All melting points were determined using Electrothermal Capillary melting point apparatus and are uncorrected. Infrared (IR) spectra were recorded as thin film (for oils) in NaCl discs or as KBr pellets (for solids) with JASCO FT/IR-6100 spectrometer and values are represented in cm−1. 1H-NMR (500 MHz) and 13C-NMR (125 MHz) spectra were carried out on Jeol ECA 500 MHz spectrometer using TMS as internal standard and chemical shift values were recorded in ppm on δ scale. The 1H-NMR data were represented as follows: chemical shifts, multiplicity (s. singlet, d. doublet, t. triplet, m. multiplet, br. broad), number of protons, and type of protons. The 13C-NMR data were represented as chemical shifts and type of carbons. Mass spectral data were obtained with electron impact (EI) ionization technique at 70 eV from a Finnigan Mat SSQ-7000 Spectrometer. Elemental analyses were carried out in Microanalytical Units at National Research Centre and Cairo University. Silica gel TLC (thin layer chromatography) cards from Merck (silica gel precoated aluminum cards with fluorescent indicator at 254 nm) were used for thin layer chromatography. Visualization was performed by illumination with UV light source (254 nm). Column chromatography was carried out on silica gel 60 (0.063–0.200 mm) obtained from Merck.
3.1.6. General Procedure for the Synthesis of 6-Aryl-9-substituted-6,9-diazaspiro-[4.5]decane-8,10-diones (6a–i) and 1-Aryl-4-substituted-1,4-diazaspiro[5.5]undecane-3,5-diones (6m–u)
To a mixture of the appropriate diketopiperazine derivative 5a–f (0.01 mol) in acetone (100 mL), was added the proper alkylating agent (0.07 mol), namely methyl bromoacetate, benzyl chloride or phenethylbromide in the presence of K2CO3 (1.38 g, 0.01 mol) and a catalytic amount of tetrabutylammoniun bromide (0.32 g, 0.001 mol) as a phase transfer catalyst. The reaction mixture was heated under reflux for 7 h, cooled to room temperature, filtered and the filtrate was evaporated under vacuum. The residue was purified using column chromatography (chloroform:ethyl acetate, 9:1) to furnish the target compounds 6a–i and 6m–u.
Methyl 2-(8,10-dioxo-6-phenyl-6,9-diazaspiro[4.5]decane-9-yl)acetate (6a). Yield: 65%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1752 (carbonyl ester), 1720, 1685 (imide carbonyls), 609, 557; 1H-NMR (CDCl3) δ ppm 1.80 (br.s, 4H, 2 × CH2, cyclopentyl), 2.00–2.37 (m, 4H, 2 × CH2, cyclopentyl), 3.76 (s, 3H, COOCH3), 4.32 (s, 2H, O=C-CH2-N), 4.58 (s, 2H, N-CH2-COO), 7.02–7.32 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 25.08, 36.25 (4 × CH2, cyclopentyl), 40.12 (CH2-COOCH3), 52.59, 56.59 (O=C-CH2-N, COOCH3), 69.65 (Cq), 124.82, 128.48, 129.32 (CHar.), 148.71 (Car.), 169.91, 170.11, 176.18 (3 × C=O); MS (EI) m/z (%): 316.2 ([M]+, 17), 91 (100), 172.2 (90); Anal. Calcd for C17H20N2O4 (316.35): C, 64.54%; H, 6.37%; N, 8.86%. Found: C, 64.51%; H, 6.15%; N, 8.66%.
9-Benzyl-6-phenyl-6,9-diazaspiro[4.5]decane-8,10-dione (6b). Yield: 60%; Yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1678 (imide carbonyls), 604, 555; 1H-NMR (CDCl3) δ ppm 1.79–2.30 (m, 8H, 4 × CH2, cyclopentyl), 4.27 (s, 2H, O=C-CH2-N), 5.10 (s, 2H, CH2-C6H5), 6.85–6.86 (m, 2H, Har.), 7.05–7.17 (m, 3H, Har.), 7.30–7.34 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 25.50, 36.70 (4 × CH2, cyclopentyl), 42.6 (CH2-C6H5), 56.91 (O=C-CH2-N), 67.27 (Cq), 124.71, 126.96, 127.49, 128.21, 128.40, 129.42 (CHar.), 136.81, 148.76 (2 × Car.), 170.33, 176.00 (2 × C=O); MS (EI) m/z (%): 334.3 ([M]+, 15), 91 (100), 77.1 (40); Anal. Calcd. for C21H22N2O2 (334.41): C, 75.42%; H, 6.63%; N, 8.38%. Found: C, 75.32%; H, 6.61%; N, 8.17%.
9-Phenethyl-6-phenyl-6,9-diazaspiro[4.5]decane-8,10-dione (6c). Yield: 71.5%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1677 (carbonyl imides), 575, 500; 1H-NMR (CDCl3) δ ppm 1.77 (br.s, 4H, 2 × CH2, cyclopentyl), 1.96 (s, 2H, CH2, cyclopentyl), 2.25 (s, 2H, CH2, cyclopentyl), 2.85 (t, 2H, J = 7.5 Hz, CH2-C6H5) , 4.09 (t, 2H, J = 7.5 Hz, CH2-CH2-C6H5), 4.24 (s, 2H, O=C-CH2-N), 6.95–7.12 (m, 3H, Har.), 7.26–7.32 (m, 7H, Har.); 13C-NMR (CDCl3) δ ppm 25.05, 33.92 (4 × CH2, cyclopentyl), 36.59, 40.53 (CH2-C6H5, CH2-CH2-C6H5), 56.92 (O=C-CH2-N), 63.71 (Cq), 124.53, 124.62, 126.52, 128.45, 128.61, 129.05 (CHar.), 138.27, 148.82 (2 × Car.), 170.03, 175.97 (2 × C=O); MS (EI) m/z (%): 348.23 ([M]+, 22), 91 (100), 172.1 (65), 229 (65), Anal. Calcd. for C22H24N2O2 (348.44): C, 75.38%; H, 6.94%; N, 8.04%. Found: C, 75.41%; H, 6.91%; N, 8.23%.
