Dimephosphone analogs: I. synthesis and Structure of Some Dimephosphone Aryl- and Acylhydrazones

Article abstract of DOI:10.1134/S1070363212100027

Dimephosphone (2-dimethoxyphosphoryl-2-methylpentan-4-one) phenyl-, nitrophenyl-, benzoyl-, and 4-nitrobenzoylhydrazones were synthesized. The compounds in crystals were shown to have a steric form exclusively of the E-isomer. The structure of hydrazones in solution is defined by the nature of the substituents and the solvent and the time of storage of the solution. The dimephosphone aroylhydrazones in acid solutions exist in several possible forms: the isomers at the imine bond, the conformers at the amide bond, and a cyclic tautomer (1,3,4-oxadiazoline). Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212100027

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 10, pp. 1629–1645. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © B.I. Buzykin, V.N. Nabiullin, E.V. Mironova, A.A. Kostin, D.A. Tatarinov, V.F. Mironov, I.A. Litvinov, 2012, published in Zhurnal
Obshchei Khimii, 2012, Vol. 82, No. 10, pp. 1600–1618.
Dimephosphone Analogs: I. Synthesis and Structure
of Some Dimephosphone Aryl- and Acylhydrazones
B. I. Buzykin, V. N. Nabiullin, E. V. Mironova, A. A. Kostin,
D. A. Tatarinov, V. F. Mironov, and I. A. Litvinov
A.E. Arbuzov Institute of Organic and Physical Chemistry, Arbuzov str. 8, Kazan, Tatarstan, 420088 Russia
e-mail: buz@iopc.ru
Received August 9, 2011
Abstract—Dimephosphone (2-dimethoxyphosphoryl-2-methylpentan-4-one) phenyl-, nitrophenyl-, benzoyl-,
and 4-nitrobenzoylhydrazones were synthesized. The compounds in crystals were shown to have a steric form
exclusively of the E-isomer. The structure of hydrazones in solution is defined by the nature of the substituents
and the solvent and the time of storage of the solution. The dimephosphone aroylhydrazones in acid solutions
exist in several possible forms: the isomers at the imine bond, the conformers at the amide bond, and a cyclic
tautomer (1,3,4-oxadiazoline).
DOI: 10.1134/S1070363212100027
Aqueous solutions of 2-(dimethoxyphosphoryl)-2-
methylpentane-4-one [dimethyl (2-methyl-4-
oxopentan-2-yl)phosphonate], more known as
dimethyl 1,1-dimethyl-3-oxobutylphosphonic acid (I)
are used as a dimephosphone drug, which has a wide
range of applications in medicine [1–3].
The dimephosphone is a bright example of the suc-
cessful pursuit of drugs among the organophosphorus
compounds. By its chemical nature, the dimephos-
phone belongs to γ-phosphorylated ketones and
therefore it is of interest as a precursor in the synthesis
of new potential biologically active compounds. Along
with other approaches, the principle of analogy with
the known drugs is widely used in pharmacology.
Despite the great synthetic chemical potential of the
dimephosphone as a ketone, its chemical properties, in
contrast to pharmacological ones, have been poorly
studied [1]. Among its derivatives only the dimephos-
phone oxime is described [4, 5]. The aim of this work
was the synthesis of some dimephosphone aryl- and
acylhydrazones that might be of interest as objects of
theoretical and structural chemistry, and as
biologically active compounds and precursors in the
synthesis of heterocyclic systems (indoles, oxadi-
azoles, triazoles, etc.).
The dimephosphone belongs to organophosphorus
compounds. Unlike most of the used organophos-
phorus compounds, it does not exhibit anticholine-
sterase activity and is even recommended as an anti-
dote at the poisoning by toxic products. The dimephos-
phone has been used since 1973 as an antiacidotic
means at the acidosis of various etiologies, a
vasoactive drug in the treatment of cerebral circulation
disfunction and respiratory diseases. The drug exhibits
membrane-stabilizing and anti-inflammatory properties.
At the external use it exhibits an antiseptic effect,
enhances the protective function of the skin and
mucous membranes. The dimephosphone was found to
have also cardiotropic, neurotrophic, neuroprotective,
antihypoxic, antiallergic, immunocorrection, anti-
aggregation, antioxidant, and radioprotective proper-
ties. This drug improves blood circulation and nor-
malizes metabolic processes in the brain tissue. The
dimephosphone was proposed for the treatment of
autoimmune thyroiditis, gastric and duodenal ulcer,
purulent sinusitis, and other diseases [1, 2].
The dimephosphone arylhydrazones II–V and
aroylhydrazones VI, VII unknown previously were
obtained in the classical way [6]: by the reaction of the
corresponding hydrazine derivative in alcohol with
dimephosphone along the scheme below (see the
Experimental and Table 1).
The synthesized dimephosphone arylhydrazones,
including phenylhydrazone II, are crystalline colored
1629

1630
BUZYKIN et al.
O
ArNHNH2
P(OMe)2
N
HN
Ar
II_V
O
P(OMe)2
O
O
P(OMe)2
I
RC(O)NHNH2
N
HN
R
O
VI, VII
Ar = Ph (II), 4-O2NC6H4 (III), 2-O2NC6H4 (IV), 2,4-(O2N)2C6H3 (V); R = Ph (VI), 4-O2NC6H4 (VII).
substances. The color depends on the position rather
than the number of the nitro groups: light beige
crystals of phenylhydrazone II (almost white after
reprecipitation from methanol with water), pale brown
4-nitrophenylhydrazone III and orange 2-nitro- IV and
2,4-dinitrophenylhydrazones V. Deeper color of the
two latter compounds is presumably due to the
presence in their molecules of a strong intramolecular
hydrogen bonds of NO2···HN type involving the nitro
groups in ortho-positions to the hydrazone fragment
[6]. The hydrogen bonding in the hydrazone molecules
was confirmed by X-Ray analysis.
at elevated temperature (in 12–15 h) and in solution,
especially in chloroform. At storage in a dark brown
closed bottle the changes occur in 30–35 days.
Because of this we failed to grow a crystal suitable for
the X-ray analysis.
We fixed by IR spectroscopy the presence of
dimephosphone in the products of the spontaneous
decomposition of phenylhydrazone II. Such behavior
is typical of the phenylhydrazones of aliphatic and
cycloaliphatic ketones and arylhydrazones containing
donor substituents in the arene ring [6, 7]. These
transformations are not related to tautomeric trans-
formations into the azo compounds, which have been
sometimes postulated up to now [8], but result from
the oxidation processes. It has been already found long
ago [6, 7] that similar arylhydrazones readily form by
the mechanism of ene reaction the azohydroperoxides
of the ArC(OOH)–N=N–Ph type, which decompose
spontaneously in the reaction medium. This leads to
The stability of dimephosphone arylhydrazones II–
V depends strongly on the nature of the aryl
substituent and the storage conditions. At storage in air
even in a closed vessel the dimephosphone phenyl-
hydrazone crystals soon turn red (in 1–2 days). They
gradually gutter, turning first into a dark red, then dark
brown resinous mass. This process occurs even faster
Table 1. Some characteristics of dimephosphone arylhydrazones II–V and acylhydrazones VI, VII
IR, ν, cm–1
Found, %
Calculated, %
Comp. Yield,
mp,
°С
Formula
no.
%
NH
C=N
C
H
N
P
C
H
N
P
61
114–118
(decomp.)
3265
1599
56.46 7.86 9.55 10.28 C14H23N2O3P
56.37
7.77
9.39 10.38
II
88
37
75
90
193–194
65–66
3272
3328
1613
1616
1615
48.53 6.63 12.41 9.28 C14H22N3O5P
48.49 6.37 12.30 8.65 C14H22N3O5P
43.43 5.57 14.38 8.08 C14H21N4O7P
55.04 7.22 8.62 9.28 C15H23N2O4P
48.98
48.98
43.30
55.21
6.46
6.46
5.45
7.10
12.24
12.24
14.43
8.58
9.02
9.02
7.98
9.49
III
IV
V
121–121.5 3327
144–146
(decomp.)
