Organic Chemistry

1. Purification Methods

For TLC/paper chromatography the retardation factor is \(R_f = \dfrac{\text{distance moved by solute}}{\text{distance moved by solvent front}}\), always between 0 and 1. A higher \(R_f\) means the compound is less adsorbed by the stationary phase.

2. Qualitative Analysis — Lassaigne's Sodium Fusion Test

Fusing the compound with sodium converts covalent N, S and halogens into ionic forms (NaCN, Na₂S, NaX) detectable in the water extract (SFE):

3. Quantitative Analysis

• Carbon & hydrogen: Liebig combustion over CuO; CO₂ absorbed in KOH, H₂O in anhydrous CaCl₂.
• Nitrogen: Dumas method (measure N₂ volume) or Kjeldahl method (back-titrate the liberated NH₃). Kjeldahl fails for N in aromatic rings, nitro, azo and N–N / N–O compounds.
• Halogens & sulphur: Carius method — halogen precipitated as AgX, sulphur as BaSO₄.

Electronic Effects

Four effects govern electron distribution and reactivity in organic molecules:

Hyperconjugation in 3D — In a carbocation the C⁺ is sp² and its 2p orbital is empty. In the ethyl cation a C–H bond of the next carbon lined up with that 2p overlaps it, and its electrons spread into it: this is hyperconjugation. The overlap goes as cos θ, with θ the angle between the C–H bond and the 2p: lined up, one C–H overlaps fully (100%) and the other two half as much (50%); turn the CH₃ by 90° and that C–H lies in the node (0%) while the other two swing to 87%. The three together give the same total at any angle, so what counts is the number of α-H: 3 in CH₃CH₂⁺, 6 in (CH₃)₂CH⁺ and 9 in (CH₃)₃C⁺, which is why 3° > 2° > 1°. Sizes are not to scale.

Reaction Intermediates

Reaction intermediates in 3D — In the carbocation CH₃⁺ the carbon is sp²: its three bonds lie in one plane, 120° apart, and the unhybridised 2p orbital, at right angles to that plane, is empty, so C⁺ has only six electrons round it. In the carbanion CH₃⁻ the carbon is sp³: a lone pair fills the fourth corner of the tetrahedron, so the three bonds make a pyramid (109.5° at the ideal angle) and C⁻ has eight electrons. The methyl radical CH₃• is planar like the cation, with its odd electron in the 2p and seven electrons round C; radicals with bulkier or more electronegative groups can be slightly pyramidal. A carbene, CH₂, has only two bonds and six electrons round C. In singlet CH₂ the carbon is sp², its two non-bonding electrons are paired in the third sp² orbital and the 2p is empty. In triplet CH₂ the same two electrons are unpaired, one in the sp² orbital and one in the 2p, with parallel spins. Both carbenes are drawn at the ideal sp² angle, 120°; the measured H–C–H angles are about 102° (singlet) and 134° (triplet). Orbitals are schematic and sizes are not to scale.

Types of Organic Reactions

Homolytic vs. Heterolytic Fission

Acidity & Basicity in Organic Chemistry

Isomerism

Geometric isomerism and restricted rotation in 3D — In but-2-ene, CH₃–CH=CH–CH₃, the two ends cannot turn about the C=C double bond (133 pm) without breaking its π bond: twisting one end by 90° costs about 262 kJ/mol (ChemPRIME’s calculation for cis-but-2-ene), so cis- and trans-but-2-ene do not interconvert at room temperature and can be separated. In cis-but-2-ene both methyl groups lie on the same side of the double bond (C–C=C–C dihedral 0°); in trans-but-2-ene they lie on opposite sides (dihedral 180°). The C–C single bonds are 154 pm. Geometric isomerism needs both restricted rotation and two different groups on each double-bonded carbon. Each isomer is shown beside its mirror image: a turn lays the image on the original, so neither is chiral (both are optically inactive).

