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Synlett 2011(17): 2495-2498  
DOI: 10.1055/s-0030-1261237
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

C-N Bond Cleavage of Benzylic Enaminones in the Presence of Acetyl or Aroyl Chlorides: A Novel One-Pot Synthesis of N-Acetyl or N-Aroyl β-Benzylidene α-Amino Acid Esters

Abdolali Alizadeh*a, Hamideh Sabahnooa, Nasrin Zohreha, Zohreh Noaparasta, Long-Guan Zhub
a Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
Fax: +98(21)88006544; e-Mail: abdol_alizad@yahoo.com; e-Mail: aalizadeh@modares.ac.ir;
b Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
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Publication History

Received 1 July 2011
Publication Date:
13 September 2011 (online)

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Abstract

Benzylic enaminones generated by addition of benzyl­amines to dialkyl acetylenedicarboxylates are trapped in situ by chloroacetyl or aroyl chlorides in refluxing toluene. Good yields of E-isomers of N-acetyl or N-aroyl α-amino acid esters were produced exclusively via C-N bond cleavage and C-C bond formation resulting from a 1,3-benzyl shift.

Key words

enaminone - benzylic enaminone - aroyl chloride - chloroacetyl chloride - α-amino acid ester - C-N bond cleavage

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10

Typical Procedure: To a magnetically stirred 5-mL flat-bottom flask containing benzylamine (0.22 g, 2 mmol) and toluene as solvent was added dimethyl acetylenedicarboxylate (0.28 g, 2 mmol). After 30 min, a solution of chloroacetyl chloride (0.37 g, 2 mmol) for 5a or p-nitrobenzoyl chloride (0.44 g, 2 mmol) for 7a was added to the reaction mixture and stirring was allowed to continue at 100-120 ˚C for 8 h. After the completion of the reaction, the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane-EtOAc, 9:1) to obtain 5a and crystallized from Et2O to obtain 7a. Compound 5a was obtained as a yellow oil (0.28 g, yield: 80%). IR (KBr): 3430 (NH), 1738 (CO2Me), 1706 (CO2Me), 1652 (NC=O) cm-¹. ¹H NMR (500.13 MHz, CDCl3): δ = 3.77 (s, 3 H, OMe), 3.87 (s, 3 H, OMe), 4.04 (AB system, ³ J H,H = 15.2 Hz, 2 H, CH2Cl), 5.75 (d, ³ J H,H = 8.8 Hz, 1 H, CHN), 7.33-7.35 (m, 2 H, 2 × CH of Ar), 7.44-7.46 (m, 1 H, CH of Ar), 7.55-7.57 (m, 1 H, CH of Ar), 7.68 (d, ³ J H,H = 9.2 Hz, 1 H, NH), 8.01 (s, 1 H, s, C=CH). ¹³C NMR (125.7 MHz, CDCl3): δ = 42.37 (CH2Cl), 49.97 (CHN), 52.59 (OMe), 53.19 (OMe), 127.09 (CH of Ar), 128.84 (C=CH), 129.75 (CH of Ar), 130.07 (CH of Ar), 130.71 (CH of Ar), 132.61 (C ipso -Cl), 134.20 (C ipso -C=C), 141.62 (C=CH), 165.36 (CON), 166.50 (CO2Me), 169.71 (CO2Me). MS (EI, 70 eV): m/z (%) = 324 (15), 296 (69), 268 (71), 236 (73), 207 (63), 125 (100), 111 (74). Anal. Calcd for C15H15Cl2NO5: C, 50.02; H, 4.20; N, 3.89. Found: C, 50.00; H, 4.17; N, 3.87. Compound 5c: white