CC BY 4.0 · SynOpen 2019; 03(02): 67-70
DOI: 10.1055/s-0039-1690326
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Click Chemistry Approach to Isoindole-1,3-dione Tethered 1,2,3-Triazole Derivatives

a  Department of Chemistry, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana, Haryana, 133207, India   Email: singh@orgsyn.in
,
a  Department of Chemistry, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana, Haryana, 133207, India   Email: singh@orgsyn.in
,
Antresh Kumar
b  Department of Biotechnology, Central University of South Bihar, Panchanpur, Gaya-824236, India
,
a  Department of Chemistry, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana, Haryana, 133207, India   Email: singh@orgsyn.in
› Author Affiliations
Science and Engineering Research Board, New Delhi (Grant / Award Number: CS-017/2014). R.K. thanks SERB New Delhi for a Fellowship.
Further Information

Publication History

Received: 28 May 2019

Accepted after revision: 06 June 2019

Publication Date:
25 June 2019 (online)

  

Abstract

A convenient and efficient approach for the synthesis of novel 1,2,3-triazole tethered isoindol-1,3-dione conjugates by a nucleophilic substitution reaction of phthalic anhydride with 1,2,3-triazole containing carbohydrazide is described. The latter were prepared by using click chemistry.

 
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  • 16 General procedure for the synthesis of carboxylates 5a–d: To an equimolar solution of azide 6 and alkyne 10 in t-BuOH and water (1:1), sodium ascorbate (20 mmol%) and Cu(OAc)2 (10 mmol%) were added. The reaction was stirred at room temperature until completion of reaction (TLC monitoring). The reaction mixture was filtered, extracted with ethyl acetate, dried over sodium sulfate, filtered, concentrated, and, with the exception of 5a, purified by recrystallization.Ethyl 1-(o-methylphenyl)-1H-1,2,3-triazole-4-carboxylate (5a) (ref. 20): Yield: 82%; orange oil. 1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H), 7.47–7.44 (m, 1 H), 7.40–7.38 (m, 1 H), 7.36–7.33 (m, 2 H), 4.47 (q, J =7.12 Hz, 2 H), 2.22 (s, 3 H), 1.44 (t, J = 7.16 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 160.8, 140.1, 135.7, 133.7, 131.6, 130.4, 128.9, 127.0, 125.9, 61.5, 17.8, 14.3. FTIR (thin film): 3361, 3311, 1725, 1019 cm–1.Ethyl 1-(o-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (5b) (ref. 21): Yield: 72%; orange amorphous solid; mp 78–80 °C. 1H NMR (400 MHz, CDCl3): δ = 8.43 (s, 1 H), 8.16 (dd, J = 8.08, 1.48 Hz, 1 H), 7.88–7.83 (m, 1 H), 7.80–7.76 (m, 1 H), 7.65 (dd, J =1.44, 7.8 Hz, 1 H), 4.46 (q, J = 7.12 Hz, 2 H), 1.44 (t, J = 7.12 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 160.2, 144.2, 140.7, 134.2, 131.6, 129.6, 129.3, 128.3, 125.9, 61.7, 14.3. FTIR (thin film): 3125, 1690, 1510, 1342, 1250 cm–1.Ethyl 1-(p-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (5c) (ref. 22): Yield: 81%; yellow amorphous solid; mp 166–168 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 9.61 (s, 1 H), 8.46–8.42 (m, 2 H), 8.35–8.31 (m, 2 H), 4.42 (q, J = 7.08 Hz, 2 H), 1.41 (t, J = 7.12 Hz, 3 H). 13C NMR (100 MHz, DMSO-d 6): δ = 159.7, 146.9, 140.4, 140.3, 127.1, 125.1, 120.8, 60.8, 14.0. FTIR (thin film): 3123, 1695, 1505, 1338, 1257 cm–1.Ethyl 1-(m-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (5d) (ref. 23): Yield: 79%; yellow amorphous solid; mp 110–112 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 9.62 (s, 1 H), 8.90 (t, J = 2 Hz, 1 H), 8.48–8.46 (m, 1 H), 8.35–8.33 (m, 1 H), 7.87 (t, J = 8.2 Hz, 1 H), 4.42 (q, J = 7.12 Hz, 2 H), 1.42 (t, J = 7.12 Hz, 3 H). 13C NMR (100 MHz, DMSO-d 6): δ = 159.8, 148.4, 140.1, 136.7, 131.3, 127.5, 126.2, 123.4, 115.1, 60.7, 14.1. FTIR (thin film): 3378, 3101, 1697, 1516, 1337, 1251 cm–1
