2nd Year Organic Reactions Flashcards
Malonic Ester Synthesis
Start with dicarbonyl ester, add weak base (NaOMe) to form enolATE (charged O), Nucleophilic carbon attacks new alkyl halogen in SN2 reaction (I think it’s Sn2), then add NaOH + kick out one OEt group to form deprotonated CA, Add acid to form CO2 and rearrange enol to form (MONO) ester
Product in Malonic Reaction and driving force?
Create ester from dicarbonyl ester species and form CO2.
Claisen Condensation
Create diCarbonyl species from ester - add base to form enolate, enolate reacts with normal ester form, add acid to kick out one HOEt group.
Aldol Reaction
Use Acid to form Enol - React with non enol form to form dicarbonyl species (as multiple enol forms potentially - start with ketone with phenyl ring to limit possibilities)
Diels Alder - how to speed up reaction?
Add EWG to dienophile
Diels Alder - how to influence endo or exo?
Endo - EWG on dienophile ends up on SAME SIDE as outside group of Diene - KINETIC PRODUCT
Exo - EWG opposide side as outside group in diene - THERMODYNAMIC PRODUCT
LDA vs NaOME to form Enolates
LDA forms kinetic product and NaOME forms thermodynamic
Mannich Reaction
Use Acid to form Enol (Acid as Manic = crazy) and add amine group to alpha position on enol. Do this by making imine with positive charge on nitrogen (ketone and amine. Add acid which creates ROH+, nitrogen attacks carbonyl carbon, is deprotonated, OH attacks another H+, Nitrogen uses lone pair and water leaves - Have IMINE). Enol then attacks carbon in imine.This is MANNICH BASE. Do you know how to form michael acceptor then?
How to form Michael acceptor from ketone?
Mannich reaction - once mannich base formed, add MeI so that Nitrogen forms RN+Me3. Add base to form enolate by deprotonation of carbon gama to carbonyl and kick out amide (nitrogen) group
Robinson Reaction
Cyclic Ketone forms enolate which reacts with michael acceptor, the O- can then be neutralised by addition of acid or if basic condition and enolate form kept, the enolate can attack carbonyl position of original cyclic ketone and this can form a ring
What type of nucleophiles react at beta position of michael acceptors?
Soft nucleophiles (large)
Why is it better to add ketone to benzene ring and then reduce to primary alkyl chain than add a primary alkyl chain directly ?
Rearrangement to tertiary carbon when doing friedal crafts alklyation means there are two products
How to reduce product of friedal crafts alklyation to alkyl chain substituent ?
Zn/Hg and conc HCl
How to reduce product of friedal crafts acylation to imine ? - then to alkyl side group
N2H4, then KOH
OR
Zn (Hg) and HCl
OR
R-NH2 and H+
How to reduce product of friedal crafts acylation to alkyl chain substituent using sulfur ?
HS CH2 CH2 SH and BF3
Creates like cross where carbon is nucleophilic (retro senge)
Add H2 and Ni (Raney Reaction)
not too sure what i meant here
if use acylation, have extra Me group that’s not good LG, can react with HSC3H6SH with HCl and CHCl3 to form cross which makes the carbon nucleophilic after addition of BuLi, get rid of thiol ester with H2 and Ni (Raney)
Zaitsev Rule
Hydrogen is removed from the beta carbon with the fewest hydrogens - this means that the subsequent formation of the alkene is the alkene that has the most R substituents, as the empty p orbitals on the carbons on the R substituents can donate electron density to the pi orbitals of carbon in double bond (hyperconjugation).
E1 reaction
LG leaves due to polar interactions in solvent, forms carbocation and removal of beta hydrogen to form double bond.
E2 Reaction
Concerted mechanism, nucleophile attacks beta hydrogen instead of alpha carbon.
Sn2
backward attack. walden inversion. 5 bond intermediate. Occurs if base can act as nucleophile and attack carbon.
Sn1 reaction
LG leaves due to polar interactions. Attack of nucleophile on alpha carbon.
Nucleophilic Aromatic Substitution - main requirements
- LG (e.g. Halogen)
- Electron Withdrawing group in ORTHO or PARA position (META DOES NOT WORK)
- Nucleophile
- the more EWG, the fast rate
Fluorine as a LG
Okay for NAS but doesn’t work for Sn1 and Sn2 due to strength of C-F bond and F being unpolarisable (electron cloud can’t be distorted easily as it is small and electronegative)
How to substitute bromobenzene with NH2 or OH? (Form phenol or phenylamine) or how to make benzaldehyde
Phenol - 350 degreees,
Phenylamine - Liq NH3?
Benzaldehyde - use Mg to make MgBr and thne attack amide at carbonyl and have leaving group
what is structure of toluene?
Benzene ring with methyl group attached
