The Isopropyl Cresols

Abstract

The Friedel-Crafts reaction has been found to be well adapted to the synthesis of thymol (1). For this preparation m-cresol is alkylated with isopropyl chloride in the presence of aluminum chloride, using ethylene dichloride as solvent. When this procedure was applied to o-cresol there was obtained in good yield a product which, after crystallization, melted sharply at 36-36.5°. This material, which will be referred to as pseudo-carvacrol, gave several derivatives melting correctly for those of carvacrol; however, subsequent investigation showed that it is actually a difficultly separable mixture of carvacrol and 3-isopropyl-2-methylphenol. The latter compound, which has not previously been reported, was synthesized from 2-methyl-3-chloroaniline by two different routes, the most direct of which proceeded through 2-bromo-6-chlorotoluene and 2-isopropyl-6-chlorotoluene. Infrared analysis, using the bands at 12.34 and 12.82 µ, indicated that psewdo-carvacrol contains about 25 % of 3-isopropyl-2 methylphenol and 75% of carvacrol. Absorption curves for the mixture and its two components are given in Fig. 1.The other two isopropyl o-cresols have been reported: 6-isopropyl-2-methylphenol (2, 3) and 4-isopropyl-2-methylphenol (4), but it was considered desirable to prepare them anew and to characterize them more accurately. 6-Isopropyl-2-methylphenol was prepared by two methods. In the first, the Grignard reagent of 6-bromo-2-methylanisole was treated with isopropyl sulfate and the resulting 6-isopropyl-2-methylanisole was demethylated to the phenol.The second synthesis was an adaptation of the method first described by Behai and Tiffenau (3) in which an ester group is converted to an isopropyl group by the steps: CH, CH, CH, SUMMARY 1. Of the ten possible isomeric isopropyl cresols, nine have been described in the literature. The unknown isomer, 3-isopropyl-2-methylphenol, has been syn-

Catalytic Hydrogenation Using Abnormal N‐Heterocyclic Carbene Palladium Complexes: Catalytic Scope and Mechanistic Insights

“…Similar isomerization processes also took place with more complex substrates, such as carvone (Scheme 1). Under standard hydrogenation conditions, complex 4 b induced a double-bond isomerization to yield 5-isopropyl-2-methylphenol [19] without further reaction.…”

Studies on the Constituents of the Leaves of Baccharis dracunculifolia (Asteraceae) and their Cytotoxic Activity

“…1). Therefore, the MeOH fraction was further separated on a silica gel column eluted with stepwise gradients of nhexane-EtOAc and then purified by HPLC to give compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) as shown in Fig. 2 .…”

“…Two new compounds (1, 2) and seventeen known compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) were isolated from the leaves of B. dracunculifolia and the chemical structures were determined by spectroscopic means. Cytotoxicity testing of the compounds isolated in this study revealed the monoterpene phenols like compounds 4, 6, and 17 (dimer) and the sesquiterpene alcohols such as compounds 8, 10, 11, 13, and 16 exhibited strong cytotoxicity.…”

“…Our biological studies of the alcoholic extracts of the leaves found that the extracts exhibited potent cytotoxic activity against leukemia cells (L 1210). In this paper, we describe the isolation and structure elucidation of two new compounds, baccharisketone (1) and p-methoxythymol acetate (2), along with seventeen known compounds; caryophyllene oxide (3), 6) thymol (4), 7) carvacrol (5), 8) p-methoxythymol (6), 8) 4-isopropyl-2-methylphenol (7), 7) spathulenol (8), 9) p-cymene-2,3-diol (9), 10) bisacumol (10), 11) 2-methyl-6-(4Ј-methylphenyl)-3-hepten-2-ol (11), 12) 1b-hydroxyeudesma-4(15),7-diene (12), 13) cadinol (13), 14) an oppositanetype sesquiterpene (14), 15) germacra-1(11),5(12),6(E)-trien-2-ol (15), 16) a tricyclic sesquiterpene (16), 15) 3,4,3Ј,4Ј-tetrahydroxy-5,5Ј-diisopropyl-2,2Ј-dimethylbiphenyl (17), 17) 3-acetoxy-4Ј,5-dihydroxy-7-methoxyflavanone (18), 18) and naringenin (19), 19) and discuss their growth inhibitory activities against L 1210.…”

Selective alkylation of m-cresol with isopropyl alcohol under solvent-free conditions

“…23 The small amount of vic-thymol and the improvement in rate of sym-thymol can be explained by the thermal stability of the mono-alkylated cresol in the presence of acid catalyst, the order being as follows: sym-thymol > thymol > p-thymol > vic-thymol. 24 Sym-thymol is the thermodynamically favoured isomer as it has higher stability compared to the other isomers. This increased stability arises from the fact that the inductive effect of the propyl and methyl groups in the meta-positions does not prevent delocalisation of the lone pair electrons on the hydroxyl group into the aromatic system to the same extent as would be the case for these substituents in the para and ortho-positions.…”