ORGANOHALOGEN

DR. ROSWANIRA ABDUL WAHAB

DEPARTMENT OF CHEMISTRY FACULTY OF SCIENCE UNIVERSITI TEKNOLOGI MALAYSIA C18-311 [email protected]
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Classes 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:
H H H C C Br H H alk yl halide

I
H C C H H Cl vinyl halide

aryl halide
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Polarity 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.

Classes 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.

Dihalides
Geminal dihalide: two halogen atoms are bonded to the same carbon Vicinal dihalide: two halogen atoms are bonded to adjacent carbons.

H H C

H C Br
H

H H C C Br Br H vicinal dihalide
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H Br geminal dihalide

IUPAC Nomenclature
Name as haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those Cs. Use lowest possible numbers for position.

CH3

CH CH2CH3 Cl

CH2CH2Br CH3(CH2)2CH(CH2)2CH3

2-chlorobutane

4-(2-bromoethyl)heptane
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Trivial 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.

Uses 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 CFCs Freon 12, CF2Cl2, now replaced with Freon 22, CF2CHCl, not as harmful to ozone layer Pesticides - DDT

PHYSICAL PROPERTIES

Dipole Moments
m = 4.8 x d x d, where d is the charge (proportional to DEN) and d is the distance (bond length) in Angstroms. Electronegativities: F > Cl > Br > I

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

Bond dipoles:

< C-I

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 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 73C CH3(CH2)3Br 102C

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Densities
Alkyl fluorides and chlorides less dense than water.
Alkyl dichlorides, bromides, and iodides more dense than water.

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Preparation of Alkyl Halides

Free radical halogenation of alkanes
produces mixtures, not good lab synthesis unless: all Hs 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 Alkanes
All Hs equivalent. Restrict amount of halogen to prevent di- or trihalide formation
H H + Br2 H h Br + HBr

Highly selective: bromination of 3 carbon

CH3 CH3 C H CH3 + Br2 h CH3 CH3 C Br + CH3 90%
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HBr

Allylic 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 halogenation

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Reaction Mechanism
Free radical chain reaction initiation, propagation, termination
Br2 h 2 Br

H Br

H +
Br Br H Br + Br
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HBr

Preparation of Alkyl Halides (2)

b) Halogenation of Alkene (Addition of HX)

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Preparation of Alkyl Halides (3)

c) Halogenation of Alkene (Addition of Halogens)

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Preparation of Alkyl Halides (4)

d) RX from ROH (alcohol)
(Reaction with HX)

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(Reaction with HCl Lucas Test)

(Reaction with PBr3)

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(Reaction with SOCl2)

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REACTIONS OF ALKYL HALIDES

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Nucleophilic Substitution & Elimination Reactions

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Nucleophilic Substitution Reactions

C C H X

Nuc:

C C H Nuc

X:

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.
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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 28 molecule).

Second-Order Nucleophilic Substitution: The SN2 Reaction

SN2 : substitution, nucleophilic, bimolecular hydroxide ion is a strong nucleophile (donor of an electron pair)
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SN2 Mechanism

Bimolecular : the transition state of the rate-limiting step involves the collision of two molecules. Concerted reaction: new bond forming and old bond breaking at same time.
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SN2: Reactivity of Substrate

Carbon must be partially positive. Must have a good leaving group

Carbon must not be sterically hindered.

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Structure of Substrate
Relative rates for SN2:

CH3X > 1 > 2

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

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Uses for SN2 Reactions

Synthesis of other classes of compounds. Halogen exchange reaction.
Nucleophile R-X + I
-

Product R-I R-OH R-OR' R-SH R-SR'

+ R-NH3 X

Class of Product akyl halide alcohol ether thiol thioether amine salt azide alkyne nitrile ester
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R-X + OH
-

R-X + OR' R-X + SH R-X + SR' R-X + NH3 R-X + N3

-

R- N3 R-CC-R' R-CN R-COO-R'

R-X + CC-R' R-X + CN R-X + R-COO

FACTORS AFFECTING SN2 REACTIONS:

Nucleophilic Strength Steric Effects Solvent Effects
Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic.

