Oxidation alcohol, Pfitzner-Moffatt

Dimethyl sulfoxide dicyclohexylcarbodiimide Oxo compds. from alcohols Pfitzner-Moffatt oxidation... 

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

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

This fluorine-containing, oxidation-resistant alcohol is best oxidized by the Pfitzner-Moffatt reaction, using dichloroacetic acid as catalyst. Observe the use of toluene, instead of carcinogenic benzene, as solvent. A Swern oxidation was not reproducible, and caused substantial epimerization of the isobutyl side chain. Collins oxidation was successful, but ... 

A good yield in the oxidation of this hindered secondary alcohol was obtained employing the Pfitzner-Moffatt method, by using ortophosphoric acid as a strong acidic activator. Collins oxidation delivers only a 38% yield. 

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. 

Quite puzzingly, thiols are reported14b to be unreactive under Pfitzner-Moffatt conditions, while this being one of the few oxidation methods for alcohols compatible with this functionality. Sulfides also resist the action of Pfitzner-Moffatt oxidations.42,43... 

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. 

A large number of other materials have been used to activate dimethyl sulfoxide for the oxidation of primary and secondary alcohols and new methods are still being introduced. The vast majority of these reactions proceed via an alkoxysulfonium salt and consequently are variants of the original Pfitzner-Moffatt procedure. Very few of tiiese methods have been exhaustively tested and their advantages are often not apparent. 

Different electrophiles have been used to effect this oxidation. For example, in Pfitzner-Moffatt oxidation, alcohols are oxidized to aldehydes and ketones by the DMSO and DCC (dicyclohexylcarbodiimide). The resulting alkoxysulfonium ylide C rearranges to generate aldehydes and ketones (Scheme 7.6). 

Pfitzner-Moffatt oxidation Oxidation of primary and secondary alcohols with DCC/DMSO to giye the corresponding aldehydes and ketones. 346... 

In the Pfitzner-Moffatt oxidation,4 an alcohol is oxidised by treatment with a mixture of dicydohexylcarbodiimide (DCC) (22), DMSO and an acid source, e.g. polyphosphoric acid, sulfur trioxide-pyridine, pyridine trifluoroacetate or acetic... 

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. 

Pfitzner-Moffatt oxidation (1, 304-307 2, 162). The highly strained tetracyclic ketone quadricyclanone (2), 7-quadricyclo[2.2.1.02-6.03-5]heplanone, was first prepared13 by oxidation of quadricyclanol (1) with t-butyl hypochlorite in pyridine-carbon tetrachloride (method of Grob and Schmid, 1, 90, ref. 6) but the yield was only 14% and it was difficult to separate the ketone from unchanged alcohol. The oxidation later14 was considerably improved by conversion of (1) into the tosylate... 

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 ol 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. 

In a total synthesis of the alkaloid di-camptothecin, Rapoport et al. investigated the oxidation of the alcohol (1). The Pfitzner-Moffatt reagent proved... 

The Pfitzner-Moffatt reagent was also shown to be effective for oxidation of the related alcohol (3) to the corresponding ketone (76% yield). 

Oxidation of an allylic alcohol. This reagent has been used successfully to oxidize the benzyl ester of the /S-lactam antibiotic clavulanic acid (1) to the labile allylic aldehyde 2. Attempted oxidation with the Pfitzner-Moffatt reagent resulted in formation of a 1,3-diene by a 1,4-elimination. ... 

Reaction of 6-methoxy-l-tetralone (30) with methylmagnesium iodide gave the dihydronaphthalene (31) in high yield (Scheme 4). However, the transformation of 31 to the tetralone 33, via perbenzoic acid epoxidation followed by acid workup, was capricious and resulted in low yields. A better route was developed, involving hydroboration (hydrogen peroxide oxidation) to the alcohol 32, followed by Pfitzner-Moffatt oxidation to the tetralone 33 in an overall yield of 61%. Other oxidation methods were tried but with varied and poor results. Alkylation of the tetralone 33 with 3-bromopropyne yielded 34, which underwent hydration [mercury (II) acetate in acetic acid-formic acid] to the diketone (35). The enone (36) obtained by base catalyzed cyclization was ster-eospecifically reduced with lithium aluminum hydride to the allylic alcohol... 

Oxidation of Primary Alcohols. One example of EDC substituting for DCC in the Pfitzner-Moffatt oxidation is shown in (eq 7). The use of DCC in this example resulted in a difficult purification of the product and lower yields. 

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... 

Note Pfitzner-Moffatt reaction represents oxidation of primaiy and secondary alcohols by dimethyl sulfoxide (DMSO) activated with carbodiimides, usually dicyclohexylcarbodiimide (DCC). Intermediary alkoxysulfonium ylides rearrange to aldehydes or ketones. This reaction yields urea as a by-product that is difficult to... 

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