Abstract
A convenient method for the synthesis of functionalized spiroindolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazoles from indolo[2,1-b]quinazoline-6,12-diones and 13 hydrazonoyl chlorides in refluxing MeCN is described. These transformations are highlighted by inert atmosphere and lack of activator or metal promoters.
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Introduction
Development of heterocyclic synthesis has always been an important area in synthetic organic chemistry [1]. Spiro heterocycles are regarded as a privileged framework because of their rigidity, three-dimensional geometries, and wide distribution in various natural products and synthetic molecules. Currently, these spirans are attracting considerable interest in organic chemistry because of their molecular structure and diverse biological activities [2]. In particular, spiroindoles represent important structural motifs that can be found in many biologically active synthetic compounds and natural products [3, 4].
Synthesis of spirooxindoles is significant in medicinal chemistry due to their biological and pharmacological properties [5, 6]. Spirooxindoles are found in many natural products [7, 8], which often possess antitumor [9], antimicrobial [10], antibacterial [11], antimalarial [12], and anti-inflammatory [13] activities.
Heterocyclic systems containing 1,3,4-oxadiazole moiety are synthetic interest due to their potential biological activities [14]. Beside the numerous applications in medicinal chemistry [15, 16], 1,3,4-oxadiazoles are building blocks in the synthesis of natural products [17]. Furthermore, oxadiazoles have found practical applications as organic light-emitting diodes and liquid crystals [18].
Quinazolines are important nitrogen-containing heterocyclic systems that have been studied because of their presence in different natural products and synthetic drugs [19]. Quinazoline derivatives are also used in veterinary, agrochemical, and pharmaceutical industries [20].
Natural alkaloid tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and its analogs are found to exhibit anti-tubercular activity [21]. Tryptanthrin (Fig. 1) consists of a quinazoline ring fused to an indole moiety with carbonyl groups in the 6 and 12 positions [22]. Various approaches have been explored for efficient construction of this skeleton [23]. The derivatives of tryptanthrin, such as methylisatoid, candidine, ophiuroidine, phaitanthrin A–E, (±)-cruciferane, and cephalanthrine A–B (Fig. 1), have been found in plants and show broad spectrum of biological activities [24,25,26,27].
Tryptanthrin and related biologically active alkaloids
Results and discussion
Stimulated by the structure and biological significance of tryptanthrin motif, the construction of this type of nucleus has received much attention from the organic chemistry community [28,29,30]. Reaction between isatoic anhydride and isatin derivatives, in the presence of a base, is a convenient method for the synthesis of tryptanthrin derivatives [19, 31]. The synthesis of tryptanthrins has been previously reported under different reaction conditions [28, 32, 33].
Nitrile imines are easily generated in situ by treatment of hydrazonoyl chlorides [34] with Et3N [35]. The reaction of these 1,3-dipoles with a carbonyl group constitutes an effective method for the synthesis of structurally complex spiroindolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazoles from readily available precursors [36]. In continuation of our interest in the synthesis of heterocyclic compounds using nitrile imines [37], we describe an efficient procedure for the synthesis of 5′-aryl-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-ones 3 from tryptanthrins 1 and hydrazonoyl chlorides 2. Thus, stirring a mixture of 1a and 2a in MeOH in the presence of Et3N at 60 °C for 4 h led to the formation of 3a in 10% yield (Table 1, entry 1). Product 3a was obtained in 40% yield in CH2Cl2 (Table 1, entry 5). The use of MeCN as solvent led to an improved yield of 53% (Table 1, entry 6). Compound 3a was obtained in 76% yield in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) (Table 1, entry 7). Finally, when the reaction was performed in MeCN at 80 °C in the presence of Et3N, the yield was 85%.
Then, we used the optimized reaction conditions to prepare a series of functionalized spirooxadiazoles 3a–3 m from 1 to 2. The reactions proceeded smoothly providing the spirooxadiazole derivatives in moderate-to-good yields (Table 2).
The structures of products 3a–3 m were confirmed by their IR, 1H NMR, and 13C NMR spectroscopic data. The mass spectra of products 3 displayed the molecular ion peaks at appropriate m/z values. The 1H NMR spectrum of 3a showed characteristic multiplets for the aromatic protons at 6.75–8.68 ppm. The 1H-decoupled 13C NMR spectrum of 3a showed 24 signals in agreement with the proposed structure.
