Ch 07 - Alcohols, Phenols and Ethers12th Chemistry

Structural Distinction

• Allylic Alcohols: The -OH group is attached to an sp³-hybridized carbon adjacent to a carbon-carbon double bond (C=C).
• Benzylic Alcohols: The -OH group is attached to an sp³-hybridized carbon immediately next to an aromatic ring.

Note: Both types can be further classified as primary (1°), secondary (2°), or tertiary (3°).

Defining Feature

In vinylic alcohols, the hydroxyl (-OH) group is bonded directly to a carbon-carbon double bond (C=C).

• The carbon atom carrying the -OH group is strictly sp² hybridized.
• Example: Vinylic alcohol: $CH_2=CH-OH$

Common Names

• 1,2-Benzenediol: Catechol (ortho position)
• 1,3-Benzenediol: Resorcinol (meta position)
• 1,4-Benzenediol: Hydroquinone or Quinol (para position)

The Bond Angle Anomaly

• Value: The bond angle in methanol is 108.9°.
• Reason: It is slightly less than the standard tetrahedral angle ($109.5^{\circ}$) due to the repulsive interaction between the two unshared electron pairs (lone pairs) on the oxygen atom, which compresses the bond angle.

Core Reasons for Shorter Bond

1. Partial Double Bond Character: Conjugation of the unshared electron pair on oxygen with the aromatic ring creates resonance, imparting a partial double bond character to the C-O bond.
2. Hybridization: In phenol, oxygen is attached to an sp² hybridized carbon (which has more s-character and is more electronegative, resulting in a shorter bond), whereas in methanol, it is attached to an sp³ hybridized carbon.

Steric Repulsion

While the four electron pairs (two bond pairs, two lone pairs) on oxygen are arranged roughly tetrahedrally, the repulsive interaction between the two bulky alkyl (-R) groups pushes them apart.

This steric strain overcomes the typical lone pair repulsion, making the angle (e.g., $111.7^{\circ}$ in methoxymethane) greater than the tetrahedral angle ($109.5^{\circ}$).

Variables & Reagents:

• Reactant: Unsymmetrical alkene (e.g., Propene)
• Reagent: $H_2O$ in presence of dilute acid catalyst (e.g., dilute $H_2SO_4$)
• Product: Alcohol (e.g., Propan-2-ol)

Boundary Conditions / Exceptions:

• Markovnikov's Rule: The addition strictly follows Markovnikov's rule; the nucleophilic water attacks the more substituted carbon.
• Because it proceeds via a carbocation, rearrangements to a more stable carbocation are possible.

Intermolecular Forces and Trends

• Comparison: Alcohols and phenols have significantly higher boiling points than comparable hydrocarbons/ethers due to the presence of intermolecular hydrogen bonding, which requires substantial extra energy to break.
• Molecular Mass: Boiling point increases with an increase in the number of carbon atoms (due to stronger van der Waals forces).
• Branching: Boiling point decreases with an increase in branching (branching makes the molecule more spherical, decreasing surface area and weakening van der Waals forces).

1. Boiling Points

Ethers have boiling points comparable to alkanes but significantly lower than alcohols.
Reason: Ethers lack the -OH group and therefore cannot form intermolecular hydrogen bonds with themselves.

2. Solubility in Water

The solubility of lower ethers in water is comparable to that of alcohols.
Reason: Although ethers cannot H-bond with themselves, the ethereal oxygen atom can form hydrogen bonds with water molecules.

Variables & Reagents:

• Step 1 (Hydroboration): Diborane ($B_2H_6$ or $BH_3$). Boron attaches to the less sterically hindered carbon.
• Step 2 (Oxidation): Hydrogen peroxide ($H_2O_2$) in aqueous sodium hydroxide ($OH^-$).

Boundary Conditions:

• Anti-Markovnikov Addition: The overall reaction yields an alcohol that looks as if water was added strictly opposite to Markovnikov's rule.
• Provides excellent yields of primary alcohols from terminal alkenes.

