Convenient preparation of diethyl (2-thienyl)methanephosphonate

Article abstract of DOI:10.1081/SCC-200066689

This article describes a convenient preparation of diethyl (2-thienyl)methanephosphonate in 88% overall yield. Copyright Taylor & Francis, Inc.

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Convenient
Preparation of Diethyl
(2‐Thienyl)methanephosphonate
Matthew C. Davis a
a Chemistry and Materials Division, Michelson
Laboratory, Naval Air Warfare Center, China Lake,
California, USA
Version of record first published: 16 Aug 2006.
To cite this article: Matthew C. Davis (2005): Convenient Preparation of Diethyl
(2‐Thienyl)methanephosphonate, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 35:15, 2079-2083
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Synthetic Communicationsw, 35: 2079–2083, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200066689
Convenient Preparation of Diethyl
(2-Thienyl)methanephosphonate
Matthew C. Davis
Chemistry and Materials Division, Michelson Laboratory,
Naval Air Warfare Center, China Lake, California, USA
Abstract: This article describes a convenient preparation of diethyl (2-thienyl)meth-
anephosphonate in 88% overall yield.
Keywords: Arbuzov, chlorination, phosphite
As part of a program to develop optical devices composed of polymers, a con-
sistent supply of diethyl (2-thienyl)methanephosphonate (3) was necessary.
There are several reports of its preparation, and those[1–4] starting from the
readily available 2-thiophenemethanol (1) were more attractive than
others.[5–7] In general, these procedures start by chlorinating 1 to form
2-(chloromethyl)thiophene (2) and subsequently reacting it with triethyl
phosphite in the classic Michaelis–Arbuzov condensation to form 3
(Scheme 1).
We began making 2 with concentrated hydrochloric acid.[8,9] We could
obtain the product in moderate yield, but it came with a dark color, presu-
mably from acid-catalyzed polymerization of 1. This method required extrac-
tive workup followed by distillation. The noxious nature of 2 made us seek a
method that would minimize postreaction processing.
The use of thionyl chloride for this transformation would be a simpler
approach because the by-products generated in the reaction are gases: sulfur
Received in the USA March 28, 2005
Address correspondence to Matthew C. Davis, Chemistry and Materials Division
(Code 498220D), Michelson Laboratory, Naval Air Warfare Center, China Lake,
CA 93555, USA. E-mail: matthew.davis@navy.mil
2079

2080
M. C. Davis
Scheme 1.
dioxide and hydrogen chloride.[3,4] Our first attempt was dropwise addition of
thionyl chloride into a solution of 1. Because this places 1 in direct contact
with the hydrogen chloride generated, the formation of the dark color
occurred rapidly at ambient or ice bath temperature. When the addition was
reversed and the by-product gases were swept away by a steady flow of
nitrogen, the chlorination ran cleanly. The alcohol (1) is immediately
converted to the chlorosulfite ester, which rearranges to 2.[10] The nitrogen
flow protects 1 from the hydrogen chloride while in the addition funnel. It
was easy to determine reaction completion by the evolution of gas from the
reaction. The isolation and purification of 2 involved a simple fractional dis-
tillation directly from the reaction pot. The method provided 2 in high yield,
and it could be stored at 2208C for one month without noticeable
decomposition.[11]
For the Michaelis–Arbuzov reaction, the conditions reported by Zhang
et al.[8] for the 5-bromo analog of 3 indicated it should be high yielding.
However, triethyl phosphite was made the limiting reagent (slightly less
than 1 equivalent) rather than 2 to capitalize on the boiling point difference
between 2 and 3: 1308C and 3258C at 760 torr, respectively. This method
provided 3 in nearly quantitative yield with a simple isolation and purification
by fractional distillation directly from the reaction pot.
In summary, the final conditions for the two-step transformation are shown
in Scheme 2. Here is a convenient method to prepare diethyl (2-thienyl)methane-
phosphonate (3) in 88% overall yield starting from 2-(hydroxymethyl)thiophene
(1). The method is robust and minimizes postreaction processing.
EXPERIMENTAL
Warning! The products 2 and 3 as well as triethyl phosphite, all have noxious
odor and are most likely toxic. All of the unit processes described below
should be performed in a well-ventilated fume hood. All the glassware
Scheme 2. Optimized conditions. Reagents and conditions: a) SOCl2, CH2Cl2,
reverse addition, rt; b) 1 equiv. P(OEt)3, 1508C.

