Abstract
A new compound, 1,3,5-tris-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-1,2,3,4,5,6-hexahydro-s-triazine was obtained by the reaction of ortho-phenylenediamine 1 with 1,3,5-triacryl-1,2,3,4,5,6-hexahydro-1,3,5-triazine 2. Spectroscopic (IR, 1H-NMR, 13C-NMR and MS) data are supplied to support the proposed structure for the title compound.
A method for the preparation of 1,5-benzodiazepine derivatives corresponds to the condensation reaction between aromatic o-diamines with 1,3-dielectrophilic compounds such as acrylic acid, acrylic esters and acrylamides. This approach is quite versatile, which makes it appropriate for synthetic purposes [1,2,3,4,5,6]. Benzodiazepine moieties are well-known due to their wide range of pharmacological activities [7,8]. Previous outcomes reported by us have shown that other systems based on the diazepine core, introduced special properties against different cancer types; turning them into promising pharmacophores [9,10].
On the other hand, the (1,3,5-triacryl)-s-triazine fragments have been used as cross-linking agents for improving the fixation of dyes on polyamide fibers [11].
Synthesis of 1,3,5-tris-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-1,2,3,4,5,6-hexahydro-s-triazine (3)
A mixture of ortho-phenylenediamine 1 (345 mg, 3.2 mmol) and 1,3,5-triacryl-1,2,3,4,5,6-hexahydro-1,3,5-triazine 2 (248 mg, 1 mmol) in methanol (10 mL) with triethylamine (1 mL) was refluxed for 16 h (see Scheme 1). The precipitate formed was filtered off and then purified by column chromatography on silica gel, using CH2Cl2:MeOH (20:1) as eluent.
Scheme 1.
Synthesis of 1,3,5-tris-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-1,2,3,4,5,6-hexahydro-s-triazine 3.
The 1,3,5-tris-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-1,2,3,4,5,6-hexahydro-s-triazine 3 was obtained as a pale-yellow solid (yield: 467 mg, 90%), this compound showed high solubility in solvents such as CHCl3, CH2Cl2, DMF and DMSO. Studies on the generality of this procedure to obtain new analogues and on some biological properties of compound 3 are in progress.
Melting point: >350 °C.
IR (KBr, cm-1): 3385–3338 (NH), 1647 (C=N), 1508 (C=C).
1H-NMR (CDCl3, 400 MHz): δ = 6.82-6.78 (m, 3H, Ar-H); 6.69-6.66 (m, 9H, Ar-H); 5.23 (s, 6H, N-CH2-N); 3.45 (t, J = 6.0 Hz, 6H, CH2); 3.44 (bs, 3H, NH); 2.86 (bs, 6H, CH2) ppm.
13C-NMR (CDCl3, 100 MHz): δ = 171.4, 137.2, 135.4, 120.8, 119.6, 116.9, 112.9, 56.1, 39.7, 32.3 ppm.
EI-MS (m/z, %): 519.2 (M+, 100%), 374.5 (21), 230.1 (16), 145.3 (49),107.3 (35).
Elemental Analysis: Calculated for C30H33N9: C, 69.34%, H, 6.40%, N, 24.26%. Found: C, 69.30%, H, 6.37%, N, 24.24%.
Supplementary materials
Supplementary File 1Supplementary File 2Supplementary File 3Acknowledgements
The authors are grateful to Colciencias, Universidad del Valle (Colombia) and Universidad de Jaén (Spain) for financial support.
References and Notes
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