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Organic Chemistry 1 Study Guide

Rules, trends, reaction tables and worked examples for a first-semester university organic chemistry course.

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Abbreviations: Nu = nucleophile · LG = leaving group · R = alkyl · X = halogen · Δ = heat · hν = light · equiv = equivalents · cat. = catalytic · Ts/Ms/Tf = tosyl/mesyl/triflyl (sulfonate LGs) · DMS = (CH₃)₂S · NMO = N-methylmorpholine N-oxide (reoxidant) · NBS = N-bromosuccinimide · DBU/DBN = bulky amidine bases.

≈ marks approximate textbook values; books differ slightly, so use your instructor’s numbers on exams.

1 Structure and bonding

Lewis structures and formal charge

  • Formal charge = valence electrons − nonbonding electrons − bonds. Formal charges add up to the overall charge.
  • C, N, O and F never exceed an octet. In skeletal structures each carbon carries implied H up to 4 bonds; lone pairs are often omitted.
Bonding patterns and formal charge
Atom+10−1
C3 bonds, no lone pair (carbocation)4 bonds3 bonds + 1 lone pair (carbanion)
N4 bonds3 bonds + 1 lone pair2 bonds + 2 lone pairs
O3 bonds + 1 lone pair2 bonds + 2 lone pairs1 bond + 3 lone pairs
Cl, Br, I2 bonds + 2 lone pairs1 bond + 3 lone pairs4 lone pairs (halide)

Hybridization and geometry

Steric number = σ bonds + lone pairs. Single bond = 1 σ; double = 1 σ + 1 π; triple = 1 σ + 2 π.

Steric number, hybridization and shape
Steric no.Hybrid, geometryExamples
4sp³, tetrahedral, 109.5°CH₄; NH₃ pyramidal (≈107°); H₂O bent (≈104.5°)
3sp², trigonal planar, 120°C=C, C=O, carbocation C⁺
2sp, linear, 180°C≡C, C≡N, the C of CO₂

A lone pair next to a π bond is usually delocalized in a p orbital, so that atom is sp² (e.g. the N of an amide).

Resonance

  • Move only π electrons and lone pairs. Never move atoms, break a σ bond, exceed an octet on C/N/O, or change the overall charge.
  • Patterns: lone pair next to a π bond; + charge next to a π bond (allylic cation; allylic = on the sp³ carbon next to a C=C, benzylic = next to a benzene ring); lone pair next to a + charge; polar π bond (C=O ↔ C⁺–O⁻); alternating π bonds in a ring.
  • Contributors are joined by ↔ (not ⇌); the real molecule is the hybrid. Equivalent contributors give extra stability (both C–O bonds of a carboxylate are the same length).

Major contributor (criteria in order):

  1. Most atoms with full octets.
  2. Fewest formal charges.
  3. Negative charge on the more electronegative atom (positive on the less).

Example: in CH₃–O–CH₂⁺ ↔ CH₃–O⁺=CH₂, the second form is major: every atom has an octet (rule 1), even with + on O.

Intermolecular forces (strongest first)

  1. Ion–dipole: ion + polar molecule (Na⁺ in water).
  2. Hydrogen bonding: H on N, O or F (donor) to a lone pair on N, O or F (acceptor).
  3. Dipole–dipole: permanent dipoles (acetone, CH₃Cl).
  4. London dispersion: all molecules; grows with surface area and polarizability.

Ethanol (H-bond donor, bp ≈78 °C) vs dimethyl ether (same formula, bp ≈−24 °C). Longer chains raise bp; branching lowers it. Like dissolves like: water solubility of alcohols falls as the carbon chain grows.

1°, 2°, 3° (primary, secondary, tertiary): a carbon bonded to one, two or three other carbons. An alkyl halide or alcohol takes the degree of the carbon bearing –X or –OH; for amines the degree counts the carbons on N instead.

Practice formal charge and bonding, arrow by arrow →

2 Acids and bases

  • Brønsted acid donates H⁺, base accepts H⁺. Lewis acid accepts an electron pair, base donates one.
  • Lower pKa = stronger acid = weaker conjugate base. Each pKa unit is a factor of 10 in Ka.
Approximate pKa values (sources differ by about ±1)
Acid → conjugate basepKa ≈
HI → I⁻−10
HBr → Br⁻−9
HCl → Cl⁻−7
H₂SO₄ → HSO₄⁻−3 (some tables −9)
ROH₂⁺ → ROH (protonated alcohol)−2
H₃O⁺ → H₂O−1.7
RCOOH → RCOO⁻ (acetic acid)4.8
NH₄⁺ → NH₃9.2
PhOH → PhO⁻ (phenol)10
R₃NH⁺ → R₃N (alkylammonium)10–11
H₂O → HO⁻15.7
ROH → RO⁻ (ethanol; t-BuOH)16; 18
Ketone α-C–H → enolate19–20
RC≡CH → RC≡C⁻ (acetylide)25
H₂ → H⁻ (NaH); (i-Pr)₂NH → LDA; NH₃ → NH₂⁻35; 36; 38
Alkene C–H; alkane C–H44; 50

