Two Step Synthesis of

Cinnamate Ester Sunscreen

Analog

4/3/2008
Chem 213
Joshua Bailey
Introduction

Esters derived from trans-4-methoxycinnamic acid are effective absorbers of UV

radiation. These types of compounds are highly conjugated, absorb UVB radiation between 290

– 320 nm, and are oil soluble. UVB radiation can cause dermal cell DNA damage, which causes

skin cancer. There are to objectives to this experiment. The first is to synthesize trans-4-

methoxycinnamic acid. Synthesis of ethyl trans-4-methoxycinnamate is the second objective of

the experiment. Trans-4-methoxycinnamic acid will be analyzed by melting point, infrared

spectroscopy, and nuclearmagnetic resonance. Ethyl trans-4-methoxycinnamate will be analyzed

by infrared spectroscopy.

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Data Analysis

Mass of trans-4-methoxycinnamic acid: 0.85 g

Mass of ethyl trans-4-methoxycinnamate: 0.20 g

MELTING POINT
mp
Compound (°C) Literarure melting point (°C)
Trans-4-methoxycinnamic acid 173 173-175

IR of Trans-4-methoxycinnamic acid
Peak (cm-
1
) Represents Lit Value Peak (cm-1)
1702 C=O (carboxylic acid) 1700-1725
2848 O-H (carboxylic aid) 2500-3200
1633 C=C 1620-1680
1260 C-O (ester) 1000-1300
1601 C=C (aromatic) 1440-1625

IR of Ethyl trans-4-methoxycinnamate
-1
Peak (cm ) Represents Lit Value Peak (cm-1)
1703 C=O (esters) 1715-1730
1603 C=C 1600-1650
1260 C-O (ester) 1000-1300
1601 C=C (aromatic) 1440-1625

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H+ NMR of Trans-4-methylcinnamic acid
Shift (ppm) Represent O
0 HA HB HC
O HA
3.876 HC and HE
HD
6.982 HB
7.003 HB HE
7.816 HD
7.837 HD H3 C O HB
(F)
9.87 HF
HD

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Percent Yield 4-methoxy benzaldehyde

? mol 4-methoxy benzaldehyde = 0.804 mL 1 cm3 1.00 g 1 mol

= 5.9 x 10-3 mol
1 mL 3 136.15 g
1 cm

? mol molanic acid = 1.75 g 1 mol

= 11.68 x 10-3 mol molanic acid
104.03 g

? mol  analine = 0.1 g 1 mol

= 1.1 x 10-3mol  analine
89.09 g

Fewest moles of mol alanine theref ore  alanine is the limiting reagant

6 mol trans-4-
? g trans-4-methoxycinnamic acid = 1.70 x 10-3 mol alanine methoxycinnamic acid 178.2 g
= 1.176 g
1 molalanine 1 mol trans-4-
methoxycinnamic acid

experimental
% Yield =
theoretical
X 100 ; 0.88 grams
1.176 grams
X 100 = 72.3%

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Percent Yield of ethyl trans-4-methoxycinnamate

? mol ethyl trans-4-methoxycinnamte = 0.6 g 1 mol

= 3.37 x 10-3 mol
178.2 g

1 cm3 0.944 g 1 mol

? mol DMF = 10 mL
= 1.29 x 10-1 mol DMF
1 mL 1 cm 3 73.09 g

? mol cesium carbonate = 1.65 g 1 mol

= 5.06 x 10-3mol cesium carbonate
325.82 g

1 cm3 1.950 g 1 mol

? mol iodoethane = 1 mL
= 1.25 x 10-2 mol iodoethane
1 mL 1 cm3 155.98 g

Fewest moles of mol of cesium carbonate theref ore cesium carbonate is the limiting reagant

2 mol ethyl trans-4-

? g ethyl trans-4-methoxycinnamate = 5.06 x 10-3 mol Cs2CO3 methoxycinnamate 206.25 g
= 0.696 g
3 mol cesium carbonate 1 mol trans-4-
methoxycinnamic acid

experimental
% Yield =
theoretical
X 100 ; 0.20 grams
0.696 grams
X 100 = 28.7%

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Discussion

Benzaldehyde and malonic acid were dissolved in pyridine and heated to give the product

trans-4-methoxycinnamic acid. The reactants underwent a Verley-Doebner modification of the

Knoevenagei condensation, the reaction is shown in (figure 1).

O
O

O O
H OH
N
+

HO OH
O O

Figure 1

The first step is the deprotonation of malonic acid by pyridine (figure 2).

O O O O

HO OH HO OH

H H
N

Figure 2

After malonic acid has been deprotonated three different resonance structures can be drawn

displacing the negative charge over the molecule (figure 3).

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 O O O O O O

HO OH HO OH HO OH

Figure 3

Attack of benzaldehyde by the deprotonated malonic acid can now occur. Benzaldehyde bonds

to the middle carbon, and a proton transfer occurs (figure 4).

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 O O O O

HO OH HO OH

O
H

Proton Transf er
O

O O

Figure 4 HO O

OH

The Verley-Doebner modification of the Knoevenagei condensation reaction occurs in refluxing

pyridine. Carbon dioxide and the hydroxide are both expelled from the molecule to give trans-4-

methoxycinnamic acid (figure 5).

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 O O O

HO OH HO
- CO2

OH - OH

O O

Figure 5

Trans-4-methoxycinnamic acid was converted to ethyl trans-4-methoxycinnamate in the

second part of the lab by the process of esterification. The net reaction is shown in figure 6.

COOH

Cs2CO3, DMF O

C2H5I

O
O

Figure 6

The first step that occurs is the iodoethane is attacked by a lone electron pair on trans-4-

methoxycinnamic acid. If two electrons come in two must leave which results in I - being

expelled from the molecule (figure 7).

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 O
O

O H
OH

O
O
H H

H C C I

Figure 7
H H

Oxygen now has a positive charge so the base, cesium carbonate, comes in and deprotonates

the compound to give ethyl trans-4-methoxycinnamate (figure 8).

O
O

O H
O
Cs2CO3

O
O

Figure 8

All of the results obtained in lab suggests that both trans-4-methoxycinnamic acid and

ethyl trans-4-methoxycinnamate were successfully synthesized in lab. The melting point of

trans-4-methoxycinnamic acid was found to be 173°C and the accepted literature value is 173°C

- 175°C. The IR obtained for trans-4-methoxycinnamic acid showed the following peaks: C=O

(carboxylic acid), O-H (carboxylic aid), C=C, C-O (ester), C=C (aromatic). All of these

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functional groups are present on trans-4-methoxycinnamic acid The H+ NMR obtained for

trans-4-methoxycinnamic acid showed the correct structure of the molecule (see data section).

The IR for ethyl trans-4-methoxycinnamate showed the following peaks: C=O (esters), C=C, C-

O (ester), and C=C (aromatic). Using all this data it was determined that the desired product

were successfully obtained.

Conclusion

The compounds trans-4-methoxycinnamic acid and ethyl trans-4-methoxycinnamate were

successfully synthesized. The melting point of of trans-4-methoxycinnamic acid was 173°C and

the literature value is 173°C - 175°C. The IR of both -4-methoxycinnamic acid and ethyl trans-

4-methoxycinnamate suggested that the desired products were obtained. The H+ NMR obtained

for trans-4-methoxycinnamic acid suggested that structure of the product was correct (see data

section).

References

Smith, Janice G. Organic Chemistry. 1st ed. New York: McGraw-Hill, 2006. 801.

Mohrig, Jerry R., Christina N. Hammond, and Paul F. Shatz. Techniques in Organic Chemistry.
2nd ed. New York: Craig Bleyer, 2006. IR table.

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