1,2-Pyridazines. reduction

In the course of probing the range of reactivity accessible to decamethyl-samarocene, substrates containing C=N double bonds as part of 6-membered heterocycles have been tested. In the reaction with pyridazine reductive carbon-carbon bond formation occurred (compare Sect. 3.2) [99], The coupled ligand bridges two Sm(III) centers via the four nitrogen positions. In the phenazine reaction one phenazine ligand is placed between the Sm(III) centers (Fig. 20 Table 16) [203]. 

Eeduction with sodium and ethanol has been used in the synthesis of hexahydropyridazine which is obtained together with 1,4-diaminobutane. Similarly, reduction of 3-(p-tolyl)-pyridazine gave besides the corresponding hexahydropyridazine also a substituted pyrrolidine. 3,6-Dimethylpyridazine, when reduced in this way, can give its dihydro or hexahydro analog.In all other cases of pyridazine reductions, no dihydro- and tetrahydropyridazines have been isolated, probably on account of their more ready reduc-ibility compared to aromatic pyridazines. 

Reduction of nitroaminopyridazines yields the corresponding aminopyridazines. Reductive cleavage of hydrazinopyridazines to give amino compounds is of practical significance in cases when halogen atoms are resistant to ammonolysis. Many substituted 3,4-diamino-, 4,5-diamino- and 3,5-diamino-pyridazines can be prepared in this way. 

Few reactions of this type are recorded. The azidopyridazinone ester (349) on reduction with triethyl phosphite, hydrazine or borohydride furnished the pyrido[2,3-c]pyridazin-7-one (350) (79JHC1559), whilst an A-aminopyrido[2,3-c]pyridazine (352) resulted from the... 

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... 

A further example of an azo coupling reaction with an activated methylene compound (12.91), followed by ring closure to give a pyridazine derivative (12.92) in good yield (66%) was decribed by Gewald and Hain (1984). The reductive treatments of 12.92 give the pyrrole compounds 12.93 and 12.94 in 70% yield (Scheme 12-45). 

Compound 248 treated with (EtOhP in refluxing xylene provides an 89% yield of 19 (Equation 37) <2005AGE7089>. Similarly, [l,2,3]triazolo[4,5- /]pyridazine 249 provided a 68% yield of the corresponding mesomeric betaine 250 (Equation 38). However, reductive cyclizations of the analogous 3-(2-nitrophenyl)-377-[l,2,3]triazolo[4,5-//Jpyrimidine, 3-(3-nitropyridin-2-yl)-3//-[l,2,3]triazolo[4,5-. 

A study of the a-arylation of diazine mono iV-oxides, under Heck-like conditions, also gave emphasis to pyrazines but a number of examples using pyrimidines and pyridazines were also described (Scheme 1). A wide range of aryl chlorides, bromides and iodides was used and the products were easily deoxygenated by catalytic reduction. An interesting feature was the use of a copper additive, which was only required for the pyrimidine reactions, to give a very substantial improvement in yield <06AG(I)7781>. 

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). 

To corroborate the proposed mechanism, the catalytic reductive aldol coupling of acrolein with phenyl glyoxal monohydrate was performed under 1 atmos. elemental deuterium. Exposure of the aldol product to excess hydrazine in situ results in formation of the pyridazine, which incorporates precisely one deuterium atom in a manner consistent with the general mechanism proposed in Scheme 22.4 (Scheme 22.9). 

The electroreductive hydrogenation of pyridazine-3-ones performed at the first wave, in acidic or basic medium, takes place at the 4,5-double bond. A further reduction of 4,5- dihydropyridazin-3-ones in basic media, affords the corresponding tetrahydro derivatives (Scheme 139) [252]. 

When the hydrochloride salt of 2,3,4,4a,5,6-hexahydro-l//-pyridazino [1,6-a]quinoline was subjected to catalytic hydrogenation in ethanol over Pt02, 3-[2-(l,2,3,4-tetrahydroquinolyl)]propylamine was obtained (66YZ608). Catalytic reduction of perhydropyrido[l,2-ft]pyridazine over a skeletal nickel catalyst in ethanol at 30 atm gave ring-opened 2-(3-aminopropyl)piperidine (66KGS91). 

Perhydropyrido[l,2-6]pyridazine was prepared from perhydropyrido [l,2-fc]pyridazin-2-one by reduction with LAH (65MI1, 65URP170506 66KGS91 78JA4012), and from 4,4a,5,6,7,8-hexahydro-3//-pyrido[l,2-b] pyridazine by catalytic reduction over Pt02 in acetic acid (68YZ216). Re-... 

Reduction of 2-methyl-4-phenyl-3//-pyrido[l,2-Z)]pyridazin-3-one (44) with NaBH4 in ethanol afforded the 5,6,7,8-tetrahydro derivative [76JCS(CC)275 78JOC2892],... 

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