ChemInform Abstract: ORGANOBORON COMPOUNDS. CCCXVIII. ON THE PROBLEM OF THE AROMATIC CHARACTER OF BORON HETEROCYCLIC COMPOUNDS

Mikhaĭlov, B. M.; Kuimova, M. E.

doi:10.1002/chin.197645313

Cited by 2 publications

(4 citation statements)

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“…Because there is little variation in the 11 B NMR resonance (<1 ppm), this behavior may be attributable to the intractable dimerization (reversible B–O–B anhydride formation) observed with related heterocycles . Remarkably, it was found possible to isolate the tetramethylammonium salt of the conjugate bases of 2a and 2b as hygroscopic solids from organic solvent (toluene/methanol), and these anionic species display upfield 11 B NMR chemical shifts (DMSO- d 6 : 1.3 ppm for 2a , 2.4 ppm for 2b ), in full agreement with a Lewis basic structure (i.e., 2a - I / 2b - I) (see Supporting Information). Consistent with their predicted high p K a , according to 1 H and 11 B NMR these anionic species cleanly revert to their acid form 2a and 2b when exposed to a pH 13.5 solution (H 2 O/CH 3 CN, 1:1) (see Figures S88, S89).…”

Section: Resultsmentioning

confidence: 74%

“…In our hands, back-titration of a high-pH sample to a neutral pH and analysis by both 1 H and 11 B NMR spectroscopy reproduced these findings and confirmed that 2a and 2b observed with related heterocycles. 37 Remarkably, it was found possible to isolate the tetramethylammonium salt of the conjugate bases of 2a and 2b as hygroscopic solids from organic solvent (toluene/methanol), 38 and these anionic species display upfield 11 B NMR chemical shifts (DMSO-d 6 :…”

Section: Journal Of Thementioning

confidence: 99%

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Lewis or Brønsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles

et al. 2021

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Boron-containing heterocycles are important in a variety of applications from drug discovery to materials science; therefore a clear understanding of their structure and reactivity is desirable to optimize these functions. Although the boranol (B−OH) unit of boronic acids behaves as a Lewis acid to form a tetravalent trihydroxyborate conjugate base, it has been proposed that pseudoaromatic hemiboronic acids may possess sufficient aromatic character to act as Brønsted acids and form a boron oxy conjugate base, thereby avoiding the disruption of ring aromaticity that would occur with a tetravalent boronate anion. Until now no firm evidence existed to ascertain the structure of the conjugate base and the aromatic character of the boron-containing ring of hemiboronic "naphthoid" isosteres. Here, these questions are addressed with a combination of experimental, spectroscopic, X-ray crystallographic, and computational studies of a series of model benzoxazaborine and benzodiazaborine naphthoids. Although these hemiboronic heterocycles are unambiguously shown to behave as Lewis acids in aqueous solutions, boraza derivatives possess partial aromaticity provided their nitrogen lone electron pair is sufficiently available to participate in extended delocalization. As demonstrated by dynamic exchange and crossover experiments, these heterocycles are stable in neutral aqueous medium, and their measured pK a values are consistent with the ability of the endocyclic heteroatom substituent to stabilize a partial negative charge in the conjugate base. Altogether, this study corrects previous inaccuracies and provides conclusions regarding the properties of these compounds that are important toward the methodical application of hemiboronic and other boron heterocycles in catalysis, bioconjugation, and medicinal chemistry.

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Section: Resultsmentioning

confidence: 74%

Section: Journal Of Thementioning

confidence: 99%

Lewis or Brønsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles

et al. 2021

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“…Another NMR study of 4 and 5a and other related heterocycles was reported by Mikhailov and Kuimova in 1976. 23 By comparing the 11 B chemical shifts of these boron heterocycles with those of the acyclic analogs, the authors concluded that the central boron-containing ring of both 4 and 5a was nonaromatic; additionally, 4 and 5a were concluded to be Lewis acids in hydroxylic solvents, behaving as very weak Brønsted acids only in anhydrous organic solvents (e.g., upon the addition of n-BuLi, both were alleged to form the hydrolytically unstable boroxide B−OLi 24 ). Interestingly, 5a formed a tetravalent Lewis base through a reaction with Me 4 NOH (but not NH 4 OH) in benzene−methanol and other nonaqueous solvents (e.g., ethanol and DMSO), but no such anionic species were observed when 5a was reacted with KOH in water.…”

Section: ■ Resultsmentioning

confidence: 99%

“…Another NMR study of 4 and 5a and other related heterocycles was reported by Mikhailov and Kuimova in 1976 . By comparing the 11 B chemical shifts of these boron heterocycles with those of the acyclic analogs, the authors concluded that the central boron-containing ring of both 4 and 5a was nonaromatic; additionally, 4 and 5a were concluded to be Lewis acids in hydroxylic solvents, behaving as very weak Brønsted acids only in anhydrous organic solvents ( e.g.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Silent Hydrolysis of Cyclic B–X/C═C Isosteres: The Striking Impact of a Single Heteroatom on the Aromatic, Acidic, and Dynamic Properties of Hemiboronic Phenanthroids

et al. 2022

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Although heterocyclic hemiboronic acids are represented in several recently approved drugs, many questions remain unanswered regarding the physical properties and reactivity of these boranol (BOH)-containing compounds in aqueous media. Over the past 60 years, studies on the acidic and aromatic character of 10-hydroxy-10,9-boroxarophenanthrene and its boraza analog have been conflicting. In contradiction with the Lewis acidic behavior of arylboronic acids in aqueous conditions, it has been proposed that the central boroheterocyclic ring of these borophenanthroids confers sufficient aromatic character to compel the boranol unit to behave as a Brønsted acid and favor the boron oxy conjugate base, thereby avoiding the disruption of cyclic resonance that would otherwise occur with a tetravalent boronate anion. These questions are addressed with a combination of physical and spectroscopic characterizations, X-ray crystallographic analysis, and computational studies. Although both oxa and aza derivatives are conclusively shown to behave as Lewis acids in aqueous solutions, according to pK a measurements and MO and NICS calculations, only the boraza derivatives possess an appreciable aromatic character within the boroheterocyclic ring. For the first time, the possibility of dynamic chemical exchange via a reversible hydrolysis of the endocyclic B–heteroatom bond was examined using VT and EXSY NMR with suitable probe compounds. Whereas the boraza analog is static at neutral pH, its oxa analog undergoes a rapid hydrolytic ring opening–closing equilibrium with the transient boronic acid. Altogether, this study will guide the methodical application of these heterocycles as reaction catalysts, in bioconjugation, and as new-drug chemotypes and bioisosteres of pharmaceutically important classes of heterocycles.

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ChemInform Abstract: ORGANOBORON COMPOUNDS. CCCXVIII. ON THE PROBLEM OF THE AROMATIC CHARACTER OF BORON HETEROCYCLIC COMPOUNDS

Abstract: Untersucht wird die Fähigkeit zur Salzbildung von Borheterocyclen, wobei 10‐Hydroxy‐10,9‐borazarophenanthren und 10‐Hydroxy‐10,9‐boroxarophenanthren keine nennenswerten Unterschiede zeigen.

Cited by 2 publications

References 1 publication

Lewis or Brønsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles

Lewis or Brønsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles

Unraveling the Silent Hydrolysis of Cyclic B–X/C═C Isosteres: The Striking Impact of a Single Heteroatom on the Aromatic, Acidic, and Dynamic Properties of Hemiboronic Phenanthroids

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