ARIO: what stabilizes the conjugate base

More stable A⁻ = stronger acid. Usual order of importance (when factors disagree, trust measured pKa values):

  1. Atom. Across a row, electronegativity: CH₄ < NH₃ < H₂O < HF. Down a group, size wins over electronegativity: HF < HCl < HBr < HI (the large, polarizable I⁻ spreads the charge); likewise thiols RSH (≈10) are more acidic than alcohols.
  2. Resonance. Delocalized charge: acetic acid (≈4.8) vs ethanol (≈16).
  3. Induction. Nearby electron-withdrawing groups, fading with distance: ClCH₂COOH (≈2.9) vs CH₃COOH (≈4.8).
  4. Orbital. More s-character holds the lone pair closer: sp C–H (≈25) > sp² (≈44) > sp³ (≈50) in acidity.

Equilibrium direction

The equilibrium favors the side with the weaker acid (higher pKa), which is also the weaker-base side. log K ≈ pKa(acid formed) − pKa(acid consumed).

Example: HC≡CH + NH₂⁻ ⇌ HC≡C⁻ + NH₃. Acid consumed HC≡CH (≈25), acid formed NH₃ (≈38): log K ≈ 38 − 25 = 13, so it lies right. With HO⁻ the acid formed is H₂O (≈15.7): log K ≈ −9, so NaOH can’t deprotonate an alkyne.

Curved arrows for proton transfer

Two arrows: (1) base lone pair → H; (2) H–A bond → A. For CH₃COOH + HO⁻ → CH₃COO⁻ + H₂O: HO⁻ lone pair → acidic H, and O–H bond → carboxylate O. Never start an arrow at H⁺ (it has no electrons).

Practice acid–base reasoning with feedback →

3 Functional groups and IUPAC naming

Functional group priority for naming (highest first)
GroupSuffixPrefix
Carboxylic acid RCOOH-oic acidcarboxy-
Ester RCOOR′alkyl -oate—
Amide RCONH₂-amide—
Nitrile RC≡N-nitrilecyano-
Aldehyde RCHO-aloxo-, formyl-
Ketone RCOR′-oneoxo-
Alcohol ROH-olhydroxy-
Amine RNH₂-amineamino-
Alkene, alkyne-ene, -yne(in parent name)
Halide, ether, nitro—halo- (chloro- …), alkoxy-, nitro-

Naming steps

  1. The highest-priority group gives the suffix.
  2. Parent chain: the longest chain containing that group. Most Ochem 1 textbooks also make it include the C=C/C≡C; the 2013 IUPAC rules prefer chain length, so follow your course.
  3. Number for lowest locants, in order: (a) the suffix group; (b) C=C/C≡C (on an ene/yne tie, the double bond gets the lower number); (c) all substituents at the first point of difference; (d) alphabetical order.
  4. Alphabetize substituents, ignoring di-, tri-, sec- and tert-, but not iso (isopropyl files under “i”).
  5. Assemble: stereodescriptors (in locant order, in parentheses) + substituents + parent + suffix: (2E,4R)-4-chloropent-2-ene; (R)-butan-2-ol, older style (R)-2-butanol.

Rings: the carbon bearing the suffix group is C1 (3-methylcyclohexan-1-ol); in a cycloalkene the C=C carbons are C1 and C2. Roots C1–C10: meth, eth, prop, but, pent, hex, hept, oct, non, dec.

Practice functional groups →

IUPAC naming rules with worked examples

4 Conformations

Newman projections

  • Looking down one C–C bond: front carbon = where three bonds meet, back carbon = circle. Staggered (60°) is lower in energy than eclipsed (0°).
  • Torsional strain comes from eclipsed bonds; steric strain from crowded groups (gauche, eclipsed).
  • Ethane: eclipsed lies ≈12 kJ/mol (≈2.9 kcal/mol) above staggered, ≈4 kJ/mol per H/H eclipsing.
Butane about C2–C3 (approximate energy above anti)
Conformation (CH₃/CH₃ dihedral)Energy ≈
Anti, staggered (180°)0, lowest
Gauche, staggered (60°)3.8 kJ/mol (0.9 kcal/mol)
Eclipsed, CH₃ over H (120°)16 kJ/mol (3.8 kcal/mol)
Totally eclipsed, CH₃ over CH₃ (0°)19 kJ/mol (4.5 kcal/mol), highest

Ring strain: cyclopropane > cyclobutane > cyclopentane > cyclohexane (≈0 in the chair).

