Nucleophilic Substitution Swapping

Nucleophilic Substitution Swapping

Generic Equation: SwapR-X + Nu:  R-Nu + :X-The problem lies in the mechanism.

Importance of Alkyl HalidesPrecursor to many others

NUCLEOPHILIC SUBSTITUTION

Theory

- nucleophile means ‘liking positive’

- a

dipole is induced (by a Nu:) in the C-X bond and it is polar polar bond, why is it polar with chlorine? Answer: ∆E=0.4, electronegativity difference

OH¯ CN¯ NH

3

H

2

O

These are the 4 Nu: NaOH, NaCN the 2 moleculars are as is

SN

2

:NUCLEOPHILIC SUBSTITUTION

MECHANISM

MECHANISM: 2 Steps The NU: electrons attacks the slightly positive carbon atom The polar bond breaks unevenly (heterolytic) and Br- released

Back

attack

Polar Bond

Note/Points:-attack from back (electronegative halogen will forces this)-show the polar bond

Both e-To halogen

2 products

SN2

All 1

0

(primary)halides react as SN

2

reactions.

The 2 does NOT mean steps

S = substitution

N = Nucleophile

2 = second order (

both reactants determine rate

)

Note: this is for primary halides, tertiary will under go SN

1

as we will see later, secondary will do both – but we are not responsible to know about secondary reactions

1O Haloalkanes SN2

https://www.youtube.com/watch?v=h5xvaP6bIZI

There are 4 Substitutions

1)

WITH HYDROXIDE

C

2

H

5

Br(l) + OH-

(aq)

-->C

2

H

5

OH(l) +Br-(aq)

2) WITH A CYANIDE

C

2

H

5

Br(l) + CN- (

aq/alc

) —>C

2

H

5

CN + Br-(aq)

3) WITH 2 AMMONIAS

C

2

H

5

Br(l) +

2

NH

3

(aq/alc)

—> C

2

H

5

NH

2

+ NH

4

Br

4) WITH H

2

O (solvolysis) solvent and reactant at same time

C

2

H

5

Br(l) + H

2

O

(l)

—> C

2

H

5

OH(l) + HBr (aq)

Chapter 6

8

SN2 Energy Diagram

The SN2 reaction is a one-step reaction.Transition state is highest in energy.

Substitution Reactions : The Nu: will be one of these 4 reactants

These four reactants will be

similar in result and mechanismThey will ALL be refluxedNote: NaOH or KOH, NaCN etc is the source ofThe OH¯ , and CN¯ above as they are ionicBut we can ignore the metals as spectatorsNaOH ---> Na⁺ + OH⁻

OH¯ CN¯ NH3 H2O

AQUEOUS

HYDROXIDE



ALCOHOLSReagent Aqueous* NaOH or KOH (aq) (OH¯)Conditions Reflux in aqueous solution (SOLVENT IS IMPORTANT)Product AlcoholNucleophile hydroxide ion ( : OH¯)Equation e.g. C2H5Br(l) + Na OH-(aq) ——> C2H5OH(l) + Na Br-(aq) Spectator SpectatorMechanismSTEP 1 Nu: attackSTEP 2 :Br- forms and leaves* WARNING It is important to quote the solvent when answering questions. Elimination takes place when ethanol is the solvent - SEE LATER

NUCLEOPHILIC SUBSTITUTION

CYANIDE makes Nitriles AND makes chain LONGER

Reagent

Alcohol/ Aqueous,

NaCN

/ KCN Conditions Reflux in aqueous , alcoholic solutionProduct Nitrile (cyanide)Nucleophile cyanide ion (CN¯)Equation e.g. C2H5Br + Na CN (aq/alc) ——> C2H5CN + Na CN-(aq) Mechanism 1-bromoethane propanenitrile Br-Importance extends the carbon chain by one carbon atom, called propanenitrile .

NUCLEOPHILIC SUBSTITUTION

NUCLEOPHILIC SUBSTITUTION

AMMONIA makes an amine

Reagent

Aqueous, alcoholic ammonia (

in EXCESS, or 2 Ammonia’s)Conditions Reflux in aqueous , alcoholic solution under pressureProduct AmineNucleophile Ammonia (NH3 (aq/alc) )Equation e.g. C2H5Br + 2NH3 (aq / alc) ——> C2H5NH2 + NH4Br (i) C2H5Br + NH3 (aq / alc) ——> C2H5NH3 + HBr (ii) C2H5NH3 + NH3 (aq / alc) ——> C2H5NH2 + NH4Br _______________________________________________ C2H5Br + 2NH3 (aq / alc) ——> C2H5NH2 (l) + NH4Br (aq/alc)Mechanism Ethaneamine Bromide

NUCLEOPHILIC SUBSTITUTION

AMMONIA

Why excess ammonia?

The second ammonia molecule ensures the removal of the H to make an amine. A large excess ammonia ensures that further substitution doesn’t take place.

Problem

Amines are also nucleophiles (lone pair on N) and can attack another molecule of haloalkane to produce a 2° amine. This too is a nucleophile and can react further producing a 3° amine and, eventually an ionic quarternary ammonium salt. ..C2H5NH2 + C2H5Br ——> HBr + (C2H5)2NH diethylamine, a 2° amine ..(C2H5)2NH + C2H5Br ——> HBr + (C2H5)3N triethylamine, a 3° amine(C2H5)3N + C2H5Br ——> (C2H5)4N+ Br¯ tetraethylammonium bromide a quaternary (4°) salt

NUCLEOPHILIC SUBSTITUTION

WATER Makes Alcohols

Details

A similar reaction to that with OH¯ takes place with water.

