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Synthesis of Phenylalanine
January 26, 2006 – March 2, 2006
Introduction and Background Information
Proteins are made up of amino acids subunits. In the human body there are only amino
acids of the L configuration. (Amino acids of the D configuration have been found in
some bacteria species.) Valine, leucine, isoleucine, threonine, methionine, lysine,
phenylalanine, and tryptophan are 8 essential amino acids so called because our body is
unable to synthesize and thus we must obtain through out diet.
The disease phenylketonuria (PKU) is caused by the lack of the functional enzyme
phenylalanine hydroxylase. This enzyme converts phenylalanine into tyrosine. When
this enzyme is not working, phenylalanine can accumulate to toxic levels and cause
mental retardation and organ damage. PKU is treated by a low phenylalanine diet at a
young age, where the levels of phenylalanine are enough for normal growth and
development, but low enough for it to be hydrolyzed and removed by absorption.
Amino acids can be isolated from natural sources, but it is also possible to synthesize it in
a chemical laboratory. In this experiment, phenylalanine was synthesized by a malonic
ester synthesis involving three key steps: first malonic ester is benzylated to obtain the
intermediate diethyl benzylmalonate, then this undergoes saponification, bromination,
and decarboxylation, to produce another intermediate, 2-bromo-3propanoic acid, and
finally, aminolysis is carried out to obtain ()-phenylalanine (see Overall Reacion
Scheme). The intermediates and product were analyzed by physical properties, infrared,
and 1H NMR spectroscopy. This experiment successfully synthesized and purified ()phenylalanine, with a yield of 0.46%.
References
Chemistry 361/363 Laboratory Manual 2005-2006 Edition L.M. Browne pp 173-185
Organic Chemistry Experiments Chemistry 161/163 2002-2003 Edition L.M. Browne pp
317-322
Chemfinder www.chemfinder.com
SDBS http://www.aist.go.jp/RIODB/SDBS/cgi-bin/cre_index.cgi
Balanced Equations
2 Na(s) + 2CH3CH2OH  2NaOCH2CH3 + H2(g)
(1)
2 Na(s) + 2H2O  2NaOH + H2(g)
(2)
(3)
(4)
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(5)
(6)
(7)
(8)
(9)
Overall Synthetic Scheme
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Table 1. Table of Reagents
Compound
M.W.
(g/mol)
Acetic Acid
60.05
Wt/Vol
Density Moles
(g/mL)
1.140
0.818
bp/mp
(oC)
mp=115116
bp=56.5
Acetone
Ammonium Hydroxide
58.08
35.05
80mL
Anhydrous ethanol
Anhydrous hexanes
Benzyl Chloride
46.0688
86.18
126.5853
50mL
25mL
12.7g
0.789
0.659
1.1
0.856
0.1104
bp=78.3
bp=69
bp=179.3
Bromine
159.82
2.3mL
3.102
0.0446
bp=59.5
Calcium Chloride
CDCl3
Charcoal
Chloroform
D2O
Diethyl Ether
Diethyl Malonate
Ethyl Acetate
Hydrochloric Acid
110.99
120.38
1.5
bp=60.8
119.38
20.0274
74.12
160.1694
88.11
36.46
1.5
1.107
0.708
1.055
0.90
1.200
bp=61-61
bp=101.3
bp=34.6
mp=199
bp=76-77
Methanol
32.04
Potassium Hydroxide
Sat. Sodium Chloride
Sodium Bicarbonate
Sodium Bisulfite
56.11
58.44
84.01
104.056
8.6g
Sodium Metal
22.99
2.38g
0.9
Sodium Sulfate
Toluene
142.04
92.14
25mL
0.867
16.7g
0.1043
0.791
mp=64.6
0.1533
mp=801
0.1035
mp=97.8
mp=884
bp=111
Hazardous
Properties
corrosive,
hygroscopic
flammable, irritant
corrosive,
lachrymator
flammable
flammable, irritant
lachrymator,
combustible,
moisture sensitive
highly toxic,
oxidizer
irritant, hygroscopic
highly toxic
highly toxic
hygroscopic
flammable, irritant
flammable, irritant
highly toxic,
corrosive
highly toxic,
flammable
corrosive, toxic
irritant, hygroscopic
moisture sensitive,
irritant
flammable,
dangerous when wet
flammable, toxic
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Part 1: Preparation of Diethyl Benzylmalonate
Objective
1. React ethanol and sodium metal to produce a base (sodium ethoxide).
2. Use the sodium ethoxide to depronate diethyl malonate and form a carbanion.
3. React depronated diethyl malonate with benzyl chloride to produce diethyl
benzylmalonate.
