Isophorone epoxidation

The blank test in liquid phase yields less than 1% conversion. Unlike non-zeolitic catalysts, except for H-Nafion, most zeolites yield complete conversion. A high yield of the keto aldehyde 24 up to 81%, was surprisingly attained by using H-FER as a heterogeneous catalyst. For the rearrangement of isophorone oxide, the presence of acidic sites is necessary for the catalytic activity. The reactivity of H-FER can be explained by the acidic outer surface of the catalyst Molecular modeling showed that the isophorone epoxide is too bulky for the small pore size of ferrierite. 

Figure 2. Comparison of initial rates and selectivities (related to olefin and peroxide) for the epoxidation of a-isophorone with t-butyl hydrojjeroxide at 60 C over (a) low-temperature aerogel (LT) (20 wt% Ti02), (b) titania-on-silica, (c) TS-1 and (d) xerogel.

Functional groups were selectively introduced at the C-2 position of isophorone by epoxide ring-opening by several nucleophiles with active methylene groups. Different behavior was observed depending on the reaction conditions and the nature of the nucleophilic agents [57]. The best experimental systems involved PTC or KF-alumina under solvent-free conditions and MW irradiation (Eq. 37 and Tab. 5.15). 

Isophorone oxide has been prepared by the epoxidation of isophorone with alkaline hydrogen peroxide.2 3... 

Isocyanic acid, 4-methyl-m-phenylene ester, see 2,4-Toluene diisocyanate Isodrin epoxide, see Endrin Isoforon, see Isophorone Isoforone, see Isophorone Isoheptane, see 2-Methylhexane... 

The 4a,5a-oxido isomers of Formulas 302 and 303 give the same products (Formulas 304 and 305) (122). Irradiation of mesityl oxide epoxide 306 gives 3-methyl-2,4-pentanedione (Formula 307) in low yield (123). Similar irradiation of isophorone oxide (Formula 308) gives both Formulas 309 and 310 (123). 

Keywords epoxyisophorone, diethyl malonate, epoxide ring-opening, KF-alumi-na, microwave irradiation, isophorone... 

Terpene epoxides are very reactive compounds. Some products formed by isomerization of such epoxides are valuable raw materials for perfumes, synthetic flavourings and pharmaceuticals, and also provide useful intermediates in organic syntheses. The isomerization of isophorone oxide 23 (Eq. 15.2.9) was originally investigated by H.O. House and R.L. Wasson using boron trifluoride etherate as a homogeneous catalyst (24). 

Iron(III)sulfate, 223-224 Isatin, 331 Isatoic acid, 331 Isoatlantolactone, 263, 264 Isobutenyl acetate, 153 Isobutyronitrile, 110 Isocyanates, 14-15 Isoflavones, 410 Isopavine, 217 Isopenams, 325 Isophorone, 197, 198 Isopinocampheylborane, 224 Isoprene epoxide, 4 Isopropenyl phenyl sulfone, 316 Isopropenyltriphenylphosphonium bromide, 225... 

Reactions with unsaturated compounds. /-Butyl hydroperoxide decomposes smoothly at 95-105° and hydroxylates double bonds, and even a,)3-unsaturated ketones the reactions are catalyzed by small amounts of osmium tetroxide and afford cir-glycols. In benzene solution in the presence of Triton B as catalyst it converts a ,/3-unsaturated ketones into the corresponding epoxides in yields of 50-90%. The steric requirement of the base-catalyzed reaction are indicated by the failure to react with isophorone or A -3-ketosteroids. Payne effected smooth preparation of /3-phenylglycidaldehyde by allowing cinnamaldehyde and /-butyl... 

Further reactions on these compounds lead to other oxidised products in which the lack of stereochemical control in the epoxidation is unimportant, so, for example isophorone oxide rearranges with various catalysts to the cyclopentanone 182 (80% yield) while both isomers of pulegone oxide 179 gives the cycloheptadione29 183 (78% yield). Exhaustive methylation of the extended enolate produced by reduction of 181 gives 184 in good yield.28... 

Most of the earlier studies described the oxidation of simple (electron-rich) cycloalkenes, such as cyclohexene euid cyclododecene. Here we report the catalytic behaviour of titania-silica aerogels in the oxidation of cycloalkenones. The model reactions are the epoxidation of a- and P-isophorone, depicted in scheme 1. 

The oxidation reactions were performed in a closed, mechanically stirred 100 ml glass batch reactor under Ar. For the epoxidation of a-isophorone, 0.2 g catalyst, 9 ml solvent, 7.2 mmol cumene (internal standard) and 77 mmol olefin were introduced into the reactor. The slurry was heated to the reaction temperature and the reaction stauted by adding 13.4 mmol t-butyl hydroperoxide (TBHP, ca. 3 M in isooctane) from a dropping funnel to the vigorously stirred slurry (n = 1000 min ). For the epoxidation of P-isophorone, 20 ml ethylbenzene solvent, 61 mmol P-isophorone, 7.2 mmol cumene and 5.6 mmol TBHP or ciunene hydroperoxide (CHP) were introduced into the reactor in this order. The solution was heated to 80 °C and... 