3219
1615
[ν(С=О) 1673]
VI
83
161–163
3232
1604
[ν(С=О) 1668]
48.66 5.81 11.24 8.47 C15H22N3O6P
48.52
5.97
11.32
8.34
VII
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DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1631
the formation of diverse products, including carbonyl
compounds corresponding to the ylidene fragment of
the parent hydrazone. It was proved that a mysterious
change in the color of benzaldehyde phenylhydrazone
observed during its storage in the light, at transfer in
the darkness and back again, also is due to such
oxidative processes rather than to the change in the
geometry of the hydrazone group [9]. Perhaps these
processes underlie the fact that the only known analog
of the dimephosphone phenylhydrazone, the diethyl
(2-methyl-4-oxopent-2-yl)phosphonate phenylhydra-
zone, was characterized not as a crystalline substance,
but as a dark brown liquid [10].
Despite numerous attempts, we were not able to
perform indolization of nitrophenylhydrazones III, IV
or even phenylhydrazone II. The attempted reaction in
acidic medium (hydrochloric acid of different
concentrations, polyphosphoric acid, etc. [6], a mixture
of hydrochloric acid and AcOH [11]), in most cases
yielded the dimephosphone and arilhydrazine salts.
After boiling phenylhydrazone II in glacial AcOH for
3 h the acetic acid phenylhydrazide was isolated nearly
quantitatively, while 4-nitrophenylhydrazone III
remained unchanged at boiling in AcOH for a longer
time. In the aliphatic ketone phenylhydrazones,
including the phenylhydrazone II, the most basic
nitrogen atom is the imine nitrogen of the hydrazo
group [12]. Therefore, in glacial AcOH the
phenylhydrazone acylation can proceed at this atom,
and the resulting hydrazonium salt of the type VIII, as
is well known [6], is readily hydrolyzed to the
corresponding phenylhydrazide. The introduction of a
nitro group in the benzene ring of such phenyl-
hydrazones significantly reduces their basicity, and the
most basic center in nitrophenylhydrazones takes
another position.
The ability of the phenylhydrazone II, which is
prone to autoxidation, to remain unchanged for three
months or more at keeping in water is surprising.
Introduction of nitro groups in the benzene ring
stabilizes the dimephosphone phenylhydrazone mole-
cule. Crystals of 2-nitrophenylhydrazone III are changed
only in 3–3.5 months, and the crystals of 4-nitro- IV
and 2,4-dinitrophenylhydrazones V can be kept for
more than three years without any changes.
Ph
H
H
Ac
N N
N
N+
O
AcOH
II
I
+
P(OMe)2
Ac
Ph
H
VIII
According to GLC, prolonged (25 h) boiling of
phenylhydrazone II in toluene or xylene leads to the
reaction products containing no methanol, and the
isolated liquid is dimephosphone. This fact indicates
that at the thermolysis neither indolization reaction
proceeds to form IX or X, nor intramolecular phos-
phorylation at the amino group of hydrazone fragment
occurs giving diazaphosphorinane XI derivatives, nor
dimethyl phosphite cleavage with subsequent
cyclization of intermediate mesityl oxide phenylhyd-
razone into the corresponding pyrazoline XII, but only
take place the processes of oxidative destruction.
H
N
O
O
P(OMe)2
P(OMe)2
+
N
H
X
IX
II
+
N
P O
N
N
Ph
XII
N
OMe
Ph
XI
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1632
BUZYKIN et al.
Theoretically, the asymmetrically substituted
substituents in the aryl fragment is not high enough to
restrict significantly the internal rotation around this
bond. The introduction of nitro groups in the benzene
ring redistributes the electron density in the
arylhydrazone fragment even more reducing the N–N
bond order [6, 13, 14]. Therefore, the Z'N–N conformers
of the hydrazones of various types are generally not
realized due to steric hindrances [6, 7], and therefore
EZ'- and ZZ'-conformers are not considered in this
paper.
ketone arylhydrazones, including dimephosphone, can
exist as four flat steric forms due to different positions
of the fragments relative to the C=N double bond
(EC=N and ZC=N isomers, further for the convenience
denoted as E- and Z-isomers) and relative to the N–N
bond (E'N–N and Z'N–N conformers, further E'- and Z'-
conformers). The N–N bond is not a single bond due to
n–p-conjugation [6]. However, its double-bonding
order determined mainly by the nature of the
R'
R'
R'
R'
H
N
N
H
N
Ar
N
H
N
N
Ar
N
Ar
N
Ar
'
H
'
E
C=N, EN N (E,E )
Z,E'
Z,Z'
E,Z'
--
R' = CMe2P(O)(OMe)2.
According to IR spectra, the dimephosphone
arylhydrazones II–V exist in the crystals in a single
form (Table 1). The presence in the IR spectra of the
absorption bands corresponding to only one N–H bond
and the absence of absorption bands belonging to the
multiple C=C bonds show the presence of the
arylhydrazone tautomers and the absence of the ene-
hydrazine forms. Apparently, the location of the
acceptor dimethoxyphosphoryl group in the γ-position
to the imine fragment does not contribute to the
stabilization of the latter, although one it is possible to
detect a small amount of enol form in the dimephos-
phone [1]. The less strong absorption of the N–H bond
of dimephosphone phenylhydrazone (Table 1) com-
pared with crystalline sample of benzaldehyde phenyl-
hydrazone (3315 cm–1) and acetophenone phenyl-
hydrazone (3350 cm–1) [15] can be attributed to its par-
ticipation in intermolecular N–H···O=P (or N–H···O–P)
hydrogen bond with dimethoxyphosphoryl group.
the transformation of the original E-isomer into another
(see Table 2). However, an unambiguous conclusion
about the structure of the more stable form of
arylhydrazones II–V basing on the data in these tables
is difficult. One should take into account the possible
stereochemical lability of dimethoxyphosphoryliso-
butyl fragment (several single bonds: P–C, C–C),
which in many ways can determine the spatial require-
ments of the substituted methylene group compared
with the methyl one. Therefore to obtain an une-
quivocal result we studied the structures of nitro-
phenylhydrazones III–V using X-ray diffraction
analysis. We failed to grow a crystal of phenyl-
hydrazone II suitable for X-ray study because of its
propensity to oxidation. The geometry of molecules of
nitrophenylhydrazones III–V is shown in Figs. 1–3,
and Tables 3 and 4 list their structural parameters. The
data show that in all cases the crystals contain only
EC=N isomers existing as the EN–N conformers, with
noticeable difference in the stereochemistry of the
phosphorylalkyl fragment.
In freshly prepared solutions of arylhydrazones II–
V in CDCl3, CD3CN, and DMSO-d6 also only one
form was found. Over time, in the NMR spectra of the
solutions the signals of the other form appear (Table 2),
in the amount determined by the nature of the aryl
substituent, the nature of the solvent, and the time
interval between the preparation of the solution and
recording the spectrum. The introduction of nitro
groups in ortho-position of the benzene ring impedes
Bond lengths and bond angles in the hydrazone
fragment of the molecules of nitrophenylhydrazones
III–V (Table 3) are close to those of the corresponding
sterically non-hindered arylhydrazones [14, 16] and
suggest the p–π-conjugation in the arylhydrazone frag-
ment usual for such systems [6]. As a consequence, the
bond order of the imine bond is reduced to ~1.9, and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1633
Table 2. Principal parameters of 1H and 31P–{1H} NMR spectra of dimephosphone arylhydrazones II–V and acylhydrazones
VI, VII
RNHN=C(Me)CH2CMe2P(=O)(OMe)2
1H, δ, ppm (J, Hz)
>CMe2 (3J, d) =CMe >CH2 (3J, d) OMe (3J, d)
Comp.
no.
