Chinese Journal of Chemical Physics  2020, Vol. 33 Issue (1): 48-52

#### The article information

Jun-hua Chen, Juan Wang, Gang Feng, Qian Gou

Rotational Spectra of 2, 3, 6-Trifluoropyridine: Effect of Fluorination on Ring Geometry
2, 3, 6-三氟吡啶的转动光谱：氟化对吡啶环结构的影响
Chinese Journal of Chemical Physics, 2020, 33(1): 48-52

http://dx.doi.org/10.1063/1674-0068/cjcp1910184

### Article history

Received on: October 22, 2019
Accepted on: November 10, 2019
Rotational Spectra of 2, 3, 6-Trifluoropyridine: Effect of Fluorination on Ring Geometry
Jun-hua Chen , Juan Wang , Gang Feng , Qian Gou
Dated: Received on October 22, 2019; Accepted on November 10, 2019
Department of Chemistry, School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China
Abstract: The ground state rotational spectrum of 2, 3, 6-trifluoropyridine has been investigated in the 2.0$-$20.0 GHz region by pulsed jet Fourier transform microwave spectroscopy. The experimental rotational constants are $A$ = 3134.4479(2) MHz, $B$ = 1346.79372(7) MHz, and $C$ = 941.99495(6) MHz. The transitions are so intense that rotational transitions of all mono-$^{13}$C and $^{15}$N isotopologues are measured in natural abundance. The semi-experimental equilibrium rotational constants of the 7 isotopologues were derived by taking account of the anharmonic vibrational corrections, which allowed a semi-experimental determination of the equilibrium structure of 2, 3, 6-trifluoropyridine.
Key words: 2, 3, 6-Trifluoropyridine    Fluorination    Semi-experimental structure    Rotational spectra
Ⅰ. INTRODUCTION

Fluorination of small organic compounds is one of the most common methods to alter their physiochemical characteristics and biological activities, which in some cases are substantially modified in comparison with their non-fluorinated counterparts [1]. For example, the modulation of acidity and lipohilicity, or the control of conformational bias, can be achieved by rational substitution of hydrogen atoms or functional groups by fluorine atoms. Fluorination can also dramatically impact the interaction topologies of other small molecules [3, 4], which can shed light on how fluorination affects the binding affinity and selectivity. Structural information at the molecular level is believed to be essential for understanding the fluorination effects. For this purpose, Fourier transform microwave (FTMW) spectroscopy associated with quantum calculations is especially suitable to describe the molecular geometries by interpreting the corresponding rotational spectra.

Rotational studies of pyridine (PY) [5-10] and its mono-/di-fluorinated derivatives [11-14] yield accurate descriptions of their structural information, which provides an interesting prototype to study the effect of fluorine substitution on the molecular geometry and electronic structure. These studies revealed that fluorination at the ortho position gives rise to a more pronounced deviation from the PY ring geometry with respect to the substitution at the meta position, which is in agreement with earlier ab initio calculations at various levels of theory [15-18]. In addition, the valence angles of the ring at the sites of fluorinations increase by a few degrees for each difluoropyridine (DFPY) with the exception of 23DFPY (less than one degree) with respect to PY. Meanwhile neighboring angles decrease to compensating this change.

Even with small alterations of geometries upon fluorination, the interaction topologies of PY fluorides with water can be quite different [19-22]. It would be interesting to find the border where the interaction topologies change upon multi-fluorination. The alteration on geometries and electronic structures with different fluorination would lay the ground for investigating the microsolvation system. With respect to 23DFPY and 26DFPY [14], we aim to investigate the rotational spectrum of 2, 3, 6-trifluoropyridine (236TFPY) with pulsed jet Fourier transform microwave technique, which is also the first step towards the investigation of 236TFPY-H$_2$O.

Ⅱ. EXPERIMENTS

Rotational spectra of 236TFPY were measured by using the highly integrated pulsed jet FTMW spectrometer [23] (of COBRA-type [24]) built at Chongqing University, covering 2.0$-$20.0 GHz frequency range and operated with the FTMW++ set of programs [25]. Helium at a backing pressure of about 0.2 MPa passed over the 236TFPY (97%, commercial product from Adamas-Beta used without further purification) and expanded through the solenoid valve (Parker-General Valve, Series 9, nozzle diameter 0.5 mm) into the Fabry-Pérot-type resonator. Each rotational transition displays a Doppler splitting that originates from the supersonic jet expanding coaxially along the resonator axis. The rest frequency of the transition line is calculated as the arithmetic mean of the frequencies of the two Doppler components. The bandwidth is 1 MHz, and the spectrum is automatically integrated by each step of 0.4 MHz. The estimated accuracy of the frequency measurements is better than 2 kHz. Lines separated by more than 5 kHz are resolvable.

The rotational spectra of mono-substituted $^{15}$N and $^{13}$C isotopologues were measured in natural abundance.

