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 anti-

hypertensive 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): δ (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) δ (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: δ (nm) 434; Emission Spectroscopy: δ (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 4-

diethylamino 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 NMR’s 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 blue-

violet 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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Efficiency Coumarin Dye For Stable Dye-Sensitized Solar Cells. Adv. Mater. Advanced
Materials. 2007, 19, 1138–1141.
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