Alkylation of phenol by myrtenol

Abstract

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.Terpenophenols are known to exhibit a variety of biological activities [1][2][3]. The presence of isoprenyl substituents modifies the role of the aromatic compounds, mainly by increasing their lipophilicity. This enhances the retention of the prenylphenols in lipid cell membranes and the penetration through them [4]. The structure of the terpene substituent and the terpenophenol in general can determine the type of activity. In this respect, studies elucidating the relationship between the alkylation conditions and the resulting products are interesting. The goal of such investigations is to find the parameters that facilitate the selective production of compounds with a given structure.Herein the influence of two organoaluminum catalysts, aluminum phenoxide and aluminum isopropoxide, on the products formed by alkylation of phenol (1) with myrtenol (2) (Scheme 1) is evaluated taking into account various thermal regimes and reagent ratios. According to the literature [5][6][7][8], both catalysts are ortho-orienting.Phenol, aluminum phenoxide, and aluminum diisopropoxide-phenoxide were alkylated by myrtenol at 120, 140, and 160°C. The catalysts were aluminum phenoxide (PhO) 3 Al and aluminum isopropoxide (i-PrO) 3 Al. (PhO) 3 Al was produced in situ by reacting phenol with metallic Al. (i-PrO) 3 Al was transformed during the reaction into the mixed aluminum alkoxidephenoxide by reaction of equimolar amounts of phenol and (i-PrO) 3 Al.The alkylation with an equimolar ratio of aluminum alkoxides and myrtenol was carried out for 3 h with practically complete conversion of myrtenol regardless of the nature of the organoaluminum component. The reaction with a catalytic amount of the aluminum alkoxides occurred at temperatures of at least 160°C and continued for 8-15 h. The conversion of myrtenol was 50-60%. The reaction products were a mixture of O-and C-alkylated phenols and myrtenol derivatives (numbering of C atoms is given for convenience of reading spectra). These were monoalkylated phenols (3, 4); cyclic ethers (5, 8); a linear ether (9); substituted phenols (10-16); dialkylated phenols 17 (chromone and o-substituted), 18 and 19 (ortho and o-substituted), 20 and 21 (ortho-and para-substituted); ortho-disubstituted phenol (22); myrtenol derivatives (22-27); and myrtenol derivatives with two aromatic cores (28-33) (Scheme 1).A variety of structures for the terpene substituent was noted in the alkylation products. The presence of a strained cyclobutane moiety in th...

Structural and spectroscopic characterizations of aluminum phenoxide

“…The 1 H, 13 C, and 27 Al NMR spectra were obtained in CDCl 3 and THF-d 4 (vs. Me 4 Si in ppm) using a Bruker AVANCE 200, 300, and 600 MHz spectrometers.…”

“…Despite the long-lasting utilization of aluminum aryloxides, and specifically metal derivatives of phenol in various industrial processes such as catalysts for synthesis of fragrance and flavoring materials, synthesis of new class of antioxidants, selective alkylation of phenols, lubricants, surfactants, disinfectants, fungicides, and insecticides, its molecular structure is still not unambiguously determined [25][26][27][28]. 4 Aluminum phenoxide was synthesized and used differently in several chemical processes.…”

“…4 Aluminum phenoxide was synthesized and used differently in several chemical processes. It has been utilized in an isolated or in situ generated forms [27,[29][30][31]. In fact, the synthesis of aluminum phenoxide was first reported over 130 years ago [32].…”

“…In 1984 Kriz et al. based on 27 Al NMR spectra and molecular weight measurements concluded the presence of dimeric and trimeric aggregates in solution [33]. Further characterization was provided by Gilje and coworkers [34] with 1 H and 13 C NMR spectra, which showed that either the OPh groups are chemically equivalent or in fast exchange.…”

“…Nevertheless, attempts to crystallize or purify aluminum phenoxide have not been successful, as it decomposes upon heating during distillation or sublimation [35]. However, the presence of tri-and tetranuclear aggregates in the solid state could be elucidated by 27 Al MAS NMR [36]. To continue our exploration of aluminum compounds, we report here the preparation, purification, single-crystal structure determination, and solution behavior of aluminum phenoxide.…”