Organic Chemistry Study Notes: Substitution, Elimination, and Addition Reactions (Chapters 6–8)

Special Topics

Carbocation Rearrangements and Reaction Overview

Carbocation rearrangements are possible for any reaction that involves a carbocation intermediate. Understanding the behavior of nucleophiles, electrophiles, bases, and leaving groups is essential for predicting reaction outcomes in organic chemistry.

• Carbocation Rearrangement: Occurs in reactions with carbocation intermediates (e.g., SN1, E1).

• Strong base/strong nucleophile: Favors SN2 or E2 mechanisms.

• Weak base/weak nucleophile: Favors SN1 or E1 mechanisms.

• Nucleophile: Electron-rich species that attack electron-poor centers (electrophiles).

• Electrophile: Electron-poor species, often the substrate in substitution/elimination.

• Bases: Remove protons (H+).

• Pi bonds: Can act as nucleophiles or bases.

• Carbocation stability: Tertiary > secondary > primary > methyl; stabilized by alkyl groups and resonance (e.g., benzylic, allylic).

Example: In SN1 reactions, a tertiary alkyl halide forms a stable carbocation intermediate, which may undergo rearrangement (hydride or methyl shift) to yield a more stable carbocation before nucleophilic attack.

Chapter 6: Substitution Reactions

Mechanisms: SN1 and SN2

Substitution reactions involve the replacement of a leaving group by a nucleophile. The two main mechanisms are SN1 (unimolecular) and SN2 (bimolecular).

• SN2 Mechanism:

  • Concerted, one-step process.

  • Backside attack: nucleophile attacks 180° opposite the leaving group, causing inversion of configuration (Walden inversion).

  • Transition state is trigonal planar at the reactive carbon.

  • Favored by strong nucleophiles and less hindered (primary) substrates.

• SN1 Mechanism:

  • Two-step process: (1) Leaving group departs, forming a carbocation; (2) Nucleophile attacks the carbocation.

  • Carbocation rearrangements (hydride/methyl shifts) possible for greater stability.

  • Favored by weak nucleophiles, polar protic solvents, and more substituted (tertiary) substrates.

Table: Comparison of SN1 and SN2 Mechanisms

Feature	SN1	SN2
Nucleophile	Weak	Strong
Primary halides	Not good	Good
Tertiary halides	Good	Not good
Solvent	Very polar protic	Less polar solvents (polar aprotic)
Stereochemistry	Racemization	Inversion
Rearrangement	Common	Never

Solvent Effects

• Protic solvents: Stabilize nucleophiles via hydrogen bonding, favoring SN1.

• Aprotic solvents: Do not hydrogen bond with nucleophiles, favoring SN2.

Example: Acetone, DMSO, and DMF are common polar aprotic solvents used in SN2 reactions.

Nucleophiles, Electrophiles, and Intermediates

• Nucleophile: Lewis base (electron pair donor), often negatively charged or with lone pairs.

• Electrophile: Lewis acid (electron pair acceptor), often a carbon attached to a leaving group or a carbonyl carbon.

• Intermediates: Carbocations (tertiary, secondary, etc.), radicals, carbanions.

Arrow Pushing Patterns

• Nucleophilic attack: Arrow starts at nucleophile, points to electrophilic center.

• Proton transfer: Requires at least two arrows: base attacks proton, acid is converted to conjugate base.

• Loss of leaving group: Arrow from bond to leaving group, forming lone pair on leaving group.

• Concerted mechanism: Multiple arrows in a single step (e.g., SN2, E2).

Chapter 7: Structure and Synthesis of Alkenes; Elimination

Degrees of Unsaturation

Degrees of unsaturation indicate the number of rings and/or multiple bonds in a molecule.

• Double bond: 1 degree of unsaturation

• Ring: 1 degree of unsaturation

• Triple bond: 2 degrees of unsaturation

• Halogen: Counts as one hydrogen

• Oxygen: Ignored in calculation

• Nitrogen: Counts as half a carbon

Formula: $\text{Degrees of Unsaturation} = \frac{2C + 2 + N - H - X}{2}$ Where C = number of carbons, N = number of nitrogens, H = number of hydrogens, X = number of halogens.

Alkene Nomenclature and Stereochemistry

• Sec, tert, etc.: Used when substituent attaches to a non-primary carbon.

• Vinyl: Directly attached to parent C=C.

• Allyl: Attached one carbon away from C=C.

• Phenyl: Benzene ring attached via one carbon.

• Diene, triene, tetraene: Indicate 2, 3, or 4 double bonds, respectively.

• Trans-cycloalkenes: Not stable unless ring has at least 8 carbons; otherwise, assume cis.

• Cahn-Ingold-Prelog rules: Assign priorities for E/Z nomenclature based on atomic number and connectivity.

• Conjugated double bonds: More stable due to less steric hindrance (double bonds separated by one single bond).

Elimination Reactions: E1 and E2

Elimination reactions form alkenes by removing atoms/groups from adjacent carbons. Two main mechanisms are E1 (unimolecular) and E2 (bimolecular).

• E1 Mechanism:

  • Two-step: (1) Leaving group departs, forming carbocation; (2) Base removes proton to form alkene.

  • Favored by weak bases, polar protic solvents, and tertiary substrates.

  • Carbocation rearrangements possible.

