Reactions of Monoterpenes

In addition, monoterpenes can provide some useful chiral reagents, such as the pinene-based organoborane reagents for chiral reductions that have been reviewed extensively [42]. The use of camphor-derived organic acids such as camphenesulfonic acid can be used for the resolution of racemic bases and is a common practice in industry (see Chapter 8). 

Other camphor analogs with the C-8 methyl group replaced by larger and more hindered groups can significantly increase the stereoselectivity of the alkylation and result in much higher enantiomeric purity of the products [48], 

One of the earliest industrial applications of monoterpenes is in the steroid synthesis. Robinson annelation is used frequently in these transformations as a key step. 

Because of their biological importance and widespread medical and industrial utilities, estrogens and related hormones are among the earliest targets in steroid total synthesis. Major efforts in the synthesis of these aromatic steroids were to set the correct chirality in the C,D rings since the A,B rings are mostly achiral. 

All of the optically active terpenes mentioned in this chapter are commercially available in bulk ( kg) quantities and are fairly inexpensive. Although many of them are isolated from natural sources, they can also be produced economically by synthetic methods. In fact, two thirds of these monoterpenes sold in the market today are manufactured by synthetic or semisynthetic routes. These optically active molecules usually possess simple carbocyclic rings with one or two stereogenic centers and have modest functionality for convenient structural manipulations. These unique features render them attractive as chiral pool materials for 

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Yokouchi, Y. and Ambe, Y. Aerosols formed from the chemical reaction of monoterpenes and ozone, Atmos. Environ., 19(8) 1271 1276,1985. 

The most important reaction of monoterpenes is hydration (31). a-Pinene can be converted to a-terpineol with water in the presence of a mineral acid. This is the procedure used to make the commercial product known as pine oil. Further hydration converts it to terpine hydrate. 

Arey, J, R. Atkinson, and S.M. Aschmann (1990a), Product study of the gas-phase reactions of monoterpenes with the hydroxyl radical in the presence of NQi, J. Geophys. Res., 95, 18539-18546. 

Docherty, K.S, W. Wu, Y.B. Lim, and P.J. Ziemann (2005), Contributions of organic peroxides to secondary aerosol formed from reactions of monoterpenes with O3, Environ. Sci. TechnoL, 39, 4049 059. 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Gas-phase products from the reactions of ozone with the monoterpenes (-)-p-pinene and (+)-sabinene included the ketones formed by oxidative fission of the exocyclic C=C bonds as well as ozonides from the addition of ozone to this bond (Griesbaum et al. 1998). 

Atkinson R, SM Aschmann, AM Winer, JN Pitts (1985a) Kinetics and atmospheric implications of the gas-phase reactions of NOj radicals with a series of monoterpenes and related organics at 294 2 K. Environ Sci Technol 19 159-163. 

The above system has been used for the reaction of EtjNH with myrcene to give a mixture of hydroamination products (53% yield) containing 80% of N,N-diethylgeranylamine [208], a key intermediate for the synthesis of industrially important monoterpenes [208, 209-211], including (-)-menthol (Tagasako process) [212]. 

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. 

Winer, A.M., Lloyd, A.C., Damall, KR., Pitts, Jr., J.N. (1976) Relative rate constants for the reaction of the hydroxyl radical with selected ketones, chloroethenes, and monoterpene hydrocarbons. J. Phys. Chem. 80, 1635-1639. 

The selective diene hydrogenation of monoterpenes such as myrcene, which contain both isolated monoene and diene moieties, forms a particular challenge [84]. The catalyst [RhH(CO)(PPh3)3] (60) has been reported to perform remarkably well for such hydrogenation reactions, and the diene moiety was shown to be selectively reduced to the monoene, while the isolated double bond remained unaffected under the reaction conditions used (Scheme 14.20). The rates of reaction expressed as average TOF (determined at ca. 80% conversion) ranged from ca. 640 (in benzene, 20 atm H2 at 100 °C) to 7600 mol mol 1 h 1 (in cyclohexane, 20 atm H2 at 80 °C). The hydrogenation in benzene solution resulted in... 

