Conformational analysis, spectroscopic, structure–activity relations and quantum chemical simulation studies of 4–(trifluoromethyl)benzylamine

Accepted Manuscript Conformational analysis, spectroscopic, structure–activity relations and quantum chemical simulation studies of 4–(trifluoromethyl)benzylamine

V. Arjunan, L. Devi, S. Mohan PII:

S0022-2860(18)30078-4

DOI:

10.1016/j.molstruc.2018.01.049

Reference:

MOLSTR 24771

To appear in:

Journal of Molecular Structure

Received Date:

02 January 2018

Revised Date:

17 January 2018

Accepted Date:

18 January 2018

Please cite this article as: V. Arjunan, L. Devi, S. Mohan, Conformational analysis, spectroscopic, structure–activity relations and quantum chemical simulation studies of 4–(trifluoromethyl) benzylamine, Journal of Molecular Structure (2018), doi: 10.1016/j.molstruc.2018.01.049

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ACCEPTED MANUSCRIPT Conformational analysis, spectroscopic, structure–activity relations and quantum chemical simulation studies of 4–(trifluoromethyl)benzylamine V. Arjunan1*, L. Devi2, S. Mohan3 1Department

of Chemistry, Kanchi Mamunivar Centre for Post–Graduate Studies, Puducherry 605 008. India.

2Research 3School

and Development Centre, Bharathiar University, Coimbatore – 641 046.

of Sciences and Humanities, Vel Tech University, Avadi, Chennai – 600 032.

Abstract The FT–IR and FT–Raman spectra of 4–trifluoromethylbenzylamine (TFMBA) have been recorded in the range 4000–450 and 4000–100 cm−1 respectively. The conformational analysis of the compound has been carried out to attain stable geometry of the compound. The complete vibrational assignment and analysis of the fundamental modes of the compound are carried out using the experimental FTIR and FT–Raman data and quantum chemical studies. The experimental vibrational frequencies are compared with the wavenumbers obtained theoretically from the B3LYP gradient calculations employing the standard high level 6–311++G** and cc–pVTZ basis sets for the optimized geometry of the compound. The structural parameters, thermodynamic properties and vibrational frequencies of the normal modes obtained from the B3LYP methods are in good agreement with the experimental data. The 1H (400 MHz; CDCl3) and 13C (100 MHz; CDCl3) nuclear magnetic resonance (NMR) spectra were also recorded. The electronic properties, highest occupied molecular orbital and lowest unoccupied molecular orbital energies are measured by DFT approach. The charges of the atoms by natural bond orbital (NBO) analysis are determined by B3LYP/cc–pVTZ method. The structure–chemical reactivity relations of the compound are determined through chemical potential, global hardness, global softness, electronegativity, electrophilicity and local reactivity descriptors by conceptual DFT methods.

ACCEPTED MANUSCRIPT Key words: 4–trifluoromethylbenzylamine; FTIR; FT–Raman; NMR; DFT; NBO. *Author

for correspondence: [email protected] (V. Arjunan)

1. Introduction Benzylamine (α–aminotoluene) is used in the chemical industry as a starting material for other products or as a corrosion inhibitor. Benzylamine and its derivatives are used as chemical intermediate for the manufacture of dyestuffs, pigments, optical brighteners, textile auxiliaries, agrochemicals, amino acids and other organic compounds. α–Methylbenzylamine is well known chiral reagent and used as effective chiral adjuvants in the resolution of racemates, as ligands in asymmetric catalysts [1]. Synthesis and evaluation of 4–substituted benzylamine derivatives as β–tryptase inhibitors, since β–tryptase is considered a critical mediator of asthma [2]. The Pd(II) catalyzed ortho–C–H trifluoromethylation of benzylamines has been achieved utilising an electrophilic CF3 reagent [3]. Some non– aromatic analogues of amphetamine and α–methylbenzylamine were prepared and evaluated as competitive inhibitors of norepinephrine N–methyltransferase [4]. In view of the biological and industrial significance of benzylamine derivatives, a detailed infrared, Raman, NMR spectral studies, structure–chemical reactivity relations and NBO analysis of 4– (trifluoromethyl)benzylamine (TFMBA) have been undertaken for the first time. 2. Experimental The liquid sample of 4–(trifluoromethyl)benzylamine was purchased from Aldrich chemicals, U.S.A and used as such to record the FT–IR, FT–Raman and NMR spectra. The FT–IR spectrum is recorded by CsI windows on a Bruker IFS 66V spectrometer equipped with a Globar source, Ge/KBr beam splitter and a TGS detector in the range of 4000 to 450 cm–1. The spectral resolution is 2 cm–1. The FT–Raman spectrum is also recorded in the range 4000 to 100 cm–1 using the same instrument with FRA106 Raman module equipped with Nd:YAG laser source operating at 1.064 μm with 200 mW powers. A liquid nitrogen cooled– Ge detector is used. The frequencies of all sharp bands are accurate to 2 cm–1. The 1H (400 MHz; CDCl3) and

13C

(100 MHz; CDCl3) nuclear magnetic resonance (NMR) spectra are

recorded on a Bruker HC400 instrument using CDCl3 solvent. Chemical shifts for protons are reported in parts per million scales (δ scale) downfield from tetramethylsilane. 3. Computational details The LCAO–MO–SCF restricted DFT–B3LYP correlation functional calculations of TFMBA have been performed with Gaussian–09 [5] program, invoking gradient geometry 2

ACCEPTED MANUSCRIPT optimisation [6]. The gradient corrected density functional theory (DFT) [6] with the three– parameter hybrid functional (B3) [7,8] for the exchange part and the Lee–Yang–Parr (LYP) correlation function [9] with the standard 6–31G**, cc–pVTZ and high level 6–311++G** basis sets have been used for the computation of molecular structure parameters, energy, vibrational frequencies and thermodynamic properties of the compound. The harmonic vibrational frequency calculations resulting in IR and Raman frequencies together with intensities and Raman depolarisation ratios. The Raman scattering activities (Si) of the fundamental modes are converted to relative Raman intensities (Ii) using the relationship [10].

f ( 0  i ) 4 Si Ii   i [1  exp(hc i / kT )] where, v0 is the laser exciting frequency (v0 = 9398.5 cm−1) which corresponds to the wavelength of 1.064 μm for Nd:YAG laser, vi is the vibrational wavenumber of the ith normal mode, h–Plank constant, c–velocity of light and k–Boltzmann constant, f is the suitably chosen normalisation factor (10–38) for all the peak intensities and T–temperature in Kelvin (298.15 K). The molecular electrostatic potential (MEP) and the total electron density [11,12] were calculated by using B3LYP/6–311++G** method. The molecular electrostatic potential (MEP) at a point ‘r’ in the space around a molecule (in atomic units) can be expressed as: V (r )   A