4. Purify diethyl benzylmalonate by vacuum distillation.
5. Characterize the diethyl benzylmalonate by infrared, 1H NMR, and 13C NMR
spectra.
6. Begin the saponification of diethyl benzylmalonate.
Mechanism
Procedure and Observations
Procedure
Preparation of Sodium Ethoxide
- Pre-weigh 25mL of anhydrous hexanes in
a beaker
-weight 2.4g of sodium metal
-cut sodium into 15 to 20 portions
(~250mg) and place in beaker of hexane
Observations
January 26, 2006
- instead of using hexane, we used toluene
-Darren (TA) weighed out the sodium
-2.38g sodium ( 0.1035 moles)
-Heat dry all glassware (setup a 3 neck
-heat dried with Bunsen burner
round-bottom flask with an addition funnel,
a stopper, a reflux condenser, stir bar,
graduated cylinder, and a drying tube)
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-put CaCl2 into drying tube and place onto
of condenser
-add 50mL of anhydrous ethanol (98%)
and add through the addition funnel
-stir mixture
-added 50mL of anhydrous ethanol (98%)
directly to round-bottom flask through
stoppered neck
-blot sodium dry with filter paper and add
one piece at a time through stoppered neck
over 30 minutes
-maintain gentle reflux
-cut sodium chunks into smaller pieces and
added through stoppered neck
-pieces of sodium stuck together in the
ethanol
-bubbles of gas released (H2)
-turned on heating mantle (about 30-40 on
the rheostat) and continued to add pieces
slowly
-cool to room temperature
-cooled to room temp after all pieces of
sodium were gone (clear solution)
Preparation of diethyl benzylmalonate
-add 16.6g (0.103mol) of diethyl malonate
through addition funnel dropwise, with
stirring
-stir for another 10 minutes

-add 12.7g (0.100mol) benzyl chloride
dropwise, with stirring
-gently heat at reflux for 40 minutes
-added 15.8mL of diethyl malonate
(0.1041 moles)
m
16.6g
V 
 15.7mL
D 1.055g /mL
-stirred for another 10 minutes
-white gel-like appearance
-added 11.5mL of benzyl chloride
(0.0999 moles)
m
12.7g
V 
 11.5mL
D 1.10g /mL
-refluxed for 40 minutes
-white milky solution
-transfer to one neck round bottom flask

and concentrate with a rotovap
-concentrated by distillation (bp = 76 oC)
-add 50mL of 0.2M HCl
-swirl to decompose all solids
-test to make sure solution is acidic, if not
add up to 0.5mL concentrated HCl (swirl
and test pH)
-added 50mL 0.2M HCl
-tested pH with universal indicator strips,
dark pink ~ pH 1
-placed solution in drawer until following
week
February 2, 2006
-tranfered to separatory funnel
-rinsed flask with 30 mL of diethyl ether
and added to separatory funnel
-transfer solution to separatory funnel
-add 30mL ether to round-bottom flask,
swirl and add to funnel
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-draw off aqueous phase (ether should be
colorless to slightly yellow)
-top layer: ether (D=0.7134g/mL)
clear and slightly yellow
-bottom layer: aqueous (D=1.000g/mL)
clear and colourless
-wash ether layer with two x 10mL distilled -ether layer = slightly yellow
water
aqueous layer = clear colourless
-wash with 10mL 5% NaHCO3
-ether layer = cloudy pale yellow
aqueous layer = clear yellow
-wash with 10mL saturated salt solution
-skipped drying steps (brine and Na2SO4)
-transfer to Erlenmeyer flask and stand
over anhydrous sodium sulfate for 5
minutes, swirling occasionally
-concentrate with rotovap
-concentrated with rotovap
-obtained an oily residue
-purify crude diethyl benzylmalonate by
vacumm distillation
set up apparatus
collect fractions
-set up the vacuum distillation apparatus,
but had problems and it bumped
