Short Communication - (2020) Volume 11, Issue 2
Received: 16-Mar-2020
Published:
04-Apr-2020
, DOI: 10.37421/csj.2020.11.206
Citation: Parshuram MP, Vinod TK, Ravi V and Pradip BG. "Visible Light Promoted One-Pot, Three Component Reaction for the Synthesis of Quinolones". Chem Sci J 11 (2020) doi: 10.37421/csj.2020.11.206
Copyright: © 2020 Parshuram MP, et al. This is an open-access article distributed under the terms of the creative commons attribution license which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Highly efficient one-pot three component approach was developed for the synthesis of biological active quinazoline derivatives. By the application of visible light via SP3 C-H bond activation, desired products were obtained in high yields. The advantages of this method are application of green chemistry approach, avoidance of toxic organic solvents, easily available starting material, simple operation and shorter reaction times.
In a 25 mL round-bottom flask, the mixture of 2-aminobenzophenone (1 mmol), benzaldehyde (1 mmol), ammonium acetate (2.5 mmol) was placed under irradiation using an LED bulb (λmax=450 nm) as the light source for the appropriate time shown in Table 1. The progress of reaction was monitored by TLC (PET ether: ethylacetate 8:2). After completion of reaction, the reaction mixture was cooled at room temperature and crude product was recrystallized by ethyl alcohol.
Spectral data of representative compounds
2, 4-diphenylquinazoline (4a):Yellow solid, m. p:117-1190C; IR (KBr, cm-1): 3410, 1622, 1534, 1445; 1H NMR: (400 MHz, CDCl3 ): δ = 7.62-7.45 (m, 7H), 7.88-7.83 (m, 3H), 8.12-8.15 (m, 2H), 8.69 (m, 2H);13CNMR: (400 MHz, CDCl3 ):δ=121.7, 126.9, 127.7, 127.9, 129.9, 132.2, 131.3, 134.4, 136.7, 138.1, 153.2, 160.0, 168.1, MS: m/z =283.
2- (4- nitrophenyl)-4-phenylquinazoline (4b):White solid; m. p: 2090C; IR (KBr, cm-1): 3440, 1609, 1542, 1524, 1339, 837, 772, 706; 1H NMR (400 MHz, CDCl3): δ = 6.59 (t, J = 4.27 Hz, 4H), 7.20 - 7.30 (m, 3H), 7.41 (t, J = 6.6 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H), 8.37 (d, J = 8.3, 2H); 13C NMR (400 MHz, CDCl3): δ = 72, 78, 115, 117, 118, 123.1, 130.9, 131.2, 131.9, 134.5, 139.2, 147.3, 148.1, 150.0, 167.1; MS: m/z =330.
2- (2-Nitrophenyl-4-phenylquinazoline (4c):Brown solid; m. p: 1270C; IR (KBr, cm-1):3481, 1614, 1561, 1524, 1347, 862, 787, 713;1H NMR (400 MHz, CDCl3):δ = 7.63-7.48 (m, 7H), 7.83-7.74 (m, 2H), 8.14-8.06 (m, 4H); 13C NMR (400 MHz, CDCl3): δ = 118.3, 121.5, 121.8, 122.2, 124.1, 127.2, 128.1, 128.6, 128.9, 129.5, 130.1, 130.2, 132.1, 137.8, 149.1, 149.7, 161.6; MS:m/z =328.
2- (4-chlorophenyl)-4- phenylquinazoline (4e):Yellow solid, m. p: 1860C; IR (KBr, cm-1): 3476, 2918, 2189, 1647, 1577, 874; 1H NMR (400 MHz, CDCl3):δ = 6.65-6.86 (m, 5H), 7.16-7.91 (m, 4 H), 7.5 (d, J = 9.6 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H); 13C NMR (400 MHz,CDCl3):δ = 70, 77.1, 77.6, 77.9, 113, 117.2, 117.6, 127.2, 127.8, 127.9, 131.2, 132.5, 138.12, 141.23, 147.11, 166.3; MS: m/z =319.
