Chapter 3 Theory Practice

Question 1

Define and differentiate between constitutional isomers and stereoisomers. Provide examples.

Question 2

Explain the significance of functional groups in organic molecules with respect to their reactivity and properties.

Question 3

Describe the chemical transformation of shikimic acid to oseltamivir.

Question 4

Highlight the importance of functional group modifications in drug synthesis.

Question 5

Why are esters used in pharmaceutical compounds? Discuss with examples.

Question 6

What is the role of hydroxyl groups in increasing the solubility of organic compounds? Provide an example.

Question 7

Compare the chemical reactivity of carboxylic acids and esters. Provide examples of typical reactions they undergo.

Question 8

Describe the mechanism of nucleophilic substitution in the formation of esters.

Question 9

Why are ethers considered relatively inert compared to alcohols? Discuss with examples.

Question 10

How does the presence of double bonds in a molecule affect its stability and reactivity? Use cyclohexene as an example.

Question 11

Discuss the biological importance of amine functional groups in the structure of drugs like oseltamivir.

Question 12

Problem 3.5
Intermolecular forces present in each compound:

Answer 12

a) Cyclohexane (C6H12):

London dispersion forces (weak, nonpolar molecule).
b) Tetrahydrofuran (THF):

London dispersion forces.
Dipole-dipole interactions (due to the polar C-O bond).
c) Triethylamine ((CH3CH2)3N):

London dispersion forces.
Dipole-dipole interactions (due to the polar C-N bond).
d) Vinyl chloride (CH2=CHCl):

London dispersion forces.
Dipole-dipole interactions (due to the polar C-Cl bond).
e) Propanoic acid (CH3CH2COOH):

London dispersion forces.
Dipole-dipole interactions (due to the polar C=O and O-H bonds).
Hydrogen bonding (between the O-H groups).
f) 2-Butyne (CH3-C≡C-CH3):

London dispersion forces (weak, nonpolar molecule).
Summary:
Hydrogen bonding: Present in e (Propanoic acid).
Dipole-dipole interactions: Present in b (THF), c (Triethylamine), d (Vinyl chloride), and e (Propanoic acid).
London dispersion forces: Present in all compounds.

Question 13

Explain why n-hexane has a higher boiling point than 2,2-dimethylbutane, even though both have the same molecular formula (C6H14).

a) What role does molecular structure play in boiling point trends?
b) How do London dispersion forces vary with molecular shape?
.

Question 14

Compare the boiling points of 2-propanol and propane.

a) Which type of intermolecular force is dominant in 2-propanol but absent in propane?
b) Why do compounds with hydrogen bonding generally have higher boiling points than those with only dispersion forces?

Question 15

Identify the types of intermolecular forces present in the following compounds:

a) 2-propanol
b) n-hexane
c) 2,2-dimethylbutane
d) Propane

Question 16

What is the relationship between molecular polarity and boiling point?

a) Why do polar molecules tend to have higher boiling points than nonpolar molecules of similar size?
b) Provide an example to illustrate this.

Question 17

Discuss the effect of branching on the boiling points of hydrocarbons.

a) Why does branching reduce the boiling point?
b) Give examples of two hydrocarbons with the same molecular formula but different boiling points due to branching.

Question 18

Hydrogen bonding significantly raises boiling points.

a) What is required for a molecule to form hydrogen bonds?
b) Why is the -OH group in 2-propanol crucial for hydrogen bonding?

Question 19

Consider the following pair of molecules: ethanol (C2H5OH) and dimethyl ether (CH3OCH3).

a) Both have the same molecular formula (C2H6O). Why does ethanol have a much higher boiling point than dimethyl ether?
b) Which intermolecular forces are present in each compound?

Question 20

For molecules with only London dispersion forces (e.g., alkanes), what factors affect the strength of these forces and thus boiling points?

a) How does molecular size influence dispersion forces?
b) How does surface area relate to boiling point?

Question 21

Why do compounds with polar bonds not always exhibit dipole-dipole interactions?

a) How does molecular symmetry affect polarity?
b) Provide an example of a nonpolar molecule with polar bonds.

Question 22

Rank the following in terms of boiling point, from lowest to highest: propane, ethanol, 2,2-dimethylbutane, and 2-propanol.

Justify your answer based on the types of intermolecular forces in each compound

Question 23

Melting Point Trends

a) Why do linear alkanes generally have higher melting points than branched alkanes of the same molecular weight?
b) Explain why a linear alkane packs more efficiently than a branched alkane in the solid state.

