chapter18: aldehydes and ketones · chapter18: aldehydes and ketones 206. ... buli 3) practice...

53
Chapter18: Chapter18: Aldehydes and Ketones Aldehydes and Ketones Aldehydes and Ketones Aldehydes and Ketones 206

Upload: dokiet

Post on 22-Mar-2019

251 views

Category:

Documents


3 download

TRANSCRIPT

Page 1: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Chapter18:Chapter18:Aldehydes and KetonesAldehydes and KetonesAldehydes and KetonesAldehydes and Ketones

206

Page 2: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Carbonyl compounds are often classified as Class I or Class II depending if they have a group on the C=O that can be replaced by a nucleophile or not.

O O

cannot be replaced by a nucleophile

207

R H R R

Class IIaldehyde ketone

R OH

O

R OR

O

R O

O

R X

O

R NH2

OO

R

carboxylicacid

ester anhydride acyl halides amides

compounds with groups that can be replaced by a nucleophile

Class I

Page 3: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Physical PropertiesPhysical Properties

� Structure:

� While most reaction of aldehydes and ketones are at � While most reaction of aldehydes and ketones are at the electrophilic site, there are two other reactive sites on the structure.

208

R

OR

H Helectrophilic

nucleophilic

acidic protoncan be removedwith base

Page 4: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Boiling point: since there are no hydrogen bonding in aldehydes or ketones, the boiling point will be lower than those of alcohols of similar molecular weights but higher than those non-polar molecules like alkanes, ethers, etc…because of the like alkanes, ethers, etc…because of the strong dipole.

209

Page 5: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� While aldehydes and ketones do not H-bond with themselves, they can hydrogen bond with other molecules bearing acidic hydrogen. They are therefore very good solvent for alcohols and amines.

210

Page 6: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Synthesis of Aldehydes and KetonesSynthesis of Aldehydes and Ketones(Review(Review) ) 18.718.7

• Oxidation of Alcohols

211

Page 7: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Ozonolysis of Alkenes

• Friedel-Crafts Acylation of Aromatics

212

Page 8: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Hydration of Alkynes

213

Page 9: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

New Synthesis of Aldehydes and KetonesNew Synthesis of Aldehydes and Ketones

• From 1,3-dithiane (18-8)1,3-dithiane has 2 weakly acidic protons that can be removed and alkylation of the carbon is possible. Once alkylated, the 1,3-dithiane becomes a “protected” carbonyl as it can be hydrolyzed to the corresponding carbonyl hydrolyzed to the corresponding carbonyl structure.

214

Page 10: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Dithiane AlkylationMechanism of Dithiane Alkylation

Requires strong bases: RLi, NaNH2

215

Requires strong bases: RLi, NaNH2

Works with primary halides only, Cl, Br, I

Page 11: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� It is also possible to obtain ketones in this reaction simply by performing a second alkylation prior to the hydrolysis of the substituted dithiane.

216

Page 12: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Ketones from Carboxylic Acids (18-9)Deprotonation of a carboxylic acid give the normally unreactive carboxylate anion. However, with a very strong nucleophile (RLi), alkylation is possible leading to the ketone hydrate….hence the ketone.

217

Page 13: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Formation of Ketones Mechanism of Formation of Ketones from Acidsfrom Acids

Any RLi reagents can be used

218

can be used

Page 14: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Ketones from Nitriles (18-10)Nitriles have a structure similar to carbonyl, ie the C-N bond is strongly polarized and susceptible to nucleophilic attack. Nucleophiles such as Grignard reagents can add to the nitrile function and produce and imine which is hydrolyzed creating a ketone.ketone.

219

Page 15: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Imine HydrolysisMechanism of Imine Hydrolysis

R C NH

R'H+ R C NH2

R'

+

H2O

RNH2

OH2

R' +

H+ transferR

NH3

OHR'

+

H2O

220

R R'

OH

R R'

OH+

+R R'

O

Page 16: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Reduction of Acid ChloridesWe have seen in section 1 (alcohols) that LiAlH4 reduces all carbonyl compounds to the corresponding alcohols. Acid chlorides are also reduced by this reagent to the 1o alcohols.

