Simple method for the preparation of dialkyl (2,3-dihydro-1,3-thiazol-2-YL) -phosphonates

Article abstract of DOI:10.1080/10426501003767110

A simple synthesis of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates from thiazolium salts and trialkyl phosphites is described. The series of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates with various substituents in positions 3, 4, and 5 of the thiazole ring were prepared. However, only phosphonates with an aryl on the nitrogen atom were stable enough for chromatographic purification, although all the new phosphonates are very sensitive to oxidation. We made efforts to apply dialkyl (2,3-dihydro-1,3- thiazol-2-yl)-phosphonates in a Horner-Wadsworth-Emmons reaction, but the generated antiaromatic anion of phosphonate decomposed quickly, even at -70°C. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426501003767110

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Phosphorus, Sulfur, and Silicon and the
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Simple Method for the Preparation of
Dialkyl (2,3-Dihydro-1,3-thiazol-2-YL)-
phosphonates
Karolina Janikowska a & Sławomir Makowiec a
a Department of Organic Chemistry, Faculty of Chemistry, Gdansk
University of Technology, Gdańsk, Poland
Version of record first published: 13 Jan 2011.
To cite this article: Karolina Janikowska & Sławomir Makowiec (2010): Simple Method for the
Preparation of Dialkyl (2,3-Dihydro-1,3-thiazol-2-YL)-phosphonates, Phosphorus, Sulfur, and Silicon
and the Related Elements, 186:1, 12-20
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Phosphorus, Sulfur, and Silicon, 186:12–20, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003767110
SIMPLE METHOD FOR THE PREPARATION OF DIALKYL
(2,3-DIHYDRO-1,3-THIAZOL-2-YL)-PHOSPHONATES
Karolina Janikowska and Sławomir Makowiec
Department of Organic Chemistry, Faculty of Chemistry, Gdansk University
of Technology, Gdan´sk, Poland
GRAPHICAL ABSTRACT
R1
R1
R2
S
P(O)(OCH3)2
H
S
P(OCH3)3 / KI
CH3CN, bp, 4h
H
R2
N
N
R3
PF6
R3
Abstract A simple synthesis of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates from thia-
zolium salts and trialkyl phosphites is described. The series of dialkyl (2,3-dihydro-1,3-thiazol-
2-yl)-phosphonates with various substituents in positions 3, 4, and 5 of the thiazole ring were
prepared. However, only phosphonates with an aryl on the nitrogen atom were stable enough
for chromatographic purification, although all the new phosphonates are very sensitive to
oxidation. We made efforts to apply dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates in a
Horner–Wadsworth–Emmons reaction, but the generated antiaromatic anion of phosphonate
decomposed quickly, even at −70◦C.
Keywords Dithiadiazafulvalenes; organic metals; phosphonates
INTRODUCTION
The tetraheterofulvalenes belong to a class compounds that are in the circle of interest
of many laboratories, from physics to organic chemistry. Their popularity is due to the great
variety of applications of these compounds.
Most of the applications of tetraheterofulvalenes are as a result of their high electron-
donating properties; this group of compounds is usually an integral part of synthetic metals,1
semiconductors, and other advanced materials.2 The majority of applied tetraheteroful-
valenes contain four sulfur atoms or sulfur and selenium atoms due to their availability,
relative oxidation stability, and easy modification in side chain, and also due to the possi-
bility of preparing unsymmetrical tetrathiafulvalenes (TTF).3
Received 16 February 2010; accepted 10 March 2010.
We warmly thank Gdansk University of Technology for financial support under DS 014668/008.
Address correspondence to Dr. Sławomir Makowiec, Department of Organic Chemistry, Faculty of Chem-
istry, Gdansk University of Technology, Narutowicza 11/12, Gdan´sk 80-952, Poland. E-mail: mak@chem.
pg.gda.pl
12

DIALKYL (2,3-DIHYDRO-1,3-THIAZOL-2-YL)-PHOSPHONATES
13
The Horner–Wadsworth–Emmons reaction is successfully used for the preparation
of unsymmetrical tetrathiafulvalenes with high selectivity.4–7 The Wittig reaction may also
be used for the preparation of unsymmetrical tetrathiafulvalenes, however, with lower
selectivity.8–10 The aforementioned methods use 1,3-dithio-2-yl phosphonates esters or
1,3-dithio-2-yl phosphonium salts, respectively, as key intermediates.
