Menthenes Isomerism

The elimination of HC1 from the isomeric menthyl and neomenthyl chlorides shown in Figure 11.20 gives a good illustration of this trans-diaxial requirement. Neomenthyl chloride undergoes elimination of HC1 on reaction with ethoxide ion 200 times as fast as menthyl chloride. Furthermore, neomenthyl chloride yields 3-menthene as the major alkene product, whereas menthyl chloride yields 2-nienthene. 

The difference in reactivity between the isomeric menthyl chlorides is due to the difference in their conformations. Neomenthyl chloride has the conformation shown in Figure 11.20a, with the methyl ancl isopropyl groups equatorial and the chlorine axial—a perfect geometry for L2 elimination. Loss of the hydrogen atom at C4 occurs easily to yield the more substituted alkene product, 3-menthene, as predicted by Zaitsev s rule. 

When the dehydration of menthol is carried out on an acidic alumina or at a long contact time the 2-menthene can isomerize to the more stable 1- and 3-menthenes. In order to avoid the consecutive reactions which proceed by acid catalysis, the alumina can be modified either by adding pyridine to the menthol or by passing ammonia over the catalyst during dehydration. 

Isomerization of cycloolefins has been carried out using base catalysis. Sodium-organosodium catalysts were used by Pines and Eschinazi (7) for isomerizing 1-, 2-, and 3-p-menthenes the same distribution of 1-, 3-, and 8(9)-p-menthenes was obtained from each of the starting materials (B). 

On the other hand, menthyl chloride is only slowly converted by treatment with base, and into a single prodnct, i.e. 2-menthene. In the preferred conformation of menthyl chloride, all three snbstitnents are equatorial, and no adjacent hydrogen is in a planar relationship to the chlorine leaving gronp. The fact that slow elimination occnrs at all is a resnlt of conformational isomerism into the less-favonred con-former that has all three snbstitnents axial. In this con-former, there is a single hydrogen anft-periplanar with the chlorine, so elimination occnrs giving jnst one product. The conformational eqnilibrinm is slowly disturbed because the elimination removes the small concentration of unfavoured conformer. 

Menthol from (+)-3-Carene. An Indian manufacturing process for (—)-menthol starts from 3-carene, the major component of Indian turpentine oil (55-65%). (+)-3-Carene isomerizes to (+)-2-carene, which can be pyrolyzed to (+)-tra s-2,8-/ -menthadiene. Isomerization of the latter yields (+)-isoterpi-nolene, which is hydrogenated to give >50% (+)-3-/ -menthene. Epoxidation and subsequent rearrangement lead to a menthone isomenthone mixture,... 

Alternatively, (+)-tew-isolimonene can be isomerized to (+)-2,4(8)-/>-menthadiene (34), which is partially reduced to (+)-3-menthene (35). Epoxidation of (+)-3-menthene gives the epoxide, which can be isomerized to (—)-menthone. 

Of the two isomeric alcohols menthol and neomenthol, the former dehydrates preferably into menthene-2, while the latter gives menthene-3 preferably. 

The reaction of (-)-menthyl chloride with sodium diphenylphosphide in tetra-hydrofuran requires 48-54 hr at reflux temperature for completion. The elimination side reaction is still observed. However, by-products (isomeric menthenes and diphenylphosphine) arising from the elimination reaction are easily removed by distillation. The overall conversion of (-)-menthyl chloride to (+)-NMDPP is about 34%, not counting the (+)-NMDPP oxide produced during a typical work-up. The (+)-NMDPP ligand is rather sensitive to air oxidation in solution and (+)-NMDPP oxide can be a very tenacious impurity, but careful crystallization of the phosphine from deoxygenated ethanol gives (+)-NMDPP in 95% (or higher) purity. 

Isomerism.—From an examination of the above formulas it will be seen that the positions occupied by the added hydrogen atoms in the original cymene molecule or, what is the same thing, the positions occupied by the double bonds, makes isomerism possible both in the tetra-hydro cymenes or menthenes with one double bond and the dihydro cymenes or mentha-di-enes with two double bonds. In the former case six isomers are possible while in the latter there are fourteen. This will be clear if we give the skeleton formulas for the six possible menthenes. 

