Features of the reaction of 4-bromobut-2-enylphosphonium salts with monosubstituted hydrazines

Article abstract of DOI:10.1134/S1070363214030141

(4-Bromobut-2-en-1-yl)triphenylphosphonium bromide reacted with phenylhydrazine at 2°C in the presence of sodium carbonate to form triphenyl[4-(2-phenylhydrazinylidene)but-2-en-1-yl]phosphonium bromide in 62% yield. The obtained N-phenylhydrazine derivati

Full text of DOI:10.1134/S1070363214030141

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 3, pp. 496–500. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © M.Zh. Ovakimyan, G.Ts. Gasparyan, M.R. Grigoryan, A.S. Bichakhchyan, 2014, published in Zhurnal Obshchei Khimii, 2014,
Vol. 84, No. 3, pp. 438–442.
Features of the Reaction of 4-Bromobut-2-enylphosphonium Salts
with Monosubstituted Hydrazines
M. Zh. Ovakimyan, G. Ts. Gasparyan, M. R. Grigoryan, and A. S. Bichakhchyan
Scientific and Technological Center of Organic and Pharmaceutical Chemistry,
Institute of Organic Chemistry, National Academy of Sciences of the Republic of Armenia,
pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: meri-grigoryan19@rambler.ru
Received May 14, 2013
Abstract―(4-Bromobut-2-en-1-yl)triphenylphosphonium bromide reacted with phenylhydrazine at 2°C in the
presence of sodium carbonate to form triphenyl[4-(2-phenylhydrazinylidene)but-2-en-1-yl]phosphonium
bromide in 62% yield. The obtained N-phenylhydrazine derivatives cyclized into the corresponding pyrazoline
derivatives of phosphonium salts. Unlike phenylhydrazine, ethylhydrazine reacted with (4-bromobut-2-ene-1-
yl)triphenylphosphonium bromide under the same conditions to afford triphenyl[(1-ethyl-4,5-dihydro-1H-
pyrazol-3-yl)methyl]- and -[(1-ethyl-1H-pyrazol-3-yl)methyl]phosphonium bromides in yields of 60 and 40%.
DOI: 10.1134/S1070363214030141
It is known that α,β- and β,γ-unsaturated phos-
phonium salts as well as their 1,3-diene analogs are
convenient substrates for the preparation of β- and δ-
substituted phosphonium salts. The latter are both of
theoretical and practical interest due to their possible
use in various fields of national economy and medicine
[1–6].
with a three-fold molar amount of phenylhydrazine
under heating in chloroform to form the 1,4-adducts.
The latter undergo dehydrogenation to afford the
corresponding hydrazone derivatives [7, 8].
In the continuation of these studies we performed
the reaction of (4-bromobut-2-enyl)triphenylphos-
phonium bromide I with phenylhydrazine in chloro-
form at 2°C using sodium carbonate as a base. Tri-
phenyl[4-(2-phenylhydrazinylidene)but-2-en-1-yl]-
phosphonium bromide II was obtained in a 62% yield.
Previously we have showed that triphenyl- and
tributylphosphonium salts containing potential buta-
1,3-diene or 3-chlorobuta-1,3-diene fragments reacted
Ph3P+
Br_
Ph3P+
Br_
Na2CO3
Br
I
Ph3P+
Br_
PhNHNH2
Ph3P+
Br_
_H2
NNHPh
NHNHPh
II
In order to suppress the 1,4-cleavage we carried out
reactions of salt I and its tributyl analog III with a
two-fold molar amount of phenylhydrazine in the
presence of aqueous acetic acid at room temperature.
The reactions proceeded exclusively as nucleophilic
substitution involving the substituted nitrogen atom of
phenylhydrazine to give the desired products IV and V
in high yields.
R3P+
Br _
R3P+
PhNHNH2, CH3COOH, H2O
room temperature
Br_
NNH2
Ph
Br
IV, V
I, III
I, IV: R = Ph; III, V: R = C4H9.
496

FEATURES OF THE REACTION OF 4-BROMOBUT-2-ENYLPHOSPHONIUM SALTS
497
However, we failed to obtain only the products of
nucleophilic substitution under the same conditions
proceeding from triphenyl- and tributyl(4-bromo-3-
chlorobut-2-en-1-yl)phosphonium bromides VI and
VII. In both cases compounds X and XI were obtained
along with the substitution products VIII and IX.