However in recent years, there has been an interest in dithiadiazafulvalenes
(DTDAFs)11 as donor materials, but research in this area is limited due to the low stability
of DTDAFs and the lack of methods for modification of already prepared DTDAFs, as well
as a lack of a method for selective preparation of unsymmetrical dithiadiazafulvalenes.12
It is not difficult to deduce the hypothesis that unsymmetrical dithiadiazafulvalenes
1 could be prepared by the route similar to the strategy used for the preparation of un-
symmetrical TTF4–10 (Scheme 1) by the coupling of dialkyl (2,3-dihydro-1,3-thiazol-2-
yl)-phosphonates 2 and 2-piperidin-1,3-thiazolium salts or (2,3-dihydro-1,3-thiazol-2-yl)-
phosphonium salts 3 and 1,3-thiazolium salts.
Scheme 1 Possible routes of synthesis of unsymmetrical dithiadiazafulvalenes.
However it must be pointed out that required key intermediates dialkyl (2,3-dihydro-
1,3-thiazol-2-yl)-phosphonates 2 or (2,3-dihydro-1,3-thiazol-2-yl)-phosphonium salts 3 are
not common compounds, with only three examples of these phosphonates described in the
chemical literature. The first was published in 1967; Razumow et al.13 prepared (2,3-
dihydro-benzothiazol-2-yl)-phosphonate in the reaction of o-aminothiophenol with dialkyl
(dimethoxy)methylphosphonate. Takamizawa et al. obtained a phosphonate derivative of
thiamine14 in a multistep reaction. One example of (3-methyl-2,3-dihydro-benzothiazol-2-
yl)-phosphonate was also prepared in the cleavage of bis(3-methylthiazolidyn-2-ylidene)
with diethyl phosphite.15
Therefore we made an attempt to find an easy and efficient method for the preparation
of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates 2.

14
K. JANIKOWSKA AND S. MAKOWIEC
RESULTS AND DISCUSSION
It is well known that dithiadiazafulvalenes are very susceptible to oxidation by air
oxygen.11 Therefore, for our research, we needed models of thiazolium salts and phospho-
nates with an electron-withdrawing group to ensure the stability of possible unsymmetrical
DTDAF.12e 3H-Thiazole-2-thiones 5 with one electron-withdrawing group were prepared
from ethyl 2-chloroacetylacetate or 3-chloroacetylacetone and dithiocarbamate salts. They
were subsequently oxidized to thiazolium salts 4, based on adopted literature methods16
(Scheme 2). 3-Phenyl-4,5-dimethoxycarbonyl-3H-thiazole-2-thione 5j was prepared by the
cycloaddition of 2-phenylimino-1,3-dithiolane with dimethyl acetylenedicarboxylate.12e
We also attempted to obtain 3-methyl-4,5-diethoxycarbonyl-1,3-thiazolium tetrafluorobo-
rate 4b in a very inefficient process of condensation of 3-chloro-2-oxo-butanedioic acid with
thioformamide followed by alkylation with trimethyloxonium tetrafluoroborate (Scheme 2).
Scheme 2 Synthesis of dialkyl (2,3-dihydro-1,3-thiazol-2-yl)-phosphonates.
The first experiments were performed by treating a solution of 4b in acetonitrile
with trimethyl phosphite in the presence of potassium iodide (Scheme 2). Even though
we observed the formation of the new compound, any attempts to isolate it failed, as
the compounds decompose during chromatography. Next we tried to obtain (3-methyl-
2,3-dihydro-benzothiazol-2-yl)-phosphonate 2a from easily available N-methyl benzothia-
zolium iodide19 and trimethyl phosphite; we again observed the formation of a new product,
which decomposed during chromatography isolation.

