Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Fluorite crystals, Industrial preparations of fluorocarbons CaF2 “The most • Major source of fluorine is from fluorspar (CaF2), and from colorful phosphate rock (3.8 % F) mineral in • HF produced by distillation (Bp 20 oC) from fluorspar and the world” H2SO4 • Most fluorocarbons are produced from HF by either direct Primary text : reaction, electrolyzing solutions, fluorination with F2 or Chambers, R. D. Fluorine in metal fluorides organic chemistry. Blackwell, • Reactive halides are easily displaced with fluoride (Swarts 2004. reaction) ‘Fun’ fluorine facts Cl Cl KF Cl Cl F Cl Cl F • Highy toxic, pale yellow Cl NMP F F Cl Cl Cl Cl F F diatomic gas o 200 C F th Cl Cl F • 13 most abundant Cl Cl F element in crust Henri Moisson Chambers et al. J. Chem. Soc., Perkin Trans 1, 1997, 3623. 58 % • 1529, named ‘Fluo’ for ”In recognition of the great services rendered by him in his F “flow” since ores were low F F investigation and isolation of the pyrolysis Br o melting element fluorine ... The whole Br 500 - 700 C F F • Fluorocarbons are world has admired the great Br F Pt, Ni and Ni tubes greenhouse gases with experimental skill with which F global-warming-potentials you have studied that savage 30 % beast among the elements.” 100 – 200 000 x CO2 Wall et al. US2927138, 1960. Important events in the history of fluorocarbons • The most important fluorocarbon, tetrafluoroethylene, has • 1890-1938 Pioneering work by Swartz / “fluorine martyrs” many methods of product involving F2C: dimerization O o • 1886 Moisson isolated F2, later wins Nobel 800 C F F 600 - 800 oC CHF Cl • 1930 Midgey/Henne discover fluorocarbon refrigerants F3C OH 2 -CO2 F F -HCl • 1937 Simons isolates CF4, C2F6, C3F8, C4F10, C6F14 -HF • 1938 Plunkett accidentally discovers Teflon at Dupont 700 - 800 oC • 1940-1945 WWII drives discovery as stable materials -HF CF3H 1 235 intolerant to UF6 in U production Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Sterics Electronic effects • C-F is very only slightly larger than C-H bond Factors comparing fluorocarbons with hydrocarbons • C-F is isosteric with C-O 1. Electronegativity • CF3 occupies a significantly larger volume than CH3 2. Unshared electron pairs 3. Leaving groups / displacement of F- H F 4. C-F vs. C-H bond strengths H H F F 5. Size difference 16.8 Å3 42.6 Å3 H F Cl Seebach. Angew. Chem., Int. Ed., 1990, 29, 1320. Electronegativity (Pauling) 2.20 3.98 3.16 Ionization energy (kcal/mol) 314 403 299 Halogen bonding : Fact or fiction ? Electron affinity (kcal/mol) 17.7 79.5 83.3 Bond energy X-X (kcal/mol) 104 37.5 57.8 • There has been an ongoing debate on whether fluorine Bond length C-X (Angst.) 1.091 1.319 1.767 can form halogen bonding Van der Waals radius (Angst.) 1.20 1.47 1.75 • Consensus appears to suggest that no σ-hole is present, and therefore does not classify as a halogen bond • F+ not observed (unlike other halogens) LP repulsion • Slightly larger radius than hydrogen sigma-hole • Electron affinity and X-X bond strength Halogen bond Halogen bond donor δ- acceptor is lower than chlorine b/c unshared F F δ+ electron repulsion R3C X δ+ LB δ- Fluorine forms very strong bonds anisotropic X = Cl, Br, I • B-F, Si-F, H-F and C-F are strongest bonds due to ionic - e distribution sigma-hole bonding character • Pauling proposed no-bond resonance, now used often C-F bond BDE length (Å) (kcal/mol) qC qF F F CH3F 1.385 109.9 0.01 -0.23 F F F F CH2F2 1.357 119.5 0.40 -0.23 CHF3 1.332 127.5 0.56 -0.21 F F CF4 1.319 130.5 0.72 -0.18 Pauling, The Nature of the Chemical Bond, Cornell Univ. Press, Ithaca, Eskandari and Lesani. Chem. Eur. J. 2015, 21, 4739. 2 NY, 1960. Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Hyperconjugation Lipophilicity, viscosity and volatility • C-F bonds are strong hyperconjugative acceptors b/c of • Low intramolecular attractive forces b/c electroneg. of their low LUMO fluorine reduces polarizability and therefore the London- C-C C-H C-F dispersion force • Results in low viscosities, low surface tension and σ* σ* heats of vaporization, higher volatility and lipophilicity H F σ* Polarizeability H H H H F F F F E H H F F Best acceptor (for CH X, x10-24cm3) 3 H vs. F H F H H H H H F F F F F σ H 2.59 σ F 2.97 n-hexane n-perfluorohexane Best donor Cl 4.72 o o σ Bp = 68 C Bp = 56 C Br 6.03 Density = 0.66 g/mL Density = 1.68 g/mL Gauche effect • Vicinal fluorocarbons adopt gauche conformation to • Comparably higher densities maximize hyperconjugation Saturated fluorocarbons δ+ H H F H F F C F F C F F C F H H δ- * * F H H H * σC-F and σ C-F 2 x σC-F and σ C-F 2 x σC-H and σ C-F F anti gauche H Highly polarized No-bond resonance F F F H H H F F Unsaturated fluorocarbons vs. • Opposing contributions leads to variable reactivity H H H H C-H is better donor F H F F • Useful for explaining many phenomena δ- δ+ δ+ δ- F F F Polarized π-bond Pauli repulsion N N N N Why ? F Stability of hybridization ν = 1720 cm-1 ν = 1780 cm-1 109o 90o 2 x 90o O O Most H vs. F Why ? F > F > F H H H F stable 3 H H 3 2 H H H F sp sp sp Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Carbocations Carbanions • Carbocations are stabilized when bearing fluorine by • Carbanions are destabilized when bearing fluorine by mesomeric stabilization and destabilized when alpha to Pauli repulsion and stabilized when alpha to fluorine fluorine More stable More stable F F C > C F C F C F > C Pauli repulsion • George Olah discovered several long-lived • Base-catalyzed deuterium exchange experiments show carbocations stabilized by fluorine from strong LA fluorine is least stabilizing halogen when bound directly F Haloform Rate of exchange (105k)(l.mol-1s-1) SbF5 CHF Too slow to measure R R R R R R SbF6 3 o CHCl3 820 F -60 C F F CHBr3 101 000 SO2 R = aryl, alkyl CHI3 105 000 CHCl2F 16 CHBr2F 3600 Olah et al. J. Am. Chem. Soc., 1967, 89, 1268. CHI2F 8800 Hine et al. J. Am. Chem. Soc., 1957, 79, 1406. • Electrophilic aromatic substitution also demonstrates the counterintuitive stabilization of fluorine • Carbanions bearing fluorine will often adopt a pyramidal H Br structures to avoid repulsion Br H Me Me Me Me Me Me Br 13 kcal/mol H F H F H more stable than H Me Me Me Me Me Me X X X Burdon et al. J. Chem. Soc., Perkin 1, 1979, 1205. X Rel. Rate Br H • Carbanions with alpha fluorines are stabilized Me Me H 1 F F F F H F CF3 F 4.62 H F3C H F3C C F C C C C H Cl 0.145 Me Me 3 F F Br 0.062 F CF3 CF3 F Rel. rate D/H exchange 1 6 105 109 Approx. pKa 31 30 Mare and Ridd, Aromatic Substitution, Butterworths, London,4 1959. 20 411 Andreades, J. Am. Chem. Soc., 1964, 86, 2003. Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Carbon radicals • Fluorocarbons produce electrophilic radicals • Unlike other heteroatoms, fluorine offers little electrophilic radical stabilization to bound radicals, likely due to repulsion C8F17 C8F17 Least Most R add R stable CF3 < CH3 < CF2H < CFH2 stable R K rel OMe 1.41 Me 1.33 H 1.0 H H Cl 0.77 C F C F pyramidal CF 0.53 H H Me 3 Avila et al. J. Am. Chem. Soc., 1994, 116, 99. Me Carbenes H H C C F • Fluorine, a σ-acceptor and π-donor, leads to a very F F F F o By EPR at -108 C stable, singlet, ambiphilic carbenes Non-planar radical repulsion • Singlet state in energetically favored due to orbital Pasto et al. J. Org. Chem., 1987, 52, 3062. mixing and Pauli repulsion E - E Kawamura et al. J. Am. Chem. Soc., 1977, 99, 8251. Triplet singlet Worthington et al. (kcal/mol) H C: -9 • Adjacent fluorines (or other EWGs) are destabilizing, J. Phys. Org. Chem. 2 FHC: 15 but steric crowding can lead to kinetically stable 1997, 10, 755. F2C: 57 radicals Least Most • π-MO description of singlet and triplet F2C: stable CF CH stable * * 3 2 < CH3 < F2CHCH2 < FCH2CH2 < CH3CH2 π π Pross et al. Tetrahedron, 1980, 36, 1999. pz py p py • Steric crowding allows Scherer radical to be stable at rt z with oxygen present ! Observed by EPR vs. F CF sp2 3 F CF3 F3C CF3 F (σ) 2 F3C CF3 sp3 sp3 F π π F C F 3 F3C F F CF F 3 F CF3 F F F Stable Scherer radical 5 Scherer et al. J. Am. Chem. Soc., 1985, 107, 718. singlet triplet More stable Burns / Xia group meeting Fluorocarbon fundamentals Mar. 29, 2019 Ben Boswell Reactivity Nucleophilic aromatic substitution • Two-step mechanism of addition of nucleophiles to Displacement electron-poor arenes.