chem a225 notes page 67 chapter 20: aldehydes and ketones

Chem A225 Notes Page 67

Lecture Notes © 2017 Dr. Thomas Mucciaro. All rights reserved.

Chapter 20: Aldehydes and Ketones

I. Introduction

Aldehydes and ketones contain a carbonyl group (C=O) with no other heteroatoms attached. An aldehyde has at least one hydrogen attached; a ketone has only carbon groups attached.

The three-dimensional structure and hybridization of aldehydes and ketones is shown below:

All C=O compounds have a minor contributing resonance structure that heavily influences their chemistry:

Review: Oxidation States of Carbon (handout on next page)

aldehyde ketone

abbreviation: R—CHO abbreviation: R—C(O)—R’

R C

O

H R C

O

R'

C OR'

R

trigonal planar

sp2 hybridized

C OR'

R

pi bond

lone pairs in sp2

hybridized orbitals

R C R'

O

R C R'

O

electrophiles react here

nucleophiles react here

Chem A225 NotesCh 20: Aldehydes and KetonesPage 68


Oxid

ation S

tates of Carbon

Most R

educedM

ost Oxidized

Oxidation S

tate N

ame

alkanealcohol

aldehyde/ketonecarboxylic acid

carbon dioxide

Representative

Structure

Num

ber of Bonds

to Heteroatom

s(O

, N, F, P, S

, Cl,

Se, B

r, I)

01

23

4

Direction of

Change in Types of

Reactions

Reduction

(increase bonds to H or C

, decrease bonds to heteroatom

s)

Heteroatom

E

xchangeO

xidation(decrease bonds to H

or C,

increase bonds to heteroatoms)

CC OH

C O

COH

O

OC

O

Chem A225 Notes Ch 20: Aldehydes and Ketones Page 69


II. Nomenclature of Aldehydes and Ketones

A. IUPAC Nomenclature of Aldehydes

1) Find the longest carbon chain which contains the aldehyde (CHO) carbon.

2) Count the number of carbons in this chain and determine the parent stem name.

3) Add the suffix “-anal.”

4) Number the carbon chain starting from the aldehyde (CHO) carbon (CHO carbon is carbon one).

5) Add substituent names, with appropriate numbers, in front of the aldehyde name.

B. Special Common Names of Aldehydes (MEMORIZE):

formaldehyde acetaldehyde benzaldehyde

H C

O

H H C

O

CH3

CH

O



C. IUPAC Nomenclature of Ketones

1) Find the longest carbon chain which contains the carbonyl (C=O) carbon.

2) Count the number of carbons in this chain and determine the parent stem name.

3) Add the suffix “-anone.”

4) Number the carbon chain starting from the end closest to the carbonyl (C=O) carbon.

5) Indicate the position of the carbonyl (C=O) carbon by adding the number, separated by dashes, in between the stem name and the -one suffix (ie. stem-#-one).

6) Add substituent names, with appropriate numbers, in front of the ketone name.

7) In complex molecules, the carbonyl (C=O) carbon can be named as an “oxo” group.

D. Common Nomenclature of Ketones (Systematic)

1) Name each carbon group attached to the carbonyl (C=O) carbon as an alkyl group.

2) List the alkyl groups, separated by spaces, in front of the word “ketone.”

E. Special Common Names of Ketones (MEMORIZE)

acetone acetophenone benzophenone

CH3 C

O

CH3

CCH3

O

C

O



III.Synthesis of Aldehydes and Ketones

A. Oxidation of Alcohols (to aldehydes and ketones) (Review Section 13.10)

Observed Reaction: 1o Alcohols to Aldehydes

Observed Reaction: 2o Alcohols to Ketones

Jones reagent can’t be used to make aldehydes; it oxidizes them to carboxylic acids.

B. Ozonolysis of Alkenes (Review section 9.11)

Observed Reaction

An alkene carbon with a hydrogen attached becomes an aldehyde. If the alkene carbon has two carbon groups attached, it forms a ketone.

C. Friedel-Crafts Acylation (Review section 19.6)

Observed Reaction

R C

OH

H

H R C H

OPCC

(CrO3, HCl, pyridine)

PCC = pyridinium chlorochromate1o alcohol aldehyde

R C

OH

H

R' R C R'

O

2o alcohol ketone

Na2Cr2O7, H2SO4

(Jones reagent)

C CR1

H R3

R2

1) O3

2) CH3SCH3C CR1

H R3

R2O O

R C

O

Cl

AlCl3

CR

O



D. Hydration of Alkynes (Review section 10.7)

Observed Reaction

Works best to use symmetric alkynes. Unsymmetric alkynes form two regioisomers.