ZA 



RA  r



 (r ')dr ' 



r ' r

where ZA is the charge on nucleus A, located at RA and ρ(r′) is the electronic density function for the molecule. The first and second terms represent the contributions to the potential due to nuclei and electrons, respectively. V(r) is the resultant electric potential at each point r, which is the net electrostatic effect produced at the point r by both the electrons and nuclei of the molecule. GaussView 5.0.8 visualisation program [13] has been utilised to display the MEP surface and the shape of the frontier molecular orbitals. The stabilisation energy E(2) associated with i (donor) → j (acceptor) delocalisation is estimated from the second–order perturbation approach [14] as given below

E

( 2)

F 2 (i, j )  qi  j  i 3

ACCEPTED MANUSCRIPT where qi is the donor orbital occupancy, εi and εj are diagonal elements (orbital energies) and F(i,j) is the off–diagonal Fock matrix element. The B3LYP method allows calculating the shielding constants with accuracy. The 1H and

13C

NMR isotropic shielding are calculated using the GIAO method [15,16] using the

optimised parameters obtained from B3LYP/cc–pVTZ method. The effect of CDCl3 solvent on the theoretical NMR parameters is included using the PCM model. The isotropic shielding constant values are used to calculate the isotropic chemical shifts δ with respect to tetramethylsilane (TMS) using the relation δiso(X) = σiso

TMS(X)

– σiso(X), where δiso–

isotropic chemical shift and σiso – isotropic shielding constant. Both the global and local reactivity descriptors are determined using finite difference approximation to reveal the reactivity of the molecule. The vertical ionization potential (I), electron affinity (A) and the electron populations are determined on the basis of B3LYP/cc– pVTZ method. The energy of the N electron species of TFMBA has been determined by restricted B3LYP method while N–1 and N+1 electronic species are calculated by using restricted open B3LYP method using the geometry optimised with B3LYP/cc–pVTZ method. The site–selectivity of a chemical system can be determined by using Fukui functions [17,18] which can be interpreted either as the change of electron density ρ(r) at each point r when the total number of electrons is changed or as the sensitivity of chemical potential (μ) of a system to an external perturbation at a particular point r.      (r )   f (r )       N  v ( r )  v(r )  N

Yang and Parr introduced local softness s(r) to predict the reactivity [18]. The s(r) describes the sensitivity of the chemical potential of the system to the local external perturbation and is obtained by simply multiplying Fukui function f(r) with global softness S. The local softness values are generally used in predicting the reactivities such as electrophilic, nucleophilic and free radical reactions, regioselectivity etc.   (r )   and s (r )  f (r ) S s (r )      v( r )

where, S is the global softness which is inversely related to global hardness (η). The generalised philicity descriptor, ω(r) contains almost all informations about hitherto known different global and local reactivity and selectivity descriptors, in addition to the information regarding electrophilic/nucleophilic power of a given atomic site in a molecule [19,20]. The local quantity called philictiy associated with a site k in a molecule 4

ACCEPTED MANUSCRIPT can be calculated as ka  f ka where    2 / 2 and a = +, – and 0 represents local philic , quantities describing nucleophilic, electrophilic and radical attacks respectively. 4. Results and discussions 4.1. Conformational analysis The most stable geometry and other possible conformations of the compound, has been determined from the potential energy surface (PES) using B3LYP/6–31G** method. During the analysis all the geometrical parameters are simultaneously relaxed while the C6– C1–C7–N18 dihedral angle is varied in steps of 10o from 0o to 360o. The potential energy profile which reflects the stability of the possible conformers of the molecule is shown in Fig. 1. Four different conformers I, II, III and IV have been determined for TFMBA by PES and are shown in Fig. 2. In the most stable geometry (I) of 4–(trifluoromethyl)benzylamine all the atoms present in the benzene moiety lie in the molecular plane. The –NH2 group does not lie in the molecular plane. It deviates by a mean angle of 89.1o from the ring molecular plane. This is confirmed by the dihedral bond angles C2–C1–C7–N18 and C6–C1–C7–N18 (89.1o). This clearly indicates that the conformer I corresponds to the global minimum energy. The conformer II has 0.0311 kcal mol–1 more energy than I which is second least stable conformer. In conformer II, the dihedral angles are C2–C1–C7–N18 (180o) and C6– C1–C7–N18 (0o). In conformer II the amino group nitrogen atom lie in the molecular plane. There are two transition structures III and IV. The conformer III is 0.3647 kcal mol–1 less stable than the more stable conformer I. The conformer IV is the least stable by 0.3807 kcal mol–1 than that of the more stable conformer I. In order to provide the accurate structural parameters of the compound, the most stable conformer is optimised with B3LYP method using 6–311++G** and cc–pVTZ basis sets. The optimised molecular geometry of TFMBA by B3LYP/cc–pVTZ method is shown in Fig. 3. The non–planar TFMBA is 194.53 cal mol–1 more stable than that of planar molecule. 4.2. Structural properties The optimised geometrical parameters of TFMBA obtained by B3LYP method with 6–311++G** and cc–pVTZ basis sets are listed in Table 1. The computed bond length, bond angle and dihedral angle of TFMBA are compared with the X–ray diffraction data of similar compound [21]. From Table 1, it can be observed that the computed geometrical parameters are agreed very well with the single crystal XRD data.

5

ACCEPTED MANUSCRIPT The average C–C bond length of aromatic benzene ring of TFMBA is 1.40 Å. The bond length of C1–C7 and C4–C8 are 1.52 Å and 1.50 Å, respectively. The bond length of C7–N18 is 1.47 Å shows an excellent agreement with that experimental data. The average bond length of C8–F15, C8–F16 and C8–F17 is 1.35 Å. The bond angle of benzene ring C2–C1–C6 (118.3o), C1–C2–C3 (121.1o), C2–C3– C4 (119.7o), C3–C4–C5 (120.0o), C4–C5–C6 (119.7o) and C5–C6–C1 (121.1o) shows some distortion due to the presence of substituents such as trifluoromethyl and ethyl amino groups. Due to the cumulative –I effect of fluorine atoms in –CF3 group, the ring electrons move towards the –CF3 group and thus the bond angles C2–C3–C4 and C4–C5–C6 are less than 120o. The bond angle C2–C1–C6 where the –CH2NH2 group is attached is equal to 118.3o which is less than 120 o and the bond angles at the ortho positions to –CH2NH2

substitution

namely C1–C6–C5 (121.1o) and C1–C2–C3 (121.1o) are more than 120o reveals the electron donating nature of the ethylamino group. The average bond angle of C4–C8–F (111.9o) and F–C8–F (107o) shows trifluoromethyl group attached to C4 atom slightly agree with tetrahedral geometry. The dihedral angles C2–C1–C7–N18 and C6–C1–C7–N18 (89.1o) clearly reveal that the amino group is almost perpendicular to the plane of the benzene ring. The thermodynamic parameters namely total energy, heat capacity, entropy, rotational constants, dipole moments, vibrational and zero–point vibrational energies of the compound have also been computed at B3LYP levels using 6–311++G** and cc–pVTZ as basis sets and are presented in Table 2. The total dipole moment of TFMBA determined by B3LYP level using 6–311++G** and cc–pVTZ basis sets are 2.01 and 1.91 Debye, respectively. The high dipole moment is due to the presence of electron donating and attracting groups present in the opposite ends of the molecule. 4.3. Analysis of molecular electrostatic potential Total SCF electron density surface mapped with MEP of the title compound is shown in Fig. 4. The MEP displays molecular shape, size and electrostatic potential values. The extreme limits of the total electron density lie in the range –3.849e × 10–2 to +3.849e × 10–2. The colour scheme for the MEP surface is red–electron rich or partially negative charge; blue–electron deficient or partially positive charge; light blue–slightly electron deficient region; yellow–slightly electron rich region, respectively. The electron density varies significantly around the title molecule of the electron withdrawing and donating groups. The most electron rich region is around amino nitrogen (N18) where the electron density is – 3.849e × 10–2 and slight electron rich region is around Fluorine atoms (F15, F16 and F17) are 6

