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
