Synthesis, spectroscopic analysis, and in-vitro antimicrobial evaluation of some tetrahydrobenzo[A]xanthene-11-thiones

Article abstract of DOI:10.1080/10426507.2012.757611

A series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones were synthesized by the reaction of substituted 12-aryl-8,9,10,12-tetrahydrobenzo[a] xanthene-11-ones with Lawesson's Reagent in toluene under standard reaction conditions. All synthesize

Full text of DOI:10.1080/10426507.2012.757611

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Synthesis, Spectroscopic Analysis, and
In-Vitro Antimicrobial Evaluation of some
Tetrahydrobenzo[a]Xanthene-11-Thiones
Annamalai Sethukumar a , Chandran Udhaya Kumar a &
Balasubramaniyam Arul Prakasam a
a Department of Chemistry , Annamalai University ,
Annamalainagar , 608002 , India
Accepted author version posted online: 02 Jan 2013.Published
online: 20 Sep 2013.
To cite this article: Annamalai Sethukumar , Chandran Udhaya Kumar & Balasubramaniyam Arul
Prakasam (2013) Synthesis, Spectroscopic Analysis, and In-Vitro Antimicrobial Evaluation of some
Tetrahydrobenzo[a]Xanthene-11-Thiones, Phosphorus, Sulfur, and Silicon and the Related Elements,
188:11, 1652-1660, DOI: 10.1080/10426507.2012.757611
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Phosphorus, Sulfur, and Silicon, 188:1652–1660, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.757611
SYNTHESIS, SPECTROSCOPIC ANALYSIS, AND IN-VITRO
ANTIMICROBIAL EVALUATION OF SOME
TETRAHYDROBENZO[a]XANTHENE-11-THIONES
Annamalai Sethukumar, Chandran Udhaya Kumar,
and Balasubramaniyam Arul Prakasam
Department of Chemistry, Annamalai University, Annamalainagar 608002, India
GRAPHICAL ABSTRACT
Abstract A series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones were synthe-
sized by the reaction of substituted 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones
with Lawesson’s Reagent in toluene under standard reaction conditions. All synthesized com-
pounds were characterized by IR, NMR (1H and 13C), and mass spectra. Moreover, 2D-NMR
(HOMOCOSY, HSQC, and HMBC) studies were also performed for compound 10b. The syn-
thesized compounds were also screened for their antibacterial activities.
[Supplementary materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental
files: Additional figures.]
Keywords Lawesson reagent; xanthene-11-thiones; 2D-NMR; antibacterial activity
INTRODUCTION
Xanthenes, one of the most widely distributed classes of natural compounds, and
benzoxanthenes constitute an important class of biologically active heterocycles; thus,
their synthesis has received great attention in medicinal and pharmaceutical chemistry. They
have antibacterial, anti-inflammatory, antiviral, and anticancer activities.1–4 Xanthene-based
compounds serve as antagonists for paralyzing the action of zoxalamine, in photodynamic
therapy (PDT), and as antagonists for drug-resistant leukemia lines.5–7 In addition, their
Received 24 September 2012; accepted 20 November 2012.
Address correspondence to Balasubramaniyam Arul Prakasam, Department of Chemistry, Annamalai Uni-
versity, Annamalainagar 608002, India. E-mail: arul7777@yahoo.com
1652

