Direct Phosphorylation of Thiazoles and Naphtothiazoles by Phosphorus(V) Acid Chlorides

Article abstract of DOI:10.1081/SCC-120027709

Direct C(2)-phosphorylation of 4,5,6,7-tetrahydrobenzothiazole, isomeric naphtho[1,2-d][1,3]- and naphtho[2,1-d][1,3]thiazoles with HgCl₂ as catalyst is reported. An analogous reaction of unsubstituted thiazole did not require catalyst.

Full text of DOI:10.1081/SCC-120027709

This article was downloaded by: [Mount Allison University 0Libraries]
On: 04 June 2013, At: 10:42
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
Direct Phosphorylation of Thiazoles and
Naphtothiazoles by Phosphorus(V) Acid Chlorides
Aleksandr V. Strizhak a , Mikhail Yu. Kornilov a , Andrey A. Tolmachev b & Igor V. Komarov
a
a Department of Chemistry, Kiev Taras Shevchenko University, Vladimirskaya Street, 64,
Kiev, 01033, Ukraine
b Institute of Organic Chemistry of National Academy of Sciences of Ukraine, Kiev,
Ukraine
Published online: 16 Aug 2006.
To cite this article: Aleksandr V. Strizhak , Mikhail Yu. Kornilov , Andrey A. Tolmachev & Igor V. Komarov (2004): Direct
Phosphorylation of Thiazoles and Naphtothiazoles by Phosphorus(V) Acid Chlorides, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 34:4, 615-624
To link to this article: http://dx.doi.org/10.1081/SCC-120027709
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
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.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses
should be independently verified with primary sources. The publisher shall not be liable for any loss, actions,
claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 4, pp. 615–624, 2004
Direct Phosphorylation of Thiazoles and
Naphtothiazoles by Phosphorus(V)
Acid Chlorides
Aleksandr V. Strizhak,1 Mikhail Yu. Kornilov,1
Andrey A. Tolmachev,2 and Igor V. Komarov1,
*
1Department of Chemistry, Kiev Taras Shevchenko University,
Kiev, Ukraine
2Institute of Organic Chemistry of National Academy of Sciences
of Ukraine, Kiev, Ukraine
ABSTRACT
Direct C(2)-phosphorylation of 4,5,6,7-tetrahydrobenzothiazole, isomeric
naphtho[1,2-d][1,3]- and naphtho[2,1-d][1,3]thiazoles with HgCl2 as
catalyst is reported. An analogous reaction of unsubstituted thiazole did
not require catalyst.
Key Words: Direct phosphorylation; Thiazoles; Naphtothiazoles;
Phosphorus(V); Acid chlorides.
*
Correspondence: Igor V. Komarov, Department of Chemistry, Kiev Taras
Shevchenko University, Vladimirskaya Street, 64, Kiev 01033, Ukraine; E-mail:
ik214@mail.yahoo.com.
615
DOI: 10.1081/SCC-120027709
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
616
Strizhak et al.
1,3-Azoles undergo smooth C2-phosphorylation by P(III) and P(V) acid
halides in pyridine-triethylamine solution.[1] In our previous work[2] we
reported Hg(II)-catalyzed C-phosphorylation of benzothiazole and 4-methyl-
thiazole by both P(III) and P(V) acid halides. It is of interest to investigate the
scope of this reaction, which can lead to different thiazolylphosphinic acids
and their derivatives which are of great preparative and biological inter-
est.[1,3,4] We now report simple procedures for the direct C(2)-phosphorylation
of thiazole, 4,5,6,7-tetrahydrobenzothiazole and naphtho[2,1-d][1,3]thiazole
by P(V) acid chlorides.
We found that 4,5,6,7-tetrahydrobenzothiazole 1 did not undergo
phosphorylation under standard conditions (Py/NEt3 solution, 258C) even
after 2 weeks, but catalytic amounts of HgCl2 (like in the case of
benzothiazole) promoted smooth phosphorylation of 1 by MePOCl2 (2a) and
PhPOCl2 (2b). The reaction was complete in one day according to 31P NMR
spectroscopy. It was carried out in a pyridine-triethylamine solution and the
products are the corresponding phosphinic acid chlorides 3a and 3b which
were characterized by 31P NMR spectroscopy and transformed into the
corresponding potassium salts 4a-b without isolation (Sch. 1):
Scheme 1.
The resulting salts 4a-b were easily transformed back to the acid chlorides
by PCl5 in phosphorus oxychloride solutions in high yield (Sch. 2). This
reaction 4a-b to 3a-b is a good synthetic method for obtaining acid chlorides
3a-b and much better then the isolation of acid chlorides from the pyridine
solutions after phosphorylation 1a-b to 3a-b. The resulting phosphinic acid
chlorides 3a-b were transformed into the amides 5a-l, 6a-g as shown in Sch. 2:
Scheme 2.
It turned out that the unsubstituted thiazole 7 reacts slowly with PhPOCl2
in pyridine-triethylamine solution without Hg (II) catalyst. The reaction is
complete in about 2 weeks. The product of the reaction is the expected C-2

