Beckmann mixture

Oxoisodrimenin (136) has been isolated from Porella cordeana [90], though much earlier it had been synthesised on the Beckmann 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 ... 

Beckmann Rearrangement. Prepare the 85% sulphuric acid by adding 50 ml. of the concentrated acid cautiously to 10 ml. of water, stirring the mixture meanwhile, and then cool the diluted acid in ice-water. Place 16 ml. of the cold acid in a 500 ml. beaker, add 8 g, of the pure oxime, and warm the mixture cautiously until effervescence begins, and then at once remove the heat. A vigorous reaction occurs, and is soon complete. Repeat this operation with another 8 g. of the oxime in a second beaker the reaction is too vigorous to be carried out with larger quantities. 

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. 

A regio- and stereoselective Beckmann rearrangement utilized diastereose-lective host guest interactions of the inclusion complexes 225 and 228 in a solid state reaction. Initially, a 1 1 mixture of the chiral host 223 and the racemic oximes 224 and 227, respectively, was treated with ultra sound in the solid state to induce the optical resolution. Then H2SO4 was added to start the Beckmann rearrangement, the corresponding c-caprolactams 226 and 229 were isolated in 68 % and 64 % yields and ee of about 80 % and 69 % (determined by HPLC analysis on chiracel OC) (Scheme 43) [46]. 

It can be obtained from cyclohexane. Cyclohexane is air oxidised to yield a mixture of cyclohexanol and cyclohexanone. Cyclohexanol is dehydrogenated to cyclohexanone over copper catalyst. Cyclohexanone when treated with hydroxylamine sulphate at 20°-95°C gives an oxime. The oxime when treated with concentrated sulphuric acid undergoes Beckmann rearrangement to yield caprolactam. 

N-Methylhydroxylamine.—An aqueous solution of nitromethane is mixed with about its own weight of ammonium chloride, the mixture is then cooled (temperature about 10°) and three parts of zinc dust are added in small portions with constant shaking. Zinc dust is now removed by filtration, and it is found that the filtrate reduces ammoniacal silver and Fehling s solutions. The preparation of this easily accessible alkylhydroxylamine as hydrochloride is described by Beckmann, Annalen, 1909, 365, 204. 

C. Beckmann fission of 2-methoxycyclooctanone oxime. In a 500-ml., three-necked, round-bottomed flask equipped with a mechanical stirrer, a dropping funnel, and a calcium chloride tube is placed a suspension of 62.5 g. (0.30 mole) of phosphorus pentachloride (Note 4) in 150 ml. of absolute ether, and the reaction vessel is cooled with ice. A solution of 42.8 g. of crude 2-methoxycyclooctanone oxime (0.25 mole) in 100 ml. of absolute ether is added over 30 minutes with vigorous stirring and the reaction is continued for 50 minutes at 5°. The reaction mixture, which becomes a transparent reddish brown solution (Note 5), is poured with mechanical stirring into 500 g. of ice in a 2-1. beaker. Stirring is continued for 1.5 hours at 5° (Note 6). I he ether layer is separated and the aciueous layer is extracted with... 

An acid-rhenium catalyst mixture acts on ( )-4-(4-hydroxyphenyl)butan-2-one oxime (44) to produce a high yield of the spiro compound (45), which then rearranges to the substituted quinoline (46)." ° The Beckmann rearrangement product (47)... 

A mixture of benzothieno[2,3-d]- and benzothieno[3,2-d]-azocines (194 and 195) is produced in 43% overall yield by the Beckmann rearrangement of the mixture of oxime isomers 193 with phosphorus pentoxide in dichloromethane (90JCS(P1)1083 Scheme 53). 

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... 

A variety of ketones 249 can be directly converted into the secondary amides 253 (the expected product of a Beckmann rearrangement of the corresponding oximes 250) in high yield, by heating them with hydroxylamine hydrochloride and anhydrous oxalic acid (equation 75). Aromatic aldehydes afforded mixtures of nitriles and amides. The... 

Due to its Lewis acidic properties, the use of chloral (trichloroacetaldehyde) in the Beckmann rearrangement was investigated . When a variety of ketoximes is admixed with chloral hydrate and the mixture is heated at low pressure in nitrogen atmosphere, the Beckmann rearrangement afforded the corresponding amides in excellent yields (73-98%). The transformation occurs under neutral, relatively mild and solvent-free conditions. 

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. 

The furan oxime 320 was boiled with hydrochloric acid and a mixture of the Beckmann rearranged heterocycle 321 and 2-acetylfuran derivative 322 (resulting from the oxime hydrolysis) was obtained (equation 117). 

Benzodiazocines 429 were prepared to be tested as calcium-sensitizing agents (equation 181). A mixture of isomeric lactams was obtained when the Schmidt rearrangement was applied to 427, but only one product 428 was produced using the Beckmann reaction. 

Beckmann fragmentation of the hydroxy-oxime (119) gave the 16,17-seco-compound (120) which can be converted, by NaBH4 reduction and acid hydrolysis, into the lactone (121). The lactone (121) may also be obtained directly upon acidification of the reaction mixture from heating the hydroxy-oxime (119) with... 

Beckmann rearrangement of substituted hydroxy-glyoxime and peroxides of glyoxime derivatives 3, 64, 65, 66, 71, 76, 78) (see p. 826, 828). These reactions often yield a mixture of both 3- and 5-hydroxy isomers. 

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