Improvements in the synthesis of a coumaromethacrylate dye

Article abstract of DOI:10.1080/00397910701410996

A new method to prepare a coumaromethacrylate dye has been devised. The older three-step route was shortened to a one-pot, solvent-free step. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701410996

This article was downloaded by: [University of Auckland Library]
On: 09 April 2015, At: 14:21
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Improvements in the Synthesis of a
Coumaromethacrylate Dye
Matthew C. Davis a
a Chemistry and Materials Division, Michelson Laboratory , Naval Air Warfare
Center , China Lake, California, USA
Published online: 11 Jul 2007.
To cite this article: Matthew C. Davis (2007) Improvements in the Synthesis of a Coumaromethacrylate Dye,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:14, 2383-2389, DOI: 10.1080/00397910701410996
To link to this article: http://dx.doi.org/10.1080/00397910701410996
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 37: 2383–2389, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410996
Improvements in the Synthesis of a
Coumaromethacrylate Dye
Matthew C. Davis
Chemistry and Materials Division, Michelson Laboratory, Naval Air
Warfare Center, China Lake, California, USA
Abstract: A new method to prepare a coumaromethacrylate dye has been devised. The
older three-step route was shortened to a one-pot, solvent-free step.
Keywords: coumarin, methacrylate, one pot, solvent-free
A new research initiative required a steady supply of the coumaromethacrylate
dye (4) that was first prepared here in the early 1990s.[1,2] The original
synthesis was devised and carried out by Dr. Ronald A. Henry (Scheme 1).
After carrying out the three-step preparation as described, there appeared to
be opportunities for improvement.
Since 4-diethylamino-2-hydroxybenzaldehyde (1) continues to be com-
mercially available, it remained the starting material. Recent research in
solvent-free reactions showed that the 3-methoxycarbonylcoumarin (2)
might be made as shown in Scheme 2.[3,4] Mixing 1, dimethyl malonate,
and piperidine gave a sticky mixture that could not be stirred efficiently.
The formation of 2 was also slow at room temperature. However, running
the reaction at 808C gave a mixture that could be magnetically stirred.
Using 0.3 molar equivalents of piperidine, the reaction was typically
complete in 1 to 2 h. No chromatography was necessary with this solvent-free
Received in the USA December 8, 2006
Address correspondence to Matthew C. Davis, Chemistry and Materials Division,
Michelson Laboratory, Naval Air Warfare Center, China Lake, CA 93555, USA.
E-mail: matthew.davis@navy.mil
2383

2384
M. C. Davis
Scheme 1. Original method to prepare the coumaromethacrylate monomer. Reagents
and conditions: a) MeOH, piperidine, rt; b) H2NCH2CH2OH, PhH, reflux; c) DCC,
DMAP, methacrylic acid, CH2Cl2.
procedure. The product was indeed a solid and was recrystallizable from
methyl tert-butyl ether, providing 2 in 70% yield.
The previously obtained low yield of ethanolamide (3) by reaction of 2
with ethanolamine in refluxing benzene was confirmed. Complete consump-
tion of the ester could not be achieved without the concomitant increase in
polar impurity. A second molecule of ethanolamine may have been conden-
sing upon 3 and opening the coumarin ring. After recrystallization from
toluene, the product appeared to be pure 3 by nuclear magnetic resonance
(NMR) spectroscopy, but its melting point of 1158C was noticeably lower
than 1268C, reported by Henry. Most likely, a small amount of ethanolamine
was contaminating the product, which is removed by the polar solvent system.
Recrystallizing crude 3 from a mixture of water and ethanol raised the melting
point sufficiently, although the product became a hemihydrate.
It was a surprise to find that reaction between 2 and ethanolamine without
solvent gave 3 in good yield without the polar impurity seen when the reaction
Scheme 2. Reagents and conditions: a) dimethyl malonate, piperidine, 808C; b) H2
NCH2CH2OH, 808C; c) methacrylic anhydride, DMAP, THF.

Figure 1. Proton NMR progress in the one-pot conversion of 1 into 3 as described in the Experimental section. For clarity, the region between 9.6
and 6 ppm is shown. The reaction was sampled at 15-min intervals by dissolving an aliquot in CDCl3. At 1 min, piperidine was added to the mixture.
At 46 min, ethanolamine was added to the reaction.

