Organic Chemistry-4 (NMR, Enolates and Natural Products) BCH5T09

Syllabus topics (RTMNU)

• Basic principles
• Concept of nuclear spin
• Equivalent and non-equivalent protons
• Reference compound TMS
• Factors affecting chemical shift
• Nuclear Magnetic Resonance (NMR) spectroscopy
• Proton Magnetic Resonance spectroscopy
• Nuclear shielding and deshielding
• Chemical shift
• Spin-spin splitting and Coupling constant
• Areas of signals
• Interpretation of NMR spectra of organic molecules and structure elucidation of simple organic molecules on the basis of NMR data such as ethyl bromide, ethanol, acetaldehyde, 1,2-dibromoethane, ethyl acetate, toluene, acetophenone, acetyl acetone

Basic Principles of NMR and Concept of Nuclear Spin

Nuclear Magnetic Resonance (NMR) spectroscopy is the study of the absorption of radio-frequency radiation by certain nuclei placed in a strong magnetic field. It tells us the number of different kinds of protons (or carbons), their chemical environment and their neighbours — the best tool for finding the structure of organic compounds.

Nuclear spin: nuclei with an odd number of protons or neutrons spin and have a spin quantum number I ≠ 0, e.g. ¹H, ¹³C, ¹⁹F, ³¹P (all I = ½). ¹²C and ¹⁶O have I = 0 and are NMR-inactive. A spinning charged nucleus behaves like a tiny magnet.

In an external magnetic field (B₀) a nucleus with spin I takes (2I + 1) orientations. A proton (I = ½) has two: α-spin (aligned with the field, lower energy) and β-spin (opposed, higher energy). The energy gap ΔE = hγB₀/2π increases with field strength. When radio waves of exactly this energy (ν = γB₀/2π, the resonance condition) are applied, the proton "flips" from α to β — this absorption is nuclear magnetic resonance. For protons, a field of 1.41 tesla needs 60 MHz and 2.35 tesla needs 100 MHz.

Equivalent and Non-Equivalent Protons

Equivalent protons are protons in the same chemical environment; they absorb at the same position and give one signal. Non-equivalent protons give separate signals. So the number of signals = number of sets of equivalent protons. Examples: CH₄, C₆H₆, CH₃OCH₃ — 1 signal each; CH₃CH₂Br — 2 signals; CH₃CH₂OH — 3 signals; (CH₃)₂CHCl — 2 signals.

Shielding, Deshielding, Chemical Shift and Reference Compound TMS

Electrons around a proton circulate in the applied field and create a small opposing field. This shielding means a higher applied field is needed for resonance — the signal moves upfield (right, low δ). When electron density around the proton is reduced (e.g. by an electronegative atom), the proton is deshielded and absorbs downfield (left, high δ).

Chemical shift is the position of a signal relative to a reference, expressed in parts per million (ppm):

Tetramethylsilane (TMS), (CH₃)₄Si, is the reference (δ = 0) because: (1) its 12 protons are equivalent and give one sharp signal; (2) silicon is less electronegative than carbon, so its protons are highly shielded and appear upfield of almost all organic protons; (3) it is chemically inert; (4) volatile (b.p. 27 °C), easy to remove; (5) soluble in most organic solvents.

Factors Affecting Chemical Shift

1. Electronegativity (inductive effect): electronegative atoms pull electrons away and deshield nearby protons: CH₃F (δ 4.3) > CH₃Cl (3.0) > CH₃Br (2.7) > CH₃I (2.2). The effect falls off with distance.
2. Magnetic anisotropy (π-electron circulation): the ring current of benzene strongly deshields aromatic protons (δ 6.5–8); aldehyde proton δ 9–10; alkene protons δ 4.5–6. Acetylenic protons are shielded (δ 2–3) because they lie along the axis of the cylindrical π-cloud.
3. Hydrogen bonding: H-bonded protons (OH, NH) are deshielded; their δ varies with concentration, solvent and temperature (alcohol OH δ 1–5; carboxylic acid OH δ 10–13).
4. Hybridisation of the carbon bearing the proton, and van der Waals deshielding in crowded molecules.