Reagents:

• Catalytic hydrogenation: $H_2$ gas with finely divided metals (Pd/Pt/Ni).
• Chemical hydrides: Sodium borohydride ($NaBH_4$) or Lithium aluminium hydride ($LiAlH_4$).

Regioselectivity:

• Aldehydes strictly yield Primary (1°) Alcohols.
• Ketones strictly yield Secondary (2°) Alcohols.

Mechanism Steps

1. Protonation: Electrophilic attack of the hydronium ion ($H_3O^+$) on the alkene double bond to form a stable carbocation.
2. Nucleophilic Attack: The unshared electron pair of the water molecule ($H_2O$) attacks the electrophilic carbocation intermediate.
3. Deprotonation: Loss of a proton ($H^+$) from the protonated alcohol intermediate to yield the final neutral alcohol product.

Laboratory Method:

• Use $LiAlH_4$, a very strong reducing agent. (Note: $NaBH_4$ is too weak and cannot reduce carboxylic acids).

Commercial / Industrial Method:

• $LiAlH_4$ is too expensive for bulk use.
• Workaround: Commercially, carboxylic acids are first converted to esters (using alcohol/acid). The ester is then reduced via cheaper catalytic hydrogenation ($H_2$ / catalyst) to yield the primary alcohol.

Reactivity Pattern:

1. Methanal (Formaldehyde, HCHO): Yields Primary (1°) Alcohols.
2. Other Aldehydes (RCHO): Yields Secondary (2°) Alcohols.
3. Ketones (RCOR): Yields Tertiary (3°) Alcohols.

Variables & Units:

• $C_6H_5Cl$ = Chlorobenzene
• T = 623 K
• P = 320 atm (or 300 atm depending on specific industrial setup)

Process Breakdown:

• Chlorobenzene is extremely unreactive. Extreme heat and pressure fuse it with NaOH to form sodium phenoxide.
• Acidification of the phenoxide yields phenol.

Variables:

• Cumene: Isopropylbenzene
• Byproduct: Acetone ($CH_3COCH_3$)

Conditions/Notes:

• Air oxidation of cumene forms cumene hydroperoxide.
• Dilute acid treatment cleaves it into phenol and acetone.
• Industrial Significance: Most of the worldwide production of phenol uses this method because the byproduct (acetone) is obtained in large, commercially valuable quantities.

Reagents & Process

• Primary amines ($R-NH_2$) react with Nitrous Acid ($HNO_2$) to form primary alcohols.
• Since $HNO_2$ is highly unstable, it is prepared in situ by reacting Sodium Nitrite ($NaNO_2$) with a strong mineral acid like $HCl$.

Visual Indication

• The reaction yields an alcohol, water, and Nitrogen gas ($N_2$).
• The evolution of $N_2$ gas produces a brisk effervescence (bubbling), serving as a definitive visual test for primary aliphatic amines.

(Exception: Methylamine reacts with $HNO_2$ to yield $CH_3OCH_3$ and $CH_3ONO$ rather than pure methanol).

Variables:

• R-O-H = Alcohol
• Na = Active metal (Sodium, Potassium, or Aluminium)
• $R-O^-Na^+$ = Sodium alkoxide

Chemical Concept:

• The evolution of hydrogen gas proves that alcohols are Brønsted acids (they can donate a proton to a stronger base or active metal).

Variables:

• Ar/R-OH: Phenol or Alcohol
• R'-COOH: Carboxylic acid
• $H^+$: Acid catalyst (concentrated $H_2SO_4$ or dry HCl gas)

Boundary Conditions:

• The reaction is highly reversible. Water must be removed continuously (Le Chatelier's principle) to drive the equilibrium to the right.
• Esterification can also be achieved using acid anhydrides or acid chlorides (the latter requires a base like pyridine to neutralize formed HCl).

