Synthesis and properties of O,O-dialkyl [1-hydroxy-3-(dialkylamino)-2,2- dimethylpropyl]phosphonates

Article abstract of DOI:10.1134/S1070363211040050

O,O-Dialkyl [1-hydroxy-3-(dialkylamino)-2,2-dimethylpropyl]phosphonates were prepared for the first time. By means of NMR ¹H, IR spectroscopy and quantum-chemical calculations the presence in them of various H-bonds was established. In the crys

Full text of DOI:10.1134/S1070363211040050

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 4, pp. 647–657. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.B. Gazizov, V.V. Zverev, R.A. Khairullin, R.R. Shagidullin, A.I. Alekhina, L.V. Avvakumova, V.I. Kovalenko, O.G. Sinyashin,
2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81, No. 4, pp. 554–564.
Synthesis and Properties of O,O-Dialkyl
[1-Hydroxy-3-(dialkylamino)-2,2-dimethylpropyl]phosphonates
M. B. Gazizova, V. V. Zverevb, R. A. Khairullina, R. R. Shagidullinb, A. I. Alekhinaa,
L. V. Avvakumovab, V. I. Kovalenkob, and O. G. Sinyashinb
a Kazan State Technological University, ul. K. Marksa 68, Kazan, Tatarstan, 420015 Russia
e-mail: mukattisg@mail.ru
b Arbuzov Institute of Organic and Physical Chemistry, Kazan Scentific Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received April 1, 2010
Abstract—O,O-Dialkyl [1-hydroxy-3-(dialkylamino)-2,2-dimethylpropyl]phosphonates were prepared for the
1
first time. By means of NMR H, IR spectroscopy and quantum-chemical calculations the presence in them of
various H-bonds was established. In the crystalline state P=O···HO intermolecular hydrogen bonds favor the
formation of cyclic dimer associates DP=O. In the liquid state and concentrated solutions P=O···HO and N···HO
intermolecular hydrogen bonds cause the formation of cyclic dimer associates DP=O and DN, and intramolecular
hydrogen bonds provide the existence of different conformations of the monomer form MN, the most stable
among them with the non-strained six-membered ···NCCCOH··· ring.
DOI: 10.1134/S1070363211040050
Organic derivatives of P(IV) phosphorus acids func-
tionalized in various positions occupy an important
place in organic chemistry. Among them aminoalkyl-
phosphoryl compounds are distinguished by structural
variety, availability, and broad spectrum of useful
applied properties [1–2]. Their structural variety is
determined by broad possibility of variation of the
nature of substituents at P(IV) and N(III), different
mutual location of the phosphoryl and amino groups,
and the location of the additional characteristic group,
for example, of the hydroxy group with respect to both
the phosphoryl and the amino groups. Though the first
representatives of hydroxyl-substituted aminoalkyl-
phosphonates were prepared more than 40 years ago
[3], they were insufficiently studied. Moreover, some
types of them, for example, 1-hydroxy-3-(dialkylamino)-
alkylphosphonates, compounds with competing func-
tional groups, were not yet described, though their
positional analogs, 3-hydroxy-1-aminoalkylphospho-
nates, were already prepared [4].
The aim of this work was the synthesis and NMR,
IR, and quantum-chemical studies of the structure of
O,O-dialkyl [1-hydroxy-2,3-dimethyl-3-(dialkylamino)
propyl]phosphonates III.
Compounds III were synthesized by the reaction of
dialkyl hydrogen phosphites I with 3-(dialkylamino)-
substituted aldehydes II. At the addition of ethanol
solution of sodium alcoholate or the insignificant
amount of sodium to the mixture of compounds I and
R1ONa
(R1O)2P(O)CH(OH)CMe2CH2NR22
(R1O)2PHO + R22NCH2CMe2CHO
or Δ
I
III
II
−
+
(R1O)2P
O
I + II
R22NCH2CMe2CHO
IV
+
(R1O)2P(O)CHO−
R22NHCH2CMe2CHO
II + IV
II + III
CMe2CH2NR22
III, R1 = R2 = Me (а), Et (d); R1 = Me, R2 = Et (b); R1 = Et, R2 = Me (c).
647

648
GAZIZOV et al.
II the exothermic reaction takes place. After neutra-
lization the reaction mixture with the acetic acid com-
pounds III were isolated pure by vacuum distillation.
The synthesis of compounds III may be also carried
out by heating the mixture of compounds I and II at
80°C. Due to the presence of tertiary amino group in
starting aldehydes the nucleophilic catalysis takes place.
In the course of solving structural problems phos-
phonates V containing amino group in the position 2
with respect to the phosphoryl group, compounds VI
con-taining amino group in the aromatic ring, and also
thiophosphonate VII were synthesized for comparison.
Two analogs of compound VI were prepared before
[5–6].
