EXAM STRATEGY & IMPORTANT QUESTIONS GUIDE

Classification of Organic Compounds:
Organic compounds are classified both by carbon skeleton and by functional group.
By carbon skeleton:
Acyclic (open-chain or aliphatic) compounds such as alkanes, alkenes and alkynes.
Cyclic compounds are subdivided into carbocyclic rings — alicyclic (cyclohexane) and aromatic (benzene) — and heterocyclic rings that may be saturated (pyrrolidine) or aromatic (pyridine, furan).
By functional group: hydrocarbons, halides, alcohols, ethers, aldehydes, ketones, carboxylic acids, esters, amides, amines, nitriles, nitro compounds and thiols.

IUPAC Rules — Step by Step:
(1) Identify the longest continuous carbon chain containing the principal functional group; this gives the parent name.
(2) Number the chain from the end that gives the principal group (and any substituents) the lowest set of locants.
(3) Name the substituents as alphabetical prefixes, using multiplying prefixes (di, tri, tetra) when they are repeated.
(4) Add the functional-group suffix according to the priority order:
COOH (-oic acid) > COOR (-oate) > CONH₂ (-amide) > CN (-nitrile) > CHO (-al) > CO (-one) > OH (-ol) > NH₂ (-amine) > C=C (-ene) > C≡C (-yne) > alkane (-ane) (5) Insert locants (Arabic numerals) before the suffix to show the positions.

Chain Names (C1 – C10):
The standard stem names are meth (C1), eth (C2), prop (C3), but (C4), pent (C5), hex (C6), hept (C7), oct (C8), non (C9) and dec (C10). The family suffixes are -ane (alkane), -ene (alkene) and -yne (alkyne).

Illustrative Examples:
CH₃ – CH₂ – CH₃ is propane.
CH₃ – CH(CH₃) – CH₂ – CH₃ is 2-methylbutane.
CH₃ – CH=CH – CH₃ is but-2-ene.
CH₃ – CH(OH) – CH₃ is propan-2-ol.
CH₃ – CH₂ – CHO is propanal.
CH₃ – CO – CH₃ is propan-2-one (common name, acetone).
CH₃ – COOH is ethanoic acid (common name, acetic acid).
HOOC – COOH is ethanedioic acid (common name, oxalic acid).
C₆H₁₂ is cyclohexane and C₆H₅ – COOH is benzoic acid (benzenecarboxylic acid).

Types of Isomerism:
Isomerism is broadly of two kinds. Structural (constitutional) isomers differ in the way in which the atoms are connected, while stereoisomers have the same connectivity but differ in their spatial arrangement (geometrical or optical).

Structural Isomerism — Five Types:
(a) Chain isomerism arises from a different arrangement of the carbon skeleton. For example, n-butane (CH₃CH₂CH₂CH₃) and isobutane ((CH₃)₃CH) both have the formula C₄H₁₀ but different skeletons.
(b) Position isomerism occurs when the same skeleton and functional group are present but the functional group sits at different positions on the chain. For example, propan-1-ol (CH₃CH₂CH₂OH) differs from propan-2-ol (CH₃CH(OH)CH₃), and but-1-ene differs from but-2-ene.
(c) Functional isomerism occurs when compounds have the same molecular formula but different functional groups. For example, ethanol (CH₃CH₂OH) and dimethyl ether (CH₃OCH₃) both have the formula C₂H₆O, while propanal and acetone both have the formula C₃H₆O.
(d) Metamerism 🔊 occurs when different alkyl groups lie on either side of the same functional group. For example, methyl propyl ether (CH₃OC₃H₇) and diethyl ether (CH₃CH₂OCH₂CH₃) are both C₄H₁₀O. It is common in ethers, thioethers, secondary amines and ketones.
(e) Tautomerism 🔊 is the spontaneous interconversion of two forms that differ in the position of a hydrogen atom and an adjacent double bond. The classical keto–enol tautomerism is shown by acetone:
CH₃ – CO – CH₃ ⇌ CH₃ – C(OH)=CH₂ The reaction is catalysed either by acid or by base.

Stereoisomerism (Brief):
Geometrical (cis–trans) isomerism arises around a C=C double bond or a ring; classical examples are cis- and trans-but-2-ene, and maleic acid versus fumaric acid.
Optical isomerism occurs in molecules that contain a chiral centre and produces a pair of non-superimposable mirror-image enantiomers. A 1 : 1 mixture of the two is called a racemic mixture and is optically inactive.

sp³ Hybridisation:
In sp³ hybridisation, one 2s and three 2p orbitals of carbon combine to give four equivalent sp³ hybrid orbitals, each having 25 % s and 75 % p character. The four orbitals are directed to the corners of a regular tetrahedron, with bond angles of 109.5°, and form four σ-bonds by head-on orbital overlap. Methane (CH₄) is the classical example.

