Introduction

In the twenty-first century, research in the field of chemistry has been directed towards the green chemical approach, thereby decreasing the usage of organic solvents, byproducts, and reaction time [1, 2]. Recently, development of environmentally benign synthetic methodologies have become an urgent need for several organic synthesis and chemical transformations [3].

The Multi-Component Assembly Process (MCAP) is a process in which more than two starting materials were reacted to give a highly reactive single product [4, 5]. A few examples for MCAP are Mannich, Gewald, Biginelli, Hantzsch pyridine, Ugi, and Passerini reactions for the construction of N-heterocycles [6–8]. The MCAP is an advanced technique for the construction of complex moiety with the help of readily available starting material with high atom economy and selectivity [9, 10]. Microwave energy is considered one of the top most energy sources that will increase the reaction rates and reduce the reaction time [11]. Microwave (MW) irradiation reactions promote green chemistry principles such as high reaction rates, more economic value, easy work-up, good atom economy, and environment-friendly methods.

N-heterocycles are found commonly and abundantly present in plants and animals, and posses various properties such as therapeutic, nutraceutical, and deterrent [12–14]. Quinazolinone is a fused bicyclic scaffold construct that is present in nature and possess a variety of medicinally important properties such as anti-inflammatory [15], anticonvulsant [16], antioxidant [17], antitumor [18], antiviral [19], antitubercular [20, 21], diuretic [22, 23], sedative/hypnotic [24], antihypertensive [25], anticancer [26, 27], and antimicrobial activities [28–30]. An example of a ring junction N-heterocyclic compound is luotonin A, a quinazolin-one-based ring junction nitrogen heterocycle [31], which is used as a traditional medicine to treat inflammation, abscesses, and rheumatism. Similarly, camptothecin and mappicine (Fig. 1) are two other alkaloids used in cancer treatment chemotherapy [32]. Similarly [1,2,4], triazoles also possess various pharmacological and biological properties such as anticholinergic, antihypertensive, anti-asthmatic, anti-inflammatory, diuretic, antibacterial, analgesic, and antifungal activities [33, 34]. The [1,2,4]triazoles are considered to be important structural scaffolds found in a large number of functionalized molecules with a wide variety of uses, including applications in medicinal chemistry, materials science, and organocatalysis, also found in medicinal drugs such as fluconazole, triazolam, rizatriptan, and alprazolam (Fig. 2). They also have medicinal activities, such as antifungal, anticonvulsant, analgesic, anxiolytic, antiemetic [35, 36]. Both moieties show individually promising properties. Hence, coupling of both bioactive components would lead to the introduction of a new, fused system. The literature reveals that [1,2,4]-triazolo- and [1,2,4]-triazino[4,3-c]quinazolines were used in the medical field for blood platelet aggregation inhibitors, antidepressants, analgesics, and antihistaminics [37, 38]. Based on the importance of triazolo and quinazolinone, we have decided to synthesize triazolo-quinazolinone as a hybrid molecule.

Fig. 1
figure 1

Medicinally important alkaloids containing a nitrogen ring junction

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Fig. 2
figure 2

Drugs containing [1,2,4]triazole nucleus

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Free radicals are single group of atoms with an odd number of electrons, which are responsible for large number of diseases in the biological system of the human body, including neural disorders, Parkinson’s disease, cardiovascular disease, ulcerative colitis, mild cognitive impairment, Alzheimer’s disease, atherosclerosis, aging, and liver disease [39]. The formation of free radicals are due to oxidation in the body, and are initiators of a chain reaction and often damage/death to a cell. Antioxidants are chemicals that inhibit the oxidation process of other molecules, even at relatively small concentrations, and thus damage of key cell components can be prevented by removing free radical intermediates [40, 41].

