Isopulegols

AH (A)-menthol is made by synthetic methods. One method involves the cyclization of (+)-citroneIlal (68). Using a mild acid catalyst, (+)-citroneIlal [2385-77-5] undergoes an ene-reaction to produce a mixture of isopulegols (142). Catalytic hydrogenation of the isopulegol mixture gives a mixture of menthol and its isomers. The (A)-menthol is obtained after efficient fractional distillation and the remaining isomers can be equilibrated, usually with sodium menthol ate or aluminum isopropoxide. An equilibrium mixture is obtained, comprised of 62 wt % (A)-menthol, 23 wt % (+)-neomenthol, 12 wt % (+)-isomenthol, and 3 wt % (+)-neoisomenthol. The equilibrium mixture can be distilled to recover additional (+)-mentbol. 

Fig. 4. Mild acid treatment of (+)-citroneUal (68) produces a mixture, 70% (-)-isopulegol (69), 23% (+)-neoisopulegol (70), 8% (+)-isoisopulegol (71), and 2% (+)-neoisoisopulegol (72). Catalytic hydrogenation produces (-)-menthol (73) from (69) (+)-neomentho1 (74) from (70) (+)-isomentho1 (75) from (71) ...

Isopulegol, Cj Hj O, does not appear to exist in essential oils, but it results from the action of acids on citronellal. The last-named body, for example, when boiled with acetic anhydride yields isopulegyl acetate, from which the alcohol is obtained by hydrolysis. 

Isopulegol is an oil having an odour resembling that of menthol. Its characters are as follows —... 

Its optical rotation has usually been recorded as from - 2° to - 3", but recently Pickard, Lewcock, and Yates have prepared f-isopulegol by fractional crystallisation of the magnesium and cinchonine salts of the hydrogen phthalate, and found its specific rotation to be - 22-2°. 

On oxidation isopulegol yields isopulegone, which can be characterised by its oxime, which melts at 121° for the active, and about 140" for the inactive variety or its semi-carbazone, which melts at 172° to 173° for the active, and 182° to 183" for the inactive variety. 

It is probable that the isopulegol was first changed to pulegol and ihis to methylcyclohexanol. 

This view would explain the observation made by Tiemann and Schmidt, that citronellal when heated with acetic anhydride, only yields about 50 per cent, isopulegol or the fact noted by Harries and... 

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). 

Isonicotinic acid hydrazide reagent 318 Isoprenaiine 395,396 Isoprenoid compounds 44 Isopulegol 59 Isoquercitrin 279, 280, 323 Isoquinoline alkaloids 46, 66, 262 Isorhamnetin 323 Isothiazolones, microbiocidal 45 Isothiocyanates 75 Isotopes, j8-radiation-emitting 41 -, detection limits 41 Itaconic acid 61... 

On the contrary, the Lewis acid sites present on the snrface of sepiolite make the Cn/sepiolite catalyst extremely active in promoting the ene reaction of citronellal. Thns, citronellal never accnmnlates in the reaction mixtnre bnt it is com erted into isopulegol as soon as it forms. Hydrogenation of isopnlegol is very slow nnder these reaction conditions, bnt this simple catalyst is able to produce menthol in a one-pot-one-step reaction under very mild experimental conditions. Notably dehydration products, which give account of 40% of the reaction mixture obtained over Ni-H-MCM-41 [4], are kept under 20% over both Cu catalysts. 

Citronellol is formed through selective hydrogenation of the C=C bond activated by the presence of the OH group, whereas menthol 3 is the product of a three-functional process involving isomerization of the allylic alcohol 1 to citronellal 4, ene reaction to isopulegol 5 and final hydrogenation (Scheme 2). 

Isopulegol (Tech, as obtained from Aldrich-Chemie GmbH Company KG,... 

Corma and Renz6 developed an effective heterogeneous catalyst system. Incorporation of tin into a beta zeolite network (Sn-Beta) gave a catalyst that was used to convert citronellal 5 to racemic isopulegol (6, Equation (3)) with 85% diastereoselectivity. It was calculated that each metal site performed 11,500 reaction cycles. No leaching of the tin was detected. This catalyst system is advantageous over normal Lewis acids, since precautions against humidity are not required, and it is suitable for use in a fixed bed continuous reactor. 

It was observed that no leaching of Ti occurs during the catalytic reaction in the anhydrous medium. The acidity of the catalysts (which gave rise to many side products) was evaluated by a comparison of their reaction rates in the acid-catalyzed conversion of citronellol into isopulegol (Scheme 7). The acidity of the catalysts decreased in the following order A>C>D>B = E. The catalytic activity and epoxidation selectivities are compared in Table XIII. 

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