As each of these menthenes will yield isomeric mentha di-enes the number of isomers possible in this group is still larger. That is, one men-thane yields six menthenes and these a larger number, viz., fourteen, mentha-di-enes. Furthermore, stereo-isomerism with accompanying optical activity due to the presence of asymmetric carbons, increases the number of possible isomers. It will not be necessary to dwell further upon the isomerism of the terpenes it being necessary simply to explain the fact of the existence of structural isomers and of stereo-isomers with optical activity. The system of nomenclature of the isomers will not be considered. Reference to larger books will be necessary to make this plain. 

Monoterpenes derive fi om fra 5-/ -menthane (4-isopropyl-1-methyl-cyclohexane), respectively from the unsaturated menthene, CioHig, or menthadiene, CioHie a-terpinene and S-limonene are isomeric forms of menthadiene see H. Beyer, W. Walter, Lehrbuch fur Organische Chemie, Hirzel Verlag, Stuttgart, 1984. 

Menthone was elegantly transposed into carvomenthone by the sequence (196)->(197).439 Piperitol was isomerized into isomenthone over cobalt catalysts.440 Piperitone, p-menth-3-en-2-one, and 8,9-dihydrocarvone can by pyrolysed to aromatics that have lost the Pr group in fair yields (30—50%),441 and menthone can be converted into piperitone and other p-menthen-3-ones via bromination and Zn treatment.442 Pulegone on reaction with HOC1 formed 4-chloro-/>-menth-8-en-3-one,448 and O-acetylated dienolates of pulegone have been prepared.444 Carvo-menthene oxide was isomerized to p-menth-1 (7)-en-2-ol, carvotanacetol, and cyclopentane derivatives over solid acids and bases,445 and 6-thiophenoxy-8,9-... 

The conversion of a-pinene over the Ce-promoted, zeolite-supported Pd catalysts proceeds via an acid-catalysed ring opening of the bicyclic terpene to a monocyclic terpene, e.g. a-limonene. This is followed by dehydrogenation, possibly via isomerization to a-terpinene or y-terpinene. 1,8-Cineole is dehydrated on the acid sites to p-menthadiene prior to dehydrogenation to p-cymene on the Pd sites of the catalyst. The conversion of all reactants is complete during the test run of 8 h. The results are quite similar to a-limonene conversion, as expected from the reaction pathway via p-menthenes and p-menthadienes. 

The stereochemistry of the product alkene for acyclic 1,2-disubstituted or trisub-stituted alkenes is determined by the configuration of the tertiary amine oxide. A stereospecific syn elimination pathway is followed. With cyclic substrates, the ring conformation is important, such that heating dimethylmenthylamine oxide 22 gave a mixture of 2- and 3-menthene, whereas the isomeric neomenthylamine oxide 23 gave only 2-menthene (2.21). This result contrasts with the antiperiplanar (3-elimination (2.6). 

The ease of reduction of an alkene decreases with the degree of substitution of the double bond, and this sometimes allows selective reduction of one double bond in a molecule which contains several. For example, limonene 7 can be converted into p-menthene (by reduction of the terminal alkene) in almost quantitative yield by hydrogenation over platinum oxide if the reaction is stopped after absorption of one molar equivalent of hydrogen. In contrast, the isomeric diene 8, in which both double bonds are disubstituted, gives only the completely reduced product (7.7). 

The activity and selectivity of the bound Wilkinson catalyst parallels in many ways the homogeneous system. Terminal olefins are hydrogenated more rapidly than internal olefins, cw-olefins react faster than rran5-olefins, and olefins are reduced faster than acetylenes.There were some differences with the sterically hindered l(7)-p-menthene the polymeric catalyst, for example, produced appreciably more isomerized material. Furthermore, the attached complex was more selective in the hydrogenation of 1,3-cyclooctadiene. 

When menthene is irradiated in a methanol solution in the presence of alkylbenzene as a sensitizer, its isomeric compound and methanol addition products are obtained as shown in Scheme 8 (Marshall and Carroll, 1966 Kropp and Drauss, 1967). The mechanism of this reaction could be a radical reaction, which is activated by the excited sensitizer, followed by hydrogen abstraction from solvent or methene itself. 

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