Synthesis, spectroscopic, structural characterization, and antimicrobial studies of 1,3-dithia-2-arsacyclopentane derivatives with oxygen and sulfur donor ligands

Article abstract of DOI:10.1080/10426507.2010.505742

Some mixed 1,3-dithia-2-arsacyclopentane derivatives with oxygen and sulfur donor ligands have been synthesized by the reaction of 2-chloro-1,3-dithia-2- arsacyclopentane and oxygen and sulfur donor ligands (benzoic acid, thiobenzoic acid, sodium acetate, thioacetic acid, phenol, thiophenol, sodium salicylate, and thioglycolic acid) in equimolar ratio (1:1) in refluxing anhydrous benzene solution. These white or yellow solids/liquids derivatives have been characterized by melting points, molecular weights, elemental analyses (C, H, S, and As), and spectroscopic [UV, IR as well as NMR (¹H and ¹³C)] studies. Tentative structures are proposed on the basis of the spectroscopic results. The free ligands and the corresponding arsenic compounds exhibited good activities as antibacterial and antifungal agents on some selected bacterial and fungal strains. Chloroamphenicol and terbinafin were used as standards for comparison. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.505742

Phosphorus, Sulfur, and Silicon, 186:511–519, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.505742
SYNTHESIS, SPECTROSCOPIC, STRUCTURAL
CHARACTERIZATION, AND ANTIMICROBIAL STUDIES
OF 1,3-DITHIA-2-ARSACYCLOPENTANE DERIVATIVES
WITH OXYGEN AND SULFUR DONOR LIGANDS
H. P. S. Chauhan,1 Sumit Bhatiya,1 Abhilasha Bakshi,1
and K. S. Makwana2
1School of Chemical Sciences, Devi Ahilya University, Takshashila Campus,
Indore, India
2School of Studies in Botany, Vikram University, Ujjain, India
GRAPHICAL ABSTRACT
S
S
S
Benzene
As R + NaCl / HCl
As Cl + NaR / HR
S
R = C6H5-CO-O-, C6H5-CO-S-, CH3-CO-O-, CH3-CO-S-,
C6H5-O-, C6H5-S-, HO-C6H4-CO-O-, HO-CO-CH2-S
Abstract Some mixed 1,3-dithia-2-arsacyclopentane derivatives with oxygen and sulfur donor
ligands have been synthesized by the reaction of 2-chloro-1,3-dithia-2-arsacyclopentane and
oxygen and sulfur donor ligands (benzoic acid, thiobenzoic acid, sodium acetate, thioacetic
acid, phenol, thiophenol, sodium salicylate, and thioglycolic acid) in equimolar ratio (1:1) in
refluxing anhydrous benzene solution. These white or yellow solids/liquids derivatives have
been characterized by melting points, molecular weights, elemental analyses (C, H, S, and
As), and spectroscopic [UV, IR as well as NMR (1H and 13C)] studies. Tentative structures
are proposed on the basis of the spectroscopic results. The free ligands and the corresponding
arsenic compounds exhibited good activities as antibacterial and antifungal agents on some
selected bacterial and fungal strains. Chloroamphenicol and terbinafin were used as standards
for comparison.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Antimicrobial studies; dithiolatoarsenic(III); 1H and 13C NMR
Received 14 April 2010; accepted 21 June 2010.
Financial assistance from the University Grants Commission, New Delhi, is gratefully acknowledged. We
thank NMR Research Center (SIF), IISc., Bangalore, and SAIF, Central Drug Research Institute (CDRI), Lucknow,
for providing spectral data (1H and 13C NMR) and elemental analysis (C and H), respectively.
Address correspondence to Professor H. P. S. Chauhan, School of Chemical Sciences, Devi Ahilya University,
Takshashila Campus, Khandwa Road, Indore-452 001, India. E-mail: hpsc@rediffmail.com
511