R3P+
Br_
Br
Cl
VI, VII
PhNHNH2,
CH3COOH, H2O
R3P+
Br_
R3P+
Br_
NNH2
Ph
NNHPh
Cl
Cl
X, XI
VIII, IX
VI, VIII, X: R = Ph; VII, IX, XI: R = Bu.
Compounds IV and V readily undergo hetero-
cyclization. Their interaction with 25% aqueous solu-
tion of sodium hydroxide in benzene even at room
temperature afforded the corresponding pyrazolines
XII and XIII in >50% yield. Apparently, the reaction
proceeds according to the following scheme.
OH−
R3P+
R3P+
Br_
Br_
NNH2
H2N
Ph
N
IV, V
Ph
R3P+
R3P+
Br _
Br_
HN
_H2
N
N
N
Ph
Ph
XII, XIII
IV, XII: R = Ph; V, XIII: R = Bu.
α,β-Unsaturated intermediates formed from IV and
V as a result of the prototropic isomerization undergo
heterocyclization into N-phenylpyrazolidine derivatives.
Under the reaction conditions the latter were subjected
to spontaneous dehydrogenation [4, 5] resulting in the
corresponding pyrazolines XII and XIII. Compounds
XII and XIII have been previously prepared by
reacting phenylhydrazine with triphenyl- and tributyl-
(4-bromobut-2-yn-1-yl)phosphonium bromide [9].
a base. Probably, the reaction proceeds via the inter-
mediate formation of the substitution product A of
linear structure subjected to heterocyclization under
the reaction conditions (Scheme 1).
Different behavior of phenyl- and ethylhydrazine
may be due to the difference between their nucleo-
philicity. Probably, the formation of compound XV is
due to the release of a hydride ion owing to the transfer
of a lone electron pair on the nitrogen in the dihydro-
pyrazole molecule by the above mentioned scheme,
which is in agreement with the literature data on hyd-
ride-donor properties of dihydroaromatic compounds [10].
Unlike phenylhydrazine, ethylhydrazine reacted
with salt I to form pyrazoline XIV and pyrazole XV
derivatives in acetonitrile at 30–35°C in the absence of
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498
OVAKIMYAN et al.
Scheme 1.
C2H5NHNH2
Ph3P+
Br _
Ph3P+
Br_
Br
NNH2
C2H5
A
Ph3P+
Br_
Ph3P+
Br _
NC2H5
HN
:
NH2
N
C2H5
H
Ph3P+
Br_
Ph3P+
Br_
Ph3P+
Br_
−H2
_H2
:
H
HN
N
N
N
N
N
C2H5
C2H5
C2H5
XIV
XV
EXPERIMENTAL
NNH). 31Р NMR spectrum: δР 26.28 ppm. Found, %:
Br 15.73; P 5.87. C28H26BrN2P. Calculated, %: Br
15.97; P 6.19.
1H (300.077 MHz) and 31P (121.47 MHz) NMR
spectra were recorded on a Varian Mercury-300
spectrometer at 303 K using a mixture DMSO-d6–CCl4
(1 : 3) as a solvent. Chemical shifts are shown relative
to internal refernce TMS (1H) and external reference
85% H3PO4 (31P), respectively.
Triphenyl[4-(1-phenylhydrazinyl)but-2-en-1-yl]-
phosphonium bromide (IV). A mixture of 0.12 mL of
acetic acid and 0.45 g (4.2 mmol) of phenylhydrazine
was added to a suspension of 1 g (2.1 mmol ) of salt I
in 15 mL of water at room temperature. The reaction
mixture was stirred for 4 h. Then the reaction product
was extracted with chloroform. The organic layer was
separated, dried over MgSO4, filtered, and evaporated.
The residue was thoroughly washed with benzene and
anhydrous diethyl ether, and dried in a vacuum. Yield
Triphenyl- and tributyl(4-bromobut-2-en-1-yl)phos-
phonium bromides I and III, triphenyl- and tributyl(4-
bromo-3-chlorobut-2-en-1-yl)phosphonium bromides
VI and VII were synthesized according to known
methods [11, 12].