It is

slower as water is a poor nucleophile. Water may be looked at as HOH THE OH AND BR SWAPEquation C2H5Br(l) + H2O(l) ——> C2H5OH(l) + HBr(aq)We show the product as HBr and not just Br- because it is molecular and the H in the water is not an ion like Na+ or K+. As well, H3O+ forms, which we rewrite as H+ and the water from the H3O+ is part of the (aq)

SN1 V SN2

There is very little difference in these reactions.

Both have 2 steps and the same product , the same reactants. Hard to see any difference

S = substitution (both will swap)

N= Nucleophile (both will use the same Nu

:

1 =Rate of reaction (depends on 1 reactant)

called 1st order

2 =

Rate of reaction (depends on 2

REACTANTS)

called 2nd

order

called 1st order

Steric Hinderance

With a tertiary halogenoalkane, NU: attack is impossible. The back of the molecule is completely cluttered with CH3 groups.It has to go by an alternative mechanism.

Tertiary Haloalkenes SN1

Steric hindrance means the Nu: cannot approach and has no effect on the reactions first stepThe [Nu:] nucleophile has no effect. Only the [haloalkane] affect the reaction rate. Thus it is first order. rate = k [haloalkane] 1

Mechanism for3o Halides SN1

Carbocation Intermediate

SLOW (RDS)

STEP

FAST

STEP

http://ibchem.com/IB16/10.34.htm

Chapter 6

19

SN1 Energy Diagram

Forming the carbocation is an endothermic step.Step 2 is fast with a low activation energy.

Film Clip 30 HaloalkanesSN2 (single step)

https://www.youtube.com/watch?v=JmcVgE2WKBE

Secondary Halides

They undergo both SN1 and SN2 reactions so on an exam if you are given a secondary halide, either mechanism will receive full credit in marks

LAST REACTION

ELIMINATION

3 WAYS to Favor Elimination

T

o favor

elimination rather

than substitution

use:

1) More heat

2) More concentrated hydroxide in ALCOHOL

3) pure

ethanol as the solvent

24

The :OH- is a BASE, in alcohol and takes a hydrogen (H+) to form water. This sets off a cascade where a C=C forms and the halide ion is lost. (as always Reflux)

Elimination

Elimination Via OH- BASE

Step 1: The :OH- is NOT a nucleophile, it is a BASE, and attacks HStep 2: The H+ leave and e- pair make C=CStep 3: The halogen (here as :Br-) leaves GENERIC CASCADING REACTION

+ H

2

O + :Br-

+ H2O + :Br-

An Example

ELIMINATION

Reagent

Alcoholic

sodium

(or potassium) hydroxideConditions Reflux in alcoholic solution, ALL alcoholProduct AlkeneMechanism EliminationEquation C3H7Br + NaOH(alc) ——> C3H6 + H2O + NaBrMechanism the OH¯ ion acts as a base and picks up a proton the proton comes from a carbon atom next to that bonded to the halogen the electron pair left moves to form a second bond between the carbon atoms the halogen is displaced overall there is ELIMINATION of HBr.Complication:Cis / Trans with unsymmetrical halalkanes, you get mixture of products

ELIMINATION

Complication

If

the haloalkane is unsymmetrical

a

mixture of isomeric alkene products is obtained.

but-1-ene (Minor Product)

but-2-ene (Major Product)

can

exist as cis and trans isomers

2-bromobutane

2-bromobutane

ELIMINATION v. SUBSTITUTION

The products of reactions between haloalkanes and OH¯ are influenced by the solvent

SOLVENT

ROLE OF OH

–

MECHANISM

PRODUCT

WATER

NUCLEOPHILE

SUBSTITUTION

ALCOHOL

ALCOHOL

BASE

ELIMINATION

ALKENE

Modes of attack

Aqueous

soln

OH

¯ acts as a nucleophile

Alcoholic

soln

OH

¯ acts as a base

(A BASE IS A PROTON ACCEPTOR)

Both reactions take place at the same time but by varying

the solvent you can influence which mechanism dominates.

Elimination Clips

https://

www.learnnext.com/CBSE/Class-12/Chemistry/Haloalkanes-and-Haloarenes/Chemical-Reactions-Of-Alkyl-Halides-Elimination-Reactions/L-1804203.htm

Franklychem

https://

www.youtube.com/watch?v=o3lk77sdFHY

Aprotic solvents

ε

Protic solvents

ε

Hexane

1.9Acetic acid6.2Benzene2.31-Methyl-2-propanol11Diethyl ether4.3Ethanol34.3Chloroform4.8Methanol33.6Hexamethylphosphoramide (HMPT)30Formic acid58.0Dimethyl formamide (DMF)38Water80.4Dimethyl sulfoxide (DMSO)48  

The ability of solvents to stabilize ions through solvation is directly associated

with their polarity. Polar solvents, such as water, can stabilize the ions 3X more

than alcohol

(see chart)

Methanol can stabilize ions through solvation, but water is best at controlling

ions. The :OH- is a super strong ion and needs controlling. Alcohol controls less

and is better to dissolve weak :Nu’s such as NH

3

and CN, as they do not need

to be controlled like OH- as they are weak ions