Coupling of methylene-active compounds through a methylene bridge by the action of bis(dimethylamino)methane 1. Synthesis of 2,4-bis(diphenylphosphoryl) glutaronitrile

Article abstract of DOI:10.1007/s11172-012-0169-4

The reaction of diphenylphosphorylacetonitrile with bis(dimethylamino) methane gave 2,4-bis(diphenylphosphoryl)glutaronitrile. Its rac form was obtained by the synthesis followed by crystallization. However, the reaction of the latter with bases or acids

Full text of DOI:10.1007/s11172-012-0169-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 6, pp. 1250—1254, June, 2012
1250
Brief Communications
Coupling of methyleneꢀactive compounds
through a methylene bridge by the action of bis(dimethylamino)methane
1. Synthesis of 2,4ꢀbis(diphenylphosphoryl)glutaronitrile
Yu. G. Gololobov, S. V. Barabanov, A. S. Peregudov, P. V. Petrovskii, and V. N. Khrustalev
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
The reaction of diphenylphosphorylacetonitrile with bis(dimethylamino)methane gave
2,4ꢀbis(diphenylphosphoryl)glutaronitrile. Its rac form was obtained by the synthesis followed
by crystallization. However, the reaction of the latter with bases or acids in solution yielded the
meso diastereomer.
Key words: phosphorylacetonitriles, aminals, organophosphorus compounds, diastereoꢀ
isomerism, Xꢀray diffraction study.
2,4ꢀDisubstituted glutaronitriles are of great interest
undesirable reaction accompanying the classical Mannich
aminomethylation.6 We believed that the aboveꢀmentioned
processes undesirable for the aminomethylation can be
used for the preparation of methyleneꢀbridged functionalꢀ
ized acetonitriles. Hence, we performed the reaction of
diaminomethanes with various methyleneꢀactive comꢀ
pounds. In the present work, we describe the reaction of
diphenylphosphorylacetonitrile (1) with bis(dimethylꢀ
amino)methane (2).
Due to rather high CHꢀacidity of compound 1 (see
Ref. 7), its reaction with aminal 2 (benzene, 80 C, 3—4 h)
proceeds smoothly to give 3,4ꢀbis(diphenylphosphoryl)ꢀ
glutaronitrile (3, Scheme 1) in 70—75% yield.
for organic synthesis.1 In particular, 2,4ꢀdiphosphorylatꢀ
ed glutaronitriles can serve as reagents in the synthesis of
conjugated electroactive polymers.2 Unfortunately, the
known3 method for the synthesis of such compounds is
laborious. With the aim of developing a general and facile
approach to 1,3ꢀdisubstituted propanes, we turned our atꢀ
tention to the poorly known coupling of methyleneꢀactive
compounds with diaminomethanes (formaldehyde amiꢀ
nals). It was reported4 that the reactions of malonic ester
with bisꢀpiperidinomethane gives a small amount of
a highꢀboilingꢀpoint compound, and the hydrolysis of the
latter affords glutaric acid. The reaction of methyl nitroꢀ
acetate with bis(dimethylamino)methane giving dimethylꢀ
ammonium salts of the corresponding bisꢀCHꢀacids was
described.5 Similar coupling of ketones takes place as an
The isolation of the product by crystallization affords
exclusively its racemic form, which was confirmed by eleꢀ
mental analysis, IR spectroscopy, 1H, 31P, and 13C NMR
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1236—1240, June, 2012.
1066ꢀ5285/12/6106ꢀ1250 © 2012 Springer Science+Business Media, Inc.

2,4ꢀBis(diphenylphosphoryl)glutaronitrile
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 6, June, 2012
1251
Scheme 1
spect to each other (the C(6)—P(1)...P(2)—C(18) pseudoꢀ
torsion angle is 54.6) and are slightly twisted, whereas
the phenyl rings C(12)—C(17) and C(24)—C(29) are in
the trans conformation (the C(12)—P(1)...P(2)—C(24)
pseudotorsion angle is 147.6) and are almost parallel to
each other.
