Organohalogen Notes

ORGANOHALOGEN

DR. ROSWANIRA ABDUL WAHAB

DEPARTMENT OF CHEMISTRYFACULTY OF SCIENCE

UNIVERSITI TEKNOLOGI MALAYSIAC18-311

[email protected] 1

Classes of HalidesClasses of Halides

Alkyl: Halogen, X, is directly bonded to sp3 carbon.

Vinyl: X is bonded to sp2 carbon of alkene.

Aryl: X is bonded to sp2 carbon on benzene ring.

Examples:

C

H

H

H

C

H

H

Br

alkyl halide

C CH

H

H

Cl

vinyl halide

I

aryl halide

2

Polarity and ReactivityPolarity and Reactivity

Halogens are more electronegative than C.

Carbon-halogen bond is polar, so carbon has partial positive charge.

Carbon can be attacked by a nucleophile.

Halogen can leave with the electron pair.

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Classes of Alkyl HalidesClasses of Alkyl Halides

Methyl halides: only one C, CH3X

Primary: C to which X is bonded has only one C-

C bond.

Secondary: C to which X is bonded has two C-C

bonds.

Tertiary: C to which X is bonded has three C-C

bonds.

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DihalidesDihalides

Geminal dihalide: two halogen atoms are bonded

to the same carbon

Vicinal dihalide: two halogen atoms are bonded

to adjacent carbons.

C

H

H

H

C

H

Br

Br

geminal dihalide

C

H

H

Br

C

H

H

Br

vicinal dihalide

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IUPAC NomenclatureIUPAC Nomenclature

Name as haloalkane.

Choose the longest carbon chain, even if the

halogen is not bonded to any of those C’s.

Use lowest possible numbers for position.

CH3 CH CH2CH3

Cl CH3(CH2)2CH(CH2)2CH3

CH2CH2Br

2-chlorobutane 4-(2-bromoethyl)heptane

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““Trivial” NamesTrivial” Names

CH2X2 called methylene halide.

CHX3 is a haloform.

CX4 is carbon tetrahalide.

Examples:

CH2Cl2 is methylene chloride

CHCl3 is chloroform

CCl4 is carbon tetrachloride.

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Uses of Alkyl HalidesUses of Alkyl Halides

Solvents - degreasers and dry cleaning fluid

Reagents for synthesis of other compounds

Anesthetic: Halothane is CF3CHClBr

CHCl3 used originally (toxic and carcinogenic)

Freons, chlorofluorocarbons or CFC’s

Freon 12, CF2Cl2, now replaced with Freon 22,

CF2CHCl, not as harmful to ozone layer

Pesticides - DDT

8

PHYSICAL PHYSICAL PROPERTIESPROPERTIES

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Dipole MomentsDipole Moments

= 4.8 x x d, where is the charge (proportional

to EN) and d is the distance (bond length) in

Angstroms.

Electronegativities: F > Cl > Br > I

Bond lengths: C-F < C-Cl < C-Br < C-I

Bond dipoles: C-Cl > C-F > C-Br > C-I

1.56 D 1.51 D 1.48 D 1.29 D

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Boiling PointsBoiling Points

Greater intermolecular forces, higher b.p.

dipole-dipole attractions not significantly

dissimilar for different halides

London forces greater for larger atoms

Greater mass, higher b.p.

Spherical shape decreases b.pt. (due to branching that

lower surface area that reduces intermolecular interaction)

Example:

(CH3)3CBr CH3(CH2)3Br

73C 102C

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12

DensitiesDensities

Alkyl fluorides and chlorides less dense than

water.

Alkyl dichlorides, bromides, and iodides more

dense than water.

13

Preparation of Alkyl HalidesPreparation of Alkyl Halides

Free radical halogenation of alkanes

produces mixtures, not good lab synthesis

unless: all H’s are equivalent, or

halogenation is highly selective.

Free radical allylic halogenation

produces alkyl halide with double bond on

the neighboring carbon.

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Halogenation of AlkanesHalogenation of Alkanes All H’s equivalent. Restrict amount of halogen to

prevent di- or trihalide formation

Highly selective: bromination of 3carbon

+ HBr

H

BrhBr2+

H

H

90%

+ HBrCH3 C

CH3

CH3

Brh

Br2+CH3 C

CH3

CH3

H

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Allylic HalogenationAllylic Halogenation

Allylic radical is resonance stabilized.

Bromination occurs with good yield at the allylic position (sp3 carbon next to C=C).

Avoid a large excess of Br2 by using

N-bromosuccinimide (NBS) to generate Br2 as

product.

