Analysis of the Nitration Process of Trifluoromethoxybenzene Based on Density Functional Theory (DFT) Calculations

doi:10.6023/cjoc202511003

Abstract

The nitration products of trifluoromethoxybenzene (TFMB) are important chemical intermediates, and widely used in the synthesis of pharmaceuticals, pesticides, and functional materials. The efficient preparation and clear elucidation of their reaction mechanisms are of significant guiding importance for the optimization of related industries. The nitration of aromatic compounds is essentially a typical electrophilic aromatic substitution (EAS) reaction. To explore the intrinsic nature of the EAS reaction of TFMB in the mixed acid system, density functional theory (DFT) was employed to perform simulation calculations and analyses on the process at the M06-2X/6-311＋G** theoretical level. The results show that the electrochemical potential difference between TFMB and the actual nitrating agent NO＋2 is 6.28 eV, indicating a good electron transfer capability. Analyses of average local ionization energy (ALIE) and electrostatic potential (ESP) reveal that the para position is the optimal site for electrophilic attack. Thermodynamic calculations demonstrate that the reaction enthalpies for the formation of ortho-, meta-, and para-nitrotrifluoromethoxybenzene are －97.3, －122.2, and －127.6 kJ/mol, respectively, with all Gibbs free energy changes being negative. The reaction follows a two-step mechanism, with the energy barrier of the rate-determin- ing step ranging from 16.7 kJ/mol to 32.6 kJ/mol. The para reaction pathway exhibits the lowest energy barrier, followed by the ortho pathway, while the meta pathway accounts for the smallest proportion due to its highest energy barrier and the instability of the intermediate, which is consistent with experimental results. This study not only clarifies the microscopic mechanism and regulatory rules of the nitration reaction of TFMB, but also provides an important theoretical basis for the design and optimization of nitration reactions of similar aromatic compounds.

Key words: trifluoromethoxybenzene (TFMB), nitration reaction mechanism, density functional theory (DFT), electrophilic aromatic substitution (EAS), nitronium (NO₂⁺)

Cite this article

Fan Zhang, Song Guo, Weicheng Yang, Jigang Zhao, Yong Luo. Analysis of the Nitration Process of Trifluoromethoxybenzene Based on Density Functional Theory (DFT) Calculations[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2121-2128.

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Compd.	μ/eV	η/eV	ω/eV	N/eV
NO₂⁺	－10.04	11.17	4.51	－5.68
TFMB	－3.76	6.71	1.05	2.05
C₆H₆	－3.46	6.78	0.88	2.29

Compd.	μ/eV	η/eV	ω/eV	N/eV
NO₂⁺	－10.04	11.17	4.51	－5.68
TFMB	－3.76	6.71	1.05	2.05
C₆H₆	－3.46	6.78	0.88	2.29

Compd.	ε_ele/a.u.	ZPE/a.u.	H(0)/a.u.	H(T)/a.u.	S/(J∙mol^－1∙K^－1)	G(T)/a.u.
TFMB	－644.5139	0.1069	－644.4069	－644.3973	386.137	－644.4411
HNO₃	－280.8910	0.0263	－280.8647	－280.8603	265.052	－280.8904
H₂O	－76.4320	0.0208	－76.4111	－76.4073	188.644	－76.4288
3	－849.0093	0.1100	－848.8994	－848.8873	436.349	－848.9368
4	－849.0185	0.1096	－848.9089	－848.8968	440.178	－848.9467
5	－849.0206	0.1097	－848.9109	－848.8988	436.040	－848.9483

Compd.	ε_ele/a.u.	ZPE/a.u.	H(0)/a.u.	H(T)/a.u.	S/(J∙mol^－1∙K^－1)	G(T)/a.u.
TFMB	－644.5139	0.1069	－644.4069	－644.3973	386.137	－644.4411
HNO₃	－280.8910	0.0263	－280.8647	－280.8603	265.052	－280.8904
H₂O	－76.4320	0.0208	－76.4111	－76.4073	188.644	－76.4288
3	－849.0093	0.1100	－848.8994	－848.8873	436.349	－848.9368
4	－849.0185	0.1096	－848.9089	－848.8968	440.178	－848.9467
5	－849.0206	0.1097	－848.9109	－848.8988	436.040	－848.9483

Reaction	Δ_rH/(kJ∙mol^－1)	ΔS/(J∙mol^－1∙K^－1)	Δ_rG/(kJ∙mol^－1)
Reaction 1	－97.3	－26.2	－89.5
Reaction 2	－122.2	－22.5	－115.5
Reaction 3	－127.6	－26.8	－119.6

基于密度泛函理论(DFT)计算的三氟甲氧基苯硝化反应过程分析