Synlett 2012(5): 731-736  
DOI: 10.1055/s-0031-1290603
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Two-Step Synthesis of 1H-Tetrazolyl-1H-1,4-benzonitriles and 1H-Tetrazolyl-benzo[b][1,4]diazepines

Ahmad Shaabani*, Hamid Mofakham*, Sajjad Mousavifaraz
Department of Chemistry, Shahid Beheshti University, G. C., P. O. Box 19396-4716, Tehran, Iran
Fax: +98(21)29903247; e-Mail: a-shaabani@cc.sbu.ac.ir;
Weitere Informationen

Publikationsverlauf

Received 10 December 2011
Publikationsdatum:
28. Februar 2012 (online)

Abstract

A two-step synthetic protocol for the title heteroannulated diazepines has been developed. The approach includes a pseudo five-component isocyanide-based condensation reaction between diamines, ketones, isocyanides and trimethylsilyl azide and proceeds in good yields.

    References and Notes

  • 1a Sternbach LH. J. Med. Chem.  1979,  22:  1 
  • 1b Lee SC. Park SB. Chem. Commun.  2007,  3714 
  • 2a Evans BE. Rittle KE. Bock MG. DiPardo RM. Freidinger RM. Whitter WL. Lundell GF. Veber DF. Anderson PS. J. Med. Chem.  1988,  31:  2235 
  • 2b Herpin TF. Kirk KGV. Salvino JM. Yu ST. Labaudiniere RF. J. Comb. Chem.  2000,  5:  513 
  • 3a Ohtake Y, and Fukaya Y. inventors; E. Patent,  1 820 799 A1. 
  • 3b Finch H, Shah P, and Carr RAE. inventors; U.S. Patent,  5 585 376. 
  • 4 Tranquillini ME. Cassara PG. Corsi M. Curotto G. Donati D. Finizia G. Pentassuglia G. Polinelli S. Tarzia G. Ursini A. Amsterdam FTMV. Arch. Pharm. (Weinheim, Ger.)  1997,  330:  353 
  • 5a Kruse H. Drug Dev. Res.  1982,  2:  145 
  • 5b Ursini A. Capelli AM. Carr RAE. Cassara P. Corsi M. Curcuruto O. Curotto G. Cin MD. Davalli S. Donati D. Feriani A. Finch H. Finizia G. Gaviraghi G. Marien M. Pentassuglia G. Polinelli S. Ratti E. Reggiani A. Tarzia G. Tedesco G. Tranquillini ME. Trist DG. Amsterdam FTMV. J. Med. Chem.  2000,  43:  3596 
  • 5c Herpin TF. Kirk KGV. Salvino JM. Yu ST. Labaudiniere RF. J. Comb. Chem.  2000,  2:  513 
  • 5d Cepanec I. Litvic M. Pogorelic I. Org. Process Res. Dev.  2006,  10:  1192 
  • 5e Zhao HY. Liu G. J. Comb. Chem.  2007,  9:  1164 
  • 5f Silva RAD. Santra S. Andreana PR. Org. Lett.  2008,  10:  4541 
  • 5g Butini S. Gabellieri E. Huleatt PB. Campiani G. Franceschini S. Brindisi M. Ros S. Coccone SS. Fiorini I. Novellino E. Giorgi G. Gemma S. J. Org. Chem.  2008,  73:  8458 
  • 5h Reid W. Stahlofen P. Chem. Ber.  1957,  90:  825 
