Isopulegol hydrate

Hong and co-workers have described a formal [3-t-3] cycloaddition of a,P-unsaturated aldehydes using L-proline as the catalyst (Scheme 72) [225], Although the precise mechanism of this reaction is unclear a plausible explanation involves both iminium ion and enamine activation of the substrates and was exploited in the asymmetric synthesis of (-)-isopulegol hydrate 180 and (-)-cubebaol 181. This strategy has also been extended to the trimerisation of acrolein in the synthesis of montiporyne F [226],... 

Scheme 72 Iminium ion catalysed [3+3] addition in the synthesis of isopulegol hydrate and cubebaol...

The palladium [Pd(Ph3)4]-catalysed 3 + 3-cycloaddition of trimethylenemethane with azomethineimines produced hexahydropyridazine derivatives under mild conditions (40 °C).171 The Lewis acid-catalysed formal oxa-[3 + 3]-cycloaddition of a,f+ unsaturated aldehydes with 6-methyl-4-hydroxy-2-pyrone, 1,3-diketones, and viny-logous silyl esters yielded a variety of pyrones at room temperature.172 Croton-aldehyde has been converted to 6-hydroxy-4-methylcyclohex-l-enecarboxaldehyde by an enantioselective 3 + 3-cycloaddition catalysed by proline. This methodology was used in the synthesis of (—)-isopulegol hydrate, (—)-cubebaol, and (—)-6-hydroxy-4-methylcyclohex-l-ene-1-methanol acetate, an intermediate in the total synthesis of the alkaloid magellanine.173... 

Hydroxy-(x,(x,4-trimethylcyclohexanemethanol, 9CI. Menthoglycol. Isopulegol hydrate. Cubebaol [42822-86-6]... 

Hong BC, Wu MF, Tseng HC, Liao JH (2006) Enantioselective Organocatalytic Formal [3-l-3]-Cycloaddition of a,P-Unsaturated Aldehydes and Application to the Asymmetric Synthesis of (-)-Isopulegol Hydrate and (-)-Cubebaol. Org Lett 8 2217... 

Yet another method for the preparation of hydroxycitronellal (35) has been developed it depends on the fact that the immonium salt (36) is hydrated by aqueous sulphuric acid, hydrolysis of the imine group taking place with sodium hydroxide. The effect of catalysts supported on silica gel on the well-known thermal conversion of citronellal to isopulegol has been studied. The abstract... 

Composition 30-55% (-)-menthol, 14-32% (-)-menthone, 1.5-10% (-i-)-iso menthone, 2.8-10% menthyl acetate, 3.5-14% 1,8-cineole, 1-9% menthofuran, up to 4% pule-gone [220], as well as 3-octanol, trans-sabinene hydrate, piperitone, viridrflorol, mono- and sesquiterpene hydrocarbons. For further constituents see [221, 222, 223[. On the differentiation between peppermint oils and the detection of dementholised commint oil as a major adulterant see the results of Lawrence et al. [224], The ratio of 1,8-cineole limonene (min. 2) was even implemented in the European Pharmacopoeia. The latter also limits the isopulegol content for Mentha piperita oil to 0.2%. 

Composition 70-80 % (-)-menthol. The commercially available oils are dementholised and again rectified, contain mainly menthol (33 6%), menthone (18-32%), isomenthone (8-14%) and menthyl esters, and are employed for diluting the more expensive piperita oils. The composition of the unrectrfied oil is similar to that of piperita oil, whereas (E)-sabinene hydrate, viridiflorol and menthofuran are only present in traces. Isopulegol occurs up to 3%. 

Direct hydration of citronellal to hydroxycitronellal is not possible because of the competing Prins reaction that produces isopulegol or the 3,8-p-menthanediols described above. However, it is possible to protect the aldehyde function by formation of a bisulfite, an enol acetate, an enamine, an imine or an oxazolidine [288-291]. As an example. Fig. 8.48 shows the use of diethanolamine as a protecting group. Addition of diethanolamine to citronellal (135) in the presence of an acid catalyst leads to the oxazolidine (227). When this is treated with cone, sulfuric acid. 

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