Reaction Mechanisms

SN1, SN2, E1, E2

SN1 or E1

• Weak base

• Weak nucleophile

• Secondary or tertiary substrate

SN1

• Weak base

• Strong nucleophile

• Tertiary substrate

SN2

• Weak base

• Strong nucleophile

• Primary or secondary substrate

Favors SN2, could be E2

• Strong base

• Strong nucleophile

• Primary substrate

Favors E2, could be SN2

• Strong base

• Strong nucleophile

• Secondary substrate

E2

• Strong base

• Strong nucleophile

• Tertiary substrate

E2*

• Strong base

• Weak nucleophile

• Primary, secondary, or tertiary substrate

No reaction (too slow)

• Weak base

• Weak nucleophile

• Primary (and sometimes secondary) substrate

Substrate

The starting organic molecule that undergoes a reaction and is modified by a reagent

Strong bases

• LiOH

• NaOH

• KOH

• RbOH

• Ca(OH)2

Bulky strong bases

• LDA

• KOtBu

• DBN

• DBU

• n-BuLi

Steric hindrance

Describes the slowed reaction rate (or complete prevention) or a chemical reaction due to the bulkiness and spatial arrangement of atoms in a molecule

Strong nucleophiles

• -OH

• -OR

• cyanide (CN-)

• N3

• -SH

• negatively charged species

Weak nucleophiles

• H2O

• alcohols

• thiols

• neutral amines

• carboxylic acids

Weak bases

• ammonia (NH3)

• Al(OH)3

• CO3

• Mg(OH)2

• pyridine

Good leaving groups

• halides (I, Br, Cl)

• TsO-

• H2O

• have good resonance stabilization

• often weak bases

• neutral molecules that can stabilize themselves

• weakly bonded to molecule

Polar aprotic solvents

Favors SN2 and E2 reactions.

• acetone

• DMSO

• dichloromethane

• DMF

• THF

• acetonitrile

Polar protic solvents

Favors SN1 and E1 reactions

• H2O

• methanol

• ethanol

• acetic acid

• ammonia

Constitutional isomer

Same molecular formula, different atomic connectivity.

Diastereomer

Same molecular formula and atomic connectivity, different spatial arrangement.

Enantiomer

Same molecular formula and atomic connectivity, inverted spatial arrangement (mirrored).

Hammond’s postulate

States that a transition state resembles the structure of the nearest stable species (whether that be a reactant, intermediate, or product). 

dextrorotatory

Compound rotates plane polarized light in the clockwise (+) direction (right)

levorotary

Compound rotates plane polarized light in the counterclockwise (-) direction (left)

R/S configuration

Configurations at a chiral center, determined by Cahn-Ingold-Prelog rules (right-handed or left-handed)

E/Z configuration

“Opposite” or “same” configuration system used for naming alkenes

Inductive effect

The permanent polarization of a sigma bond caused by the unequal sharing of electrons due to differences in electronegativity (can be + or -)

Hyperconjugation

The delocalization of electrons from a sigma bond (usually a C-H bond of an alkyl group) into an adjacent unfilled orbital, like a p-orbital in a carbocation or a pi system in an alkene

Catalyst

A substance that accelerates a chemical reaction by offering an alternative pathway with lower activation energy

Endergonic

Describes a nonspontaneous reaction that absorbs free energy from its surroundings, requires an input of energy to occur (ΔG>0)

Exergonic

Describes a spontaneous reaction that releases energy (products have lower free energy than the reactants), can occur without external energy input (ΔG<0) Examples include combustion reactions and certain steps in metabolic pathways

Endothermic

Positive enthalpy change. Absorbs energy from surroundings into system

Exothermic

Negative enthalpy change. Releases energy from system into surroundings

Nucleophilic center

Electron-rich (has excess electrons or a negative charge) and donates an electron pair to form a new covalent pi bond

Electrophilic center

Electron-deficient (has a lack of electrons or a positive charge) and accepts an electron pair to form a new covalent pi bond

Heterolytic cleavage

An unequal split where one atom takes both electrons, forming a cation and an anion. Seen clearest in SN1/E1 reactions

Concerted mechanism

Single step reaction with no intermediates (SN2/E2). Favored by higher ΔG

Step-wise mechanism

Occurs in two or more distinct steps, involving one or more unstable intermediates (SN1/E1)

Regiochemistry

identifying the specific atom or region where a chemical reaction occurs in a molecule, or describing the position of the functional group (especially when multiple sites are possible)

Markovnikov’s Rule

predicts the regioselectivity of the addition of a protic acid to an asymmetrical alkene or alkyne, stating that the hydrogen atom attaches to the carbon atom with more hydrogen atoms already bonded to it

Zaitsev product

more substituted and more stable alkene, usually the major product because it is more thermodynamically stable

Hoffman product

less substituted and less stable alkene, but can be favored in the presence of a bulky base or having a poor leaving group

Leveling effect

Phenomenon that occurs when a solvent masks the differences in the strengths of acids or bases that are stronger than the solvent's conjugate acid or base (ex: in water, all acids stronger than H3O+ appear to have the same strength because they all completely donate a proton to water, so H3O+ is the strongest acid present)

Unimolecular

One molecule is involved in the reaction mechanism (SN1/E1)

Bimolecular 

Two molecules or ions collide (SN2/E2)

Intermediates

Species that are produced in one elementary step and consumed in a subsequent step; not present at the beginning or end of the overall reaction

Rate-determining step

The slowest elementary step in the reaction mechanism, which controls the overall rate of the reaction (usually loss of LG/carbocation formation)

Transition states

Short-lived, high-energy, unstable species that exist between reactants and intermediates; each elementary step has its own one of these

Stereoselective

Favors the formation of one stereoisomer over others, but doesn’t exclusively produce a single stereoisomer. Can yield a mixture of stereoisomers (one major product and other minor products)

Stereospecific

Produces a single stereoisomer as the exclusive product (ex: hydrogenation of an alkene)

Mesocompound

An achiral molecule with 2 or more chiral centers. Superimposable on its mirror image (symmetrical), rendering it optically inactive