Chapter 9: Carboxylic Acid Derivatives Flashcards
(30 cards)
What mechanism forms carboxylic acid derivatives?
In a condensation reaction, two molecules are combined to form one, with the loss of a small molecule – water
Carboxylic acid derivatives are formed by condensation reactions
Water is created from the hydroxyl group of the carboxylic acid and a hydrogen associated with the incoming nucleophile
What are the three carboxylic acid derivatives studied in this chapter?
Amides, esters, anhydrides
Each of them replace the -OH with -NR2, -OR, and -OCOR, respectively.
What are amides?
How are they named?
How are amides formed?
Will tertiary amines undergo this reaction?
Condensation reaction by carboxylic acid derivatives and either ammonia or primary and secondary amines.
Loss of hydrogen from the nucleophile is necessary for the reaction to take place (produce water in combination with the -OH leaving group)
For this reason, tertiary amines will not react with carboxylic acid (and their derivatives) to form amides.
What are cyclic amides named?
How are they named?
Cyclic amides are called LACTAMS
They are named according to the carbon atom bonded to the nitrogen.
Beta lactam: nitrogen bound to the beta carbon (remember it’s a ring structure)
Do amides participate in h bonding?
What’s up with their boiling point?
Amides may or may not participate in hydrogen bonding, depending on the number of alkyl groups they have bonded
Therefore, they’re boiling points may be lower or on the same level as the boiling points of carboxylic acids
What are esters?
How are they named?
Esters are the dehydration synthesis, product of other carboxylic acid, derivatives and alcohols
They are named by placing the esterifying group (the substituent bonded to the oxygen) as a prefix
-oate suffix is used (replacing -oic acid)
How are esters made (two ways)?
What kind of reaction?
Draw a Fischer esterification
Under acidic conditions, mixtures of carboxylic acids, and alcohols will condense into esters (condensation reaction, water produced by -OH leaving group and a hydrogen from an H on the attacking group)
Esters can also be obtained from the reaction of anhydrides with alcohols
What are cyclic esters called?
How are they named?
Click esters are called lactones
Their named according to the carbon atom bonded to the oxygen, just like naming lactams (cyclic amides)
Do esters have hydrogen bonding?
What does it say about their boiling points related to carboxylic acids?
Because they lack hydrogen bonding, esters usually have lower boiling points than their related carboxylic acids
What are triacylglycerols?
What is saponification?
Triacylglycerols (triglycerides) are the storage form of fats in the body
They are esters of long chain carboxylic acids (fatty acids) and glycerol (1,2,3 propanetriol)
Upon vacation is the process by which fats are hydrolyzed under basic conditions to produce soap.
Subsequent acidification of the soap regenerates the fatty acid
What are anhydrides (aka acid anhydrides)?
How are they named?
Anhydrides are the condensation dimers of carboxylic acids
Have general formula RC(O)OC(O)R
Symmetrical anhydrides are named by substituting the word anhydride for the word acid in a carboxylic acid
When anhydrides are asymmetrical, simply named the two chains alphabetically, followed by anhydride
How are amhydrides made?
Draw the synthesis of a generic anhydride
Acid anhydrides are synthesized by a condensation reaction between two carboxylic acids (one molecule of water is lost by the -OH leaving group and a hydrogen on the attacking group)
Can certain cyclic and hydrides be formed simply by heating carboxylic acids?
Certain cyclic and hydrides can be formed, simply by heating carboxylic acids
The reaction is driven forward by the increased stability of the newly formed ring
ANHYDRIDES WITH FIVE OR SIX MEMBER RINGS ARE EASILY MADE
The hydroxyl group of one -COOH acts as a nucleophile, attacking the carbonyl on the other -COOH
Compare and hydride boiling points with their related carboxylic acids
Anhydrides often have higher boiling points than their related carboxylic acids
This is due to stronger intermolecular forces, primarily due to their larger size and greater surface area
Concept check 9.1
Rate the reactivity of the carboxylic acid derivatives toward a nucleophilic attack
Anhydrides are the most reactive,
Followed by esters,
Followed by carboxylic acids
Followed by amides
Speak about the relative reactivity of carboxylic acid derivatives
In a nucleophilic substitution reaction, the reactivity of the carbonyl is determined by its substituents
Anhydrides are the most reactive
Followed by esters (actually tied with carboxylic acids but whatev)
Followed by carboxylic acids
Anhydride residence stabilization in three electron withdrawing oxygen atoms are the most electrophilic
Esters lack one electron withdrawing carbon oxygen, and are slightly less reactive
Aides, with an electron donating amino group, are the least reactive toward nucleophiles
Followed by amides
Speak about steric effects in carboxylic acid derivatives
Steric hindrance is always worth keeping in mind when considering reactivity
Stair hindrance describes when a reaction does not proceed due to the size of the substituent
Recall that SN2 reactions will not occur at tertiary carbons do a significant steric hindrance
What is induction?
Induction refers to the distribution of charge across sigma bonds.
Electrons are attracted to atoms that are more electronegative, generating a dipole across the sigma bond
The less electronegative atom requires a slightly positive charge, and the more electronegative atom requires a slightly negative charge
This effect gets increasingly weaker as one moves further away within the molecule from the more electronegative atom
This effect is responsible for the dipole character of the carbonyl group (and therefore susceptibility to nucleophilic attack of carboxylic acids)
What is conjugation?
Residence and conjugation also affect the reactivity of a molecule
Conjugation refers to the presence of alternating single and multiple bonds
This set up implies that all of the atoms involved in these bonds are either sp2 hybridized or sp hybridized, and therefore have unhybridized P orbitals
When these P orbitals align, they can delocalize by electrons through residence, forming clouds of electron density above and below the plane of the molecule
Why are beta lactams biologically significant?
What are beta lactamases?
Many antibiotic families contain beta lactams, including the penicillin family, cephalosporins, carbapenems, and monobactams
Speak about strain in cyclic carboxylic acid derivatives
Lactams and lactones are cyclic amides and esters, respectively
Certain lactase and lactones are more reactive to hydrolysis because they contain more strain
Beta lactams, for example, or four member cyclic amides and are highly reactive due to significant ring strain
Four member rings, have both torsional strain from eclipsing interactions and angle strain from compressing the normal sp3 angle of 109.5° to a smaller angle
Concept check 9.2
