Organic Chemistry: Unit 3

What happens to the π bond during alkene addition?

The π bond breaks and two new σ bonds form.

What is Markovnikov's rule?

H adds to the less substituted carbon; the other group adds to the more substituted carbon.

When can a carbocation rearrange?

When a hydride or alkyl shift forms a more stable carbocation.

What is a hydride shift?

A hydrogen moves with its bonding electron pair to an adjacent carbocation.

What is an alkyl shift?

An adjacent carbon group moves with its bonding electron pair.

What is the carbocation stability order?

3° > 2° > 1°.

What role do carbonyls usually play in reactions?

Electrophiles; nucleophiles attack the partially positive carbonyl carbon.

What are the three basic carbonyl types discussed?

Formaldehyde, aldehydes, and ketones.

What are Grignard reagents?

Organomagnesium compounds (RMgX) that act as strong carbon nucleophiles and bases.

What are the two steps of Grignard carbonyl addition?

1. Grignard reagent in dry ether/THF. 2. H₃O⁺ acid workup.

What happens when a Grignard reagent attacks a carbonyl?

A new C–C bond forms; acid workup produces an alcohol.

What must Grignard reagents avoid?

Acidic protons, including those in water and alcohols.

What does NaBH₄ do?

Reduces aldehydes and ketones to alcohols through hydride addition.

How does NaBH₄ differ from a Grignard reagent?

NaBH₄ adds hydrogen; Grignards add a carbon group.

Do NaH and LiH typically reduce carbonyls?

No; they act primarily as bases rather than nucleophilic reducing agents.

What is a cyanohydrin?

A compound containing OH and CN attached to the same carbon.

Which reagents form cyanohydrins?

KCN and acetic acid (AcOH).

Why are cyanohydrins unstable in basic conditions?

Deprotonation of OH allows reversal to the carbonyl and CN⁻.

What forms when a primary amine reacts with a carbonyl under acid catalysis?

An imine (C=N) and water.

Why is strong acid problematic for imine formation?

It protonates the amine, reducing its nucleophilicity.

What is reductive amination?

Conversion of a carbonyl into an amine through imine/iminium formation and reduction.

What does NaBH₃CN selectively reduce?

Iminium ions; it is too weak to reduce ordinary ketones and aldehydes under these conditions.

How do you identify a hemiacetal?

A carbon attached to one OH and one OR group.

How do you identify an acetal?

A carbon attached to two OR groups.

What conditions form an acetal?

Alcohol and an acid catalyst; the reaction is reversible.

What conditions cleave an acetal?

Aqueous acid, which regenerates the carbonyl.

What does PCC/CH₂Cl₂ do to a secondary alcohol?

Oxidizes it to a ketone.

How do PCC and H₂CrO₄ differ when oxidizing primary alcohols?

PCC produces an aldehyde; H₂CrO₄ produces a carboxylic acid.

What is Fischer esterification?

Carboxylic acid + alcohol ⇌ ester + water under acid catalysis.

What is saponification?

Base-promoted ester hydrolysis producing a carboxylate and an alcohol.

What type of reaction occurs when HBr adds to an alkene?

Electrophilic addition.

What is the first step of acid-catalyzed alkene hydration?

The alkene π bond attacks H⁺, forming a carbocation.

Why does Markovnikov addition favor one regioisomer?

The pathway generally forms the more stable carbocation intermediate.

What is the major product of propene + HBr?

2-bromopropane.

What is the major product of propene + H₂O/H₂SO₄?

2-propanol.

Can carbocation rearrangements occur during acid-catalyzed alkene additions?

Yes, if a hydride or alkyl shift produces a more stable carbocation.

Can a secondary carbocation rearrange into a tertiary carbocation?

Yes, through a favorable adjacent hydride or alkyl shift.

What is the driving force for a favorable carbocation rearrangement?

Formation of a more stable carbocation.

What is the role of water in acid-catalyzed alkene hydration?

It attacks the carbocation and ultimately forms the alcohol.

What is cationic polymerization?

Repeated alkene addition to a positively charged growing carbon chain.

Which carbonyl compound is generally most reactive toward nucleophilic addition?

Formaldehyde.

What is the relative nucleophilic addition reactivity of formaldehyde, aldehydes, and ketones?

Formaldehyde > aldehydes > ketones.

Why are ketones generally less reactive than aldehydes?

Greater steric hindrance and electron donation from two carbon groups.

What is the nucleophilic site of a Grignard reagent?

The carbon bonded to magnesium.

What reaction forms a Grignard reagent from an alkyl halide?

R–Br + Mg in dry ether or THF → R–MgBr.

Why is THF suitable for Grignard reactions?

It is an ether solvent that supports the organometallic reagent without protonating it.

What happens if water is added to a Grignard reagent before carbonyl addition?

The reagent is protonated and loses its carbon nucleophile reactivity.

What product forms when formaldehyde reacts with CH₃MgBr followed by H₃O⁺?

Ethanol, a primary alcohol.

