Structural Analysis of 2-Fluorophenol and 3-Fluorophenol Based on FTMW Rotational Spectra Aimee Bell, Omar Mahassneh, James Singer, Durell Desmond, Jennifer van Wijngaarden Department of Chemistry, University of Manitoba MI04 ISMS 71st Meeting June 20, 2016

Fluorinated Compounds Fluorinated compounds are used in a variety of industrial applications Fluorination can be used to manipulate chemical and physical properties Figures: Faslodex – breast cancer drug Fluorine substituted liquid crystals – used in LCDs Fluorine Substituted Liquid Crystals2 Faslodex1 1S. Purser et al. Chem. Soc. Rev. 2008, 37, 320-330. 2R. Berger et al. Chem. Soc. Rev. 2011, 40, 3496-3508.

Interactions Involving Fluorine FTMW techniques allow for H-F interactions to be studied in isolation Intermolecular interactions well documented with FTMW; intramolecular interactions not widely studied -intramolecular interactions more commonly studied with IR Intermolecular Interaction in CH3F•CHF33 Intramolecular Interaction in 2,3,5,6-tetrafluorohydroquinone4 3W. Caminati et al. Angew. Chem. Int. Ed. 2005, 44, 3840-3844. 4A. Kovacs et al. Chem. Phys. 2007, 335, 205-214.

Ecis - Etrans = -2.9 kcal/mol5 2-Fluorophenol Cis-2-FPh Trans-2-FPh -cis stabilized by intramolecular interaction (OH---F) Ecis - Etrans = -2.9 kcal/mol5 5MP2/aug-cc-pVDZ value from M.A. Moreira et al. J. Mol. Struct. 2012, 1009, 11-15.

Ecis - Etrans = 0.2 kcal/mol5 3-Fluorophenol Cis-3-FPh Trans-3-FPh -neither conformer has an intramolecular interaction Ecis - Etrans = 0.2 kcal/mol5 5MP2/aug-cc-pVDZ value from M.A. Moreira et al. J. Mol. Struct. 2012, 1009, 11-15.

Previous MW Studies of FPh MW spectrum of cis-2-FPh A. Dutta et al., J. Mol. Spec. 1985, 114, 274-279. MW spectrum of 3-FPh A.I. Jaman et al., J. Mol. Spec. 1981, 86, 269-274. A.I. Jaman et al., J. Mol. Struct. 1982, 82, 17-21. A. Dutta, A.I. Jaman, Pramana. 1985, 24, 499-502. A.I. Jaman J. Mol. Spec. 2007, 245, 21-25. Proposed r0 Structure of Trans-3-FPh (1982)

Instrumentation Sample Mixing Manifold Microwave Circuit Microwave Source Vacuum Chamber Balle-Flygare FTMW Spectrometer at the University of Manitoba6 6G. Sedo, J. van Wijngaarden, J. Phys. Chem. 2009, 131, 044303.

Experimental Conditions Spectral range: 6 to 26 GHz 13C isotopologues observed in natural abundance ~1 bar of Ar bubbled through heated liquid samples -samples had high boiling points (171-172 C for 2FPh, 178 C for 3FPh) -glass vessels were heated in a bath to raise the vapour pressure Glass Bubbler Vessel in a Heated Bath

2-Fluorophenol Dipole Moments MP2/6-311++G(2d,2p) a Cis-2-FPh μa = 1.17 D, μb = 0.45 D Parent and 13C isotopologues detected Trans-2-FPh μa = -0.74 D, μb = -3.04 D Not detected b μ b μ -trans-2-FPh was not detected; too high energy for observation a

2-Fluorophenol Spectroscopic Constants   Parent 13C1 13C2 13C3 13C4 13C5 13C6 Rotational Constants/MHz A 3337.90081(11) 3326.28501(44) 3328.71441(44) 3295.56795(45) 3326.82647(44) 3328.75201(44) 3295.84576(43) B 2231.934257(95) 2229.887691(53) 2229.894183(53) 2227.103182(53) 2196.063557(53) 2195.168560(53) 2226.174953(53) C 1337.551323(69) 1334.949793(35) 1335.343376(35) 1328.982992(39) 1322.837015(35) 1322.816067(35) 1328.697116(35) Centrifugal Distortion Constants/kHz ΔJ 0.0819(15) 0.0819 ΔJK 0.0546(41) 0.0546 ΔK 0.6050(48) 0.6050 δJ 0.02902(68) 0.02902 δK 0.1074(28) 0.1074 RMS/kHz 1.2 0.63 0.88 0.64 1.7 1.4 # of lines 79 16 15 Δ/amu•Å2 0.0018(4) 0.0016(3) 0.0015(3) 0.0018(3) 0.0020(3) 0.0021(3) 0.0019(3) *Watson’s A-reduced Hamiltonian Ir Representation in Pickett’s SPFIT

3-Fluorophenol Dipole Moments MP2/6-311++G(2d,2p) a a Cis-3-FPh μa = 0.73 D, μb = 0.13 D Parent detected Trans-3-FPh μa = 2.07 D, μb = 2.29 D Parent and 13C isotopologues detected b μ μ b

Sample Transitions of 3-Fluorophenol Cis S/N = 25 Cycles = 310 Trans S/N = 25 Cycles = 115 -cis has weaker signal due to smaller dipole and higher energy

