Aldehyde/Ketone Reactions Flashcards
If an aldehyde or a ketone reacts with H2O What kind of product does it form?
A geminal diol which is a compound that has two alcohol groups attached to the same carbon.
What product forms if an aldehyde or a ketone reacts with a primary amine?
An imine
What product forms if an aldehyde or a ketone reacts with a secondary amine?
An enamine
If a nucleophile had to pick whether it will react with a ketone or aldehyde, which one would it choose?
The aldehyde, because aldehydes are more electrophilic.
Ketones are sterically hindered by the extra alkyl group, so they are less reactive to nucleophiles.
If an aldehyde reacts with an alcohol, it produces…?
A hemiacetal
If a ketone reacts with an alcohol, it produces…
A hemiketal
Explain the mechanism for forming a ketal
-FORMATION OF KETAL/ACETAL ONLY occurs in ACIDIC conditions
1.Ketone gets protonated by acid generating a better electrophile
2. Alcohol attacks electrophilic C
3. OH group (from ketone originally) gets protonated to form H2O+, a good leaving group
4. The alpha carbon now is a carbocation that is susceptible to attack by the 2nd alcohol
5. 2nd OH attacks forming an oxonium + charged intermediate
6. 2nd OH is deprotonated forming the final ketal product
Under what conditions do you perform hydrolysis of an acetal?
ONLY under acidic conditions.
What are the steps of acetal hydrolysis?
- Protonation of one OR group to form positively charged intermediate.
- Formation of double bond from 2nd OR group causes loss of +ROH leaving group.
- H2O nucleophilically attack C=O
- Deprotonation of newly attached H2O
When given an acetal, how do you figure out the products of the acetal hydrolysis w/o going through the mechanism?
-Find the two OR groups connected to the central carbon and circle them
-Erase the bonds that connect them to the central carbon
-To form your ketone/aldehyde, figure out how many leftover alkyl groups are connected to the central C, if only 1 alkyl, add a H
-Lastly, add a =O to the central C to form your correct carbonyl
What is the first step of an acid-catalyzed hydration of an aldehyde/ketone?
- Protonation of the carbonyl, forming a + charged intermediate
What is the first step of a base-catalyzed hydration aldehyde/ketone?
- Nucleophilic attack of the carbonyl, forming a - charged tetrahedral intermediate
What product will we get if an aldehyde or ketone reacts with hydrogen cyanide?
A cyanohydrin which is a molecule with an alcohol (OH) and CN bound to the same carbon.
How can an aldehyde be created?
It is created when a primary alcohol is partially oxidized with PCC reagent.
It CANNOT be oxidized with regular oxidizing agents like chromic acid.
What product is created if a secondary alcohol is oxidized?
A ketone
What oxidizing reagents are used to convert a secondary alcohol into a ketone?
Na2Cr2O7, K2Cr2O7, CrO3, and PCC
If we mix LiAlH4 and a ketone, what product do we get?
A secondary alcohol
In order to react with Tollen’s reagent, what is necessary for the reactant to have?
The reactant has to have hemiacetals, or in other words be able to be reduced. (Having an OH group on the anomeric carbon).
What is the chemical formula for Tollens Reagent?
Ag(NH3)2OH
What happens when Tollen’s reagent reacts with a ketone?
There will be no reaction, no shiny silver mirror product will be produced.
What oxidizing reagents can be used to oxidize an aldehyde?
Benedict’s reagent, KMnO4, CrO3, Ag2O, H2O2
If an aldehyde is oxidized, what product does it produce?
A carboxylic acid
True or false:
Ketones can’t be oxidized as readily as aldehydes.
True, the H on the aldehyde facilitates the oxidation process. However, for ketones the extra R group acts as a hinderance, so oxidizing is more difficult.
Name the functional groups which LiAlH4 reduces to primary alcohols
Carboxylic acids, acyl halides, anhydrides, esters, aldehydes
Name the functional groups which LiAlH4 reduces to secondary alcohols.
Ketones
Explain the mechanism of a typical reducing agent such as LiAlH4.
- LiAlH4 attacks the carbonyl, delivering a H to the carbonyl C, pushing the double bond up on the O as electrons
- The alkoxide intermediate gets protonated to form an OH
What does the reagent borane (BH3) do?
It specifically reduces only carboxylic acids to primary alcohols. It doesn’t reduce any other carbonyl compounds.
True or false:
A ketone and its enol form exist in equilibrium with each other.
