Reaction of CH-acidic phosphorylated acetamidines with chlorotrimethylsilane

Article abstract of DOI:10.1134/S1070363212020090

A reaction of sodium derivatives of C-phosphorylated acetamidines with clorotrimethylsilane was investigated. The reaction proceeds selectively with the formation of the acetamidines silylated derivatives. Using the CH-acid properties of C-phosphorylated acetamidines a convenient method was developed for the synthesis of a new type of organophosphorus-silicon amidines. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212020090

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 217–219. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.E. Shishkin, E.V. Mednikov, M.A. Shevchenko, O.V. Anishchenko, Yu.V. Popov, E.V. Gurba, B.D. Emenka, 2012, published in
Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 2, pp. 221–223.
Reaction of CH-Acidic Phosphorylated Acetamidines
with Chlorotrimethylsilane
V. E. Shishkin, E. V. Mednikov, M. A. Shevchenko,
O. V. Anishchenko, Yu. V. Popov, E. V. Gurba, and B. D. Emenka
Volgograd State Technical University, pr. Lenina 28, Volgograd, 400131 Russia
e-mail: tons@vstu.ru
Received November 18, 2010
Abstract—A reaction of sodium derivatives of C-phosphorylated acetamidines with clorotrimethylsilane was
investigated. The reaction proceeds selectively with the formation of the acetamidines silylated derivatives.
Using the CH-acid properties of C-phosphorylated acetamidines a convenient method was developed for the
synthesis of a new type of organophosphorus-silicon amidines.
DOI: 10.1134/S1070363212020090
Organophosphorus amidines are of practical
interest due to the possibility of their use in various
branches of economics like agriculture and medicine
[1]. This work is a continuation of investigations of the
reactions of amidines based on the use of the CH-acid
properties of activated methylene group in these com-
pounds [2, 3]. In order to synthesize new structures of
amidines extending the range of application of these
compounds the silylation was carried out of the C-
phosphorylated acetamidine sodium derivatives with
chlorotrimethylsilane. These reactions are expressed
by the Eqs. (1) and (2).
The initial sodium derivatives were prepared by the
action of metallic sodium on the C-phosphorylated
acetamidines in the dioxane medium. Reaction (1) was
carried out at heating to 40–50°C with vigorous
stirring until complete conversion of sodium. Since the
yield of the sodium derivative is close to quantitative,
the second stage of the process, silylation [reaction
(2)], was carried out without isolation of the sodium
derivative. To the reaction mixture obtained was added
dropwise while stirring a calculated amount of
chlorotrimethylsilane in dioxane at 20–30°C. To com-
plete the silylation, the temperature was raised to 50°C
and the mixture was stirred for 3 h. The sodium : P-
phosphorylated acetamidine : chlorotrimethylsilane
molar ratio was 1:1:(1–1.1). To isolate the target
substance, the reaction mixture was cooled to a tem-
perature of 20–30°C, sodium chloride was filtered off,
and the solvent was removed by distillation in a
vacuum. The chemically pure target product was
obtained by purification by adsorption column
chromatography on silica gel of μLC 5/40 grade. The
composition and structure of the synthesized com-
pounds was established from elemental analysis,
O
NC(O)C6H5
(RO)2PCH2C
+ Na
NR12
O
NC(O)C6H5
NR12
(1)
(2)
(RO)2PCHNaC
−1/2 H2
O
NC(O)C6H5
+ (CH3)3SiCl
(RO)2PCHNaC
1
NR12
O
molecular refraction, H NMR and IR spectroscopy.
The yield of the reaction products was 82–87%.
NC(O)C6H5
NR12
Physicochemical properties of compounds IV are
listed in Table 1.
(RO)2PCHC
− NaCl
The synthesized compound are viscous pale-orange
liquids, readily soluble in organic solvents (dioxane,
acetone) and poorly soluble in water.
(CH3)3Si
R = i-C3H7, C4H9; R1 = C2H5, C3H7, C4H9.
217

