Functional group chem 7& 8 amides

Acyl group

what are amides ?

the carbonly compoenent is called ?

amide is?

R-C=O

• Amides like esters are carbonyl compounds substituted by an atom more electronegative (and therefore more basic) than carbon.

The carbonyl component of the structure is termed an Acyl group

• An amide is essentially an acyl substituted amine

Are amides reactive?

No very unreactive

Are amides more stable than esters?

Yes, more stable chemically and in vivo

How is lone pair on nitrogen stabilised?

Resonance

Amide bonds are present in which biological molecule?

proteins (peptide bonds)

What hydrolyses amines in body?

enzymes in body

How many H does a 1° amide have?

2

How many H does a 2° amide have?

1

How many H does a 3° amide have?

0

Cyclic amines are called

β- lactams

Naming convention of amides

name of substituent bonded to nitrogen stated first

Amides drug examples

paracetamol 2°, melatonin 2°(sleep hormone)

Are amides acidic basic or neutral?

neutral

pKa of amides

35 ish

BP of amides

high due to strong imfs between molecules

What IMFs can amides form?

hydrogen bonding, strong dipole-dipole interactions

Example of amide polymer

kevlar

Nitrogen shape and hybridisation

trigonal planar, sp2 with lone pair in p orbital

Are electrons shared evenly in amides?

shared unequally due to greater electron density on the oxygen

Can you rotate around amide bond?

restricted rotation gives rise to the possibility for cis /trans orientations

Is an amide more likely to be cis or trans?

trans

In what sort of solvent is rotation fastest?

least polar solvent- cyclohexane

Is there much rotation of drugs in body?

no because lots of water and water interacts because it has a strongle dipole moment

chargers and dipoles help bring moelcules togather

What allows resonance of amide?

electron overlap from nitrogen lone pair

How do amides behave in acidic environment?

no protonation on nitrogen as this would destroy resonance stabilisation and oxygen has greater electron density so oxygen is protonated which allows for resonance stabilisation of cation

Synthesis of amides

acid anhydride + primary amine -> secondary amide
(can use to make drugs)
ester + NH3 -> amide
acid -harsh conditions---> amide (not often done)

COOH + amine ->

salt and water

Coupling reagents

reagents that change product, can join two intermediates together e.g.

Importance of amides

present in penicillin with r group and when you vary r group you get, amoxicillin, all cillins. r- group allows for organism specificity, overcoming resistance to penicillinase and acid sensitivity (allows drug to be taken orally

Most to least reactive: acid chloride, anhydride, ester, amide

acid chloride, anhydride, ester, amide

Why is amide so unreactive?

O has large amount of electron density, carbon also has more than usual, electron density left on N will bond into resonance form but also into antibonding orbitals too which lowers energy of antibonding orbitals which makes them less reactive

Reactions of amides

acid hydrolysis of amide -> carboxylic acid
basic hydrolysis of amide -> carboxylate ion
dehydration of amide ---SOCl2--> nitrile
reduction of amide ---LiAlH4---> amine
amide ---> unsymmetrical amine

Imide--OH- --->

amine

what is an amide?

• amides are carbonyl compounds subsuited by an atom more electronegative than carbon.

• they are susceptibile to displasement

• essentially an acyl subsuited amine