Question 24

Effect of Functional Groups on Melting Points

a) How does the presence of an -NH2 group in a molecule affect its melting point compared to a simple alkane?
b) What role do hydrogen bonds play in determining the melting points of amines?

Question 25

Ionic vs. Molecular Compounds

a) What type of intermolecular forces dominate in acetic acid, and how do these forces contribute to its melting point?
b) Why does sodium acetate have a much higher melting point than acetic acid? Discuss the difference in bonding types.

Question 26

Comparison of Intermolecular Forces

a) Identify all intermolecular forces present in sodium acetate.
b) Compare the strength of ionic bonding in sodium acetate to hydrogen bonding in acetic acid. Which requires more energy to break?

Question 27

Packing Efficiency in Solids

a) Why do linear molecules typically exhibit greater packing efficiency in a crystalline lattice compared to branched molecules?
b) Provide examples of two isomers with different melting points due to differences in packing.

Question 28

Hydrogen Bonding vs. Ionic Bonding

a) Why is ionic bonding stronger than hydrogen bonding?
b) How does the ionic nature of sodium acetate contribute to its high melting point?

Question 29

Crystalline Structure and Melting Points

a) How does the crystalline structure of ionic compounds affect their melting points?
b) Why are molecular compounds, like acetic acid, generally less crystalline than ionic compounds?

Question 30

Energy Requirements for Phase Changes

a) Which factors determine the amount of energy needed to melt a compound?
b) Compare the energy required to melt sodium acetate versus acetic acid and explain the difference.

Question 31

Predicting Melting Points

a) Between n-pentane and neopentane, which has a higher melting point and why?
b) Between a straight-chain alkane and an amine with a similar molecular weight, which is expected to have a higher melting point and why?

Question 32

Practical Applications

a) Why is the high melting point of sodium acetate advantageous in industrial applications?
b) What role does hydrogen bonding in acetic acid play in its use in biological and chemical processes?

Question 33

Hydrophobic vs. Hydrophilic

a) Define hydrophobic and hydrophilic regions in a molecule.
b) Why is the steroid ring structure in norethindrone considered hydrophobic?
Fatty Acids

a) Explain why the long carbon chain in arachidonic acid is hydrophobic.
b) How does the -COOH group in fatty acids interact with water?

Question 34

Polarity and Solubility

a) Discuss how the presence of both hydrophobic and hydrophilic regions in a molecule affects its solubility in water.
b) Provide an example of an amphiphilic molecule and explain how it interacts with water.

Question 35

Functional Groups

a) Identify the hydrophilic functional groups in norethindrone and arachidonic acid.
b) Explain how these groups enhance the water solubility of the molecules.
Biological Relevance

Question 36

a) Why is the balance between hydrophobic and hydrophilic regions important for biological molecules like hormones and fatty acids?
b) Discuss how the hydrophilic region of arachidonic acid contributes to its role as a precursor in biochemical reactions.

Question 37

Hydrogen Bonding

a) Which groups in norethindrone and arachidonic acid are capable of hydrogen bonding?
b) How does hydrogen bonding affect the behavior of these molecules in aqueous environments?

Question 38

Structure and Function

a) How does the structure of norethindrone relate to its function as a contraceptive?
b) Explain why arachidonic acid’s long hydrophobic chain makes it suitable for incorporation into cell membranes.

Question 39

Functional Groups and Solubility:

a) Which functional groups in Vitamin B3 contribute to its water solubility?
b) How does the long hydrocarbon tail in Vitamin K1 affect its solubility in water?
?

Question 40

Hydrogen Bonding:

a) Explain the role of hydrogen bonding in the water solubility of Vitamin B3.
b) Why is hydrogen bonding insufficient to make Vitamin K1 water-soluble?

Question 41

Polarity vs. Nonpolarity:

a) Discuss how the balance between hydrophilic and hydrophobic regions determines solubility in water.
b) Why do fat-soluble vitamins, such as Vitamin K1, accumulate in body fat rather than dissolving in the bloodstream?

Question 42

Solubility and Function:

a) How does the water solubility of Vitamin B3 relate to its role in metabolic pathways?
b) Why is the fat solubility of Vitamin K1 important for its function in blood clotting?

