4H-[1,3,5,2]Oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine-1-oxides: Synthesis and Computational Studies †
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Instrumentations
2.2. Computational Details
3. Results and Discussion
3.1. General Synthetic Procedure
- N,N,6-trimethyl-5,6-dihydro-4H-[1,3,5,2]oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine 1-oxide(2a). White crystals. Yield—17.2%, m.p =163–164 °C (ether); IR, ν: 1609.86 (C=N), 1254.07(P=O), 1004.56 (O-P=O) cm−1; 1H NMR (CDCl3)δ: 2.52 (1H, ddd, J = 7.2 Hz, 11.1 Hz, 14.5 Hz, OCH2); 2.66 (6H, d,JP-H = 10.9 Hz, CH3NCH3); 2.70 (1H, ddd, J = 21 Hz, 6.7 Hz, 14.4 Hz, OCH2); 2.83 (3H, s, CH3N); 3.19 (1H, ddd, J = 2.1 Hz, 7.2 Hz, 10.2 Hz, CH2N); 3.47 (1H, ddd, J = 6.7 Hz, 10.4 Hz, 10.9 Hz CH2N);7.11 (1H, dt, J = 1.4 Hz, 7.6 Hz, H-9); 7.14 (1H, m, H-7); 7.31 (1H, m, H-8); 7.52(1H, m, H-10) ppm; 13C NMR (CDCl3)δ: 24.90 (d, JCP = 3.5 Hz, C-4); 36.25 (d, JCP = 5.5 Hz, C‘-1); 41.61(C-1);56,79 (C-5); 120.75 (C-7); 122.74 (C-8); 123.88 (C-10); 128.00 (C-9); 129.02 (d, JCP = 6.7, C-10a); 142.27 (d, JCP = 4.4 Hz, C-6a);159.96 (d, JCP = 24.9 Hz, C-3a) ppm; 31P NMR (CDCl3) δ = 21.94 ppm.C12H17N4O2P(280,26), Rf = 0.85.Elemental Analysis, %: C, 51.43; H,6.11; N, 19.99; P, 11.05. Found: C, 51.29; H,6.14; N, 20.08; P, 11.09.
- N,N,4,6-tetramethyl-5,6-dihydro-4H-[1,3,5,2]oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine 1-oxide(2b). White crystals. Yield—28.6%, m.p = 158–160 °C (ether); IR, ν:1602.37 (C=N), 1253.89(P=O), 1014.98 (O-P=O) cm−1;1H NMR (CDCl3)δ: 1.22 (3H, d, J = 6.4 Hz, CH3), 2.61 (6H, d, 3JP-H = 10.9 Hz, 2CH3), 2.65–2.74 (1H, m, CH) [centras 2.69], 2.80 (3H, s, CH3), 3.10–3.22 (2H, m, CH2), 7.06–7.58 (4H, m, Ar) ppm;13C NMR (CDCl3)δ: 11.7(4-C); 31.3 (d,3JP-N-C = 3.6 Hz, C-4); 36.3 (2C, 2J = 5.3 Hz, 1-CH3); 41.3 (6-CH3); 65.1 (C-6); 120.2(C-7); 123.0(C-8); 123.8 (C-10); 127.9 (C-9); 128.7 (d, J = 6.5 Hz, C-10a); 143.5 (d, J = 4.9 Hz, C-6a); 162.3 (d, J = 23.6 Hz, C-3a) ppm; 31P NMR (CDCl3) δ = 22.60 ppm.C13H19N4O2P(294,29), Rf = 0.77. Elemental Analysis, %: C, 53.06; H,6.51; N, 19.04; P, 10.52. Found: C, 52.87; H,6.54; N, 19.11; P, 10.58.
- N,N,5,6-tetramethyl-5,6-dihydro-4H-[1,3,5,2]oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine 1-oxide(2c). White crystals. Yield—20.2%, m.p = 172–173 °C (ether); IR, ν: 1604.69 (C=N), 1263.03 (P=O), 1009.25 (O-P=O) cm−1;1H NMR (CDCl3)δ:1.14 (3H, d, J = 7.0 Hz, CH3), 2.78 (6H, d, 3JP-H = 10.8 Hz, 2CH3), 2.77–2.88 (1H, m, CH), 2.79 (3H, s, CH3), 3.10 (1H, dd, 3J = 8.4 Hz, 2J = 10.3 Hz, CH2), 3.30 (1H, dd, 3J = 7.1 Hz, 2J = 10.3 Hz, CH2), 7.03–7.31 (4H, m, Ar) ppm. 13C NMR (CDCl3)δ: 13.4 (5-CH3); 31.0 (d, 3JP-N-C = 3.5 Hz, C-4); 36.1 (2C, d, 2J = 5.3 Hz, 1-CH3); 41.6 (6-CH3); 64.3 (C-5); 120.4 (C-7); 121.6 (C-8); 123.4 (C-10); 127.9(C-9); 128.8 (d, J = 5.7 Hz, C-10a); 144.5 (d, J = 4.0 Hz, C-6a); 162.5 (d, J = 23.4 Hz, C-3a) ppm; 31P NMR (CDCl3) δ = 21.25 ppm. C13H19N4O2P(294.29), Rf = 0.75. Elemental Analysis, %: C, 53.06; H,6.51; N, 19.04; P, 10.52. Found: C, 53.01; H,6.49; N, 19.09; P, 10.46.
3.2. The Plausible Reaction Pathways
3.3. Prediction of Biological/Drug-like Activity
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Anusevičius, Ž.; Kosychova, L.; Kairys, V.; Krikštopaitis, K.; Šarlauskas, J. 4H-[1,3,5,2]Oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine-1-oxides: Synthesis and Computational Studies. Chem. Proc. 2023, 14, 22. https://doi.org/10.3390/ecsoc-27-16162
Anusevičius Ž, Kosychova L, Kairys V, Krikštopaitis K, Šarlauskas J. 4H-[1,3,5,2]Oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine-1-oxides: Synthesis and Computational Studies. Chemistry Proceedings. 2023; 14(1):22. https://doi.org/10.3390/ecsoc-27-16162
Chicago/Turabian StyleAnusevičius, Žilvinas, Lidija Kosychova, Visvaldas Kairys, Kastis Krikštopaitis, and Jonas Šarlauskas. 2023. "4H-[1,3,5,2]Oxadiazaphospholo[3,4-a][1,5]benzodiazepin-1-amine-1-oxides: Synthesis and Computational Studies" Chemistry Proceedings 14, no. 1: 22. https://doi.org/10.3390/ecsoc-27-16162