Synthesis of 2-(Thiophen-3-yl)vinylphosphonic acid

Article abstract of DOI:10.1080/00397910902784462

A simple and efficient synthesis of 2-(thiophen-3-yl)vinylphosphonic acid has been developed. The title compound is obtained in 70% yield by addition of thiophene-3-carbaldehyde to lithium diethyl methylenephosphonate, followed by dehydration and hydrolysis. 1H, 13C, and 31P NMR spectra are presented for each of the intermediates. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910902784462

Synthetic Communications1, 39: 1511–1515, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902784462
Synthesis of 2-(Thiophen-3-yl)vinylphosphonic
Acid
1
Irma Linzaga-Elizalde, Jaime Escalante, Marıa E. Nicho, and
1
2
´
2
´
Marisol Gu¨izado-Rodrıguez
1Chemical Research Center, Morelos Autonomous State University,
Morelos, Mexico
2Center of Research in Engineering and Applied Sciences,
Morelos Autonomous State University, Morelos, Mexico
Abstract: A simple and efficient synthesis of 2-(thiophen-3-yl)vinylphosphonic
acid has been developed. The title compound is obtained in 70% yield by addition
of thiophene-3-carbaldehyde to lithium diethyl methylenephosphonate, followed
by dehydration and hydrolysis. 1H, 13C, and 31P NMR spectra are presented
for each of the intermediates.
Keywords: Diethyl methylphosphonate, 2-(thiophen-3-yl)vinylphosphonic acid,
thiophene-3-carbaldehyde
INTRODUCTION
There is a wide spectrum of applications for phosphonic acids, and
because of their physical characteristics, they can be applied in polymer
manufacture,[1] in the paper industry as additives,[2] as anticorrosion pro-
ducts,[3,4] as fire retardants, and as dental adhesives.[5] Polythiophenes
have attracted attention as a result of their good electrical conductiv-
ities,[6] easy processability, high environmental stability, and amenity to
a wide range of potential technological applications.[7] For these reasons,
Received May 4, 2007.
Address correspondence to Irma Linzaga-Elizalde, Centro de Investigaciones
´
ꢀ
Quımicas, Universidad Autonoma del Estado de Morelos, Av. Universidad 1001,
Col. Chamilpa, C.P. 62209 Cuernavaca, Morelos, Mexico. E-mail: linzaga@ciq.
´
uaem.mx
1511

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I. Linzaga-Elizalde et al.
we decided to develop a convenient methodology for the preparation of
the thiophene derivative of phosphonic acid.
DISCUSSION
The addition reaction of thiophene-3-carbaldehyde to lithium diethyl
methylenephosphonate,[8] which has been generated from n-BuLi
and diethyl methylphosphonate under anhydrous conditions, affords
the diethyl 2-hydroxy-2-(thiophen-3-yl)ethylphosphonate 1, purified by
column chromatography, in good yield.
The dehydration of phosphonate 1 was achieved by heating it
to 90–100 ꢀC in 3 N HCl in a sealed tube to afford the expected a,b,-
unsaturated phosphonate compound 2 in good yield.
The final step of the conversion of thiophene-3-carbaldehyde to 2-
(thiophen-3-yl)vinylphosphonic acid 3 was achieved by stirring a solution
of 2 in bromotrimethylsilane at room temperature for 16 h, according to
the method reported by Yuan et al.[9]
In conclusion, in this study we have prepared 2-(thiophen-3-yl)vinyl-
phosphonic acid in good yield starting from diethyl methylphosphonate
and thiophene-3-carbaldehyde.
EXPERIMENTAL
The diethyl methyl phosphonate was prepared according to a Michaelis–
Arbuzov reaction.[10] Thiophene-3-carbaldehyde was purchased from
Aldrich. Tetrahydrofuran was distilled from sodium=benzophenone ketyl
prior to use. The melting points are uncorrected. The compounds were
characterized by 1H NMR (200 MHz), 13C NMR (50 MHz), and 31P
NMR (80.98 MHz) spectroscopy. Mass spectrometry (MS) and high-
resolution mass spectrometry (HRMS) were performed using the fast
atom bombardment (FABþ) mass spectra technique. The thiophene-3-
carbaldehyde was distilled before use.
Diethyl Methylphosphonate
A mixture of triethyl phosphite (5.0 g, 30 mmol) and methyl iodide
(4.69 g, 33 mmol) was refluxed for 5 h. Ethyl iodide was eliminated by
distillation. Then, the diethyl methylphosphonate was distilled in a
Kugel–Rohr apparatus, bp 55ꢀC=2 mm Hg (54ꢀC=1.5 mm Hg),[10b]
3.7 g, yield 80%.

