Campholene 3-Campholenic acid

Cyclopentanes, including Iridoids.—The long-known campholenyl skeleton (87) (a non head-to-tair isoprenoid) has been identified in the oil of Juniperus com-munis Whereas the nitrile of a-campholenic acid (87a R = CN) reacts normally with Grignard reagents, / -campholenonitrile (87b R = CN) dimerizes, and the -campholenones (87b R = CO-alkyl) must be made by heating the a-series (87a R = CO-alkyl) in hydrochloric acid. ... 

Acid-catalysed rearrangement of epoxides is another widely used reaction in the fine chemicals industry. Here again the use of solid acid catalysts such as zeolites is proving advantageous. Two examples are shown in Fig. 2.25 the isomerization of rsophorone oxide (Elings et al., 1997) and the conversion of a-pinene oxide to campholenic aldehyde (Holderich et al., 1997 Kunkeler etal., 1998). Both products are fragrance intermediates. 

Campholenic Aldehyde Manufacture. Campholenic aldehyde is readily obtained by the Lewis-acid-catalyzed rearrangement of a-pinene oxide. It has become an important intermediate for the synthesis of a wide range of sandalwood fragrance compounds. Epoxidation of (+)- Ct-pinene (8) also gives the (+)-o -a-pinene epoxide [1686-14-2] (80) and rearrangement with zinc bromide is highly stereospecific and gives (-)-campholenic aldehyde... 

The selectivity towards campholenic aldehyde can be boosted further to 65% if the O.Olmmolg 1 Zn(0Tf)2/Si02 catalyst is pretreated under N2 at 200°C prior to use. This increase in selectivity is attributed to loss of Bronsted acid sites by dehydration of the catalyst surface, which in turn reduces the amount of side reactions. 

Alpha-Pinene oxide 9 (Eq. 15.2.5) is known as a reactive molecule which rearranges easily under the influence of an acid catalyst (6, 7). Thereby many products can be formed. For example compounds such as the isomeric campholenic aldehyde 11, trans-carveol 12, trans-sobrerol 13, p-cymene 14 or isopinocamphone 15 are observed as main by-products. At temperatures higher than 200°C more than 200 products can be formed. The industrially most desired compound among these is campholenic aldehyde 10. It is the key molecule for the synthesis of various highly intense sandalwood-like fragrance chemicals (7, 8). 

The performance of different H-US-Y zeolites strongly depends on the bulk Si02/Al203 ratio, as shown in Figure 15.3 for catalysts B to D. The activity as well as the selectivity to campholenic aldehyde 10 increases with decreasing aluminum content. The Bronsted acid sites do not seem to be responsible for the desired reaction, since the number of these sites is equal to the number of aluminum atoms... 

H. van Bekkum et al. (17) reported that the alpha-pinene oxide 9 can be succesfully converted to campholenic aldehyde 10 (Eq. 15.2.5) in the presence of a BEA-zeolite. Ti-BEA proves to be an excellent catalyst for the rearrangement of a-pinene oxide to campholenic aldehyde in both the liquid and vapor phase. This is mainly attributed to the presence of isolated, well-dispersed titanium sites in a Bronsted-acid-free silica matrix. Furthermore, the unique molecularsized pore structure of the zeolite may enhance selectivity by shape-selectivity. 

For example, rearrangement of a-pinene oxide produces, among the ten or so major products, campholenic aldehyde, the precursor of the sandalwood fragrance santalol. The conventional process employs stoichiometric quantities of zinc chloride but excellent results have been obtained with a variety of solid acid catalysts (see Fig. 2.23), including a modified H-USY [70] and the Lewis acid Ti-Beta [71]. The latter afforded campholenic aldehyde in selectivities up to 89% in the liquid phase and 94% in the vapor phase. 

As shown in Table 1, a pretreatment of the mother catalyst (A) with dilute acid (0.01 M HCl at 25 °C for 24 h), subsequent washing and calcination at 550 °C gives a better catalyst (B), resulting in major enhancement of activity but without any loss in selectivity for the desired reaction to campholenic aldehyde. The performance of these catalysts, especially the high selectivities observed, seem to result from Lewis acid sites [33]. 

The preparation of campholenic aldehyde (12) from a-pinene oxide (13) is currently a commercial process in which zinc bromide is used as the catalyst. Ravasio et al. [20] have investigated replacing the zinc bromide with a commercial mixed co-gel solid-acid catalyst. They found that by use of Si02-Al203 (1.2 %) or Si02-Zr02 (4.7 %) they could readily achieve a 72 % yield of 12 under relatively mild conditions (25-60 °C, toluene) although small quantities of several side-products were also still formed (Scheme 2). 

Heterogeneous solid-acid catalysis has the potential to make a major contribution towards improving the environmental acceptability of terpene rearrangement and isomerization processes. There are potential heterogeneously catalyzed replacement processes for the production of campholenic aldehyde, an important intermediate for many fragrance compounds. With continuing advances in the field of solid-acid catalysis it is likely that other industrially useful heterogeneous catalysts will be discovered. 

The members of the second family of synthetic sandalwood materials are derived from campholenic aldehyde (6.72). This aldehyde is prepared by treatment of a-pinene oxide (6.71) with a Lewis acid, usually zinc chloride or bromide. a-Pinene oxide is, in turn, prepared from a-pinene... 

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