Synthesis and Antimicrobial Activity of New Dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenylethenyl)pentylphosphonium Salts

Article abstract of DOI:10.1134/S1070363218090062

New dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenylethenyl)pentylphosphonium salts bearing various substituents at the phosphorus atom were synthesized. Antimicrobial activity of the salts obtained was estimated. Derivatives with 2-methoxyphenyl substituents at the phosphorus atom are most active against grampositive bacteria. Herewith, dibenzyl-substituted phosphonium derivatives possess the best antifungal activity.

Full text of DOI:10.1134/S1070363218090062

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 9, pp. 1800–1805. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © D.A. Tatarinov, N.V. Terekhova, A.D. Voloshina, A.S. Sapunova, A.P. Lyubina, V.F. Mironov, 2018, published in Zhurnal Obshchei
Khimii, 2018, Vol. 88, No. 9, pp. 1453–1459.
Dedicated to the 110th anniversary of M.I. Kabachnik’s birth
Synthesis and Antimicrobial Activity
of New Dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-
2
-(phenylethenyl)pentylphosphonium Salts
a,b
a,b
a
D. A. Tatarinov *, N. V. Terekhova , A. D. Voloshina ,
a
a,b
a,b
A. S. Sapunova , A. P. Lyubina , and V. F. Mironov
a
Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
*
e-mail: datint@iopc.ru
b
Kazan (Volga Region) Federal University, Kazan, Tatarstan, Russia
Received June 28, 2018
Abstract―New dialkyl(diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenylethenyl)pentylphosphonium salts bearing
various substituents at the phosphorus atom were synthesized. Antimicrobial activity of the salts obtained was
estimated. Derivatives with 2-methoxyphenyl substituents at the phosphorus atom are most active against gram-
positive bacteria. Herewith, dibenzyl-substituted phosphonium derivatives possess the best antifungal activity.
Keywords: phosphonium salts, antimicrobial activity, antifungal activity
DOI: 10.1134/S1070363218090062
The search for new antimicrobial agents is one of
the urgent tasks of modern medicine and chemistry.
The emergence of new antibiotic-resistant bacteria,
and especially hospital strains, is a serious threat to
human health due to the slow process of replacement
of medications that have lost their efficacy. One of the
classes of antimicrobial agents, to which the
development of resistance in microorganisms is
complicated, is cationic surfactants [1–3].
negatively charged cell membrane [10, 11]. The
antimicrobial properties of biocides based on cationic
surfactants, including quaternary ammonium and
phosphonium salts, depend on the number and length
of the hydrocarbon chain of aliphatic substituents
[12–14]. Phosphonium salts show a higher activity
than ammonium analogs [14, 15].
Previously, we report a new method for obtaining
phosphonium salts based on the reactions of cyclic
quasiphosphonium salts with organomagnesium
compounds [16]; the resulting phosphonium salts
exhibited high antimicrobial activity.
In recent years there is an increasing interest in the
class of cationic surfactants like phosphonium salts
due to their pronounced antimicrobial effect [4, 5] and
anti-tumor activity [6–8], often due to their ability to
selectively permeate and accumulate in mitochondria
owing to the difference in the negative membrane
potential of healthy and tumor cells [9]. The latter
circumstance, as well as high selectivity, sometimes
reaching a difference of a thousand times, promote the
interest in phosphonium salts [9].
The aim of this work was to synthesize new dialkyl
(
diaryl)-2-(5-chloro-2-hydroxyphenyl)-2-(phenyl-
ethenyl)pentylphosphonium salts with various sub-
stituents at the phosphorus atom and evaluate their
antimicrobial activity.
The starting compounds were synthesized accord-
ing to the previously described two-step procedure.
The first step involves the reaction of trichlorobenzo-
phosphole 1 [17] obtained from pyrocatechin and
One of the key stages in the interaction of a
bactericide with a pathogen is its adsorption on a
1
800

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
1801
Scheme 1.
(
1) 2RMgBr, THF
O
OH
O
O
O
Cl
P Cl
Cl
Ph
O
P
P
(2) H O, HCl
2
R
R
Cl
CH Cl ,
2
2
Cl
97%
Cl
Ph
Ph
_
1
2
3а 3c
6 4
R = Me (а), Bn (b), 2-MeOC H (c).
phosphorus pentachloride with phenylacetylene and
leads to benzo[e]-1,2-oxaphosphorine 2 [18] (Scheme 1).
