物理有机化学复旦大学王全瑞.pptx

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1、 proton transfer to N,O,S is fast;proton transfer to carbon(C)is slow proton transfer from H3O+to N or O is diffusion-controlled:k-1 1011 l.mol-1.s-1Formation of the hydrogen bond between the proton donor and the proton acceptor is the rate determining step:this step is slower than the actual proton

2、 transfer!Typical for cases where a proton is both bound to and transferred to oxygen or nitrogen atoms,where the negative charge is localized on one atom.1第1页/共34页Nevertheless,diffusion of H+in water is much faster than diffusion of other ions:2第2页/共34页Proton Transfer from/to Carbon Acids/Basesk1=4

3、x10 8 l.mol 1.s1,slow process due to:-lack of hydrogen bond formation before proton transfer-low acidity of the hydrogen atoms.k-1=16 l.mol 1.s1,also much slower than diffusion rate,because:-upon protonation a considerable redistribution of charge has to take place,including the concomitant change o

4、f solvation.12:carbon acid,k1 and k-1 relatively small23:oxygen acid,k1 and k-1 relatively large(H-bond formation)Another example:3第3页/共34页4Most carbon acids are stabilized by resonance.Hence significantstructural reorganization must accompany deprotonationThe greater the structural reorganization d

5、uring deprotonation,the lower the kinetic acidity第4页/共34页Influence of pH on Reaction RateThe hydrolysis of esters is catalysed by both acid and base:pHlog kobs7.05第5页/共34页Another example:the mutarotation of glucosepHlog kobs7.06第6页/共34页Another example:imine formationpHlog kobs4.5pH optimum 4.5Slope

6、of plot of log kobs vs.pH is often close to 1:linearly dependent on H+or OH-7第7页/共34页Two mechanisms for acid catalysisSpecific acid catalysis:-A proton is transferred to the substrate in a rapid pre-equilibrium;subsequently,the protonated substrate reacts further to the product(s)in the rate determi

7、ning step:General acid catalysis:-Proton transfer occurs in a slow,rate-determining step;subsequently,the protonated substrate rapidly reacts to give the product(s):8第8页/共34页Specific acid/base catalysisUsually found for electronegative elements(O,N),where proton transfer is fast:The second step is r

8、ate-determining and can be mono-or bimolecular:Reaction rate:sincewe can now write:So the rate is only dependent on the pH,not on HA!9第9页/共34页Example of specific acid catalysis:hydrolysis of acetals(A1 mech.)xxxxxxkobsH+kobs is directly proportional to H+;addition of more acid(buffer)at constantpH h

9、as no effect on kobs.Proton transfer is not rate limiting,so the mechanism probably reads:kobsClCH2COOH/ClCH2COO-(2:1)xxxxxx10第10页/共34页Example of a reaction that is specific acid catalysed accordingto the A2 mechanism:the hydrolysis of ethyl acetate:11第11页/共34页Specific Base CatalysisExample:the retr

10、o-aldol reaction of I:xxxxxxkobsOH-kobs is directly proportional to OH.Addition of more base(in buffer)at constant pH has no effect on kobs;OH-is the only base that occurs in the rate equation.12第12页/共34页Therefore,the reaction mechanism most probably reads:Reaction equation:there is the acid-base eq

11、uilibrium in water:rewriting:soIt is clear that only OH-occurs in the rate equation!13第13页/共34页General Acid/Base CatalysisProton transfer is the rate-determining step.Example:the hydrolysis of ortho esters:The reaction is studied in a series of buffers(m-NO2-C6H4-OH/m-NO2-C6H4-O):reaction rate incre

12、ases with increasing buffer concentration,even if the pH remains constantn=k(H2O)H2O+k(H3O+)H3O+k(m-NO2-Ph-OH)m-NO2-Ph-OHIIIbuffernk(H3O+)H3O+k(H2O)H2OIIIk(buffer)14第14页/共34页General acid/base catalysis:the reaction rate is dependent on all acids/bases present in solutionGeneral acid catalysis:kobs=S

13、 kiHAiGeneral base catalysis:kobs=S kiBiExample of general base catalysis:The reaction rate is dependent on the buffer concentration,at constant pH.There is also a contribution of OH-and H2O.ClCH2COO-/ClCH2COOHkobs15第15页/共34页So,the reaction mechanism is most probably:=k(H2O)H2OIV+k(ClCH2COO)ClCH2COO

14、IV+k(OH)OHIV16第16页/共34页SummarizingSpecific acid/base catalysis:n=kSH3O+orn=kSOHGeneral acid/base catalysis:n=kxH3O+kyH2O+kzHA+.S=SHAiS,or with bases:n=SBiS.When kxH3O+or kxOH are large,the contributions of other acids/bases become negligible and the kinetics resemble specific acid/base catalysis.For

15、 this reason,general acid/base catalysis usually only occurs around neutral pH.17第17页/共34页How effective is a general acid catalyst:the Brnsted relationThe effectiveness of a general acid catalyst depends on its acid strength(=the Brnsted relation):log kHA=a log KHA+a constantkHA =rate constant of th