  • 6a Slusarchyk WA. Vite G. Yan N. Manne V. Hunt JT. J. Med. Chem.  1999,  42:  5241 
  • 6b Borisov RS. Polyakov AI. Medvedeva LA. Khrustalev VN. Guranova NI. Voskressensky LG. Org. Lett.  2010,  12:  3894 
  • 7a Schmidt B. Schieffer B. J. Med. Chem.  2003,  46:  2261 
  • 7b Bekhit AA. El-Sayed OA. Aboulmagd E. Park JY. Eur. J. Med. Chem.  2004,  39:  249 
  • 7c Rajasekaran A. Thampi PP. Eur. J. Med. Chem.  2004,  39:  273 
  • 7d Kozikowski AP. Zhang J. Nan F. Petukhov PA. Grajkowska E. Wroblewski JT. Yamamoto T. Bzdega T. Wroblewska B. Neale J. J. Med. Chem.  2004,  47:  1729 
  • 7e Upadhayaya RS. Jain S. Sinha N. Kishore N. Chandra R. Arora SK. Eur. J. Med. Chem.  2004,  39:  579 
  • 7f Faucher A.-M. White PW. Brochu C. Grand-Maitre C. Rancourt J. Fazal G. J. Med. Chem.  2004,  47:  18 
  • 7g Park H. Merz KM. J. Med. Chem.  2005,  48:  1630 
  • 7h Bekhit AA. El-Sayed OA. Al-Allaf TAK. Aboul-Enein HY. Kunhi M. Pulicat SM. Al-Hussain K. Al-Khodairy F. Arif J. Eur. J. Med. Chem.  2004,  39:  499 
  • 8a Biot C. Baver H. Schirmer RH. Davioud-Charvet E. J. Med. Chem.  2004,  47:  5972 
  • 8b Herr RJ. Bioorg. Med. Chem.  2002,  10:  3379 
  • 8c KoharaY . Kubo K. Imamiya E. Wada T. Inada Y. Naka T. J. Med. Chem.  1996,  39:  5228 
  • 8d Schelenz T. Schafer W. J. Prakt. Chem.  2000,  342:  91 
  • 8e Joo Y.-H. Shreeve JM. Angew. Chem. Int. Ed.  2010,  49:  7320 
  • 8f Gutmann B. Roduit J.-P. Roberge D. Kappe CO. Angew. Chem. Int. Ed.  2010,  49:  7101 
  • 8g Kaim LE. Grimaud L. Patil P. Org. Lett.  2011,  13:  1261 
  • 9 Butler RN. Tetrazoles, In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Pergamon; Oxford: 1996.  p.621-678  
  • 10a May BCH. Abell AD. Tetrahedron Lett.  2001,  42:  5641 
  • 10b Schroeder GM. Marshall S. Wan H. Purandare AV. Tetrahedron Lett.  2010,  51:  1404 
  • 10c Al-Hourani BJ. Sharma SK. Mane JY. Tuszynski J. Baracos V. Kniess T. Suresh M. Pietzsch J. Wuest F. Bioorg. Med. Chem. Lett.  2011,  21:  1823 
  • 11 Nonoshita K, Ogino Y, Ishikawa M, Sakai F, Nakashima H, Nagae Y, Tsukahara D, Arakawa K, Nishimura T, and Eiki J. inventors; PCT Int. Appl. WO  2004-JP19843.  ; Chem. Abstr. 2005, 143, 153371
  • 12 Seki M, Tarao Y, Yamada K, Nakao A, Usui Y, and Komatsu Y. inventors; PCT Int. Appl. WO  2005-JP2974.  ; Chem. Abstr. 2005, 143, 266938
