Phosphonium Ylides Stabilized with Cyano Group and 5-Acylamino-4-phenyl-2-thiazolyl Residue

Article abstract of DOI:10.1023/A:1013986223340

Available ylide reagent Ph3P=C(CN)C(S)NH2 readily enters cyclocondensation with N-(chlorophenacyl)benzamide and its analogs. By this route were prepared new stabilized phosphonium ylides con-taining cyano group and the corresponding 5-acylamino-4-phenyl-2-thiazolyl fragment. All these compounds even under standard conditions are dephosphorylated under the action of hydrogen chloride in acetic acid to form 5-acylamino-4-phenyl-2-cyanomethylthiazoles in high yields. Their structure was proved by spectroscopic studies and independent synthesis.

Full text of DOI:10.1023/A:1013986223340

Russian Journal of General Chemistry, Vol. 71, No. 11, 2001, pp. 1734 1736. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 11, 2001,
pp. 1830 1832.
Original Russian Text Copyright
2001 by Smolii, Panchishin, Pirozhenko, Drach.
Phosphonium Ylides Stabilized with Cyano Group
and 5-Acylamino-4-phenyl-2-thiazolyl Residue
O. B. Smolii, S. Ya. Panchishin, V. V. Pirozhenko, and B. S. Drach
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received June 21, 2000
Abstract Available ylide reagent Ph3P=C(CN)C(S)NH2 readily enters cyclocondensation with N-(chloro-
phenacyl)benzamide and its analogs. By this route were prepared new stabilized phosphonium ylides con-
taining cyano group and the corresponding 5-acylamino-4-phenyl-2-thiazolyl fragment. All these compounds
even under standard conditions are dephosphorylated under the action of hydrogen chloride in acetic acid to
form 5-acylamino-4-phenyl-2-cyanomethylthiazoles in high yields. Their structure was proved by spectro-
scopic studies and independent synthesis.
Recently we have developed a convenient proce-
dure for preparing a series of C-thiocarbamoyl-sub-
stituted phosphonium ylides of the general formula
Ph3P=C(X)C(S)NH2 [1]. The most important of them
is triphenylphosphoranylidenecyanothioacetamide I,
which readily reacts with methyl chloroacetate and
chloroacetonitrile [1]. In this work we found that re-
agent I under mild conditions enters cyclocondensation
with available polyfunctional electrophilic substrates
II containing the characteristic COCHClNHCO group.
R = C6H5 (a), 4-CH3C6H4 (b), 4-ClC6H4 (c); R = CH3CO (VI), CH3 (VII).
As the chlorine in this group is very labile [2], it
can be suggested that initially intermediate acyclic
products III are formed, which under the action of tri-
ethylamine and insignificant heating undergo Hansch
cyclization to form previously unknown stable phos-
phonium ylides of the thiazole series IV, stabilized by
the nitrile group and the corresponding 5-acylamino-
4-phenyl-2-thiazolyl residue. The presence of the cy-
1070-3632/01/7111-1734$25.00 2001 MAIK Nauka/Interperiodica