Ⅲ. THEORETICAL CALCULATIONS

To aid the rotational spectrum assignment, geometry optimization of 236TFPY has been performed at the B3LYP/6-311++G(2df, 2pd) level of theory by using the Gaussian09 program package [26]. The structure of 236TFPY is shown in FIG. 1, where the principal axes and the atom numbering are also indicated. The resulting spectroscopic parameters are summarized and listed in the first line of Table Ⅰ. The zero value of the inertial defect ($\Delta$ = $I_c $$-$$ I_a $$-$$ I_b$) indicates the planarity of 236TFPY. The dipole moment components are along $a$- and $b$-principal inertial axes ($\mu_a$ = 2.2 D and $\mu_b$ = 3.3 D).

 FIG. 1 Molecular structure of 236TFPY with the principal axes and atom numbering
Ⅳ. ROTATIONAL SPECTRA

Following the prediction from the model calculation, a scan has been first performed in the frequency region where the most intense $\mu_ \rm{b}$-type transitions would fall. It was easy to identify the R-branch family ($J$+1)$_{0, J+1} $$\leftarrow$$ J_{1, J}$ with $J$ = 2 to 10 based on their $^{14}$N ($I$ = 1) nuclear quadrupole hyperfine structure pattern, as shown in FIG. 2 for the 4$_{0, 4} $$\leftarrow 3 _{1, 3} transition. It was then possible to record more \mu_ \rm{b} -transitions, including some \mu_b -Q branch transitions, from which the rotational constants were well determined. Some less intense \mu_ \rm{a} -transitions, with rotational quantum number J ranging from 3 to 8 being afterwards measured.  FIG. 2 Recorded 4 _{04} -3 _{13} transition of 236TFPY showing the ^{14} N nuclear hyperfine structure (64 averages). Each line exhibits the Doppler doubling The measured transition frequencies were fitted with Pickett's SPFIT program [27], according to the following Hamiltonian:  \begin{eqnarray} H = H_{\rm{R}}+H_{\rm{CD}}+H_{\rm{Q}} \end{eqnarray} (1) where H_{\rm{R}} represents the rigid rotational parts of the Hamiltonian. The centrifugal distortion contributions (analyzed by using the A reduction and I^{\rm{r}} representation) [28] are represented by H_{\rm{CD}} . H_{\rm{Q}} is the operator associated with the ^{14} N nuclear quadrupolar interaction. The standard deviation was recalculated with the code PIFORM [29]. Experimental spectroscopic parameters obtained from a non-linear least squares fit are reported in the second line of Table Ⅰ. The experimental and theoretical rotational constants are in good agreement with the largest discrepancy of \sim 0.3%. Table Ⅰ Experimental and calculated (B3LYP/6-311++G(2df, 2pd)) spectroscopic parameters of 236TFPY (A reduction and Ir representation). After empirical scaling to the rotational constants of the parent species, the rotational spectra of the mono-substituted ^{15} N and ^{13} C isotopologues are possible to be measured and assigned in natural abundance. The transition lines of ^{15} N isotopologue are unsplit due to a ^{15} N nuclear spin quantum number I = 1/2. The obtained experimental spectroscopic parameters are reported in Table Ⅱ. As much fewer transitions were measured, the values of centrifugal distortion constants of the six minor isotopologues were fixed at those of parent species, respectively. Table Ⅱ Semi-experimental (SE) rotational constants (in unit of MHz) of 236TFPYa. All the measured transition frequencies are available in the supplementary materials. Ⅴ. SEMI-EXPERIMENTAL STRUCTURE Values of inertial defect ( \Delta ) of all isotopologues were calculated from the experimental rotational constants and reported in Tables Ⅰ and , respectively, which remain unchanged (all close to zero) upon the isotopic substitutions, as expected for a planar molecule. The small positive values of \Delta are typical for planar molecules when there is also the contribution from the vibrational motions in plane [30]. The semi-experimental rotational constants of all 7 isotopologues were calculated by taking account the vibrational corrections calculated from the B3LYP/6-311++G(2df, 2pd) anharmonic force field, and are reported in Table Ⅲ. A semi-experimental determination of the equilibrium structure ( r_{\rm{SE}} ) was then obtained by a least-squares fit with all the rotational constants being equally weighted [31]. The structural parameters of the heavy-atom frame of 236TFPY are reported in Table Ⅳ, with which the semi-experimental rotational constants were then well reproduced, with the largest discrepancy less than 0.003%. The substitution structures ( r_{\rm{s}} ) of the six heavy atoms are calculated from Kraitchman's equation [32] and summarized in Table Ⅳ, where also the corresponding B3LYP/6-311++G(2df, 2pd) calculated coordinates ( r_{\rm{e}} ) are given. To have an idea on the structural changes upon trifluorination, the same process was repeated for PY with previous reported rotational results [6], with the same atom numbering of the heavy atoms. The r_{\rm{e}} , r_{\rm{s}} , and r_{\rm{SE}} structures of PY are reported in Table Ⅳ. The r_{\rm{SE}} structure of PY with B3LYP/SNSD vibrational corrections [33] was also summarized in Table Ⅳ, where the parameters are in good agreement with this work. B3LYP/6-311++G(2df, 2pd) calculated full geometries of PY and 236TFPY are available in the supplementary materials. Table Ⅲ Semi-experimental (SE) rotational constants of 236TFPY. Table Ⅳ rs structures and semi-experimental equilibrium structures (rSE) of PY and 236TFPY. The trifluorination causes noticeable shrinking ( \sim 0.03 Å) of the bond length of N1 - C2 and N1 - C6 bonds. Such results are analogous to those of 2FPY [13], 23DFPY, and 26DFPY [14]. This is most likely due to the electron withdrawing of fluorines which leads to a disruption to the \pi system. Natural population analyses (NPA) on PY and 236TFPY were performed at the B3LYP/6-311++G(2df, 2pd) level of theory to elucidate the electronic transfer upon trifluorination. The charge distributions in PY and 236TFPY are graphically represented in FIG. 3. Trifluorination leads C2, C3, and C6 to be much more positive, while N1, C4, and C5 become slightly more negative. Consequently, the electrostatic attraction N1 \cdots C2, N1 \cdots C6, C3 \cdots C4, and C5 \cdots C6 increase to a certain degree, i.e. the bond lengths are shortened with respect to PY. The C2C3 and C4C5 bonds also show a little bit decrease which might be for the stability of the whole ring structure.  FIG. 3 Charge distributions in PY and 236TFPY The angles \angle N1C2C3 and \angle C2C3C4 show increases of less than one degree. Such deviations are very similar to those of 23DFPY [14]. It seems that the fluorination on C6 would not lead to any change in the angles of \angle N1C2C3 and \angle C2C3C4 with respect to 23DFPY. The largest difference of valence angles takes place at \angle C5C6N1 with a \sim 1.9 ^\circ increase according to the r_0 structure, which is much smaller than 2FPY [13] or 26DPY [14] with a \sim 3 ^\circ increase. This can be explained by the balance of competing effects for the stability of the ring structure. Ⅵ. ELECTROSTATIC POTENTIAL To better visualize the electron densities, the molecular electrostatic potential (ESP) analysis was performed for PY and 236TFPY by using Gaussian09 within their B3LYP/6-311++G(2df, 2pd) geometries. As indicated in FIG. 4, trifluorination leads to more acidic C - H groups and less electronegativity of N atom. The \pi -electron density decreases a lot to form a \pi -hole above the ring, which is slightly positive and could act as the electron acceptor in forming lone-pair \cdots$$ \pi$ interaction. As a result, when forming complexes with partner molecules, the interaction topologies can be quite different with respect to that of PY.