  • 13 Luo G, Chen L, Degnan AP, Dubowchik GM, Macor JE, Tora GO, and Chaturvedula PV. inventors; PCT Int. Appl. WO  2004-US40721.  ; Chem. Abstr. 2005, 143, 78091
  • 14 Miao Z, Sun Y, Nakajima S, Tang D, Wu F, Xu G, Or YS, and Wang Z. inventors; U. S. Pat. Appl. Publ. US  2005153877.  ; Chem. Abstr. 2005, 143, 153709
  • 15a Duncia JV. Carini DJ. Chiu AT. Johnson AL. Price WA. Wong PC. Wexler RR. Timmermans PBMWM. Med. Res. Rev.  1992,  12:  149 
  • 15b Smith RD. Duncia JV. Lee RJ. Christ DD. Chiu AT. Carini DJ. Herblin WF. Timmermans PBMWM. Wexler RR. Wong PC. Methods Neurosci.  1993,  13:  258 
  • 16a Huang R.-Q. Bell-Horner CL. Dibas MI. Covey DF. Drewe JA. Dillon GH. J. Pharmacol. Exp. Ther.  2001,  298:  986 
  • 16b Jung ME. Lal H. Gatch MB. Neurosci. Biobehav. Rev.  2002,  26:  429 
  • 17a Daya S. Kaye PT. Mphahlele MJ. Med. Sci. Res.  1996,  24:  137 
  • 17b Ek F. Manner S. Wistrand L.-G. Frejd T. J. Org. Chem.  2004,  69:  1346 
  • 18a Forster MO. J. Chem. Soc.  1909,  95:  184 
  • 18b Schroeter G. Ber. Dtsch. Chem. Ges.  1909,  42:  2336 
  • 18c von Braun J. Rudolph W. Ber. Dtsch. Chem. Ges. B  1941,  74:  264 
  • 18d Harvill EK. Herbst RM. Schreiner EC. Roberts CW. J. Org. Chem.  1950,  15:  662 
  • 19a Wu S. Fluxe A. Sheffer J. Janusz JM. Blass BE. White R. Jackson C. Hedges R. Murawsky M. Fang B. Fadayel GM. Hare M. Djandjighian L. Bioorg. Med. Chem. Lett.  2006,  16:  6213 
  • 19b Boyko V. Rodik R. Danylyuk O. Tsymbal L. Lampeka Y. Suwinska K. Lipkowski J. Kalchenko V. Tetrahedron  2005,  61:  12282 
  • 19c Yu KL. Johnson RL. J. Org. Chem.  1987,  52:  2051 
  • 19d Kennedy LJ. Tetrahedron Lett.  2010,  51:  2010 
  • 20a Shaabani A. Maleki A. Moghimi-Rad J. J. Org. Chem.  2007,  72:  6309 
  • 20b Shaabani A. Maleki A. Mofakham H. Moghimi-Rad J. J. Org. Chem.  2008,  73:  3925 
  • 20c Shaabani A. Maleki A. Mofakham H. Khavasi HR. J. Comb. Chem.  2008,  10:  323 
  • 20d Shaabani A. Maleki A. Mofakham H. J. Comb. Chem.  2008,  10:  595 
  • 20e Shaabani A. Maleki A. Hajishaabanha F. Mofakham H. Seyyedhamzeh M. Mahyari M. Weng NgS. J. Comb. Chem.  2010,  12:  186 
  • 20f Shaabani A. Rezayan AH. Sarvary A. Keshipour S. Ng SW. Org. Lett.  2009,  11:  3342 
  • 20g Shaabani A. Soleimani E. Rezayan AH. Sarvary A. Khavasi HR. Org. Lett.  2008,  10:  2581 
  • 20h Shaabani A. Mofakham H. Maleki A. Hajishaabanha F. J. Comb. Chem.  2010,  12:  630 
  • 21a Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005. 
