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Chapter 20: Aldehydes and Ketones [Chapter 20 Sections: 20.1-20.7, 20.9-10.10, 20.13] 1. Nomenclature of Aldehydes and Ketones 2. Review of the Synthesis of Aldehydes and Ketones B. Oxidation of Alcohols (most common method) R R' O R H O ketone aldehyde O O H Br CHO Br for both aldehydes and ketones, the parent chain is the longest continuous carbon chain that contains the carbon of the carbonyl group numbering (locant) priority is given to the carbonyl carbon aldehydes always have the carbonyl group at carbon 1, so a number is not needed ketones have the "one" suffix, aldehydes have the "al" suffix O OH PCC H O OH O KMnO 4 or K 2 Cr 2 O 7 , H 2 SO 4 , H 2 O A. Friedel-Crafts Acylation Cl O AlCl 3 O P: 20.1(a-d), 20.2, 20.44(a,d), 20.45(b-d,g,h), 20.49

Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

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Page 1: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

Chapter 20: Aldehydes and Ketones[Chapter 20 Sections: 20.1-20.7, 20.9-10.10, 20.13]

1. Nomenclature of Aldehydes and Ketones

2. Review of the Synthesis of Aldehydes and Ketones

B. Oxidation of Alcohols (most common method)

R R'

O

R H

O

ketone aldehyde

O

O

H

BrCHO

Br

• for both aldehydes and ketones, the parent chain is the longest continuous carbon chain that contains the carbon of the carbonyl group• numbering (locant) priority is given to the carbonyl carbon• aldehydes always have the carbonyl group at carbon 1, so a number is not needed• ketones have the "one" suffix, aldehydes have the "al" suffix

O

OHPCC

H

O OH OKMnO4

orK2Cr2O7, H2SO4, H2O

A. Friedel-Crafts Acylation

Cl

O

AlCl3

O

P: 20.1(a-d), 20.2, 20.44(a,d), 20.45(b-d,g,h), 20.49

Page 2: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

3. Review of Reactions of Aldehydes and Ketones

A. Oxidation of Aldehydes

OHPCC

H

O KMnO4

orK2Cr2O7, H2SO4, H2O

orO2 in air (slowly)

OH

O

KMnO4or

K2Cr2O7, H2SO4, H2O

• aldehydes may be oxidized using KMnO4 or Jones reagent to the carboxylic acid• since aldehydes are usually synthesized via oxidation of 1° alcohols, the synthesis of carboxylic acids is usually accomplished via direct oxidation of 1° alcohols with the strong oxidizing agents• ketones CANNOT be oxidized further

B. Reduction of Aldehydes and Ketones

O Zn(Hg), HClor

N2H4, KOH, heat

• Clemmensen or Wolff-Kishner reduction of aldehydes and ketones leads to reduction of the carbonyl group to a CH2 group

H

O Zn(Hg), HClor

N2H4, KOH, heat

O

HH2, Pd°

OH2, Pt°

OH

• hydrogenation of ketones forms 2° alcohols (the opposite reaction of the oxidation process)• hydrogenation of aldehydes forms 1° alcohols

4. Reactivity of Aldehydes and Ketones

• both aldehydes and ketones have partial positive charge at the carbon of the carbonyl group due to the polar C=O bond• the partial charge on the aldehyde is greater since it is flanked by a single electron-donating alkyl group • while both aldehydes and ketones are reactive towards nucleophilic addition, aldehydes are more reactive due to i) the greater partial positive charge and ii) less steric interference

P: 20.25(predict product)

P: 20.50

R R'(H)

O

R R'

O

R H

O

Page 3: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

5. Mode of Attack of Strong Nucleophiles on the Carbonyl Group of Aldehydes and Ketones

Nu

(H)R'R

O

Nu

O(H)R'

R

Nu

O(H)R'

R

• nucleophiles attack the partially positively charged carbon of the carbonyl group by pushing electrons into the polarized pi bond• the pi electrons are forced onto the electronegative oxygen atom• these reactions are often followed up by addition of acidic water (HCl, H2O or H3O+) to protonate the negatively charged oxygen and form a neutral product

6. Addition of Strong Nucleophiles to Aldehydes and Ketones

A. Addition of Organometallic Reagents

NaNH2

O

H

O

1.2. H3O+

2. H3O+

1.

