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Synlett 2021; 32(07): 708-712
DOI: 10.1055/s-0040-1706682
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Expedient Synthesis and Antibacterial Activity of Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives Using Piperidine as Catalyst

Nangagoundan Vinoth
a   Department of Chemistry, Periyar University, Salem-636011, Tamilnadu, India
,
Pullar Vadivel
b   Department of Chemistry, Salem Sowdeswari College, Salem-636010, Tamilnadu, India
,
Appaswami Lalitha∗
a   Department of Chemistry, Periyar University, Salem-636011, Tamilnadu, India
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Abstract

A convenient synthesis of 2′-amino-7′,7′-dimethyl-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile derivatives has been designed using different substituted isatins, various 5,5-dimethyl-3-(2-phenylhydrazinyl)cyclohex-2-enones (arylhydrazones of dimedone) and malononitrile in ethanol with piperidine as catalyst at room temperature. The structures of the synthesized compounds have been elucidated by various spectroscopic techniques. The selected compounds have also been evaluated for their antibacterial activities against human pathogenic bacteria.

Key words

antibacterial activity - base catalysts - quinolines - indoline - multistep synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706682.
  • Supporting Information


Publication History

Received: 19 October 2020

Accepted after revision: 21 December 2020

Article published online:
22 January 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • 42 Synthesis of Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives; General Procedure: All the chemicals used for this study were commercially available and were freshly used after being purified by standard procedures. All the conventional reactions were performed with 50 mL RB flasks. TLC was performed on Merck pre-coated aluminum sheets of 60 F-254 silica gel plates with visualization by UV-light using a 1:1 mixture of ethyl acetate and n-hexane as solvent system. Melting points were determined in capillary tubes with a Büchi melting point BB-545 apparatus and are uncorrected. 1H and 13C NMR spectra were recorded with Bruker 400 MHz high-resolution NMR spectrometers. DMSO-d 6 was used as a solvent for the NMR spectral measurements and the spectra were recorded in parts per million with TMS as internal standard. Spectral Data for Tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile Derivatives
    2′-Amino-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6a):     Yield: 87%; white solid; mp 230–232 °C. IR (KBr): 3413.80, 3261.14, 3030.31, 2952.89, 2184.18, 1717.19, 16630.76 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.22 (s, 1 H, -NH), 8.79 (s, 1 H, -NH), 7.38–6.42 (m, 11 H, Ar-H and –NH2), 2.19–1.91 (m, 4 H, 2 × CH2), 0.93–0.81 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.17, 28.67 (C(CH3)2), 31.17 (-CH), 38.36 (-CH2), 49.60 (CH2-CO), 58.74 (C-CN), 109.39, 110.73, 111.03, 120.79, 121.89, 122.02, 128.16, 130.10, 137.09, 142.15, 153.09, 179.82, 190.10 (Ar-C). 2′-Amino-6-methoxy-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6b): Yield: 80%; white solid; mp 226–228 °C; IR (KBr): 3429.77, 3248.56, 3030.35, 2957.27, 2186.55, 1723.40, 1650.66 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.05 (s, 1 H, -NH), 8.80 (s, 1 H, -NH), 7.35–6.43 (m, 10 H, Ar-H and –NH2), 3.66 (s, 3 H, OCH3), 2.19–1.93 (m, 4 H, 2 × CH2), 0.93–0.74 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.13, 28.56 (C(CH3)2), 32.18 (-CH), 38.34 (-CH2), 49.41 (CH2-CO), 55.63 (-OCH3), 58.80 (C-CN), 109.55, 111.02, 120.66, 129.89, 135.53, 147.25, 155.24, 179.67 (Ar-C). 2′-Amino-6-chloro-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6c): Yield: 76%; white solid; mp 230–232 °C; IR (KBr): 3327.35, 3096.69, 2958.88, 2876.92, 1722.43, 1691.16, 1644.67 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.99 (s, 1 H, -NH), 8.86 (s, 1 H, -NH), 7.44–6.65 (m, 10 H, Ar-H and –NH2), 1.94–1.84 (m, 4 H, 2 × CH2), 0.94–0.80 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 26. 44, 27.04, 28.73 (C(CH3)2), 33.68 (-CH2), 50.63 (CH2-CO), 59.10 (C-CN), 100.59, 108.51, 111.70, 112.99, 121.99, 126.89, 133.56, 144.76, 167.54, 180.32, 194.66, 203.54 (Ar-C). 2′-Amino-6-bromo-2,5′-dioxo-1′-(phenylamino)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6d): Yield: 79%; white solid; mp 232–234 °C; IR (KBr): 3422.48, 3246.68, 3029.36, 2954.58, 2186.34, 1724.50 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.04 (s, 1 H, -NH), 8.94 (s, 1 H, -NH), 7.50–6.58 (m, 9 H, Ar-H and –NH2), 2.16–2.03 (m, 4 H, 2 × CH2), 0.94–0.82 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.65, 28.01 (C(CH3)2), 38.18 (-CH2), 110.26, 111.55, 113.53, 119.10, 125.91, 130.78, 139.35, 146.42, 155.81, 179.41, 194.33 (Ar-C). 