In the crystal structure, molecules racꢀ3 form zigzag
chains along the a axis through the intermolecular hyꢀ
drogen bonds C(1)—H(1)...N(2) [–x, 1 – y, –z] and
C(3)—H(3)...N(1) [1 – x, 1 – y, –z]. The zigzag chains
are linked to each other to form a threeꢀdimensional
framework through intermolecular C—H...O=P hydrogen
bonds (C(9)—H(9)...O(1)=P(1) [x, 1.5 – y, –0.5 + z],
C(14)—H(14)...O(2)=P(2) [–1 + x, y, z], and C(15)—
H(15)...O(1)=P(1) [–x, 1 – y, 1 – z]) and C—H... atꢀ
tractive interactions C(21)—H(21)... (C(15)—C(16))
[–x, –0.5 + y, 0.5 – z]). As can be expected in the case of
bisꢀdiphenylphosphine oxides containing an odd number
of carbon atoms in the central aliphatic chain, linear
bipolar P=O...P=O...P=O interactions are not observed
in the crystal structure of the compound under consꢀ
ideration.8
The 31P NMR spectrum of individual compound racꢀ3
shows one signal at  27.51. In the 1H NMR spectrum, the
methylene protons are equivalent, as expected for such
structures having a plane of symmetry. The protons and
13C nuclei of two phenyl rings are diastereotopic, which is
manifested in the nonequivalence of the nuclei in the corꢀ
responding positions of these rings (cf. Fig. 1).
spectroscopy, Xꢀray diffraction, and chiral and achiral colꢀ
umn chromatography.
The structure of diastereomer racꢀ3 was established by
Xꢀray diffraction (Fig. 1, Table 1). Compound racꢀ3 crysꢀ
tallizes in the monoclinic centrosymmetric space group
P21/c with one independent molecule per asymmetric unit.
Molecule racꢀ3 has the idealized molecular symmetry C2
(2), which is only slightly distorted in the crystal structure
due to the crystal packing effects. The P—C—C—C—P
backbone of the molecule is in the transꢀtrans conformaꢀ
tion. Two cyano groups are located on opposite sides of
the backbone. Consequently, the asymmetric carbon atꢀ
oms C(1) and C(3) have identical relative configurations
(the crystal is a racemate). The latter fact casts doubt
upon the suggestion3 that there is an intramolecular doꢀ
norꢀacceptor bond between the cyano group and the phosꢀ
phorus atom in compound 3. Two P=O groups have gauche
orientation both with respect to each other and to other
cyano groups and, like cyano groups, are on the opposite
sides of the backbone. The phenyl rings C(6)—C(11) and
C(18)—C(23) are in the gauche conformation with reꢀ
The IR spectrum of compound racꢀ3 has an intense
band at 1210 cm–1 (P=O) and a lowꢀintensity band at
2242 cm–1 (CN).
Table 1. Selected bond lengths (d) and bond angles () in compound racꢀ3
Parameter Value Parameter
Bond length d/Å Bond angle
Value
/deg
P(1)—O(1)
P(1)—C(12)
P(1)—C(6)
P(1)—C(1)
P(2)—O(2)
P(2)—C(24)
P(2)—C(18)
P(2)—C(3)
N(1)—C(4)
N(2)—C(5)
1.524(3)
1.817(4)
1.844(4)
1.868(9)
1.525(4)
1.789(3)
1.850(5)
1.861(5)
1.180(7)
1.180(7)
1.441(8)
1.598(11)
1.557(11)
1.440(8)
/deg
O(1)—P(1)—C(1)
C(12)—P(1)—C(1)
C(6)—P(1)—C(1)
O(2)—P(2)—C(24)
O(2)—P(2)—C(18)
C(24)—P(2)—C(18)
O(2)—P(2)—C(3)
C(24)—P(2)—C(3)
C(18)—P(2)—C(3)
C(4)—C(1)—C(2)
C(4)—C(1)—P(1)
C(2)—C(1)—P(1)
C(3)—C(2)—C(1)
C(5)—C(3)—C(2)
C(5)—C(3)—P(2)
C(2)—C(3)—P(2)
N(1)—C(4)—C(1)
N(2)—C(5)—C(3)
113.3(4)
101.9(2)
105.5(3)
109.3(3)
115.1(4)
111.28(11)
105.6(4)
103.22(16)
111.6(3)
111.4(8)
114.2(8)
104.7(5)
113.6(9)
112.3(7)
110.1(6)
107.1(6)
177.9(14)
174.1(8)
C(1)—C(4)
C(1)—C(2)
C(2)—C(3)
C(3)—C(5)
Bond angle
O(1)—P(1)—C(12)
O(1)—P(1)—C(6)
C(12)—P(1)—C(6)
113.7(3)
111.2(3)
110.67(17)

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 6, June, 2012
Gololobov et al.
