Straightforward synthesis of 2-aryl-1-alkynylphosphonates and arylpropiolates

Article abstract of DOI:10.1080/00397910701226830

A protocol for the direct cross coupling of trialkylsilyl-alkynes bearing electron-withdrawing groups and aryl halides using a Pd/Ag catalytic system is described. The procedure allows the straightforward synthesis of a variety of alkynylphosphonates and aryl propiolates derivatives in good yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701226830

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Straightforward Synthesis of
2‐Aryl‐1‐alkynylphosphonates and
Arylpropiolates
Delphine Lecerclé a , Céline Mothes a & Frédéric Taran a
a Atomic Center of Energy, Saclay Institute of Biology and Technology,
Department of Bioorganic Chemistry and Isotopic Labelling , Yvette, France
Published online: 12 Apr 2007.
To cite this article: Delphine Lecerclé , Céline Mothes & Frédéric Taran (2007) Straightforward Synthesis of
2‐Aryl‐1‐alkynylphosphonates and Arylpropiolates, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 37:8, 1301-1311, DOI: 10.1080/00397910701226830
To link to this article: http://dx.doi.org/10.1080/00397910701226830
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Synthetic Communicationsw, 37: 1301–1311, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701226830
Straightforward Synthesis of 2-Aryl-1-
alkynylphosphonates and Arylpropiolates
´
´
´ ´
Delphine Lecercle, Celine Mothes, and Frederic Taran
Atomic Center of Energy, Saclay Institute of Biology and Technology,
Department of Bioorganic Chemistry and Isotopic Labelling,
Yvette, France
Abstract: A protocol for the direct cross coupling of trialkylsilyl-alkynes bearing
electron-withdrawing groups and aryl halides using a Pd/Ag catalytic system is
described. The procedure allows the straightforward synthesis of a variety of alkynyl-
phosphonates and aryl propiolates derivatives in good yields.
Keywords: alkynylphosphonates, arylpropiolates, cross-coupling reactions, Pd/Ag-
catalyzed reactions
INTRODUCTION
1-Alkynylphosphonates are common precursors to a range of useful functio-
nalized organophosphorus compounds[1] such as b-ketophosphonates,[2]
vinylogous phosphonamides,[3] amino-alkenylphosphonates,[4] cyclopropyl-
methylphosphonates,[5] substituted vinylphosphonates,[6] and bisallylphos-
phonates.[7]
Besides classical methods,[1] several new methodologies have emerged for
the efficient preparation of these compounds, but all require the preparation of
precursors.[8] During the course of our work studying the reactivity of
activated alkynes,[9] we have been interested in ameliorating the Sonogashira
reaction using terminal alkynyl phosphonates and aryl-halides. Although this
reaction appears to be the more straightforward way to produce
Received in Poland August 4, 2006.
´ ´
Address correspondence to Frederic Taran, Department of Bioorganic Chemistry
and Isotopic Labelling, CEA, iBiTecS, Gif sur Yvette F-91191, France. E-mail:
frederic.taran@cea.fr
1301

´
D. Lecercle et al.
1302
alkynylphosphonates, few studies have been made on this cross-coupling reaction
using these particular substrates.[10] It is well known that terminal alkynes bearing
electron-withdrawing groups directly attached to the ethynyl carbon atom
undergo side reactions such as Michael additions or self condensation under
the classical Sonogashira reaction conditions. The present work describes our
attempts to adapt the Sonogashira reaction conditions to the reactivity of
electron-deficient terminal alkynes. This study conducted a simple procedure
that allows the preparation of 2-aryl-1-alkynyl-phosphonates in good yields
and was further successfully extended to the synthesis of arylpropiolates.
RESULTS AND DISCUSSION
As expected, our preliminary attempts to prepare 1 from iodobenzene and
ethynyl-diethylphosphonate[11] using classical Sonogashira catalytic systems
involving the use of Pd0, CuI, and tertiary amines resulted in only trace
amounts of the desired product (Table 1, entry 1). Comparable results were
given with PdII complexes such as Cl2Pd(PPh3)2 or Pd(OAc)2.[10] These poor
yields were probably caused by the observed degradation of the starting
terminal alkyne, and we thought of using catalytic systems developed by P.
Pale for ene-yne cross-coupling reactions.[12] These systems are based on the
use of silver salts that are supposed to form silver acetylides as less nucleophilic
intermediates than copper acetylides, therefore avoiding the side reactions
observed with sensitive alkynes.[13] Replacement of copper cocatalyst by
AgCl did allow the formation of alkynylphosphonate 1 but with poor
Table 1. Optimization of the reaction conditionsa
Entry
1
R
Cocatalyst
CuI
Conditions
Yields of 1 (%)b
H
H
DIPEA or
,5
TEA (10 eq.)
TEA (10 eq.)
or TBAF
2
AgCl
15
(1 eq.)
3
4
5
6
(iPr)3Si-
(iPr)3Si-
(iPr)3Si-
(iPr)3Si-
—
CuCl
AgCl
AuCl
TBAF (1 eq.)
TBAF (1 eq.)
TBAF (1 eq.)
TBAF (1 eq.)
10
76
.95
77
aReactions were conducted with 10% of palladium catalyst, 1.5 eq. of alkyne, and
0.2 eq. of cocatalyst.
bYields were determined by HPLC.

