The Carbonyl Group in Biology - Johnathan Cox Flashcards
What is a nucleophile?
A species that attacks centres of positive charge
What is an example of a nucleophile?
OH-
What is an electrophile?
A species that attacks centres of negative charge
What is an example of an electrophile?
A carbonyl carbon
What two types of nucleophile/electrophile can there be?
Neutral and charged
What is the rate of an SN2 reaction?
k[Nu][Substrate]
What happens when a nucleophile and a substrate meet?
The nucleophile causes the substrate to adopt a trigonal bipyramidal transition state
What is the symbol for the transition state?
Double dagger
Why does SN2 only have one step?
Because the nucleophile enters as the leaving group leaves
At what angle does the nucleophile enter?
180 degrees to the leaving group
What happens when the transition state collapses?
Inversion of chirality
How is chriality affected by SN2?
The product is of different chirality to the substrate
What is a transition state?
The least stable state
What does an SN2 reaction profile look like?
It only has one hump
Which step in SN1 is the slow step?
The first step
What is left after the first step of SN1?
A carbocation and a leaving group
What is the rate for SN1?
k[R-X]
How many peaks does the energy diagram have for SN1?
Two
Why does the energy level diagram have two peaks for SN1?
For the two transition states and intermediate (R+)
Which section of the energy level diagram is the R+?
The dip between two humps
How do the carbocation and transition state differ?
The carbocation can be isolated, the transition state cannot
Which activation energy is higher in SN1?
The first
What feature does the SN1 intermediate have?
It is trigonal planar
Why does SN1 result in a racemic mixture?
Because the intermediate is trigonal planar, so can be attacked from either side
Which type of substrate has the fastest SN1 rate?
Tertiary
Which type of substrate has the fastest SN2 rate?
0
What is an intermediate
A reactive, short lived substance formed in the middle of a reaction step
What are the features of an SN1 reaction?
Unimolecular, 2 steps, carbocation intermediate, racemisation
What is the Hammond Postulate?
Anything that stabilises the intermediate also stabilises the transition state
What features do the best leaving groups have?
They are stable or have conjugate acids with low pKas
Does the leaving group influence the substitution mechanism?
No
Does the substrate influence the substitution mechanism?
Yes
Why do tertiary substrates never undergo SN2?
Because the nucleophile cannot get past the R groups due to steric hindrance
The better the leaving group…
…the faster the reaction
What are the three types of solvent?
Non-polar, polar protic, polar aprotic
What is a soft species?
Large and polarisable electron cloud
What is a hard species?
Small and non-polarisable electron cloud
Does the nucleophile influence the reaction mechanism?
Yes
What are the factors affecting nucleophile strength?
Negative charge, electronegativity, size
What kind of nucleophile does SN1 require?
Weak
What kind of nucleophile does SN2 require?
Strong
What is an example of a strong nucleophile?
OH-
What is an example of a weak nucleophile?
H2O
What is an example of a non-polar solvent?
CCl4
What is an example of a polar protic solvent?
H2O, alcohols
What is an example of a polar aprotic solvent?
THF, acetone
Why are non-polar solvents not suited to SN1?
They cannot solvate anything charged
Why are non-polar solvents not suited to SN2?
They cannot solvate Nu- or M+
Why are polar protic solvents not suited to SN2?
Nu- reactivity is reduced
Why do polar aprotic solvents favour SN2?
M+ stabilised, nucleophile not solvated, reactivity increased
Do polar aprotic solvents favour SN1?
Yes
What type of functional groups do carbonyl groups occur in?
Aldehydes, ketones, carboxylic acids, esters, thioesters
Why is the carbonyl group susceptible to nucleophilic attach?
Because it has a dipole, which pushes the electron density to the oxygen
Why is the alpha proton of a carbonyl group weakly acidic?
After the removal of it by a base, the conjugate base is obtained and resonance stabilised
What is an example of nucleophilic addition?
Cyanohydrin formation
What property does cyanohydrin formation have?
It is reversible
Where is cyanohydrin reversibility employed in nature?
When millipedes come under attack, converted back to ketone and HCN
What is a hemiacetal?
An alcohol and ether attached to the same carbon, RO and OH
What is an acetal?
Two ethers attached to the same carbon (RO)
What can hemiacetal formation be catalysed by?
Either an acid or a base
What are general properties of carbonyl compounds?
Susceptible to Nucleophilic attack, pi bond breaks, alpha hydrogen weakly acidic
What are the 4 types of reactions of carbonyls?
Nucleophilic addition, Nucleophilic substitution, substitution with loss of Oxygen, substitution at the alpha carbon
What is hydride transfer a result of?
Soft-soft interaction
What type of nature does hydride transfer have?
It is stereospecific
What type of mechanism is hydride transfer?
Nucleophilic addition
What is DCC?
Dicyclohexylcarbodiimide
What does DCC do to the OH group of a carboxylic acid?
Turns it into a very good leaving group
Why does DCC drive equilibrium to the RHS?
It locks up water generated in peptide bond formation
What can be used as a protecting group?
A polystyrene bead (50 micrometres)
What is an advantage of solid phase peptide synthesis?
It allows you to purify the product as you proceed with synthesis by washing
What are the disadvantages to solid phase peptide synthesis?
Linear synthesis, with 3 steps of ~90% yield only gives overall yield of 73%
Limit of polypeptide chain is approx 100 amino acids
What is used to remove the carbonyl oxygen in acetal formation?
ROH
How can a hemiacetal be converted into an acetal?
With excess alcohol and H+
Is acetal formation reversible?
No
What is the reagent in imine formation?
RNH2
What else can an imine be called?
A Schiff base
What is the only way in which an acetal can be formed?
Acid catalysis
What is acetal formation favoured by?
Excess alcohol and removal of water
What feature does imine formation have?
It is reversible
What is imine formation dependent on?
pH
What property do imines have?
They are weak bases
What are examples of acetals in nature?
Lactose and agarose
In imine formation, what is blocked if there is too much H+?
The nucleophilic attack on the carbonyl
In imine formation, what is blocked if there is too little H+?
Protonation with H3O+
What is the catalyst in imine formation?
H3O+
What is the catalyst in acetal formation?
H3O+
What are examples of imines in nature?
Cytosine has an imino form, and it is present in optical proteins
What is the first reactant for forming glutamic acid?
Alpha-ketoglutarate
What is needed for the last step of glutaic acid synthesis?
NADH and glutamate dehydrogenase
What feature does amino acid synthesis have?
It is reversible