C(15)
C(16)
C(17)
C(14)
C(13)
N(2)
C(20)
C(22)
C(19)
C(18)
O(2)
C(12)
C(5)
C(3)
C(21)
C(2)
C(7)
P(1)
C(8)
P(2)
C(1)
C(4)
C(23)
C(25)
C(9)
C(6)
O(1)
N(1)
C(24)
C(29)
C(11)
C(10)
C(26)
C(27)
C(28)
Fig. 1. Molecular structure of compound racꢀ3 with displacement ellipsoids drawn at the 50% probability level. An alternative position
of the disordered diphenylphosphinoyl substituent at the carbon atom C(3) with occupancy of 0.4 is not shown.
Achiral column chromatography of racemate racꢀ3
(Fig. 2) showed one peak (а), whereas chiral column chroꢀ
matography of the same sample showed two peaks in an
equal ratio assigned to enantiomers racꢀ3 (b). The UV
characteristics of the eluates of both chromatograms are
identical.
Racemate racꢀ3 is stable both in the solid state and in
neutral solutions for an indefinite time; however, it underꢀ
goes isomerization to the meso form (Scheme 2) in the
presence of catalytic amounts of triethylamine (or acid,
cf. lit. data3). Apparently, the isomerization in the presꢀ
ence of triethylamine occurs through the formation of fairly
planar carbanion 4, and stabilization of the latter affords
an equilibrium mixture of diastereomers 3.
I (arb. units)
a
2.238
500
400
300
200
Scheme 2
1.921
100
1.444
0
2
4
6
8
10
12 14 t/min
I (arb. units)
b
10.482
10.102
400
300
200
100
0
The chromatogram of solutions of both diastereomers
(Fig. 3) obtained with the use of chiral columns has three
peaks: two peaks of equivalent area (D and L isomers of the
racemate) and a peak with an area close to the total area of
the first two peaks (meso form). The UV characteristics of
the three compounds are identical.
8.744
2
4
6
8
10
12 14 16 t/min
The cooling of a solution of the equilibrium mixture of
diastereomers results in the crystallization of the less soluꢀ
Fig. 2. Achiral (а) and chiral (b) column chromatographic patꢀ
terns of racꢀ3.

2,4ꢀBis(diphenylphosphoryl)glutaronitrile
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 6, June, 2012
1253
I (arb. units)
dergoes isomerization to the meso form under the action
of organic bases in CDCl3. In solution, the meso form
gives an equimolar (1 : 1) equilibrium mixture with the
racemate.
9.729
160
120
10.095
10.482
80
Experimental
40
0
The NMR spectra were recorded on a Bruker Avanceꢀ400
spectrometer (operating at 400.13 MHz for 1H). The IR spectra
(0.15 M solutions in CHCl3) were measured on a MagnaꢀIRꢀ750
Fouirerꢀtransform infrared spectrometer (Nicolet). The UV—Vis
absorption spectra were recorded on a Specord Mꢀ40 spectroꢀ
meter in acetone. The chromatograms were obtained using a Halo
C18 achiral column (4.6×150 mm, acetonitrile —water, 7 : 3, as
the eluent, 0.8 mL min–1, 20 C, UV signal at 210 nm) and
a WelkꢀO1 chiral column (250×4.6 mm, dichloromethane—isoꢀ
propyl alcohol, 80 : 20, as the eluent, 0.3 mL min–1, 15 C,
UV signal at 219 nm, the racemate was kept for 3 h in dry
dichloromethane). The reactions were performed under dry arꢀ
gon atmosphere.