Straightforward Synthesis
1303
yield (Table 1, entry 2). We therefore decided to use 2-triisopropyl-1-
alkynyl-diethylphosphonate[11] as starting substrate and to generate the
terminal alkyne in situ through the addition of nBu4NF-3H2O (TBAF) in the
presence of the Pd/Ag catalytic system, according to a previously described
procedure.[14] These conditions were the most efficient, allowing the coupling
reaction to proceed in quantitative yield (Table 1, entry 5). In the absence of
AgCl or in the presence of other cocatalysts, lower yields were observed
(Table 1, entries 3, 4, and 6), highlighting the crucial role of silver salts.
To explore the generality of these reaction conditions, we studied the
cross-coupling reaction on a range of aryl halides (Table 2). This optimized
reaction was applicable to a variety of aromatic substrates bearing either
electron-withdrawing (Table 2, entry 3) or electron-donating groups
(Table 2, entries 4 and 5). The reaction conditions are also compatible with
the use of heteroaromatic compounds (Table 2, entries 6 and 7), although
some of them induced low yields of the expected product (Table 2, entries
9 and 10). Alkynylphosphonates were also obtained starting from arylbromide
substrates but only with low (nonoptimized) yields (Table 2, entries 2 and 8).
Finally, a double coupling reaction was carried out on 1,4-diiodobenzene,
affording the bis-alkynylphosphonate 9 in excellent yield; this result showed
that the presented method is more efficient than those previously described
using Pd/Cu systems.[10]
To expand the scope of the reaction to other electron-deficient alkynes,
we investigated the formation of arylpropiolates using aryl iodides and com-
mercially available trimethylsilyl-ethylpropiolate as reagents. The reaction
proceeded smoothly under our optimized conditions and afforded the
desired product in reasonable yields even when electron-rich aromatic sub-
strates are used (Scheme 1). This result highlights again the superior
activity of the Pd/Ag catalytic system over the Pd/Cu ones.[15]
In summary, we have developed a convenient method for the one-pot
preparation of alkynylphosphonates using a Pd/Ag catalytic system. The
reaction appears tolerant to a range of functional groups including hetero-
cyclic substrates and was easily extended to the synthesis of aryl propiolates.
This methodology is complementary to other existing procedures and should
find use in the field of C-C bond formation involving sensitive alkynes.
EXPERIMENTAL
Dry DMF was used without further purification. Purifications of products were
carried out by flash chromatography using Merck silica gel (40–63 mm).
Analytical thin layer chromatography (TLC) was performed on Merck
silica-gel 60-F plates. Visualization was accomplished with UV light and
iodine. Infrared spectra (IR) were obtained on a Perkin-Elmer system 2000
FTIR spectrophotometer and are reported as wavelength numbers (cm21).
IR spectra for liquid products were obtained as a thin film on a NaCl disk,

´
D. Lecercle et al.
1304
Table 2. Synthesis of alkynyl-phosphonatesa
Entry
1
ArX
Product
Yields(%)b
95
1
2
3
4
5
1
20
60
80
96
2
3
4
6
7
66
57
5
6
8
6
11
9
10
11
27
20
97
7
8
9
aReactions were conducted with 10% of palladium catalyst, 20% of AgCl, 1.5 eq. of
alkyne, and 1.5 eq. of TBAF. Concentration of substrates was 0.05 M.
bIsolated yields.