Spin–Spin Splitting, Coupling Constant and Area of Signals

Spin–spin splitting: a proton's signal is split by protons on adjacent carbons (usually up to three bonds away), because their spins add to or subtract from the field it feels. (n + 1) rule: a signal is split into (n + 1) peaks by n equivalent neighbouring protons: 0 → singlet, 1 → doublet (1:1), 2 → triplet (1:2:1), 3 → quartet (1:3:3:1), 4 → quintet. Relative intensities follow Pascal's triangle. Equivalent protons do not split each other; protons on O–H often do not split because of fast exchange.

Coupling constant (J): the distance between adjacent peaks of a multiplet, in hertz. It does not depend on the applied field. Protons that split each other have the same J (e.g. about 7 Hz for CH₃–CH₂), which helps to match signals.

Area of signals (integration): the area under each signal is proportional to the number of protons producing it. The integration curve (step heights) gives the proton ratio, e.g. 3 : 2 in ethyl bromide.

Interpretation of NMR Spectra of Simple Molecules

Structure elucidation example: A compound C₂H₄O shows a doublet at δ 2.2 (3H) and a quartet at δ 9.8 (1H). The δ 9.8 signal shows –CHO; the doublet/quartet pair shows CH₃ next to CH. Structure: CH₃CHO (acetaldehyde).

Likely exam questions

1. (Long, 8 marks) Explain the basic principle of NMR spectroscopy. What is chemical shift? Discuss the factors affecting chemical shift.
2. (Long, 8 marks) What is spin–spin splitting? Explain the (n + 1) rule and coupling constant. Interpret the PMR spectra of ethyl bromide and ethyl acetate.
3. (Short, 4 marks) Why is TMS used as a reference compound in NMR?
4. (Short, 4 marks) Distinguish between shielding and deshielding of protons.
5. (Short, 4 marks) Predict the number of signals, their multiplicity and relative areas in the PMR spectrum of acetaldehyde.

Syllabus topics (RTMNU)

• Concept of active methylene group
• Explanation of acidity and reactivity of methylene hydrogen atoms
• General mechanism of enolate formation and its nucleophilic character
• Factors affecting acidity
• Malonic ester: Preparation and synthetic applications in preparation of monocarboxylic acids (Acetic acid, n-butyric acid, n-valeric acid, Dimethyl acetic acid, 2-methyl butanoic acid), dicarboxylic acids (Succinic acid, Adipic acid), α,β-unsaturated acids (Crotonic acid, Cinnamic acid), β-keto acids (Acetoacetic acid) and heterocyclic compounds (Barbituric acid)
• Acetoacetic ester: Synthesis by Claisen condensation reactions
• Keto-enol tautomerism of acetoacetic ester
• Application of acetoacetic ester in preparation of monocarboxylic acids, dicarboxylic acids, α,β-unsaturated acids, ketones (Acetone, Methyl propyl ketone), diketones (Acetyl acetone, Acetonyl acetone) and heterocyclic compounds (4-methyl uracil, Methyl iso-oxazolone)

Concept of Active Methylene Group, Acidity and Reactivity

An active methylene group is a –CH₂– group placed between two electron-withdrawing groups (C=O, COOR, CN, NO₂). Its hydrogens are unusually acidic and the carbon is very reactive. Examples: diethyl malonate CH₂(COOC₂H₅)₂ (pK_a ≈ 13), ethyl acetoacetate CH₃COCH₂COOC₂H₅ (pK_a ≈ 11), acetylacetone CH₃COCH₂COCH₃ (pK_a ≈ 9), ethyl cyanoacetate.

Why acidic: (1) both groups withdraw electrons by −I and −M effects and weaken the C–H bond; (2) the carbanion formed after losing H⁺ is resonance-stabilised — the negative charge spreads over the carbon and both oxygens (an enolate ion).

General mechanism of enolate formation: a base such as sodium ethoxide removes a proton:

Nucleophilic character: the enolate carbon attacks alkyl halides (alkylation), acyl chlorides (acylation), aldehydes (Knoevenagel) and halogens. A second alkylation is possible because one acidic H remains.

Factors affecting acidity: number and strength of electron-withdrawing groups (ketone C=O > ester C=O, so EAA is more acidic than malonic ester); extent of resonance stabilisation of the anion; alkyl substituents on the carbon decrease acidity (+I effect); solvent and base strength.