DIALKYL (2,3-DIHYDRO-1,3-THIAZOL-2-YL)-PHOSPHONATES
15
It should be pointed out that Kucukbay et al.15 had prepared 2a from bis(3-
methylthiazolidyn-2-ylidene).17
We therefore repeated the experiment as described in the literature15 and compared
this reaction mixture with the crude reaction mixture composed of N-methyl benzothia-
zolium iodide and trimethyl phosphite in the 31P NMR experiment. We observed a signal
at 17,32 ppm, which increased after addition of an authentic sample.
The failure of the first experiments and the fact that 1,3-dithio-2-yl phosphonates4–7
and 1,3,4-thiadiazol-2-yl phosphonate18 are stable and easily isolable led us to the sup-
position that the instability may be related to the higher electron-donating properties of
nitrogen.
In the next experiments, we used a series of thiazolium salts with aryl on nitrogen
atom and ethoxycarbonyl, or acetyl in the 5 position of the ring. Reactions of thiazolium
salts with trimethyl phosphite in the presence of potassium iodide allowed us to produce the
desired phosphonates, which were stable enough in the cases of 2d–g for chromatography
purification under argon. However, we observed that any contact of the sample with air,
for example, during preparation of the NMR sample caused rapid decomposition of the
purified product to a complicated mixture of compounds. As we could only measure 13C
and 1H NMR spectra, our attempts to obtain good elemental analysis failed.
Surprisingly, in the case of salt 4c with an acetyl group, the obtained phosphonate
2c was not stable enough to isolate as a clean product. On the other hand, the instability
of phosphonate 2h, having the bulky 2-tert-butylphenyl group, seems to confirm our sup-
position that electron-donating properties of nitrogen have an influence on the stability of
(2,3-dihydro-1,3-thiazol-2-yl)-phosphonates.
In order to increase the stability of the produced phosphonates, we tried to obtain a
model with two electron-withdrawing groups at positions 4 and 5. Unfortunately 3-phenyl-
4,5-dimethoxycarbonyl-3H-thiazole-2-thione 5j was completely resistant to oxidation, and
we were not able to prepare thiazolium salt in this manner. We also tried to introduce
a 3-nitrophenyl substitutent on a nitrogen atom to enhance the stability of the prepared
phosphonate, but the obtained thione 5i was also resistant to oxidation to the thiazolium
salt.
As we indicate in our hypothesis, an alternative way to synthesize unsymmetrical
DTDAF can be led through (2,3-dihydro-1,3-thiazol-2-yl)-phosphonium salts. However,
we observed that thiazolium salts do not react with triphenylphosphine. From the reaction
mixtures of 3-methyl-4,5-diethoxycarbonyl-1,3-thiazolium tetrafluoroborate or 3-phenyl-
4-methyl-5-ethoxycarbonyl-1,3-thiazolium hexafluorphosphate with triphenylphosphine
in boiling acetonitrile, after 3 hours we recovered quantitatively unreacted substrates
(Scheme 2).
Despite the fact that only part of the prepared phosphonates showed moderate sta-
bility, we tried to perform Horner–Wadsworth–Emmons reactions between the prepared
phosphonate and benzaldehyde as the simplest model. We treated freshly prepared and puri-
fied 2d in the THF with tBuOK or LDA at −70◦C followed by the addition of benzaldehyde.
We obtained a complex mixture of products; we therefore tried another experiment where
we generated the anion from 2d at −70◦C with LDA, and after 0.5 hours quenched it with
D2O. Surprisingly we did not recover deutered starting material, but instead again obtained
a complex mixture of products. These results suggest that the antiaromatic anion of the
phosphonate decomposes after generation, similar to the decomposition of 1,3-dithiol-2-
yl-phophonate anion observed by Fourmigue et al.4

16
K. JANIKOWSKA AND S. MAKOWIEC
EXPERIMENTAL
Reagents were purchased from Sigma-Aldrich. Acetonitrile was distilled from CaH2
under argon. Analytical TLC was performed on aluminum sheets of silica gel UV-254
from Merck. Flash chromatography was carried out using 40–63 microns silica gel from
Zeochem. The 1H, 13C, and 31P spectra were recorded on a Varian Gemini 200 and a Varian
Unity Plus 500.