Straightforward Synthesis
1305
Scheme 1. Extension of the methodology to the preparation of aryl propiolates. Reac-
tions were conducted with 10% of palladium catalyst, 20% of AgCl, 1.5 eq. of alkyne,
and 1.5 eq. of TBAF. Isolated yields. ꢀThis reaction was conducted at room temperature.
and spectra for solid products were collected by preparing a KBr pellet con-
1
taining the title compound. H NMR (400 MHz), 13C NMR (100 MHz), and
31P NMR (160 MHz) were measured on a Brucker Avance 400-MHz
spectrometer. Chemical shifts are reported in parts per million (ppm, d)
downfield from residual solvents, peaks, and coupling constants are
reported as Hertz (Hz). Splitting patterns are designated as singlet (s),
doublet (d), triplet (t). Splitting patterns that could not be interpreted or
easily visualized are designated as multiplet (m). Electrospray mass spectra
were obtained using a ESI/TOF Mariner mass spectrometer. Unless
otherwise noted, all commercially available reagents and solvents were used
without further purification.
Typical Procedure for the Preparation of Alkynyl-phosphonates
To a mixture of iodobenzene (208 mg, 1 mmol), AgCl (29 mg, 0.2 mmol), and
Pd(PPh3)4 (117 mg, 0.1 mmol) in dry DMF (10 mL), [(triisopropylsilanyl)-
ethynyl]-phosphonic acid diethyl ester (477 mg, 1.5 mmol) in 5 mL of dry
DMF was added. The mixture was stirred at room temperature for 5 min,
and then TBAF (400 mg, 1.5 mmol) in 5 mL of dry DMF was added slowly.
The solution was next heated at 508C for 12 h. Then water was added, and
the solution was extracted with DCM. The combined organic layers were
dried with MgSO4, filtered, and concentrated under reduced pressure. The
resulting residue was purified by flash-column chromatography on silica gel.
Phenylethynyl-phosphonic Acid Diethyl Ester (1)
Purification by column chromatography on silica gel (cyclohexane–acetone
1:1) provided the desired product as a pale yellow oil (95%). 1H NMR

´
D. Lecercle et al.
1306
(CDCl3, 400 MHz): d 1.38 (t, J ¼ 7 Hz, 6H); 4.17–4.24 (m, 4H); 7.35
(m, 2H); 7.43 (m, 1H); 7.54 (d, J ¼ 7.2 Hz, 2H).13C NMR (CDCl3,
100 MHz): d16.04 (d, J ¼ 7 Hz); 63.15 (d, J ¼ 5.5 Hz); 80.5
(d, J ¼ 297 Hz); 98.95 (d, J ¼ 52.4 Hz); 119.49 (d, J ¼ 6 Hz); 128.48;
130.61; 132.53 (d, J ¼ 2.4 Hz). 31P NMR (CDCl3, 160 MHz): d 25.91.
MS: m/z 261 (100%, [M þ 23]þ). IR (NaCl): n 2986, 2189, 1264, 1029 cm21
.
(4-Nitro-phenylethynyl)-phosphonic Acid Diethyl Ester (2)
Purification by column chromatography on silica gel (cyclohexane–acetone
1
1:1) provided the desired product as a pale yellow oil (60% yield). H NMR
(CDCl3, 400 MHz): d 1.41 (t, J ¼ 7 Hz, 6H); 4.18–4.26 (m, 4H); 7.69–
7.71 (m, 2H); 8.20–8.22 (m, 2H). 13C NMR (CDCl3, 100 MHz): d 16.06
(d, J ¼ 6.8 Hz); 63.53 (d, J ¼ 5.5 Hz); 83.06 (d, J ¼ 295 Hz); 95.43
(d, J ¼ 52 Hz); 123.665; 126.07 (d, J ¼ 5.5 Hz); 133.45; 148.47. 31P NMR
(CDCl3, 160 MHz): d 2 7.29. MS: m/z 284 (100%, [M þ 1]þ). IR (NaCl):
n 2985, 2928, 2192, 1596, 1525, 1347, 1269, 1022, 980, 867 cm21
.
(4-Methoxy-phenylethynyl)-phosphonic Acid Diethyl Ester (3)
Purification by column chromatography on silica gel (cyclohexane–acetone
1
1:1) provided the desired product as a pale orange oil (80% yield). H NMR
(CDCl3, 400 MHz): d 1.34 (t, J ¼ 7 Hz, 6H); 3.77 (s, 3H); 4.12–4.20
(m, 4H); 6.82 (d, J ¼ 8.8 Hz, 2H); 7.45 (d, J ¼ 8.8 Hz, 2H). 13C NMR
(CDCl3, 100 MHz): d 16.01 (d, J ¼ 7 Hz); 55.29; 62.98 (d, J ¼ 5.5 Hz);
77.07(d, J ¼ 302 Hz); 99.69(d, J ¼ 54 Hz); 111.17 (d, J ¼ 5.8 Hz); 114.16;
134.29; 161.36. 31P NMR (CDCl3, 160 MHz): d 2 5.38. MS m/z: 269
(100%, [M þ 1]þ). IR (NaCl): n 3169, 2987, 2181, 2063, 1510, 1439, 1261,
1024, 977, 783 cm21
.
(2,3-Dihydro-benzo[1,4]dioxin-6-ylethynyl)-phosphonic Acid
Diethyl Ester (4)
Purification by column chromatography on silica gel (cyclohexane–acetone
1:1) provided the desired product as a red oil (96% yield). 1H NMR
(CDCl3, 400 MHz): d 1.38 (t, J ¼ 7 Hz, 6H); 4.15–4.21 (m, 4H); 4.22–
4.27 (m, 4H); 6.81 (d, J ¼ 8 Hz, 1H); 7.04 (d, J ¼ 8 Hz, 1H); 7.05 (s, 1H).
13C NMR (CDCl3, 100 MHz): d 16.05 (d, J ¼ 7 Hz); 63.08 (d, J ¼ 5.5 Hz);
64.07; 64.48; 111.88 (d, J ¼ 5.8 Hz); 117.64; 121.54 (d, J ¼ 2.5 Hz);
126.42 (d, J ¼ 2.4 Hz); 143.29; 146.15. 31P NMR (CDCl3, 160 MHz): d
25.49 (s). MS m/z: 297 (100%, [M þ 1]þ). IR (NaCl): n 3483, 2985, 2180,
1575, 1504, 1309, 1292, 1257, 1023, 961, 809 cm21
.

