Reactions of allenyl- and vinylphosphonates with imidazole

Article abstract of DOI:10.1134/S107042800711019X

Dialkyl 3-methylbuta-1,2-dienyl- and vinylphosphonates take up imidazole at the β-carbon atom in the unsaturated fragment to give the corresponding β-(1H-imidazol-1-yl)alkenyl-and alkylphosphonates.

Full text of DOI:10.1134/S107042800711019X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 11, pp. 1703–1705. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © N.G. Khusainova, E.A. Berdnikov, O.A. Mostovaya, S.M. Rybakov, R.A. Cherkasov, 2007, published in Zhurnal Organicheskoi
Khimii, 2007, Vol. 43, No. 11, pp. 1703–1705.
Reactions of Allenyl- and Vinylphosphonates with Imidazole
N. G. Khusainova, E. A. Berdnikov, O. A. Mostovaya, S. M. Rybakov, and R. A. Cherkasov
Butlerov Chemical Institute, Kazan State University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia
e-mail: narkis.khusainova@ksu.ru
Received January 4, 2007
Abstract—Dialkyl 3-methylbuta-1,2-dienyl- and vinylphosphonates take up imidazole at the β-carbon atom in
the unsaturated fragment to give the corresponding β-(1H-imidazol-1-yl)alkenyl- and alkylphosphonates.
DOI: 10.1134/S107042800711019X
Derivatives of alkenyl- and alkylphosphonic acids
having nitrogen-containing groups in the β-position
attract interest as potential biologically active com-
pounds with a broad spectrum of action, complexing
agents, and extractants [1–4]. The simplest and con-
venient method for the synthesis of β-aminophospho-
nates is based on reaction of unsaturated four-coor-
dinate phosphorus acid derivatives with primary and
secondary amines [5–7]. However, methods of syn-
thesis and properties of alkenyl- and alkylphospho-
nates having nitrogen-containing heterocyclic substit-
uents in the β-position have been studied insufficiently
[1]. The present article reports on the results of our
study on the reactions of dialkyl allenyl- and vinyl-
phosphonates with imidazole with a view to obtain
new potential biologically active derivatives.
signals from two methyl groups attached to a double-
bonded carbon atom. These findings suggest that
imidazole adds at the 1,2-double bond of cumulene I to
give diethyl 2-(1H-imidazol-1-yl)-3-methylbut-2-en-1-
ylphosphonate (II) (Scheme 1). Protons in the imida-
zole ring of compound II give rise to three broadened
signals at δ 6.88, 7.00, and 7.40 ppm in the H NMR
spectrum, in keeping with published data for N-sub-
stituted imidazole derivatives [8].
1
Apart from signals belonging to adduct II, the
1H NMR spectrum of the reaction mixture contained
the following weak signals, δ, ppm: 1.27 m (3H, 3JHH
=
5
7, JHH = 1 Hz), 4.00 m (2H), 6.96 br.s (1H), 7.02 br.s
(1H), 7.06 br.s (1H); these signals were assigned to
N-ethylimidazole (III). Presumably, the reaction is
accompanied by partial dealkylation of the phospho-
nate fragment of compound I or II with formation of
acidic ester IV and N-ethylimidazole (III). The forma-
tion of ethyl hydrogen phosphonate IV is confirmed by
The 31P NMR spectrum of the reaction mixture
obtained from diethyl 3-methylbuta-1,2-dien-1-ylphos-
phonate (I) and imidazole contained two phosphorus
signals at δP 26.2 and 25.4 ppm with an intensity ratio
of 10:1. Distillation of the mixture gave compound II
which showed only one signal at δP 26 ppm in the
31P NMR spectrum. In the 1H NMR spectrum of adduct
1
the presence in the H NMR spectrum of a methylene
proton signal at 3.01 ppm with a coupling constant 2JPH
of 20.9 Hz; in addition, several triplets from methyl
protons in the ethoxy groups of II and IV are over-
lapped in the δ region 1.2–1.3 ppm. Protons of the
OCH2 groups in structures II and IV appear as over-
lapped multiplets at δ 4.00 ppm. Compound IV is
II we observed a doublet at δ 2.86 ppm (2JPH
=
21.3 Hz), which is typical of methylene protons in the
α-position with respect to phosphorus, and doublet
Scheme 1.
N
N
N
N
Me
Me
Me
Me
N
Me
Me
N
O
·
+
+
+
N
N
P(O)(OEt)2
P(O)(OEt)2
P
H
OH
OEt
Et
III
I
II
IV
1703