Forms
ratio, %
31P, δP,
ppm
R
Solvent
Form
NH
а
Ph
CDCl3
E
Z
E
E
88
12
1.28 (17.1)
1.34 (17.4)
1.20 (16.9)
1.15 (16.9)
0.90 (16.5)
0.98 (17.1)
1.25 (17.0)
1.44 (15.5)
1.21 (16.8)
1.16 (16.8)
0.91 (16.7)
0.81 (16.6)
1.38 (17.0)
1.22 (18.8)
1.18 (16.8)
0.89 (16.8)
1.97
2.18
1.92
1.91
2.15
2.17
1.99
2.14
1.97
1.99
2.21
2.20
2.07
2.03
2.06
2.25
2.59 (11.8) 3.79 (10.5) 7.28
38.9
40.2
38.5 b
38.5
35.4
38.3
37.9
II
2.66 (10.8) 3.71 (10.8) 7.34
2.49 (11.1) 3.72 (10.2) 7.55
CD3CN
>98
>99
75
DMSO-d6
CF3COOНc E+Н+
2.42 (10.7) 3.67 (10.2) 8.67
c
2.59 (18.1) 3.38 (10.5)
2.74 (17.1) 3.43 (10.8)
–
–
Z+Н+
25
c
а
4-NO2C6H4
CDCl3
E
Z
E
E
98
2.57 (12.2) 3.76 (10.4) 7.71
III
IV
d
d
2
2.72 (11.9) 3.95 (10.4)
–
–
CD3CN
>99
>99
87
2.52 (11.7) 3.71 (10.3) 8.39
38.1
37.8
34.7
38.1
DMSO-d6
2.46 (11.4) 3.68 (10.3) 9.80
CF3COOНа E+Н+
Z+Н+
2.69 (18.1) 3.39 (10.8)
2.68 (18.0) 3.38 (10.7)
–
–
c
c
13
4-NO2C6H4
CDCl3
E
E
E
100
100
100
>90
2.64 (11.7) 3.79 (10.4) 10.66 37.9
2.57 (11.7) 3.72 (10.3) 10.50 38.6
2.54 (11.2) 3.69 (10.3) 10.44 39.2
CD3CN
DMSO-d6
CF3COOНe E+Н+
2.73 – d
3.37 (10.7)
9.72 36.7
br.s
Z+Н+
~5
100
100
100
86
0.96 (18.2)
1.28 (17.8)
1.24 (16.7)
1.20 (16.8)
0.90 (17.3)
0.98 (16.8)
1.31 (16.1)
1.24 (18.4)
1.21 (16.7)
1.17 (16.9)
0.74 (18.2)
0.84 (17.1)
0.91 (16.7)
1.35 (16.1)
1.29 (17.4)
1.22 (17.4)
1.33 (16.0)
1.18 (17.0)
1.20 (16.9)
2.28
2.15
2.13
2.07
2.08
2.34
2.13
2.09
2.01
2.00
1.67
2.14
2.57
2.18
2.12
2.08
2.12
2.08
2.02
–
–
3.56 (10.7)
39.2
d
d
2,4-(NO2)2C6H3
CDCl3
E
E
E
2.67 (12.6) 3.79 (10.5) 11.02 37.3
2.62 (11.3) 3.72 (10.3) 10.87 37.4
2.59 (11.4) 3.70 (10.3) 10.78 38.1
2.69 (16.2) 3.41 (10.8) 10.29 37.0
V
CD3CN
DMSO-d6
CF3COOНа E+Н+
Z+Н+
d
d
14
2.74 (16.8) 3.34 (10.8)
–
–
PhC(=O)
CDCl3
EE'E''
EE'Z''
56
2.46 (18.4) 3.68 (10.6) 10.98 37.0
VI
44
2.59 (10.6) 3.71 (10.5)
9.01 38.4
9.02 38.3
CD3CN
EE'Z'
>95
>98
41
2.54 (~16)
2.50 (– d)
3.68 (10.2)
DMSO-d6
CF3COOН
EE'Z'
3.69 (10.2) 10.46 38.7
d
Cycle
EE'E''+Н+
EE'Z''+Н+
EE'E''
EE'Z''
2.21 (13.3) 3.25 (10.9)
2.64 (18.1) 3.31 (10.9)
–
–
–
36.1
38.4
39.1
d
d
49
10
2.60 (~16)
3.28 (10.8)
4-NO2C6H4C(=O) CDCl3
CD3CN
>90
~4
2.50 (18.8) 3.47 (10.6) 11.50 39.5
VII
2.61 (10.6) 3.79 (10.3)
8.98 37.2
9.40 38.2
11.38 40.5
EE'Z''
80
2.57 (12.2) 3.72 (10.9)
2.21 (– d)
~2.5 (– d)
d
EE'E''
EE'Z''
10
3.70 (– d)
DMSO-d6
~86
~7
3.69 (10.9) 10.80 38.1
3.67 (10.6) 11.18 39.1
EE'E''
–
(– d)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1634
BUZYKIN et al.
Table 2. (Contd.)
1H, δ, ppm (J, Hz)
Comp.
R
Forms
ratio, %
31P, δP,
ppm
Solvent
Form
no.
>CMe2 (3J, d) =CMe >CH2 (3J, d)
OMe (3J, d)
NH
4-NO2C6H4C(=O) CDCl3
VII
Z E'Z''
~7
~42
~37
~7
1.24 (– d)
1.96
1.72
2.19
~2.6
2.63 (16.6) ~3.55 (– d)
2.26 (13.0) 3.30 (10.5)
2.70 (18.46) 3.36 (10.9)
–
–
–
–
37.4
35.0
37.6
40.0
CF3COOН
0.78 (18.1)
0.88 (16.7)
0.96 (16.7)
A
B
C
d
d
–
–
3.35 (10.6)
a
After 2 h the freshly prepared solution contains only the EC=N.form. b For the second isomer (less that 5%), δP = 39.3 ppm. c The signals
of NH group protons are not recordable due to exchange processes. Not identified. After 8 days the freshly prepared solution
contained only one form, with admixture of the third form, δ(CMe2) 0.80 ppm (J ~ 18 Hz), δ(=CMe) 2.41 ppm, δ(OMe) 3.18 ppm
(10.7 Hz), δP 35.6 ppm.
d
e
N–N and C–Ar bond orders increase to 1.2 and 1.5,
respectively. The values of the bond angles involving
the atoms of the hydrazone fragment in the studied
nitrophenylhydrazones (Table 3) indicate the absence
of a steric hindrance in this part of the molecules. It
was previously shown that in the molecules of the
sterically hindered arylhydrazones the value of, for
example, the N–N=C bond angle, increased to 122–
125° compared with 115–117° in the sterically
unloaded derivatives (see [16] and Table 3).
distances (Tables 3 and 4). In the molecules of 2-nitro-
and 2,4-dinitrophenylhydrazones IV, V the C1 atom is
removed considerably from the P(1) plane [the C1
atom deviations from the P(1) plane in the molecular
crystals IV and V are –1.382(3) and –1.369(3) Å,
respectively, see Table 4]. Dimethoxyphosphoryliso-
propyl fragment is turned around the C2–C3 bond in
the same direction by 96° and 78°, respectively, in the
molecules of compounds IV, V, which confirms our
assumption on the stereochemical lability of the
fragment. Moreover, in crystals of 2,4-dinitrophenyl-
hydrazone V one of the methoxy groups of the
dimethoxyphosphoryl fragment is disordered over two
positions with occupancy ratio 0.62:0.38 (Fig. 3).
