Oximes rearrangement reactions

Cyclohexanone oxime is converted quantitatively to caprolactam by Beckmann rearrangement in the presence of oleum, which is of sufficient strength to consume the several percent water in the molten oxime. The reaction mass is neutralized with aqueous ammonia to a cmde caprolactam layer and a saturated solution of ammonium sulfate. Approximately 1.5 kg of the total 4.4 kg ammonium sulfate per kilogram of caprolactam is produced in this step. Purification is by multistage vacuum crystallization from aqueous solution in neatly quantitative yield. 

Dibenzo[l,3]diazepines 9, together with amidines and benzimidazoles, are produced by a rearrangement reaction when certain A.A -diarylamide oximes 7 are treated with tosyl chloride. The intermediate 0-tosyl derivatives 8 cannot be isolated.176... 

The Beckmann rearrangement of oximes to produce amides is promoted by perrhenate ions under phase-transfer catalytic conditions, in the presence of trifluoro-methanesulphonic acid in nitromethane [6]. Under these conditions, the rearrangement reaction is frequently accompanied by the solvolysis of the oxime to the ketone. This can be obviated by the addition of hydroxylamine hydrochloride. No reaction occurs in the absence of the ammonium catalyst or with the O-acetyl oximes. 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Rearrangement reactions of hydroxylamines (1), oximes (2) and hydroxamic acids (3) will be covered in this chapter with emphasis on the developments made during the last 15 years. All referred compounds possess a relatively low energy N—O bond ca 53 kcalmol" ) which facilitates the ability of these compounds to rearrange. 

The initial adsorption of the oxime in zeolites was studied through a combination of solid-state NMR spectroscopy and theoretical calculations ". The calculated adsorption complexes formed over silanol groups and complexes over Brpnsted acid sites in zeolites are depicted. This study suggests that the A-protonated oxime is formed over Brpnsted acid centers, but not over weakly acidic silanol groups. It has been also suggested that weakly acidic or neutral silanol groups or silanol nests are active catalysts of the rearrangement reaction ... 

However, the stereochemistry of the oxime cannot be easily controlled and this may be a drawback for the synthetic utility of the Beckmann rearrangement. When a mixture of oximes is obtained from the ketone and when the isomerization of the oxime cannot be prevented during the rearrangement reaction, a mixture of amides is obtained. In other less favourable cases, the intended oxime cannot be obtained and the wrong amide will result from the rearrangement reaction. 

Several steroidal cyclobntanone oximes were nsed to investigate the rearrangement reaction. The oxime 338, treated with thionyl chloride in benzene solution at room temperature, gave the expected pyrrolidinone 339 in 71% isolated yield (equation 127). 

Expansions of oximes of B-ring steroid systems are much less common. Recently, during the synthesis of a 6-aza-pregnane derivative 387, the introduction of the nitrogen was made using the Beckmann rearrangement reaction (equation 156). 

The most widely used rearrangement reactions of hydroxylamine, oximes and hydroxamic acids are reported in previous sections of this chapter, but there are other relevant rearrangements which were less exploited. 

The benzenesulfonate of cycloheptanone oxime rearranges readily at room temperature to give the very electrophilic O- benzenesulfonate (7), which reacts with pyridine to give the salt (8) (67CB3024). Treatment of (8) with water gives (2), and with H2S the thione (9) is produced (58CB972). The reaction of aluminum alkyls with cycloheptanone oxime mesylate provides a direct route to 2-alkyl-substituted octahydroazocines (81JA7368). 

In conclusion, decrease in cyclohexanone oxime yield and caprolactam selectivity with time on stream is a major factor in the use of boria on alumina catalyst in the rearrangement reaction. Coke deposition and basic by-product adsorption have been suggested as a means of deactivation. In addition the conversion of water soluble boron, which is selective to lactam formation, to an amorphous water insoluble boron species is another factor that can account for the catalyst deactivation. 

Oximes rearrange when heated with a strong acid, and this reaction provides a useful synthesis of amides ... 

Pearson et al. (1952) employed this approach to derive a series of substituent parameters for electron-deficient reactions of substituted benzenes. These constants, designated as sigmae, were based on a study of the Beckmann rearrangement of -substituted acetophenone oximes. These authors considered the rates of the rearrangement reaction of the oximes to deviate from the Hammett eq. (1). It is pertinent that, with the sole exception of the yi-OMe group, the deviations were not major. The entropy of activation, AS, for the -anisyl derivative was, however, 20 e.u. different from the essentially constant values for the other substituents. To remedy the deviations, Pearson and his associates suggested the sigmae constants. It was indicated that these constants were more suitable for the correlations of electron-deficient reactions than the conventional cr-values. 

The second route to 2,4-disubstituted adamantanes involves a 7r-route ring closure of substituted bicyclo[3.3.1]nonenes. Thus, lactone 85 28S) rearranges in 50 % sulfuric acid to 4-hydroxy-2-adamantanone (86) via the acylium ion 87 278>. Adamantanone oxime rearranges in 96 % sulfuric acid to 86 (mixture of isomers) in an analogous manner 109h Similarly, the Schmidt reaction of... 

Cyclopentanone Oxime. Violent reaction occurred on heating the oxime with 85% sulfuric acid to effect a Beckmann rearrangement.12... 

Another process utilizes a photochemical reaction in which cyclohexane is converted into cyclohexanone oxime hydrochloride (Fig. 2), from which cyclohexanone is produced. The yield of cyclohexanone is estimated at about 86 percent by weight. Then, in a rearrangement reaction, the cyclohexanone oxime hydrochloride is converted to e-caprolactam. 

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,P-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2]. 

This compound is in turn converted to the corresponding oxime by reaction with hydroxy-lamine, and cyclohexanone oxime is made into caprolactam by the Beckmann rearrangement. 

In classical processes cyclohexanone is converted to the corresponding oxime by reaction with hydroxylamine (see Fig. 2.27). The oxime subsequently affords caprolactam via the Beckmann rearrangement with sulphuric or phosphoric acid. Alternatively, in a more recent development, not yet commercialized, a mixture of cyclohexanone, ammonia and hydrogen peroxide is directly converted to cyclohexanone oxime over a titanium(IV)-silicalite (TS-1) catalyst. This route is more direct than the classical route and reduces the amount of salt formation but it involves the use of a more expensive oxidant (H2O2 rather than O2). 

Simunic-Meznaric, V., Mihalic, Z., Vancik, H. Oxime rearrangements ab initio calculations and reactions in the solid state. J. Chem. Soc., Perkin Trans. 2 2002, 2154-2158. 

Beckmann rearrangement The rearrangement reaction that occurs when a ketone is treated with hydroxylamine, NH2OH, followed by, for example, PC15. The reaction proceeds via an oxime to... 

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