Fremy’s salt oxidation

Calculations by the Pariser-Parr-Pople method on the quinoneimine obtained by Fremy s salt oxidation of dibenz[6,/]azepine indicate that the carbon adjacent to the carbonyl group is the most nucleophilic center. This is confirmed by nitration [Cu(N03)2-Ac0H] and bromination [NBS-(PhC0)202] studies, in which the 1-substituted derivatives are obtained. However, acylation by Vilsmeier or Friedel-Crafts reaction fails, extensive decomposition of the ring system taking place. 

A completely different approach to hydroxylation at the S-position (indole numbering) in tryptophans was reported by Hino and coworkers. Their synthesis involved either LTA or Fremy s salt oxidation of... 

An adduct (9) could be isolated when Fremy s salt oxidation was applied to an analogous system. This intermediate, when treated with concentrated hydrochloric acid, is immediately transformed into the quinone 10 (59CB667). 

Epoxyquinomicin B (583), an antirheumatic agent, was synthesized in 22% overall yield in 8 steps starting from commercially available 3-hydroxy -nitrobenzaldehyde (584), which was easily converted to the amidophenol 585. Fremy s salt oxidation of 585 in Et0Ac-H20 was carried out at room temperature overnight to afford selectively in 82% yield the desired p-benzoquinone (586). This was treated with H202-NaHC03 in MeOH to yield the target molecule 583 (Scheme 109) . 

Fremy s salt oxidation of norglaucine leads to oxoglaucine. 

Oxosarcocapnidine (22) shows a bathochromic shift on addition of acid or base. The latter shift indicates the presence of a phenolic group (77). The H-NMR spectrum reveals two methoxy groups (3.98 and 3.95 ppm) and three aromatic AB spin systems, corresponding to a 7,4, 5 -substituted skeleton, which is confirmed by 0-methylation to oxosarcocapnine (24). The position of the phenolic function at C-5 has been established by chemical correlation with sarcocapnidine (13). Fremy s salt oxidation of the 5 -0-methoxymethyl derivative of 13, followed by aeid deprotection, gives 22 in 58% yield. 

Hypoxanthine analogs were formed by Fremy s salt oxidation (eq4).> ... 

Tetrahydroisoquinoline Oxidation. Papaveraldine could be produced by Fremy s salt oxidation over 7 days in 30% yield (eq 12). The corresponding A( alkyl tetrahydroisoquinolines give cleavage products (eq 13). ... 

The oxidation of primary aliphatic amines to nitriles is generally accomplished with nickel peroxide however it has now been found that electrolytic oxidation at a nickel hydroxide electrode offers distinct advantages of applicability, yield, and ease of work-up. It has also been reported that Fremy s salt oxidizes benzylamines to benzonitriles. ... 

Castedo L, Puga A, Saa JM, Suau R (1981) Fremy s salt oxidation of some isoquinoline alkaloids. 

Hibino and Weinreb (54) have reported approaches to synthesis of the AB-quinoline-quinone system of (1) (Scheme 7). In a classical Fried-lander synthesis, the known aminobenzaldehyde (60) was combined with 2-acetylpyridine to afford quinoline (61) after removal of the sulfonyl protecting group. Fremy s salt oxidation of (61) gave methoxyquinone (62) which was readily converted to the compound (59) previously prepared by Rao (16). 

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