Transesterification of α-Substituted Esters Mediated by Potassium Carbonate

Abstract

α-Substituted esters were efficiently and easily transesterificated at room temperature in the presence of potassium carbonate. α-Halo esters can be transesterificated without substitution of the halogen atom.

Key words

transesterification - catalysis - α-substituted esters - potassium carbonate - haloesters

References

• 1 March J. Advanced Organic Chemistry   Wiley and Sons; New York: 1985.  p.351 
• 2 Loder DJ, and Teetars WO. inventors; US patent, US  2290128.  ; Chem. Abstr. 1943, 37, 387(7)
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• The product of halogen substitution was obtained in case a by application of a stronger base (sodium hydride). Similar examples were reported:
• 8a Troostwijk JE. Kellogg RM. J. Chem. Soc., Chem. Commun.  1977,  932 
• 8b Asthana P. Prasad M. Rastogi SN. Indian J. Chem., Sect. B  1987,  26:  330 
• 9a

  Procedure I (for 3a-i): The amount of 0.02 mol of alcohol 2, 13.8 g (0.1 mol) of K₂CO₃, corresponding amount of ester 1 (see Table [1] ) and 40 mL of THF were placed in a round-bottomed flask. The reaction mixture was vigorously stirred at r.t. (g - at boiling point) with a glass stirrer (blade dimension 4 cm) at 1200 rpm.

• 9b

  Procedure II (for 3a-f): Procedure II as in procedure I. After reaching the final reaction time of procedure I, THF and alcohol 4 were evaporated with a rotary evaporator (30 °C, 120 hPa, 1 h). Fresh THF, 40 mL, was added to the solid residue, and the reaction mixture was vigorously stirred again for the same time. Evaporation and stirring were repeated once more.

• 9c

  Isolation and Purification: The crude reaction mixture was filtrated through a layer of celite and silica gel in order to separate the potassium carbonate. Solvent, excess of ester 1, unreacted alcohol 2h, 2i and alcohol 4 were evaporated with a rotary evaporator (40 °C, 3 hPa). In the case of 3a, 3h, 3i the products were pure enough for spectral analysis. In the case of 3b-g unreacted 1 was recrystallized from dichloromethane, the filtrate was evaporated under reduced pressure to give the product. Compounds 3a-3f were additionally crystallized from ethanol at -10 °C for mp, spectral and CHN analysis.

