Introduction

Diazepine nuclei are candidates for use in a wide range of drugs due to their anticoagulant, analgesic, sedative, and antifungal activities [1,2,3,4,5]. Most studies conducted on diazepines concern with the 1,5-benzodiazepine framework. Due to their wide range of biological properties, including their antioxidant, antiparasitic, anti-inflammatory, anti-Alzheimer’s, and anti-anxiety activities, benzodiazepines have been of interest to chemists for the synthesis and conducting research on their analogues [6,7,8,9]. Clobazam, triclobazam, quetiapine, and olanzapine are used as benzodiazepine scaffold in the treatment of schizophrenia and mental disorders [10,11,12]. 1,5-Benzodiazepine scaffolds containing the triazole group have unique biological properties [13,14,15,16,17]. During the recent years, 1,2,3-triazoles have attracted much attention among the heterocyclic compounds due to their biological activities such as anti-HIV, antifungal, and anti-allergy activities as well as easy synthesis by the click method [18,19,20]. Anti-corrosion coatings, pigments, and ligand agents for measuring metals are some applications of the triazoles [21,22,23,24]. The thermal 1,3-dipolar cycloaddition reaction between alkynes and organic azides has been known for more than a century [25]. It has been shown that using the Cu(I) salts increases the cycloaddition reaction rate up to 107 times and also leads to the formation of the regioselective 1,4-isomer as the dominant form [26]. Given that 1,2,3-triazoles have special pharmaceutical applications, the introduction of simple and effective methods for synthesizing the derivatives of these compounds can be very noteworthy. The organic azides are valuable intermediates in the organic synthesis [27]. Although nucleophilic substitution reaction of azide ion (N3−) with alkyl halides is introduced as one of the most efficient methods among the various ones of preparing azides, it has problems such as complexity and toxicity of the reactants, long times, difficult reaction conditions, and also low yields. Despite numerous reports released on the ring-opening reactions of the epoxides, to the best of the authors’ knowledge, only a few studies deal with opening the epoxide rings using N3− [28]. Knowing the history of the research group in the preparation of various triazole derivatives [29,30,31,32,33,34,35,36], a green, gentle, and effective method has been presented in this paper for the synthesis of β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones in water (Scheme 1). In the present method, different types of epoxides were converted into β-hydroxyazides in a green, very practical, and simple method through reacting with sodium azide in water without increasing any catalyst or other additives with high efficiency and short time. After preparing the desired β-hydroxyazides, the final reaction step involves the synthesis of β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3 via a cycloaddition of [4πs + 2πs] type in a copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). In the final section of the study, density functional theory (DFT) calculations at the B3LYP/6-31+G(d,p) level have been undertaken on the characterized structure 3a to obtain some of its physicochemical properties such as 1H NMR and 13C NMR data and electrophilicity index (Scheme 1).

Scheme 1
scheme 1

General method for the efficient synthesis of β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3

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Experimental and computational details

General information

All the chemicals required for the synthesis of β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3 were supplied from Sigma-Aldrich, Fluka, and Merck companies. The all synthesized products were confirmed by spectroscopic data (Experimental section and supplementary information). A Bruker (DRX-400 Avance) NMR was used to record the 1H and 13C NMR spectra in CDCl3 or acetone-d6 at room temperature. FT-IR spectra were taken by a Nicolet spectrometer (Magna 550) using KBr pellets. High-resolution MS spectra (HRMS) were recorded on an LTQ Orbitrap XL using electrospray ionization (ESI) on a Waters Micromass AutoSpec Ultima. The reactions are monitored by thin-layer chromatography (TLC).

Computational details

The geometry of the considered structure 3a is optimized at the DFT/B3LYP level with the 6-31+G(d,p) basis set using the Gaussian 09 software [37]. The structure was visualized in the GaussView 5.0 program. After geometry optimization and frequency calculation, zero-point energy (ZPE) and thermal correction are obtained at 298 K. NMR data calculations were performed using the gauge-independent atomic orbital (GIAO) method [38]. Relative chemical shifts were calculated by using the corresponding tetramethylsilane (TMS) shielding calculated at the same level of theory as the reference.