Variables & Reagents:

• Reactant: Salicylic acid (o-hydroxybenzoic acid)
• Reagent: Acetic anhydride, $(CH_3CO)_2O$
• Catalyst: Acid ($H^+$)

Clinical Note:

• Aspirin possesses potent analgesic (pain-relieving), anti-inflammatory, and antipyretic (fever-reducing) properties.

Ease of Dehydration:

• Tertiary (3°) > Secondary (2°) > Primary (1°)
• Because tertiary carbocations are most stable, 3° alcohols dehydrate under very mild conditions (e.g., 20% $H_3PO_4$ at 358 K).

Mechanism Note:

• Proceeds via a carbocation intermediate; rearrangements are possible.
• If multiple alkenes can form, the major product is dictated by Saytzeff's Rule (the most highly substituted alkene).

The Dual Nature of Alkoxides

Alkoxides ($R-O^-$) are not only strong nucleophiles but also strong bases.

The Elimination Competition

• If a secondary (2°) or tertiary (3°) alkyl halide is used, the basic nature of the alkoxide causes elimination to dominate over substitution.
• Outcome: Using a 3° alkyl halide (like tert-butyl bromide) yields exclusively an alkene (like 2-methylpropene) rather than the desired ether.

Reagents & Selectivity:

• To Aldehyde: Use mild oxidants like PCC (Pyridinium chlorochromate) or anhydrous $CrO_3$. This stops oxidation at the aldehyde stage.
• To Carboxylic Acid: Use strong oxidants like acidified $KMnO_4$ or acidified $K_2Cr_2O_7$. This blows right past the aldehyde to form the acid.

The Nucleophilic Substitution Barrier

• The Williamson synthesis relies on an $S_N2$ mechanism, where the nucleophile attacks the alkyl/aryl halide.
• Bromobenzene is unreactive: In bromobenzene, the lone pairs on bromine are in resonance with the benzene ring, imparting a partial double bond character to the C-Br bond.
• Furthermore, the $sp^2$ hybridized carbon is highly electronegative, and the bulky arene ring sterically repels the incoming nucleophile.
• Result: $CH_3O^-Na^+$ cannot displace $Br^-$ from the benzene ring, resulting in no reaction.

Reaction Type Differences:

• 1° and 2° Alcohols: Undergo dehydrogenation (loss of $H_2$ gas) to form aldehydes and ketones, respectively.
• 3° Alcohols: Resist oxidation/dehydrogenation and instead undergo dehydration (loss of a water molecule, $H_2O$) to form an alkene.

Order of Acidity

Primary (1°) > Secondary (2°) > Tertiary (3°)

The Inductive (+I) Effect

• Alkyl groups are electron-releasing groups (+I effect).
• As the number of alkyl groups increases (from 1° to 3°), they push more electron density onto the oxygen atom.
• This decreases the polarity of the O-H bond, making it harder to release the $H^+$ ion, thereby decreasing acid strength.

Note: Alcohols are generally weaker acids than water.

Reasons for Higher Acidity

1. Hybridization: The -OH group in phenol is attached to an sp² hybridized carbon, which is more electronegative than an sp³ carbon, drawing electron density away from oxygen and increasing O-H bond polarity.
2. Resonance Stabilization: After losing a proton, the resulting phenoxide ion is highly stabilized by resonance (delocalization of the negative charge over the aromatic ring). Alkoxide ions from aliphatic alcohols lack this resonance stabilization.

Reagents & Selectivity:

• Dilute $HNO_3$ (Low Temp): Yields a mixture of mono-substituted ortho and para nitrophenols.
• Concentrated $HNO_3$: Over-nitrates the ring to yield 2,4,6-Trinitrophenol, commonly known as Picric Acid.

Industrial Note:

• Direct reaction with conc. $HNO_3$ gives a poor yield due to oxidation. Industrially, phenol is first treated with conc. $H_2SO_4$ to form phenol-2,4-disulphonic acid, followed by conc. $HNO_3$.