(MeO)2PHO + Et2NCMe2CHO
(MeO)2PHO + 4-Me2NC6H4CHO
(MeO)2P(O)CH(OH)CMe2NEt2
V
(MeO)2P(O)CH(OH)C6H4NMe2-4
VI
(PrO)2P(S)H + Me2NCH2CMe2CHO
(PrO)2P(S)CH(OH)CMe2CH2NMe2
VII
The composition of the products III-VII was
confirmed by elemental analysis, and their structure,
by the 1H, 13C, and 31P NMR spectra. 1H and 13C NMR
spectral characteristics of these substances are
compiled in Table 1.
in compounds VI containing the amino group in the
rigid aromatic fragment it is also located upfield at δ
4.13 and 4.35 ppm respectively. Besides, methyl and
methylene group protons and carbon atoms of methyl
groups in CMe2CH2N fragment are magnetically
4
3
3
nonequivalent and have different JHH, JPH, and JPC
values (Table 1) indicatibg their definite orientation
with respect to the phosphorus atom and the CH
proton. Starting from these data it was possible to
suggest the formation of cyclic structure with a strong
hydrogen bond between the hydroxy and the
dialkylamino groups in compounds III.
31P NMR spectra of compounds V–VI contain a
singlet at δP 27–28 ppm, and for compounds VII a
singlet at δP 92 ppm was observed. It confirms that the
nearest surrounding of phosphorus atoms is O2P(O)C
and O2P(S)C respectively. Note the form and location
of the signal of the hydroxy proton in compounds III.
It is strongly broadened and shifted downfield to δ 7.10–
8.52 ppm. In functionalized 1-hydroxyalkyl-phos-
phonates lacking an amino group this signal is narrow,
and its chemical shift is located in the range 4.8–5.5 ppm
[7, 8]. In 2-amino-1-hydroxyalkyl-phosphonate V and
Indirect chemical confirmation of this suggestion is
the upfield shift of the hydroxy proton at the
conversion of compounds III to quaternary ammonium
salts VIII.
+
III + R3Hlg
(R1O)2P(O)CH(OH)CMe2CH2NR22R3 Hlg−
VIII
VIII, R1 = R2 = Me, R3 = Bn, Hlg = Br (а); R1 = R2 = R3 = Me, Hlg = I (b); R1 = Et, R2 = R3 = Me, Hlg = I (c).
It follows from the comparison of 1H and 13C NMR
hydroxyalkylphosphonate V, and in compound VI
containing amino group in the aromatic fragment. The
quaternization of N(III) is proved by the downfield
shift of signals of protons of the methylene and methyl
groups directly bound to the nitrogen (δ, ppm): 2.15 d
→ 3.15 d, 3.15 d → 3.84 m, and 2.25 s → 3.59 s.
Signals of carbon atoms in these groups are also
shifted downfield (δC, ppm): 68.68 d → 74.10 d
(CH2N+), 46.87 s → 56.5 s (NMe3).
spectra of starting amine IIIc and its salt VIIIc that the
1
main changes in the H NMR spectra occur in the
location of the hydroxy protons and in the signals of
hydrogen atoms at the carbon atoms directly bound
13
with the quaternary nitrogen. In the C NMR spectra
changes are observed in the range characteristic of the
signals of the above-mentioned carbon atoms. For
example, the hydroxy proton singlet is shifted upfield
from δ 7.5 ppm to δ 5.05 ppm, namely, to the range
where it is observed in the case of 1-hydroxyalkyl-
phosphonates having no amino group, in 2-amino-1-
Proton-acceptor ability of thionophosphoryl group
is significantly lower as compared to the phosphoryl
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SYNTHESIS AND PROPERTIES OF O,O-DIALKYL
649
9
8
1
7
6
Table 1. Characteristics of 1H and 13C NMR spectra (δ, ppm; J, Hz) of
(R1CH2O)2P(X)CH(OH)YN(CH2R2)2
C1
C2
C3
C4,5
4JНН
3JPC
C6
C7
C8
C9,10
3JНН
3JPC
2JPН
4JНН
1JPC
4JPН
2JНН
3JPC
3JНН 3JНН
3JPН
3JНН
2JPC
NMR
nE
R1
H
R2
H
X
O
Y
Solvent
OH
2JPC
1H Acetone-d6 3.79
–
2.15, 3.23 0.95, 1.20 2.40
–
–
3.74, 3.82
–
–
7.25
7.56
4,5
3
CMe2CH2
12.5
2.0
–
2.0
14.2
14.0
–
3.81, 3.90
12.9
CDCl3
3.95
12.7
–
2.15, 3.23 1.00, 1.20 2.38
3.0
2.0
2.0
12.7
–
4,5
2
3
H
Me
O
1H CDCl3
3.79
7.8
–
–
2.32, 2.81 0.99, 1.03 2.57 0.90 3.62, 3.73
–
–
–
8.56
7.40
–
CMe2CH2
5.4
0.6
7.2
7.2
10.2
–
0.6
13.75
CCl4
3.32
1.96, 2.85 0.64, 0.85 2.42 0.75 3.50, 3.35
16.5
0.9
78.2 36.54
0.9
13.8
66.57
–
0.9
7.5
7.5
9.9
–
13C CDCl3
23.40,
26.50
47.61 10.98
54.20,
54.04
7.13
–
8.66
161.1
10.35
0.6, 19.1
Me
H
O
1H Acetone-d6 3.45
–
1.99, 3.09 0.83, 1.08 2.25
–
–
3.92, 4.04
7.5
1.19
7.5
7.10
–
4,5
3
CMe2CH2
8.75
1.5
–
1.5
13.75
68.68
7.5
13C CDCl3
76.70 36.11
23.04,
25.53
11.5
46.87