2,4ꢀBis(diphenylphosphoroyl)glutaronitrile (racꢀ3). A mixture
of nitrile (1) (1 g, 4.15 mmol) and bis(dimethylamino)methane
(2) (0.42 g, 4.15 mmol) was stirred in benzene (40 mL) at 80 C
for 3 h. After 1—1.5 h, a crystalline precipitate formed in soluꢀ
tion. After the heating was stopped, the solvent was removed
in vacuo. The repeated crystallization of the resulting mixture
from toluene or ethyl acetate afforded racꢀ3 in 70—75% yield as
fiberꢀlike crystals, m.p. 262—263 C (cf. lit. data3: m.p. 260 C).
Found (%): C, 70.11; H, 4.61; N, 5.47; P, 12.59. C28H22N2O2P2.
2
4
6
8
10 12
14 t/min
Fig. 3. Chiral column chromatographic pattern of a mixture of
racꢀ and mesoꢀ3.
ble racemic form. Therefore, the meso isomer is completeꢀ
ly transformed into the racemic modification. The recrysꢀ
tallyzation of a mixture of racꢀ and mesoꢀ3 from toluene or
ethyl acetate also leads to the precipitation of the pure
racemate. Due to the nonequivalence of the protons of the
CH2 group in mesoꢀ3, the signals of CH2 appear as a comꢀ
plex multiplet at  2.5. The 1H, 13C, and 31P NMR spectra
of diastereomers show signals of both forms.
The aboveꢀmentioned properties of diastereomers 3
account for the fact that the reaction 1 + 2 (see Scheme 1)
in the presence of an excess of reactant 2 having basic
properties affords not the individual racemate but its mixꢀ
ture with the meso form.
Apparently, the mechanism of the formation of strucꢀ
ture 3 (Scheme 3) involves the formation of aminomethylꢀ
ation product 5 in the first step followed by its transformaꢀ
tion into acrylonitrile derivative 6.6 The latter compound,
being a strong Michael acceptor, binds CHꢀacid 1 in an
alkaline medium to give product 3.1 Presumably, comꢀ
pound 3 is formed also by the direct deamination of prodꢀ
uct 5 with CHꢀacid 1.
Calculated (%): C, 70.00; H, 4.58; N, 5.83; P, 12.91. IR, /cm–1
:
2241 (CN), 1210 (PO). 31P NMR, : 27.55. 1H NMR (400.13 MHz,
CDCl3), : 2.42 (tt, 2 H, CH2, 3JH,P = 14.8 Hz, 3JH,H = 7.6 Hz);
3.90 (dt, 2 H, CHP, 3JH,H = 7.5 Hz, 3JH,P = 15.3 Hz); 7.53—7.63
3
(m, 12 H, mꢀPh, pꢀPh); 7.81 (dd, 4 H, oꢀPh, JH,H = 7.2 Hz,
3
3
3JH,P = 11.8 Hz); 7.89 (dd, 4 H, oꢀPh, JH,H= 7.2 Hz, JHP
=
= 11.4 Hz). 13C NMR (CDCl3), : 23.8 (s, CH2); 31.6 (dd, CHP,
1JC,P = 59.7 Hz, 3JC,P = 7.7 Hz); 115.82 (d, CN, JC,P = 5.2 Hz);
127.8 (d, ipsoꢀPh, JC,P = 210 Hz); 128.1 (d, ipsoꢀPh, JC,P
=
= 210 Hz); 129.23 (d, mꢀPh, JC,P = 22.5 Hz); 129.31 (d, mꢀPh,
C6H5, JC,P = 22.5 Hz); 131.18 (d, oꢀPh, JC,P = 10.6 Hz); 131.89
(d, oꢀPh, JC,P = 10.6 Hz); 133.49 (d, pꢀPh, JC,P = 1.5 Hz);
133.56 (d, pꢀPh, JC,P = 1.5 Hz).
Scheme 3
Isomerization of racemate racꢀ3mesoꢀ3. Triethylamine
(10 mol.%) dissolved in CH2Cl2 was added to a solution of comꢀ
pound racꢀ3 (20 mg) in CH2Cl2 (3 mL). After 10 min, the
31P NMR spectrum showed two signals at  25.56 and 29.04 in
an equal ratio. After the removal of volatile compounds in vacuo,
the crystalline product was obtained in a yield of 20 mg, m.p.