Chirality and CIP R/S assignment in 3D — In butan-2-ol, CH₃–CH(OH)–CH₂–CH₃, C2 is a chiral centre: it carries four different groups, –OH, –C₂H₅, –CH₃ and –H. The Cahn–Ingold–Prelog (CIP) rules rank them by atomic number at the first point of difference: priority 1 is –OH (oxygen, Z = 8); priority 2 is ethyl, whose carbon carries (C, H, H); priority 3 is methyl, whose carbon carries only (H, H, H); priority 4 is –H. Seen with the lowest priority (H) pointing away, 1 → 2 → 3 runs clockwise in (2R)-butan-2-ol and anticlockwise in its mirror image, (2S)-butan-2-ol. The two are non-superimposable mirror images (enantiomers): the best turn lays the image’s C–H and C–OH bonds on the original’s, but then its methyl sits where the ethyl was and its ethyl where the methyl was. R and S describe the arrangement only; whether a compound turns plane-polarised light to the right (+) or the left (−) has to be measured.

Meso compounds and diastereomers in 3D — Tartaric acid, HOOC–CH(OH)–CH(OH)–COOH, has two stereocentres, C2 and C3, carrying the same groups. In meso-tartaric acid (2R, 3S), held eclipsed about C2–C3, an internal plane of symmetry (σ, shaded) reflects the –COOH, –OH and –H on C2 onto those on C3. A turn lays its mirror image on it, so meso-tartaric acid is achiral and optically inactive: its two halves rotate light equally and oppositely (internal compensation). Two stereocentres allow 2² = 4 R/S assignments, but (2R, 3S) and (2S, 3R) are the same meso compound, so tartaric acid has only 3 stereoisomers: the meso form and the optically active pair (2R, 3R) and (2S, 3S), which have no internal mirror plane and are enantiomers. The meso form and either active form are diastereomers: they are not mirror images, they differ in physical properties such as melting point and solubility, and they can be separated by fractional crystallisation.

Fischer and wedge–dash projections in 3D — A Fischer projection draws a stereocentre as a cross. For lactic acid, CH₃–CH(OH)–COOH, C2 sits at the intersection, with the carbon chain vertical and the most oxidised carbon, –COOH, at the top. By convention the horizontal bonds (–OH and –H) point out of the page towards the observer (wedges) and the vertical bonds (–COOH and –CH₃) point into the page away from the observer (dashes); seen from the side, the vertical bonds lean back and the horizontal ones forward. Both views in the figure are the same molecule. Rotating a Fischer projection 180° in the plane keeps the horizontal bonds horizontal and the vertical bonds vertical, so it preserves the configuration; a 90° rotation in the plane swaps horizontal and vertical directions, inverting the stereocentre. To read R/S from a Fischer projection, trace 1 → 2 → 3: if the lowest-priority group (–H) lies on a horizontal bond (pointing towards you), the true configuration is the opposite of the one traced. Here 1 → 2 → 3 runs anticlockwise (apparently S) and H is horizontal, so this lactic acid, the D form, is (R).

Conformations in 3D: staggered vs eclipsed, seen as Newman projections — Turning about a carbon–carbon single bond (154 pm) gives different arrangements in space, called conformations. The figure looks almost straight down the C–C bond, as a Newman projection does: the front carbon is at the centre and the back carbon sits behind the disc. In ethane, CH₃–CH₃, the staggered conformation (dihedral 60°) has each front C–H bond between two back ones and the least torsional strain (relative energy 0.0 kJ/mol); in the eclipsed conformation (dihedral 0°) each front C–H bond covers a back one, and the energy is higher by 12.5 kJ/mol (NCERT, Class XI Hydrocarbons). That barrier is small: at 25 °C it is crossed about 4 × 10¹⁰ times a second (an estimate from the Eyring equation), so the conformations cannot be isolated. In n-butane, CH₃–CH₂–CH₂–CH₃, turning about the central C2–C3 bond gives four key conformations: anti (dihedral 180°, 0.0 kJ/mol, most stable), gauche (dihedral 60°, 3.8 kJ/mol above anti, from the two methyl groups crowding each other), partially eclipsed (dihedral 120°, 16.0 kJ/mol: two CH₃/H eclipsings at 6.0 and one H/H at 4.0) and fully eclipsed (dihedral 0°, 19.0 kJ/mol: CH₃/CH₃ at 11.0 and two H/H at 4.0). The interaction energies are McMurry’s (Organic Chemistry, Table 3.5); NCERT gives ethane’s barrier only. The stability order is anti > gauche > partially eclipsed > fully eclipsed.