59.97, 15.7, 15.8
3.98
62.12
–
13.5
–
–
158.7
6.0
6.6, 7.5
Me
Me
O
1H Acetone-d6 3.55
–
–
2.18, 2.98 0.75, 1.00 2.60
0.8 4.00, 4.08
1.2
7.5
7.18
4.13
4,5
3
CMe2CH2
8.75
0.6
2.3
0.6
6.5
6.5
7.5
7.5
13.75
1H Acetone-d6 3.80
–
1.05, 1.15 2.5
0.95 3.60, 3.68
–
4,5
H
Me
H
O
S
CMe2
7.8
–
–
7.0
7.0
10.0
–
1H Acetone-d6 3.82
2.13, 2.22 1.0, 1.3
2.5
–
–
4.0–4.5 m 1.78 m; 7.48
9
10
4,5
3
CH3CH2
CMe2CH2
7.8
–
–
–
1.05, 1.37,
7.0
13.75
3
H
H
O
1H Acetone-d6 4.95
–
7.5–6.6 m
–
2.5
–
3.79, 3.75
–
4.35
C6H4
9.5
–
10.0
–
one. Therefore we expected that formation of N···OH
hydrogen bond will take place instead of P=S···HO
bond. Actually, the signal of the hydroxy group
hydrogen in thionophosphonate IV has downfield
location (δ 7.48 ppm) similarly to compound III.
Note also that compounds III-VI under study
contain the competing proton-acceptor groups (R2N >
P=O > P–) demonstrating different trend to the
formation of various intermolecular and intramolecular
hydrogen bonds, particularly to the formation of the
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650
GAZIZOV et al.
non-strained six-membered ···NCCCOH··· and the
strained five-membered ···O=PCOH··· and ···O–COH···
cycles. That is why we have carried out investigation
of hydrogen bonds in compounds III by means of the
IR spectroscopy and quantum-chemical methods.
crystal and the diluted solutions, and variability of the
observed ν(OH).
Experiments with the variation of medium, phase,
and temperature showed a clear ν(OH) peak at
~3300 cm–1, broad bands at ~3150 cm–1, and flattened
diffuse absorption, a wing, at ~2730 cm–1. Differential
spectrograms showed that the band at ~3150 cm–1 is
two-component [ν(OH) 3200 cm–1 and ν(OH)
3100 cm–1]. The band at 3300 cm–1 is dominant in
liquid phase, and its intensity increases during the
cooling of condensed phase and the increase in
concentration of solutions. It becomes a single one in
the crystalline state. The absorption band at ~2780 cm–1
clearly seen in the differential spectra is revealed as a
long-wave slope of the ν(CH) absorption in the
concentrated solutions and accompanies the growth in
intensity of the band at 3300 cm–1 on cooling.
Absorption bands with maxima at ~3300 and
~2730 cm–1 disappear in diluted solutions. At the same
time absorption bands of free hydroxy groups are not
observed either in liquids or in concentrated or diluted
solutions. From the above-mentioned and the reported
data [10–13] it follows that they must be attributed to
the dimeric associates OH···O=P (DP=O) and OH···NR22
(DN) with intermolecular hydrogen bonds.
IR spectra of compound IIIa agree with the as-
sumed structural formula. They contain a broad strong
absorption band at 3000–3500 cm–1 [ν(OH)], a series
of peaks at ~2700–3100 cm–1, ~1300–1500 cm–1
[δ(CH3), CH2, CH, ω, τ(CH2)], comparatively high
absorption maximum at ~1245 cm–1 [ν(PO)]; a very
intense doublet at 1070–1045 cm–1 [ν(C–OH), ν(PO–C)],
the bands of middle intensity at 835, 766 cm–1 [ν(P–O),
ν(P–C)], and a series of comparatively weak bands in
the range 400–700 cm–1 (deformational vibrations of
molecular skeleton) [9, 10].
Experiments with phase variation, heating and
cooling (+75 to –160°C) of the liquid film and
solutions (c = 2×10–3 M, t = +50 to –15°C), using
differential spectroscopy and expansion methods
showed that the molecules of compound IIIa are
conformationally non-uniform and form different types
of hydrogen bonds. It is confirmed by the variation of
the intensities in the series of doublets (2828/2815,
2881/2763 etc.), simplifying the spectral picture in
R2
O
O
(R1O)2
HO
O
P=O
N
H
H
N
P(OR1)2
R2
O
CH
R2
(R1O)2P HC
Y CH
HC Y
(OR1)
O=P
OH
2
R2
DP=O (Y = CMe2CH2NR22)
DN
Free hydroxy group in 1-hydroxyalkylphosphoryl
compounds as well as the phenol one absorbs at ~3610
cm–1 [9, 10]. Shifts Δν(OH) in CCl4 for the OH···O=P
and OH···N hydrogen bonds in the PhOH···O=P and
PhOH···NEt3 dimers are ~300 and 800 cm–1
respectively resulting in the bands shifts to ~3300 and
2730 cm–1 [9]. Hence, absorption band at ~3300 cm–1
must be attributed to the OH···O=P hydrogen bridge,
and the band at ~2730 cm–1, to the OH···N one.