General synthesis procedure for β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3

A total of 2.4 mmol sodium azide (0.117 g) was added to a stirred solution of 2.2 mmol of epoxide 1 in water (5 mL), and the resulting mixture was stirred at room temperature for 16 h. Dipropargyl benzodiazepine 2 (1 mmol, 0.225 g) and CuI (0.2 mmol, 0.038 g) were added to the reaction mixture, and the mixture was extracted at room temperature for 8 h. After the completion of the reaction (monitored by TLC), water (5 mL) was added to the reaction mixture and extracted with CH2Cl2 (3 × 5 mL) and then dried over Na2SO4. The crude was concentrated under vacuum and was purified by preparative TLC (eluent: ethyl acetate/methanol 2:1) to afford the desired products 3.

Spectral data of the β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3

3a: yellow solid; m.p.: 106–110 °C; FT-IR: 3675, 3612, 3412, 3157, 2952, 2936, 1690, 1667, 1599, 1551, 1501, 1459, 1432, 1368, 1081, 1051, 1034, 937, 412 cm−1; 1H NMR (400 MHz, acetone-d6) δ: 7.91–7.72 (m, 4H), 7.31 (dd, J = 6.2, 3.5 Hz, 2H), 5.07–4.99 (m, 4H), 4.45–4.00 (m, 8H), 3.45 (dd, J = 12.2, 1.3 Hz, 1H), 3.16 (dd, J = 12.2, 1.1 Hz, 1H), 1.13 (dd, J = 9.3, 6.2 Hz, 6H); 13C NMR (100 MHz, acetone-d6) δ: 164.95, 143.18, 136.06, 126.55, 124.70, 123.80, 66.02, 56.77, 44.36, 43.35, 20.18; HRMS (ESI) exact mass calculated for C21H26O4N8Na: 477.19692, found: 477.19651. 3b: white solid; m.p.: 140–143 °C; FT-IR: 464, 952, 1034, 1051, 1060, 1374, 1433, 1461, 1501, 1550, 1599, 1665, 1690, 2855, 2881, 2930, 2969, 3158, 3417, 3617 cm−1; 1H NMR (100 MHz, CDCl3) δ: 7.72–7.61 (m, 3H), 7.45–7.20 (m, 3H), 5.29–4.82 (m, 4H), 4.46–4.33 (m, 2H), 4.25–4.08 (m, 2H), 4.05–3.86 (m, 3H), 3.33–3.21 (m, 2H), 1.54–1.37 (m, 4H), 1.03–0.82 (m, 7H); 13C NMR (400 MHz, CDCl3) δ: 165.34, 142.71, 135.48, 127.41, 125.49, 123.86, 71.57, 55.83, 43.99, 42.95, 27.52, 9.87; HRMS (ESI) exact mass calculated for C23H31O4N8: 483.24628, found: 483.24573. 3c: yellow viscous liquid; FT-IR: 3616, 3402, 3157, 2959, 2934, 2874, 2863, 1689, 1666, 1599, 1550, 1501, 1460, 1433, 1380, 1660, 1502, 1036, 952, 24 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.75–7.57 (m, 3H), 7.39–7.26 (m, 3H), 5.36–4.79 (m, 4H), 4.38 (dd, J = 16.5, 12.8 Hz, 2H), 4.23–3.94 (m, 4H), 3.29 (s, 2H), 1.54–1.20 (m, 14H), 0.89 (td, J = 7.1, 4.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 165.42, 142.86, 135.52, 127.46, 125.73, 123.84, 69.96, 56.22, 44.22, 42.66, 34.23, 27.60, 22.56, 13.99; HRMS (ESI) exact mass calculated for C27H38O4N8Na: 561.29082, found: 561.29038. 