Exam 3 Flashcards
Structure of formaldehyde
Name this structure
acetaldehyde
Structure of butyraldehyde
Aldehydes and ketones are class [ ] carbonyls
Aldehydes and ketones are class II carbonyls
Name this compound
Draw the structure of cyclohexanecarbaldehyde
Name this compound
2-naphthalenecarbaldehyde
Name this compound
benzaldehyde
Draw the structure of acrolein
Name this compound
crotonaldehyde
Draw the structure of acetone
Name this compound
3-hexanone
Name this compound
trans-hept-5-en-2-one
Name this compound
1.3-cyclohexandione
Draw the structure for 3-oxohexanal
Draw the structure of benzophenone
Name this compound
acetophenone
Do Class I carbonyls have leaving groups attached?
yes
Do Class II carbonyls have leaving groups attached?
no
Leaving groups are relatively weak
bases
Draw the general mechanism of class II carbonyl nucleophilic addition
nucleophile attacks carbonyl
Name the class I carbonyl groups
acid halide
acid anhydride
carboxylic acid
ester
amide
Are nucleophiles electron rich or deficient?
Nucleophiles are electron rich and search for electron deficient species such as a carbonyl carbon
When a nucleophile attacks, we immediately create a
tetrahedral intermediate, this is the RDS. The tetrahedral intermediate then takes a proton and completes rxn.
The the nucleophile is strong the reaction is considered
irreversible. (ex. Grignard, reduction from higher order alcohol to alcohol or alcohol to higher order alcohol)
If the nucleophile is weak the reaction is considered
reversible
Rate acetaldehyde, formaldehyde, and acetone in order from most reactive to least reactive
Formaldehyde (fastest) > acetaldehyde > Acetone (slowest)
Why is formaldehyde faster and more reactive than acetone?
- Steric effects (electron clouds) of acetone slow the reaction down. Hydrogens on formaldehyde take up less space, less sterics = faster rxn
- Resonance structure/electron effects of acetone creates a more stable secondary carbocation making it less reactive
Name the reactivity trend for the following ketones
- STERICS
- electronics (less of a contributing factor)
Draw the mechanism for hydration of class II carbonyls (formation of unstable hydrate) under acidic conditions
- equilibrium rxn
- class II carbonyl added to water to form a hydrate
Draw the overall transformation of hydration of a class II carbonyl
Draw the mechanism for hydration of class II carbonyls (formation of unstable hydrate) under basic conditions
What is the % hydrate rates of class II carbonyls acetaldehyde, formaldehyde, and acetone?
formaldehyde: 99.9%
acetaldehyde: 58%
acetone: 0 % sterically hindered
Draw the products of the following cyanohydrin reactions
Draw the mechanism for this cyanohydrin rxn
Draw the products of the following cyanohydrin reactions
Are cyanohydride rxns with class II carbonyls reversible? Will the product of ketone or aldehyde with resonance be favorable or unfavorable?
Yes. Unfavorable, low yield product.
Draw the product of the following class II carbonyl and primary amine rxn
Draw the product of the following class II carbonyl and primary
Draw the mechanism of the following class II carbonyl and primary amine rxn
Draw the mechanism of the following class II carbonyl and secondary amine rxn
What is the rxn of tertiary amines and class II carbonyls?
NR
Derivative of amine
Derivative of amine
Derivative of amine
Draw the mechanism
A ketone and a methanol (R-OH) create
ketal
An aldehyde and ethanol (R-OH) create
acetal
overall rxn of ketone to ketal
overall rxn aldehyde to acetal
mechanism of ketone to ketal
Why are ketals and acetals good protecting groups for ketones and aldehydes?
- Stable to all basic conditions
-labile (reactive) in acidic conditions
Mechanism with protecting group
Draw the mechanism formation of acetal
Show how acetals/ketals can be hydrolyzed by H3O+
can be hydrolyzed back into ketone with HCl and excess water
Draw the product for this Wittig Rxn
What is an ylide?
(+) and (-) charge separated by a single bond
Mechanism
Properties of wittig (ylides) reactions
- choice of yield
- diastereomers selectivity (Z with non resonance stabilized and E stabilized with resonance)
- Resonance stabilized ylides have 3+ resonance structures
What selectivity do Wittig reactions have?
(Z)
Is this an example of a non-resonance stabilized ylide?
No, this is resonance stabilized with 3 structures and E selectivity
What are hard nucleophiles (direct addition)?