Absorption band ν(OH) at ~3100 cm–1 decreases
while cooling of liquid phase and becomes the only
one in the diluted solution (c < 0.1 M). Absorption
band at ~3200 cm–1 is observed in differential spectra
(c = 2 M) on heating. These data permit to attribute the
bands at ~3100 and 3200 cm–1 to intramolecular
hydrogen bonds. Though both the amine N(III) and
phosphoryl oxygen possess expressed proton-acceptor
properties [10–13], the first fragment is the stronger
electron-donor group than the second one (I1 ~8 eV
[14] and 10.5 eV [10] in tertiary amines and alkyl
phosphonates respectively).
Formation of non-strained six-membered ring
stabilizes the intramolecular hydrogen bond, and the
formaition of the strained five-membered one destab-
ilizes it [10]. According to these two factors the
interaction with N(III) in compound IIIa proves to be
more effective than the interaction with P=O and P–O
in the competition for the formation of intramolecular
hydrogen bond. Therefore this bond is formed by
means of the OH···NR2 bridge. At the same time note
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SYNTHESIS AND PROPERTIES OF O,O-DIALKYL
651
that the conditions of interaction of the lone electron
pair of nitrogen with the hydroxy group proton are less
favorable here than at the formation of linear inter-
molecular hydrogen bonds.
method on the DFT/PBE/TZ2P [15,16] and B3LYP/6-
31G** [15] levels.
According to the calculated data molecules of the
compound IIIa have significant number of stable
conformations (we have localized 18) resulting from
the rotational isomerism of methoxy groups and the
internal rotation about C–P, C–O, C–C, and C–N
groups. In Tables 2 and 3 the results of calculation of
four stable conformers IIIaa, IIIac, IIIad are listed.
Spatial arrangement of these substances is presented in
Fig. 1.
This fact explains the smaller shift of the absorption
band of intramolecular hydrogen bonds (3600 – 3100 =
500 cm–1) as compared to intermolecular ones (3600 –
2730 = 870 cm–1). The appearance of two bands
(~3200 and ~3100 cm–1) attributed above to the
OH···N intramolecular hydrogen bond must be con-
nected with the conformational nonuniformity of intra-
molecular hydrogen bonds of the ring.
PBE/TZ2P and B3LYP/6-31G** calculations gave
close values of free energies and the geometrical
parameters of conformers (Table 2). Relative values of
total and free energies of three conformers IIIaa,
IIIac, and IIIad with the intramolecular hydrogen
bonds via the N, O=P, and O-P fragments calculated
by means of B3LYP/6-31G** method are 0.00, 6.23,
6.77 and 0.00, 3.88, and 4.62 kcal mol–1 respectively.
Thus they are close to the values obtained by the PBE/
TZ2P method (Table 2). ν(OH) Frequencies of
compound IIIa calculated by means of B3LYP/6-
31G** method exceed the values [for conformers
IIIaa, IIIac, IIIad ν(OH) are equal to 3284, 3756, and
3794 cm–1, their intensities being 706, 35, and 64]
obtained by means of the PBE/TZ2P method (Table 2),
but both methods in the same manner indicate the
spectral difference of the obtained conformers.
It is confirmed also by the doublet of characteristic
peaks of the NMe2 group: 2828/2815 and 2871/2763 cm–1.
IR spectra of some other representatives of the
group of compounds III under discussion were also
studied. For example, compounds IIIb and IIIc differ
from compound IIIa only in the nature of substituents.
Compound IIIc contains EtO group at the P(IV) atom
instead of MeO groups, and in compound IIIb NEt2
group is present instead of NMe2 one. It could be
expected that these differences can hardly bring
significant variations in the properties of molecules
under discussion. Really, spectrograms of liquid
samples and the solution of compound IIIb in CCl4
repeat all the characteristic specific features of
compound IIIa.
In all the wavelength range 400–4000 cm–1 the
spectrograms are much alike. The spectrum of com-
pound IIIc differs from the spectrum of substance IIIa
mainly by the appearance of a strong band at 980 cm–1
characteristic of EtOP(O) fragment. In the case of
compound IIIb main difference is observed in the
range of ν(CH) and δ(CH) absorption according to the
difference in the alkyl substituents at nitrogen. In the
spectra of diluted solutions of compounds IIIb, IIIc
absorption band at 3320 cm–1 disappears as well as in
the spectra of compound IIIa. Only the bands forming
the base in the spectrum of condensed phase remains.
Short-wave part of the absorption band with the
maximum at ~3100 cm–1 is the same as in the spectrum
of phosphonate IIIa. Hence, the main conclusions
concerning the structure and hydrogen bonds of
molecule in the case of compound IIIa correspond also
to substances IIIb, IIIc.
