Nathan Lisbin

Synthetic FFR #2
Synthesis of a Coumarin Laser Dye
Introduction
Knoevenagel Condensations are a well understood set of reactions in organic chemistry
that describe the synthesis of small molecules to higher order intermediates such as antihypertensive drugs and calcium antagonists.5 In this experiment we look at the synthesis of
Coumarin laser dye analog 110 (3-acetyl-7-(diethyl amino)-2H-1-benzopyran- 2-one) through
the use of Knoevenagel Condensation reaction. Coumarins are a naturally occurring compound
that hold many fluorescent properties which have a high sensitivity to their local environment.2
Due to the sensitivity of Coumarins, they have been used as fluorescent probes in many systems
including homogeneous and heterogeneous mixtures and solutions.2 However, Coumarins and
many analogs are also involved in many substances used in everyday life.1 Some examples of
this everyday use is that a small amount of Coumarin analogs are used in perfumery, cosmetics,
therapeutic ointments, flavoring, and as an odor-masking agent.4 Coumarins can also be used for
other purposes such as being involved in alternative energy. The property of Coumarin laser
dyes that involves them in alternative energy is that they tend to have a high photoelectric
conversion allowing for efficient energy transfer in certain systems. One such system being
tested was Dye-sensitized Solar Cells. Coumarins were integrated into these solar cells with as a
solid candidate for an efficient light harvesting compound.3 Due to the importance of
Condensation reactions and Coumarins, this experiment explored the properties and synthesis of
Coumarin laser dye 110 analogue. The synthesis of Coumarin laser dye 110 analogue from this
experiment can be seen below in Figure 1.

Figure 1. Synthesis of Coumarin Laser Dye 110 analogue

The reaction mechanism for the Knoevenagel Condensation of 4-diethyl amino salicylaldehyde
and Ethyl acetoacetate with piperidine to Coumarin Laser Dye 110 analogue can be seen below
in Scheme 1. This reaction is initiated by the addition of piperidine. In the first step, piperidine
deprotonated ethyl acetoacetate to form an enolate intermediate. The carbonyl group then is
remade allowing the carbon to attack the nucleophilic carboxylic acid group on 4-diethyl amino
salicylaldehyde. This creates a higher order intermediate where the oxygen from the alcohol
group can deprotonate the piperidine to reform the neutral piperidine. Piperidine then
deprotonates the hydrogen on the carbon between the two carbonyl groups to form a carbon
double bond and kicks off a water leaving group (condensation). From here a self-attack occurs
where the oxygen on the alcohol group attacks the carbonyl carbon which is also part of an ester
complex to create the second ring in our product. The oxygen anion reforms its double bond and
kicks off an ethoxide leaving group. The ethoxide group can then deprotonate the oxygen
involved in the ring structure to form neutral ethanol yielding our product of Coumarin laser dye
110 analogue and ethanol.
The overall purpose of this experiment was to synthesize our product by the knoevenagel
condensation reaction. The Coumarin laser dye was then purified through reflux and
recrystallization. This product was characterized by 400 MHz 1H NMR, 100 MHz 13C NMR,
UV/Vis, and Emission Spectroscopy.

Scheme 1. Knoevenagel Condensation of 4-diethylamino salicylaldehyde and Ethyl acetoacetate

Experimental
Coumarin Laser Dye 110. 4-diethylamino salicylaldehyde (0.406g, 2.1 mmol), ethyl
acetoacetate (0.53mL, 4.2mmol), and 3 drops of piperidine were combined and stirred for 30
minutes at room temperature. Upon completion, absolute ethanol (5.0mL) was added to the
mixture. The mixture was then refluxed for 20 minutes and then cooled. The solid crystals were
isolated by vacuum filtration and then recrystallized in 95% ethanol (20 mL). The product was
then dried to yield a bright yellow crystalline solid. 1H NMR (400 MHz, CDCl3): (ppm) 8.43
(s, 1H), 7.39 (d, 1H), 6.63 (d, 1H), 6.46 (s, 1H), 3.46 (q, 4H), 2.68 (s, 3H), 1.25 (t, 6H); 13C NMR
(100 MHz, CDCl3) (ppm) 195.81, 160.98, 158.83, 147.97, 132.01, 116.10, 109.96, 108.22,
96.61, 45.25, 30.72, 12.53; UV/Vis: (nm) 434; Emission Spectroscopy: (nm) 476.
Results and Discussion
The synthesis of Coumarin Laser Dye 110 analogue was produced through an
knoevenagel condensation of 4-diethylamino salicylaldehyde, ethyl acetate, and piperidine. The
addition of piperidine allowed for condensation of the 4-diethylamino salicylaldehyde and ethyl
acetate to initiate. After the product was form, it was recrystallized and characterized through
400 MHz 1H NMR, 100 MHz 13C NMR, UV/Vis, and Emission Spectroscopy.
In the first step of the experiment, a knoevenagel condensation was performed to yield
the solid product. This was achieved through the addition of piperidine to the 4-diethylamino
salicylaldehyde, ethyl acetate mixture. Piperidine deprotonates and reforms throughout this
reaction as a proton transfer molecule, inducing nucleophilic attacks to eventually kick off a
water molecule and an ethanol molecule to form the Coumarin product. This reaction was