Commercially unavailable reagents were prepared by the procedures in the literature
as follows: bis(3-methylthiazolidyn-2-ylidene),17 N-methyl benzothiazolium iodide 4a,19
2-phenylimino-1,3-dithiolane,20 and 3-phenyl-4,5-dimethoxycarbonyl-1,3-thiazol-2(3H)-
thion 5j.12e
4,5-Diethoxycarbonyl-1,3-thiazol
To the cooled to −10◦C suspension of diethyl oxalacetate sodium salt (10.5 g, 50
mmol) in dry ether (100 mL), SO2Cl2 (7.42 g, 55 mmol) was added over 0.5 h. Then, the
reaction was stirred for 3 h, filtered, and solvent was removed under reduced pressure. The
residue was dissolved in EtOH (100 mL), cooled to −10◦C, and a suspension of HC(S)NH2
in EtOH (100 mL) that was freshly prepared from HC(O)NH2 (4.5 g, 100 mmol) and P2S5
(4.44 g, 20 mmol) was added dropwise. The reaction was stirred 24 h at rt. EtOH was
removed under reduced pressure, and the oil was dissolved in 100 mL of AcOEt, washed
off with 1 M NaOH (3 × 25 mL), and dried with MgSO4, and the solvent was removed
under reduced pressure. The crude product was purified by flash chromatography on silica
gel using CH2Cl2 as eluent.
Oily liquid. Yield: 1.61 g, 14%, 1H NMR (500 MHz, CDCl3) δ: 8.86 (s, 1H), 4.47 (q,
2H, J = 7.32 Hz), 4.40 (q, 2H, J = 7.32 Hz), 1.43 (t, 3H, J = 7.32 Hz), 1.39 (t, 2H, J =
7.32 Hz).
3-Methyl-4,5-diethoxycarbonyl-1,3-thiazolium Tetrafluoroborate 4b
4,5-Diethoxycarbonyl-1,3-thiazol (1.6 g, 7 mmol) was dissolved in CH2Cl2, and
trimethyloxonium tetrafluoroborate (1.47 g, 10 mmol) was added. The solution was stirred
for 24 h. Methanol (1 mL) was added, the solvent was removed under reduced pressure,
and the residue was crystallized from CH2Cl2/Et2O.
White solid. Yield: 1.85 g, 79%, mp: 110–111◦C, 1H NMR (500 MHz, acetone-d6)
δ: 10.38 (s, 1H), 4.61 (q, 2H, J = 7.3 Hz), 4.51 (q, 2H, J = 6.8 Hz), 4.49 (s, 2H), 1.43
(m, 6H) 13C NMR (125 MHz, acetone-d6) δ: 164.0, 157.5, 157.1, 141.7, 134.2, 64.7, 64.2,
42.5, 13.5, 13.3.
General Procedure for the Preparation of 3H-Thiazole-2-thiones 5c–i
3H-Thiazole-2-thiones 5c–i were obtained by the adopted method described in lit-
erature for analogous compounds.16 To a solution of derivative of aniline (100 mmol) in
DMSO (50 mL), 20 M NaOH (5 mL) was added. The mixture was cooled to 0◦C, and
CS2 (100 mmol, 7.61 g, 6 mL) was added. The reaction was stirred for 1 h at rt, cooled
again to 0◦C, and ethyl 2-chloroacetylacetate (100 mmol, 16.45 g), or in the case of 5c,
3-chloroacetylacetone (100 mmol, 13.45 g), was added. The reaction mixture was stirred
for an additional 1 h at rt, and ice (100 g) was added. The solidified product was filtered,

DIALKYL (2,3-DIHYDRO-1,3-THIAZOL-2-YL)-PHOSPHONATES
17
suspended in EtOH (100 mL), treated with conc. HCl (5 mL), and heated to reflux for 1 h.
