Phenols with Fremy salt

The 9,10-dihydrodiol of 3-MC (24a) was synthesized from 9-hy-droxy-3-MC by Method IV (86). Oxidation of this phenol with Fremy s salt in the presence of Adogen 464, a quaternary ammonium phase transfer catalyst, furnished 3-MC 9,10-dione. Reduction of the qui-none with NaBH -C gave pure 24a in good yield. Treatment of 24a with m-chloroperbenzoic acid was monitored by HPLC in order to optimize the yield of the anti diol epoxide (25 ) and minimize its decomposition. 

The oxidation of phenols with Fremy s radical, dipotassium nitrosodisulfonic acid [N0(S03K)2, 7.34], to hydroquinones is known as the Teuber reaction . The disodium salt of nitrosodisulfonic acid [N0(S03Na)2] is also used for the oxidation of phenols. 

The phenolic ring in estrone can be readily oxidized. Reaction of estrone with Fremy salts (peroxylamine disulfonate) affords a mixture of the two isomeric catechols. In a more controlled manner, treatment of estrone with 2-iodoxybenzoic acid (22-1) leads intially to a mixture of the 2,3-quinone (22-2) and its 3,4-isomer (22-3) (Scheme 3.22). These products are then reduced in situ with ascorbic acid to afford 2-hydroxyestrone (22-4) and 4-hydroxyestrone (22-5). 

There are two important factors that influence the oxidation. One is electronic stabilization of the incipient phenoxy radical and the other is the steric requirements that are connected with the formation of the cyclohexadiene intermediate. The presence of electron-withdrawing groups can cause the oxidation to fail or at least lead to a poorer yield. Oxidation of phenols with Fremy s salt can be applied to more... 

Oxidation of phenols with Fremy s salt requires a buffered medium, since the salt is stable in only a limited pH range, as previously mentioned. Many o-quinones are unstable to acidic conditions and may give other... 

The 7,8-dihydrodiol of 5-MC (30b) was prepared from 8-hydroxy-5-MC by Method IV (60,103). It was necessary to utilize the 8-rather than the Ot-phenol (i.e. 8-HO-5-MC rather than 7-HO-5-MC), since oxidation of the latter with Fremy s salt was anticipated to take place predominantly in the para position. The 8-hydroxy-5-MC was prepared in our laboratories by a modification of the procedure in Figure 18. An alternative preparation of 8-hydroxy-5-MC via photocyclization of methyl 3-phenyl-2-(l-(6-methoxynaphthyl) propenoate has also recently been described (103). 

The classical and the most useful laboratory method for the preparation of quinones is the oxidation of monohydric phenols with the radical reagent, potassium nitrosodisulphonate [(K03S)2NO] (Fremy s salt) (the Teuber reaction).5 Details for the conversion of 3,4-dimethylphenol into 3,4-dimethyl-1,2-benzoquinone may be regarded as typical55 the probable mechanistic pathway is formulated below. 

Oxidation of the phenol (108 R = H) with Fremy s salt gives an orthoquinone that is reducible to (108 R = OH) the same sequence of reactions with the bromo-phenol (108 R = Br) is accompanied by a shift of bromine to position 4.201... 

Sec. 17.10) from phenols by oxidation with Fremy s salt [(KSC NO]... 

The synthesis of quinones from arenes is an area which demands further research, despite the number of reagents presently available for this transformation. This is highlighted by the synthesis of the naphthoquinone (3). Direct oxidation of the dibromoarene (1) was unsatisfactory, and therefore Bruce and coworkers had to resort to a multistep sequence involving nitration, reduction, diazotization, displacement by hydroxide and finally oxidation of the phenol (2) with Fremy s salt (Scheme 1). Although there are examples of the oxidation of polynuclear aromatic hydrocarbons to quinones, the direct oxidation of an arene to a quinone is a process not encountered in the synthesis of more complex mt ecules. 

Simple phenols (574, 575, 576 and 247) were treated with Fremy s salt in acetone and buffer solution to afford the corresponding benzoquinones (577, 578, 579 and 248) in 53, 60, 58 and 87% yields, respectively. In the cases of both 576 and 247, the initially formed phenoxy radicals were attacked by the second Fremy s salt at the ortho- and para-positions, respectively. The resulting radical coupled products were further converted into the corresponding quinones (Scheme 107). From these data, the product selectivity seems to be due to the finely balanced situation of electronic and steric factors - . ... 