A descriptor for an enzyme active site that permits binding of a family of related compounds (e.g., mimics of the reaction intermediate) that can be derived from the initial binding and conformational changes in the substrate. This concept arose from the observation that a number of monoterpene cyclases were incapable of discriminating between enantiomers of the reaction intermediate, even though the enzyme catalyzes the synthesis of an enantiomerically pure product from an achiral substrate. An example is trichodiene synthase which catalyzes the cyclization of farnesyl diphosphate to trichodiene. 

SCHEME 29. Singlet oxygen ene reaction of selected bicycUc monoterpenes... 

Chew, A. A., and R. Atkinson, OH Radical Formation Yields from the Gas-Phase Reactions of 03 with Alkenes and Monoterpenes, J. Geophys. Res., 101, 28649-28653 (1996). 

Hakola, H., J. Arey, S. M. Aschmann, and R. Atkinson, Product Formation from the Gas-Phase Reactions of OH Radicals and 03 with a Series of Monoterpenes, J. Atmos. Chem., 18, 75-102 (1994). 

Martinez, E B. Cabanas, A. Aranda, and P. Martin, Kinetics of the Reactions of NOj Radical with Selected Monoterpenes A Temperature Dependence Study, Environ. Sci. Technol., 32, 3730-3734 (1998). 

IPP and DMAPP lead to geranylpyrophosphate (GPP), which is an immediate precursor of monoterpenes. The formation of nerylpyrophosphate (NPP) from GPP gives rise to a wide range of acyclic, cyclic, bicyclic or tricyclic skeletons. Reactions like rearrangement, oxidation, reduction and hydration via various terpene cyclases result in the formation of numerous terpene derivatives. Condensation of GPP and IPP leads to farnesylpyrophosphate (FPP), the immediate precursor of sesquiterpenoids. Likewise, FPP and IPP are conducive to diterpenoids. 

In the eighties, the bioconversion of monoterpene alcohols by fungi had not been studied intensively [32]. However, a strain of Aspergillus niger was isolated from garden soil, able to transform geraniol, citronellol and linalool to their respective 8-hydroxy derivatives. This reaction was called fu-hydroxylation [39,40]. 

The range of monoterpenes encountered is extended considerably by cyclization reactions, and monocyclic or bicyclic systems can be created. Some of the more important examples of these ring systems are shown in Figure 5.11. Such cyclizations would not be expected to occur with the precursor geranyl diphosphate, the E stereochemistry of the double bond being unfavourable for ring formation (Figure 5.9). Neryl PP or linalyl PP, however, do have favourable stereochemistry, and either or both... 

Fick, J. (2003) Chemical reactions in ventilation systems ozonolysis of monoterpenes. Department of Chemistty, Umea, Sweden, Umea University, PhD. 

As Barr et al. (2003) pointed out, the importance of such emissions is determined mainly by their impact on the three processes taking place in the atmosphere. The first consists in that such NMHCs as isoprene form in the course of carboxylization in plants and contribute much thereby to the formation of biospheric carbon cycle. The second process is connected with NMHCs exhibiting high chemical activity with respect to such main oxidants as hydroxyl radicals (OH), ozone (03), and nitrate radicals (N03). Reactions with the participation of such components result in the formation of radicals of alkylperoxides (R02), which favor efficient transformation of nitrogen monoxide (NO) into nitrogen dioxide (N02), which favors an increase of ozone concentration in the ABL. Finally, NMHC oxidation leads to the formation of such carbonyl compounds as formaldehyde (HCHO), which stimulates the processes of 03 formation. Finally, the oxidation of monoterpenes and sesquiterpenes results in the intensive formation of fine carbon aerosol with a particle diameter of <0.4 pm... 

One of the earliest industrial applications of monoterpenes is in the steroid synthesis. Robinson annelation is used frequently in these transformations as a key step. The first example of this reaction was by Robinson himself to synthesize a-cyperone from dihydrocarvone.56 This synthesis has been shown to follow a stereospecific course to give (+)-a-cyperone (37) from (+)-dihydrocar-vone (38) (Scheme 5.14).57-59 Since then, numerous modifications and improvements have been made to apply this type of reaction for syntheses of a variety of natural and unnatural products.60... 

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