After cooling to rt, the crude precipitated product was filtered and crystallized from EtOH.
3-Phenyl-4-methyl-5-acetyl-3H-thiazole-2-thione 5c. Yellow solid. Yield:
1
13.44 g, 54%, mp: 171–174◦C, H NMR (500 MHz, CDCl3) δ: 7.62–7.54 (m, 3H),
7.28–7.23 (m, 2H), 2.43 (s, 3H), 2.33 (s, 3H) 13C NMR (125 MHz, CDCl3) δ: 189.7,
188.5, 147.6, 137.4, 130.5, 130.4, 128.4, 121.3, 30.6, 16.5.
3-Phenyl-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione
5d. White
1
solid. Yield: 20.64 g, 74%, mp: 158–160◦C, H NMR (500 MHz, CDCl3) δ: 7.61–7.54
(m, 3H), 7.28–7.23 (m, 2H), 4.34 (q, 2H, J = 7.3 Hz), 2.34 (s, 3H, Me), 1.37 (t, 3H, J =
7.3 Hz) 13C NMR (125 MHz, CDCl3) δ: 190.7, 160.4, 148.8, 137.6, 130.4, 130.3, 128.4,
112.6, 61.9, 15.8, 14.5.
3-(4-Methylphenyl)-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione 5e.
White solid. Yield: 19.04 g, 65%, mp: 143–145◦C, 1H NMR (200 MHz, CDCl3) δ: 7.37 (d,
2H, J = 8.4 Hz), 7.10 (d, 2H, J = 8.4 Hz), 4.32 (q, 2H, J = 7.2 Hz), 2.44 (s, 3H), 2.32 (s,
3H), 1.36 (t, 3H, J = 7.2 Hz), 13C NMR (125 MHz, CDCl3) δ: 190.8, 160.4, 148.9, 140.6,
134.9, 131.1, 128.1, 112.5, 61.9, 21.7, 15.8, 14.5.
3-(4-Bromophenyl)-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione 5f.
White solid. Yield: 22.19 g, 62%, mp: 145–148◦C, 1H NMR (500 MHz, CDCl3) δ: 7.72 (d,
2H, J = 8.3 Hz), 7.14 (d, 2H, J = 8.3 Hz), 4.33 (q, 2H, J = 6.8 Hz), 2.34 (s, 3H), 1.37 (t,
3H, J = 6.8 Hz), 13C NMR (125 MHz, CDCl3) δ: 190.2, 159.9, 147.9, 136.1, 133.4, 129.8,
124.3, 112.6, 61.6, 15.4, 14.2.
3-(4-Chlorophenyl)-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione 5g.
White solid. Yield: 19.43 g, 62%, mp: 136–138◦C, 1H NMR (500 MHz, CDCl3) δ: 7.57 (d,
2H, J = 8.3 Hz), 7.20 (d, 2H, J = 8.3 Hz), 4.34 (q, 2H, J = 7.3 Hz), 2.34 (s, 3H), 1.37 (t,
3H, J = 7.3 Hz), 13C NMR (125 MHz, CDCl3) δ: 190.6, 160.2, 148.3, 136.5, 135.9, 130.8,
129.9, 112.9, 62.0, 15.8, 14.5.
3-(2-Tert-butylphenyl)-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione
1
5h. White solid. Yield: 8.71 g, 26%, mp: 107–109◦C, H NMR (500 MHz, CDCl3) δ:
7.70 (d, 1H, J = 8.3 Hz), 7.50 (t, 1H, J = 7.3 Hz), 7.36 (t, 1H, J = 7.3 Hz), 6.88 (d, 1H,
J = 8.3 Hz), 4.33 (q, 2H, J = 7.3 Hz), 2.32 (s, 3H), 1.39 (t, 3H, J = 7.3 Hz), 1.30 (s, 9H),
13C NMR (125 MHz, CDCl3) δ: 191.2, 160.48, 149.6, 147.4, 134.4, 131.4, 130.5, 130.4,
128.0, 112.6, 61.9, 36.7, 32.0, 16.3, 14.5.
