Benzo phthalazines

Isolated and benzo-fused diazine rings are key structural elements in many natural and synthetic compounds of current interest. This contribution relates highlights from many of the studies on the diazines pyridazine, pyrimidine, pyrazine, and their benzo-fused derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine published in English in the journal literature during 1996, as covered by Chem. Abstr. through volume 126, issue 5. 

The steric course of electrophilic additions of BrN3, IN3, and iV-bromosuccinimide (NBS) to the tetrahydropyridazine ring of benzo[g]pyridazino[l,2- ]phthalazine-6,13-dione system, for example, 130, has been studied and the results are shown in Scheme 12 <1997CJC348>. 

C4N2-C4N2-C6-C6 1,4,6,13-T etrahy dro-benzo[g]pyridazino[l,2-b] phthalazine 8, 37... 

Several applications of established ring-closure methodologies have been applied for the syntheses of the benzo-logues of the triazolopyridazine ring system - all these refer to cyclization to [l,2,3]triazolo[3,4- ]phthalazine derivatives. In Table 13, such products are shown together with yields and literature references. The product in entry 8 is somewhat outstanding in this list these compounds have been synthesized by solid-phase methodology, and the yields refer to the amounts of the crude products mostly of 90% purity. 

Antwerp (2004), and Strasbourg (2006) in the covered period of this chapter. Certainly there has been a lot of activity in the pyridazine and benzo derivative field in the 1996-2006 period. A search on the Web of Science revealed 1756 articles for the topic pyridazin , 574 for phthalazin and 168 for cinnolin . The same search on the Scifinder database revealed 5203, 1943 and 462 hits for the concepts pyridazin , phthalazin , and cinnolin , respectively. Patents have only been taken into account in Section 8.01.12. In this chapter emphasis has been put on new and adapted older methods, as well as new interesting examples of well established methods. Selections necessarily had to be made due to the large amount of material published within the considered timeframe. Fully conjugated pyridazines, phthalazines and cinnolines as well as (partly) reduced and oxo forms (both only in the 1,2-diazine ring) are covered in this work. 

Macrocyclic 1,2-diazines were also investigated as ligands <2000AGE1968>. Especially interesting is the reaction of 1,2-diazines (pyridazine 26, phthalazine, and benzo[clcinnoline) with tungsten(ii)aryloxide complexes 33 as the N-N bond is cleaved (Equation 6) <2002CC2482>. 

The annelation of benzo rings on pyridazines was covered in CHEC-II(1996) <1996CHEC-II(6)1>. Maes and Matyus reported new examples in their synthesis of the dibenzo[// ]phthalazin-l(27r)-one and dibenzo[//]cinnolin-3(27/)-one skeleton. Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one yielded 2-benzyldibenzo[/,4]phthalazin-l(2//)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl) -phenylpyridazin-3(2//)-one via a Pschorr-type reaction was also investigated. Similarly, the con-stmction of 2-methyldibenzo[/, ]cinnolin-3(2//)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(27T)-one and 2-methyl-5-(2-aminophenyl)-6-phenyl-pyridazin-3(2//)-one was performed <2003T5919>. 

The interest for applications of pyridazines, phthalazines, and cinnolines as pharmaceuticals, agrochemicals, and materials certainly increased in the period 1996-2006. The database Scifinder revealed that 669 patents containing the topic pyridazine were published in this time frame. Similarly, for the benzo analogs phthalazine and cinnoline ... 

Pyridazine (1,2-diazine) (1) and its benzo analogs cinnoline (1,2-diazanaphthalene) or benzo[c]pyridazine (2) and phthalazine (benzo[rf]pyridazine) (3) have been known since the nineteenth century. Although the basic synthetic principles and reactivity were investigated in the early years, interest in these compounds was not very intense, compared with pyrimidines and their bicyclic analogs, as they were not found in nature. However, during the last three decades intensive research has been stimulated because many derivatives have found application as a result of their biological activity. 

There are also reviews on the biological activity of certain phthalazines (59MI21203) and on Reissert compounds from phthalazines (80H(14)1033). The chemistry of benzo[c]cinnolines has also been covered (79AHC(24)l5l). 

Biologically active pyridazines and benzo-fused derivatives were still avidly sought. For example, pyridazines were prepared as inhibitors of a protein tyrosine phosphatase <02BMC3197>, trisubstituted pyridazines as inhibitors of p38 MAPK <02BMCL689>, and phthalazines as... 

The acid-catalyzed hydrolysis continues to be used as a highly satisfactory method for the synthesis of quinaldic acids. The reaction of Reissert compound (7) with hydrobromic acid in acetic acid gave near quantitative yields of quinaldic acid hydrobromide with no contamination from other acid derivatives and would appear to be the method of choice for this conversion. This method has subsequently been used to produce high yields of benzo(/)quinoline-3-carboxylic acid and phthalazine-1-carboxylic acid. ... 

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