250—252 C. IR, /cm–1: 2241 (CN), 1210 (PO). 31P NMR
(CDCl3), : 27.55, 29.01. 1H NMR, : 2.35—2.60 (m, 2 H, CH2
(racꢀ3 + mesoꢀ3)); 3.90 (dt, 2 H, CHP, 3JH,H = 7.5 Hz, 3JH,P
= 15.3 Hz (racꢀ3)); 4.29 (dt, 2 H, CHP, 3JH,H = 7.4 Hz, 3JH,P
=
=
= 14.5 Hz (mesoꢀ3); 7.46—7.68 (m, 12 H, mꢀPh, pꢀPh); 7.76—7.84
3
(m, 4 H, oꢀPh); 7.87—7.91 (dd, 4 H, oꢀPh; JH,H = 7.2 Hz,
3JH,P = 12.0 Hz). 13C NMR, : 23.8 (s, CH2); 25.3 (s, CH2); 30.9
1
3
(dd, CHP, JC,P = 61.9 Hz, JC,P = 6.0 Hz); 31.6 (dd, CHP,
1JC,P = 59.7 Hz, 3JC,P = 7.7 Hz); 115.82 (d, CN, JC,P = 5.2 Hz);
116.35 (d, CN, JC,P = 4.5 Hz); 127.66 (d, ipsoꢀPh, JC,P = 221.9 Hz);
Therefore, the reaction of bis(dimethylamino)methane
2 with diphenylphosphoroylacetonitrile smoothly gives
2,4ꢀbis(diphenylphosphoroyl)glutaronitrile. The latter unꢀ
127.8 (d, ipsoꢀPh, JC,P = 222 Hz); 128.1 (d, ipsoꢀPh, JC,P
=
= 210 Hz); 128.9 (d, ipsoꢀPh, JC,P = 222 Hz); 129.2 (m, mꢀPh);

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Gololobov et al.
131.18 (d, oꢀPh, JC,P = 10.6 Hz); 131.25 (d, oꢀPh, JC,P = 10.6 Hz);
131.88 (d, oꢀPh, JC,P = 10.6 Hz); 131.89 (d, oꢀPh, JC,P = 10.6 Hz);
133.49 (m, pꢀPh).
bond angles, and anisotropic thermal parameters for compound
racꢀ3 were deposited with the Cambridge Crystallographic Data
Centre.
Xꢀray diffraction study. Crystals of compound racꢀ3
(C29H24N2O2P2, M = 494.44) are monoclinic, space group
P21/c, at 100 K a = 8.592(4) Å, b = 24.975(12) Å, c = 12.949(6) Å,
We thank V. A. Davankov, S. E. Lyubimov, and E. I.
Goryunov for useful advice and help in the work.
 = 92.684(12), V = 2776(2) Å3, Z = 4, dcalc = 1.183 g cm–3
,
F(000) = 1032,  = 0.183 mm–1. The unit cell parameters and
the intensities of 13449 reflections (2582 independent reflecꢀ
tions, Rint = 0.094) were measured on a Bruker SMART 1K CCD
automated threeꢀcircle diffractometer equipped with an Oxꢀ
ford Cryosystem lowꢀtemperature device ((MoꢀK) radiation,
graphite monochromator, ꢀ and ꢀscanning technique,
References
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2
= 40). The structure was solved by direct methods and
max
refined by the fullꢀmatrix leastꢀsquares method based on F2 with
anisotropic displacement parameters for nonhydrogen atoms.
One of the two oxo(diphenyl)phosphine substituents is diꢀ
sordered over two positions with occupancies of 0.6 : 0.4. The
hydrogen atoms were positioned geometrically and refined isoꢀ
tropically with fixed positional (riding model) and thermal
(Uiso(H) = 1.2Ueq(C)) parameters. The final R factors were
R1 = 0.104 for 666 independent reflections with I > 2(I) and
wR2 = 0.312 for all independent reflections, GOF = 0.899. It
should be taken into account that the crystal under study with
a size of 0.40×0.01×0.01 mm was a thin needle with an insignifiꢀ
cant contribution of a twin component, resulting in a low quality
of the experimental data. Unfortunately, we failed to obtain highꢀ
erꢀquality crystals of this compound. Nevertheless, the model of
compound racꢀ3 was reliably established and is beyond doubt.
All calculations were performed with the use of the SHELXTL
program package.9 Tables of atomic coordinates, bond lengths,
Received April 25, 2011;
in revised form February 17, 2012