MP1 workshop answers 2022 v3 PDF

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SID: .................................................................SID: .................................................................SID: .................................................................Date: ......................Molecular properties Workshop 1Acid/BasesDissociation/Ionisati...

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Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

SID: ................................................................. SID: ................................................................. SID: ................................................................. Date: ......................

Molecular properties Workshop 1 Acid/Bases Dissociation/Ionisation

Students are to revise the relevant material from lectures MP1, MP2, MP3 & MP4. After completing this workshop assignment, students should be able to: • define acids and bases according to accepted definitions • understand the concept of conjugate pairs • identify acidic, basic and neutral functional groups in chemical structures of drugs • correlate the pKa of a functional group with their ionisation behaviour in solutions of various pH • explain what determines if a functional group is a strong/weak acid or base • write correction dissociation equations for molecules containing more than one acidic and or basic functional group This report is to be completed in week 3-5 and the completed report must be submitted through Turnitin by 11:59pm on the day of your workshop in week 5. Marked report with marks and feedback will be provided by week 8.

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Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

(1) Define acids and bases according to Arrhenius, Lewis and Brønsted definition. Support your definitions with examples and chemical equations (Try to give different examples than those discussed in lectures). [1 mark].

Arrhenius: acid when dissolved in water increases the concentration of H+ base when dissolved in water increases the concentration of OHLewis: Acid is an electron pair acceptor, base is an electron pair donor Bronsted: Acid is a proton donor, base is a proton acceptor

(2) Write equations for the equilibrium constant, Keq and the dissociation constant, Ka for the reaction given below. [1 mark]. CH3COO- + H3O+

CH3COOH + H2O

𝑲𝒆𝒒 =

𝑲𝒂 =

[𝑪𝑯𝟑 𝑪𝑶𝑶− ][𝑯𝟑 𝑶+] [𝑪𝑯𝟑 𝑪𝑶𝑶𝑯][𝑯𝟐 𝑶] [𝑪𝑯𝟑 𝑪𝑶𝑶− ][𝑯𝟑 𝑶+] [𝑪𝑯𝟑 𝑪𝑶𝑶𝑯]

(3) Define pKa by an equation relating it to Ka. pka = -log Ka Define pH by an equation relating it to [H3O+]. pH = -log [H3O+] Write a single Henderson-Hasselbalch equation applicable to both an acid and a base. [1 mark]. pH = pKa + log [base form]

or

pH = pKa - log [acid form]

[acid form]

[base form]

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Molecular Properties Workshop 1

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PHAR1812 / 2022

(4) An acid (HA) has Ka = 10-7. What is its pKa? Another acid (HB) has Ka = 3, what is its pKa? Which is the stronger acid? [1 mark] HA: pKa = -log Ka = -log 10-7 = 7 HB: pKa = -log Ka = -log 3 = -0.48 HB is a stronger acid than HA because the greater the Ka the stronger the acid OR the greater the pKa, the weaker the acid

(5) The pKa of the anilinium ion (C6H5NH3+) is equal to 4.6. On the basis of this fact, decide whether aniline (C6H5NH2) is a stronger or weaker base than methylamine (pKa of its conjugate acid 10.6). Give explanation. [1 mark] anilinium is a stronger acid than methylammonium ion, as it has lower pKa THUS methylamine must be a stronger base than aniline other explanation: for bases, the higher the pKa, the stronger the base

(6) Use the dissociation constants for the conjugate acids of theses bases to predict whether the CH3COO- ion or the OH- ion is the stronger base. [1 mark] CH3COOH: Ka = 1.8 x 10-5 H2O: Ka = 1.8 x 10-16 CH3COOH: Ka = 1.8 x 10-5 ; pKa = -log 1.8 x 10-5 = 4.7 H2O: Ka = 1.8 x 10-16 ; pKa = -log 1.8 x 10-16 = 15.7 CH3COOH is a stronger acid than H2O, thus OH- is a stronger base than CH3COO-

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Molecular Properties Workshop 1

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PHAR1812 / 2022

(7) Which would you expect to be the stronger acid? Explain your reasoning in each instance. [2 marks] a) CH2ClCOOH or CHCl2COOH (more e- withdrawing groups) b) CHCl2COOH or CCl3CH2OH (CHCl2COOH is an acid, not an alcohol) c) CH2FCOOH or CH2FCH2COOH (F closer to the carboxyl group) d) CH2FCOOH or CH2BrCOOH (F has higher electronegativity, thus stronger e- withdrawing effect than Br)

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Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

(8) What is the conjugate base of each of the following acids? Based on structural considerations, list the bases you give as answers in order of increasing basicity and give reasons based on structure for the order. [2 marks] H2 O