General Methods of Preparation:
(1) Hydrogenation of alkenes or alkynes (Sabatier–Senderens): C₂H₄ + H₂ → C₂H₆ over Ni, Pt or Pd.
(2) Wurtz reaction 🔊: 2 R – X + 2 Na → R – R + 2 NaX (3) Kolbe's electrolysis 🔊 of sodium acetate: 2 CH₃COONa + 2 H₂O → C₂H₆ + 2 CO₂↑ + H₂↑ + 2 NaOH (4) Reduction of alkyl halides: R – X + Zn / HCl → R – H.
(5) From Grignard reagent: R – MgX + H₂O → R – H + Mg(OH)X.
(6) Decarboxylation of a sodium carboxylate on heating with sodalime: CH₃COONa + NaOH (CaO, Δ) → CH₄ + Na₂CO₃

Halogenation (Free-Radical Chain Mechanism):
Methane reacts with chlorine in sunlight to give successively CH₃Cl, CH₂Cl₂, CHCl₃ and CCl₄.
CH₄ + Cl₂ → (hν, UV) → CH₃Cl + HCl The reaction proceeds through three steps.
Initiation: homolytic fission of Cl₂ by UV light gives two chlorine radicals.
Propagation: Cl· + CH₄ → HCl + CH₃·, and CH₃· + Cl₂ → CH₃Cl + Cl·.
Termination: Cl· + Cl· → Cl₂, CH₃· + Cl· → CH₃Cl, or CH₃· + CH₃· → C₂H₆.
The reactivity order of halogens is F₂ > Cl₂ > Br₂ ≫ I₂; fluorine is too violent to control and iodine does not react thermodynamically.
Selectivity: tertiary hydrogens are abstracted in preference to secondary, which are in turn preferred to primary, because of the stability order of the resulting radical (3° > 2° > 1°).

Uses of Paraffins:
Liquid paraffin (mineral oil) is used as a laxative, an ointment base and a lubricant.
Soft paraffin (petrolatum) is used as an ointment base and a skin protectant.
Hard paraffin (paraffin wax) is used to stiffen suppository bases, to make candles, in paper waterproofing and for embedding in histology.
Alkanes are also important fuels (natural gas, LPG, petrol, diesel, kerosene) and feedstocks for the petrochemical industry.

E1 Reaction (Unimolecular Elimination):
The E1 mechanism has two steps.
Step 1 (slow, rate-determining): heterolysis of the C – X bond gives a carbocation. R – X → R⁺ + X⁻ Step 2 (fast): a base removes a β-hydrogen, forming the π-bond.
Kinetics: Rate = k [R – X] — first order overall.
It is favoured by a tertiary (3° > 2° > 1°) substrate, a weak base, a polar protic solvent (water, ethanol) and higher temperature. Because a carbocation is formed, carbocation rearrangement can occur.

E2 Reaction (Bimolecular Elimination):
E2 is a single concerted step: a strong base removes the β-hydrogen while the C – X bond simultaneously breaks, and the new π-bond forms. The reaction requires an anti-periplanar geometry (dihedral angle 180°) between the β-H and the leaving group for proper orbital overlap.
Kinetics: Rate = k [R – X][Base] — second order overall.
It is favoured by a strong bulky base (t-BuOK, NaNH₂), a polar aprotic solvent (DMSO) and a higher temperature. No intermediate is formed, so rearrangement is not possible.

Saytzeff's Rule:
According to Saytzeff's rule, the more substituted (more stable) alkene is the major product of elimination. Alkene stability follows the order tetrasubstituted > trisubstituted > disubstituted > monosubstituted > ethylene.
Example: 2-bromobutane with KOH gives but-2-ene as the major product (about 80 %) and but-1-ene as the minor (about 20 %).
Hofmann's rule 🔊 is the opposite: when a bulky base (t-BuOK) is used, the less substituted alkene predominates because the bulky base cannot reach the more substituted β-hydrogen.