Question 43

Predicting Solubility:

a) Given a compound with multiple hydroxyl and carboxyl groups, would you expect it to be water-soluble or fat-soluble? Why?
b) How would the addition of a long hydrocarbon chain to a water-soluble vitamin affect its solubility

Question 44

Soap Structure:

a) What structural features define a soap?
b) Why are short-chain carboxylate salts, like sodium acetate, ineffective as soaps?

Question 45

Mechanism of Soap Action:

a) Describe how the hydrophobic and hydrophilic parts of a soap molecule work together to remove dirt.
b) What role does micelle formation play in the cleaning process?

Question 46

Detergent vs. Soap:

a) How do detergents differ from soaps in their molecular structure?
b) Why are detergents more effective than soaps in hard water?

Question 47

Chemical Reactions:

a) Write the reaction to produce a soap from lauric acid (CH3(CH2)10COOH) and sodium hydroxide (NaOH).
b) Explain why this reaction is necessary to convert a fatty acid into a soap.

Question 47

Applications of Detergents:

a) Why are synthetic detergents preferred over soaps for laundry?
b) How does the sulfonate group (SO3⁻) in detergents enhance their performance?

Question 48

Environmental Concerns:

a) Discuss the biodegradability of soaps versus synthetic detergents.
b) Why are biodegradable detergents important for reducing environmental pollution?

Question 49

Functional Groups in Molecules:

a) Identify the two functional groups present in nonactin and their role in its biological function.
b) Explain the difference in functional groups between nonactin and valinomycin.

Question 50

Aspirin and Membrane Transport:

a) Why is the neutral form of aspirin more likely to cross a cell membrane than its conjugate base?
b) How does the structure of a cell membrane affect the solubility and transport of ionic versus nonionic molecules?

Question 51

Role of pH:

a) How does the pH of the stomach favor the absorption of aspirin as a carboxylic acid?
b) Predict what would happen to aspirin absorption in an environment with a higher pH, such as the intestines.

Question 52

Biological Significance:

a) Why is it important for drugs like aspirin to have both hydrophilic and hydrophobic properties?
b) How does the presence of functional groups in valinomycin facilitate its role as an ionophore?

Question 53

Structure-Function Relationship:

a) Describe how the cyclic ester and ether groups in nonactin contribute to its molecular flexibility and biological activity.
b) Why are amide groups important in the structure of valinomycin for binding ions?

Question 54

Transport Mechanisms:

a) Compare passive diffusion and active transport for molecules crossing cell membranes.
b) Explain why aspirin crosses membranes by passive diffusion.

Question 55

Drug Design Implications:

a) How can understanding the solubility of a drug influence its design for better absorption?
b) Provide an example of a drug that, like aspirin, utilizes its neutral form for transport across membranes.

Question 56

Problem 3.18
Label the electrophilic and nucleophilic sites in each molecule:

Answer 56

a) Cyclohexyl bromide (C6H11Br):

Electrophilic site: The carbon atom attached to the bromine.
Reason: The electronegative bromine atom withdraws electron density from the carbon, making it partially positive and susceptible to nucleophilic attack.
Nucleophilic site: The bromine atom.
Reason: Bromine can act as a leaving group, carrying a lone pair of electrons.
b) Water (H2O):

Nucleophilic site: The oxygen atom.
Reason: Oxygen has lone pairs of electrons that can be donated to an electrophile.
c) Benzene (C6H6):

Nucleophilic site: The π-electrons in the aromatic ring.
Reason: The delocalized π-electrons in benzene can be donated to an electrophile during electrophilic aromatic substitution.
d) Cyclohexyl imine (C6H11N=CH3):

Electrophilic site: The carbon atom in the C=N bond.
Reason: The nitrogen atom withdraws electron density from the carbon, making it partially positive.
Nucleophilic site: The nitrogen atom in the C=N bond.
Reason: Nitrogen has a lone pair of electrons that can act as a nucleophile.

Question 57

Electrophilic Sites:

a) Why is the carbon atom in cyclohexyl bromide electrophilic?
b) Identify another functional group where a carbon atom commonly acts as an electrophile.

Question 58

Nucleophilic Sites:

a) Explain why the oxygen atom in water is nucleophilic.
b) Why can bromine in cyclohexyl bromide act as a nucleophilic leaving group?

Question 59

Aromatic Systems:

a) How do the π-electrons in benzene participate in electrophilic aromatic substitution?
b) Provide an example of a reaction where benzene acts as a nucleophile.

