Synthesis of C-phosphorylated benzenesulfonyl-containing acetamidines

Article abstract of DOI:10.1134/S1070363214060139

Reactions of sodium derivatives of C-phosphorylated acetamidines with benzenesulfonyl chloride were studied. The reactions proceed selectively to form benzenesulfonyl-containing acetamidine derivatives. A convenient method for the synthesis of a new type of C-phosphorylated acetamidines was developed utilizing CH-acid properties.

Full text of DOI:10.1134/S1070363214060139

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 6, pp. 1130–1132. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.E. Shishkin, E.V. Mednikov, Yu.V. Popov, M.A. Shevchenko, O.V. Anishchenko, E.V. Gurba, 2014, published in Zhurnal Obshchei
Khimii, 2014, Vol. 84, No. 6, pp. 948–951.
Synthesis of C-Phosphorylated Benzenesulfonyl-containing
Acetamidines
V. E. Shishkin, E. V. Mednikov, Yu. V. Popov,
M. A. Shevchenko, O. V. Anishchenko, and E. V. Gurba
Volgograd State Technical University, pr. Lenina 28, Volgograd, 400131 Russia
e-mail: tons@vstu.ru
Received July 29, 2013
Abstract—Reactions of sodium derivatives of C-phosphorylated acetamidines with benzenesulfonyl chloride
were studied. The reactions proceed selectively to form benzenesulfonyl-containing acetamidine derivatives. A
convenient method for the synthesis of a new type of C-phosphorylated acetamidines was developed utilizing
CH-acid properties.
Keywords: CH-acids, organophosphorus compounds, C-phosphorylated amidines, benzenesulfonyl chloride
DOI: 10.1134/S1070363214060139
A large number of organophosphorus compounds
used as insecticides, plasticizers, and pharmaceuticals
are known [1]. Many scientists actively study the
relationship between biological activity and chemical
structure of organophosphorus compounds [2].
tives of C-phosphorylated acetamidines with benzene-
sulfonyl chloride.
Reaction of sodium derivatives of C-phos-
phorylated acetamidines with benzenesulfonyl chloride
resulted in benzenesulfonyl-substituted acetamidines
(Scheme 1).
In this work we continued research on acetamidine
reactions involving CH-acid properties of the activated
methylene group [3, 4]. Aiming to synthesize new
amidines exhibiting a high potential biological activity,
we performed benzenesulfonylation of sodium deriva-
Sodium derivatives of C-phosphorylated acetami-
dines were prepared according to [5]. Acetamidines
containing the least toxic butoxy and isopropoxy
groups at the phosphorus atom as well as a benzoyl-
Scheme 1.
O
O
O
NCR2
O
NCR2
(R1O)2PCHC
(R1O)2PCHNaC
+
C6H5SO2Cl
_NaCl
N(R3)2
N(R3)2
C6H5SO2
I_III
O
O
O
O
NCC6H5
NCC6H5
(R1O)2PCHC
(R1O)2PCHNaC
+
C6H5SO2Cl
_NaCl
N
O
N
O
C6H5SO2
IV, V
R1 = i-C3H7, C4H9; R2 = СН3, С6Н5; R3 = C2H5, C3H7, C4H9.
1130