Malonic Ester: Preparation

Diethyl malonate is prepared from chloroacetic acid:

Key idea: alkylate the sodio-malonic ester, then hydrolyse to the substituted malonic acid, which loses CO₂ on heating (a gem-dicarboxylic acid decarboxylates easily):

Synthetic Applications of Malonic Ester

Acetoacetic Ester: Synthesis by Claisen Condensation

Ethyl acetoacetate (EAA) is made by the Claisen condensation of two molecules of ethyl acetate in the presence of sodium ethoxide:

Mechanism: (1) ethoxide removes an α-H from ethyl acetate → enolate ⁻CH₂COOEt; (2) the enolate attacks the carbonyl carbon of a second ethyl acetate → tetrahedral intermediate; (3) it expels ethoxide → EAA; (4) EAA (more acidic) is deprotonated by ethoxide to its stable sodio-enolate — this drives the reaction; (5) acidification gives EAA.

Keto–Enol Tautomerism of Acetoacetic Ester

EAA exists as an equilibrium mixture of two forms (about 92% keto and 8% enol at room temperature):

Evidence for keto form: forms a cyanohydrin with HCN, bisulphite compound with NaHSO₃, hydrazone with phenylhydrazine (C=O group). Evidence for enol form: decolourises bromine water (C=C), gives a violet/red colour with neutral FeCl₃ (enolic –OH), liberates H₂ with sodium, reacts with acetyl chloride. The enol is stabilised by conjugation and an intramolecular hydrogen bond (six-membered chelate).

Synthetic Applications of Acetoacetic Ester

Sodio-EAA is alkylated or acylated, then hydrolysed in one of two ways:

Likely exam questions

1. (Long, 8 marks) What is an active methylene group? Explain the acidity of its hydrogens. How is malonic ester prepared? Give its use in the synthesis of n-butyric acid, adipic acid and barbituric acid.
2. (Long, 8 marks) Describe the synthesis of acetoacetic ester by Claisen condensation with mechanism. Explain its keto–enol tautomerism with evidence.
3. (Short, 4 marks) How will you prepare acetylacetone from acetoacetic ester?
4. (Short, 4 marks) Distinguish between ketonic hydrolysis and acid hydrolysis of acetoacetic ester.
5. (Short, 4 marks) Synthesise cinnamic acid from malonic ester (or malonic acid).

Syllabus topics (RTMNU)

• Introduction to lipids, classification
• Oils and fats: classification of oils
• Common fatty acids present in oils and fats
• Omega fatty acids
• Trans fats
• Hydrogenation
• Saponification value, Iodine number
• Biological importance of triglycerides, phospholipids, glycolipids, and steroids (cholesterol)
• Natural fats, edible and industrial oils of vegetable origin
• Glycerides
• Hydrogenation of unsaturated oils
• Definition of Saponification value, Iodine value, Acid value
• Soaps - different types of soaps
• Cleansing action of soap
• Synthetic detergents
• Alkyl and aryl sulfonates

Introduction to Lipids and Classification

Lipids are naturally occurring organic compounds that are insoluble in water but soluble in non-polar solvents (ether, chloroform, benzene); they are esters of fatty acids or substances related to them. Examples: fats, oils, waxes, phospholipids, steroids.

Classification (Bloor):

1. Simple lipids: esters of fatty acids with alcohols — (a) fats and oils (triglycerides: esters of glycerol); (b) waxes (esters of long-chain alcohols, e.g. beeswax).
2. Compound (complex) lipids: contain other groups besides fatty acid and alcohol — phospholipids (lecithin, cephalin), glycolipids (cerebrosides), lipoproteins.
3. Derived lipids: obtained by hydrolysis of the above — fatty acids, glycerol, steroids (cholesterol), fat-soluble vitamins.

Oils and Fats: Classification, Common Fatty Acids, Omega Fatty Acids and Trans Fats

Fats and oils are triglycerides (glycerides) — triesters of glycerol with fatty acids. Fats are solid at room temperature (rich in saturated acids, e.g. ghee, lard); oils are liquid (rich in unsaturated acids, e.g. groundnut, sunflower).

Classification of oils: (1) by source — vegetable (groundnut, coconut, mustard) and animal (fish oil, lard); (2) by use — edible and industrial (linseed, castor); (3) by drying property — drying oils (iodine value > 130, e.g. linseed, tung — form a hard film; used in paints), semi-drying oils (100–130, e.g. cottonseed, soybean), non-drying oils (< 100, e.g. coconut, olive, groundnut).