The second step include the reaction of compound 2
with the corresponding Grignard reagents to form
δ-hydroxyalkenylphosphine oxides 3, which are the
starting compounds for the subsequent obtaining of
phosphonium salts [19, 20].
changed. Thus, the initial dialkyl derivatives of
phosphine oxides are characterized by the signals with
δ 33 (3a) and 29 ppm (3b), and for diarylphosphine
P
3
1
oxide 3c δ is 23 ppm. In the P NMR spectra of the
P
intermediate dialkyl quasiphosphonium salts 5a and 5b
there are the signals in the range of 80–86 ppm,
whereas in the case of compound 5c the phosphorus
atom resonates at 54 ppm. For the target salts 4, the
chemical shift of the phosphorus nucleus is equal to
The resulting phosphine oxides 3a–3c reacted with
thionyl chloride to give the quasiphosphonium salts
1
~20 (4a, 4b) and 14.5 ppm (4c). In the H NMR
5
a–5c [21], which were isolated in a quantitative yield
spectra of the alkyl-substituted phosphonium salts the
signals of alkyl substituents appear in the upfield
(
99%) by removal of the volatile components [excess
of thionyl chloride, hydrogen chloride, and sulfur
oxide(IV)] in a vacuum. Further reaction of com-
pounds 5 with the corresponding Grignard reagents in
tetrahydrofuran led to the formation of phosphonium
salts 4a–4c with high yield (Scheme 2).
region. Thus, methyl protons resonate as triplets at
3
0.8 ppm ( J = 6.9–7.2 Hz). The signals of methylene
НН
groups are observed as ABMX-systems. In phos-
phonium salts 4, the protons of 2-(5-chloro-2-hyd-
roxyphenyl)-2-phenylethenyl substituent are charac-
teristic. Thus, in the most upfield aromatic region, the
2
In the course of the transformations described
proton H of the ethenyl fragment resonates as a
2
above the δ values of compounds present significantly
doublet (δ = 6.3–6.7 ppm, J = 15–19 Hz). The
P
PH
Scheme 2.
R1
O
O
R
R
OMgX
+
P
R
R
R
−
Cl
b
P
c
a
+
−
3
P
R X
R1
Cl
Cl
Cl
Ph
Ph
Ph
5
6
7
7
7
a
OH
6
5
R
R
1
d
+
P
−
3
Cl
15
Cl
3a
8
4
3
2
14
1
2
16
9
11
10
4
H CO
18
3
1
9
20
19
1
7
17 18
17
a, SOCl ; b, C H MgBr, THF; c, MgXCl; d, H O, HCl; R = Me (а), H C
2
1
(b),
20
(c).
2
5
11
2
2
2
2
21
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1
802
TATARINOV et al.
Antimicrobial activity of phosphonium salts 8a–8c
Trichophyton
mentagrophytes
Staphylococcus aureus
Bacillus сereus
Candida albicans
Compound
MIC,
MBC,
MIC,
MBC,
MIC,
MFC,
MIC,
MFC,
μg/mL
μg/mL
μg/mL
μg/mL
μg/mL
μg/mL
μg/mL
μg/mL
а
8
8
8
а
b
c
25±10
07.8±0.7
03.9±0.2
125±11
125±11
125±12
125±13
–
–
–
–
–
–
15.6±1.3 31.3±2.6
62.5±5.7
250±20
15.6±1.4
125±11
31.3±2.6
250±22
07.8±0.6 31.3±2.7 31.3±2.8
62.5±5.6
Chloramphenicol 62.5±5.4
Norfloxacin
7.5±0.7
7.5±0.6
24.4±1.9 48.8±4.3
Ketoconazole
07.3±0.7
7.3±0.7
07.3±0.6
07.3±0.6
а
MIC > 500 μg/mL.
7
proton H of the hydroxyphenyl substituent appears as a
robial activity increases with the length of the alkyl
substituent at the phosphorus atom. The most active
compounds were those containing pentyl and hexyl
substituents [16]. In order to evaluate the effect of the
replacement of the phenyl group at the phosphorus
atom in the phosphonium salt with the short-chain
alkyl, alkylaryl benzyl or substituted aryl substituent
and to search for new promising series of antimicrobial
agents, the salts 4a–4c were investigated for antimic-
robial activity against a number of bacteria and fungi
strains. As a reference, chloramphenicol, norfloxacin
and ketoconazole were used. The obtained results are
presented in the table.
