Aryl Halide and Vinyl Halide

Aryl halide and vinyl halide

Aryl Halides

Aryl halides are halides in which the halogen is attached directly to an aromatic ring.

Carbon-halogen bonds in aryl halides are shorter and stronger than carbon-halogen bonds in alkyl halides.

X

What’s the Difference Between Ar- and Ph-?

Phen yl refers specifically to this:

Aryl is a general term for all aromatic ring systems:

C

N

N

O

Nomenclature Aryl halides are named by prefixing the name of the halogen to benzene. For example:

Numbering of the ring begins at the halogen-substituted carbon and proceeds in the direction of the next substituted carbon that possesses the lower number.

Ortho, meta or para ? Mono-substituted aryl halides are characterised using the prefix ortho (o-), meta (m-) or para (p-) depending on the placement of the substituent from the halogen or the halogen from a higher priority functional group: 1,2-, 1,3- or 1,4- respectively.

Cl

1-chloro-2-ethylbenzene or o-ethylchlorobenzene

Cl

1-chloro-3-ethylbenzene or m-ethylchlorobenzene

Cl

1-chloro-4-ethylbenzene or p-ethylchlorobenzene

Cl

O

N

Br

I

Br

BrBrBr

OMe

O

Cl

1-(3-chlorophenyl)ethanone4-bromo-N ,N-dimethylaniline

(E)-1-iodo-2-(prop-1-enyl)benzene

1,2,3-tribromobenzene

2-bromobiphenyl

methyl 2-(3-chlorophenyl)acetate

Physical properties

The physical properties of unsubstituted aryl halides are much like those of the corresponding alkyl halides.

Thus, boiling points, melting points, and solubilities of aryl halides are very similar to those of alkyl halides containing the same number of carbon atoms.

Boiling points

Chlorobenzene, bromobenzene and iodobenzene are all oily liquids. The boiling points increase as the halogen atom gets bigger.

Compounds boiling point (°C)

C6H5Cl 132

C6H5Br 156 C6H5I 189

The main attractions between the molecules will be van der Waals dispersion forces. These increase as the number of electrons in the molecule increases. This is the reason that the boiling points increase as the halogen atom gets bigger.

There will also be permanent dipole-dipole attractions involved in the chlorobenzene and bromobenzene, but very little in the iodobenzene. Iodine has much the same electronegativity as carbon.

Solubility in waterThe aryl halides are insoluble in water. They are denser than water and form a separate lower layer.

The molecules are quite large compared with a water molecule. In order for chlorobenzene to dissolve it would have to break lots of existing hydrogen bonds between water molecules and also have to break the quite strong van der Waals dispersion forces between chlorobenzene molecules. Both of these cost energy.

The only new forces between the chlorobenzene and the water would be van der Waals dispersion forces.

These aren't as strong as hydrogen bonds (or the original dispersion forces in the chlorobenzene), and so wouldn't get much energy released when they form.

It simply isn't energetically profitable for chlorobenzene (and the others) to dissolve in water.

Resonance Picture

C-X bonds in aryl halides have more double bond character than C-X bonds in alkyl halides

Synthesis of Aryl HalidesThe two most common methods of preparing aryl halides are by direct halogenation of benzene and via diazonium salt reactions.

Preparing chlorobenzene and bromobenzene by reacting chlorine or bromine with benzene, and preparing iodobenzene from benzenediazonium chloride.

Preparation of Chlorobenzene

Benzene reacts with chlorine in the presence of a catalyst, replacing one of the hydrogen atoms on the ring by a chlorine atom.

The reaction happens at room temperature. The catalyst is either aluminium chloride or iron.

Strictly speaking iron isn't a catalyst, because it gets permanently changed during the reaction. It reacts with some of the chlorine to form iron(III) chloride, FeCl3.

The reaction between benzene and chlorine in the presence of either aluminium chloride or iron gives chlorobenzene.

Preparation of BromobenzeneThe reaction between benzene and bromine in the presence of either aluminium bromide (rather than aluminium chloride) or iron gives bromobenzene.

Iron is usually used because it is cheaper and more readily available. If we use iron, it is first converted into iron(III) bromide by the reaction between the iron and bromine.

Preparation of Iodobenzene

Iodobenzene can be made from the reaction of benzene with iodine if they are heated under reflux in the presence of concentrated nitric acid, but it is normally made from benzenediazonium chloride solution. That's what we will concentrate on here.