IUPAC Nomenclature Rules

1. Choose the longest carbon chain containing the principal functional group — this is the parent chain.
2. Number from the end nearest the principal functional group (or nearest branch if no FG).
3. Principal group suffix (highest priority): –COOH (–oic acid) > –CHO (–al) > C=O (–one) > –OH (–ol) > –NH₂ (–amine).
4. Substituents listed alphabetically as prefixes (ignore multiplying prefixes di/tri in alphabetisation).
5. Multiple bonds: –ene (alkene), –yne (alkyne); get lowest locants.

Alkanes — Nomenclature and Free Radical Halogenation

• General formula CₙH₂ₙ₊₂ (acyclic). Sp³ hybridised, tetrahedral. Only σ bonds.
• Free radical halogenation mechanism: Initiation (X₂ → 2X•), Propagation (X• + RH → HX + R•; R• + X₂ → RX + X•), Termination (two radicals combine).
• Selectivity (BDE of C–H): 3° > 2° > 1° C–H bonds — 3° radicals most stable. Cl• is less selective (Cl₂ reactive); Br• is highly selective (Br₂ more stable, less reactive).
• Anti-Markovnikov product in free radical addition of HBr to alkenes (peroxide/ROOR condition): Br• adds to less substituted C.

Alkenes — Addition Reactions

Anti addition of \(\text{Br}_2\) through a bromonium ion in 3D — Bromine adds to an alkene in two steps. Br₂ approaches one face of the π bond and leaves a bromonium ion: one Br⁺ bonded to both carbons, a three-membered ring on that face. Br⁻ can then reach a carbon only from the other face, straight behind its C–Br bond, so the two Br atoms end up on opposite faces: anti addition. The geometry decides the product. From cis-but-2-ene the product is (2R,3R)-2,3-dibromobutane when Br⁻ opens the ring at C2, and its mirror image, (2S,3S), when it opens it at C3; both are equally likely, so the product is racemic. From trans-but-2-ene either route gives (2R,3S)-2,3-dibromobutane, a meso compound: as formed, with the two Br atoms anti, it has a centre of symmetry. The fading of bromine’s reddish-orange colour in CCl₄ is the test for an alkene (NCERT, Class XI Hydrocarbons).

Alkynes — Key Reactions

• Terminal alkynes: Acidic C≡C–H (\(pK_a \sim 25\)). React with NaNH₂, Na metal, AgNO₃ → Ag salt (white ppt), CuCl → Cu salt (red ppt) — diagnostic tests for terminal alkynes.
• Hydration: H₂O/H₂SO₄/HgSO₄ (Markovnikov addition) → enol → tautomerises to ketone. Exception: CH≡CH → ethanal (CH₃CHO, anti-Markovnikov product if Wacker).
• HX addition: Two additions possible (Markovnikov each time) → geminal dihalide (1,1-dihalide).
• Lindlar catalyst: H₂/Pd-BaSO₄ (poisoned) → syn addition → cis alkene. Na/NH₃(l): anti addition → trans alkene (Birch-like).

Syn and anti additions in 3D — But-2-yne, CH₃–C≡C–CH₃, is straight (sp carbons, 180°; C≡C 120 pm). Adding one H₂ can give either but-2-ene, depending on how the two H atoms arrive. Over Lindlar’s catalyst (palladium on charcoal partly deactivated with sulphur compounds or quinoline), both H atoms come from the metal surface onto the same face: syn addition, giving cis-but-2-ene, with the two new H atoms on the same side (H–C=C–H 0°). Sodium in liquid ammonia adds one electron and one H⁺ at a time, and the intermediate takes the trans shape: anti addition, giving trans-but-2-ene (H–C=C–H 180°) (NCERT, Class XI Hydrocarbons). Additions that deliver both parts together are syn for the same reason: a peroxyacid adds one O atom to one face of cis-but-2-ene, so the methyl groups stay cis in cis-2,3-dimethyloxirane, a meso compound (2S,3R); hydroboration likewise adds H and B to one face.

