidos carboxílicos testados, o ácido p-nitrobenzóico mostrou ser o mais versátil para a preparação de derivados de 1,5-benzodiazepinas a partir de uma série de o-fenilenodiaminas substituídas e cetonas. Os produtos foram obtidos em bons rendimentos (62-92%) sob condições brandas, usando acetonitrila como solvente, a temperatura ambiente. Adicionalmente, o reagente pode ser facilmente recuperado e re-utilizado.

Introduction

1,5-benzodiazepine derivatives have received significant attention and the core is indeed a "privileged scaffold" found in compounds active against a variety of target types including peptide hormones (such as CCK), interleukin converting enzymes (ICE) and potassium blockers (I_k).¹ More recently, the area of biological interest of 1,5-benzodiazepines has been extended to various diseases such as cancer, viral infection (non-nucleoside inhibitors of HIV-1 reverse transcriptase), cardiovascular disorders.² In addition, 1,5-benzodiazepines show antidepressive, antifungal, antibacterial, antifeedant, antiinflammatory, analgesic and anticonvulsant activities.³ Besides these derivatives are also used as dyes for acrylic fibre in photography.⁴ Moreover, 1,5-benzodiazepines are valuable synthons used for the preparation of other fused ring compounds such as triazolo-, oxadiazolo-, oxazino-, or furano-benzodiazepines.⁵

Despite their importance from a pharmacological, industrial and synthetic point of view, comparatively few methods for their preparation are reported in the literature, a great number of which have appeared only very recently employing BF₃-etherate, NaBH₄, polyphosphoric acid or SiO₂, MgO/POCl₃, Yb(OTf)₃, and InBr₃ as catalysts or as stoichiometric reagents.⁶ However, many of these methods have some drawbacks such as low yields of the products, high temperatures, drastic reaction conditions, long reaction times, and relatively expensive reagents. From the viewpoints above, the development of environmentally benign, less expensive and easily handled promoters for the preparation of 1,5-benzodiazepines (hereafter 1,5-BDPs) is still highly desirable.

Very recently, we have reported synthesis of 1,5-BDPs using CAN as catalyst in methanol.⁷ In recent years, lot of attention has been paid to organocatalysts owing to their eco-friendliness and can proceed under aerobic atmosphere, other notable advantages are: usually less expensive and commercially available.⁸ Intrigued by the results achieved by Zhao et al.⁹ in allylation of aldehydes using carboxylic acids as Bronsted organocatalysts and Gopal's report⁹ which was limited only for the reaction between acetone and o-phenelynediamine (o-PD) involving supramolecular chemistry, we have undertook advantage of both the reports and tried to explore the utility of several organo acids in the preparation of various structurally and electronically divergent 1,5-BDPs.

Results and Discussion

In continuation of our efforts to develop novel synthetic routes for carbon-carbon and carbon-heteroatom bond formations and heterocycles,¹⁰ we have studied the efficacy of chosen organoacids (1 equiv. as standard) for the model reaction using o-PD (1 mmol) and acetophenone (2.2 mmol) in acetonitrile at ambient temperature to afford the corresponding 1,5-benzodiazepine (Table 1).

Among the acids screened, p-nitrobenzoic acid (p-NBA) was found to be the best promoter in terms of reaction times and yields (entry 2, Table 1). To the best of our knowledge, there are no earlier reports on the preparation of 1,5-benzodiazepines using p-nitrobenzoic acid (Scheme 1). The optimum yields of the product were obtained when a ratio of o-PD to ketone 1:2.2 is used. The reaction is found to be sluggish when carried out using even 0.5 equiv. of catalyst amounts. In all cases, the reactions are clean and are completed within 3.5-15 h. The benzodiazepines were the only products obtained and the rest of the material was essentially starting material.

The crude product was filtered and washed with DCM to recover the p-nitrobenzoic acid, the filtrate was extracted with DCM and after usual workup and further purification by silica gel column chromatography yielded the desired pure product. Furthermore, p-NBA could be recovered and repeated minimum three times with slight decrease in the yield (88%, 80%, 77%) due to the loss of p-NBA in recovery.

