Kinetic Isotope EffectsIsotope effects more interesting when they tell us about character of rate-determining transition state.Example:BrD/HHHH3CD/HBrH/DHHH3CD/HEtOHHD/HH3C+BrEtO(H/D)EtOHow should isotopic substitution affect rate in this reaction?orHow does isotopic substitution affect relative energies of starting material and transition state?δ-δ-Primary Kinetic Isotope Effects1° KIE: Isotope participates directly in reaction.BrD/HHHH3CD/HBrH/DHHH3CD/HEtOHHD/HH3C+BrEtO(H/D)EtOTransition-state theory says:Reaction coordinate mode has no frequency at TS.C-(H/D) stretchC-HC-DC- -H- -OC- -D- -OΔG‡HΔG‡DEδ-δ-Primary Kinetic Isotope Effects1° KIE: Isotope participates directly in reaction.BrD/HHHH3CD/HBrH/DHHH3CD/HEtOHHD/HH3C+BrEtO(H/D)EtOC-(H/D) stretchC-HC-DC- -H- -OC- -D- -OEΔG‡HΔG‡DΔG‡H< ΔG‡DkH> kDkHkD> 1(= 6.7here)δ-δ-C-(H/D) stretchC-HC-DC- -H- -OC- -D- -OEΔG‡HΔG‡DRTRTGGRTGRTGeeehTkehTkkkD)ZPE(CH)ZPE(CBBDH‡H‡D‡D‡H−−−Δ−ΔΔ−Δ−===Secondary Kinetic Isotope EffectsIsotope effects still observed when isotope is not directly involved in reaction coordinate. (Called 2° KIE.)CH3D/HBrCH3D/HOHCH3D/HBrCH3D/Hδ+δ-kHkD= 1.1(seems small, butvery reproducible)Here, C-(H/D) bond is not part of reaction coordinate.Secondary Kinetic Isotope EffectsCH3D/HBrCH3D/HOHCH3D/HBrCH3D/Hδ+δ-reaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3Before, we asked how vibrational modes changed over course of reaction.How about now?Secondary Kinetic Isotope Effectsreaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3Before, we asked how vibrational modes changed over course of reaction.How about now?BrHPhH3CHH3CPh2950 cm-13050 cm-1νstretch =Csp3-H Csp2-HstartingmaterialintermediateBrHPhH3CHH3CPh1350 cm-11350 cm-1νin-plane wag =BrHPhH3CHH3CPh1350 cm-1800 cm-1νout-of-plane wag =Largest Δν. We’ll consider this mode.Secondary Kinetic Isotope Effectsreaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3BrHPhH3CHH3CPh1350 cm-1800 cm-1Secondary Kinetic Isotope Effectsreaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3BrHPhH3CHH3CPh1350 cm-1800 cm-1Secondary Kinetic Isotope Effectsreaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3BrHPhH3CHH3CPh1350 cm-1800 cm-1We don’t know what transition-state frequency is; assume is between starting material and product.Secondary Kinetic Isotope Effectsreaction coordinate(C-Br bond breaking)(C-O bond making)BrCH3H/DH/DCH3BrHPhH3CHH3CPh1350 cm-1800 cm-11350 cm-1< νwag< 800 cm-1ΔG‡HΔG‡DΔG‡H< ΔG‡DkH> kDkHkD> 1(= 1.1here)BrCH3H/Dδ+δ-> 1 because ν decreasedin rate-determining step (relative to starting material)Secondary Kinetic Isotope EffectskHkDcan also be < 1:kHkD= 0.95sp2→ sp3hybridization at C-H/D shows opposite trend from previous example;OOOH/DH/DOOOOOOH/DH/DH/DD/HDiels-AlderΔG‡H> ΔG‡DkH< kDkHkD<