Monocyclic pyridazines

Hitherto, only two papers appeared in the literature in which an alkynyl group was introduced into the 4 position of a monocyclic pyridazine using a Sonogashira reaction [52, 81]. Besides the previously mentioned 4-chloro-3,6-dimethylpyridazine (185), Bourguignon showed that electronically rich and sterically hindered A benzyl-4-bromo-and 4-bromo-6-phenyl-pyridazin-3-amine (82) are valuable coupling partners for different alkynes. 

The review of Stanovnik (1991) concentrates on diazoalkane additions to some nitrogen containing heteroaromatic systems, namely to monocyclic pyridazines, and to bicyclic and polycyclic azolo- and azinopyridazines with a bridgehead N atom. 

Reissert compounds.M Pyridine does not form a Reissert compound, but pyridazine and pyrimidine react with cyanotrimethylsilane and benzoyl chloride to form a monocyclic Reissert compound.12 Example ... 

Magnetic susceptibility anisotropy has been used to estimate relative aromaticities of some azines <1977JOC897>. If the extent of -electron delocalization for benzene is taken as 1.0, the corresponding values for azines are pyridine 0.7, pyridazine 0.7, pyrimidine 0.5, and 1,3,5-triazine 0.3. Another quantitative magnetic index is the exaltation of the total magnetic susceptibility (A). All aromatic systems reveal large A values, whereas for nonaromatic compounds A is close to zero and it is assumed that aromaticity increases with A. For six-membered monocycles the following values of A have been reported (in units of cm3 mol-1 x —106) benzene (17.9), pyridine (18.3), pyridazine (8.7), pyrimidine (18.2), pyrazine (12.7), l-ethyl-2-pyridone (13.0), and 1,3,5-triazine (19.0). 

Many neutral heteroaromatic molecules have been shown to form anionic amino (T-complexes in liquid ammonia in the presence of the amide anion. While no PMR spectral evidence could be obtained for an adduct between pyridine and amide ion in liquid ammonia, the monocyclic diazines do readily form (T-complexes.351 Thus, pyridazine, pyrimidine, and pyrazine generate the adducts 202-204, respectively. Several unidentified weak signals in the PMR spectra of 202 and 203 suggest the possibility of the presence of minor amounts of other adducts as well. For these diazines, K > 105 1... 

Simple unsubstituted monocycles such as pyridine, pyrazine, pyrimidine, pyridazine and pyrrole show little or negligible binding to either enzyme [3, 10, 173], However, we have shown that fusion or substitution of a phenyl group significantly increases the affinity of the compounds towards aldehyde oxidase, and in some cases the heterocycles are substrates for xanthine oxidase (Table 3.6) [50, 173]. Furthermore, studies with compounds containing a... 

In general, pyrolysis of monocyclic 1,2,3-triazines 1 leads to acetylenes, nitriles and nitrogen.46, 295 297 300 Heating simple 1,2,3-triazines in a sealed tube led to the isolation of pyridines, pyrimidines, pyrazoles, pyrroles, pyridazine, and indeno[3,2-/>]pyridine, depending on the substituents bound to the 1,2,3-triazine ring and the reaction conditions.46 A mechanism formulated for the formation of these products involves an azete as an intermediate. 

The MM3 force field has been extended by Allinger and co-workers to cover aromatic heterocycles of the pyridine and pyrrole types <93JA11906>. Structures (32 compounds), dipole moments (35 compounds), heats of formation (35 compounds), and vibrational spectra (11 compounds) were examined. The results are good for structure and fair for the other items resonance energies were reported for the series benzene (17.79 kcal mol ), pyridine (17.02 kcal mol ), pyridazine (14.35 kcal mol ), pyrazine (17.01 kcal mol ), pyrimidine (15.60 kcal mol ), 1,3,5-triazine (13.51 kcal mol ), and 1,2,4,5-tetrazine (17.72 kcal mol ). Finally, ab initio studies of the dipole polarizabilities of conjugated molecules have been reported in which monocyclic azines (pyridine, pyridazine, pyrimidine, pyrazine, 5-triazine, and 5-tetrazine) are compared <94JST(304)109>. 

Heterocyclic aromatic compounds contain C and H atoms other than carbon and hydrogen (Fig. 6). For the monocyclic molecules Hiickel s rule is applicable. For example both pyridine and pyrrole contain six ti electrons. Unlike the former the lone pair of the latter is delocalized. Armit and Robinson have shown a connection between the electronic sextet and the heteroaromaticity. Due to the electronegativity difference between carbon and nitrogen the bonds in pyridine are not of equal length and the delocalization is not perfect. Five membered heteroaromatics with oxygen and sulfur are furan and thiophene respectively. Pyrazole/imidazole, triazoles and tetrazoles are five membered heteroaromatics with two, three and four nitrogen atoms respectively. Three important aromatic six membered heterocyclic molecules are pyrimidine, pyrazine and pyridazine. Benzofused... 

Fragmentation Same as for the corresponding monocyclic heteroaromatics pyridazine, pyrimidine, and pyrazine. Characteristic for pyridazine, cinnoline, and phthalazine is the elimination of N2 (Am 28) and of N2H (Am 29) from their alkyl derivatives. Phthalazine loses HCN (Am 27) twice. 

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