OH-

HCl

Cl-

CH3CO2H

CH3COO-

CH3OH

CH3O-

Based on principle: - strong acid has weak conjugate base - weak acid has strong conjugate base Students need to identify the order of acids so they can decide the order of bases. • HCl is the strongest acid, thus Cl- is the weakest base • CH3CO2H is weaker acid than HCl, thus CH3COO- is a stronger base than Cl• electron withdrawing effect of NO2 makes p-nitrophenol (pKa 7.2) a stronger acid than phenol (pKa 10.0) thus p-nitrophenol is a stronger base than phenolate • water (pKa ~ 16) and methanol (pKa ~ 17) are both very weak acids, therefore both are the strongest bases as the negative charge can not be delocalised – methoxide is slightly stonger than hydroxide due to electron donating CH3

Increasing basicity

Cl-

CH3COO-

-

OH

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CH3O-

Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

(9) What is the conjugate acid of each of the following bases? List the acids you give as answers in order of increasing acidity. [2 marks]

H2 O

H3O+

HSO4-

H2SO4

CH3NH2

CH3NH3+

Based on principle: - strong base has weak conjugate acid - weak base has strong conjugate acid Students need to identify the order of acids so they can decide the order of bases and explain why a base is stronger/weaker based on the structure. • CH3NH2 is the strongest base, it is stronger than (CH3)3N because the additional alkyl group shields the lone pair of (CH3)3N making it less accessible to H+, thus CH3NH2+ is a weaker acid than (CH3)3NH+ • Aniline is a weaker base than alkyl amines because the lone pair of electrons overlaps with the aromatic pi electrons, and is less available to form a bond with a hydrogen • water is a weak base thus H3O+ is a strong acid (pKa ~ -1.7) • H2SO4 is a very strong acid (pKa < -3), thus its base HSO4is the weakest base, H2SO4 is stronger than H3O+ since it is able to delcoalise the -ve charge around the 4 oxygens.

Increasing acidity

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Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

(10) List the following bases in order of their strength (WEAKEST BASE FIRST). Provide reasoning for your answer. [2 marks]

Answer:

pKa:

weakest base -4

strongest base app 3.2

app 4.6

app 5.2

app 6

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Reasoning: • Imidazole has 2 nitrogens in the ring, one of them contributes the electron to the 4n+2 π electrons required for the aromatic system and the other N is able to be protonated, once protonated, the +ve charge is able to be delocalised and is therefore more stable than the pyridinium ion, therefore a stronger base than pyridine. • 2-Me-pyridine stronger base than pyridine due to the electron donating effect of the methyl • anilines are weaker bases than pyridines because the e- pair of nitrogen is overlapping with the aromatic array of the π electrons • 2-F-aniline is a weaker base than aniline due to the electron withdrawing effect of the fluorine • pyrrole much weaker than imidazole (and all of the other bases of the row) because epair already involved in the aromatic array of the π electrons, protonation results in a loss of aromaticity, thus very unreal and unfavourable

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Molecular Properties Workshop 1

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Pyrrole Pyridine

PHAR1812 / 2022

Aniline Imidazole

+ve charge (11) Draw a set of equations for the ionisation of the amino acid tyrosine [pKa 2.2, 9.21 and 10.46 (phenolic OH)]. [2 marks] OH

COOH H2N

COOH H 3N

OH

COO

H+ pH 2.2

OH

H+ pH 9.21

H3N

OH

COO H 2N pH 10.46

COO

H+

O

H 2N

Notes Always start by identifying the functional groups and whether they are acidic/basic or neutral. The number of pKa’s tells you how many ionisable functional groups are in the molecule, e.g. in tyrosine there are 3 pKa’s, therefore there are 3 ionisable functional groups. You need to be able to identify the functional groups and identify whether they are acidic or basic, and know their approximate pka’s so that you can assign the correct pKa to each functional group. The most protonated form should be drawn on the left as the first structure, this means that bases will be protonated in their conjugate acid form (think of what form a molecule would take in a highly acidic solution). Each pKa should represent the loss of one proton, in order of pKa (think of the highly acidic solution and imagine what form a molecule would take if you were gradually making the solution more basic). NB never add a proton to an amine at a high pH!!

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Molecular Properties Workshop 1

ANSWERS

PHAR1812 / 2022

(12) In the third workshop session, you will be assigned a group of four substances (with pKa values) that are drugs, pharmaceutical materials or compounds of biological interest. Identify the functional groups and write chemical equations with structures that show the equilibrium described by each pKa. [4 marks] Important note: By convention, write the organic molecular species which exists at the lower pH on the left, and that which exists at the higher pH on the right. In other words, start on the left-hand side with all protons attached.

Substance A: Substance B: Substance C: Substance D: Some common mistakes – Nitrogens directly next to a carbonyl group are Amides, which are neutral so they do not gain an extra proton.

H N

R

R

H2 N

R

O

R

O

Nitrogens in between 2 carbonyl group are Imides, which are acidic so they give up their protons and do not gain an extra proton H R N R R N R

O

O

O

O

Sulfonamides are amines directly next to an SO2, sulfonamides are also acidic and therefore give up their proton, they do not accept an additional proton either.

H O R N S O

N

O R S O

Structures and reactions in the additional document

Marks (out of 20):___________ Signature:__________________

Date:___________________

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