  • 21b Dömling A. Chem. Rev.  2006,  106:  17 
  • 22a Horiguchi E. Shirai K. Jaung J. Furusyo M. Takagi K. Matsuoka M. Dyes Pigm.  2001,  50:  99 
  • 22b Shirai K. Matsuoka M. Fukunishi K. Dyes Pigm.  2000,  47:  107 
  • 22c Handa M. Farida A. Thompson L. Hayashibara C. Sugimori T. Hiromitsu I. Kasuga K. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A  2000,  342:  75 
  • 23a Begland RW. Hartter DR. Jones FN. Sam DJ. Shepperd WA. Webster OW. Weigert FJ. J. Org. Chem.  1974,  39:  2341 
  • 23b Ohtsuka Y. J. Org. Chem.  1976,  41:  629 
  • 23c Ohtsuka Y. Tohma E. J. Org. Chem.  1979,  44:  4871 
  • 23d Mague JT. Eduok EE. J. Chem. Crystallogr.  2000,  30:  311 
  • 24a Jin T. Kamijo S. Yamamoto Y. Tetrahedron Lett.  2004,  45:  9435 
  • 24b Kennedy LJ. Tetrahedron Lett.  2010,  51:  2010 
25

Melting points were measured with an Electrothermal 9200 apparatus. Mass spectra were recorded with a Finnigan-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. IR spectra were recorded with a Shimadzu IR-470 spectrometer. ¹H NMR spectra were recorded with a Bruker DRX-300 Avance spectrometer at 300.13 MHz; chemical shifts (δ) are reported in units of parts per million(ppm). ¹H NMR spectra are reported in the order: multiplicity, approximate coupling constant (J value) in hertz (Hz), and integration. ¹³C NMR spectra were recorded at 75.47 MHz; chemical shifts (δ) are reported in ppm. Elemental analyses were performed with an Elementar Analysensysteme GmbH VarioEL. All the products are new compounds, which were characterized by IR, ¹H and ¹³C NMR spectra and Mass spectral data.
Synthesis of 1 H -tetrazolyl-1 H -1,4-diazepine-2,3-dicarbonitriles 6a-g and 1 H -tetrazolyl-benzo[ b ]-[1,4]diazepines 7a-f; General Procedure: A solution of the diamine (1.00 mmol) and ketone (2.20 mmol) in the presence of p-TsOH˙H2O (0.095 g, 5 mol%) was stirred for 4 h in MeOH (5 mL) at ambient temperature. After completion of the reaction, as indicated by TLC (EtOAc-n-hexane, 3:1), the isocyanide (1.00 mmol) and H2O (0.50 mL) were added to the reaction mixture. The resulting mixture was stirred for 12 h at ambient temperature. After completion of the reaction, as indicated by TLC (EtOAc-n-hexane, 4:1), the product was filtered off, washed further with H2O, and then crystallized from acetone to give the 1,4-diazepine derivative.
To a solution of the 1,4-diazepine (0.50 mmol) and pyridine (3.00 mmol) in CH2Cl2 (5.00 mL) was added PCl5 (0.75 mmol) and the resulting mixture was heated to reflux. After 6 h the reaction mixture was cooled to ambient temperature and TMSN3 (2.00 mmol) was added and stirred for 24 h at ambient temperature. After completion of the reaction, as indicated by TLC (EtOAc-n-hexane, 4:1), the product was filtered off, washed further with H2O and MeOH, and then crystallized from acetone to give 6a-g and 7a-f.
5-(1-Cyclohexyl-1 H -tetrazol-5-yl)-5,7,7-trimethyl-4,5,6,7-tetrahydro-1 H -1,4-diazepine-2,3-dicarbonitrile (6a): Colorless crystals; mp 229-231 ˚C. IR (KBr): 3350, 3135, 3078, 2940, 2865, 2213, 1656, 1625, 1478, 1390 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 20 H, 5 × CH2 of c-Hex, 3 × CH3 and 1 H CH), 2.79 (ABq, J = 14.2 Hz, 1 H, CH2), 4.75 (m, 1 H, CH of c-Hex), 5.75 (s, 1 H, NH), 6.78 (s, 1 H, NH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 25.0, 25.3, 30.5, 31.6, 31.8, 33.9, 34.2, 46.5, 54.8, 56.8, 58.1, 106.0, 109.7, 116.3, 116.8, 158.8. MS: m/z = 340 (20) [M]+, 258 (15), 189 (55), 173 (20), 153 (20), 133 (100), 111 (15), 83 (20), 56 (65). Anal. Calcd for C17H24N8: C, 59.98; H, 7.11; N, 32.92. Found: C, 59.92; H, 7.00; N, 32.82.