SPECTRAL ANALYSIS OF XANTHENES AND BENZOXANTHENES
1653
derivatives can be used as dyes, pH-sensitive fluorescent materials for the visualization of
biomolecular assemblies, agricultural bactericides, and in laser technologies.8–12
.
Organosulfur compounds occupy a uniquely important place in synthetic organic
chemistry due to their rich and versatile chemistry.13 Furthermore, they are of widespread
interest because of their ubiquitous biological activities and rich photochemistry.14,15 These
compounds are usually synthesized using thionation, which converts a carbonyl group to
thiocarbonyl. The larger and less electronegative sulfur atom, relative to oxygen, might
alter the hydrogen bonding ability and/or induce conformational changes in the modified
molecule. In addition, these derivatives can be used as intermediates for further transfor-
mations due to the increased reactivity of the thione function. Lawesson’s Reagent (1, LR)
is the most efficient and broadly utilized reagent in this transformation.16
S
S
S
H3CO
P
P
OCH3
S
1
(1)
In the course of a program devoted to the synthesis of new heterocyclic scaffolds of
bioactive compounds, here we proposed the synthetic strategy for 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-thiones. The synthesized compounds were characterized
by IR, NMR (1H and 13C), and also tested for antibacterial activities. 2D-NMR (HOMO-
COSY, HSQC, and HMBC) spectroscopic studies of compound 10b were also performed
for the unambiguous assignment of signals.
RESULTS AND DISCUSSION
Chemistry
The synthetic route to the target compounds is outlined in Scheme 1. Starting com-
pounds (12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones) 1a–10a were prepared by
the synthetic procedure described earlier.17
Thionation of the parent compounds 1a–10a was achieved with LR. The respective
12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones 1a–10a were refluxed with Lawes-
son’s Reagent in toluene for 45 min to afford the purple color solid 12-aryl-8,9,10,12-
tetrahydrobenzo[a]xanthene-11-thiones 1b–10b. The synthesized compounds were char-
acterized by IR and NMR spectra as well as mass spectrometry. Spectroscopic data are
listed in the Experimental Section. They are in accordance with the assigned structures.
IR Spectroscopic Analysis of Compounds 1b–10b
Since the C S bond is not as strongly polar as the C O bond, the absorption band is
not very intense and appears in the low-frequency region of the spectrum. The compounds
1b–10b also showed a moderate intense band in the region 1210–1225 cm−1 characteristic
of thiocarbonyl (C S) stretching frequencies. The disappearance of the carbonyl (C O)
stretching frequency and the appearance of new stretching band around 1225 cm−1 charac-
teristic for a thiocarbonyl (C S) group evidences the formation of thioketones.

1654
A. SETHUKUMAR ET AL.
O
R
OH
O
O
H
2
x
u
l
f
e
3
R
/
l
o
n
a
h
t
E
R
R
O
S
Lawesson's Reagent
O
O
1b; R = H, 2b; R = 2-Cl, 3b; R = 3-Br, 4b; R = 3-OCH3 , 5b; R = 4-Cl, 6b; R = 4-F,
7b; R = 4-OCH3, 8b; R = 4-CH3, 9b; R = 3-OCH3-4-OH, 10b; R = 3-OC2H5-4-OH
Scheme 1 Synthesis of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones 1b–10b.
1H NMR Spectroscopic Analysis of Compound 10b
Compound 10b (Figure 1 with spectroscopic numbering) was chosen as a representa-
tive compound and the 1H NMR spectral analysis is presented here in detail. The 1H NMR
spectrum of 10b is shown in Figure 2. For 10b, 2D-NMR (HOMOCOSY, HSQC, and
HMBC) spectra were also recorded for the unambiguous assignment of signals. Aromatic
protons appear in the region 6.70–8.22 ppm. In the lower frequency region of the spec-
trum, there are two sharp singlets at 1.00 and 1.14 ppm (each with three proton integrals)
due to methyl protons. The two doublets at 2.85 and 3.00 ppm are assigned to methylene
protons at C-10 adjacent to the thiocarbonyl group [AB system, C C–CHaHb, δ2.85 (d, J
= 17.0 Hz, 1H) and δ3.00 (d, J = 17.0 Hz, 1H)].18 Likewise, the other methylene protons at
C-8 appeared as two doublets at 2.62 and 2.67 ppm. [AB system, C( S)CHaCHb, δ2.62 (d,
J = 18.5 Hz, 1H) and δ2.67 (d, J = 18.5 Hz, 1H)]. The benzylic proton at C-12 resonates
at 6.27 ppm as a singlet. Methyl protons of the ethoxy group appeared as a triplet with
three-proton integration at 1.42 ppm (J = 7.0 Hz). The remaining signals due to substituents
in aromatic ring (ethoxy and hydroxyl) are observed in normal region.
13C NMR Spectroscopic Analysis of Compound 10b
The 13C NMR spectrum of 10b is shown in Figure 3. The signal at higher frequency
region of 230.7 ppm is assigned to the thiocarbonyl (C S) carbon atom. In the up-field
region three signals were observed at 14.9, 26.3, and 28.9 ppm. These were assigned to
the two methyl carbons attached to C-9 and ethoxy methyl carbon respectively. Methylene
carbon signals appear at 61.2 and 43.0 ppm17 and the signal at 61.2 ppm is assigned to