There are several strategies reported for synthesis of dihydro-triazolo-quinazolinones. The most common protocol is the condensation of 3-amino-1,2,4-triazole and substituted aldehyde with cyclic β-diketone in the presence of different catalysts followed by an oxidation process using many oxidizing agents under various solvents. The synthesis of dihydro-triazolo-quinazolinones is usually carried out by condensing the starting materials in the presence of heteropolyacids [42] or in the presence of chitosan and acetic acid under reflux conditions [43]. This can also be achieved by the following methods: molecular iodine using acetonitrile as solvent under reflux conditions [44], sulfamic acid and acetonitrile under reflux conditions [45], dimethylformamide under MW irradiation conditions [46], boric acid and ethyl acetate as solvent [47], silica gel and dichloromethane as solvent under MW irradiation conditions [48], ionic liquids [49], Nafion-H using polyethylene glycol-400 under reflux conditions [50] followed by oxidative aromatization in the presence of p-chloranil using chlorobenzene under reflux conditions [46]. Moreover, these synthetic protocols are associated with several drawbacks such as having multiple steps, use of organic solvents, tedious experimental protocol, expensive catalysts, prolonged reaction times, and unsatisfactory yields. Hence, in relevance to the present research, there appears to be no prior instant procedure for the synthesis of dihydro-triazolo-quinazolinones under ecofriendly conditions.

Results and discussion

While various methods are involved for synthesizing the dihydro-triazolo-quinazolinones, the chemistry arena is shifted towards the development of ecofriendly and economically attractive greener synthetic methodologies [51, 52]. By considering all the above-mentioned loopholes, we have put our efforts to develop an environmentally benign protocol. Microwave irradiation has been applied to form dihydro-triazolo-quinazolinones in a short time with excellent yields. We have identified two possible retro-synthetic pathways to synthesize the dihydro-triazolo-quinazolinone, outlined in Scheme 1. Among the two retrosynthetic pathways, we prefer path A because it has fewer number of steps, low cost, and easily available starting materials. The experimental procedure is simple and easy to access, and we have synthesized compounds, 4a–o (Scheme 2) with excellent isolated yields. The advantage of the present protocol over other reported methods are that it uses water as a green solvent instead of hazardous organic solvents, as well as shorter reaction time, a simple experimental procedure without expensive catalysts, and excellent yields [42–50].

Scheme 1
scheme 1

Reterosynthetic pathway to 9-phenyl-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4a synthesis

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Scheme 2
scheme 2

Synthesis of 9-phenyl substituted-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-ones, 4a–o

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We have optimized the reaction conditions for compound, 4a with respect to different methodologies (Table 1). Initially, we started the reaction in the absence of water, but we found no progress in the reaction. Our second option was to carry out the same reaction in both the conventional and non-conventional sources in the presence of water. In the conventional method, we operated the reaction at various temperatures, 50, 70, 100, and 150 °C, for 1 h and we could not find a positive response. Then we chose the non-conventional energy sources such as MW irradiation, ultrasonic (US) energy, and ultraviolet (UV) energy. From the optimization, the MW conditions with 300 W at 90 °C for 3 min show 70 % of product formation. To increase the yield of the isolated product 4a, we fine-tuned the reaction conditions by varying power, temperature, and mole ratio of ceric ammonium nitrate (CAN) (Table 2). From the above optimization, we observed that 150 W at 70 °C for 3 min with 1.5 equiv of CAN was found to be the optimized conditions.

Table 1 Optimizing the method for the synthesis of compound, 4a
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Table 2 Optimization of the reaction parameters with respect to power, temperature, and CAN for the synthesis of compound, 4a
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Table 3 Synthesis of 9-phenyl-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-ones, 4a–o
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DPPH radical scavenging activity

The radical scavenging activity of dihydro-triazolo-quinazolinones, 4a–o was evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. DPPH is widely used to evaluate the antioxidant activity of natural products as well as synthetic molecules [53]. DPPH is a well known radical scavenger, with maximum absorption at 517 nm in ethanol. DPPH shows a deep violet colour in solution form, and it becomes colourless or pale yellow when it gains the electron or hydrogen from an oxidant, becoming a more stable molecule with decrease in the absorbance [54]. The IC50 values of dihydro-triazolo-quinazolinones, 4a–o in terms of the scavenging of DPPH radicals are given in Table 4. The results demonstrated that all dihydro-triazolo-quinazolinones, 4a–o exhibit moderate activity. Among the all compounds, 4e and 4f shown good activity when compared with the standard ascorbic acid.

