A. A. Koroleva

Reaction of menthol and phenol in the presence of aluminium alkoxides

Phenol was alkylated with menthol in the presence of organoaluminium catalysts such as aluminium phenoxide and aluminium isopropoxide. Reaction products were isolated and characterized. Certain features of the process were determined.

Alkylation of phenol by nerol in the presence of organoaluminum compounds

Alkylation of aluminum phenolate by nerol and of phenol by nerol in the presence of the organoaluminum compounds aluminum phenolate and aluminum isopropylate was studied. The reaction products were isolated and characterized. Several features of the process were determined. It was found that ortho-substitution of the aromatic ring occurred primarily. In several instances nerol was cyclized. The fraction of allyl rearrangement was insignificant.

Synthesis from Polyprenols and Biological Activity of Polyprenylacetic Esters

Narrow fractions of polyprenols isolated from birch (C35-C45) and fir (C70-C85) greenery were used to prepare esters of polyprenylacetic acids that exhibited high anti-ulcer activity comparable and in several instances exceeding that of the known anti-ulcer preparation omeprazole (omez).

Alkylation of Phenol And Hydroquinone by Prenol in the Presence of Organoaluminum Catalysts

Prenylphenols and 2,2-dimethylbenzopyrans were synthesized via alkylation of phenol and hydroquinone with prenol in the presence of organoaluminum catalysts, i.e., aluminum phenoxide and isopropoxide. Reaction products were isolated and characterized. Several reaction features were determined.

Synthesis of Natural Geranylhydroquinone Analogs

Hydroquinone was alkylated by geraniol in the presence of aluminum-phenoxide and -isopropoxide catalysts. The reaction products were isolated and characterized. Several features of the process were determined.

Alkylation of phenol by myrtenol

Alkylation of phenol by myrtenol in the presence of aluminum phenoxide and aluminum isopropoxide was studied in the temperature range 120–160°C. The reaction occurred with the formation of an array of alkylated phenols. Isomerization of the terpene substituent as a result of rearrangements of the bicyclic myrtenol structure was observed. The side reaction of myrtenol reduction occurred during the alkylation in the presence of aluminum isopropoxide. A significant number of compounds with two aromatic moieties was formed in the presence of aluminum phenoxide.

Oxidative transformations of polyprenols

Oxidative transformationsinvolving the hydroxylsand ω-methylsof polyprenolsisolated from birch greenery (7-9 isoprene units in the chain) were used to produce α,ω-diols, diesters, aldehydoalcohols, and hydroxyacids. The products are of interest as potential anti-inflammatory, antiulcer, hepatoprotective, and cardio-active preparations.

Alkylation of o-cresol by polyprenols

Aromatic compounds containing a prenyl moiety are found among biologically active compounds that regulate important metabolic processes [1–3]. In this respect prenylated phenol derivatives, which can be prepared using several methods, are certainly interesting. In our opinion, one of the most interesting preparation methods is direct Friedel–Crafts alkylation of phenols by polyprenols. This method was widely used recently even for catalytic asymmetric alkylation [4]. Herein we communicate results for the alkylation of o-cresol by polyprenols isolated from cotton leaves [5] and containing 10–12 isoprene units. The choice of o-cresol was due to the presence of two strong oand p-orienting groups, i.e., methyl and hydroxyl, through the action of which the prenyl moiety could be directed into the oand p-positions to form a mixture of polyprenol isomers. Furthermore, the expected compounds could exhibit new biological properties owing to the high biological activity [6]. Alkylation of cresol by polyprenols (1) was carried out according to the method developed for alkylation of phenol by geraniol in the presence of aluminum alkoxides [7, 8]. The Friedel–Crafts alkylation catalyst was aluminum o-cresolate (2). Aluminum phenolates are known to be ortho-selective catalysts of phenol alkylation by camphene, -pinene, and dipentene [9]. Polyprenols C50–C60 of 95% purity (according to PMR spectroscopy) that were isolated from Gossypium hirsutum L. leaves (cotton line L-4) grown on the experimental plot of the Institute of Genetics and NPO Biolog in Tashkent Oblast were used for alkylation of o-cresol. PMR spectra of the polyprenols exhibited singlets for methyl protons at 1.65 and 1.72 ppm that belonged to internal transand cis-isoprenoid units, respectively. Methyl protons of the chain and -terminuses resonated as singlets at 1.46 and 1.63 ppm, respectively. A broad triplet (J = 7.0 Hz) corresponding to methylene protons of the isoprenoid chain was observed at 2.01 and 2.13 ppm. A doublet characteristic of methylene protons of a hydroxyl appeared at weaker field (4.11 ppm). Olefinic protons of the chain middle (cisand trans-) formed a broad multiplet at 5.16 ppm. The olefinic proton of the terminal unit resonated at 5.47 ppm (triplet). Scheme 1 diagrams shows the alkylation of o-cresol by polyprenols C50–C60.

Synthesis and Biological Activity of Prenylated Phenols

Prenylphenols and 2,2-dimethylbenzopyrans were synthesized via alkylation of resorcinol and pyrocatechol with prenol in the presence of aluminum isopropylate and phenolate catalysts. Several process features were determined. The antiradical, membrane-protective, and antioxidant activity of the synthesized compounds were assessed using various models. 2,2-Dimethyl-7-isobornylchroman-6-ol was found to have higher activity than 2,6-di-tert-butyl-4-methylphenol (ionol or BHT).

Alkylation of Phenol by Limonene as a Method for Preparing Chromanes

Natural terpenophenols display broad spectra of biological activity. In particular, their benzopyran derivatives, e.g., chromanes, which are represented by tocopherols, cannabinoids, flavonoids, coumarins, anthocyans, etc., exhibit vitamin and antioxidant activity and affect the central nervous system [1–6], which is responsible for the interest in synthesizing their analogs [7–11]. Alkylation of phenol by terpenes is an effective method for preparing terpenophenols with various structures. Chromanes, the structures and amounts of which are determined by the terpene involved in the alkylation and the reaction conditions, are practically always identified among the reaction products [12–14]. Herein we communicate results from the alkylation of phenol (1) by limonene (2) in the presence of catalytic amounts of aluminum phenolate Al(OPh)3 under various reaction conditions. Phenol (1) was alkylated by 2 in the presence of Al(OPh)3 (10 mass% of the starting phenol) by holding the temperature at 160 or 180°C until 2 was fully converted. The course of the reactions was monitored by TLC on Sorbfil plates using petroleum ether–Et2O (3:1) and GC on a Shimadzu GC-2010AF chromatograph with an SLB TM-5ms capillary column (Supelco, 60 m 0.25 mm 0.5 m) at 70–230°C with heating rate 6°C/min, a flame-ionization detector, and He carrier gas. Products were separated by column chromatography over SiO2 (70 – 230 mesh) using petroleum ether–Et2O with increasing fraction of the latter. The alkylating agent was limonene (Alfa Aesar, 96%). Al(OPh)3 was synthesized in situ. Phenol was purchased (Alfa Aesar) and was used without further purification.