Phenol ortho selectivity

Cu-Mn mixed-oxide binary spinel catalysts (CuxMn3 x04, where x = 0, 0.25, 0.5, 0.75 and 1) prepared through co-precipitation method exhibit phenol methylation activity imder vapor phase conditions [75]. All of the catalysts, irrespective of the compositions, produced only C-methylated phenols. However, a total ortho selectivity of 100% with 2,6-xylenol selectivity of 74% was observed over x = 0.25 compositions at 400°C. This composition was found to be relatively stable under reaction conditions compared with the other compositions studied. The catalysts with high copper content suffered severe reduction under methylation conditions whereas, catalysts with low copper content had a hausmannite phase (Mu304) that sustained... 

Quantum yields determinations lead to analogous conclusions, although differences in the ortho-to-para ratio are found probably because of experimental reasons. However, the ortho selectivity seems to be well established. Phenyl acetate irradiated in water gives the following quantum yields of product formation 0.16 (ortho), 0.067 (para), and 0.048 (phenol) in the presence of an excess of (3-cyclodextrin, they change to 0.23 (ortho), 0.053 (para), and 0.27 (phenol) [260]. As can be seen, the ortho product is favored in the hydrophobic microenvironment of the cyclodextrin. Phenol quantum yield is enhanced with respect to the irradiation without cyclodextrin, which has been interpreted in terms of H abstraction from the inner walls of the host oligosaccharide. 

Analogous to the acid catalyzed hydroxylation of phenol on H-ZSM-5 with hydrogen peroxide [92], benzene and chlorobenzene can be oxidized with dinitrogen oxide on HZSM-5 [125-126]. In the hydroxylation of benzene, the selectivity for phenol is high at conversions below 10%, with selectivities in N2O of about 30%. A small amount of ortho-diphenol or catechol was formed. The hydroxylation of chlorobenzene was also ortho-selective (58%). The reaction was proposed to proceed via scheme 7. 

As reported in the literature, the acylation of aromatic hydrocarbons can be carried out by using zeolites as catalysts and carboxylic acids or acyl chlorides as acylating agents. Thus toluene can be acylated by carboxylic acids in the liquid phase in the presence of cation exchanged Y-zeolites (ref. 1). The acylation of phenol or phenol derivatives is also reported. The acylation of anisole by carboxylic acids and acyl chlorides was obtained in the presence of various zeolites in the liquid phase (ref. 2). The acylation of phenol by acetic acid was also carried out with silicalite (ref. 3) or HZSM5 (ref. 4). The para isomer has been generally favoured except in the latter case in which ortho-hydroxyacetophenone was obtained preferentially. One possible explanation for the high ortho-selectivity in the case of the acylation of phenol by acetic acid is that phenylacetate could be an intermediate from which ortho-hydroxyacetophenone would be formed intramolecularly. 

Ortho hydroxylation of phenols can be accomplished by molecular oxygen in the presence of copper(I) chloride and metallic copper in acetonitrile. This particular ortho selectivity, which is similar to that of enzymic tyrosinases, has been attributed to the formation of a stable copper(II) catecholate resulting from the reaction of copper(I) phenates with dioxygen (equation 274).605... 

Kirste A, Nieger M, Malkowsky IM, Stecker F, Fischer A, Waldvogel SR (2009) ortho-Selective phenol-coupling reaction by anodic treatment on boron-doped diamond electrode using fluorinated alcohols. Chem-Eur J 15 2273-2277... 

Another example of the effect of confined medium is found during photo-Fries rearrangement of naphthyl esters in zeolites [103,104]. Upon photolysis in isotropic solution 1-naphthyl benzoate undergoes the photo-Fries rearrangement to yield both ortho (2-) and para (4-) phenolic ketones (Sch. 4). When this ester is included in NaY zeolite and irradiated the main product (96%) is the ortho isomer. This remarkable ortho-selectivity within zeolites has been rationalized on the basis of interactions of the reactant 1-naphthyl benzoate and intermediate radicals with the sodium ion. Due to restrictions imposed by the medium the benzoyl radical, once formed, is compelled to react only with the accessible ortho position. 

Oxidation of phenols (10,23-24). The earlier report of oxidation of phenols with 1 mainly to o-quinones has been confirmed recent reports of oxidation to p-quinones has been shown to involve contamination of 1 with benzeneseleninic acid, C(,H5Se02H (2), which is para-selective for this oxidation. Solvents also can play a role. THF and benzene are the solvents of choice for 1, and CH2C12 is the best solvent for para-oxidation with 2. In acetic anhydride, both 1 and 2 are ortho-selective. In addition, phenylselenoquinones can be formed in oxidations with both 1 and 2, but this reaction can be inhibited by addition of indole. 

The pioneering study of ruthenium-catalyzed regioselective alkylation using olefins as an alkylating reagent was reported by Lewis and Smith [24]. The ortho-selective ethylation of phenols with ethylene can be attained with the aid of a ruthenium(II) phosphite complex as a catalyst. This alkylation takes place exclusively at the position ortho to the hydroxyl group, and the corresponding 1 2 addition product is the major product (Eq. 6). The use of potassium phe-noxide is the key in this catalytic reaction. Unfortunately, however, the applicability of this reaction is narrow. Thus, phenol is the only applicable substrate in this reaction. 