Encouraged by these results, at first, we studied the condensation of acetophenone with divergent o-PD's for the synthesis of corresponding 1,5-benzodiazepine derivatives under standardized conditions and the results were quite satisfactory (Table 2). The scope and generality of the present procedure was then extended to electronically divergent acetophenones towards o-PD and the results are presented in Table 3. It is interesting to note that under our optimized conditions, exclusively one regioisomer is favoured para position in relation to the imine moiety as confirmed by ¹H NMR spectroscopic data. (entries 2, 4, 6 and 7, Table 2).

In a similar fashion, cyclic ketones such as cyclopentanone and cyclohexanone also reacted well with o-PD to furnish the corresponding 1,5-BDPs in good yields (entries 6-7, Table 3). In case of unsymmetrical ketones such as 2-butanone (entry 8, Table 3), the ring closure occurred selectively giving a single product.

Conclusions

In conclusion, we have developed a practical and novel procedure for the synthesis of 2,3-dihydro-1H-1,5-benzodiazepine derivatives using p-NBA in acetonitrile. The present protocol has several advantages: mild reaction conditions (at room temperature), operational and experimental simplicity, readily availability, study of wide range of electronically divergent ketones and o-PDs, easily recoverable and reusable organo promoter for applicability in large scale synthesis. We believe that this p-NBA promoted methodology will be a valuable contribution to the existing processes in the field of synthesis of 1,5-benzodiazepines.

Experimental

General

Melting points were measured using a Buchi R-535 apparatus. IR spectra were taken on a Bruker Vector-22 spectrometer in KBr pellets and reported in cm^-1. ¹H NMR spectra were recorded at 300 MHz on a Bruker Avance-300 spectrometer in CDCl₃ with chemical shifts (d) given relative to TMS as an internal standard. ¹³C NMR spectra were recorded on a Bruker Avance-300 (75.5 MHz) spectrometer with complete proton decoupling; chemical shifts are reported in ppm relative to the solvent resonance as the internal standard (CDCl₃, d 77.16 ppm. CHN analyses were recorded on a Vario EL analyzer.

Representative procedure

To a suspension of p-nitrobenzoic acid (1 mmol) in acetonitrile (3 mL) were added successively o-phenylenediamine (1 mmol) and acetophenone (2.2 mmol) at room temperature for the time specified in Table 2. After the reaction was over, the reaction mixture was filtered and washed with DCM to recover p-nitrobenzoic acid. The filtrate was extracted with DCM (20 mL) and the combined organic layer was dried over Na₂SO₄, concentrated under reduced pressure to furnish the crude product, which was purified by silica gel chromatography using EtOAc/Hexane (1:5), to afford corresponding pure product. All compounds gave satisfactory spectroscopic data in accordance to their proposed structures.

Spectral data for compounds

Entry 1, Table 2

Yellow solid. mp 150–152 ºC. IR (KBr) n_max/cm^-1: 3320, 1631, 1597. ¹H NMR (300 MHz, CDCl₃) d: 1.80 (s, 3H), 2.95 (d, 1H, J 12.8 Hz), 3.15 (d, 1H, J 12.8 Hz) 3.45 (br s, NH), 6.55–7.01 (m, 3H), 7.15–7.35 (m, 7H), 7.55–7.65 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 29.7, 42.9, 73.3, 121.2, 121.4, 125.2, 126.1, 126.8, 126.9, 127.8, 128.1, 128.5, 129.5, 137.9, 139.5, 139.9, 147.4, 167.3. MS (EI), m/z [M⁺] = 312. Anal. Calc. for C₂₂H₂₀N₂: C, 84.58; H, 6.45; N, 8.97: Found: C, 84.55; H, 6.51; N, 8.94.