Question 60

Imines:

a) Why is the carbon in the imine group electrophilic?
b) How does the presence of a lone pair on nitrogen in the imine group make it nucleophilic?

Question 61

General Principles:

a) Define an electrophile and a nucleophile with examples from the molecules above.
b) Discuss how electronegativity differences in bonds influence the electrophilic or nucleophilic character of atoms.

Question 62

Reaction Pathways:

a) Predict the product when cyclohexyl bromide reacts with a strong nucleophile like hydroxide (OH⁻).
b) What type of reaction mechanism is likely involved in the above reaction?

Question 63

Electrophilic Sites:

a) Why is the carbon atom in cyclohexyl bromide electrophilic?
b) Identify another functional group where a carbon atom commonly acts as an electrophile.

Question 64

Nucleophilic Sites:

a) Explain why the oxygen atom in water is nucleophilic.
b) Why can bromine in cyclohexyl bromide act as a nucleophilic leaving group?

Question 65

Aromatic Systems:

a) How do the π-electrons in benzene participate in electrophilic aromatic substitution?
b) Provide an example of a reaction where benzene acts as a nucleophile.

Question 66

Imines:

a) Why is the carbon in the imine group electrophilic?
b) How does the presence of a lone pair on nitrogen in the imine group make it nucleophilic?

Question 67

General Principles:

a) Define an electrophile and a nucleophile with examples from the molecules above.
b) Discuss how electronegativity differences in bonds influence the electrophilic or nucleophilic character of atoms.

Question 68

Reaction Pathways:

a) Predict the product when cyclohexyl bromide reacts with a strong nucleophile like hydroxide (OH⁻).
b) What type of reaction mechanism is likely involved in the above reaction?

Question 69

Substitution Reactions:

a) Why does the hydroxide ion (⁻OH) react with CH3CH2-Br?
b) Explain the role of the bromine atom in facilitating the reaction.

Question 70

Nucleophiles and Electrophiles:

a) Why is Br⁻ unable to react with CH3-C≡C-CH3?
b) Contrast the nucleophilic strength of Br⁻ and ⁻OCH3.

Question 71

Carbonyl Compounds:

a) Why is the carbon in CH3-C(=O)-Cl electrophilic?
b) Describe the mechanism for the reaction of ⁻OCH3 with CH3-C(=O)-Cl.

Question 71

Electrophilic Addition:

a) How do the π-electrons in CH3-C≡C-CH3 facilitate the reaction with Br⁺?
b) Predict the product of the reaction between CH3-C≡C-CH3 and Br⁺.

Question 71

Mechanism Application:

a) Write the step-by-step mechanism for the reaction in (a).
b) Explain why nucleophilic substitution at a carbonyl carbon is faster than at an sp-hybridized carbon.

Question 71

General Principles:

a) Define a good leaving group and provide examples from the reactions above.
b) What factors influence whether a reaction involving an electrophile and nucleophile will occur?

Question 72

Reaction Rates:

a) Why does the strength of the nucleophile affect the rate of substitution reactions?
b) Compare the reactivity of ⁻OH and Br⁻ in substitution and addition reactions.

Question 74

Functional Groups:

a) Identify the role of the carboxylic acid group in determining the solubility of aspartame in water.
b) Explain how the ester group influences the chemical properties of aspartame.

Question 75

Hydrogen Bonding:

a) Which functional groups in aspartame are capable of donating hydrogen bonds to water?
b) Which functional groups in aspartame can accept hydrogen bonds from water?
?

Question 76

Water Solubility:

a) How do the functional groups in aspartame contribute to its overall water solubility?
b) Would you expect aspartame to be more or less soluble in organic solvents compared to water? Explain.

Question 77

Biological Relevance:

a) How does the presence of multiple hydrogen bonding sites influence the interaction of aspartame with enzymes in the body?
b) Why is the peptide linkage important for the sweetness of aspartame?

Question 78

Chemical Interactions:

a) Predict what would happen if the amine group (-NH2) in aspartame were replaced with a hydroxyl group (-OH).
b) How does the aromatic ring contribute to the stability and flavor profile of aspartame?

Question 79

Hydrophobic vs. Hydrophilic Regions:

a) Which parts of the aspartame molecule are hydrophilic, and why?
b) Which parts are hydrophobic, and how do they affect its solubility and interaction with biological membranes

Question 80

Hydrophilic and Hydrophobic Regions:

a) Identify the hydrophilic and hydrophobic regions in caffeine and explain why it dissolves well in water.
b) How does the long carbon chain in carotatoxin reduce its water solubility?

