Krohnke oxidation

Acid hydrolysis of the nitrone provides the aldehyde corresponding to the original alkyl halide (the Krohnke oxidation) (Scheme 67) (53AG605). 

Another reagent that convert benzylic halides to aldehydes is pyridine followed by /7-nitrosodimethylaniline and then water, called the Krohnke reaction. Primary halides and tosylates have been oxidized to aldehydes by trimethylamine N-oxide, and by pyridine N-oxide with microwave irradiation. ... 

The versatility of 5-nitrosopyrimidines in pteridine syntheses was noticed by Pachter (64MI21603) during modification of the Timmis condensation between (262) and benzyl methyl ketone simple condensation leads to 4-amino-7-methyl-2,6-diphenylpteridine (264) but in the presence of cyanide ion 4,7-diamino-2,6-diphenylpteridine (265) is formed (equation 90). The mechanism of this reaction is still uncertain (63JOC1187) it may involve an oxidation of an intermediate hydroxylamine derivative, nitrone formation similar to the Krohnke reaction, or nucleophilic addition of the cyanide ion to the Schiff s base function (266) followed by cyclization to a 7-amino-5,6-dihydropteridine derivative (267), oxidation to a quinonoid-type product (268) and loss of the acyl group (equation 91). Extension of these principles to a-aryl- and a-alkyl-acetoacetonitriles omits the oxidation step and gives higher yields, and forms 6-alkyl-7-aminopteridines, which cannot be obtained directly from simple aliphatic ketones. 

AP (protected by acetylation at N-10, (650)) was prepared in an unequivocal fashion by a different strategy starting with 2-amino-3-cyano-6-formylpyra-zine (647), which was itself prepared by two independent procedures Scheme 3.141) [261], In the first, 2-amino-3-cyano-6-chloromethylpyrazine (645) was converted to (647) via (646) by the KrOhnke procedure in excellent overall yield. In the second, the 1-oxide (644) was treated with w-propylamine,... 

The first preparation of 1,3,4-thiadiazole aldehydes was described by Ohta and Isowa, who used the Krohnke reaction on 2,5-dimethyl- and 2-methyl-5-phenyl-l,3,4-thiadiazole. They described 2,4-dinitrophenylhydrazones and thiosemicarbazones, oxidation to acid, and acyloin condensation. Bacchetti has shown that 2-phenyl-... 

Krohnke-King oxidative degradation of acetyl and chloroacetyl groups at various positions led to carboxylic acids. 

The net outcome of the Sommelet reaction is the oxidation of the benzyl methylene position into the corresponding carbonyl, and in that sense, the Krbhnke reaction may be considered a close variant. The KrOhnke reaction transforms benzyl halides to benzaldehydes using pyridine and an aromatic nitroso compound 16.16,17 As shown below, quaternary pyridinium salt (15) is formed from addition of pyridine to benzyl halide 1. Oxidation of 15 with p-nitrosodimethylaniline (16) affords nitrone 17, which is then hydrolyzed to benzaldehyde 3 and hydroxylamine 18. 

Attack of pyridine on the bis-dibromocarbene adduct (474) results in formation of a pyridinium benzocyclobutene (475). Krohnke reaction of the latter with p-nitro-sodimethylaniline affords the benzocyclobutenone (476), which is opened by sodium hydroxide to the arylacetic acid (477 R = H, n = 1). Direct oxidation of (475) with alkaline permanganate gives a mixture of the phthalate (478) and benzoate (477 R = Br, = 0) the latter probably being formed via (476). °... 

The Ortoleva-King-Krdhnke sequenee was frequently used to prepare multisubstituted pyridines. In fact, the acylpyridinium salt, obtained from the Ortoleva-King reaetion, was often referred to the Krdhnke salt . For example, a pyridine A-oxide based ehiral ligand 31 was synthesized by Maikov et a/." Prepared from 2-fIuoroacetophenone 27, Krohnke salt 28 underwent condensation with pinocarvone 29 and ammonium acetate, affording pyridine derivative 30. Further elaboration of 30 led to the... 

Oxidation of Alkyl Halides. Pyridine iV-oxide oxidizes even unactivated alkyl halides to carbonyl compounds (eqs 7-9). This is of some importance as most related methods (e.g. Krohnke and Kornblum oxidations) are limited to activated halides. The reaction can be performed in two ways. In the first, the halide is treated with thelV-oxide in the presence of a base such as NaHCOs. In the second, the intermediate N- alkoxypyridinium salt is isolated before base treatment. " 2-Picoline IV-oxide may be used in a similar oxidation reaction. ... 

New syntheses of 6-chloropterin (266) and 6-formylpterin (269) have been elaborated. The chloro-compound is available in one step by the action of acetyl chloride in trifluoroacetic acid on pterin 8-oxide (265), whereas the aldehyde is the product of the multi-stage process outlined in Scheme 62, the first stage of which is the production of the pyrazine-aldehyde (268) by a Krohnke aldehyde synthesis on the chloromethyl derivative (267). The chloropterin condenses easily with arylthiols and alkyl mercaptans, but not with alkylamines. 

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