Entry 2, Table 2

Yellow solid. mp 92-94 ºC. IR (KBr) n_max/cm^-1: 3275, 1659, 1614. ¹H NMR (300 MHz, CDCl₃) d: 1.80 (s, 3H), 2.41 (s, 3H), 3.01 (d, J 13.2 Hz, 1H), 3.15 (d, J 13.2 Hz, 1H), 3.51 (br s, 1H, NH), 6.70–7.69 (m, 13H); ¹³C NMR (75 MHz, CDCl₃) d: 20.9, 28.7, 45.9, 51.0, 113.5, 123.5, 125.7, 126.3, 127.4, 128.2, 128.3, 128.5, 128.6, 129.0, 130.8, 131.2, 134.0, 136.9, 164.6. MS (EI), m/z [M⁺] = 326. Anal. Calc. for C₂₃H₂₂N₂: C, 84.63; H, 6.79; N, 8.58: Found: C, 84.53; H, 6.85; N, 8.62.

Entry 3, Table 2

Yellow solid. mp 115-116 ºC. IR (KBr) n_max/cm^-1: 3285, 1635, 1609. ¹H NMR (300 MHz, CDCl₃) d: 1.70 (s, 3H), 2.25 (s, 6H), 2.90 (d, 1H, J 12.8 Hz), 3.10 (d, 1H, J 12.8 Hz), 3.45 (br s, 1H), 6.60 (s, 1H), 7.15 (s, 1H), 7.18-7.30 (m, 6H), 7.50–7.60 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 18.6, 19.3, 29.7, 43.2, 73.0, 122.3, 125.4, 126.8, 126.9, 127.8, 128.2, 129.3, 129.4, 129.6, 134.8, 135.7, 137.6, 139.7, 147.8, 166.8. MS (EI), m/z [M⁺] = 340. Anal. Calc. for C₂₄H₂₄N₂: C, 84.66; H, 7.10; N, 8.22: Found: C, 84.78; H, 7.25; N, 8.35.

Entry 4, Table 2

Yellow solid. mp 121–123 ºC. IR (KBr) n_max/cm^-1: 3290, 1647, 1598, 854. ¹H NMR (300 MHz, CDCl₃) d: 1.76 (s, 3H), 2.96 (d, J 12.8 Hz, 1H), 3.15 (d, J 12.8 Hz, 1 H), 3.35 (br s, NH), 6.78-6.81 (m, 1H), 6.95-6.98 (m, 1H), 7.15-7.27 (m, 6H), 7.42-7.58 (m, 3H), 7.91-7.96 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) d: 29.6, 44.7, 71.2, 120.9, 122.9, 124.1, 128.9, 139.9, 130.5, 132.0, 137.6, 138.2, 146.0, 169.1. MS (EI), m/z [M⁺] = 346. Anal. Calc. for C₂₂H₁₉ClN₂: C, 76.18; H, 5.52; N, 8.08: Found: C, 76.07; H, 5.49; N, 8.12.

Entry 5, Table 2

Yellow crystalline solid. mp 158–160 ºC. IR (KBr) n_max/cm^-1: 3304, 1638, 1603, 761. ¹H NMR (300 MHz, CDCl₃) d: 1.75 (s, 3 H), 2.93 (d, J 12.8 Hz, 1 H), 3.12 (d, J 12.8 Hz, 1 H), 3.49 (br s, NH), 6.88 (s, 1 H), 7.13-7.30 (m, 5 H), 7.36 (s, 1H), 7.50-7.53 (m, 5 H); ¹³C NMR (75 MHz, CDCl₃) d: 29.9, 43.2, 72.9, 121.9, 124.1, 125.3 127.3, 128.4, 128.7, 130.1, 137.8, 139.3, 146.8, 168.8. MS (EI), m/z [M⁺] = 381. Anal. Calc. For C₂₂H₁₈Cl₂N₂ : C, 69.30; H, 4.76; N, 7.35: Found: C, 69.28; H, 4.81; N, 7.32.

