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

Abdolali Alizadeh; Atieh Rezvanian

doi:10.1055/s-0031-1290487

Synlett, Table of Contents

Synlett 2012; 23(6): 859-862
DOI: 10.1055/s-0031-1290487

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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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Abstract

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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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References

References and Notes

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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): ν_max = 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 (C_ipso –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): ν_max = 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 (C_ipso –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): ν_max = 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 (C_ipso –CO), 154.20 (NCN), 161.78 (C_ipso –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): ν_max = 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 (C_ipso –CO), 154.74 (NCN), 161.83 (C_ipso –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): ν_max = 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 (C_ipso –CO), 148.89 (C_ipso –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): ν_max = 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 (C_ipso –CO), 148.82 (C_ipso –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

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

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