3d: yellow solid; m.p.: 155–160 °C; FT-IR: 478, 908, 1022, 1061, 1075, 1367, 1431, 1452, 1501, 1548, 1599, 1666, 1689, 2864, 2946, 3158, 3379, 3606 cm−1; 1H NMR (400 MHz, acetone-d6) δ: 7.88–7.65 (m, 4H), 7.32 (d, J = 6.9 Hz, 2H), 5.13–4.95 (m, 4H), 4.31–4.16 (m, 3H), 3.91 (dt, J = 18.1, 10.2 Hz, 2H), 3.45 (d, J = 12.1 Hz, 1H), 3.16 (d, J = 12.1 Hz, 1H), 2.14–2.07 (m, 2H), 2.04–1.72 (m, 8H), 1.52–1.26 (m, 7H); 13C NMR (100 MHz, acetone-d6) δ: 164.85, 142.67, 136.20, 126.50, 123.85, 123.19, 72.09, 66.44, 44.35, 43.75, 34.79, 31.83, 24.70, 24.02; HRMS (ESI) exact mass calculated for C27H34O4N8Na: 557.25952, found: 557.25963. 3e: yellow viscous liquid; 1H NMR (400 MHz, CDCl3) δ: 7.74–7.53 (m, 4H), 7.53–7.22 (m, 10H), 5.66–5.58 (m, 2H), 5.20–5.01 (m, 2H), 4.92–4.81 (m, 2H), 4.63–4.48 (m, 2H), 4.20–4.11 (m, 4H), 3.28 (s, 2H); 13C NMR (100 MHz, CDCl3) δ: 165.19, 142.79, 136.06,135.22, 129.08, 128.81, 127.19, 125.75, 125.17, 124.83, 67.29, 66.06, 64.61, 43.86; MS (ESI): 579 [M + H]+; Anal. Calcd for C25H30N8O2: C, 63.35; H, 5.23; N, 19.37.O, 11.06, found: C, 63.43; H, 5.31; N, 19.43; O, 11.83. 3f: yellow solid; m.p.: 127–133 °C; FT-IR: 3609, 3370, 3157, 2943, 2873, 1689, 1667, 1599, 1547, 1501, 1453, 1444, 1374, 1077, 1048, 998, 920, 461 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.76–7.49 (m, 3H), 7.34–7.21 (m, 3H), 6.00–5.84 (m, 2H), 5.40–4.68 (m, 8H), 4.42–3.90 (m, 5H), 3.28 (dd, J = 5.3, 2.4 Hz, 2H), 2.75–2.62 (m, 2H), 2.32–1.60 (m, 13H); 13C NMR (100 MHz, CDCl3) δ: 165.25, 142.47, 140.37, 139.77, 135.50, 127.19, 123.92, 115.54, 72.40, 68.25, 66.72, 63.14, 44.40, 35.69, 28.41, 27.68; HRMS (ESI) exact mass calculated for C31H38O4N8Na: 609.29082, found: 609.29072. 3g: white solid; m.p.: 132–135 °C; FT-IR: 3614, 3428, 3155, 2942, 2873, 1668, 1663, 1599, 1550, 1502, 1460, 1434, 1375, 1049, 1003, 917, 462 cm−1; 1H NMR (400 MHz, acetone-d6) δ: 7.81 (dd, J = 6.2, 3.5 Hz, 2H), 7.72 (s, 2H), 7.31 (dd, J = 6.2, 3.5 Hz, 2H), 5.93–5.78 (m, 4H), 5.06 (s, 4H), 4.99 (dt, J = 5.9, 1.2 Hz, 4H), 4.07 (t, J = 4.1 Hz, 4H), 4.00 (q, J = 5.6 Hz, 2H), 3.46 (d, J = 12.1 Hz, 1H), 3.16 (d, J = 12.2 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ: 165.00, 143.65, 135.96, 135.68, 126.61, 123.82, 123.50, 123.14, 61.20, 51.17, 44.37, 43.50; HRMS (ESI) exact mass calculated for C23H25O4N8: 477.20042, found: 477.20037. 