Methyl 2-(8,10-dioxo-6-(4-methylphenyl)-6,9-diazaspiro[4.5]decane-9-yl)acetate (6d). Yield: 79%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1752 (carbonyl ester), 1722, 1686 (imide carbonyls), 607, 564; 1H-NMR (CDCl3) δ ppm 1.73–1.77 (m, 8H, 4 × CH2, cyclopentyl), 2.29 (s, 3H, CH3), 3.75 (s, 3H, COOCH3), 4.23 (s, 2H, O=C-CH2-N), 4.65 (s, 2H, CH2-COOCH3), 6.91 (d, 2H, J = 8.6 Hz, Har), 7.05 (d, 2H, J = 8.6 Hz, Har.); 13C-NMR (CDCl3) δ ppm 21.31 (CH3), 25.62, 36.85 (4 × CH2, cyclopentyl), 40.16 (CH2-COOCH3), 52.53, 56.89 (O=C-CH2-N, COOCH3), 69.81 (Cq), 124.90, 130.57, (CHar.), 134.56, 146.22 (2 × Car.), 170.17, 176.01 (2 × C=O); MS (EI) m/z (%): 330.24 ([M]+, 24), 105.1(100), 186.2 (53); Anal. Calcd. for C18H22N2O4 (330.38): C, 65.44%; H, 6.71%; N, 8.48%. Found: C, 65.21%; H, 6.63%; N, 8.38%.
9-Benzyl-6-(4-methylphenyl))-6,9-diazaspiro[4.5]decane-8,10-dione (6e). Yield: 90%; colourless viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1678 (imide carbonyls), 634, 582; 1H-NMR (CDCl3) δ ppm 1.75–1.91 (m, 8H, 4 × CH2, cyclopentyl), 2.23 (s, 3H, CH3), 4.20 (s, 2H, O=C-CH2-N), 5.01 (s, 2H, CH2-C6H5), 6.71 (d, 2H, J = 8.6 Hz, Har.), 7.25 (d, 2H, J = 8.6 Hz, Har.), 7.27–7.33 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 20.85 (CH3), 25.12, 36.71 (4 × CH2, cyclopentyl), 42.72 (CH2-C6H5), 56.89 (O=C-CH2-N), 69.97 (Cq), 124.98, 127.57, 128.50, 128.94, 129.76 (CHar.), 134.57, 136.92, 146.27 (3 × Car.), 170.59, 176.19 (2 × C=O); MS (EI) m/z (%): 364.26 ([M]+, 28), 91(100), 105 (98); Anal. Calcd. for C22H24N2O3 (364.44): C, 72.50%; H, 6.64%; N, 7.69%. Found: C, 72.43%; H, 6.75%; N, 7.81%.
6-(4-Methylphenyl)-9-phenethyl-6,9-diazaspiro[4.5]decane-8,10-dione (6f). Yield: 71.2%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1678 (imide carbonyls), 646, 606; 1H-NMR (CDCl3) δ ppm 1.73–2.17 (m, 8H, 4 × CH2, cyclopentyl), 2.20–2.27 (m, 3H, CH3), 2.84 (t, J = 7.7 Hz, 2H, CH2-C6H5), 4.04 (t, 2H, J = 7.7 Hz, CH2-CH2), 4.16 (s, 2H, O=C-CH2-N), 7.21 (d, 2H, J = 6.7 Hz, Har.), 7.24 (d, 2H, J = 6.7 Hz, Har.), 7.25–7.26 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 20.83 (CH3), 25.09, 34.08, (4 × CH2, cyclopentyl), 36.59, 40.58 (CH2-C6H5, CH2-CH2-C6H5), 56.90 (O=C-CH2-N), 69.88 (Cq), 124.63, 126.56, 128.68, 128.68, 129.13 (CHar.), 134.40, 138.39, 146.30 (3 × Car.), 170.30, 176.18 (2 × C=O); MS (EI) m/z (%): 362.2 ([M]+, 15), 81(100); Anal. Calcd. for C23H26N2O2 (362.46): C, 76.21%; H, 7.23%; N, 7.73%. Found: C, 76.02%; H, 7.15%; N, 7.89%.
Methyl 2-(6-(4-methoxyphenyl)-8,10-dioxo-6,9-diazaspiro[4.5]decan-9-yl)acetate (6g). Yield: 71.4%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands 1752 (carbonyl ester), 1720, 1685 (imide carbonyls), 609, 557; 1H-NMR (CDCl3) δ ppm 1.79–1.82 (m, 4H, 2 × CH2, cyclopentyl), 2.25–2.28 (m, 4H, 2 × CH2, cyclopentyl), 3.82 (s, 6H, COOCH3, OCH3), 4.25 (s, 2H, O=C-CH2-N), 4.61 (s, 2H, CH2-COOCH3), 6.83 (d, 2H, J = 9.0 Hz, Har.), 7.12 (d, 2H, J = 9.0 Hz, Har.); 13C-NMR (CDCl3) δ ppm 24.95, 36.24 (4 × CH2, cyclopentyl), 40.19 (CH2-COOCH3), 51.97, 52.44, 55.45 (O=C-CH2-N, COOCH3, OCH3), 70.68 (Cq), 114.40, 114.99 (CHar.), 133.40, 157.42, (2 × Car.), 169.69, 170.59, 176.19 (3 × C=O); MS (EI) m/z (%): 346.23 ([M]+, 17), 121.14 (100), 77.1 (29); Anal. Calcd. for C18H22N2O5 (346.38): C, 62.42%; H, 6.40%; N, 8.09%. Found: C, 62.22%; H, 6.35%; N, 8.22%.
9-Benzyl-6-(4-methoxyphenyl)-6,9-diazaspiro[4.5]decane-8,10-dione (6h). Yield: 90%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1678 (imide carbonyls), 634, 582; 1H-NMR (CDCl3) δ ppm 1.78 (br.s, 4H, 2 × CH2, cyclopentyl), 1.92–2.21 (m, 4H, 2 × CH2, cyclopentyl), 3.78 (s, 3H, OCH3), 4.17 (s, 2H, O=C-CH2-N), 5.51 (s, 2H, CH2-C6H5), 6.67 (d, 2H, J = 8.5 Hz, Har.), 6.75 (d, 2H, J = 8.5 Hz, Har.), 7.28–7.39 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 25.58, 36.40 (4 × CH2, cyclopentyl), 39.0 (CH2-C6H5), 42.63 (O=C-CH2-N), 55.48 (OCH3), 73.15 (Cq), 114.27, 114.96, 126.50, 127.54, 128.18 (CHar.), 135.47, 136.78, 141.35 (3 × Car.), 170.43, 172.47 (2 × C=O); MS (EI) m/z (%): 364.2 ([M]+, 28), 91(100), 121 (85); Anal. Calcd. for C22H24N2O3 (364.44): C, 72.50%; H, 6.64%; N, 7.96%. Found: C, 72.33%; H, 6.46%; N, 7.79%.