 FIG. 4 Electrostatic potential surfaces of PY and 236TFPY. The blue shading is the maximum (positive) potential, and red shading is the minimum (negative) potential
Ⅶ. CONCLUSION

The rotational spectra of seven isotopologues of 236TFPY have been investigated by using the pulsed jet FTMW technique. The structural changes and electron density distributions upon trifluorination are reported for PY and 236TFPY. The ortho-fluorination causes the largest shortening of the bond length. Notable increase of the valence bond angle occurs at $\angle$C5C6N1, which also results in decreases in its adjacent bond angles to compensate for the ring angle opening upon the substitution. Due to electron withdrawing of the fluorine atom, the electron density above the aromatic ring is dramatically reduced upon the trifluorination, which might create new active sites when forming complexes with other molecules.

Supplementary materials: All experimental transition frequencies of 7 isotopologues and the differences between experimental and calculated frequencies of 2, 3, 6-trifluoropyridine are summarized in Tables S1, S2 and S3). Theoretical geometry of 2, 3, 6-trifluoropyridine at B3LYP/6-311++G(2df, 2pd) level of theory is available in Table S4.

Ⅷ. ACKNOWLEDGMENTS

This work was supported by the National Natural Science Foundation of China (No.21703021 and No.U1931104), the Natural Science Foundation of Chongqing, China (No.cstc2017jcyjAX0068 and No.cstc2018jcyjAX0050), Venture & Innovation Support Program for Chongqing Overseas Returns (No.cx2018064), Foundation of 100 Young Chongqing University (No.0220001104428), and Fundamental Research Funds for the Central Universities (No.106112017CDJQJ228807 and No.2018CDQYHG0009).

Supplementary Material

Content:

1) Three tables of experimental transition frequencies of 2,3,6-trifluoropyridine.

2) B3LYP/6-311++G(2df,2pd) geometry of 2,3,6-trifluoropyridine.

1) Tables of experimental transition frequencies normal and 13C isotopologues of 2,3,6-trifluoropyridine.

Table S1 Experimental transition frequencies of normal and 13C isotopologues of 2,3,6-trifluoropyridine.
Table S2 Experimental transition frequencies of the 13C isotopologues
Table S3 Experimental transition frequencies of the 15N isotopologue.

2)

Table S4 B3LYP/6-311++G(2df,2pd) geometry of 2,3,6-trifluoropyridine.
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2, 3, 6-三氟吡啶的转动光谱：氟化对吡啶环结构的影响