Cyclohexane chairs

  • Each carbon has one axial bond (parallel to the ring axis, alternating up/down) and one equatorial bond (pointing outward).
  • Ring flip: axial ↔ equatorial for every group, but up stays up (a wedged group stays on the top face).
  • Groups prefer equatorial to avoid 1,3-diaxial interactions (methylcyclohexane ≈95% equatorial at 25 °C). The best chair puts the largest groups equatorial; A-values are roughly additive, and t-Bu effectively locks the ring.
Approximate A-values (cost of axial vs equatorial)
GroupkJ/mol ≈kcal/mol ≈
–Cl, –Br20.4–0.5
–OH (solvent-dependent)2.5–40.6–0.9
–CH₃7.11.7
–CH(CH₃)₂9.22.2
–C(CH₃)₃≈20≈4.9

cis/trans on rings

cis = same face (both wedges or both dashes); trans = opposite faces. A ring flip never converts cis into trans: they are diastereomers.

Disubstituted cyclohexanes: chair options (a = axial, e = equatorial)
PatterncistransMore stable
1,2-a,e ↔ e,ae,e ↔ a,atrans
1,3-e,e ↔ a,aa,e ↔ e,acis
1,4-a,e ↔ e,ae,e ↔ a,atrans

Practice conformations and chair flips →

5 Stereochemistry

CIP priority rules

  1. Higher atomic number of the attached atom wins: I > Br > Cl > S > F > O > N > C > H. Isotopes: higher mass wins (D > H).
  2. Tie: list the three atoms on each tied atom (highest first) and compare pair by pair; the first point of difference decides. Move outward one sphere at a time.
  3. Multiple bonds count as duplicated atoms: C=O counts as C bonded to (O, O); C≡C as C bonded to (C, C, C).

Example: –CH₂OH (O, H, H) outranks –C(CH₃)₃ (C, C, C): O beats C at the first comparison.

Assigning R/S

  1. Rank groups 1–4 and point group 4 away from you (dash).
  2. Trace 1 → 2 → 3: clockwise = R, counterclockwise = S.
  • Group 4 on a wedge: read the direction, then reverse it.
  • Swap trick: any one swap of two groups inverts the configuration. Swap group 4 onto the dash, assign, then reverse. Two swaps return the original.
  • R/S does not predict the sign of rotation (+/−).

E/Z for alkenes

  • Rank the two groups on each alkene carbon. Higher-priority groups on the same side = Z; opposite sides = E.
  • cis/trans can disagree with Z/E: 2-bromobut-2-ene with its two CH₃ groups trans is Z, because Br outranks CH₃.
  • A C=C in a ring of fewer than eight atoms must be cis.

Isomer relationships

  • Different connectivity → constitutional isomers. Same connectivity, different 3-D arrangement → stereoisomers: mirror images → enantiomers; not mirror images → diastereomers (includes cis/trans, E/Z).
  • Comparing descriptors: all centers inverted → enantiomers (unless meso: then the same compound); some inverted → diastereomers; none → same compound.
  • Chiral = not superimposable on its mirror image. An internal mirror plane makes a molecule achiral.
  • Meso = has stereocenters but is achiral (internal mirror plane): (2R,3S)-butane-2,3-diol, cis-1,2-dimethylcyclopentane.
  • 2ⁿ rule: n stereocenters (count stereogenic C=C too) give at most 2ⁿ stereoisomers, fewer with meso forms. Tartaric acid: 2 centers, 3 stereoisomers (enantiomer pair + meso).

Optical activity

  • Enantiomers: same mp, bp and solubility; equal but opposite rotation of plane-polarized light. Diastereomers differ in all physical properties.
  • [α] = α ⁄ (c · l), c in g/mL, l in dm. Racemic (50:50) mixtures and meso compounds: [α] = 0.
  • ee = % major − % minor = observed [α] ⁄ [α] of pure enantiomer × 100%. 75% R + 25% S = 50% ee.

Fischer projections

  • Each cross point is a stereocenter. Horizontal bonds point toward you (wedges), vertical bonds away (dashes); the carbon chain runs vertically.
  • A 180° rotation in the plane keeps the molecule; a 90° rotation gives the enantiomer. One swap of two groups inverts that stereocenter only (enantiomer for a single center, diastereomer if other centers are present); two swaps restore it.
  • R/S: group 4 vertical → read 1 → 2 → 3 directly; group 4 horizontal → read, then reverse.
  • A horizontal mirror line through the middle reveals a meso compound.