2386
M. C. Davis
was conducted in benzene. These reaction conditions were not studied further
since the prospect of transforming 1 directly into 3 as a one-pot procedure
appeared (Scheme 2). To this end, a 140-mmol- scale reaction was
monitored by proton NMR. After 1 h, the formation of 2 peaked, and ethanola-
mine was added. After another hour of heating, all 2 was consumed and
formation of 3 was complete (Figure 1). The recrystallization solvent
(water/ethanol) was added to the reaction mixture while hot and 3 precipitated
shortly thereafter. The overall yield of the one-pot procedure to make 3 was
65% and required no chromatography.
The methacrylate ester (4) was previously made using the coupling
reagent dicyclohexylcarbodiimide and methacrylic acid. This procedure
resulted in residual N,N’-dicyclohexylurea and 3, contaminating the product
and necessitating silica-gel chromatography for purification. Instead, the ester-
ification could be performed with fresh methacryloyl chloride in methylene
chloride in the presence of 4-dimethylaminopyridine base. However, there
was a close running impurity by thin-layer chromatography (TLC) with
similar proton NMR as the product. No attempts were made to isolate and
identify the by-product. Following the example set by Vensteenkiste
et al.,[5] reaction of 3 with a slight excess of methacrylic anhydride in tetra-
hydrofuran in the presence of 4-dimethylaminopyridine eliminated the
impurity. Simply pouring the reaction mixture into water gave 4 in high
yield. The product could be recrystallized from ethanol in analytically pure
form with a yield of 62%.
In conclusion, a new process for the preparation of the coumaromethacry-
late 4 has been developed. A solvent-free, one-pot reaction was found to
rapidly furnish the coumaroethanolamide 3 in good yield. Methacrylation of
the ethanolamide (3) was achieved with methacrylic anhydride. No chromato-
graphy was necessary at any stage of the synthesis. The overall yield of the
two-step process was 40%.
EXPERIMENTAL
Melting points were collected on an electrothermal capillary melting-point
apparatus and are not corrected. All NMR data were collected on a Bruker
Avance II 300-MHz spectrometer (1H at 300 MHz, 13C at 75 MHz). NMR
data (FIDs) were processed using NUTS software from Acorn NMR
(Livermore, CA), and spectra are referenced to tetramethylsilane. The
following reagents were purchased from Sigma-Aldrich (Milwaukee) and
used as received: methacrylic anhydride 94% (inhibited with 2000 ppm
topanol A), 4-diethylamino-2-hydroxybenzaldehyde 98%, 4-methoxyphenol
ReagentPlusw 99%, dimethyl malonate 98%, ethanolamine ReagentPlusw
.99%, 4-(dimethylamino)pyridine (DMAP) 99%, piperidine ReagentPlusw
99%. Elemental analyses were performed by Atlantic Microlab, Inc.
(Norcross, GA).