A plausible mechanism for the formation of product 3 is given in Scheme 1. Presumably, the initial event involves the formation of nitrile imine intermediate 4 from the reaction of hydrazonoyl chloride and Et3N. Then, the 1,3-dipolar cycloaddition reaction of intermediate 4 with the C=O group of tryptanthrin 1 generates product 3 (Scheme 1).
Conclusion
In summary, we have developed an efficient method for the synthesis of 5′-aryl-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-ones from indolo[2,1-b]quinazoline-6,12-diones and hydrazonoyl chlorides in refluxing MeCN. This protocol has some advantages such as using available starting materials, relatively short reaction time, neutral reaction conditions, and high yields of product.
Experimental
All purchased solvents and chemicals were of analytical grade and used without further purification. Melting points and IR spectra of all the compounds were measured on an Electrothermal 9100 apparatus and a Shimadzu IR-460 spectrometer, respectively. The 1H and 13C NMR spectra were obtained with a BRUKER DRX-500 AVANCE instrument using CDCl3 as applied solvent and TMS as internal standard at 500.1 and 125.7 MHz, respectively. The abbreviations used for NMR signals: s = singlet, d = doublet, t = triplet, and m = multiplet. Mass spectra were recorded on an FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. Elemental analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer.
General procedure for the preparation of compounds 3a–3m
A mixture of tryptanthrin 1 (1 mmol), hydrazonoyl chloride 2 (1 mmol), and Et3N (1 mmol) in 5 cm3 MeCN was stirred in 80 °C for 4–6 h. After completion of the reaction (TLC), the mixture was filtered and the precipitate washed with EtOH to afford the pure products 3.
3′,5′-Diphenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3a, C28H18N4O2)
Yellow powder; yield: 0.38 g (85%); m.p.: 235 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.75–6.79 (m, 3H, Ar), 7.06 (t, 3J = 7.3 Hz, 2H, Ar), 7.38 (t, 3J = 7.55 Hz, 1H, Ar), 7.44–7.76 (m, 8H, Ar), 7.93–7.95 (m, 2H, Ar), 8.43 (d, 3J = 7.9 Hz, 1H, Ar), 8.68 (d, 3J = 8.4 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.8 (C), 114.5 (2 CH), 117.6 (CH), 121.0 (CH), 122.4 (C), 125.0 (C), 125.8 (CH), 126.2 (C), 126.5 (2 CH), 126.9 (CH), 127.5 (CH), 128.3 (CH), 128.5 (2 CH), 128.8 (CH), 129.1 (2 CH), 130.6 (CH), 132.9 (CH), 134.6 (CH), 139.4 (C), 141.9 (C), 146.9 (C), 152.0 (C=N), 153.2 (C=N), 159.3 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1696 (C=O), 1651 (C=N), 1599 (C=N) cm−1; MS (70 eV): m/z (%) = 442 (59, M+), 346 (8), 322 (54), 294 (5), 279 (8), 248 (69), 220 (22), 194 (100), 167 (17), 149 (22), 121 (11), 105 (57), 91 (89), 77 (47), 57 (18).
5′-(4-Fluorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3b, C28H17FN4O2)
Yellow powder; yield: 0.40 g (87%); m.p.: 235 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.76–6.80 (m, 3H, Ar), 7.07 (t, 3J = 7.6 Hz, 2H, Ar), 7.15 (t, 3J = 8.6 Hz, 2H, Ar), 7.38 (t, 3J = 7.55 Hz, 1H, Ar), 7.54–7.57 (m, 1H, Ar), 7.64–7.76 (m, 4H, Ar), 7.92–7.95 (m, 2H, Ar), 8.43 (d, 3J = 7.8 Hz, 1H, Ar), 8.69 (d, 3J = 8 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.7 (C), 114.5 (2 CH), 115.8 (2 CH), 117.6 (CH), 121.1 (C), 121.2 (C), 122.4 (C), 125.7 (CH), 126.0 (CH), 126.9 (CH), 127.5 (CH), 128.4 (CH), 128.6 (2 CH), 128.8 (CH), 129.1 (2 CH), 133.0 (CH), 134.6 (CH), 139.4 (C), 141.8 (C), 146.9 (C), 151.3 (C=N), 153.1 (C=N), 159.3 (C=O), 164.1 (C–F) ppm; IR (KBr): \( \bar{v} \) = 1692 (C=O), 1663 (C=N), 1593 (C=N) cm−1; MS (70 eV): m/z (%) = 460 (29, M+), 367 (4), 322 (7), 246 (4), 212 (66), 192 (2), 177 (2), 149 (2), 123 (19), 91 (100), 69 (17), 55 (10).