1
0.75 g (71%), mp 98–101°C. H NMR spectrum, δ,
Triphenyl[4-(2-phenylhydrazinylidene)but-2-en-
1-yl]phosphonium bromide (II). A mixture of 1.5 g
(3.2 mmol) of salt I and 1.32 g (9.6 mmol) of
powdered sodium carbonate in 20 mL of chloroform
was stirred for 18 h at room temperature. The reaction
mixture was filtered. Then 0.38 g (3.5 mmol) of
phenylhydrazine was added dropwise to the filtrate at
2°C. After heating to room temperature, water was
added to the reaction mixture. The organic layer was
separated, dried over MgSO4 and evaporated. The
residue was recrystallized from ethyl acetate–isopropyl
ppm (J, Hz): 2.95 br.s (2Н, NH2), 3.9–4.1 m (2Н,
CH2NPh, J1 7.35, J2 1.50), 4.63 d.d (2H, P+CH2, J1
16.12, J2 7.95), 5.45–5.55 m (1Н, P+CH2CH=CH),
5.83–6.01 m (1Н, P+CH2CH=CH), 6.6–7.0 m (5Н,
31
NPh), 7.6–7.92 m (15Н, P+Ph). Р NMR spectrum: δР
26.8 ppm. Found, %: Br 15.67; P 5.79. C28H28BrN2P.
Calculated, %: Br 15.90; P 6.16.
Tributyl[4-(1-phenylhydrazinyl)but-2-en-1-yl]-
phosphonium bromide (V) was obtained similarly
from 1 g (2.4 mmol) of the salt III and 0.5 g
(4.8 mmol) of phenylhydrazine in the presence of
0.14 mL of acetic acid in 15 mL of water. Yield 0.9 g
1
alcohol mixture. Yield 1 g (62%), mp 218–220°C. H
NMR spectrum, δ, ppm (J, Hz): 4.8 d.d (2Н, P+CH2, J1
16.10, J2 7.95 ), 5.48–5.87 m (1Н, P+CH2CH=CH),
1
(84.7%). H NMR spectrum, δ, ppm (J, Hz): 0.99 br.t
6.37–6.49 m (1Н, P+CH2CH=CH), 6.64 t.t (1H, H4Ph, J1
(9H, 3CH3, J 6.70), 1.4–1.5 m (12H, 3CH2), 2.11–2.29
m (6H, 3CH2), 2.95 br.s (2Н, NH2), 3.24 d.d (2H,
P+CH2, J1 16.30, J2 8.00), 4.19 d.d (2Н, CH2NPh, J1
7.30, J2 1.50), 5.58–5.72 m (1Н, P+CH2CH=CH), 5.85–
3,5
7.30, J2 1.30), 6.98 d.d (2H, H , J1 8.41, J2 7.33),
Ph
2,6
Ph
7.10 d.d (2H, H , J1 8.41, J2 1.30), 7.48 d (1Н,
CH=N, J 7.3), 7.6–8.0 m (15Н, P+Ph), 10.25 s (1H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

FEATURES OF THE REACTION OF 4-BROMOBUT-2-ENYLPHOSPHONIUM SALTS
499
6.07 m (1Н, P+CH2CH=CH), 6.8 t.t (1H, H4Ph, J1 7.30,
chloroform were added to the residue. Triphenyl-
phosphine oxide (mp 156°C) was isolated from the
benzene layer (0.2 g, 24%). The chloroform extract
was dried over MgSO4, filtered and evaporated. The
residue was washed with anhydrous diethyl ether,
dried in a vacuum, and recrystallized from ethyl
acetate–2-propanol mixture. Yield 0.8 g (53%). 1H and
31P NMR spectra coincided with those of the known
sample [9].
3,5
J2 1.30), 6.98–7.1 m (2H, H ), 7.15–7.25 m (2H,
Ph
HP2h,6). 31Р NMR spectrum: δР 37.75 ppm. Found, %: Br
17.85; P 6.74. C22H40BrN2P. Calculated, %: Br 18.06;
P 6.99.
Triphenyl[4-(1-phenylhydrazinyl)-3-chlorobut-
2-en-1-yl]phosphonium bromide (VIII) was obtained
similarly from 2.5 g (4.9 mmol) of the salt VI and
1.1 g (9.8 mmol) of phenylhydrazine in the presence of
0.28 mL of acetic acid in 20 mL of water. The product
was isolated by fractional recrystallization from ethyl
Tributyl[(1-phenyl-4,5-dihydro-1Н-pyrazol-3-yl)-
methyl]phosphonium bromide (XIII) was prepared
similarly from 1.5 g (3.4 mmol) of salt V and 1.1 g
(6.8 mmol) of 25% aqueous sodium hydroxide in
1
acetate–2-propanol mixture. Yield 1.5 g (56.8%). H
NMR spectrum, δ, ppm (J, Hz): 2.98 br.s (2Н, NH2),
3.58 д (2Н, CH2NPh, J 1.30), 4.87 d.d (2H, P+CH2, J1
16.30, J2 8.00), 5.96–6.12 m (1Н, P+CH2CH=CCl),
1
20 mL of benzene. Yield 0.76 g (51%). H and 31P
NMR spectra coincided with those of the known
sample [9].