What type of alcohol forms when a Grignard reagent adds to formaldehyde?

A primary alcohol.

What type of alcohol forms when a Grignard reagent adds to an aldehyde other than formaldehyde?

A secondary alcohol.

What type of alcohol forms when a Grignard reagent adds to a ketone?

A tertiary alcohol.

What is the first mechanistic step in Grignard addition to a ketone?

Carbon nucleophile attacks the carbonyl carbon, pushing π electrons onto oxygen.

What intermediate forms immediately after Grignard addition to a carbonyl?

An alkoxide.

What does H₃O⁺ do during the Grignard acid workup?

Protonates the alkoxide to produce an alcohol.

What happens when CH₃MgBr reacts with acetone, followed by H₃O⁺?

2-methyl-2-propanol forms.

What does an organolithium reagent contribute to a carbonyl?

A carbon nucleophile that creates a new C–C bond.

Why can Grignard addition produce a racemic mixture?

Attack on a planar carbonyl can occur from either face, creating both enantiomers.

What type of reaction converts a ketone into a secondary alcohol?

Reduction.

What changes at the carbonyl carbon during reduction to an alcohol?

A C=O double bond becomes a C–OH single bond, with addition of hydrogen.

What is the nucleophile delivered by NaBH₄?

Hydride, H⁻.

What occurs first when NaBH₄ reacts with an aldehyde?

Hydride attacks the carbonyl carbon and forms an alkoxide.

What is a common solvent used for NaBH₄ reduction in your notes?

Ethanol (EtOH).

What product forms when NaBH₄ reduces acetone?

2-propanol.

What product forms when NaBH₄ reduces propanal?

1-propanol.

Does NaBH₄ create a new carbon–carbon bond?

No, it delivers hydride rather than a carbon group.

Which is the appropriate reagent for adding a methyl group to a ketone: NaBH₄ or CH₃MgBr?

CH₃MgBr followed by H₃O⁺.

What is the first step of cyanohydrin formation?

CN⁻ attacks the carbonyl carbon to form an alkoxide.

What happens after CN⁻ attacks the carbonyl?

The alkoxide is protonated, forming a cyanohydrin.

What product forms when acetone reacts with KCN/AcOH?

(CH₃)₂C(OH)CN, acetone cyanohydrin.

Is cyanohydrin formation reversible?

Yes, cyanohydrins can revert to the carbonyl compound.

Why is HCN alone not an effective reagent in the example from your notes?

It provides insufficient free CN⁻ for efficient nucleophilic attack.

What happens to a cyanohydrin in strongly basic conditions?

It can revert to the starting carbonyl and cyanide.

What functional group is formed when a carbonyl reacts with a primary amine under suitable acid catalysis?

An imine, containing C=N.

What is the nitrogen nucleophile in imine formation?

A primary amine, RNH₂.

What is the first major bond-forming step in imine formation?

The amine nitrogen attacks the carbonyl carbon.

What intermediate initially forms after amine addition to a carbonyl?

A tetrahedral intermediate that becomes a carbinolamine after proton transfers.

Why must the OH group be protonated before leaving during imine formation?

Protonation converts poor leaving group OH⁻ into water.

What leaves during the dehydration step of imine formation?

Water.

What is the final step of imine formation after an iminium intermediate forms?

Deprotonation produces the neutral imine.

Why does excess water disfavor imine formation?

Water promotes hydrolysis back to the carbonyl and amine.

Are the steps of acid-catalyzed imine formation reversible?

Yes, they are equilibrium steps.

What is an iminium ion?

A positively charged nitrogen-containing C=N species.

Which is more electrophilic: a neutral imine or an iminium ion?

An iminium ion.

What combination of reagents is used for reductive amination in your notes?

An amine, AcOH, and NaBH₃CN.

What is the purpose of AcOH in reductive amination?

It facilitates formation and protonation of the imine/iminium intermediate.

What does NaBH₃CN accomplish during reductive amination?

It reduces the iminium intermediate to an amine.

What product forms when acetone undergoes reductive amination with NH₃?

Propan-2-amine.

What distinguishes reductive amination from simple imine formation?

Reductive amination includes reduction of the imine/iminium to an amine.

What does a carbonyl plus one equivalent of alcohol initially form?

A hemiacetal or hemiketal under suitable conditions.

What does continued acid-catalyzed reaction of a hemiacetal with alcohol form?

An acetal or ketal.

What is the first step in acid-catalyzed acetal formation?

Protonation of the carbonyl oxygen.

Why does protonation of a carbonyl promote alcohol attack?

It increases the electrophilicity of the carbonyl carbon.

What leaving group is generated during conversion of a hemiacetal to an acetal?

Water, after protonation of the OH group.

What reaction type resembles the hemiacetal-to-acetal step in your notes?

An SN1-like substitution through an oxocarbenium intermediate.

Can acetals be readily cleaved under ordinary basic conditions?

No, they are generally stable to base.

What product results from acetal hydrolysis with aqueous acid?

The corresponding aldehyde or ketone.