Pyridazines rearrangements

The S ->N rearrangement of pyridazinethione glycosides proceeds smoothly under the influence of mercury(II) bromide. For example, 3-(tetraacetyl-l-/3-D-glucosylmer-capto)pyridazines rearrange to 2-(tetraacetyl-l-/3-D-glucosyl)pyridazine-3(2//)-thiones. 

On the other hand, perfluoro(tetraphenylpyridazines) and some perfluoro(alkyl-pyridazines) undergo nitrogen elimination, or both nitrogen elimination and rearrangement, to give perfluoroalkynes and perfluoropyrimidines (Scheme 7) (74JCS(P1)1513). 

Photoisomerization of perfluoro(4,5-diisopropylpyridazine) is postulated to proceed through Dewar diazabenzenes (25) and (26) to perfluoro(2,5-diisopropylpyrazine) (27), which is in equilibrium with the isomeric perfluoro(2,6-diisopropylpyrazine) (28) after prolonged irradiation in the liquid phase (Scheme 9) (75JCS(P1)1130). Benzo-fused pyridazines do not isomerize readily under photochemical conditions. An exception is perfluorocinnoline which rearranges to perfluoroquinazoline. 

Pyridazin-3(2H)-ones rearrange to l-amino-3-pyrrolin-2-ones (29) and (30) upon irradiation in neutral methanol (Scheme 10), while photolysis of 5-amino-4-chloro-2-phenylpyridazin-3(2H)-one gives the intermediate (31) which cyclizes readily to the bis-pyridazinopyrazine derivative (32 Scheme 11). 

Photolysis of pyridazine IV-ethoxycarbonylimide results in the formation of the pyrrole derivative (56). The rearrangement is postulated to proceed via a diaziridine, followed by ring expansion to the corresponding 1,2,3-triazepine derivative and rearrangement to a triazabicycloheptadiene, from which finally a molecule of nitrogen is eliminated (Scheme 19) (80CPB2676). 

There are some recent examples of this type of synthesis of pyridazines, but this approach is more valuable for cinnolines. Alkyl and aryl ketazines can be transformed with lithium diisopropylamide into their dianions, which rearrange to tetrahydropyridazines, pyrroles or pyrazoles, depending on the nature of the ketazlne. It is postulated that the reaction course is mainly dependent on the electron density on the carbon termini bearing anionic charges (Scheme 65) (78JOC3370). 

This synthetic appproach has been used in a few cases for the preparation of pyridazines from diazo compounds and cyclopropenes. In general, cycloadducts (176) are formed first and these rearrange in the presence of acid or alkali to pyridazines (Scheme 98) (69TL2659, 76H(5)40l). Tetrachlorocyclopropene reacts similarly and it was found that the stability of the bicyclic intermediates is mainly dependent on substitution (78JCR(S)40, 78JCR(M)0582>. 

Pyridazines are formed from pyrones or their thioxo analogs or from appropriate pyridones. Pyrones or pyridones react with diazonium salts to give the corresponding hydrazones (187) and (188) which are rearranged under the influence of acid or base into pyridazinones as shown in Scheme 107. On the other hand, kojic acid is transformed with hydrazine into a 1,4-dihydropyridazine and a pyrazole derivative. 4H-Pyran-4-thiones... 

Other heterocycles which rearrange to isoxazoles are pyridazine 1,2-dioxides (77CC856) and pyridinium salts (80CPB2083), although these transformations are of little synthetic importance. 

Pyridazine, 4-diazo-5,6-dioxo-1 -phenyl-1,4,5,6-tetrahydro-rearrangement, 3, 10 Pyridazine, 4,5-di-S-butyl-perfluoro... 

Pyridazine N-ethoxycarbonylimide photolysis, 3, 13 Pyridazine, 4-gJycosyloxy-rearrangement, 3, 15 Pyridazine, halo-applications, 3, 56 Pyridazine, hexahydro-, 3, 40 photoelectron spectra, 2, 20-21 Pyridazine, hydrazino-reductive cleavage, 3, 34 synthesis, 3, 35 Pyridazine, hydroxy-acidity, 3, 4 Pyridazine, 3-hydroxyl-oxide... 