6-(4-Methoxyphenyl)-9-phenethyl-6,9-diazaspiro[4.5]decane-8,10-dione (6i). Yield: 90%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands 1722, 1687 (imide carbonyls), 634, 582; 1H-NMR (CDCl3) δ ppm 1.64–1.83 (m, 8H, 4 × CH2, cyclopentyl), 2.79 (t, 3H, J = 8.0 Hz, CH2-CH2-C6H5)), 3.68 (s, 2H, CH2-CH2-C6H5), 3.99 (s, 3H, OCH3), 4.02 (s, 2H, O=C-CH2-N), 6.68 (d, 2H, J = 9.0 Hz, Har.), 6.79 (d, 2H, J = 9.0 Hz, Har.), 7.28–7.39 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 24.94, 36.40 (4 × CH2, cyclopentyl), 39.08, 42.63 (CH2-C6H5, O=C-CH2-N), 44.75 (CH2-CH2-C6H5), 55.41 (OCH3), 73.15 (Cq), 114.27, 114.96, 126.50, 128.17, 129.00 (CHar.), 135.47, 136.78, 141.35 (3 × Car.), 170.43, 172.47 (2 × C=O); MS (EI) m/z (%): 378.24 ([M]+, 40), 121 (100); Anal. Calcd. for C23H26N2O3 (378.46): C, 72.99%; H, 6.92%; N, 7.40%. Found: C, 72.66%; H, 6.99%; N, 7.58%.
Methyl 2-(3,5-dioxo-1-phenyl-1,4-diazaspiro[5.5]undecane-4-yl)acetate (6m). Yield: 78%; white solid m.p. 118 °C; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1760 (carbonyl ester), 1726, 1675 (imide carbonyls), 633, 588; 1H-NMR (CDCl3) δ ppm 1.41–2.00 (m, 10H, 5 × CH2, cyclohexyl), 3.72 (s, 3H, COOCH3), 4.11 (s, 2H, O=C-CH2-N), 4.56 (s, 2H, CH2-COOCH3), 7.12–7.25 (m, 5H, CHar.); 13C-NMR (CDCl3) δ ppm 20.46, 25.52, 31.48 (5 × CH2, cyclohexyl), 40.19 (CH2-COOCH3), 59.11 (O=C-CH2-N), 60.59 (Cq), 126.01, 127.28, 129.36 (CHar.), 147.95 (Car.), 168.46, 170.56, 176.27 (3 × C=O); MS (EI) m/z (%): 330.1 ([M]+, 80), 186.2 (100), 91.1 (49); Anal. Calcd. for C18H22N2O4: C, 65.44%; H, 6.71%; N, 8.48%. Found: C, 65.52%; H, 6.68%; N, 8.31%.
4-Benzyl-1-phenyl-1,4-diazaspiro[5.5]undecane-3,5-dione (6n). Yield: 80%; colourless viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1678 (imide carbonyls), 634, 582; 1H-NMR (CDCl3) δ ppm 1.48–1.97 (m, 10H, 5 × CH2, cyclohexyl), 4.11 (s, 2H, O=C-CH2-N), 5.03 (s, 2H, CH2-C6H5), 6.86 (s, 2H, CHar.), 6.86–7.13 (m, 5H, CHar.), 7.38–7.39 (m, 5H, CHar.); 13C-NMR (CDCl3) δ ppm 20.53, 25.63, 31.57 (5 × CH2, cyclohexyl)), 42.66, 55.37 (CH2-C6H5, O=C-CH2-N), 60.71 (Cq), 125.84, 127.08, 128.52, 129.17, 129.31, 129.76 (CHar.), 136.94, 148.06 (2 × Car.), 170.94, 176.42 (2 × C=O); MS (EI) m/z (%): 348.2 ([M]+, 100), 186.2 (70), 91.1 (58); Anal. Calcd. for C22H24N2O2 (348.44): C, 75.83%; H, 6.94%; N, 8.04%. Found: C, 75.78%; H, 6.88%; N, 8.27%.
4-Phenethyl-1-phenyl-1,4-diazaspiro[5.5]undecane-3,5-dione (6o). Yield: 64.5%; buff solid, m.p. 138 °C; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1720, 1681 (imide carbonyls), 592, 555; 1H-NMR (CDCl3) δ ppm 1.48–1.96 (m, 10H, 5 × CH2, cyclohexyl), 2.87 (t, 2H, J = 7.6 Hz, CH2-C6H5), 4.08 (s, 2H, CH2CH2-C6H5), 4.12 (s, 2H, O=C-CH2-N), 6.99–7.00 (m, 2H, Har.), 7.23–7.29 (m, 8H, Har.); 13C-NMR (CDCl3) δ ppm 20.57, 25.63, 31.56 (5 × CH2, cyclohexyl), 34.12, 40.61 (CH2-C6H5, CH2-CH2-C6H5), 55.36 (O=C-CH2-N), 60.48 (Cq), 125.78, 126.61, 126.92, 128.56, 129.12, 129.40 (CHar.), 138.39, 148.20 (2 × Car.), 170.74, 176.56 (2 × C=O); MS (EI) m/z (%): 362.2 ([M]+, 100), 243.1 (90), 186.1 (70), 91.1 (48); Anal. Calcd. for C23H26N2O2 (362.46): C, 76.21%; H, 7.23%; N, 7.73%. Found: C, 76.41%; H, 7.42%; N, 7.91%.
Methyl 2-(3,5-dioxo-1-(4-methylphenyl)-1,4-diazaspiro[5.5]undecan-4-yl)acetate (6p). Yield: 75%; white solid, m.p. 156–158 °C; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1752 (carbonyl ester), 1726, 1675 (imide carbonyls), 619, 523; 1H-NMR (CDCl3) δ ppm 1.49–1.98 (m, 10H, 5 × CH2, cyclohexyl), 2.28 (s, 3H, CH3), 3.77 (s, 3H, COOCH3), 3.79 (s, 2H, O=C-CH2-N), 4.58 (s, 2H, CH2-COOCH3), 7.07 (s, 4H, Har.); 13C-NMR (CDCl3) δ ppm 20.94, 21.15, 31.53 (5 × CH2, cyclohexyl), 24.35 (CH3), 40.19 (CH2-COOCH3), 52.48, 54.98 (O=C-CH2-N, CH2COOCH3), 60.79 (Cq), 127.08, 129.99 (CHar.), 135.81, 145.32 (2 × Car.), 168.48, 170.64, 176.30 (3 × C=O); MS (EI) m/z (%): 344.2 ([M]+, 50), 200.1 (100), 105(37), 91.1(29); Anal. Calcd. for C19H24N2O4 (344.4): C, 66.26%; H, 7.02%; N, 8.13%. Found: C, 66.17%; H, 7.25%; N, 8.31%.