Straightforward Synthesis
1307
(3-Methyl-3H-imidazol-4-ylethynyl)-phosphonic Acid
Diethyl Ester (5)
Purification by column chromatography on silica gel (acetone–DCM 1:1)
1
provided the desired product as a pale yellow oil (66% yield). H NMR
(CDCl3, 400 MHz): 1.39 (t, J ¼ 7 Hz, 6H); 3.72 (s, 3H); 4.16–4.25
(m, 4H); 7.48 (s, 1H); 7.53 (s, 1H). 13C NMR (CDCl3, 100 MHz): 16.06
(d, J ¼ 7 Hz); 32.4; 63.38 (d, J ¼ 6 Hz); 82.94 (d, J ¼ 304 Hz); 96.29
(d, J ¼ 50 Hz); 113.40 (d, J ¼ 6 Hz); 138.45; 139.85. 31P NMR (CDCl3,
160 MHz): 26.78 (s). MS: m/z 243 (100%, [M þ 1]þ).
Imidazo[1,2-a]pyridin-3-ylethynyl-phosphonic Acid Diethyl Ester (6)
Purification by column chromatography on silica gel (acetone–cyclohexane
1
6:4) provided the desired product as a pale yellow oil (57% yield). H NMR
(CDCl3, 400 MHz): d 1.42 (t, J ¼ 7 Hz, 6H); 4.26 (m, 4H); 7.03
(t, J ¼ 7 Hz, 1H); 7.38 (t, J ¼ 7.5 Hz, 1H); 7.72 (d, J ¼ 9 Hz, 1H); 8.02
(S, 1H); 8.37 (d, J ¼ 6.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz): d 16.07
(d, J ¼ 7 Hz); 63.37 (d, J ¼ 7 Hz); 86.89 (d, J ¼ 54.3 Hz); 89.93
(d, J ¼ 297 Hz); 105.98 (d, J ¼ 6 Hz); 114.13; 118.18; 125.57; 128.32;
141.76; 146.46. 31P NMR (CDCl3, 160 MHz): d 26.13 (s, 1P). MS m/z:
279 (100%, [M þ 1]þ).
Imidazo[1,2-a]pyridin-7-ylethynyl-phosphonic Acid
Diethyl Ester (7)
Purification by column chromatography on silica gel (acetone–cyclohexane
1
6:4) provided the desired product as a pale brown oil (27% yield). H NMR
(CDCl3, 400 MHz): d 1.30 (t, J ¼ 7.2 Hz, 6H); 4.13 (dq, J ¼ 7.2, 7.2 Hz,
4H); 7.09 (d, J ¼ 9.6 Hz, 1H); 7.48 (t, J ¼ 9.6 Hz, 1H); 7.57 (s, 1H); 7.58
(s, 1H); 8.42 (s, 1H). 13C NMR (CDCl3, 100 MHz): d 16.02 (d, J ¼ 7 Hz);
63.31 (d, J ¼ 6 Hz); 79.95 (d, J ¼ 297 Hz); 95.13 (d, J ¼ 53 Hz); 105.44
(d, J ¼ 5 Hz); 113.18; 117.86; 126.06; 131.32; 135.02; 144.24. 31P NMR
(CDCl3, 160 MHz): d 26.80. MS m/z: 279 (100%, [M þ 1]þ).
Pyrimidin-5-ylethynyl-phosphonic Acid Diethyl Ester (8)
Purification by column chromatography on silica gel (acetone–cyclohexane
1
4:6) provided the desired product as a pale green oil (20% yield). H NMR
(CDCl3, 400 MHz): d 1.29 (t, J ¼ 7.2 Hz, 6H); 4.13 (dq, J ¼ 7.2, 7.2 Hz,
4H); 8.78 (s, 2H); 9.11 (s, 1H). 13C NMR (CDCl3, 100 MHz): d 15.98
(d, J ¼ 7 Hz); 63.55 (d, J ¼ 6 Hz); 85.85 (d, J ¼ 291 Hz); 91.03

