Carboxylic acids Beckmann rearrangements

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

The common name caprolactam comes from the original name for the Ce carboxylic acid, caproic acid. Caprolactam is the cyclic amide (lactam) of 6-aminocaproic acid. Its manufacture is from cyclohexanone, made usually from cyclohexane (58%), but also available from phenol (42%). Some of the cyclohexanol in cyclohexanone/cyclohexanol mixtures can be converted to cyclohexanone by a ZnO catalyst at 400°C. Then the cyclohexanone is converted into the oxime with hydroxylamine. The oxime undergoes a very famous acid-catalyzed reaction called the Beckmann rearrangement to give caprolactam. Sulfuric acid at 100-120°C is common but phosphoric acid is also used, since after treatment with ammonia the by-product becomes... 

Amines 297 and/or carboxylic acids 298 may be obtained by amide hydrolysis and the latter compound may be produced from a ketone by a Beckmann rearrangement (equation 103). Therefore, the Beckmann rearrangement of a ketone oxime followed by amide hydrolysis provides a synthetic method to cleave the C—C bond between the carbon... 

The same strategy had application in several other heterocyclic compounds, to obtain either amine or carboxylic acid derivatives. A process for the production of 4-amino-5-methylpyrazole derivative 325 using the Beckmann rearrangement as a key step was the subject of a new patent ° (equation 119). 

While metallocenes are usually acetylated with acid halides, acid anhydrides, or carboxylic acids, a number of other acylating agents have been reported. The reaction of ferrocene with various isocyanates and aluminum chlorides leads to N-substituted ferrocenecarboxamides (IX) (89). Use of ruthenocene in place of ferrocene leads to analogous results (88). The preparation of V-phenyl-ferrocenecarboxamide from phenyl isocyanate in this manner has been used as a proof of structure for the product obtained from the Beckmann rearrangement of benzoylferrocene oxime (124). 

Xanthone is unreactive towards hydrazine and phenylhydrazine. The oxime is obtained by reaction of xanthione (xanthene-9-thione) with hydroxylamine, or from xanthone and hydroxylamine in pyridine. When the oxime is heated in water with phenylhydrazine, the phenylhydrazone is formed. In acid solution, xanthone reacts normally with 2,4-dinitro-phenylhydrazine but xanthone-1 -carboxylic acid (435) gives the pyridazinone (436), possibly via the hydrazone (57JCS1922). When the oxime is heated with phosphorus pentachloride it undergoes a Beckmann rearrangement to give the amide (437) (70MI22300). 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

Into this group fall the named oxidation rearrangement reactions which proceed with carbon-carbon bond cleavage and 1,2-transfer of an alkyl group to a heteroatom, such as the Baeyer-Villiger reaction (discussed in Chapter 5.1, this volume) and the Beckmann reaction (found in Chapter 5.2, this volume) of ketones, as well as the Hofmann reaction/Schmidt reaction/Curtius reanangement of carboxylic acid derivatives. The two examples discussed here involve related reactions of alcohols. 

The reaction is closely similar to the Hofmann, Curtins, and Beckmann rearrangements. The over-all reaction consists of the conversion of RCOOR to RNH2, therefore where the carboxyl donor is the a-carboxyl group of an amino acid the resulting product would have two amino groups on the a-carbon atom. Consequently, ammonia is evolved and the corresponding aldehyde remains. On this basis the expected products from various esters are given in Fig. 10. 

Apart from esterification reactions and thermal decarboxylation of the 2-carboxylic acid, the only other reaction to be reported is the Beckmann rearrangement of the oxime of 3-acetylbenzo[c]cinnoline, which proceeds normally to give the 3-amino compound.63... 

N-Acylanilines. When electron-rich arenes are treated with a carboxylic acid, hydroxylamine hydrochloride in PPA, several reactions occur in sequence. These are the Friedel-Crafts acylation, oxime formation, and Beckmann rearrangement. Anilides are obtained in 45-95% overall yields (11 examples). 

Beckmann rearrangement Carboxylic acid amides from oximes... 

The most important reactions in this group are the Beckmann rearrangement, which converts oximes to amides a family of reactions that convert carboxylic add derivatives to amines with loss of the carbonyl carbon and the reaction of ketones with hy dr azoic acid to give amides (the Schmidt reaction). 

When the Schmidt reaction is applied to a,j8-unsaturated carboxylic acids, the product of the rearrangement is an enamine, which hydrolyzes to the corresponding ketone. Entry 3 in Scheme 8.9 is an example of this type of reaction. Reaction with hydrazoic acid converts ketones to amides, and is thus an alternative method for effecting the same transformation as the Beckmann rearrangement. A drawback of... 

Hydrazoic acid (s. a. H(PO H) OHINaN ) Isomeric carboxylic acid amides by Schmidt reaction and Beckmann rearrangement... 

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