Question 81

Role of Functional Groups:

a) Which functional groups in sucrose make it highly water-soluble?
b) Why is the hydroxyl group in mestranol insufficient to make the molecule water-soluble?

Question 82

Structure vs. Solubility:

a) Compare the solubility of mestranol and sucrose in water based on their structures.
b) How does the aromaticity of caffeine affect its water solubility?

Question 83

Biological Implications:

a) Why is water solubility important for a molecule like sucrose in biological systems?
b) Discuss how the poor water solubility of mestranol affects its administration as a drug.

Question 84

Chemical Properties:

a) Predict whether carotatoxin would dissolve better in organic solvents or water. Explain.
b) Explain the balance between hydrophilic and hydrophobic regions in caffeine and its impact on its solubility in water.

Question 85

Hydrogen Bonding:

a) How do the multiple hydroxyl groups in sucrose enable extensive hydrogen bonding with water?
b) Why does caffeine form hydrogen bonds despite containing aromatic rings?

Question 86

Carbon Classification:

a) Define 1°, 2°, 3°, and 4° carbon atoms with examples.
b) Why is a quaternary carbon considered more sterically hindered than a primary carbon?

Question 87

Hydrogen Classification:

a) How is the classification of hydrogens (1°, 2°, 3°) related to the classification of the carbon they are attached to?
b) Identify the type of hydrogen in a methyl group.

.

Question 88

Complex Molecules:

a) In bilobalide, how do the functional groups (-OH, =O) influence the classification of the carbons they are attached to?
b) Explain how the classification of carbons in a molecule like bilobalide helps in predicting its reactivity.

Question 89

Hybridization and Reactivity:

a) How does the
𝑠
𝑝
3
sp
3
-hybridization of a carbon atom affect its geometry and reactivity?
b) Compare the reactivity of primary and tertiary carbons in substitution and elimination reactions

Question 90

Ring Structures:

a) Why are all carbons in a cyclohexane ring classified as secondary?
b) How does adding a substituent to a ring affect the classification of its carbons?

Question 91

Alcohol Classification:

a) What determines whether an alcohol is classified as 1°, 2°, or 3°?
b) Classify the alcohol in cyclopropanol.

Question 92

Amines:

a) How are primary, secondary, and tertiary amines different?
b) Why are secondary amines generally more nucleophilic than tertiary amines?

Question 93

Functional Groups in Dexamethasone:

a) Identify the importance of the -OH and halogen groups in the activity of dexamethasone.
b) How does the presence of fluorine affect the hydrophobicity of the molecule?

Question 94

Substitution Reactions:

a) Explain why tert-butyl bromide (3° alkyl halide) is more likely to undergo an
𝑆𝑁1reaction than an
𝑆𝑁2 reaction.
b) Predict the product when 1-butanol is treated with
𝐻𝐵𝑟.

Question 95

Structure-Function Relationships:

a) Draw a structure for a compound containing a 1° amine and a 2° alcohol.
b) How does the classification of the nitrogen atom in spermine affect its biological function?

Question 96

Reactivity:

a) Which is more reactive in a nucleophilic substitution reaction: a primary or tertiary alkyl halide? Why?
b) How does steric hindrance influence the reactivity of 3° alcohols compared to 1° alcohols?

Question 97

Amides:

a) Differentiate between primary, secondary, and tertiary amides.
b) Why are secondary amides more common in peptides like dolastatin?

Question 98

Functional Groups:

a) Identify the role of the carboxylic acid group in shikimic acid’s water solubility.
b) Explain how the ester group in oseltamivir affects its stability and activity.

Question 99

Isomerization:

a) What distinguishes constitutional isomers from stereoisomers?
b) Why do aldehydes and ketones with the same molecular formula have different boiling points?

Question 100

Applications:

a) How do the functional groups in atenolol contribute to its biological activity as a beta-blocker?
b) Why does donepezil require both aromatic and amine groups for its activity against Alzheimer’s disease?
.

Question 101

Drawing Structures:

a) Draw a molecule with formula C₅H₁₀O containing an alcohol functional group.
b) Propose a structure for a compound with formula C₆H₁₂O₂ that contains an ether group.

Question 102

Synthetic Pathways:

a) What reaction conditions are required to convert a carboxylic acid into an ester?
b) Describe how shikimic acid can be transformed into oseltamivir