-cleaned and set it up again
-measured pressure with manometer =
90mmHg
Fraction 1: 120oC
Fraction 2: 140-180 oC
Fraction 2: 208 oC
Fraction 4: 200oC and decreasing
temperature
-at the end of distillation , the residue was a
dark red-brown oil
-used 3:2 ratio of hexane : ethyl acetate
as eluent and UV light as visualization
method
-check purity of fractions by TLC
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Characterization of diethyl
benzylmalonate
A. Infrared
B. 1H NMR
-diluted fractions with dichloromethane
and did a film cast
-compared IR spectrum of Fraction 2 and 3
with SDBS spectra of diethyl
benzymalonate and diethyl
dibenzylmalonate (decided Fraction 2
contained diethyl benzylmalonate)
-dissolved 3 drops with ~0.5mL of CDCl3
3-R-DD-CL-1-A
-obtained from TA
C. 13C NMR
C. Physical properties
-clear colourless oil
-had an odor
-bp = 220-250oC corrected
-yield: 27.096g – 24.737g = 2.259g
Saponification
-8.6g of KOH in 8.5mL water
-add to round bottom flask
-stopper flask
-stand over one week
-8.646g of KOH in 8.5mL water (dissolved
in the water before adding to the flask)
-sealed with parafilm and placed in drawer
for one week
Product – Properties and Yield
Balanced Equations and Theoretical Yield Calculations
2 Na(s)
+
2CH3CH2OH

2NaOCH2CH3
mass (m) =2.38g
moles (n)=0.1035 mol
V =50mL
n =0.856 mol
m =7.04g
n = 0.1035 mol
m =16.7g (15.8mL)
n =0.1043 mol
m =7.04g
n =0.1035 mol
m =16.47g
n =0.1035 mol
m =16.47g
n =0.1035 mol
m =12.7g (11.5mL)
n =0.0999 mol*
m =25.00g
n = 0.0999 mol
*benzyl chloride is the limiting reagent
Table 2. Table of Products
Product
MW
Properties Found
(g/mol)
diethyl
250.29 clear colourless oil,
benzylmalonate
has odor
bp=220-250oC (corr)
+
H2(g)
Yield
Theoretical
Actual
25.00g
2.259g
(0.0999
(0.00902
moles)
moles)
Theoretical  molesbenzylchloride * MW  0.0999moles*250.29g/mol  25.00g

%
9.036%
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%yield 

actual
2.259g
*100% 
*100%  9.036%
theoretical
25.00g
The diethyl benzylmalonate product was obtained as a clear, colourless oil with an odor.
The boiling point during distillation was 220-250oC, corrected to 760mmHg. This is
lower than the literature boiling point (~300oC), but that may be due to the inaccuracy of
the manometer that was used (there was water in it).
Characterization
Infrared analysis of product A, diethyl benzylmalonate, showed that the benzylation of
diethyl malonate was successful: there are absorbances for aryl C-H and C=C stretches as
well as the alkyl C-H, C=O, and C-O stretch of the ester groups. The spectrum also
matches the one in the SDBS database. The characteristic bands in the IR are listed and
explained in Table 3.
Table 3. IR Data for Diethyl Benzylmalonate
Frequency (cm-1) Intensity Shape Assignment
Structure
>3000
weak
sharp
aryl C-H stretch
2983.9
medium sharp
alkyl C-H stretch
1733.4
strong
sharp
C=O stretch
1496.3, 1455.4
weak,
sharp
aryl C=C stretch
medium
~1200
medium sharp
C-O stretch
1
H NMR analysis showed that the product contains an aromatic ring and a symmetric diester. There is some second-order splitting in signal B (J=2.35/2.42Hz) but the J=7.11Hz
indicates it is coupled to signal E. The splitting pattern of a quartet (B) and triplet (E) are
characteristic of an ethyl group. The coupling constants of C and D indicate they are
coupled to each other; and the integration and chemical shift indicate D are the hydrogens
on the C-aryl. The product is not completely pure because there appears to be some
contaminating unreacted diethyl malonate. Table 4 lists the 1H NMR data.
