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Computational study of demethylation of nitrogen-containing veratrole derivatives using BBr₃ : challenges and prospects. / Aksenova, O. D.; Martynenko, P. A.
In: Computational and Theoretical Chemistry, Vol. 1266, 116080, 12.2026.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Computational study of demethylation of nitrogen-containing veratrole derivatives using BBr₃
T2 - challenges and prospects
AU - Aksenova, O. D.
AU - Martynenko, P. A.
N1 - O.D. Aksenova, P.A. Martynenko, Computational study of demethylation of nitrogen-containing veratrole derivatives using BBr₃: challenges and prospects, Computational and Theoretical Chemistry, Volume 1266, 2026, 116080, ISSN 2210-271X, https://doi.org/10.1016/j.comptc.2026.116080.
PY - 2026/12
Y1 - 2026/12
N2 - Boron tribromide is widely used for dealkylation of aryl methyl ethers, but its mechanism remains unclear for substrates containing several Lewis-basic sites. Here, BBr₃-mediated demethylation of veratrole and nitrogen-containing veratrole derivatives was studied by DFT calculations at the B3LYP/def2-TZVP level with PCM solvent correction. Three pathways were compared: cationic intermediate formation, boron diester formation, and cyclic boron ester formation. The electronic nature of substituents strongly affects intermediate stability: amino groups stabilize cationic species, whereas the thiadiazole fragment destabilizes them. However, cyclic boron ester formation is thermodynamically favored for all studied substrates. Kinetic analysis of 5,6-dimethoxy-2,1,3-benzothiadiazole shows that double demethylation involving two BBr₃ molecules has a high activation barrier, while the cyclic pathway is more accessible. Hydrolysis is proposed to begin with water coordination to boron, followed by bromine substitution or ring opening. These results highlight cyclic boron ester intermediates as key species in BBr₃-mediated demethylation.
AB - Boron tribromide is widely used for dealkylation of aryl methyl ethers, but its mechanism remains unclear for substrates containing several Lewis-basic sites. Here, BBr₃-mediated demethylation of veratrole and nitrogen-containing veratrole derivatives was studied by DFT calculations at the B3LYP/def2-TZVP level with PCM solvent correction. Three pathways were compared: cationic intermediate formation, boron diester formation, and cyclic boron ester formation. The electronic nature of substituents strongly affects intermediate stability: amino groups stabilize cationic species, whereas the thiadiazole fragment destabilizes them. However, cyclic boron ester formation is thermodynamically favored for all studied substrates. Kinetic analysis of 5,6-dimethoxy-2,1,3-benzothiadiazole shows that double demethylation involving two BBr₃ molecules has a high activation barrier, while the cyclic pathway is more accessible. Hydrolysis is proposed to begin with water coordination to boron, followed by bromine substitution or ring opening. These results highlight cyclic boron ester intermediates as key species in BBr₃-mediated demethylation.
KW - Benzothiadiazole
KW - Boron halides
KW - Demethylation
KW - Kinetics
KW - Reaction pathway
KW - Галогениды бора
KW - Деметилирование
KW - Бензотиадиазол
KW - Кинетика
KW - Схема реакции
UR - https://www.mendeley.com/catalogue/1a28a0e9-899e-338b-87dc-2a673d176a3d/
UR - https://www.scopus.com/pages/publications/105052654294
U2 - 10.1016/j.comptc.2026.116080
DO - 10.1016/j.comptc.2026.116080
M3 - Article
VL - 1266
JO - Computational and Theoretical Chemistry
JF - Computational and Theoretical Chemistry
SN - 2210-271X
M1 - 116080
ER -
ID: 83869857