E1 versus E2 — Comparison:

Feature	E1	E2
Steps	Two (step-wise)	One (concerted)
Rate	k [R – X]	k [R – X][Base]
Order	First	Second
Intermediate	Carbocation	None
Substrate	3° > 2° (not 1°)	3° > 2° > 1°
Base strength	Weak	Strong
Solvent	Polar protic	Polar aprotic
Rearrangement	Possible	Not possible
Stereochemistry	Non-specific	Anti-periplanar
Competes with	SN1	SN2

Electrophilic Addition to Alkenes — Mechanism:
An alkene reacts with HX or X₂ to give a saturated product in two steps.
Step 1: the π-electrons attack the electrophile (H⁺ or Br⁺), producing the most stable carbocation intermediate (3° > 2° > 1°).
Step 2: the nucleophile (X⁻ or solvent) attacks the carbocation to give the final product.
Examples: CH₂=CH₂ + HBr → CH₃CH₂Br, and CH₂=CH₂ + Br₂ → CH₂Br – CH₂Br.

Markownikoff's Rule (1869):
In the ionic addition of HX to an unsymmetrical alkene, the hydrogen attaches to the carbon bearing more hydrogens, and the halogen to the carbon bearing fewer. The rule is explained by the preferential formation of the more stable (more substituted) carbocation, which is stabilised by hyperconjugation and the inductive effect of the alkyl groups.
Example: CH₂=CH – CH₃ + HBr → CH₃ – CHBr – CH₃ (2-bromopropane; major product) rather than CH₃ – CH₂ – CH₂Br (1-bromopropane; minor product, less than 5 %).

Anti-Markownikoff Addition (Peroxide / Kharasch Effect, 1933):
In the presence of peroxides (R – O – O – R) or light, HBr adds to an alkene in the reverse sense by a free-radical mechanism. The mechanism proceeds as follows.
Initiation: R – O – O – R → 2 RO·
Propagation: RO· + HBr → ROH + Br·; Br· + CH₂=CH – CH₃ → CH₂Br – CH· – CH₃ (a more stable secondary radical); then CH₂Br – CH· – CH₃ + HBr → CH₂Br – CH₂ – CH₃ (1-bromopropane) + Br·.
Only HBr shows the peroxide effect; HCl does not, because its H – Cl bond is too strong, and HI does not, because the H – I bond is too weak for the radical chain to propagate.

Ozonolysis:
Ozonolysis is the oxidative cleavage of a C=C bond by ozone, followed by reductive work-up.
Steps: the alkene first reacts with O₃ to give a molozonide, which rearranges to an ozonide. The ozonide is then treated with Zn/H₂O or Me₂S, giving two carbonyl compounds.
CH₃ – CH=CH – CH₃ + O₃ → ozonide → (Zn, H₂O) → 2 CH₃CHO Ozonolysis is used for structure determination of alkenes, because the two carbonyl fragments identify the position of the original double bond.

Stability of Conjugated Dienes:
In 1,3-butadiene (CH₂=CH – CH=CH₂), the π-electrons are delocalised over all four carbons by resonance, as shown below.
CH₂=CH – CH=CH₂ ⇌ ⁺CH₂ – CH=CH – CH₂⁻ The heat of hydrogenation of 1,3-butadiene is 57 kcal/mol, compared with 60 kcal/mol expected for two isolated double bonds; the difference of about 3 kcal/mol represents extra (resonance) stabilisation.
The C2 – C3 bond length (1.48 Å) is shorter than a normal single bond (1.54 Å), indicating partial double-bond character.

Diels–Alder Reaction ([4+2] Cycloaddition):
Reactants: the diene (four π-electrons) must be in the s-cis conformation, and the dienophile 🔊 (two π-electrons) is an alkene or alkyne that bears an electron-withdrawing group (CHO, CN, NO₂, COOR or C=O).
Mechanism: a single concerted step in which six π-electrons shift simultaneously, forming two new σ-bonds and one new π-bond.
Example: 1,3-butadiene reacts with maleic anhydride to give cyclohex-4-ene-1,2-dicarboxylic anhydride.
Features: the reaction is stereospecific (a cis dienophile gives a cis product), suprafacial on both diene and dienophile, and obeys the endo rule (the endo product is kinetically preferred). At high temperature the reaction is reversible (retro-Diels–Alder).
Uses: synthesis of six-membered rings, natural products (including steroids) and pharmaceutical intermediates.

