Carboxylic Acids Flashcards
T or F: for nomenclature, carboxylic acids have the highest priority
true (they’re woke that way)
what happens to a carb acid in water
water deprotonates it, making an equilibrium. H is the electrophile, and a hydronium ion and the conj. base is formed. The conj. base is resonance stabilized
when carb acids get deprotonated by water, is the conjugate base unstable?
no, it’s resonance stabilized
how can we manipulate the stability of the acid
by changing the R group
addition of electron withdrawing substituents to the acid ___ the acidity
INCREASES
how does adding electron withdrawing substituents to the acid increase acidity
due to the inductive effect
stronger acids have (stable/unstable) conjugate bases
stable, because they have electron withdrawing groups
T or F: carb acids may be protonated by a stronger acid (one with lower pKa)
true. The one with the higher pKa acts as a base
how can you form a carb acid from an alcohol
oxidize a primary alcohol
when oxidizing a 1o alcohol to form a carb acid, what kind of oxidizing agent do we want to use
a strong one
give examples of oxidizing agents we may use to make carb acids from alcohols
KMnO4, K2CrO7, Jones
how can we oxidize aldehydes into carb acids
by using HNO3
T or F: we can use HNO3 to oxidize any aldehyde into the carb acid
false, we cannot use this method if our molecule is sensitive to acids
if we can’t use HNO3 to oxidize an aldehyde into a carb acid, what do we do instead
use a Tollen’s test
describe a tollen’s test
1) 2Ag(NH2)2OH (basic conditions)
2) [H+] (mild acid wash)
= carb acid from aldehyde
how can we form a carb acid from a nitrile
do hydrolysis of nitriles
in what conditions can we do hydrolysis of nitriles
acidic or basic
what do the arrows look like in the hydrolysis of nitriles
acidic: use [H+]
basic: 1) use [OH-} 2) use [H+]
describe hydrolysis of nitriles
it’s protons in water or hydroxide in water. We’re hydrolyzing the nitrogen away
how can we make carb acids from alkyl halides
grignard reaction with carbon dioxide
describe how the grignard reaction is used to form carb acids
make the grignard reagent forst, then react with with CO2 and THF (solvent), which forms a new C-C bond. Then we do hydrolysis ([H+]) and we have our carb acid
can we use water in the grignard reaction
NO. conditions must be anhydrous until the work up
which carbon acts as the nucleophile in the grignard reaction? why
the carbon of the alkyl halide is the nucleophile and attacks the CO2 electrophile, because once the Mg was inserted the dipole was reversed
why do we use THF as a solvent in the grignard reaction
its polar and aprotic (we don’t want anything protic in this step)
what happens in the reduction of a carb acid
it turns into an alcohol (it’s the opposite of how we make them)
how do we do the reduction of carb acids
1) LAH
2) [H+]
= primary alcohol
why must we use LAH in the reduction of carb acids
NaBH4 is too weak
what do we do if we want to reduce a carb acid to an aldehyde
the reduction won’t stop until alcohol is reached, so we make an alcohol, then use PCC to oxidize it to an aldehyde
describe the addition elimination reaction
we convert the OH of the carb acid into a better leaving group, then react it with a nucelophile, giving us a carb acid derivative (carbonyl attached to R and Nuc)
what happens if the carb acid derivative reacts with water? what is the implication of this
hydrolysis converts it back to a carb acid (bad), so we don’t want to add water in this reaction. Instead, use a different nuc
T or F: we can convert carb acids to acyl halides in one step
false
why cant we convert carb acids to acyl halides in one step
OH is a bad LG, so we must come up with a better one
what are 3 useful reagents to use to make an acyl halide
SOCl2, PBr3, PCl5
describe the mechanism of acyl halide formation
the OH of the acid attacks the reagent (probably SOCl2) which then attaches. A Cl leaves as a carbonyl is formed, then the lone O is deprotonated, and we are left with a good LG
in the first step of the mechanism to form acyl halides, what acts as the nucleophile
the OH of the carb acid
why is the product of the first part of the acyl halide mechanism a good LG
it has resonance and the inductive effect when it leaves
now that there’s a good LG in the acyl halide mechanism, what happens
Cl attacks the molecule, we get electrons moving, LG leaves, and we have an acyl halide
other than an acyl halide, what is produced during the mechanism
SO2 gas (which is a good driving force of the reaction)
how can we form a carb acid from an alkyne
1) O2, DCM, -78 degrees
2) An, AcOH
AcOH=acetic acid
produces 2 carb acids
what is the product when a C type nucleophile (ie grignard) reacts with an acyl halide
a 3o alcohol
how many times does a C type nuc attack an acyl halide
2
what is the product when an H type nucleophile (ie LAH) attacks an acyl halide
a 1o alcohol
how many times does an H type nuc attack an acyl halide
2
what is the exception for H type nuc attacking acyl halides twice
LTTBA (it attacks only once)
what is the product when LTTBA reacts with an acyl halide
aldehyde
what is the other exception to the twice attack rule on acyl halides
cuprates! (they attack once) (ie Me2CuLi)
what is the product when cuprates (ie lithium diakyl cuprates) attack acyl halides
X is removed, and the alkyl group of the cuprate is added
how many times do all other nucleophiles (S, O, N) attack acyl halides
only once
what is an anhydride
basically 2 esters merged together (2 ketones on either side of a lone oxygen)
what is the starting reagent for anhydride preparation
an acyl halide
describe how anhydrides are made from acyl halides
we react an acyl halide with a carb acid and a pyridine base (this would happen when we make an acyl halide which then reacts from the acid it came from)
in anhydride preparation, what acts as the nucleophile
the deprotonated acid (which acts as a good LG)
what is the driving force for anhydride reactions (ie why do they proceed)
the deprotonated acid is a GOOD leaving group
describe the anhydride reaction mechanism
anhydride is attacked by the nuc causing electrons to move around, the deprotonated acid LG leaves, and we have two products: a deprotonated acid, and a ketone attached to the nuc
what is the term for how esters are made
transesterification
what are esters made from
carboxylic acids
how are esters made from carboxylic acids
react it with excess ROH and use [H+]
how do you convert an ester back into a carb acid
hydrolysis (excess H+, or OH- and then H+)
when may transesterification be intermolecular
when it produces a 5 or 6 membered lactone
describe the basics of intramolecular transesterification
the OH at the far end of the carb acid reacts with the carbonyl on the other side = cyclizes into an ester
what is an amide
ketone attached to NR2 (R may be alkyl group or H)
are amides difficult or easy to reaction; what is the effect of this
difficult to react, so we must use brute force
why are amides difficult to react
we cannot make them more electrophilic with H+, because if we did the N would grab it before the O, and we would have a good LG which we don’t want
what harsh conditions must we use for amide reactions
high temperature, catalysts, time
what 3 things can we make from amides and what are the names of those reactions
hydrolysis=acids
reduction=amines
dehydration=nitriles
describe hydrolysis of amides
- produces carboxylic acids
- can use H2SO4, heat, and wait 3 hours
- or we can do 1) NaOH with heat 2) [H+]
describe reduction of amides
- produces an amine
- use 1) LAH and Et2O 2) [H+]
describe dehydration of amides
- produces a nitrile
- use SOCl2 or P2O5
- essentially this reaction makes more bonds to the nitrogen
how do we convert a nitrile back into an amide
use [H3O+]
how can we covert an amide into an aldehyde
amide –> nitrile via dehydration, and then reduce the nitrile to an aldehyde (using DIBAL and H+)
