Metalations pyridazine

Other ortV o-metallated pyridazine complexes (134, where R = -Me, -CH2CI2) were reported by Guang et For n = m= Q, the free ligand showed a SmA phase (Cr 79 SmA 102 I), as did the /i-Cl precursor complex (Cr 163 SmA 212 I) and the chloro- and bromoacetates (Cr 160 SmA 185 I and Cr 160 SmA 174 I, respectively) the simple /i-acetato complex was non-mesomorphic at all chain lengths reported. The lower symmetry complexes ( = 6, m= 10) were mesomorphic for the chloro- but not the bromoacetate, and a more extensive series where n was fixed as 10 and m was varied from 6 to 12 showed enantiotropic SmA phases for all except that with m = i>. 

Several 3-substituted 6-methylmercuriothiopyridazines and complexes of perfluoro-pyridazine with metal carbonyl anions have been prepared <67MI21200). 

Pyridazines form complexes with iodine, iodine monochloride, bromine, nickel(II) ethyl xanthate, iron carbonyls, iron carbonyl and triphenylphosphine, boron trihalides, silver salts, mercury(I) salts, iridium and ruthenium salts, chromium carbonyl and transition metals, and pentammine complexes of osmium(II) and osmium(III) (79ACS(A)125). Pyridazine N- oxide and its methyl and phenyl substituted derivatives form copper complexes (78TL1979). 

There seems to have been no systematic study of tautomerism in the pyridopyridazines, but isolated observations in the pyrido[3,4-d]pyridazinedione (75BSF702, 69CPB2266) and pyrido[2,3-d]pyridazinedione (74JHC351) series have involved methylation studies. The pyrido[2,3-d]pyridazine-5,8-diones are believed to be enolized at the 8-position, from metal complexation results (67MI21500). 

The Ni11 complex of bis(pyridazine)carboxamide can act as a bidentate ligands towards other metal ions, e.g., in (841). 7-2049 3,6-Bis(2-pyridyl)pyridazine (dppn, (842)) forms a tetranickel... 

The diazines pyridazine, pyrimidine, pyrazine, and their benzo derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine once again played a central role in many investigations. Progress was made on the syntheses and reactions of these heterocycles, and their use as intermediates toward broader goals. Some studies relied on solid-phase, microwave irradiation, or metal-assisted synthetic approaches, while others focused attention more on the X-ray, computational, spectroscopic, and natural product and other biological aspects of these heterocycles. Reports with a common flavor have been grouped together whenever possible. 

A metal-iodine exchange has been carried out on all three diazine systems under very mild conditions using lithium tri- -butyl magnesate, although only one substrate from each system was used 3-iodo-6-phenylpyridazine, 4-iodo-2-methylthiopyrimidine and 2-iodopyrazine. The pyridazine example was most problematic, possibly due to solubility problems. Aldehydes, benzophenone and diphenyl disulfide were used as the electrophiles <06SL1586>. 

The preparation of oxygen substituted porphyrazines as analogues to the thiol appended porphyrazines proved to be a formidable challenge. Unlike the sulfur appended porphyrazines for which Na2(mnt) was a readily available precursor, no simple dinitrile precursor could be prepared for the analogous oxygen systems. In 1997, this hurdle was overcome through the preparation of a chiral dispiroketal appended pz (11), which could be further deprotected to form the diol and then either peripherally metalated or converted to the pyridazine (10). These oxygen appended porphyrazines are described in Section VI. 

The direct metalation of 5-methylpyrimidine and 5,5 -bipyrimidinyl in the 4-position has been reported with LDA in low yield [74TL2373 75AG(E)713], but apart from that there are few other reports on the direct metalation of unactivated diazines. However, as with pyridine and quinoline, directed metalation can readily be achieved with all three of the diazine systems when the appropriate substituent groups are present [91AHC(52)187]. Thus, the direct lithiation of pyridazine in the 4-position has now been achieved with both the 3,6-dichloro and the... 

The directed metalation chemistry of pyrimidine is more extensive than that of pyridazine, and both 4- and 5-substituted derivatives can be prepared by this route (Table XV). 

Examples of the 3-lithiation of both 2- and 2,6-disubstituted chloro- and methoxypyrazines, as well as 2-thiomethylpyrazine are known (88S881 90JOC3410 91JHC765, 91JOM(412)301] (Scheme 117). As with pyridazine, LiTMP has so far been the only base employed, and this same base system has also recently been used for the directed metalation of pyrazine... 

Electrophilic attack of a metal complex on one of the nitrogen atoms of 1,2-diazines has been reported to occur in the mechanism of new metal mediated methods to prepare C-N bonds. Pyrrolo-fused pyridazines and phthalazines for instance were synthesized via attack of the 1,2-diazine on a palladacyclobutane intermediate 34 formed via oxidative addition of an alkylidenecyclopropane to Pd(PPh3)2 (Equation 7) <2004JOC3202>. 

The metallation, especially the lithiation, of pyridazines, mentioned briefly in CHEC-II(1996) <1996CHEC-11(6)1 >, has been developed extensively since 1995 by Queguiner and co-workers for the derivatization of pyridazines and benzopyridazines. The bases of choice are usually lithium 2,2,6,6-tetramethylpiperidide (LTMP) and lithium diisopropylamide (EDA). Special efforts have been made to achieve regioselective lithiations. 

More recently we have begun to use the ligand 3,6-bis(2 -pyridyl)pyridazine (dppnH) which, after deprotonation of the pyridazine ring, gives a monoanion (dppn") capable to coordinate two metal ions on opposite sides by means of a N-N and a C -N chelating moieties (Figure 1). 

Another remarkable difference that can be predicted for these grids is a consequence of the existence of a spacer carbon atom between the N-donor atoms of the pyrimidine or triazine rings that is absent in the pyridazine heterocycle. This leads to a greater distance between the metal centers in the former systems and, consequently, the cavity in the grid should be bigger. All of these envisaged differences are demonstrated in Section 3.3.2, in which X-ray structures are discussed. 

Pyridazino[l,2-pyridazine derivatives are easily reduced with either hydrogen over a catalyst or with metal hydrides. Reaction of the pyridazino[l,2- ]pyridazine-l,4,6,9-tetrone (44) with hydrogen over platinum oxide gives the hydrogenated product (45) (66JOC1311). This product can be further reduced with lithium aluminum hydride to give the octahy-dropyridazino[l,2- ]pyridazine (24) (67JA4875). 

Pyridazine resembles pyrazole and the triazoles with regard to bonding, as it has the ability to bridge between two metal ions. Unsubstituted pyridazine, however, yields few stable compounds, and only when chelating substituents are present at positions 3 and 6 can stable compounds (10) be obtained with transition metal ions.60... 

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