Structure of Haloalkanes• Haloalkane (alkyl halide): A compound

containing a halogen atom covalently bonded to an sp3 hybridized carbon.• often represented as RX

Haloalkanes

Nomenclature of Haloalkanes• Locate the parent alkane.• Locate each halogen on the parent chain.• Number the parent chain to give the substituent

encountered first the lower number.• Show halogen substituents by the prefixes

fluoro-, chloro-, bromo-, and iodo- and list them in alphabetical order with other substituents.

Common names of haloalkanes• Several polyhaloalkanes are common solvents

and are generally referred to by their common or trivial names.

• Simple haloalkanes can also be named as alkyl halides. • The focus is the halogen atom (fluoride, chloride,

bromide or iodide) and becomes the second half of the name.

• The carbon branch attached to the halogen is named as usual and becomes the first half of the name.

CH3F

H2CH3C Br

CH3C I

CH3

CH3

methyl fluoride

IUPAC: fluoromethane

ethyl bromide

IUPAC: bromoethane

t-butyl iodide

IUPAC: 2-iodo-2-methyl propane

Some Applications of Haloalkanes• Refrigerants

• Freons are chlorofluorocarbons (CFCs)• Release of CFC gases into the atmosphere contributes to

ozone destruction.• Montreal Protocol is an international treaty (1989) to

phase-out use of CFCs.

• Much lower ozone-depleting alternatives are the hydrofluorocarbons (HFCs) and the hydrochlorofluorocarbons (HCFCs).

• Solvents• Methylene chloride, chloroform, trichlor, carbon

tetrachloride (among others) are used to dissolve grease (in machine shops and dry cleaners!).

• Propellents• HFC-134a (1,1,1,2-tetrafluoroethane) is used as a

propellent in “canned air”.

• Anesthetics• Many hydrochlorofluorocarbons are using in anesthesia. • The earliest anesthetics were ethers; thus, many modern

anesthetics are halogenated ethers.

O

CHF2

F3C

Cl

isoflurane

O

CHF2

F3C

F

desflurane

O

CHF2

F3C

CF3

sevoflurane

Reactions of Haloalkanes

• Nucleophilic substitution (SN1 or SN2)

• -elimination (E1 or E2)

Nucleophilic Substitution

• Substitution takes place on an sp3 hybridized (tetrahedral) carbon.

• Nucleophile attacks carbon making a new bond.• Functional group that is being replaced is called

the leaving group.

Examples of Nucleophiles and their Products

Nucleophilic Substitution Mechanisms SN2 Mechanism

• Chemists propose two limiting mechanisms for nucleophilic substitutions.• A fundamental difference between them is the timing

of bond breaking and bond forming steps.

• At one extreme, the bond making and bond breaking take place simultaneously

• Such a reaction is designated SN2.• S = substitution• N = nucleophilic• 2 = bimolecular (two species are involved in the rate-

determining step)• rate = k[haloalkane][nucleophile]

• Both reactants are involved in the creation of the transition state of the rate-determining step.

• The nucleophile attacks the reactive center from the side opposite the leaving group. The key step is reaction of a nucleophile and an electrophile to form a new covalent bond.

http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.html

• The product of an SN2 reaction at a stereocenter maintains a specific chirality.

The Energy Diagram for the SN2 Reaction

• Note the transition state has a carbon with 5 bonds (high energy, indeed!).

• No intermediate is formed.

• In the other limiting mechanism, bond breaking between carbon and the leaving group is entirely completed before bond forming with the nucleophile begins.

• This mechanism is designated SN1 where• S = substitution• N = nucleophilic• 1 = unimolecular (only one species is involved in the

rate-determining step)• rate = k[haloalkane]

SN1 Mechanism

• SN1 is illustrated by the solvolysis of tert-butyl bromide.• Step 1: Break a bond to form a stable ion or

molecule. Ionization of the C-X bond gives a carbocation.

• Step 2: Reaction of a nucleophile and an electrophile to form a new covalent bond.

• Step 3: Take a proton away (deprotonation). Proton transfer to methanol completes the reaction.

The Energy Diagram for the SN1 Reaction

• Note the formation of two transition states.• Note especially the formation of a carbocation

intermediate.• The formation of the carbocation in an SN1 reaction is

the key distinction between it and an SN2 reaction.

• For an SN1 reaction at a stereocenter, the product is a racemic mixture.• The carbocation is planar so that the

nucleophile can attack either side of the intermediate.

Determination of Reaction Path in SN Reactions

• Whether an alkyl halide substrate reacts with a nucleophile according to an SN1 or SN2

mechanism depends on several factors.1. Structure of the nucleophile

2. Structure of the haloalkane

3. Structure of the leaving group

4. Polarity of the solvent

1. The Nucleophile

• Nucleophilicity: a kinetic property measured by the rate at which a Nu: attacks a reference compound under a standard set of experimental conditions.• For example, nucleophilicity could be measured by

examining the rate at which a set of Lewis bases displaces bromide ion from bromoethane in ethanol at 25 °C.

• Those Lewis bases that yield faster reaction rates are better nucleophiles.

• OH- will react with CH3CH2Br faster than NH3. Therefore, OH- is better nucleophile than NH3.