Practice R/S configuration →

6 Arrow pushing

  • Arrows move electrons. Tail on a lone pair or bond; head on an atom (new lone pair) or between atoms (new bond). Full head = 2 electrons; fishhook (half head) = 1 electron.
  • Electrons flow from Nu/base (lone pair, π bond) to electrophile/acid (C⁺, δ+ C bearing a LG, C=O carbon, acidic H).
  • A new bond to an atom that already has an octet means another bond to it must break. Never start at H⁺ or a + charge. Each step keeps the total charge.
The four electron-flow patterns
PatternArrowsExample
Nucleophilic attack1: Nu → electrophilic atomBr⁻ + (CH₃)₃C⁺ → (CH₃)₃CBr
Loss of LG1: C–LG bond → LG(CH₃)₃C–OH₂⁺ → (CH₃)₃C⁺ + H₂O
Proton transfer2: base → H; H–A bond → AROH + H₃O⁺ → ROH₂⁺ + H₂O
Rearrangement1: C–H or C–C bond next to C⁺ → C⁺1,2-hydride or 1,2-methyl shift

Concerted steps combine patterns: SN2 = attack + loss of LG (2 arrows); E2 = proton transfer + loss of LG (3 arrows).

Carbocation stability and 1,2-shifts

  • 3° > 2° > 1° > methyl (alkyl donation: hyperconjugation, induction). Resonance (allylic, benzylic, or next to an O or N lone pair) adds strong stabilization. Vinyl and aryl cations are too unstable to form here, so no SN1/E1 at sp² carbons.
  • A 1,2-hydride or 1,2-alkyl shift occurs when it gives a more stable cation (2° → 3°, or → resonance-stabilized). A strained ring next to C⁺ can expand by a 1,2-alkyl shift (4- → 5-, 5- → 6-membered) when that relieves strain or gives a more stable cation.
  • Expect shifts wherever a free C⁺ forms: SN1, E1, HX addition, acid-catalyzed hydration, 2°/3° ROH + HX. None in SN2, E2, oxymercuration, hydroboration or X₂ addition.

Example: 3-methylbutan-2-ol + HBr: protonate OH, lose H₂O (2° C⁺), 1,2-hydride shift (3° C⁺), add Br⁻. Major product: 2-bromo-2-methylbutane.

Energy diagrams

  • Transition state (‡) = energy maximum with partial bonds, never isolable; intermediate = a valley between steps (C⁺, radical). SN2/E2 show one hump; SN1/E1 show two or more (a small extra hump when a neutral Nu like H₂O must lose H⁺), and the first (C⁺ formation) has the highest barrier: it is the rate-determining step, so only [RX] appears in the rate law.
  • Rate depends on the barrier ΔG‡, not on ΔG; a catalyst lowers ΔG‡ only. ΔG = ΔH − TΔS; ΔG < 0 means products are favored (K > 1). Elimination makes more molecules (ΔS > 0), so heat (larger TΔS) favors E over S.
  • Hammond postulate: a transition state resembles the species closest to it in energy, so endothermic steps have late, product-like transition states. That is why carbocation stability controls SN1/E1 rates.

Draw real curved arrows with instant feedback: free tour →

7 Substitution and elimination

SN2, SN1, E2 and E1 compared
FeatureSN2SN1E2E1
Steps1, concerted backside attack2: C⁺ forms, then Nu adds1, concerted (β-H and LG leave together)2: C⁺ forms, then β-H lost
Rate lawk[RX][Nu]k[RX]k[RX][base]k[RX]
Substratemethyl > 1° > 2°; never 3°3° > 2°; allylic, benzylic3° > 2° > 1° (needs β-H)3° > 2°
Reagentgood Nu, often anionicweak Nu (H₂O, ROH)strong baseweak base; or acid + Δ
Solventpolar aprotic (DMSO, DMF)polar protic (H₂O, ROH)less decisivepolar protic
Stereoinversionmostly racemizationanti-periplanar; stereospecificmore stable (E) alkene favored
Regio——Zaitsev (more substituted alkene); Hofmann (less substituted) if bulky baseZaitsev
Rearrangementnopossiblenopossible

Decision flow

  1. Leaving group on an sp³ carbon? –OH and –OR must first be protonated or converted; vinyl and aryl halides don’t do SN1 or SN2.
  2. Classify the reagent: Nu only (strong Nu, weak base): I⁻, Br⁻, Cl⁻, HS⁻, RS⁻, H₂S, RSH, N₃⁻, CN⁻. Base only (strong base, poor Nu): t-BuOK, DBU, DBN, LDA, NaH. Strong base + strong Nu: HO⁻, CH₃O⁻, EtO⁻, acetylides. Weak Nu + weak base: H₂O, ROH.
  3. Classify the substrate and read the table below.
  4. Adjust: heat favors elimination; polar aprotic solvent boosts SN2; polar protic supports SN1/E1; branching near the reacting carbon (e.g. neopentyl) slows SN2.
Usual major pathway by substrate and reagent (real reactions often give mixtures)
SubstrateNu onlyStrong base/Nu (HO⁻, RO⁻)Bulky base (t-BuOK)Weak (H₂O, ROH)
MethylSN2SN2SN2 (no β-H)no reaction
1°SN2SN2 major, E2 minorE2no reaction (allylic/benzylic: SN1)
2°SN2E2 major, SN2 minorE2SN1 + E1 (slow)
3°SN1 (protic)E2E2 (Hofmann)SN1 + E1 (Δ favors E1)