ACCEPTED MANUSCRIPT –2.10e × 10–2. Likewise the most electron deficient region around amino hydrogen where the electron density is 3.849e × 10–2 and the slightly electron deficient region is around phenyl hydrogen atoms where the electron density is 2.59e × 10–2 and around methylene hydrogen atoms where the electron density is 1.37e × 10–2. The electrostatic potential surface of TFMBA is shown in Fig. 5. The contour map of electrostatic potential is shown in Fig. 6. It confirms the different negative and positive potential sites of the molecule in accordance with the total electron density surface. The isoelectron density and MEP surfaces clearly indicates the probable sites readily available for the electrophilic and nucleophilic reactions. 4.4. Frontier molecular orbital analysis The HOMO and LUMO implies the possibility of π → π* and n → π* transitions in TFMBA. The frontier molecular orbitals are sketched in Fig. 7. The frontier orbital energy gap (ELUMO−EHOMO) of 4–(trifluoromethyl)benzylamine is found to be 5.6959 eV by cc– pVTZ basis set. The energy gap reflects the chemical reactivity of the molecule. A lower HOMO–LUMO energy gap explains the fact that eventual charge transfer interaction is taking place within the molecule [22,23]. 4.5. NBO analysis Table 3 depicts the bonding concepts such as type of bond orbital, their occupancies, the natural atomic hybrids of which the NBO is composed, giving the percentage of the NBO on each hybrid, the atom label, and a hybrid label showing the hybrid orbital (spx) composition (the amount of s–character, p–character, etc.) of TFMBA molecule determined by B3LYP/cc–pVTZ method. The bonding orbital occupancies represent the bonds perfectly. The percentage character of the individual atoms involved in the sp2 and sp3 hybrid orbitals of the compounds are exactly determined by NBO analysis. For example, the bonding orbital for C1–C2 with 1.976 electrons has 49.93% C1 character in a sp1.90 hybrid and has 50.07% C2 character in a sp1.73 hybrid orbital. In the case of C4–C8 bonding orbital with 1.985 electrons has 50.14% C4 character a sp2.68 hybrid and has 49.86% C8 character a sp1.89 hybrid. A bonding orbital for C1–C7 with 1.979 electrons has 50.90% C1 character in a sp2.22 hybrid and has 49.10% C7 character in a sp2.28 orbital. The C7–N18 with 1.986 electrons has 41.46% C7 character in a sp2.96 hybrid and has 58.54% N18 character in a sp2.19 orbital. NBO analysis provides the most accurate and possible natural Lewis structure of orbits, because all orbital details are mathematically chosen to provide the highest possible percentage of the electron density. It gives useful information about interactions in both filled and virtual orbitals that could enhance the analysis of intra and intermolecular interactions. 7

ACCEPTED MANUSCRIPT The second order Fock matrix was carried out to verify the donor–acceptor interactions in the NBO analysis [24]. The interactions result is a loss of occupancy from the localised NBO of the idealised Lewis structure into an empty non–Lewis orbital. Delocalisation of electron density between occupied (bonding) and unoccupied (antibonding or Rydberg) NBO orbitals corresponds to a stabilising donor–acceptor interactions. In NBO analysis large E(2) value shows the effective interaction between electron–donors and electron–acceptors and greater the extent of conjugation of the whole system, the possible effective interactions are given in Table 4. The intramolecular interactions are formed by the orbital overlap between bonding and antibonding orbital which results in intramolecular charge transfer causing stabilisation of the system. The electron density of conjugated bond of aromatic ring clearly demonstrates strong delocalisation. The strong intramolecular hyperconjugative interaction of the π electrons of C–C bond to the π* anti C–C bond leads to stabilisation of some part of the ring is evident from the E(2) energy for hyperconjugative intramolecular interactions were more than 5 kcal mol–1 for TFMBA. The strong intramolecular hyperconjugative interaction of TFMBA is between π(C1–C6) → π*(C2–C3) is stablised by 19.04 kcal mol–1. Similarly π(C1–C6) → π*(C4–C5) have the stablisation energy 23.69 kcal mol–1. The π(C2–C3) → π*(C1–C6) is the second most stabilised interaction with an energy 22.12 kcal mol–1. The other interactions stabilized more are π(C2–C3) → π*(C4–C5) is 20.06 kcal mol–1, π(C4–C5) → π*(C1–C6) is 17.75 kcal mol– 1

and π(C4–C5) → π*(C2–C3) is 21.48 kcal mol–1.

4.6. Vibrational analysis The molecule TFMBA belongs to C1 symmetry with 54 fundamental normal modes. All the modes are both IR and Raman active. The theoretical IR and Raman spectra of TFMBA simulated by B3LYP method using 6–311++G** and cc–pVTZ basis sets are also compared with the observed FT–IR and FT–Raman spectra and presented in Figs. 8 and 9, respectively. The observed and theoretical wavenumbers of TFMBA are summarised in Table 5. 4.6.1. N–H Vibrations The –NH2 asymmetric stretching vibration is assigned to strong IR band at 3368 cm–1 and –NH2 symmetric stretching vibration is assigned to the strong IR band at 3291 cm–1. The strong IR band observed at 1620 cm–1 and a medium Raman band at 1611 cm–1 are assigned to the –NH2 deformation. The medium band in IR seen at 592 cm–1 is assigned to the –NH2 wagging mode. The twisting mode of amino group is observed as a strong bond in IR at 1164 cm–1 and medium intensity band in Raman spectra at 1172 cm–1. The stretching vibrational 8

ACCEPTED MANUSCRIPT modes corresponding to the –NH2 group is strong in infrared while these are not observed in Raman spectrum. But the Raman wavenumbers are theoretically determined by B3LYP method. This is the reason why the difference between the observed FTIR spectra and the theoretical Raman spectra simulated by 6–311++G** and cc–pVTZ basis sets as given in Fig. 9. 4.6.2. C–H Vibrations The aromatic C–H stretching vibrations are assigned to medium IR bands at 3011 cm– 1

and very weak to weak Raman bands at 3035 and 3000 cm–1 and are in the expected range