Coumaromethacrylate Dye Synthesis
2387
3-Methoxycarbonyl-7-(diethylamino)coumarin (2)
A 500-mL, round-bottomed flask equipped with magnetic stirbar was charged
with 25 g of 4-diethylamino-2-hydroxybenzaldehyde (1, 0.13 mol) and 18.7 g
of dimethyl malonate (0.14 mol, 1.1 equiv). The mixture was set to stir in a
708C oil bath. After a few minutes, all the solids had dissolved, and 3.3 g of
piperidine in one portion (0.04 mol, 0.3 equiv) were added. The mixture
immediately became yellow-orange in color, and MeOH was seen collecting
1
on the headspace of the flask. Analysis by H NMR showed complete con-
sumption of the aldehyde in 2.5 h. The oil bath was removed, and after
cooling to rt, the mixture was partitioned between 50 mL of H2O and
200 mL of CHCl3. While stirring, 2.2 mL of glacial HOAc (0.04 mol) were
added to neutralize the piperidine. The organic layer was separated and
washed again with 50 mL of H2O followed by 100 mL of brine. The
organic layer was dried for 30 min over 10 g of anhydrous MgSO4 and
filtered. The organic layer was treated with 2 g Darcow G-60 for 30 min
and filtered through a pad of diatomaceous earth on a coarse glass frit. The
solvent was rotary evaporated, leaving an orange-colored oil. After storage
under vacuum, the oil solidified into a yellow solid (33.9 g, 96%). The
crude was recrystallized from methyl tert-butyl ether to give 25.1 g of the
title compound 2 as a bright yellow, crystalline powder (70%). Mp 70–
728C. dH (CDCl3): 8.48 (s, 1H), 7.38 (d, J ¼ 9.0 Hz, 1H), 6.63 (dd, J ¼ 9.1
and 2.4 Hz, 1H), 6.48 (d, J ¼ 2.6 Hz, 1H), 3.93 (s, 3H), 3.47 (q, J ¼ 7.2 Hz,
4H), 1.25 (t, J ¼ 7.2 Hz, 6H); dC (CDCl3): 165.11, 158.67, 158.47, 153.11,
149.78, 131.27, 109.76, 108.59, 107.84, 96.79, 52.45, 45.26, 12.55.
Elemental analysis calculated for C15H17NO4: C, 65.44; H, 6.22; N, 5.09.
Found: C, 65.57; H, 6.22; N, 5.14.
3-N-(2-Hydroxyethyl)carboxamido-7-(diethylamino)coumarin
hemi-hydrate (3)
A 250-mL, round-bottomed flask equipped with magnetic stirbar was charged
with 25 g of 4-diethylaminosalicylaldehyde (1, 0.129 mol) and 20.4 g of
dimethyl malonate (17.7 mL, 0.16 mol, 1.2 equiv). The mixture was stirred
in an 808C oil bath, and all the solids dissolved. In one portion, 3.83 mL of
piperidine (3.29 g, 0.039 mol, 0.3 equiv) were added to the mixture. The
color immediately became yellow-orange, and methanol was seen to
1
condense in the headspace of the flask. The reaction was monitored by H
NMR of aliquots from the reaction dissolved in CDCl3. After 1 h, all the
aldehyde was consumed, and, in one portion, 11.57 g ethanolamine
(11.34 mL, 0.19 mol, 1.47 equiv) were added to the reaction. Again,
methanol is seen to condense in the headspace of the flask. The reaction
was monitored as done previously. After 1 h, a mixture of 60 mL of H2O
and 40 mL of EtOH was added to the mixture. The reaction mixture