Leaving groups and nucleophiles

  • Good LGs are weak bases: sulfonates (TsO⁻, MsO⁻, TfO⁻), I⁻ > Br⁻ > Cl⁻, and H₂O from a protonated alcohol. Poor: F⁻, HO⁻, RO⁻, NH₂⁻, H⁻. Turn –OH into a LG by protonating it or converting it to OTs, Br or Cl (section 11).
  • Nucleophilicity: an anion beats its conjugate acid (HO⁻ > H₂O). Protic solvents (O–H or N–H: H₂O, ROH) H-bond to and cage small anions, so in them nucleophilicity rises down a group (I⁻ > Br⁻ > Cl⁻ > F⁻; RS⁻ > RO⁻). Polar aprotic solvents (DMSO, DMF, acetone, CH₃CN: no O–H) leave anions bare, so the order follows basicity (F⁻ > Cl⁻ > Br⁻ > I⁻) and SN2 is much faster. Bulk lowers nucleophilicity far more than basicity.
  • E2 needs H and LG anti-periplanar (180°). On a cyclohexane both must be axial (trans-diaxial): use the chair with the LG axial. If the only anti-periplanar β-H is on the less substituted carbon, that alkene forms even with a small base.
  • E2 is stereospecific: when the β-carbon has one H, the anti-periplanar geometry decides E vs Z.

Example: cis-1-chloro-2-methylcyclohexane (Cl axial, CH₃ equatorial) has an axial H on C2, so NaOEt gives 1-methylcyclohexene (Zaitsev). In the trans isomer, putting Cl axial also puts CH₃ axial and the C2–H equatorial; only C6 has an axial H, so it gives 3-methylcyclohexene, and reacts more slowly.

Practice SN1 and SN2 mechanisms → · E1 and E2 →

8 Alkene reactions

  • Markovnikov: the electrophile (H⁺, Br⁺, ⁺HgOAc) adds first, and the nucleophile ends up on the carbon that best bears positive charge, the more substituted one, because that gives the more stable carbocation (or the more δ⁺ end of a bridged ion). Anti-Markovnikov happens when the first species to add is not H⁺: Br• (radical HBr) or boron (hydroboration) goes to the less substituted carbon.
  • Syn = same face, anti = opposite faces (visible only when both carbons become stereocenters). Achiral alkene + achiral reagents → optically inactive products (achiral, racemic or meso).
  • Stereospecific = each stereoisomer of the starting material gives a different stereoisomer of product (cis-but-2-ene + Br₂ → racemic, trans → meso). Stereoselective = one stereoisomer is simply preferred (E over Z in E1).
  • Alkene stability (from heats of hydrogenation): tetrasubstituted > tri- > disubstituted (trans > cis) > monosubstituted. More alkyl groups mean more hyperconjugation; this is why Zaitsev and E1 favor the most substituted, E alkene.
Alkene addition and cleavage reactions
ReactionReagentsRegiochemistryStereochemistryIntermediate, notes
HydrohalogenationHCl, HBr, HIMarkovnikovsyn + anti mixturecarbocation; shifts possible
Radical HBr additionHBr, ROOR (hν or Δ)anti-Markovnikovsyn + anti mixtureBr• adds → more stable C•; HBr only
Acid-catalyzed hydrationH₂O, cat. H₂SO₄Markovnikovsyn + anti mixturecarbocation; shifts possible
Oxymercuration1) Hg(OAc)₂, H₂O; 2) NaBH₄Markovnikovstep 1 anti; the NaBH₄ step is radical, so overall stereochemistry is lostmercurinium ion; no shifts; ROH gives ether
Hydroboration1) BH₃·THF; 2) H₂O₂, NaOHanti-Markovnikovsyn (H and OH)concerted; no shifts; H₂O₂/NaOH swaps B for OH with retention, so H and OH end up syn
HalogenationBr₂ or Cl₂ (CH₂Cl₂)—antibridged halonium ion
HalohydrinBr₂ or Cl₂, H₂OOH on more substituted Cantihalonium ion; H₂O attacks its more δ⁺ end, as in acid epoxide opening
EpoxidationmCPBA (RCO₃H)—syn; cis → cis epoxideconcerted
Anti dihydroxylation1) mCPBA; 2) H₃O⁺—anti (trans diol)epoxide opened by H₂O
Syn dihydroxylationOsO₄ (cat.), NMO; or cold KMnO₄, NaOH—syn (cis diol)cyclic osmate/manganate ester
HydrogenationH₂; Pt, Pd/C or Ni—synmetal surface → alkane
Cyclopropanation (some courses)CH₂I₂, Zn(Cu) (Simmons–Smith); or CHCl₃, KOH (→ dichlorocyclopropane)—syn, stereospecific (cis → cis)carbenoid or carbene adds in one step
Ozonolysis1) O₃; 2) DMS or Zn/H₂OC=C → two C=O—R₂C= → ketone; RCH= → aldehyde. Hot acidic KMnO₄ also cleaves but over-oxidizes: RCH= → RCOOH, =CH₂ → CO₂
Worked mini-examples: 1-methylcyclohexene + reagents
ReagentsMajor product
HBr1-bromo-1-methylcyclohexane
HBr, ROOR1-bromo-2-methylcyclohexane (cis + trans)
H₃O⁺; or 1) Hg(OAc)₂, H₂O; 2) NaBH₄1-methylcyclohexan-1-ol
1) BH₃·THF; 2) H₂O₂, NaOHtrans-2-methylcyclohexan-1-ol (racemic)
Br₂trans-1,2-dibromo-1-methylcyclohexane (racemic)
Br₂, H₂Otrans-2-bromo-1-methylcyclohexan-1-ol (racemic)
OsO₄, NMOcis-1-methylcyclohexane-1,2-diol (racemic)
1) O₃; 2) DMS6-oxoheptanal (ring opens to one chain)