9a-(1-Cyclohexyl-1 H -tetrazol-5-yl)-1,4,5a,6,7,8,9,9a-octahydrospiro[benzo[ e ][1,4]diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6b): Colorless crystals; mp >300 ˚C. IR (KBr): 3345, 3135, 2983, 2935, 2857, 2225, 2206, 1622, 1495, 1454, 1404, 1297 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 28 H, 14 × CH2 of c-Hex), 2.64 (m, 1 H, CH), 4.69 (m, 1 H, CH of c-Hex), 4.80 (s, 1 H, NH), 6.85 (s, 1 H, NH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 19.0, 20.9, 21.6, 25.0, 25.4, 30.5, 34.2, 34.8, 37.4, 46.2, 49.0, 56.5, 57.9, 59.8, 61.2, 106.1, 110.0, 116.1, 116.5, 161.1. Anal. Calcd for C23H32N8: C, 65.69; H, 7.67; N, 26.64. Found: C, 65.60; H, 7.60; N, 26.55.
4′,7-di- tert -Butyl-9a-(1-cyclohexyl-1 H -tetrazol-5-yl)-1,4,5a,6,7,8,9,9a-octahydrospiro[benzo[ e ][1,4]-diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6c): Colorless crystals; mp >300 ˚C. IR (KBr): 3358, 3128, 3072, 2941, 2867, 2217, 1657, 1620, 1473, 1398, 1294 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 0.76 (s, 9 H, 4 × CH3), 0.85 (s, 9 H, 4 × CH3), 1.10-2.70 (m, 27 H, 12 × CH2 of c-Hex and 3 × CH), 4.56 (s, 1 H, NH), 4.67 (m, 1 H, CH of c-Hex), 6.71 (s, 1 H, NH). Anal. Calcd for C31H48N8: C, 69.89; H, 9.08; N, 21.03. Found: C, 69.79; H, 9.01; N, 21.00.
9 a -(1-Cyclohexyl-1 H -tetrazol-5-yl)-4′,7-diphenyl-1,4,5 a ,6,7,8,9,9 a -octahydrospiro[benzo[ e ][1,4]- diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6d): Brown powder; mp >300 ˚C. IR (KBr): 3419, 3351, 3090, 3021, 2938, 2862, 1619, 1495, 1453, 1398 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.20 (m, 24 H, 12 × CH2 of c-Hex), 2.43 (m, 1 H, CH), 2.64 (m, 1 H, CH), 3.10 (m, 1 H, CH), 4.79 (m, 1 H, CH of c-Hex), 5.02 (s, 1 H, NH), 7.03 (s, 1 H, NH), 7.00-7.15 (m, 3 H, ArH), 7.15-7.30 (m, 3 H, ArH), 7.32 (m, 4H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 25.1, 25.4, 28.1, 28.5, 29.2, 30.4, 33.4, 34.2, 34.9, 42.7, 43.0, 46.4, 58.1, 59.2, 106.2, 110.3, 116.1, 116.5, 126.3, 126.6, 127.0, 127.2, 128.7, 128.9, 146.8, 147.3, 161.1. MS: m/z = 421 (10) [M+ - 151], 309 (30), 227 (35), 184 (15), 145 (35), 117 (45), 91 (100), 55 (23). Anal. Calcd for C35H40N8: C, 73.40; H, 7.04; N, 19.56. Found: C, 73.33; H, 7.00; N, 19.46.