In the molecules of the nitrophenylhydrazones III–
V the carbon atoms of methyl and methylene groups of
the ylidene fragment and the atoms of hydrazo group
are located in the same plane P(1) [N1N2C2C3C4]. The
atom C1 linked to the phosphorus atom and two methyl
groups is in the same plane only in the molecules of 4-
nitrophenylhydrazone III (see torsion angles in Table 3).
This atom is in the eclipsed conformation with respect
to the imine nitrogen atom N2 [the torsion angle
N2C3C2C1 is ~3°], its deviation from the P(1) plane is
small and amounts to –0.036(3) Å. The methyl groups
are located on both sides of this plane at nearly equal
It is interesting to note that in the molecules of
arylhydrazones III–V the benzene rings and nitro
groups also lie in this P(1) plane. The rotation angles
of the benzene rings relative to the P(1) plane and nitro
groups relative to the plane of the benzene ring are
small (see Table 3), which also indicates a large extent
of delocalization (conjugation) of electronic systems of
the aryl and hydrazone fragments.
Fig. 1. Molecular geometry and numbering of atoms in the crystal of dimephosphone 4-nitrophenylhydrazone III.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1635
Fig. 2. Molecular geometry and numbering of atoms in the crystal of dimephosphone 2-nitrophenylhydrazone IV.
С7
С7А
O5
O6
O3А
O1
O3
С13
С9
С5
С2
N3
С10
С14
С1
С8
P1
N2
O2
N1
С12
С3
С11
N4
С6
С4
O7
O8
Fig. 3. Molecular geometry and numbering of atoms in the crystal of dimephosphone 2,4-dinitrophenylhydrazone V.
Analysis of the molecular packing of molecules of
nitrophenylhydrazones III–V in crystals shows that the
decisive role plays the nitro group position. Thus, in
the crystal of 4-nitrophenylhydrazone III due to N1–
H1···O1 intermolecular hydrogen bonding (Table 5)
molecular chains are formed along the 0y axis (Fig. 4).
In crystals of the arylhydrazones IV, V containing a
nitro group in the ortho position of benzene ring are
was already repeatedly shown that, depending on the
state of aggregation, the nature of substituents in the
ylidene and acyl fragments, and the solvent, the
acylhydrazones may exist in a variety of steric forms,
or as mixtures of several forms [6, 7, 17–20], including
the cyclic 1,3,4-oxadiazol-2-ine form [21]. It was
previously considered that aldehyde acylhydrazones
existed only in the form of the E-isomer with respect to
the C=N double bond regardless of the nature of
substituents at the amine nitrogen atom, while the
acylhydrazones of the unsymmetrically substituted
ketone could exist as two isomers about the double
C=N bond [6, 7, 17]. However, it was shown by the
method of infrared spectroscopy that acetyl- and
benzoylhydrazones of symmetrically substituted
ketones like acetone also existed in the solutions as
two conformers due to another factor, the hindered
internal rotation around the amide N–C bond [17].
Later on, using the methods of dipole moments, IR and
1H NMR spectroscopy it was revealed that arylal-
dehyde aroylhydrazones in crystal and in solution are
mixtures of two amide forms, EC=N, EN–N, EN–C and
formed
only
the
intramolecular
N1–H1···O6
(N1–H1···O8) hydrogen bonds (Table 5, Figs. 3 and 4)
typical of the ortho-nitroaniline derivatives [14].
In a crystal of 4-nitrophenylhydrazone III there are
also short contacts of C–H···O=P type (Table 4), which
stabilize additionally the molecular chains (Fig. 2, 1D).
In crystals of arylhydrazones IV, V due to the same
contacts the molecules form dimeric fragments, which
in the crystal of IV form a belt along the 0z axis, and
in the crystal of V they form a chain along
the side diagonal of the a0c plane (Figs. 5 and 6,
respectively).
The introduction of a carbonyl group between the
aryl and hydrazone fragments greatly complicates the
stereochemistry of the obtained aroylhydrazones. It
E
C=N, EN–N, Z
(further for convenience, EE'E” and
N–C
EE'Z”) [18]. The possible formation of intramolecular
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1636
BUZYKIN et al.
Table 3. Selected geometric parameters of the dimephosphone aryl- and aroylhydrazones III–VII molecules
Parameter
IVа
Vb
III
VI
VIIA
VIIB
Bond length, Å
1.436(3)
1.537(3)
1.563(3)
1.801(3)
1.383(4)
1.349(5)
1.280(5)
1.227(5)
1.224(6)
1.460(5)
1.355(6)
1.459(11)
–
P1–O1
P1–O2
P1–O3
P1–C1
1.459(2)
1.567(2)
1.573(2)
1.811(2)
1.377(3)
1.362(3)
1.275(3)
1.228(3)
1.230(3)
1.443(4)
1.414(4)
1.448(3)
–
1.536(4)
1.529(4)
1.533(4)
1.511(3)
1.496(4)
–
1.459(2)
1.571(3)
1.562(3)
1.802(3)
1.383(4)
1.360(5)
1.283(5)
1.235(5)
1.230(5)
–
1.415(5)
1.390(6)
–
1.554(4)
1.531(5)
1.544(5)
1.505(5)
1.502(6)
–
1.458(2)
1.573(2)
1.562(2)
1.806(2)
1.397(3)
1.352(3)
1.276(3)
–
1.461(2)
1.564(2)
1.565(2)
1.812(3)
1.415(3)
1.355(4)
1.275(3)
1.236(6)
1.229(6)
1.470(4)
1.413(4)
1.425(4)
1.221(3)
1.548(4)
1.554(4)
1.535(4)
1.517(3)
1.495(4)
1.513(4)
1.464(2)
1.560(3)
1.561(3)
1.806(3)
1.417(3)
1.349(3)
1.269(3)
1.211(5)
1.200(4)
1.475(4)
1.357(4)
1.398(4)
1.219(3)
1.555(4)
1.539(4)
1.532(4)
1.509(3)
1.500(4)
1.514(4)
N1–N2
N1–C12(15)
N2–C3
N3–O5
N3–O6
N3–C9
O2–C8
O3–C7
O4–C15
C1–C2
C1–C5
C1–C6
C2–C3
C3–C4
C12–C15
–
–
1.422(4)
1.402(4)
1.213(3)
1.552(3)
1.530(4)
1.537(4)
1.504(3)
1.498(3)
1.500(3)
1.544(5)
1.530(5)
1.534(5)
1.502(5)
1.482(6)
–
Bond angle, deg
107.0(2)
108.1(2)
109.7(2)
127.5(3)
119.9(6)
116.9(3)
–
P1C1C5
105.8(2)
108.1(2)
107.8(2)
124.4(2)
119.3(2)
117.2(2)
–
108.7(2)
110.3(2)
105.8(2)
121.3(2)
124.6(3)
115.4(3)
–
110.5(2)
107.3(2)
105.7(2)
120.0(2)
124.9(2)
115.2(2)
114.5(2)
123.5(2)
119.2(2)
124.6(2)
116.2(2)
113.1(1)
114.6(1)
104.9(1)
122.0(2)
115.5(1)
108.7(2)
107.2(2)
107.7(2)
123.9(2)
122.5 (2)
116.9(2)
115.7(2)
123.5(2)
120.5(2)
125.4(2)
114.2(2)
113.3(1)
113.1(1)
105.6(2)
120.8(3)
116.2(1)
110.1(2)
107.9(2)
106.5(2)
128.8(3)
124.4(3)
116.6(2)
115.5(2)
123.6(2)
121.2(2)
126.4(2)
114.9(2)
113.9(2)
114.3(2)
103.8(2)
120.9(3)
115.8(1)
P1C1C6
P1C1C2
P1O2C8
P1O3C7
N1N2C3
N1C15C12
N1C15O4
N2N1C12(15)
N2C3C4
N2C3C2
O1P1O3
O1P1O2
O2P1O3
O4C15C12
C1P1O1
–
–
–
119.3(2)
126.3(2)
119.5(2)
114.8(1)
113.5(1)
103.1(1)
–
119.3(3)
124.8(3)
115.2(3)
114.1(1)
114.2(2)
104.3(2)
–
119.2(3)
125.3(3)
115.3(3)
121.8(2)
115.0(2)
85.4(3)
–
115.4(1)
116.1(1)
116.2(2)
C1P1O3
C1P1O2
C1C2C3
C2C1C5
C2C1C6
C2C3C4
C5C1C6
103.4(1)
105.3(1)
120.9(2)
112.0(2)
112.1(2)
114.2(2)
110.6(2)
103.5(2)
103.0(1)
116.0(3)
109.9(2)
112.3(3)
120.0(3)
109.7(3)
108.9(2)
104.5(2)
115.3(3)
112.1(3)
110.5(3)
119.5(3)
109.4(3)
105.2(1)
102.2(1)
115.3(2)
111.1(2)
112.0(2)
119.0(2)
110.2(2)
103.9(1)
103.5(1)
114.3(2)
112.1(3)
110.1(2)
120.3(2)
110.8(3)
103.9(1)
103.8(1)
114.1(2)
111.6(3)
110.6(2)
118.7(2)
110.1(3)
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DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1637
Table 3. (Contd.)