In the Table 2 the differences in total and free
energies (ΔE, ΔG) of conformers calculated by means
of PBE/TZ2P method are listed. They include the
difference in conformational energies proper, and the
difference in the H-bonding energy. Hence, the
correlation is absent between ΔE values and the
parameters characterizing H-coordination, among them
the frequencies of the OH-vibrations. At the same time
such parameters of intramolecular hydrogen bond as
the frequency and the intensity of ν(OH) bond vibra-
tions, interatomic distance IOH, and the charges on
oxygen and hydrogen atoms of the OH group vary
proportionally decreasing in the series of conformers
IIIaa, IIIab, IIIac, IIIad.
According to theoretical data all four stable con-
formations of molecules of compounds IIIa are charac-
terized by intramolecular coordination of hydroxy group
to one of the proton-acceptor groups like nitrogen (IIIaa
and IIIab), phosphoryl (IIIac), and ester (IIIad) oxygen.
Local minimum point related to hydroxy group free
from intramolecular coordination was not found at all.
On the basis of the IR studies of compound IIIa a
conclusion about its conformational non-uniformity
was made above. This fact was confirmed by quantum-
chemical calculations using the density functional
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652
GAZIZOV et al.
H
N
C
H
C
H
H
H
H
H
H
H
H
H
H
O
C
O
H
H
H
H
H
H
C
O
O
C
H
O
H
H
P
H
O
H
H
N
P
C
C
H
C
C
O
C
H
C
H
C
H
H
H
H
H
H
H
O
H
C
C
H
C
C
C
H
H
H
H
H
H
H
H
IIIаb
IIIаа
H
H
C
H
C
O
O
H
H
H H
C
H
H
P
N
H
C
C
C
H
O
O
C
H
H
H
H
H
H
H
C
H
C
H
H
H
IIIаc
IIIаd
Fig. 1. Models of most stable conformers of compound IIIa.
Let us carry out more detailed consideration of
geometrical parameters of stable conformations.
Structures IIIaa and IIIab differ significantly in the
orientation of methoxy groups. Structure IIIaa is
characterized by the gauche, gauche conformation in
the C–O–P–O chains of atoms, and the structure IIIab
by the gauche, trans one which is less stable. Note that
conformation of methoxy groups in P(IV) derivatives
was considered previously [18]. Similarly to the case
of simpler compounds having no intramolecular
hydrogen bonds IIIab conformation with the transoid
orientation of one of methoxy groups with respect to
the P=O bond is less stable. Hydrogen bond
parameters of the conformers IIIaa and IIIab are
close. Conformation IIIac is characterized by the
gauche,gauche orientation of methoxy groups with
respect to the P=O bond, but the conformer IIIad with
intramolecular coordination through the ester oxygen
Table 2. Relative values of total and free energy of conformers IIIa–IIId (ΔE, ΔG, kcal mol–1)a
Conformation
IIIаа
X
ΔE
∆G
lH···X
lOH
lСO
QO
QH
δΗ
ν(OH)
2954
2946
3578
3660
I
ν1(ОН) exp
~3100
~3200
3562b
N
N
0.00
1.66
0.00
1.96
2.72
3.58
1.732
1.727
2.287
2.147
1.013
1.014
0.980
0.975
1.425
1.418
1.445
1.432
–0.218
–0.218
–0.187
–0.193
0.091
0.091
0.141
0.141
9.11
9.35
2.27
1.74
122
148
51
IIIаb
O=P 5.80
IIIаc
О–Р 6.44
67
3600b
IIIаd
a
X is the place of coordination, IH···X, IOH, and ICO are the bond lengths (Å); QO, QH are the charges on oxygen and hydrogen of the OH
group; δH is the chemical shift, ppm; ν(OH) are the frequencies, cm–1; I is a relative ν(OH) intensities. DFT/PBE/TZ2P method.
For hydroxyalkylphosphinates having no amino group.
b
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SYNTHESIS AND PROPERTIES OF O,O-DIALKYL
653
Table 3. Place of intramolecular coordination of the OH groups (X) and torsion angles (deg) of internal rotation (DFT/PBE/
TZ2P and DFT/B3LYP/6-31G**)
Conformation
Х
N
COPO
–50
–53
–39
31
COPO
–36
–38
–178
52
OPCO
74
PCOH
–92
–90
–88
48
OPCC
–52
–54
–93
80
PCCC
64
CCCN
52
CCNC
96
CCNC
–142
–140
–139
–109
–112
–111
–113
IIIаа
IIIааа
IIIаb
IIIаc
IIIаcа
IIIаd
IIIаdа
N
72
61
53
96
N
88
65
49
96
P=O
P=O
P–O
P–O
–45
–52
–84
–83
–171
–175
172
174
–59
–57
–57
–57
124
120
123
118
35
56
56
73
–44
–42
–6
–46
–47
39
–1
40
a DFT/B3LYP/6-31G** method.
has less stable gauche,cis-structure which cannot take
place without the intramolecular hydrogen bond [14].
possibility of the maximum H-interaction. In the
conformers IIIac and IIIad the hydroxy group is
included in the composition of the five-membered ring
impeding the maximum approach and optimal OH
bonding with proton acceptors like the phosphoryl and
the ester oxygen atoms (Fig. 2).
