Beckmann oxidizing mixture

Chromic acid dehydrogenates primary alcohols between 0° and 100° yields of aldehyde lie between 40% and 60%, by-products being mainly carboxylic acids and their esters. A proven oxidation mixture consists of l.mole of dichromate, 2.5 moles of sulfuric acid, and 300 g of water (Beckmann mixture), into which the alcohol is dropped C02 or N2 is led through the mixture so as to prevent the aldehyde s being further oxidized and, if possible, cooling is arranged so that only the alcohol is condensed. The aldehyde that distils off is best collected in cooled receivers. It is best to use an excess of chromic acid calculated according to the equation ... 

With phenyl and naphth>l isocyanates only liquid derivatives were obtained. No diphenylurethane was formed. Jqdging by the Cfdour, oxidation with Beckmann s mixture appears to give rise to an aldehyde. 

Beckmann has examined the characters of the optically active men-thones. The oxidation of natural Z-menthol by chromic acid mixture yielded Z-menthone [a]n = - 28 5° which when treated with 90 per cent, sulphuric acid is converted into a d-menthone [ajn = 4- 28 1°, which, however, is not the optical antipode of the first it behaves as a mixture of d- and Z-menthone, but is more strongly dextro-rotatory than it would be if it were only a mixture of the two optical antipodes. 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

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). 

Beckmann rearrangements applied to 2-furyl ketones are abortive there is no skeletal rearrangement. Many studies have failed to elucidate exactly what happens, but recently it has been demonstrated by methods including alternative synthesis that the products from oxime tosylates in methanol are actually 2,5-dimethoxy-2,5-dihydrofurans (e.g., Ill from 2-acetylfuran) as mixtures of geometrical isomers exactly as if they had been formed by furan oxidation techniques Section VI Part I).226... 

The TS-1 catalyzed hydroxylation of phenol to a 1 1 mixture of catechol and hydroquinone has already been commercialized by Enichem. Another reaction of considerable commercial importance is the ammoximation of cyclohexanone to cyclohexanone oxime, an intermediate in the manufacture of caprolactam. It could form an attractive alternative to the established process that involves a circuitous route via oxidation of ammonia to nitric acid followed by reduction of the latter to hydroxylamine (see Fig. 10). The ammoximation route employs a more expensive oxidant (H202) but is shorter and produces considerably less salt. However, we note that is does not provide a complete solution to the salt problem as substantial amounts are also produced in the subsequent Beckmann rearrangement of the oxime. The answer to this problem is probably also in the deployment of an efficient solid catalyst. 

Z-Menthone can be made by the oxidation of rhodinol with a chromic-sulphuric acid mixture.1 A Sabatier-Senderens reduction of thymol gives a mixture containing 30 per cent menthone.2 Z-Menthone is also obtained by treating menthol with copper at 3000.3 The method used in these directions is that of Beckmann.4... 

Beckmann fragmentation. Autrey and Scullard have shown that Beckmann fragmentation rather than Beckmann rearrangement is favored by introduction of a methylsulfenyl group a to the oxime group in addition, the termini of the bond that is cleaved are obtained in different oxidation states. Thus cleavage of the oxime of 2-methylthio-7-methoxytetralone-l (4), prepared as shown, leads to approximately 1 1 mixtures of the enol thioethers (5) and (6). 

The first step consists of the air oxidation of cyclohexane to a mixture of cyclohexanol and cyclohexanone as described in Section 9.2.2.1. The mixture is fractionated by distillation and the cyclohexanol is dehydrogenated to cyclohexanone over a catalyst such as copper. The combined cyclohexanone fractions are then treated with aqueous hydroxylamine sulphate at 20—95°C to form the oxime. The reaction mixture is neutralized with aqueous ammonia or sodium hydroxide and the crude oxime separated as an oily layer. This is stirred with concentrated sulphuric acid at 120 C and the oxime undergoes the Beckmann rearrangement to give caprolactam. In one process, the solution containing the lactam is continuously withdrawn from the reactor and rapidly cooled to below 75°C to minimize hydrolysis. The solution is then further cooled and neutralized with aqueous ammonia. Crude caprolactam separates as an oil and is purified by distillation under reduced pressure. 

Among the industrially produced lactams, e-caprolactam has by far the highest production capacity due to its important role as monomer in the polyamide business. There exist several synthetic routes to produce e-caprolactam. The most important one starts from benzene (Scheme 5.3.7). Benzene is hydrogenated in a first step to cyclohexane, followed by oxidation of the latter to a mixture of cyclohexanone and cydohexanol. This mixture is then reacted with NH2OH to give cyclohexanone oxime, which is converted under add catalysis in a so-called Beckmann rearrangement reaction to e-caprolactam. Alternative routes try to avoid the oxime intermediate (UCC peracetic add process via e-caprolactone), try to avoid the cydohexanone intermediate (e.g., DuPont process converting cydohexane directly into the oxime intermediate by reaction with nitric add), or start from toluene (Snia-Viscosa process). 

Ring expansion with Tamura et al. s Beckmann reagent, followed by dechlorination with Zn-Cu couple in methanol saturated with ammonium chloride, provided key pyrrolidinone intermediate 197 in 72% overall yield from 193. The intermediate 197 was then converted by using selenium dioxide and tcrt-butyl hydroperoxide into allylic alcohol (62%), which yielded the desired 1,3-diol 198 through rhodium-catalyzed hydroboration and oxidation as a 1 1 mixture of diastereomers in 72% yield. A seven-step reaction sequence then converted the diol 198 into (-l-)-retronecine 199, which was indistinguishable from an authentic sample of the natural product obtained by hydrolysis of natural monocrotaline (Scheme 16.29). ... 

---