[25–28]. The predicted bands are very well agreed with the observed bands. The C–H in– plane bending vibrations are substitution sensitive, normally showing the bands in the region 1300–1000 cm–1 [25,26]. The bands observed at 1142, 1018 and 999 cm–1 in IR and Raman spectra are assigned to the C–H in–plane bending vibrations. Bands involving the out–of– plane C–H vibrations appear in the range 1000–675 cm–1 [25,26]. These vibrations are assigned to weak to medium IR bands at 959 and 898 cm–1. 4.6.3. C–C vibrations The C–C stretching vibrations occur in a wider spectral range covering 1650–1200 cm–1 [27]. The strong IR bands at 1475 and 1420 cm–1 and a very weak Raman bands found at 1475 cm–1 are assigned to the C–C stretching vibrations. The IR band at 819, 763 and 624 cm–1 are assigned to the CCC in–plane bending vibrations. The Raman counterparts are observed at 813 and 621 cm–1 for CCC in–plane bending vibrations. The CCC out of plane bending vibrations is observed in the low frequency range [29,30]. 4.6.4. CF3 group vibrations The band due to C–F stretching vibration in aromatic compounds may be found over a wide frequency range 1360–1000 cm–1 since the vibration is easily influenced by adjacent atoms or groups. Polyfluorinated compounds have a series of very intense bands in the region 1360–1090 cm–1. Compounds with a –CF3 group in a aromatic ring have very strong bands near 1320 cm–1 ,1180 cm–1 and 1140 cm–1 . In the present investigation, the very strong IR band observed at 1327 cm–1 in infrared spectrum of TFMBA is assigned to –CF3 symmetric stretching vibrations. The –CF3 asymmetric stretching vibration is attributed to the very strong mode seen at 1123 cm–1. The symmetric deformation of –CF3 group is observed at 733 cm–1 while the asymmetric deformation of the same is determined at 561 cm–1 by DFT method. The rocking and twisting modes are observed in the low frequency region. The vibrational modes of –CF3 group presented in Tables 5 are in close agreement with the literature values [31]. 9

ACCEPTED MANUSCRIPT 4.6.5. Methylene vibrations The asymmetric methylene group vibration a(CH2) is assigned to a strong IR band at 2928 cm–1. The symmetric methylene group vibration s(CH2) is assigned to a strong IR band at 2866 cm–1. The methylene deformation (CH2) is assigned to the medium IR band at 1374 cm–1. The methylene wagging mode is observed as a very strong Raman band at 1351 cm–1. The methylene twisting mode is assigned to the medium Raman band at 1197 cm–1. 4.6.6. Scale factors A better agreement between the computed and experimental frequencies can be obtained by using scale factors for different types of fundamental vibrations. The correlation of the experimental and theoretical scaled wavenumbers of TFMBA is presented in Fig. 10. To determine the scale factors, the scaling equation method is used [32–36] that minimises the residual separating experimental and theoretically predicted vibrational frequencies. The scaling equations y = 1.0011x – 5.0936 and y = 0.9953x + 4.2252 are utilised to obtain the scaled frequencies with 6–311++G** and cc–pVTZ basis sets, respectively and compared with the experimentally observed frequencies of TFMBA. The RMS deviation between the experimental and observed wavenumbers for both the methods is 7.7. The resultant scaled frequencies are listed in Table 5. 4.7. NMR spectral studies To provide an explicit assignment and analysis of

13C

and 1H NMR spectra,

theoretical calculations on chemical shift of the title compound are carried out through GIAO method at B3LYP/cc–pVTZ method with CDCl3 solvent using “gauge independent atomic orbital” (GIAO) method [37–41]. The 1H and

13C

theoretical and experimental chemical

shifts, isotropic shielding constants and the NMR spectral assignments are presented in Table 6. The 1H and 13C NMR spectra of the compound are represented in Figs. 11 and 12. Unsaturated carbons give signals with chemical shift values from 100 to 200 ppm [42]. The external magnetic field experienced by the carbon nuclei is affected by the electronegativity of the atoms attached to them. The effect of this is that the chemical shift of the carbon increases if the carbon atoms are attached with electronegative amino group and fluorine atom. Thus, the carbon atoms C1 and C8 in TFMBA show downfield effect and the corresponding observed chemical shift of C1 is 147.22 ppm. The carbon atom C8 which is attached to the fluorine atoms is assigned to the chemical shift 126.96 ppm. The chemical shift values of other carbon atoms of TFMBA observed at 125.66 ppm (C4) and the chemical shift values 125.30 ppm is assigned to C2 and C6 carbon atoms. The line observed at 122.41 10

ACCEPTED MANUSCRIPT ppm is attributed to C3 and C5 carbon atoms present in the same chemical environment. The methylene carbon atom C7 of TFMBA shows NMR signal at 45.49 ppm. 1H

chemical shifts of TFMBA are obtained by complete analysis of their NMR

spectra and interpreted critically in an attempt to quantify the possible different effects acting on the shielding constant and in turn to the chemical shift of protons. The hydrogen atoms H9 and H12 attached with the aromatic carbons of TFMBA are in the same chemical environment and shows peak at 7.49 ppm and the hydrogen atoms H10 and H11 are also in the same chemical environment and shows peak at 7.62 ppm, respectively. In the title compound, the methylene (–CH2–) hydrogen atoms are in the same chemical environment and shows peaks at 3.97 ppm and the amino (–NH2) hydrogen atoms shows peaks in the upfield at 1.49 ppm due to the high electronegativity of nitrogen atom. The calculated and experimental shift values are given in Table 6 shows very good agreement with each other. The correlation between the experimental and theoretical 1H and

13C

NMR chemical shifts

are presented in Fig. 13. 4.8. Atomic charge distribution analysis The atomic charges of the neutral, cationic and anionic species of TFMBA calculated by natural population analysis (NPA) using B3LYP/cc–pVTZ method are presented in Table 7. The aromatic ring carbon atoms possess negative charge. The positive charge on C8 atom is due to the cumulative –I effect of fluorine atoms attached to it. The negative charge on fluorine atom and nitrogen atom shows electron rich centres. The correlation of the atomic charges of TFMBA is depicted in Fig. 14. 4.9. Analysis of structure–activity descriptors The global parameters ionization potential (I), electron affinity (A), electrophilicity (ω), electronegativity (χ), hardness (η), and softness (S) of the molecule are determined and displayed in Table 2. The site–selectivity of a chemical system, cannot, however, be studied using the global descriptors of reactivity. Fukui functions and local softness are extensively applied to probe the local reactivity and site selectivity. The formal definitions of all these descriptors and working equations for their computation have been described [43–46]. The Fukui functions of the individual atoms of the neutral, cationic and anionic species of TFMBA calculated by B3LYP/cc–pVTZ method are presented in Table 7. The molecule under investigation mainly gives substitution reactions.