Stereospecific pairs: Br₂ (anti) + trans-but-2-ene → meso-2,3-dibromobutane; + cis-but-2-ene → racemic (2R,3R) + (2S,3S). OsO₄ (syn) is the reverse: cis → meso diol, trans → racemic diol.

Practice alkene additions →

9 Alkyne reactions

Alkyne reactions
ReagentsProduct, selectivity
H₂ (excess), Pt, Pd/C or Nialkane
H₂, Lindlar’s catalyst (poisoned Pd)cis (Z) alkene (syn addition; stops at the alkene)
Na or Li, NH₃(l)trans (E) alkene from an internal alkyne (dissolving metal; terminal alkynes are deprotonated instead and reduce slowly)
H₂O, H₂SO₄, HgSO₄Markovnikov enol → ketone (terminal alkyne → methyl ketone)
1) R₂BH (disiamylborane or 9-BBN); 2) H₂O₂, NaOHanti-Markovnikov enol → aldehyde from a terminal alkyne (bulky borane adds once)
HX: 1 equiv; 2 equivMarkovnikov vinyl halide; then a geminal dihalide (both X on one C)
HBr, ROOR (terminal)anti-Markovnikov vinyl bromide (E/Z mixture)
X₂: 1 equiv; 2 equivmainly (E)-dihaloalkene (anti); then tetrahalide
  • Tautomerization: the enol converts (acid or base catalysis) to the more stable C=O form. Unsymmetrical internal alkynes give ketone mixtures.
  • Terminal alkyne acidity (pKa ≈25): deprotonate with NaNH₂ (NH₃ ≈38) or NaH, not NaOH or NaOEt.
  • Alkylation: RC≡C⁻ + CH₃X or 1° RX → RC≡CR′ by SN2 (new C–C bond). With 2°/3° halides the acetylide acts as a base (E2).
  • Making alkynes: vicinal or geminal dihalide + excess NaNH₂ (double E2; 3 equiv for a terminal alkyne), then H₂O.

Example: acetylene → (Z)-hex-3-ene: 1) NaNH₂; 2) CH₃CH₂Br; 3) NaNH₂; 4) CH₃CH₂Br; 5) H₂, Lindlar. Na, NH₃(l) in step 5 gives (E)-hex-3-ene.

Practice alkyne reactions →

10 Radical reactions

Radicals form by homolysis and are drawn with fishhook arrows. Stability: allylic/benzylic > 3° > 2° > 1° > methyl.

Halogenation mechanism (CH₄ + Cl₂, hν)

  1. Initiation (makes radicals): Cl₂ → 2 Cl• (light or heat).
  2. Propagation (chain; radical count unchanged): Cl• + CH₄ → HCl + •CH₃; then •CH₃ + Cl₂ → CH₃Cl + Cl•.
  3. Termination (uses up radicals): any two combine, e.g. Cl• + •CH₃ → CH₃Cl; 2 •CH₃ → ethane.

Selectivity: Cl₂ vs Br₂

  • Chlorination: exothermic H-abstraction (≈thermoneutral for CH₄), early transition state, poorly selective: ≈1 : 4 : 5 per H (1° : 2° : 3°, 25 °C). Propane → ≈45% 1-chloro + ≈55% 2-chloropropane.
  • Bromination: endothermic H-abstraction, so the transition state is late and radical-like (Hammond postulate, section 6) and the full 3° > 2° > 1° radical stability difference shows up in the rates: highly selective, ≈1 : 80 : 1600. Propane → ≈97% 2-bromopropane. Use Br₂, hν to target the most substituted C–H.
  • F₂ is too violent, I₂ too unreactive. A new stereocenter formed at a planar radical carbon comes out racemic.