E. Hydroboration of Alkynes (Review section 10.7)

Observed Reaction

F. Alkyl Cuprate Coupling to Acid Chlorides

Observed Reaction

Formation of R2CuLi (lithium dialkylcuprates)

C CR R R CH2 C

O

RHgSO4, H2SO4, H2O

C C H1) Sia2BH

2) H2O2, NaOHC C H

OH

H

Chem A225 Notes Ch 20: Aldehydes and Ketones 3


Cuprates allow R:– to act like a nucleophile on alkyl halides and acyl halides:

Other R:– reagents (Grignards and alkyllithiums) are too basic and do elimination instead of substitution when reacted with alkyl halides:

IV.Reactivity of Aldehydes and Ketones

A. Reaction with Strong Nucleophiles

Strong nucleophiles are strongly basic and usually have a negative charge.

The negative charge of the strong nucleophile is attracted to the + charge on the carbon of the carbonyl (C=O) group.

When the nucleophile makes a bond to the C=O carbon, the pi bond is broken and the electrons from the bond are moved up to the oxygen:

The product is called the tetrahedral intermediate. The tetrahedral intermediate is very unstable because the electrons and negative charge on oxygen are pushing on the tetrahedral carbon (this is sometimes called electron pressure).



If there is a reasonable leaving group on the tetrahedral carbon, it will be pushed out by the electron pressure and the C=O pi bond will be reformed.

In general, any group other than a carbon group or a hydrogen can be pushed off the tetrahedral intermediate. If there is more than one possible leaving group, then the least basic group will be pushed out.

Therefore, aldehydes and ketones will react by addition of strong heteroatom nucleophiles (such as OH– or Cl–); however, these nucleophiles are quickly pushed back off the tetrahedral intermediate, so no net reaction is observed.

B. Reaction with Weak Nucleophiles

Many weakly basic, uncharged species (like alcohols [ROH] and water) can behave like nucleophiles. Most of these are also excellent leaving groups.

Because these weak nucleophiles are uncharged, they are much less strongly attracted to the carbonyl (C=O) carbon.

Because these weak nucleophiles are good leaving groups, they are rapidly pushed off the tetrahedral intermediate if they do add to the C=O.



To help weak nucleophiles add to carbonyls (C=O), we usually must add an acid catalyst. The acid catalyst protonates on the C=O oxygen. This creates a positive formal charge on the C=O oxygen. As a result, the oxygen more strongly attracts electrons, which increases the amount of + charge on the C=O carbon.

The increased + charge on the C=O carbon increases the reactivity of the C=O, and helps attract the weak nucleophile.

The proton on oxygen also stabilizes the tetrahedral intermediate, reducing the electron pressure and helping the weak nucleophile stay bonded to the carbon.

C. Relative Reactivity of Aldehydes and Ketones

Aldehydes are more reactive than ketones to addition of nucleophiles. There are two factors that make aldehydes more reactive than ketones:

1) Aldehydes are less sterically hindered than ketones.

2) The + charge on the aldehyde C=O carbon is larger than on the ketone C=O carbon, because the aldehyde has fewer electron donating carbon groups attached.



V. Reactions of Aldehydes and Ketones

A. Oxygen Addition (formation of hydrates and acetals)

Observed Reactions

Mechanism [Very important!]

To understand and remember the mechanism of heteroatom exchange reactions, we will break them into phases that describe the overall changes. For this mechanism, there are three phases:

1) Add the first alcohol (Add ROH)

2) Remove C=O oxygen (Remove OH)

3) Add the second alcohol (Add ROH)

Each of these phases will have several steps that will always occur as part of a pattern. For example, any time that we remove an OH (Phase 2), we will use the same 3 types of step in the same order. We will learning the mechanism by learning the patterns in the three phases.

The mechanism is a series of reversible, equilibrium driven steps. In many steps there are other possible reactions; however, these don’t lead to any products, and are eventually reversed back to the product forming pathway.

Sometimes, one of the substeps of a phase will be skipped.



