Phosphorus-containing 1,3-zwitterions formed in the reaction of tributylphosphine with 3-aryl-2-cyanoacrylates

Article abstract of DOI:10.1007/s11172-009-0332-8

Tributylphosphine reacts with 3-aryl-2-cyanoacrylates in acetonitrile to afford adducts, viz., phosphorus-containing betaines, thermodynamic stability of which depends on both the nature of the solvent and electronic and spatial characteristics of the ary

Full text of DOI:10.1007/s11172-009-0332-8

Russian Chemical Bulletin, International Edition, Vol. 58, No. 11, pp. 2397—2399, November, 2009
2397
Phosphorusꢀcontaining 1,3ꢀzwitterions formed in the reaction
of tributylphosphine with 3ꢀarylꢀ2ꢀcyanoacrylates
N. V. Slepchenkov, A. S. Peregudov, N. G. Senchenya, P. V. Petrovskii,
V. N. Khrustalev, I. A. Garbuzova, and Yu. G. Gololobov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Еꢀmail: yugol@ineos.ac.ru
Tributylphosрhine reacts with 3ꢀarylꢀ2ꢀcyanoacrylates in acetonitrile to afford adducts,
viz., phosphorusꢀcontaining betaines, thermodynamic stability of which depends on both the
nature of the solvent and electronic and spatial characteristics of the aryl substituent in 3ꢀarylꢀ
2ꢀcyanoacrylates.
Key words: tributylphosphine, 3ꢀarylꢀ2ꢀcyanoacrylates, phosphorusꢀcontaining zwitterions,
Xꢀray diffraction analysis.
Substituted ethylenes containing electronꢀwithdrawꢀ
ing substituents at the carbon atoms of the double bond
easily add rather nucleophilic compounds of trivalent
phosphorus to produce the corresponding phosphorusꢀ
containing 1,3ꢀzwitterions.1 We have described2 the reacꢀ
tion of highly nucleophilic tertiary phosphines with
unsubstituted alkyl 2ꢀcyanoacrylates. This allowed
involvement of alkyl 2ꢀcyanoacrylates, which usually
instantly polymerize under the action of phosphines, in
the reaction with trialkylphosphines and triamidophosꢀ
phites under special conditions. Reactions of 3ꢀsubstiꢀ
tuted 2ꢀcyanoacrylates have not been studied. At the same
time, synthesis of phosphorusꢀcontaining 1,3ꢀzwitterions
substituted with aryl group in the position 3 is of essential
interest since it allows considerable extension of the search
for the synthesis of potential medicines.
Scheme 1
3ꢀArylꢀ2ꢀcyanoacrylates3 1 were obtained by the
Knoevenagel reaction of ethyl cyanoacetate with aromatic
aldehydes (Scheme 1).
3ꢀArylꢀ2ꢀcyanoacrylates 1 are crystalline compounds
comparatively well soluble in polar solvents. All of them
are formed in a single configuration, since only one signal
for the vinyl proton is observed in the 1Н NMR spectrum.
The attempts to accomplish their reactions with triphenylꢀ
phosphine or diphenylphosphine aimed at obtaining
the corresponding Pꢀzwitterions were unsuccessuful. The
reactants remained unchanged regardless of the solvent
used. However, 3ꢀarylꢀ2ꢀcyanoacrylates 1 smoothly react
with more nucleophilic triꢀnꢀbutylphosphine in acetoꢀ
nitrile to produce zwitterions 2 (see Scheme 1).
1, 2
a
b
R1
H
OH
OMe
R2
H
H
1, 2
R1
Br
H
R2
H
NO2
H
d
e
f
c
H
NO2
due to spatial screening of the reaction center by the
chlorine atoms. The yield of zwitterions 2 was almost
quantitative based on the 31Р NMR spectra of the reaction
mixtures in acetonitrile, the isolated yield was 70—90%.
The structure of compounds obtained as zwitterions 2 was
confirmed by elemental analysis, physicochemical charꢀ
acteristics and Xꢀray diffraction study (Fig. 1, Table 1).