KHUSAINOVA et al.
1704
likely to be characterized by a high boiling point, so
that it cannot be isolated by distillation. The ability of
unsaturated methyl and ethyl phosphonates to undergo
dealkylation of the ester moiety was noted by us
previously [9, 10].
In the reaction of dibutyl vinylphosphonate (X)
with imidazole we obtained dibutyl 2-(1H-imidazol-1-
yl)ethylphosphonate (XI) as the only product.
Thus nucleophilic addition of imidazole to allenyl-
and vinylphosphonates occurs at the β-carbon atom of
the unsaturated fragment to give the corresponding
β-imidazolylalkenyl- and -alkylphosphonates.
Likewise, the reaction of imidazole with diiso-
propyl 3-methylbuta-1,2-dien-1-ylphosphonate (V)
afforded diisopropyl 2-(1H-imidazol-1-yl)-3-methyl-
but-2-en-1-ylphosphonate (VI) via addition of the
heterocycle at the central carbon atom of the cumulat-
EXPERIMENTAL
1
ed bond system. As followed from the H and 31P
The IR spectra were recorded on a UR-20 spec-
1
trometer. The H and 31P NMR spectra were obtained
NMR spectra of the reaction mixture, the process is not
accompanied by dealkylation of the phosphonate frag-
ment. On the other hand, the addition of imidazole to
allene activated by an ethoxycarbonyl group, catalyzed
by stoichiometric amount of triphenylphosphine,
occurred at the terminal carbon atom of the cumulene
system [8].
1
on a Varian Unity-300 instrument at 300 MHz for H
31
and 121.42 MHz for P from solutions in CDCl3. The
chemical shifts were measured relative to the residual
solvent signal (1H; CHCl3, δ 7.24 ppm) or 85% phos-
phoric acid (31P, external reference).
Reaction of imidazole with dialkyl allenylphos-
phonates (general procedure). A mixture of 1 mmol of
phosphonate I or V and 1 mmol of imidazole was
heated at 85–90°C until the cumulene absorption band
at 1955 cm–1 (νC=C=C) disappeared from the IR spec-
trum of the mixture. The products were isolated by
distillation under reduced pressure.
1
According to the H and 31P NMR data, diethyl
vinylphosphonate (VII) reacted with imidazole to give
β-imidazolylethylphosphonate VIII, ethyl hydrogen
phosphonate IX, and ethylimidazole III (Scheme 2).
The 31P NMR spectrum of the reaction mixture con-
tained two signals at δP 27.2 and 26.9 ppm at a ratio of
1:0.1. The signal at δP 26.9 ppm was assigned to the
phosphorus nucleus in ethyl hydrogen 2-(1H-imidazol-
1-yl)ethylphosphonate (IX). The formation of IX is
Diethyl 2-(1H-imidazol-1-yl)-3-methylbut-2-en-
1-ylphosphonate (II). Yield 1.23 g (33%), mp 36°C,
1
1
bp 123°C (0.04 mm). H NMR spectrum, δ, ppm:
also confirmed by the presence in the H NMR spec-
3
1.18 t (6H, CH3CH2O, JHH = 7.3 Hz), 1.46 d (3H,
trum of the reaction mixture of overlapping multiplets
at δ 2 and 4 ppm from the PCH2 and OCH2 protons
in VIII and IX. Methyl protons in the ethoxy group of
acidic ester IX resonate as a triplet at δ 1.31 ppm
(3JHH = 7.1 Hz). Distillation of the reaction mixture
gave compound VIII which displayed only one signal
at δP 27 ppm in the 31P NMR spectrum.
5
5
=CCH3 , JPH = 6.1 Hz), 1.84 d (3H, =CCH3 , JPH
=
2
4.9 Hz), 2.86 d (2H, CH2P, JPH = 21.3 Hz), 3.92 m
3
4
(4H, CH2O), 6.88 d.d (1H, 4-H, JHH = 1.2, JHH
=
0.9 Hz), 7.00 d.d (1H, 5-H, JHH = 1.2, 4JHH = 0.9 Hz),
7.40 d.d (1H, 2-H, 4JHH = 0.9, 4JHH = 0.9 Hz). 31P NMR
spectrum: δP 26 ppm. Found, %: C 52.58; H 7.9;
P 10.89. C12H21N2O3P. Calculated, %: C 52.93; H 7.77;
P 11.32.
3
Scheme 2.
N
Diisopropyl 2-(1H-imidazol-1-yl)-3-methylbut-2-
en-1-ylphosphonate (VI). Yield 2.2 g (72%), bp 122–
124°C (0.03 mm), nD20 = 1.4858. 1H NMR spectrum, δ,
+
H2C
N
H
P(O)(OEt)2
3
VII
ppm: 1.00 d [6H, (CH3)2CHO, JHH = 6.2 Hz], 1.06 d
3
[6H, (CH3)2CHO, JHH = 6.2 Hz], 1.31 d (3H, CH3C=,
O
P
5
5JPH = 6.0 Hz), 1.70 d (3H, CH3C=, JPH = 4.6 Hz),
N
N
OEt
2
2.68 d (2H, CH2P, JPH = 21.2 Hz), 4.44 d.sept (2H,
OEt
3
CHOP, JHH = 6.2, 3JPH = 7.6 Hz), 6.75 d.d (1H, 4-H,
VIII
3
3JHH = 1.3, 4JHH = 1.1 Hz), 6.84 d.d (1H, 5-H, JHH
=
4
4
O
P
1.3, JHH = 0.9 Hz), 6.95 d.d (1H, 2-H, JHH = 1.1,
4JHH = 0.9 Hz). 31P NMR spectrum: δP 22.7 ppm.
Found, %: C 56.32; H 8.18; P 9.91. C14H25N2O3P. Cal-
culated, %: C 56.01; H 8.33; P 10.32.
N
+
N
+
N
N
OH
Et
OEt
III
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 11 2007