O

1. CH3CH2Li

2. H3O+

CHO 1. CH3MgBr

2. H3O+

O OH1. ?

2. H3O+

• these types of nucleophilic additions to aldehydes and ketones are critical reactions since they result in the formation of NEW C-C bonds!• these reactions, therefore, provide a way in which to create larger molecules from readily available smaller molecules

P: 20.54

Page 4: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

B. Addition of HCN

O 1. NaCN

2. H3O+

H

O

catalytic NaCN

HCN

• there are two methods for addition of HCN to a carbonyl group. The net result is the same• the product of addition is referred to as a "cyanohydrin" to reflect the presence of both the cyanide AND hydroxyl groups• as with the organometallics, this reaction forms a new C-C bond

C. Addition of Hydride (hydride reduction)

Hhydride

NaH

sodium hydride

• a "hydride" is a hydrogen with an extra electron, giving it a negative charge• sodium hydride is the simplest form of hydride, but in this form it acts only as a strong base and never as a nucleophile• NaBH4 and LiAlH4 are both sources of nucleophilic hydride

H3C–O–H

B

H

H

H

HNa

NaBH4sodium borohydride

Al

H

H

H

HLi

LiAlH4 (LAH)lithium aluminum hydride

O1. NaBH4

2. H3O+

H

O1. LiAlH4

2. HCl, H2O

Examples

• reduction of aldehydes with either NaBH4 OR LiAlH4 results in the formation of 1° alcohols• reduction of ketones with either NaBH4 OR LiAlH4 results in the formation of 2° alcohols

R R'

O

P: 20.31, 20.33

Page 5: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

Summary of Nucleophilic Addition Reactions of Aldehydes and Ketones

nucleophile catalyst type of productH– (hydride, NaBH4 or LiAlH4) none alcohol (1° from aldehyde,

2° from ketone)

R R'(H)

Onu

product

R R'(H)

H OH

R– (Grignard, alkyllithium) none alcohol (2° from aldehyde,3° from ketone) R R'(H)

R OH

C N (cyanide) none cyanohydrinR R'(H)

NC OH

D. Addition of Alcohols

R OH R R'(H)

O

• alkoxides are strong nucleophiles but alcohols are poor nucleophiles• alcohols will not react with aldehydes or ketones in the absence of an acid catalyst• an acid catalyst protonates a lone pair of the oxygen atom of the carbonyl group• protonation increases the partial positive charge on the carbon and enhances the reactivity of the carbonyl towards nucleophilic addition• under acidic conditions, aldehydes and ketones will react with the weaker alcohol nucleophile• the most common acid catalysts are H3PO4, H2SO4, HCl or para-toluenesulfonic acid (TsOH)

R R'(H)

OROHH+ R R'(H)

O

R R'(H)

OH

R R'(H)

O

R R'(H)

O H

unprotonated protonated

O CH3OHcat. H2SO4

O

EtOHTsOH H

OHO OH

cat. H2SO4

• reaction of aldehydes or ketones with alcohols under acid catalysis results in the addition of TWO equivalents of the alcohol to the carbonyl group. Τthe product is called a "ketal"• if a diol such as ethylene glycol is used, both ends of the diol add across the carbonyl group to form a cyclic ketal• cyclic ketals are the most often utilized type of ketal

Page 6: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

OHO

OH

TsOH

• ketals are "ether-like" compounds that behave like ethers, i.e., they are fairly unreactive• the ketal formation process can be reversed by addition of water under acidic conditions• ketals act as carbonyl "protecting groups" in that they can be placed on a carbonyl group to keep it from reacting and then removed when desired

