Pyridazine hydroxy

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... 

Pyridazino[4,5-d]pyridazine, hydroxy-IR spectra, 3, 333 methylation, 3, 343 tautomerism, 3, 333... 

When epichlorohydrin is used for the cyclization reaction with piperidazine or tetrahydro-pyridazine, hydroxy derivatives (408) and (40 ) are formed, respectively (Scheme 89) <81BRP2105707, 92BMC1293>. 

Pyridazines with a hydroxy group at an a- or y-position to a ring nitrogen atom, i.e. 3-and 4-hydroxypyridazines (4) and (5), exist predominantly in the oxo form. This conclusion is based on spectroscopic evidence from UV spectra of unsubstituted compounds and their A-methyl and O-methyl derivatives in alkaline, neutral and acidic solutions. In some instances, as for example for 6-oxo-l,6-dihydropyridazine-3-carboxamide, there is also evidence from X-ray analysis <54AX199, 63AX318). Maleic hydrazide and substituted maleic hydrazides exist in the monohydroxymonooxo form (6). 

IV-Oxidation of 3,6-dialkoxypyridazines (OMe, OEt, OPr", OBu") gives monoxides, while 3,6-di-r-butoxy- and 3,6-dibenzyloxy-pyridazine cannot be IV-oxidized, but give 6-hydroxy-pyridazin-3(2/f)-one and 6-benzyloxypyridazin-3(2//)-one as hydrolysis products. Methyl-thiopyridazines give both 5-oxidation and IV-oxidation products with various oxidizing agents in some instances. 

Amino groups in pyridazine A-oxides can be diazotized and the diazonium group further replaced by halogens, hydroxy group or hydrogen. So, 3-, 4-, 5- and 6-bromopyridazine 1-oxides can be prepared from the corresponding amino A-oxides. 

When 6-amino-3-chloropyridazine 1-oxide is diazotized in 50% sulfuric acid, 6-hydroxy-3-pyridazinediazonium anhydro salt is formed. An azido group at either position in pyridazine A-oxides can readily be replaced with sodium alkoxides. 

In pyridazin-3(2//)-one only the hydrogen at position 6 is replaced at 180 °C, while in 3-hydroxypyridazine 1-oxide the deuterium exchange takes place first at position 6 and then at position 4 at 140 °C. 5-Hydroxy- and 5-methoxy-pyridazine 1-oxide exchange only the hydrogen at position 6 at 150 °C. 

Because of the electron-attracting properties of the ring nitrogen atoms, methyl groups undergo aldol-like condensations. For example, 3- and 4-methylpyridazine react with chloral to give 3- or 4-(2-hydroxy-3,3,3-trichloropropyl)pyridazine, and 4-methylpyridazine reacts with anisaldehyde to yield 4-(p-methoxystyryl)pyridazine. 

The UV spectra of pyrido[2,3-d]pyridazine-l,4-diones have been recorded (68MI21501), whilst several of the latter were also used in chemiluminescence studies. Quinolinic and cinchomeronic hydrazides showed no chemiluminescence (60NKK173, 37JPR(148)135), but it was observed in the 8-hydroxy derivative (305) (72YZ703). 

Pyrazino[2,3-d]pyridazin-8-one, 5-chloro-synthesis, 3, 347 Pyrazino[l, 2-a]pyrimidine reactions, 3, 350 structure, 3, 339-340 synthesis, 3, 256, 365 Pyrazino[ 1,2-a]pyrimidine, 2-hydroxy-alkylation, 3, 351... 

Both pK and ultraviolet spectral data indicate that 3- and 4-mono-hydroxy-pyridazines and -cinnolines exit predominantly in the oxo... 

Ratio of the Oxo Form to the Hydroxy Form (pKr) for 3- AND 4-Monohydroxy-pyridazines and -cinnolines... 

On boiling the methiodide with 70% sulfuric acid an N-methyl-oxo derivative was obtained, and this in turn gave 3-amino-2-phenyl-quinoline, methylamine, and ammonia on fusion with soda lime. The bulk of the evidence therefore favors quaternization at N-2 (cf, 154), in which case the acid-hydrolysis product is 155. Quaternization at N-2 would be expected because of the steric influence of the 10-phenyl group and the influence of the 4-amino group (cf. 4-hydroxy-pyridazine ) in the pyridazine-type ring, although the partial double-bond character of that ring is probably different from that in pyridazine itself. 

The intramolecular cyclization of 2-alkynylaryldiazonium salts (Richter reaction) leads not only to 4-hydroxy- but also to 4-bromo- and 4-chlorocinnolines. The behavior of alkynylpyrazolediazonium chlorides differs from that of their benzene analogs. The Richter reaction of the series of alkynylaminopyrazoles gives only 4-halo derivatives of l//-pyrazolo[3,4-c]pyridazines and l//-pyrazolo[4,3-c] pyridazines, and mainly hydroxy derivatives of 2//-pyrazolo[3,4-c]pyridazines. 

Likewise, l-[4-methylbenzyl]-4,7-dihydroxy-l,2,3-triazolo[4,5-d]pyridazine 275 reacts with phenylhydrazine, HMDS 2, and (NH4)2S04 to give the monoamino product 276 in 60% yield [83]. Reaction of l-benzyl-3-n.-butyl-4-hydroxy-l,2,3-triazo-lo[4,5-d]-pyrimidine 277 for 8 h at 120°C with cyclopentylamine, HMDS 2, and (NH4)2S04 affords the aminated product 278 in 49% yield [84] (Scheme 4.33). 

The coupling of enals and glyoxals was realized by hydrogen-mediated reaction with the cationic Rh complex and PI13P [35]. The intermediate aldehyde enolates derived via Rh-catalyzed hydrogenation were trapped with glyoxals to form (l-hydroxy-y-kclo-aldchydes, which were treated sequentially with hydrazine to give pyridazines in a one-pot transformation to provide, for example, a 62% yield of 72 (Scheme 21). 

---