Biphilic properties of substituted triphenylphosphoranylideneacetonitriles bearing 4,5-Di(arylsulfonyl)-1,3-thiazol-2-yl fragments at the ylide center

Article abstract of DOI:10.1134/S107036320907010X

Phosphonium ylides stabilized by nitrile and 4,5-di(arylsulfonyl)-1,3- thiazol-2-yl fragments show biphilic reactivity. They react with aromatic aldehydes upon heating revealing a noticeable activity of ylide center and are condensed with typical nucleoph

Full text of DOI:10.1134/S107036320907010X

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 7, pp. 1467–1472. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © K.V. Turov, E.B. Rusanov, B.S. Drach, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 7, pp. 1110–1115.
Biphilic Properties
of Substituted Triphenylphosphoranylideneacetonitriles
Bearing 4,5-Di(arylsulfonyl)-1,3-thiazol-2-yl Fragments
at the Ylide Center
K. V. Turova, E. B. Rusanovb, and B. S. Dracha
a Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev-94, 02660 Ukraine
e-mail: drach@bpci.kiev.ua
b Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received February 2, 2009
Abstract—Phosphonium ylides stabilized by nitrile and 4,5-di(arylsulfonyl)-1,3-thiazol-2-yl fragments show
biphilic reactivity. They react with aromatic aldehydes upon heating revealing a noticeable activity of ylide
center and are condensed with typical nucleophiles at C4 center of the thiazole ring with the elimination of
arylsulfonyl group under mild conditions. New 1,3-thiazole derivatives were obtained whose structures were
proved by chemical, spectal and X-ray structural investigations.
DOI: 10.1134/S107036320907010X
In the recently initiated investigation of nucleo-
philic substitution reactions of 2,4,5-tri(arylsulfonyl)-
1,3-thiazoles [1,2] we found that accessible polycentric
processes of nucleophilic substitution at the С4 center
of thiazole ring was mainly established by Н NMR
1
spectroscopy that allowed the unequivocal identifica-
tion of both leaving and remaining arylsulfonyl groups
at varied substituents in 4 and 5 positions of the
thiazole ring (Table 2). However, for establishing the
structure of the product of reaction between substrate
IIa, Ar1 = Ts, and piperidine we had to apply the X-ray
diffraction analysis. The general view of molecule
VIIa and its principal geometric parameters are shown
in the figure.
electrophilic substrates
I
reacted readily with
triphenylphosphoranylideneacetonitrile at the С2 center
of thiazole ring with the formation of earlier unknown
stable phosphonium ylides II. In turn, on this basis we
successfully synthesized a series of new functional
thiazole derivatives III–IX, as shown in the scheme
and in Table 1.
It is noteworthy that despite the presence of three
strong electron-acceptor substituents, ylides II enter
Wittig reaction upon heating to 140ºС with excess
benzaldehyde or p-fluorobenzaldehyde (see pathway
II → IV). On the other hand, the ylide center of
substrates II can be involved into acidic dephos-
phorylation II → III; the mechanism of this reaction
has been considered earlier [3, 4].
Thiazole heterocycle S1N2C21–23 has usual bond
lengths and bond angles. The thiazole ring is
practically planar: the maximal deviation of atoms
from the mean square plane is not greater than
0.016(1) Å. Bond C19–C21 length is 1.428(3) Å, that is
noticeably less than the value 1.48 Å characteristic of a
single С(sp2)–C(sp2) bond [5]. The bond P1–C19
1.743(2) Å also is noticeably shorter than Р–С bond
with phenyl substituents (average value 1.798 Å)
indicating conjugation in the P1–C19–С21 system and
ylide character of Р1–С19 bond. The length of C19–C20
bond is 1.408(3) Å, namely, it is shortened to the
typical value of aromatic systems and indicates the
In such transformations the nucleophilic character
of polycentric substrates II is clearly seen.
