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Acetic Acid-catalyzed formation of N-phenylphthalimide from phthalanilic Acid: a computational study of the mechanism.

Takahashi O, Kirikoshi R, Manabe N - Int J Mol Sci (2015)

Bottom Line: Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor.The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor.In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. ohgi@tohoku-pharm.ac.jp.

ABSTRACT
In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

No MeSH data available.


Related in: MedlinePlus

The geometry of IC2, the intermediate complex directly connected to TS2 (the second-step transition state shown in Figure 7). Selected interatomic distances are shown in Å. Also shown are the definitions of interatomic distances i–p.
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ijms-16-12174-f006: The geometry of IC2, the intermediate complex directly connected to TS2 (the second-step transition state shown in Figure 7). Selected interatomic distances are shown in Å. Also shown are the definitions of interatomic distances i–p.

Mentions: Figure 1 shows the MP2/6-31G(d,p) energy diagram for the acetic acid-catalyzed, two-step formation of N-phenylphthalimide from phthalanilic acid, and Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7 and Figure 8 show optimized geometries. All relative energies reported in the present work correspond to the electronic energy and are corrected for the zero-point vibrational energy (ZPE). Interatomic distances showing bond reorganizations in the first and second steps are tabulated in Table 1 and Table 2, respectively.


Acetic Acid-catalyzed formation of N-phenylphthalimide from phthalanilic Acid: a computational study of the mechanism.

Takahashi O, Kirikoshi R, Manabe N - Int J Mol Sci (2015)

The geometry of IC2, the intermediate complex directly connected to TS2 (the second-step transition state shown in Figure 7). Selected interatomic distances are shown in Å. Also shown are the definitions of interatomic distances i–p.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490437&req=5

ijms-16-12174-f006: The geometry of IC2, the intermediate complex directly connected to TS2 (the second-step transition state shown in Figure 7). Selected interatomic distances are shown in Å. Also shown are the definitions of interatomic distances i–p.
Mentions: Figure 1 shows the MP2/6-31G(d,p) energy diagram for the acetic acid-catalyzed, two-step formation of N-phenylphthalimide from phthalanilic acid, and Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7 and Figure 8 show optimized geometries. All relative energies reported in the present work correspond to the electronic energy and are corrected for the zero-point vibrational energy (ZPE). Interatomic distances showing bond reorganizations in the first and second steps are tabulated in Table 1 and Table 2, respectively.

Bottom Line: Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor.The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor.In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. ohgi@tohoku-pharm.ac.jp.

ABSTRACT
In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

No MeSH data available.


Related in: MedlinePlus