Our previous research showed that aliphatic amines were put in order of high reactivit y as “ethylamine > ammonia > t-butylamine > diethylamine” on the aromatic nucleophilic substitution of 1-dimetylamino-2,4-bis(trifluoroacetyl)-naphthalene 1 in acetonitrile. The DFT calculation study (B3LYP/6-31G* with solvation model) for the reactions of 1 with above four amines rationally explained the difference of each amines reactivity based on the energies of their Meisenheimer complexes 3 which are assumed to formed as the reaction intermediates in the course of the reaction giving the corresponding N-N exchange products 2. Intramolecular hydrogen bond between amino proton in 1-amino group and carbonyl oxygen in 2-trifluoroacetyl group stabilizes Meisenheimer complexes 3 effectively, and accelerates the substitution reaction from 1 to 2. Our calculation results also predicted that the above order of amines is also true if less polar toluene is used as a solvent instead of acetonitrile even though more enhanced conditions are required.
In our previous research, we found that dimethylamino group on naphthalene system activated by two trifluoroacetyl groups is easily substituted with various nucleophiles, even though such substituent is commonly understood to have a poor leaving-group ability [
Therefore, these situations prompted us to demonstrate the DFT calculation (RB3LYP/6-31G*) study on the reaction of 1 with the above four kinds of amines to have led to an interesting outcome rationalizing the reaction rate order of the four amines. Moreover, we discuss an elucidation of the solvent effect on the present substitution by making use of C-PCM model calculation.
First, we calculated the optimized structure of 1-dimetylamino-2,4-bis(trifluoroacetyl)- naphthalene 1 which is the key substrate of the present nucleophilic substitution. In
Scheme 1. The reaction of 1-dimetylamino-2,4-bis(trifluoroacetyl)naphthalene 1 with amines.
Scheme 2. The substitution pathway from 1 to N-N exchanged products 2.
within the margin of error, from ones estimated by the simple DFT calculations without using solvation model. The Meisenheimer complexes 3a-c have intramolecular hydrogen bond between amino proton and carbonyl oxygen in 2-trifluoroacetyl group respectively, but 3d does not due to the absence of amino proton. In respect to these hydrogen bonds, in
Energy diagrams of the present substitution course from 1-dimetylamino-2,4- bis(trifluoroacetyl)naphthalene 1 to the corresponding N-N exchanged products 2a-d are depicted in
Compound | E (au.) | ||
---|---|---|---|
Solv.: Nonea | Acetonitrile | Toluene | |
1 3a 3b 3c 3d | −1420.55312 −1555.19499 −1476.57275 −1633.81209 −1633.79469 | −1420.56579 −1555.26133 −1476.64055 −1633.87740 −1633.86033 | −1420.55988 −1555.23358 −1476.61229 −1633.84997 −1633.83274 |
a. Simple DFT calculation results without using solvation model.
the solvation models. The energy values of
We also calculated ΔE1 about the reaction in toluene. As shown in
The ΔE1 values in toluene predict that the order of amines on the substitution rate in toluene is the same as the one in acetonitrile. Differences of ΔE1 values between the reactions in toluene and the corresponding ones in acetonitrile are summarized in
Nucleophile | Process | ΔE1 (kcal/mol) | ||
---|---|---|---|---|
Solv.: Nonea | Acetonitrile | Toluene | ||
EtNH2 NH3 t-BuNH2 Et2NH | 1 à 3a 1 à 3b 1 à 3c 1 à 3d | 101.8 114.4 105.6 109.1 | 7.2 10.1 16.7 20.9 | 45.8 52.2 53.1 57.0 |
a. Simple DFT calculation results without using solvation model.
Nucleophile | Process | ΔE1 (kcal/mol) | ΔE1(toluene) − ΔE1(acetonitrile) (kcal/mol) | |
---|---|---|---|---|
Solv.: Toluene | Acetonitrile | |||
EtNH2 NH3 t-BuNH2 Et2NH | 1 à 3a 1 à 3b 1 à 3c 1 à 3d | 45.8 52.2 53.1 57.0 | 7.2 10.1 16.7 20.9 | 38.6 42.1 36.4 36.1 |
proton in addition to the other one which is used for intramolecular hydrogen bond (
The unexpected order of the reaction rate (ethylamine > ammonia > t-butylamine > diethylamine) on the aromatic nucleophilic substitution of 1-dimetylamino-2,4-bis(trifluoroacetyl)naphthalene 1 with nucleophiles (ammonia and three kinds of aliphatic amine) giving the corresponding N-N exchanged products 2 is rationalized by the energy changes for forming the corresponding Meisenheimer complexes 3, i.e. the rate determining step of the present substitution reaction. These energy changes are closely correlated with the relative stabilities of 3 under the reaction conditions. Intramolecular hydrogen bond between amino proton in 1-amino group and carbonyl oxygen in 2-trifluoroacetyl group stabilizes Meisenheimer complexes 3 effectively, and accelerates the substitution reaction from 1 to 2, consequently. Our calculation results also predict that the above order of amines is also true if less polar toluene is used as a solvent instead of acetonitrile even though more enhanced conditions are required.
All calculations employed in this paper were accomplished by making use of the computer programs packages PC SPARTAN 16 [
The authors declare no conflicts of interest regarding the publication of this paper.
Ota, N., Nakada, T., Shintani, T., Kamitori, Y. and Okada, E. (2018) Computational Study for the Aromatic Nucleophilic Substitution Reaction on 1-Dimethylamino-2,4-bis(trifluoroacetyl)- naphthalene with Amines. International Journal of Organic Chemistry, 8, 273-281. https://doi.org/10.4236/ijoc.2018.83020