Ethane, ethene and ethyne in 3D — In ethane each carbon is sp³, its four σ bonds pointing to the corners of a tetrahedron: H–C–H is 109.5° and the C–C single bond is 154 pm (drawn staggered). In ethene each carbon is sp²: three σ bonds 120° apart in one plane, and all six atoms lie in that plane; the C=C double bond, σ + π, is 133 pm. In ethyne each carbon is sp: two σ bonds 180° apart, so all four atoms lie on one line; the C≡C triple bond, σ + 2π, is 120 pm. Ethane has 7 σ bonds, ethene 5 σ and 1 π, ethyne 3 σ and 2 π. The angles come from the hybrids, \(\cos\theta = -1/n\) for spⁿ; the C–C lengths are NCERT’s and are drawn to scale.

Arenes — Aromaticity and EAS

• Hückel rule: Aromatic if cyclic, planar, fully conjugated, with (4n+2) π electrons.
  Benzene: 6π (n=1). Naphthalene: 10π. Pyridine: 6π (N sp², lone pair not in π system). Pyrrole: 6π (N sp², its lone pair in the 2p and IN the π system). Cyclobutadiene: 4π (anti-aromatic).
• EAS mechanism: Electrophile (E⁺) attacks benzene ring → arenium (Wheland) intermediate → deprotonation restores aromaticity.

Benzene’s π cloud in 3D — Benzene’s six carbons are sp² and the ring is flat (C–C–C 120°, every C–C 139 pm). Each carbon keeps one electron in a 2p orbital at right angles to the ring, and each 2p overlaps both its neighbours side by side. In the lowest π orbital all six combine in phase: a ring of electron density above the plane and one below, with the plane itself a node. The six π electrons exactly fill the three bonding levels (Hückel levels 2, 1 and 1, in units of β), which is the 4n + 2 rule with n = 1: benzene is aromatic. Every C–C has the same π bond order, 0.67, which is why all six bonds are the same length. Surfaces enclose 90% of the probability and are drawn to scale.

Pyridine, pyrrole and cyclobutadiene in 3D — Every ring atom is sp², and the 2p orbital each holds at right angles to the ring brings its π electrons. In pyridine each atom gives one: 6 π electrons, aromatic, and nitrogen’s lone pair sits in an sp² orbital in the plane of the ring, outside the π system and free to take H⁺. In pyrrole the four carbons give one each and nitrogen gives its lone pair, held in its 2p: again 6 π electrons, aromatic, with the N–H in the plane. Cyclobutadiene has 4 π electrons, 4n with n = 1: Hückel’s levels leave two of them unpaired in two equal non-bonding levels, so it is anti-aromatic and very unstable. Orbitals are drawn as polar plots, not to scale.

Directing Effects in EAS

Haloalkanes and Haloarenes

• Nature of the C–X bond: polar (halogen more electronegative than carbon), so the carbon is electrophilic and open to nucleophilic attack. Bond strength falls C–F > C–Cl > C–Br > C–I, so iodides are the most reactive.
• Substitution mechanisms: SN1 — two steps via a carbocation, favoured by 3° halides and polar protic solvents, gives racemisation; SN2 — one step, backside attack, favoured by 1° halides, gives inversion (Walden inversion).
• Haloarenes are far less reactive to nucleophilic substitution than haloalkanes (partial double-bond character from resonance + sp² carbon).
• Uses & environmental effects: chloroform (CHCl₃) — solvent/former anaesthetic, oxidises in air/light to poisonous phosgene; iodoform (CHI₃) — antiseptic; freons (CFCs) — refrigerants that deplete the ozone layer; DDT — a persistent insecticide that bioaccumulates and is now largely banned.