Structures IIIaa and IIIab have gauche,gauche,-
gauche conformation in the O=P–C–C–C–N chain of
atoms, and the conformers IIIac and IIIad are
characterized by gauche,trans,gauche and gauche,trans,-
gauche conformations respectively. Conformations
IIIaa–IIIad differ from one another by the value of
PC–OH torsion angle (Table 3) which is determined by
the maximum degree of interaction between the
hydroxy proton and the acceptors. The torsion angle
CCCN of four conformations under consideration is
mainly gauche with respect to the C–C bond. Transoid
configurations are less stable.
As it was shown above the resonance signal of the
hydroxy proton in compound VI (4.35 ppm) unlike
compounds III is observed near the upfield range
where it appears in 2-aminoalkyl-1-hydroxyphos-
phonate V (4.13 ppm) and hydroxyalkylphosphoryl
compounds having no amino group (4.8–5.54 ppm).
Therefore we expected that the difference observed in
1
the H NMR spectra of compounds III and VI will be
revealed also in the IR spectra.
In the conformers IIIaa and IIIab the hydroxy
group is included in the non-strained six-membered
···NCCCOH··· cycle with the CO–HN and OH···NC
torsion angles close to zero (–14°, 7°) providing the
Really, in the case of compound VI the picture
differs significantly as compared to the spectra of
compounds III. Aromatic fragment containing NMe2
O
H
H
1.732
2.287
N
H
H
C
2.147
O
O
O
H
H
O
C
P
C
C
P
C
C
OH···N
IIIаа
OH···O=P
OH···O–P
IIIаc
IIIаd
Fig. 2. Three types of coordination of H-interaction in the conformers of compounds IIIaa, IIIac, and IIIad.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 4 2011

654
GAZIZOV et al.
H
C
H
H
H
H
H
H
H
N
C
C
O
H
H
H
H
H
C
H
H
C
C
H
H
C
C
H
H
H
P
H
C
O
H
H
C
C
H
N
H
C
C
C
H
H
H
O
H
H
H
C
H
H
H
H
H
H
C
O
H
O
H
O
O
C
H
H
H
H
O
H
P
H
C
H
H
H
H
H
O
C
C
H
O
H
O
H
H
H
C
C
H
H
C
H
H
C
O
H
P
C
H
H
N
C
H
H
C
C
H
C
H
H
C
C
P
O
O
C
H
H
HO
O
H
H
H
H
H
H
H
C
C
N
H
H
C
H
C
H
H
H
H
H
H
H
DP=O
DN
Fig. 3. Models of DP=O (OH···O=P) and DN(OH···N) dimers of compound IIIa.
group in the position 4 makes the molecule more rigid, solution and its intensity significantly decreases. Under
and the formation of intramolecular hydrogen bond further dilution it disappears, but new peaks appear at
between the hydroxy group and the tricoordinate 3603 and 3562 cm–1 which were absent in the spectra
nitrogen atom does not take place. Besides, nN,π- of compounds III. Considering the data on 1-hyd-
orbital interaction decreases the electron-acceptor roxyalkylphosphonates having no amino group [11]
properties of N(III) and its ability to form hydrogen these absorption bands can be attributed as follows.
bonds [10].
The band at ~3277 cm–1 in crystal and at 3305 cm–1 in
solution must be related to ν(OH) of cyclic H-
phosphodimers DP=O prevailing in the condensed state
as well as in sufficiently concentrated solutions. New
ν(OH) absorption bands with the high-frequency
maxima relate to monomeric forms with the intra-
molecular hydrogen bond, particularly, the band at
3562 cm–1 to MP=O, and the band at 3603 cm–1, to
MP–O [11].
In the spectrum of compound VI recorded from the
mull in mineral oil the absorption bands of benzene
fragment at ~3000 cm–1 [ν(CH)], ~1614, 1527, 1449 cm–1
[ν(C=C)] are revealed. In the range of the hydroxy
group only one strong symmetric band with maximum
at 3277 cm–1 is registered. It is much like the band
observed for the crystalline compound IIIa. Evidently
it is an analog of the absorption band of compounds III
O
and V attributed to the cyclic H-phosphodimers DP=O
.
P−O
P=O
O
- CH
MP=O
-
4-Me2N-C6H4
4-Me2N-C6H4 CH
H
H
HO
P=O
OH
O
- CH
- C6H4-NMe2-4
HC
4-Me2N-C6H4
MPO
O=P
According to DFT/PBE/TZ2P calculations dimeric
structure (DP=O) of compound IIIa is significantly
more preferable than the OH···N dimer DN. The
difference is 12 and 16 kcal mol–1 according to
evaluations by the total and free energy respectively
due to the sterical hindrances in the dimer DN (Fig.3).
