Capture of benzotriazole-based Mannich electrophiles by CH-acidic compounds

Monbaliu, Jean‐Christophe M.; Beagle, Lucas K.; Hansen, Finn K.; Stevens, Christian V.; McArdle, Ciarán B.; Katritzky, Alan R.

doi:10.1039/c3ra22826f

“…Nucleophilic attack by an organometallic reagent into a transient 1-N-ethylidenepiperazinium has a literature precedent, but nucleophilic attack into the more sterically congested 1-N-propylidenepiperazinium intermediate by an alkynyl Grignard reagent is presented here for the first time. Four potential synthetic routes were identified including Katritzky benzotriazole trapping of an iminium (Monbaliu et al, 2013;Ingram et al, 2006;Katritzky, 1998;Katritzky et al, 1989Katritzky et al, , 1991Katritzky et al, , 2005Katritzky & Rogovoy, 2003;Katritzky & Saczewski, 1990), a Bruylants (Bruylants, 1924) trapping of an iminium, sequential addition of two methyl groups into an amide, and rearrangement to the gem-dimethyl group. All in-house attempts at the Katritzky benzotriazole (Tang et al, 2013;Pierce et al, 2012;Albaladejo et al, 2012) or triazole (Prashad et al, 2005) reactions failed.…”

Section: Chemical Contextmentioning

confidence: 99%

Crystal structure of tert-butyl 4-[4-(4-fluorophenyl)-2-methylbut-3-yn-2-yl]piperazine-1-carboxylate

Gumireddy

¹

,

DeBoyace

²

,

Rupprecht

³

et al. 2021

Acta Cryst E

1

0

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The title sterically congested piperazine derivative, C20H27FN2O2, was prepared using a modified Bruylants approach. A search of the Cambridge Structural Database identified 51 compounds possessing an N-tert-butyl piperazine substructure. Of these only 14 were asymmetrically substituted on the piperazine ring and none with a synthetically useful second nitrogen. Given the novel chemistry generating a pharmacologically useful core, determination of the crystal structure for this compound was necessary. The piperazine ring is present in a chair conformation with di-equatorial substitution. Of the two N atoms, one is sp 3 hybridized while the other is sp 2 hybridized. Intermolecular interactions resulting from the crystal packing patterns were investigated using Hirshfeld surface analysis and fingerprint analysis. Directional weak hydrogen-bond-like interactions (C—H...O) and C—H...π interactions with the dispersion interactions as the major source of attraction are present in the crystal packing.

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Crystalline 2π Aromatic Azadiboriridinylium: A BN Analogue of Cyclopropenylium Cation

Zhu,

Kinjo

2023

Angewandte Chemie

0

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N‐Substitution of a thermally unstable diboratriazole 1 with a trimethylsilyl group affords a remarkably stable diboratriazole derivative 2. Ring contraction of 2 with an N‐heterocyclic carbene accompanied by the release of N2 as well as 1,4‐hydrogen shift affords a carbene‐stabilized azadiboriridine 3. Abstraction of the H−B3mem hydride in 3 with methyl trifluoromethanesulfonate leads to the isolation of a hitherto unknown azadiboriridinylium 4, the first BN analogue of cyclopropenylium cation. X‐ray diffraction analysis and computational studies confirmed the delocalization of π electrons over the B2N three‐membered ring, indicating the 2π aromatic feature. Compound 4 undergoes ring expansion reactions with azobenzene and pyridazine to furnish triazadiborolidinylium species 5 and 6, the latter of which possesses a cationic B2N3 ring with a pronounced 6π aromatic property. Moreover, the reaction of 4 with a diazo compound produces a cationic B2N3C pentafulvene derivative 7.

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Crystalline 2π Aromatic Azadiboriridinylium: A BN Analogue of Cyclopropenylium Cation

Zhu,

Kinjo

2023

Angew Chem Int Ed

3

0

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N‐Substitution of a thermally unstable diboratriazole 1 with a trimethylsilyl group affords a remarkably stable diboratriazole derivative 2. Ring contraction of 2 with an N‐heterocyclic carbene accompanied by the release of N2 as well as 1,4‐hydrogen shift affords a carbene‐stabilized azadiboriridine 3. Abstraction of the H−B3mem hydride in 3 with methyl trifluoromethanesulfonate leads to the isolation of a hitherto unknown azadiboriridinylium 4, the first BN analogue of cyclopropenylium cation. X‐ray diffraction analysis and computational studies confirmed the delocalization of π electrons over the B2N three‐membered ring, indicating the 2π aromatic feature. Compound 4 undergoes ring expansion reactions with azobenzene and pyridazine to furnish triazadiborolidinylium species 5 and 6, the latter of which possesses a cationic B2N3 ring with a pronounced 6π aromatic property. Moreover, the reaction of 4 with a diazo compound produces a cationic B2N3C pentafulvene derivative 7.

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Capture of benzotriazole-based Mannich electrophiles by CH-acidic compounds

Abstract: The Mannich-type capture reaction of aminoalkylbenzotriazoles by CH acidic compounds is documented. The pK a of the benzotriazole counteranion is key to the success of such reactions, whereas the global electrophilicity of the reactive iminium moiety is secondary.

Cited by 3 publications

References 50 publications

Crystal structure of tert-butyl 4-[4-(4-fluorophenyl)-2-methylbut-3-yn-2-yl]piperazine-1-carboxylate

Crystal structure of tert-butyl 4-[4-(4-fluorophenyl)-2-methylbut-3-yn-2-yl]piperazine-1-carboxylate

Crystalline 2π Aromatic Azadiboriridinylium: A BN Analogue of Cyclopropenylium Cation

Crystalline 2π Aromatic Azadiboriridinylium: A BN Analogue of Cyclopropenylium Cation

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