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H. P. S. CHAUHAN ET AL.
INTRODUCTION
Arsenic andtheir metal complexes are well known1–3 for their utility as analytical
reagents, as lubricant additives for regeneration of cracking catalysts, and as antitumor
agents. Dithiolato arsenic compounds4 have been widely used in industry as rodent re-
pellents, vulcanization additives in rubber manufacturing, and in agriculture as fungicides
on almond trees, stone fruits, and vegetables. Arsenic trioxide is an active ingredient of a
traditional Chinese medicine that has been used successfully for treating acute promyelo-
cyte leukemia (APL)5 and has been shown to be an effective inducer of apoptosis in some
solid cancer cells such as esophageal, prostate, and ovarian carcinoma.6,7 The chemistry
of arsenic(III) dithiolato complexes is well explored, including the X-ray single crystal
structure of a number of compounds.8–10
In continuation of our recent interest in main group metal complexes with sulfur
donor ligands,11–13 we report in this article the synthesis, characterization, and antimicrobial
studies of 1,3-dithia-2-arsacyclopentane derivatives with oxygen and sulfur donor ligands.
RESULTS AND DISCUSSION
Mixed dithiolato arsenic(III) derivatives of oxygen and sulfur donor ligands have
been prepared by the reaction of 2-chloro-1,3-dithia-2-arsacyclopentane with oxygen and
sulfur donor ligands like benzoic acid, thiobenzoic acid, sodium acetate, thioacetic acid,
phenol, thiophenol, sodium salicylate and thioglycolic acid in equimolar (1:1) molar ratios
in refluxing benzene (Scheme 1) for ∼5 hours.
S
S
S
S
benzene
As R + NaCl / HCl
As Cl + NaR / HR
Scheme 1 Reactions of 2-chloro-1,3-dithia-2-arsacyclopentane with oxygen and sulfur donor ligands in 1:1
molar ratio. Where (compound no.) R = (1) C6H5-CO-O-, (2) C6H5-CO-S-, (3) CH3-CO-O-, (4) CH3-CO-S-,
(5) C6H5-O-, (6) C6H5-S-, (7) HO-C6H4-CO-O-, (8) HO-CO-CH2-S.
All these newly synthesized derivatives are either white/yellow solids or nonvolatile
viscous liquids. All the derivatives are soluble in common organic solvents such as benzene,
chloroform, acetone, dichloromethane, dimethyl formamide, dimethyl sulfoxide, etc.
Electronic Spectra
The electronic absorption spectral data of the new arsenic(III) derivatives are listed
in Table 1, and tentative assignments of the important characteristic bands have been made
with the help of earlier publications.11–13 The electronic spectra of these newly synthe-
sized arsenic compounds exhibit two bands. The 1,3-dithia-2-arsacyclopentane compounds
exhibit one strong absorption band in the region 204–243 nm, corresponding to a π–π∗
transition and other weak absorptions at 240–306 nm, which may be due to n–π∗ transitions
(Table 1).