According to the calculations the bond vibrations of
two OH groups in the dimers give two close
In the spectrum of diluted solution (c = 1 M) of
compound VI in carbon tetrachloride another picture
as compared to the spectra of compounds III is
observed. In this case there is no signs of association
by the N(III) atom (~3100-~2800 cm–1), but the ab-
sorption band of H-cyclodimer by P=O remains. It
shifts from 3277 cm–1 in crystal to 3305 cm–1 in
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SYNTHESIS AND PROPERTIES OF O,O-DIALKYL
655
frequencies ν(OH) of the symmetric and antisymmetric
OH vibrations which for DP=O are 3288 and 3269 cm–1
and the intensities 1844 and 25 respectively.
the ether solution of acetic acid. Then solvent and
volatile products were removed under the reduced
pressure, and the reaction mixture was distilled in a
vacuum to give 10.39 g (76%) of compound IIIa, bp
82–83°C (0.06 mm Hg), nD20 1.4587.
Hence, theoretical studies lead to conclusions
analogous to the experimental data about the pre-
valence of the DP=O dimeric form with intermolecular
hydrogen bond via the phosphoryl oxygen OH···O=P,
but the preference of the MN monomeric form with the
OH···N hydrogen bond. Calculations reproduce
experimentally observed shifts of ν(OH) and δH in H-
complexes of different composition and coordination.
b. To a mixture of 6.82 g of dimethyl hydrogen
phosphite Ia and 8 g of 3-(dimethylamino)-2,2-di-
methylpropanal IIa a solution of sodium methylate in
methanol was added dropwise under nitrogen until the
end of temperature growth (62°C). After stirring for
5 h at 25oC the reaction mixture was neutralized with
the ether solution of acetic acid. Solvent and volatile
products were removed under the reduced pressure,
and the residue was distilled in a high vacuum to give
11.56 g (78%) of compound IIIa, bp 82–83°C
(0.06 mm Hg), nD20 1.4589.
EXPERIMENTAL
IR spectroscopic studies were carried out on a
Fourier Vector 22 spectrometer (Bruker) with the
resolution of 4 cm–1. Spectra of liquid products were
recorded from thin films pressed between KBr plates.
Crystalline substances were dispersed in mineral oil,
and the solutions in CCl4 and CHCl3 were placed in the
cells of various thickness. Temperature studies were
carried out in special cryostate. OPUS complex of
programs (Brucker) was used.
c. A mixture of 2.2 g of dimethyl hydrogen phos-
phite Ia and 2.58 g of 3-(dimethylamino)-2,2-di-
methylpropanal IIa was kept at 80oC for 3 h. After
removing volatile substances the residue was distilled
in a vacuum to give 3.65 g (76.5%) of compound IIIa,
bp 82–83°C (0.06 mm Hg), nD20 1.4584. 31P NMR
spectrum, δP, ppm: 27. Found, %: N 5.72, P 12.81.
C9H22NO4P. Calculated, %: N 5.85, P 12.95.
Molecular and electronic structure of compounds
III and also the vibrational spectra of conformers were
calculated by the density functional method (DFT)
with the non-empiric Perdew-Burke-Ernzerhof func-
tional (PBE/TZ2P) [15] and the three-component basis
with two sets of polarizational TZ2P functions. The
optimization of geometry and calculations of the
vibration frequencies were carried out according to the
PRIRODA program [16]. Atomic charges were
evaluated by the spatial integration method according
to Hirshfeld [17].
O,O-Dimethyl [1-hydroxy-3-(diethylamino)-2,3-
dimethylpropyl]phosphonate (IIIb). This compound
was prepared from 1.85 g of dimethyl hydrogen
phosphite Ia and 2.62 g of 3-(diethylamino)-2,2-dime-
thylpropanal IIb according to the procedure b. Yield
3.21 g (72.3%), bp 92–94°C (0.045 mm Hg), nD20
31
1.4596. P NMR spectrum, δP, ppm: 27. Found, %: N
5.31, P 11.43. C11H26NO4P. Calculated, %: N 5.24, P
11.60.
1H NMR spectra were taken on a Tesla BS-567A
spectrometer (100 MHz) with respect to CDCl3,
acetone-d6, and acetonitrile-d3. P NMR spectra were
recorded on a Spectrospin WH-80 (32.31 MHz) spec-
trometer with respect to the external 85% phosphoric
acid. 13C NMR spectra were taken on a Varian Unity
300 (75.43 MHz) with respect to internal CDCl3 and
acetone-d6.
O,O-Diethyl [1-hydroxy-3-(dimethylamino)-2,2-
dimethylpropyl]phosphonate (IIIc). This compound
was prepared from 5 g of diethyl hydrogen phosphite
Ib and 4.67 g of 3-(dimethylamino)-2,2-dimethyl-
propanal IIa according to the procedure b, yield 7.44 g
(77%) bp 87–88°C (0.05 mm Hg), nD20 1.4532. 31P
NMR spectrum, δP, ppm: 27. Found, %: N 5.41, P
11.33. C11H26NO4P. Calculated, %: N 5.24, P 11.60.
31
O,O-Diethyl {1-hydroxy-3(diethylamino)-2,2-di-
methylpropyl]phosphonate (IIId). This compound
was prepared from 2.1 g of diethyl hydrogen phosphite
Ib and 2.4 g of 3-(diethylamino)-2,2-dimethylpropanal
IIb according to the procedure b. Yield 3.28 g (73%),
bp 95–96°C (0.07 mm Hg), nD20 1.4512. 31P NMR
spectrum, δP, ppm: 27. Found, %: N 4.79, P 10.35.