3h: yellow solid; m.p.: 115–120 °C; FT-IR: 3617, 3391, 3157, 2944, 2851, 1689, 1665, 1599, 1550, 1501, 1459, 1433, 1370, 1060, 1051, 1021, 885, 462 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.73–7.57 (m, 3H), 7.38–7.27 (m, 3H), 5.89–5.72 (m, 2H), 5.37–4.80 (m, 8H), 4.45–4.33 (m, 2H), 4.26–3.90 (m, 5H), 3.63 (dd, J = 52.2, 4.7 Hz, 1H), 3.30 (d, J = 1.7 Hz, 2H), 2.35–2.10 (m, 4H), 1.65–1.47 (m, 4H); 13C NMR (100 MHz, CDCl3) δ: 165.32, 142.68, 137.82, 135.52, 127.29, 125.22, 123.92, 115.41, 69.54, 56.17, 44.21, 42.58, 33.42, 29.67; HRMS (ESI) exact mass calculated for C27H34O4N8Na: 557.25952, found: 557.25908. 3i: yellow viscous liquid; 1H NMR (400 MHz, CDCl3) δ: 7.62–7.59 (m, 3H), 7.28–7.18 (m, 3H), 4.98–4.90 (m, 2H), 4.47–4.14 (m, 6H), 3.96–3.23 (m, 12H), 1.52–1.39 (m, 4H), 1.34–1.21 (m, 6H), 0.88–0.82 (m, 8H); 13C NMR (100 MHz, CDCl3) δ: 165.16, 142.96, 139.13, 130.91, 127.17, 125.27, 71.77, 69.04, 58.09, 53.34, 44.44, 38.65, 31.57, 19.21, 19.18, 14.05; MS (ESI): 613 [M + H]+. 3j: yellow viscous liquid; 1H NMR (400 MHz, CDCl3) δ: 7.80–7.67 (m, 4H), 7.30–7.16 (m, 2H), 5.02–4.98 (m, 3H), 4.50–4.23 (m, 5H), 4.10–4.08 (m, 2H), 3.53–3.16 (m, 10H), 1.18–0.81 (m, 12H); 13C NMR (100 MHz, CDCl3) δ: 165.18, 142.97, 135.40, 127.18, 125.68, 123.82, 72.37, 69.28, 62.01, 53.22, 44.47, 44.09, 43.61, and 21.99; MS (ESI): 571 [M + H]+. 3k: colorless viscous liquid; FT-IR: 3671, 3575, 3382, 3158, 2954, 2867, 1689, 1666, 1599, 1548, 1501, 1454, 1433, 1367, 1113, 1081, 1050, 952, 462 cm−1; 1H NMR (400 MHz, acetone-d6) δ: 7.87–7.82 (m, 2H), 7.80–7.74 (m, 2H), 7.40–7.25 (m, 12H), 5.14–5.03 (m, 4H), 4.63–4.49 (m, 8H), 4.47–4.36 (m, 2H), 4.20 (t, J = 7.90 Hz, 2H), 3.53–3.41 (m, 5H), 3.18 (dd, J = 12.1, 1.0 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ: 166.02, 144.30, 139.69, 137.11, 129.33, 128.71, 128.53, 127.67, 126.01, 124.93, 74.01, 72.84, 70.12, 54.16, 45.44, 44.58; HRMS (ESI) exact mass calculated for C35H38O6N8Na: 689.28065, found: 689.28047. 3l: orange viscous liquid; FT-IR: 3570, 3407, 3157, 2952, 2912, 2865, 1689, 1666, 1599, 1550, 1502, 1460, 1432, 1365, 1112, 1061, 1051, 880, 409 cm−1; 1H NMR (400 MHz, acetone-d6) δ: 7.88–7.72 (m, 4H), 7.32 (dd, J = 6.1, 3.5, 2H), 5.91 (dd, J = 17.2, 10.6 Hz, 2H), 5.28 (dq, J = 17.3, 1.8 Hz, 2H), 5.17–5.04 (m, 6H), 4.61–4.44 (m, 4H), 4.44–4.31 (m, 2H), 4.15 (dd, J = 13.3, 7.7 Hz, 2H), 4.00 (dq, J = 5.5, 1.3 Hz, 4H), 3.50–3.31 (m, 5H), 3.17 (dt, J = 12.1, 1.2 Hz, 1H); 13C NMR (100 MHz, acetone-d6) δ: 164.91, 143.20, 136.04, 135.12, 126.57, 124.90, 123.82, 115.90, 71.82, 69.08, 53.05, 44.35, 43.49, 43.27; HRMS (ESI) exact mass calculated for C27H34O6N8Na: 589.24935, found: 589.24898.