3′-Phenyl-5′-(p-tolyl)-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3c, C29H20N4O2)
Yellow powder; yield: 0.36 g (80%); m.p.: 220 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 2.42 (s, 3H, Ar), 6.75–6.81 (m, 3H, Ar), 7.06 (t, 3J = 7.8 Hz, 2H, Ar), 7.27 (d, 3J = 7.7 Hz, 2H, Ar), 7.37 (t, 3J =7.5 Hz, 1H, Ar), 7.54–7.76 (m, 5H, Ar), 7.84 (d, 3J =7.9 Hz, 2H, Ar), 8.43 (d, 3J = 7.8 Hz, 1H, Ar), 8.69 (d, 3J = 8.0 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.62 (Me), 98.4 (C), 114.5 (2 CH), 117.6 (CH), 120.9 (CH), 122.2 (C), 122.4 (C), 125.8 (CH), 126.2 (C), 126.5 (2 CH), 126.9 (CH), 127.5 (CH), 128.3 (CH), 128.8 (CH), 129.0 (2 CH), 129.3 (2 CH), 132.9 (CH), 134.6 (CH), 139.4 (C), 141.0 (C), 142.0 (C), 146.9 (C), 152.3 (C=N), 153.3 (C=N), 159.3 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1691 (C=O), 1651 (C=N), 1600 (C=N) cm−1; MS (70 eV): m/z (%) = 456 (60, M+), 363 (7), 322 (2), 246 (5), 208 (100), 181 (4), 119 (15), 91 (57), 64 (5).
5′-(3-Chlorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3d, C28H17ClN4O2)
Yellow powder; yield: 0.41 g (86%); m.p.: 220 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.77–6.80 (m, 3H, Ar), 7.07 (t, 3J = 7.8 Hz, 2H, Ar), 7.37–7.44 (m, 3H, Ar), 7.55–7.75 (m, 5H, Ar), 7.82 (d, 3J = 7.6 Hz, 1H, Ar), 7.92 (s, 1H, Ar), 8.43 (d, 3J = 7.9 Hz, 1H, Ar), 8.69 (d, 3J = 8.3 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.8 (C), 114.5 (2 CH), 117.6 (CH), 121.3 (C), 122.4 (C), 124.5 (CH), 125.7 (CH), 125.9 (C), 126.4 (CH), 126.7 (CH), 127.0 (CH), 127.5 (CH), 128.4 (CH), 128.8 (CH), 129.1 (2 CH), 129.9 (CH), 130.5 (CH), 133.1 (CH), 134.6 (CH), 134.7 (C), 139.5 (C), 141.6 (C), 146.8 (C), 150.9 (C=N), 152.9 (C=N), 159.3 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1686 (C=O), 1649 (C=N), 1598 (C=N) cm−1; MS (70 eV): m/z (%) = 476 (42, M+), 383 (5), 368 (4), 322 (31), 246 (7), 228 (66), 165 (5), 138 (12), 111 (9), 91 (100), 77 (8), 64 (10).
5′-(4-Chlorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3e, C28H17ClN4O2)
Yellow powder; yield: 0.43 g (90%); m.p.: 240 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.77–6.79 (m, 3H, Ar), 7.07 (t, 3J = 7.8 Hz, 2H, Ar), 7.38 (t, 3J = 7.55 Hz, 1H, Ar), 7.43 (d, 3J = 8.55 Hz, 2H, Ar), 7.54–7.60 (m, 1H, Ar), 7.64–7.67 (m, 2H, Ar), 7.71–7.76 (m, 2H, Ar), 7.86 (d, 3J =8.5 Hz, 2H, Ar), 8.42 (d, 3J = 7.85 Hz, 1H, Ar), 8.68 (d, 3J = 8.3 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.7 (C), 114.5 (2 CH), 117.6 (CH), 121.2 (CH), 122.4 (C), 123.5 (C), 125.7 (CH), 125.9 (C), 127.0 (CH), 127.5 (CH), 127.7 (2 CH), 128.4 (CH), 128.8 (CH), 128.9 (2 CH), 129.1 (2 CH), 133.0 (CH), 134.6 (CH), 136.6 (C), 139.4 (C), 141.7 (C), 146.8 (C), 151.3 (C=N), 153.0 (C=N), 159.3 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1690 (C=O), 1652 (C=N), 1601 (C=N) cm−1; MS (70 eV): m/z (%)=476 (34, M+), 383 (4), 322 (8), 246 (4), 228 (57), 138 (13), 111 (8), 91 (100), 78 (6), 64 (8).