4-Benzyl-1-(4-methylphenyl)-1,4-diazaspiro[5.5]undecane-3,5-dione (6q). Yield: 70%; white solid m.p. 110 °C; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1717, 1673 (imide carbonyls), 615, 516; 1H-NMR (CDCl3) δ ppm 1.47–1.87 (m, 10H, 5 × CH2, cyclohexyl), 1.92 (s, 3H, CH3), 4.07 (s, 2H, O=C-CH2-N), 5.07 (s, 2H, CH2-C6H5), 6.92 (d, 2H, J = 7.5 Hz, Har.), 7.30 (d, 2H, J = 7.5 Hz, Har.), 7.38-7.40 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 20.57, 20.89, 31.60 (5 × CH2, cyclohexyl), 25.62 (CH3), 42.66 (CH2-C6H5), 55.31 (O=C-CH2-N), 60.91 (Cq), 126.91, 127.61, 128.49, 128.68, 129.19 (CHar.), 129.90 130.16, 145.41 (3 × Car.), 170.99, 176.41 (2 × C=O); MS (EI) m/z (%): 362.3 ([M]+, 84), 91.1(100), 200.2 (93); Anal. Calcd. for C23H26N2O2 (362.46): C, 76.21%; H, 7.23%; N, 7.73%. Found: C, 76.31%; H, 7.19%; N, 7.75%.
1-(4-Methylphenyl)-4-phenethyl-1,4-diazaspiro[5.5]undecane-3,5-dione (6r). Yield: 59%; white solid, m.p. 92 °C; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1719, 1674 (imide carbonyls), 597, 559; 1H-NMR (CDCl3) δ ppm 1.48–1.94 (m, 10H, 5 × CH2, cyclohexyl), 2.25 (s, 3H, CH3), 2.87 (t, J = 7.7 Hz, 2H, CH2-C6H5), 4.04 (s, 2H, CH2-CH2-C6H5), 4.06 (s, 2H, O=C-CH2-N), 7.04 (d, 2H, J = 8.4 Hz, Har.), 7.28 (d, 2H, J = 8.4 Hz, Har.), 7.29–7.30 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 20.61, 20.91, 25.63 (5 × CH2, cyclohexyl), 31.58 (CH3), 34.12, 40.58 (CH2-C6H5, CH2-CH2-C6H5), 55.32 (O=C-CH2-NH2), 60.63 (Cq), 126.58, 126.72, 128.53, 129.10, 129.97 (CHar.), 135.53, 138.44, 145.56 (3 × Car.), 170.81, 176.58 (2 × C=O); MS (EI) m/z (%): 376.25 ([M]+, 70), 257.23 (100); Anal. Calcd. for C24H28N2O2 (376.49): C, 76.56%; H, 7.50%; N, 7.44%. Found: C, 76.33%; H, 7.75%; N, 7.29%.
Methyl 2-(1-(4-methoxyphenyl)-3,5-dioxo-1,4-diazaspiro[5.5]undecan-4-yl)acetate (6s). Yield: (53.5%); yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1752 (carbonyl ester), 1626, 1675 (imide carbonyls), 619, 523; 1H-NMR (CDCl3) δ ppm 1.07–1.47 (m, 10H, 5 × CH2, cyclohexyl), 3.61 (s, 3H, COOCH3), 3.73 (s, 3H, OCH3), 4.22 (s, 2H, O=C-CH2-N), 4.64 (s, 2H, CH2-COOCH3), 6.75 (d, 2H, J = 8.6 Hz, Har.), 7.04 (d, 2H, J = 8.6 Hz, Har.); 13C-NMR (CDCl3) δ ppm 22.88, 25.51, 32.94 (5 × CH2, cyclohexyl), 37.70 (CH2COOCH3), 51.84, 52.10 (O=C-CH2-N, CH2COOCH3), 55.24 (OCH3), 67.64 (Cq), 113.38, 127.76 (CHar.), 141.72, 156.29 (2 × Car.), 168.2, 170.13, 178.70 (3 × C=O); MS (EI) m/z (%): 360 ([M]+, 0.5), 218.2 (100), 77 (5); Anal. Calcd. for C19H24N2O5 (360.40): C, 63.32%; H, 6.71%; N, 7.77%. Found: C, 63.33%; H, 6.81%; N, 7.91%.
1-(4-Methoxyphenyl)-4-benzyl-1,4-diazaspiro[5.5]undecane-3,5-dione (6t). Yield: 63%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibited bands at 1725, 1675 (imide carbonyls), 615, 516; 1H-NMR (CDCl3) δ ppm 1.41-1.90 (m, 10H, 5 × CH2, cyclohexyl), 2.28 (s, 3H, OCH3), 4.16 (O=C-CH2-N), 4.94 (s, 2H, CH2-C6H5), 6.67 (d, 2H, J = 7.6 Hz, Har.), 6.90 (d, 2H, J = 7.6 Hz, Har.), 7.23–7.29 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 20.80, 25.59, 36.66 (5 × CH2, cyclohexyl), 42.66 (CH2-C6H5), 56.84, 59.07 (O=C-CH2-N, OCH3), 69.94 (Cq), 114.35, 124.97, 127.53, 128.46, 128.87 (CHar.), 129.782, 136.89, 146.25 (3 × Car.), 170.62, 176.18 (2 × C=O); MS (EI) m/z (%): 378.4 ([M]+, 7), 91.12 (100); Anal. Calcd. for C23H26N2O3 (378.46): C, 72.99%; H, 6.92%; N, 7.40%. Found: C, 72.75%; H, 6.78%; N, 7.52%.
1-(4-Methoxyphenyl)-4-phenethyl-1,4-diazaspiro[5.5]undecane-3,5-dione (6u). Yield: 66.5%; yellow viscous oil; IR (KBr, ν, cm−1) absence of NH band at 3100 and exhibit bands at 1725, 1685 (imide carbonyls), 671, 538; 1H-NMR (CDCl3) δ ppm 1.23–2.05 (m, 10H, 5 × CH2, cyclohexyl), 2.81 (s, 2H, CH2-C6H5), 3.72 (s, 3H, OCH3), 3.77(s, 2H, CH2-CH2-C6H5), 4.20 (s, 2H, O=C-CH2-N), 6.80–6.81 (m, 5H, Har.), 7.13 (s, 4H, Har.); 13C-NMR (CDCl3) δ ppm 22.78, 22.99, 32.11 (5 × CH2, cyclohexyl), 32.78, 38.02 (CH2-C6H5, CH2-CH2-C6H5), 55.52, 55.70 (O=C-CH2-N, OCH3), 68.20 (Cq), 113.66, 114.60, 117.64, 127.65, 128.23 (CHar.), 138.23, 140.11, 157.74 (3 × Car.), 170.22, 176.11 (2 × C=O); MS (EI) m/z (%): 392.39 ([M]+, 14), 105 (60); Anal. Calcd. for C24H28N2O3 (392.49): C, 73.44%; H, 7.19%; N, 7.14%. Found: C, 73.59%; H, 7.15%; N, 7.24%.