3-(3-Nitrophenyl)-4-methyl-5-ethoxycarbonyl-3H-thiazole-2-thione 5i.
1
White solid. Yield: 11.98 g, 37%, mp: 175–177◦C, H NMR (500 MHz, CDCl3) δ: 8.44
(dd, 1H, J = 8.3 Hz, J = 1.5 Hz), 8.17 (t, 1H, J = 1.5 Hz), 7.83 (t, 1H, J = 7.3 Hz), 7.64
(dd, 1H, J = 8.3 Hz, J = 1.5 Hz), 4.36 (q, 2H, J = 7.3 Hz), 2.38 (s, 3H), 1.39 (t, 3H, J =
7.3 Hz).
General Procedure for the Preparation of 1,3-Thiazolium
Hexafluorophosphates 4c–h
1,3-Thiazolium hexafluorophosphates 4c–h were obtained by the adopted method
described in literature for analogous compounds.16 Compounds 5c–h (2 mmol) were dis-
solved in acetic acid (5 mL), and 30% H2O2 (0.67 mL) was added. The solution was stirred
at rt for 1 h for 4c–e or 2.5 h for 4f–g. Acetic acid was removed under reduced pressure. To
the oily residue, 60% HPF6 solution in water (0.29 mL) and water (20 mL) were added. The
precipitate was filtered, washed with water, dissolved in CH2Cl2, and dried with MgSO4.

18
K. JANIKOWSKA AND S. MAKOWIEC
The solvent was removed under reduced pressure, and the residue was crystallized from
CH2Cl2/Et2O.
3-Phenyl-4-methyl-5-acetyl-1,3-thiazolium hexafluorophosphate 4c.
White solid. Yield: 0.465 g, 64%, mp: 87–90◦C, 1H NMR (500 MHz, acetone-d6) δ: 10.49
(s, 1H), 7.85- 7.81 (m, 5H), 2.84 (s, 3H), 2.76 (s, 3H), 13C NMR (125 MHz, acetone-d6)
δ = 189.3, 161.5, 150.6, 136.9, 136.7, 132.3, 130.7, 126.7, 29.7, 14.2.
3-Phenyl-4-methyl-5-ethoxycarbonyl-1,3-thiazolium
hexafluorophos-
1
phate 4d. White solid. Yield: 0.621 g, 79%, mp: 157–158◦C, H NMR (500 MHz,
acetone-d6) δ: 10.53 (s, 1H), 7.86- 7.79 (m, 5H), 4.55 (q, 2H, J = 7.3 Hz), 2.75 (s, 3H),
1.44 (t, 3H, J = 7.3 Hz), 13C NMR (125 MHz, acetone-d6) δ = 162.0 159.0, 152.9, 136.8,
132.4, 130.7, 127.5, 126.7, 63.6, 13.7, 13.6.
3-(4-Methylphenyl)-4-methyl-5-ethoxycarbonyl-1,3-thiazolium hexafluo-
1
rophosphate 4e. White solid. Yield: 0.651 g, 80%, mp: 130–132◦C, H NMR (200
MHz, acetone-d6) δ: 9.63 (s, 1H), 7.45–7.38 (m, 4H), 4.46 (q, 2H, J = 7.2 Hz), 2.62 (s,
3H), 2.48 (s, 3H), 1.42 (t, 3H, J = 7.2 Hz) 13C NMR (125 MHz, acetone-d6) 160.1, 158.6,
152.2, 143.2, 133.6, 131.4, 127.9, 125.8, 63.8, 21.6, 14.3, 14.1.