It should be noted that judging from the 31Р NMR
spectroscopy data ethyl 3ꢀ(2,6ꢀdichlorophenyl)ꢀ2ꢀcyanoꢀ
acrylate does not react with tributylphosphine probably
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2320—2322, November, 2009.
1066ꢀ5285/09/5811ꢀ2397 © 2009 Springer Science+Business Media, Inc.

2398
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009
Slepchenkov et al.
C(11)
C(15)
C(10)
C(8)
C(48)
C(47)
O(6)
C(9)
C(13)
C(39)
N(4)
C(14)
C(38)
P(2)
N(5)
C(46)
C(26)
C(49)
C(36)
C(28)
C(29)
C(30)
C(31)
C(33)
C(12)
C(5)
C(37)
C(27)
C(50)
P(1)
C(4)
C(18)
C(19)
C(17)
C(16)
C(25)
O(3)
N(1)
O(4)
C(41)
C(42)
C(43)
O(7)
N(3)
O(5)
O(1)
C(6)
C(1)
C(40)
C(45)
C(44)
C(21)
C(20)
C(2)
C(3)
C(32)
C(7)
C(23)
C(22)
N(2)
C(35) C(34)
O(2)
O(8)
C(24)
Fig. 1. Molecular structure of zwitterion 2f.
Table 1. Selected bond lengths (d) and
bond angles (ω) in molecule 2f
Table 2. Percentage of the zwitterion 2 in various solvents
Solvent
ε
2a
2b
2c
2d
2e
2f
Parameter
Value
MeCN
DMSO
37.5 91.3 98.8 96.9 100.0 100.0 100.0
48.9 87.9 94.3 95.9 97.7 96.8 98.2
Bond
O(1)—C(3)
O(2)—C(3)
N(2)—C(22)
C(1)—C(2)
C(2)—C(3)
C(2)—C(22)
O(5)—C(27)
d/Å
1.2352(13)
1.3802(13)
1.1549(15)
1.5165(14)
1.4134(14)
1.4057(14)
1.2390(12)
1.3710(12)
1.1647(14)
1.5088(14)
1.4110(14)
1.4051(14)
ω/deg
118.66(9)
120.12(9)
121.12(9)
117.84(9)
121.67(9)
120.35(9)
Me2CO 20.70 40.0 21.6 30.7 21.4 27.9 29.2
CHCl3
THF
4.806 1.1
7.4
3.1
3.8
1.7
1.3
2.5
2.6
2.8
2.2
3.3
3.1
0
of dissociation of zwitterions 2 was determined based on
the integrated ratio of signals for the phosphorus atoms in
the solution for zwitterion 2 and tributylphosphine. The
percentage of zwitterion 2 in the solution after dissolution
of crystalline zwitterion 2 in one or another solvent is
given in Table 2.
The structure of compound 2f was determined by
Xꢀray diffraction analysis (see Fig. 1). Compound 2f
contains a chiral carbon atom and crystallizes in the triꢀ
clinic space group P1– with two crystallographically indeꢀ
pendent molecules in the unit cell. Two crystallographiꢀ
cally independent molecules differ only in the conformaꢀ
tion of the ethoxy group in the carboxylate substituent
(the torsion angles C(3)—O(2)—C(23)—C(24) and
C(27)—O(6)—C(47)—C(48) are 173.6(1) and –89.8(1)°,
respectively). Compound 2f is a zwitterion containing
positive phosphonium and negative carbanion centers.
Zwitterionic structure of compound 2f is stabilized
due to the delocalization of the negative charge over the
O=C—C—C≡N fragment (see Table 1).