3
doublet (δ = 7.1–7.7 ppm, J = 8.8 Hz), whereas the
НН
4
proton H resonates as a doublet (δ = 6.4–6.9 ppm,
4
6
JНН = 2.6 Hz). The proton H participates in the spin-
spin coupling with the protons H and H , appearing as
a doublet of doublets (δ = 6.7–7.7 ppm, J = 8.8,
JНН = 2.6 Hz). The methylene protons of the benzyl
moiety of the phosphonium salt 4b are magnetically
nonequivalent and appear in the H NMR spectrum as
an ABX-system. At the same time, the multiplet is
simplified to six lines due to the closeness of the
values of the spin-spin coupling constants ( JPHА = 14.8,
7
4
3
НН
4
1
2
2
2
JPHB = 14.8, J А B = 14.8 Hz). The signals of the
H
H
remaining protons were assigned on the basis of their
multiplicity and integral intensity.
Among the compounds studied 4c was the most
active salt, which showed a high activity against
Staphylococcus aureus, analogous to the previously
described pentyldiphenyl derivative [16]; it was also
inactive for Trichophyton mentagrophytes and Candida
albicans fungi strains. At the same time, compound
1
3
1
In the C{ H} NMR spectra of phosphonium salts
4
a–4c, the carbon atoms coupled with phosphorus
1
2–14
nucleus appear as doublets. The carbon atoms C
appear in the upfield region as doublets, which in the
1
3
4
b, which is also active against gram-positive bacteria,
C NMR spectrum acquire an additional multiplet.
2
13
showed good antifungal activity.
The C atom resonates in the C NMR spectrum at
~
1
1
105 ppm as a doublet of doublets ( J = ~160, J
=
HC
PC
In summary, in the series of new 2-(5-chloro-2-
hydroxyphenyl)-2-(phenylethenyl)phosphonium salts,
the derivatives with benzyl and 2-methoxyphenyl
substituents at the phosphorus atom are promising for
further studies. Alkyldibenzyl derivatives would show
good antifungal activity when increasing the alkyl
substituent chain.
8
1–94 Hz). The configuration of the double bond of
the ethenyl fragment was determined from the values
3
3a
8
of the vicinal constants J = for C and C atoms that
PC
3
are in the cis- and trans-positions, respectively ( J
=
PC
6
–7 and 16–17 Hz for cis- and trans-orientation,
respectively), which unambiguously indicates Z-con-
figuration of the double bond.
EXPERIMENTAL
Previously it has been shown that in the series of
alkyl-(Z)-[2-(5-chloro-2-hydroxyphenyl)-2-phenyl-
ethenyl]diphenylphosphonium chlorides the antimic-
1
31
1
H and P{ H} NMR spectra were recorded on a
1
31
Bruker Avance-400 spectrometer [400 ( H), 161.0 ( P
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
1803
1
13
{
H}), 100.6 MHz ( C)] from CDCl or DMSO-d
General procedure for the synthesis of 2,2-di-
alkyl(diaryl)-6-chloro-4-phenyl-benzo[e]-1,2-oxa-
phosphorine-2-onium chlorides (5a–5c) [16]. Thionyl
chloride (0.05 mL, 0.089 g, 0.75 mmol) was added
with stirring to a solution of 0.5 mmol of phosphine
oxide 3 in 2 mL of CH Cl under argon. The reaction
mixture was stirred for 15 min, after which the volatile
components were removed in a vacuum (80°C,
20 mmHg).
3
6
solution measuring the chemical shifts with respect to
the residual solvent signals. IR spectra were taken on a
Bruker Vector-22 instrument from suspensions in
mineral oil or thin film. Mass spectra (MALDI) were
obtained on an Ultra Flex III TOF/TOF mass spec-
trometer (Bruker Daltonik GmbH, Germany) in the
mode of positively charged ions registration. 2,5-
Dihydroxybenzoic acid was used as the matrix.
2
2
Gram-positive bacteria (Staphylococcus aureus
ATCC 209p, Bacillus cereus ATCC 8035) gram-negative
bacteria (Escherichia coli CDC F-50, Pseudomonas
aeruginosa ATCC 9027), and fungi (Aspergillus niger
BKMF-1119, Trichophyton mentagrophytes var.
gypseum 1773, Candida albicans 855-653) were used
as test objects. As a reference drug for studying
antibacterial activity chloramphenicol and norfloxacin
were used. Ketoconazole was used as the reference
drug for the study of antifungal activity.
6-Chloro-2,2-dimethyl-4-phenylbenzo[e]-1,2-oxa-
phosphorine-2-onium chloride (5a). Yield 0.162 g
3
1
1
(99%), oil. P{ H} NMR spectrum (CDCl ): δ
3 P
86.4 ppm. The main characteristics coincide with those
previously described [16].