3.1.7. General Procedure for the Synthesis of 2-(6-Aryl-8,10-dioxo-6,9-diazaspiro[4.5]decan-9-yl)acetamides (7a–c) and 2-(1-Aryl-3,5-dioxo-1,4-diazaspiro[5.5]undecan-4-yl)acetamides (7d–f)
Chloroacetamide (6.55 g, 0.07 mol) was added to a cold solution of the appropriate cyclized compound 5a–f in acetone (100 mL) in the presence of K2CO3 (1.38 g, 0.01 mol) and a catalytic amount of tetrabutylammoniun bromide (0.32 g, 0.001 mol) as a phase transfer catalyst. The reaction mixture was heated under reflux for 7 h. The reaction mixture was filtered off and acetone was evaporated under reduced pressure to give compounds 7a–f. The crude 7a–f were purified via recrystallization from ethanol.
2-(8,10-Dioxo-6-phenyl-6,9-diazaspiro[4.5]decan-9-yl)acetamide (7a). Yield: 95%; yellowish white solid m.p. 104 °C; IR (KBr, ν, cm−1) exhibited bands at 3383.14, 3180.62 (NH2), 1674.21, 1647.21, 1614 (3 × C=O); 1H-NMR (CDCl3) δ ppm 1.75–1.96 (m, 6H, 3 × CH2, cyclopentyl), 2.35 (br.s, 2H, CH2-cyclopentyl), 4.05, 4.44 (2 × s, 4H, O=C-CH2-N, CH2-C=O), 5.97 (s, 2H, NH2), 6.51 (s, 3H, Har.), 7.01–7.24 (m, 2H, Har.); 13C-NMR (CDCl3) δ ppm 25.23, 36.73 (4 × CH2, cyclopentyl), 41.36 (CH2-C=O), 56.67 (O=C-CH2-N), 69.83 (Cq), 124.83, 129.30, 131.03 (CHar.), 148.58 (Car.), 169.08, 169.20, 176.02 (3 × C=O); MS (EI) m/z (%): 301.26 ([M]+, 7), 77.11 (100); Anal. Calcd. for C16H19N3O3 (301.34): C, 63.77%; H, 6.36%; N, 13.94%. Found: C, 63.79%; H, 6.35%; N, 13.92%.
2-(8,10-Dioxo-6-(4-methylphenyl)-6,9-diazaspiro[4.5]decan-9-yl)acetamide (7b). Yield: 98%; yellowish white solid m.p. 120 °C; IR (KBr, ν, cm−1) exhibited bands at 3383.14, 3197.98 (NH2), 1658.78, 1645.28, 1620.21 (3 × C=O); 1H-NMR (CDCl3) δ ppm 1.31-1.93 (m, 8H, 4 × CH2, cyclopentyl), 3.73 (s, 3H, CH3), 3.99, 4.48 (2s, 4H, O=C-CH2-N, CH2-C=O), 6.14 (s, 2H, NH2), 6.78 (d, 2H, J = 8.7 Hz, Har.), 7.18 (d, 2H, J = 8.6 Hz, Har.); 13C-NMR (CDCl3) δ ppm 20.55, 31.52 (4 × CH2, cyclopentyl), 25.51 (CH3), 41.37 (CH2-C=O), 55.45 (O=C-CH2-N), 61.26 (Cq), 114.48, 128.67 (CHar.), 140.59, 157.7 (2 × Car.), 169.56, 171.05, 176.44 (3 × C=O); MS (EI) m/z (%): 317.28 ([M + 2]+, 16), 121.16 (100); Anal. Calcd. for C17H21N3O3 (315.37): C, 64.74%; H, 6.71%; N, 13.32%. Found: C, 64.77%; H, 6.69%; N, 13.34%.
2-(8,10-Dioxo-6-(4-methoxyphenyl)-6,9-diazaspiro[4.5]decane-9-yl)acetamide (7c). Yield: 98%; yellowish white solid m.p. 73 °C; IR (KBr, ν, cm−1) exhibited bands at 3383.93, 3294.42 (NH2), 1658.78, 1639.49, 1616.35 (3 × C=O); 1H-NMR (CDCl3) δ ppm 1.02–1.47 (m, 4H, 2 × CH2, cyclopentyl), 1.68–2.26 (m, 4H, 2 × CH2, cyclopentyl), 3.77 (s, 3H, OCH3), 4.10, 4.13 (2 × s, 4H, O=C-CH2-N, CH2-C=O-N), 6.41 (s, 2H, NH2), 6.80 (d, 2H, J = 7.5 Hz, Har.), 7.05 (d, 2H, J = 7.5 Hz, Har.); 13C-NMR (CDCl3) δ ppm 23.87, 36.40 (4 × CH2, cyclopentyl), 42.05 (CH2-C=O), 55.66 (O=C-CH2-N, OCH3), 70.27 (Cq), 114.35, 126.88 (CHar.), 141.71, 157.07 (2 × Car.), 169.26, 169.29, 176.12 (3 × C=O); MS (EI) m/z (%): 331.3 ([M]+, 0.44), 67.17 (100); Anal. Calcd. for C17H21N3O4 (331.37): C, 67.62%; H, 6.39%; N, 12.68%. Found: C, 67.61%; H, 6.37%; N, 12.65%.
2-(3,5-Dioxo-1-phenyl-1,4-diazaspiro[5.5]undecan-4-yl)acetamide (7d). Yield: 97%; yellowish white solid m.p. 110 °C; IR (KBr, ν, cm−1) exhibited bands at 3385.07, 3188.3 (NH2), 1670, 1647.2, 1618.2 (3 × C=O); 1H-NMR (CDCl3) δ ppm 1.18–2.01 (m, 10H, 5 × CH2, cyclohexyl), 4.07, 4.47 (2 × s, 4H, O=C-CH2-N, CH2-C=O), 6.66 (s, 2H, NH2), 7.08-7.13 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm of 24.03, 25.07, 33.15 (5 × CH2, cyclohexyl), 53.85, 54.93 (CH2-C=O, O=C-CH2-N), 58.92 (Cq), 127.34, 129.07, 129.3 (CHar.), 147.97 (Car.), 169.45, 169.78, 171.27 (3 × C=O); MS (EI) m/z (%): 315.26 ([M]+, 4.7), 58.17 (51), 100.2 (100); Anal. Calcd. for C17H21N3O3 (315.37): C, 64.74%; H, 6.71%; N, 13.32%. Found: C, 64.77%; H, 6.73%; N, 13.35%.
