Unit 5 - Reactivity

Enthalpy

Heat energy exchange between reaction and its surroundings (thermodynamics)

Breaking Bonds

Absorbs energy

Homolytic Cleavage

Each atom gets an electron when EN is similar

Heterolytic Cleavage

1 atom gets both electrons when EN is different

BDE 

Bond breaking corresponds to homolytic bond cleavage

Exothermic

Energy gained by bonds exceeds energy needed for bonds broken, products more stable than reactants

Endothermic

Energy needed for bonds broken exceeds stability gained by bonds formed, products less stable than reactants

Entropy

Molecular disorder

Delta S is positive when

1. More moles of product than reactant

2. Cyclic becomes acyclic 

If H and S is negative

Spontaneous at low temperatures

If H and S is positive

Spontaneous at high temperatures

Reaction Rates are based on

• Concentration of rate law substances

• Ea

• Temperature

• Geometry, orientation, steric

• Catalysts

Transition States

Have lifetime bond vibration, high energy state

Intermediates

Have lifetime longer than bond vibration, actually exists

Nucleophile

Electron rich species, lewis bases

Electrophile

Electron deficient, lewis acid

Electron Movement Patterns

• Nucleophile attack

• Loss of leaving group

• Protein transfer

• Rearrangement

Nucleophile Attack

Nucleophile (even pi bond) attacks electrophile, sometimes followed by resonance arrows

Loss of Leaving Group

Heterolytic bond cleavage

Proton Transfers

Deprotonation or protonation

Hyperconjugation Level 2

Sigma and p orbital overlap from substitution, increasing stability of carbocation from adjacent sigma bond with empty p orbital

1,2-Hydride Shift

Overlap causes electron to jump when stabilization is better

1,3-Alkyl Shift

Methyl group will jump to other carbon

Carbocation Rearrangement Scenarios

1. 4-5 Ring Expansion

2. Increase conjugation

3. Increase degree of carbocations

Elimination Reaction

Reaction with base and pi bond forms

Substitution Reaction

Nucleophile replaces halogen

Concerted Mechanism

Breaking bond and bond to nucleophile happens at the same time

Stepwise Mechanism

Leaving group leaves, then nucleophile attacks

Sn2 Inversion

Stereo centres invert from nucleophile attacks from the backside to get proper arrangement of the nucleophile’s HUMO with electrophile LUMO

More stable transition state

Slow reaction rate

Alpha and Beta Carbons hinder

Backside attack, making it slower

Polarizable

Size of electron cloud, larger cloud = better pulling and nucleophiles

E2 Elimination

Concerted reaction where strong base removes beta proton causing loss of leaving group and double bond 

Trans isomers are more

Stable than cis isomers

More substitution in alkenes is more

Stable from hyperconjugation

Regiochemistry

Determines which region reacts

Zaitsev Product

More substituted (unhindered bases)

Hoffman Product

Less substituted alkene (bulky bases)

Stereospecific

Substrate has stereoisomerism and has one stereoisomers as the product

Alkyne and Na NH₃

Partial trans alkene

When alpha and beta are chiral

Must consider co planar arrangement using newman projection

Anti Periplanar

Around 180 degrees for E2

If there are 2 beta hydrogens and a chiral alpha centre

2 products will form

Stereoselective

Substrate can make two stereoisomers as products, where 1 is the major product

Sn2 Favours

Primary halides, unhindered neighbours

E2 Favours

Tertiary Halides

Sn1

Loss of leaving group, then weak nucleophile

Solvolysis

Nucleophile is the solvent

E1

Leaving group followed by pi bond formation

Sn1 Reactions produce two different

Configuration, inversion and retention

Sn1 and E1 favours

Tertiary Halides

Sliver in Sn1 and E1 allows

Secondary Halides to go forward

Steps to Predict Mechanism

1. Determine Reagent

2. Analyze the substrate and temperature

3. Consider regio and stereochemistry

Alkyl Sulfonates

Alternatives to alkyl halides with sulphur but more stable and resonance stabilized

