Chapter 7

Organohalides

• Alkyl halide: a compound containing a halogen atom covalently bonded to an sp3 hybridized carbon atom

– given the symbol RX

• If the halogen is bonded to an sp2 hybridized carbon, the compound is called a vinylic halide

• If the halogen is bonded to a benzene ring, it is called an aryl halide, given the symbol Ar-X

A haloalkene (a vinylic halide)

C C

R

R

X

R

X

A haloarene (an aryl halide)

Naming Alkyl Halides

Step 1: Find the longest chain, and name it as the parent.

Step 2: Number the carbons of the parent chain beginning at the end nearer the first substituent, regardless of whether it is alkyl or halo.

Step 3: Write the name– halogen substituents are indicated by the prefixes fluoro-,

chloro-, bromo-, and iodo- and listed in alphabetical order with other substituents

Preparing Alkyl Halides

1. Addition reactions of HX and X2 with alkenes

2. The reaction of an alkane with Cl2

3. The most general method for preparing alkyl halides is to make them from alcohol

Thionyl chloride

Phosphorus tribromide

• Primary and secondary alcohols are best converted into alkyl halides by treatment with thiony chloride or phosphorus tribromide

Reactions of Alkyl Halides:Grignard Reagents

• Grignard Reagents: alkyl halides react with magnesium metal in ether solvent

• Organometallic compounds

• A Grignard Reagents is formally the magnesium salt, R3C

-+MgX, of a carbon acid, R3C-H, and is a carbon anion, or carbanion

• Carbon anions are very strong bases

Nucleophilic Substitution Reactions

• Alkyl halides react with nucleophiles/bases (such as hydroxide ion); either they undergo

– Substitution of the X group by the neucleophile

– Elimination of HX to yield an alkene

Walden’s cycle of reactions interconverting (+)- and (-)-malic acids.(1896)

• Nucleophilic substitution reaction: a reaction in which one nucleophile is substituted for another

• Nucleophile: an atom or group of atom that can donate a pair of electrons to another atom or group of atom to form a new covalent bond; a Lewis base

• a nucleophile (Nu: or Nu:-) reacts with substrate R-X and

substitutes for a leaving group X:- to yield the product R-Nu

• Two major pathways:– SN1 reaction

– SN2 reaction

• If the nucleophile is negatively charged, the atom donating the pair of electrons in the substitution reaction becomes neutral in the product

• If the nucleophile is uncharged, the atom donating the pair of electrons in the substitution reaction becomes positively charged in the product

The SN2 Reaction

An SN2 reaction takes place in a single step without intermediates when the entering nucleophile attacks the substrate from a direction 180o away from the leaving groupS = substitution

N = nucleophilic

2 = bimolecular

Bond breaking and bond forming occur simultaneously

Rate of SN2 ReactionsAn SN2 reaction takes place in a single step when

substrate and nucleophile collide and react– If we double the concentration of OH-, the frequency of

collision between the two reactants double and the reaction rate also double

– If we double the concentration of CH3Br, the reaction rate doubles

SN2 reactions are said to be Bimolecular reaction Bimolecular reaction because the rate of the reaction depends on the concentrates of two substances– alkyl halide and nucleophile

Stereochemistry of SN2 ReactionsAs the incoming nucleophile attacks the substrate and

begins pushing out the leaving group on the opposite side, the configuration of the molecule inverts (S→R)

Steric effects in SN2 Reactions• Methyl halides (CH3-X) are the most reactive substrates,

followed by primary alkyl halides (RCH2-X)

• Alkyl branching next to the leaving group slows the reaction greatly for secondary halides (R2CH-X)

• Branching effectively halts the reaction for tertiary halide (R3C-X)

Vinylic (R2C=CRX) and aryl (Ar-X) halides are completely unreactive toward SN2 displacement

This lack of reactivity is due to steric hindrance

The leaving groups in SN2 Reactions

• The best leaving groups are those that give the most stable anions (anions of strong acids)

• A halide ion (I-, Br-, Cl-) is the most common leaving groups

• F-, OH-, OR-, and NH2- are rarely found as leaving

groups

The SN1 Reaction

• Most nucleophilic substitutions take place by the SN2 pathway

• The SN1 reaction takes place only – on tertiary substrates

– under neutral or acidic conditions in a hydroxylic solvent (water or alcohol)

• Loss of the leaving group before the incoming nucleophile approaches

• Loss of the leaving group gives a carbocation intermediate

• The reactivity order is 3o>2o>1o>methyl

? R-OH + HBr → R-Br + H2O

Stereochemistry of SN1 Reactions

• For an SN1 reaction at a stereocenter, the product is a racemic mixture

Rates of SN1 Reactions

• The rate of an SN1 reaction depends only on the concentration of the substrate

The leaving groups in SN1 Reactions

• The SN1 reactivity order of leaving groups is:

Eliminations: The E2 Reaction

1. The nucleophile/base can substitute for the leaving group in an SN1 or SN2 reaction

2. The nucleophile/base can also cause elimination of HX, leading to formation of an alkene

• Zaitsev’s rule: in the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates

• Three different mechanisms

The mechanism of the E2 reaction

Eliminations: The E1 and E1cB Reactions

• E1 mechanism: breaking of the R-X bond is complete before reaction with base to break the C-H bond begins.

• Only R-X is involved in the rate-limiting step

The mechanism of the E1 reaction

• The E1 and SN1 reactions normally occur in competition whenever an alkyl halide is treated in a hydroxylic (protic) solvent with a nonbasic nucleophile

• The E1cB reaction– Take place through a carbanion intermediate

– Have a poor leaving group, such as –OH

– Predominates in biological pathways

A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2

• Primary alkyl halide (RCH2X) reacts by an

– SN2 if a good nucleophile is used

– E2 if a strong base is used (OH-, OR-)– E1cB if the leaving group is two carbons away from a carbonyl

group (HO-C-C-C=O)

• Secondary alkyl halide (R2CHX) reacts by

– SN2 if a weakly basic nucleophile is used

– E2 if a strong base is used

• Tertiary alkyl halide (R3CX) reacts by an – E2 if a strong base is used

– Mixture of SN1 and E1 pathways under neutral or acidic condition