5′-(4-Nitrophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3f, C28H17N5O4)
Orange powder; yield: 0.41 g (85%); m.p.: 240 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.79–6.83 (m, 3H, Ar), 7.09 (t, 3J = 7.0 Hz, 2H, Ar), 7.39-7.73 (m, 6H, Ar), 8.06 (d, 3J = 8.0 Hz, 2H, Ar), 8.30 (d, 3J = 8.15 Hz, 2H, Ar), 8.42 (d, 3J = 7.6 Hz, 1H, Ar), 8.69 (d, 3J = 7.75 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 99.2 (C), 114.6 (2 CH), 117.7 (CH), 121.8 (C), 122.4 (C), 123.9 (2 CH), 125.4 (C), 125.7 (CH), 126.9 (2 CH), 127.0 (CH), 127.6 (CH), 128.6 (CH), 128.7 (CH), 129.2 (2 CH), 130.8 (CH), 133.3 (CH), 134.7 (CH), 139.5 (C), 141.0 (C), 146.7 (C), 148.5 (C=N), 150.2 (C=N), 152.6 (C), 159.1 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1692 (C=O), 1651 (C=N), 1597 (C=N) cm−1; MS (70 eV): m/z (%) = 487 (49, M+), 458 (4), 394 (6), 322 (17), 296 (4), 239 (43), 225 (5), 204 (39), 179 (5), 150 (7), 91 (100), 77 (8), 51 (5).
8-Chloro-3′,5′-diphenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3g, C28H17ClN4O2)
Yellow powder; yield: 0.41 g (86%); m.p.: 260 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.78–6.83 (m, 3H, Ar), 7.07–7.12 (m, 2H, Ar), 7.44–7.75 (m, 8H, Ar), 7.92–7.95 (m, 2H, Ar), 8.42 (d, 3J = 7.9 Hz, 1H, Ar), 8.64 (d, 3J = 8.55 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.0 (C), 114.5 (2 CH), 118.7 (CH), 121.3 (CH), 122.2 (C), 124.7 (C), 126.0 (CH), 126.5 (2 CH), 126.9 (C), 128.1 (C), 128.5 (CH), 128.6 (2 CH), 128.9 (CH), 129.2 (2 CH), 130.7 (CH), 133.0 (CH), 133.2 (CH), 134.8 (CH), 137.8 (C), 141.6 (C), 146.8 (C), 152.0 (C=N), 152.7 (C=N), 159.1 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1697 (C=O), 1650 (C=N), 1599 (C=N) cm−1; MS (70 eV): m/z (%) = 476 (61, M+), 380 (10), 356 (49), 328 (8), 313 (7), 282 (71), 254 (19), 228 (100), 201 (17), 183 (20), 155 (9), 139 (55), 125 (42), 111 (39), 91 (89), 77 (42), 57 (15).
8-Chloro-3′-phenyl-5′-(p-tolyl)-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3h, C29H19ClN4O2)
Yellow powder; yield: 0.41 g (83%); m.p.: 250 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 2.44 (s, 3H, Me), 6.79–6.82 (m, 3H, Ar), 7.08–7.11 (m, 2H, Ar), 7.27.29 (m, 2H, Ar), 7.56–7.76 (m, 5H, Ar), 7.83 (d, 3J =8.2 Hz, 2H, Ar), 8.42 (d, 3J = 7.95 Hz, 1H, Ar), 8.63 (d, 3J = 8.6 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.63 (Me), 97.9 (C), 114.5 (2 CH), 118.7 (CH), 121.2 (CH), 121.9 (C), 122.2 (C), 126.0 (CH), 126.5 (2 CH), 126.9 (C), 128.2 (C), 128.5 (CH), 128.9 (CH), 129.2 (2 CH), 129.3 (2 CH), 132.9 (CH), 133.1 (CH), 134.7 (CH), 137.7 (CH), 141.2 (C), 141.7 (C), 146.8 (C), 152.2 (C=N), 152.7 (C=N), 159.2 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1690 (C=O), 1649 (C=N), 1602 (C=N) cm−1; MS (70 eV): m/z (%) = 490 (50, M+), 397 (12), 356 (8), 280 (11), 242 (100), 215 (9), 153 (25), 125 (21), 91 (65), 64 (8).
