Trifluoroacetic anhydride, DMSO

The triphosgene/DMSO reagent may be a good substitute for trifluoroacetic anhydride/DMSO as well as acetic anhydride/DMSO, which are often employed in such oxidation reactions. The former usually gives the corresponding oxidized products along with variable amounts of trifluoroacetate esters [1373] and although... 

Acid anhydrides behave in a similar way to acid chlorides. In this paragraph is included an accident that is the result of a very violent interaction of trifluoroacetic anhydride with DMSO. This reaction can only be controlled by cooling at -40°C, in a solution with dichloromethane. 

Several laboratories have reported that Swern oxidation of alcohols can be accompanied of a-chlorination of keto or (1-keto ester groups. Undesired electrophilic chlorination can be avoided by use of oxalyl chloride (1.05 equiv.) and DMSO (2.5 equiv.) in stoichiometric amounts or by use of acetic anhydride or trifluoroacetic anhydride in place of oxalyl chloride.1... 

Marchand and co-workers reported a synthetic route to TNAZ (18) involving a novel electrophilic addition of NO+ NO2 across the highly strained C(3)-N bond of 3-(bromomethyl)-l-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium hydroxide under reduced pressure. The product of this reaction, A-nitroso-3-bromomethyl-3-nitroazetidine (22), is formed in 10% yield but is also accompanied by A-nitroso-3-bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the ferf-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both processes achieved in one pot with an alkaline solution of sodium nitrite, potassium ferricyanide and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large scale manufacture. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed which involve DMSO and any one of several electrophilic reagents, such as dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, or... 

The use of trifluoroacetic anhydride for the activation of DMSO in the oxidation of alcohols was first attempted by Albright and Goldman in 196 5.119,120 According to these authors, who tried the reaction at room temperature, trifluoroacetic anhydride is not effective in the activation of DMSO. Later, Swern et al. made a detailed study of the interaction of DMSO with TFAA,121 and proved that the resulting activated DMSO is stable at low temperature and can be used in the oxidation of alcohols. In... 

Neat trifluoroacetic anhydride and DMSO interact in an explosive manner at room temperature.121 Nevertheless, at low temperature and in the presence of CH2CI2, as solvent and moderator, DMSO and TFAA react almost instantaneously, yielding a white precipitate described as trifluoroa-cetoxydimethylsulfonium trifluoroacetate (22). 

Interestingly, although trifluoroacetic anhydride reacts very quickly with alcohols, the reaction with DMSO is even quicker. Therefore, the formation of the activated DMSO species 22 can be made in the presence of the alcohol, resulting in little erosion of the oxidation yield. 

The activation of DMSO by electrophilic reagents such as oxallyl chloride or trifluoroacetic anhydride (TFAA) (among many others) produces an oxidant capable of oxidizing primary alcohols to aldehydes in high yields. This oxidation is called the Swern oxidation and yields the aldehyde (oxidized product) by reductive elimination of dimethylsulfide (reduced product) and proceeds under mild, slightly basic conditions. It is a second widely used and effective oxidative method for the production of aldehydes from primary alcohols. 

The presence of amino substituents in the 2- or 5-position activates the oxazole ring (4-aminooxazoles are unknown). Thus 2-amino-3-aryloxazoles yield the derivatives (127 X = Cl or Br) on halogenation, and nitration of 2-dimethylamino-4-phenyloxazole afforded 2-dimethylamino-5-nitro-4-(4-nitrophenyl)oxazole, the sole example of direct nitration of the oxazole ring. 5-Dialkylamino-2-phenyloxazoles react with trifluoroacetic anhydride to form the ketones (128) and they couple with arene diazonium fluoroborates the products (129) readily rearrange to 1,2,4-triazoles (130) in DMSO solution. 

Similar oxidation of alcohols has been carried out with DMSO and other reagents in place of DCC acetic anhydride, S03-pyridine-triethyla-mine, " trifluoroacetic anhydride, tosyl chloride, Ph3P Br, ... 

Trifluoroacetic anhydride (TFAA) is also a very potent activator for DMSO and concomitant trifluoroacetylation of the starting alcohol is usually not observed [27]. Both the Swem and the TFAA procedure are carried out at low temperature to prevent undesired side reactions, particularly formation of the methylthiomethyl ether. Before these two methods became developed, acetic anhydride was often used for DMSO activation. Flowever, the oxidation under these conditions is slower and the methylthiomethyl ether byproduct is often observed [27]. 

Derived reagents. Mancuso and Swern2 have reviewed activated dimethyl sulfoxide reagents (100 references). Activation of DMSO with either trifluoroacetic anhydride (7, 136) or oxalyl chloride (8, 200) provides the most generally useful... 

Cr is also advantageous from an environmental point of view. Various methods for the activation of DMSO have been developed, and activation with trifluoroacetic anhydride (TFAA) is frequently employed in modern organic synthesis. It is well known that a reactive species generated by the... 

The likely reactive species and source of electrophilic chlorine is thought to be 7 and/or its decomposition product 8, which reacts with the enol of the ketone or P-ketoester, that is, the expected oxidised product. This side reaction can be avoided by employing one equivalent of the oxalyl chloride or by using either trifluoroacetic anhydride or acetic anhydride with DMSO. 

Kobayashi and co-workers report an interesting ring opening reaction which occurs when the Swem conditions are applied to pyrazine-fused bicycles.5 Exo-cis diol 81 when treated with DMSO and oxalyl chloride gave alcohol 82 in 63%. The same product was obtained in the same yield using trifluoroacetic anhydride instead of oxalyl chloride. 

C.i. Swern Oxidation. The variation that is probably the most common in synthesis was discovered by Swern, who found that DMSO can be activated for the oxidation of alcohols by addition of trifluoroacetic anhydride. 6 The reaction is usually done in dichloromethane at temperatures below -30°C. The initially... 

In the absence of a moderating solvent, admixture of DMSO and trifluoroacetic anhydride proceeds explosively. ... 

The resulting reagent is superior to the DMSO-trifluoroacetic anhydride reagent. The reaction probably proceeds via intermediate complex (55), which is unstable above -60°C. The reaction is, therefore, performed... 

Other oxidation reactions using DMSO as an oxidant include the Pfitzner-Moffatt Oxidation (DMSO/dicyclohexylcarbodiimide), Swem oxidation (DMSO/oxalyl chloride or trifluoroacetic anhydride), Onodera oxidation (DMSO/phosphorus pentoxide), Parikh-Doering Oxidation (DMSO/pyridine-sulfur trioxide), Corey-Kim Oxidation (dimethyl sulfide/Ai-chlorosuccinimide), and Liu oxidation (DMSO/phenyl dichlorophosphate). 

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