Carveol oxidation

On oxidation with chromic acid in acetic acid solution, dihydrocarveol yields dihydrocarvone, which has a specific gravity 0 928 at 19°, and refractive index 1-47174. The dihydrocarvone from Zae o-dihydro-carveol is dextro-rotatory, and -vice versa. Its oxime melts at 88° to 89° for the optically active variety, and at 115° to 116° for the optically inactive form. 

Microalgae were used for oxidation and hydroxylation of organic compounds (Fig. 3). For example, hydroxylation of (5 )-limonene affords a mixture of cis and trans carveols. " By hydroxylation and oxidation using Chlorella, " ... 

The oxidation of various secondary alcohols, including the allylic alcohols carveol (5) and P-ionol (4), leads to the corresponding ketones in 70-80 % yield (Eq. (3), Table 7). Oxidation of (—)-carveol (J) with nickel peroxide (2.5 eq., 50 °C, benzene) yielded only 33 % ketone. 

Perhaps more important, Foote has shown that chemically generated singlet oxygen gives the same product distribution from (+)-limonene as obtained by the rose bengal-photosensitized oxidation.467 Moreover, the (—)-tra 5,-carveol formed in both types of oxidation has the same large optical activity. 

Limonene is the major monoterpene in orange oil. This is a colorless and odorless compound at high purity. However, it rapidly oxidizes to carveol and carvone in the presence of air. Under acidic conditions, a-terpineol, P-terpineol, and y-terpineol are also produced. Many of the impurities present in limonene have much higher odor potencies. These odor potent compounds can be perceived as limonene odor . 

An interesting example, although it cannot be described as functional interconversion but rather as isomerisation, was reported by Motherwell and collaborators in 2004 [58]. In this case a polymer was imprinted with a /ram-carvyl amine (97), which was used as TSA, for the isomerisation of a-pinene oxide (98) to trans-carveol (99) that was obtained with 45% yield. 

This method is of value when the alcohol is readily available from natural sources, or when it can be prepared, for example, by the reaction of an alkenyl-organometallic reagent with an aldehyde. An example of the former is the oxidation of the terpenoid alcohol carveol to carvone (Expt 5.88) using pyridinium chlorochromate-on-alumina reagent. 

Ce4+ is easily exchanged on resins such as Nation. Ce-Nafion catalyzed the oxidation of carveol to carvone with t-BuOOH as the oxidant no data characterizing leaching were provided (59). CeC>2 on AI2O3 was used as a solid catalyst for the cooxidation of cyclohexane and cyclohexanone. Products are dibasic acids and e-caprolactone. It was claimed that in water-free reaction conditions, Ce is not eluted from the solid (342). 

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). 

Examples of the use of chromium(VI) reagents to effect the allylic oxidation of alkenes to give a,3-unsaturated carbonyl compounds are very common in the literature. "-" The reaction was first report by Treibs and Schmidt" for the allylic oxidations of a-pinene to verbenone and veibenol, of dipentene to carvone and carveol, and of cyclohexene to cyclohexenol and cyclohexenone, using a solution of chromium trioxide in a mixture of acetic anhydride and carbon tetrachloride. However, yields were low and no synthetic use of this observation was made. 

In the oxidation of a diastereomeric mixture of carveol (syrr.anti = 42 58), the syn alcohol is stereoselectively oxidized and the anti alcohol is recovered in 98 % diastereomeric purity. This shows that the catalytic activity of (C6p5)2BOH is very sensitive to steric hindrance in the alcohols (Eq. 108). In oxidations of equimolar mixtures of geraniol and j8-citronellol, geranial is obtained in 96 % yield and most of the /8-citro-nellol is recovered imchanged (Eq. 109). The selective conversion of allylic alcohols in the presence of saturated alcohols is particularly noteworthy. 

Maruoka has successfully developed a highly accelerated Oppenauer oxidation [31,32] system using a bidentate aluminum catalyst [29]. This modified, catalytic system effectively oxidizes a variety of secondary alcohols to the corresponding ketones as shown in Sch. 9. For example, reaction of (2,7-dimethyl-l,8-biphenylene-dioxy)bis(dimethylaluminum) (8, 5 moI%) with carveol (14) at room temperature in the presence of 4-A molecular sieves, and subsequent treatment with pivalaldehyde (3 equiv.) at room temperature for 5 h yielded carvone (15) in 91 % yield. Under these oxidation conditions, cholesterol (16) was converted to 4-cholesten-3-one (17) in 75 % yield (91 % yield with 5 equiv. t-BuCHO). 

Similarly CrAPO-5, derived from isomorphous replacement of A1 by Cr in AlPO-5, was shown to be an active and selective catalyst for the oxidation of secondary alcohols [191]. For example, carveol was chemoselectively oxidised by tertiary butyl hydrogen peroxide (TBHP) at the alcohol group (94% selectivity at 62% conversion) rather than at the carbon-carbon double bond. The initial assumption that Cr coordinated tetrahedrally in the lattice is the active species was later revoked and it seems now that Cr " is present as an octahedral species associated with the framework [192]. 

Position of the Double Bond.—Two points must be established in connection with the constitution of these menthene compounds, viz., the position of the hydroxyl and ketone groups and the position of the double bond. Both of these points are proven by the following oxidation of di-hydro carveol to i-methyl 2-hydroxy 4-carboxy benzene. 

Alkylation of isovaleramide with 1,3-dichlorobut-2-ene yields (139) after methyl-ation acid-catalysed hydrolysis and internal aldol condensation gives ( )-piperitone. The value of piperitenone and isopiperitenone formation, probably via electrocyclic reaction of the pyrolytic acetic acid-elimination product from A - and A -isomers of (49), cannot be assessed in the absence of reaction yields. (S)-(-)-Pulegone is obtained in good yield from (- )-citronellol by oxidation with pyridinium chlorochromate followed by double-bond isomerization. Low-temperature reduction of ( —)-carvone to ( —)-cz5-carveol (140) and... 

Other useful p-menthane syntheses of no great novelty are of cis- and trans-piperitol from 2a,3o -epoxycarane (silica-catalysed rearrangement to ds-p-menth-2-en-l,8-diol is also reported), of ( )-dihydrocarvone, isopulegone, and p-menthofuran via /S-keto-sulphoxides, of p-mentha-l,4(8)-diene via a bromination-dehydrobromination sequence, and of trans-carveol by benzoyl peroxide-CuCl oxidation of a-pinene. Further details for the conversion of (-)-(142) into (+)-(142), via its epoxide, are reported (Vol. 5, p. 25 cf. Vol. 3, p. 44). " ... 

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