\(\text{S}_\text{N}2\): backside attack and Walden inversion in 3D — In an \(\text{S}_\text{N}2\) reaction the nucleophile bonds as the leaving group leaves, in one step, so the rate depends on both: rate = k[RBr][OH⁻] (NCERT, Class XII Haloalkanes and Haloarenes). OH⁻ attacks the carbon from the side opposite the C–Br bond: in the transition state O, C2 and Br lie on one straight line (180°), and the other three groups, CH₃, C₂H₅ and H, are flat, 120° apart. As Br⁻ leaves, those three groups turn inside out like an umbrella in the wind: before, each leans 70.5° from the line of attack; after, 109.5°. This is Walden inversion. Here (2R)-2-bromobutane gives (2S)-butan-2-ol: OH takes Br’s place as the highest-priority group, so the R/S letter changes with the shape. With other groups the letter can stay the same even though the shape inverts.

\(\text{S}_\text{N}1\): the flat carbocation and racemisation in 3D — An \(\text{S}_\text{N}1\) reaction goes in two steps. First the C–Br bond breaks on its own, slowly, so the rate depends only on the haloalkane: rate = k[RBr]. That leaves a carbocation whose carbon is sp²: its three groups lie flat, 120° apart, with the empty 2p orbital at right angles, one lobe on each face. In the fast second step the nucleophile, here water, can bond on either face. On the face Br left from it gives the starting arrangement (retention); on the other face, the inverted one. From (2R)-2-bromobutane these are (2R)- and (2S)-butan-2-ol, mirror images formed in equal amounts, so the product is racemic, (±)-butan-2-ol, and optically inactive. This is NCERT’s example: hydrolysis of optically active 2-bromobutane gives (±)-butan-2-ol (Class XII, Haloalkanes and Haloarenes).

E2 elimination and Saytzeff's rule in 3D — Heating a haloalkane with alcoholic KOH removes HBr in one step (E2): the base takes a β-hydrogen as the C–Br bond breaks and the new π bond forms. The H and the Br must be anti-periplanar: in one plane, on opposite sides of the C–C bond (dihedral angle 180°), so that the breaking \(\sigma_{\text{C–H}}\) orbital lines up with the \(\sigma^*_{\text{C–Br}}\) orbital and the two overlap to form the \(\pi\) bond. 2-Bromopentane, CH₃–CH(Br)–CH₂–CH₂–CH₃, has two β-carbons, and the figure holds it in a conformation in which each has an H anti to Br. Losing the H on C3 gives pent-2-ene, CH₃–CH=CH–CH₂–CH₃, a disubstituted alkene and the major product (81%); losing an H on C1 gives pent-1-ene, CH₂=CH–CH₂–CH₂–CH₃, monosubstituted and minor (19%) (NCERT, Class XII Haloalkanes and Haloarenes). This is Saytzeff’s (Zaitsev’s) rule: the H goes from the β-carbon with fewer hydrogens (C3 has 2, C1 has 3), and the alkene with more alkyl groups on its double bond predominates, because more \(\alpha\)-hydrogens (5 in pent-2-ene, 2 in pent-1-ene) give more hyperconjugation and a lower-energy transition state.

Alcohols

• Classification: 1° (–CH₂OH), 2° (–CHOH), 3° (–COH). Acidity: H₂O > ROH (alkyl groups donate electrons, destabilise RO⁻).
• Lucas test: ZnCl₂ + conc. HCl. 3° → immediate turbidity; 2° → turbidity in 5 min; 1° → no turbidity at room temp.
• Oxidation: 1° → aldehyde (PCC/CrO₃/pyridine) → carboxylic acid (KMnO₄/K₂Cr₂O₇). 2° → ketone. 3° → no oxidation.
• Dehydration: Conc. H₂SO₄ at 170°C → alkene (Saytzeff's rule: more substituted alkene preferred); at 130°C → ether.
• Esterification: RCOOH + R′OH ⇌ RCOOR′ + H₂O (Fischer esterification; acid catalyst; reversible).

Phenols

• Acidity: phenol (\(pK_a \approx 10\)) is more acidic than alcohols because the phenoxide ion is resonance-stabilised. Electron-withdrawing groups (–NO₂, especially ortho/para) increase acidity; electron-donating groups decrease it.
• Electrophilic substitution: –OH is ortho/para-directing and activating — halogenation (Br₂/H₂O → 2,4,6-tribromophenol), nitration and sulphonation occur readily.
• Reimer–Tiemann reaction: phenol + CHCl₃ + NaOH → ortho-hydroxybenzaldehyde (salicylaldehyde), via a dichlorocarbene intermediate.
• Kolbe's reaction: sodium phenoxide + CO₂ (under pressure) → sodium salicylate → salicylic acid (used to make aspirin).

