Flashcards in Organic Chemistry- Carboxylic Acid Derivatives Deck (100)
Carboxylic acids derivatives replace what, on the carboxyl group with what?
The -OH on the carboxyl group with another leaving group (-HR2, -OR, and -OCOR)
Do the carboxylic acid derivatives react similarly to carboxylic acids?
What are the carboxylic acid derivatives?
How are the carboxylic acids derivatives formed?
By condensation reaction iwth a carboxylic acid
What is condensation?
A reaction that combines two molecules into one, while losing a small molecule.
During the condensation of carboxylic acid, what small molecule is lost?
How is the water molecule formed during the condensation of the carboxylic acid?
From the hydroxyl group of the carboxylic acid and a hydrogen associated with the incoming nucleophile.
What should you focus on when dealing with derivatives of carboxylic acid?
The relevant nucleophile that forms the derivative and the nomenclature of the functional group.
What are amides?
Compounds with the general formula RCONR2
How are amides named?
They are named by replacing the -oic acid suffic with -amide. Alkyl substituents on the nitrogen atom are listed as prefixes, and their location is specified with the letter N-
What are examples of Amides?
How are amides synthesized?
By the reaction of other carboxylic acid derivatives with either ammonia or an amine
Why will only primary and secondary amides undergo a reaction?
The loss of hydrogen from the nucleophile required for this reaction to take place
cyclic amides are called what?
How are lactams named?
They are named according to the carbon atom bonded to the nitrogen.
Beta-lactams contain a bond between what?
The beta-carbon and the nitrogen
y-lactams contain a bond between what?
The y-carbon and the nitrogen
What are 4 examples of lactams?
Why or why not do amides participate in hydrogen bonding?
Depending on the number of alkyl groups they have bonded
What are the boiling points of amides dependent on?
They're hydrogen bonding makes their boiling poits lower or on the same level as the boiling points of carboxylic acids.
What are esters?
The dehydration synthesis products of other carboxylic acid derivatives and alcohols
How are esters named?
By placing the esterfying group (The substituent bonded to the oxygen) as a prefix; the suffix -oate replaces -oic acid
How is ethyl acetate formed?
From the condensation of acetic acid and ethanol
What is ethyl acetate called in IUPAC?
What are examples of esters?
What is Fischer esterification?
Under acidic conditions, mixtures of carboxylic acids and alcohols will condense into esters
How can esters also be obtained?
From the reaction of anhydrides with alcohols.
Cyclic esters are called what?
How are lactones named?
In the same manner as lactams with the name of the precursor acid molecules also included.
Why do esters usually have lower boiling points then carboxylic acids?
Because they lack hydrogen bonding
What are triacylglycerols?
The storage form of fats in the body, are esters of long-chain carboxylic acids (fatty acids0 and glycerol (1,2,3-propanetriol)
What is sponification?
The process by which fats are hydrolyzed under basic conditions to produce soap
What regenerates the fatty acids from soap?
Subsequent acidification of the soap
What's another name for anhydrides?
What are anhydrides?
the condensation dimers of carboxylic acids. These molecuels have the general formula (RC(O)OC(O)R)
How are symmetrical anhydrides named?
By subtituting the word anhydride for the word acid in a carboxylic acid.
How are asymmetrical anhydrides named?
Name the two chains alphabetically followed by anhydride
What are two examples of cyclic anhydrides?
Phthalic and succinic anhydrides
How are cyclic anhydrides derived?
Arising from intramolecular condesnation or dehydration of diacids
What are examples of anhydrides?
Ethanoic propanoic anhydride
Ehanoic anhydride (acetic anhydride)
How are acid anhydrides synthesized?
By a condensation reaction between two carboxylic acids, with one molecule of water lost in the condensation.
Certain cyclic anhydrides can be formed by what?
Simply by heating carboxylic acid.
How is the formation of certain cyclic anhydrides moved forward?
By the increased stability of the newly formed ring.
Only anhydrides with _____ can be made by heating carboxylic acids.
5 or six membered rings
All anhydride formations involve one ________ acting as the _____, attacking _______.
One -COOH acting as the nucleophile, attacks the carbonyl on the other -COOH.
What is anhydrides boiling point compared to carboxylic acids boiling point? Why?
They have higher boiling points then Carboxylic acids because of their much greater weight.
In nucleophilic subsitution reactions, the reactivity of the carbonyl is determined by what?
Of the carboxylic acid derivates, which are more reactive and least reactive?
Anhydrides are most reactive
Followed by esters (Tied with carboxylic acids)
The reactivity of the carboxylic acid derivaties can be explained by what?
The structure of these molecules
Why are anhydrides the most reactive?
Their resonance stabilization and three electron-withdrawing oxygen atoms, are the most electrophilic
Why are esters less reactive then anhydrides?
They lack one lectron-withdrawing carbonyl oxygen and are slightly less reactive.
Why are amides the least reactive?
They have an electron-donating amino group
What is also important to keep in mind when determining reactivity?
What is steric hinderance?
When a reaction does not proceed due to the size of the substituents
What is a good example of steric hinderance?
Sn2 reactions, which will not occur at tertiary ccarbons.
