4-Methylpyridine A-oxide

Treatment of 2-methylpyridine A -oxide with trifluoroacetic anhydride gives rise to 2-hydroxymethylpyridine. 

Pyridylmethyl chloride 11 was obtained by direct chlorination of alcohol 10 using thionyl chloride The hydroxymethyl-pyndine 10, in turn, was synthesized from 3,5-dimethylpyndine in 6 steps utilizing a Boekelheide reaction that transformed the 2-methylpyridine-A -oxide to the corresponding hydroxymethyl-pyridine 10. 

Some amine A -oxides are reduced by phosgene. Thus, in the presence of base, 2-methylpyridine A -oxide is deoxygenated with phosgene (Ash and Pews, 1981). 

The reaction of N,N- dimethylaniline with pyridine (equation 55) should also be considered in this category. Enamines usually attack acylated N- oxides at position 2 unless it is blocked, as in 2-methylquinoline 1-oxide, when attack takes place at C-4. Methyl /3-aminocrotonate attacks quinoline and isoquinoline AT-oxides at the position a to the N- oxide function in the presence of tosyl chloride (78JHC1425). However, pyridine and 2-methylpyridine 1-oxides react at the 4-position (equation 142). A low yield of by-product (242) is formed in each case, probably as a result of self-condensation of methyl /3-aminocrotonate. 4-Hydroxyquinoline 1-oxide is exceptional in that it reacts with an enamine in the presence of tosyl chloride at the /3-position (Scheme 170) (B-71MI20500). 5-Amino-3-methylisoxazole reacts with quinoline 1-oxide at the a-position, and the product can be degraded, to afford ultimately 2-methylquinoline (Scheme 171) (78CPB2759). 

For Negishi reactions in which the pyridines are nucleophiles, the pyridylzinc reagents are usually prepared from the corresponding halopyridines [6, 20, 21]. An excess of 2-chlorozincpyridine A oxide (26), arising from 2-bromopyridine IV-oxide hydrochloride (25), was coupled with vinyl triflate 27 in the presence of Pd(Ph3P)4 to furnish adduct 28 [20]. Recently, an efficient Pd-catalyzed cyanation of 2-amino-5-bromo-6-methylpyridine (29) using zinc cyanide has been reported to afford pyridyl nitrile 30 [22],... 

Salts of [ZnLe]2+ (L = pyridine N-oxide) have recently been shown to undergo facile solid state reactions with alkali metal halides, an observation to be taken into account when recording the IR spectra of these and related compounds.706 A crystal structure of the complex [ZnL6] [C104]2 (L = 4-methylpyridine A-oxide) has been reported.707 The metal is in a near-octahedral 06 environment, with an average Zn—O distance of 2.114 A. 

There are numerous investigations of the reactivity of di- and polyhalo-pyridazines, particularly polyfluoropyridazines. Aminolysis of l-phenyl-4,5-dichloropyridazin-6-one has been studied in detail. In this and other reactions with nucleophiles, the halogen atom at position 4 is substituted preferentially, although a mixture of 4-amino and 5-amino derivatives is formed in the reaction between 4,5-dihalopyridazin-6-ones and ammonia or amines. It has been now firmly established that displacement reactions on 3,6-dichloropyridazine 1-oxide with sulfur nucleophiles take place at position 6 in contrast to nitrogen or oxygen nucleophiles, where the 3-chlorine atom is replaced preferentially. In connection with the previously observed self-condensation of 3-chloro-6-methylpyridazine to a tricyclic product, the reaction between 3,6-dichloropyridazine and pyridine N-oxides was investigated. 3,6-Dichloropyridazine with 2-methylpyridine N-oxide at 100°-110°C affords three compounds (171, 172, and 173). With 2,6-dimethylpyridine N-oxide, an ether (174) is also formed. The isolation of... 

Certain heteroaromatic compounds that have acidic methyl groups are effective in the Knoevenagel condensation. 6-Methyl-1,3,5-triazine (156), 2-methylpyridine V-oxides (157), quinolines and pyrimidines all condense with aromatic aldehydes in the presence of the usual catalysts. An example of a doubly activated methylene compound in which one activation group is a heterocycle is the 2-oxopro-pylthiazole (158), which condenses with a number of aldehydes. " ... 

---