ORDER
REPRINTS
Direct Phosphorylation of Thiazoles and Naphtothiazoles
617
substituted phosphinic acid chloride 8 which was characterized by 31P NMR
spectroscopy and transformed into phosphinic acid potassium salt 9 without
isolation (Sch. 3):
Scheme 3.
We have studied the analogous phosphorylation of isomeric naphtho[1,2-
d][1,3]- and naphtho[2,1-d][1,3]thiazoles (10 and 11 respectively). We found
out that without HgCl2 catalyst neither 10 nor 11 reacts with MePOCl2, only
starting materials were recovered. However in the presence of a catalytic
amount of HgCl2 compound 11 undergoes phosphorylation by MePOCl2, the
naphtothiazole 10 does not react (even after 2 weeks). The reaction was
carried out in pyridine-triethylamine and followed by 31P NMR spectroscopy.
The product of reaction is the expected phosphinic acid chloride 12, which
was transformed into the acid 13 without isolation (Sch. 4):
Scheme 4.
We propose the following mechanistic explanation of the facts described
above. One can postulate that the phosphorylation of azoles proceeds through
formation of carbene species 14 stabilized by p-delocalization (Sch. 5). These
carbenes can be generated in the basic reaction medium after the formation of
the N-phosphoryl intermediate 15 that increase the acidity of the C(2)H
fragment.
It is interesting to note that generation of analogous carbenes was
achieved by Wanzlick already 40 years ago.[5] What is particular relevant to
this work is that he has obtained carbenes 16 from the corresponding
benzothiazolium salts by deprotonation with NEt3 (Sch. 6).

ORDER
REPRINTS
618
Strizhak et al.
Scheme 5.
Scheme 6.
The chemistry of the heterocyclic carbenes was boosted when Arduengo
et. al. reported the isolation of a stable, crystalline imidazol-derived carbene
17.[6] The analogous stable thiazol-derived carbene 18 had also been
synthesized.
The carbenes like 17 and 18 exist in the singlet ground state, unlike
“normal” triplet carbenes, and are highly nucleophilic. They also readily form
complexes with transition metals acting as neutral two-electron ligands. One
of such a complex 19 with Hg2þ was obtained by Wanzlick already in 1968
(Sch. 7):[7]
Scheme 7.
We suggest that an analogous complex is formed during the
phosphorylation of benzothiazoles 4a, 4b, 11 in the presence of HgCl2
which facilitate the phosphorylation. In the case of naphtho[1,2-d][1,3]-
thiazole (10), however, the corresponding N-phosphoryl intermediate 15

