One-Pot Oxidative Cleavage of Olefins to Synthesize Carboxylic Acids by a Telescoped Ozonolysis–Oxidation Process

Abstract

A mild one-pot ozonolysis–oxidation process of alkenes to synthesize carboxylic acids is described. Conducting the ozonolysis in an aqueous organic solvent eliminates secondary ozonide formation and the intermediates generated are readily converted into a carboxylic acid by adding sodium chlorite. Following a reductive quench, the desired acids are isolated in high purity and high yield by simple extraction.

Key words

ozonolysis - carboxylic acids - green chemistry - alkenes - oxidation

• References and Notes

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• 25 Aging the reaction overnight with 3 equiv of sodium chlorite resulted in 90–95% conversion.
• 26 It is known that NaClO₂ can be reduced with hypochlorite ions and with hydrogen peroxide in acidic media. An additional gaseous byproduct was formed detectable by the yellow color of the nitrogen bubbler oil. The exact identity of this gas is not known but is presumed to be Cl₂ or ClO₂, see ref. 23.
• 27 Representative Ozonolysis–Oxidation Procedure: Formation of 3-Phenylpropanoic Acid (Table 1, Entry 1) To a vial was added a solution of 4-phenyl-1-butene (1 mL, 0.88 g, 6.66 mmol, 1 equiv) dissolved in MeCN (15.8 mL, 18 mL/g) and H₂O (1.8 mL, 2 mL/g). The solution was cooled to 0 °C and sparged with ozone at a rate of <2 scfh (standard cubic feet per hour) while purging the head space of the vial with nitrogen. Once ozone was detected in the head space, the ozone was stopped and reaction completeness was confirmed by LC–MS. A magnetic stir bar was added to the vial and the solution stirred rapidly. An aqueous solution of NaClO₂ (80 wt%, 3.01 g, 26.6 mmol, 4 equiv) in H₂O (14 mL) was added portionwise to the reaction while maintaining a internal reaction temp <15 °C. The cold bath was removed from the reaction and the mixture stirred for >12 h at r.t. under 1 atm of nitrogen. A solution of NaHSO₃ was made by dissolving Na₂S₂O₅ (2.77 g, 14.58 mmol, 2.19 equiv) in H₂O (14 mL). This solution was slowly added to the reaction maintaining a internal temperature <35 °C and the mixture stirred for 10 min. EtOAc (10 mL) was added to the mixture, and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers combined, dried over MgSO4, filtered, and concentrated to provide a colorless oil (0.95 g, 95% yield). 1H NMR (400 MHz, CDCl3): δ = 2.71 (t, J = 8.0 Hz, 2 H), 2.96 (t, J = 8.0 Hz, 2 H) 7.18–7.32 (m, 5 H), 10.30–11.30 (br s, 1 H).