4′,7-di- tert -Butyl-9a-(1- tert -butyl-1 H -tetrazol-5-yl)-1,4,5a,6,7,8,9,9a-octahydrospiro[benzo[ e ][1,4]- diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6e): Colorless crystals; mp 170-171 ˚C. IR (KBr): 3340, 3089, 2935, 2856, 2215, 1570, 1545, 1450 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 0.80-2.40 (m, 43 H, 7 × CH2 of c-Hex, 9 × CH3 and 2 × CH), 3.03 (m, 1 H, CH), 4.70 (s, 1 H, NH), 6.67 (s, 1 H, NH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 21.8, 22.1, 22.8, 26.1, 27.5, 27.8, 31.5, 32.5, 32.8, 33.0, 33.7, 46.9, 57.3, 60.6, 65.1, 104.1, 105.8, 110.6, 115.3, 163.4. Anal. Calcd for C29H46N8: C, 68.74; H, 9.15; N, 22.11. Found: C, 68.62; H, 9.05; N, 22.07.



9a-(1- tert -Butyl-1 H -tetrazol-5-yl)-4′,7-diphenyl-1,4,5a,6,7,8,9,9a-octahydrospiro[benzo[ e ][1,4]- diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6f). Brown powder; mp >300 ˚C. IR (KBr): 3406, 3236, 3160, 3040, 3021, 2926, 2850, 2219, 2194, 1634, 1544, 1443, 1366, 1316 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.20 (m, 23 H, 7 × CH2 of c-Hex and 3 × CH3), 2.40 (m, 1 H, CH), 2.64 (m, 1 H, CH), 3.30 (m, 1 H, CH), 4.92 (s, 1 H, NH), 6.92 (s, 1 H, NH), 7.16 (m, 3 H, ArH), 7.18 (m, 3 H, ArH), 7.32 (m, 4 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 27.9, 28.6, 29.3, 30.8, 31.6, 33.4, 37.7, 42.9, 43.1, 48.8, 60.7, 61.2, 65.2, 105.8, 111.6, 116.6, 117.0, 126.3, 126.6, 127.1, 127.2, 128.6, 128.8, 146.9, 147.4, 163.5. Anal. Calcd for C33H38N8: C, 72.50; H, 7.01; N, 20.50. Found: C, 72.42; H, 6.91; N, 20.41.
9a-(1-(2,4,4-Trimethylpentan-2-yl)-1 H -tetrazol-5-yl)-1,4,5a,6,7,8,9,9a-octahydrospiro[benzo[ e ][1,4]- diazepine-5,1′-cyclohexane]-2,3-dicarbonitrile (6g): Colorless crystals; mp 167-169 ˚C. IR (KBr): 3406, 3282, 3128, 3021, 2946, 2850, 2215, 2200, 1618, 1529, 1454, 1304 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 35 H, 9 × CH2 of c-Hex, 1 × CH2 and 5 × CH3), 2.94 (m, 1 H, CH), 4.69 (s, 1 H, NH), 6.70 (s, 1 H, NH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 20.6, 20.7, 21.1, 21.6, 24.7, 25.4, 25.5, 25.6, 31.1, 31.2, 31.5, 48.8, 61.0, 61.8, 65.1, 105.7, 107.1, 111.2, 116.5, 163.4. Anal. Calcd for C25H38N8: C, 66.63; H, 8.50; N, 24.87. Found: C, 66.58; H, 8.41; N, 24.77.
2-(1-Cyclohexyl-1 H -tetrazol-5-yl)-2,4,4-trimethyl-2,3,4,5-tetrahydro-1 H -benzo[ b ][1,4]diazepine (7a): Colorless crystals; mp 241-242 ˚C. IR (KBr): 3383, 2924, 2861, 1600, 1508, 1478, 1450, 1302, 1259 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.00 (m, 20 H, 5 × CH2 of c-Hex, 3 × CH3 and 1 × CH), 2.80 (ABq, J = 13.8 Hz, 1 H, CH2), 3.99 (br s, 1 H, NH), 4.96 (t, J = 10.9 Hz, 1 H, CH of c-Hex), 5.88 (br s, 1 H, NH), 6.40-6.50 (m, 2 H, ArH), 6.57 (dd, J = 6.8, 7.4 Hz, 1 H, ArH), 6.73 (ABq, J = 7.6 Hz, 1 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 25.0, 25.4, 31.6, 32.0, 32.5, 32.9, 34.3, 51.5, 53.2, 55.8, 57.9, 117.3, 119.2, 120.7, 120.9, 135.2, 136.9, 160.1. MS: m/z = 440 (75) [M]+, 189 (80), 173 (100), 133 (80), 90 (10), 55 (15). Anal. Calcd for C19H28N6: C, 67.03; H, 8.29; N, 24.68. Found: C, 69.90; H, 8.22; N, 24.60.