Entry 6, Table 2

Yellow solid. mp 114-116 ºC. IR (KBr) n_max/cm^-1: 3327, 1681, 1649, 1601, 1249, 1178, 981, 820. ¹H NMR (300 MHz, CDCl₃) d: 1.78 (s, 3H), 2.96 (d, 1H, J 12.8 Hz), 3.31 (d, 1H, J 12.8 Hz), 3.51 (br s, 1H, NH), 7.12-7.26 (m, 5H), 7.34-7.61 (m, 7H), 7.72-7.78 (m, 2H), 7.81-7.85 (m, 1H), 7.88-7.92 (m, 2H), 7.98-8.01 (m, 1H); MS (FAB), m/z [M⁺+H] = 417. Anal. Calc. for C₂₉H₂₄N₂O: C, 83.63; H, 5.81; N, 6.73; Found: C, 83.49; H, 5.94; N, 6.69.

Entry 7, Table 2

Yellow solid. mp 136-138 ºC. IR (KBr) n_max/cm^-1: 3318, 1638, 1554, 1356. ¹H NMR (300 MHz, CDCl₃) d: 1.79 (s, 3H), 3.06 (d, 1H, J 13.4 Hz), 3.32 (d, 1H, J 13.4 Hz), 4.41 (br s, 1H, NH), 6.92-6.94 (d, 1H, J 8.7 Hz), 7.17-7.55 (m, 10H), 7.92-7.96 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) d: 29.1, 45.8, 65.8, 111.8, 116.9, 124.2, 125.8, 127.6, 128.8, 129.2, 132.2, 132.5, 133.4, 135.6, 137.8, 139.6, 143.1, 166.8. MS (EI), m/z [M⁺] =357. Anal. Calc. for C₂₂H₁₉N₃O₂ : C, 73.93; H, 5.36; N, 11.76; Found: C, 73.87; H, 5.41; N, 11.67.

Entry 1, Table 3

Pale yellow crystalline solid. mp 98-99 ºC. IR (KBr) n_max/cm^-1: 3318, 1630, 1598. ¹H NMR (300 MHz, CDCl₃) d: 1.72 (s, 3H), 2.26 (s, 3H), 2.32 (s, 3H), 2.98 (d, 1H, J 13.4 Hz), 3.05 (d, 1H, J 13.4 Hz), 3.43 (br s, 1H, NH), 6.74-6.76 (m, 1H), 6.98-7.02 (m, 6H), 7.21-7.23 (m, 1H), 7.47-7.50 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 20.7, 21.2, 29.8, 42.9, 73.1, 121.3, 121.4, 125.2, 126.0, 127.1, 128.5, 128.6, 128.9, 129.2, 136.4, 137.0, 138.2, 139.7, 140.3, 145.0, 166.8. MS (EI), m/z [M⁺] = 340. Anal. Calc. for C₂₄H₂₄N₂: C, 84.70; H, 7.05; N, 8.23: Found: C, 84.68; H, 7.13; N, 8.18.

Entry 2, Table 3

Yellowish solid. mp 114-116 ºC. IR (neat) n_max/cm^-1: 3325, 1135, 1640, 1594, 1190. ¹H NMR (200 MHz, CDCl₃) d: 1.71 (s, 3H), 2.85 (d, 1H, J 12.8 Hz), 2.98 (d, 1H, J 12.8 Hz), 3.73 (s, 3H), 3.77 (s, 3H), 6.65-6.78 (m, 4H), 6.95-7.02 (m, 2H), 7.18-7.25 (m, 2H), 7.42-7.55 (m, 4H); MS (EI), m/z [M⁺] = 372. Anal. Calc. for C₂₄H₂₄N₂O₂ : C, 77.37; H, 6.52; N, 7.50: Found: C, 77.18; H, 6.64; N, 7.52.

Entry 3, Table 3

Yellow crystalline solid. mp 219-220 ºC. IR (KBr) n_max/cm^-1: 3339, 1636, 1599. ¹H NMR (200 MHz, CDCl₃) d: 1.65 (s, 3H), 2.77 (d, 1H, J 12.6 Hz), 2.89 (d, 1H, J 12.6 Hz), 4.18 (br s, NH), 6.57-6.64 (m, 4H), 6.81-7.00 (m, 1H), 7.10-7.18 (m, 1H), 7.28-7.55 (m, 4H). ¹³C NMR (75 MHz, CDCl₃) d: 29.2, 42.0, 72.6, 114.4, 114.6, 120.5, 120.9, 124.9, 125.8, 127.0, 128.2, 130.0, 137.9, 139.5, 155.3, 158.6, 166.8. MS (EI), m/z [M⁺] = 344. Anal. Calc. for C₂₂H₂₀N₂O₂ : C, 76.74; H, 5.81; N, 8.15: Found: C, 76.76; H, 5.84; N, 8.13.

