Pyridazines. to pyrazines

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... 

Some aspects of the pyridazine-to-pyrazine isomerization have already been mentioned in this review. The work described in ref. 7 concerning isolation of the intermediate diaza-Dewar isomers in this conversion has been extended, and the... 

Chambers RD, MacBride JAH, Maslakiewicz JR, Srivahtava KC (1975) Photochemistry of halogenocarbon compounds. Part I. Rearrangement of pyridazines to pyrazines. J Chem Sos Perkin Trans 396 00... 

A study of the a-arylation of diazine mono iV-oxides, under Heck-like conditions, also gave emphasis to pyrazines but a number of examples using pyrimidines and pyridazines were also described (Scheme 1). A wide range of aryl chlorides, bromides and iodides was used and the products were easily deoxygenated by catalytic reduction. An interesting feature was the use of a copper additive, which was only required for the pyrimidine reactions, to give a very substantial improvement in yield <06AG(I)7781>. 

It is a major challenge to keep our coverage of this immense field up to date. One strategy is to publish Supplements or new Parts when merited by the amount of new material, as has been done, inter alia, with pyridines, purines, pyrimidines, quinazolines, isoxazoles, pyridazines and pyrazines. The chemistry and applications to synthesis of 1,3-dipolar cycloaddition reactions in the broad context of organic chemistry were first covered in a widely cited two-volume treatise edited by Prof. Albert Padwa that appeared in 1984. Since so much has been published on this fascinating and broadly useful subject in the intervening years, we felt that a Supplement would be welcomed by the international chemistry community, and we... 

Much effort has been devoted to the study of the electronic spectra of aza analogues of pyridine (pyridazine, pyrimidine, pyrazine, sym. (l,3,5-)triazine, and sym. (l,2,4,5-)tetrazine) as well as of derivatives of all these compounds. Most of these absorption spectra are similar to those of the parent compounds, except for a band corresponding to the n -> it transition which appears in the long-wavelength... 

The introduction of a pyridine-like nitrogen into a benzene ring tends to make a derivative more crystalline and less volatile this effect is greater for the diazines, especially pyridazine and pyrazine. Wien a hydrogen-bond donor substituent is also carried, the difference from the benzenoid compound becomes even more marked. 

The basicity of the diazines is sharply reduced from that of pyridine (pAfa 5.2) the pKa of pyrazine is 0.4, pyrimidine is 1.1 and pyridazine is 2.1. The significantly higher basicity of pyridazine as compared to pyrazine, unexpected for mesomeric and inductive effects, is attributed to the lone pair-lone pair repulsion which is removed in the cation. 

Diphenylcyclopropenone has proved to be a useful synthetic reagent for preparing indolizines.91 It reacts readily with pyridine to give the indolizine 79 in 50% yield, and the yields of cyclized compounds tend to be greater when pyridazines and pyrazines are used instead of pyridines to give azaindolizines. 

There are few reports of the nitration of the pyridazines and pyrazines. The nitration of phenylpyridazines has been stated to occur exclusively in the phenyl ring (73MI1). The use of fuming nitric acid at 0°C forms only the 4-nitrophenyl derivative (95%), as does 4-chloro-2-phenyl-3-pyridazone (100%), and 4-amino-2-phenyl-3-pyridazone (60%) (47JCS549). 

Earlier work on the photolytic or thermal rearrangement of polyhalogenated pyridazines to corresponding pyrazines has been continued,14,161,774,1690 but the fascinating results offer little of preparative value. It has been reported that 300-nm irradiation of 3,4,5,6-tetra-tert-butylpyridazine (66) gave a quantitative yield of the Dewar isomer (3,4,5,6-tetra-tert-butyl-l,2-diazabicyclo [2.2.0]hexa-2,5-diene 67] that subsequently afforded 2,3,5,6-tetra-tert-butylpyrazine (68) in 18% yield on 254-nm irradiation.1464... 

RING TRANSFORMATIONS OF PYRIDAZINES AND OTHER HETEROCYCLES TO PYRAZINES... 

The rearrangement of 4,5-disubstituted pyridazine to a 2,5-disubstituted pyrazine was postulated to follow a similar mechanism, rearrangement of a perfluoroalkyl group taking place by an addition-elimination mechanism (Scheme 40).102... 

If this mechanism applied to perfluoro(4,5-diisopropylpyridazine), perfluoro(2,3-diisopropylpyrazine) should be obtained. However, the 2,5-substituted isomer is obtained together with its Dewar isomer 163). In a more detailed study, a 2,5-bonded Dewar pyridazine was isolated which isomerized to the Dewar pyrazine. Therefore, another mechanism involving isomerization of the Dewar pyridazine to the Dewar pyrazine which does not proceed via the prismane has been proposed (151)164). 

Moderate to good yields of trapped products can be obtained either by using very short lithiation times (pyridazine and pyrazine) or by in situ trapping, where the electrophile is added before the metaUating agent.4-Lithiopyridazine can be prepared by transmetallation of the corresponding tri-n-butylstannane using n-butyllithium. 

Although pyridazine and pyrazine A-oxides can be readily prepared by oxidation of the parent heterocycles, pyrimidine A-oxides are more difficult to obtain in this way, but they can conveniently be prepared by ring... 

Pyridazine and pyrazine A-oxides behave like their pyridine counterparts in electrophilic substitution. Displacement of nitro P to the A-oxide function occurs about as readily as that of a y-nitro group, but certainly, displacements on A-oxides proceed faster than for the corresponding base. 

Williams and Weller " made a systematic investigation of lone pair site models for pyridine, pyridazine, pyrimidine, pyrazine, s-triazine, and s-tetrazine. They found that the 6-3IG electric potential of these molecules was significantly better fitted when lone pair sites were included. The population analysis (PA) charge model for the electric potential of these molecules is notably poor, as is shown in Table 8. For pyridine, PA charges have a relative error of fit to the electric... 

The ultra-violet absorption spectra of nitrogen containing heteroaromatic compounds (see Chapter 6) like pyridine23, diazabenzenes (pyridazine, pyrimidine, pyrazine)28, triazenes24 and diazanaphthalenes25 have been studied by Hirt and co-workers. All of them show long wavelength bands due to 7r transitions in addition to intense tt tt transitions at lower... 

When two CH groups of benzene are replaced by nitrogen atoms in the ortho-, para- and meta- positions to form, pyridazine, XII, pyrazine, XIII, and pyrimidine, XIV, the position of the n - bands are not greatly affected compared with pyridine (Figure 6.1). 

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