16、e catalytic stepKHA=dissociation constant of the acid HAa =Brnsted coefficient(normally 0 a 1)indicates the sensitivity of the catalytic step forchanges in acid strength of HA(pKa)18第18页/共34页Example:Plot log kHA against log KHA,slope=aa indicates to what extent a proton is transferred from the acid

17、to the substrate in the transition state:a=1:Every change in acid strength fully affects catalysis.The proton is(almost)completely transferred to the substrate in the transition state.a=0:The reaction is insensitive to changes in acid strength.All acids catalysethe reaction equally strongly(log kHA=

18、constant).The proton is hardlytransferred in the transition state of the reaction.a=0.5:The proton is transferred halfway between the acid anion A and thesubstrate in the transition state:AH+S,symmetrical TS.19第19页/共34页There is also a Brnsted relation for general base catalysis:log kB=-b log KHB+a c

19、onstantThe coefficient b has the same meaning as a for generalacid catalysis20第20页/共34页The relation between general and specific catalysisWhy is there sometimes general and sometimes specific acid/base catalysis?pH:H+and OH are very low in neutral solution,whereas HA or B can be high beneficial for

20、general catalysis rate of proton transfer:H transfer to and from C atoms is slower than transfer to N,O,etc.beneficial for general catalysis stability of reaction intermediates plays an important role.Example:compare the hydrolysis of ortho esters and acetals21第21页/共34页Ereaction co-ordinate1a,2aEa1E

21、a2products1b,2b2c1c1c is more stabilised than 2c protonation becomes the rate limiting step general acid catalysis!22第22页/共34页General Acid/Base Catalysis by EnzymesEnzymes often use general acid or base catalysis:u They work at neutral pH,so low H+and OH u High effective concentration of general aci

22、d/baseu Correct orientation of the acidic/basic group around thesubstrateu Optimum catalysis at pH around pKaAmino acid residues often have a pKa that is close to neutral pH and are therefore able to act as a general acid or base catalyst:23第23页/共34页 Prototropic Groups of EnzymesAmino acid Acidic gr

23、oup Basic grouppKaN-terminusa-NH3+a-NH2 7.8C-terminusa-COOHa-COO3.8aspartic acidb-COOHb-COO4.4glutamic acidg-COOHg-COO4.6histidine imidazolium ionimidazole7.0cysteineSHS8.7tyrosineC6H4OHC6H4O9.6lysinee-NH3+e-NH210.4serineb-OHb-O13threonineb-OHb-O13arginineNH(C=NH2+)NH2 NH(C=NH)NH212.5peptide bond RC

24、ONHRRCONR 14.8The pKa is strongly influenced by its environment:e.g.,in enzymes the pKa of lysine can drop to 724第24页/共34页Metal Ion CatalysisRoles of metals in catalysis:As“super acid”:comparable to H+but stronger As template:metal ions are able to coordinate to more than 2 ligands and can thereby b

25、ring molecules together As redox catalyst:many metal ions can accept or donate electrons by changing their redox stateSuper acid catalysisFeatures:Introduces positive charge into the substrate,making it more susceptible toward nucleophilic attack.Exchange of metal ions is fast(105-109 s-1),but slowe

26、r than exchange of H+(1011 s-1)25第25页/共34页Metal Ion Catalysis in C-C Bond CleavageDecarboxylation of oxalosuccinate by isocitrate dehydrogenase:Mn2+is very well able to accept the developing negative charge(“electron sink”);M3+like Al3+are also good,M+like Na+,K+(and H+!)are much less effective.Othe

27、r acceptable substrates:-both COO-and C=O are needed for correct binding of Mn2+-cleaving COO group on b-position26第26页/共34页Metal ion catalysis in additions to C=O(N)bondsCu2+ions are very effective catalysts for the hydrolysis of a-amino acid esters:They are less effective in the hydrolysis of amid

28、es,because of a tighter bond between the metal and the substrate(=ground state stabilisation):Ereaction co-ordinateamideesteruncatalysedcatalysed27第27页/共34页Metal ion catalysis in the hydrolysis of phosphate esters and anhydridesHydrolysis of phosphate esters(e.g.acetyl phosphate)or anhydrides(e.g.AT

29、P)is always catalysed by metal ions,usually Mg2+:The role of the metal ion is twofold:neutralization of the negative charge in the substrate,to enable the the approach of the nucleophile;stabilisation of the leaving group (neutralization of charge)28第28页/共34页Summary Super Acid CatalysisPolarisation

30、of bonds,especially C=OAccepting negative charge(“electron sink”)Neutralization of negative charge in the substrate,to facilitate the approach of the nucleophileStabilization of the leaving group(reduction of charge)29第29页/共34页Metal ions as template:the Sharpless epoxidationMechanism proposed by E.J

31、.Corey:30第30页/共34页31Sc3+-Catalyzed Aldol-Type Additions of N-Benzoylcyclopropanecarboxamides via Iodide-Mediated Ring-Opening:Stereoselective Synthesis of -Lactams第31页/共34页32Postulated catalytic cycle第32页/共34页Summary:Advantages of Metal Ions Compared to H+uHigher charge(M2+,M3+)uAlso works at neutral pHuCoordination with several groups is possible(template effect)uMany metal ions have redox properties33第33页/共34页34谢谢您的观看！谢谢您的观看！第34页/共34页