Parameter
IVа
Vb
III
VI
VIIA
VIIB
Torsion angle, deg
P1C1C2C3
176.4(2)
1.7(3)
126.4(3)
125.5(3)
60.3(2)
–63.5(2)
–173.1(2)
179.1(2)
–59.2(2)
59.4(2)
–53.1(2)
66.8(2)
–174.6(2)
54.7(2)
174.6(2)
–66.8(2)
178.2(2)
0.5(4)
–
177.4(3)
–50.4(4)
74.9(3)
–177.2(3)
21.0(4)
–104.3(4)
148.2(3)
57.7(3)
–60.4(2)
179.3(2)
–176.7(2)
65.3(2)
–55.1(3)
–68.2(2)
173.7(2)
53.4(3)
179.6(3)
0.9(5)
–
179.2(2)
–16.8(6)
106.3(6)
–145.3(5)
–39.1(8)
–155.8(7)
100.4(7)
170.8(2)
49.0(3)
–68.7(3)
–61.4(3)
176.8(3)
59.1(3)
28.7(3)
–93.1(3)
149.2(3)
–179.4(3)
0.7(5)
–169.6(2)
–55.3(3)
69.4(3)
179.0(2)
4.0(3)
171.7(2)
32.7(3)
–91.8(3)
159.3(3)
–44.3(3)
80.0(3)
–171.3(3)
–59.5(3)
178.9(3)
59.0(3)
175.9(2)
54.3(3)
–65.6(2)
65.7(2)
–55.9(3)
–175.9(2)
178.1(3)
–4.1(6)
–13.4(4)
168.7(3)
–166.4(2)
15.0(4)
–166.0(2)
–
175.5(2)
–24.4(5)
100.3(4)
–151.4(4)
30.7(4)
–94.2(4)
157.5(4)
61.3(2)
–177.6(3)
–57.5(3)
–172.6(2)
–51.5(3)
68.6(3)
–64.4(2)
56.8(3)
176.8(3)
–177.1(3)
6.0(5)
O1P1O2C8
O3P1O2C8
C1P1O2C8
O1P1O3C7
O2P1O3C7
C1P1O3C7
O1P1C1C2
O1P1C1C5
O1P1C1C6
O2P1C1C2
O2P1C1C5
O2P1C1C6
O3P1C1C2
O3P1C1C5
O3P1C1C6
N1N2C3C2
N1N2C3C4
N1C15C12C11
N1C15C12C13
N2N1C15C12
N2N1C15O4
N2N1C15C12
N2N1C12C11
N2N1C12C13
O4C15C12C11
O4C15C12C13
O5N3C9C14
O5N3C9C10
O6N3C9C10
O6N3C9C14
O6N3C11C10
–121.6(3)
131.0(3)
60.4(2)
–179.3(2)
–59.2(2)
–174.4(1)
–54.1(2)
66.0(2)
–65.1(2)
55.3(2)
175.3(2)
179.2(2)
–5.1(3)
26.5(3)
–156.6(2)
–178.9(2)
–2.5(3)
–179.2(2)
–
–
–
–
–
–4.9(5)
174.6(3)
167.2(3)
–13.6(5)
166.9(2)
–
–
–
–
–
–
–
–
–
–
1.6(4)
–178.6(2)
–
–177.3(3)
2.6(5)
–
–179.4(3)
–0.1(5)
–
–
–
–
–150.0(2)
26.9(3)
–
165.2(3)
–12.6(4)
169.0(4)
9.7(5)
169.9(4)
–11.5(5)
–
175.9(4)
–4.6(5)
173.7(4)
–6.5(6)
173.9(5)
–6.0(6)
–
–
–
–
–
–
–
177.1(3)
–2.2(5)
177.7(3)
–3.0(4)
–
1.3(6)
–178.4(4)
1.6(6)
–178.7(4)
–178.1(3)
–
–
–
–
–
–177.7(4)
O6N3C11C12
O5N3C11C10
O5N3C11C12
C1C2C3N2
–
–
1.7(6)
–1.2(6)
178.2(4)
96.1(4)
–85.1(4)
1.3(5)
0.7(4)
–
–
–
–
–
–
–
–
–179.9(3)
78.1(4)
–
–
–2.8(4)
178.3(3)
–94.8(2)
89.3(3)
–104.2(3)
77.9(5)
86.9(3)
–95.9(3)
C1C2C3C4
–102.0(4)
C3N2N1C12
C3N2N1C15
C3C2C1C5
C3C2C1C6
178.9(3)
–
60.4(4)
–64.7(4)
–
176.6(3)
–
–65.4(4)
57.0(4)
–
175.7(3)
–
–62.1(4)
60.1(4)
–
–
–
–
158.6(2)
70.5(2)
–53.1(3)
158.8(2)
–71.5(4)
–68.9(3)
55.1(3)
–72.1(4)
67.9(4)
55.3(3)
–67.6(3)
68.6(4)
C3N2N1C15
Bond lengths in the disordered fragment given for the maximum population 0.62; N4–O7 1.223(4) Å, N4–O8 1.230(4) Å, N3–C9 1.460(5) Å,
a
N4–C11 1.445(4) Å. b N3–C11 bond length is 1.438(6) Å.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1638
BUZYKIN et al.
