Sulfuric acid, reaction with oximes

Baeyer confirmed his results by the total synthesis of oxindole, isatin and indole. Nitration ofphenylacetic acid, isolation of the o-nitro isomer, and reduction of the latter followed by ring closure gave oxindole. Reaction with nitrous acid ( .e. potassium nitrate and sulfuric acid) gave isatin oxime, from which by reduction, dehydrogenation with iron(lll) chloride and final hydrolysis, isatin itself was obtained. 

Dichlorobenzaldehyde is activated for the phase transfer step as the cyano-diethylamino-adduct. 3-Chloromethylpyridine is prepared from 3-hydroxymethyl pyridine by treatment with thionylchloride. The hydrochloride salt of the product is taken up in water and the solution is tised directly in the phase transfer step. Strict temperature control, proper speed of addition of the 3-chlormethyl -pyridine solution and the use of a cosolvent like e.g. hexane ensure a reliable yield of enamine greater than 95%. The enamine reacts at room temperature quantitatively with the hydrochloride salt of 0-methylhydroxylamine to give the corresponding oxime ether as an E/Z-mixture of 3 7. Addition of sulfuric acid to this oximation reaction and an increase of reaction temperature to about 50 C yields pyrifenox rapidly in the desired E/Z-equilibrium ratio of about 1 1. No special purification processes are required in the whole synthesis. 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

The rearrangement of 120 g. (1.06 moles) of pure cyclo-hexanoneoxime (Org. Syn. ii, 56) (Note i) is carried out in the following fashion. In a 250-cc. Erleruneyer flask are placed 10 g. of cyclohexanoneoxime and 20 cc. of sulfuric acid (sp. gr. 1.783) (Note 2). The flask is placed on a wire gauze over a small free flame and heated slowly, with occasional shaking, until the first appearance of bubbles. The flame is then removed immediately, and the very vigorous exothermic reaction which occurs is allowed to run to completion (Note 3). This requires only a few seconds. This solution is then poured into a 3-I. round-bottomed flask, and another lo-g. portion of the oxime is introduced into the Erlen-meyer flask and treated with sulfuric acid as before. These operations are repeated until the twelve lo-g. portions have been treated. 

Reaction of nitromalon-bis-A -methylanilide (105) with sulfuric acid gives A -methylisatin- -oxime (107) and not 4-methylquinoxalin-3-one 1-oxide (108) as originally suggested. This transformation may involve a Beckmann-type rearrangement of the protonated aci-nitro compound (106) prior to dehydrative ring closure. ... 

Heating the oxime with 85% sulfuric acid to prepare 2-piperidone caused eruption of the stirred flask contents. Benzenesulfonyl chloride in alkali is a less vigorous reagent [1], A similar reaction using 70% acid and methanol solvent proceeded uneventfully until vacuum distillation to remove volatiles had been completed at 90° C (bath)/27 mbar when the dark residue exploded [2],... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

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... 

The lactam (2) is obtained in 87% yield by treating cycloheptanone with sodium azide and concentrated hydrochloric acid (54JA2317). Beckmann rearrangement of cycloheptanone oxime with concentrated sulfuric acid gives (2) in 88% yield (58JA1510). Alternatively, the ketone gives (2) directly by reaction with hydroxylamine sulfonate in 95% formic acid (79S537). 

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

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

The participation of nitrilium salts has also been postulated42 in the Schmidt reaction and in some Beckmann rearrangements when concentrated sulfuric acid is employed. Hill43 has demonstrated recently that some Beckmann rearrangements carried out in a concentrated sulfuric acid medium are Ritter-type reactions in which the nitrile formed in situ from the oxime combines with a carbonium ion to yield a nitrilium salt, which, when diluted with water, leads to the N-alkylamide. 

In the continuous process the oxime solution (which is acidified with sulfuric acid) is passed through the reaction zone that is kept at the rearrangement temperature of 90 to 120°C. The rearrangement is complete within a few minutes, and the resulting lactam sulfate solution is converted into... 

Several complex diazepines have been prepared through Beckmann and Schmidt reactions.312-316 Treatment of the oxime (263) with acetic anhydride and sulfuric acid gave a product116 at one time believed to be 264.317 An independent synthesis of 264 has been carried out by cyclization of 265115 and, although a direct comparison was not possible, it appears that 264 was not the product obtained from 263. 

Deoximatiou. Oximes arc converted into aldehydes and ketones in yields of 70-95% when treated with TTN in methanol ai room temperature. The reaction is complete within a few minutes. The precipitated thallium(I) nitrate is removed, the filtrate shaken with dilute sulfuric acid, and the aldehyde or ketone extracted with ether or chloroform. The process is formulated as shown. One limitation is that the method... 

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