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Free radical allylic halogenationFree radical allylic halogenation

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Reaction MechanismReaction Mechanism

Free radical chain reaction– initiation, propagation, termination

H H

BrH

+ HBr

BrBr

H Br

+ Br

2 BrBr2h

19

Preparation of Alkyl Halides (2)Preparation of Alkyl Halides (2)

b)b) Halogenation of Alkene (Addition of HX)Halogenation of Alkene (Addition of HX)

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c) Halogenation of Alkene (Addition of Halogens)c) Halogenation of Alkene (Addition of Halogens)

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d) RX from ROH (alcohol)d) RX from ROH (alcohol)

(Reaction with HX)(Reaction with HX)

22

(Reaction with HCl – Lucas Test)(Reaction with HCl – Lucas Test)

(Reaction with PBr(Reaction with PBr33))

23

(Reaction with SOCl(Reaction with SOCl22))

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REACTIONS OFREACTIONS OF ALKYL HALIDESALKYL HALIDES

25

Nucleophilic Substitution & Nucleophilic Substitution & Elimination ReactionsElimination Reactions

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Nucleophilic Substitution ReactionsNucleophilic Substitution Reactions

The halogen atom on the alkyl halide is replaced with

another group.

Since the halogen is more electronegative than carbon, the

C-X bond breaks heterolytically and X- leaves; halide is a

good leaving group (conjugate base for strong acid).

The group replacing X- is a nucleophile.

C C

H X

+ Nuc:-C C

H Nuc

+ X:-

27

What are Nucleophiles? Species rich in electrons

(in the form of -ve charge, lone pair of electrons, or )

Eg: a) Strong Nu-: NaOH, NaBr, NaOCH3, NaNH2, HCN

b) Weak Nu-: NH3, H2O, ROH, RNH2

The –vely charge Nu- in (a) have more electrons and therefore are stronger Nu- than neutral molecules in (b) with just lone pair of electrons, meaning (a) can react by donating its electrons much easier than (b).

Also I- > Br-> Cl-.

* Spesies in (a) can attack neutral R-X since it is a strong Nu- but

* Species in (b) prefers attacking a charged R-X in order to react since it is less powerful Nu- (since it itself is still a neutral molecule).

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Second-Order Nucleophilic Substitution: Second-Order Nucleophilic Substitution: The SThe SNN2 Reaction2 Reaction

SN2 : substitution, nucleophilic, bimolecular

hydroxide ion is a strong nucleophile (donor of an

electron pair)

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SSNN2 Mechanism2 Mechanism

Bimolecular Bimolecular : the transition state of the rate-limiting step

involves the collision of two molecules.

Concerted reactionConcerted reaction: new bond forming and old bond

breaking at same time.30

SSNN2: Reactivity of Substrate2: Reactivity of Substrate Carbon must be partially positive.

Must have a good leaving group

Carbon must not be sterically hindered.

31

Structure of SubstrateStructure of Substrate

Relative rates for SN2:

CH3X > 1° > 2°

Tertiary (3) halides do not react via the SN2 mechanism, due to steric hindrance.

32

Uses for SUses for SNN2 Reactions2 Reactions Synthesis of other classes of compounds. Halogen exchange reaction.

33

Nucleophilic StrengthNucleophilic Strength Steric EffectsSteric Effects Solvent EffectsSolvent Effects

Stronger nucleophiles react faster.

Strong bases are strong nucleophiles, but not all

strong nucleophiles are basic.

FACTORS AFFECTING SFACTORS AFFECTING SNN2 REACTIONS:2 REACTIONS:

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35

A base is always a stronger nucleophile than its A base is always a stronger nucleophile than its conjugate acidconjugate acid

36

BasicityBasicity is defined by the equilibrium constant for abstracting a proton.

NucleophilicityNucleophilicity is defined by the rate of attack on an electrophilic carbon atom.

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a) A species with a negative charge is a stronger

nucleophile than a similar neutral species. In particular, a

base is a stronger nucleophile than its conjugate acid.

OH- > H2O, NH2- > NH3

b) Nucleophilicity decreases from left to right in the

periodic table, following the increase in

electronegativity from left to right. The more electronegative

elements have more tightly held

nonbonding electrons that are less reactive toward

forming new bonds.

OH- > F-, NH3 > H2O

Trends in Nucleophilic StrengthTrends in Nucleophilic Strength

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Trends in Nucleophilic StrengthTrends in Nucleophilic Strength

c) Nucleophilicity increases down the Periodic Table, following the increase in size and polarizability.

I- > Br- > Cl- > F-

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Polarizability EffectPolarizability Effect

40

Bulky Nucleophiles: Steric EffectsBulky Nucleophiles: Steric Effects

Sterically hindered for attack on carbon, so weaker nucleophiles.