11

ACCEPTED MANUSCRIPT The local softness, relative electrophilicity ( sk / sk ) and relative nucleophilicity ( sk / sk ) indices, the dual local softness Δsk and the multiphilicity descriptors (Δωk) have also

been determined to predict the reactive sites of the molecule and are summarised in Table 8. The dual descriptors Δfk, Δsk and multiphilicity descriptor Δωk quantities provide a clear difference between nucleophilic and electrophilic attacks at a particular site with their sign. That is, they provide positive value for site prone for nucleophilic attack and a negative value at the site prone for electrophilic attack. From the dual local softness Δsk and the multiphilicity descriptors (Δωk) one can understand that the atoms C2, C6, N18 are favorable for nucleophilic attack. The local reactivity descriptors and the relative nucleophilicity index favours C7 for nucleophilic attack. The atoms C7 and C8 are favorable for electrophilic and free radical attack. The Fukui functions and dual descriptors which represents the relative nucleophilic, electrophilic and free radical attack in TFMBA are presented in the Figs. 15 and 16. 5. Conclusions (i)

In the most stable geometry of 4–(trifluoromethyl)benzylamine, the –NH2 group does not lie in the molecular plane. It deviates by a mean angle of 89.1o from the ring molecular plane.

(ii)

The non–planar TFMBA is 194.53 cal mol–1 more stable than that of planar molecule.

(iii) The total dipole moment of TFMBA determined by B3LYP level using 6–311++G** and cc–pVTZ basis sets are 2.01 and 1.91 Debye, respectively. (iv) The geometrical structure shows a little distortion in benzene ring due to the substitution of highly electronegative ethylamino group and trifluoromethyl group. (v)

The NMR data clearly indicates the downfield effect in chemical shift of C1 and C8 atom of TFMBA due to presence of amino group and fluorine atoms.

(vi) The total electron density lie in the range –3.849e × 10–2 to +3.849e × 10–2. (vii) The amino nitrogen (N18) shows red colour which is electron rich of the molecule. (viii) The HOMO and LUMO energy gap explains the eventual electronic transition taking place within the molecule, particularly π → π* and n → π* type transitions. (ix) The local reactivity descriptors favour C7 for nucleophilic attack. The atoms C7 and C8 are favorable for electrophilic and free radical attack.

12

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15

ACCEPTED MANUSCRIPT

Fig. 1. The potential energy profile of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 2. The possible conformers of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 3. The optimised geometry of 4–trifluoromethylbenzylamine with numbering of atoms.

ACCEPTED MANUSCRIPT

Fig. 4. The total electron density surface mapped with molecular electrostatic potential of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 5. The molecular electrostatic potential surface of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 6. The contour map of molecular electrostatic potential surface of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 7. The frontier molecular orbitals of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 8. (a) Observed FT–IR and theoretical infrared (b) 6–311++G** and (c) cc–pVTZ spectra of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 9. (a) Observed FT–Raman and theoretical Raman (b) 6–311++G** and (c) cc–pVTZ spectra of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 10 The linear regression between the experimental and theoretical wavenumbers of 4– (trifluoromethyl)benzylamine.

ACCEPTED MANUSCRIPT

Fig. 11. 1H NMR spectrum of 4–trifluoromethylbenzylamine.

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Fig. 12. 13C NMR spectrum of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 13. The correlation between the experimental and theoretical 1H & 13C NMR chemical shifts of 4–trifluoromethylbenzylamine.

ACCEPTED MANUSCRIPT

Fig. 14. Correlation of the atomic charges of 4–(trifluoromethyl)benzylamine.

ACCEPTED MANUSCRIPT

Fig. 15. The Fukui functions which represents the relative (a) nucleophilic and (b) electrophilic descriptors of 4–(trifluoromethyl)benzylamine

ACCEPTED MANUSCRIPT

Fig. 16. The Fukui functions which represents the (a) free radical attacking sites and (b) Fukui dual descriptor (Δfk), the dual local softness (Δsk) and the multiphilicity descriptors (Δωk) of 4– (trifluoromethyl)benzylamine

ACCEPTED MANUSCRIPT

Highlights (i)

The stable conformer is non-planar.

(ii)

The downfield chemical shift of C1 and C8 atom is due to presence of amino group and fluorine atoms.

(iii) The amino nitrogen (N18) shows red colour which is more electron rich. (iv) The π → π* and n → π* type electronic transitions taking place within the molecule. (v)

The reactive sites are determined by global and local reactivity descriptors.

ACCEPTED MANUSCRIPT Table 1. Structural parameters of 4–trifluoromethylbenzylamine by B3LYP method with 6–311++G** and cc–pVTZ basis sets. Structural

4–Trifluoromethylbenzylamine B3LYP/

B3LYP/

6–311++ G**

cc–pVTZ

C1–C2

1.40

1.40

1.38

C1–C6

1.40

1.40

1.38

C1–C7

1.52

1.52

1.50

C2–C3

1.39

1.39

1.38

C3–C4

1.40

1.40

1.35

C4–C5

1.40

1.40

1.37

C4–C8

1.50

1.50

C5–C6

1.39

1.39

1.39

C7–N18

1.47

1.47

1.46

C–H(methylene)

1.10

1.10

0.97

C–H(ring)

1.09

1.09

0.93

C–F

1.35

1.36

N–H(amino)

1.02

1.02

0.87

C2–C1–C6

118.3

118.3

118.5

C2–C1–C7

120.8

120.8

119.9

C6–C1–C7

120.8

120.8

121.5

C1–C2–C3

121.1

121.1

120.4

C2–C3–C4

119.8

119.7

120.8

C3–C4–C5

119.9

120.0

120.0

C3–C4–C8

120.0

120.0

C5–C4–C8

120.0

120.0

C4–C5–C6

119.8

119.7

119.7

C4–C5–H11

119.8

120.0

120.2

C6–C5–H11

120.4

120.2

120.2

C1–C6–C5

121.1

121.1

120.5

C1–C6–H12

119.5

119.6

119.8

parameters

Expt.a

Internuclear distance (Å)

Bond Angle (degree)

ACCEPTED MANUSCRIPT C5–C6–H12

119.4

119.3

119.8

C1–C7–H13

109.6

109.5

109.3

C1–C7–H14

109.6

109.5

109.3

C1–C7–N18

115.3

115.6

111.5

H13–C7–H14

106.7

106.7

108.0

H13–C7–N18

107.6

107.5

109.3

H14–C7–N18

107.6

107.5

109.3

C4–C8–F15

111.9

112.4

C4–C8–F16

111.9

112.4

C4–C8–F17

111.8

111.9

F15–C8–F16

107.5

107.1

F15–C8–F17

106.7

106.3

F16–C8–F17

106.7

106.3

C7–N18–H19

109.3

110.9

109.5

C7–N18–H20

109.3

110.9

109.5

H19–N18–H20

105.6

107.0

C6–C1–C2–C3

–0.5

–0.5

–0.1

C7–C1–C2–C3

177.2

177.6

–179.1

C2–C1–C6–C5

0.5

0.5

0.3

C7–C1–C6–C5

–177.2

–177.6

179.2

C6–C1–C7–N18

89.7

89.1

C1–C2–C3–C4

0.2

0.3

C2–C3–C4–C5

0.1

–0.0

C2–C3–C4–C8

–177.6

–177.9

C3–C4–C5–C6

–0.1

0.0

C8–C4–C5–C6

177.6

177.9

C4–C5–C6–C1

–0.2

–0.3

Dihedral angle (degree)

avalues

taken from Ref. [21]

