Phosphazenes: I. Reactions with electron-deficient alkenes

Article abstract of DOI:10.1134/S1070428012070068

Triphenylphosphazenes reacted with methyl vinyl ketone, methyl acrylate, methyl methacrylate, and dimethyl maleate to give the corresponding substituted dihydropyrazoles.

Full text of DOI:10.1134/S1070428012070068

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 7, pp. 924–927. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © T.A. Yangirov, G.R. Zubairova, R.M. Sultanova, R.Z. Biglova, V.A. Dokichev, Yu.V. Tomilov, 2012, published in Zhurnal
Organicheskoi Khimii, 2012, Vol. 48, No. 7, pp. 929–932.
Phosphazenes: I. Reactions with Electron-Deficient Alkenes
T. A. Yangirova, G. R. Zubairovaa, R. M. Sultanovaa, R. Z. Biglovaa,
V. A. Dokicheva, and Yu. V. Tomilovb
a Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: dokichev@anrb.ru
b Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received February 24, 2012
Abstract—Triphenylphosphazenes reacted with methyl vinyl ketone, methyl acrylate, methyl methacrylate,
and dimethyl maleate to give the corresponding substituted dihydropyrazoles.
DOI: 10.1134/S1070428012070068
Well known 1,3-dipolar cycloaddition of diazo
compounds to unsaturated compounds provides a con-
venient method for the synthesis of dihydropyrazole
derivatives [1–3] which attract interest as intermediate
products for the preparation of polyfunctional physio-
logically active substances [4–6]. For example, 2,5-di-
and 3,4,5-trimethoxydihydropyrazole analogs of com-
bretastatin A4 exhibit anticancer activity [5], while
3-(2-furyl)dihydropyrazoles act as antidepressants and
anticonvulsants [6]. The use of aliphatic diazo com-
pounds in organic synthesis is limited due to their
instability and risk of explosion [7]. Phosphazenes are
adducts derived from organophosphorus compounds
and diazo compounds available via Staudinger reaction
[8]; they are used for the identification of unstable
diazo compounds and preparation of various organic
compounds [9, 10]. However, there are no published
data on the use of phosphazenes as synthetic equiv-
alents of diazo compounds in 1,3-dipolar cycloaddition
to unsaturated compounds. It was shown recently that
triphenylphosphine activates the cycloaddition of
methyl diazoacetate to methyl acrylate [11], and we
presumed that phosphazenes may be formed as inter-
mediates in 1,3-dipolar cycloaddition of diazo com-
pounds to those containing a C=C bond.
the corresponding diazo compounds, reactions of tri-
phenylphosphazenes Ia–Ic with olefins can be carried
out at a temperature of up to 110°C. According to the
data of thermogravimetric analysis, decomposition of
crystalline compounds Ia–Ic starts at 140, 120, and
110°C, respectively (see figure); under these condi-
tions, a weight loss of 1% is observed.
The reactions under study were carried out with
equimolar amount of the reactants in benzene at 70°C
(reaction time 5 h). Phosphazenes Ia–Ic reacted with
methyl acrylate to form methyl 4,5-dihydro-1H-pyr-
azole-3(5)-carboxylates IIa–IIc in 48, 18, and 55%
yield, respectively (Scheme 1). The yield of IIa–IIc
was considerably improved by raising the reaction
temperature or extending the reaction time. Methyl
4,5-dihydro-1H-pyrazole-5-carboxylate (IIa) was
formed in quantitative yield in the reaction of phos-
phazene Ia with methyl acrylate at 70°C (16 h) or at
100°C (toluene, argon, sealed ampule, 5 h). The poor
yield (18%) of compound IIb may be rationalized
assuming that 1-[(triphenyl-λ5-phosphanylidene)hydra-
Scheme 1.
OMe
CHR1
N
H2C
+
N
Ph3P
O
In the present work we examined the reaction of
phosphazenes with electron-deficient alkenes and syn-
thesized some new dihydropyrazole derivatives from
formaldehyde (triphenyl-λ5-phosphanylidene)hydra-
zone (Ia), 1-[(triphenyl-λ5-phosphanylidene)hydrazi-
nylidene]propan-2-one (Ib) and methyl [(triphenyl-λ5-
phosphanylidene)hydrazinylidene]acetate (Ic). Unlike
Ia–Ic
R2
R1
18–55%
HN
N
IIa–IIc
I, R1 = H (a), Ac (b), MeOC(O) (c); II, R2 = H, R3 = MeOC(O) (a);
R2 = MeOC(O), R3 = Ac (b); R2 = R3 = MeOC(O) (c).
924

