Chapter 6: Nucleophilic Reactions - Substitution Reactions of Alkyl Halides

Organohalide =

organic compounds that contain at least one halogen

Oranohalides trends:

in the image

Physical properties of organohalides:

• Most are not very soluble in water

• They are used as solvents for nonpolar & moderately polar compounds

Alkyl halide =

a halogen bonded to a sp3 hybridized carbon

The alkyl piece can have other functional groups just as long as:

the halogen is bonded to an sp3 carbon

Alkenyl halide =

halogen directly connected to an alkene (sp2)

Aryl halide =

halogen directly connected to an aromatic ring (also connected to sp2 C)

What can’t be done with this?

reactions

Alkyl halides can undergo:

substitution and/or elimination reactions

Na or K are:

spectator ions

General rxn for a nucleophilic substitution:

• The nucleophile can be negatively charged or a neutral molecule; it usually has one unshared pair of electrons

• X is a halogen/leaving group

Good leaving groups are:

very weak bases — KNOW THIS TABLE

Leaving groups =

• A good leaving group is a substituent that can leave as a relatively stable, weakly basic molecule or ion

• Most halides are good leaving groups

• Water is also a good leaving group

  • Usually from a protonated alcohol

2 types of substitution reactions:

SN2 = substitution, nucleophilic, 2nd order kinetics

SN1 = substitution, nucleophilic, 1st order kinetics

Substitution: SN2

• takes place in one step

• It is a bimolecular reaction (nucleophile & alkyl halide in the rate determining step) → 2nd order kinetics

• It has a pentavalent transition state

• Inversion of configuration (R→S or S→R)

• Concerted reaction – bond breaking & forming takes place simultaneously

• Rate = k[CH3Cl][–OH]

  • If the concentration of CH3Cl or –OH doubles, the rate doubles

  • If you double volume = ¼ Rate

SN2 Mechanism:

The nucleophile attacks from the opposite side that the leaving group leaves (backside attack) — So stereochemistry changes

What do the Energy & Reaction graphs looks like for SN2 and SN1?

like the graphs in the imag

SN2 reactions typically work the best for:

 methyl, 1° and 2° alkyl halides — will not happen in tertiary

What do the reactivity schemes look like?

flipped for SN2 and SN1

Substitution: SN1

• takes place in more than one step

• It is a unimolecular reaction (only alkyl halide in the rate determining step) → 1 st order kinetics

• It has a carbocation intermediate

• If the alkyl halide is chiral, the product will be a racemic mixture (50:50 R & S)

• Rate = k[(CH3)3CCl]

What is different about the SN1 rate equation?

only the concentration of the substrate is included

In SN1, the step where the carbo cation forms is considered to be:

slow

Carbocation stability is due to:

Hyperconjugation

What is the most stable carbocation?

tertiary

The SN1 reaction of an alkyl halide with water is an example of:

solvolysis — a reaction in which the nucleophile is a molecule of solvent

Common solutes for Solvolysis:

H2O, MeOH, EtOH, Any Alcohol

Polar protic solvents:

• increase the rate of an SN1 reaction also helps stabilize the intermediate carbocation

• Solvation of the carbocation is that factor

SN1 reactions have a faster rate in strongly:

polar solvents than in less polar solvents

What are polar protic solvents?

liquids that have a high dipole moment and contain a hydrogen atom attached directly to a strongly electronegative atom—most commonly an oxygen (such as in an -OH group) or a nitrogen (such as in an -NH group)

Hammond Postulate:

• In an exergonic step, the transition state resembles the reactant of that step more

• In an endergonic step, the transition state resembles the product of that step more

How do we predict if a reaction follows the SN1 or SN2 pathway?

1. Structure of the alkyl halide (or substrate)

2. Concentration & strength of the nucleophile

3. Effect of solvent

4. Nature of the leaving group

What does the carbocation stability flow look like?

greatest is tertiary & extremely rate is alkenyl

SN1 rxns ___ depend on the strength or concentration of the nucleophile?

do not

SN2 rxns ____ depend on the strength or concentration of the nucleophile?:

do — good nucleophiles react fast; poor nucleophiles react slow

Nucleophilicity is the same as:

basicity when the same atom is involved

• stronger base = better Nu

What is the horizontal trend?

image

What is the vertical trend?

solvent dependent

What is an aprotic solvent?

a liquid that cannot donate a hydrogen atom (proton) for hydrogen bonding, because it lacks acidic hydrogen atoms attached directly to electronegative atoms such as oxygen or nitrogen (no -OH or -NH bonds)

Protic =

has a hydrogen attached to an electronegative element

Aprotic =

does not have a hydrogen attached to an electronegative element (like N, O, or F)

Solvent Effects: SN2

• H-bonding to small nucleophiles is stronger than to larger ones:

  • (largest atom, best Nu) I– > Br– > Cl– > F–

• Nucleophilicity of common nucleophiles in protic solvent:

  • image

• Nucleophilicity in aprotic solvents decrease as you go down a group on the periodic table:

  • (best Nu) F– > Cl– > Br– > I–

SN1: Dielectric constants are a good indication of a solvent’s —

polarity

Dielectric Constant: Hexane

Nonpolar, 1.9

Dielectric Constant: Water

polar protic, 80.4

Dielectric Constant: DMSO

Aprotic, 45

Good leaving groups

Cl-, Br-, I-, H2O

What is a sulfonate and how can it be made?

there are 3 ways to make it and they are used to make alcohols better leaving groups

With sulfonates, stereochemistry is:

retained

 Best leaving groups are:

weak bases after they leave (for example halides: I– > Br– > Cl– >>> F–)

An SN2 reaction with an alcohol requires:

conversion to an alkyl chloride or an alkyl bromide

Summary slide 1

1

Summary slide 2

2