True
What is the most important step that occurs during a keto-enol tautomerization?
Abstraction of a H on the adjacent carbon, to form a C=C double bond
What are the steps of keto-enol tautomerization under acidic conditions?
1.) O in the carbonyl gets protonated, becoming a positively charged intermediate.
2.) H on the beta carbon is extracted, forming a C=C double bond and pushing double bond between the C=O up as electrons.
3.) Under acidic conditions, no negatively charged intermediates can form.
What are the steps of keto-enol tautomerization under basic conditions?
1.) H on the beta carbon is extracted, forming a new C=C double bond and pushing double bond between the C=O up as electrons. Forming a negatively charged enolate intermediate.
2.) Negatively charged O becomes protonated, forming neutral enol.
What reactants are required for an aldol reaction to occur?
Excess aldehyde/ketone or two different aldehydes/ketones
What is the product of an aldol addition reaction?
beta-hydroxy aldehyde/ketone
What is the product of an aldol condensation reaction?
alpha-beta unsaturated aldehyde/ketone
*look out for a double-single-double bond O
How do you determine the product of an aldol addition/condensation reaction when a ketone is used (gives you multiple carbanions to use for a nucleophilic attack)?
- Look at the base being used.
-Bulky base like LDA favors the less substituted alpha carbon.
-Non-bulky base such as (OH-, OCH3, OCH2CH3) favors more substituted alpha carbon for attack.
What is the difference between the kinetic and thermodynamic enolate product of an aldol condensation reaction?
Kinetic product - favored by a bulky base (LDA), using less substituted alpha carbon
Thermodynamic product - more stable; uses more substituted alpha carbon, favored by non-bulky base (NaH)
The thermodynamic enolate forms under (high/low) temperatures, while the kinetic enolate forms under (high/low) temperatures.
High reaction temp, low reaction temp
What reaction occurs between a conjugated carbonyl and an enolate?
A 1,4 Michael addition where.the enolate is added to the beta position of the double bond on the conjugated carbonyl (electrophile).
For a Michael addition reaction, what are the possible electrophiles?
Any conjugated carbonyls, amides, esters,
For a Michael addition reaction, what are the possible nucleophiles?
Any nucleophile with a carbanion between two EWGs, or a Gilman reagent which is R2CuLi
Which one is the nucleophile and which one is the electrophile? What is the product of this reaction?
The CN is the nucleophile, the enamine is the electrophile (conjugated carbonyl). The product would have the CN added to the beta position of the double bond on the enamine.
When a ketone/aldehyde reacts with a Grignard reagent, what product is formed?
An alcohol with an additional R group added to the same carbon
Compare a reaction with a Grignard Reagent and reaction with a Gilman reagent. What is the difference?
Grignard reagent is a strong nucleophile which adds an alkyl group directly to the carbonyl C (1,2 addition).
A Gilman reagent is a soft/weak nucleophile which adds an alkyl group to the beta C of the double bond (1,4 addition).
How do you determine the reactants of an aldol addition reaction when given the product?
-Split the alpha C-beta bond between the two carbonyls
-Where the OH was, put a carbonyl
-Put an H on the new carbonyl once separated
Intramolecular aldol addition reaction example
*Always have a hydroxy group on the beta carbon
*Carbanion is numbered 1 until you get to the carbonyl which is attacked –> this gives you # of carbons in the ring
How do you determine the reactants of an aldol condensation reaction when given the product?
-Split the double bond and draw a C=O carbonyl on the beta position of the double bond.
-Draw H’s on both carbonyls
How do you determine the reactants of a michael addition when given the product that had an extra alkyl group added?
-If there was an alkyl group added, that means a Gilman reagent was used such as (CH3)2CuLi.
-Draw a double bond starting from the same position of the alkyl group to the alpha position between the carbonyl
How do you determine the reactants of a Michael Addition when there is a 1,5 dicarbonyl as the product.
- First find your nucleophile (either can be an enolate or a compound that is 1,3 substituted w/ two EWGs.
- Find the electrophile, which is a conjugated carbonyl, cyano, or nitro group.
- Break the bond between the electrophile and nucleophile.
- Draw a double bond starting at the beta position of the electrophile going towards the alpha C.
What kinds of rings do intramolecular aldol reactions favor?
They favor 5, 6, and 7 membered rings. Anything under 5 isn’t favored. (Even in cases where a certain base is used, the carbanion that will form the favored ring will be the more stable product.