4-phenyl-2-p-tolyquinazoline (4k):White solid; m. p:166-1680C; IR (KBr, cm-1):3312, 1609, 1569, 1533, 1339, 1070, 771, 697; 1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3H), 7.30 (d, J = 7.7 Hz, 2H), 7.69 - 7.47 (m, 4H), 7.78 - 7.65 (m, 3H), 8.11 (t, J = 7.55, 2H), 8.53 (d, J = 8.1 Hz, 2H); 13C NMR (400 MHz, CDCl3): δ = 21.6, 121.3, 125.1, 125.52, 126.8, 126.9, 126.9, 127.4, 128.2, 129.3, 132.8, 133.2, 139.2, 143.7, 151.2, 158.6; MS: m/z = 297.
Visible light • Quinazolines • Solvent-free • Photo catalysis
The C-H bonds are abundant in organic compounds, but they do not seem to be operative functional groups owing to the low relativities and high thermodynamic stabilities [1,2]. Therefore, the development a mild and effective organic transformation with clean and renewable energy is of high interest. Solar energy is a unique and renewable resource in nature [3]. Recently, application of visible light in organic transformation was reported by several prominent groups 3 for the formation of new chemical bonds (C–C and C–X). In the past five years, owing to its significant advances in energysaving and environmentally benign features, visible-light photo redox catalysis has witnessed rapid development and attracted considerable attention in both academia and industry [4]. Quinazoline moiety plays a vital role in pharmacological and medicinal chemistry, which is the building block for several naturally occurring alkaloids [5-9]. Microorganisms [10-15], It shows other remarkable biological activity such as anti-diabetic [16], antihypertensive [17], anticancer [18], antitumor [19], antitubercular [20,21], antibacterial [22], anti-inflammatory [23], antiviral [24], and it also act as selective inhibitors of the tyrosine kinase activity of the epidermal growth
factor receptor (EGFR) [25], 3, 4-dihydroquinazoline derivatives shows the excellent T-type calcium channel blocking activity [26,27], it also use as ligand for benzodiazepine and neurotransmitter gamma-aminobutyric acid [GABA] receptors in the central nervous system [CNS] [28], DNA binders [29,30]. In the literature, different methodologies are reported for the synthesis of quinazolines under different reaction condition and reagents, such as Bu3SnH [31], microwave [32], CsOH [33], Zn (OTf)2 [34], Microwave- NaOH [35], NH4OAc-H2O [36], I2 [37]. However many reported methods suffer from drawback such as drastic reaction condition, high temperature, volatile organic solvents, toxic reagents, use of expensive metal catalysts, and long reaction time. All such types of drawbacks prompt researchers to develop alternate route for the synthesis of quinazolines.
The present method
In the present method, quinazoline derivatives have been synthesized using visible light from the reaction of 2- aminobenzophenone, aldehyde and ammonium acetate under catalyst-free and solvent-free conditions. Respective was shown in Figure 1.
Figure 1. Synthesis of quinazoline derivatives.
Reaction conditions
2-aminobenzophenone (1 mmol), benzaldehyde (1 mmol), ammonium acetate (2.5 mmol) was kept under visible light (using an LED bulb (λmax=450 nm) for the appropriate time.
We have developed highly efficient method for the synthesis of quinazoline derivatives via visible light mediated C-H activation. The advantages of the present method are use of eco-friendly conditions, easily available starting materials; high yields, short reaction time and less energy consume process.
| Entry | Catalyst | Loading | Reaction Conditions | Time (h/min) | Solvent |
|---|---|---|---|---|---|
| 1 | Bu3SnH/Triethyl Borane | 0.76/3.6 equiv. | inert | 10/ | dry toluene |
| 2 | Nil | --- | 300 W hn at 150°C | 10/ | Solvent-free |
| 3 | Zn (OTf)2 | 5 mol | reflux | 6-12/ | toluene |
| 4 | Moelcular iodine | 10 mol | 40°C | 2.5/ | neat or ethanol |
| 5 | CsOH | 0.5 mmol | 60°C | 24/ | acetonitrile |
| 6 | NaOH | 2 mol | Hg Lamp 335 nm | 2-5.5/ | acetonitrile |
| 7 | HCOONH4 | 20 equiv. | Microwave, | /4-20 | Nil |
| PhCOCl, Et3N | high pressure | ||||
| 8 | HCOONH4 | 2.5 equiv. | Visible light (450 nm) | /30-40 | Solvent-free |
Table 2. Comparative studies of catalyst with present methods.
Dr. Ravi Varala thanks Dr. Ch. V. Rajasekhar for his kind support and encouragement.
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