Aldehydes and Ketones

• Nucleophilic addition to C=O: Nu attacks electrophilic C. Aldehyde more reactive than ketone (less steric hindrance + more electrophilic C).
• Tollens' test: Ag(NH₃)₂OH → silver mirror. Positive for aldehydes ONLY (not ketones). Formic acid (HCOOH) and glucosealso positive.
• Fehling's test: Cu²⁺ (blue) → Cu₂O (red ppt). Positive for aliphatic aldehydes and reducing sugars. Negative for aromatic aldehydes and ketones.
• Iodoform test: I₂/NaOH. Positive for: CH₃CHO, CH₃COR, CH₃CH(OH)R — all have CH₃CO– or CH₃CHOH– group. Yellow CHI₃ ppt (triiodomethane, mp 119°C).
• Aldol condensation: Base + aldehyde/ketone having α-H → β-hydroxy carbonyl compound → dehydration → α,β-unsaturated compound.
• Cannizzaro reaction: Aldehydes WITHOUT α-H + conc. NaOH → disproportionation (one → acid, one → alcohol). E.g., 2HCHO → CH₃OH + HCOO⁻.
• Clemmensen reduction: C=O → CH₂ (Zn–Hg/HCl). For acid-sensitive substrates.
• Wolff–Kishner reduction: C=O → CH₂ (NH₂NH₂/KOH/ethylene glycol, heat). For base-sensitive substrates.

Nucleophilic addition to \(\text{C}=\text{O}\): the Bürgi–Dunitz angle in 3D — The carbonyl carbon of an aldehyde is flat: in ethanal, CH₃CHO, the O, CH₃ and H around it are 120° apart in one plane, and the polar C=O bond leaves the carbon electron-poor (NCERT, Class XII Aldehydes, Ketones and Carboxylic Acids). A nucleophile such as CN⁻ attacks it from above or below that plane, but not straight down: it comes in at about 107° to the C=O bond, tilted away from the oxygen, where it overlaps best with the empty \(\pi^*\) orbital of C=O and keeps clear of oxygen’s electrons. Bürgi and Dunitz found this angle in crystal structures (105 ± 5°) and by calculation (about 107°). As CN⁻ bonds, the carbon becomes sp³: the O (now O⁻), CH₃ and H fold away from the incoming group to the tetrahedral angle, 109.5°, and CN stays on the face it came from. Adding H⁺ to O⁻ gives the cyanohydrin, CH₃CH(OH)CN.

Carboxylic Acids and Derivatives

• Acidity order: RCOOH > carbonic acid > phenol > water > alcohol (inductive effects). Electron-withdrawing groups increase acidity.
• Reactivity of derivatives: Acid chloride > anhydride > ester > amide (decreasing leaving group ability).
• Hofmann bromamide degradation: RCONH₂ + Br₂/KOH → RNH₂. Product has ONE LESS carbon than starting acid. Used to prepare primary amines.
• Hell–Volhard–Zelinsky: RCOOH + Br₂/P → α-bromoacid. Only at α position (via acid enolisation).

Amines

• Basicity order in solution: 2° > 1° > 3° > ArNH₂. (3° has no H for solvation; aromatic amine has lone pair delocalised.)
• Gabriel synthesis: Phthalimide + RX → N-alkylphthalimide → hydrolysis → 1° amine (pure, no 2°/3° contamination).
• Carbylamine test: 1° amines + CHCl₃ + KOH → isocyanide (R–NC, foul smell). Negative for 2° and 3° amines.
• Diazonium salts (ArN₂⁺Cl⁻): ArNH₂ + NaNO₂/HCl (0–5°C) → ArN₂⁺Cl⁻. Reactions: Sandmeyer (Cl, Br, CN), Balz–Schiemann (F), reduction (N=N coupling → azo dyes).
• Coupling reaction: ArN₂⁺ + phenol/amine → azo dye (orange/red colour). Occurs at pH 5–7.

