Electron Deficient Dienes. 4. [1] A Synthetic Equivalent of 4-Methylene­glutaconic Acid, its Mono and Diethyl Esters and their Use in a Concise General Synthesis of Isophthalic Acids and Isophthalates

Abstract

Reaction of a series of 2′-hydroxybenzophenone-3-carboxylic acid ethyl esters under Dakin reaction conditions affords isophthalic acid monoethyl esters, which can be converted into the corresponding diethyl isophthalates (6 examples) and isophthalic acid (1 example) by esterification and hydrolysis, respectively. This transformation renders the direct precursor of the benzophenones a synthetic equivalent of 4-methyleneglutaconic acid (4-methylenepent-2-enedioic acid) and its mono and diethyl esters.

Dakin reaction - Diels-Alder - inverse electron demand - isophthalates - isophthalic acids

References

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Bodwell, G. J.; Hawco, K. M. unpublished results.

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Sample Procedure: 4,6-Indandicarboxylate Diethyl Ester ( 4): [9] [10] To a stirred suspension of NaH (60% dispersion in mineral oil, 35.2 mg, 0.88 mmol) in THF (15 mL) was added dropwise a solution of 11 (219.5 mg, 0.71 mmol) in THF (5 mL) and the resulting yellow solution was stirred for 10 min. To the resulting solution was added H₂O₂ (30% aq solution, 95.3 mg, 0.84 mmol) and the mixture was stirred for 20 h. The reaction mixture was concentrated under reduced pressure, and concentrated aq HCl solution (5 mL) was added. The resulting precipitate was collected by suction filtration and washed with a small amount of H₂O. The solid was dried in vacuo and then suspended in absolute EtOH (25 mL). To this suspension was added concentrated H₂SO₄ (0.5 mL) and the mixture was heated at reflux for 11 h. The solvent was removed under reduced pressure and H₂O (25 mL) was added. The mixture was then extracted with CH₂Cl₂ (3 × 25 mL). The combined organic layers were washed with sat. aq NaHCO₃ solution, and dried over MgSO₄. The solvent was removed under reduced pressure and the residue was subjected to silica gel column chromatography (20% EtOAc/hexane) to afford diester 4 (144.2 mg, 78%) as pale yellow crystals: Mp 43-45 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.49 (s, 1 H), 8.04 (s, 1 H), 4.390 (q, J = 7.2 Hz, 2 H), 4.384 (q, J = 7.1 Hz, 2 H), 3.32 (t, J = 7.4 Hz, 2 H), 2.97 (t, J = 7.4 Hz, 2 H), 2.13 (quint, J = 7.4 Hz, 4 H), 1.411 (t, J = 7.2 Hz, 3 H), 1.407 (t, J = 7.5 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 166.7, 166.5, 152.1, 146.6, 129.9, 129.1, 127.1, 61.3, 61.1, 34.3, 32.5, 25.2, 2 × 14.6. IR(nujol): ν = 1724 (s), 1299 (m), 1227 (s)cm^-1. UV/Vis (CH₂Cl₂): λ_max (log ε) = 302 (3.38) nm; MS (EI. 70 eV): m/z (%) = 262 (69) [M⁺], 233 (100), 117 (99). HRMS (EI): m/z calcd for C₁₅H₁₈O₄ [M⁺]: 262.1205. Found: 262.1223. All other products were characterized as above.

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