2-(Thiophen-3-yl)vinylphosphonic Acid
1513
1H NMR (CDCl3, 200 MHz): d 1.33 (t, J ¼ 7.2 Hz, 6H), 1.47
(d, J ¼ 17.6 Hz, 3H), 4.09 (m, 4H).
Diethyl 2-Hydroxy-2-(thiophen-3-yl)ethylphosphonate (1)
Diethyl methylphosphonate (3.12 g, 20 mmol) in anhydrous tetrahydro-
furan (100 mL), was placed in a round-bottom flask, and a solution of
n-buthyllithium (2.5 M in n-hexane, 9 mL, 22 mmol) was added at
ꢁ78ꢀC under a nitrogen atmosphere. After stirring the solution at this
temperature for 20 min, thiophene-3-carbaldehyde (2.56 g, 22 mmol)
was added. The mixture was stirred at ꢁ78ꢀC for 45 min and then at
room temperature for 20 min. A saturated solution of ammonium
chloride was added, and the mixture was extracted with dichloro-
methane (3 ꢂ 50 mL). The combined organic phases were dried over
anhydrous sodium sulfate and evaporated, and the residue was purified
by column chromatography on silica gel using n-hexane–ethyl acetate
(80:20!10:90) as eluent to give the product as a colorless oil (4.35 g,
83% yield).
1H NMR (CDCl3, 200 MHz): d 1.27 (t, J ¼ 7.0 Hz, 3H), 1.30
(t, J ¼ 7.0 Hz, 3H), 2.23 (m, 2H), 4.05 (m, 4H), 4.43 (s, OH), 5.17
(ddd, J ¼ 5.6 Hz, 7.3, 12.3 Hz, 1H), 7.15 (m, 3H). 13C NMR (CDCl3,
3
3
50 MHz): d 16.6 (d, JCP ¼ 3.0 Hz), 16.7 (d, JCP ¼ 3.0 Hz), 35.3
1
2
2
(d, JCP ¼ 136.0 Hz), 62.1 (d, JCP ¼ 9.4 Hz), 62.3 (d, JCP ¼ 6.1 Hz),
2
3
65.4 (d, JCP ¼ 4.5 Hz), 120.9, 125.5, 126.3, 145.0 (d, JCP ¼ 15.9 Hz).
31P NMR (CDCl3, 80.98 MHz): d 29.9. EM: m=z: 264 (69%), 152
(71%), 125 (100%), 111 (30%), 97 (61%), 84 (8%). HRMS calcd for
C10H17O4PS:264.0585; found:264.0550.
Diethyl 2-(Thiophen-3-yl)vinylphosphonate (2)
A suspension of diethyl 2-hydroxy-2-(thiophen-3-yl)ethylphosphonate 1
(0.70 g, 2.65 mmol) in 10 mL of 3N HCl was heated in a sealed tube to
90–100ꢀC for 1.5 h. The solution was then allowed to cool to ambient
temperature and evaporated at reduced pressure to afford the crude pro-
duct, which was purified by column chromatography on silica gel using
n-hexane–ethyl acetate (80:20 ! 0:100) as eluent to afford the product
as a colorless oil (0.60 g, 91% yield).
1H NMR (CDCl3, 200 MHz): d 1.31 (t, J ¼ 7.1 Hz, 6H), 4.08 (m, 4H),
6.01 (dd, J ¼ 17.8 Hz, 2JHP ¼ 35.6 Hz, 1H), 7.39 (m, 4H), 7.46 (dd masked,
3
J ¼ 17.6 Hz, JHP ¼ 22.8 Hz, 1H). 13C NMR (CDCl3, 50 MHz): d 16.6
3
2
1
(d, JCP ¼ 6.45 Hz), 61.9 (d, JCP ¼ 5.3 Hz), 113.2 (d, JCP ¼ 190.95 Hz),

1514
I. Linzaga-Elizalde et al.
3
124.9, 127.0, 127.7, 138.0, 138.5, 142.4 (d, JCP ¼ 6.8 Hz). 31P NMR
(CDCl3, 80.98 MHz): d 20.9. EM: m=z 246 (43%), 190 (23%), 173
(36%), 155 (44%), 137 (100%), 108 (5%), 97 (30%), 83 (8%), 82 (21%).
HRMS calcd for C10H15O3PS:246.0480; found:246.0501.
2-(Thiophen-3-yl)vinylphosphonic Acid (3)
In a round-bottom flask, trimethylsilylbromide (0.61 g, 0.52 mL, 4 mmol)
was added to a cold solution of diethyl 2-(thiophen-3-yl)vinylphospho-
nate 2 (0.5 g, 2 mmol) in anhydrous dichlorometane. After stirring the
mixture at room temperature for 16 h, the solvent was removed under
reduced pressure, and water (5 mL) was added to the residue. The solid
obtained was washed with n-hexane and ethyl acetate and then recrystal-
lized from methanol–ethyl acetate (1:3) (mp ¼ 149–151ꢀC, (0.27 g, 70%
yield).
2
1H NMR (CDCl3, 200 MHz): d 6.26 (dd, J ¼ 17.8 Hz, JHP
¼
35.6 Hz), 7.26 (br s, 1H), 7.40 (m, 3H), 7.60 (br s, 1H). 13C NMR
1
(CDCl3, 50MHz): d 117.8 (d, JCP ¼ 186.8 Hz), 126.0, 128.0, 128.2,
139.9, 140.5 (d, JCP ¼ 6.1 Hz). 31P NMR (CDCl3, 80.98MHz): d 18.0.
3
EM: m=z 192 (14%), 191 (23%), 190 (22%), 111 (79%), 110 (100%),
109 (56%), 84 (21%), 81 (9%). HRMS calcd. for C6H7O3PS:189.9854;
found:189.9815.
ACKNOWLEDGMENTS
´
We are grateful to Consejo Nacional de Ciencia y Tecnologıa
(CONACYT) for financial support through grants 48356-Q and
ꢀ
C02-44704. We are indebted to Graciela I. Gonzalez-Castillo for techni-
cal support and Dr. Herbert Ho¨pfl for many important observations.
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