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A base is always a stronger nucleophile than its conjugate acid

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

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

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Trends in Nucleophilic Strength

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,

b)

NH2- > NH3

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

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Trends 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 Effect

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Bulky Nucleophiles: Steric Effects

Sterically hindered for attack on carbon, so weaker nucleophiles.

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

CH3 H3C C O CH3 t-butoxide (hindered) stronger base, but weak er nucleophile
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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.

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Solvent Effects (2)

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

CH3 C N acetonitrile

CH3 CH3

O H3C CH3 acetone

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dimethylformamide (DMF)

Leaving Group Ability

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

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SUMMARY OF SN2 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.

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First-Order Nucleophilic Substitution: The SN1 Reaction

Unimolecular nucleophilic substitution. Two step reaction with carbocation intermediate.

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Reactivity of SN1 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.

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Rearrangements 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 Hs are available.

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Hydride Shift
Br H CH3 C C CH3 H CH3 CH3 H C C CH3 H CH3

H CH3 C C CH3 H CH3

H CH3 C C CH3 H CH3 Nuc

H CH3 C C CH3 H CH3

H Nuc CH3 C C CH3 H CH3
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Methyl Shift
Br CH3 CH3 C C CH3 H CH3 CH3 CH3 C C CH3 H CH3

CH3 CH3 C C CH3 H CH3

CH3 CH3 C C CH3 H CH3 Nuc

CH3 CH3 C C CH3 H CH3

CH3 Nuc C C CH3 H CH3
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CH3

SUMMARY OF SN1 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 Reactions

C C H X

B:

C C

X:

+ HB

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).

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First-Order Elimination: The E1 Reaction

Unimolecular elimination Two groups lost (usually X- and H+)

Nucleophile acts as base (weak base)

Also have SN1 products (mixture)

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E1 Mechanism

Halide ion leaves, forming carbocation.

Base removes H+ from adjacent carbon. Pi bond forms.
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 Draw both of substitution and elimination mechanism of following reaction:

CH3 H3C Br and CH3OH CH3

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SUMMARY 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 Saytzeffs rule (alkene)
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Saytzeffs 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
H Br CH3 H C C C CH3 H H H CH3

OH

C C C CH3 + H C C C H CH3 H H H H

CH3

minor

major
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Second-Order Elimination: The E2 Reaction

Bimolecular elimination Requires a strong base

Halide leaving and proton abstraction happens simultaneously - no intermediate.

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E2 Mechanism

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Stereochemistry of E2

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SUMMARY 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 Saytzeffs rule (alkene)

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Substitution 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 Good Nucleophiles Poor Nucleophiles

HO-, RO- (if R is not bulky) RCC:K+ -OC(CH3)3 other hindered alkoxides

Weak Bases
I-, Br-, RS-, CN-, N3-

Cl-, F-, RCO2H2O, 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 2o 2o good nucleophile, weaker base (e.g. RS-, I-) weak nucleophile, weak base (e.g. H2O, ROH) strong base, weaker nucleophile (e.g RO-) SN2 SN1 E2
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Type of Alkyl Halide 3o 3o

Nucleophile/Base

Mechanism

weak nucleophile, weak base SN1 and some E1 stronger base or stronger nucleophile E2

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

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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

ethanol AgX

CH2

CH2=CH CH2X

AgNO3

AgX

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 yellow
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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 R2-CH-Br + NaI R3-C-Br + NaI R-CH2-I + NaBr (precipitate) precipitate after 5 minutes very slow
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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) 1 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) 3 halides give pure E2. 3) 2 halides give a mixture of E2 and SN2 productsmostly E2.

II)

If there is a weak base and a good nucleophile?

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

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

1) 1 halides give SN2. This SN2 is very slow with H2O, ROH, or RCO2H 2) 2 and 3 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

H3C CHCH2I CH3 1-iodo-2-methylpropane

CH3 H3C C I CH3 2-iodo-2-methylpropane

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Predict the products and mechanisms of the following reactions. 1. 2. 3. 4. Ethyl bromide + sodium ethoxide t-butylbromide + sodium ethoxide Isopropyl bromide + sodium ethoxide Isobutylbromide + potassium hydroxide in ethanol/ water

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