4-(1-Cyclohexyl-1 H -tetrazol-5-yl)-2,2,4-trimethyl-7-nitro-2,3,4,5-tetrahydro-1 H -benzo[ b ][1,4]diazepine (7b): Red powder; mp 196-198 ˚C. IR (KBr): 3400, 3374, 2928, 2859, 1644, 1594, 1530, 1461, 1404, 1309 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 20 H, 5 × CH2 of c-Hex, 3 × CH3 and 1 × CH), 3.09 (ABq, J = 13.2 Hz, 1 H, CH2), 4.67 (m, 1 H, CH of c-Hex), 5.75 (br s, 1 H, NH), 6.50 (br s, 2 H, ArH and ABq, J = 9.3 Hz, ArH), 6.38 (ABq, J = 7.7 Hz, 1 H, ArH), 7.76 (br s, 1 H, NH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 24.7, 24.9, 25.2, 31.0, 32.5, 33.0, 33.6, 34.4, 49.2, 53.8, 55.8, 57.7, 112.9, 116.8, 117.9, 134.7, 138.9, 144.2, 159.6. MS: m/z = 385 (50) [M]+, 234 (65), 218 (100), 177 (50), 132 (45), 83 (10), 55 (35). Anal. Calcd for C19H27N7O2: C, 59.20; H, 7.06; N, 25.44. Found: C, 59.07; H, 7.01; N, 25.34.
(4-(1-Cyclohexyl-1 H -tetrazol-5-yl)-2,2,4-trimethyl-2,3,4,5-tetrahydro-1 H -benzo[ b ][1,4]diazepin-7-yl)(phenyl)methanone (7c): Yellow powder; mp 293-295 ˚C. IR (KBr): 3349, 3084, 3040, 2970, 2935, 2850, 1631, 1570, 1492, 1402, 1342, 1301 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.28 (br s, 3 H, CH3), 1.32 (br s, 3 H, CH3), 1.44 (br s, 3 H, CH3), 1.00-2.00 (m, 11 H, 5 × CH2 of c-Hex and 1 × CH), 3.08 (ABq, J = 13.5 Hz, 1 H, CH2), 4.69 (m, 1 H, CH of c-Hex), 5.16 (br s, 1 H, NH), 6.30 (br s, 1 H, NH), 6.47 (ABq, J = 8.1 Hz, 1 H, ArH), 6.83 (ABq, J = 7.5 Hz, 1 H, ArH), 7.41 (s, 1 H, ArH), 7.45-7.60 (m, 5 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 24.9, 25.0, 25.1, 31.2, 32.4, 33.1, 33.4, 34.5, 49.9, 53.5, 55.8, 57.6, 118.1, 119.2, 123.9, 127.7, 128.6, 129.2, 131.6, 135.1, 139.3, 141.8, 160.0, 194.2. Anal. Calcd for C26H32N6O: C, 70.24; H, 7.26; N, 18.90. Found: C, 70.15; H, 7.20; N, 18.81.
