1.4- Dihydropyridazines, synthesis

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

Ring synthesis via the transformation of 3-amino-277-pyran-2-ones (including fused derivatives) have been further investigated <2006H(70)235, 2006T9718>. 3-Amino-2//-pyran-2-ones could be transformed into the corresponding pyridazine-3-carboxylates via reaction with hydrazine followed by oxidation of the carbohydrazide moiety and 1,4-dihydropyridazine nucleus with CAN. 

The 3-chloro-l,7-dimethylpyridazino[3,4-(7][l,3]oxazine-4,5-dione (149) was prepared in a four-step synthesis starting with (Z)-methyl-3-(3,6-dichloro-l-methyl-4-oxo-l,4-dihydropyridazin-5-yl)-2-methylacrylate (146) which is converted with sodium azide into the 6-azido compound (147). Heating in o-dichlorobenzene at 150°C results in cyclization to methyl 3-chloro-l,6-dimethyl-4-oxo-1,4-dihydro(7//)pyrrolo[2,3-c]pyridazine-5-carboxylate (148) via a nitrene intermediate. Ozonolysis effects ring-enlargement of the pyrrole ring into the 3-chloro-l,7-dimethylpyridazino[3,4-d][l,3]oxazine-4,5-dione (149) (Scheme 26) <79JHC1213>. 

Other methods for synthesizing dihydropyridazines have been recorded but have not been generally applied. Hauser and co-workers,87 for example, have reported the synthesis of dihydropyridazines 28a and 35 by an intramolecular coupling reaction [Eq. (5)]. However, it has been shown that 35 exists in the... 

Carboni and Lindsey90 have also pointed out the significant role played by steric restrictions, which may be important for the reactivity of dienophiles in the synthesis of dihydropyridazines. For instance, 2,3-dimethyl-2-butene (an electron-rich but sterically hindered olefin) reacts only with the polyfluoroalkyl substituted tetrazines 39a and 39b, giving correspondingly 4,5-dihydropyridazine 40a95 and 40b.90 Even with these highly reactive tetrazines, the rate... 

Synthesis of dimethyl l-(hetero)aryl-4-oxo-l,4-dihydropyridazine-3,5-dicarboxylates from dimethyl 3-oxopentane-l,5-dioates (08ZN863b)407)... 

Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. Thus, bicyclic lactams 112 with hydrazine dichloride in a dioxan/water mixture produced the desired 6-phenyl-4,5-dihydropyridazin-3-ones 113. However, reacting the bicyclic lactam with phenylhydrazine hydrochloride yields 2,6-diphenyl-4,5-dihydropyridazin-3-one 115 as a sole product (2004TL7799 Scheme 20). 

H. Sheibani, M. A. AmroUahi, Z. Esfandiarpoor, Mol. Divers. 2010, 14, 277-283. A convenient one-pot synthesis of 3-amino-2,5-dihydropyridazine and pyrimidine derivatives in the presence of high surface area MgO as a highly effective heterogeneous base catalyst. 

Reaction of enaminonitfiles with a, -unsaturated aldehydes catalysed by BF3 OEt2 gives 1-azatrienes which undergo 1,6-electrocyclizations to 1,2-dihydropyridines. A Br0nsted-acid-catalysed asymmetric 6 r-electrocyclization reaction has been reported for the synthesis of enantiomerically enriched 1,4-dihydropyridazines (Scheme 39). ... 

Barlow MG, Haszeldine RN, Pickett JA (1978) Heterocyclic polyfluoro-compounds. Ptut 26. Synthesis of 3,6-bis-trifluoromethyl-pyridazines and -dihydropyridazines. J Chem Soc Perkin Trans 1 378—380... 

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