物理有机化学PPT-复旦大学-王全瑞 4.catalyst by acid and base.ppt

Catalysis by Acids, Bases and Metal Ions,Mechanism:,1) The diffusion-controlled formation of a hydrogen bond between the base B and the acid HA 2) The transfer of a proton, leading to the formation of a new hydrogen bonded complex 3) The diffusion-controlled dissociation of the product,The rate of proton transfer,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-1,Formation 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 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.,2,Nevertheless, diffusion of H+ in water is much faster than diffusion of other ions:,3,Proton Transfer from/to Carbon Acids/Bases,k1 = 4x10 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 of solvation.,1,2: carbon acid, k1 and k-1 relatively small,2,3: oxygen acid, k1 and k-1 relatively large (H-bond formation),Another example:,4,5,Most carbon acids are stabilized by resonance. Hence significant structural reorganization must accompany deprotonation,The greater the structural reorganization during deprotonation, the lower the kinetic acidity,Influence of pH on Reaction Rate,The hydrolysis of esters is catalysed by both acid and base:,6,Another example: the mutarotation of glucose,7,Another example: imine formation,Slope of plot of log kobs vs. pH is often close to 1: linearly dependent on H+ or OH-,8,Two mechanisms for acid catalysis,Specific 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 determining step:,General acid catalysis: - Proton transfer occurs in a slow, rate-determining step; subsequently, the protonated substrate rapidly reacts to give the product(s):,9,Specific acid/base catalysis,Usually found for electronegative elements (O, N), where proton transfer is fast:,The second step is rate-determining and can be mono- or bimolecular:,Reaction rate:,since,we can now write:,So the rate is only dependent on the pH, not on HA !,10,Example of specific acid catalysis: hydrolysis of acetals (A1 mech.),kobs is directly proportional to H+; addition of more acid (buffer) at constant pH has no effect on kobs. Proton transfer is not rate limiting, so the mechanism probably reads:,kobs,ClCH2COOH/ ClCH2COO- (2:1),x,x,x,x,x,x,11,Example of a reaction that is specific acid catalysed according to the A2 mechanism: the hydrolysis of ethyl acetate:,12,Specific Base Catalysis,Example: the retro-aldol reaction of I:,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.,13,Therefore, the reaction mechanism most probably reads:,Reaction equation:,there is the acid-base equilibrium in water:,rewriting:,so,It is clear that only OH- occurs in the rate equation!,14,General Acid/Base Catalysis,Proton 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 increases with increasing buffer concentration, even if the pH remains constant,n = k(H2O)H2O + k(H3O+)H3O+ + k(m-NO2-Ph-OH)m-NO2-Ph-OHIII,15,General acid/base catalysis: the reaction rate is dependent on all acids/bases present in solution General acid catalysis: kobs = S kiHAi General base catalysis: kobs = S kiBi,Example 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-/ClCH2COOH,kobs,16,So, the reaction mechanism is most probably:,= k(H2O)H2OIV + k(ClCH2COO)ClCH2COOIV + k(OH)OHIV,17,Summarizing,Specific acid/base catalysis:,n = kSH3O+ or n = kSOH,General 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 this reason, general acid/base catalysis usually only occurs around neutral pH.,18,How effective is a general acid catalyst: the Brnsted relation,The effectiveness of a general acid catalyst depends on its acid strength (= the Brnsted relation):,log kHA = a log KHA + a constant,kHA = rate constant of the catalytic step KHA = dissociation constant of the acid HA a = Brnsted coefficient (normally 0 a 1) indicates the sensitivity of the catalytic step for changes in acid strength of HA (pKa),19,Example:,Plot log kHA against log KHA, slope = a a indicates to what extent a proton is transferred from the acid 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 catalyse the reaction equally strongly (log kHA = constant). The proton is hardly transferred in the transition state of the reaction. a = 0.5: The proton is transferred halfway between the acid anion A and the substrate in the transition state: AH+S, symmetrical TS.,20,There is also a Brnsted relation for general base catalysis: log kB = -b log KHB+ + a constant The coefficient b has the same meaning as a for general acid catalysis,21,The relation between general and specific catalysis,Why 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 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 acetals,22,1c is more stabilised than 2c protonation becomes the rate limiting step general acid catalysis!,23,General Acid/Base Catalysis by Enzymes,Enzymes often use general acid or base catalysis: They work at neutral pH, so low H+ and OH High effective concentration of general acid/base Correct orientation of the acidic/basic group around the substrate Optimum catalysis at pH around pKa Amino 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:,24,Prototropic Groups of Enzymes Amino acid Acidic group Basic group pKa N-terminus a-NH3+ a-NH2 7.8 C-terminus a-COOH a-COO 3.8 aspartic acid b-COOH b-COO 4.4 glutamic acid g-COOH g-COO 4.6 histidine imidazolium ion imidazole 7.0 cysteine SH S 8.7 tyrosine C6H4OH C6H4O 9.6 lysine e-NH3+ e-NH2 10.4 serine b-OH b-O 13 threonine b-OH b-O 13 arginine NH(C=NH2+)NH2 NH(C=NH)NH2 12.5 peptide bond RCONHR RCONR 14.8 The pKa is strongly influenced by its environment: e.g., in enzymes the pKa of lysine can drop to 7,25,Metal Ion Catalysis,Roles 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 bring molecules together As redox catalyst: many metal ions can accept or donate electrons by changing their redox state,Super acid catalysis Features: Introduces positive charge into the substrate, making it more susceptible toward nucleophilic attack. Exchange of metal ions is fast (105-109 s-1), but slower than exchange of H+ (1011 s-1),26,Metal Ion Catalysis in C-C Bond Cleavage,Decarboxylation 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. Other acceptable substrates:,- both COO- and C=O are needed for correct binding of Mn2+ - cleaving COO group on b-position,27,Metal ion catalysis in additions to C=O(N) bonds,Cu2+ ions are very effective catalysts for the hydrolysis of a-amino acid esters:,They are less effective in the hydrolysis of amides, because of a tighter bond between the metal and the substrate (= ground state stabilisation):,28,Metal ion catalysis in the hydrolysis of phosphate esters and anhydrides,Hydrolysis of phosphate esters (e.g. acetyl phosphate) or anhydrides (e.g. ATP) is always catalysed by meta