´
D. Lecercle et al.
1308
(d, J ¼ 51 Hz); 116.58 (d, J ¼ 6 Hz); 158.20; 159.53 (d, J ¼ 2 Hz). 31P NMR
(CDCl3, 160 MHz): d 27.94. MS m/z: 242 (100%, [M þ 2H]þ).
[4-(Diethoxy-phosphorylethynyl)-phenylethynyl]-phosphonic Acid
Diethyl Ester (9)
Purification by column chromatography on silica gel (acetone–cyclohexane
1
1:1) provided the desired product as a pale orange oil (97% yield). H NMR
(CDCl3, 400 MHz): d 1.26 (t, J ¼ 7 Hz, 12H); 4.05–4.12 (m, 8H); 7.43
(s, 4H).13C NMR (CDCl3, 100 MHz): d 15.95 (t, J ¼ 7 Hz); 63.27
(d, J ¼ 5.6 Hz); 81.09 (d, J ¼ 296 Hz); 97.03 (d, J ¼ 52 Hz); 121.54
(d, J ¼ 5.6 Hz); 132.46. 31P NMR (CDCl3, 160 MHz): d 26.92 (s, 2P). MS
m/z: 399 (100%, [M þ 1]þ). IR (NaCl): n 3488, 2985, 2188, 1266, 1024,
978, 842 cm21
Typical Procedure for the Preparation of Arylpropiolates
To a mixture of iodobenzene (208 mg, 1 mmol), AgCl (29 mg, 0.2 mmol), and
Pd(PPh3)4 (117 mg, 0,1 mmol) in dry DMF (10 mL), trimethylsilanyl-
propynoic acid ethyl ester (285 mL, 1.5 mmol) in 5 mL of dry DMF was
added. The mixture was stirred at room temperature for 5 min, then TBAF
(400 mg, 1.5 mmol) in 5 mL of dry DMF was added. The mixture was
stirred at room temperature for 5 min, then TBAF (400 mg, 1.5 mmol) in
5 mL 07 dry DMF was added slowly. The solution was next heated at 508C
for 12 h. Then water was added, and the solution was extracted with DCM.
The combined organic layers were dried with mgSO4, filtered, and concen-
trated under reduced pressure. The resulting residue was purified by flash-
column chromatography on silica gel.
Phenyl-propynoic Acid Ethyl Ester (10)
Purification by column chromatography on silica gel (DCM–cyclohexane
7:3) provided the desired product as a pale yellow oil (64% yield). Spectral
data are in agreement with commercially available sample.
(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-propynoic Acid Ethyl Ester (11)
Purification by column chromatography on silica gel (cyclohexane–acetone
1
9:1) provided the desired product as a pale yellow solid (66% yield). H
NMR (CDCl3, 400 MHz): d 1.31 (t, J ¼ 7.2 Hz, 3H); 4.21–4.27 (m, 6H);
6.80 (d, J ¼ 8 Hz, 1H); 7.05 (d, J ¼ 8 Hz, 1H); 7.06 (s, 1H). 13C NMR

