2- aminopyridine N-oxide

Other simple chelate ligands which have been found to give six-coordinate complexes NiX2L2 are 2-acetylpyridine N-oxide oxime,2495 2-acetamidopyridine,2496 pyridine-2-(acetic acid methyl ester)2497 and -substituted 2-aminopyridine N-oxides.2498... 

Treatment of 5-cyanomethylisoxazolines 1 with a catalytic amount of DBU in boiling xylene gives good to excellent yields of 6-substituted-2-aminopyridine N-oxides. 

A cooled aq. soln. of NaNOa added dropwise with vigorous stirring at -5° to a soln. of 2-aminopyridine N-oxide in 40%-fluoroboric acid [1,2,3,5]-oxatriazolo-... 

Aminopyridine N-oxides and ethereal thiophosgene in the presence of base (NaHCOs) yield 2if-[l,2,4]oxadiazolo[2,3-a]pyridine-2-thiones (66), These bicycles are noteworthy in that they explode on heating. Photolysis of pyridine iV-oxide at 10 K in an argon matrix produces a species which, by i.r. and u.v. spectra, has been identified tentatively as the isocyano-aldehyde (67) or (68). ... 

Diazotization of 2- and 4-aminopyridines leads to the corresponding diazonium salts which, as they cannot be stabilized by mesomeric donation of electrons from the heterocyclic ring, tend to be highly unstable. Under normal aqueous diazotization conditions, therefore, the major products tend to be 2-pyridones (equation 85). 2-Chloro- and 2-bromo-pyridines can be obtained in moderate to good yield if the diazotization is carried out in concentrated hydrochloric or hydrobromic acid. In contrast to this situation which pertains with simple aminopyridines, the diazonium salts obtained on diazotization of 2- and 4-aminopyridine N-oxides are stabilized by resonance and therefore undergo normal diazonium salt reactions (equation 86). 

Azaaromatic systems are usually oxidized to their A-oxides. Peracetic acid is the oxidant most used though for unstable substrates perbenzoic or perphthalic acids are preferable. They permit the use of non-polar solvents and milder conditions. Heterocycles relatively inert to oxidation can be converted to N-oxides by the more active performic or trifluoroperacetic acids. m-Chloroperbenzoic acid (MCPBA) also gives good results, especially when other easily oxidizable groups are present in heterocyclic molecule and therefore the question of selectivity is important. Thus, 2-aminopyridine was successfully converted with MCPBA into 2-aminopyridine A-oxide. 

The preparation of 5-azatryptamine (192) is summarized in Scheme 61 (64FES741). It is interesting in starting from diazotized 4-aminopyridine N- oxide and important because pyrrolo[3,2-c]pyridine does not readily react at position 3. 

The nitro group of 4-nitropyridine-N-oxide (1) was hydrogenated preferentially over palladium in neutral medium -2 but in acid the N-oxide was also reduced (Eqn. 19.1).2 Hydrogenation of 1 or 4-nitroquinoline-N-oxide over Raney nickel at elevated temperatures and pressures resulted in the reduction of both the nitro group and the N-oxide.3.4 Hydrogenation of 2-nitropyridine-N-oxide gave only 2-aminopyridine.5... 

Direct formation of N-oxides of amino-aza-heterocycles can be troublesome. Welcome, therefore, is a report that m-chloroperbenzoic acid in acetone can be used as oxidizing agent without the need to protect the amino-function. " 2-Aminopyridine AT-oxide (71%), 2-aminopyrimidine N-oxide (68%), and 1-aminoisoquinoline A"-oxide (66%) are amongst the examples cited. An alternative method of synthesizing O-aryl-oxypyridinium salts has been proposed " and is illustrated in Scheme 12. The unsymmetrical diaryliodonium tetrafluoro-borate (56) suffers preferential attack at the electron-poor aryl ring, and the yields of W-aryloxy-pyridinium (57) are good when X = N02-... 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

A different strategy (see Scheme 60) consisted in forming the N-N bond by oxidation of an amidine with MnOz. The amidine was obtained by ICl3-mediated addition of a 2-aminopyridine on acetonitrile. A series of compounds 237 <2003IJB2901> and 238 was obtained in this way <2005ARK21>. 

Treatment of various 2-aminopyridines and of 1-aminoisoquinoline with dimethyl sulfide and N-chlorosuccinimide gives the corresponding salt which on deprotonation with base provides a sulfilimine (e.g. 98) (76JCS(P1)2166>. Oxidation of the latter with m-chloroperben-zoic acid gives the corresponding nitroso heterocycle (Scheme 85). 

Dimethyl 3,5,6-trichloro-2-pyridyl phosphate, known as Fospirate or Dowco 217, is an rnsechcide useful rn anlrllea collars for dogs and cats. The compound 4-aminopyridine, known as Avilrol 100, and 4-nitropyridine-N-oxide, known as Avitrol 200, are useful as bird repellents. 

On treatment of a solution of the pyrido[l,2-a]pyrimidinium salt (16) with potassium permanganate in 2 N sulfuric acid, 11% 2-aminopyridine, 1% 4-oxo-4H-pyrido[l,2-a]pyrimidine, and traces of 2-nitropyridine were isolated from the reaction mixture.9 When 2,4-dimethylpyrido[l,2-a]-pyrimidinium iodide was oxidized with aqueous potassium permanganate at 50-60°C, 2-acetamidopyridine was obtained in 65% yield.2... 

Similar reactions have been carried out with amidines (67NEP6610627). Thus tri-chloroacetamidine (309) reacts with chlorothioformate esters to produce thioacyl products (310) which are readily oxidized to 5-alkoxy-3-trichloromethyl-l,2,4-thiadiazoles (311). The yields in both steps are about 80% (Scheme 111). The bromine oxidation of N-thiocarbamyl derivatives (312) of cyclic amidines (2-aminopyridine, 2-aminothiazole, 2-aminopyrimidine) yields thiadiazolium salts (313) (71JPR1148). In the 2-aminopyridine series, products of type (230 Scheme 81) are obtained in 20-73% yield when R is an ethoxycar-bonyl group (750PP55). 

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