Results and discussion

Synthesis of the β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3

The starting material dipropargyl benzodiazepine 2 is readily prepared from the commercial available o-phenylenediamine in high yield (70–80%) and excellent purity in-house [32]. With the dipropargyl benzodiazepine 2 in hand, attention was focused on copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) 2 to produce the β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3. We began our investigation with the reaction of 2-methyloxirane 1a (2.2 mmol), sodium azide (2.4 mmol), and dipropargyl benzodiazepine 2 (1 mmol) as a model reaction. Screening of solvents indicated that water is the best choice, affording the desired product 3a up to 50% yield (Table 1, entries 1–3). Undoubtedly, water is one of the greenest solvents in the organic synthesis due to its cheapness, availability, and safety in terms of the work and environment.

Table 1 Optimization conditions for the model reaction of dipropargyl benzodiazepine 2, NaN3, and 2-methyloxirane 1a
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The model reaction was performed in the presence of Sharpless catalytic system in water (Table 1, entry 2). Using copper(II) acetate in the presence of sodium ascorbate for an in situ reduction, a good degree of conversion to the desired product 3a was observed (80%). The yield was decreased to 51% when CuCl was used as the copper source (Table 1, entry 3). No better yields were obtained when organic solvents or the mixture system such as EtOH, DMSO, t-BuOH, and H2O/t-BuOH (1:1) was used (Table 1, entries 4–8). Optimal reaction conditions were determined to be CuI (10 mol%) as the catalyst and water as the solvent at room temperature for 8 h (Table 1, entry 1). With the optimized reaction conditions in hand, we next explored the scope of the CuAAC reaction of dipropargyl benzodiazepine 2 with different types of epoxide derivatives 1a-l, giving rise to the corresponding β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3 in good to excellent yields (Fig. 1).

Fig. 1
figure 1

Chemical structures of synthesized β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3

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It should be noted that the corresponding β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3 were synthesized as a single regioisomer in excellent yields. As would be observed from Fig. 1, the product of the styrene oxide (3e) formed exclusively by the attack of the azide ion at benzylic carbon of styrene oxide, due to the stabilization of the partial positive charge by the phenyl ring (electronic interaction is dominated over steric hindrance). However, other epoxide derivatives, despite the presence of Cu(I) Lewis acid, gave single regioisomers with preferential attack at the less hindered terminal carbon atom, which was confirmed by the reported literature [31, 39]. The structure of all desired products 3a-3l was confirmed by FT-IR, 1H NMR, 13C NMR, and HRMS (ESI) analysis (Experimental section and supplementary information). As a representative example, 1H NMR and 13C NMR spectra of 3a are discussed in the following section (computation section) and compared with the DFT calculated data.