3-(4-Bromophenyl)-4-methyl-5-ethoxycarbonyl-1,3-thiazolium hexafluo-
rophosphate 4f. White solid. Yield: 0.585 g, 62%, mp: 132–134◦C, 1H NMR (500 MHz,
acetone-d6) δ: 10.5 (s, 1H), 7.97 (dd, 2H, J = 9.1 Hz, J = 2.5 Hz), 7.80 (dd, 2H, J = 9.1
Hz, J = 2.5 Hz), 4.52 (q, 2H, J = 7.3 Hz), 2.75 (s, 3H), 1.42 (t, 3H, J = 7.3 Hz), 13C
NMR (125 MHz, acetone-d6) δ: 162.2, 158.9, 152.9, 135.9, 133.8, 128.8, 127.5, 126.1,
63.6, 13.7, 13.6.
3-(4-Chlorophenyl)-4-methyl-5-ethoxycarbonyl-1,3-thiazolium hexafluo-
rophosphate 4g. White solid. Yield: 0.469 g, 55%, mp: 96–98◦C, 1H NMR (500 MHz,
acetone-d6) δ: 10.55 (s, 1H), 7.90 (dd, 2H, J = 8.8 Hz, J = 2.5 Hz), 7.85 (dd, 2H, J =
8.8 Hz, J = 2.5 Hz), 4.55 (q, 2H, J = 7.3 Hz), 2.78 (s, 3H), 1.45 (t, 3H, J = 7.3 Hz),
13C NMR (125 MHz, acetone-d6) δ: 162.4, 158.9, 152.9, 137.9, 135.4, 130.7, 128.7, 127.5,
63.6, 13.7, 13.6.
3-(2-Tert-butylphenyl)-4-methyl-5-ethoxycarbonyl-1,3-thiazolium hexa-
fluorophosphate 4h. White solid. Yield: 0.666 g, 74%, mp: 138–143◦C, 1H NMR (500
MHz, acetone-d6) δ: 10.75 (s, 1H), 7.97 (d, 1H, J = 8.3 Hz), 7.77 (t, 1H, J = 8.3 Hz),
7.55 (m, 2H, J = 7.3 Hz), 4.55 (q, 2H, J = 7.3 Hz), 2.70 (s, 3H), 1.45 (t, 3H, J = 7.3 Hz),
1.26 (s, 9H), 13C NMR (125 MHz, acetone-d6) δ: 163.8, 159.5, 154.2, 146.4, 134.6, 133.2,
131.5, 129.9, 129.0, 128.8, 64.2, 36.9, 31.9, 14.7, 14.2.
General Procedure for the Preparation Dimethyl (2,3-Dihydro-1,3-
thiazol-2-yl)-phosphonates 2d–g
To the solution of thiazolium salt 4d–g in acetonitrile (20 mL) under argon, KI
(0.5 mmol, 83 mg) and trimethyl phosphite (0.5 mmol, 59 µL) were added. The reaction
mixture was stirred and heated to reflux for 4 h. After removing the solvent under reduced
pressure, the residue was purified by flash chromatography. All operations must be done
under an argon atmosphere.
Dimethyl 3-phenyl-4-methyl-5-ethoxycarbonyl (2,3-dihydro-1,3-thiazol-
2-yl)-phosphonate 2d. Eluent AcOEt/hexane (3:1). Oil. Yield: 0.144 g, 80%, 1H NMR
2
(500 MHz, CDCl3) δ: 7.40 (m, 2H), 7.28 (m, 3H), 5.48 (d, 1H, JPH = 5.8 Hz), 4.20 (q,
3
3
2H, J = 7.3 Hz), 3.78 (d, 3H, JPH = 2.9 Hz), 3.76 (d, 3H, JPH = 3.4 Hz), 2.09 (s, 3H),
1.30 (t, 3H, J = 7.3 Hz), 13C NMR (125 MHz, CDCl3) δ: 164.0, 151.7, 142.24 (d, 3JPC
=

DIALKYL (2,3-DIHYDRO-1,3-THIAZOL-2-YL)-PHOSPHONATES
19
2.2 Hz), 129.8, 127.6, 127.3, 100.06 (d, 3JPC = 2.2 Hz), 65.6 (d, 1JPC = 178 Hz), 60.6, 54.5
(d, 2JPC = 6.8 Hz), 15.3, 14.6. 31P NMR (200 MHz, CDCl3) δ: 17.36.