SN2 Reaction (Bimolecular):
Mechanism: SN2 is a single concerted step. The nucleophile attacks the carbon from the back face, 180° away from the leaving group; a pentacoordinate transition state forms, in which the C – Nu bond develops while the C – LG bond breaks. The result is Walden inversion 🔊 of configuration.
Kinetics: Rate = k [R – X][Nu⁻] — second order overall.
Favoured by: primary (1° > 2° ≫ 3°) substrates (because steric hindrance blocks tertiary carbons); strong nucleophiles (OH⁻, CN⁻, I⁻); polar aprotic solvents such as DMSO, DMF and acetone (which solvate the cation but leave the nucleophile "naked" and reactive); and good leaving groups in the order I > Br > Cl ≫ F.
Stereochemistry: a chiral substrate gives the opposite-handed product (inversion).

SN1 Reaction (Unimolecular):
Mechanism: SN1 has two steps.
Step 1 (slow, rate-determining): the substrate ionises to a carbocation. R – X → R⁺ + X⁻ Step 2 (fast): the nucleophile attacks the flat carbocation from either face.
Kinetics: Rate = k [R – X] — first order overall.
Favoured by: tertiary substrates (3° > 2° ≫ 1°, because the carbocation is more stable); weak or neutral nucleophiles (water, alcohols); polar protic solvents (water, ethanol), which solvate and stabilise the carbocation; and good leaving groups.
Stereochemistry: because the planar carbocation is attacked from either face, the product is racemic (approximately 50 : 50). Carbocation rearrangement is possible, converting a less stable cation (1° → 2° or 2° → 3°) by 1,2-hydride or 1,2-methyl shift.

SN1 versus SN2 — Comparison:

Feature	SN1	SN2
Steps	Two (step-wise)	One (concerted)
Rate	k [R – X]	k [R – X][Nu]
Order	First	Second
Substrate	3° > 2° ≫ 1°	1° > 2° ≫ 3°
Intermediate	Planar carbocation	None (pentacoordinate TS)
Nucleophile	Weak or neutral	Strong or anionic
Solvent	Polar protic	Polar aprotic
Stereochemistry	Racemisation	Inversion (Walden)
Rearrangement	Possible	Not possible
Competes with	E1	E2

Structure and Uses:

Compound	Structure	Principal uses
Ethyl chloride	CH₃ – CH₂ – Cl	Topical local anaesthetic spray (cooling effect on evaporation), refrigerant, ethylating agent
Chloroform 🔊	CHCl₃	Former general anaesthetic (now discontinued because of hepatotoxicity), solvent, preservative in paracetamol preparations, analytical extraction solvent
Trichloroethylene	CHCl=CCl₂	Metal degreasing, dry cleaning, historical anaesthetic, industrial solvent
Tetrachloroethylene (perchloroethylene)	CCl₂=CCl₂	Dry cleaning, metal degreasing, veterinary anthelmintic
Dichloromethane (methylene chloride)	CH₂Cl₂	Paint stripper, pharmaceutical solvent, extraction of caffeine from coffee, aerosol propellant
Tetrachloromethane (CCl₄) 🔊	CCl₄	Former fire extinguisher, dry-cleaning solvent, anthelmintic — now banned because it is hepatotoxic and ozone-depleting
Iodoform	CHI₃	Yellow crystalline topical antiseptic; dental dressings and wound packing; has a characteristic odour and is the positive result of the iodoform test for methyl ketones

Preparation Highlights:
Chloroform is prepared by the haloform reaction of acetone with bleaching powder (Cl₂/NaOH).
CH₃ – CO – CH₃ + 4 Cl₂ + NaOH → CHCl₃ + CH₃COONa + 3 HCl Chloroform is stored in dark amber bottles containing 1 % ethanol, which prevents its photo-oxidation to toxic phosgene 🔊.
Iodoform test: methyl ketones, acetaldehyde, ethanol and secondary alcohols with a CH₃ – CH(OH) – group react with I₂/NaOH to give a yellow precipitate of CHI₃.
CCl₄ is made industrially from carbon disulphide: CS₂ + 2 Cl₂ → CCl₄ + S₂Cl₂.

