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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 transition vectors of (a) TS1 (the first-step transition state, Figure 4) and (b) TS2 (the second-step transition state, Figure 7).
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ijms-16-12174-f009: The transition vectors of (a) TS1 (the first-step transition state, Figure 4) and (b) TS2 (the second-step transition state, Figure 7).

Mentions: Concomitantly with the N–C bond formation, a double proton transfer mediated by the AA molecule occurs, so that the resultant tetrahedral intermediate is a gem-diol species having two OH groups on the same carbon atom. This may be seen from the transition vector (i.e., the vibrational mode corresponding to the imaginary frequency) of TS1 shown in Figure 9a and interatomic distances of RC, TS1, and IC1 shown in Table 1. More specifically, the NH hydrogen moves toward the C=O oxygen of AA, the OH hydrogen of AA moves toward the carboxyl C=O oxygen of phthalanilic acid, and the single and double bonds are interchanged in the COO moiety of AA. The AA molecule thus acts as both proton donor and acceptor in the double proton transfer. The bond reorganization in the first step can be represented as Figure 10. In the resultant intermediate complex IC1, the newly-formed AA molecule forms two hydrogen bonds to the intermediate molecule. One is between the amide nitrogen in the five-membered ring and the OH hydrogen of AA (1.899 Å); the other is between the C=O oxygen of AA and the hydrogen of the newly-formed OH on the five-membered ring (1.778 Å).


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 transition vectors of (a) TS1 (the first-step transition state, Figure 4) and (b) TS2 (the second-step transition state, Figure 7).
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-12174-f009: The transition vectors of (a) TS1 (the first-step transition state, Figure 4) and (b) TS2 (the second-step transition state, Figure 7).
Mentions: Concomitantly with the N–C bond formation, a double proton transfer mediated by the AA molecule occurs, so that the resultant tetrahedral intermediate is a gem-diol species having two OH groups on the same carbon atom. This may be seen from the transition vector (i.e., the vibrational mode corresponding to the imaginary frequency) of TS1 shown in Figure 9a and interatomic distances of RC, TS1, and IC1 shown in Table 1. More specifically, the NH hydrogen moves toward the C=O oxygen of AA, the OH hydrogen of AA moves toward the carboxyl C=O oxygen of phthalanilic acid, and the single and double bonds are interchanged in the COO moiety of AA. The AA molecule thus acts as both proton donor and acceptor in the double proton transfer. The bond reorganization in the first step can be represented as Figure 10. In the resultant intermediate complex IC1, the newly-formed AA molecule forms two hydrogen bonds to the intermediate molecule. One is between the amide nitrogen in the five-membered ring and the OH hydrogen of AA (1.899 Å); the other is between the C=O oxygen of AA and the hydrogen of the newly-formed OH on the five-membered ring (1.778 Å).

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