When it comes to choosing between ortho and para positions we need to consider steric effects as well. You will have noticed that we have seen one ortho selective reaction—the formation of salicylic acid from phenol—and several para selective reactions such as the bromination of an amide just discussed. 

Catalyst Ortho/para Phenol conversion (%) Selectivity Ref. 

Trimethyl phenol has heen produced selectively hy gas phase methylation of m-cresol with methanol at 300-4 00° C rmder normal pressme on ortho-selective metal oxide catalysts as used for selective methylation of phenol. The reaction occurs in mriltituhe reactors with a fixed catalyst. Iron oxide catalysts modified with oxides of other metals (Zn, Cr, and Sn) or Mg and Si are particularly suitahle. At a temperature of approx. 350°C and an LHSV of Ihr an initial mixture of m-cresol, methanol and steam in a molar ratio of 1.6 1 gives... 

The product distribution in the t-butylation of phenol with isobutanol may be explained based on the nature of acid-base strengths and the mode of adsorption of phenol. It has been reported in the literature that phenol is adsorbed horizontally on acid-catalysts like AI2O3 and a vertical mode of adsorption is proved on basic catalysts like MgO [16,17], The horizontal adsorption of phenol results in O-alkylation and also C-alkylation at ortho and para positions which are close to the surface of the catalyst whereas in the vertical adosrption mode, only the ortho selectivity is observed. The extent of C-alkylation depends on the strength of the acid site. However, a combined participation of acid-base properties is also reported in the methylation of phenol over hydrotalcites [18]. Hence, a scheme depicting the correlation between the acid-base properties of the catalysts with the product distribution in the t-butylation of phenol is shown below as. 

More recently, basic heterogeneous catalysts have been tested for the hydroxyalkylation of phenols [16]. Examples of yields and selectivity obtained with different substrates are shown in Eqs 5 and 6. The reaction in basic medium is much more ort/to-selective than in acidic medium, and ortho selectivity can be enhanced by choice of a suitable catalyst. For example, in the synthesis of 2,2,2 trifluoro-1-... 

LjPt(CF3)X complexes (with L = tetraaryldiphosphines and X = CH CIj, OH, OPh) are hydroxylation catalysts of phenol and phenol ethers, with 70% HjO [46]. In all cases, high ortho-selectivity (up to 95%) is observed. Phenylalanine is hydroxylated by a water-soluble iron porphyrin complex to tyrosine and dihydroxy phenylalanine (DOPA) in good yields [47]. Other hydroxylation catalysts of various aromatic substrates are halogenated porphyrin complexes of Fe and Mn [48-49],... 

In 1986, a highly regioselective catalytic hydroarylation [118] ofalkenes was disclosed by Lewis, whereby a cyclometaUated ruthenium catalyst 94 allowed for a directed (hence ortho-selective) alkylation of phenols through the in situ formation of the corresponding phosphites (Scheme 1.36) [119]. 

As mentioned in Section 2, incorporation of catalysts in porous matrices not only presents the advantages of heterogeneous catalysts (easy separation of the catalyst from the reaction mixture) but also prevents deactivation pathways. This is demonstrated with the example of dicopper acetate dimers incorporated in various mesoporous inorganic matrices. Tested for phenolase and catecholase activity, they displayed a 10-fold increase of the TON compared to neat copper acetate, which was ascribed to the isolation of the active site. Chemoselectivity (hydroxyaryls vs other aryls) and regio selectivity (phenol ortho hydroxylation) have been reported with this system. ... 

The selective oxidative phenolic ortho-coupling reaction turned out to be challenging when... 

Alkylation with Alkenes. The alkylation of phenols by olefins and cyclo-olefins has been reviewed, in Russia Several papers on the alkylation of phenols have appeared. Thus, p-t-butyiphenol has been prepared with good selectivity by treatment of phenol with isobutene and a Lewis acid catalyst followed by HCIO4 as an isomerization catalyst. The ort/io-alkylation of phenol by alkenes can be improved by using Al(OPh)3 and an aluminosilicate catalyst.Much greater ortho-selectivity in the alkylation of phenol with 4-bromostyrene is obtained if aluminium diphenylphosphorodithioate rather than BF3-OEt2 or BF3-H3P04 is used as catalyst. Relative reactivities of the various ring positions towards... 

Triaryl phosphates are produced from the corresponding phenols (usually mixtures) by reaction with phosphoms oxychloride, usually in the presence of a catalyst (94—96). They are subsequently distilled and usually washed with aqueous bases to the desired level of purity. Tricresyl phosphate was originally made from petroleum-derived or coal-tar-derived cresyflc acids, ie, cresols, variously admixed with phenol and xylenols. Discovery of the toxicity of the ortho-cresyl isomers led manufacturers to select cresols having very Httle ortho-isomer. 

---