Phase One: ADD ROH (add weak nucleophile)

Steps: Protonate C=O --> Add nucleophile --> Make stable (remove H+)

Protonating the C=O oxygen activates C=O for addition of the weak nucleophile

Phase Two: REMOVE OH

Steps: Protonate OH --> Remove LG --> (Make stable)

Protonation of OH makes it into a good leaving group (LG)

The make stable step is skipped because there is no H+ available to remove

Phase Three: ADD ROH

Steps: (Protonate C=O) --> Add Nu: --> Make stable

The first step is not needed in this case, because the intermediate is already activated by the carbon group, and is still unstable from the end of phase 2.



Hemiacetals are usually unstable, especially in base.

However, cyclic hemiacetals are reasonably stable (found in sugar chemistry, for example glucose).

Acetals can be converted back to ketone/aldehyde and alcohols using acid in water (H3O+). This is called acid-catalyzed hydrolysis of acetals. (Observed reaction)



The mechanism of hydrolysis is exactly the same as the mechanism of formation, just in reverse. As an exercise, write out the mechanism of acid-catalyzed hydrolysis of acetals in the space below:

By using a diol (for example, HOCH2CH2OH [ethylene glycol]), cyclic acetals can be formed:

Cyclic acetals are often used as protecting groups, to prevent a C=O from doing an unwanted reaction. They can be removed by acid-catalyzed hydrolysis:



B. Nitrogen Addition (formation of imines, hydrazones, oximes)

Observed Reaction (general)

Requires that the nitrogen atom have at least two hydrogens attached (we will study the reaction when there is only one hydrogen on nitrogen in a later chapter).

Different Z groups lead to similar products with different names:

Z Group H2N–Z Name Product Name Product Structure

R or Hamine

H2N–R imine

–OHhydroxylamine

H2N–OH oxime

–NH2hydrazineH2N–NH2

hydrazone

–NH–Phphenylhydrazine,

H2N–NH–Ph phenylhydrazone

C

N R

C

N OH

C

N NH2

C

N NH Ph



Mechanism

If we analyze the change in structure from the reactant to the product, we see two major changes. A nitrogen group has been added, and the oxygen has been removed. This implies two phases: Add RNHZ --> Remove oxygen

Phase One: Add RNHZ

Protonate C=O --> Add Nu: --> Make Stable

Phase Two: Remove oxygen

Protonate OH --> Remove LG --> Make Stable

C=N can be converted back to C=O by acid-catalyzed hydrolysis. Mechanism is exact reverse of mechanism for formation of C=N from C=O. Practice writing the reverse mechanism on a separate page.



C. Hydride Addition (to form alcohols) (review section 13.4)

Observed Reactions

Formal Mechanism:

Sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4) are sources of “H:–”(hydride).

Hydride is a hydrogen nucleophile. It reacts with the C=O carbon:

NaBH4 only reacts with ketones and aldehydes.

LiAlH4 is more reactive; it will reduce aldehydes and ketones, and also will reduce esters, carboxylic acids, amides, and nitriles.



D. Organometallic Additions (Grignard Reagents) (Review section 13.6)

Observed Reactions

Mechanism:

Formation of Grignard reagents and alkyllithiums (Observed Reactions)

Restrictions on Grignard reagents and alkyllithiums: Carbanions (R:–) are very strong bases. They will do acid-base reaction and deprotonate O–H, N–H, S–H, and P–H bonds. This irreversibly destroys the carbanion.

Therefore, O–H, N–H, S–H, or P–H bonds can’t be present in the Grignard reagent/alkyllithium or in the carbonyl substrate.



E. Cyanide Addition (formation of cyanohydrins)

Observed Reaction

Mechanism

Cyanohydrin formation is readily reversed by treating the cyanohydrin with base:



F. Wittig Reaction (formation of alkenes)

Observed Reaction

Mechanism

Formation of Wittig Reagent from triphenylphosphine (PPh3)



G. KMnO4 Oxidation of Aldehydes (aldehydes only)

Observed Reaction

H. Jones Reagent Oxidation of Aldehydes (aldehydes only)

Observed Reaction

This reaction prevents us from using Jones reagent to make aldehydes from 1o alcohols.

I. Tollens Reagent (oxidation of aldehydes) (aldehydes only)

Observed Reaction

This reaction was used as a chemical test for aldehydes (before IR/NMR). This test was called the silver mirror test.

An aldehyde will be oxidized, and at the same time Ag+ ions will be reduced to Ago (silver metal). The Ago deposits on the glass walls of the reaction container, forming a mirror.

Formation of a mirror was considered a positive test, indicating that an aldehyde was present.

chem a225 notes page 67 chapter 20: aldehydes and ketones

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