STUDIES OF 1,3-DITHIA-2-ARSACYCLOPENTANE DERIVATIVES
513
Table 1 Some relevant UV (nm) and IR (cm−1) spectral data of 1,3-dithia-2-arsacyclopentane derivatives
Compound No.
I
II
ν(C-H) ν(C O) ν(C S) ν asym.(COO) ν sym.(COO) As-O As-S
1
2
3
4
5
6
7
8
210 240
243 270
212 243
210 241
204 244
2970
3050
2962
2930
3020
2950
3007
3408
1690
1640
1650
1652
—
—
1659
1636
610
620
625
610
630
640
659
646
1690
—
1650
—
—
—
1260
—
1261
—
—
—
540
—
510
—
530
—
532
—
320
331
315
335
320
330
325
335
—
—
240 306
220 241
1659
1636
1249
1280
Infrared Spectra
The infrared spectra of all newly synthesized compounds were recorded as KBr and
CsI discs in the range 4000–200 cm−1, and the important characteristic bands (Table 1)
have been assigned on basis of earlier published work.13–18
The bands of medium to strong intensity observed in the region 1636–1690 cm−1
and 1249–1280 cm−1 may be attributed to asymmetric and symmetric carboxylate group
stretching vibrations, respectively. This asymmetric carboxylate stretching vibration is
shifted towards higher frequencies in all the carboxylate derivatives. This shifting indicates
most probably monodentate behavior of carboxylate ligands with arsenic. The infrared spec-
trum of sulfur donor ligand13,16 derivatives displays two characteristic bands at 1636–1690
and 610–646 cm−1 due to C O and C S stretching vibrations, respectively. Bands of
medium to weak intensity present in the region 315–335 cm−1 are due to AsS stretching
vibrations.
1H NMR Spectra
1
The H NMR spectra of these derivatives have been recorded in CDCl3 solution
using TMS as an internal standard. The spectra exhibit the expected pattern without any
appreciable shifts from the reported values.11–13,19 One characteristic sharp singlet signal
of four protons of the ethane-1,2-dithiolato group (equivalent CH2S ring protons) was
observed in the region 3.41–3.76 ppm.11,12 The phenyl ring protons of the ligands appear
as a multiplet between 6.84–8.15 ppm.
In addition, some of these compounds (3, 4, 7, 8) also exhibit characteristic proton
resonances due to the corresponding protons of the ligands moieties (Table 2).
13C NMR Spectra
The 13C NMR spectra of these derivatives have been recorded in CDCl3 solution
using TMS as an internal standard. The 13C NMR spectra of 1,3-dithia-2-arsacyclopentane
derivatives with oxygen and sulfur donor ligands contained chemical shifts due to the
carbons of ethane-1,2-dithiolato and the ligands moieties. The 13C NMR spectra show a
sharp singlet in the region 44.44–44.69 ppm due to carbons of the ethane-1,2-dithiolato
group, indicating that these two carbons are magnetically equivalent,11–13,20 thus supporting
the results of the 1H NMR spectra. In addition, these compounds also exhibit the expected
signals due to the corresponding carbons of the ligands moieties (Table 2).

514
H. P. S. CHAUHAN ET AL.
Table 2 1H and 13C NMR spectral data (δ) of 1,3-dithia-2-arsacyclopentane derivatives
Compound no.
1H NMR chemical shift (δ)
13C NMR chemical shift (δ)
1
3.76, s, 4H (CH2S)
44.46 (CH2S)
7.46–8.14, m, 5H (C6H5)
128.46 {C6H5 C(3 and 5)}
129.23 {C6H5 C(2 and 6)}
130.17 {C6H5 C(1)}
133.77 {C6H5 C(4)}
171.82 (COO)
2
3
3.61, s, 4H (CH2S)
7.41–8.15, m, 5H (C6H5)
44.44 (CH2S)
127.35 {C6H5 C(2 and 6)}
128.65 {C6H5 C(3 and 5)}
133.77 {C6H5 C(4)}
136.68 {C6H5 C(1)}
188.87 (COS)
1.54, s, 3H (CH3)
3.41, s, 4H (CH2S)
20.21 (CH3)
44.48 (CH2S)
171.85 (COO)
4
5
2.46, s, 3H (CH3)
32.20 (CH3)
44.49 (CH2S)
44.45 (CH2S)
3.63, s, 4H (CH2S)
3.72, s, 4H (CH2S)
6.84–7.35, m, 5H (C6H5)
115.23{C6H5 C(2 and 6)}
120.70 {C6H5 C(4}
129.61 {C6H5 C(3 and 5)}
155.41 {C6H5 C(1)}
44.47 (CH2S)
127.55{C6H5 C(4)}
128.10 {C6H5 C(3 and 5)}
129.0 {C6H5 C(2 and 6)}
133.77 {C6H5 C(1)}
44.69 (CH2S)
111.27 {C6H5 C(2)}
117.80 {C6H5 C(6)}
119.58 {C6H5 C(4)}
130.91 {C6H5 C(5)}
136.96 {C6H5 C(3)}
162.14 {C6H5 C(1)}
174.81 (COO)
6
7
3.69, s, 4H (CH2S)
7.19–7.55, m, 5H (C6H5)
3.63, s, 4H (CH2S)
6.85–7.82, m, 4H (C6H4)
10.31, s, 1H (OH)
8
3.07, s, 2H (CH2)
3.63, s, 4H (CH2S)
9.22, s, 1H (OH)
31.71 (CH2)
44.45 (CH2S)
176.13 (COO)
Note: s = singlet; m = multiplet.
Structural Elucidation
Although it is quite difficult to comment on the actual structure of these derivatives
in solid state without an actual X-ray crystal structure analysis of at least one of the
products, one can tentatively conclude on the basis of the spectroscopic data that these
ligands exhibit a monodentate mode of attachment to the arsenic(III) metal, thus leading to
a three-coordinated distorted pyramidal geometry (Figure 1).

