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Synlett 2012; 23(6): 859-862
DOI: 10.1055/s-0031-1290487
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© Georg Thieme Verlag Stuttgart · New York

Isoquinoline-Catalyzed Reaction of Phenacyl Bromide and N,N-Dialkyl­carbodiimides: Novel Synthesis of Azirines

Abdolali Alizadeh*
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran, Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Atieh Rezvanian
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran, Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
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Further Information

Publication History

Received: 26 September 2011

Accepted after revision: 02 February 2012

Publication Date:
16 March 2012 (online)

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Abstract

A practical and efficient procedure for the synthesis of polysubstituted azirines and in some cases benzamides was developed through reaction of phenacyl bromides and N,N-dialkylcarbodiimides, in the presence of catalytic amount of isoquinoline in dry acetonitrile under mild conditions at ambient temperature. The salient features of this process include operational simplicity, high yields, and easily accessible starting materials.

Key words

azirine - benzamide - phenacyl bromide - dialkylcarbodiimide - isoquinoline
 

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  • 13 In a 25 mL round-bottom flask, the requisite phenacyl bromide (1 mmol) and N,N-dialkyl carbodiimide (1 mmol) were taken up in the presence of 10 mol% of isoquinoline in MeCN (5 mL). Then K2CO3 (1 mmol) was added, and the mixture was stirred continuously for 6 h at r.t. After completion of the reaction (monitored by TLC), the solvent was removed under reduced pressure, and the residue was purified by column chromatography using n-hexane–EtOAc (8:1).[1-Isopropyl-3-(isopropylamino)-1H-aziren-2-yl](phenyl)methanone (3a)Yellow powder; mp 150–152 °C; yield: 0.20 g (82%). IR (KBr): νmax = 3274 (NH), 1698 (NC=C), 1620 (C=O), 1248 (CN) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 0.98 (d, 3 J HH = 6.6 Hz, 6 H, CH3), 1.43 (d, 3 J HH = 6.7 Hz, 6 H, CH3), 3.80–3.85 (m, 1 H, CH), 4.37–4.41 (m, 1 H, CH), 6.70 (s, 1 H, NH), 7.25–7.51 (m, 5 H, 5 CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 20.31 (2 CH3), 21.72 (2 CH3), 42.16 (CH), 49.80 (CH), 125.83 (CCO), 125.84 (2 CH of Ph), 128.12 (2 CH of Ph), 136.06 (CH of Ph), 136.67 (Cipso –CO), 153.60 (NCN), 171.87 (CO). MS (EI, 70 eV): m/z (%) = 244 (6) [M+], 227 (100), 214 (20), 201 (52), 170 (31), 145 (26), 115 (92), 97 (45), 77 (80), 57 (88), 43 (87). Anal. Calcd for C15H20N2O (244.335): C, 73.74; H, 8.25; N, 11.47. Found: C, 73.72; H, 8.26; N, 11.46.[1-Cyclohexyl-3-(cyclohexylamino)-1H-aziren-2-yl](phenyl)methanone (3b)Yellow powder; mp 170–172 °C; yield: 0.310 g (77%). IR (KBr): νmax = 3429 (NH), 1699 (NC=C), 1599 (C=O), 1211 (CN) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 0.86 (m, 20 H, CH2), 3.45–3.50 (m, 1 H, CH), 3.94–4.10 (m, 1 H, CH), 6.04 (s, 1 H, NH), 7.38–7.75 (m, 5 H, 5 CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 24.84 (2 CH2), 25.53 (CH2), 26.23 (2 CH2), 30.71 (2 CH2), 32.29 (CH2), 33.23 (2 CH2), 48.64 (CH), 57.58 (CH), 126.59 (CCO), 126.79 (2 CH of Ph), 128.53 (2 CH of Ph), 131.18 (CH of Ph), 135.16 (Cipso –CO), 154.29 (NCN), 171.46 (CO). MS (EI, 70 eV): m/z (%) = 395 (1), 347 (100), 318 (36), 241 (47), 171 (92), 98 (83), 55 (61). Anal. Calcd for C21H28N2O (403.37): C, 77.74; H, 8.70; N, 8.83. Found: C, 77.48; H, 8.71; N, 8.82.