CH3 CH2 O ethoxide (unhindered)weaker base, but stronger nucleophile

C

CH3

H3C

CH3

O

t-butoxide (hindered)stronger base, but weaker nucleophile

41

Solvent Effects (1)Solvent Effects (1)

Polar protic solvents (O-H or N-H) reduce the strength of the nucleophile.

Hydrogen bonds must be broken before nucleophile can attack the carbon.

42

Solvent Effects (2)Solvent Effects (2)

Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile

Examples:

CH3 C Nacetonitrile C

O

H3C CH3

acetone

dimethylformamide (DMF)

CH

O

NCH3

CH3

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Leaving Group AbilityLeaving Group Ability

Electron-withdrawing Stable once it has left Polarizable to stabilize the transition state.

44

SUMMARY OF SSUMMARY OF SNN2 REACTION2 REACTION

Substrate : CH3X > 1 RX > 2 RX (3 RX is not suitable)

Nucleophile: Strong nucleophile

Solvent: Less polar solvent

Rearrangement: Impossible (one step reaction)

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Tertiary (3) halides do not react via the SN2 mechanism, due to steric hindrance.

46

Unimolecular nucleophilic substitution. Two step reaction with carbocation intermediate.

First-Order Nucleophilic Substitution: First-Order Nucleophilic Substitution: The SThe SNN1 Reaction1 Reaction

47

Reactivity of SReactivity of SNN1 Reactions1 Reactions

3° > 2° > 1° >> CH3X

Order follows stability of carbocations (opposite to SN2)

More stable ion requires less energy to form

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Better leaving group, faster reaction (prefer SN2)

Polar protic solvent best: It solvates ions strongly with hydrogen bonding.

49

Rearrangements of CarbocationsRearrangements of Carbocations

Carbocations can rearrange to form a more stable

carbocation.

Hydride shift: H- on adjacent carbon bonds with C+.

Methyl shift: CH3- moves from adjacent carbon if

no H’s are available.

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51

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Hydride ShiftHydride Shift

CH3 C

Br

H

C

H

CH3

CH3CH3 C

H

C

H

CH3

CH3

CH3 C

H

C

H

CH3

CH3CH3 C

H

C

CH3

CH3

H

CH3 C

H

C

CH3

CH3

HNuc

CH3 C

H

C

CH3

CH3

H Nuc

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Methyl ShiftMethyl Shift

CH3 C

Br

H

C

CH3

CH3

CH3CH3 C

H

C

CH3

CH3

CH3

CH3 C

H

C

CH3

CH3

CH3CH3 C

H

C

CH3

CH3

CH3

CH3 C

H

C

CH3

CH3

CH3

NucCH3 C

H

C

CH3

CH3

CH3 Nuc

54

SUMMARY OF SSUMMARY OF SNN1 REACTIONS1 REACTIONS

Substrate : benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely)

Nucleophile: weak nucleophile

Solvent: polar protic solvent

Rearrangement: common to form most stable carbocation

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Elimination ReactionsElimination Reactions

The alkyl halide loses halogen as a halide ion, and

also loses H+ on the adjacent carbon to a base.

A pi bond is formed. Product is alkene.

Also called dehydrohalogenation (-HX).

C C

H X

+ B:- + X:- + HB C C

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Unimolecular elimination

Two groups lost (usually X- and H+)

Nucleophile acts as base (weak base)

Also have SN1 products (mixture)

First-Order Elimination: First-Order Elimination: The E1 ReactionThe E1 Reaction

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58

E1 MechanismE1 Mechanism

Halide ion leaves, forming carbocation.

Base removes H+ from adjacent carbon.

Pi bond forms. 59

Draw both of substitution and elimination mechanism of following reaction:

CH3

H3C Br

CH3

and CH3OH

60

SUMMARY OF E1 REACTIONSSUMMARY OF E1 REACTIONS

Substrate : benzyl > allyl > ~3 RX > 2 RX (1 RX and CH3X are unlikely)

Nucleophile: weak base

Solvent: polar protic solvent

Kinetics: first-order rate equation, kr [RX]

Stereochemistry: no particular geometry

Rearrangement: common to form most stable carbocation

Product follows Saytzeff’s rule (alkene) 61

Saytzeff’s RuleSaytzeff’s Rule

If more than one elimination product is possible,

the most-substituted alkene is the major product

(most stable).

R2C=CR2>R2C=CHR>RHC=CHR>H2C=CHR

tetra > tri > di > mono

C C

Br

H

C

H

CH3

H

H

H

CH3

OH-

C CH

HC

H H

CH3

CH3

C

H

H

H

C

H

CCH3

CH3

+

minor major

62

Bimolecular elimination

Requires a strong base

Halide leaving and proton abstraction happens

simultaneously - no intermediate.

