CHEM 263 - Chapter 5

Created by Ameera Gani

What can primary alcohols be oxidized to? 2
Aldehydes or Carboxylic acids

1/78

TermDefinition
What can primary alcohols be oxidized to? 2
Aldehydes or Carboxylic acids
What can secondary alcohols be oxidized to?
Ketones
What can tertiary compounds be oxidized to? Why?
- Tertiary compounds cannot be oxidized to C=O - there are no H's to take
What are the solvents involved in the PCC oxidation? 2
- PCC - CH2Cl2 or DCM
Does the PCC oxidation happen under aqueous or anhydrous (no water) conditions?
Anhydrous
What are primary alcohols converted to during the PCC oxidation?
Aldehydes
What are secondary alcohols converted to during the PCC oxidation?
Ketones
T/F: the solvent participates in the reaction
False
What are the solvents involved in the Jones oxidation? 2
- H2CrO4 - H2O/Acetone
Does the Jones oxidation happen under aqueous or anhydrous conditions?
Aqueous
What are primary alcohols converted to during the Jones oxidation?
Carboxylic acids
What are secondary alcohols converted to during the Jones oxidation?
Ketones
What solvents are involved during the Swern oxidation?
- DMSO, (COCl)2 - NEt3
Does the Swern oxidation happen under aqueous or anhydrous conditions?
Anhydrous
What are primary alcohols converted to during the Swern oxidation?
Aldehydes
What are secondary alcohols converted to during the Swern oxidation?
Ketones
What hybridization are all carbonyl functional groups? What are their bond angles and geometry?
Sp2 - 120 degrees, trigonal planar
If the C=O bond is polarized, is it electrophilic at the C or the O?
Electrophilic at the C
Which undergo nucleophilic addn faster: aldehydes or ketones? Why
- Aldehydes - Due to steric and electronic factors
What are steric and electronic factors?
Steric: Aldehydes only have one alkyl group = less sterically congested Electronic: Aldehydes are more electrophilic because it is only stabilized by one EDG (alkyl group)
What happens when a carbonyl is attacked by a Nu? What happens to hybridization?
The weakest bond (DB) breaks = tetrahedral intermediate - Sp2 to Sp3
What happens under basic conditions during a nucleophilic attack? 2
- Nu directly attacks carbonyl carbon - Protonates after w/ H-A (acidic workup)
What happens under acidic conditions during a nucleophilic attack? 3
- Carbonyl first protonated to make it more electrophilic - Nu-H attacks carbonyl carbon - A- takes H from Nu-H
Why can Nu attack create steroisomer?
Because you can attack from either face of the DB
Why do you need to remove moisture and oxygen during organometallic rxns?
Radical intermediates can form side-products
Which bears more electron density in the C-M bond? Why
- C - C has a higher electronegativity
T/F: acidic protons can be present during organometallic rxns
False, all organometallic reagents are BASIC and nucleophilic
How can carbonyl compounds be converted to alcohols by reduction?
Using metal hydrides under BASIC conditions
What does sodium borohydride reduce? 2
Aldehydes and Ketones
What solvents does NaBH4 use?
Protic solvents - MeOH, EtOH
What does lithium aluminium hydride reduce? 5
- Aldehydes - Ketones - Esters - Amides - Nitriles
What solvents does LiAlH4 use?
Aprotic solvents - THF, Et2O
Which is more reactive: LiAlH4 or NaBH4
LiAlH4
What step is always requires no matter what hydride you use?
Acidic workup to quench (stop) rxn
T/F: 0.5 eq of NaBH4 (or LAH) can reduce 1 eq of ketone
False - 0.25 eq of NaBH4 (or LAH) can reduce 1 eq of ketone - All 4 hydride anions are transferred to electrophiles
What forms when aldehydes/ketones react w/ water under acidic or basic conditions?
Hydrates
Describe what a hydrate looks like
Two hydroxyl groups (OH) attached to same sp3 carbon
Is the synthesis of a hydrate reversible or irreversible?
Reversible
What can you do to push the hydrate synthesis rxn forward or backward?