6
-Chloro-2,2-dibenzyl-4-phenylbenzo[e]-1,2-oxa-
phosphorine-2-onium chloride (5b). Yield 0.238 g
1
(
99%), cream powder. H NMR spectrum (CDCl ), δ,
3
15–17
ppm (J, Hz): 7.49–7.28 m (10H, Н
), 7.23–7.19 m
10–12
8 3
(
5H, Н
), 7.17 d (1H, Н , J = 8.8), 7.13 d.d (1Н,
НН
7
3
4
3
2
Н , J = 7.2, J = 2.2), 6.87 d (1Н, Н , J =
Bacteriostatic and fungistatic properties were
studied by the method of serial dilutions in liquid
nutrient media by procedures described in [22, 23],
determining MIC, which inhibit the growth and
production of the test microorganism.
НН
НН
PH
5
4
3
0.5), 6.79 d (1Н, Н , J = 2.5), 4.81–4.70 m (4H,
НН
1
3
31
1
Н ). P{ H} NMR spectrum (CDCl ): δ 80.5 ppm.
3
P
6
-Chloro-2,2-di-(2-methoxyphenyl)-4-phenyl-
benzo[e]-1,2-oxaphosphorine-2-onium chloride (5c).
1
Yield 0.254 g (99%), colorless crystals. H NMR spec-
The bactericidal (MBC) and fungicidal activity
1
6 3
trum (CDCl ), δ, ppm (J, Hz): 7.86 d.d (2Н, Н , J
=
=
(
MFC), causing complete death of the pathogen was
3
НН
3
18
3
3
7
7
.6, J = 7.7), 7.66 d.d (2Н, Н , J = 15.7, J
determined according to the previously described
procedure [24].
НН РH
НН
1
0–11
.4), 7.60–7.42 m (4H, Н
,), 7.35–7.20 m (4H,
), 7.27 d (1H, Н , J = 8.0), 6.59 d (1Н, Н ,
JPH = 29.9), 5.67 br.d (2Н, Н , J = 7.2,), 3.86 s
6Н, Н ). P{ H} NMR spectrum (CDCl ): δ 54.2 ppm.
1
5,17
8
3
3
Н
НН
2
5,7 3
Compounds 3a–3c were prepared according to the
procedure reported in [19, 20].
НН
19
31
1
(
3 P
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
General procedure for the synthesis of (Z)-diaryl-
dialkyl)-[2-(5-chloro-2-hydroxyphenyl)-2-phenyl-
ethenyl]pentylphosphonium chlorides (4a–4c). The
appropriate bromo derivative (1.0 mmol) was added to
ethenyl]dimethylphosphine oxide (3a). Yield 0.941 g
96%), pale yellow powder, mp 172–175 C. P{ H}
NMR spectrum (DMSO-d ): δ 32.7 ppm. The main
(
○
31
1
(
6
P
characteristics coincide with those previously
described [19].
2
6 mg (1.2 mmol) of magnesium turnings in 2 mL of
THF under argon. The reaction mixture was stirred for
0 min while boiling THF. The Grignard reagent
1
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
prepared in this way was added to a solution of
0.5 mmol of compound 5 in THF under argon
atmosphere with stirring. The reaction mixture was
stirred at room temperature for 30 min, then
hydrolyzed with a solution of 0.1 mL of hydrochloric
acid in 10 mL of water. The aqueous layer was
separated and extracted with CH Cl (3×10 mL). The
ethenyl]dibenzylphosphine oxide (3b). Yield 1.327 g
○
31
1
(
90.5%), white powder, mp 210–211 C. P{ H} NMR
spectrum (DMSO-d ): δ 29.1 ppm. The main charac-
6
P
teristics coincide with the previously described [20].
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
ethenyl]di-(2-methoxyphenyl)phosphine oxide (3c).
2
2
○
Yield 1.365 g (87%), white powder, mp 172–175 C.
organic layer was dried with Na SO , the solvent was
2 4
3
1
1
P{ H} NMR spectrum (DMSO-d ): δ 22.7 ppm. The
removed (12 mmHg, 60°C). The residue was separated
by flash chromatography on a dry column using ethyl
acetate as an eluent for weakly polar impurities,
6
P
main characteristics coincide with those previously
described [19].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1
804
TATARINOV et al.
3
7a
followed by elution of the reaction products with ethyl
alcohol. The alcohol fraction was concentrated
Hz): 161.1 m (br.s) (C ), 155.2 br.m (br.s) (C ), 139.2
8
3
11 1
m (d) (C , J = 17.3), 130.6 d.t (c) (C , J = 162.8,
PC
HC
3
6
1
2
(
1
50 mmHg, 60°C), then dried in vacuum (5×
0 mmHg, 80°C).