Nevertheless, they display even more pronounced
electrophilic properties, as seen from the pathways
II → V, II → VI and II → VII proceeding under very
mild conditions. A high regioselectivity of these
1467

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TUROV et al.
N
Ts
Ar1SO2
SO2Ar2
S
Iа, Ib
Ph3P = CH−CN, Et3N
Ts
Ar1SO2
Ar3CHO
POCl3/MeC(O)OH
Ar1 = 4-MeC6H4
N
Ar1 = 4-MeC6H4
CN
PPh3
S
IIа, IIb
Ts
Ts
Ts
N
N
Ar3CHO
Ar3
Ts
S
S
CN
CN
IVа, IVb
III
R1R2NH
4-MeOC6H4ONa
Ar1 = 4-MeC6H4
PhSNa
PhS
Ar1SO2
2 N
R1R
4-MeOC6H4O
Ar1SO2
4-NO2C6H4CHO
R2R1N
N
N
S
N
N
CN
CN
CN
PPh3
Ts
S
S
PPh3
VIа, VIb
PPh3
VIIа−VIIc
Vа, Vb
O
X
H
Ts
Ts
(1)
O
N
OH
N
O
H3O+
(2)
N
S
Ts
C6H4NO2-4
S
X
CN
VIIIа, VIIIb
IX
Ar1 = 4-MeC6H4 (Iа, IIa, Va, VIa), 4-ClC6H4 (Ib, IIb, Vb, VIb, VIIb); Ar2 = 4-MeC6H4 (Ia), Ph (Ib); Ar3 = Ph (IVa),
4-FC6H4 (IVb); X = H (VIIIa), OH (VIIIb); R1R2N =
PhCH NH (VIIc).
N (VIIа), O
N (VIIb),
2
Table 1. Yields, constants and the data of elemental analyses of compounds II−VIII
Found, %
Cl (P)
(4.45)
Calculated, %
Comp.
no.
Yield,
%
mp, °С (solvent)
Formula
S
Cl (P)
(4.49)
S
83
74
79
42
154–155 (EtOH–CH3CN, 10:1)
164–165 (CH3CN)
164–165
14.04
13.05
22.34
18.61
С37H29N2O4PS3
13.88
13.49
22.24
18.48
IIа
IIb
III
4.81 (4.38)
С36H26ClN2O4PS3
4.97 (4.34)
a
−
−
С19H16N2O4S3
−
−
b
156–157 (EtOH)
С26H20N2O4S3
IVa
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BIPHILIC PROPERTIES
Found, %
1469
Table 1. (Contd.)
Calculated, %
Cl (P) S
Comp.
no.
Yield,
%
mp, °С (solvent)
Formula
Cl (P)
S
17.54
9.68
c
47
78
82
73
77
81
74
83
87
82
225–226 (EtOH)
195–196 (EtOH)
181–182 (EtOH)
225–226 (EtOH)
194–195 (EtOH)
210–211 (EtOH)
226–227 (EtOH)
238–239 (EtOH)
271–272 (EtOH)
266–267 (EtOH)
−
С26H19N2FO4S3
−
17.86
9.71
IVb
Vа
(4.64)
С37H29N2O4PS2
(4.69)
4.93 (4.49)
(4.74)
9.56
С36H26ClN2O4PS2
С36H27N2O2PS3
С35H24ClN2O2PS3
С35H32N3O2PS2
С34H30N3O3PS2
С37H30N3O2PS2
5.20 (4.55)
(4.79)
5.31 (4.64)
(4.98)
(4.97)
(4.81)
−
9.41
Vb
14.69
14.87
14.42
10.31
10.28
9.96
VIа
5.07 (4.57) 14.70
VIb
VIIа
VIIb
VIIc
VIIIа
VIIIb
(4.93)
(4.92)
(4.76)
−
10.37
10.30
9.89
d
17.69
17.42
С26H19NO6S3
17.89
17.37
e
−
С26H19NO7S3
−
a
Found, %: S 52.41; Н 3.95. Calculated, %: S 52.76; Н 3.73. b Found, %: S 59.63; Н 4.02 Calculated, %: S 59.98; Н 3.87. c Found, %: S
57.53; Н 3.80 Calculated, %: S 57.98; Н 3.56. d Found, %: S 57.85; Н 3.73 Calculated, %: S 58.09; Н 3.56. e Found, %: S 56.17; Н 3.80
Calculated, %: S 56.41; Н 3.46.
