Ochem 2 Chapter 22-23 Review

Reagents and notes

Haloform reaction

1.) NaOH (excess) X2 (excess) to form an enolate that reacts with X2.
2.) Mild acidic workup

Ketone/aldehyde → carboxylic acid

Aldol Addition

NaOH, H2O
Enolate retains C=O, OH group where the double bond was on the electrophile.

Aldol Condensation

NaOH, H2O, HEAT
Enolate retains the C=O bond, double bond forms where the electrophile is.

Rules for crossed aldol

1. Ketone is the nucleophile (enolate), aldehyde is the electrophile.

2. If both are same group, the least hindered will form the enolate.

Claisen Condensation

1.) NaOEt/EtOH
2.) H+ workup
Both groups keep the C=O; the enolate part keeps everything; the electrophile loses an O-CH2 or a H.

Rules for Crossed Claisen

1. Must have 2 alpha hydrogens avaliable

2. Ketone = enolate, Aldehyde = electrophile

3. Less O atoms is enolate

4. Less sterically hindered is enolate

Malonic Ester

1. NaOEt/EtOH (acid/base) enolate formation

2. 1-bromopropane (Sn2)

3. OH, H2O (saponification)

4. H3O+/H2O (acid workup)

5. heat (decarboxylation)

product: carboxylic acid and CO2

Direct Alkylation

Adding a group onto the ketone (weird…)
1.) LDA, THF, -78oC (LDA acts as a base and helps make that enolate)
2.) DMSO, 1-bromopropane (Sn2)

Reactions of alpha, beta, unsaturated carbonyls

1.) H3O+/H2O (aldol)
2.) NaCN, HCN, EtOH
Can either attack positive carbonyl carbon (faster) OR alkylation with the double bond (slower but more stable)

Reducing amides to amines

1.) LAH (Deprotonates amide)
2.) H3O/H2O
3.) -OH/H2O

Nitrile to amine

1.) LAH
2.) H3O+/H2O
3.) -OH/H2O

Amide hydrolysis

1) H3O+/H2O

OR

1)-OH/H2O

2)H3O+/H2O

Reductive amination

Primary/secondary amines + aldehyde/ketone → imine → reduction to amine.

Reducing agents:
1) H2,Pt, 30 psi, EtOH
OR
1)NaBH(OAc)3, which is less reactive than NaBH4

2) NaOH workup

Borch Reduction (Reductive amination with NaBH4CN)

1.) NaBH4CN/HOAc, MeCN, H2O
2.) KOH

Replacing Hs with methyl groups

Hoffmann Elimination

1.) MeI, HEAT, H2O (exhuastive methylation)
2.) Ag2O H2O (ion exchange)
3.) Heat (E2)

Making a less substituted alkene

Diazotization

NaNO2, HCl
Makes a diazonium salt with a really good LG.

Gabriel amine synthesis

1.) KOH, EtOH (deprotonate NH)
2.) butyl-OTs (Sn2)
3.) HBr, AcOH, H2O (hydrolyze amide)
4.) NaOH (deprotonate -NH3 amine)

Sn2 electrophile becomes the amine.

Curtius rearrangement

Acid chloride → isocyanate

1.) NaN3 (nucleophilic attack)
2.) heat, N2 (flippy thing)

Hoffman rearrangement

Amide → isocyanate
Br2, NaOH (makes enolate)
enolate reacts with Br2, deprotonation, flippy

Dempsky degradation

Ester → isocyanate
1) H2N-NH2 (NAS, oxidation to add N-N+(triple bond_ N)

2)NaNO2, HCl (diazotization)