Grignard Reagent

• RMgX (in dry ether). Strong nucleophile and base. Reacts with C=O, C≡N, CO₂, esters, epoxides.
• HCHO + RMgX → 1° alcohol (after H₃O⁺). RCHO + R′MgX → 2° alcohol. R₂CO + R′MgX → 3° alcohol. CO₂ + RMgX → RCOOH.

Carbohydrates

• Classification: Monosaccharides (cannot hydrolyse), disaccharides (hydrolyse to 2 monosaccharides), polysaccharides (many units).
• Glucose (C₆H₁₂O₆): Aldohexose. Open chain: CHO–(CHOH)₄–CH₂OH. Cyclic: α-D-glucopyranose (OH at C1 axial) and β-D-glucopyranose (OH at C1 equatorial) — anomers. Undergoes mutarotation in solution.
• Fructose: Ketohexose. Sweetest sugar. Cyclic form is furanose (5-membered ring).

Glucose: the pyranose chair, α and β — The six-membered ring of glucopyranose, five carbons and the ring O, is puckered into a chair: in the ideal chair drawn here its ring torsions are 60°, alternating in sign all the way round. Each ring carbon has one bond along the ring’s axis (axial) and one pointing out round the ring (equatorial). In β-D-glucopyranose every group, the OH on C1, C2, C3 and C4 and the CH₂OH on C5, is equatorial, and every H on the ring is axial. α-D-glucopyranose differs only at C1: its OH is axial, on the face opposite the CH₂OH. The two interconvert through the open chain. The ring opens to the aldehyde, C1 becomes flat (sp²), and the O on C5 can add to either face of the C=O: turning the CHO group 180° about the C1–C2 bond swaps the faces, so the ring closes to α or to β. This is mutarotation: in water α ([α]D +112.2°) and β (+18.7°) each change to +52.7°, which puts the equilibrium at 36% α and 64% β, β being favoured because all its groups are equatorial. The chair is drawn ideal, with equal ring bonds and ring angles of 109.5°; H atoms on O and on C6 are not shown.

• Reducing sugar: Has free anomeric –OH (hemiacetal/hemiketal) → can reduce Tollens/Fehling → glucose, fructose, maltose, lactose. Non-reducing: sucrose, trehalose.
• Starch: Amylose (linear, α-1,4) + Amylopectin (branched, α-1,4 + α-1,6 at branches). Gives blue-black colour with I₂.
• Cellulose: β-1,4 glucose units (humans lack β-glucosidase → indigestible). Most abundant organic polymer on Earth.

Starch coils, cellulose lies flat: α-1,4 against β-1,4 — Both are chains of glucose joined C1 to C4; only the link differs. In amylose (15–20% of starch) the α-1,4 link leaves C1 below the ring, so each glucose sits turned 60° from the last and the chain coils into a left-handed helix of 6 glucose units a turn, every ring facing the same way out. I₂ fits in the channel down the middle of the coil, which gives the blue-black colour of the iodine test. Amylopectin (80–85% of starch) is made of the same α-1,4 chains, branched by α-1,6 links from C1 of the branch to C6 of a glucose in the chain, about once every 24–30 glucose units. In cellulose the β-1,4 link leaves C1 in the plane of the ring, so each glucose is turned 180° from the last: every other ring is flipped over and the chain runs straight and flat. The flat chains lie side by side and hydrogen-bond into sheets, between the OH groups at C3 and C6 of neighbouring chains; the sheets stack into strong, insoluble fibres, and humans have no enzyme for the β links. The rings are drawn flat, with the top face blue and the bottom face green: in the coil every ring has its blue face outwards, so the green seen through the coil is the inside of the rings at the back, while along each cellulose chain blue and green alternate.

