Carvone, formation

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the me.so-diacetate with lipase, was converted into the optically pure cyclohexenone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343],... 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

The oil possesses moderate antibacterial and strong antifungal properties. Thus the appHcation of the oil to the cmst of cheese could serve to prevent the formation of mycotoxia ia the cheese. The optical purity of the carvone ia caraway has been determined usiag a chiral gc column (72). It was found to be (i )(+) = 97.64% and (5 )(—) = 2.36%. 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

By reduction carvone fixes 2 atoms of hydrogen on to the ketonic group, and 2 atoms in the nucleus, with the formation of dihydrocarveol, CijHjgO, whose corresponding ketone, dihydrocarvone, Cj Hj O, exists in small quantities in caraway oil. 

The activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

Where multiple products are possible, the CMR and MBR have been employed to optimize conditions for formation of specific components of a reaction sequence. Examples discussed below, were obtained by heating organic substrates such as allyl phenyl ether [46] and carvone [47] in water. Rearrangements, addition or elimination of water and isomerizations occurred, with each transformation favored under tightly defined conditions. 

Towards the end of this section it may be worthwhile to point out some new reactions with high-valent metals and TBHP. The first is a pyridinium dichromate PDC-TBHP system134. Nonsubstituted or alkyl-substituted conjugated dienes, such as 1,3-cyclooctadiene (87) and others (also linear dienes), yield keto allyl peroxides 88 (equation 18), whereas phenyl-substituted dienes such as 1,4-diphenylbutadiene (89) gave diketo compounds, 90 (equation 19). In further research into a GIF-type system135 with iron and TBHP, limonene gave a mixture of products with carvone as the major product. The mechanism is thought to proceed initially by formation of a Fe(V)-carbon... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

Further details of the photoaddition of N-nitrosopiperidine to a-pinene have been published.The claim of a-fenchen-6-one oxime formation (Vol. 7, p. 43) has been retracted the product is optically active carvone oxime. The stereochemistry and conformations of amino-oximes derived from a-pinene nitroso-chloride have been examined. ... 

C. Samples were withdrawn every two days from the samples stored at 45 C and every three days from the samples stored at 37 C. Pulled samples were stored in screw cap vials at 0 C until analsis by gas chromatography (GC). The products were monitored for the formation of limonene-1,2-epoxide and L-carvone, both oxidation products of d-limonene (3). 

Limonene (92) is the most widely distributed terpene in nature after a-pinene [68]. The (+)-isomer is present in Citrus peel oils at a concentration of over 90% a low concentration of the (-)-isomer is found in oils from the Mentha species and conifers [26]. The first data on the microbial transformation of limonene date back to the sixties. A soil Pseudomonad was isolated by enrichment culture technique on limonene as the sole source of carbon [69]. This Pseudomonad was also capable of growing on a-pinene, / -pinene, 1-p-menthene and p-cymene. The optimal level of limonene for growth was 0.3-0.6% (v/v) although no toxicity was observed at 2% levels. Fermentation of limonene by this bacterium in a mineral-salts medium resulted in the formation of a large number of neutral and acidic products. Dihydrocarvone, carvone, carveol, 8-p-menthene-1,2-cw-diol, 8-p-menthen-1 -ol-2-one, 8-p-menthene-1,2-trans-diol and 1 -p-menthene-6,9-diol were among the neutral products isolated and identified. The acidic compounds isolated and identified were perillic acid, /Msopropenyl pimelic acid, 2-hydroxy-8-p-menthen-7-oic acid and... 

Nevertheless, in the hydrogenation of poly-unsaturated molecules the catalyst effects are more evident in the selectivity patterns, as is shown in Table 2 and 3. The selectivity behavior for the various catalysts, show that Rh/MgO is the most selective for carvotanacetone formation. The addition is mainly limited, in these catalysts, to one hydrogen molecule, although in carvone there are three possible sites at which reduction can occur. 

The following important conclusions emerge from this study (i) precursor effect is exhibited in carvone hydrogenation activity, (ii) the Rh/MgO catalysts results to be more selective towards carvotanacetone formation than... 

Harries et al(Refs 2 3) claimed to prepare the diozonide and the diozonide peroxide of carvone. Their structures were not detd. The diozonide was obtained as a yel oil on treating carvone in CCl4 with ozone, followed by purification with pett ether. It deconpd on standing with formation of formaldehyde. Further treatment of diozonide with ozone yielded diozonide peroxide, which exploded by itself after standing for several hrs in a freezing mixt. It expld almost instantly when treated with warm w or when rubbed with a glass rod Refs l)Beil 7, 153, (101) [l28] 2)Beil 7,... 

In the conjugate hydrocyanation of (-)-carvone (79), Djerassi and co-workers (32) observed the formation of the axial cyanoepimer 80 as the major prod-uct. Similarly, Alexander and Jackson (33) found that substrate 81 gave p... 

Ionene, a commercial fragrance, has been prepared traditionally by treatment of a- and /3-iononcs with hydriodic acid containing phosphorus or by distillative heating in the presence of 0.5% iodine. In an unoptimized demonstration, cyclization occurred more cleanly and simply by MBR with /3-ionone in water at 250 °C (Scheme 19) [83]. Work-up also was facilitated, as the need for removal of catalyst or the formation and separation of bi-products was avoided. At elevated temperature, the addition of water to olefins can occur readily, without adding catalyst. (S)-(+)-carvone in water for 10 min at 180 °C afforded optically pure 8-hydroxy-p-6-mcnlhcn-2-one as an intermediate toward carvacrol [84], Addition of water across the 8,9-double bond of carvone occurred regioselectively, by Markovnikov addition. Carvacrol itself was obtained almost quantitatively from carvone at 250 °C after 10 min (Scheme 19) [84]. 

Intramolecular reactions of cyclohexenones follow pathways similar to those of cyclopentenones, both with regard to regio- and stereocontrol. The initially mentioned intramolecular [2 + 2]-photocycloaddition of carvone (1) is a typical example for five-membered ring formation with high diastereofacial control (Scheme 6.1). In this case, the rule of five requires the terminal carbon atom of the intermolecular... 

Other papers related to p-menthanes concern vinylaziridine formation from pulegone oxime and from carvone-NN-dimethylhydrazone methiodate,234 non-ozonolytic cleavage of 10-trichloromethyl-limonene,235 and the stereochemistry of 1-chloro-l-nitroso-p-menthanes236 and of dihydropinol rearrangements (cf. Vol. 2, p. 34).237... 

The monoterpenes 5(-i-)-carvone (10 Scheme 2, Nicolaou et al.) and / (—)-a-phellandrene (20 Scheme 3, Danishefsky et al.) are chosen as the starting materials for the syntheses of the diterpenoid skeleton of eleutherobin (1). Again, both routes require the separation of diastereo-mers by chromatography. The addition of 1-ethoxyvinyllithium to the TBS-protected aldehyde 13 (Scheme 2) leads to a mixture of diastereomeric alcohols (5 4 ratio in favor of the desired configuration at C8), which is separated by Nicolaou et al. after the alkynylation with ethynyl magnesium bromide in a later step. 13 was synthesized in close analogy to Trost et al. with bond formation between C9 and CIO via Claisen rearrangement (Scheme 2) [17]. 

---