Moffatt oxidation, of alcohols

Almost any electrophile, able to react with DMSO, can generate an active DMSO species that can be used for the oxidation of alcohols. Dozens of such activators have been described in the literature as shown in Table 2.2. Many of these activators have been the subject of very superficial analyses and, therefore, their potential for Moffatt oxidation of alcohols is not known in detail. Some of these activators particularly... 

Polymers with pendant carbodiimide groups 27 are also synthesized from crossUnked polystyrene. In this synthetic route crossUnked polystyrene beads are chloromethylated and converted to the amines. Reaction with isopropyl isocyanate gives the corresponding ureas, which are treated with tosyl chloride and triethylamine to produce the crossUnked polycarbodiimides. This polymer is used in the polymer supported Moffatt oxidation of alcohols into aldehydes or ketones using benzene/DMSO. ... 

Polystyrene carbodiimide is useful for the synthesis of anhydrides It can also be used for the Moffatt oxidation of alcohols to aldehydes and ketones. Even the labile prostaglandin intermediate (A) is readily converted to the desired aldehyde (B) (Scheme 6). 

Oxidation of alcohols using DCC and DMSO, also known as Pfitzner-Moffatt oxidation . 

Sulfoxides (essentially DMSO) can be used for oxidation of alcohols to v carbonyl compounds as in the Moffatt, Swem and related oxidations [237,... 

During some couplings of nucleosides, promoted by dicyclohexylcarbodii-mide (DCC), Pfitzner and Moffatt.13 decided to try dimethyl sulfoxide (DMSO) as solvent. Instead of obtaining the expected couplings, they observed oxidation of alcohols to aldehydes and ketones. These oxidations were very remarkable, because at that time, on the nucleosides tested, no oxidants were known to be able to deliver efficiently the observed aldehydes and ketones. Furthermore, contrary to many other oxidants, no over-... 

General Procedure for Oxidation of Alcohols by Pfitzner-Moffatt Method... 

Carboxylic acids react under Pfitzner-Moffatt conditions, resulting in the formation of methylthiomethyl esters and /V-acylureas.41 Nevertheless, although the authors are not aware of any report involving the selective oxidation of alcohols in the presence of a carboxylic acid, such outcome would be likely with carboxylic acids with little nucleophilicity, as standard Pfitzner-Moffatt oxidations are performed in the presence of trifluoroacetate that is known for not to interfere. 

Although amides can react under Pfitzner-Moffatt conditions, resulting in the formation of a number of compounds, including N-methylthiomethylamides and A -acylsulfilimines,46 normally, these reactions are slower than the oxidation of alcohols, so that selective oxidations can be possible.23 4... 

The simplest sulphoxide, dimethyl sulphoxide, is an important aprotic solvent (Section 4.1.55, p. 412). Its use as a reagent in carbon-carbon forming reactions and as a reagent for the oxidation of alcohols to carbonyl compounds (p. 608) (the Pfitzner-Moffatt and Swern oxidations) has been extensively reviewed.244 An illustrative example of carbon-carbon bond formation using dimethyl sulphoxide is noted in Expt 7.3. 

Equimolar quantities of benzhydrol and the phosphorane (3a) were also reacted in dimethyl sulphoxide solution. Apart from bis(benzhydryl) ether (18%) and catechol monobenzhydryl ether (39%), a small amount of benzophenone (17%) was obtained. It was shown that, in the absence of phosphorane, benzhydrol is not oxidised to benzophenone by dimethyl sulphoxide. Reaction similar to that outlined in Scheme 1 is a likely possibility. Again, the alcohol is activated by reaction with the phosphorane toward nucleophilic attack, in this case by dimethyl sulphoxide. Significantly, oxidation of alcohols by dimethyl sulphoxide is usually carried out using the Pfitzner-Moffatt reagent (dicyclohexyl carbodiimide and anhydrous phosphoric acid in dimethyl sulphoxide) (13) whereas the reaction using the phosphorane (3a) is carried out under neutral conditions. Unfortunately, however, attempts to improve the yield of benzophenone have hitherto failed. 