2-(3,5-Dioxo-1-(4-methylphenyl)-1,4-diazaspiro[5.5]undecan-4-yl)acetamide (7e). Yield: 94%; yellowish white solid m.p. 100 °C; IR (KBr, ν, cm−1) exhibited bands at 3456.14, 3383.14 (NH2), 1662.6, 1647.2, 1614.4 (3 × C=O); 1H-NMR (CDCl3) δ ppm of 1.32–1.57 (m, 10H, 5 × CH2, cyclohexyl), 2.18 (s, 3H, CH3) 3.94, 4.50 (2 × s, 4H, O=C-CH2-N, CH2-C=O), 5.97, 6.58 (2 × s, 2H, NH2), 6.98–7.29 (m, 4H, Har.); 13C-NMR (CDCl3) δ ppm 20.35, 22.86, 23.49 (5 × CH2, cyclohexyl), 25.44 (CH3), 41.36 (CH2-C=O), 53.58 (O=C-CH2-N), 60.58 (Cq), 127.16, 135.49 (CHar.), 129.41, 145.36 (2 × Car.), 169.0, 169.50, 176.29 (3 × C=O); MS (EI) m/z (%): 329.32 ([M]+, 50), 257.28 (40), 100.16 (100), 142.18 (63); ); Anal. Calcd. for C18H23N3O3 (329.39): C, 65.63%; H, 7.04%; N, 12.76%. Found: C, 65.66%; H, 7.12%; N, 12.78%.
2-(3,5-Dioxo-1-(4-methoxyphenyl)-1,4-diazaspiro[5.5]undecan-4-yl)acetamide (7f). Yield: 97%; buff solid, m.p. 94 °C; IR (KBr, ν, cm−1) exhibited bands at 3383.14, 3186.4 (NH2), 1678.07, 1670.35, 1654.92 (3 × C=O); 1H-NMR (CDCl3) δ ppm 1.80–2.38 (m, 10H, 5 × CH2, cyclohexyl), 4.03 (s, 3H, OCH3), 4.28, 4.51 (2s, 4H, O=C-CH2-N, CH2-C=O), 7.01 (d, 2H, J = 8.4 Hz, Har.), 7.08 (d, 2H, J = 8.4 Hz, Har.) 7.26 (s, 2H, NH2); 13C-NMR (CDCl3) δ ppm 21.25, 25.19, 36.51 (5 × CH2, cyclohexyl), 41.50, 42.14 (CH2-C=O, O=C-CH2-N), 56.39 (OCH3), 70.43 (Cq), 124.64, 129.81 (CHar.), 135.25, 145.33 (2 × Car.), 169.04, 169.76, 175.66 (3 × C=O); MS (EI) m/z (%): 315.28 ([M-OCH3]+, 13), 105.14 (100), 287.31(10); Anal. Calcd. for C18H23N3O4 (345.39): C, 62.59%; H, 6.71%; N, 12.17%. Found: C, 62.57%; H, 6.74%; N, 12.19%.
3.1.8. General Procedure for the Synthesis of 2-(6-Aryl-8,10-dioxo-6-phenyl-6,9-diazaspiro[4.5]decan-9-yl)acetonitriles (8a–c) and 2-(1-Aryl-3,5-dioxo-1,4-diazaspiro[5.5]undecan-4-yl)acetonitriles (8d–f)
Trifluroacetic anhydride (6.61 g, 0.03 mol) was added to a solution of the appropriate amide 7a–f (0.02 mol) in THF (40 mL) at 0–5 °C. The reaction mixture was stirred at room temperature for 2 h (monitored by TLC). Ammonium bicarbonate (12.43 g, 0.16 mol) was added portion-wise during 5–10 min. and the reaction mixture was stirred at room temperature for a further 45 min., concentrated under vacuum, washed with water (2 × 20 mL) and extracted with ethyl acetate (3 × 30 mL). The organic layer was dried (Na2SO4) and evaporated under reduced pressure to afford compounds 8a–f. The crude compounds 8a–f were purified using column chromatography (chloroform:ethyl acetate, 9:1).
2-(8,10-Dioxo-6-phenyl-6,9-diazaspiro[4.5]decan-9-yl)acetonitrile (8a). Yield: 97%; yellowish white solid m.p.70 °C; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 2848.86 (CN), 1743.65, 1687.71 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.20–2.30 (m, 8H, 4 × CH2, cyclopentyl), 4.25, 4.64 (2 × s, 4H, O=C-CH2-N and CH2-CN), 6.68–7.27 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 25.18, 26.33 (4 × CH2, cyclopentyl), 29.54 (CH2-CN), 56.61 (O=C-CH2-N), 69.70 (Cq), 114.36 (CN), 124.60, 124.91, 129.27 (CHar.), 148.29 (Car.), 169.36, 175.26 (2 × C=O); MS (EI) m/z (%): 283.25 ([M]+, 25), 91.09 (100), 243.23 (15); Anal. Calcd. for C16H17N3O2 (283.33): C, 67.83%; H, 6.05%; N, 14.83%. Found: C, 67.85%; H, 6.15%; N, 14.82%.
2-(8,10-Dioxo-6-(4-methylphenyl)-6,9-diazaspiro[4.5]decan-9-yl)acetonitrile (8b). Yield: 90%; yellowish white solid m.p. 82 °C; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 2226.71 (CN), 1735.93, 1689.64 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.26–1.79 (m, 8H, 4 × CH2, cyclopentyl), 2.34 (s, 3H, CH3), 4.09 (s, 2H, O=C-CH2-N), 4.71 (s, 2H, CH2-CN), 6.80 (d, 2H, J = 8.6 Hz, Har.), 6.90 (d, 2H, J = 8.6 Hz, Har.); 13C-NMR (CDCl3) δ ppm 20.51, 29.69 (2 × CH2, cyclopentyl), 26.26 (CH3), 29.54 (CH2-CN), 54.87 (O=C-CH2-N), 61.33 (Cq), 114.46 (CN), 127.97, 128.69 (CHar.), 140.16, 157.65 (2 × Car.), 170.66, 175.48 (2 × C=O); MS (EI) m/z (%): 299.26 ([M + 2]+, 16), 121.15 (100); Anal. Calcd. for C17H19N3O2 (297.35): C, 68.67%; H, 6.44%; N, 14.13%. Found: C, 68.68%; H, 6.42%; N, 14.15%.
2-(8,10-Dioxo-6-(4-methoxyphenyl)-6,9-diazaspiro[4.5]decane-9-yl)acetonitrile (8c). Yield: 77%; yellow viscous oil; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 2310.70 (CN), 1743.65, 1629.85 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.27–1.55 (m, 4H, 2 × CH2, cyclopentyl), 1.79–2.21 (m, 4H, 2 × CH2, cyclopentyl), 3.77 (s, 3H, OCH3), 4.13 (s, 2H, O=C-CH2-N), 4.78 (s, 2H, CH2-CN), 6.89 (d, 2H, J = 7.5 Hz, Har.), 6.97 (d, 2H, J = 7.5 Hz, Har.); 13C-NMR (CDCl3) δ ppm 26.19, 38.30 (2 × CH2, cyclopentyl), 29.06 (CH2-CN), 55.44 (O=C-CH2-N), 56.16 (OCH3), 65.11 (Cq), 114.62 (CN), 127.98, 131.32 (CHar.), 142.62, 157.30 (2 × Car.), 169.54, 175.16 (2 × C=O); MS (EI) m/z (%): 312.43 ([M − 1]+, 4), 57.15 (100); Anal. Calcd. for C17H19N3O3 (313.35): C, 65.16%; H, 6.11%; N, 13.41%. Found: C, 65.14%; H, 6.13%; N, 13.42%.