monitored through color changes. Upon the addition of piperidine, the mixture immediately
turned a light yellow. This reaction product eventually turned a pasty dark yellow indicating a
successful condensation reaction. The addition of ethanol was added to dissolve the solid in a
reflux reaction to further purify the sample. The reason for the use for ethanol as the choice of
solvent will be described below in the recrystallization discussion.
The isolation of the sample after reflux via vacuum filtration yielded bright yellow
crystals which were purified using recrystallization in 95% ethanol. Ethanol contains a very
polar hydroxyl group and a nonpolar hydrocarbon tail but overall, due its small size, is relatively
polar. Coumarin Laser Dye 110 is also polar containing many carbonyl groups as well as an
oxygen and nitrogen which shift the electronegativity in the molecule. However, a hydroxyl
group is much more polar due its ability to hydrogen bond making ethanol slightly more polar
then the Coumarin laser Dye 110. This small difference in polarity makes ethanol a very ideal
solvent in recrystallization as it only slightly dissolves the product at room temperature but
completely dissolves it at high temperatures. The recrystallization yielded 0.461g of purified
product which overall had a percent recovery of 80.6%. From literature the percent recovery for
this experiment is typically between 45-60% yielding about 2.4-3.2g.1 The percent recovery in
this experiment was much higher than the average experiment which may have been caused by a
purer crude sample that had its reaction gone further to completion.
This high recrystallization recovery also led to a higher than expected percent yield of
84.6% where the typical percent yield for this experiment is 45-60%. Similar to percent
recovery, the higher percent yield is a probably a result of the reaction going further to
completion than usual, yielding more product. To further investigate our Coumarin laser dye 110
product, a melting point test was performed. From literature the melting point of Coumarin laser

dye 110 is 151-153 C. The melting point of our product was determined to 151.4 C which falls
in range of the theoretical melting point indicating that a pure sample of our product had been
synthesized. It is important to note that the melting point of the starting materials of 4diethylamino salicylaldehyde and Ethyl acetoacetate are 60-62 C and -43 C separately.
Contamination of the starting products would have caused depression in melting point which is
not evident in this product indicating a pure sample of our product.
To further prove that Coumarin laser dye 110 was synthesized, 400 MHz 1H NMR, 100
MHz 13C NMR, UV/Vis analysis, and Emission Spectroscopy was performed on the sample.
First 400 MHz 1H NMR was ran to characterize the product. The 1H NMR spectrum can be view
in the Spectral Data (Figure 2, Supplemental Data). The first noticeable feature about this
spectrum are the two singlets and two doublets that occur between 8.43 ppm and 6.46 ppm each
having an integration value of 1H. These peaks represent the 4 aromatic hydrogens present in
Coumarin laser dye 110. The singlet peak at 8.43 ppm is much higher than the other aromatics.
This peak is indicative of the hydrogen that is clumped between the oxygen and nitrogen species
in the molecule which increase the overall electronegativity felt by the hydrogen. A quartet at
3.47 ppm with an integration of 4H represents the hydrogens that are near the nitrogen and split
by the methyl group. The singlet at 2.68 ppm with an integration value of 3H represents a
methyl group that is near the carbonyl group. Finally, the triplet at 1.25 ppm with an integration
value of 6H represents the two methyl groups that are attached to the hydrocarbon chain
connected to nitrogen. In 4-diethylamino salicylaldehyde there are only 3 aromatic hydrogens as
well as a hydroxyl group hydrogen which is different from the product made as seen in the 1H
NMR. Also there is no methyl group attached to the carbonyl in 4-diethylamino salicylaldehyde
like there is in the Coumarin laser dye 110 which also shown on the 1H NMR spectrum

