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

Abstract
This experiment undergo by Grignard reaction method. 4,4-Diphenyl-but-3-en-2one 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 HO O O O O O O OH Ph Ph

OH

PhMgBr Et2O O OH Ph Ph

O ethyl acetoacetate O Ph

H3O+

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

Br Mg Bromo-benzene magnesium turning Mg Br

Phenyl 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 diethyl ether iodine bromobenzene MgSO4 acetone magnesium sodium bicarbonate Quantity -2 crystals 7.85g -1.34g -MW(g/mol) 74.12 253.81 157.01 120.366 58.08 24.31 84.01 Bp(C) 34.6 112.73 156.12 -48.96 1091 851 Mp(C) -116.58 -67.77 -30 1124 -100 650 50 Major hazard Flammable. Toxic, reproductive damage flammable, irritation irritation Irritant, Flammable. flammable 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-2yl)-acetic acid ethyl ester Mass of product before recrystallition Mass of product after recrystallition Volume Density (g/ml) Melting point (C) % yield 4,4-Diphenyl-but-3-en-2-one

6.527 g .789 g 5.96 ml 1.095 92-94 11.09 %

-.389 g 0.21 ml 1.85 -72 %

Table 2: Analysis of IR spectrum for 2-(2-Methyl-[1,3]dioxolan-2-yl)-1,1-diphenylethanol (see appendix D)

(cm-1) 699.62 730-850 1058 2995 3362.12

Function group C-H aromatics C=C aromatic C-O ester stretch alkane OH stretch, Hbonded

Peak Strength medium 2 band small medium small small

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

(cm-1) 1592.32 1661.99 1682.19 3057.29 3441.75

Function group C=C aromatic -c=c- stretch alkenes C=O stretch ketenes unsaturated CH stretch alkenes Hbonded phenol

Peak Strength small medium small medium medium

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3.2. Discussion
This experiment relies on the concept of Grignard reaction. This reaction doesnt 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.
Mg Br H2O + Et OH + Et2NH +EtNH2 H MgOHBr

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.
ether

R X aryl halide

Mg

R O

Mg H

X H

R Mg X
Grignard Reagent

O R MgX R

O MgHX H

OH R R R H2O

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-en2-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 CH stretch alkenes signal at 3057.29cm-1 .This reaction can be done by other ways such as:

Ph
1)

O Ph

HO

Ph Ph -HX Ph x O

Ph Ph

a-halogenation

2) O

Ph

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 18-122011. 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* 7.85g* 4.35g* =.055 mol Magnesium =.05 mol bromobenzene =.025 mol ethyl 3-oxobutanoate ketal

So ethyl 3-oxobutanoate ketal will be the limiting reagent =.025 mol * % yield = = 7.108 g (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester *100% = 11.09%

The % yield of second part product 0.6927g* 2.43E-3 mol* % yield = =2.43E-3 mol (2-Methyl-[1,3]dioxolan-2-yl)-acetic acid ethyl ester = 0.5414 g 4,4-Diphenyl-but-3-en-2-one *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

3.90 3.90

O O
7.19 7.19 7.19 7.19 7.19 2.32 1.46

OH

2.0

7.19

7.19 7.19

7.19

PPM

Analysis of 1H NMR spectrum of 4,4-Diphenyl-but-3-en2-one

2.30 7.45 7.35

O H
6.60 7.45 7.35

7.24 7.35

7.45 7.45 7.35

7.24

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See references 4

Analysis of 13C NMR spectrum of 2-(2-Methyl-[1,3]dioxolan-2-yl)-1,1-diphenyl-ethanol

70.6 70.6

O
129.0 126.0 129.0 128.4 143.0 128.4 128.4 129.0 126.0 57.2

100.5 O 26.4

70.0

OH

143.0 128.4

129.0

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140

120

100

80 PPM

60

40

20

Analysis of 13C NMR spectrum of 4,4-Diphenyl-but-3-en-2-one

O
196.5 25.1 126.2 128.4 134.9 127.7 128.4 134.9 127.7 128.4 115.6 153.0 126.2 128.4

126.2 126.2

200

180

160

140

120

100 PPM

80

60

40

20

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Appendix C: General reaction mechanism

HO O OH H Ph O Ph H O H O OH HO HO Ph Ph HO Ph Ph O H OH H O Ph Ph HO O OH

H HO O

hemiacetal
OH OH H O O H H Ph Ph O Ph Ph

-hydroxykwtone
H H O

OH get protonate HO

O Ph

Ph H

Ph Ph H H O

H O H H O Ph O Ph HO H OH O H H

Ph H Ph

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H O

H O

HO H O H Ph

Ph

HO Ph

Ph

E2
Ph H O O Ph HO

E1

Ph

Ph

Ph

Ph

Ph

HO

Ph

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