Table 4 DPPH radical scavenging activities of dihydro-triazolo-quinazolinones, 4a–o
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Experimental section

Materials and methods

The reagents used for the reactions were commercially procured and used without further purification. The completion of the reaction were monitored by TLC. All the MW reactions were carried out in a UWave-1000 MW·Uv·Us Synthesis/Extraction Reactor. IR spectrum was recorded on a SHIMADZU Infrared spectrophotometer (400–4000 cm−1; resolution: 1 cm−1) using KBr pellets. The 1H NMR (at 400 MHz) and 13C NMR (at 100 MHz) were analysed using a Bruker Avance 400 Mz spectrometer in CDCl3 solution with TMS as an internal standard. Chemical shift values (δ) were expressed in parts per million (ppm). The abbreviations are as follows: s, singlet; d, doublet; t, triplet; m, multiplet. The melting points were measured on an Elchem Microprocessor-based DT apparatus using an open capillary tube and are corrected with standard benzoic acid. The ESI–MS data were obtained using high resolution mass spectroscopy (HRMS).

General procedure for synthesis of dihydro-triazolo-quinazolinones, 4a–o

Equimolar quantities of 3-amino-1,2,4-triazole, 1 (10 mmol), substituted benzaldehyde, 2a–o (10 mmol), 1,3-cylohexanedione, 3 (10 mmol) were mixed and irradiated at 150 W for 60 s. About 15 mmol of ceric ammonium nitrate was dissolved in 10 mL of water, and this was added to the reaction mixture dropwise. Further, it was subjected to MW irradiation for another 2 min at 150 W. The reaction process was monitored by TLC. The reaction mass was washed with water to get 9-phenyl susbtitued-6,7-dihydro-[1,2,4] triazolo[5,1-b]quinazolin-8(5H)-ones, 4a–o.

DPPH radical scavenging assay

The radical scavenging activity was carried out by the reported method [55]. Briefly, 1 mL of 0.1 mM DPPH in DMSO was added to 2.5 mL of synthesized samples, 4a–o, at different concentrations (0.001, 0.002, 0.003, 0.004 mM) and placed for incubation for 30 min at room temperature. The absorbance of incubated solutions and control (without sample) were measured using a Hitachi U2910 spectrophotometer at 517 nm. Ascorbic acid was used as a standard antioxidant. The percentage inhibition was calculated according to the following formula.

$$\% {\text{ Inhibition }} = \, \left[ {A_{ 0} - A_{\text{t}} /A_{ 0} } \right] \, \times 100$$

here A 0 is the absorbance of control and A t is the absorbance of tested samples at particular time. The antioxidant activity was expressed as IC50. IC50 is the half minimal inhibitory concentration of a substance or drug.

The yields of all the synthesized compounds, 4a–o, are summarized in Table 3 and the spectral data are given below.

9-phenyl-6,7-dihydro-[1,2,4] triazolo[5,1-b]quinazolin-8(5H)-one, 4a

Pale yellow solid; mp 198–200 °C; IR (KBr, υ max/cm−1): 3030, 2856, 1687, 1593, 1577, 1485, 736; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.23–2.29 (m, CH2, 2H), 2.74 (t, J = 6.4 Hz, CH2, 2H), 3.35 (t, J = 6 Hz, CH2, 2H), 7.42–7.44 (m, ArH, 2H), 7.56–7.62 (m, ArH, 3H), 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.4 (CH2), 40.0 (CH2), 115.7, 128.4 (2C), 128.6 (2C), 129.5, 130.8, 151.3, 154.8 (N–HC=N), 157.9, 169.31, 194.8 (C=O). HRMS: m/z calcd for C15H12N4O: 264.1011, found: 264.1010.

9-(4-nitrophenyl)-6,7-dihydro-[1,2,4] triazolo[5,1-b]quinazolin-8(5H)-one, 4b

Half white solid; mp 168–170 °C; IR (KBr, υmax/cm−1): 3051, 2852, 1695, 1589, 1525, 1489, 740; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.26–2.33 (m, CH2, 2H), 2.76 (t, J = 6.4 Hz, CH2, 2H), 3.39 (t, J = 6.4 Hz, CH2, 2H), 7.61 (d, J = 8.8 Hz, ArH, 2H), 8.44 (t, J = 8 Hz, ArH, 3H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.5 (CH2), 29.7 (CH2), 34.3 (CH2), 39.8, 115.6, 123.9 (2C), 129.7 (2C), 136.1, 148.6, 148.8, 154.8 (N–HC=N), 158.2, 169.3, 194.7 (C=O). HRMS: m/z calcd for C15H11N5O3: 309.0862, found: 309.0860.

