3-Carene oxidation

M (+)-trans-2-carene oxide (2-epoxycarene), 1M olivetol or analog, 0.05 M p-toluenesulfonic acid in 10L benzene reflux two hours and evaporate in vacuum (or can separate the unreacted olivetol as above) to get about 30% yield THC. Olivetol can also be separated as described below. For synthesis of 2-epoxycarene (A4 carene oxide) from A4 carene (preparation given later) see p-methadieneol preparation (Method 2). 3-carene oxide gives 20% yield of AH6) THC. 

Pillay and Sunonsen18 8 have stated, for example, that a substance formulated by them ae d-A -carene oxide is stable to aqueous sgllurii aoid. Arbuzov and Michailov,30 on the other hand, also claim to have prepared this epoxide, but report success in forming the corresponding 1,2-diol on exposure to conventional hydrolysis conditions (Eq. 

A THC (332), 11 % A iso-THC (335), and 13% of citrylidenecannabis (340) (not a component of the natural material). If more carene oxide than olivetol is used in the reaction, or alternatively if boron trifluoride etherate is used as the catalyst, 28% of a mixture of A -traus-THC and A -cis-THC is obtained, but no A ( THC. The authors suggest that A -trans- and A -cis-THC are formed first, more strenuous conditions then leading to the other products. ... 

Carene oxide can be converted to limonenol with metatitanic acid(Eq. 124). 

Japanese authors have made comprehensive investigations of the rearrangements of oxiranes in the presence of solid acids, bases, and salts.The model compounds employed were cyclohexene oxide and 1-methylcyclohexene oxide. The effects of the acidic and basic properties of the catalysts on the selectivity were interpreted on the basis of the products obtained. The main products are carbonyl compounds and allyl alcohol isomers. Rearrangements of limonene oxide over acids and bases were studied on five different types of Al203 similar research has been carried out on 2- and 3-carene oxides, cis- and trans-carvomenthene oxides and a-pinene oxide. ... 

The isomerization of many terpene oxides (see Section 5.4) has been investigated using a wide range of solid acids (and bases). Arata and Tanabe are responsible for much of this work which includes d-limonene oxide [16], 2- and 3-carene oxide [17], and carvomenthene oxide [18]. 

To 136 g A carene in 330 ml methylene chloride and 120 g anhydrous sodium acetate, add dropwise with vigorous stirring in an ice bath, 167 g of 50% peracetic acid and continue stirring for ten hours. Heat to boiling for two hours, cool, wash with water, sodium carbonate, water, and dry, evaporate in vacuum the methylene chloride to get about 100 g p-menthadieneol. Apparently [CA 65,22063(1968)] substituting sodium carbonate for sodium acetate results in the production of A carene oxide (2-epoxycarene) in about 50% yield (can distill 63/7). 

The turpentine fraction is gasified during the process, and valuable chemicals, such as a-pinene and carene can be separated by distillation. They can be further processed by catalytic treatment, such as isomerization and oxidation [6-8]. 

Shibasaki and co-workers used an intramolecular nitrile oxide cycloaddition to prepare the skeleton of phorbol (272) (Scheme 6.99), a tumor promoter that activates protein kinase C (PKC) (333). Nitroalkene 268 was elaborated in several steps from (+)-3-carene (267) and was subjected to cycloaddition by means of -chlorophenyl isocyanate-triethylamine to give cycloadduct 269 in 88% yield. Reductive hydrolysis employing Raney Ni and boric acid afforded hydroxyketone 270, that was subsequently used for the construction of the optically active derivative 271, which contains the phorbol skeleton (333). 

Hallquist, M I. Wangberg, and E. Ljungstrom, Atmospheric Fate of Carbonyl Oxidation Products Originating from a-Pinene and A3-Carene Determination of Rate of Reaction with OH and N03 Radicals, UV Absorption Cross Sections, and Vapor Pressures, Environ. Sci. TechnoL, 31, 3166-3172 (1997). 

The oxidation of 3-carene to 3-caren-5-one (Figure 3.46) is a key step in the synthesis of the pyrethroid ester insecticide Deltamethrin [162,163]. This reaction is performed with air as the oxidant, catalyzed by 2 mol% of a Cr-pyridine complex (the catalyst precursors are CrCl3 and pyridine). Table 3.1 shows the turnover frequencies obtained using various Cr/pyridine ratios. 

Figure 3.46 a Catalytic oxidation of 3-carene to 3-caren-5-one b molecular structure of Deltamethrin, showingthe incorporation of the carenone precursor in the final product. 

Among the other terpenes that have been used as substrate in the MTO-catalyzed oxidation reactions are the bicyclic monoterpenes carene and camphene, the acyclic monoterpene myrcene, fi-citronellene (the reduced form of myrcene), and the bicyclic sesquiterpene (i-caryophyllene (Fig. 6). 

Cyclodextrins have been covalently modified for catalytic oxidation, such as compounds 57, 62-65 (Schemes 3.14 to 3.16) [44, 45]. Enantioselective epoxidation of styrene derivatives, and carene using 20-100 mol% of the CD-ketoester 57 has been achieved. The inclusion-complex formation was confirmed by aH NMR titration experiments, confirming the 1 1 substrate catalyst stoichiometry under the reaction conditions. In the oxidation of carene, NOE and ROESY experiments showed different behavior according to the size of the R group (Scheme 13.14). Evidence was found for the formation of inclusion complexes with compounds 58 and 59. On the other hand, compounds 60 and 61 proved to interact with the catalyst via a tail inclusion vide infra). The increased diastereoselectivity observed with compounds 58 and 59 might be explained by a closer proximity to the covalently linked dioxirane. 

Variety/ compound Limonene P-Pinene P-Caryophyllene Sabinene Caryophyllene oxide 8-3-Carene a-Pinene Myrcene p-Cymene Elemol... 

Oxidation with singlet oxygen is subject to sterk effects but can show poor regioselectivity. For example, (+)-3-carene (52) is oxidized to produce a mixture of all three possible regioisomeric hydroperoxides with oxygenation occurring at the face of the allyl systm 0 qx>site the gem-dimethylcyclo-propane unit in each case (equation 22). - ... 

Allylic oxidation reactions employing chiomium(VI) reagents therefore appear to be very much dependent upon the intrinsic nature of the substrate as to their regiochemical outcome. This is exemplified by the r-butyl chromate allylic oxidation of (+)-3-carene (67 equation 28) where no great preference for either piquet exists. 

PFC is also a reasonable oxidant for activated C— H bonds. Allylic oxidation to a variety of ketonic products was observed upon treatment of A -carene with PFC." Benzylic C— H oxidation with PFC is also known. 

---