Entry 4, Table 3

Red crystalline solid. mp 156-158 ºC. IR (KBr) n_max/cm^-1: 3325, 1642, 1597. ¹H NMR (300 MHz, CDCl₃) d: 1.83 (s, 3H), 2.96 (d, 1H, J 13.4 Hz), 3.27 (d, 1H, J 13.4 Hz), 3.52 (br s, NH), 6.97-6.98 (m, 1H), 7.00-7.02 (m, 6H), 7.21-7.22 (m, 1H), 7.45-7.47 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 30.0, 42.9, 73.4, 121.3, 122.2, 123.5, 123.4, 126.8, 127.6, 127.7, 129.6, 137.2, 138.8, 144.6, 146.9, 148.4, 154.1, 163.8. MS (EI), m/z [M⁺] = 402. Anal. Calc. for C₂₂H₁₈N₄O₄ : C, 65.67; H, 4.47; N, 13.93: Found: C, 65.65; H, 4.40; N, 13.98.

Entry 5a, Table 3

Pale yellow crystalline solid. mp 104-105 ºC. IR (KBr) n_max/cm^-1: 3271, 1651, 1603, 1231. ¹H NMR (300 MHz, CDCl₃) d: 1.75 (s, 3H), 2.87 (d, 1H, J 13.6 Hz), 3.04 (d, 1H, J 13.6 Hz), 3.30 (br s, NH), 6.75-6.79 (m, 1H), 6.82-6.92 (m, 4H), 7.00-7.05 (m, 2H), 7.19-7.25 (m, 1H), 7.48-7.62 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 29.7, 42.9, 73.4, 114.7, 114.8, 115.0, 115.1, 126.2, 127.0, 128.5, 129.2, 135.5, 137.4, 140.3, 143.2, 160.2, 162.2, 165.3, 165.5, 163.5. MS (EI), m/z [M⁺] = 348. Anal. Calc. for C₂₂H₁₈ F₂N₂: C, 75.86; H, 5.17; N, 8.04: Found: C, 75.82; H, 5.20; N, 8.07.

Entry 5b, Table 3

Pale yellow crystalline solid. mp 143-145 ºC. IR (KBr) n_max/cm^-1: 3269, 1636, 1593, 765. ¹H NMR (200 MHz, CDCl₃) d: 1.70 (s, 3H), 2.79 (d, 1H, J 13.3 Hz), 2.97 (d, 1H, J 13.3 Hz), 3.25 (br s, NH), 6.68-6.75 (m, 1H), 6.92-7.02 (m, 1H), 7.12-7.20 (m, 5H), 7.38-7.52 (m, 5H); ¹³C NMR (75 MHz, CDCl₃) d: 29.7, 42.8, 73.4, 121.4, 121.9, 126.6, 127.0, 128.2, 128.3, 128.6, 133.0, 137.5, 137.7, 139.8, 145.8, 165.9. MS (EI), m/z [M⁺] = 381. Anal. Calc. for C₂₂H₁₈Cl₂N₂ : C, 69.29; H, 4.72; N, 7.34: Found: C, 69.30; H, 4.78; N, 7.31.

Entry 5c, Table 3

Yellow solid. mp 145-146 ºC. IR (KBr) n_max/cm^-1: 3325, 1640, 1589, 1198, 574. ¹H NMR (200 MHz, CDCl₃) d: 1.72 (s, 3H), 2.87 (d, 1H, J 13.6 Hz), 3.00 (d, 1H, J 13.6 Hz), 2.65 (br s, NH), 6.97-6.98 (m, 1H), 7.00-7.04 (m, 6H), 7.18-7.24 (m, 1H), 7.45-7.48 (m, 4H). MS (FAB), m/z [M⁺+H] = 471. Anal. Calc. for C₂₂H₁₈Br₂ N₂: C, 56.17; H, 3.82; N, 5.95: Found: C, 56.19; H, 3.78; N, 5.89.

