Chemistry II Lesson 9: Aldehydes and Ketones Part II

Your lab instructor asks you to reduce the carboxylic acid of a compound that contains both a carboxylic acid and a ketone. You run the reaction, but end up with two alcohol groups instead of an alcohol group and a ketone. What important step did you forget?

You forgot to protect your ketone group by turning it into an ketal. A ketal would have been resistant to the reducing agent.

You try the experiment again, but this time you end up with an alcohol and an acetal instead of an alcohol and a ketone. What should you do next to get the desired result?

You should add water and acid to the reaction to convert the acetal back into a ketone.

Compare the mechanisms of transforming aldehydes into acetals and thioacetals.

The only difference is that acetal formation uses alcohols as a reagent and thioacetal formation uses thiols (Sulfur replacing Oxygen).

Draw the Mozingo Reduction Mechanism (Hint: it starts with an aldehyde and a dithiol)

Mozingo Reductions is another way to reduce a ketone/aldehyde while not affecting other groups

Draw the Imine Formation Reaction Mechanism in acid.

Draw the Enamine Formation Reaction Mechanism in acid.

CRB Fill in the blanks: When a primary amine (RNH2) reacts with an aldehyde or ketone, an ___________ forms. When a secondary amine (RNHR') reacts with an aldehyde or ketone, an _________ forms.

(A) Imine, Enamine

(B) Imine, Imine

(C) Enamine, Enamine

(D) Enamine, Imine

(A) Imine, Enamine

When a primary amine (RNH2) reacts with an aldehyde or ketone, an Imine forms. When a secondary amine (RNHR') reacts with an aldehyde or ketone, an Enamine forms.

An Enamine is composed of what two functional groups?

(A) Amide, Alkane

(B) Amide, Alkene

(C) Amine, Alkane

(D) Amine, Alkene

(D) Amine, Alkene

An Enamine is composed of an amine and an alkene functional group.

CRB When comparing amine reactions with carbonyls to ketos and enols, which structure does Enamine correlate to?

Enols

Enamine and Enols are both generally the less stable forms and have double bonds involving the α-carbon.

Draw the general structure of an imine vs. oxime vs. hydrazone.

Which is more stable? An Oxime or an Imine? Why?

Oximes are more stable than Imines because Oximes are resonance stabilized.

True or False? If the starting product of an Oxime-reaction is symmetrical, you will end up with two stereoisomers as products.

False. If the starting product of an Oxime-reaction is UNsymetrical, you will end up with two stereoisomers as products.

Draw Hydrazine, the reactant used in a Hydrazone formation reaction.

CRB Compare and contrast Alkyl and Aryl Amines.

Both Alkyl and Aryl amines have Nitrogen bound to hybridized carbons.

Alkyl amines have sp3-hybridized carbons bound to the Nitrogen.

Aryl amines have sp2-hybridized carbons bound to the Nitrogen, and are aromatic.

Draw 2,4-dinitrophenylhydrazine (2,4-DNP. What is it used for?

2,4 DNP is reacted with ketones and aldehydes to form hydrazones that have certain melting points that allow you to characterize the original ketone or aldehyde.

Draw the reaction mechanism for CN- reacting with an aldehyde.

Draw the reaction mechanism for Grignard Reagent (R-MgX) reacting with an aldehyde.

NOTE: The same mechanism is found when reacting an aldehyde with other organometallic compounds such as R-Li.

CRB Why must the Gringard Reagent be added in an aprotic solvent?

(A) The Gringard Reagent is very acidic and would react with solvent.

(B) The Gringard Reagent is very basic and would react with the solvent.

(C) The Gringard Reagent is very bulky and cannot move easily in different solvents.

(D) Gringard Reagents have no solvent limitations.

(B) The Gringard Reagent is very basic and would react with the solvent.

CRB Based on the previous card, water cannot be present when the Gringard Reagent is added. How can the reaction proceed if acidic water is needed to finish the reaction?

You add the water after giving the Gringard reagent enough time to work! Using acidic water in excess will also react with any extra Gringard reagent, so make sure you do give enough time to react.

Draw the reaction mechanism for Sodium Borohydride (NaBH4) reacting with an aldehyde.

NOTE: A similar mechanism is seen with LiAlH4.

CRB Why would this reaction not work as well with NaH?

The previous reaction would not work well with H- because H- is a good base, but not a good Nucleophile.

CRB True or false? The strong reducing agents often work by adding a proton (H+) to a carbonyl.

False. the strong reducing agents often work by adding a HYDRIDE (H-) to the carbonyl.

Reactions with the Gringard's Reagent will turn aldehydes into _____ and ketones into _______.

(A) Tertiary alcohols, hemiacetals

(B) Secondary alcohols, tertiary alcohols

(C) Secondary alcohols, primary alcohol

(D) Tertiary alcohols, esters

(B) Secondary alcohols, tertiary alcohols

Reactions with the Gringard's Reagent will turn aldehydes into secondary alcohols and ketones into tertiary alcohols.

Why does Lithium Aluminum Hydride (LiAlH4) need to be used in dry conditions whereas Sodium Borohydride (NaBH4) does not?

LiAlH4 will react with water to form H2 gas, which could be dangerous. NaBH4 is not as reactive, so it isn't an issue.

Sodium Borohydride (NaBH4) will react with an ester to form a(n) ____________ and Lithium Aluminum Hydride (LiAlH4) will react with an ester to form a(n) ____________.

(A) Ester, Alcohol

(B) Alcohol, Ester

(C) Alcohol, Alcohol

(D) Ester, Ester

(A) Ester, Alcohol

Sodium Borohydride (NaBH4) will react with an ester to form an ester and Lithium Aluminum Hydride (LiAlH4) will react with an ester to form an alcohol. This is due to the greater reactivity of Aluminum Hydride (LiAlH4), whereas sodium borohydride is not reactive enough to affect the ester.

Why is Sodium Borohydride (NaBH4) less reactive than Lithium Aluminum Hydride (LiAlH4)?

Aluminum is less electronegative than Boron, resulting in greater electron density on the hydrogen for LiAlH4 (larger dipole moment).

LiAlH4 is strong enough to reduce all of the following functional groups, however, NaBH4 is only strong enough to reduce:

I. Aldehydes

II. Ketones

III. Carboxylic Acids

IV. Esters

(A) I Only

(B) II Only

(C) I and II Only

(D) I, II, III, and IV

(C) I and II Only

NaBH4 is strong enough to reduce Aldehydes and Ketones but not Carboxylic Acids and Esters.