ORDER
REPRINTS
Direct Phosphorylation of Thiazoles and Naphtothiazoles
619
cannot form because of steric hindrances at the nitrogen atom. Obviously, as
formation of the N-phosphoryl intermediate, and consequently the carbene
from the parent compound, thiazole, proceeds more easily, phosphorylation of
this heterocycle does not require the catalyst.
EXPERIMENTAL
NMR spectra were recorded on a Bruker WP-100SY spectrometer
(100.13 MHz for protons), TMS was used as an internal standard for 1H NMR
spectra, 85% H3PO4 was an external standard for 31P NMR measurements.
Melting points were measured on a hot stage and are uncorrected. Pyridine and
triethylamine were dried over KOH and distilled.
Phosphorylation of 4,5,6,7-tetrahydro-1,3-benzothiazole by PhPOCl2
and CH3POCl2 was performed using the following standard procedure. (All
the operations must be carried out under a dry, inert atmosphere). To a stirred
mixture of 4,5,6,7-tetrahydro-1,3-benzothiazole (1 equiv., usually 8 mmol),
triethylamine (1.2 equiv., usually 9.6 mmol), HgCl2 (0.1 equiv., usually
0.8 mmol) and pyridine (to obtain approximately 1 M solution of the hetero-
cyclic compound) phosphorylating reagent (1.1 equiv.) in pyridine (1 : 1 vol.)
was added dropwise during 10 min. The reaction is slightly exothermic,
.
formation of crystals (NEt3 HCl) was observed. The course of the reaction
can be easily followed by 31P NMR spectroscopy. After no changes in the 31
P
NMR specta were observed, the reaction mixture was worked-up as described
below.
Methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic acid pot-
assium salt (4a) was obtained from 4,5,6,7-tetrahydro-1,3-benzothiazole
(1, 10 g, 71.8 mmol) and MePOCl2 (2a). After reaction was complete the
mixture was poured carefully into water (about 200 mL) and solid potassium
carbonate was added with stirring until no CO2 was evolved. The resulting
solution was evaporated to dryness under reduced pressure and the solid
residue was extracted by dry methanol. The methanol solution was
concentrated and salt 4a was precipitated by the large excess of dry acetone.
The formed precipitate was dried in vacuo over P4O10. Pale yellow solid
(16.87 g, 92%). 1H NMR (CD3OD, d) 2.8–2.5 (m, 4H), 1.9–1.6 (m, 4H), 1.40
(d, 2JP–H ¼ 15.4 Hz, 3H). Anal. Calcd for C8H11KNO2PS [255.32]: C, 37.63;
H, 4.34; N, 5.49. Found: C, 37.05; H, 4.56; N, 5.66.
Phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic acid pot-
assium salt (4b) was prepared analogously to 4a from 8 g (57.5 mmol) of 1
and PhPOCl2 (2b). After the working-up the salt was recrystallized from
ethanol. Colorless solid (15.67 g, 86%). 1H NMR (DMSO-D6, d): 7.8–7.5 (m,
2H), 7.3–7.1 (m, 3H), 2.8–2.5 (m, 4H), 1.8–1.5 (m, 4H). Anal. Calcd for

ORDER
REPRINTS
620
Strizhak et al.
C13H13KNO2PS [317.39]: C, 49.20; H, 4.13; N, 4.41. Found: C, 49.01; H,
4.20; N, 4.49.
Synthesis of chloroanhydrides 3a-b from phosphinic acid salts 4a-b
was performed using the following standard procedure. (All the operations
must be carried out under a dry, inert atmosphere). To a 30 mL of phos-
phorus oxychloride phosphinic acid potassium salt 4a or b (8 g) was added
carefully with stirring. After that fine powdered phosphorus pentachloride
(1.5 eq. per 1 eq. of salt) was added and the formed mixture was carefully
heated to the beginning of vigorous reaction. Then the mixture was refluxed
for 15 min. The precipitate of potassium chloride was filtered off and the
filtrate was evaporated under reduced pressure to give choloanhydride as pale
yellow oil.
Methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic chloride
(3a) was prepared from 4a and was distilled in vacuo. B.p. 160–1708C
(0.08 Hg mm). Pale yellow viscous oil (6.05 g, 82%). 31P NMR (CDCl3, d):
1
2
39; H NMR (CDCl3, d): 3.1–2.6 (m, 4H), 2.33 (d, JP–H ¼ 15.1 Hz, 3H),
2.0–1.7 (m, 4H). Anal. Calcd for C8H11ClNOPS [235.67]: C, 40.77; H, 4.70;
N, 5.94. Found: C, 40.95; H, 4.83; N, 6.11.
Phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic chloride
(3b) was prepared from 4b and was used for synthesis of amides 6a-f without
further purification. Yellow viscous oil (7.15 g, 95%). 31P NMR (CDCl3, d):
28; 1H NMR (CDCl3, d): 8.2–7.7 (m, 2H), 7.6–7.3 (m, 3H), 3.0–2.6 (m, 4H),
1.9–1.6 (m, 4H). Anal. Calcd for C13H13ClNOPS [297.75]: C, 52.44; H, 4.40;
N, 4.70. Found: C, 52.78; H, 4.72; N, 4.98.
Synthesis of amides 5a-l, 6a-f from corresponding phosphinic acid
chlorides (3a-b) was carried out in dry atmosphere using the following
procedure. To a solution of appropriate acid chloride (5 mmol) in 10 mL of
dioxane solution of appropriate amine (5 mmol) and triethylamine (5.5 mmol)
in 5 mL of dioxane was added dropwise during 3 min. The mixture was stirred
for 1 h, evaporated under reduced pressure and 10 mL of 5% solution of
potassium carbonate was added. The resulting oily or solid amide was
crystallized from acetone.
Methyl-N-phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic
amide (5a) was synthesized from 3a and aniline. Colorless crystals, m.p.
1
1348C (1.330 g, 91%). 31P NMR (acetone-D6, d): 22; H NMR (acetone-D6,
d): 7.48 (d, 2JP–H ¼ 13.7 Hz, 1H), 7.2–7.0 (m, 3H), 6.9–6.7 (m, 2H), 2.9–2.6
(m, 4H), 1.9–1.6 (m, 7H). Anal. Calcd for C14H17N2OPS [292.34]: C, 57.52;
H, 5.86; N, 9.58. Found: C, 57.36; H, 5.98; N, 9.75.
Methyl-N-(2-methylphenyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-
ylphosphinic amide (5b) was synthesized from 3a and o-toluidine. Colorless
crystals, m.p. 1388C (1.255 g, 82%). 1H NMR (CDCl3, d): 7.39 (d, 1H), 7.2–
6.8 (m, 3H), 5.41 (d, 2JP–H ¼ 10.0 Hz, 1H), 2.9–2.7 (m, 4H), 2.0–1.7 (m, 7H).