Qualitative Tests for Alcohols:
(1) Sodium metal test: the alcohol reacts with sodium to give sodium alkoxide with brisk effervescence of hydrogen; this test is positive for any –OH.
(2) Ester test: the alcohol reacts with a carboxylic acid or acetyl chloride to give a fruity-smelling ester.
(3) Lucas test 🔊 (concentrated HCl with anhydrous ZnCl₂) distinguishes the three classes of alcohol by the rate of turbidity formation: tertiary gives immediate turbidity, secondary in 5 – 10 minutes, and primary gives no turbidity at room temperature.
(4) Victor Meyer's test gives a red colour with a primary, blue with a secondary and no colour with a tertiary alcohol.
(5) Iodoform test: alcohols containing a CH₃ – CH(OH) – group (such as ethanol and secondary alcohols bearing a methyl group) react with I₂ / NaOH to give yellow CHI₃.
(6) Oxidation (with K₂Cr₂O₇ or KMnO₄): primary alcohols are oxidised first to aldehydes and then to carboxylic acids, secondary alcohols to ketones, and tertiary alcohols are resistant under mild conditions.

Structure and Uses of Important Alcohols:

Alcohol	Structure	Principal uses
Ethyl alcohol (ethanol)	CH₃ – CH₂ – OH	Solvent, tinctures, 70 % hand sanitiser, topical antiseptic, beverages, biofuel
Methyl alcohol (methanol) 🔊	CH₃ – OH	Industrial solvent and fuel; highly toxic — metabolised to formaldehyde and formic acid, producing blindness, metabolic acidosis and death; antidote is fomepizole or ethanol
Chlorobutanol 🔊	1,1,1-trichloro-2-methyl-2-propanol (CCl₃ – C(CH₃)₂ – OH)	0.5 % antimicrobial preservative in eye, nasal and parenteral preparations; mild sedative, local anaesthetic, antifungal
Cetostearyl alcohol 🔊	Mixture of cetyl (C₁₆H₃₃OH) and stearyl (C₁₈H₃₇OH) alcohols	Emulsifier and stiffening agent in creams and ointments
Benzyl alcohol	C₆H₅ – CH₂ – OH	Bacteriostatic preservative in parenterals (1 – 2 %), local anaesthetic, solvent
Glycerol (glycerin) 🔊	HOCH₂ – CH(OH) – CH₂OH (1,2,3-propanetriol)	Humectant, sweetener, solvent, osmotic laxative, vehicle for cough syrups, cryoprotectant
Propylene glycol	CH₃ – CH(OH) – CH₂OH (1,2-propanediol)	Solvent, humectant, cryoprotectant and IV co-solvent for drugs such as diazepam and phenytoin

Nucleophilic Addition Mechanism:
Step 1: a nucleophile (HCN, H₂O, ROH, RNH₂, RMgX or NaHSO₃) attacks the electrophilic carbonyl carbon, the π-bond breaks and the electrons move on to the oxygen to give an alkoxide intermediate.
Step 2: the alkoxide is protonated by the solvent to give the final addition product.
Example: CH₃CHO + HCN gives CH₃ – CH(OH) – CN (a cyanohydrin).
Reactivity: HCHO > higher aldehydes > ketones, because alkyl groups donate electrons inductively and also cause steric hindrance.

Aldol Condensation:
Two molecules of aldehyde or ketone containing an α-hydrogen combine in the presence of dilute base (NaOH or K₂CO₃) to give a β-hydroxycarbonyl (an "aldol"); on heating the aldol loses water to give an α,β-unsaturated carbonyl.
Mechanism: (1) the base removes an α-hydrogen to form a carbanion or enolate; (2) the enolate attacks the carbonyl carbon of a second molecule; (3) protonation of the resulting alkoxide gives the aldol; (4) dehydration on heating yields the α,β-unsaturated carbonyl.
2 CH₃CHO → (dilute NaOH) → CH₃ – CH(OH) – CH₂ – CHO → (Δ) → CH₃ – CH=CH – CHO (crotonaldehyde)

Crossed (Claisen–Schmidt) Aldol:
A crossed aldol is performed between two different aldehydes or ketones; it is useful when one of them has no α-hydrogen (for example benzaldehyde or formaldehyde), because then only the other partner can give the enolate.
Example: benzaldehyde (no α-H) with acetophenone in the presence of dilute alkali gives the α,β-unsaturated ketone benzalacetophenone (a chalcone) together with water.

Cannizzaro Reaction:
Aldehydes that have no α-hydrogen (such as formaldehyde and benzaldehyde) undergo self-disproportionation in concentrated NaOH (about 50 %). One molecule is oxidised to the carboxylate salt and another is reduced to the corresponding alcohol.
2 HCHO + NaOH → CH₃OH + HCOONa
2 C₆H₅CHO + NaOH → C₆H₅CH₂OH + C₆H₅COONa Mechanism: (1) hydroxide attacks the carbonyl carbon to form a tetrahedral hydrate anion; (2) the hydrate transfers hydride (H⁻) to a second molecule of aldehyde; (3) the result is an alcohol and a carboxylate salt.

