Heterocycles pyridazines

As we will see, pyridine is also very stable and, by any reasonable assessment, pyridine is aromatic. We could continue the process of replacing, on paper, more CH groups with nitrogen atoms, and would find three new aromatic heterocycles—pyridazine, pyrimidine, and pyrazine ... 

In the series of six-membered heterocycles pyridazine has a high boiling point (208°/760 mm, 207.4°/762.5 mm ) which suggested association. A reinvestigation of intermolecular association in liquid p5U idazine, in which evidence for the existence of a discrete dimer has been adduced, has shown that such a dimer does not exist. The intermolecular attraction can therefore be attributed to electrostatic forces arising from the high permanent dipole. 

Can the pyridine ring be changed to other aromatic heterocycles pyridazine (f), pyrimidine (g), pyrazine (h), triazines (i), thiazoles (j), etc ... 

Adding an extra nitrogen atom (in thought only ) to the pyridine ring system creates three new heterocycles, pyridazine 9, pyrimidine 10, and pyrazine 11, and in all three the extra nitrogen is of the pyridine type with localised lone pairs on both nitrogen atoms. These three heterocycles are more electrophilic and even less nucleophilic than pyridine. 

The aza-transfer reaction between 3-hydrazinopyridazines and aromatic diazonium salts or heterocyclic diazo compounds affords the corresponding tetrazolo[l,5-6]pyridazines, while 3-hydrazinopyridazine 1-oxide gives 3-azidopyridazine 1-oxide (76TL3193, 76X725). 

Recently, many transformations of various heterocycles into pyridazines have been reported. From the synthetic point of view it appears that furan derivatives are the most valuable. 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

The nucleophilic substitution reactions in pyrido-[2,3-f>]- and -[3,4-f ]-pyridazines in general follow the usual pattern of polyaza heterocycles. Oxo groups in the 2-, 3- and 6-positions of [2,3-f ]-ones, and in the 2- and 3-positions of [3,4-f ]-ones have been... 

There are several useful syntheses which effectively commence with the cycloaddition of oxygen, a nitroso compound, an azo compound or a sulfinylamine to a 1,3-diene leading to the corresponding 1,2-dioxins, 1,2-oxazines, pyridazines or 1,2-thiazines. Examples of the transformation of these adducts into five-membered heterocycles are shown in Scheme 114 together with leading references. 

Other heterocycles which rearrange to isoxazoles are pyridazine 1,2-dioxides (77CC856) and pyridinium salts (80CPB2083), although these transformations are of little synthetic importance. 

R] Simpson, ]. C. E. Cinnolines. In The Chemistry of Heterocyclic Compounds. Condensed Pyridazine and Pyrazine rings (Cinnolines, Phthalazines, and Quinoxalines)-, Weissberger, A. Ed. Interscience Publishers New York-London, 1953 p3. 

R] Singerman, G. M. Cinnolines. In Heterocyclic Compounds. Condensed Pyridazines Including Cinnolines and Phthalazines-, Weissberger, A., Taylor, E. C. Eds. John Wiley Sons New York-London, 1973 pi. 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

In work on 6-methoxypyrimidines (130), the 4-methylsulfonyl group was found to be displaced by the sulfanilamide anion more readily than were 4-chloro or trimethylammonio groups. This reactivity may be partly due to the nature of the nucleophile (106, Section II, D, 1). However, high reactivity of alkyl- and aryl-sulfonyl heterocycles with other nucleophiles has been observed. A 2-methylsulfonyl group on pyridine was displaced by methoxide ion with alkaline but not acidic methanol. 3,6-Bis(p-tolylsulfonyl)-pyridazine reacts (100°, 5 hr) with sulfanilamide anion and even the... 

Chemistry of conjugated heterocycles built from pyridazine or pyrazine ring fused with bicyclic (norbomadiene, bomene, or azanorbomene) skeletons 98YGK192. 

Pyrrole derivatives substituted in positions 1-, 3-, or 4- have also been electrochemically polymerized (positions 2- and 5- must be free for polymerization). Besides homopolymers, copolymers can also be prepared in this way. Other nitrogen heterocycles that have been polymerized by anodic oxidation include carbazole, pyridazine, indole, and their various substitution derivatives. 

A special class of synthesis is the utilization of retro-Diels-Alder (RDA) reactions. A double RDA sequence was used to prepare the pyrimido[l,2-A]pyridazin-3-one 118. In this versatile method both reactants of the parent compound were constructed from cyclopentadiene. The parent compound 117 contains two norbornene units and decomposes on heating in toluene in a double RDA reaction leaving two double bonds in the target heterocycle. Similarily, the parent compound 119 decomposes in a single RDA reaction to yield the benzologue, pyridazino[6,l-3]-quinazolin-10-one 120 (Scheme 13) <2000SL67>. 

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