Ch 9 - Carboxylic Acid Derivatives Flashcards
What are amides and their nomenclature?
- the condensation products of carboxylic acids and ammonia or amines
- given the suffix -amide
- the alkyl groups on a substituted amide are written at the beginning of the name with the prefix N-
What are lactams and their nomenclature?
- cyclic amides
- named by the greek letter of the carbon forming the bond with nitrogen (beta-lactam, gamma-lactam, and so on)
What are esters and their nomenclature?
- the condensation products of carboxylic acids with alcohols (Fischer esterification)
- given the suffix -oate
- the esterifying group is written as a substituent, without a number
What are lactones and their nomenclature?
- cyclic esters
- named by the number of carbons in the ring and the Greek letter of the carbon forming the bond with the oxygen (alpha-acetolactone, beta-propiolactone, and so on)
What are triacylglycerols and how are they formed?
a form of fat storage
- include 3 ester bonds between glycerol and fatty acids
What is saponification?
the breakdown of fat using a strong base to form soap (salts of long-chain carboxylic acids)
What are anhydrides?
the condensation dimers of carboxylic acids
How are symmetric/asymmetric anhydrides named?
- symmetric: named for the parent carboxylic acid, followed by anhydride
- asymmetric: named by listing the parent carboxylic acids alphabetically, followed by anhydride
How can some cyclic anhydrides be synthesized and what form is most stable?
- by heating dioic acids
- 5- or 6-membered rings are generally stable
How does the reactivity of amides, anhydrides, and esters compare in nucleophilic substitution reactions?
anhydrides are more reactive than esters, which are more reactive than amides (need a strong acid/base to react)
What does steric hindrance describe?
when a reaction cannot proceed (or significantly slows) because of substituents crowding the reactive site
What are protecting groups?
- like acetals
- can be used to increase steric hindrance or otherwise decrease the reactivity of a particular portion of a molecule
What is induction?
- refers to uneven distribution of charge across a sigma bond because of differences in electronegativity
What is conjugation?
- refers to the presence of alternating single and multiple bonds, which creates delocalized pi electron clouds above and below the plane of the molecule
How does resonance affect stability?
electrons experience resonance through unhybridized p-orbitals, increasing stability
How does electronegativity of carbonyl-containing compounds affect reactivity?
- the more electronegative groups in a carbonyl-containing compound, the greater its reactivity
Why are conjugated carbonyl-containing compounds more reactive?
because they can stabilize their transition states
How does strain affect reactivity?
- increased strain in a molecule can make it more reactive
- beta-lactams are prone to hydrolysis because they have significant ring strain
What causes ring strain?
due to torsional strain from eclipsing interactions and angle strain from compressing bond angles below 109.5 degrees.
Which carboxylic derivatives undergo nucleophilic substitution reactions?
all can undergo these reactions, the rates at which they do are determined by their relative reactivities
How can anhydrides be cleaved?
by the addition of a nucleophile
- addition of ammonia/amine results in an amide and a carboxylic acid
- addition of an alcohol results in an ester and a carboxylic acid
- addition of water results in 2 carboxylic acids
What is transesterification?
the exchange of one esterifying groups for another on an ester
- the attacking nucleophile is an alcohol
How can amide be hydrolyzed to carboxylic acids?
under strong acidic or basic conditions
- the attacking nucleophile is water or the hydroxide anion
What happens in a condensation reaction?
- 2 molecules combine to form 1, with the loss of a small molecule (water)
- how carboxylic acid derivatives are formed
What properties account for the difference in reactivity seen between anhydrides, esters, and amides with nucleophiles?
- electronic effects like induction have some effect on the reactivity of the carbonyl in these 3 functional groups
- differences in resonance also explains increased reactivity of anhydrides in particular
- steric effects could also be significant, depending on the specific leaving group present
How do strongly acidic/basic conditions catalyze the hydrolysis of an amide?
- strongly acidic conditions catalyze amide hydrolysis by protonation of the oxygen in the carbonyl, increasing the electrophilicity of the carbon, making it more susceptible to nucleophilic attack
- strong basic conditions greatly increase the concentration of OH-, which can act as a nucleophile on amide carbonyls
What is formed when an anhydride and ammonia combine?
amide and carboxylic acid
What happens in a Fischer esterification?
reacting a carboxylic acid and an alcohol with an acid catalyst
How do dicarboxylic acids react to heat?
anhydrides, specifically cyclic anhydrides, will form spontaneously from dicarboxylic acids when heated
How do substituents affect reactivity?
the less substituted the nucleophile, the easier it will be for the nucleophile to attack the carbonyl carbon and form the amide
What are beta lactams?
- amides in the form of 4-membered rings; amides are generally the least reactive type of carboxylic acid derivative
- experience significant ring strain from both eclipsing interactions (torsional strain) and angle strain, and are therefore more susceptible to hydrolysis than the linear form of the same molecule
Why would a positive charge on a molecule have greater stability when cyclic than when straight-chain alkane of the same molcule?
conjugation which permits delocalization of the charge through resonance