ORDER
REPRINTS
Direct Phosphorylation of Thiazoles and Naphtothiazoles
621
Anal. Calcd for C15H19N2OPS [306.37]: C, 58.81; H, 6.25; N, 9.14. Found: C,
58.56; H, 6.32; N, 9.21.
Methyl-N-(3-methylphenyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-
ylphosphinic amide (5c) was synthesized from 3a and m-toluidine. Colorless
1
crystals, m.p. 1538C (1.286 g, 84%). H NMR (CDCl3, d): 7.1–6.6 (m, 4H),
6.44 (d, 2JP–H ¼ 13 Hz, 1H), 2.9–2.7 (m, 4H), 2.23 (s, 3H), 2.0–1.7 (m, 7H),
Anal. Calcd. for C15H19N2OPS [306.37]: C, 58.81; H, 6.25; N, 9.14. Found: C,
58.73; H, 6.29; N, 9.18.
N-(4-fluorophenyl)methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide (5d) was synthesized from 3a and p-fluoroaniline.
Colorless crystals, m.p. 1378C (1.459 g, 94%). 1H NMR (CDCl3, d): 7.2–6.7
2
(m, 4H), 6.32 (d, JP–H ¼ 11 Hz, 1H), 3.0–2.7 (m, 4H), 2.0–1.7 (m, 7H).
Anal. Calcd. for C14H16FN2OPS [310.33]: C, 54.18; H, 5.20; N, 9.03. Found:
C, 54.06; H, 5.22; N, 9.12.
N-(3-chlorophenyl)methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide (5e) was synthesized from 3a and m-chloroaniline.
Colorless crystals, m.p. 848C (1.291 g, 79%). 1H NMR (acetone-D6, d): 7.70
(broad s, 1H), 7.30 (s, 1H), 7.14 (d, 2H), 6.9–6.8 (m, 1H), 2.9–2.6 (m, 4H),
1.9–1.6 (m, 7H). Anal. Calcd. for C14H16ClN2OPS [326.79]: C, 51.46; H,
4.94; N, 8.57. Found: C, 51.55; H, 5.04; N, 8.69.
N-(4-chlorophenyl)methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide (5f) was synthesized from 3a and p-chloroaniline.
1
Colorless crystals, m.p. 1538C (1.373 g, 84%). H NMR (CDCl3, d): 7.37
2
(d, JP–H ¼ 13.4 Hz, 1H), 7.03 (dd, 4H), 2.9–2.7 (m, 4H), 2.0–1.7 (m, 7H).
Anal. Calcd. for C14H16ClN2OPS [326.79]: C, 51.46; H, 4.94; N, 8.57. Found:
C, 51.51; H, 4.78; N, 8.77.
N-(2,5-dichlorophenyl)methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide (5g) was synthesized from 3a and 2,5-dichloroaniline.
Colorless crystals, m.p. 1778C (1.336 g, 74%). 1H NMR (CDCl3, d): 7.64 (d,
1H), 7.19 (d, 1H), 6.85 (dd, 1H), 5.99 (d, 2JP–H ¼ 11.3 Hz, 1H), 2.9–2.7 (m,
2
4H), 2.01 (d, JP–H ¼ 15.5Hz, 3H), 1.8–1.7 (m, 4H). Anal. Calcd. for
C14H15Cl2N2OPS [361.23]: C, 46.55; H, 4.19; N, 7.76. Found: C, 46.67; H,
4.21; N, 7.91.
Methyl-N-(2-nitrophenyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-
ylphosphinic amide (5h) was synthesized from 3a and o-nitroaniline. Yellow
1
2
crystals, m.p. 1438C (1.130 g, 67%). H NMR (CDCl3, d): 9.15 (d, JP–
¼ 13.8 Hz, 1H), 8.17 (d, 1H), 7.81 (d, 1H), 7.47 (t, 1H), 6.98 (t, 1H), 2.9–2.6
H
(m, 4H), 2.2–1.7 (m, 7H). Anal. Calcd. for C14H16N3O3PS [337.34]: C, 49.85;
H, 4.78; N, 12.46. Found: C, 50.01; H, 4.82; N, 12.66.
Methyl-N-(3-nitrophenyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-
ylphosphinic amide (5i) was synthesized from 3a and m-nitroaniline. Pale
1
yellow crystals, m.p. 1158C (1.250 g, 74%). H NMR (CDCl3, d): 8.06 (d,