Entry 5d, Table 3

Pale yellow crystalline solid. mp 143-144 ºC. IR (KBr) n_max/cm^-1: 3259, 1636, 1579, 462. ¹H NMR (200 MHz, CDCl₃) d: 1.71 (s, 3H), 2.85 (d, 1H, J 12.8 Hz), 2.99 (d, 1H, J 12.8 Hz), 3.32 (br s, NH), 6.73-6.75 (m, 1H), 6.98-7.03 (m, 2H), 7.21-7.33 (m, 5H), 7.53-7.58 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 30.3, 43.4, 74.1, 93.4, 97.4, 122.1, 122.6, 127.3, 128.2, 129.2, 129.3, 137.8, 138.0, 139.4, 140.4, 147.6, 166.8. MS (FAB), m/z [M⁺+H] = 565. Anal. Calc. for C₂₂H₁₈ I₂N₂: C, 46.97; H, 3.20; N, 4.98: Found: C, 46.92; H, 3.22; N, 5.01.

Entry 6, Table 3

Yellow solid. mp 137-138 ºC. IR (KBr) n_max/cm^-1: 3290, 1640, 1600. ¹H NMR (200 MHz, CDCl₃) d: 1.23-1.85 (m, 16H), 2.30-2.70 (m, 3H), 4.49 (br s, 1H), 6.65-7.35 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 21.6, 21.7, 23.2, 24.5, 25.3, 33.2, 34.4, 39.3, 40.5, 52.4, 63.1, 121.3, 121.5, 126.3, 129.6, 138.1, 142.6, 178.9. MS (EI), m/z [M⁺] = 268. Anal. Calc. for C₁₈H₂₄N₂: C, 80.55; H, 9.01; N, 10.44: Found: C, 80.26; H, 9.54; N, 10.31.

Entry 7, Table 3

Yellow solid. mp 138-140 ºC. IR (KBr) n_max/cm^-1: 3338, 1659, 1600. ¹H NMR (200 MHz, CDCl₃) d: 1.30-1.90 (m, 12H), 2.30-2.61 (m, 3H), 4.50 (br s, 1H), 6.70-7.39 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 23.4, 24.1, 24.3, 28.7, 33.4, 38.5, 39.2, 54.4, 67.3, 118.6, 119.3, 126.9, 132.1, 139.2, 143.4, 178.0. MS (EI), m/z [M⁺] = 240. Anal. Calc. for C₁₆H₂₀N₂: C, 79.96; H, 8.39; N, 11.66: Found: C, 79.64; H, 8.22; N, 11.45.

Entry 8, Table 3

Yellow solid. mp 137-139 ºC. IR (KBr) n_max/cm^-1: 3329, 1637, 16057. ¹H NMR (200 MHz, CDCl₃) d: 0.99 (t, J 6.9 Hz, 3H), 1.25 (t, J 6.9 Hz, 3H), 1.70 (q, J 6.9 Hz, 2H), 2.15 (m, 2H), 2.35 (s, 3H), 2.69 (q, J 6.9 Hz, 2H), 3.27 (br s, 1H, NH), 6.78-7.35 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) d: 8.7, 10.8, 26.9, 35.5, 35.7, 42.1, 70.5, 121.8, 125.4, 126.2, 127.0, 137.9, 140.8, 175.6. MS (FAB), m/z [M⁺+H] = 216. Anal. Calc. for C₁₄H₂₀N₂: C, 77.73; H, 9.32; N, 12.95: Found: C, 77.71; H, 9.36; N, 12.93.

Acknowledgments

Ravi Varala thanks DIICT, Dr. J. S. Yadav and Council of Scientific Industrial Research (CSIR, India) for financial support.

