Electrochemical Reduction of O-Substituted Phenylchloroacetates at a Silver Cathode: A Synthetic Route to Coumarins

Coumarins are encountered extensively in biology, medicine, polymer science, and industry.¹  There are many ways to synthesize coumarins chemically, but the most famous method is the Pechmann reaction, which involves condensation of a β-ketonic ester with a phenol.²  A major downfall of the Pechmann reaction is that the identities of the two starting materials greatly affect the  yield of the desired coumarin.

     Despite the importance of coumarins, only a few publications^3–5 have explored the electrochemical synthesis of coumarins.  In previous work⁶ from our laboratory, the direct and cobalt(I)-catalyzed reduction of 2-acetylphenyl 2-chloroacetate and 2-acetylphenyl 2,2-dichloroacetate was investigated, the goal being to produce 4-methylcoumarin; the yields of the desired product were 20–30% for the direct reduction and 50% for the catalytic system.

     Silver cathodes have been found to show catalytic ability for the reduction of carbon–halogen bonds.⁷  This knowledge led us to explore the same reaction that was investigated in our earlier work,⁶ but with the use of a silver cathode.  Our specific goal was to study the formation of several coumarins, while examining the effects of solvent and concentration by means of cyclic voltammetry and controlled–potential (bulk) electrolysis.

     Figure 1 is a cyclic voltammogram for the reduction of 2-formylphenyl 2-chloroacetate at both a glassy carbon and silver cathode.  With both electrode materials, the first cathodic peak is attributed to cleavage of the carbon–chlorine bond; a positive shift in peak potential can be seen when a silver cathode is employed instead of a glassy carbon electrode.  We believe that the second cathodic peak is due to the reduction of the coumarin product that is formed at potentials corresponding to the first peak.  When a carbon electrode is employed, the first two cathodic peaks have similar potentials, whereas these two stages of reduction are nicely separated when a silver cathode is used.  Thus, silver allows more selectivity between the two electron-transfer processes during a controlled-potential (bulk) electrolysis. 

     A generalized reaction sequence for the electrochemical formation of substituted coumarins is shown in Scheme 1.  A carbon–chlorine bond is cleaved via a one-electron process, and the resulting radical can cyclize at the o-substituted carbonyl moiety, followed by addition of a proton and loss of water to form the coumarin.  This mechanism leaves intact the substituents on the benzene ring of the coumarin.  Controlled-potential (bulk) electrolyses have revealed that the substituent (R = H, CH₃, or OCH₃) on the aryl ketone affects the extent of the reductive intramolecular cyclization, and we have observed the formation of the desired coumarin in a  yield as high as 40%.

 

References

 

1. Trenor, R.S.; Shultz, A.R; Love, B.J.; Long, T.E Chem. Rev. 2004, 104, 3059–3077.

2. Sethna, S.; Phadke, R. in Organic Reactions. John Wiley & Sons, New York, 2011, pp. 1–25.

3. Batanero, B.; Pérez, M. J.; Barba, F. J. Electroanal. Chem. 1999, 469, 201–205.

4. Batanero, B.; Barba, F. Electrochem. Commun. 2001, 3, 595–598.

5. Dolly; Batanero, B.; Barba, F. Tetrahedron 2003, 59, 9161–9165.  

6. Du, P.; Mubarak, M.S.; Karty, J.A.; Peters, D.G. J. Electrochem. Soc. 2007, 154, F231–F237.

7. Isse, A. A.; Berzi, G.; Falciola, L.; Rossi, M.; Mussini, P. R.; Gennero, A. J. Appl. Electrochem. 2009, 39, 2217–2225.

8. All potentials are cited with respect to a reference electrode consisting of a saturated cadmium amalgam in contact with DMF saturated with NaCl and CdCl₂; the potential of this electrode is –0.76 V vs. SCE at 25 °C.