FIGURE 3.2 Reaction of uncondensed phenolic groups with Fremy s salt. 

The mechanism of the oxidation of phenols to benzoquinones with Fremy s salt is fairly well understood [59a], and the kinetics of this reaction have been studied recently [62]. Fremy s radical abstracts the phenolic hydrogen atom to generate a resonance-stabilized phenoxy radical intermediate (Scheme 20). Trapping of the carbon radical with another equivalent of Fremy s salt, followed by elimination of the aminosulfonate group gives the ortho or para benzoquinone products, depending on the ring substitution. 

Scheme 20. General mechanism for the oxidation of phenols to benzoquinones with Fremy s salt...

As examples of functionalised compounds aurogalaucin (ref.35) and flavoglaucin provide a link with synthetic monoprenyl dihydric phenols of the type discussed in 12.4. Although these two compounds (Table 12.1) do not appear to have been synthesised a study of their biosynthesis (ref. 36) illustrates a potential laboratory route through oxidation of 7-heptylsalicylic acid, synthesised by standard methods (ref. 83), by procedures such as Teuber oxidation with Fremy s salt followed by reduction, conversion of the methoxycarbonyl to the formyl group by hydride reduction and oxidation of the benzylic alcohol and finally prenylation, which would probably be non-specific. 

Phenols are aromatic counterparts of alcohols but are much more acidic (pkia 10) because their anions are resonance stabilized by delocalization of the negative charge into the aromatic ring. Phenols can he oxidized to quinones by reaction with Fremy s salt (potassium nitrosodisulfonate), and quinones can he reduced to hydroquinones by reaction with NaBH4. 

However, conversion of cularines into the corresponding oxocularines has been achieved by Fremy s salt and lead tetraacetate in acetic acid, the former reagent giving much better yields than the latter. Thus treatment of sarcocapnine (3a) with Fremy s salt in pyridine-water has furnished oxosarcocapnine (6a) in 50% yield (Campello et al. 1982). Oxidation of phenolic cularines as (3b) to the... 

The phenanthrene 1,2- and 3,4-diones are synthetically accessible from the related 8 phenols. Oxidation of 2-phenanthrol with either Fremy s salt ((KS0 )2N0) or phenylseleninic anhydride gave phenanthrene 1,2-dione directly (55). Unexpectedly, oxidation of 3-phenanthrol with (KSOg NO yielded 2,2-dihydroxybenz(e)indan-l,3-d-ione (Figure 10). However, phenanthrene 3,4-dione was readily obtained from 3-phenanthrol by Fieser s method entailing diazonium coupling, reduction, and oxidation of the resulting 4-amino-3-phen-anthrol with chromic acid (56). 

The nitrosodisulfonate salts, particularly the dipotassium salt called Fremy s salt, are useful reagents for the selective oxidation of phenols and aromatic amines to quinones (the Teuber reaction). - Dipotassium nitrosodisulfonate has been prepared by the oxidation of a hydroxylaminedisulfonate salt with potassium permanganate, " with lead dioxide, or by electrolysis. This salt is also available commercially. The present procedure illustrates the electrolytic oxidation to form an alkaline aqueous solution of the relatively soluble disodium nitrosodisulfonate. This procedure avoids a preliminary filtration which is required to remove manganese dioxide formed when potassium permanganate is used as the oxidant. " ... 

Phenols —> o-Quinones.2 This nitroxide is comparable to Fremy s salt for oxidation of monohydric phenols to quinones, but yields are low with simple phenols. The final step in a recent synthesis of methoxatin (4, a cofactor for a bacterial methanol dehydrogenose) required oxidation of the phenolic ring of 2 to an o-quinone (3) and ester hydrolysis. The usual oxidant, Fremy s salt, is not useful for... 

Uncondensed phenolic units in lignin have been estimated by a color reaction based on oxidation with potassium nitrosodisulfonate (Fremy s salt) (Adler and Lundquist 1961) as illustrated below ... 

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