Polonovski reactions, acetic anhydride

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. 

A modification of the Polonovski reaction where trifluoroacetic anhydride is used in place of acetic anhydride. Because the reaction conditions for the Polonovski-Potier reaction are mild, it has largely replaced the Polonovski reaction. 

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. 

Another remarkable reaction is the methoxymercuration which leads, when applied to derivatives of lysergic acid, to the unique 10-methoxy-A8,9-ergolene derivatives (50) after treatment of the addition product with base and NaBH4 (51). In another recent paper (127) the synthesis of a new structural isomer of lysergic acid methyl ester (28) has been reported in which a novel modification of the Polonovski reaction has been used to introduce the 7,8 double bond. Thus, the A-oxide 51 on treatment with acetic anhydride and excess base, yielded the enamino ester (52) in about 50% yield. 

Studies of the Polonovski reaction in conformationally rigid polycyclic systems reveal the stereochemical requirements for the elimination step. For example, the 6p,7p-dideutero derivative (22) of nu-pharidine is converted on reaction with acetic anhydride into A -dehydrodeoxynupharidine (24) containing a single deuterium atom at Ca (Scheme 4). ... 

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. 

The enamino ketone (54) can also be prepared by a Polonovski approach, involving either sequential addition of wi-chloroperbenzoic acid, acetic anhydride and triethylamine to a cooled solution of (52) in methylene chloride or reaction of the A -oxide (53) with trifluoroacetic anhydride (Scheme 10). ° Although the latter approach involves three distinct steps, the overall yield of (54) is higher. 

The mitosane A -oxide derivative (57) is similarly converted into the pyrroloindole derivative (58) in high yield upon reaction with acetic anhydride in chloroform (equation 17). The corresponding reaction of the 1,2-diacetoxy derivative (59) is more complex, however, as there is no directing functionality to orient the reaction (Scheme 11). One of the reaction products (62) is viewed as being formed via intermediates (60) and (61). If this mechanistic rationale is correct then the transformation of (59) to (62) represents a new manifestation of the Polonovski reaction. 

There is one special example involving the reaction of 1,4-diazepine A -oxides such as (76), a trisub-stituted nitrone, with acetic anhydride which has repeatedly been referred to as a Polonovski reaction, because the acetate group is intr uced at the saturated C-3 position in the product (77). However, an alternative mechanism proposed for this reaction appears more likely (Scheme 17) as it conserves all the aspects of the chemistiy of nitrones with the slight variation that the elements of acetic acid are eliminated through loss of the C-3 proton. ... 

The total synthesis of (+)-dynemicin A was achieved by S.J. Danishefsky et al. As part of the synthetic studies, highly sensitive enediyne containing quinone imine systems were prepared, and their biological properties were evaluated. The first step in the sequence leading to one such quinone imine began with the oxidation of the nitrogen of the phenanthridine substrate, and the resulting A/-oxide was heated in neat acetic anhydride to induce the Polonovski reaction. 

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. 

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 ... 

Mannich reagent. French chemists reported that use of trifluoroacetic anhydride rather than acetic anhydride in the Polonovski reaction resulted in improved yields (2, 7, 8). They1 now find that the reaction of trifluoroacetic anhydride with the N-oxide of trimethylamine leads to the trifluoroacetate of N,N-dimethylformaldimmonium (1). This ion is considered to be the actual reagent in... 

Phthalic acid, 259 Phthalic anhydride, 104 a-Picoline, 161 a-Picoline N-oxide, 161 Picolinic acid, 16 Picramic acid, 271 Picric acid, 271 Pinacol reduction, 7 Pinosylvin, 31 Piperazines, 322 Piperidine, 33, 291 2-Piperidone, 194 Pivaldehyde, 105 Podophyllotoxin, 337 Podophyllotoxone, 337 Polonovski reaction, 308 Polyisoprenoids, 300-301 Polymethoxybenzophenones, 30—31 Polymethylhydrosiloxane, 294 Polyphosphate ester (PPE), 229-230 Polyphosphoric acid, 227, 231—232 Potassium, 232, 233 Potassium acetate, 96 Potassium amide, 232—233, 310 Potassium azodicarboxylate, 100 Potassium r-butoxide, 26, 45, 47, 77-78, 85, 133, 188, 212, 222, 225, 233-234, 236, 246... 

The Polonovsky reaction (246) whereby a 3-pyrroline ring system is oxidized to the N-oxide and treated with acetic anhydride to give the pyrrole, has been employed by Dann (247) to detect pyrrolizidine alkaloid iV-oxides on paper chromatograms, the fluorescence of the pyrrole being observed. The method has been developed by Mattocks (248) as a spectrophotometric procedure, applicable also to biological material... 

Category Ilae cyclizations play a prominent role in the synthesis of isoindoles. Simple 2-alkyl-2/f-isoindoles can be prepared from l,2-bis-(bromomethyl)benzene via dihydroisoindole-A(-oxides. The oxides undergo Polonovsky elimination in acetic anhydride/triethylamine <88CZ85>. A similar reaction sequence can be applied to the synthesis of 2-aryl analogs (Scheme 72) <87CZI55>. 

Polonovski reaction (3, 7 5, 3). French chemists have modified this reaction by use of trifluoroacetic anhydride rather than acetic anhydride and have applied this version to a useful synthesis of compounds related to antitumor alkaloids of Catharanthus roseus. Thus treatment of the N-oxide (1) of catharanthine, an iboganc alkaloid, with TFAA in CH2CI2 at -78" in the presence of vindoline (2) and then with NaBHi leads to three products, one of which is the desired (3),... 

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. ... 

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