Advanced Organic lab

Experiment # 36

Grignard reagents: addition of phenylmagnesium

bromide to ethyl 3-oxobutane ketal

xxx /Id: xxxxx

Submitted to: Dr. xxxx

Date Submitted: 2011/12/25

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Abstract

This experiment undergo by Grignard reaction method. 4,4-Diphenyl-but-3-en-2-

one was prepared from (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester which has a

protected ketene group and Grignard reagent that was Phenyl Magnesium Bromide.

This reaction occurred spontaneously since Grignard reagent works as nucleophile. The

reaction achieved by two stages: the first one was preparation of Grignard reagent. The

second stage was hydrolysis of ketal. In addition, this reaction is very reactive

toward oxygen and moisture so the condition is an important factor in this reaction.

Keywords: Grignard reaction, protecting group, Grignard reagent, ketal

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1. Introduction

Grignard reagents (also called the organomagnesium halides) are made by any organic

derivatives of magnesium (Mg) usually represented by the general formula RMgX in

which R is a hydrocarbon radical: CH3, C2H5, C6H5; and X is a halogen element such as:

chlorine, bromine, or iodine. These mixture worms up in a flask containing

ethoxyethane (commonly called diethyl ether).

Grignard reagents are prepared by reaction of halogen with magnesium in present of

inert gas such as nitrogen because the reagent is very reactive toward oxygen and

moisture.

Halogens are varying in their rates of reaction with magnesium. For instance, alkyl

iodides are very reactive, whereas most aryl chlorides react very slowly. This is why

everything has to be very dry during the preparation.

Grignard reagents behave as a strong base (strong nucleophile) because of the

attraction between the relatively negative side of the carbon atom in the Grignard

reagent and the positive side of the carbon in the carbonyl compound.

In this experiment, 4,4-Diphenyl-but-3-en-2-one was prepared from ethyl 3-oxobutane

ketal [ (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester ] with Grignard reagent

which was phenylmagnesium bromide(see fig.1).The Grignard reagent form from

reaction of bromobenzene with turning magnesium (see fig.2)

O O

Oethyl acetoacetate

HOOH

O

O

OO PhMgBr

Et2O

OH

Ph

OO

H3O+OHO

PhPh

Ph

PhO

Ph

4,4-Diphenyl-but-3-en-2-one

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Figure.1: scheme of preparation of 4,4-Diphenyl-but-3-en-2-one

MgBrBr

Bromo-benzene

Mg

magnesium turningPhenyl Magnesium Bromide

Figure.2: scheme of preparation of Grignard reagent

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2. Experimental

Apparatus condition:

Two neck flasks and reflux flask were drying in a hot oven

(Since only a trace of water will destroy the Grignard reagent)

figure. 3 Two neck flask

Name of compound

Quantity MW(g/mol) Bp(°C) Mp(°C) Major hazard

diethyl ether -- 74.12 34.6 -116.58 Flammable.

iodine 2 crystals 253.81 112.73 -67.77

Toxic, reproductive damage

bromobenzene 7.85g 157.01 156.12 -30 flammable, irritation

MgSO4 -- 120.366 -- 1124 irritation

acetone - 58.08 48.96 -100 Irritant, Flammable.

magnesium 1.34g 24.31 1091 650 flammable

sodium bicarbonate

-- 84.01 851 50 irritant

*Caution * Diethyl ether is highly volatile and highly flammable so the work must be always in the fume hood.

2.1 Preparation of the Grignard reagent

Two neck flasks with reflux flask were set up; pour magnesium turning, 10 ml dry diethyl

ether and 2 crystals of iodine to the first flask. The second flask was filled with 10 ml dry

diethyl ether and the bromobenzene. The second solution was added from its funnel to

the main flask drop by drop with stirring at this moment Grignard reagent start to form.

An extra 20 ml diethyl ether was added to wash the funnel. The mixture was refluxed

gently .After refluxing, it was heated up with stirring for 10 min. It left to cool in ice

bath.

2.2 stating Grignard reaction

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A solution of ethyl 3-oxobutanoate ketal with 10 ml dry diethyl ether were added to the

two neck flask drop by drop from the addition funnel .It was stirred with magnetic bar

for 30 min at room temperature. 20ml of ice water with 10 ml diethyl ether were added

to the flask (the gummy solid material started to dissolve).The mixture was separated by

using a separatory funnel and the aqueous layer was extracted by 10 ml diethyl ether.

