Acid-Base Chemistry. Chapter Brønsted Acid-Base Chemistry R P

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1 Chapter 5 Acid-Base Chemistry 5.1 Brønsted Acid-Base Chemistry R P The equilibrium constant (K eq ) gives quick insight into whether the reactant or product is more stable, and the extent to which the reactant or product is preferred. Brønsted acid: a proton donor, Brønsted base: a proton acceptor base acid acid base When in solution, all four species will be solvated, and solvation is one of the major Factors controlling which side of the equilibrium is preferred. Pyridine -> pyridinium, RO -> RO 2+, 3 O +

2 5.2 Aqueous solutions pk a The pka values reflect the relative stabilities of the species on the different sides.

3 5.2.2 p enderson-asselbalch equation The p gives the proton donor ability of the solution, and the pk a gives the proton donor ability of an acid. [A - ] = [A] -> p = pk a 1. When the p is the same as the acid s pk a, the solution has the same ability to protonate the conjugate base A - as the acid A has the ability to protonate the solvent, and hence the acid exists as a 1:1 ratio of its A and A - form. 2. When the p is above the pk a, the solution does not have enough donor ability to protonate the conjugate base, and therefore the acid exists mostly in its conjugate base form A When the p is below the pka, the donor ability of the solution is strong enough to protonate A -, and mostly A exists. p indicators: molecules that change color as a function of their protonation state.

4 5.2.6 Super acids : extremely strong acid Solution formed from BF 3, PF 5, AsF 5 and especially SbF 5 in liquid F, often diluted with FSO 3 and SO 2 ClF. This creates acids of the extremely non-nucleophilic and noncoordinating anions BF 4-, PF 6-, AsF 6- and SbF 6-. Such solutions can protonate bases as weak as benzene or alkanes to create persistent carbocations. C- protonation :C O: C-C protonation

5 5.3 Nonaqueous systems Most of the times pka values change significantly when measured in different solvents, although there are examples where acidities are nearly identical in different solvents. 2,4,6-trinitrophenol: DMSO and 2 O, similar pk a values CN is stronger acid than malonitrile (NCC 2 CN) in 2 O, but CN is weaker acid than malonitrile (NCC 2 CN) in DMSO. -> solvation has a large influence in altering the intrinsic ability of a compound to act as a proton donor. 1. The pk a values are almost always in the organic solvent than in water. 2. The pk a differences are accentuated in the organic solvent, meaning that they tend to spread out over a larger pk a range. The lower the polarity of the solvent, the higher the pk a s of the various acids.

6 The lower the polarity of the solvent, the higher the pk a s of the various acids. -> organic solvents are not very effectively stabilizing the charges created when the acid donates its proton to the solvent. Strong solvating nature -> effectively stabilizes the anionic conjugate bases -> making the intrinsic stability of the bases less important -> the corresponding acidity differences between acids becomes smaller. Deprotonated anions of picric acid and malononitrile are highly delocalized, thus solvation effects would be expected to be less important -> similar pk a values in both solvents.

7 5.3.1 pk a shifts at enzyme active sites Organic solvents generally lower acidity, whereas polar solvents increase acidity. Electrostatic interactions influence acidity. The second pk a of a dicarboxylic acid is higher than the first pk a due to the formation of a distance with the associated electrostatic repulsion. The active site of enzymes are not identical to water, and in fact are often considered quite organic in nature. owever, they also can possess charges. Therefore, acids at enzyme active sites often have pk a that are quite different than the normal pk a for those acids in water. If a neutral acid, such as carboxylic acid, is placed in proximity to a positive charge, the acid will become more acidic because the resulting anionic conjugate base is stabilized due to electrostatic attraction. Conversely, when a positive acid, such as ammonium, is placed near a negative charge, it will become less acidic. Now the electrostatic attraction is lost when the acid donates its proton and becomes neutral. These effects can be quite large, and changes in acidity strength of four to five orders of magnitude are common.

8 5.4 Predicting acid strength in solution - Electronegativity Acidity: F > RO > R 2 N > R 3 C O C C O O C C O O C C O C C pk a = 4.8 (DMSO) 19 (DMSO) - Inductive effects: when electronegativity effects arise from electron withdrawal by a remote group via sigma bonds, it is referred to as an inductive effect. Alkyl substituents on localized carbanions are destabilizing. PhSO 2 C PhSO 2 C C 3 pk a = 29 (DMSO) 31 (DMSO)

9 - Resonance Acetic acid: 4.76 (O 에의한 inductive effect 가더중요한 factor 임 ) 참조, Cyclohexanol: 17 C 3 -O 16.0 o-nitrophenol: 7.22 m- : 8.36 p- : 7.15 Phenol: Acetone: 20 C 3 COC 2 COC 3 : 8.84

10 Acidity of α-: ketone > ester > amide > carboxylate

11 - Electrostatic effects Neighboring charges greatly influence the ability to create further charges in close proximity. ylides + N 3 C 2 CO 2 : 2.31, C 3 C 2 CO 2 : (C 3 )S + -C 2 COPh 8.3

12 - ybridization pk a : Acidity: sp > sp 2 > sp 3 pk a : (pyridinium) sp > sp 2 > sp 3 - Aromaticity pk a : 16 61

13 - Solvation The bulkier the alkyl group, the more difficulties it is for the solvent molecules to make close contact with and thereby to stabilize the O - in the alkoxide or carboxylate. - Cationic organic structures pk a : A positive charge on a very electronegative group

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18 5.5 Acids and bases of biological interest Isoelectric points

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20 N 3 + N 2 + N +

21 Positive nitrogen pk a of α- of mandelic acid: 22 O 2 C O pk a of lysine-n 3+ : 10 ow can a base (Lys) in enzyme abstract a- of mandelic acid? 1. Raise the pka of the conjugate acid of the base bt changes in the environment around this base, making it more basic. 2. Present a microenvironment around the anionic conjugate base of the mandelate that is so stabilizing that it induces the large increase in acidity. -> low barrier B, ionic pairing effects and metal coordination

22 triple helical DNA

23 5.6 Lewis acids/bases and electrophiles/nucleophiles Lewis acid (electrophile): an electron pair acceptor Lewis base (nucleophile): an electron pair donor Lewis acid decreases pk a. Principle of hard and soft acids and bases ( 앞에서언급 )