DFT studies on the structure of β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinedione 3a

DFT is a quantum computational modeling technique utilized in chemical, physical, and material sciences to investigate the structural/electronic data of atoms, molecules, and condensed phases. Nowadays, it is widely accepted that DFT methods provide a valuable and in some cases the only alternative to obtain accurate physicochemical properties of organic molecules. On the other hand, it has been found that the hybrid functional B3LYP provides a good balance between placed and localized bond structures. It has emerged as a good compromise in computational cost and accuracy in results. Recently, the performance of DFT methods in the calculation of NMR properties has also been the subject of many theoretical studies. With the encouraging experimental data of the β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinedione derivatives 3, attention was focused on DFT calculations of the characterized product 3a to obtain its physicochemical data such as structural and electronic data, HOMO-LUMO analysis, and spectral data calculations. Optimized geometry of 3a by using the B3LYP/6-31+G(d,p) method is shown in Fig. 2.

Fig. 2
figure 2

The B3LYP/6-31+G(d,p) optimized geometry of 3a (distance in Å)

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The representative calculated bond lengths and bond angles of 3a are listed in Table 2. All bond lengths and bond angles are in the normal range. The bond lengths C=O and C-O were found to be 1.228 and 1.424 Å, respectively. The bond length in triazole ring was calculated as 1.365 Å for single-bonded N49=C52atoms. The C1-C2-C3 and C55-N27-N50 angles in the phenyl and triazole ring are 119.7 and 110.4°, respectively. In the carbonyl group, N11-C13-O16 was calculated as 122.7°.

Table 2 The representative B3LYP/6-31+G(d,p) calculated bond lengths and bond angles of 3a
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Structural analysis of compound 3a revealed the presence of two noncovalent intramolecular H-bond interactions. Strong intramolecular hydrogen bonding was observed in 3a [H59…N50, 2.022 Å] with the hydrogen atom (H59) in the hydroxyl group as a donor and the nitrogen atom (N50) in the triazole ring as an acceptor. On the other hand, a weak intermolecular C-H bonding (2.743 Å) was also observed with the hydrogen atom (H57) in the triazole ring and the nitrogen atom (N51) in other triazole ring (Fig. 2).

Calculated total energy, dipolar moment, and electronic data such as electrophilicity for 3a in gas phase by using the B3LYP/6-31+G(d,p) method are collected in Table 3. The dipole moment (μD) is an important parameter of the electronic distribution in a molecule, which can be related to the interaction strength of molecules and metal. The dipole moment value of 3a is 5.1 D.

Table 3 The calculated electronic data of 3a by the B3LYP/6-31+G(d,p) computational method
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The gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels (Eg) of an organic molecule was an important parameter that determined the reactivity of the molecule and stability index [40]. As Eg decreases, the reactivity of the molecule increases, leading to a decrease in the stability of the molecule [41]. Eg is the energy gap between HOMO and LUMO and is calculated as Eq. (1):

$$ {E}_{\mathrm{g}}={E}_{\mathrm{HOMO}}-{E}_{\mathrm{LUMO}} $$
(1)

where ELUMO is the energy of LUMO and EHOMO is the energy of HOMO. The energy gap of 3a was found to be 0.137 eV. According to the molecular orbital theory, the HOMO and LUMO orbitals are the most important factors affecting the bioactivity of organic compounds. Topologies of HOMO and LUMO orbitals of 3a are demonstrated in Fig. 3. As can be seen in Fig. 2, LUMO electron clouds were located mainly in the benzodiazepine ring and not in the triazole rings. The HOMO orbital having the energy levels of − 0.335 eV is localized on triazole rings and benzodiazepine ring.

Fig. 3
figure 3

Molecular orbitals of HOMO and LUMO for 3a

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The hardness and softness are commonly used as criteria of chemical reactivity and stability. The hardness (η) can be estimated from the calculated HOMO and LUMO energies. The smaller value of hardness implies higher reactivity. A molecule with a small HOMO-LUMO gap is more reactive. The hardness value of 3a is 0.098 eV. Electrophilicity index (ω) as a fundamental object of organic compounds is calculated according to Eq. (2) [42]:

$$ \omega ={\mu}^2/2\eta $$
(2)
$$ \mu =\left(\mathrm{ELUMO}+\mathrm{EHOMO}\right)/2\kern0.5em \mathrm{and}\kern0.5em \eta =\left(\mathrm{ELUMO}\hbox{--} \mathrm{EHOMO}\right)/2 $$
(3)

where μ and η are the chemical potential and chemical hardness, respectively, given by Eq. (3). The electrophilicity index of 3a equals to 0.520 eV.

