Nucleophilic mechanism - alcohols alkyl halides and amines

Question 1

What are the two types of amines

Answer 1

Aliphatic (attached to hydrocarbon chain) or aromatic (attached to benzene ring)

Question 2

Are alcohols water soluble?

Answer 2

Yes, only small alcohols up to 5C

Question 3

Are amines water soluble?

Answer 3

Yes, only small amines up to 5C

Question 4

Are alkyl halides water soluble?

Answer 4

No, they are non-polar despite containing an electronegative halogen. This makes them able to dissolve non-polar substances and hence they are great organic solvents.

Question 5

What is nucleophilic substition?

Answer 5

Replacement of one nucleophile with another

Question 6

Are halogens of an alkyl halide good or bad leaving groups?

Answer 6

They are excellent leaving groups as they are considered weak bases

Question 7

Rank the halogens in order of ability to leave a molecule?

Answer 7

I > Br > Cl

Question 8

What are examples of poor leaving groups?

Answer 8

H, NH2, OH, RO

Question 9

What are the two mechanisms for nucleophilic substitution?

Answer 9

SN1 (unimolecular) and SN2 (bimolecular) mechanisms

Question 10

What is the SN1 mechanism and when does it apply?

Answer 10

SN1 mechanism is the unimolecular mechanism - hence its rds depends on a single molecule (the electrophile)

Thus, SN1 acts as a two step process involving a carbocation intermediate therefore molecules which form a more stable carbocation favour SN1 (tertiary>secondary>primary)

The quality of the leaving group determines the rate at which the reaction occurs (good leaving groups will mean faster rate of reaction)

Question 11

What happens to the stereochemistry of R and S enantiomers undergoing nucleophilic substitution by SN1 mechanism?

Answer 11

The carbocation that forms is sp2 hybridised forming a planar shape. Hence, the nucleophile is able to join from the top or the bottom therefore it will lead to the formation of a racemic mixture with an even composition of both R and S enantiomers.

Question 12

What is the SN2 mechanism and when does it apply?

Answer 12

SN2 mechanism is the bimolecular mechanism - hence its rds depends on two molecules - the electrophile and the nucleophile

Thus, SN2 is a one step process with a transition state in which both the nucleophile and the leaving group are bonded to the carbon atom at the same time. Because there is no involvement of a carbocation intermediate molecules favour SN2 in order of primary>secondary>tertiary. Also, tertiary electrophiles will cause more steric interference as the transition state forms

Question 13

What happens to the stereochemistry of R and S enantiomers undergoing nucleophilic substitution by SN2 mechanism?

Answer 13

As the nucleophile comes in at one side the transition stage will have the nucleophile and leaving group at opposite ends of the molecule. As the leaving group breaks its bond to the carbon atom we get an inversion of configuration meaning all of R and S enantiomers are exchanged.

Question 14

What determines the strength of a nucleophile?

Answer 14

Nucleophiles are electron donors = hence, the availability of a pair of electrons based on their electronegativity affects the strength of the nucleophile?

Question 15

What are examples of weak nucleophiles?

Answer 15

Compounds with neutral oxygens will be weak nucleophiles as oxygen has a high electronegativity meaning its lone pair less available for reaction

e.g. water, alcohols, carboxylic acids

Weak nucleophiles are more likely to act via the SN1 mechanism as the quality of the nucleophile does not affect the rate of reaction in this case.

Question 16

What are examples of a moderate nucleophile?

Answer 16

The conjugate base formed from a salt dissociating in water as they are weakly basic.

These substances are negatively charged and are therefore decent nucleophiles

This means they are likely to react in the SN2 pathway where the quality of the nucleophile is important

Question 17

What are examples of strong nucleophiles?

Answer 17

Oxygens with a negative charge are excellent nucleophiles

Carbones with a negative charge also make excellent nucleophiles

A very strong base is required to generate this sort of nucleophile

Question 18

Are nitrogens weak, moderate or strong nucleophiles?

Answer 18

Because nitrogen contains a more available lone pair compared to oxygen (due to its lower electronegativity) both charged and uncharged species containing nitrogen are strong nucleophiles

Because nitrogen containing molecules are strong nucleophiles they favour the SN2 mechanism

Question 19

What are the factors affecting whether the mechanism is SN1 or SN2?

Answer 19

Primary, secondary or tertiary molecule?

• stability of carbocation intermediate
• steric interference in formation of transition state

Strength of the nucleophile

Question 20

What happens when an ammonia is the nucleophile of a reaction?

Answer 20

Provided the electrophile is in excess, amines which are good nucleophiles will cause nucleophilic substitution to keep occurring until a mixture of primary, secondary, tertiary and the quaternary ammonium salt forms.

Question 21

Can an alcohol act as the nucleophile for nucleophilic substitution?

Answer 21

Standard -OH of an alcohol is a weak nucleophile as the O atom is highly electronegative making the lone pair of electrons less available.

Question 22

What must you do to allow nucleophilic substitution to occur with alcohols as the nucleophile?

Answer 22

This can be done by adding NaNH2 to form alkoxide anion. The alkoxide anion will replace the leaving group to form an ether

Question 23

Can an alcohol act as as the electrophile for nucleophilic substitution?

Answer 23

Although the -OH group is polar, it is a poor leaving group hence it must first be converted to a good leaving group in order to act as the electrophile.

Question 24

What must you do to an alcohol to allow it to act as the electrophile in a nucleophilic reaction?

Answer 24

Add a concentration of H+ ions converting the OH group into a O(+)H2 group.
Water is very stable and hence an excellent leaving group therefore it will undergo nucleophilic substitution like alkyl halides.

Question 25

Which mechanism does a tertiary alcohol follow?

Answer 25

SN1 - a stable carbocation forms as the H2O group leaves the alcohol

Question 26

Which mechanism does a primary alcohol follow?

Answer 26

SN2 - if it were to follow SN1 the carbocation intermediate would be highly unstable therefore it follows SN2 - less steric interference also

HOWEVER, the process in which the alcohol is converted to the alkyl halide is too slow - reaction is not feasible

Question 27

How are primary alcohols converted to alkyl halides?

Answer 27

By adding SOCl2 - carrying out the usual method of adding conc. HCl will take too long for primary alcohols

Question 28

What is the reagent for formation of nitrile from alkyl halide?

Answer 28

Add NaCN

Question 29

What is the reagent for formation of alkyne from alkyl halide?

Answer 29

Add (-)C(triplebond)CR

Question 30

What is the reagent for formation of alcohol from alkyl halide?

Answer 30

Add (-)OH

Question 31

What is the reagent for formation of alkyl halide from alcohol?

Answer 31

add conc HCl if tertiary alcohol

add SOCl2 if primary alcohol

Question 32

What is the reagent for formation of alkyl halide from alcohol?

Answer 32

to form alkoxide anion add NaNH2 to alcohol

Then add alkoxide anion to alkyl halide