Second-Order Elimination: Second-Order Elimination: The E2 ReactionThe E2 Reaction

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E2 MechanismE2 Mechanism

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Stereochemistry of E2Stereochemistry of E2

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SUMMARY OF E2 REACTIONSSUMMARY OF E2 REACTIONS

Substrate : benzyl > allyl > ~3 RX > 2 RX (poor SN2 substrate)

(1 RX and CH3X are unlikely)

Nucleophile: strong base

Solvent: polarity is not so important

Rearrangement: none

Product follows Saytzeff’s rule (alkene)

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Substitution or EliminationSubstitution or Elimination

Strength of the nucleophile determines order:

Strong nuc. will go SN2 or E2.

Primary halide usually SN2.

Tertiary halide mixture of SN1, E1 or E2

High temperature favors elimination

Bulky bases favor elimination

Good nucleophiles, but weak bases, favor

substitution.

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Strong Bases Weak Bases

Good Nucleophiles HO-, RO- (if R is not bulky)RCC:-

I-, Br-, RS-, CN-, N3-

Poor Nucleophiles K+ -OC(CH3)3

other hindered alkoxidesCl-, F-, RCO2

-

H2O, ROH, RCO2H

Type of Alkyl Halide Nucleophile/Base Mechanism 1o strong or weak, non-bulky SN2 1o strong and bulky E2(Note: even with a non-bulky base, it is also possible to force elimination in 1o by heating)

2o good nucleophile, weaker base SN2 (e.g. RS-, I-) 2o weak nucleophile, weak base SN1 (e.g. H2O, ROH) 2o strong base, weaker nucleophile E2 (e.g RO-) 69

3o weak nucleophile, weak base SN1 and some E13o stronger base or stronger nucleophile E2

(Notes : SN2 never occurs for 3o because of steric hindrance; carbocations are formed easily in 3o halides)

Type of Alkyl Halide Nucleophile/Base Mechanism

70

Visual tests for alkyl halides

a) Reagent AgNO3 / ethanol

This reaction proceeds by abstracting a halogen by the Ag+ to form carbocation. Therefore it is an SN1 type of reaction. Thus we can use this reaction to differentiate classes of alkyl halides & types of halogen.

Since SN1: benzylic~ allylic> 3o > 2o > 1o.

CH2X+ AgNO3

ethanolAgX + CH2+

+ AgNO3AgX +CH2=CH CH2X CH2=CH CH2

+

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Observations:

i) Immediate precipitation with benzylic, allylic

and 3o R-X.

ii) Precipitate formed after 5 mins with 2o R-X.

iii) No reaction with aryl or vinyl R-X!

iv) This reagent can also differentiate between the type of

halogens present in the halides.

Eg: AgCl = white, AgBr & I = pale yellow72

b) Reagent NaI/ acetone

This reaction proceeds by displacement of bromide ion by the I- ions (strong Nu-), thus it is an SN2 type of reaction. Therefore is used to differentiate classes of R-Br.

Sequence of reactivity:

1o > 2o> 3o. No reaction with aryl or vinyl R-X.

R-CH2-Br + NaI R-CH2-I + NaBr (precipitate)

R2-CH-Br + NaI precipitate after 5 minutes

R3-C-Br + NaI very slow 73

I) Is there strong base?

If YES, there is strong base:A) There will be no E1/SN1.B) The products will come from E2 and/or SN2, depending upon the halide:

1) 1º halides give SN2 unless they are very hindered on the back side or the base is very hindered (a poor nucleophile). With potassium tert-butoxide you get a good yield of E2 products.2) 3º halides give pure E2.3) 2º halides give a mixture of E2 and SN2 products—mostly E2.

II) If there is a weak base and a good nucleophile?

If YES, there is a weak base/good nucleophile:A) 1º and 2º alkyl halides will give SN2. 3º halides will give mostly SN1/E1.

III) If there is no good nucleophile and no strong base:

1) 1º halides give SN2. This SN2 is very slow with H2O, ROH, or RCO2H2) 2º and 3º halides give E1/SN1.

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Give IUPAC name for the C4H9I isomers and classify them whether they are 1o,2o or 3o

CH3CH2CH2CH2I

1-iodobutane

CH3CH2CHICH3

2-iodobutane

CHCH2I

CH3

H3C

1-iodo-2-methylpropane

C

CH3

H3C

CH3

I

2-iodo-2-methylpropane

75

Predict the products and mechanisms of the following reactions.

1. Ethyl bromide + sodium ethoxide2. t-butylbromide + sodium ethoxide3. Isopropyl bromide + sodium ethoxide4. Isobutylbromide + potassium hydroxide in ethanol/ water

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Organohalogen Notes