Substituent Effects

• EWGs (e.g., $-NO_2$): Increase acidity by stabilizing the phenoxide ion through dispersing the negative charge. The effect is maximum at ortho and para positions.
• EDGs (e.g., $-CH_3$, forming cresols): Decrease acidity by destabilizing the phenoxide ion (intensifying the negative charge via the +I effect).

Examples

• Picric acid (2,4,6-trinitrophenol) is highly acidic.
• Phenol is more acidic than o-, m-, or p-Cresol.

Solvent Effects:

• Low Polarity Solvents ($CS_2, CHCl_3$ at 273K): Restricts ionization; yields mono-substituted bromophenols (para is major).
• Aqueous Medium (Bromine Water): Phenol ionizes to form the highly activating phenoxide ion, causing multi-substitution to yield a white precipitate of 2,4,6-Tribromophenol.

Boundary Conditions:

• Unlike benzene, halogenation of phenol does not require a Lewis acid catalyst (like $FeBr_3$) because the -OH group is highly activating.

Variables & Mechanism:

• Reactant: Phenol
• Base: $NaOH$ (creates the phenoxide ion, which is even more reactive towards electrophilic aromatic substitution than phenol).
• Electrophile: $CO_2$ (a weak electrophile).
• Product: Salicylic acid (Mainly the ortho isomer).

Utility:

• Salicylic acid is the crucial precursor for synthesizing Aspirin (via acetylation).

The Role of Pyridine

• The reaction of an alcohol/phenol with an acid chloride produces Hydrogen Chloride ($HCl$) gas as a byproduct.
• Pyridine is a base. It rapidly neutralizes the generated $HCl$, removing it from the system.
• According to Le Chatelier's Principle, continuously removing the byproduct shifts the equilibrium strictly to the right, heavily favoring the forward reaction and maximizing ester yield.

Variables & Reagents:

• Reagents: Chloroform ($CHCl_3$) and aqueous Sodium Hydroxide ($NaOH$).
• Product: Salicylaldehyde (a -CHO group is introduced at the ortho position).

Intermediate:

• The reaction proceeds via an electrophilic attack by dichlorocarbene ($:CCl_2$) to form a substituted benzal chloride intermediate, which is subsequently hydrolyzed by alkali.

Reaction Breakdown:

• Reduction: Heating phenol with Zinc dust completely removes the oxygen, yielding pure Benzene ($C_6H_6$).
• Oxidation: Treating phenol with Chromic acid (or $Na_2Cr_2O_7 / H_2SO_4$) breaks the aromaticity to produce a conjugated diketone called p-Benzoquinone.

(Note: In the presence of air, phenols slowly oxidize naturally to form dark-coloured mixtures containing quinones).

Variables & Thermodynamics:

• Reagent: Protic acid ($H_2SO_4$ or $H_3PO_4$)
• Mechanism: Bimolecular Nucleophilic Substitution ($S_N2$)

Crucial Boundary Condition (Temperature):

• At 413 K: Substitution dominates, yielding Ether.
• At 443 K: Elimination strongly dominates, yielding Ethene ($CH_2=CH_2$).

Limitations:

• Only suitable for preparing symmetrical ethers from primary (1°) unhindered alcohols. Secondary and tertiary alcohols will undergo elimination to form alkenes instead.

Variables & Reagents:

• R-X: Alkyl Halide (MUST be strictly primary, 1°)
• $R'-O^-Na^+$: Sodium Alkoxide (Can be 1°, 2°, or 3°)
• Mechanism: $S_N2$ attack of the alkoxide ion on the primary alkyl halide.

Application:

• This is the most important laboratory method for preparing ethers, including those containing complex or bulky alkyl groups.

