Azines amination

Even though oxygen in small percentages catalyzes the reaction effectively, many other initiators have been disclosed, including peroxy compounds, ozonides, azo compounds, azines, amine oxides, oximes, hydrazines, and hypohalites. The pol3Tnerization reaction is highly exothermic and requires strict control and elaborate safety measures in order to prevent... 

H-Bond Acceptor-Donor (HBAD) Phenols Aromatic acids Aromatic amines Alpha H nitriles Iniines Monocarboj hc acids Other monoacids Peracids Alpha H nitros Azines Primary amines Secondary amines n-alcohols Other alcohols Ether alcohols... 

The catalytic effect of aromatic nitro groups in the substrate and product or in an added inert nitro compoimd (e.g., w-dinitrobenzene in 18) has been observed in the reaction of 2,4-dinitrochlorobenzene with an amine in chloroform. Hydrogen bonding to benzil or to dimethyl sulfone and sulfoxide also provided catalysis. It is clear that the type of catalysis of proton transfer shown in structure 18 will be more effective when hydrogen bonding is to an azine-nitrogen. 

If there is hydrogen bonding to the azine by the solvent, three effeets can result a) with an uneharged nueleophile sueh as an amine, steric hindranee to the reaetion at the oipAa-position, but not at the gumma-position, in a 4-substituted eompound (6) with an anionic... 

The effect of partial or complete cationization might be expected to be greater for a mono-azine than for a poly-azine in which the activation is greater. However, the effect in acid-catalyzed aminations was... 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

Amination of the deactivated carbanion of 4-benzylpyridine formed with excess sodamide presumably proceeds because the strong indirect deactivation is overcome by electrophilic attack by Na+ at the partially anionic azine-nitrogen and by concerted nucleophilic attack by H2N at the 2-position via a 6-membered cyclic transition state (75). However, in simple nucleophilic displacement a carbanion will be more deactivating than the corresponding alkyl group, as is true in general for anionic substituents and their non-ionic counterparts. 

In spite of the extensive kinetic work of Chapman and co-workers, much remains to be done on the reactivity of azines with nucleophiles. The data available on substitution by alkoxide ions are especially meager. The missing information on alkoxide reactions should give a better picture of the activation of different ring-positions than is possible with the data on aminations. The latter include the effects shown in 235, 276, and 277 in addition to activation by the azine-nitrogens. 

The.effect of the entropy of activation was noted above for the quaternary pyridine salts (280 and 281). In future work, it may also be found to reflect the electrostatic or hydrogen-bonding interactions in transition states of amination reactions and the effect of reversible cationization of an azine-nitrogen. Brower et observed a substantial rate difference between piperidino-dechlorinations of 2-chloropyrimidine in petroleum ether and in alcohol due partly to the higher entropy of activation in the latter solvent (Table III, lines 3 and 4). 

A search has not been made for products of displacement of halogen from the benzo-ring in polyhalo compounds, but it is clear that the major mono-substitution occurs in the azine ring. For example, 2,6- and 2,7-dichloroquinoxalines give 70-80% of the 2-amination product with )S-diethylaminoethylamine (150°, 2 hr) or y-(l-piperidyl)-propylamine (220°, 2 hr). 2,3,6-Trichloroquinoxaline gives with... 

Azines can be reduced catalytically to the disubstituted hydrazines (24,51) and then to the amine if the reduction is continued (108). The hydrogenolysis chemistry is thus that of hydrazines. The hydrazine can be formed in situ by hydrogenation of a mixture of hydrazine and 2 mol of carbonyl compound... 

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