JHC = 7.0), 130.4 d.d (s) (C , J = 165.5, J = 6.0),
HC HC
–2
19
1
3
130.2 br.d. (d) (C , J = 160.2, J = 5.5), 129.1
HC PC
1
8
1
2
br.d (d) (C , J = 160.8, J = 8.0), 129.1 br.d (d)
HC
PC
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
2
0 1
4
21
(
C , J = 160.8, J = 2.6), 128.7 br.d.d (s) (C ,
HC PC
ethenyl]dimethylpentylphosphonium chloride (4a).
Yield 0.375 g (94%), pale brown powder, mp 161–
1
2
4 1
JHC = 162.2, J = 7.3), 128.6 br.d.d (d) (C , J
165.0, JHC = 5.6, JPC = 1.3), 128.1 d.d (d) (C , JHC
=
=
HC
HC
2
4
9 1
–
1
1
2
1
64°C. IR spectrum (KBr), ν, cm : 3392, 2959, 2930,
872, 2705, 2572, 1610, 1567, 1494, 1448, 1409,
279, 1255, 1218, 1156, 1112, 1059, 1030, 970, 926,
74, 824, 771, 691, 671, 644, 618, 578, 532, 486, 469.
4
10 1
1
1
62.3, J = 3.4), 127.3 br.d.m (s) (C , J = 160.1),
PC HC
3
a
3
5 3
25.1 m (d) (C , J = 5.8), 121.3 br.d (s) (C , J
=
PC
7
HC
1
2
1
0.7), 118.0 d (s) (C , J = 162.4), 106.4 d.d (d) (C ,
HC
8
1
1
14 1
1
JHC = 160.5, JPC = 81.5), 32.2 br.t.m (d) (C , JHC =
126.6, JPC = 16.6), 28.1 br.t.d (d) (С , JHC = 133.5,
H NMR spectrum (CDCl ), δ, ppm (J, Hz): 7.52 d
3
3
17 1
7
3
10,11
(
1Н, H , J = 8.8), 7.44–7.28 m (3Н, H ), 7.28–
НН
1
15
1
4
9
6
3
4
JPC = 47.4), 20.9 t.m (d) (C , JHC = 125.4, JPC =
7
2
1
1
.13 m (2Н, H ), 7.23 d.d (1Н, H , J = 8.8, J
=
=
НН
НН
13
1
2
4
4
2 2
0.7), 20.0 br.t (d) (C , JHC = 126.4, JPC = 4.2), 18.1
.6), 6.85 d (1H, H , J = 2.6), 6.72 d (1Н, H , J
7.9), 2.16 m (2Н, Н ), 1.79 d (6Н, H , J = 13.8),
), 0.86 t (3Н, Н , J = 6.9).
C NMR spectrum ( C{ H}) (CF COOH + 20%
CDCl ), δ , ppm (J, Hz): 164.0 m (br.s) (C ), 151.8 t.m
d) (C , J = 9.0, J = 1.0), 137.8 m (d) (C , J
НН
PH
12
1
1
1
2
17
2
br.t.d (d) (С , JHC = 128.9, JPC = 47.9),13.4 q.t (s)
PH
16
1
2
31
1
1
3–15
16
2
(C Н
spectrum (CDCl
(MALDI), m/z: 513.2 [М] .