6.66 t.t (1H, H4Ph, J1 7.30, J2 1.30), 6.98–7.08 m (2H,
2,6
HP3h,5), 7.14–7.22 m (2H, H ), 7.65–8.0 m (15Н,
Ph
Triphenyl[(1-ethyl-4,5-dihydro-1Н-pyrazol-3-yl)-
methyl]phosphonium bromide (XIV) and triphenyl
[(1-ethyl-1H-pyrazol-3-yl)methyl]phosphonium
bromide (XV). A mixture of 1 g (2.1 mmol) of salt I
and 0.25 g (4.2 mmol) of ethylhydrazine in 15 mL of
acetonitrile was stirred at 30–35°C for 8 h. Then the
solvent was removed, and the reaction products were
extracted from the residue with water and chloroform.
The chloroform layer was dried over MgSO4, filtered
and evaporated. The residue was washed with benzene
and anhydrous diethyl ether, and dried in a vacuum.
Yield 0.8 g (XIV:XV = 3:2).
Compound XIV. 1Н NMR spectrum, δ, ppm
(J, Hz): 1.24 t (3Н, CH2CH3, J 7.3), 2.73 t. d (2H, CH2,
J1 10.3, J2 1.8), 3.40 q (2Н, CH2CH3, J 7.3), 3.65 t
(2H, NCH2, J 10.3), 5.2 d (2Н, P+CH2, J 15.1), 7.62–
7.8 m (15Н, P+Ph3). 31Р NMR spectrum: δР 27.3 ppm.
P+Ph). 31Р NMR spectrum: δР 26.2 ppm. In addition
triphenyl[4-(2-phenylhydrazinylidene)-3-chlorobut-2-
en-1-yl]phosphonium bromide X was obtained (0.6 g,
2 2.9%). 1H and 31P NMR spectra coincided with those
of the known sample [7]. Found,%: Br 14.43; P 6.04.
C28H27BrClN2P. Calculated, %: Br 14.86; P 5.76.
Tributyl[4-(1-phenylhydrazinyl)-3-chlorobut-2-
en-1-yl]phosphonium bromide (IX) was obtained
similarly from 1.5 g (3.3 mmol) of the salt VII and
0.8 g (7.0 mmol) of phenylhydrazine in the presence of
0.19 mL of acetic acid in 15 mL of water. The product
was isolated by fractional recrystallization from ethyl
1
acetate–2-propanol mixture. Yield 0.8 g (50%). H
NMR spectrum, δ, ppm (J, Hz): 0.99 br.t (9H, 3CH3, J
6.70), 1.32–1.58 m (12H, 3CH2), 2.38–2.47 m (6H,
3CH2), 3.05 br.s (2Н, NH2), 3.42 d.d (2H, P+CH2, J1
16.40, J2 7.10), 4.21 d (2Н, CH2NPh, J1 1.60), 5.82–
Compound XV. 1Н NMR spectrum, δ, ppm
(J, Hz): 1.12 t (3Н, CH2CH3, J 7.3), 4.05 q (2Н,
CH2CH3), 5.09 d (2Н, P+CH2, J 15.1), 5.87 d.d (1H,
H4Рyr, J1 2.4, J2 1.5), 7.45 d (1H, H5Рyr, J 2.4), 7.82–8.0
m (15Н, P+Ph3). 31Р NMR spectrum: δР 27.5 ppm.
+
6.08 m (1Н, CH2CH=СCl), 6.7 t.t (1H, H4Ph, J1 7.30,
3,5
Ph
J2 1.30), 6.94–7.04 m (2H, H ), 7.11–7.25 m (2H,
HP2h,6). 31Р NMR spectrum: δР 40.36 ppm.
In addition tributyl[4-(2-phenylhydrazinylidene)-3-
chlorobut-2-en-1-yl]phosphonium bromide XI was
1
obtained (0.4 g, 25 %). H and 31P NMR spectra
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