PHOSPHONIUM YLIDES STABILIZED WITH CYANO GROUP
1735
ano group and amide bond in compounds IV was
proved by IR spectroscopy (see Experimental). Fur-
thermore, their structure was finally confirmed in ex-
periments on their dephosphorylation, which occurs
under mild conditions when treating solutions of com-
pounds IV in acetic acid or methanol with hydrogen
chloride. Most probably, the initial protonation of the
ylide center of compounds IV gives tertiary phos-
phonium salts V, which, in turn, are evidently related
to phosphorane structures VI VIII. Further stabili-
zation of such structures by elimination of triphenyl-
phosphine oxide has some analogs [3] and seems quite
possible. In particular, phosphoranes VI must exhibit
strong acylating power, and their reaction with acetic
acid can proceed through the cyclic transition state
of type A.
dephosphorylation occurs in a mixture of acetic acid
and acetic anhydride in the absence of hydrogen chlo-
ride.
Finally, it cannot be ruled out that intermediates
VII first undergo dephosphorylation, which is fol-
lowed by conversion of the cyano group to the meth-
oxycarbonyl group. Thus, the stages of transforma-
tions of ylides IV presented in the scheme cannot
be regarded as the only possible, but the structure of
dephosphorylation products IX and X is doubtless,
because the presence of the methylene group in them
1
was proved by the H NMR spectra (see Experimen-
tal), and one of these substituted thiazoles was pre-
pared by an independent procedure.
The possible applications of this convenient meth-
od for dephosphorylation of ylides stabilized with het-
erocyclic fragments will be considered in subsequent
papers.
Ht = 5-acylamino-4-phenylthiazol-2-yl.
It is not appropriate to discuss in detail the alter-
EXPERIMENTAL
native mechanisms of transformations VI
IX and
VII VIII X without additional experimental
The IR spectrum of IVa was recorded on a UR-20
spectrometer in KBr pellets, and that of X, on a
Specord IR-71 spectrometer (0.1 M CH2Cl2 solution).
data. Note only that in formation of substituted phos-
phoranes VI and VII an important role may be played
not only by tertiary phosphonium salts V, but also
by the related phosphoranes of the general formula
Ph3P(Cl)CH(CN)Ht, which under the action of acetic
acid or methanol must be converted to intermediates
VI and VII. It is interesting that the P C bond is
cleaved not only in anhydrous acetic acid when pass-
ing thoroughly dried hydrogen chloride, but also on
addition of phosphorus trichloride, phosphorus oxy-
chloride, or acetyl chloride. At the same time, no
1
The H NMR spectra of IXa IXc and X were meas-
ured on a Varian VXR-300 spectrometer relative to
TMS. The constants, yields, and elemental analyses
of IV, IX, and X are given in the table.
5-Acylamino-4-phenylthiazol-2-yl(cyano)methy-
lenetriphenylphosphoranes IVa IVc. Compound I
[1], 0.01 mol, and 0.01 mol of triethylamine were
added to a suspension of 0.01 mol of IIa IIc in 30 ml
Constants, yields, and elemental analyses of new thiazole derivatives
Found, %
Calculated, %
H (S) C (P)
Comp. Yield,
mp, C (solvent for
recrystallization)
Formula
no.
%
H (S) C (P)
N
N
IVa
71
69
178 180 dec. (acetonitrile) (5.59) (5.61)
190 192 dec. (ethanol) (5.01) (5.32)
210 211 dec. (acetonitrile) (5.25) (5.41)
7.34
7.25
7.02
13.10
12.81
11.71
7.81
C36H26N3OPS
C37H28N3OPS
C36H25ClN3OPS (5.04) (5.22)
C18H13N3OS
C19H15N3OS
C18H12ClN3OS
C20H18N2O3S
(5.34) (5.53)
(5.22) (5.40)
7.25
7.08
6.84
13.16
12.60
11.88
7.64
IVb
IVc
IXa
IXb
IXc
X
76
82a
86a
85a
72
196 197 (ethanol)
67.67
68.58
61.18
65.59
3.94
4.70
3.56
5.03
67.69
68.45
61.10
65.56
4.10
4.53
3.42
4.95
193 194 (acetonitrile)
192 193 (acetonitrile)
126 127 (ethanol)
a
Yields of IVa IVc in procedure b.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