ORDER
REPRINTS
622
Strizhak et al.
2JP–H ¼ 13.1 Hz, 1H), 7.7–7.4 (m, 3H), 7.22 (t, 1H). 3.0–2.7 (m, 4H), 2.1–
1.7 (m, 7H). Anal. Calcd. for C14H16N3O3PS [337.34]: C, 49.85; H, 4.78; N,
12.46. Found: C, 50.02; H, 4.77; N, 12.54.
Methyl-N-(4-nitrophenyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-
ylphosphinic amide (5j) was synthesized from 3a and p-nitroaniline. Yellow
crystals, m.p. 2168C (1.301 g, 77%). 1H NMR (CDCl3, d): 8.02 (d, 2H), 7.51
2
(d, JP–H ¼ 12.5 Hz, 1H), 7.15 (d, 2H), 3.0–2.6 (m, 4H), 2.2–1.7 (m, 7H).
Anal. Calcd. for C14H16N3O3PS [337.34]: C, 49.85; H, 4.78; N, 12.46. Found:
C, 49.99; H, 4.71; N, 12.51.
Methyl-N-(2-pyridinyl)4,5,6,7-tetrahydro-1,3-benzothiazol-2-ylphos-
phinic amide (5k) was synthesized from 3a and 2-aminopyridine. Pale yellow
crystals, m.p. 1468C (0.894 g, 61%). 1H NMR (CDCl3, d): 8.14 (d, 1H), 7.48
(t, 1H), 6.98 (d, 1H), 6.79 (t, 1H), 2.84 (broad s, 4H), 2.14 (d, 2JP–H ¼ 15.9 Hz,
3H), 1.84 (broad s, 4H). Anal. Calcd. for C13H16N3OPS [293.33]: C, 53.23; H,
5.50; N, 14.33. Found: C, 53.11; H, 5.60; N, 14.56.
N-(5-chloro-2-pyridinyl)methyl(4,5,6,7-tetrahydro-1,3-benzothiazol-
2-yl)phosphinic amide (5l) was synthesized from 3a and 2-amino-5-
chloropyridine. Yellow crystals, m.p. 1378C. 1H NMR (CDCl3, d): 8.05 (s, 1H),
7.38 (d, 1H), 6.92 (d, 1H), 2.83 (broad s, 4H), 2.10 (d, 2JP–H ¼ 15.9 Hz, 3H),
1.85 (broad s, 4H). Anal. Calcd. for C13H15ClN3OPS [327.77]: C, 47.64; H,
4.61; N, 12.82. Found: C, 47.39; H, 4.66; N, 12.98.
N-(2-chlorophenyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)
phosphinic amide (6a) was synthesized from 3b and o-chloroaniline.
Colorless crystals, m.p. 1698C (1.381 g, 71%). 1H NMR (DMSO-D6, d): 8.0–
7.7 (m, 3H), 7.6–7.3 (m, 4H), 7.2–6.8 (m, 2H), 2.76 (broad s, 4H), 1.75 (broad
s, 4H). Anal. Calcd. for C19H18ClN2OPS [388.86]: C, 58.69; H, 4.67; N, 7.20.
Found: C, 58.81; H, 4.66; N, 7.31.
N-(4-chlorophenyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)
phosphinic amide (6b) was synthesized from 3b and p-chloroaniline.
Colorless crystals, m.p. 1638C (1.498 g, 77%). 1H NMR (CDCl3, d): 8.0–7.7
(m, 2H), 7.4–7.2 (m, 3H), 6.97 (s, 4H), 6.52 (d, 2JP–H ¼ 10.0 Hz), 2.75 (broad
s, 4H), 1.77 (broad s, 4H). Anal. Calcd. for C19H18ClN2OPS [388.86]: C,
58.69; H, 4.67; N, 7.20. Found: C, 58.84; H, 4.51; N, 7.39.
N-(2,5-dichlorophenyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide (6c) was synthesized from 3b and 2,5-dichloroaniline.
Colorless crystals, m.p. 1828C (1.713 g, 81%). 1H NMR (CDCl3, d): 8.1–7.9
(m, 2H), 7.6–7.3 (m, 3H), 7.22 (d, 1H), 6.9–6.7 (m, 3H), 3.0–2.7 (m, 4H),
1.87 (broad s, 4H). Anal. Calcd. for C19H17Cl2N2OPS [423.30]: C, 53.91; H,
4.05; N, 6.62. Found: C, 54.10; H, 4.11; N, 6.66.
N-(2,6-dichlorophenyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-
yl)phosphinic amide 6d was synthesized by non-standard procedure. A
mixture of 5 mmol of 3b and 15 mmol of 2,6-dichloroaniline was heated at