3
, JHC = 124.6, JHC = 3.4). P{ H} NMR
.44–1.21 m (6Н, Н
НН
1
3
13
1
3
): δ 2+0.82 ppm. Mass spectrum
Р
3
3
3
7
С
a
3
4
8 3
(
1
1
=
HC
PC
PC
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
ethenyl]di-(2-methoxyphenyl)pentylphosphonium
chloride (4c). Yield 0.215 g (74%), white powder, mp
53–156 С. IR spectrum (KBr), ν, cm : 3395, 3060,
955, 2932, 2870, 2699, 2563, 1590, 1576, 1479, 1464,
433, 1407, 1283, 1252, 1215, 1182, 1167, 1141, 1111,
086, 1043, 1014, 944, 884, 824, 800, 757, 695, 633,
80, 543, 504. H NMR spectrum (CDCl ), δ, ppm (J,
6
1
2
6.5), 132.6 d.d (s) (C , J = 167.7, J = 5.7),
HC HC
1
1
1
2
3
32.5 d.t.m (s) (C , J = 163.3, J = 5.5, J =
HC
1.5), 130.2 m (d) (C , J = 1.5), 129.6 d.d (s) (C ,
JHC = 163.0, J = 7.2), 127.8 br.d.m (s) (C , J
60.2), 127.2 d.m (s) (C , J = 9.6), 125.4 m (d) (C ,
= 7.1), 118.7 d (s) (C , J = 162.8), 105.9 d.d (d)
HC
C , J = 160.0, J = 88.2), 32.8 t.m (d) (C , J =
HC
4
HC
4
10
1
○
–1
PC
1
2
1
1
5
1
3
9 1
=
HC
HC
5
3
3a
1
HC
3
7 1
J
PC
2
1
1
14 1
(
1
HC
PC
HC
3
12
1
3
1
26.3, J = 15.8), 25.3 t.d.m (d) (С , J = 132.8,
20
3
PC
HC
Hz): 9.90 s (1Н, ОН), 7.54 d.d (2Н, Н , J = 7.9,
1
15
1
НН
JPC = 53.2), 22.1 t.m (s) (C , J = 126.0), 21.8
3
22
3
3
HC
JНН = 7.8), 7.37 d.d (2Н, Н , J = 7.7, J 14.6),
1
3
1
2
НН
РН
br.t.m (d) (C , J = 126.5, J = 4.5), 13.1 q. m (s)
9–11
7 3
HC
PC
17
7
7
6
.32–7.23 m (5Н, H ), 7.09 d (1Н, H , J = 8.8),
16
1
1
1
НН
(
5
C , J = 125.0), 8.9 q.d (d) (C , J = 135.8, J
=
21
3
3
4
HC
HC
PC
.15 t.d (2Н, H , J = 7.8, J = 7.8, J = 2.6),
31
1
НН
НН
НН
7.3). P{ H} NMR spectrum (CDCl ): δ 20.6 ppm.
Mass spectrum (MALDI), m/z: 361.2 [М] .
6
3
4
3
Р
.65 d.d (1Н, H , J = 8.8, J = 2.6), 6.56 d (1Н,
+
НН
НН
4
2
2
4
H , J = 18.6), 6.38 d (1H, H , J = 2.6), 3.70 s
(6Н, ОСН ), 2.87–2.75 m (2Н, Н , JPH = 14.7), 1.39–
PH
НН
1
2 2
(
Z)-[2-(5-Chloro-2-hydroxyphenyl)-2-phenyl-
3
1
3–15
3
13
ethenyl]dibenzylpentylphosphonium chloride (4b).
Yield 0.236 g (86%), pale cream powder, mp 249–
1.06 m (6Н, Н
), 0.73 t (3Н, СН , JНН = 7.3). C
3
1
3
1
NMR spectrum ( C{ H}) (CDCl ), δ , ppm (J, Hz):
3
С
○
–1
3
2
18 2
2
2
1
1
51 С. IR spectrum (KBr), ν, cm : 3651, 3060, 3031,
956, 2928, 2872, 2691, 2555, 1961, 1892, 1814,
602, 1587, 1568, 1495, 1467, 1455, 1406, 1353,
279, 1233, 1215, 1155, 1112, 1073, 1030, 1001, 947,
20, 872, 850, 825, 766, 727, 700, 633, 569, 531, 482.
161.3 m (d) (C , J = 1.7), 160.9 m (d) (С , J
2.3), 153.7 br.t.m (d) (C , J = ~9.2, J = 1.4, J
1.3, J = 1.3), 140.0 d.d (d) (C , J = 6.6, J
17.3), 136.6 br.d.d.m (d) (C , J = 161.8, J = 8.4,
=
=
=
PC
PC
HC
PC
7a 2
3
3
HC
HC
4
8
2
3
PC
HC
2
0
1
3
HC
22 1
HC
4
2
9
JPC = 2.2), 134.4 d.t.d (d) (С , J = 163.6, J
=
=
HC
HC
1
3
2
11 1
H NMR spectrum (CDCl ), δ, ppm (J, Hz): 10.39 s
1Н, ОН), 7.71 d (1Н, H , J = 8.8), 7.39–7.24 m
8.4, J = 2.4, J = 7.8), 130.3 d.m (s) (C , J
3
HC PC HC
7
4
6
1
2
(
(
160.2), 130.1 d.d (s) (C , J = 164.9, J = 6.1),
128.6 d.d (s) (C , J = 152.8, J = 8.6), 128.1 m
HC HC
НН
HC HC
9
–11
19–21
10
1
2
5Н, H ), 7.24–7.20 m (10Н, H
), 7.20 d.d (1Н,
6
3
4
4
4
4
4
9 1
H , J = 8.8, J = 2.6), 6.48 d (1H, H , J = 2.6),
(d) (C , J = 1.4), 127.6 d.t.m (s) (C , J = 160.0,
НН
НН
НН
17
PC HC
2
2
2
2
3a 3
6
1
1
0
.31 d (1Н, H , J = 15.2), 4.00 t (2Н, Н , J
4.8, J = 14.8), 3.94 t (2Н, Н , J = 14.8, J
4.8), 1.87–1.74 m (2Н, Н ), 1.18–0.98 m (4Н, Н
.98–0.88 m (2Н, H ), 0.73 t (3Н, СН , J = 7.2).