0.4

ACCEPTED MANUSCRIPT Table 2. The thermodynamic parameters of 4–trifluoromethylbenzylamine employing B3LYP method with 6–311++G** and cc–pVTZ basis sets. 4–Trifluoromethylbenzylamine Thermodynamic parameters (298 K) Total Energy (thermal), Etotal (kcal mol–1)

B3LYP/

B3LYP/

6–311++G**

cc–pVTZ

100.58

100.56

38.40

38.12

Heat Capacity at const. volume, Cv (kcal mol–1 K–1) Entropy, S (kcal mol–1 K–1)

100.06

99.89

Vibrational Energy, Evib (kcal mol–1)

98.80

98.78

Zero–point vibrational Energy, E0 (kcal mol –1)

94.29

94.32

X

–663.99849 2.46

–664.20548 2.48

Y

0.44

0.45

Z

0.42

0.42

2.01

1.91

μy

0

0.01

μz

0

–0.01

μtotal

2.01

1.91

SCF energy Rotational Constants (GHz)

Dipole moment (Debye)

μx

EHOMO (eV)

–6.8519

ELUMO (eV)

–1.1559

EHOMO – 1 (eV)

–7.5988

ELUMO + 1 (eV)

–0.9110

ELUMO – EHOMO (eV)

5.6959

Ionisation Potential (I)

8.9483

Electron Affinity (A)

–0.7397

Chemical Potential (μ)

–4.1043

Hardness(η)

4.8439

Global Softness (S)

0.1032

Electrophilicity (ω)

1.7388

Electronegativity (χ)

4.1043

Electrofugality (∆Ee)

10.687

Nucleofugality (∆En)

2.4785

ACCEPTED MANUSCRIPT Table 3. Bond orbital analysis of 4–trifluoromethylbenzylamine by B3LYP/cc–pVTZ method.

Orbital

C1–C2

Contribution NBO (%)

Coefficients

Bond

C1

49.93

0.7066

s(34.44) + p1.90(65.45)

C2

50.07

0.7076

s(36.56) + p1.73(63.35)

C1

49.93

0.7066

s(34.44) + p1.90(65.45)

C6

50.07

0.7076

s(36.56) + p1.73(63.35)

C1

48.77

0.6983

s(0.01) + p1.00(99.94)

C6

51.23

0.7158

s(0.00) + p1.00(99.95)

C1

50.90

0.7135

s(31.08) + p2.22(68.87)

C7

49.10

0.7007

s(30.44) + p2.28(69.49)

C2

49.86

0.7061

s(35.82) + p1.79(64.08)

C3

50.14

0.7081

s(36.50) + p1.74(63.40)

C2

51.16

0.7153

s(0.00) + p1.00(99.95)

C3

48.84

0.6989

s(0.00) + p1.00( 99.95)

C2

60.26

0.7763

s(27.57) + p2.62(72.36)

H9

39.74

0.6304

s(99.96) + p0.00(0.03)

C3

48.95

0.6996

s(35.25) + p1.83(64.64)

C4

51.05

0.7145

s(36.39) + p1.75(63.55)

C3

60.95

0.7807

s(28.20) + p2.54(71.74)

H10

39.05

0.6249

s(99.94) + p0.00(0.06)

C4

51.06

0.7145

s(36.41) + p1.75(63.53)

C5

48.94

0.6996

s(35.25) + p1.83(64.64)

C4

53.77

0.7333

s(0.02) + p99.99(99.94)

C5

46.23

0.6799

s(0.00) + p1.00(99.95)

C4

50.14

0.7081

s(27.15) + p2.68(72.69)

C8

49.86

0.7061

s(34.64) + p1.89(65.32)

C5

50.14

0.7081

s(36.50) + p1.74(63.40)

C6

49.86

0.7061

s(35.81) + p1.79(64.08)

C5

60.95

0.7807

s(28.20) + p2.54(71.74)

Occupancy Atom

1.9764

C1–C6

1.9764

C1=C6

1.6330

C1–C7

1.9786

C2–C3

1.9786

C2=C3

1.6567

C2–H9

1.9772

C3–C4

1.9760

C3–H10

1.9749

C4–C5

1.9760

C4=C5

1.6677

C4–C8

1.9845

C5–C6

1.9786

C5–H11

1.9749

from Parent

Atomic Hybrid Contributions (%)

ACCEPTED MANUSCRIPT

C6–H12

1.9772

C7–H13

1.9780

C7–H14

1.9780

C7–N18

1.9860

C8–F15

1.9951

C8–F16

1.9951

C8–F17

1.9941

N18–H19 N18–H20

1.9896 1.9896

H11

39.05

0.6249

s(99.94) + p0.00(0.06)

C6

60.26

0.7763

s(27.57) + p2.62(72.36)

H12

39.74

0.6304

s(99.96) + p0.00(0.03)

C7

59.56

0.7718

s(22.24) + p3.49(77.66)

H13

40.44

0.6359

s(99.96) + p0.00(0.03)

C7

59.56

0.7718

s(22.24) + p3.49(77.66)

H14

40.44

0.6359

s(99.96) + p0.00(0.03)

C7

41.46

0.6439

s(25.24) + p2.96(74.71)

N18

58.54

0.7651

s(31.29) + p2.19(68.45)

C8

28.46

0.5334

s(21.82) + p3.57(77.90)

F15

71.54

0.8458

s(25.13) + p2.97(74.71)

C8

28.46

0.5334

s(21.82) + p3.57(77.91)

F16

71.54

0.8458

s(25.12) + p2.97(74.73)

C8

28.50

0.5339

s(21.64) + p3.61(78.08)

F17

71.50

0.8456

s(24.47) + p3.08(75.37)

N18

67.37

0.8208

s(23.94) + p3.16(75.75)

H19

32.63

0.5712

s(99.91) + p0.00(0.08)

N18

67.37

0.8208

s(23.94) + p3.16(75.75)

H20

32.63

0.5712

s(99.91) + p0.00(0.08)

ACCEPTED MANUSCRIPT Table 4. The stabilization energies of the donor–acceptor interactions in 4–trifluoromethylbenzylamine. 4–Trifluoromethylbenzylamine Donor (i) → Acceptor (j)

E(2)a

E(j) – E(i)b

F(i, j)e

(kcal mol–1)

(a.u.)

(a.u.)

