Chap. 6 Methods of Studying Organic Rxns

Transcription

1 hap. 6 Methods of tudying rganic Rxns Determining Reaction Mechanisms. Identification of reaction products. Determination of Intermediates Determining no. of steps ( a one step reaction, with reaction T.. product, is an elementary reaction if more than one elementary steps, an intermediate is involved reactant intermediate product depending on the magnitude of,, the concentration of intermediate can be high or low Isolating intermediate quench the reaction ( by cooling, by diluting, by removing catalyst,.. pectroscopic characterization UV-VI, IR, NMR, ER If not isolable, not spectroscopically observable, trap the intermediate by a trapping agent

2 R 6 5 N 6 5 N pin trap R less reactive indicate carbocation mechanism Disprove an intermediate synthesize a proposed intermediate and compare the reaction properties rossover Experiment To differentiate intra-molecular or inter-molecular ( inter fragmental or or

3 Isotope labeling the least perturbation to a system is by isotope replacement 3,3-sigmatopic tereochemical tudies dissociative radical mech. suggest inversion of reaction center r r suggest an achiral reaction center r r r rule out

4 olvent Effect olvent affects reaction rate through relative stabilization of reactants / transition deduce T.. structure e.g - - N ( 3 3 -l ( 3 3 l ( 3 3 -Nu X - the rate increases with increasing solvent polarity. more ionic character in T.. than the reactant N - 3 -r [ 3 r ] 3 r - The rate decreases with increasing solvent polarity less ionic character in T.. than starting material Measurement of solvent polarity dipole moment ( a molecular property e -e e esu, for r -8 cm e r esu cm r 4.8 D dielectric constant, effect of substance on the E-field between an capacitor, relating to polarity and polarizability E E - ε exane l 4.3 Me 3.7 l Et 4.5 Z Kosower scale Nu - - n-pr.4 E the charge-transfer band is sensitive to solvent the transition energy ZE T

5 E T (3 charge-transfer band acidity as -bonding Donor ( the ability of the solvent to donate a proton in solvent-solute -bond basicity as -bonded cceptor

6 pplication of Kinetics in tudying Rxn Mechanism reaction rate rate of change of concentration of reactant or product For a reaction n n n n P rate - n d - n d - n d a b c r[] [] [] overall reaction order a b c. determined by experiment not by stoichiometry (For elementary reaction the order of the reaction the no. of reacting molecule molecularity P n P dp Pseudo order if one reactant doesn't change its concentration significantly, e.g. [] const rate [] a [] b, reaction order a b aq Et e.g. RTs R-Et pseudo first order zero order product d rate d Differential rate equation t t Integration rate equation e.g. aturation reaction on the surface of a metal / half life t the time for / / t, t slope

7 First order reaction P d[ ] d [ ] [ ], [ ] [ ] t ln ln t, [ ] [ ] e, t/ [ ] plot ln[ ] v.s t straigh line, slope.693 econd order reaction type plot t / [ ] [ ] [ ] [ P] d[ ] d d, [ ] P d[ ], [ ] [ ] [ ] v.s t straigh line t slope [ ] [ ] / / [ ], t t type P d ln plot [ ] d[ ] [ ] [ ] ln [ ] ln [ ] [ ] [ ] ( [ ][ ], [ ] [ ] v.s t straigh line t, slope ([ ] [ ]

8 Reversible reaction subst. into above eq. t ( ( ( ( ( ln at t, t ( ln( eq t ( ln, d d ( d ( ( d ( ( ln( bx a b bx a dx Q. ] ( ln[( const t at t ] ( ln[(. const - t ( ln( plot left hand side v.s. t slop -, - from -

9 more common simplification : Pseudo first order P let [] >> [] so that [] is relatively constant d[] '[] [] ln 't [ ] where [] third order reaction 3 product d[ ] 3 rate [ ] 3 product d[ ] d[ ] rate [ ] [ ] product d[ ] d[ ] d[ ] rate [ ][ ][ ] For consecutive and irreversible reaction d[ ] rate [ ] [ ] d[ ] t [ ] [ ], [ ], [ ] [ ] e d e t t ( e e t