T. T. Tidwell, Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides The Moffatt, Swem, and Related Oxidations, Org. React. 1990, 39, 297-572. 

Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfbnium Vlides The Moffatt, Swern, and Related Oxidations Thomas T. Tidwell 0-471-02933-0 3150.00... 

Pfitzner-Moffatt oxidation. Oxidation of alcohols to carbonyl derivatives with dimethyl sulfoxide and dicyclohexylcarbodiimide. The procedure is especially useful for the conversion of a primary alcohol to an aldehyde without further oxidation to the carboxylic acid. 

Methods involving electrophilic fluorination have been used to prepare a number of fluorophosphonates. Examples include benzylic a,a-difluoromethyl-phosphonates, e.g. 157, by the reaction of the carbanion of 156 with N-fluorobenzenesulfonimide (NFBS) (Scheme 10), which is claimed to be superior to DAST, and (a,a-difluoroprop-2-ynyl)phosphonates 159 by the direct di-fluorination of the a-ketophosphonate 158 (Scheme ll). Compound 158 is prepared by Pfitzner-Moffatt oxidation of the corresponding alcohol and it is worth noting that few such oxidations of a-hydroxyalkylphosphonates have been reported. 

Oxidation with dimethyl sulfoxide (DMSO), which is known as Swern-Moffatt oxidation, is one of the most versatile and reliable methods for the oxidation of alcohols to carbonyl compounds and is widely utilized in laboratory organic synthesis. Avoidance of heavy metals such as Mn and... 

The Pfitzner-Moffatt oxidation utilises 1,3-dicyclohexylcarbodiimide as the DMSO activator in the presence of acid to afford oxidation of alcohols to carbonyls.2,24,25 Initial work was carried out on steroids and thymidine residues although the procedure has since been found to be applicable to a large range of alcohols. In the following example, the Pfitzner-Moffatt method was used as an alternative to the Swem reaction which had resulted in the formation of an unwanted a-chloroketone (see later).26 Other oxidation procedures were attempted (PDC, PCC, Dess-Martin periodinane) however the Pfitzner-Moffatt gave the best, albeit modest, yield. 

PFITZNER- MOFFATT Oxidation Oxidation of alcohols to ketones or aldehydes by means of DCC DMSO... 

Sulfoxides (essentially DMSO) can be used for oxidation of alcohols to carbonyl compounds as in the Moffatt, Swern and related oxidations [237, 238]. These mild and useful processes proceed through an oxosulfonium salt. In the Pfitzner-Moffatt procedure the alcohol is treated with DMSO, DCC and anhydrous phosphoric acid. The proposed mechanism involves an alkylsulfonium ylide as an intermediate. 

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... 

Mild oxidation of alcohols to carbonyl compounds via alkoxysulfonium ylides is a very important transformation in organic synthesis and several reviews cover many of the practical and mechanistic aspects of the Moffatt, Swern, and related oxidations [1316-1320]. 

The liquid-phase oxidation of 1,3-dithian, and oxidation of alcoholic functional groups in the presence of the 1,3-dithian moiety by the Pfitzner-Moffatt reagent, has been studied. Both cis- and 1,3-dithian 1-A -arylimides (167) were prepared and they rearranged with high stereospecificity. 1,3-Dithian 1-imide 1,3,3-trioxide (168) has been obtained, in excellent yield, by the cleavage of the corresponding A-tosyl compound with Na and... 

An extension of the approach to additional chemical reactions has been reported by other groups. Flynn and co-workers [21] have developed some protocols for the Moffatt oxidation of secondary alcohol to ketones (Figure 8) and the addition of organometallic reagents to aldehydes. The same group has also developed the use of tetrafluorophthalic anhydride to assist in the purification of reaction mixtures [22]. 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

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