What is the advantage of steric hinderance?
It can be used to push a reaction in an Sn1 direction, rather than Sn2 and using tertiary substrate
What is a way steric hinderance is used synthetically?
In the creation of protecting groups.
How can steric hinderance effect the reactivity of the erivatives to nucleophili acyl substitution?
The size and substitution of the leaving groups can affect the ability of a nucleophile to access the carbonyl carbon.
What comes into play when dealing with carboxylic acid derivatives?
What is induction?
The distribution of charge across sigma bonds
What occurs in induction?
Electrons are attracted to atoms that are more electronegative, generating a dipole across the sigma bond. The less electronegative atom acquires a slightly positive charge, and the more electronegative atom acquires a slightly negative charge. This effect is relatively weak and gets increasingly weaker as one moves further away within the molecule from the more electronegative atom.
Induction is responsible for what?
The dipole character of the carbonyl group, as well as the increased dipole charater (and therefore susceptibility to nucleophilic attack) of carboxylic acids-- which contain an additional oxygen atom in their leaving group.
What explains there overall relative reactivity of anhydrides ester, and amides towards nucleophilic attack?
Anhydrides, have how many electron-withdrawing groups, which do what?
The leave a significant partial positive charge on the electrophilic carbon.
What effect is similar in amides to anhydrides? Why?
The partial positive charge on the electrophic carbon is still there but it is smaller because the nitrogen is less electronegative than oxygen, and the dipole is not as strong
All molecules involved in conjugation and resonance are either what?
sp2- or sp-hybridized and therefore have unhybridized p-orbitals.
What is conjugation?
The presence of alternating single and multiple bonds.
When p-orbitals align during conjugation and resonance, what happens?
They can delocalize pi electrons through resonance, forming clouds of electron density above and below the plane of the molecule
Conjugation and resonance is most commonly seen using what?
In carbonyl containing compounds, conjugation can be established with what?
With the carbonyl group
What are enomes?
alpha, beta-unsaturated carbonyls
What are common examples of conjugating carbonyl-containing compounds?
Why do enomes make for stable compounds?
The type of electron sharing
Because these compounds have multiple resonance structures. This characteristic allows for the stabilization of a positive charge once the nucleophile has bonded, making these compounds more susceptible to nucleophilic attack.
Lactams and lactones are what?
Cyclic amides and esters
Why are certain lactams and lactones more reactive to hydrolysis?
Because they contain more strain
What is an example of a lactam that has more strain?
Beta-lactams, are four-membered cyclic amides and are highly reactive due to significant rign strain; four-membered rings have both torsional strain from eclipsing interactions and angle strain from compressing the normal sp3 angle of 109.5 degrees.
Lactums and lactones with a lot of strain are usually part of the core structure of what?
Several antibiotic families
When is the ring strain increased?
By fusion to a second ring
What happnes when the beta-lactum is fused with a second ring?
Forces a trigonal pyramid bond geometry on the nitrogen atom in the ring, which reduces resonace, making hydrolysis more likely
What is penicillin?
beta-lactam containing antibiotic
What is involved in nucleophilic Acyl subsitution?
Nucleophilic attack of the carbonyl carbon with displacement of a leaving group.
All carboxylic acid derivatives can participate in nucleophilic substitution at different _______.
What is an example of nucleophilic substitution?
The formation of amides form the nucleophilic substitution reaction between ammonia and any carboxylic acid or derivative.
What is a cleavage reaction?
It splits an anhydride in two
What are the two reactions the formation of Amides are examples of?
Cleavage and Nucleophilic substitution
What's involved in the cleavage reacction of the formation of an amide?
Ammonia acts as the nucleophile, one of the carbonyl carbons acts as the electrophile, and a carboxylic acid is the leaving group.
What can act as a nucleophile toward anhydrides?
The nucleophilic subsitition reaction of alcohols and anhydrides results in what?
The formation of esters and carboxylic acids
How can anhydrides be reverted to carboxylic acids?
By exposing them to water.
To revert anhydrides to carboxylic acids, the anhydrides should be what? Why?
Otherwise you form a mixture of products
Alcohols can act as _____ and displace ____ on an ester.
Nucleophiles and displace the esterifying group on an ester.
What is transesterification?
Alcohols can act as nucleophiles and displace the esterifying group on an ester.
What occurs in transesterification?
One ester is simply transformed to another
Amides can be _______ under _______ conditions via ______.
Hydrolyzed under highly acidic conditions via nucleophilic substitution.
What do the acidic condition in nucleophilic substitution of amides allow?
The carbonyl oxygen to become protonated, making the molecule more susceptible to nucleophilic attack by a water molecule.
What is the product of nucleophilic substitution of amides in an acidic condition?
carboxylic acid and ammonia.
Hydrolysis of amides in an acidic reaction is the reverse of what?
The condensation reaction
Hydrolysis of amides can occur in what two conditions? acidic and basic conditions?
Acidic and basic
Hydrolysis of amides in a basic solution is similar to what? How is it different?
Similar to acid-catalyzed reaction
Different in that the carbonyl oxygen is not protonated and the nucleophile is a hydroxide ion