Forward: add excess H2O = hydrate Backward: remove water using drying agent = carbonyl
Do EDG favour or disfavour hydrate formation? Why?
- Disfavour - Because the carbonyl carbon is less electrophilic/reactive
Is the Keq for hydrate formation lower for aldehydes or ketones?
Low Keq for ketones
Do EWG favour or disfavour hydrate formation? Why?
- Favour - Carbonyl carbon is more electrophilic/reactive
Is the Keq higher for EDG or EWG?
Higher for EWG
What solvents are used to convert ketones/aldehydes to hydrates? 2
- H2O - H+/OH-
What solvents are used to convert ketones/aldehydes to acetals? 2
- Two eq's of an alcohol (ROH) - H+
What always forms during acetal formation? Describe what it looks like
Intermediate: Hemiacetal - 1 hydroxyl (OH) group and one alkoxy (OR) group attached to sp3 carbon
Can acetal formation occur under basic conditions? Why?
- No, only under acidic conditions - Acid needs to protonate both the carbonyl O and many LG's to create the loss of water
Does acetal formation favour aldehydes or ketones as SM?
Aldehydes
Is acetal formation reversible or irreversible?
Reversible
What would you use to hydrolyze an acetal? 2
- Acid - Excess H2O
When do you get cyclic acetals?
When both eq's of alcohol are tethered together
Are cyclic acetals more or less stable then acyclic ones?
More stable, harder to hydrolyze
Which reactions occur faster: Intramolecular or Intermolecular?
Intramolecular (cyclic)
What is a protecting group?
Group that is added to prevent a rxn from going
Acetals can protect what functional groups? 3
- Aldehydes - Ketones - Alcohols
What are dithianes?
Cyclic thioacetals
Are thioacetals more or less stable than standard acetals?
More
What solvents do you need to convert ketone/aldehyde to dithiane? 2
- 2 eq's of SH tethered together - Lewis acid (ex. BF3)
What reagents can be used to deprotect the reaction? 3
- Mercury, salts - Oxidation of S to sulfoxides - Rxn of S atoms w/ good electrophile (ex. MeI, NBS)
How can you completely reduce a thioacetal?
Raney Nickel
Do the most simple carbs have an aldehyde or ketone group?
Aldehyde
What type of molecule do monosaccharides exist as?
Cyclic due to hemiacetal formation
Acetal formation can generate 2 diff isomers at the _____ carbon to create _______
- Anomeric carbon - Alpha and beta anomers
What happens when ketones/aldehydes are treated w/ primary alcohols or ammonia?
Imine formation
What is always formed during imine formation? Describe what it looks like
Hemiaminal - 1 hydroxy group (OH) and 1 NHR group
What solvents are used during imine formation? 2
- RNH2 - H+
Are acyclic imines stable or unstable?
Unstable - Will hydrolyze easily in presence of aq acid to reform C=O
What must be removed during imine formation to drive the rxn forward?
Water
What isomer is most stable in imine formation?
One with largest R groups TRANS to eachother
What happens when you are using a secondary amine and the iminium ion is formed?
There is no proton to remove from charged N atom = proton next to iminium ion (alpha position) is removed = enamine
Which molecules react with carbonyls to generate stable imines?
- Hydroxylamine - Hydrazine - Semicarbazides
Describe the structure of an imine
Heteroatoms whose LP's are conjugated to the DB
What does the resonance form of the imine product look like?
Neg charge on imine carbon = not susceptible to Nu attack
What solvents are used during the Wolf-Kishner reduction?
KOH, Heat
What steps are reversible and irriversible during wolf-kishner reduction? Why?
- Reversible: hydrazone formation - Irreversible: final reduction step due to loss of N2 gas
What are the 3 ways to reduce a C=O to a -CH2- group?
- Wolf Kishner - Clemmensen - Desulfurization
What is the purpose of the Wittig rxn?
Convert aldehydes/ketones to alkenes
Which isomer is favoured in the Wittig rxn?
Z isomer