Table 2. Spectral data of the synthesized compounds II–VIII
Comp.
1Н NMR spectrum, δ, ppm (DMSO-d6)
no.
2.33 s (3Н, СН3), 2.46 s (3Н, СН3), 7.03–7.05 m (4Нarom), 7.42–7.44 m (2Нarom), 7.53–7.62 m (12Нarom), 7.76–7.79 m (3Нarom),
7.93–7.95 m (2Нarom
2.32 s (3Н, СН3), 6.95–7.10 m (4Нarom), 7.45–7.60 m (14Нarom), 7.70–7.85 m (3Нarom), 8.00–8.15 m (2Нarom
2.46 s (3Н, СН3), 2.52 s (3Н СН3.), 4.57 s (2Н, СН2), 7.40–7.42 m (2Нarom), 7.50–7.52 m (2Нarom), 7.72–7.74 m (2Нarom) 7.98–
8.00 m (2Нarom
IIа
)
)
IIb
III
)
2.43 s (3Н, СН3), 2.50 s (3Н, СН3), 7.39–7.41 m (2Нarom), 7.51–7.58 m (5Нarom), 7.73–7.75 m (2Нarom), 8.01–8.04 m (4Нarom),
8.40 s (1Н СН)
IVа
IVb
Vа
2.43 s (3Н, СН3), 2.50 s (3Н, СН3), 7.35–7.40 m (4Нarom), 7.50–7.52 m (2Нarom), 7.72–7.74 m (2Нarom), 7.98–8.00 m (2Нarom),
8.13–8.15 m (2Нarom), 8.41 s (1Н СН)
2.42 s (3Н, СН3), 3.67 s (3Н, ОСН3), 6.32–6.34 m (2Нarom), 6.46–6.48 m (2Нarom), 7.34–7.54 m (14Нarom), 7.68–7.71 m (3Нarom),
7.76–7.78 m (2Нarom
3.68 s (3Н, ОСН3), 6.34–6.36 m (2Нarom), 6.47–6.49 m (2Нarom), 7.40–7.60 m (14Нarom), 7.69–7.72 m (3Нarom), 7.88–7.90 m
(2Нarom
2.39 s (3Н, СН3), 6.77–6.85 m (4Нarom), 6.97–7.05 m (1Нarom), 7.31–7.57 m (14Нarom), 7.67–7.75 m (3Нarom), 7.82–7.85 m (2Нarom
6.81–6.83 m (3Нarom), 7.34–7.65 m (16Нarom), 7.68–7.70 m (3Нarom), 7.97–7.99 m (2Нarom
1.06 s (4Нpiperidine), 1.30 s (2Нpiperidine), 2.42 s (3Н, СН3), 2.83 s (4Нpiperidine), 7.31–7.33 m (2Нarom), 7.55–7.65 m (14Нarom), 7.71–
7.73 m (3Нarom
2.36 s (3Н, СН3), 2.84 s (4Нmorph), 3.15 s (4Нmorph), 7.37–7.39 m (2Нarom), 7.57–7.67 m (14Нarom), 7.73–7.76 m (3Нarom
2.36 s (3Н, СН3), 3.76 m (2Н СН2.), 6.73–6.76 m (3Нarom), 6.98–7.01 m (3Нarom), 7.29–7.32 m (3Нarom), 7.49–7.71 m (15Нarom
2.42 s (3Н, СН3), 2.49 s (3Н СН3.), 7.37–7.51 m (6Нarom), 7.77–7.82 m (3Нarom), 7.99–8.07 m (3Нarom), 9.04 s (1Н СНcoumarin
)
Vb
)
)
VIа
VIb
VIIа
)
)
)
VIIb
VIIc
)
)
VIIIа
VIIIb
2.41 s (3Н, СН3), 2.49 s (3Н СН3), 6.80–6.88 m (3Нarom), 7.36–7.88 m (2Нarom), 7.45–7.47 m (2Нarom), 7.78–7.80 m (2Нarom),
7.97–7.99 m (2Нarom), 8.89 s (1Н СНcoumarin), 11.13 s (1Н, ОН)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009

1470
TUROV et al.