3-Fluorophenol Spectroscopic Constants   Trans Conformer Parent 13C1 13C2 13C3 13C4 13C5 13C6 Cis Conformer Rotational Constants /MHz A 3748.561501(29) 3746.40579(12) 3721.79808(18) 3747.00581(11) 3713.48601(16) 3660.28816(17) 3715.55890(16) 3754.15000(45) B 1797.766571(15) 1788.232502(37) 1797.854969(60) 1789.489242(38) 1788.948278(42) 1797.774597(56) 1787.783733(66) 1792.784980(54) C 1215.094056(12) 1210.506592(18) 1212.310961(29) 1211.145098(17) 1207.374600(20) 1205.668340(20) 1207.062928(28) 1213.406193(34) Centrifugal Distortion Constants /kHz ΔJ 0.06475(11) 0.06475 0.06636(39) ΔJK -0.00562(40) -0.00562 -0.0224(16) ΔK 0.6154(10) 0.6154 0.491(93) δJ 0.022427(55) 0.022427 0.02350(21) δK 0.13276(55) 0.13276 0.1260(84) RMS/kHz 0.484 0.919 1.379 0.797 1.007 0.893 1.241 0.380 # of lines 154 44 41 39 40 36 37 47 Δ/amu•Å2 -0.0168(9) -0.017(2) -0.018(3) -0.015(2) -0.017(3) -0.019(3) *Watson’s A-reduced Hamiltonian Ir Representation in Pickett’s SPFIT

Cis-2-FPh Aromatic Ring Geometry Bond Lengths Angles 1 2 3 4 5 6 C1-C2 δre = -0.001 Å δr0 = -0.003(2) Å C2-C3 δre = -0.012 Å δr0 = -0.015(3) Å C3-C4 δre = 0.002 Å δr0 = 0.001(3) Å C4-C5 δre = 0.000 Å δr0 = 0.006(4) Å C5-C6 δre = 0.001 Å δr0 = 0.002(3) Å C6-C1 δr0 = -0.003(3) Å C1-C2-C3 δre = 2.9o δr0 = 3.1(3)o C2-C3-C4 δre = -1.8o δr0 = -1.9(4)o C3-C4-C5 δre = 0.5o δr0 = 0.3(4)o C4-C5-C6 δre = 0.0o δr0 = 0.1(3)o C5-C6-C1 δre = 0.4o C6-C1-C2 δre = -1.9o δr0 = -1.6(3)o re = eqm structures from Gaussian (MP2), r0 = ground state effective structures from STRFIT -C1-C2 not shortened since both atoms are bonded to electronegative atoms (O and F) δ = (Cis-2-FPh Value) – (Phenol re Value)

Trans-3-FPh Aromatic Ring Geometry Bond Lengths Angles C1-C2 δre = 0.001 Å δr0 = 0.001(5) Å C2-C3 δre = -0.009 Å δr0 = -0.011(5) Å C3-C4 δre = -0.008 Å δr0 = -0.011(2) Å C4-C5 δre = -0.001 Å δr0 = 0.003(3) Å C5-C6 δre = 0.000 Å δr0 = -0.001(3) Å C6-C1 δr0 = -0.005(2) Å C6-C1-C2 δre = 0.3o δr0 = 0.8(5)o C1-C2-C3 δre = -1.5o δr0 = -2.2(5)o C2-C3-C4 δre = 2.5o δr0 = 3.3(3)o C3-C4-C5 δre = -1.7o δr0 = -2.1(4)o C4-C5-C6 δre = 0.6o δr0 = 0.7(3)o C5-C6-C1 δre = -0.2o δr0 = -0.5(5)o 1 2 3 4 5 6 -deviations from phenol occur based on position of the F-atom -electronegativity of F changes the hybridization character of nearby atoms δ = (Cis-2-FPh Value) – (Phenol re Value)

Additional r0 Geometry 116.75(13)o 120.33(13)o 117.71(13)o 118.37(13)o -<(C-C-F) angles also determined in r0 analysis 118.37(13)o

NBO Analysis of Cis-2-FPh Fluorine lone pair donates to π* orbital of OH Not seen in other isomers of fluorophenol Analogous interaction in cis-2- cyanophenol: 0.72 kcal/mol7 -NBO = natural bond orbital (done with Gaussian) -analysis done for all fluorophenols and phenol -OH---F interaction energy: 0.73 kcal/mol (~3 kJ/mol) Eint = 0.73 kcal/mol MP2/6-311++G(2d,2p) 7R. Conrad et al. Phys. Chem. Chem. Phys. 2010, 12, 8350-8356.

Theoretically, Is There a Hydrogen Bond in Cis-2-FPh? IUPAC Minimum Angle for X-H•••Y H-bond: 110o 8 ( 2.212 Å 112.3o van der Waals Radii Sum of H+F: 2.56 Å 9 MP2/6-311++G(2d,2p) 8E. Arunan et al. Pure Appl. Chem. 2011, 83, 1637-1641. 9R.S. Rowland, R. Taylor. J. Phys.Chem. 1996, 100, 7384-7391.

Concurrent Work 2-FPh and 3-FPh rovibrational spectra observed in far-IR region Out-of-plane OH torsion vibration being analyzed Trans-2-FPh 344 cm-1 Cis-2-FPh 381 cm-1 Trans-3-FPh 311 cm-1 Cis-3-FPh 319 cm-1

Acknowledgements Wenhao Sun

Effects of Electronegativity -0.5 0.2 0.0 -0.4 Δ = 0.7 Δ = 0.4 Δ = 0.2 s p e- s This explains why C2-C3 is shortened in cis-2-FPh and why C1-C2 is not. -0.518 +0.518