Aromatic Compounds 4

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Questions and Answers

What is the primary role of a Brönsted base in a chemical reaction?

It donates protons to acids.

It acts as an electron pair donor.

It accepts protons from acids. (correct)

It forms water exclusively.

Which compound behaves as a Lewis base in the context of acidity?

Hydrochloric acid (HCl)

Water (H2O)

Ammonia (NH3) (correct)

Sodium hydroxide (NaOH)

Which equation represents the reaction involving a primary amine with water?

NH3 + HCl → NH4Cl

RNH2 + H2O ↔ NH4+ + OH-

RNH2 + HCl → RNH3+Cl-

RNH2 + H2O ↔ RNH3+ + HO- (correct)

What is the relationship between pKa and pKb?

pKa + pKb = 14 Signup and view all the answers

What does a lower pKb value indicate about a base?

It is a stronger base. Signup and view all the answers

What type of compound forms salts as a result of acid-base reactions, unlike sodium hydroxide?

Amines Signup and view all the answers

In the process of determining basicity, which is now more commonly measured?

The acidity of its conjugate acid. Signup and view all the answers

What does the reaction CH3NH3+ ↔ CH3NH2 + H+ illustrate?

It represents the dissociation of a conjugate acid. Signup and view all the answers

What is the boiling point of ortho-nitrophenol at 70 mm Hg?

100 °C Signup and view all the answers

Which nitro-phenol is most soluble in water?

Meta-Nitrophenol Signup and view all the answers

Why do meta- and para-nitrophenols have high boiling points?

Due to intermolecular hydrogen bonding Signup and view all the answers

What type of hydrogen bonding occurs in ortho-nitrophenol?

Intramolecular hydrogen bonding Signup and view all the answers

What is the solubility of para-nitrophenol in water?

1.69 g/100 g Signup and view all the answers

Which of the following factors contributes to the solubility of meta- and para-nitrophenols in water?

Hydrogen bonding with water molecules Signup and view all the answers

Ortho-nitrophenol has low solubility compared to meta- and para-nitrophenols mainly because:

It primarily participates in intramolecular hydrogen bonding Signup and view all the answers

Which nitro-phenol decomposes rather than boiling?

Para-Nitrophenol Signup and view all the answers

Which statement about the pKa value of drugs is accurate?

Aspirin is fully dissociated at pH 7.4 due to its low pKa. Signup and view all the answers

What distinguishes phenols from alcohols?

Phenols have the -OH group directly attached to an aromatic ring. Signup and view all the answers

Which statement regarding the solubility of phenols is correct?

Phenol dissolves in water due to hydrogen bonding. Signup and view all the answers

What is the boiling point of m-cresol primarily attributed to?

The presence of hydrogen bonding. Signup and view all the answers

Which structural feature is common in the nomenclature of phenols?

They are numbered to indicate the position of substituents. Signup and view all the answers

What is a characteristic property of most phenols?

They tend to oxidize easily. Signup and view all the answers

What is the pKa value of most phenols indicative of regarding their acidity?

They are weak acids. Signup and view all the answers

Which of the following is a method for naming phenols?

Hydroxy- compound nomenclature. Signup and view all the answers

Which nitrophenol has the lowest boiling point?

o-nitrophenol Signup and view all the answers

How does the solubility of o-nitrophenol compare to m- and p-nitrophenols?

Lower than m- and p-nitrophenols Signup and view all the answers

What compound is formed when phenols react with aqueous hydroxides?

Phenoxide salt Signup and view all the answers

Which statement correctly describes the acidity of phenols compared to alcohols?

Phenols are significantly more acidic than alcohols. Signup and view all the answers

What is the approximate difference in pKa values between phenol and cyclohexanol?

107 Signup and view all the answers

Which of the following compounds is stabilized by resonance effects?

Phenoxide anion Signup and view all the answers

What is a known side effect of salicylic acid due to its free phenolic group?

Gastric bleeding Signup and view all the answers

How can the side effect of gastric bleeding caused by salicylic acid be mitigated?

By converting it to an ester Signup and view all the answers

What is the primary reason for the lower boiling point of o-nitrophenol compared to m- and p-nitrophenols?

The lower boiling point is due to weaker intermolecular forces in o-nitrophenol. Signup and view all the answers

Why are phenols more acidic than alcohols?

Phenols are more acidic because their conjugate base (phenoxide anion) is stabilized by resonance. Signup and view all the answers

What is the effect of resonance stabilization on the pKa values of phenols?

Resonance stabilization lowers the pKa values of phenols, making them more acidic. Signup and view all the answers

How do aqueous hydroxides react with phenols?