• E2 Mechanism:

  • One-step, concerted process: Base removes proton while leaving group leaves.

  • Requires anti-periplanar geometry (leaving group and proton 180° apart).

  • Favored by strong bases and tertiary substrates.

  • Zaitsev product (more substituted alkene) usually major unless bulky base is used (Hofmann product).

Example: Dehydrohalogenation of a secondary alkyl halide with a strong base yields the more substituted alkene (Zaitsev product) via E2 mechanism.

Substitution vs. Elimination

• Determine the function of the reagent:

  • Substitution: Reagent acts as nucleophile.

  • Elimination: Reagent acts as base.

• Analyze the substrate and expected mechanism(s).

• Consider regiochemical and stereochemical requirements.

Table: Reagent, Substrate, Mechanism, and Outcomes

Reagent	Substrate	Mechanism	Outcomes
Nucleophile (weak base)	Primary, secondary, tertiary	SN2, SN1	Substitution, inversion (SN2), racemization (SN1)
Base (strong, non-nucleophilic)	Primary, secondary, tertiary	E2, E1	Elimination, Zaitsev/Hofmann product
Strong base/strong nucleophile	Primary, secondary, tertiary	SN2/E2	Substitution/elimination, depends on substrate
Weak base/weak nucleophile	Secondary, tertiary	SN1/E1	Substitution/elimination, carbocation rearrangement possible

Chapter 8: Reactions of Alkenes

Regiochemistry and Stereochemistry of Addition

Addition reactions involve two molecules combining to form one product. The orientation (regiochemistry) and spatial arrangement (stereochemistry) of addition are important for predicting products.

• Regiochemistry: Determines which part of the reagent adds to which end of the double bond.

• Markovnikov's Rule: In the addition of HX to an alkene, the hydrogen adds to the carbon with more hydrogens (less substituted), and the halide adds to the more substituted carbon.

• Anti-Markovnikov Addition: Occurs in the presence of peroxides (ROOR) with HBr; Br adds to the less substituted carbon.

• Syn Addition: Both groups add to the same side of the double bond.

• Anti Addition: Groups add to opposite sides of the double bond.

• Stereochemistry: Formation of stereocenters can lead to enantiomers or meso compounds; check for internal planes of symmetry.

Types of Addition Reactions

• Hydrogenation: Addition of H2 across a double bond using a metal catalyst (Pt, Pd, Ni); always syn addition.

• Hydrohalogenation (HX Addition):

  • Proton transfer forms carbocation intermediate.

  • Nucleophilic attack by halide.

  • Follows Markovnikov's rule unless peroxides are present (then anti-Markovnikov).

  • Carbocation rearrangements possible.

• Hydration (Addition of H and OH):

  • Markovnikov addition: OH ends up on more substituted carbon.

  • Reagents: H2O and acid source.

  • Equilibrium arrows used; can be reversed (E1 elimination).

  • If a stereocenter is formed, a pair of enantiomers results.

• Hydroboration-Oxidation (Anti-Markovnikov Addition):

  • Reagents: BH3 (or B2H6), THF, H2O2, NaOH.

  • OH ends up on less substituted carbon.

  • Syn addition: both H and OH add to the same side.

  • Concerted mechanism with unique alkyl shift during oxidation.

• Halogenation (Addition of X2):

  • Alkene attacks X2 (e.g., Br2), forming a cyclic halonium ion intermediate.

  • Backside attack by halide ion (anti addition).

  • No carbocation rearrangement.

• Formation of Halohydrins:

  • Addition of X and OH across double bond.

  • Regiochemistry: Halide adds to less substituted carbon.

  • Anti addition due to mechanism.

• Epoxidation and Dihydroxylation:

  • Epoxidation: Peroxyacid (e.g., MCPBA) reacts with alkene to form epoxide (three-membered cyclic ether).

  • Opening of epoxide by acid/base yields anti-diol (anti addition of OH groups).

  • Dihydroxylation: OsO4 or KMnO4 with hydroxide adds two OH groups across alkene (syn addition).

• Ozonolysis:

  • Oxidative cleavage of alkene with O3, followed by reduction (Zn or DMS), splits double bond into two carbonyl compounds.

  • No regiochemistry or stereochemistry concerns.

Free Radical Addition of HBr

• Initiation: Formation of radicals (e.g., by peroxides, ROOR).

• Propagation: Br radical adds to double bond, generating alkyl radical on more substituted carbon.

• Alkyl radical abstracts H from HBr, forming product and regenerating Br radical.

• Product is anti-Markovnikov: Br adds to less substituted carbon.

Key Points and Trends

• Atomic size increases down a group and decreases from left to right in the periodic table.

• The more stable the molecule, the weaker the base.

• If a halide is used as a reagent, the reaction is substitution, not elimination.

Summary Table: Regiochemical and Stereochemical Outcomes

Mechanism	Regiochemical Outcome	Stereochemical Outcome
SN2	Nucleophile attacks at position of leaving group	Inversion of configuration
SN1	Nucleophile attacks carbocation	Racemization
E2	Zaitsev product (more substituted alkene)	Anti-periplanar elimination
E1	Zaitsev product	Mixture, no strict stereochemistry

Additional info: These notes synthesize and expand upon the provided class notes, integrating standard textbook explanations, definitions, and examples for clarity and completeness. All mechanisms, trends, and rules are standard in undergraduate organic chemistry curricula.