Chapter 6 Ionic Reactions Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Organic Halides Alkyl Halides: alkane molecule in which a halogen has replaced a hydrogen

Physical Properties Of Organic Halides Low solubilities in water Miscible with each other and other relatively nonpolar solvent E.g CH2Cl2 CHCl3 CCl4

Reaction Intermediates 3 major types Carbocation (C+) Carbanion (C-) Free radical (C· )

Reaction Sites Nucleophiles: (nucleus-loving) any species containing electron pairs Electrons are (-), so Nu: are attracted to (+) site Charge Nu: are better than neutral one E.g

Reaction Sites Electrophiles (electron-loving): any species or site in molecule that’s deficient in electron density because it’s near a electronegative atom or lacking of e- altogether

Multiple bonds The electrons are available to be donated to another species

Nucleophilic Substitution Reactions General Reaction

Reaction Schemes

Leaving Groups Relatively stable, weakly basic molecule or anion Halogen atom of an alkyl halide is a good leaving group because once departed it is a weak base and table anion

A mechanism for SN2Reaction The nucleophile approaches the carbon bearing the leaving group from the back side Directly opposite the leaving group As the reaction progresses, the bond between nucleophile and the carbon strengthens, and the bond between the carbon atom and the leaving group weakens Carbon atom has its configuration turned inside out  inversion

Transition State Arrangement of the atoms in which nucleophile and the leaving group are both partially bonded to the carbon atom undegoing substitution Bond breaking and forming and occurred simultaneouly Concerted reaction

Kinetics of a Nucleophilic substitution: an SN2 reaction 1 step reaction Second order Rate of reaction depends an alkyl halides and Nu: Rate Rxn = k [alkyl halide] x [Nu:]

Stereochemistry of SN2 Reactions Nucleophiles approaches from the back side, that is directly opposite the leaving group. Consider the cis-1-chloro-3-methylclyclopentane When undergoes SN2, the product become trans

examples Give the structure of the product that would be formed when trans-1-bromo-3-methylcyclobutane undergoes an SN2 reaction with NaI

A mechanism for SN1Reaction

The Relative stabilities of Carbocations The order of stability of carbocations can be explained on the basic of hyperconjugation. Involves electrons delocalization from a filled bonding orbital to an adjacent unfilled orbital Any time a charge can be disperred or delocalized, a system will be stabilized

The Relative stabilities of Carbocations

Kinetics of a Nucleophilic substitution: an SN1 reaction 2 step reaction 1st order rate determination Rate of reaction depends the slowest step Heterocleavage of halide Rate Rxn = k [alkyl halide]

Multistep Reactions and The Rate-Determining Step The step is intrinsically slower than all other is called the rate-limiting step or rate determining step

Transition State Stabilization of leaving group I- > Br- > Cl- > F- Weaker conjugated base  stronger leaving group

Mechanism for SN1 Reaction Show a complete mechanism with stereochemisty for the following reaction

Mechanism for SN1 Reaction Show a complete mechanism with stereochemisty for the following reaction

Factors Affecting the Rates of SN1 and SN2 Reactions The structure of the substrate, The concentration and reactivity of the nucleophile The effect of the solvent The nature of the leaving group

The Effect of the Structure of the substrate SN2 reaction shows the following general order of reactivity Methyl > primary > secondary >> (tertiary – unreactive) steric hindrance SN1 reaction Tertiary > secondary > methyl Hyperconjugation between p orbitals

Hammond-Leffler Postulate The structure of a transition state resembles the stable species that is nearest it in free energy

The effect of the Concentration and Strength of the Nucleophile A negatively-charged nucleophile is always a more reactive nucleophile than its conjugated acid HO- is a better Nu: then H2O and RO- is better than ROH In a group of nucleophiles in which the nucleophilic atom is the same, nucleophilicities parallel to basicities RO- > HO- >> RCO2- >> ROH > H2O equilibrium favors the side with weaker acid

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solvent The effect of hydrogen bonding with the nucleophile is to encumber the Nu: and hinder its reactivity in a substitution reaction

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solvent Hydrogen bonds to a small nucleophile atom are more stronger than those to larger nucleophilic atoms Halide Nucleophilic in Protic Solvent I- > Br- > Cl- > F- Larger atoms have greater polarizability  larger nucleophile atom can donate a greater degree of electron density to substrate SH- > CN- > I- > -OH > N3- > Br- > CH3CO2- > Cl- > F- > H2O

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solvent Aprotic solvents are those solvents whose molecules do not have a hydrogen that is attached to an atom of an electronegative element They do the same way as protic solvents solvate cations; by orienting their negative ends around cation and by donating unshared electron pairs to vacant orbitals of the cation

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solvent They cannot form H-bond because their postive centers are well shielded by the steric effects from any interaction with anions Rate of SN2 reaction generally increased when they are carried out in a polar protic solvent

Solvent Effects on SN1 Reactions: The Ionizing Ability of the solvent The use of polar protic solvent will greatly increase the rate of ionization of an alkyl halide in SN1 reaction Able to solvate cations and anions more affectively Stabilize transition state leading to the intermediate carbocation and halide ion more than it does the reactant Lower activation energy

Summary of SN1 and SN2 Reactions Factor SN1 SN2 Substrate 3o (requires formation of a relatively stable carbocation) Methyl > 1o > 2o (requires unhindered substrate) Nu: Weak Lewis base, neutral molecule Nu: may be the solvent Strong Lewis Base, rate increased by high concentration of Nu: Solvent Polar Protic (e.g alcohol, water…) Polar protic (e.g DMF, DMSO Leaving Group: I > Br > Cl > F for both SN1 and SN2 ( the weaker the base after the group departs the better the leaving group)