=
=
),
JHC = 6.2), 123.7 d.m (d) (C , J = 6.8), 122.3 d.t
PC
PH
HH
2
17’
2
2
5
3
2
21
(s) (C , J = 11.4, J = 4.0), 122.0 d.d.d (d) (C ,
PH
НН
PH
13–14
HC
HC
1
2
1
1
2
3
7
JHC = 165.6, J = 7.1, J = 12.6), 118.0 d (s) (C ,
HC PC
1
5
3
19
1
2
JHC = 164.4), 111.8 d.d.d (d) (C , J = 160.7, J
=
3
НН
HC
HC
1
3
13
1
3
17 1
C NMR spectrum ( C{ H}) (DMSO-d ), δ , ppm (J,
7.2, J = 6.7), 105.4 d.m (d) (C , J = 92.3), 104.5
6
С
PC PC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
1805
2
1
1
d.d (d) (C , J = 160.7, J = 93.7), 56.0 q (s) (OCH ,
Kalyanaraman, B., Chem. Rev., 2017, vol. 117, no. 15,
p. 10043. doi10.1021/acs.chemrev.7b00042
0. Franklin, T.J. and Snow, G.A., Biochemistry of
Antimicrobial Action, Dordrecht: Springer, 1989,
p. 216. doi 10.1007/978-94-009-0825-3
HC
PC
3
1
14
1
3
JHC = 146.1), 32.4 t.m (d) (C , J = 125.8, J
6.5), 22.4 t.d.m (d) (С , J = 129.9, J = 4.4),
2.3 t.m (d) (C , J = 125.7, J = 55.3), 21.7
br.t.m (d) (C , J = 125.5, J = 0.6), 13.4 q.t (d)
=
HC
PC
1
3
1
2
1
1
2
HC PC
1
2
1
1
HC
PC
1
5
1
4
HC
PC
5
1
2
31
1
11. Hill, E.H., Whitten, D.G., and Evans, D.G., J. Phys.
Chem. (B), 2014, vol. 118, no. 32, p. 9722. doi
(
CН , J = 124.9, J = 3.9, J = 1.5). P{ H}
3 HC HC PC
NMR spectrum (CDCl ): δ 14.5 ppm. Mass spectrum
MALDI), m/z: 545.3 [М] .
3
Р
1
0.1007/978-94-009-0825-3
+
(
1
2. Kanazawa, A., Ikeda, T., and Endo, T., Antimicrob.
Agents Chemother., 1994, vol. 38, no. 5, p. 945. doi
ACKNOWLEDGMENTS
1
0.1128/AAC.38.5.945
This work was supported by the Russian Science
Foundation (grant no. 14-50-00014).
13. Lukáč, M., Devínsky, F., Pisárčik, M., Papapetropoulou, A.,
Bukovský, M., and Horváth, B., J. Surfactants Deterg.,
2
017, vol. 20, no. 1, p. 159. doi 10.1007/s11743-016-
CONFLICT OF INTERESTS
1908-6
1
1
4. Kanazawa, A. and Ikeda, T., Coord. Chem. Rev., 2000,
vol. 198, no. 1, p. 117. doi 10.1016/S0010-8545(99)
No conflict of interests was declared by the authors.
REFERENCES
0
0224-6
5. Zhu, D., Cheng, H., Li, J., Zhang, W., Shen, Y., Chen, S.,
Ge, Z., and Chen, S., Mater. Sci. Eng. (C), 2016,
vol. 61, p. 79. doi 10.1016/j.msec.2015.12.024
1
2
. Carmona-Ribeiro, A. and de Melo Carrasco, L., Int. J.
Mol. Sci., 2013, vol. 14, no. 5, p. 9906. doi 10.3390/
ijms14059906
. Deka, S., Sharma, A., and Kumar, P., Curr. Top. Med.