• Judging good nucleophiles from poor• A species with a negative charge is a stronger nucleophile

than a neutral molecule.• RS- is better than RSH.

• Nucleophilicity usually increases going down a column on the periodic table because of increasing size and polarizability.• RO- < RS- < RSe- < RTe-

• Nucleophilicity vs. basicity. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic.• I- is an excellent nucleophile, but a very weak base.

• A bulkier nucleophile is a weaker nucleophile.• (C2H5)3N is a weaker nucleophile than NH3.

• Good vs. poor nucleophiles (An SN2 reaction needs a good nucleophile; whereas an SN1 reaction does not.)

• Common nucleophiles and their nucleophilicity

2. The Haloalkane Substrate

• SN1 reactions • Governed by electronic factors, namely the relative

stabilities of carbocation intermediates.• Relative rates: 3° > 2° > 1° > methyl• Tertiary and secondary alkyl halides get substituted

via this mechanism

• SN2 reactions• Governed by steric factors, namely the relative ease

of approach of the nucleophile to the site of reaction.• Relative rates: methyl > 1° > 2° > 3°• Methyl, primary and sometimes secondary alkyl

halides get substituted via this mechanism.

• Steric factors• Compare access to the reaction center in

bromoethane and 2-bromo-2-methylpropane (tert-butyl chloride).

• Effect of electronic and steric factors in competition between SN1 and SN2 reactions of haloalkanes.

3. The Leaving Group• The best leaving groups are very weak bases,

e. g., the halogens I–, Br–, and Cl– are excellent leaving groups

• OH–, RO–, and NH2– are such poor leaving

groups that they are rarely if ever displaced in nucleophilic substitution reactions.

• Hydroxide ion, OH–, is a poor leaving group. • However, the –OH group of an alcohol can be

transformed into an excellent leaving group, H2O, if the –OH group is first protonated by an acid to form —OH2

+.

4. The Solvent

• Protic solvent: a solvent that contains an

–OH group and is a hydrogen bond donor.

• Polar aprotic solvent: A solvent that does not contain an –OH group and is not a hydrogen bond donor. • Polar aprotic solvents favor SN2 reactions.

• Formation of carbocations is more difficult in polar aprotic solvents.

Summary of SN1 and SN2 Reactions of Haloalkanes

• Example: Predict the product of each reaction, its mechanism, and the stereochemistry of the product.

-Elimination

-Elimination: Removal of atoms or groups of atoms from adjacent carbons to form a carbon-carbon double bond.• We study a type of -elimination called

dehydrohalogenation (the elimination of HX).• The label “” implies that a functional group and a

hydrogen atom on the second carbon away from the functional group are being eliminated.

• Zaitsev’s rule: The major product of a -elimination is the more stable (the more highly substituted) alkene. When cis-trans isomerism is possible, the trans isomer is favored.

• There are two limiting mechanisms for -elimination reactions.

• E1 mechanism: at one extreme, breaking of the C-X bond is completed before reaction with base breaks the C-H bond.• Only R-X is involved in the rate-determining step.• Formation of carbocation makes the reaction rate

unimolecular.

• E2 mechanism: at the other extreme, breaking of the C-X and C-H bonds is concerted.• Both R-X and base are involved in the rate-determining

step.• Since both substances are involved in the creation of

the transition state, the reaction is bimolecular.

• Step 1: Break a bond to give a stable molecule or ion. Rate-determining ionization of C-X gives a carbocation intermediate and halide ion.

Elimination Reaction Mechanisms

E1 Mechanism

• Step 2: Take a proton away. Proton transfer from the carbocation to a base (in this case, the solvent) gives the alkene.

E2 Mechanism• A one-step mechanism; all bond-breaking and bond-

forming steps are concerted. Simultaneously (1) take a proton away and (2) break a bond to form a stable ion or molecule.

Summary of Elimination Reactions

Substitution versus Elimination• Because many nucleophiles are also strong bases

(OH– and RO–), SN and E reactions often compete.

• The ratio of SN/E products depends on the relative rates of the two reactions.

SN1 versus E1

• Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products. Product ratios are difficult to predict.

SN2 versus E2

• It is a little bit easier to predict the ratio of SN2 to E2 products.• Stronger bases (such as NH2

-), lead to E2.

• Bulky bases (such as (CH3)3CO-), lead to E2

• More branching near the and carbons leads to E2.

• Yuck! We used instead of a and instead of b in previous overheads.

Summary of SN versus E for Haloalkanes

• For Methyl and Primary Haloalkanes

• For Secondary and Tertiary Haloalkanes

SN2 SN1 E2 E1

3º << 2º < 1º 3º > 2º >> 1º 3º < 2º < 1º 3º > 2º >> 1º

Strong nucleophile

Weak nucleophile Strong or bulky base required

Weak base

Polar aprotic solvent

Polar protic solvent

Solvent polarity not important

Good ionizing solvent

Rate = k[halide][Nuc]

Rate = k[halide] Rate = k[halide][base]

Rate = k[halide]

1 step, concerted, inversion of configuration

2 steps, C+, racemization

1 step, concerted 2 steps, C+

Substitution – Elimination matrix

Substitution – Elimination flowchart

Summary of SN versus E for Haloalkanes

• Examples: Predict the major product and the mechanism for each reaction.