ORDER
REPRINTS
Direct Phosphorylation of Thiazoles and Naphtothiazoles
623
2008C during 15 min. After colling it was washed by 5% potassium carbonate
three times and 10 mL of acetone was added. After several hours the formed
precipitate was collected by filtration and dried in vacuo over P4O10. Colorless
crystals, m.p. .2508C (1.861 g, 88%). 1H NMR (CDCl3, d): 8.0–7.8 (m, 2H),
7.7–7.3 (m, 3H), 7.21 (d, 1H) 7.0–6.7 (m, 2H), 2.9–2.6 (m, 4H), 1.9–1.6 (m,
4H). Anal. Calcd. for C19H17Cl2N2OPS [423.30]: C, 53.91; H, 4.05; N, 6.62.
Found: C, 54.12; H, 4.10; N, 6.55.
N-(5-chloro-2-pyridinyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-
2-yl)phosphinic amide (6e) was synthesized from 3b and 2-amino-5-
chloropyridine. Yellow crystals, m.p. 1048C (1.346 g, 69%). 1H NMR (CDCl3,
d): 8.2–7.8 (m, 3H), 7.6–7.2 (m, 4H), 6.95 (d, 1H), 2.83 (broad s, 4H), 1.83
(broad s, 4H). Anal. Calcd. for C18H17ClN3OPS [389.85]: C, 55.46; H, 4.40;
N, 10.78. Found: C, 55.67; H, 4.44; N, 10.99.
N-(5-bromo-2-pyridinyl)phenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-
2-yl)phosphinic amide (6f) was synthesized from 3b and 2-amino-5-
bromopyridine. Yellow crystals, m.p. 1788C (1.389 g, 64%). 1H NMR
(CDCl3, d): 8.2–7.8 (m, 3H), 7.6–7.3 (m, 4H), 6.92 (d, 1H), 2.84 (broad s,
4H), 1.83 (broad s, 4H). Anal. Calcd. for C18H17BrN3OPS [434.30]: C, 49.78;
H, 3.95; N, 9.68. Found: C, 49.87; H, 4.10; N, 9.88.
N0,N0-triphenyl(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phosphinic
hydrazide (6g) was synthesized from 5 mmol of 3b, 5 mmol of 1,1-
diphenylhydrazine hydrochloride in triethylamine solution (10 mL) by heating
during 10 min. After colling the mixture was evaporated under reduced pres-
sure and 20 mL of water was added. The formed precipitate was recrystallized
1
from acetone. Colorless solid, m.p. 1868C (1.670 g, 67%). H NMR (CDCl3,
2
d): 8.1–7.8 (m, 2H), 7.5–6.8 (m, 13 H), 5.94 (d, JP–H ¼ 32.0 Hz), 2.76
(broad s, 4H), 1.81 (broad s, 4H). Anal. Calcd. for C25H24N3OPS [445.53]: C,
67.40; H, 5.43; N, 9.43. Found: C, 67.22; H, 5.51; N, 9.55.
Phenyl(1,3-thiazol-2-yl)phosphinic acid potassium salt (9) was syn-
thesized analogously to 4a-b or without catalyst. It was followed by 31P NMR
spectroscopy. Without catalyst the reaction is much more slower and was
completed about 2 weeks. Yield 86% (without catalyst). Pale pink solid. 31P
1
NMR (DMSO-D6, d): 4.9; H NMR (DMSO-D6, d): 7.8–7.7 (m, 3H), 7.58
(q, 1H), 7.4–7.2 (m, 3H). Anal. Calcd. for C9H7KNO2PS [263.30]: C, 41.06;
H, 2.68; N, 5.32. Found: C, 40.87; H, 2.77; N, 5.25.
Methyl(naphtho[2,1-d][1,3]thiazol-2-yl)phosphinic acid (13) was syn-
thesized by reaction of 11 with MePOCl2 (2a) analogously to 4a-b, but
reaction is much more slower and is completed only in 3 days. After that
mixture was poured into 30 mL of 5% potassium carbonate end evaporated to
dryness. Then 10 mL of water was added and the starting naphtothiazole was
separated by filtration. Filtrate was acidifided to pH ¼ 5 and allowed to stand
several hours. The formed precipitate was collected by filtration and dried in