References

1. Herpin, T. F.; Van Kirk, K. G.; Salvino, J. M.; Yu, S. T.; Labaudinière, R. F.; J. Comb. Chem. 2000, 5, 513.

2. Atwal, K. S.; Bergey, J. L.; Hedberg, A.; Moreland, S.; J. Med. Chem. 1987, 30, 635; Merluzzi, V.; Hargrave, K. D.; Labadia, M.; Grozinger, K.; Skoog, M.; Wu, J. C.; Shih, C-K; Eckner, K.; Hattox, S.; Adams, J.; Rosenthal, A. S.; Faanes, R.; Eckner, R. J.; Koup R. A.; Sullivan, J. L.; Science 1990, 250, 1411; Di Braccio, M.; Grossi, G.; Roma, G.; Vargiu, L.; Mura, M.; Marongiu, M. E.; Eur. J. Med. Chem. 2001, 36, 935.

3. Schutz, H.; Benzodiazepines, Springer: Heidelberg, 1982; Landquist, J. K. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R.; Rees, C. W., eds. Pergamon: Oxford, 1984, vol. 1. pp.166–170; Randall, L. O.; Kappel, B. In Benzodiazepines, Garattini, S.; Mussini, E.; Randall, L. O.; eds., Raven Press: New York, 1973, p. 27.

4. Haris, R. C.; Straley, J. M.; U. S. Patent 1,537,757, 1968. (CA 1970, 73, 100054w)

5. El-Sayed, A. M. El.; Abdel-Ghany, H.; El-Saghier, A. M. M.; Synth. Commun. 1999, 29, 3561; Xu, J. X.; Wu, H. T.; Jin, S.; Chin. J. Chem. 1999, 17, 84; Zhang, X. Y.; Xu, J. X.; Jin, S.; Chin. J. Chem. 1999, 17, 404; Kim, K.; Volkman, S. K.; Ellman, J. A.; J. Braz. Chem. Soc. 1998, 9, 375.

6. Herbert, J. A. L.; Suschitzky, H.; J. Chem. Soc., Perkin Trans. 1 1974, 2657; Morales, H. R.; Ulbarela, B. A.; Contreras, R.; Heterocycles 1986, 24, 135; Jung, D. I.; Choi, T. W.; Kim, Y. Y.; Kim, I. S.; Park, Y. M.; Lee, Y. G.; Jung, D. H.; Synth. Commun. 1999, 29, 1941; Balakrishna, M. S.; Kaboudin, B.; Tetrahedron Lett. 2001, 42, 1127; Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Tetrahedron Lett. 2001, 42, 3193; Yadav, J. S.; Reddy, B. V. S.; Kumar, S. P.; Nagaiah, K.; Synthesis 2005, 3, 480 and references cited therein.

7. Varala, R.; Ramu, E.; Sreelatha, N.; Adapa, S. R.; Synlett 2006, 7, 1009.

8. Peter, P. I. D.; Moisan, L.; Angew. Chem., Int. Ed. 2001, 40, 3726.

9. Li, Gui-long.; Zhao, G.; J. Org. Chem. 2005, 70, 4272; Thakuria, H.; Pramanik, A.; Borah, B. M.; Das, G.; Tetrahedron Lett. 2006, 47, 3135; Yanagisawa, A.; Nakamura, Y.; Arai, T.; Tetrahedron: Asymmetry 2004, 15, 1909.

10. Varala, R.; Ramu, E.; Sreelatha, N.; Adapa, S. R.; Tetrahedron Lett. 2006, 47, 877; Varala, R.; Adapa, S. R.; Org. Process Res. Dev. 2005, 9, 853; Varala, R.; Sreelatha, N.; Adapa, S. R.; Synlett 2006, 10, 1549 and references cited therein; Varala, R.; Ramu, E.; Adapa, S. R.; Synthesis 2006, 3825.

Received: July 8, 2006

Web Release Date: February 15, 200

Publication Dates

• Publication in this collection
  13 June 2007
• Date of issue
  Apr 2007

History

• Accepted
  15 Feb 2007
• Received
  08 July 2006