Omega fatty acids: named by the position of the first double bond counted from the methyl (ω) end. ω-3: α-linolenic acid (flaxseed/alsi), EPA and DHA (fish oil) — good for heart and brain. ω-6: linoleic and arachidonic acids (sunflower, safflower oils). Linoleic and linolenic acids are essential fatty acids — the body cannot make them.

Trans fats: unsaturated fats with a trans C=C (natural fats are mostly cis). They form mainly during partial hydrogenation (vanaspati) and repeated frying. They raise "bad" LDL cholesterol and lower "good" HDL, increasing heart disease risk; FSSAI limits trans fat in oils and fats to 2% (check latest).

Hydrogenation of Unsaturated Oils

Liquid oils are converted into semi-solid fats by adding hydrogen to C=C bonds in the presence of finely divided nickel at about 150–200 °C and a few atmospheres pressure (hardening of oils). Product: vanaspati ghee; it raises melting point and keeping quality.

Saponification Value, Iodine Value and Acid Value

1. Saponification value (SV): the number of milligrams of KOH required to completely saponify 1 g of a fat or oil. It is inversely proportional to the average molar mass of the glycerides: short-chain fats (coconut, about 250–260) have high SV; most oils 185–200. It detects adulteration.
2. Iodine value (IV): the number of grams of iodine absorbed by 100 g of fat or oil. It measures unsaturation; determined by Wijs method (ICl in acetic acid). Higher IV = more unsaturated = more drying.
3. Acid value (AV): the number of milligrams of KOH required to neutralise the free fatty acids in 1 g of fat or oil. A high value shows rancidity (hydrolysis) — poor quality.

Worked numericals:

(1) SV of tristearin (C₅₇H₁₁₀O₆, M = 891.5 g/mol). 1 mol needs 3 mol KOH = 3 × 56.1 = 168.3 g. SV = 168.3 × 1000 ÷ 891.5 = 188.8 mg KOH/g.

(2) IV of triolein (C₅₇H₁₀₄O₆, M = 885.4 g/mol, three C=C). It absorbs 3 I₂ = 3 × 253.8 = 761.4 g per mol. IV = 761.4 × 100 ÷ 885.4 = 86.0.

(3) Acid value: 2.0 g of oil needs 1.5 mL of 0.1 N KOH. KOH used = 1.5 × 0.1 × 56.1 = 8.415 mg. AV = 8.415 ÷ 2.0 = 4.21 mg KOH/g.

Biological Importance of Triglycerides, Phospholipids, Glycolipids and Cholesterol

1. Triglycerides: main energy store (about 9 kcal/g, more than carbohydrates); stored in adipose tissue; insulate the body and cushion organs; carry fat-soluble vitamins A, D, E, K.
2. Phospholipids (lecithin, cephalin): have a polar head and two non-polar tails; form the lipid bilayer of cell membranes; lecithin acts as an emulsifier; part of lipoproteins and lung surfactant.
3. Glycolipids (cerebrosides, gangliosides): found in cell membranes, especially the myelin sheath of nerves; act in cell recognition and as receptors.
4. Cholesterol (a steroid, C₂₇H₄₅OH): controls membrane fluidity; precursor of steroid hormones (cortisol, testosterone, oestrogen), bile acids and vitamin D. Excess in blood leads to atherosclerosis.

Natural Fats and Oils: Edible and Industrial Oils, Glycerides

Edible vegetable oils: groundnut, mustard, soybean, sunflower, coconut, sesame (til), cottonseed, rice bran, palm oil. Industrial oils: linseed (paints, varnishes, linoleum), castor (lubricants, brake fluid, medicine), tung (varnishes), neem (soaps, pesticides). Natural fats are mixtures of mixed glycerides (different fatty acids on one glycerol); simple glycerides have the same acid in all three positions (e.g. tristearin).

Soaps: Types and Cleansing Action

Soaps are sodium or potassium salts of higher fatty acids, made by saponification — boiling fat or oil with NaOH or KOH:

Types: hard soaps (sodium salts; laundry and toilet soaps); soft soaps (potassium salts; shaving creams, liquid soaps); toilet soaps (pure, with perfume and colour); transparent soaps (dissolved in alcohol/glycerol); medicated soaps (with antiseptics like neem or carbolic acid); metallic soaps (Ca, Al salts — used in greases).

