3.6- Diaryl tetrazines

Sometimes tetrazine ring transformations lead to quite unexpected products.Thus, the reaction of 3,6-diaryl tetrazines 56 with 3-aminopyrrole 57 resulted in new heterocyclic ensemble 58 instead of the expected product 59 of normal cycloaddition (14TL5491). 

Although Cp Rh=NR compounds have not been isolated from reactions of [Cp RhCl2]2 with LiNHR an indication that Cp Rh=N(2,6-Pr2C6H3) exists for a short time at 0°C is the trapping reaction with mesityl azide, mesN3, which gives the A,A -diaryl tetrazine complex by a 1,3-dipolar cycloaddition 111... 

Mass spectra of 1,2,4,5-tetrazines are quite simple . The molecular ion loses Nj quickly with formation of ions of nitrile structure sometimes accompanied with (RCN - - H" ) and (RCN — H )ions. Diaryl tetrazines also show (M -t- 2) ions, probably by formation of 1,4-dihydro derivatives in the ion source. MS data of individual tetrazines are somewhat scattered in the experimental parts of publications dealing with 1,2,4,5-tetrazines and their reactions. 

The reaction of 3,6-diaryl-l,2,4,5-tetrazines (aryl = phenyl, 2-furyl or 2-thienyl) with 2 equivalents of Ru(acac)2(CH3CN)2 resulted in reductive tetrazine ring opening to yield diruthenium complexes <06IC821>. 

The conformation of a diaryl-dialkyl-hexahydro-l,2,4,5-tetrazine by X-ray crystallographic analysis has been reported for the first time <00SL137>. 

Alder/retrograde Diels-Alder reaction sequence of a diaryl alkyne with a 3,6-dicarbomethoxy tetrazine. The resulting diazine (14) is then reduced, cleaved and cyclized with Zn/acetic acid to the 2,3,4,5-tetrasubstituted pyrrole (15), which is then N-alkylated with a-bromo-4-methoxyacetophenone to give a pentasubstituted pyrrole (16). The synthesis of lukianol A is completed by ester hydrolysis, decarboxylation, ring closure and deprotection. 

Reaction of electron-deficient diaryl-1,2,4,5-tetrazine with Cgg may also be considered as a hetero-Diels-Alder reaction (Scheme 4.11) [82-84]. The initially formed Diels-Alder product undergoes a rapid retro-Diels-Alder reaction under loss of nitrogen, which renders the cycloaddition irreversible. The obtained diaryl-dihydropyridazine monoadducts are isolable but imstable and they react readily with water under the influence of light to afford a 1,4-hydrogenated product [82]. 

Diphenyl-l,2,4,5-tetrazin wird beim Erhitzen mit Salzsaure oder ethanolischer Kalilauge zu 2,5-Diphenyl-J, 3,4-oxadiazol und 3,6-Diphenyl-],4-dihydro-tetrazin umgewandelt558. Fiihrt man diese Reaktion mit Peressigsaure und Natriumacetat bei 50-60 durch, so erhalt man meist ausschliefilich 2,5-Diaryl-l, 3,4-oxadiazole559 ... 

Reaction of aldehydes with hydrazine, or mono- or 1,2-disubstituted hydrazines is the method used almost exclusively for the preparation of hexahydro-l,2,4,5-tetrazines (377). All types of hydrazines have been used hydrazine itself, monoalkyl-, monoaryl-, dialkyl-, diaryl-, alkylaryl-, alkylacyl- or arylacyl-hydrazines. The aldehydes used were mainly aliphatic aldehydes. An excellent review by Wiley of the literature on this reaction up to 1974 is available (78HC(33)1075, p. 1190). 

The kinetics and mechanism of the dechlorination of /V-aryl 2-oxo-2-phenylamino-ethanehydrazonyl chlorides (89) in triethylamine in aqueous dioxane at 25 °C giving the oxanilic hydrazide (91) and 1,4-diaryl-1,2,4,5-tetrazine (92) have been examined.80 The slow step of this interesting reaction is considered to be the breakup of the nitrilium imide (90). 

Although thermal decomposition of 2-trityl-5-aryltetrazoles 197 occurs specifically, the final result of the reaction may be ambiguous. For instance, these compounds on heating in benzonitrile give 3,6-diaryl-l,3,4,5-tetrazines 198. Apparently the N2 elimination in a polar solvent (benzonitrile) occurs with cleavage of triphenylmethane followed by dimerization of the intermediate arylnitrile imine (Equation 19) <2002RJ01360>. 

The conversion of diaryl-s- tetrazines into oxadiazoles is shown in Scheme 21. 

Diaryl-l,2,4,5-tetrazines, when treated with bulky amides such as lithium di-isopropylamide, undergo two competing reactions. In the first, tetrazine is reduced with concomitant formation of an imine from the amide. The imine is then attacked further by amide to give a pyridazine. For example, 3,6-diphenyl-l,2,4,5-tetrazine is converted with lithium diethylamide into 3,6-diphenylpyridazine in low yield. With lithium di-isopropylamide, 4-methyl-3,6-diphenylpyridazine is obtained in moderate yield [83JCS(P1)1601]. 

The mass spectra of 1,2,4,5-tetrazines 1 are very simple. In most cases a fragmentation to one molecule of nitrogen and two molecules of the appropriate nitriles was observed.190,373 In dialkyl-1,2,4,5-tetrazines protonated and deprotonated nitrile structures were also observed.195 In the spectra of 3,6-diaryl-l,2,4,5-tetrazines peaks at a mass unit [M+ +2] were observed, which were explained by the formation of diaryldihydro-l,2,4,5-tetrazines in the ion source.372... 

Two atypical reactions of tetrazines involve a dienatnine and a dihydropyridine. Acyclic diena-mines react with two molecules of 3,6-diaryl-l,2,4,5-tetrazines to give a mixture of 3,6-diaryl-pyridazines and the corresponding 4-dialkylamino derivatives (Scheme 112) reaction proceeds by cycloaddition to the terminal double bond and then to the enamine double bond by a second tetrazine to give the postulated intermediate (149), followed by loss of nitrogen and, finally, aromatization is achieved by an unusual carbon-carbon cleavage to give the two products <87H(26)337>. The expected inverse electron demand Diels-Alder reaction between the Ar-methyl-l,4-dihyropyridine (150) and... 

Diaryl-1,2,4,5-tetrazines react with diethylamine or triethylamine in the presence of oxidizing agents to form 3,6-diarylpyridazines <90KGS1545, 91Z0R1123> apparently an enamine is formed as an intermediate which reacts in the normal way with the tetrazine in a (4 -I- 2) cycloaddition. 

The synthesis of 1,4-diaryl-1,4-dihydro-1,2,4,5-tetrazines (255) can be achieved in good yield by the reaction between aryl-diazonium salts and phenacylidene dimethylsulphurane (254)... 

The crystal structures of six 3,6-diaryl-l,2,4,5-tetrazines have been determined and their molecular packing has been compared to the supramolecular architecture observed in related carboxylic acid dimers. In the tetrazines, covalent N-N bonds are considered to replace the intermolecular O-H- - -O hydrogen bonds of the carboxylic acids. In the system investigated, the covalent six-membered ring of the tetrazine was an appropriate replacement for the carboxylic acid synthon. This apparent interplay between molecular and supramolecular units may have applications in the crystal engineering of new materials (Figure 1) <2003HCA1205>. 

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