8-Chloro-5′-(4-chlorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3i, C28H16Cl2N4O2)
Yellow powder; yield: 0.45 g (88%); m.p.: 250 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.78–6.83 (m, 3H, Ar), 7.10 (t, 3J = 7.8 Hz, 2H, Ar), 7.45 (d, 3J = 8.4 Hz, 2H, Ar), 7.57–7.75 (m, 5H, Ar), 7.86 (d, 3J =8.4 Hz, 2H, Ar), 8.42 (d, 3J = 7.65 Hz, 1H, Ar), 8.64 (d, 3J = 8.55 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.2 (C), 114.5 (2 CH), 118.7 (CH), 121.5 (CH), 122.2 (C), 123.2 (C), 126.0 (CH), 127.0 (CH), 127.7 (2 CH), 127.9 (C), 128.6 (C), 128.8 (CH), 128.9 (2 CH), 129.2 (2 CH), 133.1 (CH), 133.2 (CH), 134.8 (CH), 136.8 (C), 137.8 (C), 141.4 (C), 146.7 (C), 151.2 (C=N), 152.5 (C=N), 159.1 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1698 (C=O), 1662 (C=N), 1612 (C=N) cm−1; MS (70 eV): m/z (%) = 510 (25, M+), 418 (8), 356 (10), 280 (5), 262 (22), 172 (9), 220 (11), 184 (73), 93 (34), 67 (23), 91 (100), 64 (8).
8-Bromo-3′,5′-diphenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3j, C28H17BrN4O2)
Yellow powder; yield: 0.44 g (85%); m.p.: 255 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.78–6.81 (m, 3H, Ar), 7.08 (t, 3J = 7.85 Hz, 2H, Ar), 7.44–8.03 (m, 10H, Ar), 8.39 (d, 3J = 8.05 Hz, 1H, Ar), 8.50–8.56 (dd, 3J = 8.55 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 97.9 (C), 114.5 (2 CH), 119.0 (CH), 119.4 (CH), 120.7 (CH), 121.3 (CH), 122.2 (C), 124.7 (C), 126.5 (2 CH), 126.9 (CH), 127.5 (C), 128.1 (C), 128.6 (2 CH), 129.2 (2 CH), 130.7 (CH), 134.7 (CH), 135.9 (CH), 138.2 (CH), 140.5 (C), 141.6 (C), 146.8 (C), 152.0 (C=N), 152.5 (C=N), 159.1 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1698 (C=O), 1648 (C=N), 1599 (C=N) cm−1; MS (70 eV): m/z (%) = 520 (5, M+), 442 (5), 402 (8), 368 (5), 328 (100), 313 (8), 298 (32), 270 (12), 248 (10), 219 (22), 191(57), 164 (35),144 (15), 117(10), 100 (20), 91 (45), 75 (18), 57 (7).
8-Bromo-5′-(4-fluorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3k, C28H16BrFN4O2)
Yellow powder; yield: 0.46 g (85%); m.p.: 255 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.77–6.82 (m, 3H, Ar), 7.09 (t, 3J = 7.85 Hz, 2H, Ar), 7.15 (t, 3J = 8.4 Hz, 2H, Ar), 7.54–7.58 (m, 1H, Ar), 7.72–7.80 (m, 4H, Ar), 7.91–7.94 (m, 2H, Ar), 8.40 (d, 3J = 8.0 Hz, 1H, Ar), 8.56 (d, 3J = 8.55 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.1 (C), 114.5 (2 CH), 115.9 (2 CH), 119.1 (C), 120.7 (C), 121.02 (C), 121.4 (CH), 122.2 (C), 127.0 (CH), 128.2 (CH), 128.6 (CH), 128.7 (CH), 128.7 (CH), 128.9 (2 CH), 129.2 (2 CH), 134.8 (CH), 136.0 (CH), 138.3 (C), 141.6 (C), 146.8 (C), 151.3 (C=N), 152.4 (C=N), 159.1 (C=O), 164.2 (C–F) ppm; IR (KBr): \( \bar{v} \) = 1696 (C=O), 1657 (C=N), 1591 (C=N) cm−1; MS (70 eV): m/z (%) = 538 (10, M+), 445 (4), 402 (6), 326 (10), 308 (12), 212 (93), 123 (57), 91 (100), 77 (8), 64 (8).
