Ketones ammoximation

A serious shortcoming of TS-1, in the context of fine chemicals manufacture, is the restriction to substrates that can be accommodated in the relatively small (5.lx5.5 A2) pores of this molecular sieve, e.g. cyclohexene is not epoxidised. This is not the case, however, with ketone ammoximation which involves in situ formation of hydroxylamine by titanium-catalysed oxidation of NH3 with H202. The NH2OH then reacts with the ketone in the bulk solution, which means that the reaction is, in principle, applicable to any ketone (or aldehyde). Indeed it was applied to the synthesis of the oxime of p-hydroxyacetophenone, which is converted, via Beckmann rearrangement, to the analgesic, paracetamol (Fig. 1.24) [75]. 

In the same spirit DFT studies on peroxo-complexes in titanosilicalite-1 catalyst were performed [3]. This topic was selected since Ti-containing porous silicates exhibited excellent catalytic activities in the oxidation of various organic compounds in the presence of hydrogen peroxide under mild conditions. Catalytic reactions include epoxidation of alkenes, oxidation of alkanes, alcohols, amines, hydroxylation of aromatics, and ammoximation of ketones. The studies comprised detailed analysis of the activated adsorption of hydrogen peroxide with... 

TS-1 is a material that perfectly fits the definition of single-site catalyst discussed in the previous Section. It is an active and selective catalyst in a number of low-temperature oxidation reactions with aqueous H2O2 as the oxidant. Such reactions include phenol hydroxylation [9,17], olefin epoxida-tion [9,10,14,17,40], alkane oxidation [11,17,20], oxidation of ammonia to hydroxylamine [14,17,18], cyclohexanone ammoximation [8,17,18,41], conversion of secondary amines to dialkylhydroxylamines [8,17], and conversion of secondary alcohols to ketones [9,17], (see Fig. 1). Few oxidation reactions with ozone and oxygen as oxidants have been investigated. 

The ammoximation reaction involves the in situ formation of hydroxylamine via TS-1 catalysed oxidation of NH3 with H2O2. Hence, there are no size restrictions with regard to the ketone substrate, because the reaction of NH2OH with the latter occurs in the bulk solution. For example, TS-1 catalyses the ammoximation of / -hydroxyacetophenone (Le Bars et al., 1996). Beckmann rearrangement of the oxime product (see Fig. 2.18) affords the analgesic paracetamol (4-acetaminophenol). 

In the absence of alcohol solvents, hydrogen peroxide is thought to coordinate with Ti by displacing an Si-O bond as shown in Fig. 6.11. This sets the stage for ammonia interaction to form hydroxylamine and subsequent ammoximation of ketones to oximes.20,56 57... 

The oxidation of NH3 to NH2OH forms the basis of a process for the ammoximation of cyclohexanone to the oxime because the NH2OH formed in solution readily reacts with the ketone (non-catalytically) to give the oxime (231). Table XXX (165) illustrates the conversions and selectivites obtained for a few typical ketones and aldehydes. The ammoximation of aldehydes is faster than that of ketones. The oxime selectivity is also higher. The ammoximation of cyclohexanone by this method offers a more eco-friendly alternative route to the cyclohexanone oxime intermediate for the production of Nylon-6. The current route coproduces large quantities of ammonium sulfate and involves the use of hazardous chemicals such as oleum, halides, and oxides of nitrogen. 

The ammoximation of cyclohexanone had been known before the discovery of TS-1, but the performances of conventional catalysts were far below the standards required for development work. In the EniChem process, the reaction is carried out in the liquid phase, at ca. 80°C, using a suspension of TS-1 in aqueous t-butanol, with a slight excess of hydrogen peroxide over the ketone. The substrate and the oxidant undergo total conversion with selectivities close to 98% and 94%, respectively. Inorganic by-products comprise minor amounts of ammonium nitrate and nitrite, N2O, and N2 produced by the oxidation of ammonia, and O2 by the decomposition of the oxidant. 

The reaction of ammoximation is generally apphcable and provides an efficient route to many other oximes in addition to the industrially relevant cyclohexanone oxime. Acetone, butanone, acetophenone, C5—Cg cycUc ketones and methyl-substituted cyclohexanones produced the corresponding oximes with high conversion and selectivity. Even the ammoximation of cyclododecanone and 4-butylcyclohexa-none, unable to diffuse in TS-1, occurred with high yields [121-123]. Other ammo-ximation catalysts are carbon-supported TS-1, TS-2, Ti-MOR and Ti-MWW, with conversions and selectivities close to those of TS-1 [124—128]. 

The TS-1 catalyzed hydroxylation of phenol to a 1 1 mixUne of catechol and hydroquinone has been commercialized by Enichem. Similarly, the ammoximation of cyclohexanone is being developed commercially as a low-salt alternative to the conventional process for the production of cyclohexanone oxime, the raw material for nylon-6. The reaction involves initial TS-1 catalyzed oxidation of NH3 by HjOj to give NH2OH. The fact that bulky ketones such as cyclododecanone undergo ammoximation is consistent with subsequent reaction of NHjOH with the ketone substrate taking place outside the molecular sieve. The method has been used [49] for the conversion of p-hydroxyacetophenone to the corresponding oxime which is the precursor of the analgesic paracetamol (Reaction 13). 

The presence of a silica framework with few defects makes TS-1 a highly hydrophobic material suitable for oxidations in the liquid phase with H2O2 as oxidant. Thus, TS-1 has proven to be successful in the oxidation of alcohols, epox-idation of linear olefins, hydroxylation of aromatics, ammoximation of cyclohexanone, oxidation of alkanes to alcohols and ketones, oxidation of amines, oxidation of sulfur-containing compounds, and oxidation of ethers [66-75]. 

Another reaction commercialized by EniChem is the ammoximation of ketones, particularly the conversion of cyclohexanone to cyclohexanone oxime (47). This latter compound is an intermediate in the manufacturing of caprolactam, the monomer for Nylon 6. This reaction, outlined in Figure 10.13, proceeds with both high conversion and selectivity for the oxime product. Again, TS-1 is uniquely active for this reaction compared to other catalysts, and TS-1 can catalyze this reaction on a variety of substrates. It is believed that in all cases the hydroxylamine is first formed, followed by reaction with the ketone. TS-1 is currently used commercially by EniChem to produce 12,000 ton per year of cyclohexanone oxime. 

The ammoximation of cyclohexanone to cyclohexanone oxime (Scheme 9.1) is an important industrial process, because the oxime is an intermediate for the formation of s-caprolactam, the monomer for nylon-6, that is currently manufactured on a scale of 4 Mton p.a. TS-1 catalyses the ammoximation of ketones, including cyclohexanone, in liquid phase in the presence of ammonia and hydrogen peroxide. The reaction proceeds through hydroxylamine as an intermediate, which is generated at the active site via complexes of framework titanium with ammonia and hydroperoxide. The hydroxylamine then reacts with cyclohexanone molecules that are weakly adsorbed within the pores or can diffuse out into solution. The reaction is a general one, and can be apphed to the ammoximation of a wide range of ketones. 

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