3.3.9.2 acylation

carboxylic acids be turned into… to be used in…

• into other functional groups

• to be used in organic synthesis

give two groups that can be formed from carboxylic acids

1. acyl chlorides

2. acid anhydrides

   → both called acid derivatives

what are acyl chlorides?

where the -OH group of the acid is replaced by a chlorine atom

how are acyl chlorides named?

they are named after the corresponding carboxylic acids → the -oate is replaced by -oyl

name the following acyl chlorides

what does this carboxylic acid derivative (acyl chlorides) possess?

a good leaving group (Cl-)

what does this good leaving group (Cl-) activate?

it activates the adjacent carbonyl group by electron withdrawal

what is a good leaving group?

its a stable species which is removed during a chemical reaction

what is the by-product of when acyl chlorides react?

HCl

what is the hazard of HCl?

it is corrosive

how do acyl chlorides + acid anhydrides react with nucleophiles?

in a reduction reaction

what mechanism do acyl chlorides + acid anhydrides undergo?

nucleophilic addition elimination

describe the nucleophilic addition elimination mechanism that acyl chlorides undergo

1. in the first step, the nucleophilic adds to the ᵟ⁺ carbon of the carbonyl causing electrons to move from the carbonyl bond onto oxygen forming an oxyanion

2. in the second step, the carbonyl bond is remade causing the elimination of the leaving group on the acyl chloride (Cl-) or acid anhydride

3. finally the nucleophile loses a proton (H) + the by-product is made

why does the carbon atom have a greatest chance of being readily attacked by nucleophiles?

because the chlorine + oxygen are more electronegative than the carbon atom

give the general equation + mechanism using the example of ethanoyl chloride

CH₃COCl + :XH → CH₃COX + HCl

what are the 4 common nucleophiles that react with acyl chlorides?

• H₂O

• NH₃

• ROH

• RNH₂

one way of forming carboxylic acids is by the oxidation of primary alcohols or aldehydes by acidified potassium dichromate, but give another way of forming them with acyl chlorides

acyl chlorides react with water to form carboxylic acids

give the general symbol equation for the formation of carboxylic acids using acyl chlorides + give an example one using ethanoyl chloride

draw + name the mechanism for the reaction between ethanoyl chloride and water

mechanism: nucleophilic addition elimination

one way of forming esters is by esterification, outline another way of forming esters using acyl chlorides

acyl chlorides react with alcohols to form esters → they undergo nucleophilic addition elimination

give the general equation for the formation fo esters from acyl chlorides

draw the mechanism for the reaction between ethanoyl chloride + methanol

give 3 reasons why acyl chlorides may be preferred to carboxylic acids in the formation of esters

1. no acid catalyst is required (esterification uses H₂SO₄)

2. purer product

3. yield of ester is higher as the reaction is not reversible (whereas esterification is)

give the general displayed formula for amides

how are amides named?

using the suffix -anamide

how are amides formed?

when using ammonia (NH₃) as the nucleophile

eg draw propanamide and 2-methylbutanamide

acyl chlorides react with ammonia to form what?

amides

give the general symbol equation for the reaction between acyl chlorides + ammonia

give an example using ethanoyl chloride

name + draw the mechanism between acyl chlorides + ammonia using the example of ethanoyl chloride

outline how N-substitued amines are named

• using an N-alkyl prefix to indicate the alkyl group attached to the N only

• and the suffix -anamide to indicate the length of carbon chain attached to the carbonyl

example in image

for these examples, name them + identify the reagents used used to form them

what are the two ways of naming amines?

either as alkyl amine or aminoalkane

• eg ethyl amine or aminoethane

• eg propyl amine or aminopropane

acyl chlorides react with amines to form what?

N-Substituted amides

give the general symbol equation for the reaction between acyl chlorides + amines

give an example using ethanoyl chloride

name + draw the mechanism for the reaction between acyl chlorides + amines using the example of ethanoyl chloride

reactants: propanol chloride + diethylamine

give the other carboxylic acid derivative

acid anhydrides

give four reasons why acid anhydrides are preferred to acyl chlorides in the formation of esters

1. acid anhydrides are cheaper

2. acid anhydrides react less exothermically meaning the reaction is less violent/dangerous

3. acid anhydrides are less vulnerable to hydrolysis

4. no corrosive HCl is formed

what are acid anhydrides?

another carboxylic acid derivative where -OH group of carboxylic acid is replaced by —OCOR

give the general displayed + structural formula for acid anhydrides

(this structural formula is only used for symmetrical acid anhydrides)

when are acid anhydrides formed?

when two molecules of carboxylic acids join together with elimination of water

outline how acid anhydrides are named

• it is named after the carboxylic acid that was used in its synthesis

• the anhydride suffix -anhydride replaces the -acid suffix at the end of the carboxylic acid name

eg name this acid anhydride

ethanoic anhydride

name these molecules + give the structural formula for 1

1. propanoic anhydride, (CH₃CH₂CO)₂O

2. ethanoic propanoic anhydride

what is the mechanism for reactions of acid anhydrides?

nucleophilic addition elimination

what do acid anhydrides possess?

a good leaving group

define what a good leaving group is + give the one of acid anhydrides

• a good leaving group is a stable species, which is removed during a chemical reaction

• RCOO-

what does the good leaving group (RCOO-) do?

it activates the adjacent carbonyl group by electron withdrawal

outline the by-product of when acid anhydrides react (by nucleophilic addition elimination)

acid anhydrides react to form the corresponding carboxylic acid as a by-product

outline the similarity + difference between the reactions of acyl chlorides + acid anhydrides

• they react in the same way to produce the same carboxylic acid

• but will produce a different side product

we have already seen 2 ways of forming carboxylic acids: oxidation of primary alcohols or aldehydes + acyl chlorides react with water

outline the third way of forming carboxylic acids

• Cos can also be prepared using acid anhydrides

• acid anhydrides react with water to form carboxylic acids

• if it is a symmetrical acid anhydride, then 2 of the same CA is formed

give the equation using skeletal formula for the reaction between ethanoic anhydride + water

write an equation for the reaction between propanoic anhydride + water

should cancel out to 2 CH₃CH₂COOH

write an equation for the reaction of the acid anhydride shown in the image with water

acid anhydrides react with alcohols to form what? give the mechanism for this

• esters

• nucleophilic addition elimination

give the general symbol equation for the reaction between acid anhydrides + alcohol

give an example using ethanoic anhydride + methanol

outline the reaction between acid anhydrides + ammonia

• acid anhydrides react with ammonia to form amides (+ carboxylic acid as a by-product)

• mechanism is nucleophilic addition elimination

give the general symbol equation for the reaction between acid anhydrides + ammonia

give an example using ethanoic anhydride

outline the reaction between acid anhydrides + amines

• acid anhydrides react with amines to form N-substituted amides

• mechanism is nucleophilic addition elimination

give the general symbol equation for the reaction between acid anhydrides + amines

give an example using ethanoic anhydride