If you add cold potassium iodide solution to ice-cold benzenediazonium chloride solution, nitrogen gas is given off, and you get oily droplets of iodobenzene formed.

There is a simple reaction between the diazonium ions present in the benzenediazonium chloride solution and the iodide ions from the potassium iodide solution.

PrimaryArylamine

Aryl DiazoniumSalt

NH H

N

NaNO2

HCl, H2O

N

KI

roomtemp.

Aryl Iodide

I

Me Me Me

Cl

o-toluidine

Sandmeyer reaction

A second method for preparing aryl halides is the Sandmeyer reaction.

During a Sandmeyer reaction, a diazonium salt reacts with copper (I) bromide, copper (I) chloride, or potassium iodide to form the respective aryl halide.

The diazonium salt is prepared from aniline by reaction with nitrous acid at cold temperatures.

PrimaryArylamine

Aryl DiazoniumSalt

NH H

N

NaNO2

HCl, H2O

N

CuCl

heat

Aryl Chloride

Cl

N+

O–

ON+

O–

ON+

O–

O

Cl

An aromatic (or heterocyclic) amine quickly reacts with a nitrite to form an aryl diazonium salt, which decomposes in the presence of copper(1) salts, such as copper (1)b chloride, to form the desired aryl halide.The reaction is a radical nucleophilic aromatic substitution

Reactions of alkyl halides 1. SN2 NR

2. E2 NR

3. organo metallic compounds similar

4. reduction similar

C C X

X

aryl halide

vinyl halide

Ag+

-OH

-OR

NH3

-CN

ArH

AlCl3

NO REACTION

Bond Lengths (Å)

C—Cl C—Br

CH3—X 1.77 1.91

C2H5—X 1.77 1.91 sp3

(CH3)3C—X 1.80 1.92

CH2=CH—X 1.69 1.86

C6H5—X 1.69 1.86sp2

•In aryl halides, the carbon to which the halogen is attached is sp2 hybrizided. The bond is stronger and shorter than the carbon-halogen bond in aliphatic compounds where the carbon is sp3 hybridized.

•Hence it is more difficult to break this bond and aryl halides resist the typical nucleophilic substitution reactions of alkyl halides.

•The same is true of vinyl halides where the carbon is also sp2 hybridized and not prone to nucleophilic substitution.

•In a manner analogous to the phenols & alcohols, we have the same functional group in the two families, aryl halides and alkyl halides, but very different chemistries.

Aryl halides, reactions:1. Formation of Grignard reagent

2. EAS (Electrophilic aromatic substitution)

3. Nucleophilic aromatic substitution (bimolecular displacement)

(Ar must contain strongly electron withdrawing groups ortho and/or para to X)

4. Nucleophilic aromatic substitution (elimination-addition)

(Ring not activated to bimolecular displacement)

1) Preparation of Grignard reagent

Br

Cl

Mg

Mg

anhyd. Et2O

THF

MgBr

MgCl

Overall an electrophilic aromatic susbtitution (EArS) can be represented as follows:

2) EAS

There are three fundamental components to an electrophilic aromatic substitution mechanism:

1.formation of the new σ bond from a C=C in the arene nucleophile2.removal of the proton by breaking the C-H σ bond3.reforming the C=C to restore the aromaticity

The mechanism is represented by the following series of events:

1.Formation of the reactive electrophile, E+from the reagents.

2.Slow reaction of the arene C=C with the E+ to give a resonance stabilised carbocation.

3. Loss of H+ from the carbocation to restore the C=C and the aromatic system

The reaction of the electrophile E+ with the arene is the slow step since it results in the loss of aromaticity even though the resulting cation is still resonance stablised. This carbocation is also described as the cyclohexdienyl cation or arenium ion or as a sigma-complex.

Electrophilic Aromatic Substitution of Aryl Halides

1. Aryl halides are themselves reactive towards EAS but they are less reactive than benzene.

2. This is because halides are weak deactivators3. Halides direct subsequent reactions ortho, para.4. This makes them a little unusual (activators are usually ortho, para-directing,

deactivators meta-directing).5. The weak deactivation is due to the electronegativity of the halogen making the

intermediate cations less stable than those produced when benzene undergoes substitution:

The directing effect is due to the resonance stabilisation of the cationic intermediates derived by ortho or para attack but not by meta attack. For example, the stabilisation during ortho attack is shown below :

However, aryl halides can undergo many of the same electrophilic aromatic substitution reactions that benzene can including nitration, sulfonation, further halogenation and Friedel-Crafts alkylation or acylation reactions.

