Chapter 2 Strain and Stability - Reactivity of a new molecule -Prediction of the lowest energy conformation of a new molecule --> a rapid evaluation of strains and stabilizing effects 2.1 Thermochemistry of stable molecules (strain and stability) 2.1.1 The concepts of internal stain and relative stability Strain: Is typically associated with a conformational distortion or nonoptimal bonding situation relative to standard organic structures. The reference structure lacks the particular strain. Internal energy: It is the energy held or stored within a molecule. Part of this energy can be released when given an outlet such as a chemical reaction. When a molecule has a higher potential energy (internal energy), it is less stable and/or more strained. 2.1.2 Types of energy Gibbs free energy (ΔGo): It is change in ΔGo between two different chemical states that determines the position of equilibrium between these states. A ← → B R = 4.184 kJ/mol ΔHo : enthalpy (kcal/mol) ΔSo : entropy (cal/mol·K) Keq is influenced by temperature Exergonic, when the Gibbs free energy of B is lower than A, spontaneous conversion Endergonic, when the Gibbs free energy of B is higher than A Enthalpy (ΔHo): The change in enthalpy is defined as the change in heat between two different compositions of an ensemble of molecules at constant pressure if no work is done. Exothermic, negative ΔHo Endotherimic, positive ΔHo Entropy (ΔSo): is a measure of the disorder of the system. -> degrees of freedom the more degrees of freedom, the greater the entropy. There are three different kinds of degrees of freedom: translational, rotational and vibrational. Translational and rotational refer to the translation of the molecule throughout space and tumbling of the molecule, respectively. Vibrational refers to every kind of internal motion of the molecule, such as bond stretches, bond rotations and various forms of bond angle vibrations. While entropy is certainly important for significant changes in chemical structure (such as cyclization), often when comparing two similar structures, the difference in entropies will be fairly small. Thus, ΔHo is mainly considered in reactions. 2.1.3 Bond dissociation energies Is defined as ΔHo. (bond strength) Homolytic cleavage A larger BDE implies a less stable radical. 1. F > OH > NH2, the larger the electronegativity difference, the stronger the bond. 2. Shorter bonds are stronger bonds; O-H > N-H> C-H 3. F > Cl > Br > I; move down the periodic table, the valence orbitals of X get progressively larger. The larger orbital size leads to a size mismatch with the carbon valence orbitals, and this weakens the bond by decreasing orbital overlap. 4. Hybridization C(sp)-H > C(sp2)-H > C(sp3)-H, more s character in a hybrid orbital makes the group more electronegative and decreases the bond length. 5. Resonance PhCH2-H (88 kcal/mol) and CH2=CH-CH2-H (86 kcal/mol) 6. O-O bonds of peroxides: generally very weak 2.1.4 An introduction to potential functions and surfaces: bond stretches Vibrational energy states X. + Y. Anharmonic oscillator X-Y E = (n + ½)hv (n=0, ZPE) frequency = v = 1/(2π) √ k/μ k = force constant μ = reduced mass, (m1 +m2)/m1m2 Infrared spectroscopy k v = 1/(2π) √ k/μ k = force constant m1 m2 μ = reduced mass, (m1 +m2)/m1m2 Hooke’s law v = 1/(2π) √ k/μ frequency v = 1/λ = v/c= 1/(2πc)√k/μ Wavenumber(cm-1) 1) C-C C=C C≡C 450-500 cm-1 1617-1640 cm-1 2100-2260 cm-1 2) C=C-C=O C=O 1690 cm-1 1730 cm-1 O O- + less double character 3) O O O Cl R MeO R Me R O- O- + MeO R +Cl R wavenumber the largest the lowest middle 2.2 Thermochemistry of reactive intermediates 2.2.1 Stability vs persistence 1. stable; thermodynamic notion <-> unstable 2. persistent; kinetic notion (kinetically inert) <-> labile (reactive) 참조 1,3-butadiene ethylene more stable less stable <- extra orbital interaction between C2 and C3 more labile less labile HOMO energy (butadiene) > HOMO energy (ethylene) LUMO energy (butadiene) < LUMO energy (ethylene) ψ 4 Π* ψ3 ψ 2 Π ψ1 1,3-butadiene ethylene Stability: determined by the energies of all the filled orbitals Lability (reactivity): must consider the energy of HOMO or LUMO 2.2.2 Radicals 1. BDE; methane > ethane > propane > isobutane <- radical stability 3o > 2o > 1o > methyl 2. Allyl and benzyl radicals -> substantially stabilized (resonance effect) Allylic radical rotation barrier ~ 15.7 kcal/mol (resonance structure) In many cases, radical species are unstable but in some cases there are stable radical species. Commercially available 2.2.3 Carbocations Hydride ion affinity (HIA), ΔHo A larger HIA implies a less stable carbocation. 