Pyridines 2-aminopyridine

R R1 Solvent (reference) Yield of products Diazepine Pyridine Aminopyridine ... 

Aminopyridine. In a 1 litre three-neoked flask, equipped with a sealed mechanical stirrer, reflux condenser, thermometer and inlet tube for nitrogen, place 300 ml. of dry toluene (1) aud 75 g. of fine granular sodamide (2) bubble a steady stream of nitrogen thi ough the toluene. Stir the mixtiue vigorously and heat the flask in an oil bath until the internal temperatime is 110° (the bath temperatime required is approximately 130°). Add 100 g. of pure dry pyridine (compare Section 11,47,22)... 

Sulphapyridine. Dissolve 18-8 g. of 2-aminopyridine in 40 ml. of dry pyridine (Section 11,47,22) in a 250 ml. flask and add 48 0 g. of p-acetamidobenzenesulphonyl chloride (4) the temperature rises to about 70°. Cool, add excess of water, filter the precipitated 2-(p-acet-amidobenzonesulphonamido)p3Tidine (s acetyl-sulphapyridine) at the pump and recrystallise it from 50 per cent, acetic acid. The yield of pm product, m.py. 224°, is 46-5 g. 

Most of them are generally classified as poisons. Exceptions to this rule are known. A notable one is 4-dimethyl aminopyridine (DMAP) (24), which is widely used in industry as a superior acylation catalyst (27). Quaternary salts of pyridines are usually toxic, and in particular paraquat (20) exposure can have fatal consequences. Some chloropyridines, especially polychlorinated ones, should be handled with extra care because of their potential mutagenic effects. Vinylpyridines are corrosive to the skin, and can act as a sensitizer for some susceptible individuals. Niacin (27), niacinamide (26), and some pyridinecarbaldehydes can cause skin flushing. 

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. 

Dipole moment data have provided valuable information for the study of the tautomerism of compounds such as isonicotinic acid, pyrid-4-one, and ethyl acetoacetate, However, this method must be used with discretion since it can lead to inconclusive results. Thus, the fact that 4-aminopyridine has a higher dipole moment than the algebraic sum of the dipole moments of pyridine and aniline was originally interpreted as proof that structure 54 exists with a strong contribution from 36, and it was stated that 55 w ould have a very low moment. Later, Angyal and AngyaF pointed out that the... 

The fact that the equilibrium for aminopyridine 1-oxides is displaced further in favor of the amino form than is the equilibrium for aminopyridines is in accord with the mesomerism of these compounds. The stabilization of the amino forms (e.g., 241) by structures of type 240 is more effective than the corresponding stabilization in the pyridine series since the negative charge is associated with the oxygen atom. The stabilization of the imino form (e.g., 242) by structures of type 243 is less than in the pyridine series because of the adverse inductive effect of the oxygen atom. ... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

All existing syntheses of pyrido[4,3-d]pyrimidines from pyridines build up the pyrimidine ring from a 3-substituted 4-aminopyridine by methods closely similar to those applied for the other systems (routes i and u). The preparation of suitable 4-aminopyridines presents some... 

The 4-aminopyridine-type resonance, one of the most interesting methods by which hydration is facilitated, is illustrated by the small resonance in the neutral species of 4-aminopyridine (34) and the far greater resonance in the cation of the same substance (35). 4-Amino-pyridine owes its strongly basic properties (pA 9.2, as compared to... 

Use of a (Substituted) Aminopyridine Derivative in Which the Nitro Group is Already Present in the Pyridine Ring as Starting Material... 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

Pyridines which failed to produce detectable quantities of 2,2 -bipyridines include 2-aminopyridine, 3-aminopyridine, 3,5-dibromo-pyridine, and ethyl isonicotinate. 2,2 -Bipyridine failed to give any 2,2 6, 2 6",2" -quaterpyridine, and this is discussed in a later section. 

The formation of 1-aminopyridinium chloride has been accomplished by the acid hydrolysis of N- ( -acetaminobenzene-sulfonimido)pyridine.4 Also, the rearrangement of a substituted diazepine has been observed to give a 1-aminopyridine derivative.5 The present procedure is an adaptation of that described by GosI and Meuwsen.1... 

Directed metallation continues to be developed as a convenient method for regiospecific substitution of pyridines. A mild and general procedure for the preparation of structurally diverse 4-alkyl-2-aminopyridines 37 involves the lithiation/alkylation of aminopyridine derivative 36 <96JOC(61)4810>. 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

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