5-(3-nitrophenyl)-8,9-dihydro-[1,2,4] triazolo[3,4-b]quinazolin-6(7H)-one, 4c

Half white solid; mp 182–184 °C; IR (KBr, υmax/cm−1): 3039, 2881, 1695, 1595, 1514, 744; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.27–2.33 (m, CH2, 2H), 2.77 (t, J = 6.4 Hz, CH2, 2H), 3.39 (t, J = 6.4 Hz, CH2, 2H), 7.78–7.81 (m, ArH, 2H), 8.47 (s, ArH, 1H) 8.46 (m, ArH, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.5 (CH2), 34.4 (CH2), 39.9 (CH2), 115.7, 124.2, 125.4, 129.7, 131.1, 134.6, 148.2, 148.2, 154.8 (N–HC=N), 158.2, 169.3, 194.7 (C=O). HRMS: m/z calcd for C15H11N5O3: 309.0862, found: 309.0860.

9-(2-nitrophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4d

Half white solid; mp 206–208 °C; IR (KBr, υmax/cm−1): IR: 3030, 2856, 1697, 1589, 1516, 734; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.32–2.31 (m, CH2, 2H), 2.70 (t, J = 6.4 Hz, CH2, 2H), 3.38 (t, J = 6.8 Hz, CH2, 2H), 7.31–7.33 (m, ArH, 1H), 7.78–7.87 (m, ArH, 2H), 8.42–8.48 (m, ArH, 2H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.1 (CH2), 39.4 (CH2), 114.8, 125.2, 126.6, 129.5, 131.3, 134.6, 146.7, 149.1, 154.8 (N–HC=N), 158.1, 169.2, 195.1 (C=O). HRMS: m/z calcd for C15H11N5O3:: 309.0862, found: 309.0860.

9-(4-isopropylphenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4e

Pale yellow solid; mp 172–174 °C; IR (KBr, υmax/cm−1): 3097, 2960, 2875, 1691, 1591, 729; 1H NMR (400 MHz, CDCl3): δ (ppm), 1.33 (d, J = 7.2 Hz, 2 × CH3, 6H), 2.23–2.29 (m, CH2, 2H), 2.74 (t, J = 6 Hz, CH2, 2H), 2.99–3.06 (m, CH, 1H), 3.34 (t, J = 6.4 Hz, CH2, 2H), 7.38–7.45 (m, ArH, 4H), 8.47 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 23.7 (CH3, 2C), 34.1 (CH), 34.4 (CH2), 40.0 (CH2), 115.8, 126.6 (2C), 126.7, 128.7 (2C), 151.7, 151.8, 154.9 (N–HC=N), 157.9, 169.2, 195.0 (C=O). HRMS: m/z calcd for C18H18N4O: 306.1481, found: 306.1480.

9-(p-tolyl)-6,7-dihydroS-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4f

Pale yellow solid; mp 200–202 °C; IR (KBr, υmax/cm−1): 3099, 2922, 1689, 1639, 1539, 1300, 748; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.22–2.29 (m, CH2, 2H), 2.47 (s, CH3, 3H), 2.74 (t, J = 6.4 Hz, CH2, 2H), 3.34 (t, J = 6 Hz, CH2, 2H), 7.33–7.40 (m, ArH, 4H), 8.45 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 21.7 (CH3), 34.4 (CH2), 40.0 (CH2), 115.7, 126.5 (2C), 128.5, 129.3 (2C), 141.3, 151.6, 154.8 (N–HC=N), 157.9, 169.2, 194.9 (C=O). HRMS: m/z calcd for C16H14N4O: 278.1168, found: 278.1165.