The –X group is electron-withdrawing and deactivating in EAS, but is an ortho/para director.

Br

HNO3, H2SO4

H2SO4,SO3

Br2,Fe

CH3CH2-Br, AlCl3

+

+

+

+

Br Br

Br

Br Br

Br

NO2

SO3H

Br

CH2CH3

Br

NO2

Br SO3H

Br CH2CH3

Aryl halides and vinylic halides are relatively unreactive toward nucleophilic substitution under conditions that give facile nucleophilic substitution with alkyl halides.

Reason:

(1) Phenyl cations are very unstable. (2) Halogen bonds of aryl (and vinylic) halides are shorter and stronger than those of alkyl, allylic, and benzylic halides because of the hybridized state and the resonance.

But aryl halides can be remarkably reactive toward nucleophiles if they bear certain substituents or when we allow them to react under the proper conditions.

3) Nucleophilic aromatic substitution (bimolecular displacement)

Chapter 21 32

• Aryl Halides and Nucleophilic Aromatic Substitution

• Simple aryl and vinyl halides do not undergo nucleophilic substitution

• Back-side attack required for SN2 reaction is blocked in aryl halides

Chapter 21 33

• SN2 reaction also doesn’t occur in aryl (and vinyl halides) because the carbon-halide bond is shorter and stronger than in alkyl halides

– Bonds to sp2-hybridized carbons are shorter, and therefore stronger, than to sp3-hybridized carbons

– Resonance gives the carbon-halogen bond some double bond character

bimolecular displacement (nucleophilic aromatic substitution)

mechanism:

1) + :ZXX

ZRDS

X

Z2) Z + :X

X

Z

Z

X

Z

X

Z

X

Z

X

Z

X

G

G

If G is an electron withdrawing group in the ortho andpara positions, it will stabilize the intermediate anion.

NUCLEOPHILIC AROMATIC SUBSTITUTION BY ADDITION – ELIMINATION: THE SNAr MECHANISM

Nucleophilic substitution can occur when strong electron-withdrawing groupsare ortho or para to the halogen atom.

Cl

NO2

OH

NO2

+ OH- aq. NaHCO3

130¡æ

H+

Cl

NO2

NO2

OH

NO2

NO2

+ OH- aq. NaHCO3

100¡æ

H+

Cl

NO2

NO2

O2N

OH

NO2

NO2

O2N

+ OH- aq. NaHCO3

35¡æ

H+

The temperature is related to the number of ortho or para nitro groups

But the meta-nitro group does not produce a similar activating effect.

Mechanism:

Cl

NO2

+ OH- additionslow

OHCl

NO2

elimination

fastOH-

+ Cl-

O-

NO2

OH

NO2

+ Cl-

HO Cl

NO O

HO Cl

NO O

HO Cl

NO O

HO Cl

NO O

The delocalized carbanion is stabilized by electron-withdrawing groups in the positions ortho and para to the halogen atom.

CF3

ClNaNH2

NH3

CF3

NH2

m-(Trifluoromethyl)aniline(¶Ô-Èý·ú¼×»ù±½°±£©

Addition-Elimination Mechanism

Two step mechanism:

Step 1

nucleophile attacks aryl halide and bonds to the carbon that bears the halogen(slow: aromaticity of ring lost in this step)

Step 2

intermediate formed in first step loses halide(fast: aromaticity of ring restored in this step)


Step 1 - AdditionStep 1 - Addition

bimolecular

consistent with second-order kinetics;

first order in aryl halide, first order in nucleophile

Rate = k [CH3ONa] [arene]


Step 1 - AdditionStep 1 - Addition

intermediate is negatively charged

formed faster when ring bears electron-withdrawing groups such as NO2 because negative charge is stabilized……..

Reaction Involves an Anionic Intermediate

Stabilization of Addition Productby Electron-Withdrawing Group

Rapid Collapse of CyclohexadienylAnion Intermediate

Step 2 - EliminationStep 2 - Elimination

•carbon-halogen bond breaking does not occuruntil after the rate-determining step

•electronegative F stabilizes negatively charged intermediate

F > Cl > Br > I is unusual, but consistentF > Cl > Br > I is unusual, but consistentwith mechanismwith mechanism

The Role of Leaving Groups

The Role of Leaving Groups

Cl

NO2

OH

NO2

Cl

NO2

NO2

OH

NO2

NO2

O2N O2N

Cl

+ NaOH NR

350oC, 4500 psi H+

OH

15% NaOH, 160oC H+

warm water

Cl

NO2

NH2

NO2

Cl

NO2

NO2

NH3

NO2

NO2

O2N O2N

Cl NH2

NH3, 170oC

NH3, room temp.