Cleansing action: a soap molecule has a long non-polar hydrocarbon tail (hydrophobic, dissolves in grease) and a polar –COO⁻ head (hydrophilic, dissolves in water). In water, soap molecules form micelles: tails point inward into the oily dirt, heads face the water. The grease is broken into tiny droplets surrounded by negative charges, which repel each other and form a stable emulsion that is washed away. Soap also lowers surface tension so water wets the cloth better.

Synthetic Detergents: Alkyl and Aryl Sulphonates

Synthetic detergents are cleansing agents that work like soap but are salts of sulphonic acids or alkyl hydrogen sulphates; their calcium and magnesium salts are soluble, so they work even in hard water and acidic solution.

1. Alkyl sulphates / sulphonates (anionic): e.g. sodium lauryl sulphate C₁₂H₂₅OSO₃Na, made from lauryl alcohol + H₂SO₄, then NaOH; used in shampoos and toothpastes. Alkane sulphonates R–SO₃Na also belong here.
2. Aryl (alkylbenzene) sulphonates (anionic): e.g. sodium dodecylbenzene sulphonate — dodecylbenzene is sulphonated with conc. H₂SO₄ and neutralised with NaOH; the main ingredient of washing powders.
3. Cationic detergents: quaternary ammonium salts, e.g. cetyltrimethylammonium bromide — germicidal, in hair conditioners. Non-ionic: polyethylene glycol esters — in liquid dishwash.

Likely exam questions

1. (Long, 8 marks) Define saponification value, iodine value and acid value and give their significance. Calculate the saponification value of tristearin (M = 891.5).
2. (Long, 8 marks) What are soaps? Describe the types of soaps and explain the cleansing action of soap. How do synthetic detergents differ from soaps?
3. (Short, 4 marks) What are omega fatty acids? Give examples.
4. (Short, 4 marks) What is hydrogenation of oils? Why are trans fats harmful?
5. (Short, 4 marks) Write the biological importance of phospholipids and cholesterol.

Syllabus topics (RTMNU)

• Definition of polymers
• Classification of polymers on the basis of nature, thermal behaviour, and structure
• Reaction mechanism of addition or chain growth polymerisation, free radical
• Ionic addition polymerisation
• Condensation or step growth polymerisation
• Preparation and uses of Polydienes (Buna-S)
• Polyacrylates (Polyacrylonitrile)
• Polyhalo-olefins (PVC)
• Polyesters (terylene)
• Polyamides (Nylon 66, Nylon 6)
• Phenol-formaldehyde resins (Bakelite)
• Urea-formaldehyde resins

Definition of Polymers

Polymers are very large molecules (macromolecules) of high molecular mass made by joining many small repeating units called monomers through covalent bonds. The process is called polymerisation. Example: n CH₂=CH₂ → –(CH₂–CH₂)_n– (polythene). The number of repeating units n is the degree of polymerisation.

Classification of Polymers

1. On the basis of nature (source):

• Natural: from plants and animals — starch, cellulose, proteins, natural rubber.
• Semi-synthetic: chemically modified natural polymers — cellulose acetate (rayon), vulcanised rubber.
• Synthetic: man-made — polythene, PVC, nylon, terylene, Bakelite.

2. On the basis of thermal behaviour:

• Thermoplastics: soften on heating and harden on cooling repeatedly; linear or slightly branched chains with weak intermolecular forces; can be remoulded and recycled — polythene, PVC, polystyrene.
• Thermosetting polymers: on heating they become permanently hard due to extensive cross-linking; cannot be remoulded — Bakelite, urea-formaldehyde resin.

3. On the basis of structure:

• Linear polymers: long straight chains — high-density polythene, PVC.
• Branched-chain polymers: linear chains with side branches — low-density polythene.
• Cross-linked (network) polymers: chains joined by strong covalent bonds in three dimensions — Bakelite, melamine.

Also: by monomers — homopolymers (one monomer, e.g. PVC) and copolymers (two monomers, e.g. Buna-S, nylon 66); by mode of polymerisation — addition and condensation.