Alcohols and Acids

OH reacts to make H2O and CB replaces it

Aprotic Solvents speed up

Sn2 reactions because aprotic molecules have a buried positive charge, decreasing stabilization of nucleophile and less Ea

Protic Solvents speed up

Sn1 because protic solvents have exposed positive charge which stabilizes the nucleophile and carbocation but create a greater Ea

If base and nucleophile is strong

• At cold, secondary Sn2

• At cold/rt primary Sn2

• At hot, tertiary E2

If base is weak but nucleophile strong

Sn2

If base and nucleophile weak

• In hot, tertiary E1

• In cold/rt, tertiary Sn1

• In sliver, secondary E1 or Sn1

If strong acid

• Primary Sn2

• If hot, poor nucleophile secondary or tertiary E1

• If good nucleophile, secondary or tertiary Sn1

Addition and Elimination Reactions are

Opposite equilibrium of each other

At low temperatures

Enthalpy dominates and addition reactions are favoured

At high temperatures

Entropy dominates, and elimination reactions are favoured

Hydrohalogenation

Addition of H-X to alkene and the major Markovnikov product is formed from carbocation stability

Markovnikov Addition

The more substituted carbon gets the nucleophile

Anti Markovnikov Addition

Less substituted carbon gets the nucleophile in the presence of oxygen

Why can hydrohalogenation create both chiral centres

Nucleophile can attack either p orbital 

Acid Catalyzed Hydration

Water is added across alkene following Markovnikov regioselectivity of 50/50 arrangement

If making alcohols

Use excess water

If making alkene

Use concentrated acid with no water added

Oxymercuration Demercuration

Follows Markovnikov addition of OH, but no rearrangement occurs due to HgAcO

Oxymercuration Demercuration Steps

1. HgAcO bounds to least substituted alkene

2. Binds to both carbons and water, replaced the more subbed carbon

3. It gets deprotonated and HgAcO reduced

Halogenation

Stereoselective anti addition of Cl or Br across C=C bond

Anti Addition makes

Trans products

Syn Addition makes

Cis products

Halohydrin

Halogenation in water creates an anti addition where the OH is added to the more substituted carbon and halide the less 

Halohydrin Steps

Dihydroxylation

Anti addition of OH and OH across pi bond in peroxyacid and O2 acts like an electrophile

Dihydroxylation Steps

If carbocation

Markovnikov addition

If no carbocation

Anti markovnikov addition

Hydroboration Oxidation

Adds H and OH with anti Markovnikov regioselectivity but syn addition

Alkene Catalytic Hydrogenation

Addition of H2 on an alkene with a metal catalyst through syn addition because metal surface delivers H on the same side

Syn Dihydroxylation

Adds 2 OH in a concerted syn fashion with OsO₄ and NMO as co-oxidant to redox OsO₄

Ozonolysis

Concerted process with O₃ and DMS to cleave alkene into two carbonyls

Geminal Dihalide

Halides are bonded to same carbon

Vicinal Dihalide

Halides are bonded to different carbons

NaNH₄ used to

Deprotonate and shift the equilibrium of alkyne to neutralize them

Alkyne Acid Catalyzed Hydration

Alkyne goes through an enol through Markovnikov addition, then turned into a carbonyl with H₂O

Tautomerization

Different location of pi and H bonds

Alkyne Hydroboration Oxidation

Anti Markovnikov addition for enol, then undergoes resonance

Enol

Alkene with an alcohol

Alkyne Catalytic Hydrogenation

Alkyne turns into alkane with metal to make a cis alkene first then trans

Lindlar’s Catalyst

Deactivated catalyst that only lowers E_A for first H₂ addition to make an alkene only

Dissolving Metal Reduction

Stereoselectively reduces alkyne into a trans alkene with Na and NH₃

Alkylation of Terminal Alkynes

Alkynes lengthened with NH₂ to deprotonate and a halide added on

For Terminal Alkynes, Markovnikov hydration makes a

Ketone

For Terminal Alkynes, Anti Markovnikov hydration makes an

Aldehyde