Cyclohexanone lactam production

Ingredients. Nylon-6 is produced commercially from caprolactam [105-60-2] which is the most important lactam industrially. AH industrial production processes for caprolactam are multistep and produce ammonium sulfate [7783-20-2] or other by-products. Approximately 95% of the world s caprolactam is produced from cyclohexanone oxime [100-64-1] via the Beckmann rearrangement (144). The starting material for cyclohexanone can be... 

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 reaction of several a-amino acid esters with 0-lactones in chloroform solution gave hydroxyamide esters (equation 50), said to be useful fungicides (74JAP(K)74127918>. Enamines derived from cyclohexanone react smoothly with 0-propiolactone to give 3-(2-cyclo-hexanonyl)propionamides in reasonable yields (equation 51). No acylation of the enamine is observed. This reaction has been used as a key step in a new synthesis of 8-aza steroids (75JOC50). Cyclohexanone imines react in the same manner, except that the expected initial product cyclizes to give bicyclic lactams and enaminones (equation 52) (80T3047). 

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. 

Another concise route to 107 featured the facile construction of the cyclohexanone derivative 109 via the Michael addition of triply deprotonated methyl dioxohexanoate to the nitrostyrene (108 (Scheme 9) (115). Ketalization of 109 followed by hydrogenation of the nitro function and then cyclization of the resulting amino ester by thermolysis in refluxing xylene furnished the lactam 110, which was reduced LiAlH4 to the amine 111. All attempts to cyclize 111 via a Pictet-Spengler reaction led to complex mixtures of products. However, when the unstable enone 112, which was obtained by acid-catalyzed hydrolysis of 111,... 

The cyclohexanone in Eq. (21.17) exists in the form of oil droplets and forms a heavier lower phase in cyclohexane. This lower phase undergoes a Beckmann rearrangement with excess sulfuric acid or oleum to give caprolactam. Hydrogen chloride is displaced by the stronger acid and recycled to nitrosyl chloride production [see Eq. (21.16)]. The rearrangement reaction mixture is neutralized with ammonia water to give crude lactam and ammonium... 

The rearrangement of cyclohexanone oxime to caprolactam is still an important step in nylon production, and the heterogeneously catalyzed Beckmann rearrangement has been extremely well investigated (4, 16-19). In order to obtain catalysts that couple a high lactam selectivity to long lifespan, careful tuning of the zeolite properties is required. Some important factors are ... 

Oxidation of cammaconine with Sarett reagent afforded two products, dehydro-oxocammaconine (23) and didehydro-oxocammaconine (24). Both products showed spectral characteristics for two methoxy-groups, an AT-ethyl group, a hydroxy-group, a cyclopentanone moiety, and a tertiary lactam in a six-membered ring. The second product also possessed an i.r. absorption band characteristic of a cyclohexanone. There was no evidence of an aldehyde proton in the n.m.r. spectra of either product. 

Early synthetic efforts involved TMSOTf-catalyzed addition of the cyclohexanone-derived TMS enolether to the /V-TMS protected 1, followed by /V-deprotection to give ketone 2. While the stereocontrol at C-4 of the p-lactam ring was complete and only trans products were obtained, the stereoselection at the newly formed stereocenter was rather poor since the reaction yields a 70 30 mixture of epimers in favor of the indicated one. 

Azepan-2-one (hexano-6-lactam, --caprolactam, 28) is industrially the most important azepine derivative. It is used in the production of perlon and is synthesized by Beckmann rearrangement of cyclohexanone oxime. Structurally related to caprolactam is the CNS stimulant pentetrazole 29 (1,5-pentamethylenetetrazole, see p 217). 

Ketones have been also used as electrophiles for the synthesis of natural products. Thus, the partial synthesis of oxybutynin (ditropan) has been accomplished by the aldol reaction between cyclohexanone (3b) and ethyl phenylglyoxylate (23, R = Ph, R =EtO, Scheme 4.9) [69]. Also using a diastereoselective approach the synthesis of 3-functionalized 3-hydroxy-P-lactams has been achieved with good yields and total diastereoselectivity [70]. 

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). 

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