Unit 4 (Lesson 21-27) Flashcards
what facilitates nucleophilic substitution occurring on CAD
facilitated by the presence of a leaving group on the carbonyl carbon
leaving group example
OR, Cl, NH2, OCOR
not leaving group example
H, R, Ar
reactivity of carboxylic acid derivatives is based on
- leaving group ability of X
- Electrophilicity of carbonyl carbon
- Steric hindrance
strongest resonance contributing structure has
negative O and positive N
why are amides particularly ureactive toward nucleophilic attack
due to the resonance contribution from N
order of reactivity of carbonyl derivatives (most to least)
acid chloride > anhydride > ester > amide > carboxylate
reactivity of carboxylic acid derivative increases/decreases with decreasing basicity of leaving group
increases
why is acid chloride not found in nature
because it is so reactive
how do you make acid chloride from an acid/carboxylate
SOCl2, or PCl3
do acid halides require any acid or base to facilitate substitution
no - already extremely reactive
three different reaction perturbations with acyl halides
1.) negatively charged nucleophile
2.) neutral nucleophile
3.) neutral nucleophile with catalytic acid
reactants for hydrolysis of an acid chloride
H2O
* deprotonate before kicking out Cl
to from amide:
- at least 2 equivalents of amine must be used to push the reaction to completion
- add 1 equivalent of a primary or secondary amine AND one equivalent of a tertiary amine (pyridine)
what are the methods for forming an anhydride
- from an acid halide
- from a carboxylic acid
anhydride to ester
ROH(alcohol) or RO- + pyridine
carboxylate/acid to an ester
ROH (alcohol)
H+ (catalytic acid)
[strong base/CH3Br, alc/pyridine] –> will work as well
what controls the rate of reaction for the esterification of carboxylic acids
steric hinderance
- proceeds through a series of reversible steps
carboxylic acids only undergo nucelophilic acyl substitution when they are in their () forms
acidic
WHY – basic form makes it resistant to an approach from an electrophile –> carboxylate ions less reactive than amides in nucleophilic acyl substitution
why are esters not strongly electrophilic
due to the strong resonance contribution from the oxygen
– reactions with esters require better nucleophiles or stronger conditions than reactions with acid chlorides and anhydrides
three different reaction perturbations for esters
1.) negatively charged nucleophile
2.) neutral nucleophile (must be good nucleophile)
3.) neutral nucleophile with catalytic acid
the strength of the () and () determines the reaction conditions and mechanisms
electrophile, nucleophile
transesterification
one alcohol is used in excess to drive the equilibrium in the desired direction
basic conditions
no (+) intermediates
acidic conditions
no (-) intermediates
true/false: esters and carboxylic acids are around the same energy/reactivity
true
will an ester and H2O molecule react
no – needs an acid catalyst
which of the carboxylic acid derivatives are unlikely to undergo a nucleophilic reaction with a Grignard reagent
amides and carboxylic acids
WHY – protic hydrogens
true/false: addition to the ketone is faster than the addition to the ester
true
true/false” addition to the aldehyde his faster than the addition to the ester
true
DiBAL-H reduction of esters leads to what
aldehyde formation
true/false: carboxylic acids can be reduced to primary alcohols with LiAlH4
true
NaBH3CN
- selective
- only reduces imines and enamines to secondary and tertiary amines
amide to carboxylate/acid
1 eq HCl, H2O, heat
or NaOH then H3O+, heat
why are amides not very electrophulluc
due to the strong resonance contribution from the nitrogen
– recall 2 peaks for N-CH3’s of an amide in an H1NMR due to the barrier of rotation around the C-N bond
are amides stable
yes - very - due to excellent orbital overlap and resonance contribution
what do reactions with amides require
very good nucleophiles and/or strong bases
2 different reaction perturbations for amides
1.) negatively charged nucleophile
2.) neutral nucleophile with catlalytic acid/base and heat
amide hydrolysis: acidic conditons
no negatively charged intermediates
pattern of intermediates: (charge –> neutral –> charge)
amide hydrolysis: basic conditions
no positively charged intermediates
pattern of intermediates: (charge –> neutral –> charge)
how can nitriles be transformed in to carboxylic acid
through hydrolysis or an amine via reduction
true/false
the sp-hydridized carbon of a nitrile is moderately electrophilic and reacts with a strong base or in the presence of a strong acid
c-c bond is made
2 reaction perturbations for nitriles
1.) negatively charged nucleophile
2.) neutral nucleophile with acid (1.0 equiv) and heat
fischer esterification only works if alcohol has less than () carbons
three
electron withdraw from the carbonyl carbon increases/decreases its electrophilicity
increases
true/false: the carbonyl carbon is electrophilic and is susceptible to nucleophilic attack under the right condittions
true