SPECTRAL ANALYSIS OF XANTHENES AND BENZOXANTHENES
1655
Table 1 Correlations in the HOMOCOSY, HSQC, and HMBC spectra of compound 10b (δ, ppm)
Correlations in the
HOMOCOSY
spectrum
Signal in the 1H
spectrum
Correlations in the
HSQC spectrum
Correlations in the
HMBC spectrum
1.00 (s, 3H, CH3)
—
—
4.08–4.11
2.67
26.3
28.9
14.8
42.9
61.2, 42.9, 33.0, 28.9
61.2, 42.9, 33.0, 26.3
1.14 (s, 3H, CH3’)
1.42 (t, 3H, OCH2CH3)
2.62 (d, 1H, H-8a)
64.4
161.2, 124.4, 61.2, 33.0,
26.3
2.67 (d, 1H, H-8b)
2.70 (d, 1H, H-10a)
3.00 (d, 1H, H-10b)
2.62
3.00
2.70
1.42
42.9
61.2
61.2
64.4
161.2, 124.4, 61.2, 33.0,
26.3
230.7, 124.4, 42.9, 33.1,
26.3
230.7, 124.4, 42.9, 33.1,
26.3
14.8
4.08–4.11 (q, 2H,
OCH2)
5.52 (s, 1H, Ar-OH)
6.27 (s, 1H, H-12)
—
—
—
37.2
—
230.7, 161.2,
113.5–146.9
6.71 (d, 1H, H-17)
6.76 (dd, H, H-18)
7.11 (d, 1H, H-14)
7.38 (d, 1H, H-5)
7.43 (t, 1H, H-2)
7.52 (t, 1H, H-3)
6.76
7.11, 6.71
6.76
7.77
7.81, 7.52
8.21, 7.43
113.9
121.7
113.5
116.8
125.0
126.9
144.9, 136.3
143.9, 113.9
144.9, 133.9, 121.7
146.8, 131.7, 118.8
131.7, 123.6
128.6, 128.5, 131.2,
116.8
7.77 (d, 1H, H-6)
7.81 (d, 1H, H-4)
8.21 (d, 1H, H-1)
7.38
7.43
7.52
128.5
128.6
123.6
146.8, 131.2
131.2, 128.6, 128.5
131.7, 131.2, 125.0,
118.8
the methylene carbon in α-position to the thiocarbonyl group (C-10). Shielding differences
between methylene carbons are about 18 ppm and this clearly exemplifies a drift of electron
density from C-10 toward the electron deficient thiocarbonyl carbon. The methylene carbon
C-12 is slightly deshielded and observed at 37.2 ppm. The C-9 carbon signal appeared at
28.9 ppm.
The individual assignment of the proton and carbon signals for 10b was achieved by
use of HOMOCOSY, HSQC, and HMBC spectroscopic measurements, and the observed
Table 2 Comparison of 1H and 13C chemical shift values of compounds 10a and 10b
Carbon numbering
10a
10b
C-8
C-9
2.54 (s, 2H), 41.4
32.2
2.62 (d, 1H), 2.67 (d, 1H), 42.9
33.1
C-10
C-11
2.25 (d, 1H), 2.30 (d, 1H), 50.9
197.1
2.84 (d, 1H), 3.00 (d, 1H), 61.2
230.7
C-12
CH3 at C-9
CH3 at C-9
5.62 (s, 1H), 34.1
0.96 (s, 3H), 27.1
1.10 (s, 3H), 29.3
6.27 (s, 1H), 37.2
1.00 (s, 3H), 26.3
1.14 (s, 3H), 28.9

