Carboxylic Acid Derivatives

Question 1

Amides, esters and anhydrides are all carboxylic acid derivatives formed by a ______ reaction with a carboxylic acid.

THe leaving molecule is _____ from the _____ group and a hydrogen coming from the nucleophile.

Answer 1

condensation

water

hydroxyl

Question 2

Amides

Answer 2

Gen Formula: RCONR2

-oic acid suffix replaced with -amide suffix
alkyl substituents on the nitrogen atom are prefixes specified with the letter N

ex: N-ethyl-N-methylbutanamide

synthesized by carboxylic acid + amine/ammonia

only primary and secondary amines

cyclic amides are called lactams

Question 3

Boiling points of amides are either _____ or _____ as carboxylic acids due to lack of ______

Answer 3

lower

same level

H bonding

Question 4

Esters

Answer 4

carboxylic acid + alcohol

Prefix is the substituent bonded to the Oxygen with suffix -oate

ex: ethyl ethanoate

cyclic esters are called lactones

Question 5

Fischer Esterification

Answer 5

under acidic conditions carboxylic acids and alcohols will condense in esters

1) carbonyl O attacks H+
2) alcohol O attacks carbonyl carbon and pi bond electrongs go to carbonyl O making alcohol
3) carboxylic hydroxyl takes H from newly attached alcohol
4) water leaves as carbonyl is formed again by top O losing H

Question 6

Lactams

Answer 6

cyclic amides

Question 7

Lactones

Answer 7

cyclic esters

Question 8

Because they ______ hydrogen bonding, esters have ____ boiling points than carboxylic acids.

Answer 8

lack

lower

Question 9

Triacylglycerols

Answer 9

storage of fats

esters of long chain cab=rboxylic acids and glycerol

Question 10

Acidification of soap _____ the fatty acids.

Answer 10

regenerates

Question 11

Anhydrides/Acid Anyhydrides

Answer 11

condensation dimers of 2 carboxylic acids

Gen For: RC(O)OC(O)R (two carbonyls seperated by O in middle)

symetrical anhydrides are named by changing acid to anhydride

ex: ethanoic anyhydride

asymmetrical anhydrides are named by labeling chains alphabetically and then adding anhydride

ex: ethanoic propanoic anyhydride

Question 12

Anhydride Formation

Answer 12

1) carboxylic hydroxyl attaks carbonyl carbon which gives pi electrongs to carbonyl Oxygen
2) H+ comes and bonds to hydroxyl group and takes away water, O- not gives electrons back for the double bond

Question 13

Certain cyclic anhydrides can be formed through ________. This is driven forward by the ________ of the newly formed rings, hence only ____ or ____ membered rings are made.

Answer 13

heating carboxylic acids

increased stability

5

6

Question 14

Anyhydrides have ______ boiling points than carboxylic acids because of _______

Answer 14

higher

increased weight

Question 15

Relative reactivity of Derivatives

Answer 15

Most to least reactive

anyhydrides > esters > amides

resonance stabilization + 3 electron withdrawing oxygens are very electrophilic

lack one less elecron withdrawing oxygen

amino group is electron donating which is less reactive

Question 16

Steric Effects

Answer 16

size of substituents impact reaction

can be used to advantage as if we want an Sn1 reaction, we can use a tertiary substrate ad to ceate protecting groups

sizee and substitution of the leaving group of carboxylic acid derivative can affect ability of nucleophile to access the carbonyl carbon

Question 17

Electronic Effects: Induction

Answer 17

distribution of charge across pi bonds

dipoles are made as electrons from pi bond may be pulled more closely to the electronegative atom

this dipole being made can increase chance for nucleophillic attack (+ for the carbonyl carbon)

hence Anyhydrides > Amides as N is less electronegative than oxygen so the carbonyl carbon is more positive for the anhydride

Question 18

Electronic Effects: Conjugation

Answer 18

presence of alternating single and multiple bonds

all atoms are either sp2 or sp hybridized and have unhybridized p orbitals

this causes delocalization of electrons as p orbitals align leading to resonance and sharing of electrons and more stable compounds

***once nucelophile bonds, this allows for positive charge stabilization so the compounds are more susceptible to nucelophilic attacks

Question 19

Strain in Cyclic Derivatives

Answer 19

certain lactams and lactones are more reactive to hydrolysis because they contain more strain

ex: 4 membered rings have significantly high ring strain

ring strain and reactivity is increased by fusion to a second ring by reducing resonance and making hydrolysis more likely

Question 20

Anyhydride Cleavage Reaction

Answer 20

splits anyhdride in two with a carboxylic acid leaving group

with ammonida, formation is amide + carboxylic acid

with an alcohol, formation is ester + carboxylic acid

with water, formation is 2 carboxylic acids

1) nucelophile (say ammonia) attacks a carbonyl carbon, carbonyl oxygen becomes O-
2) center O strips H from the nucleophile

3) positive OH splits off with a carbonyl carbon to make carboxylic acid, O- gives back electrons to form pi bond
in this case results are a carboxylic acid and amide

Question 21

Transesterification

Answer 21

alcohol acts as nuclephile to displace an esterifying group

aka new ester is made with a new R’

Question 22

Hydrolysis of Amides

Answer 22

under acidic conditions via nucleophilic substitution

carbonyl ocygen becomes protonated making it more susceptible to nucleophilic attack by water

produces carboxylic acid and ammonia (literally reverse of amide formation)

1) water attacks carbonyl carbon and pi bonds go make protonated carbonyl O to just OH
2) proton protonates NH2 to NH3 making it a leaving group and first OH gives electrons to make pi bond
3) H from positive carbonyl O dissociates

Hydrolysis can occur in basic conditions bu oxygen isnt protonated, nucleophile is a hydroxide ion, and the product is deprotonated carboxylate anion instead of carboxylic acid