3.4 Cyclization of Dopamine Quinone Analogs
67
Table 3.3 Change in dihedral angles during C6−N cyclic bonding from initial state to transition
state (θ
‡
1 , θ
‡
2 , and θ
‡
3 )
Label
o-Quinone
θ
‡
1 (deg.)
θ
‡
2 (deg.)
θ
‡
3 (deg.)
(a)
Dopaminequinone
−31.7
−51.4
–
(b)
Dopaquinone
−23.9
−23.2
–
(c)
N-Methyl-dopaminequinone
−50.2
12.3
–
(d)
N-Formyl-dopaminequinone
−36.3
−3.6
–
(a )
Homo-dopaminequinone
−23.8
−6.9
−22.72
(b )
Homo-dopaquinone
−15.1
−5.0
−13.42
(c )
N-Methyl-homo-dopaminequinone
−19.6
−4.7
20.21
(d )
N-Formyl-homo-dopaminequinone
−27.9
−6.6
24.28
Next, we discuss the effects of α-carboxylation, N-methylation, and Nformylation of dopaminequinone on the potential energy profile along the cyclic
bond formation. The C6–N bond formation proceeds as the amino lone pair orbital
(mainly appeared as the HOMO) spreads toward the benzene ring (Fig. 3.17). In
this alteration of the orbital morphology, the amino lone pair is considered to move
to the 6-carbon, making the π electron density polarized toward a quinone oxygen,
4-oxygen. Such charge transfers were observed for all the cases (Fig. 3.18). Therefore, the nucleophilicity can be enhanced when the energy level of electron-donating
orbitals at the amino group such as the HOMO is up-shifted toward the vacuum level.
In order to confirm this behavior, the activation barriers and the cyclic bond formation energies of (a)–(d) were plotted with respect to the HOMO levels (Fig. 3.19).
The resulting plots demonstrate negative correlations between the activation/reaction
energy and the HOMO level, confirming our hypothesis. It should be noted that the
N-formylated cases were out of the linear relationship observed for the other cases.
This can be explained by considering the presence of N–C π bond between the amino
and the formyl group that must be broken with an additional energy during the cyclic
bond formation. As shown in the inset of Fig. 3.19, we also found a linear relation
between the activation energies and the cyclic bond formation energies, indicating
that both are determined by the nucleophilicity of the amino group. The relatively
high HOMO level of (b) dopaquinone and (c) N-methyl-dopaminequinone compared
with the others would be due to an antibonding interaction between the amino lone
pair orbital and the carboxyl π orbital, as can be seen in Figs. 3.17 and 3.20.
From the above discussion, we have pointed out that different substituent structures result in different HOMO levels, affecting the nucleophilicity. An up-shifted
HOMO level corresponds to an increased electron-donating ability from the lone
pair orbital, and then an enhanced nucleophilicity. To directly investigate the nucleophilicity, we calculated the condensed-to-atom Fukui indices for the o-quinone side
chains of (a)–(d). Table 3.4 lists the calculated results. Since Fukui function is defined
as the functional derivative of the (electronic) chemical potential with respect to the
external potential, a highly exo-energetic electron release can occur at the site having
67
Table 3.3 Change in dihedral angles during C6−N cyclic bonding from initial state to transition
state (θ
‡
1 , θ
‡
2 , and θ
‡
3 )
Label
o-Quinone
θ
‡
1 (deg.)
θ
‡
2 (deg.)
θ
‡
3 (deg.)
(a)
Dopaminequinone
−31.7
−51.4
–
(b)
Dopaquinone
−23.9
−23.2
–
(c)
N-Methyl-dopaminequinone
−50.2
12.3
–
(d)
N-Formyl-dopaminequinone
−36.3
−3.6
–
(a )
Homo-dopaminequinone
−23.8
−6.9
−22.72
(b )
Homo-dopaquinone
−15.1
−5.0
−13.42
(c )
N-Methyl-homo-dopaminequinone
−19.6
−4.7
20.21
(d )
N-Formyl-homo-dopaminequinone
−27.9
−6.6
24.28
Next, we discuss the effects of α-carboxylation, N-methylation, and Nformylation of dopaminequinone on the potential energy profile along the cyclic
bond formation. The C6–N bond formation proceeds as the amino lone pair orbital
(mainly appeared as the HOMO) spreads toward the benzene ring (Fig. 3.17). In
this alteration of the orbital morphology, the amino lone pair is considered to move
to the 6-carbon, making the π electron density polarized toward a quinone oxygen,
4-oxygen. Such charge transfers were observed for all the cases (Fig. 3.18). Therefore, the nucleophilicity can be enhanced when the energy level of electron-donating
orbitals at the amino group such as the HOMO is up-shifted toward the vacuum level.
In order to confirm this behavior, the activation barriers and the cyclic bond formation energies of (a)–(d) were plotted with respect to the HOMO levels (Fig. 3.19).
The resulting plots demonstrate negative correlations between the activation/reaction
energy and the HOMO level, confirming our hypothesis. It should be noted that the
N-formylated cases were out of the linear relationship observed for the other cases.
This can be explained by considering the presence of N–C π bond between the amino
and the formyl group that must be broken with an additional energy during the cyclic
bond formation. As shown in the inset of Fig. 3.19, we also found a linear relation
between the activation energies and the cyclic bond formation energies, indicating
that both are determined by the nucleophilicity of the amino group. The relatively
high HOMO level of (b) dopaquinone and (c) N-methyl-dopaminequinone compared
with the others would be due to an antibonding interaction between the amino lone
pair orbital and the carboxyl π orbital, as can be seen in Figs. 3.17 and 3.20.
From the above discussion, we have pointed out that different substituent structures result in different HOMO levels, affecting the nucleophilicity. An up-shifted
HOMO level corresponds to an increased electron-donating ability from the lone
pair orbital, and then an enhanced nucleophilicity. To directly investigate the nucleophilicity, we calculated the condensed-to-atom Fukui indices for the o-quinone side
chains of (a)–(d). Table 3.4 lists the calculated results. Since Fukui function is defined
as the functional derivative of the (electronic) chemical potential with respect to the
external potential, a highly exo-energetic electron release can occur at the site having