Hydroxylation ortho

The oxidation of phenol, ortho/meta cresols and tyrosine with Oj over copper acetate-based catalysts at 298 K is shown in Table 3 [7]. In all the cases, the main product was the ortho hydroxylated diphenol product (and the corresponding orthoquinones). Again, the catalytic efficiency (turnover numbers) of the copper atoms are higher in the encapsulated state compared to that in the "neat" copper acetate. From a linear correlation observed [7] between the concentration of the copper acetate dimers in the molecular sieves (from ESR spectroscopic data) and the conversion of various phenols (Fig. 5), we had postulated [8] that dimeric copper atoms are the active sites in the activation of dioxygen in zeolite catalysts containing encapsulated copper acetate complexes. The high substratespecificity (for mono-... 

Pedersen and coworkers investigated the El mass spectra of several 2-hydroxyphenyl alkyl sulfones (39) and sulfoxides (Section II.B). The methyl derivative seemed to fragment only via sulfinate ester formation giving the primary product ions m/z 157 and 109 (equation 14). Obviously hydrogen bonding between the ortho hydroxyl and the sulfone sulfur makes the loss of CH3SO2 difficult in contrast to the situation in methyl phenyl sulfone. The sulfinate ester rearrangement is not important when R>Et in 39. 

Mitchell, D. Doecke, C. W. Hay, L. A. Koenig, T. M. Wirth, D. D. Ortho-hydroxyl assisted deoxygenation of phenones. Regiochemical control in the synthesis of mono-protected resorcinols and related polyphenolic hydroxyl systems. Terahedron Lett. 1995, 36, 5335-5338. 

The first of two conversions catalyzed by the metalloenzyme tyrosinase is the selective ortho-hydroxylation of a phenol moiety, yielding catechol. Few synthetic systems exist that are capable of selectively performing the same monooxygenase reaction [172-178]. The group of Casella has studied a series of dicopper complexes based on 2,6-disubstituted benzene hgands providing two N3 compartments [179-181] (26a,b) as well as the asymmetrically substituted tripodal amine-based ligand (27) [182]. 

Scheme 12 Ortho-hydroxylation by peroxo (or bis(/x-oxo)) dicopper intermediates derived from tridentate amine ligands [178]...

An efficient and selective Cu-assisted ortho-hydroxylation procedure for the conversion of benzoate to salicylate has been described, involving trimethylamine N-oxide (TMAO) as the oxidant [191,192]. The reaction was assumed to proceed via oxidation of a Cu carboxylate complex by TMAO to produce the active species (postulated to be a Cu hydroxo complex, but with only circumstantial evidence), followed by oxygen transfer to the benzoate group (Scheme 14). Using a set of different amide derivatives of benzoic acid, Comba and co-workers gained additional mechanistic hints in support of a reactive Cu-oxo or Cu-hydroxo intermediate that is stabilized by a five-membered chelate [193]. A pre-equilibrium involving Cu the ligand, and TMAO was proposed, but details of the reaction are far from clear. 

Scheme 14 Cu-assisted ortho-hydroxylation of benzoate to salicylate with TMAO...

While only tyrosinase catalyzes the ortho-hydroxylation of phenol moieties, both tyrosinase and catechol oxidase mediate the subsequent oxidation of the resulting catechols to the corresponding quinones. Various mono- and dinu-clear copper coordination compounds have been investigated as biomimetic catalysts for catechol oxidation [21,194], in most cases using 3,5-di-tert-butylcatechol (DTBC) as the substrate (Eq. 16). The low redox potential of DTBC makes it easy to oxidize, and its bulky tert-butyl groups prevent un-... 

In the preparation of 2-phenylazo-3-naphthol it is to be noted that the action of thionyl chloride on 2-amino-3-naphthol results in preferential attack on the amino group. This has been attributed, at least in part, to the fact that the hydroxyl group is in an ortho position. If the reaction is to be extended to aminonaphthols which do not have ortho hydroxyl groups, provisions will probably have to be made for the protection of the hydroxyl group against attack by thionyl chloride. 

The experimental data show that for photo-colourability in either the crystal or rigid solution there is required an ortho- hydroxyl group which is hydrogen bonded to the nitrogen of the same molecule. There is no direct evidence as to the quinoid nature of the coloured form— we have only the suggestive analogy with the azonaphthols and the relative behaviour of the anils from 2 3- and l 2-hydroxynaphth-aldehydes. 

P-Cleavage next to the ester carbonyl is promoted by the ortho hydroxyl group, through a six-membered ring (Scheme 5.19). The radical cation produced, with m/z 120, is resonance stabilized and is observed as a major fragment in the EI MS. 

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... 

Biologically, the para position of a substituted benzene derivative is the most common target for hydroxylation in the animal kingdom. By contrast, ortho hydroxylation is more common in microbial and plant metabolism. The... 

The 1,2-oxides of benzoic acids are also of interest as possible intermediates in the ortho hydroxylation and oxidative decarboxylation of aromatic acids. Ultraviolet studies indicate that benzene oxide 218 predominantly exists as its... 

The formation of salicylic acid from 218 and the D migration and retentions observed in the conversion of 220 to salicylic acid are in agreement with the suggestion that 218 is an intermediate in the ortho hydroxylation of benzoic acid in higher plants, notwithstanding the fact that a 2,3-oxide is an equally attractive intermediate. 

The nitrile group in cyanopyridine can participate in intramolecular reactions. The presence in chalcone 118 of an ortho-hydroxyl substituent can lead to its addition to a carbon-nitrogen triple bond, with the formation of the 2/7-pyran-2-iminic moiety (compound 119) [126, 127] (Scheme 3.36). 

These copper-mediated reactions very often involve dinuclear intermediates, but detailed mechanistic studies on stoichiometric systems are relatively few. The key features are the formation of p-peroxo or p-superoxo complexes by electron transfer from cop-per(i) to dioxygen. The co-ordinated oxygen may then act as an electrophile to the aromatic ring. A possible mechanism for the ortho-hydroxylation of phenol by dioxygen in the presence of copper catalysts is shown in Fig. 9-29. 

The presence of the oxidized metabolites is unique and may provide additional reasons for the health benefits of lignans. Classical antioxidant mechanisms show that the addition of an ortho hydroxyl group to a monophenol enhances the antioxidant activity of the original monophenol. Thus, some of the mammalian lignan metabolites may actually have greater or different activity than the parent lignan. Kitts et al (1999) reported that enterolactone and enterodiol had greater antioxidant activity than the parent... 

Hydroxylations of electron-rich arenes (phenols and hydroxyarenes) can be achieved catalytically with (P-P)Pt(CF3)X and H202 (where P-P is dppe and X is (CH2C12)C104) [31]. The ortho- and para-isomers are formed, with ortho substitution preferred. The authors propose that the higher yields of ortho-hydroxylated products are a manifestation of catalyst pre-coordination. 

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