Proteins and Amino Acids

• 20 naturally occurring α-amino acids. Each has H₂N–CH(R)–COOH. At physiological pH they exist as zwitterions: ⁺H₃N–CH(R)–COO⁻.
• Peptide bond: –CO–NH– formed by condensation of –COOH of one amino acid with –NH₂ of another (water lost). Peptide bond is planar (partial double bond character due to resonance).
• Protein structure levels:
  1° (primary): amino acid sequence.
  2° (secondary): α-helix and β-sheet (H-bonding between C=O and N–H).
  3° (tertiary): 3D folding (disulfide bridges, H-bonds, hydrophobic interactions).
  4° (quaternary): multiple polypeptide subunits (e.g., haemoglobin = 4 subunits).
• Denaturation: Disruption of 2°/3°/4° structure (not peptide bonds). Caused by heat, pH change, organic solvents, heavy metals. Reversible (renaturation) or irreversible.
• Enzymes: Biological catalysts (protein). Lock-and-key model vs induced fit. Specific: active site complementary to substrate.

The zwitterion and the peptide bond in 3D — At physiological pH an α-amino acid is a zwitterion, H₃N⁺–CH(R)–COO⁻: +1 on the N and −1 shared by the two O, net 0. In L-alanine (R = CH₃), seen with the H on the α-carbon towards you, CO, R and N run clockwise (the CORN rule): that is L. When two alanines join, the C=O of one and the N–H of the next form the peptide group, and its six atoms, Cα, C, O, N, H and Cα, lie in one plane. Its C–N bond, 133 pm, is shorter than the N–Cα single bond, 146 pm: resonance gives it partial double-bond character, so it does not turn, and the two α-carbons sit on opposite sides of it (trans, ω = 180°). The chain turns only about the N–Cα (φ) and Cα–C (ψ) bonds: turning ψ and φ from the β-sheet’s values to the α-helix’s, −47° and −57°, leaves every peptide group flat.

Secondary structure: the α-helix and the β-pleated sheet — In the α-helix the polypeptide chain coils into a right-handed helix of 3.6 amino-acid residues a turn with a pitch of 0.54 nm, so each residue rises 0.54 ÷ 3.6 = 0.15 nm and turns 100°. The C=O of each residue is hydrogen-bonded to the N–H of the residue four places on (residue i to residue i + 4): the bonds run along the axis from one turn to the next, all within one chain, and the side chains (R) point outwards. In the β-pleated sheet the chains are stretched out almost fully, about 0.35 nm a residue, and lie side by side, here running in opposite directions (antiparallel). Hydrogen bonds between C=O and N–H join neighbouring chains, each chain zigzags into pleats, and the side chains point alternately to either side of the sheet.

Nucleic Acids

• DNA: deoxyribonucleic acid. Double helix (Watson–Crick). Base pairing: A–T (2 H-bonds), G–C (3 H-bonds). Deoxyribose sugar + phosphate backbone.
• RNA: Ribonucleic acid. Single-stranded (mostly). Uracil instead of thymine. A–U pairing. Types: mRNA, tRNA, rRNA.
• Nucleotide = nitrogenous base + pentose sugar + phosphate. Nucleoside = base + sugar (no phosphate).
• Purine bases: Adenine (A), Guanine (G). Pyrimidine bases: Cytosine (C), Thymine (T, in DNA), Uracil (U, in RNA).

Vitamins and Hormones

Fat-soluble: A, D, E, K (mnemonic: ADEK). Water-soluble: B-complex and C.

Polymers

Natural rubber, gutta-percha and Bakelite in 3D — Natural rubber is cis-1,4-polyisoprene, –[CH₂–C(CH₃)=CH–CH₂]ₙ–: at every C=C the chain’s two CH₂ groups are on the same side (torsion 0°), so the chain turns back on itself and coils. Gutta-percha is the trans polymer (torsion 180°), and its chain runs straight. The two chains are drawn with the same turns about their single bonds; only the C=C differs. Coiled cis chains cannot pack closely and the forces between them are weak, so rubber is elastic; straight trans chains pack closely, so gutta-percha is hard and not elastic. Bakelite, from phenol and formaldehyde, is thermosetting: CH₂ bridges join each phenol ring to others at its ortho and para positions, branching in three directions, so the whole solid becomes one cross-linked network that cannot be melted again. The Bakelite piece is schematic; H atoms are not shown.