Crossed Cannizzaro:
The crossed Cannizzaro is carried out between two different aldehydes, one of which is formaldehyde (an excellent hydride donor). Formaldehyde is always oxidised to formate, while the other aldehyde is reduced to its alcohol.
HCHO + C₆H₅CHO + NaOH → HCOONa + C₆H₅CH₂OH

Benzoin Condensation:
Two molecules of an aromatic aldehyde that lacks α-hydrogen undergo condensation in the presence of KCN or NaCN to give an α-hydroxy ketone known as benzoin.
2 C₆H₅CHO → (CN⁻ catalyst) → C₆H₅ – CO – CH(OH) – C₆H₅ (benzoin) Mechanism: (1) cyanide adds to one PhCHO to give PhCH(CN)O⁻; (2) proton transfer gives the resonance-stabilised carbanion PhC(CN)(OH)⁻; (3) this nucleophilic carbanion attacks a second molecule of PhCHO; (4) proton transfer and loss of CN⁻ give benzoin. CN⁻ generates an umpolung (acyl-anion equivalent).
Uses: benzoin is an intermediate in the synthesis of phenytoin and other drugs.

Perkin Condensation:
An aromatic aldehyde is heated with an aliphatic acid anhydride containing α-hydrogens and the sodium salt of the same acid as base; an α,β-unsaturated aromatic acid is produced.
C₆H₅CHO + (CH₃CO)₂O + CH₃COONa → C₆H₅ – CH=CH – COOH (cinnamic acid) + CH₃COOH Mechanism: (1) sodium acetate removes an α-hydrogen from the anhydride to give a carbanion; (2) the carbanion attacks the carbonyl of benzaldehyde; (3) dehydration and hydrolysis of the residual anhydride give the α,β-unsaturated acid.
Uses: synthesis of cinnamic acid (for perfumery), coumarins and indigo dye.

Structure and Uses:

Compound	Structure	Principal uses
Formaldehyde 🔊	HCHO (gas); 40 % aqueous solution is formalin	Disinfectant, embalming fluid, preservative, tissue fixative, resin manufacture
Paraldehyde 🔊	Cyclic trimer of acetaldehyde, (CH₃CHO)₃; a six-membered ring	Sedative, hypnotic and anticonvulsant (formerly used in status epilepticus); rapid onset but unpleasant odour
Acetone	CH₃ – CO – CH₃	Solvent (nail-polish remover), extraction, paint thinner, starting material for bisphenol A
Chloral hydrate 🔊	CCl₃ – CH(OH)₂	Paediatric sedative-hypnotic; historically the "Mickey Finn"
Hexamine (methenamine; urotropine)	(CH₂)₆N₄, formed from 6 HCHO + 4 NH₃	Urinary antiseptic (releases HCHO slowly in acidic urine); industrial precursor of the explosive RDX
Benzaldehyde	C₆H₅ – CHO	Almond flavour, perfumery, dye manufacture, synthesis of cinnamic acid and triphenylmethane dyes
Vanillin 🔊	4-hydroxy-3-methoxybenzaldehyde (HOC₆H₃(OCH₃) – CHO)	Vanilla flavouring in food and pharmaceutical preparations, perfumery, intermediate in L-DOPA synthesis
Cinnamaldehyde 🔊	C₆H₅ – CH=CH – CHO	Cinnamon flavour, fragrance, antimicrobial agent, cough syrups

Acidity of Carboxylic Acids:
A carboxylic acid ionises as R – COOH ⇌ R – COO⁻ + H⁺, with a pKa of approximately 3 – 5, which makes it far more acidic than an alcohol (pKa about 16). Three factors explain this.
(1) The resonance stabilisation of the carboxylate anion, in which the negative charge is delocalised equally between the two oxygen atoms.
(2) The inductive effect of the two electronegative oxygen atoms, which withdraw electron density from the O – H bond.
(3) The carboxylate ion is much more stable than an alkoxide, because an alcohol has only a single oxygen to carry the negative charge.