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11 pply steady state approximation to [] in the case >> d[ ] [ ] [ ] [ ] [ ] d[ ] rate [ ] [ ] the s.s.a. is more accurate if / << For D - d[ D] rate [ ] applying steady state approximation d[ ] [ ][ ] [ ] [ ] [ ][ ] [ ] d[ D] [ ][ ] rate i.e. the first step is slower if << -, - - (the reverse reaction is fast rate ( [ ][ ] K[ ][ ] if >> - rate [ ][ ] Pre-equilibrium const.

12 e.g. E cb rxn Z X Z X - electronwithdrawing Z X Z X - d[ Z X ] s.s.a. [ Z X ][ ] rate [ Z d[ Z X ] [ Z [ Z [ [ Z X X ][ ] ] [ ] X ][ [ Z X ][ ] ] ( assume >> - [ ] (formation of carbanion is slow, destruction is fast rate [Z X][] ( assume - [ ]>> (the destruction of anion is slow ] ] rate [ Z [ X ][ ] ] To distinguish between ( or (, one can use a buffer.

13 Experimental methods for determination of reaction orders ( method of integration d [ ] a [ ] b [ ] ( method of half life t / -n, n is the order c evaluation of a, b, c by integration plot determine the relationship between t / and order (3 method of isolation Pseudo orders d [ ] a [ ] b [ ] c mae the concentration of and extremely large so that they don t change with progress of rxn. (4 Differential method t monitor the conc. of v.s. t d n if d t d log( log nlog d d determine several, plot log( v.s. no matter what the order is, d log( log the slope is the order of v.s. log is always a straight line, with slope n

14 rrhenius Theory & Transition tate Theory rate constant is a function of temperature activation energy Potential energy Ea Reactant rrhenius equation ln -Ea/RT ln [ Transition tate ] ln Product exp (-Ea/RT ln slope -Ea/RT Ea activation energy pre exponential factor relate to probability Transition state Theory /T ( K The starting material is in equilibrium with activated complex r treat the T as a species, rate [] frequency of T. oltzmann onstant passing over κt ( κ T / h e( G / RT e( / R e( / RT h transmission coefficient, to account for probability of reactant to product for G T (Ea RT r T κ e h ± / R r κ ln ln T h R r plot ln v. s. T e ± / RT T RT from slope, then from r, T, at one temp.

15 reflects the change in the order of the system from reactants to activated complex ( T.. ( ( 3 3 [( ( 3 3 ] 3.8 eu ( 3 3 one molecule becomes two -.7 eu two fragments connected together -6 eu two molecules combine to one For competing reaction [ ] [ ] [ ] [ ] if irreversible, the product ratio is the rate constant ratio. e G G ( cal/mol / RT activation free energy difference

16 Different product ratio for diff. reaction time (or temperature for reversible reaction : : sec N N N NNN.5 hr NNN l l l l hours a wee l different prod. ratio at diff. temperature

17 Kinetic control v.s Thermodynamic control oth time effect and temperature effect are of same origin the time required to reach the equilibrium Kinetic enolate v.s Thermodynamic enolate 3 ( ( 3 If a buly base used, non-hydroxylic solvent used, low temperature used less substituted enolate dominates ( Kinetic enolate If hydroxylic solvent used, or higher temperature equilibrium reached more substituted enolate dominates ( Thermodynamic enolate

18 urtin-ammet Principle Ph Ph l conformational equilibrium Ph Ph Ph Ph This product is favored, but not due 3 4 to a favored anti-conformation l Ph Ph For two equilibrium conformational isomer, each leading to different product, the product ratio is determined by the activation energy difference, not by the population of the isomer. [] Kc [] dp rate of Product P a[] akc[] dp Product P b[] dp / akc[] akc Product ratio dp / [] r κt e h G / RT product ratio ( κt / h e ( κt / h e b, Kc e G a / RT G e b b ( G / RT G e c / RT / RT e ( G G b a G G a b G c / RT

