Pyrimidines and Quinoxalines

Cinnoline 1 (benzo[c]pyridazine), phthalazine 2 (benzo[ /]pyridazin), quinazoline 3 (benzo[benzene-fused diazines. Of the dibenzo-annulated systems, only phenazine 5 (dibenzopyrazine) will be discussed. 

Chain-fluorinated diazines is another family of organofluorine compounds which is of great importance for synthetic, medicinal and agricultural chemistry [12, 13], The first representatives of this class, namely, chain-fiuorinated pyrimidines and quinoxalines were obtained in late 1950s. Since then, over a thousand papers dealing with synthesis and chemistry of chain-fluorinated diazines were published. 

Seggio A, ChevallierF, Vaultier M, Mongin F (2(X)7) Lithium-mediated zincation of pyrazine, pyridazine, pyrimidine, and quinoxaline. J Org Chem 72 6602-6605. doi 10.1021/jo0708341... 

Pyrimidine-2-thiones (e.g., 206) have been shown to exist as such by comparison of their ultraviolet spectra with those of both alkylated forms.The ultraviolet spectra of pyrimidine-4-thiones are different from those of 4-alkylthiopyrimidines, therefore the former compounds exist as 207 and/or 208, the predominant form not having been determined. Infrared spectral evidence suggests that quinazoline-4-thione exists as 209 and/or 210 and has been used recently to demonstrate the thione formulation for pyrimidine-2- and -4-thione, pyrazine-2-thione, and quinoxaline-2-thione. In view of this work, the report that X-ray crystallographic evidence supports the mer-... 

Introduction Pyrroles Indoles Pyridines Thiophenes and Benzo[b]thiophenes Furans and Benzo[b]furans Thiazoles and Benzothiazoles Oxazoles and Benzoxazoles Imidazoles Pyrazines and Quinoxalines Pyrimidines... 

The selected examples of six-membered heterocyclic rings containing two nitrogen atoms are based on the pyrimidine [(73), 1,3-diazabenzene], pyrazine [(74), 1,4-diazabenzene] and quinoxaline [(75), benzopyrazine] systems. 

Although the most commonly used reactive systems involve the halotriazine and sulfa-toethyl sulfone (vinyl sulfone) groups, halo-genated pyrimidines, phthalazines, and quinoxalines are also available (Fig. 13.14). For all of these systems, alkali is used to facilitate dye-fiber fixation, and fixation occurs either by nucleophilic substitution or addition (Figs. 13.15-13.16). 

Using pulse radiolysis, Moorthy and Hayon have studied radicals from pyrazine, pyrimidine, pyridazine, quinoxaline, phthalazine, and acridine.219 Electronic absorption characteristics and kinetic data were reported for the hydrodiazinyl neutral radicals, among others, and the pK values for their protonation to (V,JV -dihydrodiaziniumyl radicals were given. The neutral... 

The phenylation of pyridazine and quinoxaline has been carried out using dibenzoyl peroxide, iV-nitrosoacetanilide, and benzenedia-zonium hydroxide as the sources of phenyl radical, the first two methods giving very much better yields than the third.63 The most reactive positions in these ring systems are the 4-position in pyridazine and the 2-position in quinoxaline. Phthalazine has been phenylated with iV-nitrosoacetanilide, giving a low yield of 5-phenylphthalazine, but the main product from cinnoline in this reaction was 4,4 -bicin-nolyl, although a small quantity of 4-phenylcinnoline was obtained.63 Pyrimidine has been arylated only with the 4-nitrophenyl radical, substitution occurring at the 2- and 4-positions.12... 

The three diazines, pyridazine, pyrimidine, and pyrazine are stable, colourless compounds that are soluble in water. The three parent heterocycles, unlike pyridine, are expensive and not readily available and so are seldom used as starting materials for the synthesis of their derivatives. There are only four ways in which a benzene ring can be fused to a diazine cinnoline, phthalazine, quinazoline and quinoxaline are the bicyclic systems thus generated. 

Limitations of space preclude a more detailed discussion of the many papers dealing with the chemistry of heterocyclic thiones containing the thiolactam grouping. However, a selection of these papers, describing reactions of thiones derived from thiazoline, imidazoline, indo-line, benzo[f/]isothiazoline, pyridine, pyridazine, pyrimidine, " 1,3-thiazine, isoquinoline, quinazoline, and quinoxaline, deserve attention. 

In 2008, Itami reported a transition-metal-free C-H arylation of simple azines such as pyrazines, pyrimidines, pyridazines, and quinoxalines with aryl iodides under the influence of KOt-Bu. Unfortunately, this reaction showed no regios-electivity due to its radical reaction pathway (e.g., the ratio for the arylation of... 

Pyrimidine, Pyrazine, Quinoxaline, Quinazoline, and Related Alkaloids... 

Electron-withdrawing and electron-donating groups on the pyridine moiety were compatible. It is worth noting that ster-ics and electronics play an inportant role in governing C2- vs. C6-selectivity for C3-substituted pyridines sterically hindered substrates, such as C3-pivalamido, phenyl, and ester substrates, preferred C6-arylation, whereas, due to electronic effects, C3-chloro- and fluoro-substrates favored C2-arylation. Other azines could also be cross-coupled with 2-methylthiophene including pyrimidine, quinoline, quinoxaline, pyridine, and pytidazine. 

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