Hydroxylation pattern ortho

The pattern of microbial hydroxylation of aromatic substrates appears to occur generally according to the usual rules of electrophilic aromatic substitution as shown by the hydroxylation positions of acronycine (1) at C-9 and C-11 (para- and ortho-positions to the amino group and mefa-position to the car-... 

Simple phenolics are substituted phenols. The ortho, meta and para nomenclature refers to a 1,2-, 1,3- and 1,4-substitution pattern of the benzene ring, respectively, where in this case one of the functional groups is the hydroxyl group. With three functional groups, the substitution pattern can be 1,3,5, which, when all three substituents are identical, is designated as a mt /fl-tri-substitution pattern, whereas the 1,2,6, substitution pattern is indicated by the prefix v/c (Figure 1-1). 

The pattern of deuterium distribution in isotope exchange products of 1,8-nap-hthyridine and its methyl-, hydroxyl-, amino- and nitro derivatives indicates that the rate and pathway of this process depend on the pH of the medium as well as the nature and position of substituent (1988ACH267). In neutral D20 and a D20-DC1 mixture, hydrogen atoms are replaced with deuterons exclusively at positions 2 and 7. In D20 solutions containing NaOD, hydrogen atoms are replaced with deuterons in all positions of the naphthyridine system. In neutral D20, the replacement of the protons in monomethyl-substituted 1,8-naphthyridines occurs predominantly in the ortho positions with respect to the nitrogen atoms (positions 7 and 2, 7). The high reactivity of these positions is determined by the inductive effect of the substituent. 

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... 

Finn also showed the formation of 2H-chromenes under the same reaction conditions, using alkenylboronic acids and morpholine in dioxane at 90 °C. A more convenient route to the 2H-chromenes was then developed using a catalytic amount of dibenzylamine in the presence of alkenylboronic adds and salicylaldehyde (42, Scheme 7.11) [30]. Chromenes 43 were reported to arise from the initial Petasis borono-Mannich adducts 44 via an add promoted intramolecular S 2 attack of the ortho-hydroxyl group onto the protonated allylic amine of intermediate 45. A more likely mechanism involves elimination from 45 to intermediate 46, followed by 6n-electrocychzation to the product The reaction is tolerant of various functional groups and substitution patterns on the salicylaldehyde, and could also be promoted using a polymer-supported base, such as Merrifield resin-supported dibenzylamine (40-50 mol%) [30]. 

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