The experimental 1H NMR spectrum of 3a consisted of a multiple signal at δ = 1.13 ppm for methyl groups, an ABdd system (J = 12.2, 1.1 Hz) at δ = 3.16–3.45 ppm for two methylene protons in benzodiazepine ring, some multiple signals (12 protons) at δ = 4.00–5.07 ppm for methylene and methine groups, two signals for benzene protons at δ = 7.31 and 7.72 ppm, and one characteristic triazole protons at δ = 7.91 ppm. The 1H-decoupled 13C NMR spectrum of 3a showed 11 resonances, which is in agreement with the proposed structure, with the amide carbon appearing at δ = 164.95 ppm, 5 distinct resonances for the aromatic carbons of benzene and triazole groups between δ = 123.80 and 143.18 ppm, and five resonances at δ = 20.18–66.02 ppm for aliphatic carbons. Calculated GIAO 1H and 13C chemical shift values (regarding TMS) of 3a by using the B3LYP/6-31+G(d,p) method and experimental results in acetone-d6 as NMR solvent are tabulated in Table 4.

Table 4 1H and 13C chemical shifts in acetone-d6 for 3a
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As mentioned, the experimental NMR spectra have been carried out in acetone-d6 as solvent; therefore, the calculated NMR data for optimized geometry 3a were also obtained by 6-31+G(d,p) basis set in acetone-d6. We have employed solvent effects into account by using the conductor-like polarizable continuum model through the DFT calculations done at B3LYP/6-31+G(d,p) level of theory. The correlations of 1H and 13C NMR data in acetone for 6-31+G(d,p) basis set are shown in Fig. 3. The calculated 1H and 13C chemical shifts are in good agreement with the experimental data. Plots of experimental vs computed 1H NMR chemical shifts and experimental vs computed 13C NMR chemical shifts (Fig. 4) indicate linear relationships with r2 = 0.993 and r2 = 0.998, respectively.

Fig. 4
figure 4

The linear regression between experimental and calculated 1H and 13C NMR data of 3a

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In the 1H NMR spectrum of 3a, the chemical shift values of the methyl protons were observed to be 1.15 ppm, whereas this signal has been calculated as 1.84 ppm. The experimental chemical shifts of methylene protons in benzodiazepine ring were observed at δ = 3.85 ppm, whereas the computed 1H NMR chemical shifts of corresponding signals were found at δ = 3.47 ppm. 13C NMR spectrum of 3a shows a signal at 164.95 ppm, due to the carbon of the carbonyl group. This signal is calculated as 166.07 ppm for B3LYP levels. The most deviation is observed in the 13C chemical shift of carbons 36 and 34 of 3a, 66.02 ppm, whereas it was calculated as 75.65 ppm.

Conclusions

In this research, for the first time, a simple method has been introduced for the synthesis of the β-hydroxy-1,4-disubstituted-1,2,3-triazole-based benzodiazepinediones 3 as raw materials from dipropargyl benzodiazepine and through the azidation of epoxides and then the Cu(I)-catalyzed azide-alkyne cycloaddition reaction in mild and green conditions (room temperature and water as solvent) without any by-products. It can be claimed that the present method is an environmentally friendly approach and acceptable one in terms of observing the principles of the green chemistry and click synthesis. Then, the DFT calculations were performed on one of the derivatives prepared in order to obtain the physicochemical characteristics such as NMR data and HOMO-LUMO analysis. The structure of 3a was fully optimized by using the B3LYP/6-31+G(d,p) method. The theory showed the presence of two intramolecular hydrogen bonding in optimized structure 3a. The DFT-simulated spectra of 3a were in reasonably good agreement with the experimental spectra.