Table 4. Deviations of atoms from the [N1N2C2C3C4] plane P(1) in the molecules of the dimephosphone aryl- and aroyl-
hydrazones III–VII
Parameter
III
IV
V
VI
VIIA
VIIB
The limits of the P(1) fragment flatness
0.010(3)
0.007(4)
0.005(3)
0.021(2)
0.023(3)
0.035(3)
Deviations of atoms from the P(1) plane
C15
O4
C1
C5
C6
P1
O1
O2
O3
C7
C8
–
–
–
–0.451(2)
–0.944(2)
1.394(2)
2.155(3)
2.237(3)
1.0681(6)
0.361(2)
2.506(2)
0.318(2)
–0.868(4)
2.683(4)
1.7(1)
1.156(4)
2.102(3)
1.385(3)
1.820(5)
2.445(5)
1.245(1)
0.871(3)
2.640(3)
0.236(3)
–0.300(5)
3.168(6)
80.0(2)
–1.150(4)
–2.081(3)
–1.427(3)
–2.380(4)
–2.017(4)
–1.207(1)
–0.362(3)
–2.666(4)
–0.686(3)
0.038(6)
–
–
–
–0.036(3)
1.156(4)
–1.354(4)
0.1116(8)
0.107(2)
1.400(2)
–1.050(2)
–1.153(4)
2.485(4)
2.3(2)
–1.382(3)
–2.239(4)
–2.133(4)
–1.0465(9)
–0.325(2)
–2.471(3)
–0.320(3)
0.657(5)
–2.661(4)
3.1(2)
–1.369(3)
–1.893(5)
–2.402(4)
–1.205(1)
–2.341(2)
–0.757(4)
0.255(4)
0.54(1)
–1.085(6)
3.5(2)
–3.135(7)
60.0(2)
The angle of rotation of the benzene ring
relative to the P(1) plane
The angle of rotation of the nitro group
relative to the plane of the benzene ring
2.5(4)
3.7(5)
N3O5O6 1.5(5)
N4O7O8 2.4(4)
–
11.1(5)
6.7(6)
H-bond between the NH group of the hydrazone
fragment and the proton acceptor in the ylidene
fragment (in this case, phosphoryl group) can also
stabilize the Z-isomer relatively to the C=N multiple
bond, as has been observed in the case of pyridyl-2-
aldehyde aroylhydrazones [20].
R'
R'
R'
R'
N
O
H
R
N
R
H
O
H
O
H
R
N
O
N
R
N
N
N
N
Z,E',Z''
Z,E',E'
E,E',E''
E,E',Z''
H
H
N
N
N
N
R
R
O
O
R'
R'
XIIIa
XIIIb
R = CMe2P(O)(OMe)2.
According to IR spectroscopy, both dimephosphone
benzoyl- and 4-nitrobenzoylhydrazones VI, VII in the
crystals exist in one form, and the NH, C=O, and C=N
groups give only one absorption band each (Table 1).
In solutions, the aroylhydrazones VI, VII mostly are in
two forms, although one of them dominates. Based on
the data of analysis of the structure of dimephosphone
arylhydrazones II–V and published results [6, 7, 17–20],
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1639
Table 5. The interaction parameters in the crystals of dimephosphone aryl- and aroylhydrazones III–VII
D–H···A
D–H, Å
H···A, Å
D···A, Å
DHA, deg
Symmetry operations
III
N1–H1···O1'
C13–H13···O1'
C2–H21···O3
C2–H22···O2
C5–H53···N2
C6–H63···N2
0.80(3)
0.93
2.20(3)
2.50
2.975(3)
3.280(3)
2.984(4)
3.007(4)
3.063(4)
3.183(4)
165(3)
141.0
107.5
112.0
120.4
117.8
x, 1 + y, z
x, 1 + y, z
0.97
2.55
–
–
–
–
0.97
2.51
0.96
2.46
0.96
2.62
IV
N1–H1···O6
N1–H1···N3
C9–H9···O1'
C8–H82···O5''
C10–H10···O5
C13–H13···N2
C7–H71···O1
0.86(3)
0.86(3)
0.93
1.98(3)
2.62(3)
2.52
2.593(4)
2.894(5)
3.401(6)
3.232(5)
2.674(7)
2.742(5)
2.987(6)
127(3)
100(2)
159.0
134.0
100.0
101.0
106.0
–
–
–x, 1 – y, 1–z
0.96
2.49
–1+x, –1 + y, –1 + z
0.93
2.35
–
–
–
0.93
2.41
0.96
2.57
V
N1–H1···O8
N1–H1···N4
C14–H14···O1'
C6–H63···O5''
C13–H13···N2
C2–H21···O3
C5–H53···N2
0.84(4)
0.84(4)
0.93
1.97(4)
2.58(4)
2.53
2.611(4)
2.913(4)
3.282(5)
3.525(5)
2.731(4)
2.920(5)
3.068(5)
132(4)
105(3)
139.0
178.0
101.0
102.0
112.0
–
–
1 – x, 1 – y, –z
0.96
2.56
–1/2 + x, 1/2 – y, 1/2 + z
0.93
2.40
–
–
–
0.97
2.56
0.96
2.58
VI
N1–H1···O1'
С4–H42···O1'
C7–H72···O4''
C5–H51···O2
0.87(3)
0.96
2.06(3)
2.44
2.899(3)
3.242(3)
3.231(4)
2.998(4)
163(2)
141.0
130.0
106.0
x, 1/2 – y, –1/2 + z
x, 1/2 – y, –1/2 + z
x, 3/2 – y, 1/2 + z
–
0.96
2.53
0.96
2.59
VII
N1A–H1A···O1B
N1B–H1B···O1A
C10B–H10B···O5A'
C11A–H11A···O1B
C11B–H11B···O1A
C2B–H21B···N2A
C7A–H71A···N1B''
C13B–H13B···O4A
C13B–H13B···O4B
C4B–H41B···O4B
C4A–H43A···O4A
C5B–H51B···O2B
C5A–H53A···O2A
0.81(3)
0.87(3)
0.93
2.04(3)
1.99(3)
2.55
2.841(4)
2.826(3)
3.322(6)
3.320(5)
3.301(5)
3.518(4)
3.567(6)
3.255(5)
2.776(4)
2.954(5)
2.998(6)
2.996(5)
3.005(5)
170(3)
164(2)
140.6
138.3
157.5
168.9
170.0
138.1
100.3
107.4
112.7
108.8
110.4
–1 + x, 1 + y, z
1 + x, –1 + y, z
x, y, 1 + z
0.93
2.57
–1 + x, 1 + y, z
0.93
2.42
1 + x, –1 + y, z
0.97
2.56
1 + x, –1 + y, z
0.96
2.61
–x, 1 – y, 1 – z
0.93
2.50
–
–
–
–
–
–
0.93
2.46
0.96
2.52
0.96
2.49
0.96
2.55
0.96
2.53
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1640
BUZYKIN et al.
~27° against ~13° in the molecule of 4-nitrobenzoyl-
hydrazone VIIA and ~5° in molecules of the other
independent form VIIA. These changes can also be
attributed to the influence of the nitro group on the
electron density distribution in the acyl moiety. A
decrease in the interaction of nitro group in the
position 4 of the phenyl ring with hydrazone fragment
in the molecule of acylhydrazone VII compared with
4-nitrophenylhydrazone III appears as an increase in
the rotation angle of nitro groups with respect to the
phenyl ring. In molecules VIIA, VIIB the angles are
~11.5° and ~6°, respectively, while in the molecule of
arylhydrazone III it does not exceed 3°.
Fig. 4. The system of hydrogen bonds in the crystal of
dimephosphone 4-nitrophenylhydrazone III.
The stereochemistry of the dimethoxyphos-
phorylbutyl fragment in aroylhydrazone molecules VI
and VII is closer to that of the molecules of 2-nitro-
and 2,4-dinitrophenylhydrazones.
we can conclude that the more stable form in crystals
and in solutions is the EC=N isomer. To clarify the
conformation of the amide fragment we used the X-ray
diffraction analysis. We found that in contrast to
arylhydrazones III–V and benzoylhydrazone VI con-
taining in the unit cell of the crystal only one
independent molecule of respective compound, the
unit cell of 4-nitrobenzoylhydrazone VII includes two
independent molecules, VIIA and VIIB (Figs. 7, 8).
Although these molecules are EC=N isomers and the
EC(O)–N conformers, overall conformation of the
hydrazones and ylidene fragments differ significantly
from those observed in the molecules of
arylhydrazones III–V. Because of the presence of
carbonyl group in aroylhydrazones VI, VII the
interaction of the electronic systems of aryl and
hydrazone groups (conjugation) is weaker resulting in
a lengthening of the N–N bonds, which in the
molecules of 4-nitrobenzoylhydrazones VIIA and
VIIB reach 1.415(3) and 1.417(3) Å, respectively.