indicating insignificant amounts of starting reactants in our product. Also there were no other
significant peaks in the 1H NMR spectrum which indicates very minimal if any contaminations.
For further clarification on the Coumarin laser dye 110, a 100 MHz 13C NMR was done
on the sample. The 100 MHz 13C NMR can be viewed in the spectral data (Figure 3,
Supplemental Data). The NMR spectrum showed 13 different peaks indicating 13 chemically
distinct carbons which is in line with our product. The first important distinct peak that was
observed from this spectrum was at 161 ppm which represents the carbonyl carbon in the ring
structure of the product. This is a distinct feature of our product that does not occur in the
starting product of 4-diethylamino salicylaldehyde. Another important peak occurs at 30.7 ppm
which is indicative of the methyl group attached to the carbonyl group. This is another
difference between our starting material and product as only the Coumarin laser dye 110 has this
group. The peak at 45.25 ppm also refers to the ester carbon which only occurs in our product.
The peaks between 158.8 108.2 ppm refer to seven carbons in the aromatic ring structures.
From the 13C NMRs distinct peaks, it is indicative that our product was synthesized.
Another test done of the Coumarin laser dye 110 was UV/Vis analysis which is a type of
spectroscopy that determines the wavelength of maximum absorption for our molecule. As
described earlier, the Coumarin laser dye 110 crystals were a bright yellow. When we shine
white light through the sample, the complementary color to the wavelengths are absorbed.
Therefore, the accepted max absorption is usually between 400-430 nm which refers to the blueviolet color region. The max absorption of the synthesized product was 434 nm which is
indicative of an absorbance at the blue color region. The close absorption is another indicator
that our product was synthesized.

Finally, the emission spectroscopy of the Coumarin laser dye 110 was taken. When you
shine white light on the product, the electrons in the Coumarin laser dye 110 get excited which as
discussed above occurs at an absorbance of 434 nm. The electrons will then relax through
different forms of emission such as fluorescence and internal conversion. In this case the
Coumarin laser dye relaxes in the form of fluorescence and generally emission occurs at a
wavelength slightly longer then the absorbance. The recorded emission wavelength for our
product was 476 nm which was also visible as the sample fluoresced bluish-green (teal) upon
exposure to white light. This is in line with the probably wavelength of emission given the
absorbance wavelength of our product.
Condensation reactions are a very integral area of organic chemistry responsible for many
polymerization and biological transformations such as peptide bond formation.2 In this lab, the
Knoevenagel condensation reaction, an analog of the aldol condensation reaction, was used to
react 4-diethylamino salicylaldehyde and ethyl acetoacetate with piperidine to create Coumarin
laser dye 110. The overall experiment was successful having a percent recovery in
recrystallization of 80.6% and a percent yield in product of 84.6%. Although these percentages
were a little higher than expected, it was likely due to the reaction going further to completion
than usual. From a thermodynamics standpoint there were probably more intermolecular
interactions that occurred in the reaction vessel which lead to more reactions and more product
being formed which is a varied feature between each reaction. Hypothetically if the results were
lower than expected, the solvent used in recrystallization may be inquired as well as increasing
the amount of times recrystallization was performed to achieve a more reliable overall percent
yield and recovery. Overall, the product, Coumarin laser dye 110, was synthesized in an

acceptable yield and showed high purity in 400 MHz 1H NMR, 100 MHz 13C NMR, UV/Vis
analysis, and Emission spectroscopy.

References
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Wagner, B. D. The Use Of Coumarins as Environmentally-Sensitive Fluorescent Probes of

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3

Wang, Z.-S.; Cui, Y.; Hara, K.; Dan-Oh, Y.; Kasada, C.; Shinpo, A. A High-Light-HarvestingEfficiency Coumarin Dye For Stable Dye-Sensitized Solar Cells. Adv. Mater. Advanced
Materials. 2007, 19, 11381141.
4

Hausen, B. M.; Schmieder, M. The Sensitizing Capacity of Coumarins (I). Contact Dermatitis.
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5

Parida, K.; Rath, D. Amine Functionalized MCM-41: An Active and Reusable Catalyst for
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