STUDIES OF 1,3-DITHIA-2-ARSACYCLOPENTANE DERIVATIVES
515
S
O
As
S
S
Figure 1 Proposed structure of arsenic(III) compounds.
Antimicrobial Activity
The free ligands and their arsenic(III) derivatives were screened to evaluate their an-
timicrobial activity in vitro against four human pathogenic bacterial species and two fungal
species at three different concentrations. The results are listed in Table S1 (Supplemental
Materials, available online). Chloroamphenicol and terbinafin were used as standard and
were compared with free ligands and their arsenic(III) derivatives.
The impact of the central metal atom of the compounds was found on antimicrobial
activity against tested bacterial and fungal species. The results obtained by the disc diffusion
method indicate that these compounds have enhanced activity compared to the ligands,
which indicates that these bonded arsenic(III) atoms increase the antimicrobial effect. As
expected, the effect is proportional to the concentration of the compounds. Comparison of
the antimicrobial activities of the free ligands and their synthesized arsenic(III) derivatives
with chloroamphenicol (standard antibacterial drug) and terbinafin (standard antifungal
drug) exhibit the following results.
(i) The arsenic(III) compounds exhibit higher antibacterial and antifungal activity than
corresponding free ligands. It is noticeable here that E. coli and P. aeruguinosa
resist to free oxygen-based ligands. It may be concluded that free ligands and arsenic
compounds inhibit the growth of bacteria to a greater extent, as concentration is
increased.
(ii) All synthesized arsenic(III) derivatives showed a greater or equal activity against
Gram-positive bacterial and fungal species than standard chloroamphenicol and
terbinafin.
(iii) Compounds 1, 2, and 4 showed a greater activity against E. coli, while 3 and 5 are less
active than chloroamphenicol. The compounds 2, 4, and 5 showed a greater activity
against P. aeruguinosa, while 1, 3, and 6 are equally active as chloroamphenicol.
(iv) Compounds 2 and 4 showed modest activity against all microbial strains. The antibac-
terial activity of the common standard antibiotic chloroamphenicol was also recorded
using the same procedure as above at the same concentration and solvent. The% Ac-
tivity Index21 for the compound was calculated (Table S2, Supplemental Materials)
by use of the formula:
Zone of inhibition by test compound (diameter)
0/ Activity index =
× 100
0
Zone of inhibition by standard compound (diameter)