Despite the fact that isopropylidenehydrazone frag-
ment P(2) [C2C3(C4)=N2N1] in these molecules is also
flat, the imine bond and amide fragment are separated,
especially under the influence of 4-nitrophenyl
substituents. The decrease in the N1–N2 bond order
leads to about 20° turn of the fragments around this
bond in the benzoylhydrazone VI molecule and
approximately to 70° (in the opposite direction) in the
molecule of 4-nitrobenzoylhydrazone VIIA, VIIB)
(see torsion angles in Table 3). In the molecules of VII
there is also a turn of acyl fragments around the amide
bond C15–N1 about 14°, while in the molecule of
benzoylhydrazone VI it does not exceed 3°. On the
other hand, in the molecule VI the phenyl rings are
much more turned around the amide–aryl bond (C15–C12):
Aroylhydrazone VI molecules form in the crystals a
1D-supramolecular structure similar to that of
arylhydrazone III, namely, the chains along the axis 0z
(Fig. 9). In the crystal of compound VII a 0D structure
is formed through the classical hydrogen bonds N1A–
H1A···O1B and N1B–H1B···O1A (Table. 5), the dimers of
molecules VIIA, VIIB (Fig. 10). The short contacts of
the H···O type in molecule VI form layers parallel to
the b0c plane of the crystal, and in the crystal of VII
similar contacts lead to the formation of three-
dimensional structure (Table 5).
The NMR spectra of dimephosphone aryl- and
aroylhydrazones III–VII in solution of trifluoroacetic
acid exhibit some peculiarities. The signals of the
second forms of these hydrazones appear almost im-
mediately after the dissolution, and their intensity
increases rapidly (Table 2). The signals of methyl
groups adjacent to the phosphoryl group are shifted
upfield by 0.3–0.5 ppm compared with the spectra of
solutions in other solvents. A similar but not so clear
effect occurs at the formation of the dimephosphone
complexes with calix[4]resorcinol tetramethylsul-
fonate, which is attributed not only to the entry of a di-
mephosphone molecule into the calix[4]arene cavity,
but also by the intermolecular hydrogen bonding of the
phosphoryl oxygen with one of the hydroxyls of the
macrocycle [22]. Since the signals of methyl and
methylene groups linked to the hydrazone fragment of
arylhydrazones II–V are not shifted noticeably at dis-
solving the compound in trifluoroacetic acid (Table 2)
due to the possible protonation of nitrogen atoms, the
observed effect may be due to the interaction of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1641
Fig. 5. The system of hydrogen bonds in the crystal of
dimephosphone 2-nitrophenylhydrazone IV.
trifluoroacetic acid with the phosphoryl group of
hydrazones II–V, which consists most probably in the
formation
of
intermolecular
F3CCOOH···O=P
Fig. 6. The system of hydrogen bonds in the crystal of
dimephosphone 2,4-dinitrophenylhydrazone V.
hydrogen bonds.
1
In the H NMR spectrum of aroylhydrazones VI,
VII in trifluoroacetic acid the signals of three forms
always appear (Table 2). The third form in these
spectra is characterized by an upfield shift of not only
the signals of the Me2C fragment but also of the
signals of methyl and methylene groups linked to the
hydrazone fragment of aroylhydrazones VI, VII,
which can be due to the change of hybridization of the
carbon atom of azomethine group from sp2 in the
hydrazones VI, VII to sp3 at the formation of a cyclic
tautomer XIIIa (or XIIIb), which seldom but certainly
are detected in the acylhydrazones [6, 7, 21]. Most
likely, 1,3,4-oxadiazol-2-ine XIII can exist in the
trifluoroacetic acid solution in a protonated form. Un-
fortunately, we failed to isolate the cyclic isomers of
type XIII of acylhydrazones VI, VII, or their salts
despite numerous attempts. When passing HCl gas into
the solutions of a hydrazone in various solvents we
isolated most frequently a salt of the corresponding
hydrazide and dimephosphone.
benzoylhydrazone XIV (Table 6). According to the IR
spectra, the crystals of this compound contain only one
amide conformer: there are single absorption peaks
due to the stretching vibrations of groups NH, C=O,
and C=N at 3261, 1654, and 1634 cm–1, respectively.
The rate of appearance of the second conformer in
solution depends on the nature of the solvent.
According to [18], in polar solvents dominates the
more polar EN–NZ(O=)C–N conformer (the Z'' conformer)
(Table 6). In CDCl3 and in less polar CD3CN the EN–N
,
E(O=)C–N conformer (E'' conformer) appears together
with the more polar one just in the process of prepar-
ation of the solutions. In a more polar solvent DMSO-
d6 the less polar EN–N, E(O=)C–N conformer (E'' con-
former) appears only in several days after the
dissolution.
In trifluoroacetic acid solution of acetone 4-
nitrobenzoylhydrazone XIV only two forms are found.
One of them we regard as the protonated form of Z''
conformer, and we suggest that the other is the
protonated form of the cyclic tautomer.
A situation similar to the described for di-
mephosphone aroylhydrazone VII is observed in the
case of related model compound, acetone 4-nitro-
N
O
H
+N
O
H
N
H
O
N
H
N
N
O
N
+
H
N
H
NO2
NO2
NO2
NO2
E(O=)C-N (E')
Z(O=)C-N (Z'')
[Z'']+H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1642
BUZYKIN et al.
Fig. 7. Molecular geometry and numbering of atoms in the crystal of dimephosphone benzoylhydrazone VI.
Fig. 8. The geometry of the independent molecules and the numbering of atoms in a crystal of dimephosphone 4-nitrobenzoyl-
hydrazone VII.
EXPERIMENTAL
software [25]. The hydrogen atoms in structures III–
VII were placed in geometrically calculated positions
and included in the refinement in the rider model. All
calculations were performed using the WinGX [26]
and APEX2 [27] softwares. All figures and analysis of
molecular interactions were made with the PLATON
software [28]. The study of single crystals of
compounds III–VII was carried out in the Federal
Spectroanalytic Center for Collective Use of the
Arbuzov Institute of Organic and Physical Chemistry,
Kazan Scientific Center of Russian Academy of
Sciences on the basis of the Laboratory of Diffraction
Methods. Table 7 lists crystallographic parameters and
details of the structure refinement of compounds III–
VII, selected geometric parameters of these molecules
are given in Table 3.
1H and 31P–{1H} NMR spectra were recorded on a
1
Bruker Avance 600 instrument (600 MHz, H), and a
1
Bruker Avance-400 (400 MHz, H, 162 MHz, 31P)
spectrometer, solvent CDCl3, relative to the signal of
the solvent, and relative to the external H3PO4. The
spectra of solutions in trifluoroacetic acid were
recorded relative to an external reference, acetone-d6.
IR spectra were obtained on a Bruker Vector-22
instrument from suspensions of substances in mineral
oil or from the KBr pills. The melting points were
determined on the Boetius heating block.
X-ray analysis of the crystals of hydrazones III–
VII was performed on an automatic diffractometer
Bruker Smart APEX II CCD: graphite monochro-
mator; λMoKα = 0.71073 Å; ω-scanning, temperature
293 K. The semiempirical accounting for extinction
was carried out using SADABS software [23]. The
structure was solved by the direct method with SIR
program [24] and refined initially in isotropic, then in
anisotropic approximation with the SHELXL-97
Dimethyl (2-methyl-4-oxopent-2-yl)phosphonate
phenylhydrazone (dimephosphone phenylhydrazone)
II. A mixture of 15 g (0.072 mol) of dimethyl (2-
methyl-4-oxopent-2-yl)phosphonate (dimephosphone),
10.5 g (0.072 mol) of phenylhydrazine hydrochloride,
and 50 ml of methanol was stirred until homogeneous
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1643
Fig. 9. The system of hydrogen bonds in the crystal of dimephosphone benzoylhydrazone VI.