C13H30NO4P. Calculated, %: N 4.74, P 10.49.
O,O-Dimethyl
[1-hydroxy-3-(dimethylamino)-
2,2-dimethylpropyl]phosphonate (IIIa). a. To a mix-
ture of 6.27 g of dimethyl hydrogen phosphite Ia and
7.4 g of 3-(dimethylamino)-2,2-dimethylpropanal IIa
small piece of sodium was added under nitrogen. The
temperature of the reaction mixture increased to 76°C.
After stirring the reaction mixture for 6 h and
subsequent keeping for 3 days it was neutralized with
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 4 2011

656
O,O-Dimethyl
methylpropyl]phosphonate (V). This compound was
prepared from 6.65 g of dimethyl hydrogen phosphite
Ia and 8.65 g of 2-(diethylamino)-3-methylpropanal
according to the procedure b. Yield 10.25 g (67%), bp
94–96°C (0.065 mm Hg), nD20 1.4593. 31P NMR
spectrum, δP, ppm: 28. Found, %: N 5.69, P 12.38.
C10H22NO4P. Calculated, %: N 5.53, P 12.25.
GAZIZOV et al.
[1-hydroxy-2-(diethylamino)-2-
This compound was prepared from 2 g of O,O-di-
methyl [1-hydroxy-3-(dimethylamino)-2,2-dimethyl-
propyl]phosphonate IIIa and 1.43 g of methyl iodide.
31
Yield 3.15 g (91%). P NMR spectrum, δP, ppm: 24.
Found, %: N 3.85, P 8.69. C12H29NO4PI. Calculated,
%: N 3.67, P 8.13.
Benzyl[3-hydroxy-2,2-dimethyl-3-(dimethoxy-
phosphoryl)propyl]dimethylammonium bromide
(VIIIa). This compound was prepared from 4.85 g of
O,O-dimethyl [1-hydroxy-3-(dimethylamino)-2,2-di-
methylpropyl]phosphonate IIIa and 3.82 g of benzyl
bromide, yield 7.66 g (92%), mp 134–135°C (from
O,O-Dipropyl
[1-hydroxy-3-(dimethylamino)-
2,2-dimethylpropyl]thionophpsphonate (VII). This
compound was prepared from 5 g of dimethyl-
thiophosphorous acid VI and 3.54 g of 3-(dimethyl-
amino)-2,2-propanal IIa. Yield 6.75 g (79%), bp 95–
1
acetone). H NMR spectrum (acetonitrile-d3), δ, ppm:
7.58 s (5H, Ph), 4.65 s (1H, OH), 3.98 d (1H, JPH
96°C (0.07 mm Hg), nD20 1.4769. P NMR spectrum,
31
2
δP, ppm: 92. Found, %: N 4.75; P 10.25.
C13H32NO3PS. Calculated, %: N 4.50; P 9.97.
11.25 Hz, PCH), 3.6–3.85 m (10H, 2POCH3, CH2N,
NCH2Ph), 3.11 d (6H, JPH 3 Hz, NMe2), 1.3 s., 1.4 s
(6H, CMe2). P NMR spectrum, δP, ppm: 26. Found,
%: N 3.75, P 8.02. C16H29NO4PBr. Calculated, %: N
3.41, P 7.56.
2
31
O,O-Dimethyl {1-hydroxy-[4-(diphenylamino)-
phenyl]methyl}phosphonate (IX). This substance
was prepared from 12.05 g of dimethyl hydrogen
phosphite Ia and 16.32 g of 3-(dimethylamino)-
benzaldehyde in 45 ml of anhydrous benzene. Yield
20.14 g (71%), mp 105–106°C (from benzene). 31P
NMR spectrum δP, ppm: 28. Found, %: N 5.52, P
12.03. C11H18NO4P. Calculated, %: N 5.4, P 11.97.
ACKNOWLEDGMENTS
The work was carried out with the financial support
of Federal Target Program “Scientific and Scientifico-
Pedagogical Stuff of Innovational Russia in 2009–
2013 years” (state contract no. P-1108).
Synthesis of [3-hydroxy-2,2-dimethyl-3-(dieth-
oxyphosphoryl)propyl]trimethylammonium iodide
(VIIIc). To a solution of 7 g of O,O-diethyl [1-
hydroxy-3-(dimethylamino)-2,2-dimethylpropyl]phos-
phonate IIIc in 25 ml of anhydrous acetonitrile 4.43 g
of methyl iodide was added dropwise with stirring at
room temperature under the dry nitrogen flow. After
stirring for 8 h at room temperature and 3 h at 40°C the
volatile products were removed under a high vacuum.
The residue was washed with ether, and after several
days the crystalline product was formed. Yield 10.11 g
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