Mechanism Dependence:

• With 1° or 2° Alkyl Groups: Follows an $S_N2$ mechanism. The halide ($I^-$) attacks the less sterically hindered (smaller) alkyl group, forming the smaller alkyl iodide.
• With a 3° Alkyl Group: Follows an $S_N1$ mechanism. The departure of the leaving group creates a highly stable 3° carbocation. The halide attacks this stable cation, forming the tertiary alkyl iodide.

(Note: Cleavage requires drastic conditions and excess HX. Reactivity: HI > HBr > HCl).

Directing Influence:

• The alkoxy group (-OR) is strongly ortho, para directing and activates the aromatic ring via the resonance (+R) effect.

Boundary Conditions:

• Because the ring is so highly activated by the methoxy group, bromination occurs successfully in ethanoic acid even in the absence of an Iron(III) bromide ($FeBr_3$) catalyst.
• The para isomer is typically the major product (approx 90% yield) due to less steric hindrance.

Separation Technique

They are separated by steam distillation.

Chemical Principle

• o-Nitrophenol: Is steam volatile because it forms intramolecular hydrogen bonds (bonding within the same molecule), preventing molecules from strongly associating with one another.
• p-Nitrophenol: Is less volatile (non-steam volatile) because it forms intermolecular hydrogen bonds with neighbouring molecules, creating a strong molecular association that significantly raises its boiling point.

Steps & Mechanism:

1. Diazotization: Aniline ($C_6H_5NH_2$) reacts with nitrous acid ($NaNO_2 + HCl$) strictly at ice-cold temperatures (273-278 K) to form Benzene diazonium chloride.
2. Hydrolysis: The highly unstable diazonium salt is simply warmed with water (or treated with dilute acids) to release nitrogen gas and yield Phenol.

Reaction Steps:

1. Sulphonation: Benzene is treated with Oleum (fuming sulfuric acid, $H_2S_2O_7$) to yield benzene sulphonic acid.
2. Alkali Fusion: The acid is heated with molten Sodium Hydroxide ($NaOH$) to form sodium phenoxide.
3. Acidification: The phenoxide salt is treated with an acid ($H^+$) to liberate free Phenol.

Variables & Reagents:

• $C_6H_5OH$: Phenol
• $C_6H_5COCl$: Benzoyl chloride
• $C_6H_5-O-CO-C_6H_5$: Phenyl benzoate (an ester)

Concept:

• The Schotten-Baumann reaction specifically refers to the benzoylation of active hydrogen compounds (like phenols or amines) using benzoyl chloride in the presence of aqueous $NaOH$.

Bond Strength Differential

• O-Aryl Bond: The carbon atom of the phenyl ring is sp² hybridized. Additionally, resonance delocalizes the oxygen lone pair into the ring, giving the O-Aryl bond a partial double bond character.
• O-Alkyl Bond: The carbon atom of the alkyl group is sp³ hybridized (single bond).
• Result: The weaker O-Alkyl bond breaks preferentially upon nucleophilic attack by $I^-$, yielding an alkyl iodide and leaving the tough O-Aryl bond intact to form Phenol.

Reactants & Catalyst:

• Substrate: A phenolic ester (e.g., Phenyl acetate, $C_6H_5OCOCH_3$).
• Catalyst: Anhydrous $AlCl_3$ (a strong Lewis acid) accompanied by heat ($\Delta$).

Mechanism Outcome:

• The acyl group ($-COR$) migrates from the phenolic oxygen to the ortho and para positions of the aromatic ring, transforming the ester into phenolic ketones.

Enzymatic Roles:

1. Invertase: Hydrolyzes the disaccharide Sucrose into equimolar amounts of the monosaccharides Glucose and Fructose.
2. Zymase: Ferments the resulting glucose/fructose into Ethanol and Carbon Dioxide gas.

(Both of these crucial enzymes are biologically sourced from yeast).