1131
SYNTHESIS OF C-PHOSPHORYLATED BENZENESULFONYL-CONTAINING ACETAMIDINES
Table 1. Physicochemical properties of С-phosphorylated acetamidines I–V
MRD20
Found, %
Calculated, %
Comp.
no.
Yield,
%
R1
R2
R3
nD20
d420
Formula
found calculated
N
P
N
P
I
C4H9
С6Н5 C3H7
87
85
89
86
87
1.5216 1.1315 156.29 155.75 5.02 5.48 C29H43N2O6PS 4.84 5.35
1.5314 1.1914 155.90 155.54 4.93 5.59 C29H43N2O6PS 4.84 5.35
1.4835 1.1821 135.92 135.08 5.67 6.11 C24H41N2O6PS 5.42 6.21
1.5014 1.1761 136.19 136.86 5.34 5.98 C25H33N2O7PS 5.22 5.77
1.5023 1.1632 145.56 146.28 5.13 5.26 C27H37N2O7PS 4.96 5.49
II
III
IV
V
i-C3H7 С6Н5 C4H9
C4H9
i-C3H7
C4H9
СН3
–
C3H7
–
–
–
Table 2. The IR spectral parameters (ν, cm–1) of С-phosphorylated acetamidines I–V
C
Comp. no.
C=N
P=O
C=O
P–O–C
C
C–S
O=S=O
I
1664
1678
1664
1666
1675
1245
1234
1248
1243
1233
1735
1738
1736
1735
1744
982–1070
982–1060
980–1072
966–1054
975–1063
1600
748
745
746
754
750
1140
1142
1139
1145
1146
II
III
IV
V
1588
–
1614
1613
Table 3. Data on 1Н NMR spectra of С-phosphorylated acetamidines I–V
Comp.
δ, ppm (J, Hz)
no.
0.94 t (12Н, СН3, JHH 6), 1.38 m (12Н, СН2, JHH 6), 3.01 d (1Н, СНР, JHР 22), 3.28 t (4Н, NСН2, JHН 7), 3.50 m
(4Н, СН2ОР, JHН 6, JHР 9), 7.35 m (10Н, С6Н5, JHH 6)
I
0.93 t (6Н, СН3, JHH 6), 1.21 d (12Н, СН3, JHH 6), 1.35 m (8Н, СН2, JHH 6), 2.94 d (1Н, СНР, JHР 22), 3.11 t (4Н,
NСН2, JHH 7), 4.62 m (2Н, СНОР, JHН 6, JHР 9), 7.38 m (10Н, С6Н5, JHH 6)
II
0.91 t (12Н, СН3, JHH 6), 1.35 m (12Н, СН2, JHH 6), 2.15 s [3Н, СН3С(О)], 2.96 d (1Н, СНР, JHР 22), 3.62 t (4Н,
NСН2, JHР 7), 3.98 m (4Н, СН2ОР, JHН 6, JHР 9), 7.41 m (5Н, С6Н5, JHH 6)
III
IV
V
1.23 d (12Н, СН3, JHH 6), 2.95 d (1Н, СНР, JHH 22), 3.42 t (4Н, NСН2, JHH 7), 3.64 t (4Н, СН2О, JHH 6), 4.62 m
(2Н, СНОР, JHH 6, JHH 9), 7.63 m (10Н, С6Н5, JHH 6)
0.94 t (6Н, СН3, JHH 6), 1.33 m (8Н, СН2, JHH 6), 2.99 d (1Н, СНР, JHР 22), 3.44 t (4Н, NСН2, JHH 7), 3.67 t (4Н,
СН2О, JHH 6), 3.81 m (4Н, СН2ОР, JHН 6, JHР 9), 7.58 m (10Н, С6Н5, JHH 6)
substituted imino group were used as substrates. These
C-phosphorylated acetamidines are most promising for
the search of biologically active substances.
temperature was gradually raised to 50–60°C. In these
reactions the C-phosphorylated acetamidines differ
little from each other by reactivity.
Physicochemical properties of compounds I–V are
shown in Table 1.
Reaction of sodium derivatives of phosphorylated
acetamidines with benzenesulfonyl chloride proceeded
even at room temperature and at a molar reactant ratio
of 1 : 1.02. The reaction rate increased as the
The obtained compounds were purified by column
chromatography eluting with a mixture of chloroform–
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1132
SHISHKIN et al.
diethyl ether–hexane (1 : 3 : 1). The individuality of
the compounds obtained was monitored by thin-layer
chromatography using Silufol plates. The structure and
composition were confirmed by H NMR and IR
spectroscopy, elemental analysis, molecular refraction
and cryoscopy data.
pared similarly from (2 g, 0.0048 mol) N1,N1-dibutyl-
N2-benzoyl(diisopropoxyphosphoryl)acetamidine, 0.11 g