1. Heteroatom effects + + + stability: NH2CH2 > HOCH2 > FCH2 .. + + X-CH2 X=CH2 Consider both inductive and resonance effects 2. Hybridization effects stability: sp3 > sp2 > sp Consider electronegativity vinyl cation and phenyl cation: ~287 kcal/mol HIA verse Ethyl cation ~ 273 kcal/mol, propyl cation ~266 kcal/mol HIA propargyl cation ~270 kcal/mol verse allyl cation ~256 kcal/mol 3. Aromaticity and antiaromaticity stability: >> HIA 201 212 258 aromaticnon-aromatic antiaromatic resonance effect 4. Planarity and pyramidalization Carbocation: planar Ring constraints prevent Planar but 2o cation the ion from achieving Planarity. But 3o cation relatively small difference in HIVs (9 kcal/mol) In solution Carbocations are formed in solution by SbF5 (Olah, 1994, Nobel Prize) Lifetimes of carbocations 3o carbocations: 10-10 s in water 2o carbocations: 10-12 s in water 2.2.4 Carbanions Stability of carbanions is related to pKa values. The smaller pKa value implies a stronger acid. aromatic anti-aromatic 2.3 Relationships between structure and energetics -basic conformational analysis 2.3.1 Acyclic systems-torsional potential surfaces rotation barrier: 3kcal/mol ethane butane t1/2 = ln2/k Barrier height Similar; consider size and bond length Lower than C-C, lone pair < C-H Allylic (A1,3) strain 2.3.2 Basic cyclic systems Cyclic propane Bent bonds (sp4~sp5) 115o larger than H-C-H (106o) (sp~sp2) C-C-C, more p character to reduce bond angle (sp 180o, sp2 120o, sp3 109.5o) -> C-H more s character -> more acidic than alkane C-H Strain energy of cyclopropane: 27.5 kcal/mol (results from deviation of bond angles from normal values and eclipsing C-H interactions) Cyclobutane and cyclopentane very small barrier (1.45 kcal/mol) Strain energy: 26.5 kcal/mol puckered conformations Strain energy: 6.2 kcal/mol Two forms are very nearly equal in energy and they interconvert very rapidly (the barrier is < 2 kcal/mol) 5’ 3’ 4’ 1’ 2’ O N NH HO 5' N N NH2 O 3' 2' 1' 4' OH H (OH) Cyclohexane Newman projection A value: ΔGo of two structures (axial and equatorial) Not much difference similar R R consider size and bond length H R H R Conformational interconversion of cyclohexane Larger rings ~ 3 kcal/mol more stable cyclodecane Bicyclic ring systems spiro: a molecule has two rings and two share only one carbon in common Strain energy 2.4 Electronic effects 2.4.1 interactions involving π systems Substitution on alkenes: The more substitution, the more stable; interaction of a filled π(CH3) orbital with the π* orbital. π* - H H+ π(CH ) H H 3 H H H Hyperconjugation: no-bond resonance trans-alkenes are more stable than cis-ones. Stability, CH2=CH2 < CH2=CHMe < cis-CHMe=CHMe < trans-CHMe=CHMe < CMe2=CMe2 < CHMe=CMe2 steric effect Conformations of substituted alkenes: Eclipsed conformers are more stable than staggered ones. 2 kcal/mol more stable although there is steric hindrance. Repulsive interactions filled π filled π filled π(CH3) H H filled π(CH3) eclipsed staggered Repulsive interactions between filled π(CH ) and filled π Attractive interaction 3 π∗ C1 C2-C3: strengthened filled π(CH ) C2 3 C1-C2:weakened C3 H Allylic (A1,3) strain eclipsed; more stable A1,3 strain H C R H3C R 3 R = CH ; ~90% 3 H CH3 R = TMS; ~98% OH HO CH3 H the most stable conformer H3C R OH H H3C H C R H3C R 3 H3C R VO(acac)3 O O + H H H tBu-OOH CH CH3 HO 3 HO CH3 hydroxyl group directing HO epoxidation 90% 10% R = H acac: acetoacetate Carbonyl compounds 1 kcal/mol more stable 1-methylallyl cation Conjugation preferred steric effect Diels-Alder rxn 5 kcal/mol more stable Aromaticity Planar, cyclic, fully conjugated π systems Homoaromatic (4n+2)π electrons: aromatic, 4nπ e-: antiaromatic Ha Hb Ha Hb Homoaromatic: systems in which a stabilized cyclic conjugated system is formed by bypassing a saturated atom. - 6π e- 6π e μ = 0.8 D (HBr; 0.828 D) Aromatic compounds: ring current, downfield shift at 1H NMR spectra H downfield (~7 ppm) H H H H H H H H H 6H: -3 ppm H H 12H: 9.3 ppm H H H H H H H Antiaromaticity Planar, cyclic, fully conjugated π systems 4nπ e- Cyclobutadiene: antiaromatic not square but rectangular structure Cyclooctatetraene: non-aromatic nonplanar Cl SbCl 5 - + SbCl6 aromatic SbCl5 Cl extremely slow antiaromatic H pKa = 16 aromatic Ph Ph Ph Ph pKa = 50 Ph Ph antiaromatic 2.4.2 Effects of multiple heteroatoms Bond length effects The more substitution, the more stable; interaction of a filled π(CH3) orbital with the π* orbital. C-O and C-N are shorter than C-C, leading to increased steric strain. C-S is significantly longer than C-C. O O 2-position 5-position R no 1,3-diaxial interaction Orbital effects .