ORDER
REPRINTS
624
Strizhak et al.
vacuo over P4O10. Grey solid, m.p. 1788C (dec.). Yield 56%. 1H NMR
(CF3COOD, d): 7.5–6.7 (m, 6H), 2.22 (d, 2JP–H ¼ 16.0 Hz). Anal. Calcd. for
C25H24N3OPS [263.26]: C, 54.75; H, 3.83; N, 5.32. Found: C, 54.87; H, 3.91;
N, 5.44.
REFERENCES
1. Komarov, I.V.; Kornilov, M.Yu.; Turov, A.V.; Gorichko, M.V.;
Popov, V.O.; Tolmachev, A.A.; Kirby, A.J. Phosphorylation of
1,3-di(n-alkyl)azoles by phosphorus(v) acid clorides—a route to potential
haptens derived from phosphinic acids. Tetrahedron 1995, 51 (45),
12417–12424.
2. Komarov, I.V.; Strizhak, A.V.; Kornilov, M.Yu.; Zarudnitskiy, E.; Tolma-
chev, A.A. Direct phosphorylation of benzothiazoles and 4-methylthiazole.
Synth. Commun. 2000, 30 (2), 243–252.
3. Maruyama, T.; Taira, Z.; Horikawa, M.; Sato, Y.; Honjo, M. Synthesis of
uracil-5- and adenine-8-phosphonic acids. Tetrahedron Lett. 1983, 24 (25),
2571–2574.
4. Honjo, M.; Maruyama, T.; Horikawa, M.; Balzarini, J.; De Clercq, E.
Synthesis and biological evaluation of phosphonopyrimidine and phos-
phonopurine ribonucleosides. Chem. Pharm. Bull. 1987, 35 (8),
3227–3234.
5. Wanzlick, H.-W. Aspects of nucleophilic carbene chemistry. Angew.
Chem. Int. Ed. Engl. 1962, 7 (2), 141–142.
6. Arduendo, A.J., III; Harlow, R.L.; Kline, M. A stable crystalline carbene.
J. Am. Chem. Soc. 1991, 113 (1), 361–363.
¨
7. Wanzlick, H.-W.; Schonherr, H.-J. Direct synthesis of a mercury salt-
carbene complex. Angew. Chem. Int. Ed. 1968, 7 (2), 141–142.
Received in the USA August 7, 2003

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request Permission/
Order Reprints" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
Fair Use in the Classroom.
(AAP) website for guidelines on
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our
Website
User Agreement for more details.
Request Permission/Order Reprints
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC120027709