SCH 206 Synthesis of Aldehydes and Ketones

Aldehydes and Ketones

Hydration

Alkynes Dr. Solomon Derese 17 I. Oxidation of Alcohols SCH 206 OH Oxidizing agent R H H 1° Alcohol Aldehyde Oxidation of a primary alcohol to an aldehyde requires careful selection of an oxidizing agent, since they are easily oxidized to carboxylic acids. OH Oxidizing agent R R' H Ketone 2 ° Alcohol Dr. Solomon Derese 18 SCH 206 OXIDIZING AGENTS Aqueous oxidants Anhydrous oxidants

H2CrO4 N Na2Cr2O7 ClCrO3 H

K2Cr2O7 Pyridinium chlorochromate (PCC)

KMnO4

Pyridinium dichromate (PCC) Dr. Solomon Derese 19 SCH 206 1° Alcohols are oxidized to aldehydes under mild

reaction conditions—using PCC or PDC in CH2Cl2.

Dr. Solomon Derese 20 SCH 206 1° Alcohols are oxidized to carboxylic acids (RCOOH) under harsher reaction conditions:

Na2Cr2O7, K2Cr2O7, or CrO3 in the presence of H2O and H2SO4.

1° Alcohol Aldehyde

Aldehyde (not isolated) Carboxylic acid Dr. Solomon Derese 21 SCH 206 OH Oxidizing agent R R' H 2 ° Alcohol Ketone

Example

Dr. Solomon Derese 22 SCH 206 Step I: Formation of a chromate ester

Step II: E2 elimination to form a carbon-oxygen p bond

Dr. Solomon Derese 23 SCH 206 PCC/PDC also oxidizes a 2° alcohol to a ketone OH O

PCC or PDC

CH2Cl2

Cyclohexanol Cyclohexanone 90% Tertiary alcohols cannot be oxidised (no carbinol C-H).

Dr. Solomon Derese 24 SCH 206 How does alcohol blow work?

Red-orange Green

Dr. Solomon Derese 25 Assignment 5 SCH 206

I. Predict the principal organic product of each of the following reactions:

II. Provide a step by step mechanism for the following transformation:

Dr. Solomon Derese 26 SCH 206 II. OZONOLYSIS OF ALKENES General reaction :O: O :O: :O : R H 3 R O H R H R R R R R R O O Molozonide Ozonide Reductive workup Zn (dust) in H O Oxidative workup 2 H2O2 or (CH ) S or Ph P R O H 3 2 3 R H O O + O + O R R R R

Dr. Solomon Derese 27 SCH 206 Mechanism of Ozonolysis

: : .. O .. O .. O O .O.: :O: :O : :O: O R H R H R H R R R R R R Molozonide

R O H .. .. O: :O.. R O O O R + Ozonide R R H R

Dr. Solomon Derese 28 SCH 206 Example

O O 1. O3 H 2. Zn in H2O or

(CH3)2S 1. O3

2. H2O2/NaOH + 3. H3O

O O

HO

Dr. Solomon Derese 29 III. Hydration of Alkynes SCH 206 Tautomerization HO H HgSO4, H2SO4, H2O

R H Markovinikov addition

H OH / THF 1) BH3

2) H2O2, -OH, H2O R H Anti-Markovinikov addition Enol Keto Terminal alkynes undergo addition of water in the same way as alkenes, except that the product is an enol. Enols are unstable, and tautomerize readily to the more stable keto form. Dr. Solomon Derese 30 SCH 206 Terminal alkynes are less reactive than internal alkynes toward the addition of water. Terminal alkynes will add water if mercuric ion, Hg2+, is added to the acidic mixture. The mercuric ion acts as a catalyst to increase the rate of the addition reaction. Internal alkynes undergo hydration with concentrated acid. Symmetrical internal alkynes give a single carbonyl compound.

Dr. Solomon Derese 31 SCH 206 Hydration of unsymmetrical internal alkynes leads to a mixture of ketones under both conditions.

Dr. Solomon Derese 32 Assignment 6 SCH 206 Draw the product formed when

is treated with each set of reagents:

a) H2O, H2SO4, HgSO4; or – b) BH3 followed by H2O2, OH.

Dr. Solomon Derese 33 IV. Friedel-Crafts acylation SCH 206 General reaction

AlCl3 Example

Dr. Solomon Derese 34 SCH 206 Mechanism of Friedel-Crafts acylation Step I: Formation of an acylium ion

O :O: .. AlCl3 R Cl : .. .. R Cl AlCl .. 3

.. R C O R C .O.

Acylium ion

Dr. Solomon Derese 35 SCH 206 Step II: Electrophilic attacks

O O H C R R

Cl .. :Cl.. Al Cl Cl O

R + HX + AlCl3

Dr. Solomon Derese 36 Assignment 7 SCH 206 Draw a stepwise mechanism for the intramolecular Friedel–Crafts acylation of compound A to form B.

Dr. Solomon Derese 37