Diazine

Diazine refers to a group of organic compounds having the molecular formula C₄H₄N₂. Each contains a benzene ring in which two of the C-H fragments have been replaced by isolobal nitrogen. There are three isomers:

pyrazine (1,4-diazine)

pyrimidine (1,3-diazine)

pyridazine (1,2-diazine)

See also

Pyrazine

Pyrazine is a heterocyclic aromatic organic compound with the chemical formula C₄H₄N₂.

Pyrazine is a symmetrical molecule with point group D_2h. Derivatives such as phenazine are well known for their antitumor, antibiotic and diuretic activities. Pyrazine is less basic than pyridine, pyridazine and pyrimidine. Tetramethylpyrazine (also known as ligustrazine) is reported to scavenge superoxide anion and decrease nitric oxide production in human polymorphonuclear leukocytes, and is a component of some herbs in traditional Chinese medicine.

Synthesis

Many methods exist for the organic synthesis of pyrazine and its derivatives. Some of these are among the oldest synthesis reactions still in use.

In the Staedel–Rugheimer pyrazine synthesis (1876) 2-chloroacetophenone is reacted with ammonia to the amino ketone, then condensed and then oxidized to a pyrazine. A variation is the Gutknecht pyrazine synthesis (1879) also based on this selfcondensation, but differing in the way the alpha-ketoamine is synthesised

Pyridazine

Pyridazine is a heterocyclic organic compound with the molecular formula (CH)₄N₂. It contains a six-membered ring with two adjacent nitrogen atoms, and is aromatic. It is a colorless liquid with a boiling point of 208 °C. It is isomeric with two other (CH)₄N₂ rings, pyrimidine and pyrazine.

Occurrence

Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. The pyridazine structure is a popular pharmacophore which is found within a number of herbicides such as credazine, pyridafol and pyridate. It is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, hydralazine, and cilazapril.

Syntheses

In the course of his classic investigation on the Fischer indole synthesis, Emil Fischer prepared the first pyridazine via the condensation of phenylhydrazine and levulinic acid. The parent heterocycle was first prepared by oxidation of benzocinnoline to the pyridazinetetracarboxylic acid followed by decarboxylation. A better route to this otherwise esoteric compound starts with the maleic hydrazide. These heterocycles are often prepared via condensation of 1,4-diketones or 4-ketoacids with hydrazines.