Diazines—

2-Diazines. - Pyridazin-4-ones (87 R = Ph or OMe) are obtained when a-oxo-hydrazones (86 R = Ph or OH) are refluxed in dimethylformamide dimethyl acetal / we reported last year on the formation of pyridazin-3-ones from similar hydrazones.  

The photorearrangement of chlorinated pyridazines to pyrazines has been further investigated. Radical-stabilizing substituents at C-4 and/or C-5 of the pyridazine appear to be essential for the reaction to proceed thus (88) gives 

Coupling of terminal acetylenes with 3-chloropyridazines has been performed, using the Pd -Cu -EtjNH system, giving 3-(alkynyl)pyridazines in yields of up to 78% phenylacetylene gives (90) with 3-chloropyridazine 1-oxide but only gives tars with the isomeric 2-oxide/ 3-(Alkynyl)cinnolines have been similarly prepared from 3-iodo- and 3-bromo-cinnolines, and attempts to couple alkenes have been reported it is not unusual, in this type of reaction, to obtain small amounts of homo-coupling products i.e. biaryls), but an excellent yield of 3,3 -bicinnolinyl (81%) was obtained from 3-bromo-cinnoline and styrene. 

The pyridine (91) is known to possess potent and long-lasting anti- 

A number of publications have appeared on the alkylation of heterocycles under phase-transfer conditions (see also pp. 295, 318, and 331) these reactions appear to proceed in high yield and with great selectivity. Alkylation of pyridazin-3-ones with primary and secondary alkyl bromides gives high yields of 2-A -alkyl derivatives electron-deficient olefins may also be used as the alkylating agents, thus acrylonitrile affords the cyanoethyl derivative (92).  

A diazabenzene, i.e. a benzene ring in which two of the CH functions have been replaced with nitrogen. 

These structures are all aromatic, the nitrogen atoms functioning in the same way as the pyridine nitrogen, each contributing one p electron to the aromatic sextet, with a lone pair in an sp orbital. The 

Halodiazines react readily with nucleophiles with displacement of the halide leaving group. This follows what we have seen with halopyridines (see Section 11.4.1), but the halodiazines are more 

The 2- and 4-haIopyrimidines are even more reactive, and snbstitnte at room temperature. This is becanse of the improved delocalization of negative charge in the addition anion. 5-Halopyrimidines are 

Diazines are generally resistant to electrophilic attack on carbon, and, as for pyridine, addition on nitrogen is observed. Alkyl halides give mono-quaternary salts di-quatemary salts are not formed under normal conditions. Of conrse, if the diazine ring carries a snbstitnent that makes the starting 

Hydrogenolysis of the readily available 2-(arylazo)furanones (201), followed by ring-closure of the resultant hydrazones (202), affords l-aryl-pyridazin-4- 

The utility of a-dicarbonylmonohydrazones ArCOC(NNH2)R (R = H or Ph) in pyridazine synthesis has been extended to the formation of 3-amino-4-cyano-pyridazines (208) by reaction with malononitrile. Oxidative ring-enlargement 

Details of studies on the n.m.r. spectra of substituted pyridazines, pyrimidines, and pyrazines have appeared. Calculated (MINDO/2) charge densities have been correlated with substituent-induced chemical shifts of these diazines.  

Thermal rearrangement of, e.g., perfluoro-4,5-di-isopropylpyridazine (211) to the corresponding pyrimidines and pyrazines (212) and (213) appears to be sensitized by the presence of its di-s-butyl analogue (214). Thus heating (211) in a sealed tube at 300 °C results in 8% conversion, whereas 90% conversion is obtained in the presence of (214). Photochemical sensitization is well known this is the first reported case of an analogous thermal process. 

Tsujimoto, C. Kobayashi, T. Nomura, M. lifura, and Y. Sasaki, Ghent. Pharm. Bull., 1979, 27, 

Bibliography 77Sg Other references 75TR,78FS  

77Sg Other reference 76TR 

Other references 68K,68RRM,75Kc,77PD,78GB, 78Ka,79TP 

Other references 68K,71KY,75Kc,78DMY, 78FSa 

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Pyrazine (1,4-diazine) will bridge two OsNCLt fragments in [Cl4NOs(pyrazine)OsNCl4]2- where the chlorines are bent slightly away from the terminal N (IR l-(Os-N) 1105cm-1, Os-N 1.63 A) [190],... 

The versatile chemistry of 1,4-diazines organic, inorganic and biochemical aspects. W. Kaim, Angew. Chem., Int. Ed. Engl., 1983, 22,171-190 (217). 