Aqueous hydroxides convert phenols into their corresponding salts. Signup and view all the answers

What is the typical pKa value of phenol compared to cyclohexanol?

The pKa of phenol is approximately 9.95, while for cyclohexanol it is about 17. Signup and view all the answers

In what way does the structure of salicylic acid contribute to its side effects?

The free phenolic group in salicylic acid leads to gastric bleeding. Signup and view all the answers

What compounds can convert phenoxide anions back into free phenols?

Aqueous mineral acids, carboxylic acids, or carbonic acid can convert phenoxide anions back to phenols. Signup and view all the answers

Why does the acidity of phenols increase compared to alcohols?

The acidity of phenols increases due to the resonance stabilization of their conjugate base. Signup and view all the answers

How does the pKa value of aspirin affect its ability to cross cell membranes?

The pKa value of aspirin is 3.5, which means it is fully dissociated at pH 7.4, preventing it from easily diffusing across cell membranes. Signup and view all the answers

What advantage does morphine have in terms of cell membrane permeability compared to aspirin?

Morphine has a pKa of 7.9, which means it is partially ionised at pH 7.4, allowing for easier diffusion across cell membranes. Signup and view all the answers

In what way do phenols differ structurally from alcohols?

Phenols have the -OH group directly attached to an aromatic ring, while alcohols have the -OH group attached to aliphatic carbon chains. Signup and view all the answers

What is the effect of hydrogen bonding on the boiling points of phenols?

Hydrogen bonding in phenols leads to relatively high boiling points compared to non-hydrogen bonded compounds. Signup and view all the answers

Why are most phenols considered to be slightly acidic?

Most phenols have Ka values around $10^{-10}$, indicating they can donate protons, thus exhibiting acidic behavior. Signup and view all the answers

How does the solubility of phenol in water compare to that of most other phenols?

Phenol is somewhat soluble in water (9g per 100g) due to hydrogen bonding, whereas most other phenols are insoluble. Signup and view all the answers

What structural feature is commonly used in the nomenclature of phenols?

Numbering is often used to denote the relative positions of substituents on the aromatic ring in phenols' nomenclature. Signup and view all the answers

What happens to phenols upon oxidation, and how does this relate to their color?

Phenols are easily oxidized to form colored substances, which can result in their appearance changing dramatically. Signup and view all the answers

What type of hydrogen bonding occurs in ortho-nitrophenol and what is its effect on solubility?

Ortho-nitrophenol exhibits intramolecular hydrogen bonding, which reduces its solubility in water compared to meta- and para-nitrophenols. Signup and view all the answers

Explain why meta- and para-nitrophenols have higher boiling points compared to ortho-nitrophenol.

Meta- and para-nitrophenols have higher boiling points due to intermolecular hydrogen bonding, which is not present in ortho-nitrophenol due to intramolecular bonding. Signup and view all the answers

How does the solubility of ortho-nitrophenol compare to that of meta- and para-nitrophenols?

Ortho-nitrophenol has lower solubility than meta- and para-nitrophenols due to intramolecular bonding which hinders hydrogen bonding with water. Signup and view all the answers

What is the reason for the decomposition of para-nitrophenol at its boiling point?

Para-nitrophenol decomposes instead of boiling due to instability at elevated temperatures. Signup and view all the answers

Why are meta- and para-nitrophenols soluble in water?

They are soluble in water due to their ability to form hydrogen bonds with water molecules. Signup and view all the answers

Identify the compound with the highest boiling point among the nitro-phenols and justify why.

Meta-nitrophenol has the highest boiling point due to significant intermolecular hydrogen bonding. Signup and view all the answers

Discuss how the positions of -NO2 and -OH groups in ortho-nitrophenol affect its physical properties.

The positions of -NO2 and -OH in ortho-nitrophenol facilitate intramolecular hydrogen bonding, affecting both its boiling point and solubility. Signup and view all the answers

What roles do hydrogen bonds play in determining the physical properties of nitro-phenols?

Hydrogen bonds influence boiling points and solubility, with stronger hydrogen bonding resulting in higher boiling points and greater solubility in water. Signup and view all the answers

How does ammonia act as a base in acid-base reactions, and what does it form when it reacts with a mineral acid?

Ammonia acts as a Brönsted base by accepting a proton to form ammonium chloride (NH4+Cl-). This reaction does not produce water, distinguishing it from reactions involving other bases like NaOH. Signup and view all the answers

In the context of basicity, what is the significance of the pKa and pKb values?

pKa and pKb values provide a measure of the strength of acids and bases, respectively, with the equation pKa + pKb = 14. A lower pKb indicates a stronger base. Signup and view all the answers

What is the equation representing the dissociation of a primary amine in water?