Effect of Substituents on Acidity:
Electron-withdrawing groups (EWGs such as –NO₂, –CN, –Cl and –F) stabilise the carboxylate by inductive withdrawal and therefore increase acidity, while electron-donating groups (such as –CH₃ and –OR) destabilise it and decrease acidity.
Typical pKa values: HCOOH (3.75) is more acidic than CH₃COOH (4.76) or C₂H₅COOH (4.87) because the alkyl group donates electrons inductively. ClCH₂COOH (2.86) is more acidic than CH₃COOH because chlorine is electron-withdrawing. The series CCl₃COOH (0.7) > CHCl₂COOH (1.3) > ClCH₂COOH (2.86) > CH₃COOH (4.76) shows that successive halogens progressively raise acidity. The position of the substituent also matters: α-chlorobutanoic acid (2.86) is more acidic than β-chloro (4.05) or γ-chloro (4.50), because the inductive effect weakens with distance.
In aromatic acids, p-nitrobenzoic acid (3.44) is stronger than benzoic (4.20), which is stronger than p-methoxybenzoic (4.47).

Structure and Uses of Important Carboxylic Acids:

Acid	Structure	Principal uses
Acetic acid	CH₃ – COOH	Vinegar, solvent, food additive
Lactic acid 🔊	CH₃ – CH(OH) – COOH	Cosmetic exfoliant, Ringer's lactate, food preservative
Tartaric acid 🔊	HOOC – CH(OH) – CH(OH) – COOH	Baking powder (cream of tartar), effervescent tablets, resolving agent in stereochemistry
Citric acid	HOOC – CH₂ – C(OH)(COOH) – CH₂ – COOH	Effervescent tablets, preservative, chelating agent, ORS
Succinic acid	HOOC – CH₂ – CH₂ – COOH	TCA-cycle intermediate, polymer precursor, pharmaceutical intermediate
Oxalic acid	HOOC – COOH	Primary standard in titrimetry, rust remover, bleach
Salicylic acid 🔊	o-HO – C₆H₄ – COOH	Keratolytic (acne and warts), antiseptic, precursor of aspirin
Benzoic acid	C₆H₅ – COOH	Preservative (as sodium benzoate), antifungal, aspirin intermediate
Benzyl benzoate	C₆H₅ – COO – CH₂ – C₆H₅	Scabicide and pediculicide (5 – 25 %)
Dimethyl phthalate	C₆H₄(COOCH₃)₂	Insect repellent
Methyl salicylate 🔊	2-HO – C₆H₄ – COOCH₃ (oil of wintergreen)	Rubefacient liniment, flavouring agent
Aspirin (acetylsalicylic acid)	2-CH₃COO – C₆H₄ – COOH	Analgesic, antipyretic, anti-inflammatory and antiplatelet agent

Tests for Carboxylic Acids:
A carboxylic acid turns blue litmus red. It liberates CO₂ with effervescence from sodium bicarbonate (this distinguishes it from phenol):
R – COOH + NaHCO₃ → R – COONa + H₂O + CO₂↑ It gives a fruity ester on warming with an alcohol and concentrated H₂SO₄ (the ester test). A neutral solution of FeCl₃ with the sodium salt of the acid gives a red-brown or buff precipitate of ferric carboxylate. It is reduced by LiAlH₄ to the corresponding primary alcohol.

Tests for Esters:
Esters usually have a fruity smell (for example amyl acetate smells of banana and ethyl butyrate of pineapple). The hydroxamic acid test gives a purple or magenta colour when the ester is treated with hydroxylamine followed by FeCl₃. On warming with NaOH, the ester undergoes saponification to a carboxylate and an alcohol. Esters are insoluble in water but soluble in organic solvents.

Tests for Amides:
Heating an amide with NaOH liberates ammonia, which has a pungent smell and turns moist red litmus blue:
R – CONH₂ + NaOH → R – COONa + NH₃↑ The biuret test (CuSO₄ in NaOH) produces a characteristic violet colour with amides (as in urea and proteins). The Hofmann degradation 🔊 converts a primary amide into a primary amine with one fewer carbon (R – CONH₂ + Br₂/NaOH → R – NH₂). Amides are hydrolysed by acid or alkali to give the parent acid together with ammonia (or an amine).