In the crystal, the molecules of compound 2f are
linked through weak hydrogen bonds: C—H...O
[C(1)—H(1A)…O(1) (1 – x, 2 – y, 1 – z), C…O 3.338(2),
H…O 2.37 Å, angle C—H…O is 162°; C(1)—H(17A)…O(1)
(1 – x, 2 – y, 1 – z), C…O 3.205(2), H…O 2.33 Å, angle
C–H…O is 153°; C(32)—H(32B)…O(5) (2 – x, 2 – y, –z),
C…O 3.135(2), H…O 2.30 Å, angle C—H…O is 141°;
C(45)—H(45A)…O(5) (2 – x, 2 – y, –z), C…O 3.282(2),
H…O 2.42 Å, angle C—H…O is 151°] and C—H…N
O(6)—C(27)
N(4)—C(46)
C(25)—C(26)
C(26)—C(27)
C(26)—C(46)
Angle
C(1)—C(2)—C(3)
C(1)—C(2)—C(22)
C(3)—C(2)—C(22)
C(25)—C(26)—C(27)
C(25)—C(26)—C(46)
C(27)—C(26)—C(46)
The IR spectra show absorption bands of the cyanoꢀ and
ethoxycarbonyl groups of compound 2 at lower frequenꢀ
cies than analogous ones for the starting cyanoacrylates.
Thus, this is the evidence of considerable delocalization
of the negative charge in zwitterions 2. The signals for the
methylene protons of the ethoxycarbonyl group appear as
two quartets due to the presence of a asymmetric center in
molecules 2. The methylene protons at the phosphorus
atom appear as complex multiplets.
All zwitterions obtained undergo dissociation in orꢀ
ganic solvents to certain extent to produce the starting
tributylphosphine and the corresponding acrylate. Dissoꢀ
ciation of these compounds is minimal in acetonitrile and
dimethyl sulfoxide, in less polar solvents the degree of
dissociation depends on the solvent polarity. The degree

Phosphonium zwitterions
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 11, November, 2009 2399
Found (%): C, 64.31; H, 8.39; N, 6.28; P, 6.85. C24H37N2O4P.
[C(28)—H(28A)…N(4) (1 – x, 2 – y, –z), C…N 3.386(2),
H…N 2.42 Å, angle C—H…O is 166°].
Calculated (%): С, 64,27; Н, 8,31; N, 6.25; Р, 6,91. IR, ν/сm–1
:
2143 (CN), 1599 (C=O). 1H NMR, δ: 0.86 (t, 9 H, CH3CH2,
JH,H = 7 Hz); 1.10 (t, 3 H, Me, JH,H = 7 Hz); 1.34 (m, 12 Н,
Experimental
СН2); 2.23 (m,
6 Н, СН2Р); 3.90 (dq, 2 H, CH2O,
1JH,H = 9 Hz, 2JH,H = 7 Hz); 4.96 (d, 1 Н, СНР, JH,H = 19 Hz);
7.71 (t, 1 Н, Нm arom., JH,H = 8 Hz); 8.03 (d, 1 Н, Ho arom.,
JH,H = 8 Hz); 8.21 (d, 1 Н, Hp arom., JH,H = 8 Hz); 8.50 (s, 1 Н,
Ho arom.). 31Р NMR, δ: 36.9.
The IR spectra were recorded on a Nicolet Magna IRꢀ750
Fourierꢀtransform spectrometer in KBr pellets. lH and 31Р NMR
spectra were recorded on Bruker АvanceTM 400 instrument (1Н,
400.13; 31Р, 161.98 MHz) in DMSOꢀd6 using Me4Si and 85%
НЗРО4 as the internal and the external standard, respectively.
Reactions were carried out under dry argon. The solvents were
used after purification and drying.
1ꢀCyanoꢀ1ꢀethoxycarbonylꢀ2ꢀ(4ꢀnitrophenyl)ꢀ2ꢀtributylphosꢀ
phonioethanide (2f). The yield was 99%, m.p. 127—128 °C.
Found (%): C, 64.21; H, 8.42; N, 6.32; P, 6.74. C24H37N2O4P.
Calculated (%): С, 64,27; Н, 8,31; N, 6.25; Р, 6,91. IR, ν/сm–1
:
2135 (CN), 1601 (C=O). 1H NMR, δ: 0.85 (t, 9 H, CH3CH2,
JH,H = 7 Hz); 1.09 (t, 3 H, Me, JH,H = 7 Hz); 1.34 (m, 12 Н,
СН2); 2.21 (m, 6 Н, СН2Р); 3.89 (dq, 2 H, MeO, 1JH,H = 9 Hz,
2JH,H = 7 Hz); 4.92 (d, 1 Н, СНР, JH,H = 19 Hz); 7.83 (d, 2 H,
Ho arom., JH,H = 8 Hz); 8.26 (d, 2 H, Нm arom., JH,H = 8 Hz).