Table 4. 1H NMR Data for Diethyl Benzylmalonate
Label (ppm)
Area Splitting
J (Hz)
Structure and Signal
Assignment
A
7.27
5
multiplet
B
4.18
4
doublet of
7.11 and
quartets
2.35/2.42
C
3.67
1
triplet
7.92/7.84
D
3.24
2
doublet
7.92
E
1.23
6
triplet
7.11
13
C NMR analysis showed the presence of symmetry in the molecule (14 carbons, but
only 9 peaks), a monosubstituted aromatic ring (4 carbons 126-136ppm), a di-ester (peak
7 is more downfield than in a normal ester), and an alkyl group. Table 5 lists the 13C
NMR data.
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Table 5. 13C NMR Data for Diethyl Benzylmalonate
Label
Structure and Signal Assignment
(ppm) Type of Carbon
1
170
C=O
2
139
3
129
aromatic C=C
4
128
5
126
6
61
C-O
7
52
ester-C-ester
8
35
C-aryl
9
17
C-CH3
Discussion and Conclusion
The 1H NMR and IR data showed that the diethyl benzylmalonate was successfully
produced because they showed an aromatic group with ester groups. By the 1H NMR,
the product is pure, except for some contaminating unreacted diethyl malonate, and did
not contain the side product, diethyl dibenzylmalonate, because the hydrogen on the
carbon between carbonyls is present. The reactions ran smoothly with the exception of
the distillation under reduced pressure, because the solution bumped and everything had
to be cleaned before beginning the distillation again. The % yield was only about 9%,
likely because some of the starting material did not react and I did not pool my fractions
from distillation.
Part 2: Preparation of 2-bromo-3-phenylpropanoic acid
Objective
1. Check progress of saponification.with TLC and complete by reflux, if necessary.
2. Carry out the work-up of saponification.
3. Extract and react product with bromine.
4. Decarboxylate benzylbromomalonic acid.
5. Begin aminolysis of 2-bromo-3-phenylpropanoic acid by reacting with
ammonium hydroxide.
Mechanism
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Procedure and Observations
Procedure
Observations
February 9, 2006
After a Week:
-Check progress with TLC, if incomplete
reflux until all starting material is reacted
-white solid clump
-added water to dissolve (not all
completely dissolved)
-used 3:2 hexane: ethyl acetate as eluent
-visualized with UV light
-cool contents and pour into beaker
containing 10g of ice
-slowly,with stirring, add concentrated HCl
until mixture is strongly acidic
-poured solution into beaker containing
~10g of ice
-added ~17mL of conc. HCl (12M) pH~1
-heat given off, ice melted
-extract with ether (3 x 15mL)
-transferred to a separatory funnel
-extracted aqueous layer with 3 x 15mL of
diethyl ether (top layer is ether, bottom
layer is aqueous)
-transferred to Erlenmeyer flask, added
CaCl2
-solution became cloudy
-transferred to separatory funnel and
washed with 20mL of brine
-transferred ether layer to Erlenmeyer flask
and dry over CaCl2 (added CaCl2until they
no longer clumped together)
-combine extracts and dry over CaCl2
-transfer to 3-neck round bottom flask
Bromination
-setup apparatus with 3-neck flask,
condenser, and addition funnel
-gravity filtered solution into 3-neck round
bottom flask
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-add 2.3mL dropwise of elemental
bromine, maintain a gentle reflux with
stirring
-add 10mL water dropwise, maintain a
gentle reflux
-added ~2.3mL (0.0446 moles) bromine
dropwise (more like leaking out of funnel)
-solution became slightly warm and dark
reddish brown
-added 10mL water dropwise
-cool
-cooled on ice
-separate solution
-transferred to separatory funnel
-20mL ether to rinse 3-neck flask (dark red
solution)
-washed with 15mL + 15mL +10mL
sodium bisulfite (ether layer changed from
dark red to orange to bright cloudy yellow
to clear colourless solution; aqueous layer,
bottom, was clear and slightly yellow)
-washed ether layer with 20mL brine
-transferred solution to Erlenmeyer and
added sodium sulfate (until it didn’t clump)
wash with sodium bisulfite
wash with saturated sodium chloride
stand in sodium sulfate
-remove ether by rotovap
-in the fume hood, decarboxylate the
benzylbromomalonic acid by heating in a
sand bath at 130-135oC until gas evolution
ceases (1-2 hours)
do NOT overheat
-check purity by TLC
-transferred to round bottom flask
-removed ether by rotovap
-placed flask in sand bath (~135oC)
-Leah supervised the decarboxylation and
placed flask in drawer after gas evolution
ceased, left for one week
February 16, 2006
-used 1:1 ethyl acetate: methanol eluent
-visualized with UV light
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Characterization of 2-bromo-3phenylpropanoic acid
IR
-diluted in CDCl3 and film cast onto salt
plates (required many drops to concentrate)
1H NMR
-about 3 drops in 0.5mL CDCl3
3-R-LM-CL-1-B
physical properties
-clear pale yellow oil
-mass obtained:
97.628g-96.087g=1.541g
Aminolysis
-add 80mL ammonium hydroxide to flask
and stopper, shake well, allow the reaction
to stand for one week
-added 80mL ammonium hydroxide
-gas was released
-shook, stoppered and placed flask in
drawer for two weeks
Product – Properties and Yield
m =2.259g
n =0.00902 mol*
excess
n =0.00902 mol
excess
n =0.00902 mol
n =0.00902 mol
n =0.00902 mol
m =2.067g
n =0.00902 mol
*starting material was limiting
Table 6. Table of Products
Product
MW
(g/mol)
2-bromo-3229.07
phenylpropanoic acid



Properties
Found
clear, pale
yellow oil
Theoretical
2.067g
(0.00902 moles)
Yield
Actual
1.541g
(0.00672
moles)
overall:
1.541
%
74.55
overall:
overall:
22.88g
6.735
(0.0999 moles)
2.259g
Theoretical  molesdiethylbenzylmalonate * MW 
* 229.07g /mol  2.067g
250.29g /mol
actual
1.541g
%yield 
*100% 
*100%  74.55%
theoretical
2.067g
Theoretical  molesbenzylchloride * MW  0.0999moles*229.07g/mol  22.88g
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After decarboxylation, the product obtained was a clear pale yellow oil. The yield was
74.55%. However, after analyzing the 1H NMR spectrum (see Characterization), there
appears to be a lot of contamination in the collected product.
Characterization
Infrared analysis showed a carboxylic acid group (broad O-H stretch with C=O stretch),
and an aromatic group (C-H and C=C stretch) . Table 7 lists and explains the
characteristic bands.
Table 7. IR Data for 2-bromo-3-phenylpropanoic acid
Frequency (cm-1)
Intensity Shape
Assignment
Structure
2800-3300
medium
broad
carboxylic O-H
stretch
3032.9
medium
sharp
aryl C-H stretch
1718.1
strong
sharp
C=O stretch
1496.0, 1410.9
weak
sharp
aryl C=C stretch
1
H NMR analysis also confirms a carboxylic acid group (broad peak at 8.0ppm), an
aromatic group, and also shows the decarboxylation reaction was successful because
there is a hydrogen on the C-Br (integration of 1 and doublet of doublets). This hydrogen
splits as a dd because the molecule is chiral so the neighbouring hydrogens experience
different chemical environments and have different coupling constants. The J value of
14.93/14.20 on D indicate germinal coupling and J value of 7.15/7.88 means it couples to
C. Table 8 lists the key 1H NMR data.
Table 8. 1H NMR Data for 2-bromo-3-phenylpropanoic acid
Label
Area
Splitting
J (Hz)
Structure and Signal
(ppm)
Assignment
A
8.0 (broad)
1
singlet
B
7.27
5
multiplet
C
4.45
1
doublet of
7.15 and
doublets
8.19
D
3.275
2
doublet of
7.15/7.88
doublets
and
14.93/14.20
13
C NMR analysis shows the compound has a carboxylic acid group (carbonyl at
175ppm), a monosubstituted aromatic group (4 peaks from 127-136ppm), a carbon next
to a bromide and a carbon next to an aromatic ring. Table 9 lists the key 13C NMR data.
