Oxidation with Potassium Nitrosodisulfonate Fremy Salt

OXIDATION WITH POTASSIUM NITROSODISULFONATE (FREMY SALT) 

A solution of 0.60S g (0.005 mol) of 2,6-dimethylaniline in 25 mL of acetone is mixed with a solution of 3 g (O.Ol mol) (10% excess) of potassium nitrosodi-sulfonate in 50 mL of 0.6 M potassium dihydrogen phosphate and 100 mL of water. After 75 min, the oxidant has reacted. The solution is extracted several times with a total of 120-150 mL of chloroform. The combined extracts are dried with anhydrous sodium sulfate, and the solvent is evaporated in vacuo at 40-50 °C to yield as a residue 0.560 g (82%) of 2,6-dimethyl-p-benzoquinone, mp 63-65 °C (dec). 

---

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 ... 

The reaction of 148 with 10% HCl-MeOH afforded selective hydrolysis of the amide to form the 3-aminopyridine 149, in which the ring was subsequently closed after treatment with palladium(O) to give the /3-carboline 150. Friedlander condensation of 150 with 2-amino-3-benzyloxy-4-bromo-benzaldehyde (151), which was synthesized in four steps (5S), gave the 2-/3-carbolinequinoline 152. Hydrogen bromide gas debenzoylation of 152 was followed by oxidation with potassium nitrosodisulfonate (Fremy s salt) to obtain Kende s intermediate 131. 

Ellipticine (E) 1 is an indolic alkaloid with antitumor activity. Some of its phenolic derivatives as N-methyl-9-hydroxyellipticine (Celiptinium), obtained from 9-hydroxy ellipticine (9-OH E), exhibit high cytotoxicity. 38 Syntheses of 9-OH E are not satisfactory considering yields and cost, justifying the attempts at the direct conversion of E to 9-OH E via 9-oxoellipticine (9-0X0 E). Potassium nitrosodisulfonate (Fremy s salt), a valuable oxidant for the synthesis of quinone-imine from heterocyclic amines,139 was used. Under these conditions the conversion of E to 9-0X0 E was observed for the first time. Its reduction to 9-OH E is then easily achieved with ascorbic acid. The radical nature of Fremy s salt [ 0-N(S03K)2] led us to carry out the oxidation reaction under sonication in order to increase the yields via an easier electron transfer.1 1... 

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. " ... 

In addition to the aforementioned syntheses of various carbazole-l,4-quinone alkaloids, many formal syntheses for this class of carbazole alkaloids were also reported. These syntheses involve the oxidation of the appropriate 1- or 4-oxygenated-3-methylcarbazoles using Fremy s salt (potassium nitrosodisulfonate), or PCC (pyridinium chlorochromate), or Phl(OCCXI F3)2 [bis(trifluoroacetoxy)iodo]-benzene. Our iron-mediated formal synthesis of murrayaquinone A (107) was achieved starting from murrayafoline A (7) (see Scheme 5.34). Cleavage of the methyl ether in murrayafoline A (7) and subsequent oxidation of the resulting intermediate hydroxycarbazole with Fremy s salt provided murrayaquinone A (107) (574,632) (Scheme 5.113). 

Reduction of ketone (81) with zinc and acetic acid produced the 4-hydroxypyrazoles (87), whereas reaction with dithionite gave the corresponding 1,4-dihydroxypyrazoles (88). These compounds could be oxidized with Fremy s salt (potassium nitrosodisulfonate) to the 3,4-diazacyclopentadienone 3-oxides. 

The presence of an amino group on an aromatic ring often results in oxidation of the ring to a quinone. The classical and industrial method is the treatment of anilines with potassium dichromate and sulfuric acid. Thus, aniline at room temperature is converted into p-benzoquinone in 86% yield [647], and 2,5-dimethylaniline at 80 °C gives a 55% yield of p-xyloquinone [648. A specific reagent for such oxidations is the Fremy salt, potassium nitrosodisulfonate (equation 528) [490. The oxidation of the amino group takes place even if it is acylated (equation 529) [1190. ... 

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. 

---