31Р NMR, δ: 37.0.
Preparation of Рꢀzwitterions 2 (general procedure). To a
solution of 3ꢀarylꢀ2ꢀcyanoethylacrylate (9 mmol) in MeCN
(15 L) an equimolar amount of tributylphosphine was added
dropwise with stirring at ~20 °C. After 1 h, the reaction mixture
was cooled to –15 °C and kept at this temperature for 24 h. The
crystals that formed were filtered off, washed with cold acetoꢀ
nitrile, dried in vacuo, and analysed.
Xꢀray diffraction analysis of compound 2f. Orange crystals of
2f • 0.5MeCN (C25H38.5N2.5O4P, M = 469.05) are triclinic,
space group P –1; at T = 100 K: a = 11.6960(4) Å, b = 12.7335(5) Å,
c = 18.7338(7) Å, α = 79.265(1)°, β = 87.532(1)°, γ = 74.366(1)°,
V = 2639.72(17) Å3, Z = 4, dcalc = 1.180 g cm–3, F(000) = 1012,
μ = 0.136 mm–1. The unit cell parameters and intensities
of 48441 reflections were measured on an automated Bruker
SMART APEX II CCD diffractometer (T = 100 K, λꢀMoꢀKα
radiation, graphite monochromator, φ and ω scanning technique,
2θ ≤ 61°). The structure was solved by the direct method and
refined using the fullꢀmatrix leastꢀsquares method in the
anisotropic approximation for nonhydrogen atoms. The crystal
of compound 2f contains the solvation molecule of acetonitrile.
The positions of the hydrogen atoms of acetonitrile solvation
molecule were located objectively from difference Fourier
syntheses and refined in the isotropic approximation with fixed
positional and thermal parameters (Uiso(H) = 1.5Ueq(C)). The
positions of the remaining hydrogen atoms were calculated
geometrically and refined in the isotropic approximation with
fixed positional (the riding model) and thermal (Uiso(H) =
1.5Ueq(C) for the methyl groups and Uiso(H) = 1.2Ueq(C) for all
remaining groups) parameters. The final divergence factors were
as follows: R1 = 0.039 based on 13311 independent reflections
with I > 2σ(I) and wR2 = 0.109 based on all 16282 independent
reflections, S = 1.002. All calculations were carried out using
the SHELXTL software.4
(1ꢀCyanoꢀ1ꢀethoxycarbonyl)ꢀ2ꢀphenylꢀ2ꢀtributylphosphonioꢀ
ethanide (2а). The yield was 83%, m.p. 62—63 °C. Found (%):
C, 71.52; H, 9.54; N, 3.41; P, 7.62. C24H38NO2P. Calculꢀ
ated (%): С, 71.43; Н, 9.49; N, 3.47; Р, 7.68. IR, ν/сm–1
:
2133 (СN), 1601 (С=O). 1H NMR, δ: 0.87 (t, 9 H, CH3CH2,
JH,H = 7 Hz); 1.09 (t, 3 H, Me, JH,H = 7 Hz); 1.32 (m, 12 Н,
СН2); 2.23 (m,
6 Н, СН2Р); 3.88 (dq, 2 H, CH2O,
1JH,H = 9 Hz, 2JH,H = 7 Hz); 4.89 (d, 1 Н, СНР, JH,H = 19 Hz);
7.12—7.27 (5 Н, H arom.). 31Р NMR, δ: 36.4.
1ꢀCyanoꢀ1ꢀethoxycarbonylꢀ2ꢀ(4ꢀhydroxyphenyl)ꢀ2ꢀtributylꢀ
phosphonioethanide (2b). The yield was 75%, m.p. 106—107 °C.