The remaining layer was washed with 10 ml water and dried over MgSO4 (it was dried in

oven to increas its function).This layer was filtered by fine glass that hold inside dropper

since the product appear in small quantity. The solvent was evaporated by using rotary

evaporator. The product appears as oily yellow liquid. It recrystallized from hot diethyl

ether.

2.3 hydrolysis of the ketal

Since the mass of last product was lower than expected, the compounds that used in

this stage were 24.39% of the actual needed masses. The tertiary alcohol that prepared

by the last stage was placed in a round bottomed flask with 0.36 ml water,0.24 ml HCl

and 6.00 ml acetone .Reflux condenser was setup over the round bottomed flask and

the mixture was heated up for 1h ( boiling stone was used to avoid bubbling). After it

cool, it was transfer to separatory funnel with 25 ml water and the aqueous layer was

extracted by 30 ml diethyl ether. The remaining layer was washed with saturated

sodium bicarbonate solution and 15 ml water then dried with MgSO4. This layer was

filtered by fine glass that holds inside dropper since the product appear in small

quantity. The solvent was evaporated by using rotary evaporator. The IR spectrum of

first product and 4,4-Diphenyl-but-3-en-2-one were predicted.

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3. Results and discussion

3.1. Results

Table 1: the calculated result of first and second products (see appendix A)

(2-Methyl-[1,3]dioxolan-2-

yl)-acetic acid ethyl ester 4,4-Diphenyl-but-3-en-2-one

Mass of product before

recrystallition 6.527 g --

Mass of product after

recrystallition .789 g .389 g

Volume 5.96 ml 0.21 ml Density (g/ml) 1.095 1.85 Melting point (°C) 92-94 -- % yield 11.09 % 72 %

Table 2: Analysis of IR spectrum for 2-(2-Methyl-[1,3]dioxolan-2-yl)-1,1-diphenyl-

ethanol (see appendix D)

Ṽ (cm-1) Function group Peak Strength

699.62 C-H aromatics medium 730-850 C=C aromatic 2 band small 1058 C-O ester medium 2995 stretch alkane small 3362.12 O–H stretch, H–bonded small

Table 3: Analysis of IR spectrum for 4,4-Diphenyl-but-3-en-2-one (see appendix D)

Ṽ (cm-1) Function group Peak Strength

1592.32 C=C aromatic small 1661.99 -c=c- stretch alkenes medium 1682.19 C=O stretch ketenes unsaturated small 3057.29 C–H stretch alkenes medium 3441.75 H–bonded phenol medium

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3.2. Discussion

This experiment relies on the concept of Grignard reaction. This reaction doesn’t gives

high achievement in normal lab condition since it is highly reactive with water and

moisture .As the following reaction shows, water, oxygen, carbon dioxide, or almost any

electrophonic organic compound will hydrolyzes Grignard reagent as each protic solvent

do.

MgBr

H2O

H

MgOHBr

+ Et OH

+ Et2NH

+EtNH2

CaCl2 was used as anhydrous condition for the Grignard reagent but it was not enough.

Inert gas such as N2 can be used to avoid moisture from this reaction. The general

mechanism of Grignard reagent and its reaction with ethyl 3-oxobutanoate ketal was

shown in the scheme below (see fig 3).The full General reaction mechanism was attached

in appendix C.

R X Mg R Mg XR Mg X

R MgXRR

O

RR

O

R

OH

H

H

RR

OH

R

H2O

aryl halide Grignard Reagent

MgHX

ether

Figure.3: General reaction mechanism for the Grignard reaction

When the electrophonic was adding to the Grignard reagent, the reaction was started

strongly and spontaneously because the nucleophile attacks the electrophile and MgBr2

start to precipitate. In addition, the ketene group of ethyl acetoacetate was protected

by react it with ethylene glycol to produce ketal. The purpose of adding cold water to

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reaction was to convert MgBr2 to MgBrOH which will eliminated later. Low yield was

obtained in part 1 of the project (11.09%) because of excess-solvent to the product in

the recrystallization step. The yield was increased in the part of 4,4-Diphenyl-but-3-en-

2-one and it come as 72%.

By examine the melting point of the products (see table 1), NMR of 13C and 1H spectrum

(see appendix B) the present of target product was proofed. Also, the IR data supported

that see appendix D). For (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester ,there was

presence of the ' C-O ester group' signal at 1058 cm-1 and ‘alkane’ signal at 2995 cm-1.

