A metal-free protocol for direct oxidative de-alkoxycarbonylation of alkyl phenyl acetate by molecular iodine Vivek T. Humne, Pradeep D. Lokhande ⇑ Center for Advance Studies, Department of Chemistry, University of Pune, Pune 411007, India article info Article history: Received 23 October 2013 Revised 12 February 2014 Accepted 16 February 2014 Available online 5 March 2014 Keywords: Carboxylic acid Ethyl phenyl acetate Iodine Oxidative de-alkoxycarbonylation abstract A metal-free protocol for the direct oxidative de-alkoxycarbonylation of alkyl phenyl acetate has been carried out by molecular iodine with good yield. In the present Letter, the vital role of iodine in oxidative de-alkoxycarbonylation is described. This method has been proven to be tolerant to a broad range of functional groups. Ó 2014 Published by Elsevier Ltd. Oxidation process has a tremendous attention from the indus- trial and academic standpoint. 1 The development of environmen- tally benign oxidation processes is the goal of various research projects. Thermal 2 and photolytic 3 oxidative decarboxylation of phenyl acetic acid by using heavy metals has been reported in pre- vious reports. It produces a large amount of waste and thus caused various environmental problems. The literature survey revealed that the oxidative decarboxylation of phenyl acetic acid possesses structural limitations such as substitution at a-position, 4 aerobic condition, stoichiometric loading of oxidants, 5 and high tempera- ture. 6 However a few reports are documented in the literature for direct oxidative decarboxylation of phenyl acetic acid. 7 There- fore, a clean, safe, and inexpensive method for the oxidation of ethyl phenyl acetate is highly desirable. Molecular iodine is favorable for organic synthesis owing to its inexpensive, non-toxic, and environmentally benign characteris- tics. 8 As a part of continuing effort in our laboratory to study iodine mediated transformations, 9 we are interested to develop a novel and efficient metal-free oxidative de-ethoxycarbonylation process for ethyl phenyl acetate. In this Letter, we disclose the oxidative de-ethoxycarbonylation of varieties of alkyl phenyl acetate by using molecular iodine in dimethyl sulfoxide. The process of oxidative de-alkoxycarbonylation of substituted alkyl phenyl acetates using iodine is represented in the Scheme 1. Varieties of alkyl phenyl acetate (1aa–1ad) were achieved by treating the commercially available phenyl acetic acid with alkyl halides and potassium carbonate in DMF. Initially, we selected allyl phenyl acetate (1aa) as a role model substrate to study the efficacy of de-alkoxycarbonylation by using catalytic amount of molecular iodine. No remarkable effect was observed at room temperature. When the temperature of reaction mixture was increased to 80 °C, exclusively deallylation was observed. This type of result was found to be in line with our previous reports. 10 A subsequent increase in the amount of iodine (1.0 equiv) yielded de-allyloxy- carbonylated product (48%) with recovery of remaining starting substrate. However, by increasing the temperature to 120 °C, the oxidative product was isolated in 62% after 9 h (Scheme 1, Entry a). A good yield was obtained with methyl and ethyl phenyl ace- tates (1ac and 1ad) while allyl and benzyl derivatives (1aa and 1ab) gave moderate yield (Scheme 1). Several solvents such as DCM, MeOH, DMF, diphenylether, and ethylene glycol were exam- ined to be used as reaction medium. Dimethyl sulfoxide was found to be an efficient solvent in the oxidative de-alkoxycarbonylation process. To test the generality of this new method and versatility of the iodine mediated oxidative de-alkoxycarbonylation, we sought to extend this protocol for various derivatives of ethyl phe- nyl acetate (Scheme 1). Substrates having electron withdrawing and donating groups undergo de-alkoxycarbonylation process affording gratifying yield. However, a clean and smooth reaction was obtained with a variety of substrates (Scheme 1, entries j, k, l); surprisingly hydrolysis was preferable for 1i under optimal condition. Wu et al. reported the domino process for the formation of hydantoins by Kornblum oxidation. 11 A mixture of iodine and http://dx.doi.org/10.1016/j.tetlet.2014.02.049 0040-4039/Ó 2014 Published by Elsevier Ltd. ⇑ Corresponding author. E-mail addresses: vivekhumne@rediffmail.com (V.T. Humne), pdlokhande@ chem.unipune.ac.in (P.D. Lokhande). Tetrahedron Letters 55 (2014) 2337–2339 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet