Synthesis of a Coumarin Laser Dye

Introduction
Laser dyes have many applications in todays world. They are versatile and
contribute to various fields including physics, biology, and chemistry. Laser dyes
can have complex structures which have unique emission and absorption spectra.
They are categorized according to their structural and chemical similarity. Some of
the common laser dyes known today are the coumarins, pyrromethenes, and
xanthenes. Specifically, coumarin laser dyes have been of much interest to
scientists because of their different uses and properties.1
Coumarins are among the most important constituents naturally found in
plants and essential oils including lavender, sweet clover, and oil of cassia. 2 They
act as bacteriostats, growth regulators 3, antioxidants, and enzyme inhibitors in
plants.4 In addition, they are biologically useful because they have anti-thrombotic,
anti-bacterial, and anti-mutagenic effects. In the past few years, it became
apparent that coumarins can be used in the treatment of renal cell carcinoma and
malignant malinoma.5 Additionally, they can be used in cosmetics and as food
additives. They still generate much interest because of their photodynamic effects
and toxicity.6 Moreover, coumarins are widely used in many industries including
perfume and pharmaceutical industries.7
Condensation reactions are dehydration reactions which are commonly used
in organic chemistry where two small molecules combine to construct a larger

molecule. They are utilized in many biological reactions and transformations like in
polypeptide synthesis. They are also used in the polymer industry.8
Coumarins, in general, can be synthesized utilizing various methods and
mechanisms including the Knoevenagel, Perkin, and Wittig reactions. 6 In this
experiment, a Knoevenagel condensation reaction was used to synthesize
coumarin laser dye which yields an , - unsaturated product from the reaction of
an aldehyde with an active methylene group.9

3
Figure 1. Synthesis of coumarin laser dye 3 from 4-(diethylamino)salicylaldehyde
1 and ethyl acetoacetate 2
The mechanism for the formation of coumarin laser dye starts with the
protonation of the basic piperidine with the acidic alpha hydrogens of ethyl
acetoacetate. The enolate ion nucleophilically attacks the aldehyde of 4(diethylamino)salicylaldehyde. The resulting negatively charged oxygen becomes
protonated. The ethoxide ion becomes protonated by attacking the proton of the
phenol. The nucleophilic oxygen of the phenol group attacks the carbonyl of the
ester group resulting in the dispelling of the ethoxide ion. The nucleophilic attack
2

of the ethoxide ion with the alpha hydrogen pushes out the alcohol in an E2
mechanism forming an , - unsaturated product.

Scheme

1.

Mechanism

of

Knoevanagel

condensation

of

4-

(diethylamino)salicylaldehyde and ethyl acetoacetate to coumarin laser dye

The purpose of this experiment was to use a Knoevenagel condensation
reaction to synthesize coumarin laser dye and purify it through recrystallization.
The final product was then characterized by 1H NMR,

13

C NMR, UV/Vis, and melting

point.

Experimental
Coumarin Laser Dye. 4-(diethylamino)salicylaldehyde (400.1 mg, 2.07 mmol),
ethyl acetoacetate (0.530 mL, 4.19 mmol), and piperidine (3 drops) were combined
and stirred for 30 minutes. Upon completion, absolute ethanol (5 mL) was added to
the reaction mixture. The mixture was refluxed for 20 minutes and the product was
3

filtered. Recrystallization ( 95% ethanol (15 mL)) afforded a yellow solid (279 mg,
52%) mp 152-155C; 1H NMR ( 400 MHz, CDCl3): (ppm)1.23-1.26 (t, 6H), 2.69 (s,
3H), 3.44-3.49 (quartet, 4H), 6.47 (s, 1H), 6.61-6.64 (d, 1H), 7.39-7.41 (d, 1H), 8.44
(s,1H); 13C NMR (400 MHz, CDCl 3): (ppm) 195.79, 160.91, 158.77, 153.00, 147.90,
131.92, 116.10, 109.84, 108.16, 96.56, 45.16, 30.66, 12.45; UV/Vis max 445.8 nm.

Results and Discussion

In this experiment, the coumarin laser dye was synthesized via a
Knoevenagel

condensation

reaction

between

ethyl

acetoacetate

and

4-

(diethylamino)salicylaldehyde. The product was purified by recrystallization and

characterized by

H NMR,

13

C NMR, UV/Vis, and melting point. To synthesize

coumarin laser dye, piperidine was specifically chosen to deprotonate ethyl

acetoacetate because it is a strong basic catalyst and can react with the strongly
acidic alpha hydrogens of ethyl acetoacetate. Ethanol was chosen to be a suitable
solvent in which the reaction could take place because coumarin laser dye is
soluble in it. The reaction turned from dark brown to a yellow/brownish paste after
the addition of piperidine. The reaction was refluxed after the addition of ethanol in
order to produce energy required for the completion of coumarin laser dye
synthesis.
Recrystallization is the main technique used to purify solids contaminated
with small amounts of impurities and thus was chosen as the method of
purification of the solid product. 95% ethanol was chosen to be the appropriate
solvent for recrystallization because it gives the best solubility results for the laser
dye. 95% ethanol completely dissolves coumarin laser dye at high temperatures
and partially dissolves it at room temperature. Coumarin laser dye was ultimately
4

obtained as a yellow solid in a 52% yield. Compared to the literature value of 4560%, the reported percent yield is within the literature value range and is relatively
efficient.3 The obtained melting point of coumarin laser dye was 152-155C which
is close to the literature value of 151-153C. 3 This shows that benzil was obtained
as a pure product after recrystallization.
The