4a′-(1-Cyclohexyl-1 H -tetrazol-5-yl)-7′-nitro-1′,2′,3′,4′,4a′,5′,10′,11a′-octahydrospiro[cyclohexane-1,11′-dibenzo[ b , e ][1,4]diazepine] (7d): Red powder; mp >300 ˚C. IR (KBr): 3394, 3368, 3065, 2932, 2857, 1594, 1524, 1493, 1467, 1327, 1272 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 28 H, 14 × CH2 of c-Hex), 2.86 (m, 1 H, CH), 4.55 (m, 1 H, CH of c-Hex), 5.08 (br s, 1 H, NH), 6.39 (br s, 1 H, NH), 6.65 (ABq, J = 8.7 Hz, 1H, ArH), 7.37 (ABq, J = 6.6 Hz, 1 H, ArH), 7.72 (br s, 1 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 21.2, 21.3, 21.5, 24.8, 24.9, 25.2, 25.4, 25.8, 31.1, 34.7, 49.0, 57.8, 58.4, 58.7, 59.4, 111.0, 115.6, 118.4, 137.6, 140.2, 141.8, 162.3. Anal. Calcd for C25H35N7O2: C, 64.49; H, 7.58; N, 21.06. Found: C, 64.39; H, 7.48; N, 21.01.
{4a′-(1-Cyclohexyl-1 H -tetrazol-5-yl)-1′,2′,3′,4′,4a′,5′,10′,11a′-octahydrospiro[cyclohexane-1,11′-dibenzo[ b , e ][1,4]-diazepine]-7′-yl}(phenyl)methanone (7e): Yellow powder; mp >300 ˚C. IR (KBr): 3381, 3354, 2926, 2856, 1625, 1575, 1500, 1445, 1398, 1336 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 28 H, 14 × CH2 of c-Hex), 2.86 (m, 1 H, CH), 4.59 (m, 2 H, CH of c-Hex and NH), 6.13 (br s, 1 H, NH), 6.60 (ABq, J = 7.7 Hz, 1 H, ArH), 6.83 (ABq, J = 8.1 Hz, 1 H, ArH), 7.38 (s, 1 H, ArH), 7.50-7.60 (m, 5 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 21.4, 21.5, 25.0, 25.3, 25.5, 25.9, 32.0, 32.9, 34.8, 37.8, 49.6, 57.6, 58.4, 58.9, 117.7, 119.7, 122.8, 128.7, 129.3, 131.7, 137.7, 139.2, 139.4, 162.7, 194.3. Anal. Calcd for C32H40N6O: C, 73.25; H, 7.68; N, 16.02. Found: C, 73.14; H, 7.58; N, 15.93.
2-(1-Cyclohexyl-1 H -tetrazol-5-yl)-2,4,4,7-tetramethyl-2,3,4,5-tetrahydro-1 H -benzo[ b ][1,4]diazepine (7f): White powder; mp 202-204 ˚C. IR (KBr): 3381, 3306, 2928, 2862, 1600, 1525, 1478, 1451, 1398, 1309 cm. ¹H NMR (300.13 MHz, DMSO-d 6): δ = 1.00-2.10 (m, 23 H, 5 × CH2 of c-Hex, 4 × CH3 and 1 × CH), 2.78 (ABq, J = 14.1 Hz, 1 H, CH2), 4.96 (m, 1 H, CH of c-Hex), 5.69 (br s, 1 H, NH), 6.37 (br s, 1 H, ArH), 6.38 (ABq, J = 7.7 Hz, 1 H, ArH), 6.56 (br s, 1 H, NH), 6.62 (ABq, J = 7.7 Hz, 1 H, ArH). ¹³C NMR (75.47 MHz, DMSO-d 6): δ = 20.6, 20.8, 25.1, 25.4, 31.5, 31.6, 31.8, 32.0, 32.3, 32.9, 34.3, 51.6, 53.1, 55.8, 57.9, 117.7, 121.2, 121.4, 127.8, 134.4, 135.3, 160.1. MS: m/z = 354 (80) [M]+, 203 (80), 187 (100), 147 (80), 55 (23). Anal. Calcd for C20H30N6: C, 67.76; H, 8.53; N, 23.71. Found: C, 67.69; H, 8.45; N, 23.61.