• 9d

  Spectroscopic and Analytical Data: ¹H NMR: (200 MHz, CDCl₃), IR: (KBr). Chloroacetic Acid 2-(1,3-dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3a): ¹H NMR: δ = 7.77 (m, 4 H, Ar), 4.41 (t, 2 H, J = 5.2 Hz, NCH₂CH₂O), 4.03 (s, 2 H, COCH₂Cl), 3.96 (t, 2 H, J = 5.2 Hz, NCH₂CH₂O). IR: ν_C=O 1770, 1752, 1708 cm^-1; ν_Ph-H 722 cm^-1. Anal. Calcd for C₁₂H₁₀ClNO₄: C, 53.85; H, 3.77; Cl, 13.25;, N, 5.23. Found: C, 53.82; H, 3.97; Cl, 13.23; N, 5.01. Mp: 129.8-130.5 °C. Bromoacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3b): ¹H NMR: δ = 7.80 (m, 4 H, Ar), 4.42 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O), 4.00 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O), 3.82 (s, 2 H, CH₂Br). IR: ν_C=O 1772, 1748, 1708 cm^-1; ν_Ph-H 724 cm^-1. Anal. Calcd for C₁₂H₁₀BrNO₄: C, 46.18; H, 3.23; N, 4.49. Found: C, 46.17; H, 3.29; N, 4.28. Mp: 124 °C. Dichloroacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3c): ¹H NMR: δ = 7.79 (m, 4 H, Ar), 5.92 (s, 1 H, COCHCl₂), 4.51 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O), 4.03 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O). IR: ν_C=O 1776, 1760, 1720, 1708 cm^-1; ν_Ph-H 724 cm^-1. Anal. Calcd for C₁₂H₉Cl₂NO₄: C, 47.71; H, 3.00; N, 4.64. Found: C, 47.31; H, 2.93; N, 4.63. Mp: 100.3-101.5 °C. 2-Chloropropionic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3d): ¹H NMR: δ = 7.79 (m, 4 H, Ar), 4.45 (m, 2 H, NCH₂CH₂O), 4.35 (q, 1 H, J = 7 Hz, CHClCH₃), 4.00 (m, 2 H, NCH₂CH₂O), 1.65 (d, 3 H, J = 7 Hz, CHClCH₃). IR: ν_C=O 1780, 1752, 1716 cm^-1; ν_Ph-H 728 cm^-1. Anal. Calcd for C₁₃H₁₂ClNO₄: C, 55.43; H, 4.29; N, 4.97. Found: C, 55.54; H, 3.99; N, 5.14. Mp: 49.1-49.7 °C. Methoxyacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3e): ¹H NMR: δ = 7.77 (m, 4 H, Ar), 4.39 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O), 3.98 (s, 2 H, COCH₂O), 3.95 (t, 2 H, J = 5.3 Hz, NCH₂CH₂O), 3.39 (d, 3 H, OCH₃). IR: ν_C=O 1772, 1752, 1712 cm^-1; ν_Ph-H 728 cm^-1. Anal. Calcd for C₁₃H₁₃NO₅: C, 59.31; H, 4.98; N, 5.32,.Found: C, 59.65; H, 5.18; N, 5.18. Mp: 67.6-67.9 °C. Ethoxyacetic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3f): [10] ¹H NMR: δ = 7.79 (m, 4 H, Ar), 4.40 (t, 2 H, J = 5.2 Hz, NCH₂CH₂O), 4.04 (s, 2 H, COCH₂O), 3.97 (t, 2 H, J = 5.2 Hz, NCH₂CH₂O), 3.56 (q, 2 H, J = 7 Hz, OCH₂CH₃), 1.20 (t, 3 H, J = 7 Hz, OCH₂CH₃). IR: ν_C=O 1776, 1760, 1712 cm^-1; ν_Ph-H 720 cm^-1. Mp: 54.5-54.8 °C. Acetic Acid 2-(1,3-Dihydro-1,3-dioxo-2 H -isoindol-2-yl)ethyl Ester ( 3g): [11] ¹H NMR: δ = 7.79 (m, 4 H, Ar), 4.31 (t, 2 H, J = 5.4 Hz, NCH₂CH₂O), 3.95 (t, 2 H, J = 5.4 Hz, NCH₂CH₂O), 2.01 (s, 3 H, CH₃). IR: ν_C=O 1776, 1740, 1712 cm^-1. ν_Ph-H 720 cm^-1. Mp: 88.1-88.4 °C. Chloroacetic Acid Phenylmethyl Ester ( 3h): [12] ¹H NMR: δ = 7.38 (m, 5 H, Ar), 5.22 (s, 2 H, PhCH₂O), 4.10 (s, 2 H, COCH₂Cl). IR: ν_C=O 1756 cm^-1; ν_Ph-H 792, 752, 704 cm^-1. 2-Chloropiopionic Acid-2-ethoxyethyl Ester ( 3i): ¹H NMR: δ = 4.42 (q, 1 H, J = 7 Hz, CHClCH₃), 4.30 (m, 2 H, CH₂CO), 3.65 (m, 2 H, OCH₂CH₂), 3.52 (q, 2 H, J = 7 Hz, CH₃CH₂O), 1.68 (d, 3 H, J = 7 Hz, CHClCH₃), 1.90 (t, 3 H, J = 7 Hz, CH₃CH₂O). IR: ν_C=O 1752 cm^-1.

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