Synthesis of 1,2,3-Triazines Using the Base-Mediated Cyclization of (<i>Z</i>)-2,4-Diazido-2-alkenoates

Sugimura, Hideyuki; Takeuchi, Reika; Ichikawa, Shiori; Nagayama, Eri; Sasaki, Ikuo

doi:10.1021/acs.orglett.8b01445

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…Although no synthesis of a monocyclic 1,2,3,5-tetrazine as a 6π aromatic system has been reported, limited numbers of heterocyclic compounds bearing the 1,2,3,5-tetrazine core have been disclosed (Figure B). − The nonaromatic 1,2,3,5-tetrazine core ( 3 ) was synthesized as part of fused heterocycles in the development of energetic materials, monocyclic tetrazinones have been described that were prepared by a 6π-electrocyclization of acyclic triazene isocyanate precursors, and the synthesis of a library of ring-fused bicyclic tetrazinones has been reported, of which a derivative (temozolomide, 4 ) is used clinically . The methods used in this work for the construction of the core ring system as well as those used for the preparation of 1,2,3-triazines , provided valuable insights into the possible synthesis of aromatic 1,2,3,5-tetrazines. With even their stable existence in question, we explored several approaches for their synthesis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cycloaddition Reactivity of a Monocyclic Aromatic 1,2,3,5-Tetrazine

Boger

2019

J. Am. Chem. Soc.

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Herein we disclose the synthesis and full characterization of the first monocyclic aromatic 1,2,3,5-tetrazine, 4,6-diphenyl-1,2,3,5-tetrazine. Initial studies of its cycloaddition reactivity, mode, regioselectivity, and scope illustrate that it participates as the 4π-component of well-behaved inverse electron demand Diels−Alder reactions where it preferentially reacts with electron-rich or strained dienophiles. It was found to exhibit an intrinsic reactivity comparable to that of the isomeric 3,6diphenyl-1,2,4,5-tetrazine, display a single mode of cycloaddition with reaction only across C4/N1 (no N2/N5 cycloaddition observed), proceed with a predictable regioselectivity (dienophile most electron-rich atom attaches to C4), and manifest additional reactivity complementary to the isomeric 1,2,4,5-tetrazines. It not only exhibits a remarkable cycloaddition reactivity, surprisingly good stability (e.g., stable to chromatography, long-term storage, presence of H 2 O even as reaction co-solvent), and broad cycloaddition scope, but it also displays powerful orthogonal reactivity with the 1,2,4,5-tetrazines. Whereas the latter reacts at extraordinary cycloaddition rates with strained dienophiles (tetrazine ligation), the new and isomeric 1,2,3,5-tetrazine displays similarly remarkable cycloaddition rates and efficiencies with amidines (1,2,3,5-tetrazine/amidine ligation). The crossover reactivities (1,2,4,5-tetrazines with amidines and 1,2,3,5-tetrazines with strained dienophiles) are sufficiently low to indicate they may be capable of use concurrently without competitive reactions.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cycloaddition Reactivity of a Monocyclic Aromatic 1,2,3,5-Tetrazine

Boger

2019

J. Am. Chem. Soc.

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“…This protocol was performed under the mild basic conditions in the absence of transition metals to afford the desired product (Scheme 81). [132] …”

Section: Six Membered Heterocycles Having Three Nitrogen Atoms (Triaz...mentioning

confidence: 99%

Recent advances in the synthesis of five‐ and six‐membered heterocycles as bioactive skeleton: A concise overview

et al. 2022

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Heterocyclic compounds play a tremendous role in the field of medicinal chemistry due to their association with diverse pharmacological properties. Most of the pharmaceutical drugs used in medicines possess a wide range of heterocyclic nucleus. It was decided basis on literature studies that various synthetic protocols like microwave‐assisted, nanocatalysed, green synthesis, click reaction, and multicomponent routes could be used for the betterment of the purity of products, selectivity, and better yields of the products. We have focused attention on the development of synthetic strategies of the above‐mentioned moieties because N‐, O‐ and S‐ containing heterocyclic compounds have seemed owing to a wide diversity of their biological activities viz. antioxidant, anticancer, anticonvulsant, anti‐inflammatory, neuroprotective, antiproliferative, anti‐obesity, antihyperglycemic, antihypercholesteroler, antiulcer, antidiabetic, antileishmanial, antitrypanosomal, antibiotic, etc. In this review article, an overview of the applications of synthetic protocols for the preparation of five‐membered and six‐membered heterocyclic compounds containing two or more heteroatoms (O, N, S) at different‐different positions along with their different potent and competent candidates against various diseases is presented in last 10–15 years.

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“…Triazine rings are aza‐aromatic scaffolds that can be distinguished from each other by the positions of their nitrogen atoms; different forms of triazines are referred to as 1,3,5‐triazines, [10] 1,2,4‐triazines, [11] and 1,2,3‐triazines [12–14] . In contrast to 1,3,5‐ and 1,2,4‐triazines, 1,2,3‐triazines have not been as thoroughly investigated because their electron‐deficient ring system is considered to be the least stable [15] .…”

Section: Introductionmentioning

confidence: 99%

“…Triazine rings are aza-aromatic scaffolds that can be distinguished from each other by the positions of their nitrogen atoms; different forms of triazines are referred to as 1,3,5triazines, [10] 1,2,4-triazines, [11] and 1,2,3-triazines. [12][13][14] In contrast to 1,3,5-and 1,2,4-triazines, 1,2,3-triazines have not been as thoroughly investigated because their electron-deficient ring system is considered to be the least stable. [15] Boger and coworkers systematically investigated the cycloaddition reactions of 1,2,3-triazines with various amine-related dienophiles and provided new perspectives into the synthesis of heterocycle-containing natural products.…”

Section: Introductionmentioning

confidence: 99%

Copper‐Mediated Synthesis of (E)‐β‐Aminoacrylonitriles from 1,2,3‐Triazine and Secondary Amines

et al. 2022

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We describe a simple protocol for the synthesis of (E)‐β‐aminoacrylonitriles via Cu(OAc)2‐mediated nucleophilic addition of secondary amines to 1,2,3‐triazine 1 and an aerobic oxidation reaction. The reactions, which were studied with a broad substrate scope, are effective with cyclic, heterocyclic, aliphatic, allylic, and benzylic amines as well as l‐proline derivatives. The reactions use catalytic Cu(OAc)2 to promote 1,2,3‐triazine addition with various secondary amines, followed by in situ loss of nitrogen and subsequent imine oxidation to generate the corresponding (E)‐β‐aminoacrylonitriles in good yields with excellent stereoselectivities. These copper(II)‐mediated aerobic oxidation reactions proceed under mild reaction conditions by oxidation of the Cu(II) species using molecular oxygen to complete the cycle without the participation of ligand, base or chemical oxidant additives.

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Synthesis of 1,2,3-Triazines Using the Base-Mediated Cyclization of (Z)-2,4-Diazido-2-alkenoates

Cited by 18 publications

References 31 publications

Synthesis, Characterization, and Cycloaddition Reactivity of a Monocyclic Aromatic 1,2,3,5-Tetrazine

Synthesis, Characterization, and Cycloaddition Reactivity of a Monocyclic Aromatic 1,2,3,5-Tetrazine

Recent advances in the synthesis of five‐ and six‐membered heterocycles as bioactive skeleton: A concise overview

Copper‐Mediated Synthesis of (E)‐β‐Aminoacrylonitriles from 1,2,3‐Triazine and Secondary Amines

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