CH3H

O O1 equivalent

NaBH4

2 equivalents

NaBH4

CH3

O OH

CH3H

O O

C OHO

HOH

OH

OH

OHO

H

HO

OH

H

H

OHOHH H

OH

glucoseα-D-glucose(hemiacetal)

OHOH

OH

OH

OH

OH

sorbitol

Glucose, Sorbitol and other Sweeteners

SNH

O

OO

Saccharin(Sweet 'N Low™)

O

OO

ClHO

Cl

HOOH

OH

ClOH

Sucralose(Splenda™)

OH

CO2H

Stevia(Truvia™)

O

OO

HOHO

HO

HOOH

OH

OHOH

Sucrose(table sugar)

P: 20.10, 20.12, 20.58, 20.63(c,e), 20.67(a,b)

H

Page 7: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

7. Addition/Elimination Reactions of Aldehydes and Ketones

A. The Wittig Reaction

R R'(H)

O

R R'(H)

H3C CH3

O

H3C CH3

O

H3C CH3

O

Overall Reaction:

Reaction Steps

C(Ph)3P CR

R'

R R'

Making the Wittig Reagent

(Ph)3P + CH3Br (Ph)3P CH3 Br strong base(Ph)3P CH2(Ph)3P CH2

(Ph)3P CHCH3

(Ph)3P CHCH3

C

(Ph)3P

H

H3C

H3C CH3

CH CH3

(Ph)3P O

ExamplesO(Ph)3P=CHCH2CH3

Br1. Ph3P

2. nBuLi

CHO

• the initial reaction is an SN2 reaction between triphenylphosphine and an alkyl halide• since it is an SN2 reaction 3° alkyl halides CANNOT be used as substrates• common bases to used deprotonate are typically NaNH2, NaH or n-BuLi

• the Wittig reaction takes place between an aldehyde or a ketone and a Wittig reagent• the final product is replacement of the C=O double bond by a C=C double bond

P: 20.37, 20.51, 20.52, 20.53

Page 8: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

B. Imine Formation

R R'(H)

O

R R'(H)

Overall Reaction:

NR • when a 1° amine reacts with a ketone

or aldehyde, an imine product results• an acid catalyst [usually TsOH or HCl] is often needed• the final product is replacement of the C=O double bond by a C=N double bond

H2N R

an imineH+

Reaction Steps

H3C CH3

OCH3NH2

H+ H3C CH3

OH

ExamplesO

CH3CH2NH2

TsOH

O NPh

TsOH

O

trans-retinal

O cis-retinal

enzyme

Protein NH2

Protein NLIGHT

N

enzyme

P: 20.15-20.18

P: 20.56(a-c,g,i-l), 20.60, 20.66(b,f)

Protein

Page 9: Chapter 20: Aldehydes and Ketonesgarybreton.com/CHM224/ewExternalFiles/Chapter_20_2017.pdf3. Review of Reactions of Aldehydes and Ketones A. Oxidation of Aldehydes OH PCC H O KMnO

Summary of Nucleophilic Addition Reactions of Aldehydes and Ketones

nucleophile catalyst type of product

H– (hydride, NaBH4 or LiAlH4) none alcohol (1° from aldehyde, 2° from ketone)

R R'(H)

Onu

product

R R'(H)

H OH

R– (Grignard, alkyllithium) none alcohol (2° from aldehyde,3° from ketone) R R'(H)

R OH

C N (cyanide) none cyanohydrinR R'(H)

NC OH

ROH (alcohols) H+ acetalR R'(H)

RO OR

single addition reactions

double addition reactions

addition-elimination reactions

(Ph)3P=CR2 (Wittig reagents) alkeneR R'(H)

noneC

R R

R-NH2 (1° amine) imineR R'(H)

H+ sometimesN

R