L-isopulegol

Cycttzation of l-isopulegol (1). This substance is cyclized to /-menthol (2) stereoselectively with ZnBrg in benzene at 5-10°. Previous methods resulted in mixtures that required extensive purification. ... 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

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],... 

Pure citronellal is a colorless liquid with a refreshing odor, reminiscent of balm mint. Upon catalytic hydrogenation, citronellal yields dihydrocitronellal, citro-nellol, or dihydrocitronellol, depending on the reaction conditions. Protection of the aldehyde group, followed by addition of water to the double bond in the presence of mineral acids or ion-exchange resins results in formation of 3,7-dimethyl-7-hydroxyoctan-l-al (hydroxydihydrocitronellal). Acid-catalyzed cycli-zation to isopulegol is an important step in the synthesis of (-)-menthol. 

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... 

A different type of cyclization by means of the rhodium complex is observed in the case of a compound containing a l-al-6-ene system.4 Thus reaction of (+)-citronellal (4) with 1 eq. of tris(triphenylphosphine)chlororhodium in freshly distilled chloroform at room temperature for 15 hr. results in the formation of (+ )-neoisopulegol (5) and (—)-isopulegol (6) in the ratio of 3 1. 

Isopropylidenecyclohexane, 452 2,3,-0-Isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane, 273 2, 3 -0-IsopropyIideneuridine, 558 Isopropyl isocyanate, 111 Isopropyl sulfide, 219 Isopulegol, 560 Isoquinolines, 45 Isosetoclavine, 318 Isotetralin, 130-131... 

The most successful application of this isomerization is the manufacture of (-)-menthol on a 1,500 ton scale annually. As shown in Eq. (13), the synthetic sequence is composed of the hydrolysis of (i )-43 to (l )-citronellal 57, the zinc bromide-catalyzed ene-reaction to (-)-isopulegol 58, and hydrogenation to (-)-men-thol 59 (see chapter 41.4 for details). 

However, the isopulegol mixture can also be hydrogenated to produce a mixture of menthols the individual stereoisomers are then separated by distillation. To obtain optically pure (-)-menthol, a resolution step involving a suitable crystalline derivative (such as the benzoate) is required. The undesired stereoisomeric menthols, mainly (+)-neomenthol and (-l-)-isomenthol, are epimerized to an equilibrium mixture (e.g., by heating in the presence of sodium menthylate). (-)-Menthol is then again separated from the mixture. 

Table 1 Percentage distribution with solvent type for citral(l), citronellal (2), geraniol+nerol (3), citronellol (4), 3,7-dimethyloctanal (5), 3,7 dimethyloctanol (6), isopulegol (7) and selectivity towards citronellal using Pd/C and towards geraniol+nerol using Pt/G at various temperatures and hydrogen pressures for 4 hours unless otherwise stated. (Abbreviations used- [CgPy] N-octylpyridinium, [emim] l-ethyl-3-methylimidazolium, [bmimj l-butyl-3-methylimidazolium, and [NTfJ ...

Despite the fact that the presence of heteroatoms on the carbon surface can induce some types of active phase-support interaction, as discussed above, it is clear that this takes place to a lesser extent that in other common catalyst supports, such as oxides (silica, alumina, titania, ceria, etc.). One clear example is provided in work carried out by Milone et al. [28], in which they investigated the influence of the surface area and the nature of the support on product distribution in the hydrogenation of citronellal (3,7-dimethyl-6-octen-l-al) on Ru supported on silica and carbon. It was found that the main products obtained on the Ru/Si02 catalyst were the unsaturated cyclic alcohols (isopulegols), which were produced via the isomerization of cinonellal on the Si02 surface. However, the main reaction products on Ru/C were the open-chain hydrogenated products (i.e., citronellol,... 

CAS 89-79-2 EINECS/ELINCS 201-940-6 Synonyms Cyclohexanol, 5-methyl-2-(1-methylethenyl)-, [1R,(1a,2p,5a)]- (1R,2S,5R)-2-lsoprenyl-5-methylcyclohexanol 2-lsoprenyl-5-methylcyclohexanol L-lsopulegol Isopulegol, tech. 

L-lsopulegol Isopulegol, tech.. See(-)-Isopulegol Isopulegone CAS 29606-79-9 FEMA 2964... 

Isopropyl hexanoate Isopropyl isobutyrate Isopropyl isovalerate Isopropyl myristate p-Isopropylphenylacetaldehyde Isopropyl phenylacetate 3-(p-lsopropylphenyl) propionaldehyde Isopropyl propionate Isopropyl tiglate Isopulegol Isopulegone Isopulegyl acetate Isoquinoline Isosafrole Isovaleraldehyde Isovaleric acid cis-Jasmone Laurie aldehyde Lauryl acetate Lauryl alcohol Lepidine Levulinic acid d-Limonene dl-Limonene l-Limonene... 

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... 

Other monoterpenoid or arylpropenoid derivatives identi ed as the active components of traditional sedatives include methyleugenol (27) (Norte et al. 2005), isopulegol (31) (Silva et al. 2007), and a terpineol (32) (de Sousa et al. 2007). It is worth mentioning the monoterpene thujone (33), the dangerous principle of the ancient Absinthii herba, Artemisia absinthium L. (Asteraceae), that induces marked central stimulatory effects, especially when used in the form of liqueur. Frequent and excessive use of this drug can cause intoxicated states accompanied by clonic convulsions among other serious consequences (Bielenberg 2007). 

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