3-Nitro-4-picoline, oxidation

METHYL-4-NITROPYRIDINE-1-OXIDE (3-Picoline, 4-nitro-, 1-oxide)... 

Phthalaldehyde, 34, 82 Phthalic acid, 32, 67 Phthalic anhydride, 32, 19 Phthalideacetic acid, 34,10 PlITHALIMIDE, N-2-BROMOETHYL-, 32, 18 3-Picoline, 4-nitro-, 1-oxide, 36, 53 3-Picoline-l-oxide, 36, 54... 

From time to time, other reagents have been used for deoxygenating pyridine 1-oxides. These include ferrous oxalate (which may be suitable for amino but not for nitro compounds) , sulphur, mercaptans and hydrazo-benzene 55a, Dichlorocarbene and fluorene carbene also deoxygenate pyridine and picoline oxides . Photolysis of pyridine 1-oxide gives pyridine in a reaction whose characteristics depend on the frequency of radiation used. 2-Picoline 1-oxide photolysed at 2,537 A gives picoline, but at 3,261 A 2-hydroxymethylpyridine is formed . ... 

As seen in many of the above examples, acetic anhydride and zinc chloride each make effective condensation catalysts for the free bases, presumably by efficient coordination with the ring nitrogen. The quaternary salts condense readily in the presence of piperidine. Potassium hydroxide, methoxide or piperidinium acetate are suitable for condensations with 2- and 4-methylpyridine AAoxides. For example, the Claisen condensation is effective with these Af-oxides using ethoxide catalyst (Scheme 45) but the reaction fails with the parent picolines unless activated by nitro substitution (69JHC775). 

The Reissert synthesis of indoles has found much success with o-nitrotoluenes, but has been tried for the s5nithesis of azaindoles in only a few cases. Herz and Murty first reported unsuccessful attempts at base-catalyzed condensation of ethyl oxalate with 4-nitro-3-picoline and its Y-oxide (45). No conditions were reported. Later,... 

C6H5N03 picolinic acid N-oxide 824-40-8 489.15 42.843 2 7020 C6H6N203 6-hydroxy-5-nitro-2-picoline 39745-39-6 377.15 32.218 2... 

For the synthesis of 13-hydroxysparteine the starting material was a-picoline iV-oxide (CXVIII) which was nitrated and the nitro group then replaced by benzyloxy. The action of acetic anhydride induced the Boekelheide rearrangement to the acetoxymethyl derivative CXIX. The latter, via the alcohol, the chloride, the cyanide, and the ester, was condensed with ethyl hydroxymethylenepyridylacetate to the quinol-izone CXX, hydrogenation and reduction of which with lithium aluminum hydride gave a separable mixture of hydroxysparteines. The... 

For the activation of pyridine, more than one alkyl group is necessary. Thus, on nitration picolines suffer extensive oxidation of the side chain, but 2,6-lutidine and 2,4,6-collidine are converted smoothly into the 3-nitro products. 

Oxidation of 3-nitro-4-picoline 443 with selenium dioxide gives... 

Simultaneous nitration-deoxygenation has also been observed by these workers. For example, pyridine-1-oxide undergoes nitration and deoxygenation with concentrated sulfuric acid and fuming nitric acid at 130 to 165° to give 4-nitropyridine in 71% yield. As additional examples, 3-picoline-l-oxide gives 4-nitro-3-picoline (81%), and 3-bromopyridine-l-oxide affords 3-bromo-4-nitro-pyridine (75%) on treatment with nitric oxide and sulfuric acid at 150 to 200°. 

When 2-halo-4-nitropyridine-l-oxides are treated with hydrazine hydrate in ethanol, 4-amino-2-halopyridine-l-oxides result. " The reaction of 4-nitro-pyridine-1-oxide (IX-20, R = H) and of 4-nitro-2-picoline-l-oxide (IX-20, R = CHj) with phenylhydrazine gives 4-hydroxylaminopyridine-l-oxide (IX-21, R = H) and 4-hydroxylamino-2-picoline-l-oxide (DC-21, R= CH3), respectively, rather than the corresponding 4-amino derivatives "" "" (See also Chapter Vlll). 

This reaction can also be achieved with an intramolecular source of nitrite ion 4-nitro-2-picoline-l-oxide (X-90, X = NO2), on treatment with acetyl chloride... 

Picolinic acid-1-oxide is readily converted to the 4-nitro derivative. The nitro group is easily replaced by nucleophiles such as alkoxide, hydroxide, hydrogen sulfide, ammonia, chloride, and phenoxide. Derivatization of the acid function and other reactions remain as expected. 

Nitro-3-picoline (MI-368) is hydrolyzed on standing to l-(3 -methyl-4 -pyridyl)-3-methyl-4-pyridone and 3-methyl-4-pyridone. 4-Nitropyridine and benzyl bromide give iV-benzyl-3,5-dibromo-4-pyridone (MI-369) in 33% yield. The quaternary salt first formed is hydrolyzed to the 4-pyridone. Oxidation of hydrogen bromide by the nitrous acid product provides the bromine and water. The yield is increased to 71%by the addition of bromine. 3,5-Dibromo-4-chloro-pyridine and benzyl bromide in base also give XII-369. Similarly, 3-methyl-4-nitropyridine and benzyl bromide give W-benzyl-3-bromo-5-methyl-4-... 

Picoline-l-oxide, 2,6-lutldine-l-oxide, and 4-nitro-2,6-lutidine-l-oxide react with ketene to form the corresponding hydroxymethylpyridine and the corresponding 3-pyridinol in relatively low yields. N-oxides of 3-picoline, 4-nitropyridine, and 4-nitro-2-picoline did not give comparable products when treated with ketene. ... 

Nitro-3-picoline, from 3-pic-oline-l-oxide, 3 hydrolysis of, 694 4-Nitro-2-picoline-l-oxide, effect of 4-nitro group, 719 reaction with acetic anhydride, 719... 

Quinoline directs alkoxylation and phenoxylation of tethered arenes. The 8-aminoquinoline directs the copper oxidation of the sp C-H bond (Scheme 76) (130L5842). A number of alcohols are tolerated, including both aliphatic (6 examples 39-85%) and aromatic alcohols (9 examples, 59-88%).The aryl amides can also have a range of functional groups including cyano, nitro, alkoxy, and alkyl groups. Picolinic acid derivatives also direct oxidative formation of the ether. 

A mixture of 3-picoline N-oxide, ferrous oxalate, and granulated lead heated 30 min. at a metal bath temp, of 300° 3-picoline. Y 12%.—This method may be of value in cases (e.g. when an amino group is present) where other methods (e.g. the use of PClg) may not be employed. Nitro groups are attacked by ferrous oxalate. F. e. and limitations s. R. A. Abramovitch and K. A. H. Adams, Can. J. Chem. 39, 2134 (1961). 

---