Dimethyl 3-(4-methylphenyl)-4-methyl-5-ethoxycarbonyl (2,3-dihydro-
1,3-thiazol-2-yl)-phosphonate 2e. Eluent AcOEt/hexane (3:1). Oil. Yield: 0.139 g,
1
2
75%, H NMR (500 MHz, CDCl3) δ: 7.20 (s, 4H), 5.47 (d, 1H, JPH = 6.3 Hz), 4.21 (q,
3
3
2H, J = 7.3 Hz), 3.78 (d, 3H, JPH = 4.8 Hz), 3.76 (d, 3H, JPH = 4.3 Hz), 2.37 (s, 3H),
2.09 (s, 3H), 1.30 (t, 3H, J = 7.3 Hz), 13C NMR (125 MHz, CDCl3) δ: 163.7, 151.9,
139.12 (d, 3JPC = 1.5 Hz), 137.5, 130.0, 127.1, 98.5, 65.2 (d, 1JPC = 177 Hz), 60.1, 54.1
(d, 2JPC = 7.6 Hz), 20.9, 14.8, 14.3, 31P NMR (200 MHz, CDCl3) δ: 17.37.
Dimethyl 3-(4-bromophenyl)-4-methyl-5-ethoxycarbonyl (2,3-dihydro-
1,3-thiazol-2-yl)-phosphonate 2f. Eluent AcOEt/hexane (3:1). Oil. Yield: 0.168 g,
77%, 1H NMR (500 MHz, CDCl3) δ: 7.48 (d, 2H, J = 8.3 Hz), 7.17 (d, 2H, J = 8.3 Hz),
5.37 (d, 1H, 2JPH = 5.3 Hz), 4.19 (q, 2H, J = 7.3 Hz), 3.78 (d, 3H, 3JPH = 10.0 Hz), 3.76
(d, 3H, 3JPH = 10.0 Hz), 2.37 (s, 3H), 2.07 (s, 3H), 1.27 (t, 3H, J = 7.3 Hz), 13C NMR (125
MHz, CDCl3) δ: 163.8, 150.6, 141.5 (d, 3JPC = 2.5 Hz), 132.9, 128.6, 121.0, 101.7, 65.51
(d, 1JPC = 179 Hz), 60.7, 54.7 (d, 2JPC = 7.1 Hz), 54.5 (d, 2JPC = 6.1 Hz), 15.2, 14.6, 31
NMR (200 MHz, CDCl3) δ: 17.11.
P
Dimethyl 3-(4-chlorophenyl)-4-methyl-5-ethoxycarbonyl (2,3-dihydro-
1,3-thiazol-2-yl)-phosphonate 2g. Eluent AcOEt/hexane (5:2). Oil. Yield: 0.137 g,
70%, 1H NMR (500 MHz, CDCl3) δ: 7.34 (d, 2H, J = 8.3 Hz), 7.23 (d, 2H, J = 8.3 Hz),
5.37 (d, 1H, 2JPH = 5.4 Hz), 4.18 (q, 2H, J = 7.1 Hz), 3.78 (d, 3H, 3JPH = 10.7 Hz), 3.76
3
(d, 3H, JPH = 10.2 Hz), 2.37 (s, 3H), 2.06 (s, 3H), 1.27 (t, 3H, J = 7.1 Hz), 13C NMR
1
(125 MHz, CDCl3) δ: 163.9, 150.8, 140.9, 133.2, 129.9, 128.4, 101.3, 65.55 (d, JPC
=
179 Hz), 60.7, 54.7 (d, 2JPC = 7.6 Hz), 54.5 (d, 2JPC = 7.6 Hz), 15.2, 14.6, 31P NMR (200
MHz, CDCl3) δ: 17.13.
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