Diazines, amination

The oxime of bromoacetylfurazan 123 was converted into the amine 125 by treatment with hexamethylenetetramine and subsequent acidic hydrolysis. Oxa-diazine derivative 126 was made from the amine and formaldehyde in 57% yield (Scheme 73) (97ROC1760, 97ZOR1844). 

More challenging are the (hetero)aryl chlorides, since they are cheaper and more widely available than the corresponding bromides and iodides. Maes et al. published the first examples of microwave-assisted Buchwald-Hartwig aminations on (hetero)aryl chlorides in a commimication in 2003 [99]. The substrates 2- and 3-chloropyridine as well as 2-chloroquinoline were smoothly coupled with N-methylaniline and p-toluidine within only 10 min using a catalyst loading of only 1 mol% (Schemes 96 and 97). The diazine... 

The reaction of 1,2-diazinamines with electrophiles is well studied while the substitution of amines-imines by nucleophiles is a highly nonstandard process. Nevertheless, even in the latter class new examples appeared since CHEC-II(1996) <1996CHEC-II(6)1>. A new section dealing with the so-called f-amino effect was added since many examples on 1,2-diazines have appeared since the mid-1990s. 

Ring-closure reactions that involve a /-amino group on a 1,2-diazine skeleton and a vinyl moiety in its t>/// t>-position occur via the so-called /-amino effect. Although this reaction does not involve reaction at the nitrogen atom itself, it is a very specific reaction that can only occur on /-amines and is therefore incorporated in this section. The reaction... 

Under the alternative low-temperature procedure, animation is conducted in liquid ammonia. The use of KNH2, which is more soluble than NaNH2 in this solvent, is preferable. The reaction occurs under homogeneous conditions and does not show the previous dependence on substrate basicity. Diazines, triazines, and tetrazines, which usually undergo destruction in the high temperature process, are aminated successfully in liquid ammonia. 

Of all the aza-heterocycles, pyridine possesses the least electron deficiency. Because of this, pyridine itself does not form a a-complex in liquid ammonia and cannot be aminated under these conditions. By the contrast, highly ir-deficient polyaza-heterocycles (diazines, triazines, tetrazines, pteridines, etc.) undergo oxidative amination, sometimes even by liquid ammonia itself. Sodamide converts 4-methylpyrimidine successively into the 2-mono- and 2,6-di-amino derivatives, and pyrazine gives... 

There have been comprehensive reviews on the coordination chemistry of aromatic JV-oxides by Garvey et al. (up to 1968)67 and Karayannis et al. (up to 1971),68 the latter including a short section on aliphatic amine (V-oxides and secondary amine nitroxide free radicals. A further review by Karayannis et al. (up to 1975)69 covers mono- and di-oxides of bipyridyl, o-phenanthroline and some diazines. 

A variety of macrocyclic complexes which have adjacent nitrogen atoms (cyclic hydrazines, hydrazones or diazines) are formed by condensations of hydrazine, substituted hydrazines or hydrazones with carbonyl compounds. The reactions parallel in diversity those of amines, but are often more facile since the reacting NH2 groups is generally not coordinated and the electrophile is thus not in competition with the metal ion. The resulting macrocycles may be capable of coordination isomerism, since either of the adjacent nitrogen atoms can act as donor atom. 

Mechanistically, the Beirut reaction is a heterocycle expansion-process where the nucleophile attack conducts, after atomic rearrangements, to a new diazine system. In general, a further elimination—i.e., of H2O, amines, acetate—aromatizes the new heterocycle. 

The monocyclic diazines, triazines, and tetrazines are all theoretically subject to electrophilic attack at one or more of their annular nitrogen atoms by protons alkylating, acylating, and aminating reagents and peracids. Coordination with metals could also be classified under this heading. 

There are numerous examples of the formation of diadducts in reactions of 1,4-diazines with water, alcohols, ammonia, amines, and other simple nucleophiles. 

In the sense of an inter molecular amination with heterocyclic amidine derivatives, such as amino azines and diazines, and 2-chloro-3-iodopyridines followed by an intramolecular amination, Maes and coworkers [93] have established a facile synthesis of dipyrido[l,2-a 3, 2 -d]imidazole and its benzo-and aza-analogs 101-106 (Scheme 36). 

Heterocyclic azadienes like di- and triazines have been used in the synthesis of pyridine rings. In general terms the reaction involves a regiospecific inverse electron demand Diels-Alder cycloaddition between the heterocycle and the enamine 280 followed by elimination of HCN (diazines) or N2 (triazines) and an amine from the primary cycloadduct 281 or 283, respectively, to give pyridines 282 and 284 (equation 61). At least in one case the latter type of intermediate has been isolated and fully characterized148. 

The 1,3-diazines have also been prepared by a reaction of enamines and S, S -dimethyl-A (A arylbenzimidoyl)sulfimides 360 in boiling tetraline220,221. The mechanism of the ring formation probably involves a thermal cleavage of the imidoylsulfimides 360 into imidoylnitrenes 361 and dimethyl sulfide. The nitrene can then react with the enamine to give an aziridine intermediate 362 which rearranges to a 3,4-dihydroquinazoline 363. Subsequent elimination of amine yields the quinazoline 364220. 

Dimethyldioxirane (1) is a mild and efficient oxidant for pyridine pyiidines and quinolines have also been oxidized in good yield by r-pentylhydroperoxide in the presence of molybdenum(V) chloride. A(-Halogenation and other oxidative reactions of pyridines and related heterocycles have been re-viewed. " Thus, pyridines and some diazines can be aminated by mesitylenesulfonylhydtoxylamine... 

HEXAHYDROBENZEN.AMINE see CPF500 HEXAHYDROBENZENE see CPBOOO HEXAHYDROBENZOIC ACID AMIDE see CPB050 HEXAHYDROCRESOL see MIQ745 HEXAHYDRO-l,4-DIAZEPINE see HGI900 HEXAHYDRO-l,4-DIAZINE see PIJOOO... 

Amines are eonsidered pharmacophore points but not azoles or diazines. 

In the oxidation of benzylamines, apart from formation of the dealkylated amine and benzaldehyde [61-64], formation of imines [65, 66], benzonitrile [64], diazines [62] anilines [67], and iV-benzylidene benzyl amines [64, 66, 67] has also been observed. 

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