The equation is RNH2 + H2O ↔ RNH3+ + OH-, showing the formation of a conjugate acid and hydroxide ion. Signup and view all the answers

What indicates the strength of a base when measuring its conjugate acid's pKa?

The ability of the conjugate acid to hold onto the proton indicates the strength of the base; a strong base has a weak conjugate acid. Signup and view all the answers

What role does the -OH group play in the basicity of compounds like phenols?

The -OH group can act as both a proton acceptor and an electron pair donor, allowing it to function as both a Brönsted and Lewis base. Signup and view all the answers

What characterizes the basicity of amines in relation to their dissociation in water?

The basicity of amines affects the extent of their dissociation in water, which correlates with their structural properties as primary, secondary, or tertiary amines. Signup and view all the answers

Why is it essential to understand the pKb scale in evaluating basicity?

The pKb scale quantifies how readily a base accepts protons, with higher pKb values indicating weaker bases. Hence, it provides a direct comparison for base strength. Signup and view all the answers

In what way can the strength of a Brönsted base be determined indirectly?

The strength of a Brönsted base can be determined indirectly by measuring the pKa of its conjugate acid; a lower pKa indicates a stronger base. Signup and view all the answers

Study Notes

Pharmaceutical Chemistry: Aromatic Compounds - Lecture 4

Lecture Content: Theory of basicity, Phenol and substituted phenols, Synthesis of Aspirin.

Theory of Basicity

Brønsted-Lowry Bases: Proton acceptors. NaOH + HCl → NaCl + H₂O. OH⁻ acts as the base, accepting a proton from HCl.
Lewis Bases: Electron-pair donors. OH⁻ donates a pair of electrons to the electron-deficient H⁺.
Ammonia (NH₃) and Amines: Act as bases differently from NaOH. Reaction with an acid forms a salt instead of water (e.g., NH₃ + HCl → NH₄Cl). Still act as proton acceptors and electron-pair donors. Amines behave similarly.
Basicity Measurement: Extent of dissociation measured by pKₐ scale. CH₃NH₂ + H₂O → CH₃NH₃⁺ + OH⁻. K₂ = [CH₃NH₃⁺] [OH⁻] / [CH₃NH₂]. pK₂ = -log₁₀ K₂. More commonly, basicity is defined in terms of pKₐ using the equation: pKₐ + pK₂ = 14.
Application: Drug pKₐ values critical for determining water solubility. Example: Aspirin (pKₐ 3.5) is fully dissociated at pH 7.4, and thus can't easily diffuse across cell membranes. Morphine (pKₐ 7.9), partially ionised at pH 7.4, crosses cell membranes more easily.

Phenols

Definition: Compounds of the general formula ArOH, where Ar is phenyl or substituted phenyl. Differ from alcohols in having the -OH group directly attached to an aromatic ring.
Nomenclature: Generally named as derivatives of phenol. Sometimes trivial names used (e.g., cresol). Numbering used for positions of substituents.
Physical Properties: Simplest phenols are liquids or low-melting solids. Phenol has high boiling points due to hydrogen bonding. Phenol slightly soluble in water, while most other phenols are insoluble. Generally colourless, easily oxidised to form coloured substances. Acidic in nature (pKₐ values ~ 10).
Nitro-phenols: Specific physical properties of ortho-, meta-, and para-nitrophenols are detailed, including boiling points, solubility in water, and factors impacting intramolecular hydrogen bonding affecting these properties
Acidity: Phenols are more acidic than alcohols (pKₐ phenol ~9.95, pKₐ cyclohexanol ~ 17). Phenolate anions are stabilised by resonance.
Acidity Applications: Aqueous hydroxides (like NaOH) convert phenols to their salts, but not with bicarbonates. Aqueous mineral acids, carboxylic acids, or carbonic acid convert the salts back into phenols.

Reactions of Phenols

Salicylic Acid and Aspirin: Salicylic acid, a precursor to aspirin, causes gastric bleeding due to a free phenolic group. Aspirin masks this group as an ester using acetic anhydride. The ester is then hydrolysed in the body to yield active salicylic acid. Aspirin itself is also an anti-inflammatory drug.

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Description

Explore the concepts of basicity in aromatic compounds during this detailed lecture. It covers Brønsted-Lowry and Lewis definitions of bases, basicity measurement using pKₐ, and the significance of drug pKₐ values in water solubility with a focus on Aspirin synthesis. Perfect for students in pharmaceutical chemistry!