9-(3,4-dimethoxyphenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4g

Yellow solid; mp 164–166 °C; IR (KBr, υmax/cm−1): IR: 3105, 2835, 1697, 1633, 1593, 1458, 763; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.23–2.30 (m, CH2, 2H), 2.76 (t, J = 6.4 Hz, CH2, 2H), 3.34 (t, J = 6 Hz, CH2, 2H), 3.9 (d, J = 6.4 Hz, 2 x OCH3, 6H), 6.99 (d, J = 1.6 Hz, ArH, 1H), 7.03–7.08 (m, ArH, 2H), 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.5 (CH2), 40.1 (CH2), 55.9 (OCH3), 56.0 (OCH3), 110.8, 112.2, 115.7, 121.2, 122.3, 148.9, 151.2, 151.2, 154.9 (N–HC=N), 157.8, 169.2, 194.9 (C=O). HRMS: m/z calcd for C17H16N4O3: 324.1222, found: 324.1220.

9-(2,4-dimethoxyphenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4h

Pale Yellow solid; mp 214–216 °C; IR (KBr, υmax/cm−1): IR: 3099, 2954, 1703, 1589, 1496, 790; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.21–2.27 (m, CH2, 2H), 2.70–2.75 (m, CH2, 2H), 3.30–3.34 (m, CH2, 2H), 3.7 (s, OCH3, 3H), 3.89 (s, OCH3, 3H), 6.59 (d, J = 1.6 Hz, ArH, 1H), 6.67–6.70 (m, ArH, 1H), 7.30 (t, J = 8.4 Hz, ArH, 1H), 8.44 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.7 (CH2), 34.3 (CH2), 39.7 (CH2), 55.5 (OCH3), 55.6 (OCH3), 99.0, 105.0, 111.2, 116.8, 130.6, 148.3, 155.0 (N–HC = N), 157.5, 158.0, 163.2, 168.5, 195.0 (C=O). HRMS: m/z calcd for C17H16N4O3: 324.1222, found: 324.1220.

9-(4-methoxyphenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4i

Half white solid; mp 194–196 °C; IR (KBr, υmax/cm−1): 3015, 2954, 2835, 1693, 1608, 1589, 1496, 752; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.24–2.29 (m, CH2, 2H), 2.75 (t, J = 6.4 Hz, CH2, 2H), 3.33 (t, J = 6 Hz, CH2, 2H), 3.90 (s, OCH3, 3H), 7.06–7.09 (m, ArH, 2H), 7.44–7.48 (m, ArH, 2H) 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.5 (CH2), 40.1 (CH2), 55.4 (OCH3), 113.9, 115.6 (2C), 121.0, 131.0 (2C), 151.0, 154.9 (N–HC=N), 157.8, 161.7, 169.2, 195.1 (C=O). HRMS: m/z calcd for C16H14N4O2: 294.1117, found: 294.1115.

9-(3-methoxyphenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4j

Half white solid; mp 190–192 °C; IR (KBr, υmax/cm−1): 3015, 2954, 2835, 1693, 1593, 1577, 1483, 750; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.23–2.29 (m, CH2, 2H), 2.74 (t, J = 6.4 Hz, CH2, 2H), 3.35 (t, J = 6.4 Hz, CH2, 2H), 3.84 (s, OCH3, 3H), 6.96–6.98 (m, ArH, 2H), 7.11–7.14 (m, ArH, 1H), 7.50 (t, J = 7.6 Hz, ArH, 1H), 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.5 (CH2), 40.0 (CH2), 55.3 (OCH3), 114.1, 115.8, 116.0, 120.3, 129.9, 130.7, 151.0, 154.8 (N–HC=N), 157.9, 159.6, 169.2, 194.6 (C=O). HRMS: m/z calcd for C16H14N4O2: 294.1117, found: 294.1115.

9-(4-bromophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4k

Half white solid; mp 242–244 °C; IR (KBr, υmax/cm−1): 3105, 2881, 1689, 1562, 1581, 1481, 750; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.23–2.30 (m, CH2, 2H), 2.75 (t, J = 6.8 Hz, CH2, 2H), 3.35 (t, J = 6.4 Hz, CH2, 2H), 7.32 (d, J = 8.4 Hz, ArH, 2H), 7.71 (d, J = 8.4 Hz, ArH, 2H), 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.5 (CH2), 34.4 (CH2), 40.0 (CH2), 115.6, 125.5 (2C), 128.3, 130.2 (2C), 131.9, 150.1, 154.8 (N–HC=N), 158.0, 169.2, 194.8 (C=O). HRMS: m/z calcd for C15H11BrN4O: 342.0116, found: 342.0115.