σ(C1–C2) → σ*(C1–C6)

2.29

1.24

0.048

σ(C1–C6) → σ*(C2–H9)

3.03

1.12

0.052

π(C1–C6) → π*(C2–C3)

19.04

0.28

0.066

π(C1–C6) → π*(C4–C5)

23.69

0.27

0.072

π(C1–C6) → σ*(C7–N18)

4.17

0.58

0.048

σ(C2–C3) → σ*(C1–C7)

4.02

1.09

0.059

σ(C2–C3) → σ*(C4–C8)

3.61

1.06

0.056

π(C2–C3) → π*(C1–C6)

22.12

0.29

0.071

π(C2–C3) → π*(C4–C5)

20.06

0.28

0.067

σ(C2–H9) → σ*(C1–C6)

5.02

1.06

0.065

σ(C2–H9) → σ*(C3–C4)

4.44

1.06

0.061

σ(C3–H10) → σ*(C1–C2)

4.8

1.06

0.064

σ(C3–H10) → σ*(C4–C5)

5.33

1.06

0.067

σ(C4–C5) → σ*(C3–C4)

3.65

1.25

0.06

π(C4–C5) → π*(C1–C6)

17.75

0.29

0.065

π(C4–C5) → π*(C2–C3)

21.48

0.29

0.071

π(C4–C5) → σ*(C8–F17)

6.63

0.5

0.055

σ(C5–C6) → σ*(C1–C7)

4.02

1.09

0.059

σ(C5–C6) → σ*(C4–C8)

3.61

1.06

0.056

σ(C5–H11) → σ*(C1–C6)

4.8

1.06

0.064

σ(C5–H11) → σ*(C3–C4)

5.33

1.06

0.067

σ(C6–H12) → σ*(C1–C2)

5.02

1.06

0.065

σ(C6–H12) → σ*(C4–C5)

4.44

1.06

0.061

σ(C7–H13) → σ*(C1–C2)

4.34

1.04

0.06

σ(C7–H14) → σ*(C1–C6)

4.34

1.04

0.06

n(F15) → σ*(C4–C8)

6.93

0.79

0.066

n(F15) → σ*(C8–F17)

5.04

0.67

0.053

n(F15) → σ*(C8–F16)

10.93

0.67

0.077

ACCEPTED MANUSCRIPT n(F15) → σ*(C8–F17)

9.13

0.67

0.071

n(F16) → σ*(C4–C8)

6.92

0.79

0.066

n(F16) → σ*(C8–F17)

5.03

0.67

0.053

n(F16) → σ*(C8–F15)

10.93

0.67

0.077

n(F16) → σ*(C8–F17)

9.12

0.67

0.071

n(F17) → σ*(C4–C8)

6.71

0.78

0.065

n(F17) → σ*(C8–F15)

4.12

0.67

0.047

n(F17) → σ*(C8–F16)

4.12

0.67

0.047

n(F17) → σ*(C8–F15)

9.91

0.67

0.073

n(F17) → σ*(C8–F16)

9.91

0.67

0.073

n(N18) → π*(C1–C6)

0.89

0.34

0.017

n(N18) → σ*(C1–C7)

8.78

0.7

0.07

aE(2)

means energy of hyperconjugative interactions.

bEnergy eF(i,j)

difference between donor and acceptor i and j NBO orbitals.

is the Fock matrix element between i and j NBO orbitals.

Table 5. The observed FT–IR, FT–Raman and calculated frequencies using B3LYP/6–311++G(d,p) and B3LYP/cc–pVTZ methods along

Assignment

intensity

Raman

intensity

IR

(cm–1)

Scaled

Calculated wavenumber

(cm–1)

intensity

Raman

intensity

(cm–1) IR

Scaled

Unscaled

Raman

FT–

FT–IR

(cm–1)

Calculated wavenumber

(cm–1)

B3LYP/cc–pVTZ

Unscaled

B3LYP/6–311++G(d,p)

wavenumber

Depolarization ratio

Observed

Depolarization ratio

with their relative intensities and probable assignments of 4–trifluoromethylbenzylaminea.

3368 s

3588

3367

1.59

18.22

0.75

3559

3356

0.67

20.17

0.75 νaNH2

3291 s

3499

3290

2.17

44.75

0.06

3482

3280

2.09

45.36

0.06 νsNH2

3215

3036

0.42

100.00

0.16

3199

3028

0.61

100.00

0.17 νCH

3214

3033

5.06

22.04

0.60

3198

3025

5.31

23.69

0.54 νCH

3178

3009

7.15

43.24

0.17

3163

3001

7.49

42.73

0.17 νCH

3178

2998

12.04

35.45

0.75

3162

2990

11.33

34.58

0.75 νCH

2928 s

3095

2926

17.24

32.80

0.75

3075

2918

16.99

33.02

0.75 νaCH2

2866 s

3051

2864

33.40

64.72

0.07

3038

2857

33.90

68.94

0.07 νsCH2

1670

1617

28.06

2.26

0.63

1664

1617

20.21

2.68

0.75 δNH2

1662

1567

19.82

42.08

0.55

1657

1567

18.26

36.69

0.51 νCC

1527 m

1624

1524

2.02

2.31

0.75

1620

1524

1.70

1.68

0.75 νCC

1475 vw

1550

1472

0.51

0.36

0.68

1551

1472

0.10

0.36

0.68 νCC

1490

1416

3.47

5.96

0.70

1493

1418

2.75

5.22

0.73 νCC

3035 vw 3011 m 3000 w

1620 s

1475 s 1420 s

1611 m

1374 m

1378 vw

1451

1374

16.94

0.09

0.75

1452

1376

18.07

0.06

0.75 δCH2

1384

1366

0.08

2.48

0.75

1386

1368

0.02

1.64

0.75 νCC

1371

1347

14.84

6.43

0.51

1367

1349

10.36

5.75

0.43 ωCH2

1354

1337

0.77

0.04

0.74

1349

1339

0.72

0.60

0.75 νCC

1341

1323

1.07

0.71

0.75

1340

1325

1.80

0.20

0.75 νCC

1327

1318

360.61

15.90

0.17

1325

1320

351.92

14.00

0.20 νsCF3

1220

1304

2.38

12.97

0.08

1221

1306

1.45

10.41

0.13 νC–CH2

1197 m

1210

1193

9.70

5.93

0.11

1211

1196

9.38

5.50

0.12 τCH2

1172 m

1170

1160

81.56

0.46

0.75

1172

1163

97.20

0.16

0.75 τNH2

1142 vw

1155

1138

77.84

0.19

0.75

1158

1141

54.21

0.13

0.75 βCH

1106 w

1118

1119

269.24

3.21

0.32

1128

1112

246.84

2.57

0.36 νaCF3

1112

1097

65.57

0.56

0.75

1114

1110

55.05

0.24

0.75 νaCF3

1079

1063

56.16

9.06

0.09

1084

1066

72.05

5.61

0.10 ρNH2

1073

1058

69.32

8.00

0.57

1077

1061

58.08

7.03

0.46 βCH

1030

1014

30.52

0.82

0.06

1039

1017

20.51

0.47

0.15 βCH

987

995

0.16

0.06

0.75

994

999

0.19

0.02

0.75 βCH

959 w

974

955

1.51

0.07

0.35

985

959

1.99

0.04

0.22 γCH

898 m

889

894

200.01

4.13

0.12

901

898

204.53

1.74

0.56 γCH

880

866

2.12

0.19

0.75

885

870

1.25

0.11

0.75 νC–NH2

854

841

0.41

0.08

0.75

863

845

69.37

0.38

0.07 γCH

851

838

86.52

2.69

0.10

859

842

0.39

0.22

0.75 γCH

1351 vs

1327 vs

1164 vs 1123 vs

1322 vw

1067 vs 1018 s 999 s

870 w

819 s

813 vw

763 w 733 m 624 m

731 m 621 w

592 m 516 w

398 w

167 m

aν–stretching;

