Unit 3 (Lesson 14-20) Flashcards
lithium reagents are typically used as
strong bases
Grignard reagents are perferred when acting as
nucleophile with epoxides and carbonyls
when the rxn is of a grignard + epoxide, you attack
the least hindered carbon and maintain stereochemistry
acidic proton with grignard
rxn will end up with starting material
reactivity of aldehydes and ketones in nucleophilic addition reactions
formaldehyde>aldehyde>ketone
alkyl groups are electron donating through
hyperconjugation and make C=O carbon less positive
as steric hindrance of the carbonyl increases
the reactivity toward nucleophilic addition decreases
order of nucleophilic reactivity
acid chlordide> acid anhydride> aldehyde > ketone > carboxylic acid > amide
grignard rxn with formaldehyde produces
primary alcohol
grignard rxn with aldehyde produces
secondary alcohol + (enantiomer sometimes)
grignard rxn with ketone produces
tertiary alcohol + (enantiomer sometimes)
what can be used to synthesize a carboxylic acid
addition of CO2 to a grignard
when a carbon is associated with a metal (Mg, Li, Cu), the carbon is the more/less electronegative atom and takes on a partial () character
more, negative
ether/solvent that Mg is added to
Et2O or THF
what conditions promote the conversion of acetone to acetone cyanohydrin
HCL, excess NaCN
cyanohydrin can be converted back into an aldehyde or ketone in the addition of a
base
strong acid/weak base =
good LG
strong base/weak acid =
poor LG
NaBH4
- more selective
- only reduces aldehydes and ketones
LiAlH4
- less selective, more reactive
- reduces aldehydes, ketones, esters, carboxylic acids, nitriles, amides
why do NaBH4 and LiAl4 require H3o+
they require an aqueous workup to protonate the alkoxide
things that add irreversibly
NaBH4, LiAlH4, RMgX, or RLi
ketone /aldehyde + water (+acid/base catalyst)
hydrate
degree of hydration at equilibrium (K)
= [hydrate]/starting aldehyde/ketone
degree of hydration trends
as K increases, more hydrate is formed
why is an aldehyde with F3C instead of CH3 so reactive
so reactive because it’s electron withdrawing
aldehydes and ketones are in equilibrium with their acetals in the presence of ()
alcohol
hemi-acetal
1OR + 1 OH
acetal
OR + OR
to favor acetal formation
add more (CH3OH], remove water
to favor aldehyde formation
increase [H2O] and remove methanol
acetal hydrolysis
- follows same mechanism as an acetal formation, but in reverse
- acetals are good protecting groups –>
reducing agents we’ve used
H2/Pd
H2NNH2, KOH, heat
NaHB4
DIBALH
LiAlH4
reduction refers to
the addition of H2 or removal of oxygen
Oxidation refers to
the addition of oxygen or removal of H2
oxidizing agents for this course
PCC
H2CrO4
hydrogenation
H2 pd/c
- only benzylic
- reduces benzylic carbonyls to methylenes
wolff-kischner – H2NNH2, KOH, heat
reduces all carbonyls to methylenes
primary alcohol oxidations - anhydrous conditions with ()
PCC
primary alcohol oxidations - aqueous with ()
Chromate (H2CrO4)
PCC + a secondary alcohol makes a ()
ketone
to form an imine you use a () amine
primary
to form an enamine you use a () amine
secondary
enamines have
2 R groups and a double bond in the ring
imines have
1 R group and a double bond between N and C on ring
imine reduction is a useful method for
synthesizing secondary amines
true/false: imines are more reactive than ketones and aldehydes
true – they can selectively reduce with H2, Pb/C, or NaBH3CN
what does a wittig reaction do
replace carbonyl with alkene
first step in wittig reaction
generate phosphonium ylide
weak compounds add via ()
conjugate addition
- more stable, weak bases
1,4 - Addition
strong compounds ad via ()
direct addition
- strong base, nuc
1,2 - Addition
addition to a weak base is () and driven by ()
reversible, thermodynamic control
secondary alcohols oxidize to form ()
ketones, regardless of oxidizing agent
primary alcohols can be oxidized to form () or ()
aldehydes (mild oxidation)
carboxylic acids (strong oxidation)
can tertiary alcohol be oxidized
no
true/fasle: when aldehydes and ketones are attacked by a carbon nucleophile or a hydride donor, there is no leaving group in the tetrahedral intermediate
true
when aldehydes and ketones react with water, alcohols, or amines (1 & 2), they undergo what
a nucleophilic-addition-elimintation mechanism
what are the optimal pH conditions for imines and enamines to be formed
~ 4.5
imine and enamine formation at a low pH
pH must be acidic enough to promote the dehydration step (elimination of H2O), however if solution is too acidic, the amine present will deprotonate, decreasing the availability of nucleophilic amine in the mixture
inamine and enamine formation at a high pH
if the solution isn’t acidic enough, protonation of the hemiaminal intermediate is less effective and the rate decreases
imine formation last step
deprotonation
enamine formation last step
elimination of an alpha hydrogen to for a C=C, which breaks the C-N Pi bond
steps to go from hemiacetal to acetal
protonate, eliminate water, nucelophilic addition, deprotonate
reversion to carbonyl occurs when acetals are reacted with ()
water and acid
