6- Substituted 3 -pyridazinones synthesis

Substituted pyridazinone herbicides directly inhibit photosystem II, chloroplast pigment biosynthesis, and membrane lipid biosynthesis. Depending on the substitution, pyridazinones can specifically inhibit the synthesis of linolenic acid in galacto-lipids and phospholipids preferentially alter the fatty acid composition of monogalactosyl diglycerides compared with digalactosyl diglycerides and cause a build-up of saturated fatty acids in the chloroplast membranes. 

Ijl] H.A. NORMAN and J.B. ST JOHN - Differential effects of a substituted pyridazinone, BASF 13-338, on pathways of monogalactosyldiacylglycerol synthesis in Arabidopsis. Plant Physiol., , 684-688 (1987). 

Substituted pyridazinones were developed as potential photosynthetic electron transport inhibitors. For this action, they have I50 activities in the range 10" -10" It was soon discovered, however, that many of these compounds (Figure 3.6) also reduced the formation of thylakoid pigments, chlorophylls, and carotenoids. In each case, the mechanism of phytotoxicity was found to vary. In some cases, there was evidence for metabolism of the pyridazinone to a more herbicidal metabolite while in others the destruction of photosynthetic function was due to an inhibition of carotenoid (and chlorophyll) synthesis. ... 

Table 3.6. Relative Effectiveness of Different Substituted Pyridazinones on Pigment Synthesis, Photosynthetic Electron Transport, and Galactolipid Fatty Acid Patterns ...

Bicyclic lactams 189 are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-277-pyridazinones 190 by hydrolysis with NH2NH2 and HC1 in dioxane at 85 °C. The reaction gave, as a side product, the ketoacid 191 in some cases (Equation 32) <2003TL7997>. 

Quite recently, a French group reported on the synthesis of 2-substituted 5-arylidene-pyridazinones as represented by the general formula (21, R1 = Ph, 2-ClC6H4 R2 = Ph(CH2)2, PhCO). These compounds were found to exhibit significant dose-dependent analgesic activity (phenylquinone-induced writhing test in mice oral administration) [92]. For a novel type of aminopyridazine-derived inhibitors of prostacyclin biosynthesis, see [93],... 

The action of hydrazine or hydroxylamine on certain other nitropyrimidine systems leads to 4-nitropyrazoles and 4-nitrooxazoles [549], When 1,5-disubstituted 4-nitro-6-pyridazinone derivatives are heated in an alkaline medium the derivatives of 4-nitropyrazole are formed with high yields. 1-Substituted 4-nitropyrazole-5-carboxyiic acids [550, 551] or 1-substituted 4-nitropyrazoles [552-554] can be obtained, depending on the conditions. Another promising method of synthesis has been opened up for the production of 4-nitropyrazole derivatives. 4-Nitropyrazole is obtained with a high yield in the reaction of 3,5-dinitro-2-pyridone with hydrazine [555] (Scheme 99). 

The formation of pyridazines from 1,4-ketoacids (10) or their esters and unsubstituted or substituted hydrazines is one of the most widely used methods of synthesis. It is possible to conduct the reaction in a single step or via the intermediate hydrazones or semicarbazones. The resulting 4,5-dihydro-3(2.fif)-pyridazinones (11) are then converted into the corresponding 3(2fl )-pyridazinones (12) upon dehydrogenation. Bromine in glacial acetic acid is the commonest and most useful... 

The reaction between substituted maleic anhydrides and hydrazines is a well-traveled route for the synthesis of amny pyridazinones. " Hydrazines with a strong electron-donor group form pyridazinones directly others give... 

Microwave-assisted reactions of 5-amino-4-hydroxy-3(2//)-pyridazinone 114 with various carboxylic acid derivatives allowed a convenient and versatile approach to substituted 1,3-oxazolo[4,5-i/]pyridazinones 115. The developed methodology is suitable for rapid, parallel, automated synthesis of oxazolopyridazinone libraries <04TL4693>. 

Okushima, H., Narimatsu, A., Kobayashi, M., Furuya, R., Tsudo, K. and Kitada, Y. 1987. A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives. J. Med. Chem. 30 1157-1161. 

Sotelo, E., Fraiz, N., Yanez, M., Terrades, V., Laguna, R., Cano, E. and Ravina, E. 2002. Pyridazines. Part XXIX Synthesis and platelet aggregation inhibition activity of 5-substituted-6-phenyl-3(2//)-pyridazinones novel aspects of their biological action. Bioorg. Med. Chem. 10 2873—2882. 

Kidwai M, Kumar R (1997) Microwave-assisted synthesis of 1,3,4-Thiadiazolyl-substituted 1, 2, 4, 5-tetrazines, pyridazinones, 1, 2, 4-triazoles, 4-thiazollidinones, oxazoles and thia-zoles. Gazz Chim Ital 127 263-267... 

During the synthesis of oxadiazolyl pyridazinones, by treating 2- crr-butyl-4-chloro-5-(ethoxycarbonylmethoxy) -3(2H)-pyridazinone (Ci) with hydrazine hydrate in ethanol at reflux for 6-8 hours (Scheme 7), we obtain an unexpected product El in good yield, instead of the anticipated product of the corresponding acetylhydrazine. Alazawe had previously reported that methoxyl group at 6-position of the pyridazinone could be replaced by the hydrazino group. For this reason, we assume that the key step of this reaction is the formation of intermediate D. In fact, we also found that 2-(un)substituted-4, 5-... 

The known methods lead to amino pyridazinones, which are useful intermediates for making agricultural and pharmaceutical chemicals, involving Raney-Ni cleavage of the hydrazino pyridazinone(7/, direct amination of the pyridazinones(72-74y), substitution of chloropyridazinone with ammonia at enhanced pressure( /5, and the dechlorination of chloropyridazinone performed in the presence of palladium on charcoal(7 / Therefore, we believe that a novel and convenient synthetic route is provided for the synthesis of aminopyridazinones, which are not easily accessible by traditional methods. 

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