Reagent & Selectivity:

• Reagent: Periodic acid ($HIO_4$).
• Mechanism: It specifically oxidatively cleaves the C-C bond between vicinal diols (1,2-glycols).
• Product: For ethylene glycol, the cleavage breaks the molecule symmetrically, yielding two moles of Formaldehyde ($HCHO$).

Reagent & Principle

• Lucas Reagent: Conc. HCl + Anhydrous $ZnCl_2$.
• The reaction forms an insoluble alkyl halide. Reactivity depends on carbocation stability (3° > 2° > 1°).

Visual Observations

• Tertiary (3°) Alcohols: Turbidity (cloudiness) appears immediately as the halide forms instantly.
• Secondary (2°) Alcohols: Turbidity appears after about 5 minutes.
• Primary (1°) Alcohols: No turbidity at room temperature (requires heating to react).

Directing Influence:

• The methoxy group ($-OCH_3$) is a powerful activating group and is strictly ortho/para directing via the +R effect.

Products:

• Alkylation: Yields 2-methoxytoluene (minor) and 4-methoxytoluene (major).
• Acylation: Yields 2-methoxyacetophenone (minor) and 4-methoxyacetophenone (major).
• The para products strictly dominate due to the large steric bulk of the methoxy group blocking the ortho position.

Test Sequence

Alcohols are treated sequentially with: $P/I_2 \rightarrow AgNO_2 \rightarrow HNO_2 \rightarrow$ Alkali ($NaOH$)

Visual Observations

• Primary (1°) Alcohols: Produce a Blood Red colour (due to the formation of a nitrolic acid salt).
• Secondary (2°) Alcohols: Produce a Blue colour (due to the formation of a pseudonitrol).
• Tertiary (3°) Alcohols: Produce No Colouration (remain colorless) because they do not react with $HNO_2$ due to the absence of an alpha-hydrogen.

Methanol ($CH_3OH$)

• Preparation: Produced commercially by the catalytic oxidation of synthesis gas ($CO$ + $H_2$) at high temperature and pressure using a $ZnO-Cr_2O_3$ catalyst.
• Toxicity: Highly toxic. Ingestion in small quantities causes blindness, and larger quantities cause death.

Ethanol ($C_2H_5OH$)

• Preparation: Commercially produced via the fermentation of sugars using enzymes (Invertase converts sugar to glucose/fructose; Zymase converts them to ethanol and $CO_2$).
• Toxicity: The active ingredient in alcoholic beverages. It acts as a central nervous system depressant in excess.

Reagents & Directing Influence:

• Nitrating Mixture: Concentrated sulfuric acid and concentrated nitric acid (generates the $NO_2^+$ electrophile).
• The strongly activating methoxy group ($-OCH_3$) directs the nitro group to the ortho and para positions.
• Steric Factor: The para isomer (4-nitroanisole) is the major product because the bulky methoxy group heavily physically obstructs the ortho positions.

Definition

Denaturation is the deliberate process of making commercial ethanol unfit for drinking to prevent its misuse as a beverage.

Specific Additives

1. Copper Sulphate ($CuSO_4$): Added to impart a distinct blue colour, making it easily identifiable visually.
2. Pyridine: A highly toxic, foul-smelling liquid added to deter ingestion.

Nitration of Glycerol

Reacting glycerol (propane-1,2,3-triol) with a mixture of concentrated nitric and sulfuric acids yields Glyceryl trinitrate (TNG), also known as nitroglycerin. It is a highly sensitive and powerful explosive.

Formulation of Dynamite

Because pure TNG is too unstable for safe transport, it is adsorbed onto Kieselguhr (a porous diatomaceous earth). This stabilized solid mixture is commercially known as Dynamite.

Historical Application

Diethyl ether was extensively used as a pioneering inhalation anesthetic during surgical procedures.

Reasons for Discontinuation

• It has a relatively slow effect compared to modern anesthetics.
• It induces an unpleasant recovery period for patients.
• It is a highly volatile and flammable compound, posing safety risks in operating rooms.