807

809

43.75

13.66

0.04

813

813

34.64

16.85

0.04 βCCC

755

743

6.73

0.79

0.25

772

748

4.64

0.63

0.42 βCCC

728

727

4.25

0.45

0.11

740

732

5.10

0.24

0.56 δsCF3

650

639

0.48

2.95

0.75

654

644

0.49

3.00

0.75 βCCC

625

617

44.81

0.34

0.53

630

622

37.10

0.59

0.46 βCCC

587

588

4.94

0.34

0.61

595

593

3.82

0.32

0.60 ωNH2

565

555

0.07

0.36

0.75

575

561

0.08

0.34

0.75 δaCF3

515

511

5.43

0.24

0.36

521

518

5.03

0.22

0.50 βC–CH2

433

424

3.91

0.57

0.75

438

431

4.03

0.58

0.74 βC–NH2

415

406

1.67

0.02

0.75

418

413

2.25

0.09

0.75 γCCC

406

393

3.06

0.19

0.75

410

400

2.06

0.18

0.75 ρCF3

344

336

8.97

0.08

0.75

347

344

8.42

0.09

0.75 γC–CH2

335

327

1.08

1.15

0.27

338

335

1.17

1.20

0.31 ρCF3

266

258

2.56

1.54

0.16

267

266

1.85

1.26

0.20 γCCC

243

236

34.77

0.08

0.75

248

244

28.32

0.50

0.75 γCCC

166

162

0.25

1.46

0.74

168

170

5.65

0.03

0.75 γCCC

166

159

6.89

0.06

0.75

167

167

0.16

1.81

0.74 τCF3

68

62

0.95

0.23

0.75

68

71

0.74

0.18

0.74 γC–NH2

37

32

0.16

1.46

0.75

35

41

0.14

1.78

0.75 γCCC

7

2

0.06

0.97

0.75

6

11

0.04

1.10

0.75 γCC

β–in–plane bending; δ–deformation; ρ–rocking; γ–out of plane bending; ω–wagging; and τ–twisting. Raman intensities are normalised to 100.

ACCEPTED MANUSCRIPT Table 6. The experimental and theoretical 1H and 13C isotropic chemical shifts (ppm) with respect to TMS of 4–trifluoromethylbenzylamine. 1H

Assignment

σiso

Theoretical

Experimental

13C

δ (ppm)

δiso (ppm)

Assignment

σiso

Theoretical Experimental δiso (ppm)

δ (ppm)

H9

24.09

7.88

7.49

C1

25.84

158.69

147.22

H10

23.82

8.15

7.62

C2

50.72

133.81

125.30

H11

23.82

8.15

7.62

C3

52.65

131.88

122.41

H12

24.09

7.88

7.49

C4

48.66

135.87

125.66

H13

27.98

3.99

3.97

C5

52.67

131.86

122.41

H14

27.98

3.99

3.97

C6

50.74

133.81

125.30

H19

30.99

0.98

1.49

C7

130.98

53.55

45.49

H20

30.99

0.98

1.49

C8

45.72

138.81

126.96

δiso – isotropic chemical shift and σiso – isotropic shielding constant.

ACCEPTED MANUSCRIPT Table 7. The local reactivity descriptors of 4–trifluoromethylbenzylamine by B3LYP/cc– pVTZ method using natural population analysis (NPA) derived charges. f k

f k

f k0

∆f(k)

0.0887 –0.2026

–0.1958

–0.0956

–0.1457

–0.1002

C2

–0.2048 –0.1602 –0.2420

–0.0372

–0.0446

–0.0409

0.0074

C3

–0.1660 –0.1470 –0.2336

–0.0676

–0.0190

–0.0433

–0.0486

C4

–0.1511

0.0102 –0.3243

–0.1732

–0.1613

–0.1673

–0.0119

C5

–0.1661 –0.1473 –0.2323

–0.0663

–0.0188

–0.0425

–0.0475

C6

–0.2048 –0.1598 –0.2432

–0.0384

–0.0450

–0.0417

0.0065

C7

–0.2035 –0.2532 –0.1984

0.0051

0.0498

0.0274

–0.0446

1.0160

–0.0134

0.0178

0.0022

–0.0312

F15

–0.3403 –0.3154 –0.3703

–0.0300

–0.0250

–0.0275

–0.0050

F16

–0.3403 –0.3153 –0.3704

–0.0301

–0.0251

–0.0276

–0.0050

F17

–0.3416 –0.3120 –0.3813

–0.0397

–0.0297

–0.0347

–0.0100

N18

–0.8035 –0.4701 –0.8547

–0.0513

–0.3334

–0.1923

0.2821

Atom

Neutral

Cation

C1

–0.0068

C8

1.0294

1.0116

Anion

H9

0.2020

0.2308

0.1633

H10

0.2183

0.2530

0.1786

H11

0.2184

0.2531

0.1787

H12

0.2020

0.2308

0.1633

H13

0.1866

0.2247

0.1515

H14

0.1866

0.2247

0.1516

H19

0.3428

0.3762

0.3252

H20

0.3428

0.3762

0.3252

ACCEPTED MANUSCRIPT Table 8. The local reactivity descriptors (s) and dual descriptors (ω) of 4–trifluoromethyl benzylamine by B3LYP/cc–pVTZ method using natural population analysis (NPA) derived charges. Atom

s

 k

s

 k

s

0 k

Δsk



 k



 k



0 k

Δωk

Relative

Relative

Eletro

Nucleo

philicity

philicity

C1

–0.0202

–0.0099

–0.0150

–0.0048

–0.3405

–0.1662

–0.2533

–0.1743

2.0488

0.4881

C2

–0.0038

–0.0046

–0.0042

0.0005

–0.0647

–0.0775

–0.0711

0.0128

0.8345

1.1984

C3

–0.0070

–0.0020

–0.0045

–0.0022

–0.1176

–0.0331

–0.0753

–0.0845

3.5528

0.2815

C4

–0.0179

–0.0166

–0.0173

–0.0015

–0.3011

–0.2805

–0.2908

–0.0206

1.0735

0.9315

C5

–0.0068

–0.0019

–0.0044

–0.0022

–0.1152

–0.0326

–0.0739

–0.0826

3.5301

0.2833

C6

–0.0040

–0.0046

–0.0043

0.0004

–0.0668

–0.0782

–0.0725

0.0114

0.8543

1.1705

C7

0.0005

0.0051

0.0028

–0.0003

0.0089

0.0865

0.0477

–0.0776

0.1033

9.6790

C8

–0.0014

0.0018

0.0002

–0.0021

–0.0233

0.0310

0.0038

–0.0543

–0.7534

–1.3274

N18

–0.0053

–0.0344

–0.0198

0.0234

–0.0892

–0.5797

–0.3344

0.4905

0.1538

6.5014