Chem., 2015, vol. 15, no. 13, p. 1179. doi
16. Tatarinov, D.A., Kuznetsov, D.M., Voloshina, A.D.,
Lyubina, A.P., Strobykina, A.S., Mukhitova, F.K.,
Polyancev, F.M., and Mironov, V.F., Tetrahedron,
2
016, vol. 72, no. 51, p. 8493. doi 10.1016/
1
0.2174/1568026615666150330110602
j.tet.2016.11.023
3
4
. Kaur, R. and Liu, S., Prog. Surf. Sci., 2016, vol. 91,
no. 3, p. 136. doi 10.1016/j.progsurf.2016.09.001
1
1
7. Ramirez, F., Bigler, A.J., and Smith, C.P., Tetrahedron,
1
968, vol. 24, no. 14, p. 5041. doi 10.1016/S0040-4020
. Nazarov, P.A., Osterman, I.A., Tokarchuk, A.V.,
Karakozova, M.V., Korshunova, G.A., Lyamzaev, K.G.,
Skulachev, M.V., Kotova, E.A., Skulachev, V.P., and
Antonenko, Y.N., Sci. Rep., 2017, vol. 7, no. 1, p. 1394.
doi 10.1038/s41598-017-00802-8
. Khasiyatullina, N.R., Vazykhova, A.M., Mironov, V.F.,
Krivolapov, D.B., Voronina, Y.K., Voloshina, A.D.,
Kulik, N.V., and Strobykina, A.S., Mendeleev
Commun., 2017, vol. 27, no. 2, p. 134. doi 10.1016/
j.mencom.2017.03.008
. Strobykina, I.Y., Belenok, M.G., Semenova, M.N.,
Semenov, V.V., Babaev, V.M., Rizvanov, I.K.,
Mironov, V.F., and Kataev, V.E., J. Nat. Prod., 2015,
vol. 78, no. 6, p. 1300. doi 10.1021/
acs.jnatprod.5b00124
. Testai, L., Strobykina, I., Semenov, V.V., Semenova, M.,
Da Pozzo, E., Martelli, A., Citi, V., Martini, C., Bre-
schi, M.C., Kataev, V.E., and Calderone, V., Int. J. Mol.
Sci., 2017, vol. 18, no. 10, p. 2060. doi 10.3390/
ijms18102060
(
01)88414-3
8. Mironov, V.F., Konovalov, A.I., Litvinov, I.A.,
Gubaidullin, A.T., Petrov, R.R., Shtyrlina, A.A.,
Zyablikova, T.A., Musin, R.Z., Azancheev, N.M., and
Il’yasov, A.V., Russ. J. Gen. Chem., 1998, vol. 68,
no. 9, p. 1414.
9. Mironov, V.F., Tatarinov, D.A., Varaksina, E.N.,
Baronova, T.A., Zagidullina, I.Ya., Mustafina, A.R.,
Konovalov, A.I., C. A., 2008, vol. 149, 153215.
0. Tatarinov, D.A., Mironov, V.F., Varaksina, E.N., and
Konovalov, A.I., Russ. J. Gen. Chem., 2008, vol. 78,
no. 6, p. 1287. doi 10.1134/S1070363208060340
1. Tatarinov, D.A., Kuznetsov, D.M., and Mironov, V.F.,
Russ. J. Org. Chem., 2014, vol. 50, no. 4, p. 544. doi
5
6
7
8
9
1
2
2
2
2
1
0.1134/S1070428014040174
2. National Committee for Clinical Laboratory Standards,
Methods for Dilution Antimicrobial Susceptibility. Tests
for Bacteria that Grow Aerobically, Wayne, 2000.
3. National Committee for Clinical Laboratory Standards,
Reference Method for Broth Dilution Antifungal
. Tsepaeva, O.V., Nemtarev, A.V., Abdullin, T.I.,
Grigor’eva, L.R., Kuznetsova, E.V., Akhmadishina, R.A.,
Ziganshina, L.E., Cong, H.H., and Mironov, V.F.,
J. Nat. Prod., 2017, vol. 80, no. 8, p. 2232. doi 10.1021/
acs.jnatprod.7b00105
Susceptibility
Filamentous Fungi, Wayne, 1998.
Testing
of
Conidium-Forming
2
4. Semenov, V.E., Mikhailov, A.S., Voloshina, A.D.,
Kulik, N.V, Nikitashina, A.D., Zobov, V.V, Kharla-
mov, S.V, Latypov, S.K., and Reznik, V.S., Eur. J.
Med. Chem., 2011, vol. 46, no. 9, p. 4715. doi 10.1016/
j.ejmech.2011.05.034
. Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O.,
Vasquez-Vivar, J., Cheng, G., Lopez, M., and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018