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Practical and Efficient Large Scale Preparation of Dimethyldioxirane (DMDO) Hannes Mikula, Dennis Svatunek, Daniel Lumpi, Florian Glöcklhofer, Christian Hametner, and Johannes Froehlich Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/op300338q • Publication Date (Web): 14 Jan 2013 Downloaded from http://pubs.acs.org on January 22, 2013
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Organic Process Research & Development
Practical and Efficient Large Scale Preparation of Dimethyldioxirane (DMDO) Hannes Mikula, Dennis Svatunek, Daniel Lumpi, Florian Glöcklhofer, Christian Hametner, and Johannes Fröhlich Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, 1060 Vienna, Austria
ABSTRACT: An improved procedure for large scale and also commercially viable preparation of dimethyldioxirane (DMDO), a common and widely used oxidation agent in organic synthesis, was developed using a conventional laboratory plant. All reaction parameters were optimized and the stability of a freshly prepared solution of DMDO in acetone was monitored over an extended period of time to ensure long-term use after preparation, transport and storage. This discontinuous approach, suitable for batch processing, is of interest basically to research laboratories, but also to suppliers in the research and fine chemicals market.
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INTRODUCTION Dimethyldioxirane (DMDO) is a frequently used reagent in organic synthesis. This nonmetal organic oxidant has the unique ability to transfer an oxygen atom to a wide variety of substrates and functionalities, including carbon-carbon double bonds, carbon hydrogen bonds, sulfides, sulfoxides and amines (Scheme 1). Usually the starting material is directly reacted with a DMDO solution in acetone at ambient or low temperatures to afford the desired product after short reaction times simply by evaporation of the solvent. In most cases nearly quantitative yields and high purities are achieved without the need of further time-consuming steps (e.g. extraction and/or chromatography). Since the evaporated acetone can be reused directly for the preparation of DMDO, solvent recycling is possible, which is of significant importance especially in the case of large scale syntheses. Detailed information on reactions as well as spectroscopic and computational data of dioxiranes were reviewed by Adam et al. as well as Murray,1, 2 but since then the scope of dimethyldioxirane as important reagent for organic synthesis was further broadened. For example oxidation of epoxy alcohols to their corresponding epoxy ketones was shown by Willard and co-workers.3 DMDO also proved to be useful for oxidation of iodoarenes,4 N-substituted indoles and oxindoles.5 Furthermore, dimethyldioxirane was applied for epoxidation of allenes to give stable spiro-fused di-epoxides6 as well as for conversion of nitroalkanes into carbonyl compounds (Nef reactions).7 Ying and Hong used DMDO for the oxidation of the amino group of protected D-lysine to the corresponding nitrone within the total synthesis of the potent cytotoxic siderophore brasilibactin A.8 Stereoelectronic factors in the stereoselective epoxidation of glycals and 4-deoxypentenosides were investigated very recently.9 Novel applications of DMDO were also reviewed in short by Srivastava.10
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Organic Process Research & Development
Scheme 1. Preparation and selected applications of dimethyldioxirane (DMDO) In particular, dimethyldioxirane is the reagent of choice for most epoxidations, due to remarkably convenient procedures and its selectivity and reactivity under mild reaction conditions. In many cases using freshly prepared DMDO solutions, pure products are obtained after removal of the solvent, mostly in higher yields compared to similar oxidation reactions, e.g. using m-chloroperbenzoic acid (MCPBA).11 DMDO is easy to handle and can be used for the oxidation of acid- or base-sensitive substrates as well as for the preparation of hydrolytically labile products. Due to simple reaction as well as work-up procedures applying a nonmetal oxidant with high reactivity and selectivity, the application of DMDO has significant advantages also compared to other methods for epoxidation, e.g. urea hydrogen peroxide (UHP)12, ironcatalyzed epoxidation13 or enzymatic methods.14 Furthermore exclusively non-toxic as well as cheap chemicals and solvents are required and used for DMDO preparation. Solutions of DMDO in acetone are usually prepared by oxidizing acetone with commercially available low-cost potassium peroxymonosulfate KHSO5 (Oxone;