Fig. 10. The system of hydrogen bonds in the crystal of dimephosphone 4-nitrobenzoylhydrazone VII.
solution formed. After stirring, a drop of conc. H2SO4
was added and the solution was refluxed for 2 h, then a
half of methanol was removed in a vacuum. The
residue was dissolved in 150 ml of water, the solution
was neutralized to pH 7.0 with saturated solution of
K2CO3. The precipitate was filtered off, washed on the
filter with distilled water (5×25 ml), and dried in air to
constant weight. Dimephosphone phenylhydrazone,
13.2 g (61%), was isolated as a light beige crystalline
powder (Tables 1 and 2).
Dimephosphone arylhydrazones III–V and aroyl-
hydrazones VI, VII. A mixture of 1.0 g (0.0048 mol)
of dimethyl (2-methyl-4-oxopent-2-yl)phosphonate (di-
mephosphone) and 0.0048 mol of the corresponding
arylhydrazine or arylhydrazide in 20 ml of anhydrous
methanol was stirred, and to the solution formed was
added a drop of conc. H2SO4. The resulting mixture
was heated under reflux for 1 h, then cooled to room
temperature. The precipitated crystals were filtered off
immediately or after removal of most part of solvent,
Table 6. 1H NMR spectral data of the acetone 4-nitrobenzoylhydrazone XIV
НА
НВ
Ratio of the
Solvent
CDCl3
Forma
Z-Me
E-Me
3J, Hz
NH
forms
δ, d
Z''
E''
Z''
E''
1.0
0.2
1.0
0.5
2.25
2.16
2.09
2.12
1.99c
8.28
8.03
8.72
9.97
9.33
b
b
b
–
–
–
b
CD3CN
–
8.25
7.97
8.24
9.26
b
a
b
b
b
–
–
–
–
–
8.98
DMSO-d6
Trifluoroacetic acid Z'' + Н+
Z''c
2.02
2.24
1.96
2.17
8.30
7.82
8.05
7.58
8.10
8.55
10.74
d
4.0
1.0
–
d
Cyclic
1.76
–
7.53
8.88
–
a
Z'' = EC=N, EN–N, Z(O =)C–N conformer, E'' = EC=N, EN–N, E(O =)C–N conformer. b Overlap of signals. c In a week the signals of E'' conformer
appear, e.g., at 2.11 ppm and others. d Not recorded due to exchange processes.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 10 2012

1644
BUZYKIN et al.
Table 7. Crystallographic parameters and refinement details of the structure of dimephosphone aryl- and aroylhydrazones
III–VII
Parameter
Color, habitus
III
IV
V
VI
VII
Colorless prismatic Yellowish needle Yellowish prismatic Colorless prismatic Colorless prismatic
Empirical formula
Crystal system
C14H22N3O5P
Triclinic
P-1
C14H22N3O5P
Triclinic
P-1
C14H21N4O7P
Monoclinic
P21/n
C15H23N2O4P
Monoclinic
P21/с
C15H22N3O6P
Triclinic
P-1
Space group
The unit cell parameters
a 7.135(1),
b 9.521(2),
c 12.739(3) Å,
α 94.593(2)
β 95.951(2)
γ 95.230(2)°
a 6.319(2),
b 10.202(2),
c 14.493(3) Å,
α 101.575(2)
β 101.383(3)
γ 104.449(2)°
a 10.191(3),
b 8.490(3),
c 21.581(7) Å
β 96.246(4)°
a 10.778(2),
b 10.514(2),
c 14.933(3) Å
β 91.306(2)°
a 12.629(6),
b 13.078(6),
c 13.985(7) Å,
α 74.347(5)
β 64.859(5)
γ 62.023(5)°
Volume, Å3
853.5(3)
2
855.7(3)
2
1856(1)
4
1691.7(5)
4
1841(2)
4
Z
Molecular weight
343.32
1.336
1.89
343.32
1.332
1.88
388.32
1.389
1.92
326.32
1.281
1.81
371.33
1.341
1.85
d
calc, g cm–3
Extinction coefficient, µMo,
cm–1
F(000)
364
364
816
696
784
Interval θ
2.16° ≤ θ ≤ 27.00° 2.14° ≤ θ ≤ 26.00° 2.31° ≤ θ ≤ 26.00° 2.37° ≤ θ ≤ 27.00° 1.95° ≤ θ ≤ 27.00°
Rint
0.0457
0.0450
0.0535
0.0353
0.0497
Range of measured indices
–9 ≤ h ≤ 9,
–11 ≤ k ≤ 12,
–16 ≤ l ≤ 16
–7 ≤ h ≤ 7,
–12 ≤ k ≤ 12,
–17 ≤ l ≤ 17
–12 ≤ h ≤ 12,
–10 ≤ k ≤ 10,
–26 ≤ l ≤ 26
–13 ≤ h ≤ 13,
–13 ≤ k ≤ 13,
–19 ≤ l ≤ 19
–16 ≤ h ≤ 16,
–16 ≤ k ≤ 16,
–17 ≤ l ≤ 17
Measured/independent
reflections
9344 / 3686
6546 / 3312
13634 / 3654
13424 / 3693
30058 / 8009
Reflections with I > 2σ(I)
2320
1788
1930
2702
5291
Final divergence factors
R 0.0602,
Rw 0.1520
R 0.0643,
Rw 0.1498
R 0.0619,
Rw 0.1641
R = 0.0542
Rw 0.1419
R 0.0589,
Rw 0.1681
R
all 0.0975
R
all 0.1179
R
all 0.1172
R
all 0.0743
Rall 0.0889
R
w all 0.1743
R
w all 0.1787
R
w all 0.1946
R
w all 0.1566
R
w all 0.1965
Fit parameter
1.044
1.017
1.027
1.022
0.958
Number of refined parameters
211
217
258
200
457
sometimes after a short keeping the syrupy mass
formed at room temperature. After washing with a
small amount of methanol, the product was dried in
air. Table 1 lists yields, selected IR spectral data, and
elemental analyses, Table 2 contains the data of 1H and
31P NMR spectra.
cm–1: 3251, 3105, 3075, 3039 1654, 1636, 1598, 1524,
1490, 1422, 1349, 1329, 1322, 1303, 1267, 1186,
1
1142, 1113, 1106, 1076, 1032, 1017, 997, 941. H
NMR spectra in different solvents are given in Table 6.
ACKNOWLEDGMENTS
This work was supported by a joint grant of
Russian Foundation for Basic Research and the
Academy of Sciences of Tatarstan Republic (grant
no. 09-03-97 007-r_Povolzhye_a).
Acetone 4-nitrobenzoylhydrazone VIII was
prepared from 4-nitrobenzhydrazide and acetone, a
slightly yellowish crystalline powder, mp 165°C (from
aqueous ethanol), published: 165°C [29]. IR spectrum,
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DIMEPHOSPHONE ANALOGS: I. SYNTHESIS AND STRUCTURE
1645
15. Buzykin, B.I., Titova, Z.S., Cherepinskii-Malov, V.D.,
Gazetdinova, N.G., Stolyarov, A.P., Litvinov, I.A.,
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SSSR, Ser. Khim., 1983, no. 3, p. 541.
16. Buzykin, B.I., Cherepinskii-Malov, V.D., Litvinov, I.A.,
Gazetdinova, N.G., and Struchkov, Yu.T., Izv. Akad.
Nauk SSSR, Ser. Khim, 1982, no. 6, 1306.
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