Found (%): C, 68.64; H, 9.18; N, 3.42; Р, 7.26. C24H38NO3P.
Calculated (%): С, 68.71; Н, 9.13; N, 3.42; P, 7.26. IR, ν/сm–1
:
2138 (CN), 1598 (C=O). 1H NMR, δ: 0.85 (t, 9 H, CH3CH2,
JH,H = 7 Hz); 1.09 (t, 3 H, Me, JH,H = 7 Hz); 1.34 (m, 12 Н,
СН2); 2.21 (m,
6 Н, СН2Р); 3.89 (dq, 2 H, CH2O,
1JH,H = 9 Hz, 2JH,H=7 Hz); 4.92 (d, 1 Н, СНР, JH,H = 19 Hz);
7.61 (d, 2 H, Ho arom., JH,H = 8 Hz); 8.09 (d, 2 H, Нm arom.,
JH,H = 8 Hz); 8.91 (s, 1 H, ОН). 31Р NMR, δ: 36.4.
1ꢀCyanoꢀ1ꢀethoxycarbonylꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀtributylꢀ
phosphonioethanide (2с). The yield was 87%, m.p. 69—70 °C.
Found (%): С, 69.30; Н, 9.21; N, 3.29; Р, 6.94. C25H40NO3P.
Calculated (%): С, 69.26; Н, 9.31; N, 3.23; Р, 7.14. IR, ν/сm–1
:
2140 (CN), 1608 (C=O). 1H NMR, δ: 0.81 (t, 9 H, CH3CH2,
JH,H = 7 Hz); 1.05 (t, 3 H, Me, JH,H = 7 Hz); 1.32 (m, 12 Н,
СН2); 2.04 (s, 3 H, MeO); 2.18 (m, 6 Н, СН2Р); 3.86 (dq, 2 H,
1
2
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ00196а).
CH2O, JH,H = 9.5 Hz, JH,H = 7 Hz); 4.89 (d, 1 Н, СНР,
JH,H = 19 Hz); 7.80 (d, 2 H, Нo arom., JH,H = 8 Hz); 8.23 (d,
2 H, Нm arom., JH,H = 8 Hz). 31Р NMR, δ: 36.3.
2ꢀ(4ꢀBromophenyl)ꢀ1ꢀcyanoꢀ1ꢀethoxycarbonylꢀ2ꢀtributylꢀ
phosphonioethanide (2d). The yield was 99%, m.p. 99—100 °C.
Found (%): C, 59.80; H, 7.79; Br, 16.48; N, 3.01; P, 6.47.
C24H37BrNO2P. Calculated (%): С, 59.75; Н, 7.73; Br, 16.56;
N, 2.90; Р, 6.42. IR, ν/сm–1: 2140 (CN), 1597 (C=O).
1H NMR, δ: 0.86 (t, 9 H, CH3CH2, JH,H = 7 Hz); 1.09 (t, 3 H,
Me, JH,H = 7 Hz); 1.34 (m, 12 Н, СН2); 2.16 (m, 6 Н, СН2Р);
3.88 (dq, 2 H, CH2O, 1JH,H = 9 Hz, 2JH,H = 7 Hz); 4.72 (d, 1 Н,
СНР, JH,H = 19 Hz); 7.52 (d, 2 H, Ho arom., JH,H = 8 Hz); 7.59
(d, 2 H, Нm arom., JH,H = 8 Hz). 31Р NMR, δ: 36.1.
References
1. F. Ramirez, J. F. Pilot, C. P. Smith, Tetrahedron, 1968, 24,
3735.
2. Yu. G. Gololobov, G. D. Kolomnikova, N. O. Krilova, Tetꢀ
rahedron Lett., 1994, 35, 1751.
3. F. TexierꢀBoullet, A. Foucaud, Tetrahedron Lett., 1982, 23,
4927.
4. G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
1ꢀCyanoꢀ1ꢀethoxycarbonylꢀ2ꢀ(3ꢀnitrophenyl)ꢀ2ꢀtributylphosꢀ
phonioethanide (2e). The yield was 94%, m.p. 124—126 °C.
Received May 20, 2009