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

Jingrong Lin; Shu Kanazaki; Setsuo Kashino; Sadao Tsuboi

doi:10.1055/s-2002-31925

LETTER

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

Jingrong Lin^a, Shu Kanazaki^a, Setsuo Kashino^b, 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;

Abstract

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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

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References

1 Friedel-Crafts and Related Reaction Olah GA. Interscience; New York: 1964.

2a Hata S. Matsuda H. Mastuda S. Kogyo Kagaku Zasshi 1967, 70(12): 2291

2b Nakamoto Y. Nakajima T. Suga S. Kogyo Kagaku Zasshi 1969, 72(12): 2594

2c Nakajima T. Nakamoto Y. Suga S. Bull. Chem. Soc. Jpn. 1975, 48(3): 960

2d Inoue M. Chano K. Itoh O. Sugita T. Ichikawa K. Bull. Chem. Soc. Jpn. 1980, 53: 458

3 Juy M. Combert JC. Coutrot PC. R. Hebd. Seances Acad. Sci., Ser. C 1974, 279: 469

4a Ubaidullaev KA. Shakairov R. Yunosov SY. Khim. Prir. Soedin. 1976, 12: 553

4b Hasse BR. John KM. J. Nat. Prod. 1997, 60: 1152

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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, R_f = 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, R_f = 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.

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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 /ρ_min: 0.23 / - 0.28 e / Å³.