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  • 18 General procedure for the synthesis of carbohydrazides 11a–d: Ester 5 (1.84 mmol) was transferred into a 50 mL flask, and ethanol (10 mL) added. A solution of hydrazine hydrate 12 (80% w/v, 37 mmol) was then added and the mixture was heated to reflux for 30 min at 80 °C. After the completion of the reaction, the solid products were isolated by filtration. 1-(o-Methylphenyl)-1H-1,2,3-triazole-4-carbohydrazide (11a): Yield: 77%; white amorphous solid; mp 80–82 °C. 1H NMR (400 MHz, CDCl3): δ = 8.44 (bs, 1 H), 8.28 (s, 1 H), 7.48–7.44 (m, 1 H), 7.41–7.32 (m, 3 H), 4.13 (bs, 2 H), 2.22 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 160.8, 141.7, 135.8, 133.6, 131.7, 130.4, 127.1, 126.9, 125.9, 17.8. FTIR (thin film): 3326, 3139, 1649, 1260 cm–1. 1-(o-Nitrophenyl)-1H-1,2,3-triazole-4-carbohydrazide (11b): Yield: 74%; white amorphous solid; mp 136–138 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 9.87 (bs, 1 H), 9.02 (s, 1 H), 8.21–8.19 (m, 1 H), 7.96–7.92 (m, 1 H), 7.87–7.82 (m, 2 H), 4.47 (bs, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 158.7, 143.9, 142.3, 134.2, 131.2, 128.9, 127.6, 127.3, 125.4. FTIR (thin film): 3303, 3100, 1666, 1519, 1344 cm–1.1-(p-Nitrophenyl)-1H-1,2,3-triazole-4-carbohydrazide (11c): Yield: 84%; white amorphous solid; mp 260–262 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 9.90 (bs, 1 H), 9.47 (s, 1 H), 8.46–8.42 (m, 2 H), 8.33–8.28 (m, 2 H), 4.50 (bs, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 159.1, 146.9, 143.1, 140.5, 125.3, 124.6, 120.7. FTIR (thin film): 3339, 3103, 1663, 1502, 1346 cm–1.1-(m-Nitrophenyl)-1H-1,2,3-triazole-4-carbohydrazide (11d): Yield: 75%; white amorphous solid; mp 182–184 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 9.91 (bs, 1 H), 9.50 (s, 1 H), 8.81 (s, 1 H), 8.46–8.44 (m, 1 H), 8.35–8.33 (m, 1 H), 7.90 (t, J = 8.2 Hz, 1 H), 4.53 (bs, 2 H). 13C NMR (100 MHz, DMSO-d 6): δ = 158.5, 148.3, 142.9, 136.8, 131.2, 125.9, 124.6, 123.1, 114.9. FTIR (thin film): 3412, 3337, 1661, 1520, 1351 cm–1.General procedure for the synthesis of carboxamides 4a–d: To a 25-mL round-bottom flask fitted with a magnetic stir bar and reflux condenser, were added carbohydrazide 11 (5 mmol), phthalic anhydride 8 (5 mmol), toluene (2 mL) and a catalytic amount of glacial acetic acid. The mixture was heated to reflux for 2 hours with stirring. Following cooling to room temperature, the resulting solid was filtered off and the crude product was purified by recrystallization using various hexane/ethyl acetate mixtures to afford the purified product. N-(1,3-Dioxoisoindolin-2-yl)-1-(o-methylphenyl)-1H-1,2,3-triazole-4-carboxamide (4a): Yield: 79%; white amorphous solid; 256–258 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 11.45 (s, 1 H), 9.07 (s, 1 H), 7.99–7.97 (m, 2 H), 7.96–7.92 (m, 1 H), 7.53–7.49 (m, 2 H), 7.47–7.40 (m, 1 H), 7.24–7.20 (m, 1 H), 7.15–7.12 (m, 1 H), 2.24 (s, 3 H). 13C NMR (100 MHz, DMSO-d 6): δ = 164.9, 164.5, 158.6, 140.1, 135.6, 134.9, 133.12, 131.2, 130.1, 129.5, 129.1, 128.7, 127.9, 126.8, 125.9, 125.1, 123.6, 17.4. FTIR (thin film): 3215, 1720, 1417, 1225 cm−1. N-(1,3-Dioxoisoindolin-2-yl)-1-(o-nitrophenyl)-1H-1,2,3-triazole-4-carboxamide (4b): Yield: 63%; white amorphous solid; mp 276–275 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 10.59 (s,1 H), 9.16 (s, 1 H), 8.23 (dd, J = 1.2, 8 Hz, 1 H), 7.96–7.95 (m, 1 H), 7.90–7.88 (m, 1 H), 7.87–7.83 (m, 2 H), 7.68–7.66 (m, 1 H), 7.63–7.59 (m, 1 H), 7.58–7.54 (m, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 167.6, 167.4, 158.0, 146.9, 142.4, 140.5, 135.8, 134.8, 131.1, 130.8, 129.5, 128.2, 125.3, 125.2, 123.4, 120.9, 120.7. FTIR (thin film): 3117, 1646, 1534, 1344, 1481, 1268 cm−1. N-(1,3-Dioxoisoindolin-2-yl)-1-(p-nitrophenyl)-1H-1,2,3-triazole-4-carboxamide (4c): Yield: 70%; white amorphous solid; mp 296–298 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 11.52 (s, 1 H), 9.74 (s, 1 H), 8.92 (t, J = 2.04 Hz, 1 H), 8.52–8.49 (m, 1 H), 8.38–8.35 (m, 1 H), 7.98–7.89 (m, 5 H). 13C NMR (100 MHz, DMSO-d 6): δ = 164.7, 158.2, 148.4, 141.2, 136.8, 134.8, 131.2, 129.5, 126.5, 126.2, 123.5, 123.4, 115.2. FTIR (thin film): 3268, 3146, 1701, 1579, 1344, 1517, 1262 cm−1. N-(1,3-Dioxoisoindolin-2-yl)-1-(m-nitrophenyl)-1H-1,2,3-triazole-4-carboxamide (4d): Yield: 72%; white amorphous solid; mp 258–260 °C (decomp.). 1H NMR (400 MHz, DMSO-d 6): δ = 11.51 (s, 1 H), 9.77 (s, 1 H), 8.89 (t, J = 1.88 Hz, 1 H), 8.51 (d, J = 1.32 Hz, 1 H), 8.38 (d, J = 1.72 Hz, 1 H), 8.01–7.91 (m, 5 H). 13C NMR (100 MHz, DMSO-d 6): δ = 167.6, 167.5, 158.2, 143.8, 141.5, 135.8, 134.2, 131.3, 131.2, 130.8, 130.3, 129.2, 128.9, 128.2, 128.1, 127.7, 125.4. FTIR (thin film): 3265, 3150, 1698, 1560, 1330, 1510, 1250 cm−1
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