H NMR analysis (Figure 2, Supplemental Information) indicates the

successful synthesis and purification of coumarin laser dye. There are seven
unique signals. The most downfield signal shows a singlet at 8.44 ppm indicative of
the alkene hydrogen. There are three different signals in the aromatic region, each
integrating to one, that represent the three aromatic hydrogens of the product and
are located between 7.41 and 6.47 ppm. There is another signal at 3.44 ppm that
splits to a quartet and represents the four hydrogens that belong to the two
methylene groups. Adjacent to the previously mentioned four hydrogens are the
six hydrogens which result in the most upfield signal at 1.23 ppm, splitting into a
triplet. The final signal at 2.68 ppm is a singlet that integrates to three and
represents the protons of the methyl group which belongs to the acetyl group. Two
key

signals

that

prove

the

absence

of

the

starting

material,

4-

(diethylamino)salicylaldehyde, and the presence of the product are the phenol

proton signal at 7-12 ppm and the aldehyde proton signal at 9-10 ppm which are
missing from the product 1H NMR. Similarly, two key signals of ethyl acetoacetate
representing the acidic alpha hydrogens at 2.1-2.4 ppm and the methylene
hydrogens at 3.5-4.8 ppm are missing from the coumarin laser dye 1H NMR.

The

13

C NMR analysis (Figure 3, Supplemental Information) supports the

formation of coumarin laser dye. The most downfield signal at 195.79 ppm
corresponds to the carbon of the ester group. The signal at 160.91 ppm represents
the carbon of the ketone group. The eight unique carbons of the aromatic ring and
the alkene are represented by signals between 158.77 and 96.56 ppm. There exist
three signals representing the three sp 3 carbons of the product. The signal at 45.16
ppm corresponds to two methylene carbons bonded to the nitrogen. The signal at
30.66 ppm corresponds to the the carbon of the methyl group belonging to the
acetyl group. The most upfield signal at 12.45 ppm depicts the two carbons of the
methyl groups bonded to the methylene groups. It can be proven that the starting
materials

do

not

co-exist

with

the

final

product.

For

example,

4-

(diethylamino)salicylaldehyde has only nine unique carbons including the aldehyde

and the phenol carbons which are missing from the product

13

C NMR. Also, ethyl

acetoacetate contains two different methylene groups resulting in producing two

different signals that would be shifted more downfield where in contrast; the
product has two similar methylene groups. The lack of any other signals demonstrates the
overall purity of the product.
UV/Vis analysis (Figure 3, Supplemental Information) of the product was performed to further
aid in characterizing coumarin laser dye. Coumarin laser dye is a fluorescent dye which absorbs light at
a certain wavelength. The maximum absorbance of coumarin laser dye occurs at 445.8 nm which lies
within the blue-violet region of the visible spectrum. The light reflected, yellow, is coumarin laser dyes
color in solution.

In

conclusion,

coumarin

laser

dye

was

successfully

synthesized

from

4-

(diethylamino)salicylaldehyde and ethyl acetoacetate in an overall yield of 52%. Its melting point, 1H
NMR, 13C NMR, and UV/Vis indicate that the product lacked impurities. The synthesis of coumarin
laser dye derivatives are now of great importance to chemists and biologists as they are extensively used
in various industries including pharmaceutical, cosmetic, and food industries. Future experiments could
aim to synthesize other coumarin laser dye derivatives utilizing a different type of reaction. Among the
simplest and most commonly used methods is the Pechman condensation reaction which involves the
reaction of a phenol with a -keto ester. An advantage of using this method is that it usually yields high
percent yields without the formation of by-products.4

References
(1)Shankarling,G.S.; Jarag,K.; Resonance, 2010, 15, 804-818.
(2)Thati, B.; Noble, A.; Rowan, R.; Creaven, B.; Walsh, M.; McCann, M.; Egan, D.;
Kavanagh, K., Toxicology in Vitro, 2007, 21, 801-808.
(3)Dicks, A.; Aktoudianakis, E., J. Chem Ed., 2006, 83, 287-289.
(4)Basar, N.; Wong, K., Jurnal Teknologi, 2012, 57, 83-98.
(5)Thati, B.; Walsh, M.; Noble, A.; Creaven, B; Egan, D.; Kavanagh, K., ChemicoBiological Interactions, 2007, 168, 143-158.
(6)Valizadeh, H.; Shockravi, A., Tetrahedron Letters, 2005, 46, 3501-3503.
(7)Song, A.; Wand, X.; Lam, K., Tetrahedron Letters, 2003, 44, 1755-1758.
(8)McCaffery, E., J. Chem Ed., 1969, 46, 59.
(9)McMurry, J.; Organic Chemistry, 8th ed.; Cengage Learning: New York, 2011;
pp 941.
Supplemental Information:
Figure 1. 400 MHz 1H NMR of coumarin laser dye

Figure 2. 400 MHz

13

C NMR of coumarin laser dye

Figure 3. UV/Vis of coumarin laser dye

Figure 4. 60 MHz 1H NMR of coumarin laser dye