Table 9. 13C NMR Data for 2-bromo-3-phenylpropanoic acid
Label
Type of Carbon
Structure and Signal Assignment
(ppm)
1
175
C=O
2
136
3
129
aromatic C=C
4
128
5
127
6
45
C-Br
7
41
C-aryl
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Discussion and Conclusion
The saponification and decarboxylation reactions were successful by evidence of a
carboxylic acid group in the IR and 1H NMR spectra. There were no problems while
carrying out the procedure. However, the recovered product was not very pure. The
extra peaks in the 1H NMR indicated a lot of contamination, from solvents and possibly
decomposed products. The %yield was 74.55%, but not necessarily accurate because of
the contamination.
Part 3: Preparation of ()-phenylalanine
Objective
1. Complete the aminolysis reaction
2. Recover phenylalanine by crystallization
3. Purify phenylalanine by recrystallization
4. Characterize phenylalanine product by IR, 1H NMR, 13C NMR spectra, and
physical properties
Mechanism
Procedure and Observations
Procedure
Aminolysis (continued…)
-transfer the reaction mixture (2-bromo-3phenylpropanoic acid and ammonium
hydroxide) to oversized beaker
-add spatulaful of charcoal
-heat for 20 minutes
-monitor reaction by TLC (6:3:1
CHCl3:HOMe:HOAc)
Observations
March 2, 2006
-transfer reaction mixture (slightly cloudy
and yellow) to 600mL beaker add scoopful
of charcoal and heated on hot plate for
about 30 minutes
-TLC: used 6:3:1 CHCl3:HOMe:HOAc as
eluent (prepared for us) and ninhydrin
staining solution with heat for visualization
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-hot gravity filter
-reduce volume to <10mL by heating on
hot plate
-allow crystals to form on cooling
(no crystals? Then concentrate further or
add acetone)
-collect crystals and wash with cold
methanol
Purification
-Recrystallize phenylalanine (two solvent
method with water and acetone)
Characterization
-physical properties
-hot gravity filtered in fumehood into an
Erlenmeyer flask
-heated on hot plate to reduce volume to
about ~10mL
-cooled to room temperature and then on
ice
-crystals didn’t form, so the solution was
reheated to reduce the volume further
-crystals formed on cooling
-vacuum filtered to recover crystals
-washed crystals with cold methanol
-crystals were a grayish colour
-did not recrystallize
-greyish coloured crystals
-mp 237-240oC (until it become a brown
liquid)
-4.472g-4.396g=0.076g
-used KBr pellet
-IR
-1H NMR
-added a little solid sample to ~0.5mL D2O
and Na solvent
-shook to dissolved
-obtained from TA
-13C NMR
Product – Properties and Yield
Balanced Equations and Theoretical Yield Calculations
m =1.541g
n =0.00673 mol*
excess
*starting material is limiting
Table 10. Table of Products
Product
MW
Properties
(g/mol) Found
()-phenylalanine 165.19 grey solid
crystals
mp=
237-240oC
m =1.111g
n =0.00673 mol
Yield
Theoretical
Actual
1.111g
0.076g
(0.00673 moles) (0.00046
moles)
overall:
overall:
16.50
0.076
(0.0999 moles)
%
6.84
overall:
0.46
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Theoretical  moles2  bromo  3  propanoicacid * MW 
%yield 

1.541g
*165.19g /mol  1.111g
229.07g /mol
actual
0.076g
*100% 
*100%  6.84%
theoretical
1.111g
Theoretical  molesbenzylchloride * MW  0.0999moles*165.19g/mol 16.50g


The ()-phenylalanine product was recovered as a grey solid crystals. The % yield for
this final step was 6.84% and the overall yield for the experiment is 0.46%. The melting
point was determined to be 237-240oC, which is lower than the literature value (283oC),
but this may be because the thermometer was not calibrated.