9-(3-bromophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4l

Half white solid; mp 198–200 °C; IR (KBr, υmax/cm−1): 3051, 2854, 1687, 1602, 1591, 1471, 752; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.24–2.30 (m, CH2, 2H), 2.75 (t, J = 6.4 Hz, CH2, 2H), 3.36 (t, J = 6 Hz, CH2, 2H), 7.35–7.37 (m, ArH, 1H), 7.46 (t, J = 8 Hz, ArH, 1H), 7.55 (t, J = 1.6 Hz, ArH, 1H), 7.72–7.75 (m, ArH, 1H), 8.47 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.5 (CH2), 34.4 (CH2), 39.9 (CH2), 115.6, 122.6, 127.0, 130.1, 131.2, 131.4, 133.7, 149.4, 154.8 (N–HC=N), 158.1, 169.2, 194.6 (C=O). HRMS: m/z calcd for C15H11BrN4O: 342.0116, found: 342.0115.

9-(2-bromophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4m

Half white solid; mp 252–254 °C; IR (KBr, υmax/cm−1): 3101, 2945, 1693, 1597, 1519, 1423, 750; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.26–2.31 (m, CH2, 2H), 2.68–2.82 (m, CH2, 2H), 3.37–3.40 (m, CH2, 2H), 7.28 (d, J = 2 Hz, ArH, 1H), 7.45–7.57 (m, ArH, 2H), 7.76–7.85 (m, ArH, 1H), 8.49 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.3 (CH2), 39.6 (CH2), 116.0, 121.0, 127.8, 129.0, 131.6, 131.8, 133.0, 149.2, 154.9 (N–HC=N), 158.2, 169.0, 194.4 (C=O). HRMS: m/z calcd for C15H11BrN4O: 342.0116, found: 342.0116.

9-(4-chlorophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4n

Half white solid; mp 220–222 °C; IR (KBr, υmax/cm−1): 57, 2854, 1691, 1587, 1562, 1487,752; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.23–2.30 (m, CH2, 2H), 2.75 (t, J = 6.4 Hz, CH2, 2H), 3.35 (t, J = 6.4 Hz, CH2, 2H), 7.39 (d, J = 8.4 Hz, ArH, 2H), 7.55 (d, J = 8.4 Hz, ArH, 2H) 8.46 (s, ArH, 1H); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.5 (CH2), 34.4 (CH2), 40.0 (CH2), 115.7, 127.8, 129.0 (2C), 130.1 (2C), 137.1, 150.1, 154.8 (N–HC=N), 158.0, 169.2, 194.8 (C=O). HRMS: m/z calcd for C15H11ClN4O: 298.0621, found: 298.0620.

9-(2-chlorophenyl)-6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-one, 4o

Pale yellow solid; mp 242–244 °C; IR (KBr, υmax/cm−1): 3103, 2897, 1693, 1600, 1589, 1469, 704; 1H NMR (400 MHz, CDCl3): δ (ppm), 2.24–2.31 (m, CH2, 2H), 2.68–2.82 (m, CH2, 2H), 3.36–3.40 (m, CH2, 2H), 7.21–7.31 (m, ArH, 1H), 7.47–7.61 (m, ArH, 3H), 8.48 (s, ArH, 1H,–NH); 13C NMR (100 MHz, CDCl3): δ (ppm), 20.6 (CH2), 34.2 (CH2), 39.6 (CH2), 116.2, 127.2, 129.0, 129.6, 129.9, 131.6, 131.9, 148.0, 154.9 (N–HC=N), 158.1, 169.0, 195.5 (C=O). HRMS: m/z calcd for C15H11ClN4O: 298.0621, found: 298.0620.

Conclusion

We have successfully reported a simple and green protocol for the synthesis of new dihydro-triazolo-quinazolinone derivatives, 4a–o, by applying views of green chemistry. The reaction proceeds in a minimal reaction time, has good atom economy, is a simple experiment with easy work-up using a benign solvent such as water, and has a high conversion with good yields. In addition, these new derivatives were evaluated for their antioxidant activities and the results reveal that the compounds 4e and 4f showed promising free radical scavenging ability towards the DPPH.