3-Bromopyridines, reaction with sodium

Treatment of 4-bromopyridine with NaNH2 in NH3 (liq.) gives two products (isomers, C5H6N2) but reaction with sodium methoxide gives a single product, C6H7NO. What are the products and why is there a difference ... 

The first amination of a halogenopyridine involving a rearrangement was carried out by Levine and Leake in 1955 in an attempt to prepare 3-phenacylpyridine. When 3-bromopyridine (27, X = Br) was allowed to react with sodium amide in liquid ammonia in the presence of sodio-acetophenone, the reaction mixture obtained consisted chiefly of amorphous nitrogenous material from which only 10% of 4-aminopyridine (34, Y = NH2) and 13.5% of 4-phenacylpyridine were isolated. 

Several of the methods of synthesis of 2,2 -bipyridines have their counterpart in the preparation of 4,4 -bipyridine. The Ullmann reaction has been used to prepare 4,4 -bipyridine. Thus 4-halogenated pyridines afford 4,4 -bipyridine. Dehalogenation and dimerization of 4-bromopyridine may be accomplished too with hydrazine and alkali at 65°C in the presence of a palladium catalyst, whereas 4-chloropyridine is converted to 4,4 -bipyridine in 46% yield by reaction with alkaline sodium formate in the presence of palladium on charcoal and a surfactant. Several extensions of the Ullmann reaction have recently been reported, especially for the synthesis of substituted 4,4 -bipyridines. Thus 4-iodo-2-methylpyridine gives 2,2 -dimethyl-4,4 -bipyridine, 3-nitro-4-chloropyridine affords 3,3 -dinitro-4,4 -bipyridine, 4-bromo- or 4-iodotetrafluoropyridine gives octafluoro-4,4 -bipyridine, and 4-iodo- or 4-bromotetrachloropyridine gives octachloro-4,4 -bipyridine. Related syntheses have been de-... 

Pyridyne 1-oxide (893) is obtained by the action of potassium amide on 2-bromopyridine 1-oxide (892), as shown by the formation of a mixture of the 2- and 3-aminopyridine oxides. Reaction of 5-bromopyrimidine with sodium amide in liquid ammonia involves 4,5-pyrimidyne as an intermediate. 

Substituted 4- or 5-halopyrimidines with sodium amide in liquid ammonia give 4-methyl-1,3,5-triazines (Scheme 317) the reaction is general and yields are good cf., the related conversion of 6-substituted 2-bromopyridines into pyrimidines (Section 4.3.3.3.4). 4-Amino-5-nitrosopyrimidines are converted into 1,3,5-triazines by acetic anhydride or phosphorus oxychloride (Scheme 318). 1,3,5-Triazines can be obtained from 1,3,5-oxadiazinium cations (Section 3.2.1.6.1.3). 

The charge distribution in pyridine leads to deactivation for electrophilic substitution, the least for the position 3 (formation of 3-bromopyridine) at higher temperatures mainly 2-bromo-pyridine is produced by radical substitution. With sodium amide 2-aminopyridine is produced as a nucleophilic substitution reaction. 

The reaction of 2-aminopyridine (28) with sodium nitrite, bromine, and HBr gives 2-bromopyridine (70) in 87% yield (34JA23I 5IJA4773). Bromine has also been introduced into quinolines by treating 2- or 4-methoxyquinolines with phosphorus tribromide in DMF to furnish 2-bromo- or 4-bromoquinoline in 78% and 68% yields, respectively... 

Pyx idine and mercuric acetate when heated at 175 to 180" C. tor 2 5 hours, and the reaction mixture diluted with 5 to 6 volumes of water, followed by the addition of sodium chloride give 3 5-dichloromercuri pyridine (I.) as a pale brown, amorphous, odourless powder, decomposing at 220" C. Bromine in sodium bromide solution converts it into 3 5-dibromopyridine. The mother-liquors from the dichloromercuri compound yield 3-iodomercuri pyridine (II.) when treated with sodium iodide. The product is a yellow, amorphous powder, M.pt. 68" to 69" C., which forms 3-bromopyridine with bromine in sodium bromide. 

Hofmaim degradations were carried out on 5pyridine carboxylic acids are treated with sodium azide in an oleum medium, a good yield (69%) of 3-aminopyridine and poorer yields (<30%) of 2- and 4-aminopyridine are realized. 3-Amino-5-nitropyridine is similarly prepared by the Schmidt reaction using 5-nitronicotinic and hydrazoic acid. ... 

Although pyridine is resistant to electrophilic aromatic substitution, it is susceptible to nucleophilic aromatic substitution. The reaction of 2-bromopyridine (44) and ammonia, for example, leads to 2-aminopyridine, 46. This is a nucleophilic aromatic substitution reaction (see Chapter 21, Section 21.10), where NHg attacks the ipso carbon to generate a carbanionic intermediate (45), which loses bromine to give 46. Pyridine (10) also reacts directly with sodium amide (NaNHg) at 100°C to give 46 in what is known as the Chichibabin reaction, after Aleksei E. Chichibabin (Russia 1871-1945). 

Bromopyridine has been aminated by reaction with sodamide or potas-samide in liquid ammonia (see also p. 214) and, in moderate yield, with sodio-methylaniline and related compounds in this connection it is interesting that sodium or potassium salts of arenesulphonamides give 2-arenesulphonyl-aminopyridines with 2-halogenopyridines, whilst sulphanilamide itself gives... 

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