516
H. P. S. CHAUHAN ET AL.
CONCLUSION
We conclude that some of the free ligands and their arsenic(III) compounds exhibited
greater antimicrobial effects as compared with certain investigated antibiotics. The more
toxic nature of these compounds in comparison to the free ligands may be due to the
presence of the toxic element arsenic in all the compounds.
EXPERIMENTAL
Instruments
All experiments were carried out under moisture-free conditions. Since all arsenic
compounds are highly toxic and dangerous in nature, appropriate precautions were taken
throughout all the experimental manipulations. Solvents (benzene, dichloromethane, n-
hexane, etc.) were dried and purified by standard methods22 before use. Ethane-1,2-dithiol
and thionyl chloride (both E. Merck) were distilled before use. Arsenic trioxide (Fluka) and
ligands [benzoic acid, thiobenzoic acid, anhydrous sodium acetate, thioacetic acid, phenol,
thiophenol, sodium salicylate and thio glycolic acid (all Fluka and Merck Germany)] were
used as received without further purification. Arsenic trichloride was prepared by the
reaction of arsenic trioxide and thionyl chloride.23 2-Chloro-1,3-dithia-2-arsacyclopentane
was synthesized by the reaction of ethane-1,2-dithiol with arsenic trichloride in equimolar
ratio in refluxing benzene.24
Sulfur was determined gravimetrically as barium sulfate.25 Arsenic was determined
iodometrically.25 Molecular weights were determined cryoscopically in benzene. Melting
points were determined in sealed capillary tubes on a B10 Tech India Melting Apparatus
and are uncorrected. Elemental analysis (C and H) was performed on a Heraeus Carlo
Erba 1108 C, H, N analyzer at SAIF, CDRI, Lucknow, India. The electronic spectra were
recorded in chloroform solution at room temperature on a Shimadzu UV-1601 UV-Visible
spectrophotometer in range 200–500 nm. Infrared spectra was recorded in region 4000–400
cm−1 using a Bruker Vertex model 70 Spectrophotometer as KBr discs and in region 600–50
cm−1 as nujol mull over CsI disks using a Magna-IR Spectrophotometer-550 instrument. 1H
and 13C NMR spectra were recorded in CDCl3 solution using TMS as an internal standard.
The 1H and 13C NMR spectra were operated at 400.23 and 100.63 MHz respectively, on a
Bruker AC-300F NMR Spectrophotometer at the NMR Research Centre, IISc., Bangalore.
Syntheses
Reaction between 2-chloro-1,3-dithia-2-arsacyclopentane and benzoic
acid in 1:1 molar ratio. The solution of 2-chloro-1,3-dithia-2-arsacyclopentane (1.041
g, 5.14 mmol) in benzene (∼30 mL) was added dropwise to benzoic acid (0.627 g, 5.14
mmol) solution in benzene (∼25 mL) in 1:1 molar ratio. The contents were then heated
under reflux for ∼5 h, and libration of HCl gas was observed. After cooling, the solvent was
removed under reduced pressure, and a white solid product thus obtained was recrystallized
in n-hexane. Yield 1.45 g; 98%, mp 105◦C.
Reaction between 2-chloro-1,3-dithia-2-arsacyclopentane and sodium
salicylate in 1:1 molar ratio. The solution of 2-chloro-1,3-dithia-2-arsacyclopentane
(1.028 g, 5.07 mmol) in benzene (∼30 mL) was added dropwise to sodium salicylate (0.813
g, 5.07 mmol) suspension in benzene (∼25 mL) in 1:1 molar ratio. The contents were heated
under reflux for ∼4 hours. Precipitated NaCl (0.24 g) was removed by filtration. Upon

517

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H. P. S. CHAUHAN ET AL.
removing the solvent from the filtrate, a white solid was obtained and was recrystallized in
dichloromethane. Yield 1.36 g; 88%, mp 48◦C.
All other derivatives were prepared by adopting similar methods. Pertinent analytical
and physicochemical data are listed in Table 3.
Antimicrobial Evaluation
All synthesized derivatives and ligands used were screened for their in vitro antimi-
crobial activities against four human pathogenic bacterial species [Staphylococcus aureus
(ATCC 9144) (G+), Bacillus subtilis (ATCC 6051) (G+), Escherichia coli (ATCC 9637)
(G−) and Pseudomonas aeruguinosa (ATCC 25619) (G−)] and two plant fungal species
[Aspergillus niger (ATCC 9029) and Trichoderma ressie (ATCC 164)] by using the disc
diffusion method.20 These strains were collected from the Microbiology Laboratory, S.S.
in Botany, Vikram University, Ujjain (M.P.). Chloroamphenicol and terbinafin were used
as standard drugs for comparison. The results of screening studies are given in Table S1
(Supplemental Materials).
The compound was dissolved in DMF, to get 200 µgmL−1 concentrated solution.
Further progressive double dilutions were performed to obtain required concentrations of
100 and 50 µgmL−1. A 0.5 mL (containing 107 microorganisms per mL) of each investigated
microorganism was added to a sterile nutrient agar (for bacteria)/dextrose agar (for fungi)
medium just before solidification, then poured onto sterile Petri dishes (9 cm in diameter)
and left to solidify. Using a sterile cork borer (6 mm in diameter), three holes (wells) were
made in each dish, and then 0.1 mL of tested compound dissolved in DMF (50, 100, and
200 µgmL−1) was poured into these holes. Finally dishes were incubated at 37◦C for 24 h
for bacteria and at 30◦C for 72 h for fungi, where clear or inhibition zones were detected
around each hole. Inhibitory activity was measured (in mm) as diameter of inhibition zones.
DMF showed no effect on organisms tested.
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