NH3, Cu2O, 200oC, 900 psi

NO2 NO2

49

– Nucleophilic Aromatic Substitution through an Elimination-Addition Mechanism: Benzyne

• Under forcing conditions, chlorobenzene can undergo an apparent nucleophilic substitution with hydroxide

– Bromobenzene can react with the powerful base amide

Chapter 21 50

• The reaction proceeds by an elimination-addition mechanism through the intermediacy of a benzyne (benzene containing a triple bond)

Chapter 21 51

A calculated electrostatic potential map of benzyne shows added electron density at the site of the benzyne bond

– The additional bond of benzyne is in the same plane as the ring

• When chlorobenzene labeled at the carbon bearing chlorine reacts with potassium amide, the label is divided equally between the C-1 and C-2 positions of the product

– This is strong evidence for an elimination-addition mechanism and against a straightforward SN2 mechanism

Chapter 21 53

Benzyne can be generated from anthranilic acid by diazotization

– The resulting compound spontaneously loses CO2 and N2 to yield benzyne

– The benzyne can then be trapped in situ using a Diels-Alder reaction

Phenylation

Acetoacetic esters and malonic esters can be phenylated by benzyne generated in situ from bromobenzene

1. Preparation of vinyl halides

Example of a vinyl halide:

RCl Cl

Example of an aryl halide:

a. Halogenation of alkynesb. Hydrohalogenation of alkynesc. Elimination in dihaloalkanesd. SEAr - halogenation

2. Elimination in aryl and vinyl halides

These reactions never proceed by E1 because of low stability of aryl and vinyl carbocations.Vinyl halides are much less reactive in E2, than alkyl halides because of a stronger C(sp2)-Cl bond .

RBr KOH, 200 oC

R H

Cl

O

NaOCH3

H3CO

O

-OCH3

Cl

O-H3CO

3. Substitution in vinyl halides

This reaction proceeds through addition, followed by elimination. It never goes via SN2, because of the lack of stabilization of the transition state. (Same reason, why vinyl cations are less stable, than alkyl cations.)

Write a structural formula for each of the following:

(a)m-Chlorotoluene (b)1-Chloro-1-phenylethane(c)p-Bromobenzyl chloride(d) 2-Chloronaphthalene(e) 1,8-Dichloronaphthalene(f) 2-Bromo-1-chloro-4-nitrobenzene

Latihan

Reactions Involving Aryl Halides

Electrophilic aromatic substitution

Bromobenzene

Br BrBrOH

(hypobromousacid) Br

Br

Br

Br

Br

35.7% 1.0% 64.3%

halide substituents are ortho-para directing & deactivating


Electrophilic aromatic substitution (Section 12.14)

ADD DDT SYNTHESIS


Formation of aryl Grignard reagents (Section 14.4)

Bromobenzene

Br MgBrMg

Et2O

Phenylmagnesiumbromide

Substitution Reactions Involving Aryl Halides

We have not yet seen any nucleophilic substitution reactions of aryl halides.

Nucleophilic substitution on chlorobenzene occurs so slowly that forcing conditions are required.

Nucleophilic Substitution of Chlorobenzene

Cl OH

(97%)

1. NaOH, H2O 370C

2. H+

This reaction does not proceed via SN2……..

•the SN2 is not reasonable because the aromatic ring blocks back-side approach of the nucleophile. Inversion is not possible.

Why is Chlorobenzene Unreactive?

SN1 Also Unlikely:Aryl Cations are Highly Unstable

Cl

C

Cl

SN1

emptysp2 orbital

Aryl Cation

SN1 not reasonable because:

1) C—Cl bond is strong; therefore, ionization to a carbocation is a high-energy process

2) aryl cations are highly unstable

What is the Mechanism of This Reaction?

Cl OH

(97%)

1. NaOH, H2O 370C

2. H+

23.5Nucleophilic

Substitution inNitro-Substituted Aryl

Halides

Aryl Halide and Vinyl Halide

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