218
SHISHKIN et al.
O
Physico-chemical properties of silylated acetamidines
NC(O)C6H5
(R1O)2PCHC
X
(CH3)3Si
MRD
calculated
Found, %
Calculated, %
Comp.
no.
Yield,
%
R1
X
nD20
d420
Formula
found
N
P
N
P
C4H9
N(C4H9)2
82
86
85
86
87
1.4775 1.0080 153.24
1.4517 1.0017 137.12
1.4881 1.0060 137.11
1.4685 1.0326 130.61
1.4965 1.0409 133.54
152.99
136.53
136.49
129.83
132.75
5.33
6.30
5.64
6.45
6.31
5.59 С28Н41N2О4PSi
7.19 С20Н43N2О4PSi
7.19 С23Н43N2О4PSi
6.38 С22Н39N2О4PSi
6.35 С28Н40N2О5PSi
5.19
6.17
5.81
6.39
5.75
6.83
6.43
7.08
I
i-C3H7 N(C3H7)2
C4H9 N(C2H5)2
II
III
IV
V
i-C3H7 N(C2H5)2
i-C3H7 N(CH2CH2)2O
6.19 6.864
We performed computer screening for biological
activity using PASS program of the Orekhovich
Institute of Biomedical Chemistry, Russian Academy
of Medical Sciences. According to the results obtained,
in the silylated acetamidines various types of activitiy
were revealed: antitumor, anti-inflammatory, fungicidal,
and a possibility of using them as a uterine relaxant.
N,N-dipropyl-N'-benzoyl(trimethylsilyl)(diisopro-
poxyphosphoryl)acetamidine (II) was synthesized
similarly from 2 g (0.0048 mol) of N,N-dipropyl-N'-
benzoyl(diisopropoxyphosphoryl)acetamidine, 0.11 g
(0.0048 mol) of sodium and 0.53 g (0.0052 mol) of
chlorotrimethylsilane. The molar ratio of N,N-di-
propyl-N'-benzoyl(diisopropoxyphosphoryl)acetami-
dine : sodium : chlorotrimethylsilane = 1: 1: 1.08.
1
EXPERIMENTAL
Yield 1.6 g (86%). H NMR spectrum (CCl4), δ, ppm:
0 s (9H, CH3Si), 0.94 d (12H, CH3), 1.3 m (6H, CH3),
1.1 m (4H, CH2), 2.77 d (1H, CHP ), 3.46 t (4H,
NCH2) 3.97 m (2H, CH2OR) 7.25 m (5H, C6H5). IR
spectrum, ν, cm–1: 784, 838–856 (C–Si); 964–1030
(POC), 1228 (P=O), 1600 (C—C); 1654 (C=N); 1720
(C=O).
N,N-Dibutyl-N'-benzoyl(trimethylsilyl)(dibutoxy-
phosphoryl)acetamidine (I). To a solution of 2 g
(0.0043 mol) of N,N-dibutyl-N'-benzoyl(dibutoxy-
phosphoryl)acetamidine in 4 ml of anhydrous dioxane
at 20–30°C was added in small portions while stirring
0.1 g (0.0043 mol) of sodium. The reaction mixture
was stirred until complete conversion of sodium. To
the solution of the resulting acetamidine sodium
derivative was added dropwise 0.34 g (0.0047 mol) of
chlorotrimethylsilane in 2 ml of dioxane at 20–30°C
while stirring. The molar ratio of N,N-dibutyl-N'-
benzoyl(dibutoxyphosphoryl)acetamidine : sodium :
chlorotrimethylsilane = 1: 1: 1.1. The temperature of
the reaction mixture was raised to 50°C and stirring
was continued for 3 h. Sodium chloride formed was
separated by filtration, the solvent was removed by
distillation in vacuo (at 15–20 hPa), and the residue
was evacuated for 1 h at 2–4 hPa at 50°C. Yield 1.9 g
(82%). The purification was performed by adsorption
column chromatography on silica gel of μLC 5/40
···
N,N-Diethyl-N'-benzoyl(trimethylsilyl)(dibutoxy-
phosphoryl)acetamidine (III) was synthesized
similarly from 1.60 g (0.0039 mol) of N,N-diethyl-N'-
benzoyl(dibutoxyphosphoryl)acetamidine, 0.09
g
(0.0039 mol) of sodium and 0.42 g (0.0039 mol) of
chlorotrimethylsilane. The molar ratio of N,N-diethyl-
N'-benzoyl(dibutoxyphosphoryl)acetamidine : sodium :
chlorotrimethylsilane = 1: 1: 1. Yield 1.6 g (85%).
1H NMR spectrum (CCl4), δ, ppm: 0 s (9H, CH3Si),
1.4 t (12H, CH3), 1.37 m (8H, CH2), 2.77 d (1H, CHP)
3.55 q (4H, NCH2 ), 3.89 m (4H, CH2OR) 7.33 m (5H,
C6H5). IR spectrum, ν, cm–1: 784, 832–844 (C–Si);
···
1030–1066 (POC), 1233 (P=O), 1590 (C—C); 1654
(C=N); 1720 (C=O).
1
grade. H NMR spectrum (CCl4), δ, ppm: 0 s (9H,
CH3Si) 0.75 m (12H, CH3), 1.21 m (16H, CH2), 2.77 d
(1H, CHP) to 3.47 (4H, NCH2 ), 3.68 m (4H, CH2O),
7.18 m (5H, C6H5). IR spectrum, ν, cm–1: 748, 856–892
(C–Si); 982–1066 (POC), 1222 (P=O), 1610 (C—C);
1654 (C=N); 1720 (C=O).
N,N-Diethyl-N'-benzoyl(trimethylsilyl)(diisopro-
poxyphosphoryl)acetamidine (IV) was synthesized
similarly from 1.40 g (0.0037 mol) of N,N-diethyl-N'-
benzoyl(diizopropoxyphosphoryl)acetamidine, 0.084 g
(0.0037 mol) of sodium and 0.42 g (0.0038 mol) of
···
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012