(0.0048 mol) of sodium, and 0.53 g (0.0052 mol) of
benzenesulfonyl chloride. The molar ratio of acet-
amidine–sodium–benzenesulfonyl chloride was 1 : 1 : 1.
Yield 1.6 g (85%).
1
The IR spectra of benzenesulfonyl derivatives of C-
phosphorylated acetamidines contained characteristic
absorption bands of the groups C=N (1664–1678 cm–1),
O=P (1234–1248 cm–1) R–O–C (982–1072 cm–1), С=О
(1735–1738 cm–1), С–СAr (1588–1600 cm–1), C–S
(745–750 cm–1), SO2 (1139–1145 cm–1).
N1,N1-Dipropyl-N2-acetyl-(2-benzenesulfonyl-2-
dibutoxyphosphoryl)acetamidine (III) was prepared
similarly from 1.60 g (0.0039 mol) N1,N1-dipropyl-N2-
acetyl(dibutoxyphosphoryl)acetamidine, 0.09
g
(0.0039 mol) of sodium, and 0.42 g (0.0039 mol) of
benzenesulfonyl chloride. The molar ratio of acet-
amidine–sodium–benzenesulfonyl chloride was 1 : 1 : 1.
Yield 1.6 g (89%).
N1-Morpholino-N2-benzoyl-(2-benzenesulfonyl-2-
diisopropoxyphosphoryl)acetamidine (IV) was
prepared similarly from 1.40 g (0.0037 mol) of N1-
morpholino-N2-benzoyl(diisopropoxyphosphoryl)acet-
amidine, 0.084 g (0.0037 mol) of sodium, and 0.42 g
(0.0038 mol) of benzenesulfonyl chloride. The molar
ratio of acetamidine–sodium–benzenesulfonyl chloride
was 1 : 1 : 1.02. Yield 1.5 g (86%).
1
In the H NMR spectra of the synthesized com-
pounds I–V there was a doublet of the methine PCH
group at 2.94–3.01 ppm indicating that the benzene-
sulfonylation occurred at the methylene group.
1
The IR and H NMR spectral data are given in
Tables 2 and 3.
In summary, we developed a convenient method of
the synthesis of new benzenesulfonyl derivatives of the
C-phosphorylated acetamidines.
N1-Morpholino-N2-benzoyl-(2-benzenesulfonyl-
2-dibutoxyphosphoryl)acetamidine (V) was prepared
similarly from 1.70 g (0.0043 mol) of N1-morpholino-
N2-benzoyl(dibutoxyphosphoryl)acetamidine, 0.099 g
(0.0043 mol) of sodium, and 0.48 g (0.0046 mol) of
benzenesulfonyl chloride. The molar ratio of acet-
amidine–sodium–benzenesulfonyl chloride was 1 : 1 : 1.02.
Yield 1.9 g (87%).
EXPERIMENTAL
N1,N1-Dipropyl-N2-benzoyl-(2-benzenesulfonyl-
2-dibutoxyphosphoryl)acetamidine (I). To a solution
of 1 g (0.0021 mol) of N1,N1-dipropyl-N2-benzoyl(dibut-
oxyphosphoryl)acetamidine in 4 mL of anhydrous
dioxane was added in small portions with stirring at
20–30°C 0.046 g (0.0021 mol) of sodium. The reaction
mixture was stirred until complete consumption of
sodium. To a solution of acetamidine sodium deri-
vative was added dropwise with stirring at 20–30°C
0.36 g (0.0021 mol) of benzenesulfonyl chloride in
2 mL of dioxane. The molar ratio of N1,N1-dipropyl-
N2-benzoyl(dibutoxyphosphoryl)acetamidine–sodium–
benzesulfonyl chloride was 1 : 1 : 1.01. The tem-
perature of the reaction mixture was raised to 55–60°C,
and the stirring was continued for 5 h. Then sodium
chloride was filtered off, and the solvent was removed
by distillation in a vacuum (15–20 mmHg). The
residue was evacuated at 50°C and 2–4 GPa for 1 h.
The target product was chromatographed on silica gel
eluting with chloroform–diethyl ether–hexane mixture
(1 : 3 : 1). Yield 87%, Rf 0.64.
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