The ‘inverse electron-demand' Diels–Alder reaction in polymer synthesis. Part 4.1 The preparation and crystal structures of some bis(1,2,4,5-tetrazines)

Abstract

Reaction of 3,6-bis(3,5-dimethylpyrazolyl)-1,2,4,5-tetrazine with mono-and di-amines gives rise to nucleophilic substitution of one or both of the pyrazolyl substituents, and reaction with diamines under appropriate conditions can lead to bis(3-amino-1,2,4,5-tetrazines), e.g. 12a, 12b and 13. The crystal structures of two of these (12a and 13) show electronic interaction between the tetrazine rings and the amino groups, but none between the tetrazine and pyrazole rings. In 12a there is an extensive network of N᎐H ؒ ؒ ؒ N hydrogen bonds.

Six‐Membered Heterocycles: Triazines, Tetrazines and Other Polyaza Systems

“…Inverse electron demand Diels-Alder reaction of 1,2,4,5-tetrazines are well known in the literature. Cycloadditions with electron-rich alkynes [759,762,774,776,[781][782][783][784][785][786][787][788] or alkenes [602,762,772,773,781,784,[789][790][791][792] Zhou et al have described an alternative Diels-Alder route to the well-known C,C cycloaddition (Carboni-Lindsey reaction). Quantum mechanical calculations showed that N,N cycloaddition of alkenes and alkynes to s-tetrazines is possible.…”

“…The electron-deficient aromatic ring of tetrazine and its reactivity towards nucleophiles have been utilized in the preparation of non-symmetrically substituted tetrazines by substitution of leaving groups, such as chloro [770,771], methylthio [770,[772][773][774][775] or dimethylpyridazolyl [755,757,776,777] with nitrogen, oxygen or sulfur nucleophiles. The use of carbon nucleophiles, such as organolithium or Grignard reagents, with 3,6-disubstituted 1,2,4,5-tetrazines 368 led to the addition of an organic group onto a ring nitrogen atom to afford 1,4-dihydrotetrazines 369 [778] (Scheme 20.109).…”

Unusual Expansion of the 1,2,4,5‐Tetrazine Ring in [1,2,4]Triazolo[4,3‐b][1,2,4,5]tetrazines Leading to [1,2,4,6]Tetrazepine Systems

“…The reactions of [1,2,4]triazolo [4,3-b] [1,2,4,5]tetrazines with nucleophilic reagents have so far been scarcely investigated. It has been reported that the 3,5-dimethylpyrazolyl substituents in [1,2,4]triazolo [4,3-b] [1,2,4,5]tetrazines can easily be displaced with aliphatic amines or alcohols.…”

“…[1][2][3][4][5][6][7] Also, some carbon modifications of 1,2,4,5-tetrazines due to displacement reactions with anhydro bases of quinaldinium salts [8] and heterocyclic carbenes [9] or by cross-coupling reactions with arylboronic acids [10] and acetylenes [11] have been reported. There are also examples where instead of nucleophilic substitution reactions at C-3 or C-6, azaphilic addition [12,13] or [4+2]cycloaddition reactions [8,14] have been observed to give rise to the corresponding 1,4-dihydrotetrazines or pyridazine derivatives, respectively.…”

Synthesis and alkylation of some [1,2,4]triazolo[4,3-b]tetrazines

“…The product distribution was interpreted on the basis of quantum chemical calculations. The triazolotetrazinium salts (9,10a-b) were found to dealkylate on workup to give the corresponding tetrafluoroborate salts (7,8). …”