Allylic bromination with NBS

NBS, hν (or ROOR), CCl₄ swaps an allylic H for Br. NBS keeps [Br₂] low, so Br₂ doesn’t add to the C=C. The allylic radical is delocalized, so Br can end up at either end: cyclohexene → 3-bromocyclohexene; but-1-ene → 3-bromobut-1-ene + 1-bromobut-2-ene (E/Z).

Practice radical mechanisms with fishhook arrows →

11 Alcohols, ethers and epoxides

Turning –OH into a leaving group or a halide
Reagent → productMechanism, stereochemistry (substrates)
HBr, HCl (+ ZnCl₂), HI → R–X3°/2°: SN1 (racemization, shifts possible); 1°: SN2
PBr₃ → R–BrSN2: inversion, no shifts (1°, 2°)
SOCl₂, pyridine → R–ClSN2: inversion, no shifts (1°, 2°)
TsCl (or MsCl), pyridine → R–OTsC–O bond untouched: retention; a later SN2 on R–OTs inverts (1°, 2°)
  • Dehydration: conc. H₂SO₄ or H₃PO₄, Δ → alkene. Ease 3° > 2° > 1°; 2°/3° by E1 (Zaitsev, shifts possible). For control: TsCl, pyridine; then t-BuOK (E2).
  • Alkoxides: ROH + NaH (or Na) → RO⁻ Na⁺ + H₂ (irreversible).
Alcohol oxidation
AlcoholPCC, CH₂Cl₂ (also DMP, Swern)Chromic acid or Jones (Na₂Cr₂O₇ or CrO₃, H₂SO₄, H₂O)
1°aldehydecarboxylic acid
2°ketoneketone
3°no reactionno reaction
Making alcohols from C=O and epoxides (the last Ochem 1 chapter in many courses)
ReagentsResult
NaBH₄, CH₃OHaldehyde → 1° alcohol; ketone → 2° alcohol (esters and acids untouched)
1) LiAlH₄, dry ether; 2) H₃O⁺same, and also reduces esters and carboxylic acids to 1° alcohols
1) RMgBr or RLi; 2) H₃O⁺new C–C bond: formaldehyde → 1°; other aldehydes → 2°; ketone → 3°; ester (2 R add) → 3° alcohol
1) RMgBr + epoxide; 2) H₃O⁺R attacks the less substituted C (SN2-like); ethylene oxide adds a –CH₂CH₂OH unit

Grignard reagents (RBr + Mg, dry ether) and RLi are strong bases: no O–H, N–H or COOH in the substrate or solvent (they would protonate R⁻ to R–H). RMgBr + CO₂, then H₃O⁺ → RCOOH.

Ethers

  • Williamson: RO⁻ + R′X → ROR′ by SN2, so R′X must be methyl or 1°; put the bulky part on the alkoxide. (CH₃)₃CO⁻ K⁺ + CH₃I → t-BuOCH₃ works; CH₃O⁻ + (CH₃)₃CBr gives E2 (2-methylpropene).
  • Cleavage: excess HBr or HI, Δ → two R–X (SN2 at methyl/1°, SN1 at 3°); an aryl alkyl ether gives phenol + RX.

Epoxides

  • Made by alkene + mCPBA (syn, stereospecific), or halohydrin + NaOH (intramolecular SN2; O⁻ and X must be anti).
  • Base or strong Nu (HO⁻, RO⁻, RS⁻, CN⁻, N₃⁻, acetylide; then a proton source): SN2 at the less substituted carbon.
  • Acid (H₃O⁺, ROH/H⁺, HX): protonate O, then Nu attacks the more substituted carbon (more δ+, SN1-like transition state). Clear-cut when that carbon is 3°.
  • Both modes attack from the back side (inversion there): anti opening, so cyclic epoxides give trans-1,2-products.

Example: 2,2-dimethyloxirane + CH₃O⁻/CH₃OH → 1-methoxy-2-methylpropan-2-ol. With CH₃OH, cat. H₂SO₄ → 2-methoxy-2-methylpropan-1-ol.

Practice alcohol reactions → · ethers and epoxides →

12 Spectroscopy basics

Degrees of unsaturation = (2C + 2 + N − H − X) ⁄ 2 (ignore O, S). Each ring or π bond = 1; C≡C = 2; benzene ring = 4. C₆H₁₂ → (12 + 2 − 12)/2 = 1: one ring or one C=C.