PHOSPHAZENES: I. REACTIONS WITH ELECTRON-DEFICIENT ALKENES
925
Scheme 2.
N
Me
Ph3P
N
O
A
Ph3P
N
Me
N
N
Me
Me
N
Me
N
N
Ph3P
N
Ph3P
O
O
O
O
B
C
Ph3P
N
D
Scheme 3.
CH2=CHC(O)Me
IIb, 60%
O
N
OMe
CH2=C(Me)C(O)OMe
COOMe
Me
N
Ph3P
–Ph3P
MeO
O
N
NH
Ic
III, 10%
COOMe
COOMe
O
O
cis-MeOC(O)CH=CHC(O)OMe
OMe
+
MeO
MeO
HN
N
O
IV, 15%
16%
zinylidene]propan-2-one (Ib) exists mainly as thermo-
dynamically more stable zwitterionic structure A
(Scheme 2) which could not produce dihydropyrazoles
in reactions with electron-deficient alkenes [12, 13].
The formation of dihydropyrazole derivatives in the
reaction of phosphazenes with activated alkenes may
be illustrated by Scheme 4. Michael addition [14] of
phosphazene as structure E at the activated C=C bond
The C=C bond in methyl methacrylate and di-
methyl maleate turned out to be low reactive in 1,3-di-
polar cycloaddition with methyl 3-[(triphenyl-λ5-phos-
phanylidene)hydrazinylidene]acetate (Ic), and the
yield of the corresponding cycloadducts III and IV did
not exceed 15% (Scheme 3). The reaction of Ic with
dimethyl maleate was accompanied by formation of
16% of dimethyl fumarate in addition to the expected
product, trimethyl trans-4,5-dihydro-1H-pyrazole-
3,4,5-tricarboxylate (IV). Dimethyl fumarate was also
formed in 19% yield in the reaction of dimethyl
maleate with ethyl [(triphenyl-λ5-phosphanylidene)-
hydrazinylidene]acetate under analogous conditions.
The absence of diethyl fumarate among the products
indicated that dimethyl fumarate is formed via
isomerization of dimethyl maleate rather than from
phosphazene. The yield of dihydropyrazole IIb from
phosphazene Ic and methyl vinyl ketone was 60%.
Weight loss, %
100
2
80
1
60
3
40
20
0
0
100
200
300
400
500
Temperature, °C
Thermogravimetric analysis of phosphazenes (1) Ia, (2) (Ib),
and (3) Ic.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012

YANGIROV et al.
926
Scheme 4.
R1
N
R1
N
R2
R2
R2
Ph3P
R3
N
CH2=CHR3
~1,3-H
R1
N
Ph3P
N
R1
–PPh3
NH
R3
R3
R2
N
N
E
F
of electron-deficient alkene yields intermediate F
which undergoes intramolecular cyclization with elim-
ination of triphenylphosphine. The subsequent 1,3-hy-
dride shift leads to final 4,5-dihydropyrazole [1, 3].
Unlike diazo compounds, phosphazenes Ia–Ic
reacted with electron-deficient alkenes in a selective
fashion with formation of 4,5-dihydro-1H-pyrazoles;
in no case mixtures of difficultly identifiable com-
pounds [1–3] or by-products resulting from elimination
of nitrogen from dihydropyrazole ring (which is typ-
ical of dihydropyrazoles under catalytic or thermal
conditions [1, 7]) were formed.
off, washed with 10 ml of diethyl ether, and recrystal-
lized from benzene. Yield 3.6 g (62%).
1-[(Triphenyl-λ5-phosphanylidene)hydrazinyli-
dene]propan-2-one (Ib). Triphenylphosphine, 12.5 g
(48 mmol), was dissolved in 50 ml of diethyl ether,
and 4 g (48 mmol) of diazoacetone was added under
stirring, After 10 min, the precipitate was filtered off,
washed with 10 ml of diethyl ether, and recrystallized
from benzene–diethyl ether (1:1). Yield 8.2 g (50%).
Methyl [(triphenyl-λ5-phosphanylidene)hydra-
zinylidene]acetate (Ic) was synthesized in a similar
way from 6 g (23 mmol) of triphenylphosphine and
2.3 g (23 mmol) of methyl diazoacetate in 15 ml of di-
ethyl ether. Yield 5.5 g (66%), white crystals, mp 110–
112°C (decomp.). IR spectrum, ν, cm–1: 2853, 2151,
1690 (N=C), 1681 (C=O), 1520 (P=N), 1437, 1377,
1321, 1261 (C–CO2), 1078, 916, 854, 719, 692, 577,
Thus, the reaction of phosphazenes with electron-
deficient alkenes gives the corresponding 4,5-dihydro-
pyrazoles.
EXPERIMENTAL
1
509. H NMR spectrum (CDCl3), δ, ppm: 3.73 s (3H,
1
The H and 13C NMR spectra were recorded on
OCH3), 7.33 s (1H, CH), 7.45–7.80 m (15H, Ph).
Bruker AM-300 (300.13 and 75.47 MHz, respectively)
and Bruker Avance III (500 and 126 MHz, respec-
tively) spectrometers using tetramethylsilane as inter-
nal reference. The IR spectra were measured on
a Shimadzu IR Prestige-21 instrument from thin films
or samples dispersed in mineral oil. The mass spectra
(electron impact, 70 eV) were obtained on a Thermo
Finnigan MAT 95 XP high-resolution mass spectrom-
eter (ion source temperature 250°C, batch inlet probe
temperature 50–270°C, heating rate 10 deg/min). The
melting points were determined on a Boetius hot stage.
Dynamic thermogravimetric analysis was performed
on a MOM Q-1000 instrument (Paulik–Paulik–Erday),
at a heating rate of 5 deg/min; balance sensitivity
1 mg per scale mark. The temperature corresponding
to a weight loss of 1% was assumed to be the decom-
position start.
13C NMR spectrum (CDCl3), δC, ppm: 51.1 (OMe),
127.5 d (Ci, JCP = 93.7 Hz), 128.8 d (Co, JCP
=
11.6 Hz), 132.46 (Cp), 133.7 d (Cm, JCP = 8.6 Hz),
137.8 d (CH, JCP = 47.7 Hz), 165.8 (C=O). Mass
spectrum, m/z (Irel, %): 277.1015 (2.1) [Ph3P=NH]+,
262.0906 (100), 183.0358 (63.1), 108.0123 (19.5).
Found, %: C 69.60; H 5.32; N 7.45; P 8.39.
C21H19N2O2P. Calculated, %: C 69.61; H 5.25; N 7.73;
P 8.56.
Reaction of phosphazens Ia–Ic with electron-
deficient alkenes (general procedure). A solution of
equimolar amounts of phosphazene Ia–Ic and the
corresponding alkene in benzene was stirred for 5 h at
70°C under argon. The solvent was removed under
reduced pressure. The yield was determined by signal
intensity ratio of the CH proton in dihydropyrazole II
and nitrometane (internal standard, δ 4.31 ppm) in the
1H NMR spectra.
Methyl 4,5-dihydro-1H-pyrazole-3-carboxylate
(IIa) was obtained from 0.5 g (1.65 mmol) of Ia and
0.1415 g (1.65 mmol) of methyl acrylate in 4 ml of
benzene. Yield 48%.
The structure of Ia, Ib, IIa, IIc, and III was con-
firmed by their IR and 1H and 13C NMR spectra which
were consistent with those reported in [15–19].
Formaldehyde (triphenyl-λ5-phosphanylidene)-
hydrazone (Ia). Triphenylphosphine, 5 g (19 mmol),
was dissolved in 50 ml of diethyl ether, 50 ml
(~30 mmol) of a 0.6 M solution of diazomethane in
diethyl ether was added, and the mixture was left to
stand for 24 h in the dark. The precipitate was filtered
Methyl 3-acetyl-4,5-dihydro-1H-pyrazole-5-car-
boxylate (IIb). a. The reaction of 0.1 g (0.29 mmol) of
Ib with 0.025 g (0.29 mmol) of methyl acrylate in 2 ml
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012