1656
A. SETHUKUMAR ET AL.
Table 3 Antimicrobial activities of 1b–10b determined by the disk diffusion method (zone of inhibition in mm)
at 10 μg/mL in Muller–Hinton agar
Compounds
B. cereus
S. aureus
P. aeruginosa
S. typhi
1b
2b
3b
4b
5b
6b
7b
8b
9
12
11
9
8
13
8
12
12
11
10
12
11
11
15
9
7
8
—
—
—
9
8
10
7
9
7
8
15
8
10
7
10
8
13
16.5
8
9b
10b
12
13
15.8
14
17.5
16
15
Control (ampicillin)
correlations are given in Table 1. The HMBC spectrum of 10b is shown in Figure 4 and its
mass spectrum is shown in Figure 5.
1
Thionation results in a shift of the H and 13C signals toward the higher frequency
region. The reason for deshielding is the strong C S anisotropy compared with the parent
ketones 1a–10a. The extent of deshielding is very high in magnitude for the α-methylene
protons and carbons (C-10). The C-10 methylene protons are deshielded to around 0.9 ppm
and the corresponding carbon is deshielded to ∼10 ppm. The trend is similar for the C-12
benzylic protons and carbons and the chemical shift differences or shielding differences for
10a and 10b given in Table 2.
Antibacterial Evaluation
All synthesized 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones 1b–10b
were tested for their in vitro antibacterial activity against Bacillus cereus, Staphylococ-
cus aureus, Pseudomonas aeruginosa, and Salmonella typhi. The antibacterial potency
of the tested compounds in 10 μg/mL was compared with the standard drug ampicillin
(10 μg/mL). The zone of inhibition is summarized in Table 3.
The biological results suggest that products 1b–10b exhibit mild to good inhibitory
effect against most of the tested microbes. Compound 4b was found to have good inhibitory
effect on Salmonella typhi, Staphylococcus aureus, and Bacillus cereus. Compounds 6b and
10b are found to have good inhibitory effect against Bacillus cereus and Staphylococcus
aureus. Most of the compounds have mild inhibitory activity against P. aeruginosa at the
tested concentration level of 10 μg/mL. The studies thus confirm the potential biological
activity and consequently the utility of these derivatives as potent drug sources.
CONCLUSION
We have carried out the synthesis of a series of 12-aryl-8,9,10,12-tetrahydrobenzo
[a]xanthene-11-thiones (1b–10b) from 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
ones (1a–10a) using Lawesson’s Reagent. Compound 10b shows potential biological ac-
tivity against all tested bacterial strains compared with other compounds 1b–9b. The
synthesized compounds are of interest as they are therapeutically noteworthy and useful
building blocks for further transformations.