  • ¹H NMR signals = sets of chemically distinct H (use symmetry). Integration = relative number of H.
  • n + 1 rule: n equivalent neighboring H split a signal into n + 1 peaks (Pascal’s triangle). Equivalent H don’t split each other; O–H usually doesn’t (fast exchange).
  • Ethyl = triplet (3H) + quartet (2H); isopropyl = doublet (6H) + septet (1H); tert-butyl = singlet (9H). J ≈ 7 Hz in alkyl chains; vinyl trans (≈12–18 Hz) > cis (≈6–12 Hz).
  • ¹³C (one line per distinct C; heights not quantitative): sp³ C 0–50; C–O 50–90; C≡C 65–90; C=C and aromatic 100–160; C≡N 115–125; C=O 160–220.
  • Mass spec: M⁺ = molecular mass (an odd M⁺ means an odd number of N). An M+2 peak about equal to M⁺ → one Br; about ⅓ of M⁺ → one Cl. Common losses: 15 (CH₃), 29 (C₂H₅), 18 (H₂O from alcohols).
Key IR absorptions (approximate)
Bondcm⁻¹ ≈Appearance
O–H alcohol3200–3600strong, broad
O–H acid2500–3300very broad
N–H3300–35001° amine 2 peaks, 2° one
C–H: sp; sp²; sp³≈3300; 3000–3100; 2850–3000sp strong, sharp; sp² just above 3000, sp³ just below
Aldehyde C–H≈2720, 2820two weak peaks
C≡N; C≡C≈2250; 2100–2260C≡C weak or absent if symmetric
C=O1650–1750strong (ketone ≈1715, ester ≈1740)
C=C1600–1680medium to weak
C–O1000–1300strong
¹H NMR chemical shifts (approximate)
Proton typeδ ≈ (ppm)
Alkyl C–H (CH₃ < CH₂ < CH)0.9–1.8
Allylic, benzylic, α to C=O1.7–2.6
Alkyne ≡C–H2–3
H–C–O, H–C–X3–4.5
Vinyl =C–H4.5–6.5
Aromatic Ar–H6.5–8.5
Aldehyde –CHO9–10
Carboxylic acid –COOH10–13, broad
O–H, N–H1–5, variable

Practice IR → · ¹H NMR →

13 Synthesis strategy

Reaction map: interconverting Ochem 1 functional groups
From → toReagents (notes)
Alkane → alkyl bromideBr₂, hν (most substituted C)
Alkyl halide → alkeneNaOEt (Zaitsev) or t-BuOK (Hofmann), E2
Alkyl halide → SN2 productsNaOH, NaOR, NaCN, NaN₃, NaSR, RC≡C⁻ Na⁺ (methyl or 1° halide best); 3° RX + H₂O → alcohol (SN1)
Alkene → alkyl halideHX (Markovnikov); HBr, ROOR (anti-Markovnikov)
Alkene → alcoholH₃O⁺, or Hg(OAc)₂/H₂O then NaBH₄ (Markovnikov); BH₃ then H₂O₂/NaOH (anti-Markovnikov, syn)
Alkene → alkane; X₂ adductsH₂, Pd/C; X₂ (dihalide); X₂/H₂O (halohydrin)
Alkene → epoxide; diol; carbonylsmCPBA; OsO₄/NMO (syn) or mCPBA then H₃O⁺ (anti); O₃ then DMS
Alkene → allylic bromide; alkyneNBS, hν; 1) Br₂, 2) excess NaNH₂, 3) H₂O
Alkyne → cis/trans alkene; alkaneH₂, Lindlar (cis); Na, NH₃(l) (trans); H₂, Pd/C (alkane)
Alkyne → ketone; aldehydeHgSO₄, H₂SO₄, H₂O; R₂BH then H₂O₂/NaOH (terminal alkyne)
Alcohol → alkyl halide; tosylatePBr₃, SOCl₂/pyridine or HX; TsCl/pyridine
Alcohol → alkeneH₂SO₄, Δ (E1, Zaitsev); or TsCl/pyridine then t-BuOK (E2)
Alcohol → aldehyde; ketone; acidPCC (1°); PCC or chromic acid (2°); chromic acid (1°)
Alcohol → etherNaH, then CH₃X or 1° RX (Williamson)
Epoxide → alcoholNu⁻ then H₂O (less substituted C); H₃O⁺ or ROH/H⁺ (more substituted C)
Aldehyde, ketone, ester → alcoholNaBH₄ (not esters), or LiAlH₄ then H₃O⁺; RMgBr or RLi, then H₃O⁺ (new C–C bond)

Retrosynthesis tips

  • Work backward (⇒) and compare carbon counts. New C–C bonds: acetylide + methyl or 1° halide, or Grignard (RMgBr/RLi) + C=O or epoxide.
  • Move a functional group: eliminate, then add with the opposite regiochemistry. Propan-2-ol → (TsCl, pyridine; t-BuOK) → propene → (BH₃; H₂O₂/NaOH) → propan-1-ol.

Common exam pitfalls

  • SN2 or Williamson at a 3°, vinyl or aryl C (E2 or no reaction).
  • Missing C⁺ shifts (SN1, E1, HX, H₃O⁺); none in oxymercuration or hydroboration.
  • Chromic acid on a 1° alcohol when you want the aldehyde (use PCC).
  • Ring E2 without a trans-diaxial H and LG.
  • Grignard with an O–H or N–H elsewhere in the molecule.
  • Dropping stereochemistry; arrows from H⁺ or a + charge; five-bonded C.

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