Chem 216 S11 Notes - Dr. Masato Koreeda Date: May 10, 2011 Topic: _Experiment 2_ page 1 of 3.

Experiment 2. Oxidation of an Alcohol (see Ege’s: pp 515-519)

CR

R' H

O-H [ox] C OR

R'

R = alkyl or aryl; R' = H1o -alcohol:

R/R' = alkyl or aryl2o -alcohol:

C OR

Haldehyde

C OR

R'ketone

• A number of chromium (VI)-based reagents have been developed for the oxidation of alcohols, e.g., Jones’ reagent [CrO3/H2SO4/acetone/water]. The oxidation of a primary alcohol by the use of the Jones’ reagent results in the formation of mostly a carboxylic acid. • Pyridinium chlorochromate (abbreviated as PCC; developed in 1975 by E. J. Corey) is one of the mildest and yet highly versatile reagents used for the oxidation of alcohols. With this reagent, the oxidation of a primary alcohol cleanly produces the corresponding aldehyde. Mechanism of the PCC oxidation of an alcohol:

CR

R' H

O-H

CrO

O

OCl

more electrophilic than the Cr in CrO3 because of Cl

CR

R'OH

CrO

OO

HCl

NH

NH

CR

R'OH

CrO

HNHO

O

-Cl

Clstill Cr+6

B:extremely acidic!

CR

R'O Cr

O

H

NH

OO

Cl

still Cr+6

often referred to as"Chromate" ester

oxidation step

B:

C OR

R'Cr

O

OO

+

Cr+4(chromium is reduced!)

• Due to the suspected toxicity of Cr(VI)-based reagents, a number of alternate reagents have been developed. Oxidation of secondary alcohols can be efficiently achieved using much environmentally safer reagents such as a 5.25% (0.75M) sodium hypochlorite (NaOCl) solution available in the grocery store as household bleach. Mechanism of the oxidation with bleach:

OHH

OCl OH

H

H2O

ClO

Cl

H

H2O

O

Cl

H

+

+ OHH H

O+ O

HH H Cl+

ketone

Na H-O-Cl H2O+ +

H3OH2O

Na-OCl +H3O

oxidation step

Chem 216 S11 Notes - Dr. Masato Koreeda Date: May 10, 2011 Topic: _Experiment 2_ page 2 of 3. Notes for experimental procedures: 1. The TLC spot of neither any of the alcohol we use nor the ketone product could be visible under the 254 nm UV lamp. Use the vanillin stain (this stain contains vanillin and conc. sulfuric acid in ethanol). After developing the spots, evaporate off the solvent from the plate and strongly heat the plate on a heater. 2. The ketone product is to be collected by the steam distillation. 3. The distillate obtained is to be extracted with ether. 4. Make the 2,4-DNP [2,4-dinitrophenylhydrazone] derivative of the ketone product and recrystallize the 2,4-DNP derivative from methanol (obtain the mp data as well as IR).

C OR

R'

ketone

NNH

H H

NO

O

NO

ONNH

NO

O

NO

ORR'

+ H2OH+

2,4-Dinitrophenyl-hydrazine

2,4-Dinitrophenyl-hydrazone

2,4-DNP derivative: usually highly crystallineand sharp melting solids

+

Mechanism of the 2,4-DNP formation: See Ege’s book (pp 575-576). Please note the mechanism for the formation of 2,4-DNP is essentially identical with that described for the formation of oximes. Simply replace the OH in the oxime formation with NHAr in the 2,4-DNP formation [Ar = 2,4-dinitrophenyl].

NNH

H H

NO

O

NO

O

not basic, not nucleohpilic

NNH

H H

NO

O

NO

O

NNH

H H

NO

O

NO

O

NNH

H H

NO

O

NO

O

NNH

H H

NO

O

NO

O

This N reacts with the ketone C=O! The internal NH lone pair electron is delocalized throughout the aromatic pi system and two nitrogroups by extensive resonance.

Chem 216 S11 Notes - Dr. Masato Koreeda Date: May 10, 2011 Topic: _Experiment 2_ page 3 of 3.

Steam distillation setup [see: textbook, pp 141-150 (distillation) and 153-155 (steam distillation)]. Modified setup for this experiment:

Extraction procedure [see: textbook, pp 128-137 (extraction) and 137-140 (drying)]

• The organic layer (i.e., ether in this case) used for extraction from an aqueous solution contains about 2%! of water in it. Thus, this organic layer needs to be dried. • The organic layer is next washed with a roughly equal volume of brine (saturated aqueous NaCl). Brine is highly ionic, thus expelling non-ionic organic compounds/solvents out of the aqueous layer (i.e., brine).

“brine and water-immiscible organic solvents separate better → drier organic layer”

• The brine washed organic layer still contains a trace amount of water. In order to further remove water in the organic layer, an inorganic drying agent, for example, anhydrous MgSO4, Na2SO4, or CaCl2, is used by taking advantage of the following chemical reactions with water.

MgSO4 + 7 H2O → MgSO4•7H2O Na2SO4 + 10 H2O → Na2SO4•10H2O CaCl2 + 2 H2O (or 6 H2O) → CaCl2•2H2O (or CaCl2•6H2O)

These are semi-transparent crystalline water-containing inorganic salts. Water molecules are not simply adsorbed on the surface of these inorganics. These water molecules are ligands and are part of their crystalline structures.

• Remove the drying agent by gravity filtration and evaporate the organic solvent from the filtrate.