C3 Acid-base chemistry 3

Question 1

how can acidity / basicity be predicted in drug molecules?

Answer 1

• look for functional groups able to donate or accept protons
• become familiar with the range of pKa values typical of organic function groups
• explore the role of structure (particularly inductive and resonance effects) on the stability of the conjugate acid / base pair

Question 2

what does a low pKa mean for an acid?

Answer 2

low pKa means strong acid because the hydrogen is weakly attracted

Question 3

what does a larger pKa mean for bases?

Answer 3

pKa is larger in conjugate acid if base is stronger

Question 4

when does acidity increase in relation to A-?

Answer 4

• acidity, and hence Ka, will increase if A- is stabilised (and hence its concentration increased) relative to HA
• increase in A- increases the numerator so it makes the Ka, and therefore acidity, greater

Question 5

what structure-related aspects can determine / affect acidity?

Answer 5

bond energies
electronegativity
inductive effects
hybridisation
resonance / delocalisation

Question 6

how can bond energies determine / affect acidity?

Answer 6

• control the ease and extent to which the proton can be lost from the acid (I.e. the strength of the acid)

Question 7

how does bond strength change in groups of the periodic table?

Answer 7

bond strength weakens on descending groups in the periodic table

Question 8

describe and explain the changes in acidity of ‘hydro-halogens’

Answer 8

increasing order of acidity:
H-F, H-Cl, H-Br, H-I

• pKa values decrease with increasing acidity
• HI is the strongest acid as the bond is the weakest (proton dissociates more easily)

Question 9

how does electronegativity change across a period / row of the periodic table?

Answer 9

• electronegativity increases across a row in the periodic table (from left to right)
• C, N, O, F

Question 10

what is electronegativity?

Answer 10

the ability of an atom to attract a pair of electrons

Question 11

what is an inductive effect?

Answer 11

• the ability of a ligand to change electron density at a nearby atom via sigma bonds
• can be transmitted through a series of sigma bonds
• image shows negative inductive effect of X

Question 12

what is the difference between inductive effects and resonance effects?

Answer 12

• ligands changing the electron density at a nearby atom through sigma bonds is an inductive effect
• ligands changing the electron density at a nearby atom through pi bonds is a resonance effect

Question 13

what are the 2 types of inductive effects and what are their effects on acidity and stability of anions?

Answer 13

electron-withdrawing inductive effect:
- stabilises anion
- enhances acidity
- negative inductive effect

electron-donating inductive effect:
- destabilises anion
- reduces acidity
- positive inductive effect

Question 14

do electron-attracting ligands provide a positive or negative inductive effect?

Answer 14

• negative
• X is the attracting group and the electrons are attracted towards it so the electron density is higher closer to X

Question 15

do electron-releasing ligands provide a positive or negative inductive effect?

Answer 15

• positive
• electron density moves towards carbon away from Y because Y is electron-releasing

Question 16

how does hybridisation contribute in determining / affecting acidity?

Answer 16

• the more s character of an orbital, the closer the electrons are to the nucleus
• this is comparable to increased electronegativity of the atom

Question 17

what is the order of effective electronegativity in carbon based on hybridisation states?

Answer 17

sp > sp2 > sp3

Question 18

how do you see how resonance determines / affects acidity of molecules?

Answer 18

• draw resonance structures for the acid and the conjugate base
• assess which is more stabilised
• if A- is more stabilised, Ka is larger so acidity is greater
• if HA is more stabilised, Ka is smaller so acidity is less

Question 19

describe and explain the series of resonance structures in the image in terms of acidity

Answer 19

• in the series in the image, resonance structures increasingly stabilise the conjugate base more than the acid
• therefore, acidity increases across the series

Question 20

what does this image show about basicity and hence Kb?

Answer 20

• basicity, and hence Kb, will increase if BH+ is stabilised relative to B
• hence its concentration increased

Question 21

describe the 2 types of inductive effects relating to basicity

Answer 21

electron-donating
- stabilises cation
- enhances basicity

electron-withdrawing
- destabilises cation
- reduces basicity

Question 22

how can inductive effects in bases also be considered?

Answer 22

electron-donating groups enhance electron density at the basic centre (B), hence encouraging protonation to occur