- Strong Bases
- React quickly and irreversibly
Examples:
Grignard, alkyl lithium, hydrides (LiAlH4, NaBH4)
What are soft nucleophiles (conj addition)?
- Weak bases
- Resonance stabilized
- Reversible
Examples
H2O, alcohols, nitriles, amines, thiols, HBr, HCl, enolates, gilman
Overall transformation of conjugate and direct addition
Draw the structure of acylic acid
Draw the structure of pyruvic acid
Draw the structure of formic acid
Draw the structure of acetic acid
Draw the structure of propionic acid
(E) - 4-methyl-3-hexenoic acid
para-chlorobenzoic acid
cyclohexane carboxylic acid
4-methylpentanenitrile
acetonitrile
benzonitrile
trans-4-hydroxy-cyclohexane carboxylic acid
Rank the priority demanding functional groups
Carboxylic acids
Nitriles
Aldehydes
Ketones
Amines
Alkene/Alkyne
5-methylhexanenitrile
Rank the following carboxylic acids by acid strength
Carboxylic acids are weaker than strong acids but stronger than alcohols and phenols
How do inductive effects impact the acidity of a carboxylic acid?
The closer an electronegative atom is to the carboxylic acid the more acidic it is
How does resonance affect the acidity of carboxylic acids?
Resonance effects are not as impactful on the acidity as inductive effects.
EDG make bases stronger
EWG make acids stronger
Oxidation of primary alcohols to aldehydes
Oxidation of an aldehyde to carboxylic acid
Oxidation cleavage of alkyl benzenes
Hydrolysis of nitrile (any class I carbonyls
Reaction of Grignard with carboxylic acids
Preparation of Nitriles
Sn2
Preparation of Nitriles
Sn2
Dehydration of Nitrile
Mechanism for dehydration of nitrile
Nitrile hydrolysis to carboxylic acid
Nitrile reduction to amide
Nitrile reaction with Grignard
Draw the mechanism
General reaction scheme of class I carbonyls
What is the relative reactivity trend for class I carbonyls?
Properties of acid halides
- the most reactive class I carbonyl
- reacts with all nucleophiles
Formation of acid anhydride
Overall alcoholysis transformation
Alcoholysis of acid halide under basic conditions
Alcoholysis of acid halide under acidic conditions
Acid halide under acidic conditions
Acid halide under basic conditions
Acid halide hydrolysis overall transformation
Acid halide reaction with amine overall transformation
Acid halide reaction with amine overall mechanism
Acid halide with Grignard mechanism
Acid halide reduction
Acid halide Gilman reaction
Anhydride with alcohol reaction mechanism
Anhydride reacts with alcohol to form
an ester
Hydrolysis of acid anhydride under acidic conditions
Hydrolysis of acid anhydride under basic conditions
Hydrolysis of acid anhydride forms
carboxylic acid
Under what conditions does transesterification occur?
Only works with acid catalyst
Acid-catalyzed transesterification overall trasformation
Acid-catalyzed transesterification mechansim
Acid catalyzed hydrolysis of ester overall transformation
Acid catalyzed hydrolysis of ester mechanism
Acid catalyzed hydrolysis of tertiary ester mechanism
Base catalyzed hydrolysis of ester overall transformation
Base catalyzed hydrolysis of ester mechanism
ester amine reaction and mechanism
Ester grignard reaction and mechanism
Reductions of esters
Acid halide synthesis from carboxylic acid
Esterification of carboxylic acid
Fischer esterification of carboxylic acid overall transformation and mechanism
Can base catalyzed work on carboxylic acids?
NO
Carboxylic acid + amine mechanism
Steglich Reaction - Peptide Coupling
Carboxylic acid + Grignard (hard nucleophile) overall transformation
Reduction of carboxylic acids
Reduction of carboxylic acids
Hydrolysis of amines
Reduction of amines
General mechanism of reduction reactions of class 1 carbonyls
Mechanism
Mechanism
Mechansim
Explain the factors that contribute to the relative reactivity of aldehydes and ketones.
Aldehydes are more reactive than ketones towards nucleophilic addition.
This is due to: a) The additional substituent on ketones causes steric hindrance.
b) The additional substituent on ketones is inductively electron donating thus reducing the electrophilicity of the carbonyl group.
What is the purpose of using an acid catalyst when doing an acid-catalyzed hydrolysis. Use actual structures to support your answer.
benzophenone
ethyl 3-bromopropanoate
4-hydroxybutanoic acid