S-N rearrangement, 3, 36 ionization constants, 3, 4 oxidation, 3, 37 quatemization, 3, 17 Pyridazine-3 (2 H) - thiones analysis, 3, 2 tautomerism, 3, 5 Pyridazinium betaine, 3-oxido-photolysis, 3, 11 Pyridazinium betaine, 5-oxido-photolysis, 3, 11 Pyridazinium dicyanomethylide photolysis, 3, 12... 

Pyrimido[5,4-c]pyridazine-6,8-diones synthesis, 3, 357 Pyrimidopyridazines rearrangement, 5, 342 Pyrimido[ 1,2- 6]py ridazines HNMR, 3, 334 reactivity, 3, 343... 

Pyrimido[5,4-c]pyridazin-8-ones chlorination, 3, 345 rearrangement, 3, 345 synthesis, 3, 357... 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

Pyridines and pyridazines bearing bulky perfluorinated groups behave similarly [149, ISO, ISI], although their photochemical rearrangement is not always clearly documented [752] Azaprismanes, however, have been isolated and fully characterized [75J] (equation 37)... 

In this work the possibility of the existence of 1,2-dihydro isomer with the core structure 42 was not considered. Recently, however, it was shown that 1,2-dihydropyridazines could be prepared by careful electroreduction of the corresponding pyridazines, and that their stability depends significantly on the ring substitutions. Thus, dimethyl l,2-dihydropyridazine-3,6-dicarboxylate 43a (R = H) is reasonably stable and rearranges into the 1,4-dihydro tautomer 43b only at a more negative potential, while the tautomerization in its tetrasubstituted analog 43a (R = COOMe) occurs more readily (Scheme 14) [00TL647]. 

The reaction of several substituted imidazo[4,5-c/]-, pyrazolo[3,4-r/]- and triazolo[4,5-zf]pyrid-azines 3 with ynamines, in competition with [4 + 2] cycloaddition, leads to [2 + 2] derivatives 4, which rearrange to l,2-diazocines5.7 8 The reaction seems to be sensitive to the substituents, as replacement of the electron-withdrawing group R on the pyridazine ring of the pyrazolo compound (A = N, B = CH) by chlorine completely inhibits both the [4 + 2] and [2 + 2] cycloaddition reactions. The X-ray structure of the imidazo derivative 5 (R = Ms, A = CH, B = N) reveals a tub conformation of the eight-membered ring. 

Prostaglandins 624, 725, 960 Prostanoids 620 Protonation 565-567, 1049 photochemical 882 Pseudopotential methods 15, 16 Pummerer rearrangement 240, 243, 470, 843 Pyramidal inversion 602, 604 Pyrazolenines 749 Pyridazine oxides 640 Pyridine aldehydes, synthesis of 310 Pyridine oxides 640 Pyrolysis 102-105 of sulphones 110, 679-682, 962 of sulphoxides 739, 740 Pyrroles 265, 744... 

Condensation of />-chlorophenylhydrazine with the diacylisoxazolopyridine 275 gives the pyrazoloindolizine 276, and not the expected pyridazine. The proposed mechanism for this reaction involves a complex series of rearrangements <1997J(P1)155> (Scheme 74). 

Literature reports on diazaquinones derived from o-benzoquinone are very rare. Compound 74 was suggested to be a common intermediate formed during heating of 2,5-bis(diazo)-3,4-diketoadipate 73 with isopropanol and with various bases (76T269). Direct reduction of the intermediate with isopropanol provided pyridazine 75. A base-catalyzed benzilic acid rearrangement of 74 followed by decarboxylation of 76 afforded pyrazole 77 (Scheme 18). 

The reaction of oxime 323 with concentrated aqueous HCl proceeded with a ring contraction and afforded pyridazine 324 as a single product (equation 140) . On the contrary, the rearrangement of pyrrol-3-one oxime in the presence of hydrazine proceeded with ring enlargement and led to l//-pyridazin-4-one oxime . ... 

Nitration of 4-amino-6-methylpyridazin-3(2-ff)-one at C-5 was performed in two steps. Treatment with concentrated nitric acid affords 6-methyl-4-(nitroamino)pyridazin-3(2f/)-one whose rearrangement in concentrated sulfuric acid led to the formation of 4-amino-6-methyl-5-nitropyridazin-3(2/0-one <2001RJ01026>. 

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