Amine oxides Polonovski reaction

Acylation. Aliphatic amine oxides react with acylating agents such as acetic anhydride and acetyl chloride to form either A[,A/-diaLkylamides and aldehyde (34), the Polonovski reaction, or an ester, depending upon the polarity of the solvent used (35,36). Along with a polar mechanism (37), a metal-complex-induced mechanism involving a free-radical intermediate has been proposed. 

In another search for an alternative to Potier s modified Polonovski reaction of catharanthine A-oxide (45), it has now been found that anhy-drovinblastine (42) can be generated directly, in 77% yield, from a reaction of catharanthine and vindoline in 0.01 N acid, promoted by ionized ferric salts, followed by reduction with sodium borohydride (Scheme 30) (Wl). Remarkably, the cation radical 106 generated by Fe(III), in accord with other simple amine oxidations by Lindsay Smith and Mead (102), resulted in isoquinuclidine fragmentation and coupling to vindoline at 0°C, without the conformational inversion observed in the modified Polonovski reaction at that temperature (see Scheme 15). Other metal oxidants or ligand-bound Fe(lll) did not promote the coupling reaction. It will be of interest to see if the overwhelming competition of C-5-C-6 bond... 

Another example is provided by the application of the modified Polonovski reaction to A3-piperideines. Treatment of amine oxides (141) with trifluoroacetic anhydride results in the formation of iminium ion (142). These compounds can behave as useful synthetic intermediates, reacting with a number of nucleophiles such as cyanide ion (80JA1064). 

POLONOVSKI REACTION. Demethylation of tertiary (or Heterocyclic) amine A-oxides on treatment with acetyl chloride or acetic anhydride 1o give A-acylated secondary amines and formaldehyde, along with (9-acylated aminophenols as a result of a side reaction. 

Decarboxylation of a-tertiary amino acids in phosphorus oxychloride results in iminium salt products197,198. Using Polonovski reaction (treatment of the tertiary amine-N-oxide with trifluoracetic acid) various iminium salts have been made199-204. Cycloaddition of keteniminium ions to olefins gives cyclobutyliminium salts205-207. Anodic oxidation208-214 and oxidation of trityl salts of tertiary amines to iminium salts215 216 has been described. 

The first step in the Polonovski reaction of an amine N-oxide with an acid anhydride, acyl chloride or chloroformate ester is the formation of the 0-acylimonium salt (1 Scheme 1). Such species are highly unstable. However, they can be detected in situ ( H NMR), and in certain cases actually isolated, if prepared using powerful acylating agents such as acetyl perchlorate. 

To date no reports of the Polonovski reaction of N-oxides of four- or seven- and higher-membered cyclic tertiary amines have appeared. Aziridine N-oxides can be prepared by ozonolysis of N-r-butylazi-ridine however, these compounds are unstable above 0 C. At higher temperatures compound (33) undergoes first-order decomposition to ethylene and 2-methyl-2-nitrosopropane (equation 11). 

Enamines can be obtained as the products of the Polonovski reaction of amine oxides and, in particular, by reaction of piperidine A -oxides with acetic anhydride. This is primarily due to the fact that when acetate is the counterion the intermediate iminium ions are labile and readily tautomerize. The formation of enamines during the Polonovski reaction is also favored by the presence of a base. In fact, enamines are often obtained in high yield from the reaction of an IV-oxide with trifluoroacetic anhydride in the presence of triethylamine or pyridine. Conversion of intermediate iminium ions, generated under modi-fred Polonovski conditions, to enamine products can also occur during hydrolytic work-up. 

In several instances reaction of an amine oxide with an acid anhydride triggers a process in which the amine oxide nitrogen is converted into a leaving group and the Co—bond is cleaved (Scheme 15). ° Interestingly, these reactions occur to the exclusion of the Polonovski pathways, i.e. elimination of the benzylic a-hydrogen or fragmentation of the phenethylamine chain. 

Cave, A., Kan-Fan, C., Potier, P., Le Men, J. Modification of the Polonovski reaction. Reaction of trifluoroacetic anhydride with an amine oxide. Tetrahedron 1967, 23, 4681-4689. 

Jessop, R. A., Smith, J. R. L. Amine oxidation. Part XII. Reactions of some N,N-dimethylbenzylamine N-oxides with acetic anhydride and of some N-acetoxy-N,N-dimethylbenzylammonium perchlorates with acetate ion. The Polonovski reaction. J. Chem. Soc., Perkin Trans. 1 1976,1801-1805. 

Russell, G. A., Mikol, G. J. Acid-catalyzed rearrangements of sulfoxides and amine oxides. The Pummerer and Polonovski reactions. Mech. 

Polonovski reaction. This reaction consists in the reaction of the N-oxide of a tertiary amine (1) with acetic anhydride to form the N-acylated secondary amine (2) as the major product and the deaminated ketone (3) as minor product ... 

Trifluoroethylidenation of activated CH2P The Polonovski reaction of dimethyl(trifluoroethyl)amine oxide with (CFjCOljO in the presence of a compound containing an active methylene group accomplishes trifluoroethylidenation at that site. 

A modified Polonovski reaction is another efficient method for iV-demethyla-tion. The amine iV-oxide is treated with trifluoroacetic anhydride instead of the more usual acetic anhydride, and the resulting immonium salt is then hydrolyzed. ... 

In a variation of the known conversion of phthalideisoquinolines into rhoeadines, the -lactone 1 derived from jS-hydrastine was converted to its iV-oxide. The secondary amine 2 was obtained from the iV-oxide by reaction with trifluoroacetic anhydride, in a modified Polonovski reaction. The papaverrubine 3 was then generated from the amine 2 as shown below ... 

An alternative procedure [32] uses a different approach, making use of the Polonovski reaction, which converts the amine oxide into an A,N-disubstituted acetamide ... 

Treatment of amine oxides containing at least one nitrogen-attached methyl group with acetic anhydride, results in the Polonovski reaction (reaction 65) product studies on which indicate the involvement of radicals . The reaction is also catalysed by Fe(ni) and by many transition-metal complexes (reaction 66) . These reactions have been studied as models for the bacterial degradation of nicotine which involves iV-oxidation as the first step . JV Arylamine oxides give considerable amounts of o-acetylarylamines on treatment with acetic anhydride, presumably via cyclisation from the N-ace-tate , and similar migrations are common for heterocyclic... 

Reaction of morphine N-oxide and Ac O. The Polonovski reaction (2, 4, 5) has been described, whereby tert-amine oxides containing at least one N-methyl group are converted by acetic anhydride into sec-amines and formaldehyde. The reaction mechanism by J.C. Craig et al. (3) proposed that it proceeded by a free radical sequence. 

Polonovski Reaction. In the Polonovski reaction, tertiary amine oxides react with acetic anhydride to give the acetamide of the corresponding secondary amine (eq 34). 

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