C16
C15
C14
C26
C17
C18
C25
C24
C12
C27
C13
P1
C11
C10
N3
C7
C8
O1
C22
N2
C28
O2
C19
C20
N1
C23
C9
S2
C29а
C21
C1
S1
C6
C2
C3
C30а
C31а
C5
C34а
C33а
C4
C32а
C35а
General view of VIIa molecule, principal bond lengths and bond angles: P1–C1 1.803(2), P1–C7 1.802(2), P1–C13 1.790(2), P1–C19
1.743(2), C19–C21 1.428(3), C19–C20 1.408(3), S1–C21 1.727(2), S1–C23 1.750(2), N2–C21 1.320(3), N2–C22 1.369(3), C22–C23 1.397(3),
N1–C20 1.142(3), N3–C22 1.358(3), S2–C23 1.714(2) Å; C21S1C23 89.15(10), N2C21S1 114.74(15), C21N2C22 112.29(18), N2C22C23
114.08(19), C22C23S1 109.68(15), N2C21C19 123.65(18), C21C19 P1 119.57(15), S2C23S1 114.68(13)°.
conjugation of the π-system with the ylide center; the
cyano group itself lies in the plane of thiazole
heterocycle [torsion angle C20–C19–C21–S1 is only
6.7(3)°]. Note that P1–C19 bond length 1.743(2) Å in
the structure VIIa is close to the respective values
1.753 and 1.743 Å found for the ylides Ph3P=C(CN)2
and PhMe2P=C(CN)2 [6, 7].
turned out to be useful for further transformations.
Thus, the stabilized ylides V–VIII enter Wittig
reaction with aromatic aldehydes but with strong
tarring that hampers isolation of compound IX and its
analogs. On the other hand, compound III was without
problems transformed into the derivatives of 3-(1,3-
thiazol-2-yl)coumarin (VIII). Other transformations of
the polycentric compounds II–VII will be considered
in future.
Short contacts in the crystal of compound VIIa are
not revealed.
Thus, at the action of piperidine, like, by the way,
of the other hard and soft nucleophiles, on the
substrates IIa, IIb predominantly occurs the
substitution of arylsulfonyl group in the 4 position of
thiazole ring, while the neighboring electrophilic
center is not practically affected, owing probably to its
deactivation by conjugation with ylide center, as
shown below.
EXPERIMENTAL
1
The Н NMR spectra were registered on a Varian
Mercury-400 instrument from solutions in DMSO-d6
with internal TMS.