REACTIONS OF ALLENYL- AND VINYLPHOSPHONATES WITH IMIDAZOLE
1705
REFERENCES
Reaction of imidazole with vinylphosphonates
(general procedure). A mixture of 1 mmol of vinyl-
phosphonate VII or X and 1 mmol of imidazole was
heated for 20–22 h at 85–90°C and was then distilled
under reduced pressure.
1. Aminophosphonic and Aminophosphinic Acids: Chem-
istry and Biological Activity, Kukhar, V.P. and Hud-
son, H.R., New York: Wiley, 2000.
2. Palacios, F., Alonso, C., and de los Santos, J.M., Chem.
Rev., 2005, vol. 105, p. 899.
3. Kafarski, P. and Lejczak, B., Curr. Med. Chem. Anti-
Cancer Agents, 2001, vol. 1, p. 301.
4. Cherkasov, R.A., Galkin, V.I., Khusainova, N.G., Mos-
tovaya, O.A., Garifzyanov, A.R., Nuriazdanova, G.Kh.,
Krasnova, N.S., and Berdnikov, E.A., Russ. J. Org.
Chem., 2005, vol. 41, p. 1481.
Diethyl 2-(1H-imidazol-1-yl)ethylphosphonate
(VIII). Yield 0.55 g (28%), bp 131–132°C (0.05 mm),
1
nD20 = 1.4834. H NMR spectrum, δ, ppm: 1.21 t (6H,
3
2
CH3CH2O, JHH = 7.0 Hz), 2.14 m (2H, CH2P, JPH
=
18.9 Hz), 3.97 m (4H, CH2OP), 4.14 m (2H, NCH2,
3JPH = 12.2 Hz), 6.86 br.s (1H, 4-H), 6.96 br.s (1H,
5-H), 7.42 br.s (1H, 2-H). 31P NMR spectrum:
δP 27 ppm. Found, %: C 42.01; H 7.18; P 12.91.
C9H17N2O3P. Calculated, %: C 42.24; H 7.33; P 13.36.
5. Pudovik, A.N. and Denisova, G.M., Zh. Obshch. Khim.,
1953, vol. 23, p. 263.
6. Khusainova, N.G., Mostovaya, O.A., Berdnikov, E.A.,
Litvinov, I.A., Krivolapov, D.B., and Cherkasov, R.A.,
Russ. J. Org. Chem., 2005, vol. 41, p. 1260.
7. Panarina, A.E., Dogadina, A.V., Zakharov, V.I., and
Ionin, B.I., Tetrahedron Lett., 2001, vol. 42, p. 4365.
8. Virieux, D., Guillouzic, A.-F., and Cristau, H.-J.,
Tetrahedron, 2006, vol. 62, p. 3710.
9. Pudovik, A.N. and Khusainova, N.G., Zh. Obshch. Khim.,
Khimiya organicheskikh soedinenii phosphora (Chem-
istry of Organic Phosphorus Compounds), 1967, p. 53.
10. Khusainova, N.G., Mostovaya, O.A., Nizamov, I.S., and
Cherkasov, R.A., Russ. J. Org. Chem., 2004, vol. 40,
p. 581.
Dibutyl 2-(1H-imidazol-1-yl)ethylphosphonate
(XI). Yield 1.3 g (43%), bp 145–147°C (0.07 mm),
1
nD20 = 1.4749. H NMR spectrum, δ, ppm: 0.93 t (6H,
3
CH3CH2, JHH = 7.3 Hz), 1.37 m (4H, CH2), 1.62 m
(4H, CH2), 2.42 m (2H, CH2P, 2JPH = 18.7 Hz), 4.01 m
(4H, CH2OP), 4.22 m (2H, NCH2, 3JPH = 11.6 Hz),
6.94 d.d (1H, 4-H, 3JHH = 1.2, 4JHH = 1.0 Hz), 7.05 d.d
3
4
(1H, 5-H, JHH = 1.2, JHH = 1.0 Hz), 7.50 d.d
(1H, 2-H, JHH = 1.0, 1.0 Hz). 31P NMR spectrum:
4
δP 26.5 ppm. Found, %: C 54.62; H 8.28. C13H25N2O3P.
Calculated, %: C 54.16; H 8.68.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 11 2007