1.2.4.5- Tetrazines, 3,6-diaryl-, reaction with

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. 

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... 

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 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>. 

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]. 

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). 

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>. 

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... 

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. 

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). 

Displacement of Sulphur. The Wittig reaction of resonance-stabilized phosphorus ylides with thioacyl-urethanes gives acylated enamines, e.g. (84), from which )ff-keto-esters are obtained by hydrolysis. Hydrazine displaces sulphur in thioanilides, giving amidrazones, but with two equivalents of arylselenoamides it gives 2,5-diaryl-1,3,4-selenadiazoles. Selenoamides react with an excess of hydrazine to give 1,2,4,5-tetrazines (see also Chap. 6, p. 294). l,2-Bis(thio-benzamido)ethane, when treated with NEt, and HgO, cyclizes to 2-phenyl-... 

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