2′-Amino-2,5′-dioxo-1′-(phenylamino)-6-(trifluoromethoxy)-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6e): Yield: 83%; white solid; mp 230–232 °C; IR (KBr): 3477.11, 3361.15, 3210.53, 3111.86, 3026.47, 2959.66, 2185.02, 1707.70 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.45 (s, 1 H, -NH), 8.82 (s, 1 H, -NH), 7.33–6.56 (m, 10 H, Ar-H and –NH2), 2.12–1.94 (m, 4 H, 2 × CH2), 0.93–0.71 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): 26.84, 27.19, 28.51 (C(CH3)2), 38.34 (-CH2), 49.44 (CH2-CO), 57.80 (C-CN), 110.04, 111.97, 116.14, 119.15, 120.71, 121.29, 129.90, 138.52, 141.26, 146.82, 147.13, 155.88, 179.92, 194.26 (Ar-C). 2′-Amino-1′-((4-chlorophenyl)amino)-6-methoxy-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6f): Yield: 85%; white solid; mp 224–226 °C; IR (KBr): 3414.56, 3273.42, 3032.56, 2953.14, 2185.96, 1717.59, 1632.96 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.66 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.39–6.47 (m, 9 H, Ar-H and –NH2), 3.66 (s, 3 H, OCH3), 2.10–1.95 (m, 4 H, 2 × CH2), 0.94–0.77 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.30, 28.57 (C(CH3)2), 39.35 (-CH2), 49.39 (CH2-CO), 55.66 (-OCH3), 58.89 (C-CN), 109.58, 110.30, 111.16, 119.30, 124.08, 129.68, 135.57, 138.28, 145.93, 152.71, 155.04, 179.63, 194.10 (Ar-C). 2′-Amino-1′-((4-chlorophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6g): Yield: 88%; white solid; mp 218–220 °C; IR (KBr): 3835.27, 3740.79, 3647.38, 3588.71, 3415.87, 3274.02, 3022.86, 2955.53, 2365.09, 2187.03, 1717.43, 1633.23 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.23 (s, 1 H, -NH), 8.92 (s, 1 H, -NH), 7.43–6.48 (m, 10 H, Ar-H and –NH2), 2.14–1.92 (m, 4 H, 2 × CH2), 0.94–0.76 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): 27.27, 28.61 (C(CH3)2), 32.21, 38.31 (-CH2), 48.98 (CH2-CO), 58.88 (C-CN), 109.41, 110.86, 113.48, 122.04, 128.15, 129.69, 142.15, 145.93, 146.15, 152.68, 179.88 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6h): Yield: 85%; white solid; mp 218–220 °C; IR (KBr): 3834.72, 3740.38, 3670.97, 3647.88, 3418.33, 3252.46, 2952.41, 2867.11, 2353.77, 2187.88, 1720.88 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.23 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.55–6.48 (m, 10 H, Ar-H and –NH2), 2.14–1.92 (m, 4 H, 2 × CH2), 0.94–0.77 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.24, 28.59 (C(CH3)2), 32.21, 38.31 (-CH2), 48.98 (CH2-CO), 58.88 (C-CN), 109.41, 110.83, 111.15, 111.68, 113.96, 119.30, 121.90, 122.05, 123.14, 128.16, 132.52, 136.98, 137.24, 142.14, 146.34, 152.65, 155.03, 179.77, 194.10 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-6-methoxy-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6i): Yield: 77%; white solid; mp 222–224 °C; IR (KBr): 3414.69, 3275.63, 3034.04, 2953.82, 2185.81, 1717.55, 1678.20, 1633.28 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.06 (s, 1 H, -NH), 8.93 (s, 1 H, -NH), 7.51–6.47 (m, 9 H, Ar-H and –NH2), 3.63 (s, 3 H, OCH3), 2.15–1.95 (m, 4 H, 2 × CH2), 1.08–0.84 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.28, 28.55 (C(CH3)2), 32.23, 49.39 (CH2-CO), 55.67 (-OCH3), 58.85 (C-CN), 109.58, 109.74, 110.33, 115.15, 112.39, 113.97, 132.50, 135.57, 138.28, 146.34, 152.68, 155.02, 179.63, 194.10 (Ar-C). 2′-Amino-6-chloro-1′-((4-chlorophenyl)amino)-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6j): Yield: 79%; white solid; mp 232–234 °C; IR (KBr): 3914.60, 3790.02, 3702.05, 3423.01, 3249.96, 3030.35, 2956.62, 2355.64, 2186.71, 1723.46, 1654.28, 1630.26 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.39 (s, 1 H, -NH), 8.98 (s, 1 H, -NH), 7.39–6.58 (m, 9 H, Ar-H and –NH2), 2.15–2.03 (m, 4 H, 2 × CH2), 0.94–0.80 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.69, 28.07 (C(CH3)2), 32.31, 38.20 (-CH2), 49.29 (CH2-CO), 58.05 (C-CN), 110.22, 113.66, 123.20, 124.15, 125.79, 127.91, 128.08, 129.68, 138.96, 139.23, 141.30, 141.37, 145.89, 152.93, 153.13, 155.60, 179.52, 194.30 (Ar-C). 2′-Amino-1′-((4-bromophenyl)amino)-6-chloro-7′,7′-dimethyl-2,5′-dioxo-5′,6′,7′,8′-tetrahydro-1′H-spiro[indoline-3,4′-quinoline]-3′-carbonitrile (6k): Yield: 76%; white solid; mp 228–230 °C; IR (KBr): 3423.43, 3242.89, 2956.16, 2871.31, 2186.75, 1725.02, 1654.56, 1630.70 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.39 (s, 1 H, -NH), 8.94 (s, 1 H, -NH), 7.51–6.58 (m, 9 H, Ar-H and –NH2), 2.15–2.03 (m, 4 H, 2 × CH2), 0.94 (m, 6 H, 2 × CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 27.65, 28.27 (C(CH3)2), 32.30, 38.19 (-CH2), 49.29 (CH2-CO), 58.02 (C-CN), 110.21, 111.73, 114.12, 123.20, 125.79, 127.92, 128.08, 132.50, 132.65, 138.94, 139.22, 141.29, 146.29, 152.90, 153.09, 155.57, 179.52, 194.31 (Ar-C).