221

Page 17: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� However, it is possible to reduce the reactivity of the hydride reagent by replacing some hydrogen atoms by alkoxy groups. In such cases, the reagent is not active enough to reduce the intermediate, and the aldehyde is obtained.

222

Page 18: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Ketones can also be obtained from acid chlorides. We have seen that grignards add to acid chlorides to give the corresponding tertiary alcohols.

223

Page 19: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� However using a weaker organometallic reagent allows the reaction to stop at the ketone stage. The Gilman reagent (an organocopper based nucleophile) is such a reagent.

224

Page 20: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Practice QuestionsPractice Questions� Complete the following reactions. Draw the structure of the major organic product in each case.

OH

O

1) BuLi (excess)

2) H3O+

225

S S1) BuLi

2) CH2=CH-CH2Br3) BuLi4) CH3I5) H+/H2O

Cl

O 1) Me2CuLi

2) H3O+

CN 1) PhMgBr

2) H3O+

Page 21: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Reactions of Aldehydes and Reactions of Aldehydes and Ketones: Ketones: Nucleophilic Additions Nucleophilic Additions (Review) (Review) (18(18--12)12)

•• ReductionWe have already seen that aldehydes and ketones can be reduced to the corresponding alcohols. NaBH4 or LiAlH4 can be used.

226

Page 22: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Similarly, aldehydes and ketones can add nucleophiles such as Grignard Reagent or alkyl lithium to produce alcohols

MgBr 1)

O

227

2) H3O+

Br

1) Li

2)

3) H3O+

OHO

OH

Page 23: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

New Reactions of Aldehydes and KetonesNew Reactions of Aldehydes and Ketones

• Nucleophilic AdditionsWe have just reviewed the addition of Grignard reagents to carbonyl. In fact, this reaction is not limited to those reagents. Many other nucleophiles can reagents. Many other nucleophiles can add to aldehydes and ketones. These nucleophiles can be charged or not, and the nature of the nucleophile will dictate the mechanism involved in the reaction.

228

Page 24: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� For charged nucleophile, H-, R-, NC-, and others, the nucleophilic addition takes place directly on the carbonyl as shown below. We already have seen this mechanism for Grignard additions.

229

Page 25: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Formation of Cyanohydrins (18-15)Cyanohydrins are important intermediates in organic synthesis since they can be hydrolyzed to the corresponding hydroxy-acids or reduced to the hydroxy-amines.

230

Page 26: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Cyanohydrin FormationMechanism of Cyanohydrin Formation

231

Page 27: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Wittig Reaction (18.13) The Wittig reaction is the addition of a phosphorus ylide to the carbonyl. The initial reaction is quickly followed by the rearrangement of the intermediate into the alkene and a phosphine oxide.

232

Page 28: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� The phosphonium ylide required for this reaction can be prepared by SN2 reaction of a phosphine and an alkyl halide, followed by deprotonation of the phosphonium salt with a strong base such as an alkyl lithium. Phosphorus ylides are stable due to resonance.

233

Page 29: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of the Wittig ReactionMechanism of the Wittig Reaction

234

Page 30: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� The formation of the ylide follows the principles discussed for SN2 reaction (CHEM201 section 8). This means that if 2 choices are available, pick the one using the least sterically hindered alkyl halide.

235

Page 31: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� The Wittig reaction is an excellent method to make alkenes since it is completely regioselective (know exactly where the double bond will be).

� How would you make this compound? How successful will you be?

236

Page 32: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� But the Wittig reaction will give only the desired product since it is regioselective. The double bond is found at the same location that was previously occupied by the carbonyl C=O.

1) CH Br

237

O

Ph3P1) CH3Br

2) BuLi

3)

Page 33: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Practice QuestionPractice Question� How would you prepare the following alkenes using a Wittig reaction?

