Bromination of 2-aminopyridine

BtURET, 1-PHENYL-2-THIO-, 42,87 Bromination, of 2-aminopyridine, 44,34 of l-bromo-3-phenylpropane with N-bromosuccinimide to give 1,3-dibromo-l-phenylpropane,... 

Kinetic studies of the bromination of 2-aminopyridines and their 5-substituted derivatives (Me, Cl, Br, NO,) using solutions of bromine in dilute sulfuric acid have demonstrated that the minority free base species react with molecular bromine at 25°C and that the usual substitutent effects on rates apply [70JCS(B)117 78APO(l6)l],... 

Bromination of 2-aminopyridine, 2-)V,)V-dimethylaminopyridine, and their 5-substituted derivatives (9.95) has been studied in detail [70J-CS(B)117]. All react as the free bases and logarithms of the true second-order rate coefficients (corrected to take account of the equilibrium con-... 

In a 5-1, 3-necked flask fitted with a mechanical stirrer (Note 1), a dropping funnel, and a thermometer for reading low temperatures is placed 790 ml. (7 moles) of 48% h drobromic acid. The fl.ask and contents are cooled to 10-20 in an ice-salt bath, and 150 g, (1.59 moles) of 2-aminopyridine (Note 2) is added over a period of about 10 minutes. While the temperature is kept at 0° or lower, 240 ml. (4.7 moles) of bromine is added dropwise (Note 3). A solution of 275 g. (4 moles) of sodium nitrite in 400 ml. of water is added dropwise over a period of 2 hours, the temperature being carefully maintained at 0° or lower (Note 4). After an additional 30 minutes of stirring, a solution of 600 g. (15 moles) of sodium hydroxide in 600 ml. of water is added at such a rate that the temperature does not rise above 20-25° (Note 5). The nearly colorless reaction mixture is extracted with... 

A. 2-Ami/no-S-bromopyridine. In a 2-1. three-necked flask equipped with stirrer, dropping funnel, and condenser is placed a solution of 282 g. (3.0 moles) of 2-aminopyridine (Note 1) in 500 ml. of acetic acid. The solution is cooled to below 20° by immersion in an ice bath, and 480 g. (154 ml., 3.0 moles) of bromine dissolved in 300 ml. of acetic acid is added dropwise with vigorous stirring over a period of 1 hour. Initially the temperature is maintained below 20°, but after about half the bromine solution has been added it is allowed to rise to 50° to delay as long as possible the separation of the hydrobromide of 2-amino-5-bromopyridine. At 50° the hydrobromide usually begins to crystallize when about three-quarters of the bromine has been added. When addition of bromine is completed, the mixture is stirred for 1 hour and is then diluted with 750 ml. of water to dissolve the hydrobromide. The contents of the flask are transferred to a 5-1. beaker and are neutralized, with stirring and cooling, by the addition of 1.2 1. of 40% sodium hydroxide solution. 

Bromoacetylthianthrene, which can be produced by direct acylation as well as via bromination of 2-acetylthianthrene (63MI2) (for comparable dibromination of 2,7-diacetylthianthrene, see 64MI1), has been used in its capacity as an a-bromo-ketone to produce thianthren-2-yl-substituted heterocycles such as 55, 56, 57 (63MI2 73BSF1460), and 2-amino-4-(thianthren-2-yl)thiazole (63MI2), by condensation with 2-aminopyridine,... 

Sulfonylation of 2-aminopyridine occurs at the 5-position under fairly harsh (140 °C) conditions of sulfur trioxide in sulfuric acid. Subsequent C-3 bromination under mild conditions affords 89. Similarly 2-hydroxy nicotinic acid when subjected to stoichiometric 30% oleum at 140 °C gave sulfonic acid 90 in 90% yield (Equations 32 and 33) <20020PD767>. 

Bromination of 3-aminopyridine (9.97) and 3-N,/V-dimethylaminopyri-dine (9.96) with 2,4,4,6-tetrabromocyclohexa-2,5-dienone shows a remarkable difference in orientation. Thus, 9.96 is brominated exclusively at the 6-position, whereas 9.97 gives 2- and 6-monosubstitution together with 2,6-disubstitution. This has been attributed to steric hindrance, which follows from the size of the reagent [73JCS(P1)68]. Both 2-amino-and 2-/V,/V-dimethylamino-pyridines are brominated solely in the 5-posi-tion in view of the previous results, some 3-derivative might also have been expected from the former. 

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... 

When a solution of 2-aminopyridine is treated with bromine, 2-amino-5-bromopyridine is obtained. Bromination of 2-amino-3-nitropyridine and 2-amino-5-nitropyridine gives 2-amino-5-bromo-3-nitropyridine and 2-amino-3-bromo-5 -nitropy ridine, respectively. ... 

Aminopyridine (I) is converted by diazotisation in the presence of bromine and concentrated hydrobromic acid Into 2 broraopyridine (II) the latter upon treatment with copper powder in the presence of p-cymene yields 2 2 -dipyridyl (III). 

Bromopyridine has been made by direct bromination of pyridine - from N-methyl-2-pyridone with phosphorus penta-bromide and phosphorus oxybromide from 2-aminopyridine by diazotization with amyl nitrite in 20% hydrobromic acid from sodium 2-pyridinediazotate by solution in concentrated hydrobromic acid and from 2-aminopyridinc by diazotization in the presence of bromine and concentrated hydrobromic acidd The method described here is essentially that of Craig. 

Aminopyrazines, like aminopyridines and aminopyrimidines, form p-aminobenzenesulfonyl derivatives, and one of these, 2-sulfanilamido-3-methoxypyrazine (11), is clinically used as an antibacterial agent.320 Bromination of compound 11 in methanol gives a product (114)321,322 which was originally incorrectly formulated as a hydrate.323 The correct structure follows from spectroscopic evidence and alkaline... 

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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