Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study
The influence of steric repulsion between the NMe<sub>2</sub> group and a second <i>ortho</i>-(<i>peri</i>-)substituent in the series of 1-dimethylaminonaphthalene and <i>N</i>,<i>N</i>-dimethylanilene <i>ortho</i>-oximes on the...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/24/5977 |
| _version_ | 1797544414291165184 |
|---|---|
| author | Alexander S. Antonov Elena Yu Tupikina Valerii V. Karpov Valeriia V. Mulloyarova Victor G. Bardakov |
| author_facet | Alexander S. Antonov Elena Yu Tupikina Valerii V. Karpov Valeriia V. Mulloyarova Victor G. Bardakov |
| author_sort | Alexander S. Antonov |
| collection | DOAJ |
| description | The influence of steric repulsion between the NMe<sub>2</sub> group and a second <i>ortho</i>-(<i>peri</i>-)substituent in the series of 1-dimethylaminonaphthalene and <i>N</i>,<i>N</i>-dimethylanilene <i>ortho</i>-oximes on the ease of the NMe<sub>2</sub> group’s intramolecular nucleophilic substitution is studied. Possible reaction intermediates for three mechanisms are calculated (ωB97xd/def-2-TZVP), and their free Gibbs energies are compared to model reaction profiles. Supporting experiments have proved the absence of studied reactivity in the case of simple 2-dimethylaminobenzaldoxime, which allowed us to establish reactivity limits. The significant facilitation of NMe<sub>2</sub> group displacement in the presence of bulky substituents is demonstrated. The possibility of fused isoxazoles synthesis via the intramolecular nucleophilic substitution of a protonated NMe<sub>2</sub> group in the aniline and naphthalene series is predicted. |
| first_indexed | 2024-03-10T14:00:10Z |
| format | Article |
| id | doaj.art-863ad433cfce4aaeaa5eedd3c256aad1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:00:10Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-863ad433cfce4aaeaa5eedd3c256aad12023-11-21T01:12:33ZengMDPI AGMolecules1420-30492020-12-012524597710.3390/molecules25245977Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical StudyAlexander S. Antonov0Elena Yu Tupikina1Valerii V. Karpov2Valeriia V. Mulloyarova3Victor G. Bardakov4Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, RussiaInstitute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, RussiaInstitute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, RussiaInstitute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, RussiaInstitute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, RussiaThe influence of steric repulsion between the NMe<sub>2</sub> group and a second <i>ortho</i>-(<i>peri</i>-)substituent in the series of 1-dimethylaminonaphthalene and <i>N</i>,<i>N</i>-dimethylanilene <i>ortho</i>-oximes on the ease of the NMe<sub>2</sub> group’s intramolecular nucleophilic substitution is studied. Possible reaction intermediates for three mechanisms are calculated (ωB97xd/def-2-TZVP), and their free Gibbs energies are compared to model reaction profiles. Supporting experiments have proved the absence of studied reactivity in the case of simple 2-dimethylaminobenzaldoxime, which allowed us to establish reactivity limits. The significant facilitation of NMe<sub>2</sub> group displacement in the presence of bulky substituents is demonstrated. The possibility of fused isoxazoles synthesis via the intramolecular nucleophilic substitution of a protonated NMe<sub>2</sub> group in the aniline and naphthalene series is predicted.https://www.mdpi.com/1420-3049/25/24/5977nucleophilic substitutionheterocyclizationisoxazolequantum chemical calculations |
| spellingShingle | Alexander S. Antonov Elena Yu Tupikina Valerii V. Karpov Valeriia V. Mulloyarova Victor G. Bardakov Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study Molecules nucleophilic substitution heterocyclization isoxazole quantum chemical calculations |
| title | Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study |
| title_full | Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study |
| title_fullStr | Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study |
| title_full_unstemmed | Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study |
| title_short | Sterically Facilitated Intramolecular Nucleophilic NMe<sub>2</sub> Group Substitution in the Synthesis of Fused Isoxazoles: Theoretical Study |
| title_sort | sterically facilitated intramolecular nucleophilic nme sub 2 sub group substitution in the synthesis of fused isoxazoles theoretical study |
| topic | nucleophilic substitution heterocyclization isoxazole quantum chemical calculations |
| url | https://www.mdpi.com/1420-3049/25/24/5977 |
| work_keys_str_mv | AT alexandersantonov stericallyfacilitatedintramolecularnucleophilicnmesub2subgroupsubstitutioninthesynthesisoffusedisoxazolestheoreticalstudy AT elenayutupikina stericallyfacilitatedintramolecularnucleophilicnmesub2subgroupsubstitutioninthesynthesisoffusedisoxazolestheoreticalstudy AT valeriivkarpov stericallyfacilitatedintramolecularnucleophilicnmesub2subgroupsubstitutioninthesynthesisoffusedisoxazolestheoreticalstudy AT valeriiavmulloyarova stericallyfacilitatedintramolecularnucleophilicnmesub2subgroupsubstitutioninthesynthesisoffusedisoxazolestheoreticalstudy AT victorgbardakov stericallyfacilitatedintramolecularnucleophilicnmesub2subgroupsubstitutioninthesynthesisoffusedisoxazolestheoreticalstudy |