Phenols ortho alkylation

In 1957 a procedure was described that selectively alkylated phenol in the ortho position (7). This approach, using aluminum catalysis, made a variety of 2,6-dialkylphenols accessible. The mechanism proposed for this ortho alkylation is outlined as follows ... 

ButylatedPhenols and Cresols. Butylated phenols and cresols, used primarily as oxidation inhibitors and chain terrninators, are manufactured by direct alkylation of the phenol using a wide variety of conditions and acid catalysts, including sulfuric acid, -toluenesulfonic acid, and sulfonic acid ion-exchange resins (110,111). By use of a small amount of catalyst and short residence times, the first-formed, ortho-alkylated products can be made to predominate. Eor the preparation of the 2,6-substituted products, aluminum phenoxides generated in situ from the phenol being alkylated are used as catalyst. Reaction conditions are controlled to minimise formation of the thermodynamically favored 4-substituted products (see Alkylphenols). The most commonly used is -/ fZ-butylphenol [98-54-4] for manufacture of phenoHc resins. The tert-huty group leaves only two rather than three active sites for condensation with formaldehyde and thus modifies the characteristics of the resin. 

Magnesium phenolates react with triethylorthoformate regiospecifically at the ortho position of the phenoxy group (normally phenols give alkyl ethers) giving diarylmethanes. This reaction is complex and the product composition depends on the phenol and the reaction conditions.52... 

Hydroxyl group assists the ortho-alkylation of phenols (Equation (15)).15 The reaction of phenols with norbornenes... 

The spectra separate Into two large well separated groups. In the first, smaller clusters can be recognized ortho dlols, para-alkyl phenols, meta-alkyl phenols, ortho-chloro phenols, and multiply chlorinated benzenes. In the second group, these subclusters can be found ortho-alkyl phenols, benzenes bearing chlorine on alkyl side chains, and ortho-chlorotoluenes. 

G. Uncatalyzed thermal ortho-alkylation of phenols./. Org. Chem. 1958, 23, 1871-1876. Bram, G. Loupy, A. Sansoulet, J. Vaziri-Zand, F. Highly selective benzylations of /j-riaphthoxide anion in heterogeneous media. Tetrahedron Lett. 1984, 25, 5035-5038. 

A three-component reaction of aromatic aldehydes, malononitrile and phenols leads to 4-aryl-2-amino-3-cyano-4//-chromenes this reaction can be carried out in aqueous media with improvements in yield and obvious environmental advantages (Scheme 35). The aromatic aldehyde undergoes a Knoevenagel condensation with malononitrile, followed by ortho-alkylation of the phenol and cyclization to form the iminopyran intermediate 114, which isomerizes to the 4//-chrorncncs (Scheme 36) <2003SL2001>. High yields for this three-component reaction can also be achieved in aqueous media when mediated by 7-alumina <2004TL2297> or cetyltrimethylammonium chloride <2001T1395>. 

Bellamy and Williams (1960) assumed that increasing volume of ortho alkyl substituents in phenols could enhance the lifetime of free 0—H groups. The 0—H group of 2,6-di-t-butylphenols was claimed to be free even in polar solvents. By contrast, Denisov et al. (1964) published... 

The same conclusion was made in a kinetic study of solvent effects in reactions of benzenediazonium tetrafluoroborate with substituted phenols As expected due to the difference in solvation, the effect of the p-sul ituents is smaller in protic than in dipolar aprotic solvents. Ortho-alkyl substitution of phenol was found to increase the coupling rate, again as would be expected for electron releasing substituents. However, this rate acceleration was larger in protic than in dipolar aprotic solvents, since in the former case the anion solvation is much stronger to begin with, and therefore steric hindrance to solvation will have a larger effect ... 

Controlled ortho alkylation of phenol by 1-hexene to produce the mono- or di-alkylated product has been achieved by using aluminum phenolate as the catsJyst under carefully optimiz reaction conditions. Sterically hindered phenols such as (15) are of particular interest as antioxidants (Scheme 4). 

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. 

The ortho alkylation of phenol (6.24) has been carried out with a catalyst that was a solid solution of cerium(IV) and magnesium oxides.86 At 32% conversion, the selectivity was 90% for o-cresol and 8.6% for 2,6-xylenol. [The latter is a monomer for a poly(phenylene oxide), an engineering plastic.] There was no decay of activity. 

MENCKE-LASZLO Nitration of Phenols Ortho nitration of phenols and nitration of others aryls by metal nitrates or alkyl nitrates catalyzed by bentonite clay (see also 1st edition). 

Cu(OAc)2 Good to high yields, very wide substrate scope, ortho-substituted phenols and ortho-alkyl-substituted boronic acids tolerated Cu(OAc)2 (1 equiv), ArB(OH)2 (1 3equiv), EtsN (5equiv), 4A MS, 18h, ambient air 8 ... 

The operating steps are the same as for the simple batch reactor. However, a pressure letdown step to a flare may be included at the completion of the reaction to bum off unreacted olefin or trace hydrocarbons. These reactors can operate at phenol to alkene mole ratios as low as 0.3 1 by designing for positive pressures in the range 30-300 psig. The use of more highly selective catalyst systems for ortho alkylations is also ideal with this reactor type. 

Despite its potential, the synthetic impact of this reaction remained very limited for a long time due to lack of selectivity. Lewis and Smith [73] described the first example of regioselective C-H bond ortho alkylation of phenols with aUcenes in the presence of an ortho-metaUated ruthenium(ll)/phosphite catalyst (Scheme 19.47). 

Scheme 19.47 Regioselective ortho alkylation of phenols with alkenes using a ruthenium...

W.D. Smith, Process for the ortho alkylation of phenols in the presence of a copper-zinc-aluminum mixed oxide catalyst, US Patent 4085150, assigned to General Electric Company, April 18,1978. 

E. Yonemitsu, S. Togo, K. Hashimoto, M. Ito, C. Nishizawa and N. Hara, Process for ortho-alkylation of phenol compounds, US Patent 3953529, assigned to Mitsubishi Gas Chemical Company, April 27,1976. 

Nozaki and Kimura found that Ca3(P04)2 is more active than MgO or CaO for ortAo-alkylation on phenol with methanol.At 773 K, the selectivity for ortho-alkylation on phenol basis was 88%, while the selectivity on methanol basis was 93%. Thus, the selectivity on methanol basis is much higher than that with ZnO —Fe203, though the activity is lower than the latter catalyst. 

The surface phenolates tue also suggested to be the intermediates for ortho-alkylation of phenol with methanol over ZnO —Fe20s and Ca3(P04)2 from infrared spectroscopic studies. Kapsi and Olah studied the methylation of phenol and the rearrangement of anisole and methyl anisole over Nafion-H , and concluded that o-methylation forming anisole is followed by intermolecular 0 C methyl transfer leading to the formation of cresols. ... 

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