Reduction of 1-phenyl-1,2-propanedione to 1-phenyl-1,2-propanediol

Asymmetric Synthesis with Baker’s Yeast:

Objectives:

1. To reduce 1-phenyl-1,2-propanedione to 1-phenyl-1,2-propanediol

2. To monitor the course of reaction by using TLC

3. To characterize the produce by FT-IR spectroscopy and gas chromatography-mass spectroscopy (GC-MS)

Introduction:

Lithium aluminium hydride and sodium borohydride are good reducing agent, in which it can reduce a ketone to an alcohol. However, they are not able to generate a chiral alcohol because they can nucleophilic attack both sides of carbonyl group, hence producing racemic mixture. In order to obtain a chiral alcohol, baker’s yeast is used.

Asymmetric reduction of 1-phenyl-1,2-propanedione by using baker’s yeast in this experiment in order to produce (-)-(1R,2S)-1-phenyl-1,2-propanediol with the enantiomeric excess of 98% or more. The completeness of reaction is determined by using thin layer chromatography (TLC). Pure 1-phenyl-1,2-propanediol is characterized by using infrared (IR) spectroscopy and mass gas chromatography-mass spectroscopy (GC-MS).

Apparatus:

Erlenmeyer flask, hotplate-stirrer, magnetic stirring bar, TLC tank, micropipette, separatory funnel, UV lamp, rotary evaporator

Materials:

1-phenyl-1,2-propanedione, freeze-dried Baker’s yeast, TLC plate, tert­-butyl methyl ether (BME), magnesium sulphate anhydrous, cylohexane

Instruments:

IR spectroscopy, gas chromatography-mass spectrometer

Procedures:

Result and calculations:
Observations on TLC plate:

Descriptions: At 0th minute, two spots present on the TLC plate. Reactant and product present in the reaction mixture. At 20th minute, two spots present on the TLC plate. Reactant and product present in the reaction mixture. At 40th minute, only one spot presents on the TLC plate. Reactants have been used up shows complete reaction. At 60th minute, only one spot present on the TLC plate. Reactants have been used up shows complete reaction.

Table 1: R_f value of each spots on TLC plate

Time (minutes)	0	20	40	60
Distance travelled by each aliquots (cm)	1st spot	2.90	2.90	2.90	2.90
2nd spot	5.20	5.20	-	-
Retardation factor, Rf	1st spot	0.41	0.41	0.41	0.41
2nd spot	0.74	0.74	-	-

*TLC is performed by using a mixture of cyclohexane:BME (3:2)

*solvent front is 7cm.

Table 2: Weight of 1-phenyl-1,2-propanediol

Weight of round bottom flask	97.6703g
Weight of (round bottom flask + 1-phenyl-1,2-propanediol)	97.9018g
Weight of 1-phenyl-1,2-propanediol	0.2315g

Table 3: Significant peaks of starting material and product in IR spectrum

Functional group	Wavenumber of Compound, v (cm-1)
1-phenyl-1,2-propanedione	1-phenyl-1,2-propanediol
C=O stretch	1715, 1676	absent
O-H stretch	absent	3369

Molecular weight of 1-phenyl-1,2,-propanedione = 148 g /mol

Molecular weight of 1-phenyl-1,2-propanediol = 152 g / mol

Density of 1-phenyl-1,2,-propanedione = 1.101 g ml^-1

Mass of 1-phenyl-1,2,-propanedione = density x volume

= 1.101 g ml^-1 x 0.23 ml

= 0.2532g

1 mole of 1-phenyl-1,2,-propanedione produces 1 mole of 1-phenyl-1,2-propanediol

Mole number of 1-phenyl-1,2,-propanedione = 0.2532g / 148 g mol^-1

= 0.0017 mol

Theoretical mass of 1-phenyl-1,2-propanediol = 0.0017 mol x 152 g mol^-1

= 0.2584g

Percentage yield = 0.2315g / 0.2584g x 100%

= 89.59%

Discussion:

In this experiment, 1-phenyl-1,2-propanedione was reduced to 1-phenyl-1,2-propanediol by using baker’s yeast. The mass of 1-phenyl-1,2-propanediol obtained experimentally is 0.2315g and its percentage yield is 89.59%.

Thin layer chromatography was used to monitor the reduction of 1-phenyl-1,2-propanedione in this experiment. Based on the observation of TLC plate, the reaction was completed at 40^th minutes since the TLC plate only shows one spot is present. After the reaction completed, the product was extracted with BME and was dried with drying agent to remove water in the organic layer.

The following mechanism shows that how ketone was reduced into alcohol by yeast.

Firstly, the hydride from baker’s yeast nucleophilic attack to carbonyl carbon (labeled as carbon 2) and caused the reduction of the carbonyl group. Oxygen of the particular carbonyl group was bearing with partial negative charge in which it can abstract a proton from water molecules to form hydroxyl group.

Then, another carbonyl group (labeled as carbon 1) was attacked by hydride from back side and hence produced an alcohol that has two carbons with different chirality. The alcohol obtained is named (1R,2S)- 1-phenyl-1,2-propanediol. However, (1S,2R)- 1-phenyl-1,2-propanediol might present with a very low yield.

From the IR spectrum, 1-phenyl-1,2-propanedione shows the presence of C=O stretch at 1715cm^-1 and 1676cm^-1. Besides, this ketone compound did not show any O-H stretch signal in the IR spectrum. From the alcohol spectrum, there shows a broad O-H stretch signal at 3369cm^-1 and it did not have C=O stretch signal. According to IR spectrum, the ketone compound has been successfully reduced to form an alcohol compound as obtained in the experiment because IR spectrum indicated the presence of O-H group.

Precaution steps:

1. Do not use separatory funnel point to anybody when releasing the vapour.

2. Do not shake the separatory funnel vigorously to avoid emulsion formation.

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