37813-54-0Relevant articles and documents
Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding
Zhu, Zixi,Glinkerman, Christopher M.,Boger, Dale L.
supporting information, p. 20778 - 20787 (2020/12/22)
An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.
Cesium carbonate-promoted synthesis of aryl methyl sulfides using: S -methylisothiourea sulfate under transition-metal-free conditions
Zhang, Caiyang,Zhou, You,Huang, Jintao,Tu, Canhui,Zhou, Xiaoai,Yin, Guodong
, p. 6316 - 6321 (2018/09/10)
In the presence of cesium carbonate, an efficient synthesis of aryl methyl sulfides by the reactions of aryl halides with commercially available S-methylisothiourea sulfate is developed. This odourless and highly crystalline solid can be used as the subst
Regioselective Inverse Electron Demand Diels-Alder Reactions of N-Acyl 6-Amino-3-(methylthio)-1,2,4,5-tetrazines
Boger, Dale L.,Schaum, Robert P.,Garbaccio, Robert M.
, p. 6329 - 6337 (2007/10/03)
The regioselective inverse electron demand Diels-Alder reactions of 6-[(tert-butyloxycarbonyl)-amino]-3-(methylthio)-1,2,4,5-tetrazine (2), 6-(acetylamino)-3-(methylthio)-1,2,4,5-tetrazine (3), and 6-(benzyloxycarbonyl)amino-3-(methylthio)-1,2,4,5-tetrazine (4) are disclosed. All three underwent regioselective [4 + 2] cycloaddition with electron-rich dienophiles to form the corresponding functionalized 1,2-diazines in excellent yields. An order of reactivity with electron-rich dienophiles was observed with both 2 and 3 being more reactive than 3,6-bis(methylthio)-1,2,4,5-tetrazine (1, i.e. 3 > 2 > 1), and both 3 and 4 were shown to be more robust than 2 at the higher temperatures necessary for [4 + 2] cycloaddition with less reactive dienophiles. The cycloaddition regioselectivity is consistent with the polarization of the diene and the ability of the methylthio group to stabilize a partial negative charge at C-3, and the N-acylamino group to stabilize a partial positive charge at C-6. While intermolecular reactions of unactivated alkynes either did not proceed or required high temperatures and long reaction times, intramolecular Diels-Alder reactions utilizing tethered unactivated acetylenes led to five- and six-membered bicyclic 1,2-diazines under mild conditions.
Inverse Electron Demand Diels-Alder Reactions of 3,6-Bis(methylthio)-1,2,4,5-tetrazine: 1,2-Diazine Introduction and Direct Implementation of a Divergent 1,2,4,5-Tetrazine--->1,2-Diazine--->Benzene (Indoline/Indole) Diels-Alder Strategy
Boger, Dale L.,Sakya, Subas M.
, p. 1415 - 1423 (2007/10/02)
A full investigation of the scope of the participation of 3,6-bis(methylthio)-1,2,4,5-tetrazine (6) in cycloaddition reactions is detailed.The use of the resulting 3,6-bis(methylthio)-1,2-diazine cycloadducts as direct precursors to the parent 4,5
