Alkylphenol hydroxylation

CYP5136 Polycyclic aromatic hydrocarbon and alkylphenol hydroxylations Detoxification of xenobiotics P. chrysosporium [466]... 

For monosubstituted alkylphenols, the position of the alkyl radical relative to the hydroxyl function is designated either with a numerical locant or ortho, meta, or para. The alkyl side chain typically retains a trivial name. Thus 4-(l,l,3,3-tetramethylbutyl)phenol, 4-/ f2 octylphenol, and para-tert-octy Tph.eno (PTOP) all refer to stmcture (1). 

The aromatic ring of alkylphenols imparts an acidic character to the hydroxyl group the piC of unhindered alkylphenols is 10—11 (2). Alkylphenols unsubstituted in the ortho position dissolve in aqueous caustic. As the carbon number of the alkyl chain increases, the solubihty of the alkah phenolate salt in water decreases, but aqueous caustic extractions of alkylphenols from an organic solution can be accomphshed at elevated temperatures. Bulky ortho substituents reduce the solubihty of the alkah phenolate in water. The term cryptophenol has been used to describe this phenomenon. A 35% solution of potassium hydroxide in methanol (Qaisen s alkah) dissolves such hindered phenols (3). 

There is a health benefit associated with hindering hydrogen bonding. Alkylphenols as a class are generally regarded as corrosive health hazards, but this corrosivity is eliminated when the hydroxyl group is flanked by bulky substituents in the ortho positions. In fact, hindered phenols as a class of compounds are utilized as antioxidants in plastics with FDA approval for indirect food contact. 

Alkylphenols can be synthesized by several approaches, including alkylation of a phenol, hydroxylation of an alkylbenzene, dehydrogenation of an alkylcyclohexanol, or ring closure of an appropriately substituted acycHc compound. The choice of approach depends on the target alkylphenol, availabihty of the starting materials, and cost of processing. The procedures discussed herein encompass commercial methods, general methods, and a few specific examples of commercial interest. 

Alkylphenols undergo a variety of chemical transformations, involving the hydroxyl group or the aromatic nucleus that convert them to value-added products. 

The unshared pairs of electrons on hydroxyl oxygens seek electron deficient centers. Alkylphenols tend to be less nucleophiUc than aUphatic alcohols as a direct result of the attraction of the electron density by the aromatic nucleus. The reactivity of the hydroxyl group can be enhanced in spite of the attraction of the ring current by use of a basic catalyst which removes the acidic proton from the hydroxyl group leaving the more nucleophiUc alkylphenoxide. 

The aromatic nucleus of alkylphenols can undergo a variety of aromatic electrophiUc substitutions. Electron density from the hydroxyl group is fed iato the ring. Besides activating the aromatic nucleus, the hydroxyl group controls the orientation of the incoming electrophile. 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

Different types of aquatic DHS were shown to exhibit comparable rate constants for trapping hydroxyl radicals. Peroxy radical photooxidants (i. e., a mixture of different HS-derived species) were shown to be important for the elimination of alkylphenols, which are typical compounds classified as antioxidants. 

Substitution of the hydroxyl group with a similar-sized propylene oxide derivative creating a propoxylated alkylphenol causes a great reduction in estrogenicity. 

The double dehydrogenation of o-alkylphenols to chromenes has also been achieved with DDQ, the reaction presumably proceeding through the alkenylphenol rather than the chroman. The latter are not known for their propensity to undergo oxidation by DDQ unless a free hydroxyl group is present to allow quinone methide formation to occur. Once again, substitution at C-3 appears to be essential for success. 

Dihydropyridine 304 under basic conditions reacts with alkylphenols 305 and alkylthiopenols 306 in a different manner [246, 247, 334, 335] (Scheme 3.106) in the first case, the reaction does not involve the hydroxyl group of the phenol, while in the second the product that is formed is due to the interaction with the thiol substituent (compounds 307 and 308, respectively). 

Over the last decades, large amounts of different man-made chemicals which can act as weak estrogens have been released into the terrestrial and aquatic environment and are distributed world-wide. Classical environmental estrogens are pesticides, such as o,p -DDT, and its metabohtes o,p -DDE and o,p -DDD, methoxychlor and its metabolites, chlordecone (Kepone ), dieldrin, Toxaphene, and endosulfan [126, 135, 136]. It is also known that many chemicals with very weak or no measurable estrogenic activity can be metabolized in organisms especially to hydroxylated compounds which may have much more estrogenic potency than the parent compound. Examples are methoxychlor and its mono- and di-demethylated derivatives [126,127] as well as the alkylphenol... 

Although the obtained alkylphenols should be more reactive than the initial alkylbenzenes, their further hydroxylation and oxidation to alkylbenzoquinones is hindered for steric reasons. Since hydroxyl and methyl groups have similar dimensions, the lower conversions of p-xylene and p-ethyltoluene compared to toluene and ethylbenzene [6] suggest the effect of the steric restrictions in catalytic oxidation over TS-1. Products of oxidation both in the ring and in the aliphatic chain, could also be formed in principle. 

Titanium siliealites TS-1 and TS-2 catalyze hydroxylation in the aromatic ring of the monoalkylbenzenes studied to corresponding alkylphenols, using hydrogen peroxide as oxidant. Para-isomers are mainly formed in methanol or ethanol as solvents. In the case of ethyl- and 1-propylbenzenes, the first carbon atom of the aliphatic chain is also oxidised both to alcohols and ketones. As expected, the terminal methyl groups in all hydrocarbons are not oxidised. The probable reasons for this behaviour of titanium silicalites are discussed. 

Formation of sub-bituminous coal seems to involve O loss through conversion of dihydroxy phenolic units (catechols) to monohydroxy units (phenols and alkylphenols), as shown in Fig. 4.7, based on the simple distribution of pyrolysis products, which are dominated by phenol, ortho-cresol (2-methylphenol) and 2,4-dimethylphenol (Hatcher 1990). Oxygenated aliphatic structures (alkyl hydroxyls and ethers) seem to be absent. Figure 4.8 shows the types of units present at various stages of biochemical coalification, based on a random hgnin polymer. 

In recent years considerable attention has been given to the biodegradability of polyethoxylates and the role of their structure in this process. In consequence, there has been a move away from multi-branched alkyl side-chain in the starting alkylphenolic raw material towards more linear chains, a circumstance already adopted in the use of kerylbenzenes for the manufacture of alkylaryl sulphonates. Another practice adopted has been that of sulphation of the terminal hydroxyl group in the polyalkoxylate. Recent studies on a comparison of ethoxylates derived from the natural alkenylphenol, cardanol and from nonylphenol have indicated a considerable difference in biodegradability (ref. 24). 

Azo dyes derived from alkylphenols have been utilised in silver halide colour photographic compositions for obtaining improved sharpness (ref. 91). In the compound illustrated, R = a phenolic or alkylphenolic group having an hydroxyl substituent o- or p- to the azo group, R = OH or NHj and R = an organic group or atom. 

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