Basicity of Amines:
An amine is protonated according to R – NH₂ + H⁺ ⇌ R – NH₃⁺. The pKa of the conjugate acid (R – NH₃⁺) is about 10 – 11 for aliphatic amines and 4 – 5 for aromatic amines; basicity is often expressed as pK_b, with a low pK_b corresponding to a strong base.
In the gas phase, the order of basicity is 3° > 2° > 1° > NH₃, because each additional alkyl group donates electrons inductively to the nitrogen.
In aqueous solution, however, the order becomes 2° > 1° > 3° > NH₃. The protonated ammonium ion R – NH₃⁺ is stabilised by hydrogen bonding with water; the more hydrogens on nitrogen, the better the solvation, so a tertiary amine (with only one N – H) is poorly solvated and appears less basic than expected.
In general, aliphatic amines are more basic than aromatic amines, because in an aromatic amine the lone pair on nitrogen is delocalised into the π-system of the ring.
Typical pKa values of R – NH₃⁺: ethylamine 10.8, dimethylammonium 10.7, trimethylammonium 9.8 and anilinium 4.6.

Effect of Substituents on Basicity:
Alkyl groups (+I, electron-donating) push electrons toward nitrogen and therefore increase basicity, though a tertiary amine loses some of this advantage because of reduced solvation and increased steric crowding.
Aryl groups (–M, electron-withdrawing by resonance) delocalise the lone pair into the ring and markedly decrease basicity.
Further EWGs on the ring (NO₂, CN, Cl) decrease basicity still more (p-nitroaniline is a very weak base).
Steric hindrance around the nitrogen slows the approach of a proton and reduces apparent basicity.

Structure and Uses of Key Aliphatic Amines:

Amine	Structure	Principal uses
Ethanolamine 🔊	HO – CH₂ – CH₂ – NH₂	Intermediate for antihistamines; component of phospholipids; surfactant; sclerosing agent for varicose veins
Ethylenediamine 🔊	H₂N – CH₂ – CH₂ – NH₂	Chelating agent (precursor of EDTA); stabiliser in aminophylline (theophylline + ethylenediamine); corrosion inhibitor
Amphetamine 🔊	C₆H₅ – CH₂ – CH(CH₃) – NH₂ (α-methylphenethylamine)	CNS stimulant used in ADHD and narcolepsy; a Schedule II controlled drug with high abuse potential

Electromeric Effect:
The electromeric effect is the temporary, complete shift of a shared pair of π-electrons from one atom of a multiple bond to another when a reagent approaches. It is reversible and disappears when the reagent is removed.
There are two sub-types. In the +E effect, the electrons move toward the attacking electrophile; for example, the π-electrons of an alkene move toward an approaching H⁺. In the –E effect, the electrons move away from the attacking nucleophile; for example, when CN⁻ approaches the carbonyl of an aldehyde, the π-electrons move on to the oxygen atom.
This effect explains why the carbonyl carbon is electrophilic and why alkenes attack electrophiles.

Allylic Rearrangement (SN1' / SN2'):
An allylic rearrangement is a substitution or addition at an allylic position that is accompanied by migration of the double bond.
Example: CH₂=CH – CH₂ – Cl on hydrolysis gives both CH₂=CH – CH₂ – OH (normal product) and CH₃ – CH=CH – OH (rearranged product).
Mechanism: the allylic cation CH₂=CH – CH₂⁺ is resonance-stabilised as ⁺CH₂ – CH=CH₂, so the nucleophile can attack at either end of the allyl system, giving two products.
The rearrangement explains the unusual product distributions observed in allylic nucleophilic substitution and addition reactions.

Carbocation Stability Order:
Carbocations follow the stability order 3° > 2° > 1° > methyl, because additional alkyl groups donate electrons inductively and through hyperconjugation to the electron-deficient carbon. Resonance-stabilised cations such as allyl and benzyl can be as stable as tertiary cations.

Types of Rearrangement:
(1) 1,2-Hydride shift: a neighbouring hydrogen migrates with its bonding pair from an adjacent carbon to the carbocation centre.
(CH₃)₂CH – CH₂⁺ (1°) → (CH₃)₂C⁺ – CH₃ (3°, more stable) (2) 1,2-Methyl (alkyl) shift: a methyl group migrates with its bonding pair when no suitable hydrogen is available.
(CH₃)₃C – CH₂⁺ (neopentyl, 1°) → (CH₃)₂C⁺ – CH(CH₃) (3°)

Examples in Reactions:
In SN1, hydrolysis of 2-bromo-3-methylbutane gives mainly 2-methylbutan-2-ol (the tertiary alcohol formed after a hydride shift) rather than the simple secondary alcohol. In E1, heating neopentyl bromide with base yields 2-methylbut-2-ene after a methyl shift. In electrophilic addition, HCl adds to 3,3-dimethyl-1-butene to give 2-chloro-2,3-dimethylbutane following Markownikoff addition and a methyl shift.