Addition (Chain-Growth) Polymerisation: Free Radical Mechanism

In addition polymerisation unsaturated monomers (alkenes, dienes) add to each other repeatedly without loss of any small molecule; the polymer has the same empirical formula as the monomer. It takes place through a chain reaction with three steps. Initiators: benzoyl peroxide, acetyl peroxide, AIBN.

Ionic Addition Polymerisation

1. Cationic polymerisation: initiated by a Lewis acid with a trace of water (BF₃/H₂O, AlCl₃) or a strong protic acid. H⁺ adds to the alkene to give a carbocation, which adds more monomer. Works for monomers with electron-releasing groups — isobutylene (butyl rubber), vinyl ethers, styrene. Termination by loss of a proton or combining with the counter-ion.
2. Anionic polymerisation: initiated by strong bases/nucleophiles — n-butyllithium, NaNH₂, sodium naphthalide. The anion adds to the alkene to form a carbanion that grows. Works for monomers with electron-withdrawing groups — acrylonitrile, methyl methacrylate, styrene. Often there is no natural termination ("living polymers") until water or acid is added.

Condensation (Step-Growth) Polymerisation

In condensation polymerisation, monomers having two (or more) functional groups react step by step with the loss of small molecules such as H₂O, HCl or CH₃OH. Any two species (monomer, dimer, oligomer) can react; molecular mass rises slowly. Examples: nylon 66, terylene, Bakelite.

Preparation and Uses of Important Polymers

1. Buna-S (polydiene; styrene–butadiene rubber, SBR): copolymer of 1,3-butadiene (about 75%) and styrene (about 25%), made by free-radical emulsion polymerisation (earlier with sodium as catalyst, hence "Bu-Na").

Uses: automobile tyres, footwear soles, cable insulation, conveyor belts.

2. Polyacrylonitrile, PAN (polyacrylate): addition polymerisation of acrylonitrile with a peroxide catalyst.

Uses: acrylic fibres (Orlon, Acrilan) as a wool substitute — sweaters, blankets; precursor of carbon fibre.

3. Polyvinyl chloride, PVC (polyhalo-olefin): free-radical polymerisation of vinyl chloride with a peroxide.

Uses: water pipes, raincoats, handbags, floor tiles, electric cable insulation, vinyl sheets.

4. Terylene / Dacron (polyester, PET): condensation of ethylene glycol with terephthalic acid (or dimethyl terephthalate) at about 420–460 K with a catalyst (zinc acetate–antimony trioxide), with loss of water (or methanol).

Uses: crease-resistant fabrics, terycot and terywool blends, sails, seat belts, PET bottles, films.

5. Nylon 66 (polyamide): condensation of hexamethylenediamine (6 C) and adipic acid (6 C). They first form "nylon salt", which is heated at about 553 K under nitrogen.

Uses: textile fibres, stockings, ropes, fishing nets, tyre cords, brush bristles, gears.

6. Nylon 6 (polyamide): made by heating caprolactam with a little water at about 533–543 K; the ring opens (to 6-aminohexanoic acid) and polymerises.

Uses: tyre cords, fabrics, ropes, mountaineering ropes.

7. Phenol–formaldehyde resin (Bakelite): phenol reacts with formaldehyde (acid or base catalyst) to form o- and p-hydroxymethylphenols, which condense (losing water) through –CH₂– bridges. A linear product, novolac, forms first; on heating with more formaldehyde (hexamethylenetetramine), it becomes a hard, infusible, three-dimensional cross-linked Bakelite.

Uses: electrical switches, plugs, handles of cookware, telephone cases, combs, varnish; novolac in paints.

8. Urea–formaldehyde resin: urea condenses with formaldehyde (mild acid or base) to form mono- and dimethylol urea, which further condense with loss of water to a cross-linked thermosetting resin.

Uses: adhesives for plywood and particle board, laminates, electrical fittings, buttons, unbreakable cups and decorative articles.

Likely exam questions

1. (Long, 8 marks) Explain the free-radical mechanism of addition polymerisation. Compare addition and condensation polymerisation.
2. (Long, 8 marks) Give the preparation and uses of nylon 66, terylene and Bakelite.
3. (Short, 4 marks) Distinguish between thermoplastic and thermosetting polymers.
4. (Short, 4 marks) How is Buna-S prepared? Give its uses.
5. (Short, 4 marks) What is anionic polymerisation? Give one example.