19 Kinetic Isotope Effect θ the KIE results from the zero point energy difference for - or D- substituted species E D -E (θ E o -(θ E o E o - E o due to anharmonicity ν e.g. for a - bond, - ~ 3cm - replaced by D, -D ~ cm - zero point energy E π µ force const. reduced mass In ground state, the zero point energy differs by E, in transition state, zpe differs by E ( usually E < E depend on the extent of - bond breaage, / D may very. / D exp {( E - E /RT} hν for - / D maximum value at room temp. ~7 for primary KIE depend on the ext. of bond cleavage, < / D <7 Information provided by primary KIE. / D > strong evidence that the - bond is broen in T... the magnitude of / D provides qualitative indication of where the T.. lies relative to.m. or Product symmetric / D small large small

20 early transition state late transition state / D ~ / D ~ (small - (or -D bond is slightly broen in the T.. - (or -D is nearly fully broen away from.m., but nearly fully from in product. ymmetric T. - (or -D is half-broen large / D [ Transition tate Theory Description ] contribute to Zero asymmetric stretching ( reaction coordinate symmetric stretching Point energy in T.. in plane bending out-of-plane bending of low energy & cancel similar bending in.m. Et - e.g. -X Et, 3 X r Ts Me NMe 3 / D ~ 7 / D for non-linear T.. KIE is also smaller N Me Me 5% -transfer

21 usual range of Primary Kinetic Isotope Effects 5~8 ome KIE are much larger than expected maximum ecause oversimplifications. - bending vibration ( ~48 if considered. Tunneling of will increase / D Tunneling Effect m Intra molecular KIE by lassical mechanical Theory the probability of finding m in the other side is zero. by Quantum mechanical Theory There is finite probability on the other side of the barrier only one Z.P.E. if R l / D.3 R r / D 4.6 Transition tate lies to the right ( occurs later

22 econdary Isotope Effect The effect of isotope substitution at a bond not broen in the transition state. result from zero-point-energy difference due to change of force constant in a vibration in going from reactant to T.. ( -, - KIE e.g. for rxn R (D X R in going from sp 3 sp, - bond will experience a decreased resistance to - bending. The effect is greater for - bond than -D bond ( - longer than -D by.9å / D > ( normal secondary isotope effect. R R (D X - 9 (stretch 8 (stretch in-plane-bend 35cm - 35cm - in-planebend out-of-planebend o.p. bend / D.4 For 35cm - 8cm - (D (D sp sp 3 / D <.7 ( Inverse IE.4 The exact value depend on the location of T..

23 -isotpoe effect N N rxn -secondary isotope effect the isotope bond to a position next to reaction center indicate N rxn sp 3 sp The hyperconjugation weaens - (or -D bond, thus a small ZPE contribution. faster for - species (- > -D

24 Isotope effect on cidity ( Not Kinetic IE, but equilibrium IE 6 D 5 6 D 5-6 D 5 6 D 5 6 D 5 D 6 D 5 D - - Ka(/Ka(D... D D - D 3 D The -D bond is shorted than - by.9å, the electron-density is closer to, equivalent to a e - -donating group. ( I effect, -D > - Path : nucleophilic addition Path : electron transfer followed by combination of radicals / D.84, implying rehybridization

25 ubstituent Effect and Linear Free Energy Relationship substituent can influence a reaction rate, equilibrium or property via inductive, resonance, steric effect. Resonance Effect Polarization of charge density through bond formation ( or -system in a structure F F Me Me N N R e-donating halogen, R, NR, alyl -R e-withdrawing -N, -N, - R, both electrostatic Inductive Effect Due to polarization of a -bond, the bond dipole, transmit through bonds by successive polarization. short range, electrostatic in nature δ Y δ δ - δδ - δ - X δ - δ - Y δδ - δδ - δ - X δ - δ Y δδ δδ δ X δ δ - Y δδ δδ favorable unfavorable unfavorable favorable δ X δ interact through bond more important Field Effect Through space electrostatic interaction δ Y X δ - Y X δ Y X δ - Y favorable unfavorable unfavorable favorable I aly -I halogen, - NR 3, - R, -X 3 X interact through space