2-(3,5-Dioxo-1-phenyl-1,4-diazaspiro[5.5]undecan-4-yl)acetonitrile (8d). Yield: 90%; yellow viscous oil; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 2254.79 (CN), 1735.9, 1705.07 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.18 (s, 4H, 2 × CH2, cyclohexyl), 1.45–1.79 (m, 6H, 3 × CH2, cyclohexyl), 4.09 (s, 2H, O=C-CH2-N), 4.69 (s, 2H, CH2-CN), 6.93-7.24 (m, 5H, Har.); 13C-NMR (CDCl3) δ ppm 25.01, 29.07, 29.25 (5 × CH2, cyclohexyl), 29.44 (CH2-CN), 54.22 (O=C-CH2-N), 60.85 (Cq), 114.29 (CN), 128.95, 129.33, 129.64 (CHar.), 147.36 (Car.), 169.76, 175.30 (2 × C=O); MS (EI) m/z (%): 297.28 ([M]+, 6), 257.2 (4), 77.14 (100); Anal. Calcd. for C17H19N3O2 (297.35): C, 68.67%; H, 6.44%; N, 14.13%. Found: C, 68.69%; H, 6.46%; N, 14.11%.
2-(3,5-Dioxo-1-(4-methylphenyl)-1,4-diazaspiro[5.5]undecan-4-yl)acetonitrile (8e). Yield: 94.5%; yellowish white solid m.p. 120–122 °C; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 1888.31 (CN), 1741.72, 1989.6 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.28 (s, 2H, CH2, cyclohexyl), 1.45–2.01 (m, 8H, 4 × CH2, cyclohexyl), 2.32 (s, 3H, CH3), 4.16 (s, 2H, O=C-CH2-N ), 4.74 (s, 2H, CH2-CN), 6.91 (d, 2H, J = 7.0 Hz, Har.), 7.15 (d, 2H, J = 7.0 Hz, Har.); 13C-NMR (CDCl3) δ ppm 22.70 (CH3), 23.06, 24.76, 25.36 (5 × CH2, cyclohexyl), 31.33 (CH2-CN), 54.92 (O=C-CH2-N), 60.98 (Cq), 114.23 (CN), 129.77, 130.24 (CHar.), 136.09, 144.74 (2 × Car.), 169.89, 175.37 (2 × C=O); MS (EI) m/z (%): 311.27 ([M]+, 16), 91.15 (100); Anal. Calcd. for C18H21N3O2 (311.38): C, 69.43%; H, 6.80%; N, 13.49%. Found: C, 69.44%; H, 6.81%; N, 13.47%.
2-(3,5-Dioxo-1-(4-methoxyphenyl)-1,4-diazaspiro[5.5]undecan-4-yl)acetonitrile (8f). Yield: 75%; brown viscous oil; IR (KBr, ν, cm−1) absence of amidic NH2 and exhibited bands at 2260.57 (CN), 1687.71, 1676.14 (2 × C=O); 1H-NMR (CDCl3) δ ppm 1.76–2.06 (m, 10H, 5 × CH2, cyclohexyl), 3.75 (s, 3H, OCH3), 4.27 (s, 2H, O=C-CH2-N), 4.69 (s, 2H, CH2-CN), 6.91 (d, 2H, J = 7.8 Hzs, Har.), 7.04 (d, 2H, J = 7.8 Hz, Har.); 13C-NMR (CDCl3) δ ppm 20.41, 26.23, 31.40 (5 × CH2, cyclohexyl), 29.75 (CH2-CN), 54.86 (O=C-CH2-N), 61.37 (OCH3) 68.26 (Cq), 114.72 (CN), 127.82, 128.09 (CHar.), 140.19, 157.88 (2 × Car.), 170.13, 175.43 (2 × C=O); MS (EI) m/z (%): 327.23 ([M]+, 85), 121.11 (100), 287.22 (20); Anal. Calcd. for C18H21N3O3 (327.38): C, 66.04%; H, 6.47%; N, 12.84%. Found: C, 66.13%; H, 6.49%; N, 12.85%.
3.1.9. General Procedure for the Synthesis of 6-Aryl-9-(1H-tetrazol-5-yl)methyl)-6,9-diazaspiro[4.5] decane-8,10-diones (6j–l) and 1-Aryl-4-((1H-tetrazol-5-yl)methyl)-1,4-diazaspiro[5.5]undecane-3,5-diones (6v–x)
Anhydrous AlCl3 (13.3 g, 0.1 mol) was added to a cold dry THF (200 mL) under stirring during 10 min. Thereafter, NaN3 (28.9 g, 0.45 mol) was added portion-wise through 10 min. The appropriate penultimate nitrile derivative 8a–f was added and the reaction mixture was stirred under refluxed for 24 h. After cooling, the reaction mixture was filtered and the filtrate was evaporated under vacuum. The crude residues were purified through column chromatography (chloroform:ethyl acetate, 9:1) to give the ultimate respective compounds 6j–l and 6v–x.
6-Phenyl-9-((1H-tetrazol-5-yl)methyl)-6,9-diazaspiro[4.5]decane-8,10-dione (6j). Yield: 71%; colorless viscous oil; IR (KBr, ν, cm−1) exhibited band at 3419 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 1.11–2.23 (m, 8H, 4 × CH2, cyclopentyl), 4.22 (s, 2H, O=C-CH2-N), 5.14 (s, 2H, N-CH2-tetrazole)), 6.75–7.07 (m, 5H, Har.), 7.37 (s, 1H, NH); 13C-NMR (CDCl3) δ ppm 25.15, 29.77 (4 × CH2, cyclopentyl), 38.86 (N-CH2-tetrazole), 56.70 (O=C-CH2-N), 69.98 (Cq), 124.92, 129.42, 132.50 (CHar.), 148.48 (Car.), 153.55 (C=N-tetrazole), 170.55, 176.06 (2 × C=O); MS (EI) m/z (%): 326.43 ([M]+, 33), 327.27 (100); Anal. Calcd. for C16H18N6O2 (326.35): C, 58.88%; H, 5.56%; N, 25.75%. Found: C, 58.66%; H, 5.51%; N, 25.72%.
