EXp-26 Mini Project
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Transcript of EXp-26 Mini Project
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.
7 | P a g e
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
15 | P a g e
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
16 | P a g e
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