Swern—Moffatt oxidation temperature

A mechanism suggested for Swern-Moffatt oxidation with TFAA is shown in Scheme 8.6. In the first step, DMSO reacts with TFAA to form cationic reactive species I, which is known to be stable only below —At higher temperatures, rearrangement of I takes place to give species II. The reaction of II with an alcohol IQ upon treatment with a base leads to formation of a major by-product, trifluoroacetic acid (TFA) ester VII. Therefore, the first step should be carried out below —50 °C. In the second step, reactive species I is allowed to react with an alcohol HI at or below —50°C to obtain intermediate IV. IV may also undergo the Pummerer rearrangement to give a methyl thiomethyl (MTM) ether VI upon treatment with a base. In the third step, IV is treated with a base (usually triethylamine) to obtain the desired carbonyl compound V and dimethyl sulfide. 

The Swern-MofFatt oxidation is a versatile metal-free oxidation method that finds application in the transformation of primary and secondary alcohols into aldehydes and ketones, respectively. However, its application in process chemistry is hampered by the low-temperature requirement, namely, 70 °C, and the highly exothermic behavior, which makes temperature control very diEBcult. The highly efficient heat transfer in the microreactor should solve the problem of limited cooling capacity in a batch reactor. 

All of the usual chromium-based oxidation reagents that have been used for the oxidation of cyclobutanols to cyclobutanones, for example, chromium(VI) oxide (Jones reagent),302 pyri-dinium chlorochromate,304 pyridinium dichromate,307 and chromium(YI) oxide/pyridine (Collins),303 are reported to do so without any serious problems. Alternatively, tetrapropylam-monium perruthenate in the presence of A-methylmorpholine A -oxide. oxalyl chloride in the presence of triethylamine in dimethyl sulfoxide (Swern),158,309,310 or phenyl dichlorophos-phate in the presence of triethylamine and dimethyl sulfoxide in dichloromethane (Pfitzner-Moffatt),308 can be used. The Pfitzner-Moffatt oxidation procedure is found to be more convenient than the Swern oxidation procedure, especially with respect to the strict temperature control that is necessary to achieve good yields in the latter, e.g. oxidation of 1 to give 2.308... 

Microflow systems serve as effective environments to perform various oxidation reactions using chemical reagents. The oxidation using dimethyl sulfoxide (DMSO), which is known as Moffatt-Swern type oxidation, is one of the most versatile and reliable methods for the oxidation of alcohols into carbonyl compounds in laboratory synthesis [1, 2]. However, it is well known that activation of DMSO leads to an inevitable side-reaction, Pummerer rearrangement, at temperatures above — 30°C (Scheme 7.1). Therefore, the reaction is usually carried out at low temperatures (—50 °C or below), where such a side-reaction is very slow [3, 4]. However, the requirement for such low temperatures causes severe limitations in the industrial use of this highly useful reaction. The use of microflow systems solves the problem. For example, the oxidation of cyclohexanol can be accomplished using a microflow... 

Oxidations using dimethyl sulfoxide activated by various reagents began with discoveries by Komblum and co-workers that primary tosylates and certain a-bromo ketones could be converted into aldehydes and glycoxals, respectively, by treatment with dimethyl sulfoxide as the oxidising agent. This was followed by the discovery several years later by Pfitzner and Moffatt that alcohols could be oxidised to carbonyl compounds with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC) and phosphoric acid at room temperature.2 Eventually the method developed by Swern and co-workers, involving activation of dimethyl sulfoxide with oxalyl chloride, came to be the most synthetically useful and widely applied of these mild oxidation procedures.3-6... 

Figure 12.1 Simplified reactor schematic for the continuous Moffatt-Swern oxidation at room temperature with dimethyl sulfoxide (DMSO) and trifluoroacetic anhydride (TFAA) of a variety of alcohols (1-decanol 71%, 2-octanol 89%, cyclohexanol 88%, ben2yl alcohol 75%).

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