powder (0.24 g, yield: 71%); mp 82-85 ˚C. IR (KBr): 3425 (NH), 1761 (CO2Me), 1697 (CO2Me), 1670 (NC=O) cm-¹. ¹H NMR (500.13 MHz, CDCl3): δ = 2.37 (s, 3 H, Me), 3.76 (s, 3 H, OMe), 3.85 (s, 3 H, OMe), 4.05 (AB system, ³ J H,H = 15.2 Hz, 2 H, CH2Cl), 6.01 (d, ³ J H,H = 9.0 Hz, 1 H, CHN), 7.24 (d, ³ J H,H = 7.9 Hz, 2 H, 2 × CH of Ar), 7.40 (d, ³ J H,H = 8.0 Hz, 2 H, 2 × CH of Ar), 7.69 (d, ³ J H,H = 9.1 Hz, 1 H, NH), 7.95 (s, 1 H, C=CH). ¹³C NMR (125.7 MHz, CDCl3): δ = 21.39 (Me), 42.41 (CH2Cl), 49.87 (CHN), 52.36 (OMe), 53.06 (OMe), 126.33 (C=CH), 129.17 (2 × CH of Ar), 129.63 (2 × CH of Ar), 130.95 (C ipso -C=C), 139.98 (C ipso -Me), 144.55 (C=CH), 165.41 (CON), 167.13 (CO2Me), 170.05 (CO2Me). MS (EI, 70 eV): m/z (%) = 340 (64) [M+ + 1], 280 (80), 248 (100), 172 (57), 157 (53), 144 (52), 129 (44), 105 (6), 91 (24), 77 (27), 59 (22). Anal. Calcd for C16H18ClNO5: C, 56.56; H, 5.34; N, 4.12. Found: C, 56.53; H, 5.32; N, 4.90. Crystal data for 5c (CCDC 695674): C16H18ClNO5, MW = 339.76, triclinic, space group P21/n, a = 13.5932 (12) Å, b = 7.9447 (7) Å, c = 16.5222 (15) Å, α = 90˚, β = 106.461 (1)˚, γ = 90˚, V = 1711.2 (3) ų, Z = 4, Dc = 1.319 mg/m³, F(000) = 712, crystal dimension: 0.31 × 0.26 × 0.23 mm, radiation, Mo Kα (λ = 0.71073 Å), 1.72≤2θ≤25.18, intensity data were collected at 295 (2) K with a Bruker APEX area-detector diffractometer, and employing ω/2θ scanning technique, in the range of -16≤h≤15, -9≤k≤9, -19≤l≤19; the structure was solved by a direct method, all non-hydrogen atoms were positioned and anisotropic thermal parameters refined from 2546 observed reflections with R(into) = 0.0734 by a full-matrix least-squares technique converged to R = 0.0614 and Raw = 0.1475 [I >2σ(I)]. Compound 7a: cream powder (0.34 g, yield: 85%); mp 118-120 ˚C. IR (KBr): 3333 (NH), 1752 (CO2Me), 1694 (CO2Me), 1668 (NC=O), 1603 (C=C), 1484, 1342 (NO2) cm-¹. ¹H NMR (500.13 MHz, CDCl3): δ = 3.80 (s, 3 H, OMe), 3.87 (s, 3 H, OMe), 6.19 (d, ³ J H,H = 8.6 Hz, 1 H, CHN), 7.43 (d, ³ J H,H = 7.2 Hz, 1 H, NH), 7.47 (t, ³ J H,H = 7.5 Hz, 2 H, 2 × CH meta of Ph), 7.49 (t, ³ J H,H = 7.5 Hz, 1 H, CH para of Ph),7.57 (d, ³ J H,H = 7.3 Hz, 2 H, 2 × CH of Ph), 7.94 (d, ³ J H,H = 8.7 Hz, 2 H, 2 × CH of Ar), 8.02 (s, 1 H, C=CH), 8.26 (d, ³ J H,H = 8.6 Hz, 2 H, 2 × CH of Ar). ¹³C NMR (125.7 MHz, CDCl3): δ = 50.32 (CHN), 52.50 (OMe), 53.25 (OMe), 123.78 (2 × CH of Ar), 127.17 (C=CH), 128.44 (2 × CH of Ar), 128.94 (2 × CH of Ar), 129.13 (2 × CH of Ar), 129.74 (CH of Ar), 133.82 (C ipso -C=C), 139.42 (C ipso -CON), 144.56 (C=CH), 149.80 (C ipso -NO2), 164.58 (CON), 167.36 (CO2Me), 170.30 (CO2Me). MS (EI, 70 eV): m/z (%) = 399 (8) [M+ + 1], 366 (16), 339 (79), 307 (100), 279 (5), 248 (16), 173 (17), 150 (75), 120 (12), 104 (33), 92 (16), 76 (18), 59 (7). Anal. Calcd for C20H18N2O7 (398.37): C, 60.30; H, 4.55; N, 7.03. Found: C, 60.28; H, 4.52; N, 7.01.