PHOSPHAZENES: I. REACTIONS WITH ELECTRON-DEFICIENT ALKENES
927
1
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of benzene gave 18% of IIb. H NMR spectrum
(CDCl3), δ, ppm: 2.41 s (3H, Me), 3.09 d.d (1H, cis-
2
4-H, J = 17.6, J4,5 = 12.6 Hz), 3.26 d.d (1H, trans-
4-H, J = 17.3, J4, 5 = 5.3 Hz), 3.77 s (3H, MeO),
4.45 d.d (1H, 5-H, Jtrans = 5.3, Jcis = 12.6 Hz), 6.75 br.s
(1H, NH). 13C NMR spectrum (CDCl3), δC, ppm: 25.30
(Me), 32.98 (C4), 52.65 (OMe), 61.37 (C5), 149.99
(C3), 172.0 (5-C=O), 193.89 (3-C=O). Found: m/z
170.0741 [M]+·. C7H10N2O3. Calculated: M 170.0693.
b. The reaction of 1 g (2.76 mmol) of Ic with
0.193 g (2.76 mmol) of methyl vinyl ketone in 4 ml of
benzene gave 60% of IIb.
Dimethyl 4,5-dihydro-1H-pyrazole-3,5-dicarbox-
ylate (IIc) was obtained from 1 g (2.76 mmol) of Ic
and 0.2376 g (2.76 mmol) of methyl acrylate in 4 ml of
benzene. Yield 55%.
2
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dicarboxylate (III) was obtained from 0.1 g
(0.28 mmol) of Ic and 0.028 g (0.28 mmol) of methyl
methacrylate in 2 ml of benzene. Yield 10%.
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(0.7 mmol) of Ic and 0.1 g (0.7 mmol) of dimethyl
maleate in 3 ml of benzene. Yield 17%. 1H NMR spec-
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(OMe), 52.46 (C4), 53.25 (4-CO2Me, 5-CO2Me),
66.15 (C5), 139.35 (C3), 161.64 (3-C=O), 169.44
(C=O), 170.16 (C=O).
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This study was performed under financial support
by the Chemistry and Materials Science Department of
the Russian Academy of Sciences (Basic Research
Program “Theoretical and Experimental Studies on the
Nature of Chemical Bonds and Mechanisms of the
Most Important Chemical Reactions and Processes”).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012