2388
M. C. Davis
dissolved in the solvent, and then the oil bath was removed. After 10 min, a
yellow crystalline solid precipitated, and stirring stopped. Another 40 mL of
the solvent mixture was added, and the solid was broken up. The product
was collected on a coarse-porosity glass frit. It was not possible to rinse the
solid thoroughly on the frit, so the crude was recrystallized from a mixture
of 60 mL of H2O and 40 mL of EtOH. After filtering on a coarse-porosity
glass frit, the small, bright yellow flakes were dried overnight (10 Torr,
608C) to remove residual H2O. The mass of product was 26.3 g, representing
a 65% yield (calculated on anhydrous product). Mp 121–1238C (lit.[1] 126–
127 C). dH (CDCl3): 9.14 (t, J ¼ 6 Hz, 1H), 8.68 (s, 1H), 7.42 (d, J ¼ 9.4 Hz,
1H), 6.65 (dd, J ¼ 9.0 and 2.5 Hz, 1H), 6.49 (d, J ¼ 2.4 Hz, 1H), 3.83
(t, J ¼ 5.1 Hz, 2H), 3.62 (q, J ¼ 4.9 Hz, 2H), 3.46 (q, J ¼ 7.1 Hz, 4H), 2.03
(bs, 1H), 1.25 (t, J ¼ 7.1 Hz, 6H); dC (CDCl3): 165.07, 162.94, 157.95,
152.96, 148.53, 131.48, 110.29, 109.96, 108.58, 96.80, 63.15, 45.33, 43.29,
.
12.65. Elemental analysis calculated for C16H20N2O4 1/2 H2O: C, 61.34; H,
6.71; N, 8.94. Found: C, 61.64; H, 6.70; N, 8.94.
3-N-(2-Methacryloxyethyl)carboxamido-7-(diethylamino)coumarin (4)
The product is light sensitive; all operations were performed under cloth or
foil covers to avoid exposure to light as far as possible.
A two-necked, 500-mL, round-bottomed flask equipped with magnetic
stirbar was charged with 26.3 g of compound 3 (0.084 mol), 21.47 g of
DMAP (0.176 mol, 2 equiv), 20 mg of 4-methoxyphenol, and 250 mL of
THF (anhydrous, inhibitor free). An N2 bubbler was equipped to one neck,
and a 10-mL pressure-equalizing addition funnel was equipped to the
second neck. The mixture was stirred in a warm H2O bath until complete
dissolution. The mixture was cooled in an ice bath, and the addition funnel
was charged with 19.55 mL of methacrylic anhydride (20.33 g, 0.132 mol,
1.5 equiv). The addition was made dropwise over 5 min. After 30 min, TLC
showed complete consumption of 3. The reaction mixture was poured into
750 mL of vigorously stirred, cold H2O. A pale yellow solid precipitated,
and after 20 min, the solid was collected on a coarse-porosity glass frit. The
solid was broken up and rinsed on the frit twice with 150-mL portions of
cold H2O. The solid was air dried under vacuum on the frit for 2 h to obtain
40.5 g of crude product. The crude contained some H2O but was otherwise
more than 95% by 1H NMR. The yellow solid was recrystallized from
400 mL of EtOH to give 19.9 g of the title compound 4 as a pale yellow
powder (62%). Mp 138–1408C (lit.[1] 143–1448C). dH (CDCl3): 9.08
(t, J ¼ 4.9 Hz, 1H), 8.71 (s, 1H), 7.45 (d, J ¼ 9.2 Hz, 1H), 6.65 (dd, J ¼ 8.9
and 2.6 Hz, 1H), 6.49 (d, J ¼ 2.4 Hz, 1H), 6.19 (pent, J ¼ 1.2 Hz, 1H), 5.59
(pent, J ¼ 1.6 Hz, 1H), 4.32 (t, J ¼ 5.6 Hz, 2H), 3.77 (q, J ¼ 5.8 Hz, 2H),
3.46 (q, J ¼ 7.2 Hz, 4H), 1.98 (m, J ꢀ 1.2 Hz, 3H), 1.24 (t, J ¼ 7.2 Hz,
6H); dC (CDCl3): 167.49, 163.62, 162.98, 157.92, 152.86, 148.44, 136.27,

Coumaromethacrylate Dye Synthesis
2389
131.40, 126.26, 110.25, 110.22, 108.59, 96.80, 63.60, 45.30, 38.65, 18.51,
12.62. Elemental analysis calculated for C20H24N2O5: C, 64.5; H, 6.50; N,
7.52. Found: C, 64.29; H, 6.51; N, 7.46.
ACKNOWLEDGMENTS
The generous financial support by the Army Research Laboratory is gratefully
acknowledged. Thanks to Dr. Geoffrey A. Lindsay (NAWCWD) for advice
and encouragement throughout the course of this research. Thanks to
Andrew P. Chafin (NAWCWD) for suggestions and corrections during the
preparation of this manuscript. Thanks to Chrissy Everett (NAWCWD) for
assistance in purchasing reagents and obtaining combustion analysis.
REFERENCES
1. Lindsay, G. A.; Henry, R. A.; Hoover, J. M.; Knoesen, A.; Mortazavi, M. A. Sub-Tg
relaxation behavior of corona-poled nonlinear optical polymer films and views on
physical aging. Macromolecules 1992, 25, 4888–4898.
2. Lindsay, G. A.; Henry, R. A.; Hoover, J. M. Coumarin dyes and side-chain
coumarin dye-substituted polymers which exhibit nonlinear optical properties.
U.S. Patent 5,286,803, February 15, 1994.
3. Scott, J. L.; Raston, C. L. Solvent-free synthesis of 3-carboxycoumarins. Green
Chem. 2000, 2, 245–247.
4. Sugino, T.; Tanaka, K. Solvent-free coumarin synthesis. Chem. Lett. 2001, 30,
110–111.
5. Vansteenkiste, S.; Matthijs, G.; Schact, E.; De Schrijver, F. C.; Van Damme, M.;
Vermeersch, J. Preparation of tailor-made multifuntional propenyl ethers by
radical copolymerization of 2-(1-propenyl)oxyethyl methacrylate. Macromolecules
1999, 32, 55–59.