[1-Isopropyl-3-(isopropylamino)-1H-aziren-2-yl](4-methoxyphenyl)methanone (3c)Yellow powder; mp 162–164 °C (decomp.); yield: 0.219 g (80%). IR (KBr): νmax = 3436 (NH), 1688 (NC=C), 1630 (C=O), 1261 (CN) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 0.99 (d, 3 J HH = 6.72 Hz, 6 H, CH3), 1.43 (d, 3 J HH = 6.99 Hz, 6 H, CH3), 3.81–3.85 (m, 1 H, CH), 3.84 (s, 3 H, OMe), 4.44–4.50 (m, 1 H, CH), 6.47 (s, 1 H, NH), 6.91 (d, 3 J HH = 8.75 Hz, 2 H, 2 CH of Ph), 7.52 (d, 3 J HH = 8.75 Hz, 2 H, 2 CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 20.95 (2 CH3), 22.33 (2 CH3), 42.70 (CH), 50.24 (CH), 55.42 (OMe), 113.85 (2 CH of Ph), 122.11 (CCO), 128.87 (2 CH of Ph), 133.24 (Cipso –CO), 154.20 (NCN), 161.78 (Cipso –OMe), 172.05 (CO). MS (EI, 70 eV): m/z (%) = 278 (54), 263 (10), 192 (100), 178 (64), 143 (36), 135 (99), 92 (41), 77 (54). Anal. Calcd for C16H22N2O2 (274.36): C, 70.04; H, 8.08; N, 10.21. Found: C, 70.03; H, 8.10; N, 10.10.[1-Cyclohexyl-3-(cyclohexylamino)-1H-aziren-2-yl](4-methoxyphenyl)methanone (3d)Yellow powder; mp 174–176 °C (decomp.); yield: 0.258 g (73%). IR (KBr): νmax = 3300 (NH), 1690 (NC=C), 1653 (C=O), 1260 (CN) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.17–2.08 (m, 20 H, CH2), 3.49–3.52 (m, 1 H, CH), 4.10–4.12 (m, 1 H, CH), 6.03 (s, 1 H, NH), 6.89 (d, 3 J HH = 8.5 Hz, 2 H, 2 CH of Ph), 7.54 (d, 3 J HH = 8.5 Hz, 2 H, 2 CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 24.49 (2 CH2), 25.29 (CH2), 25.38 (CH2), 26.28 (2 CH2), 30.85 (2 CH2), 32.41 (2 CH2), 55.43 (CH), 57.63 (CH), 113.77 (2 CH of Ph), 128.56 (CCO), 129.05 (2 CH of Ph), 130.10 (Cipso –CO), 154.74 (NCN), 161.83 (Cipso –OMe), 171.18 (CO). MS (EI, 70 eV): m/z (%) = 354 (1) [M+], 233 (19), 185 (8), 151 (33), 135 (100), 98 (16), 56 (19). Anal. Calcd for C22H30N2O2 (354.49): C, 74.54; H, 8.53; N, 7.90. Found: C, 74.53; H, 8.55; N, 7.92.[1-Cyclohexyl-3-(cyclohexylamino)-1H-aziren-2-yl](4-nitrophenyl)methanone (3e)Yellow powder; mp 152–154 °C; yield: 0.240 g (65%). IR (KBr): νmax = 3298 (NH), 1710 (NC=C), 1650 (C=O), 1248 (CN) cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 0.69–1.82 (m, 20 H, CH2), 3.11–3.13 (m, 1 H, CH), 4.01–4.03 (m, 1 H, CH), 8.29 (s, 1 H, NH), 7.67 (d, 3 J HH = 8.6 Hz, 2 H, 2 CH of Ph), 8.25 (d, 3 J HH = 8.6 Hz, 2 H, 2 CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 23.99 (2 CH2), 24.89 (CH2), 25.50 (2 CH2), 30.30 (2 CH2), 31.10 (2 CH2), 32.29 (CH2), 49.08 (CH), 53.77 (CH), 123.28 (2 CH of Ph), 128.34 (2 CH of Ph), 128.82 (CCO),143.16 (Cipso –CO), 148.89 (Cipso –NO2), 153.18 (NCN), 166.26 (CO). MS (EI, 70 eV): m/z (%) = 369 [M+], 292 (13), 248 (23), 167 (100), 104 (33), 69 (27). Anal. Calcd for C21H27N3O3 (369.46): C, 68.27; H, 7.37; N, 11.37. Found: C, 68.28; H, 7.35; N, 11.36.[1-Cyclohexyl-3-(cyclohexylamino)-1H-aziren-2-yl](3-nitrophenyl)methanone (3f)Yellow powder; mp 170–172 °C; yield: 0.258 g (70%). IR (KBr): νmax = 3302 (NH), 1705 (NC=C), 1646 (C=O), 1267 (CN). 1H NMR (500.1 MHz, CDCl3): δ = 0.91–2.17 (m, 20 H, CH2), 3.47–3.53 (m, 1 H, CH), 3.96–4.06 (m, 1 H, CH), 6.13 (s, 1 H, NH), 7.70 (d, 3 J HH = 8.6 Hz, 1 H, CH of Ph), 7.94 (d, 3 J HH = 8.7 Hz, 1 H, CH of Ph), 8.22–8.33 (t, 3 J HH = 8.5 Hz, 1 H, 1 CH of Ph), 8.27 (s, 1 H, CH of Ph). 13C NMR (125.7 MHz, CDCl3): δ = 24.45 (2 CH2), 25.24 (CH2), 26.11 (2 CH2), 30.77 (2 CH2), 32.31 (2 CH2), 33.11 (CH2), 49.85 (CH), 57.54 (CH), 122.91 (2 CH of Ph), 123.78 (2 CH of Ph), 123.92 (CCO), 127.65 (2 CH of Ph), 128.02 (2 CH of Ph), 142.68 (Cipso –CO), 148.82 (Cipso –NO2), 153.43 (NCN), 168.79 (CO). MS (EI, 70 eV): m/z (%) = 368 (1) [M+ – 1], 292 (8), 248 (23), 167 (100), 150 (98), 104 (53), 76 (37). Anal. Calcd for C21H27N3O3 (369.46): C, 68.27; H, 7.37; N, 11.37. Found: C, 68.28; H, 7.35; N, 11.36