Several solvents have been tested in the epoxidation of a- isophorone with t-butyl hydroperoxide (TBHP). The best performance of the aerogel was observed in low polarity solvents such as ethylbenzene or cumene (Table 1). In these solvents 99 % selectivity related to the olefin converted was obtained at 50 % peroxide conversion, independent of the temperature. Rasing temperature resulted in increasing initial rate and decreasing selectivity related to the peroxide. The low peroxide efficiency is explained by the homol5d ic peroxide decomposition. Protic polar solvents were detrimental to the reaction due to their strong coordination to the active sites. There was no epoxide formation in water. 

Influence of solvents and reaction temperature on initial rates and selectivities in the epoxidation of a- isophorone catalyst 20 wt% titania - 80 wt% silica, oxidant TBHP... 

Comparison of various heterogeneous catalysts in the epoxidation of a- isophorone... 

It is also interesting to compare various types of solid catalysts in the epoxidation of a-isophorone. Unfortunately, a real comparison is rather difficult, as the reaction conditions (temperature, oxidant, concentrations) are different for each catalyst. Due to the lack of information, the comparison shown in Table 2 is based only on the productivity, i.e. the amount of isophorone oxide produced in unit time using unit amount of catalyst. Two set of data were chosen for the 20 wt% titania - 80 wt% silica aerogel, and the best published data were chosen for the hydrotalcite [16, 17] and the alumina-supported KF [17, 18]. We assumed that the... 

Preliminary experiments revealed that the selectivity of titania-silica aerogel in the epoxidation of P-isophorone was moderate. The selectivity related to the olefin converted was below 90 % at low temperature, and dropped rapidly at 80 °C or above. The most important side reactions were the formation of 3,5,5-trimethyl-2-cyclohexene-4-hydroxy-l-one (2) by ring opening of the epoxide (1), and the isomerization of P- to a-isophorone (3), as shown in Scheme 2. Epoxidation of 2 and 3, and the oxidation at the OH group of 2 to a dicarbonyl compound were slow and the amounts of these by-products were usually aroimd 1 % or less. 

The importance of the acid-catalyzed side reactions are illustrated in Table 3 by the product distribution obtained using either TBHP or cumene hydroperoxide (CHP) as oxidant. The epoxidation with TBHP is faster and considerably more selective. When using CHP, about 20 mol% of the coproduct 2-phenyl-2-propanol was dehydrated to a-methylstyrene. It is likely that the simultaneously formed water increases the (Brpnsted) acidity of the aerogel and thus accelerates the ring opening and - to a smaller extent - the isomerization reactions. No oxidation products were formed in the absence of peroxide, as expected. Slow isomerization from p- to a-isophorone catalyzed by titania-silica was the only reaction observed. The data in Table 3 indicate that the simultaneous presence of peroxide and catalyst in the reaction mixture markedly accelerates the acid-catalyzed isomerization reaction. 

Influence of peroxide used as oxidant in the epoxidation of (3-isophorone at 80 °C catalyst 20 wt% TiOg-SO wt% Si02 aerogel... 

Effect of basic treatment of the 20 wt% TiO2-80 wt% SiOg aerogel on the epoxidation of P-isophorone with TBHP at 80 °C... 

The epoxidation of two cycloalkenones, a- and P-isophorone, with alkyl hydroperoxides demonstrates that active and selective titania-silica aerogels can be prepared by the sol-gel method combined with extraction of the solvent with supercritical COg at low temperature. The key factors for obtaining high activity in the epoxidation of bulky cyclic olefins are the high Ti-distribution in the silica matrix, the mesoporous structure and high surface area. 

The electron deficiency of a-isophorone seems to affect mainly the reaction rate, whereas the selectivity to epoxide is high (up to 99 %). A comparative study shows that the productivity (peroxide produced per unit time and unit amount of catalyst) of titania-silica is outstanding compared to other types of solid epoxidation catalysts. 

The epoxide selectivity is considerably lower in the other model reaction, the oxidation of P-isophorone. The acid-catalyzed side reactions could be suppressed by a treatment of the mixed oxide catalyst with a weakly basic salt prior to the reaction. The epoxide selectivity related to the olefin converted could be increased up to 94 % at 90 % peroxide conversion. 

The epoxidation of electron deficient alkenes such as methyl methacrylate has also been carried out using reaction conditions similar to those shown in Eq. (15), and with a,p-unsaturated ketones alkaline hydrogen peroxide has been generated from UHP and affords good yields of epoxides. Pulegone gave a 50% yield of the epoxide and the result obtained with isophorone is shown in Eq. (16). 

Terpene epoxides are very reactive compounds. Some are prepared conventionally by isomerization using homogeneous catalysts such as Bp3.Et20 [35,36]. The rearrangement of isophorone oxide (Figure 6) yields the keto aldehyde (13), which is an intermediate for fragrance chemicals. If the reaction is performed in the presence of zeolites the keto aldehyde (13) and the keto-enol form of the a-diketone... 

Other epoxidations by alkaline hydrogen peroxide have also been reported, e.gin preparation of isophorone oxide (2,3-epoxy-3,5,5-trimethylcyclo-hexanone)46 and mesityl oxide epoxide47 (cf. Winstein and Henderson48 and Payne49). 

---