8-Bromo-5′-(3-chlorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3l, C28H16BrClN4O2)
Yellow powder; yield: 0.48 g (87%); m.p.: 260 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.78–6.83 (m, 3H, Ar), 7.10 (t, 3J = 7.9 Hz, 2H, Ar), 7.37–7.56 (m, 3H, Ar), 7.72–7.80 (m, 5H, Ar), 7.90 (s, 1H, Ar), 8.40 (d, 3J = 8.0 Hz, 1H, Ar), 8.56 (d, 3J = 8.6 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.2 (C), 114.5 (2 CH), 119.1 (CH), 120.7 (C), 121.6 (CH), 122.2 (C), 124.5 (C), 126.4 (CH), 127.0 (CH), 127.6 (C), 128.1 (C), 128.6 (CH), 128.8 (CH), 129.3 (2 CH), 129.9 (CH), 130.7 (CH), 134.7 (CH), 134.8 (CH), 136.1 (CH), 138.3 (CH), 139.5 (C), 141.3(C), 146.7 (C), 150.8 (C=N), 152.2 (C=N), 159.1 (C=O) ppm; IR (KBr): \( \bar{v} \) = 1694 (C=O), 1653 (C=N), 1597 (C=N) cm−1; MS (70 eV): m/z (%) = 554.01 (25, M+), 461 (5), 401 (10), 324 (12), 306 (12), 262 (8), 227 (93), 203 (5), 165 (8), 138 (35), 109 (10), 91 (100), 64 (9).
8-Bromo-5′-(4-chlorophenyl)-3′-phenyl-3′H,12H-spiro[indolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazol]-12-one (3m, C28H16BrClN4O2)
Yellow powder; yield: 0.49 g (89%); m.p.: 260 °C (decomposed); 1H NMR (500 MHz, CDCl3): δ = 6.77–6.80 (m, 3H, Ar), 7.08 (t, 3J = 7.85 Hz, 2H, Ar), 7.43 (d, 3J = 6.3 Hz, 2H, Ar), 7.55–7.58 (m, 1H, Ar), 7.64–7.67 (m, 2H, Ar), 7.71–7.76 (m, 2H, Ar), 7.87 (d, 3J =8.6 Hz, 2H, Ar), 8.43 (d, 3J = 8.1 Hz, 1H, Ar), 8.69 (d, 3J = 8.2 Hz, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 98.1 (C), 114.5 (2 CH), 119.1 (CH), 120.7 (CH), 121.5 (CH), 122.2 (C), 123.2 (C), 127.0 (C), 127.7 (2 CH), 128.1 (C), 128.6 (CH), 128.8 (CH), 128.9 (2 CH), 129.2 (2 CH), 132.7 (CH), 134.8 (CH), 136.0 (CH), 136.8 (C), 138.3 (C), 141.4 (C), 146.7 (C), 151.2 (C=N), 152.3 (C=N), 159.1 (C=O) ppm; IR (KBr):\( \bar{v} \) = 1699 (C=O), 1659 (C=N), 1610 (C=N) cm−1; MS (70 eV): m/z (%) = 554 (21, M+), 462 (4), 400 (8), 324 (4), 306 (18), 216 (7), 264 (6), 228 (68), 137 (30), 111 (20), 91 (100), 64(8).
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We would like to thank the Research Council of Tarbiat Modares University for supporting this work.
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Yavari, I., Askarian-Amiri, M. & Taheri, Z. A convenient synthesis of spiroindolo[2,1-b]quinazoline-6,2′-[1,3,4]oxadiazoles from tryptanthrin and nitrile imines. Monatsh Chem 150, 1093–1099 (2019). https://doi.org/10.1007/s00706-019-2367-3
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DOI: https://doi.org/10.1007/s00706-019-2367-3