For 4,4-Diphenyl-but-3-en-2-one, there was presence of the “C=O stretch ketenes

unsaturated“ signal at 1682.19 cm-1 and “C–H stretch alkenes” signal at 3057.29cm-1

.This reaction can be done by other ways such as:

OO

HO

Ph

Ph1)

O

Ph

Ph

Ph

PhO

x

2)

Ph

PhO-HXa-halogenation

Figure.4: General reaction of 4,4-Diphenyl-but-3-en-2-one

4. Conclusion

The aim of this project was achieved. The 4,4-Diphenyl-but-3-en-2-one

compound was prepared by Grignard reaction. The yield of the product was 72% which

considerably good yield (see table 1).The IR, NMR and mp test shows that this

compound is the target compound. The source of error in this project is that the

condition is highly satisfied for this reaction since it contains moisture which will affect

the reaction.

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Acknowledgements

This work is acknowledged my instructors

References:

1. Herwood, L. M.; Moody, C. J.; Percy, J. M. Experimental Organic Chemistry,

2nd

Edition, Blackwell Science, Oxford, 1999, pp. 523-525.

2. http://classweb.gmu.edu/jschorni/chem318/grignardbenzoicacid(sonication).p

pt, accessed on 18-12-2011.

3. http://www.armourassociates.com/papers/grignard.pdf, accessed on 18-12-

2011.

4. http://www.uiowa.edu/~c004141a/grignard_nmr.pdf, accessed on 18-12-2011.

5. http://www.weylchem.com/fileadmin/Downloads/WEYL_GrignardReagents.p

df, accessed on 18-12-2011.

6. ‘2-(2-Methyl-1,3-dioxolan-2-yl)-1,1-diphenylethanol’

<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980271/> [accessed 24

December 2011].

Appendix A: Calculations

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The amount of water using in hydrolysis stage:

= 24.39% so 1.5 ml will be 1.5*27.8%=0.365

The % yield of first part product

1.34g*

=.055 mol Magnesium

7.85g*

=.05 mol bromobenzene

4.35g*

=.025 mol ethyl 3-oxobutanoate ketal

So ethyl 3-oxobutanoate ketal will be the limiting reagent

=.025 mol *

= 7.108 g (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester

% yield =

*100% = 11.09%

The % yield of second part product

0.6927g*

=2.43E-3 mol (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester

2.43E-3 mol*

= 0.5414 g 4,4-Diphenyl-but-3-en-2-one

% yield =

*100% = 71.94% =72 %

Appendix B: Spectra of 1H NMR and 13C NMR

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Analysis of 1H NMR spectrum of 2-(2-Methyl-[1,3]dioxolan-2-yl)-1,1-diphenyl-ethanol

O

O

OH

2.32

7.19

7.19

7.19

7.19

7.197.197.19

7.19

7.19 7.19

3.90

3.90

1.46

2.0

012345678PPM

Analysis of 1H NMR spectrum of 4,4-Diphenyl-but-3-en-

2-one

O

H

2.307.45

7.35

7.24

7.35

7.457.45

7.35

7.24

7.35

7.45

6.60

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A

See references 4

Analysis of 13

C NMR spectrum of 2-(2-Methyl-[1,3]dioxolan-2-yl)-1,1-diphenyl-ethanol

O

O

OH70.0

57.2

143.0

128.4

129.0

126.0

129.0

128.4

143.0

128.4129.0

126.0

129.0 128.4

100.5

70.6

70.6

26.4

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020406080100120140PPM

Analysis of 13

C NMR spectrum of 4,4-Diphenyl-but-3-en-2-one

O

25.1

196.5

115.6

153.0

134.9

126.2

128.4

127.7

128.4

126.2

134.9

126.2

128.4

127.7

128.4

126.2

020406080100120140160180200PPM

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Appendix C: General reaction mechanism

OH

Ph

OHO

PhO

O

OH

Ph

OHO

Ph

O

H

H

HO

OH

Ph

OHO

Ph

H

O

H

H

hemiacetal

HO

OH

Ph

OHO

Ph

H

O

OH

Ph

Ph

H

H

O

H

O

OH

Ph

Ph

-hydroxykwtone

O

OH

Ph

Ph

HO

O

Ph

Ph

get protonate

H H

O

OH

Ph

Ph

HO

O

Ph

Ph

H H

H

O

H

H

HH

O

H

O

H

H

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HO

O

Ph

Ph

H H

HH

O

HO

O

Ph

Ph

H H

O

Ph

Ph

E1E2

H

O

HO

Ph

Ph

HO

Ph

PhO

Ph

Ph