The X-ray structural investigation of a single
crystal of compound VIIa with linear dimensions
0.04×0.32×0.62 mm was carried out at room
temperature on a Bruker Smart Apex II diffractometer
(λMoKα radiation, graphite monochromator, θmax
28.41º, the sphere segment was –11 ≤ h ≤ 11, –9 ≤ k ≤
12, –26 ≤ l ≤ 28). Total array contained 21328 reflexes
of which 7726 were independent (average R-factor
0.0372). The crystals of compound VIIa, C35H32·
N3O2PS2, M 621.73, are triclinic, space group Р21/с
N
+
PPh3
Ar1SO2
−
S
Note in conclusion that the products of reaction of
accessible biphilic substrates II with electrophilic and
nucleophilic agents, substituted thiazoles III–VII,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009

BIPHILIC PROPERTIES
1471
(no. 14), a 8.7930(7), b 9.2612(7), c 21.1879(17) Å,
α 79.412(4), β 85.798(5), γ 68.942(4)º, V 1582.7(2) Å3,
Z 2, dcalc 1.305 g cm–3 , μ 0.255 mm–1, F(000) 652. The
structure was solved by the direct method and refined
by the least-squares method in full-matrix anisotropic
approximation using SHELXS97 and SHELXL97
programs [8, 9]. For the refinement were used
4909 reflexes with I > 2σ(I), (430 of refined param-
eters, 11.4 reflexes per a parameter, weight scheme w =
1/[σ2(Fo2) + (0.046Р)2 + 0.4482Р], where Р = (Fo2 +
2Fc2)/3 is applied, the ratio of maximal (average) shift
to error in the final cycle is 0.009 (0.003). Corrections
for extinction were introduced with SADABS program
residue was added 5 ml of ethanol, the precipitate was
filtered off and used further without purification.
2-(4,5-Ditosyl-1,3-thiazol-2-yl)-3-phenyl(p-fluoro-
phenyl)acrylonitrils (IVa, IVb). To 0.7 mmol of
compound IIa was added 7 mmol of an appropriate
aldehyde. The mixture was heated for 10 h at 140ºС,
cooled to 20ºС, 5 ml of ethanol was added, the
precipitate was filtered off and purified by
crystallization from ethanol.
2-[5-Arylsulfonyl-4-(p-methoxyphenylоxy)-1,3-
thiazol-2-yl]triphenylphosphoranylideneacetonitriles
(Va, Vb). To a solution of 0.7 mmol of compound IIa,
IIb in 5 ml of THF was added 0.7 mmol of sodium p-
methoxyphenoxide, the mixture was left for 24 h at
20ºС, the solvent was removed in a vacuum, 5 ml of
ethanol was added, the precipitate was filtered off and
purified by crystallization from ethanol.
(the minimal/maximal correction ratio Тmin/Tmax
=
0.607). The carbon atoms С29–С35 of tosyl group as
well as the respective hydrogen atoms are disordered
over two positions A and C with occupancies 53 and
47%, respectively. All hydrogen atoms were located
geometrically. Final divergence factors are: R1(F2) =
0.094, RW(F2) = 0.123, GOF = 1.034 over all reflexes
and R1(F) = 0.051 RW(F2) = 0.106, GOF = 1.034 over
the reflexes with I > 2σ(I). Residual electron density
from differential Fourier synthesis after the final
refinement cycle is 0.32 and –0.34 е Å–3.
2-[5-Arylsulfonyl-4-(phenylthio)-1,3-thiazol-2-yl]-
triphenylphosphoranylilideneacetonitriles (VIa, VIb).
To a solution of 0.7 mmol of compound IIa, IIb in
5 ml of THF was added 0.7 mmol of sodium thio-
phenoxide, the mixture was left for 24 h at 20ºС, the
solvent was removed in a vacuum, 5 ml of ethanol was
added, the precipitate was filtered off and purified by
crystallization from ethanol.
Elemental analyses and constants of newly syn-
thesized compounds are listed in Table 1, their spectral
data are collected in Table 2.
2-[4-Piperidino (morpholino, benzylamino)-5-
tosyl-1,3-thiazol-2-yl]triphenylphosphoranylidene-
acetonitriles (VIIa–VIIc). A mixture of 0.7 mmol of
compound IIa and 7 mmol of an appropriate nitrogen
base was heated for 10 h at 120ºС, cooled to 20ºС,
5 ml of ethanol was added, precipitate was filtered off
and purified by crystallization from ethanol.