6-(4-Methylphenyl)-9-((1H-tetrazol-5-yl)methyl)-6,9-diazaspiro[4.5]decane-8,10-dione (6k). Yield: 61%; yellow viscous oil; IR (KBr, ν, cm−1) exhibited band at 3419 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 1.47 (s, 3H, CH3), 1.51–1.56 (m, 4H, 2 × CH2, cyclopentyl), 1.77 (br.s, 4H, 2 × CH2 cyclopentyl), 3.91 (s, 2H, O=C-CH2-N), 4.10 (s, 2H, N-CH2-tetrazole), 5.21 (s, 1H, NH), 6.83 (d, 2H, J = 6.0 Hz, Har.), 7.12 (d, 2H, J = 6.0 Hz, Har.); 13C-NMR (CDCl3) δ ppm 25.38 (CH3), 30.02, 34.84 (4 × CH2, cyclopentyl), 50.98 (N-CH2-tetrazole), 55.59 (O=C-CH2-N), 60.89 (Cq), 125.36, 128.92 (CHar.), 140.92, 151.94 (2 × Car.), 157.55(C=N-tetrazole), 168.93, 170.71 (2 × C=O); MS (EI) m/z (%): 340.29 ([M]+, 0.5), 121.14 (100); Anal. Calcd. for C17H20N6O2 (340.38): C, 59.99%; H, 5.92%; N, 24.69%. Found: C, 59.74%; H, 5.82%; N, 24.67%.
6-(4-Methoxyphenyl)-9-((1H-tetrazol-5-yl)methyl)-6,9-diazaspiro[4.5]decane-8,10-dione (6l). Yield: 63.3%; yellow viscous oil; IR (KBr, ν, cm−1) exhibited band at 3421.72 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 1.47 (br.s, 6H, 3 × CH2, cyclopentyl), 2.19 (br.s, 2H, CH2 cyclopentyl), 3.73 (s, 3H, OCH3), 3.80 (s, 2H, O=C-CH2-N), 4.21 (s, 2H, N-CH2-tetrazole)), 6.64 (s, 1H, NH), 6.99 (d, 2H, J = 6.0 Hz, Har.), 7.25 (d, 2H, J = 6.0 Hz, Har.); 13C-NMR (CDCl3) δ ppm 23.08, 30.43 (4 × CH2, cyclopentyl), 51.01 (N-CH2-tetrazole), 55.83 (O=C-CH2-N), 59.45 (OCH3), 61.02 (Cq), 128.49, 132.02 (CHar.), 140.0, 152.0 (2 × Car.), 159.96 (C=N-tetrazole), 160.01, 169.1 (2 × C=O); Anal. Calcd. for C17H20N6O3 (356.38): C, 57.29%; H, 5.66%; N, 23.58%. Found: C, 57.11%; H, 5.64%; N, 23.38%.
1-Phenyl-4-((1H-tetrazol-5-yl)methyl)-1,4-diazaspiro[5.5]undecane-3,5-dione (6v). Yield: 75%; yellow viscous oil; IR (KBr, ν, cm−1) exhibited band at 3400 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 0.87 (br.s, 2H, CH2 cyclohexyl), 1.18–1.98 (m, 8H, 4 × CH2, cyclohexyl), 4.09 (s, 2H, O=C-CH2-N), 5.03 (s, 2H, N-CH2-tetrazole), 7.05–7.13 (m, 5H, Har and 1H, NH); 13C-NMR (CDCl3) δ ppm 13.58, 25.37, 31.36 (5 × CH2, cyclohexyl), 55.01 (N-CH2-tetrazole), 58.88 (O=C-CH2-N), 60.77 (Cq), 125.93, 127.15, 129.38 (CHar.), 147.86 (Car.), 153.74 (C=N-tetrazole), 170.57, 175.98 (2 × C=O); MS (EI) m/z (%): 340.29 ([M]+, 3), 77.13 (100); Anal. Calcd. for C17H20N6O2 (340.38): C, 59.99%; H, 5.92%; N, 24.69%. Found: C, 59.78%; H, 5.91%; N, 24.68%.
1-(4-Methylphenyl)-4-((1H-tetrazol-5-yl)methyl)-1,4-diazaspiro[5.5]undecane-3,5-dione (6w). Yield: 61%; yellow viscous oil; IR (KBr, ν, cm−1) exhibited band at 3419.79 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 1.47 (s, 3H, CH3), 1.51–1.59 (m, 6H, 3 × CH2, cyclohexyl), 2.14 (br.s, 4H, 2 × CH2 cyclohexyl), 4.05 (s, 2H, O=C-CH2-N ), 4.30 (s, 2H, N-CH2-tetrazole), 6.65 (s, 1H, NH), 7.16 (d, 2H, J = 6.0 Hz, Har.), 7.19 (d, 2H, J = 6.0 Hz, Har.); 13C-NMR (CDCl3) δ ppm 22.66, 31.50, 34.94 (5 × CH2, cyclohexyl), 29.74 (CH3), 45.801 (N-CH2-tetrazole), 50.95 (O=C-CH2-N), 60.73 (Cq), 127.83, 130.13 (CHar.), 140.10, 145.92 (2 × Car.), 151.94 (C=N-tetrazole), 168.82, 170.42 (2 × C=O); MS (EI) m/z (%): 354.7 ([M]+, 3), 105.1 (100); Anal. Calcd. for C18H22N6O2 (354.41): C, 61.00%; H, 6.26%; N, 23.71%. Found: C, 61.15%; H, 6.22%; N, 23.61%.
1-(4-Methoxyphenyl)-4-((1H-tetrazol-5-yl)methyl)-1,4-diazaspiro[5.5]undecane-3,5-dione (6x). Yield: 66%; buff solid, m.p 73 °C; IR (KBr, ν, cm−1) exhibited band at 3419 (NH) and disappearance of CN band; 1H-NMR (CDCl3) δ ppm 1.18–1.88 (m, 10H, 5 × CH2, cyclohexyl), 3.75 (OCH3), 4.20 (s, 2H, O=C-CH2-N), 5.29 (s, 2H, N-CH2-tetrazole), 6.73 (d, 2H, J = 7.0 Hz, Har.), 6.95 (d, 2H, J = 7.0 Hz, Har.), 7.19 (s, 1H, NH); 13C-NMR (CDCl3) δ ppm 20.71, 25.04, 32.60 (5 × CH2, cyclohexyl), 36.59 (N-CH2-tetrazole), 41.32 (O=C-CH2-N), 56.50 (OCH3), 70.07 (Cq), 127.79, 129.88 (CHar.), 134.86, 145.77 (2 × Car.), 153.48 (C=N-tetrazole), 170.73, 176.09 (2 × C=O); MS (EI) m/z (%): 340.3 ([M-OCH3]+, 5), 105.17 (100); Anal. Calcd. for C18H22N6O3 (370.41): C, 58.37%; H, 5.99%; N, 22.69%. Found: C, 58.32%; H, 5.79%; N, 22.54%.