Functional Groups 5&6 - carbonyls Flashcards
Describe the structure of carbonyls.
- Trigonal planar sp2 carbon and oxygen
- All sigma bonds lie in same plane - 120 degrees apart
- C-O pi bond between parallel p orbitals on carbon and oxygen
What is the driving force behind carbonyl activity?
The difference in electronegativity between carbon and oxygen - oxygen is more electronegative
Why are carbonyls higher in energy than alkenes?
The dipole in C=O means the bond is shorter, stronger and more polar
Why is hydrogen bonding important for carbonyl groups when taking drugs?
- Can bond with water so the drug can dissolve and travel around the body
- Will then interact with different physiochemical conditions e.g. pH or temp and change its bonding
- Can then find enzyme or receptor (binding site)
State the interaction of hydrogen bonding with carbonyl groups.
Short range, directional
Intramolecular or non-bonded interaction
Which two factors play an initial role in the binding of a carbonyl?
- It is a planar molecule
- It has a dipole moment
How do carbonyls interact with the binding site?
- Hydrogen bonding: carbonyl group is a hydrogen bond acceptor and two interactions are possible as there are two lone pairs on oxygen
Describe the reactions at the carbonyl carbon.
- Nucleophile attacks delta positive carbon from above or below planar
- Electron pair moves from C=O bond to electronegative oxygen atom producing tetrahedral alkoxide ion intermediate
- Lone pair on oxygen moved to proton (formation of O-H bond)
- Formation of new bonds increases steric crowding
- Possible introduction of chiral centre as carbonyl carbon changes from sp2 to sp3
Give three examples of good nucleophiles.
- Hydride
- Alkyl anions
- Alkoxides
Why are aldehydes more reactive than ketones?
- Proton in aldehyde is much smaller so approach of nucleophile at desired angle of 100-115 degrees is easier by comparison to ketone where there is more electrostatic charge to pass through
How can the reactivity of carbonyls be enhanced?
- By protonation of the carbonyl oxygen
- The carbonyl carbon becomes more electrophilic
- The carbonyl carbon is more susceptible to nucleophilic attack
Name the mechanism that carbonyls undergo
Nucleophilic Addition
What are carboxylic acids?
Weak acids (proton donors) - they transfer a proton to water to give H3O+ and carboxylate anions RCO2-
What is the acidity constant (Ka) for a typical carboxylic acid?
10^-3 - 10^-5
What is the pKa range for most aliphatic and aromatic carboxylic acids?
3-5
What is the greater acidity of carboxylic acids relative to alcohols due to?
- resonance stabilisation of the carboxylate anion
How can we identify stronger acids from pKa?
- The lower the pKa the stronger the acid
Describe the role of electron withdrawing groups in the stabilisation of carboxylic acids.
- stabilises the carbon making it more reactive
Describe the role of electron-donating groups in the stabilisation of carboxylic acids.
- destabilises the carbon as it becomes less positively charged and so less able to accept electrons
State the mechanism that carboxylic acid derivatives undergo.
addition-elimination
Name the condition for acyl substitutions.
- acid chlorides OR acid anhydrides (react more slowly)
What are aldehydes oxidised to?
Carboxylic acids - CHO hydrogen abstracted during oxidation or chemically with an oxidising agent: CrO3, KMnO4, HNO3
What is the second site of reactivity on carbonyls?
the alpha-hydrogen is acidic enough to be removed by a strong base
- The anion is stabilised by resonance
How else can we drive the process of interconversion?
Can be acid or base catalysed
Why do many drug compounds contain carbonyl groups?
As they can make hydrogen bonding interactions with receptor binding sites in the body helping drug molecules to bind strongly.
Explain why carboxylic acids are stronger acids than alcohols.
Due to resonance stabilisation of the carboxylate ion.
Why is trifluroacetic acid more acidic than acetic acid?
The CF3 group is electron withdrawing which stabilises the carboxylate ion and increases acidity.
Why do nucleophiles add to carbonyl compounds?
The carbon of the carbonyl group has a partial positive charge, which attracts nucleophiles.
Name a reagent used for the reduction of aldehydes and ketones.
NaBH4
