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Synlett 2010(12): 1854-1858  
DOI: 10.1055/s-0030-1258113
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Synthesis of α-Alkylidene-γ-butyrolacton-2-ones (Tetronic Acid Derivatives): Polar Solvent Induces a New Type of γ-Lactonization

Abdolali Alizadeh*, Hamideh Sabahnoo, Zohreh Noaparast, Nasrin Zohreh, Azadeh Mikaeili
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
Fax: +98(21)88006544; e-Mail: aalizadeh@modares.ac.ir;
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Publication History

Received 19 March 2010
Publication Date:
30 June 2010 (online)

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Abstract

An efficient, one-pot synthetic protocol toward α-alkylidene-γ-butyrolacton-2-ones, a rather unexplored class of heterocyclic scaffolds starting from primary amines, methyl acetoacetate, and chloroacetyl chloride is described. The mixture of MeCN-MeOH as a polar solvent triggers a new cycloaddition of the enaminone intermediate. The reaction is completed within 12 hours under reflux condition to produce the title compounds.

Key words

γ-lactone - α-alkylidene-γ-butyrolactone - tetronic acid - enaminone - chloroacetyl chloride - polar solvent - one-pot multicomponent reaction

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To a magnetically stirred 10 mL flat-bottom flask, containing ethylamine (0.09 g, 2 mmol) was added methyl acetoacetate (0.24 g, 2 mmol), and this mixture was stirred at r.t. under solvent-free conditions for 10 min. A solution of chloroacetyl chloride (0.22 g, 2 mmol) in MeCN (5 mL) was added dropwise to the reaction mixture. The progress of the reaction was followed by TLC. When enaminone 5 was fully consumed, MeOH (2 mL) was added and the mixture allowed to stir at 110-120 ˚C for 11 h. After completion of the reaction, the solvent was removed under reduced pressure. The residue was purified by column chromatog-raphy on silica gel (n-hexane-EtOAc = 1:1) to obtain product 4a as a white powder (0.12 g, 71%). IR (KBr): 3460 (NH), 1728 (CO2), 1638 (C=O), 1615 (C=C) cm-¹. MS (EI, 70 eV): m/z (%) = 169 (93) [M+], 151 (85), 123 (38), 95 (34), 82 (69), 68 (50), 58 (100), 42 (92). E-Isomer of 4a: ¹H NMR (500.13 MHz, CDCl3): δ = 1.35 (3 H, t, ³ J H,H = 7.3 Hz, CH2CH 3), 2.54 (3 H, s, CH3), 3.47 (2 H, q, ³ J H,H = 7.3 Hz, CH 2CH3), 4.40 (2 H, s, CH2O), 10.99 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 13.86 (CH2 CH3), 14.42 (CH3), 38.43 (CH2CH3), 69.97 (OCH2), 91.76 (C=CCH3), 170.80 (C=CCH3), 172.52 (CO2), 197.10 (C=O).
Z-isomer of 4a: ¹H NMR (500.13 MHz, CDCl3): δ = 1.32 (3 H, t, ³ J H,H = 7.3 Hz, CH2CH 3), 2.58 (3 H, s, CH3), 3.50 (2 H, q, ³ J H,H = 7.3 Hz, CH 2CH3), 4.38 (2 H, s, CH2O), 10.01 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 14.27 (CH2 CH3), 14.62 (CH3), 38.12 (CH2CH3), 72.00 (OCH2), 90.36 (C=CCH3), 169.94 (C=CCH3), 176.35 (CO2), 193.62 (C=O).
Compound 4b: yield 0.28 g (80%); white powder; mp 112-114 ˚C. IR (KBr): 3465 (NH), 1734 (CO2), 1661 (C=O), 1604 (C=C) cm-¹. MS (EI, 70 eV): m/z (%) = 183 (100) [M+], 165 (87), 154 (70), 150 (59), 137 (39), 125 (47), 97 (75), 82 (72), 67 (70).
E-isomer of 4b: ¹H NMR (500.13 MHz, CDCl3): δ = 1.05 (3 H, t, ³ J H,H = 7.4 Hz, CH2CH 3), 1.75 (2 H, q, ³ J H,H = 7.4 Hz, CH 2CH3), 2.55 (3 H, s, CH3), 3.43 (2 H, t, ³ J H,H = 6.9 Hz, CH2N), 4.42 (2 H, s, OCH2), 11.10 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 11.16 (CH2 CH3), 13.96 (CH3), 30.87 (CH2CH3), 45.18 (CH2N), 69.97 (CH2O), 91.88 (C=CCH3), 161.90 (C=CCH3), 170.96 (CO2), 197.18 (C=O).
Z-isomer of 4b: ¹H NMR (500.13 MHz, CDCl3): δ = 1.03 (3 H, t, ³ J H,H = 7.4 Hz, CH2CH 3), 1.72 (2 H, q, ³ J H,H = 7.4 Hz, CH 2CH3), 2.60 (3 H, s, CH3), 3.40 (2 H, t, ³ J H,H = 7.0 Hz, CH2N), 4.40 (2 H, s, OCH2), 10.13 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 11.16 (CH2 CH3), 14.37 (CH3), 31.22 (CH2CH3), 44.85 (CH2N), 72.04 (CH2O), 90.44 (C=CCH3), 161.93 (C=CCH3), 170.07 (CO2), 193.61 (C=O).
Compound 4e: yield 0.28 g (82%); white powder; mp 118-120 ˚C. IR (KBr): 3230 (NH), 1725 (CO2), 1639 (C=O), 1604 (C=C) cm-¹. MS (EI, 70 eV): m/z (%) = 183 (100) [M+], 165 (78), 137 (24), 110 (39), 96 (94), 83 (47), 67 (35), 55 (16).
E-isomer of 4e: ¹H NMR (500.13 MHz, CDCl3): δ = 1.30 (6 H, d, ³ J H,H = 6.2 Hz, 2 CHCH 3), 2.51 (3 H, s, CH3), 3.91-3.99 (1 H, m, 1 CHCH3), 4.33 (2 H, s, CH2O), 10.94 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 13.85 (2 CHCH3), 22.82 (CH3), 45.75 (CHCH3), 69.89 (CH2O), 91.43 (C=CCH3), 169.43 (C=CCH3), 172.53 (CO2), 196.96 (C=O).
Z-isomer of 4e: ¹H NMR (500.13 MHz, CDCl3): δ = 1.28 (6 H, d, ³ J H,H = 6.2 Hz, 2 CHCH 3), 2.56 (3 H, s, CH3), 3.91-3.99 (1 H, m, CHCH3), 4.30 (2 H, s, CH2O), 9.94 (1 H, s, NH). ¹³C NMR (125.75 MHz, CDCl3): δ = 14.31 (2 CHCH3), 22.78 (CH3), 45.41 (CHCH3), 71.84 (CH2O), 90.05 (C=CCH3), 168.61 (C=CCH3), 176.31 (CO2), 193.58 (C=O).