2,4,5-Tritosyl-1,3-thiazole (Ia) is synthesized in
accordance with [1].
4-Tosyl-2-phenylsulfonyl-5-p-chlorophenylsulfo-
nyl-1,3-thiazol (Ib) is prepared by known procedure
[2].
2-[(4,5-Ditosyl)-1,3-thiazol-2-yl]triphenylphosphor-
anylideneacetonitrile (IIa) and 2-[(4-tosyl-5-p-
chlorophenylsulfonyl)-1,3-thiazol-2-yl]triphenylphos-
phoranylilideneacetonitrile (IIb). To a solution of
0.5 mmol of compound Ia or Ib in 10 ml of THF was
added 1 mmol of triphenylphosphoranylideneaceto-
nitrile and 1 mmol of triethylamine. The mixture was
heated for 10 h at 60ºС, the solvent was removed in a
vacuum and to the residue was added 5 ml of ethanol,
the precipitate was filtered off and compound IIa was
purified by recrystallization from a mixture of ethanol
and acetonitrile (10:1), compound IIb, from acetonitrile.
3-(4,5-Ditosyl-1,3-thiazol-2-yl)-2H-chromen-2-one
(VIIIa). To a solution of 0.7 mmol of compound III in
10 ml of ethanol was added 0.8 mmol of salycilic
aldehyde and 1 drop of piperidine. The mixture was
heated to 40ºС for 1 h and left at 20ºС for 24 h, the
solvent was removed in a vacuum, 10 ml of sodium
carbonate and then 2 ml of concn. hydrochloric acid
was added, and the mixture was refluxed for 1 h. The
precipitate formed was filtered off and purified by
crystallization from a mixture of ethanol and DMF
(10:1).
2-(2,4-Ditosyl-1,3-thiazol-2-yl)acetonitrile (III).
To a suspension of 0.7 mmol of compound IIa in 6 ml
of acetic acid was added 0.14 mmol of phosphorus
oxychloride. The mixture was heated at 100ºС for
15 min, the solvent was removed in a vacuum, to the
7-Hydroxy-3-(4,5-ditosyl-1,3-thiazol-2-yl)-2H-
chrоmеn-2-one (VIIIb). To a solution of 0.7 mmol of
compound III in 10 ml of ethanol was added 0.8 mmol
of 2,4-dihydroxybenzaldehyde and 1 drop of piperi-
dine. The mixture was heated to 40ºС for 1 h and left
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009

1472
TUROV et al.
2. Turov, K.V. and Drach, B.S., Zh. Obshch. Khim., 2008,
at 20ºС for 24 h, then the solvent was removed in a
vacuum, 10 ml of sodium carbonate and then 2 ml of
concn. hydrochloric acid was added, and the mixture
was refluxed for 1 h. The precipitate formed was
filtered off and purified by crystallization from
ethanol.
vol. 78, no. 14, p. 648.
3. Smolii, O.B., Panchishin, S.Ya., Romanenko, E.A., and
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Drach, B.S., Zh. Obshch. Khim., 2001, vol. 71, no. 11,
p. 1830.
3-p-Nitrophenyl-2-(4-piperidino-5-tosyl-1,3-thia-
zol-2-yl)acrylonitrile (XI). To 0.7 mmol of compound
IIa was added 7 mmol of p-nitrobenzaldehyde. The
mixture was heated for 4 h at 140ºС, 10 ml of ethanol
was added, and the presence of triphenylphosphine
oxide and the product of Wittig reaction XI was
revealed by TLC. Alongside these substances a
mixture of several products was formed that con-
siderably hampered the separation of individual
compound XI.
5. Burke-Laing, M. and Laing, M., Acta Crystallogr. B,
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Crystal Structure, University of Gottingen, Germany,
1997.
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9. Sheldric, G.M., SHELXL97. Program for the
Refinement of Crystal Structures, University of
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 7 2009