1736
SMOLII et al.
of anhydrous acetonitrile. The mixture was heated to
40 C until a clear solution formed, and then it was
left for 24 h at 20 C. The resulting precipitate was
filtered off, washed with acetonitrile (5 ml) and water
(2 20 ml), and recrystallized. IR spectrum of IVa,
added, and the mixture was refluxed for 15 min and
left for 2 h at 20 25 C. The resulting precipitate was
filtered off and recrystallized from ethanol; yield 79%.
A mixed sample of 5-benzoylamino-4-phenyl-2-cyano-
methylthiazole IXa obtained by procedures a and b
gave no depression of the melting point.
1
, cm : 1670 (C=O), 2150 (C N), 3390 (NHassoc).
5-Acylamino-4-phenyl-2-cyanomethylthiazoles
IXa IXb. a. A suspension of 0.001 mol of IVa IVc
in 10 ml of anhydrous acetic acid (double-distilled from
P2O5) was saturated with dry hydrogen chloride for
20 min. The resulting precipitate was filtered off,
washed with 1 ml of anhydrous acetic acid, and re-
crystallized. Yields of IXa IXc 80 85%. IR spectrum
2-Methoxycarbonylmethyl-5-p-toluylamino-4-
phenylthiazole X. A suspension of 0.002 mol of IVb
in 10 ml of absolute methanol was saturated with an-
hydrous hydrogen chloride for 20 min. The resulting
precipitate was quickly filtered off and kept in a
water-jet-pump vacuum for 30 min. Then it was sus-
pended in 5 ml of methanol, 5 ml of water was added,
and the mixture was kept for 1 h at 20 C. The result-
ing precipitate was filtered off, washed with water,
1
of IXa, , cm : 1670 (C=O), 2270 (C N), 3350
1
(NHassoc). H NMR spectrum (DMSO-d6), , ppm:
1
IXa: 4.55 s (2H, CH2), 7.37 7.98 m (10H, 2C6H5),
10.96 s (1H, NH); IXb: 2.39 s (3H, CH3), 4.55 s (2H,
CH2), 7.37 7.87 m (9H, C6H5, C6H4), 10.88 s (1H,
NH); IXc: 4.56 s (2H, CH2), 7.39 7.97 m (9H, C6H5,
C6H4), 11.07 (1H, NH).
and recrystallized. IR spectrum, , cm : 1675 (C=O),
1
1750 (C=O), 3420 (NH). H NMR spectrum (CDCl3),
, ppm: 2.43 s (3H, CH3), 3.78 s (3H, OCH3), 4.07 s
(2H, CH2), 7.28 7.70 m (9H, C6H5, C6H4), 8.67 s
(1H, NH).
b. To a solution of 0.001 mol of IVa IVc in 10 ml
of glacial acetic acid was added 0.002 mol of acetyl
chloride. The resulting mixture was left for 20 min at
20 25 C, and the resulting precipitate was filtered off
and recrystallized. Phosphorus trichloride, tribromide,
or oxychloride can be used instead of acetyl chloride.
Yields of IXa IXc are approximately the same as in
the case of acetyl chloride. Mixed samples of com-
pounds obtained by procedures a and b gave no de-
pression of the melting point. The identity of the com-
pounds obtained by procedures a and b was also
ACKNOWLEDGMENTS
The study was carried out in the framework of
INTAS grant no. 96-1115 under the guidance of Prof.
G. Reiners (Louvain-la-Nueve Catholic University,
Belgium) to whom the authors express their gratitude.
REFERENCES
1. Smolii, O.B., Panchishin, S.Ya., Romanenko, E.A., and
Drach, B.S., Zh. Obshch. Khim., 1995, vol. 65, no. 4,
pp. 583 586.
1
proved by TLC and H NMR spectra.
2. Drach, B.S., Dolgushina, I.Yu., and Kirsanov, A.V.,
Zh. Org. Khim., 1973, vol. 9, no. 2, pp. 414 419.
3. Johnson, A.W., Ylides and Imines of Phosphorus, New
York: Wiley, 1993, pp. 130 133.
4. Schmidt, U. and Kubitzek, H., Chem. Ber., 1960,
c. To a solution of 0.002 mol of compound IIa in
10 ml of anhydrous THF was added 0.002 mol of thio-
cyanoacetamide [4]. The reaction mixture was kept
for 24 h at 20 25 C, and the resulting precipitate was
filtered off, washed with 2 ml of THF, and dissolved
in 10 ml of methanol. Triethylamine, 0.003 mol, was
vol. 93, no. 7, pp. 1559 1565.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001