Download PDF
Synlett 2002(6): 0899-0902
DOI: 10.1055/s-2002-31925
LETTER
© Georg Thieme Verlag Stuttgart · New York

Nucleophilic Addition Reaction of Aromatic Compounds in the Presence of Lewis Acid

Jingrong Lina, Shu Kanazakia, Setsuo Kashinob, Sadao Tsuboi*a
a Department of Environmental Chemistry and Materials, Faculty of Environmental Science and Technology, Okayama University, Okayama 700-8530, Japan
b Department of Chemistry, Faculty of Science, Okayama University, Okayama 700-8530, Japan
Fax: +81(86)2518898; e-Mail: stsuboi6@cc.okayama-u.ac.jp;
Further Information

Publication History

Received 27 February 2002
Publication Date:
07 February 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

The epoxide 1 obtained by the Darzens condensation reaction of aldehydes with methyl dichloroacetate, reacted with aromatic compounds in the presence of aluminium chloride to afford α-aryl- -chloro-α-hydroxyalkanoate 3. Scope and limitation of this reaction were studied for various aldehydes and aromatic compounds. The reaction was also studied in the presence of aluminium chloride supported on alumina or silica gel, which is thought to be a mild Lewis acid and harmless for the environment.

Key words

Darzens condensation - Lewis acid - nucleophilic addition - epoxide - aromatic compound

    References

  • 1 Friedel-Crafts and Related Reaction   Olah GA. Interscience; New York: 1964. 
    Google Scholar
  • 2a Hata S. Matsuda H. Mastuda S. Kogyo Kagaku Zasshi  1967,  70(12):  2291 
    Google Scholar
  • 2b Nakamoto Y. Nakajima T. Suga S. Kogyo Kagaku Zasshi  1969,  72(12):  2594 
    Google Scholar
  • 2c Nakajima T. Nakamoto Y. Suga S. Bull. Chem. Soc. Jpn.  1975,  48(3):  960 
    Google Scholar
  • 2d Inoue M. Chano K. Itoh O. Sugita T. Ichikawa K. Bull. Chem. Soc. Jpn.  1980,  53:  458 
    Google Scholar
  • 3 Juy M. Combert JC. Coutrot PC. R. Hebd. Seances Acad. Sci., Ser. C  1974,  279:  469 
    Google Scholar
  • 4a Ubaidullaev KA. Shakairov R. Yunosov SY. Khim. Prir. Soedin.  1976,  12:  553 
    CrossrefGoogle Scholar
  • 4b Hasse BR. John KM. J. Nat. Prod.  1997,  60:  1152 
    CrossrefGoogle Scholar
5

Typical procedure for (±)-2-hydroxy-2-(p-ethylphenyl)-3-chlorooctanoate(3f): To a stirred solution of aluminium chloride (430 mg, 3 mmol) in CH2Cl2 (4 mL) was added the solution of methyl 2-chloro-2,3-epoxyoctanoate (206 mg, 1 mmol) and ethylbenzene (319 mg, 3 mmol) in CH2Cl2 (2 mL) at room temperature. The mixture was stirred for 50 minutes, then reaction was stopped by pouring the ice (10 mL), and the aqueous layer was extracted with EtOAc. The combined extract was washed with saturated NaHCO3 solution and brine, then dried over MgSO4. Removal of the solvent gave 232 mg of a clean oil, which was purified by column chromatography (hexane-ether = 160:1) to give 161 mg (51.5%) of (S,S)-(±)-3f and 38 mg (12.1%) of (S,R)-(±)-3f.


(S,S)-(±)-3f: yellow liquid, Rf = 0.30 (hexane-ether = 2:1); 1H NMR (200 MHz, CDCl3) δ 0.83 (t, J = 6.4 Hz, 3 H), 1.24 (t, J = 7.6 Hz, 3 H), 1.18-1.76 (m, 8 H), 2.66 (q, J = 7.6 Hz, 2 H), 3.82 (s, 3 H), 3.91 (s, 1 H), 4.68 (dd, J = 1.8 Hz and 10.8 Hz, 1 H), 7.21 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4 Hz, 2 H); 13C NMR (200 MHz, CDCl3) δ 13.89, 15.28, 22.38, 26.58, 28.37, 30.51, 30.87, 53.53, 68.30, 81.23, 125.85, 127.98, 134.97, 144.34, 173.58; IR(neat): 3514, 2958, 2932, 2864, 1742, 1512, 1437, 1257, 1147, 756 cm-1; Anal. Calcd for C17H25ClO3: C, 65.27; H, 8.05; Found: C, 65.51; H, 8.22. (S,R)-(±)-3f: yellow liquid, Rf = 0.23 (hexane-ether = 2.1); 1H NMR(200 MHz, CDCl3) δ 0.90 (t, J = 6.4 Hz, 3 H), 1.24 (t, J = 7.6 Hz, 3 H), 1.20-2.10 (m, 8 H), 2.66 (q, J = 7.6 Hz, 2 H), 3.73 (s, 1 H), 3.81 (s, 3 H), 4.61 (dd, J = 1.6 Hz and 10.8 Hz, 1 H), 7.21 (d, J = 8.4 Hz, 2 H), 7.53 (d, J = 8.4 Hz, 2 H); 13C NMR (200 MHz, CDCl3) δ13.97, 15.22, 22.42, 26.57, 28.37, 31.05, 33.11, 53.58, 67.65, 81.25, 125.70, 127.83, 136.63, 144.32, 173.10; IR(neat): 3512, 2962, 2934, 2864, 1734, 1514, 1458, 1253, 1143, 835, 665 cm-1; Anal. Calcd for C17H25ClO3: C, 65.27; H, 8.05; Found: C, 65.51; H, 8.22.

6

X-ray crystallographic data of syn-3d: data collection, solution, and refinement.
Chemical formula: C14H19O3Cl; F. W. = 270.76; crystal size: 0.50 × 0.25 × 0.43 mm3; crystal system: triclinic; lattice parameters: a = 10.495(3), b = 11.755(3), c = 6.608(2) Å, α = 100.36(2), β = 107.25(3), γ = 69.213(18)º, V = 725.4(4) Å3; space group: P (#2); Z = 2; Dcalc = 1.240 g/cm3; F(000) = 288; µ(Mo Kα) = 0.26 mm-1; diffractometer: Rigku AFC5R; T: 25 ºC; no. of reflections measured: total 3880, unique 3334; structure solution: direct methods (SIR92); refinement: full-matrix least-squares on F 2; function mini-mized: Σw (Fo2 - Fc2)2; least squares weights: 1/σ2(Fo) = 4Fo2/σ2 (Fo2); no. obsd [I > 0.5σ (I)]: 2886; no. variables: 240; residuals R 1, wR 2: 0.063, 0.099; goodness of fit indicator: 1.94; max /ρmin: 0.23 / - 0.28 e / Å3.