Diethyl (2-Thienyl)methanephosphonate
2081
employed in either preparation should be rinsed with organic solvents prior to
removal from the fume hood. Chloroethane (ethyl chloride) appears on the list
of hazardous air pollutants of the 1990 Clean Air Act of the U.S. Congress.[12]
The chloroethane (bp 128C) generated in the preparation of 3 can be
condensed for safe disposal or stored for later use at 08C or below.
NMR spectra were obtained on a Bruker AC-200 spectrometer (1H at
200 MHz, 13C at 50 MHz, and 31P at 81 MHz) and are referenced to solvent
or tetramethylsilane. The 2-thiophenemethanol (1), triethyl phosphite
(98%), and SOCl2 (99%) were purchased from Aldrich Chemical Co.
(Milwaukee, WI) and used as received. Elemental analyses were performed
by Atlantic Microlab, Inc. (Norcross, GA). All other reagents were obtained
commercially and used as received.
2-(Chloromethyl)thiophene (2)
A dry, 500-mL, two-necked, round-bottomed flask was equipped with a
magnetic stirring bar, thermometer, 250-mL pressure-equalizing dropping
funnel, and gas adapters on both the flask and top of the dropping funnel (see
Figure 1). The flask was charged with 250 mL of CH2Cl2 followed by
41.5mL of SOCl2 (67.68g, 569 mmol, 1.1 equiv). The funnel was charged
with 59 g of 2-thiophenemethanol (1) (49.2 mL, 517 mmol). A source of dry
Figure 1. Apparatus for transformation of 1 into 2.

2082
M. C. Davis
N2 was connected to the-gas adapter on the dropping funnel. The gas adapter on
the flask was connected with tubing to a gas-washing bottle containing 1 L of
1 M aqueous NaOH. The reaction flask was placed in a 258C water bath and vig-
orously stirred, and the N2 flow was started at a moderate rate. The alcohol was
added dropwise over 30min. The temperature within the reaction climbed to
288C after one third of the alcohol had been added and gradually fell to 258C
by the end of the addition. The water in the bath was replaced with warm
water (328C) to facilitate completion. After 30min, no further gas evolved
and the solution was golden yellow. The thermometer, addition funnel, and
gas inlet adapter were removed from the reaction flask. A short-path, vacuum
still head was equipped to the center neck and the other necks were glass-
stoppered. The CH2Cl2 was evaporated under reduced pressure (8 Torr) and
the remaining oil was distilled (55–758C, 8 Torr) into a 500-mL, round-
bottomed flask to give 2 as a colorless liquid (62.1 g, 91%). The compound
1
was stored at 2208C. H NMR (CDCl3) d 7.3 (d, J ¼ 1.3 and 5.1 Hz, 1H),
7.08 (d, J ¼ 3.6 Hz, 1 H), 6.95 (dd, J ¼ 3.6 and 5.2 Hz, 1H), 4.79 (s, 2H); 13
C
NMR (CDCl3) d 140.21, 127.83, 127.04 (two overlapping resonances), 40.51.
Diethyl (2-Thienyl)methanephosphonate (3)
To a 500-mL, round-bottomed flask containing 62.1 g of 2 (468 mmol) was
added a magnetic stirring bar followed by 80.2 mL of triethyl phosphite
(77.7 g, 468 mmol, 1 equiv). A Claisen adapter equipped with a thermometer
(for monitoring internal reaction temperature) and reflux condenser was
attached to the flask. A gas adapter was used to connect the condenser
through tubing to a 08C trap then onto an N2 bubbler. The flask was heated
to 1608C with a heating mantle. After 7 h, analysis of the reaction mixture
by 1H NMR showed complete consumption of the starting materials. A
short-path, vacuum distillation head was attached to the reaction flask and
the mixture was distilled (1 Torr, 130–1458C) to obtain 106.3 g of 3 as a
1
colorless liquid (97%). H NMR (CDCl3) d 7.18 (dt, J ¼ 1.5 and 5.1 Hz,
3
1 H), 7.01–6.92 (m, 2H), 4.08 (dq, J ¼ 7.1 and JPOCH 7.8 Hz, 4H), 3.36
2
(d, JPCH ¼ 21 Hz, 2H), 1.28 (t, J ¼ 7.1 Hz, 6H); 13C NMR (CDCl3) d
132.32 (d, JP-C ¼ 10.2 Hz), 127.19 (d, JP-C ¼ 8.9 Hz), 126.89
2
(d, JPC ¼ 3.8 Hz), 124.61 (d, JPC ¼ 3.8 Hz), 62.23 (d, JPOC ¼ 7.0 Hz),
3
27.78 (d, JPC ¼ 144.8 Hz), 16.24 (d, JPOCC ¼ 6.4 Hz); 31P NMR (CDCl3) d
23.75 (s). Anal. calcd. for C9H15O3PS: C, 46.15; H, 6.45; S, 13.69. Found:
C, 46.00; H, 6.28; S, 13.56.
ACKNOWLEDGMENTS
Financial support from the Office of Naval Research is gratefully
acknowledged. M. C. D. thanks several people in NAWCWD: Geoffrey
A. Lindsay for advice and encouragement throughout the course of this

Diethyl (2-Thienyl)methanephosphonate
2083
work; Robert D. Chapman and Andrew P. Chafin for proofreading this
manuscript; and librarian Patricia Backes for help finding the federal
emission standards.
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