REACTION OF CH-ACIDIC PHOSPHORYLATED ACETAMIDINES
219
chlorotrimethylsilane. The molar ratio N,N-diethyl-N'-
benzoyl(diizopropoxyphosphoryl)acetamidine : sodium :
chlorotrimethylsilane=1: 1: 1.05. Yield 1.5 g (86%).
1H NMR spectrum (CCl4), δ, ppm: 0 s (9H, CH3Si),
0.93 d (12H, CH3), 5.1 t (6H, CH3), 1.27 m (16N,
CH2), 2.77 d (1H, CHP ) 3.23 q (4H, NCH2) 4.65 m
(2H, CHOP) 7.30 m (5H, C6H5). IR spectrum, ν, cm–1:
790, 820–838 (C–Si); 988–1030 (POC), 1228 (P=O),
amidine : sodium : chlorotrimethylsilane=1: 1: 1.07.
Yield 1.9 g (87%). H NMR spectrum (CCl4), δ, ppm:
1
0 s (9H, CH3Si) 1.07 d (12H, CH3), 2.73 d (1H, CHP),
3.23 t (4H, NCH2) 3.57 t (4H, CH2O ), 4.67 m (2H,
POCNO) 7.29 m (5H, C6H5); IR spectrum, ν, cm–1:
760, 838–856 (C–Si); 980–1030 (POC), 1230 (P=O),
···
1666 (C=N); 1720 (C=O), 1594 (C—C).
···
REFERENCES
1654 (C=N); 1720 (C=O), 1594 (C—C).
N-Morpholino-N'-benzoyl(trimethylsilyl)(diiso-
propoxyphosphoryl)acetamidine (V) was synt-
hesized similarly from 1.70 g (0.0043 mol) of N-mor-
pholino-N'-benzoyl(diisopropoxyphosphoryl)acetami-
dine, 0.099 g (0.0043 mol) of sodium and 0.48 g
(0.0046 mol) of chlorotrimethylsilane. The molar ratio
N,N-diethyl-N'-benzoyl(diizopropoxyphosphoryl)acet-
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p. 645.
2. Popov, Yu.V., Mednikov, E.V., Anishchenko, O.V. et al.,
RF Patent no. 2334753, Byul. Izobret., 2008, no. 3.
3. Shishkin, V.E., Mednikov, E.V, Shevchenko, M.A.,
et al., Zh. Obshch. Khim., 2010, vol. 80, no. 1, p. 64.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012