Tetrazolo pyridazines

Nitriles are formed by irradiation of several types of compounds the tetrazolo-pyridazines (60) give two nitriles ... 

When chloro compounds are treated with sodium azide in ethanol or aqueous acetone the corresponding azides or tetrazolo[l,5-6]pyridazines are obtained. For example, 3-azido-and 4-azido-pyridazine 1-oxides are obtained from the corresponding chloro compounds ... 

The aza-transfer reaction between 3-hydrazinopyridazines and aromatic diazonium salts or heterocyclic diazo compounds affords the corresponding tetrazolo[l,5-6]pyridazines, while 3-hydrazinopyridazine 1-oxide gives 3-azidopyridazine 1-oxide (76TL3193, 76X725). 

A kinetic study of thermolysis reactions of TV-crotyl substituted 1,2,4-triazoles was performed at temperatures in the range of 260-350 CC <00JHC1135>. Thermolysis of tetrazolo[l, 5- >]pyridazines, tetrazolo[l,5-a]pyrimidines and tetrazolo[l,5-a]pyridines allowed easy ring contraction to a facile preparation of cyanopyrazole heterocycles . 

Thorough nuclear magnetic resonance (NMR) investigations of some tetrazolo[l,5-/7]pyridazines and tetrazolo[l,5- J-pyrazine-7-oxides have been carried out by Cmoch et al. <1999MRC493, 2003MRC693>. Comparison of 13C and 1SN NMR chemical shifts of the ring atoms are shown in Table 1. 

Table 1 Comparison of 13C and 15N NMR shifts of the ring atoms of some tetrazolo[1,5-b]pyridazines and tetrazolo[1,5-a]-pyrazine-7-oxides...

Matrix isolation photolytic studies on tetrazolo[l,5- ]pyridazine 25 have been reported by Hill and Platz <2003PCP1051> (Scheme 5) and formation of the l-cyano-3-diazopropene 27, triazacycloheptatetraene 28, and cyano-cyclopropene 29 was detected. Upon the absence of electron spin resonance absorptions at 7 K, the authors concluded that triplet nitrene was not formed but, instead, the resulting singlet nitrene rapidly underwent further ring openings. 

Thus, unsubstituted, 6-propyl- and 5,7-dimethyl tetrazolo[l,5-tf]pyrimidines 29, 30, and 31, respectively, as well as unsubstituted 6-methoxy- and 6-phcnyltctrazolo[ 1,5-/r]pyridazines 32-34, when heated at ambient temperature (close to their melting points), gave rise to the correspondingly substituted jV-cyanopyrazolcs 35-40 in medium to good yields. 

Deeb et al. described <2003H(60)1873> a series of transformations of an ester substituent of a tetrazolo[l,5- ]-pyridazine derivative 82 (Scheme 15). 

Since the publication of CHEC(1984) <1984CHEC(2)1>, the use of NMR seriously expanded. The majority of the full papers now published contain NMR spectroscopic data. Unfortunately, this is usually only for characterization of the synthesized compounds and no interpretation of the data is provided. In CHEC-II(1996) <1996CHEC-II(6)1>, a representative and very useful table with assigned shifts of simple pyridazines and pyridazin-3(2/7)-ones was published. Phthalazin-l(27/)-ones were also briefly mentioned. As an extension we here summarize some assigned NMR data of bicyclic derivatives [l,2,4]triazolo[4,3- ]pyridazines and tetrazolo[l,5- ]-pyridazines (Table 2 and Figure 3), and isoxazolo[3,4-, pyridazin-7(6//)-ones (Table 3 and Figure 4). 

Table 2 H, and NMR values of 6-substituted [1,2,4]triazolo[4,3-fa]pyridazines and tetrazolo[1,5-fa]pyridazines...

Photolysis (245 nm) of tetrazolo[l,5-/ ]pyridazine 21 in an argon matrix at 16 K leads to nitrogen extmsion and ring opening to form (2Z)-4-diazobut-2-enenitrile 22. Further photolysis produces predominantly cycloprop-2-ene-1-carbonitrile 23 and small amounts of l,3,7-triazacyclohepta-l,2,4,6-tetraene 24. No formation of triplet pyrid-azine-3-nitrene 25 is observed (Scheme 5) <2003PCP1051>. 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

Man erhalt so aus der entsprechenden C-Azido-Verbindung z. B. 6-Amino- ( 100%) und 6-Amino-7,8-dimethyl [Pg.1133]

Reduction of tetrazolo[ 1,5- >]pyridazine (274) by sodium borohydride results in the partial reduction of the pyridazine moiety (tetrahydro compound 275 was formed) (76JHC835). The catalytic reduction of the substituted tetrazolo[ 1,5- >]pyrimidine (276) afforded the diaminopyrimidine derivative (277) (85MIP155606). 

One final interesting preparation of this ring system involves the reaction of the tetrazolo[l,5-6]pyridazine (174) with polyphosphoric acid to give 7-azido-4H-pyrimido[l,2-6]pyridazin-4-one (175). This reaction involves azido-tetrazolo valence isomerization, which has been studied in other heterocyclic systems (71JHC1055). 

The parent 1,2,3-triazepine 1 was suggested as a possible product of a gas-phase photolysis of tetrazolo[l,5-3]-pyridazine 5 <2003PCP1051> these authors further discussed the geometry of multiple electronic states for 5 under photolytic conditions. 

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