Characterization
Infrared analysis showed a carboxylic acid (broad O-H and C=O stretch) and an aromatic
(C-H and C=C stretches). There was too much noise in the 3300-4000cm-1 region to
determine the presence of an amine group. Table 11 lists and explains the key IR bands.
Table 11. IR Data for ()-phenylalanine
Frequency (cm-1)
Intensity Shape
Assignment
Structure
2500-3200
medium
broad
carboxylic O-H
stretch
3088.3
medium
sharp
aryl C-H stretch
~1600
strong
sharp
C=O stretch
1588.7, 1504.5,
strong
sharp
aryl C=C
1415.3
stretch
1
H NMR analysis indicates we were successful in creating phenylalanine by comparing
with a standard. There are solvent peaks for water and methanol, otherwise the spectrum
is very clean indicating the compound is fairly pure. The carboxylic hydrogen and amine
hydrogens cannot be seen because the compound was measured in a basic solution. B is
the hydrogen on the C-NH2 because it has the largest chemical shift of B, C, and D. B
couples to C (J=5.68Hz) and D (J=7.27Hz) C and D are on the same carbon, but because
the molecule is chiral, they have different but very similar chemical shifts (the J values of
13.68/13.62Hz confirm this by showing germinal coupling). Table 12 lists the key 1H
NMR data.
Table 12. 1H NMR Data for ()-phenylalanine
Label
Area
Splitting
J (Hz)
Structure and Signal
(ppm)
Assignment
A
7.32
5
multiplet
B
3.48
1
doublet or
7.27 and
doublets
5.68
C
2.97
1
doublet or
5.56/5.68
doublets
and 13.68
D
2.83
1
doublet or
7.33/7.2
doublets
and 13.62
Cindy Lee
1041791
The 13C NMR shows that this compound contains a carboxylic acid (C=O at 175ppm), a
monosubstituted aromatic group (4 peaks from 127-138ppm), and an amine group
(carbon next to amine is more down shifted than one next to an aromatic ring). Table 13
lists the key 13C NMR data.
Table 13. 13C NMR Data for ()-phenylalanine
Label
Type of Carbon
Structure and Signal Assignment
(ppm)
1
175
C=O
2
138
3
130
aromatic C=C
4
129
5
127
6
57
C-NH2
7
37
C-aryl
Discussion and Conclusion
In this step, ()-phenylalanine was successfully synthesized from 2-bromo-3-propanoic
acid. The recovered product was fairly pure, as shown with the IR and 1H NMR spectra.
I had some problems with crystallizing the phenylalanine, but after concentrating the
solution further, I obtained crystals. I did not have time to do a recrystallization step, but
this was not necessary because the product was already fairly pure.
The % yield for this step was 6.84 %. The product was recovered as gray solid crystals.
The melting point was 237-240oC, which is lower than the literature melting point
(283oC), but because of the sharp melting point the product is determined to be pure. The
discrepancy in the melting point may be due to the fact the thermometer was not
calibrated.
CONCLUSION
This experiment was successful in synthesizing ()-phenylalanine. The final yield was
rather low, only 0.46%. The first and last steps had very low yields, 9.036% and 6.84%
respectively. The second step had a higher yield of 74.55%, but this product was not
pure and contained solvents and decomposed products. The yield may have been higher
had I not experienced a bump during my distillation under reduced pressure. I lost some
product because I had to clean the apparatus. I also did not pool my fractions from the
distillation, which means I may not have collected all the product to carry to the
following steps.
The final product was analyzed by infrared and 1H NMR spectroscopy and it was
confirmed to be phenylalanine. Despite skipping the final purification step,
recrystallization, the 1H NMR indicated the product was fairly pure, with some traces of
solvents. Overall, this lab was successful.