Straightforward Synthesis
1309
(CDCl3, 100 MHz): d 14.01; 61.85; 64.03; 64.46; 79.62; 86.42; 111.90;
117.63; 121.93; 126.87; 143.41; 146.17; 154.11. MS: m/z 255 (100%,
[M þ 23]þ). IR (KBr): n 2988, 2944, 2208, 1717, 1581, 1510, 1252, 1200,
1154, 1121, 1066, 1020, 882, 812, 743 cm21
.
(4-Methoxy-phenyl)-propynoic Acid Ethyl Ester (12)
Purification by column chromatography on silica gel (cyclohexane–acetone
1
8:2) provided the desired product as a pale yellow oil (55% yield). H NMR
(CDCl3, 400 MHz): d 1.33 (t, J ¼ 7.2 Hz, 3H); 3.79 (s, 3H); 4.26 (qd,
J ¼ 7.2 Hz, 2H); 6.86 (d, J ¼ 8.6 Hz, 2H); 7.51 (d, J ¼ 8.6 Hz, 2H). 13C
NMR (CDCl3, 100 MHz): d 14.03; 55.28; 61.79; 80.1; 86.79; 114.21;
116.27; 134.80; 138.07; 161.41. MS m/z: 205 (100%, [M þ 1]þ). IR
(NaCl): n 2981, 2205, 1604, 1511, 1287, 1253, 1195, 1165, 1025, 834,
748 cm21
.
Thiophen-2-yl-propynoic Acid Ethyl Ester (13)
Purification by column chromatography on silica gel (cyclohexane–acetone
8:2) provided the desired product as a red oil (49% yield). 1H NMR
(CDCl3, 400 MHz): 1.32 (t, J ¼ 7.2 Hz, 3H); 4.27 (dq, J ¼ 7.2 Hz, 2H);
7.01 (dd, J ¼ 3.6 Hz, J ¼ 5 Hz, 1H); 7.43 (d, J ¼ 5 Hz, 1H); 7.45
(d, J ¼ 3.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): 14.05; 62.05; 79.99;
84.88; 119.31; 127.47; 131.10; 136.44; 153.85. MS: m/z 181 (100%,
[M þ 1]þ). IR (NaCl): n 2932, 2210, 1705, 1267, 1218, 1162, 702 cm21
.
Pyridin-3-yl-propynoic Acid Ethyl Ester (14)
Purification by column chromatography on silica gel (cyclohexane–acetone
1
7:3) provided the desired product as a pale yellow oil (53% yield). H NMR
(CDCl3, 400 MHz): 1.29 (t, J ¼ 7.4 Hz, 3Ha); 4.20–4.25 (m, 2Hb); 7.24–
7.27(m, 1H); 7.79–7.80 (m, 1H); 8.58–8.59 (m, 1H); 8.74 (s, 1H). 13C
NMR (CDCl3, 100 MHz): 13.91; 62.23; 82.14; 83.43; 116.90; 123.09;
139.672; 150.56; 153.15; 153.35. MS: m/z 176 (100%, [M þ 1]þ). IR
(NaCl): n 2983, 2215, 1711, 1292, 1200, 1020, 701 cm21
.
(3-Methyl-3H-imidazol-4-yl)-propynoic Acid Ethyl Ester (15)
Purification by column chromatography on silica gel (DCM–acetone 8:2)
1
provided the desired product as a pale yellow solid (60% yield). H NMR
(CDCl3, 400 MHz): 1.33 (t, J ¼ 7.2 Hz, 3H); 4.28 (qd, J ¼ 7.2 Hz, 2H);

´
D. Lecercle et al.
1310
7.51 (s, 1H); 7.52 (s, 1H) 13C NMR (CDCl3, 100 MHz): 14.00; 32.26; 62.11;
74.78; 89.15; 113.34; 139.26; 140.05; 153.66. MS: m/z 179 (100%,
[M þ 1]þ). IR (KBr): n 2982, 2380, 2212, 1703, 1288, 1243, 1183, 1121,
1021 cm21
.
ACKNOWLEDGMENT
This work was supported by the Nuclear Toxicology program of the CEA, for
which grateful acknowledgment is made. We also thank E. Zekri and
D. Buisson for experimental assistance with MS and LC/MS measurements.
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3103–3115.
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Straightforward Synthesis
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