With Hg2 bidentate nitrogen ligands form complexes that have chain structures. For example, 1,4-diazine III forms a complex [Hg2(C4H4N2XN03)2] (IV) that has Hg—Hg units joined in infinite chains, with the [N03] groups between the chains . ... 

In 1886 the first examples of compounds containing two adjacent nitrogen atoms in a six-membered ring were reported [ 1 ] The preparation of the parent system pyridazine or 1,2-diazine (1) was described as early as 1895 by Tauber [2]. Compared with the 1,3- and the 1,4-diazine systems (pyrimidine and pyrazine), however, the pyridazine system for a long period attracted little attention in medicinal chemistry. 

Diazines (pyrazines) afforded hexahydro derivatives by catalytic hydrogenation over palladium on charcoal at room temperature and 3-4 atm [484, 485] (yield of 2-butylpiperazine was 62% [484], yield of 2,5-diphenylpiperazine 80% [455]). Electrolytic reduction gave unstable 1,2-, 1,4- and 1,6-dihydro-pyrazines [485]. 

Of course, because of the linear inverse relationship between a and tt charges, the correlation with total charges also implies the existence of individual linear correlations with (T and tt populations, namely, upheld shifts for increasing 7r-electron densities, just as in the case of aromahc hydrocarbons. The latter result also follows from Patiser-Parr-Pople calculahons of tt charge densities reported by Witanowski et al. [161]. AU of these considerahons apply equally well to the series including pyridine, 1,3-diazine, 1,4-diazine, and 1,3,5-triazine, as revealed by their spectra in DMSO soluhon [162] (Fig. 6.8). 

Figure 6.8. Comparison between the net charges and resonance shifts of nitrogen in pyridine, 1,3-diazine, 1,4-diazine, and 1,3,5-triazine (me). (Reproduced with permission from Ref. 43.)...

Zur titrimetrischen Bestimmung von Azo-Verbindungen konnen Dihydro-1,4-diazine verwendet werden2. 

Problem 20.43 Write structures for (a) oxirane, (b) 1,2-oxazole, (c) 1,4-diazine (pyrazine), (d) l-thia-4-oxa-6-azocine, (e) 3H-1,2,4-triazole, (/) azepane. 

The silver dye bleach reaction is very slow (65MI11401), and an additional agent is needed to promote the reaction between the immobile silver image and the immobile dye. 1,4-Diazines have been used as catalysts for this reaction, 2,3-dimethylquinoxaline (65), 2,3-diphenylpyrazine (66) and 2-hydroxy-3-aminophenazine (67) being specific examples. 

Pyrimidine (1,3-diazine) and pyrazine (1,4-diazine) exhibit weak fluorescences73,74 in solutions or as vapors at room temperature, and strong phosphorescences 76-79 in dilute solid solutions at low temperatures (77 or 90°K). The phosphorescent quantum yields have never been accurately measured in these solid solutions. In the vapor phase or in ordinary solutions, at room temperature, these two compounds do not phosphoresce. Radiationless deactivation processes must be considered again and a deactivation through an isomer cannot be excluded. 

The first coordination compound of this type was the aniline complex Hg(PhNH2)2(N03)2,96 but later research revealed that up to six ligands are coordinated to Hg2(N03)2. The first X-ray crystal structure determination of this type of coordination compound was published in 1967 for Hg2(phen)(N03)2.98 In this complex one Hg atom of the Hg+—Hg+ ion is bonded to both N atoms of 1,10-phenanthroline the other Hg atom is coordinated to oxygen atoms of the nitrate ions.98 More recently X-ray structure determinations have been made with complexes of Hg2(N03)2 with either 1,4-diazine (10)99 or quinoline (11).100... 

Preparation of Pyrazines and Piperazines (1,4-Diazines), and of their Fused Derivatives... 

Diazines other than diketopiperazines can also be prepared on insoluble supports (Table 15.31 see also Figure 3.13 [382]). Most strategies are based on intramolecular nucleophilic substitutions or acylations. Several examples of the solid-phase preparation of quinoxalinones have been reported. In most cases, the compounds have been prepared from support-bound 2-fluoronitrobenzenes according to the strategies outlined in Figure 15.18. Alternatively, a-amino acid esters bound to polystyrene as IV-benzyl derivatives can be N-arylated with 2-fluoronitrobenzene. Reduction of the resulting 2-nitroaniline leads to the formation of quinoxalinones [383]. 1,4-Diazines have been chemically modified by N- or C-alkylation on insoluble supports (Entries 9 and 10, Table 15.31). 

This section deals with molecules derived from the diazines C4H4N2 pyrazine (1,4-diazine 7), pyrimidine (1,3-diazine 8) and pyridazine (1,2-diazine 9). 

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