26 higher acidity for -fluoroethanol F tabilized by inductive withdrawal through bond δ - δ or the importance of through space effect F tabilized through space field effect δ - δ X X δ - δ l δ δ - X pka 6.4 l 6.5 X pka 4.4 r 4.7 l 4.9 field effect in right orientation the - end of -l bond close to the carboxylate through space effect decr. acidity decr. acitidy imilar effect for X on acidity on the two type cpd. Field effect outweighs pka 5.7 pka 5.9 X distance three 3-bond path between X and X l distance closer to, by inductive effect through bond, should be stronger acid six 3-bond path between X and, through bond effect should be more effective

27 Transmission of electronic properties through framewor N 3 N 3 N 3 N 3 3 tabilization E F -3.8 F Linear Free Energy Relationship 3 F -3.7 F Thus field effect seems to be important. similar stabilization with or without - Ka N - N Ka Ka > Ka N N 3 > G the free energy change of the rxn by the structure change G the free energy change of the T. by the structure change log K log from G -RTlnK, G log with no substituent log log then log ρ log K o -RTln ρ log K K K ρ log let log K K i ρσ ammet equation i i σ

28 σ substituent constant log measure of the electronic effect of Ki K i substituted enzene unsubstituted the substituent at a particular position. at 5 in ρ reaction constant for ionization of benzoic acid ( the reference system for rxn favored by e - - withdrawing for rxn favored by e - -donating for e - -withdrawing for e - -donating substituted enzoic acid measure of sensitivity of the reaction to the electronic effect of a substituent P-N -.66 P P-l.3 P-N.66 P-N.78

29 For a particular rxn, plot rates v.s, if a linear curve is obtained, a linear free energy relationship exists. e.g NNN NNN semi carbazide ρ.9.9 means there is negative charge developed in the T.. at p.75 NR - NR NR - X X X at p.75, the first step is rate-determining magnitude of sensitivity to the substituent extent of charge development (not necessary e.g. 4%Et the decrease in reflect lower sensitivity not different charge formation

30 Inferring mechanism from ammet value typical N reaction has low values e.g. l δ - l l δ - δ bond breaing > bond formation l I acetone δ - I.8 I bond formation > bond breaing the large value of. for ester hydrolysis rules out a N mechanism owever - 98% Et I Et -. 3 N l benzene -.8 N

31 Nonlinear ammet orrelation If not due to expt l error, if not due to impurity, if not due to side reactions. may due to change of mechanism or change of rate determining step. favored by e-withdrawing gps. NNN NNN - For neutral p NNN favored by e- donating gps. logk eq (log / - log overall log dehyd. at Neutral p, the observed rate is the resultant of two insensitive to at p 3.9 nd step became r.d.s. the first step is r.d.s.

32 defined with respect to ubstituent onstants substituent constant depends on position - no direct resonance between and arbxyl carbon -I determine m > P the inductive effect ( and field effect are distance-dependent. the closer, the stronger R I P > m stronger interaction due to resonance resonance did not bring stronger interaction defined with respect to 3 l olvent l 3 correlate well with direct resonance interaction with reaction center. more sensitive for those can interact through resonance

33 - defined with respect to Which sets of s correlate better will depend on the nature of the reaction center. Yuawa-Tsuno equation log K K wain-lupton ρσ ρr a term to correct for the additional contribution from resonance ( σ σ depend on rxn, large r large resonance contribution r, original ammet eq. log x f F rr υ field effect (Polar resonance effect for ortho-substituents, steric effect may involve. ( dual-substituent parameter I I R R * σ : a measure of polar effect of alyl substituent in aliphatic system. * x x σ [(log (log ]/. 48 o o Taft equation log ρ σ υ E log( x * * E steric substituent constant acid-hydrolysis of aliphatic ester R R, only related to steric effect