Ortho- phenol

Vanillin (4-hydroxy-3-methoxybenzaldehyde) in ethanolic solution - as supplied as a flavouring agent - was dimerized by sunlight or more rapidly under a mercury lamp to dehydrodivanillin (3). This is a typical ortho-phenol coupling reaction [20],... 

Many compounds will undergo dimerization reactions those containing thiols (e.g., disulfide formation) olefins, alcohols, and carboxylic acids (or other carbonyl chemistry e.g., aldol condensation reactions). Indoles have been shown to dimerize under acidic conditions. The dimerization is presumed to occur as shown in Figure 120 via protonation at C3 and nucleophilic attack of a second indole on C2. Phenols have been shown to dimerize under free radical initiated oxidative conditions, usually to ortho phenols. Nalidixic acid API undergoes dimerization under thermolysis conditions to decarboxylate and produce a dimeric structure (Fig. 121) (172). 

The metabolism of atropine (227) by rat and guinea pig liver microsomes has been studied (197-199). French workers noted the formation of nora-tropine (229), apoatropine (233), and a phenolic metabolite formulated as the ortho-phenol 230 (197, 198) by liver microsomes from the rat, and they reported that hydrolysis of the ester function of 227 did not occur with enzymes from this source (197, 198). The structure of 229 was determined by TLC comparisons of the metabolite with an authentic sample and by correlation of the formation of the metabolite with the release of formaldehyde in the incubation mixture. The structure of 233 was deduced by TLC and UV spectral comparisons of isolated metabolite with authentic sample, and the phenol 230 was identified by TLC color reactions and by comparison with a phenolic sample obtained by Udenfried oxidation of atropine. In the absence of more definitive data on the phenolic products of this reaction, the structure 230 proposed for the phenolic metabolite of atropine... 

This cyclization is followed by a conjugate addition of an ortho phenolic OH group on to the enone system. The product is a flavanone structure, which is always drawn a different way up to the molecules we have just been discussing. Redrawing the last product shows the cyclization. 

Barton(29) devised a biomimetic route to thebaine (3), dihydrothebainone (13), and thus morphine following observations of Battersby.(30,3l) The alkaloid salutaridine (19) was derived from (+)-reticuline (18) by a low-yielding (0.03%) regioselective para-ortho phenolic coupling reaction according to Scheme 2.3. By the use of thallium tristrifluoracetate, Schwartz(32) improved yields to up to 23%. 

Nevertheless, in many cases, hydrogcnolysis docs not occur readily however, the ammonium salt of the Mannich base appears more suitable for a successful reaction. Thus, several ortho-phenolic Mannich bases arc hydrogenated as hydrochlorides, in order to avoid the presence of the intramolecular hydrogen bond between OH and N, which is responsible for the weak reactivity of the free Mannich base. ITie ferroccnyl Mannich base 282, containing both tertiary and quaternary amino groups, gives 2-di-methylaminomethyl-l-(2-methylferroccn-l-yl) ferrocene (283) upon reaction of the more reactive quaternary ammonium moiety. ... 

The formation of the phenoxide anion enhances the reactivity of the ortho and para positions of the aromatic ring towards electrophilic reagents. The reaction of the phenoxide anion with carbon dioxide at 130 °C leads to ortho carboxylation (the Kolbe reactior. Thus phenol gives salicylic acid (4.4), the acetate of which is aspirin. The reaction is reversible and ortho phenolic acids undergo decarboxylation on heating. 

In contrast to the formation of isothebaine by a route involving a dienone, an alternative process is implicated in the biosynthesis of another aporphine alkaloid. Bulbocapnine (78) has been shown to be derived from reticuline (75). The methylation pattern of reticuline implies a direct ortho-ortho phenol coupling in which corytuberine (77) is the first alkaloid to be formed. Further experiments have been directed towards distinguishing this mode of coupling from an alternative pathway which involves hydroxylation of reticuline at C-6 and formation of bulbocapnine via a biologically unknown dienone type (76, Scheme... 

Another way to protect ascorbic acid from oxidation consists of the chelating mechanism. As has been discussed above, flavonoids with ortho-phenol structure have the ability to chelate bivalent metals, which may undergo the oxidation of ascorbic acid, and this mechanism of protection for anthocyanins is being proposed by Sarma et al [167], These former reports might explain what was proposed by Rusznyak and Szent-Gyorgyi more than six decades ago when they observed that the administration of lemon juice decreased the fragility and permeability of the capillary wall, where ascorbic acid alone had no protective effect, and led them to propose flavonoids as vitamin P. 

Figure 10 Reactions of phenolates with fi-rj. rj -peroxo complex (7) yields an orf/ o-hydroxylation reaction reminiscent of Tyr, while reactions of phenols by both (7) and bis-/x-oxo complex (8) results in ortho-phenol coupled dimers through an apparent PCET pathway...

Aporphine Alkaloids.—Isothebaine (65) derives from orientaline (62) along a pathway which involves thedienone(63)and the dienol(64). The biosynthesis of the aporphine alkaloids of Dicentra eximia is quite different but dienone intermediates are also implicated. By comparison the biosynthesis of bulbocapnine (66) is simple, for the alkaloid arises directly from reticuline (67), in Corydalis cava, by ortho-ortho phenol oxidative coupling. 

Ortho-phenol sulfonic acid—Sozolic acid—Aseptol—C H4,OH, SO3H—which is prepared by the action of cold concentrated H3SO4 upon phenol. It is a reddish, syrupy liquid, soluble in H3O in all proportions, has a faint and not disagreeable odor. It pre-... 

The production of the ortho phenol will proceed by an identical mechanism. 

The reaction of reticuline iV-oxide (8) with cuprous chloride in methanol in the absence of oxygen afforded a 61% yield of corytuberine (9), while orientaline N-oxide (10) supplied a 5 % yield of orientalinone (11). It is assumed that cuprous chloride is oxidized by the N-oxides to an active cupric species which lends itself to ortho-ortho phenolic oxidative coupling. ... 

These alkaloids have a dibenzofuran nucleus (galanthamine type) and are obtained from a para-ortho phenol oxidative coupling. 

---