238

Page 34: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� For weak nucleophile, H2O, ROH and others, a strong acid is required to activate the carbonyl via the protonation of the oxygen. This is simply because the nucleophile is not strong enough to attack the electrophilic carbon. An example of this is the hydration of a ketone.

239

Page 35: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Hydration of Aldehydes and Ketones (18-14)Addition of water to the carbonyl is a good example illustrating the need to activate the carbonyl by protonation. This reaction is not a very useful reaction in the forward process since the carbonyl hydrate will rearrange to the carbonyl. However, when a carbonyl hydrate is formed during a reaction, the resulting product will be the ketone However, when a carbonyl hydrate is formed during a reaction, the resulting product will be the ketone or aldehyde.

240

Page 36: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Addition of Alcohols (Acetal Formation) (18.18)

Addition of alcohols follows a similar mechanism. However, this reaction is very important in organic synthesis since it represent a good method to “protect” the carbonyl group.

241

Page 37: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Acetal FormationMechanism of Acetal Formation

242

Page 38: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Acetals can also be cyclic. In these cases, a diols is used to form the acetal.

243

Page 39: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

�Use of Acetals as Protective Group (18-19)� Because the reaction is reversible, acetals can be use to protect ketones/aldehydes from unwanted reactions, then the hydrolysis of the acetal regenerate the carbonyl compound.

OCH OCH

244

O CH3OH

H+

OCH3

OCH3

Acetal Formation

OCH3

OCH3

H2O

H+

O

Acetal Hydrolysis

Page 40: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

How do protecting group work? How do protecting group work?

� Suppose you want to carry out this reduction? Not easy, since the ketone is more reactive than the ester, and we have seen that to reduce an ester LiAlH4 is required (this will also reduce the ketone).required (this will also reduce the ketone).

245

Page 41: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� The use of a protecting group can solve this problem.

246

Page 42: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Formation of Imines (18-16)Aldehydes and Ketones react with 1o and 2oamines to give either imines or enamines. These products can be used as protective groups for the carbonyl and in the formation of amines or alkanes. We will see later that they are also useful in see later that they are also useful in alkylation and condensation reactions.

247

Page 43: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Imine FormationMechanism of Imine Formation

248

Page 44: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Mechanism of Enamine FormationMechanism of Enamine Formation

249

Page 45: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Practice QuestionPractice Question� What are the product of the following reactions?

250

Page 46: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Imines can be hydrolyzed back to the corresponding carbonyl. Hence they can be used as protecting groups.

251

Page 47: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Condensations of Hydroxylamine and Hydrazines (18-17)Many imine derivatives are available via the same reaction which gives the imine.

252

Page 48: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

• Oxidation of Aldehydes (18-20)We have seen that alcohols can be oxidized to aldehyde with PCC (alcohols, section 1), and that the aldehyde product could be further oxidized to the corresponding carboxylic acid with stronger oxidizing agents.

253

Page 49: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� We have also established that ketones, because of their structures cannot be oxidized with conventional oxidizing agents.

254

Page 50: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Reductions of Ketones and Aldehydes (18-21)

� We have already seen that it is possible to reduce aldehydes and ketones with two different reagents, NaBH4 and LiAlH4

255

Page 51: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Catalytic hydrogenation with Ni is also a possible reaction, but double and triple bonds will also reaction under these conditions.

256

Page 52: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

� Deoxygenation (ie the oxygen of the original carbonyl is replaced by 2 hydrogen atoms giving an alkane) of carbonyl compounds is also possible by two different methods.◦ Clemmensen Reduction

◦Wolff-Kishner Reduction

257

Page 53: Chapter18: Aldehydes and Ketones · Chapter18: Aldehydes and Ketones 206. ... BuLi 3) Practice Question How would you prepare the following alkenes using a Wittig reaction? 238. For

Wolf-Kishner ReductionThe reaction goes through a hydrazone intermediate (imine derivative) followed by hydrolysis with base.

258