SPECTRAL ANALYSIS OF XANTHENES AND BENZOXANTHENES
1657
EXPERIMENTAL
Chemistry
Melting points (mp) were determined in open capillaries and are uncorrected. IR spec-
tra were recorded on an Avatar Nicholet FT-IR spectrophotometer (range 4000–400 cm−1
)
as KBr pellets. 1H NMR spectra were recorded on a Bruker AMX-400 spectrometer oper-
ating at 400.23 MHz and a Bruker AVIII 500 MHz spectrometer operating at 500.3 MHz
using CDCl3 as solvent and TMS as internal reference. 13C NMR spectra were recorded
on a Bruker AMX-400 spectrometer operating at 100.63 MHz and Bruker AVIII 500 MHz
spectrometer operating at 125.75 MHz. Mass spectra were recorded on a JEOL GC MATE
II spectrometer.
By employing the literature precedent,17 all parent 12-aryl-8,9,10,12-tetrahydrobenzo
[a]xanthene-11-ones 1a–10a were prepared by the condensation of appropriate aldehydes
with dimedone and 2-naphthol using BF3·OEt2 as catalyst.
General Procedure for the Preparation of 1b–10b
Lawesson’s Reagent (2.5 mmol) was added to a solution of the parent ketone 1a–10a
(1 mmol) in toluene (15 mL). The reaction mixture was refluxed for 45 min. After the
completion of the reaction, the solvent was removed and the residue was subjected to
column chromatography (CH2Cl2:MeOH, 98:2) to afford 1b–10b as purple color solids.
9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thione (1b).
◦
Purple crystals; yield: 78%; mp 106–108 C; IR: 3063, 3019, 2964, 2925, 2849, 1651,
1
1595, 1374, 1225; H NMR (400 MHz) δ: 7.01–8.19 (m, Ar-H, 11H), 6.29 (s, 1H), 2.95
(d, 1H, J = 16.8 Hz), 2.82 (d, 1H, J = 16.8 Hz), 2.67 (d, 1H, J = 18.4 Hz), 2.61 (d, 1H,
J = 18.0), 1.11 (s, 3H), 0.95 (s, 3H); 13C NMR (100 MHz) δ: 230.5, 161.3, 146.9, 144.1,
131.6, 131.2, 129.2, 128.7, 128.5, 128.2, 127.9, 127.0, 126.2, 125.0, 124.2, 123.7, 123.6,
118.7, 117.3, 116.8, 61.1, 42.9, 37.7, 33.1, 29.7, 28.8, 26.4.
12-(2-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
◦
thione (2b). Purple crystals; yield: 80%; mp 150–152 C; IR: 3057, 3002, 2953, 2923,
2854, 1630, 1578, 1370, 1220; 1H NMR (400 MHz) δ: 8.43–6.95 (m, Ar-H, 10H), 6.42 (s,
1H), 2.95 (d, 1H, J = 16.8 Hz), 2.83 (d, 1H, J = 16.8 Hz), 2.69 (d, 1H, J = 18.0 Hz), 2.62
(d, 1H, J = 18.0 Hz), 1.12 (s, 3H), 1.00 (s, 3H); 13C NMR (125 MHz) δ: 230.6, 161.9,
147.3, 140.6, 133.8, 133.2, 131.5, 130.6, 130.5, 129.1, 128.5, 127.8, 126.2, 124.9, 124.2,
122.7, 117.0, 116.8, 61.5, 43.0, 37.3, 32.9, 28.8, 26.5; MS (EI 70 eV): m/z 368.5 (100),
404.3 (M+, 16).
12-(3-Bromophenyl)-9,9-dimethyl-8,9,10,12-tetr◦ahydrobenzo[a]xanthene-11-
thione (3b). Purple crystals; yield: 84%; mp 136–138 C; IR: 3066, 2956, 2923, 1632,
1584, 1369, 1219; 1H NMR (400MHz) δ: 8.17–7.03 (m, Ar-H, 10H), 6.31 (s, 1H), 2.99 (d,
1H, J = 17.0 Hz), 2.85 (d, 1H, J = 16.5 Hz), 2.71 (d, 1H, J = 18.0 Hz), 2.64 (d, 1H, J =
18.0 Hz), 1.46 (s, 3H), 1.00 (s, 3H); 13C NMR (125 MHz) δ: 230.3, 161.5, 146.9, 146.3,
132.1, 131.7, 131.0, 129.4, 129.1, 128.6, 128.1, 127.2, 125.2, 123.5, 123.3, 122.2, 117.8,
116.9, 61.1, 42.9, 37.5, 33.2, 28.8, 26.4; MS (EI 70 eV): m/z 248.9(60), 449.8(M++1, 12).
9,9-Dimethyl-12-(3-methoxyphenyl)-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
◦
thione (4b). Purple crystals; yield: 82%; mp 158–160 C; IR: 3067, 3008, 2958, 2922,
2852, 1647, 1374, 1225; 1H NMR (400MHz) δ: 8.23–7.01 (m, Ar-H, 10H), 6.31 (s, 1H),
2.98 (d, 1H, J = 18.0 Hz), 2.84 (d, 1H, J = 17.2 Hz), 2.67 (d, 1H, J = 18.0 Hz), 2.63 (d,

1658
A. SETHUKUMAR ET AL.
1H, J = 18.0 Hz), 1.14 (s, 3H), 0.91 (s, 3H); 13C NMR (100 MHz) δ: 230.5, 161.4, 159.2,
146.8, 145.7, 131.6, 131.2, 128.8, 128.7, 128.5, 127.1, 125.1, 124.0, 123.6, 121.8, 118.5,
116.8, 115.6, 111.1, 61.1, 55.1, 42.9, 37.6, 33.1, 28.8, 26.48; MS (EI 70 eV): m/z 269.5
(100), 399.5 (M+, 5).
12-(4-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
◦
thione (5b). Purple crystals; yield: 82%; mp 164–166 C; IR: 3059, 2922, 2853, 1628,
1375, 1221; 1H NMR (400 MHz, ppm) δ: 8.11–7.09 (m, Ar-H, 10H), 6.27 (s, 1H), 2.95 (d,
1H, J = 16.8 Hz), 2.81 (d, 1H, J = 16.8 Hz), 2.66 (d, 1H, J = 18.0 Hz), 2.60 (d, 1H, J =
18.0 Hz), 1.11 (s, 3H), 0.95 (s, 3H); 13C NMR (125 MHz) δ: 230.5, 161.5, 146.8, 142.6,
131.9, 131.6, 130.9, 130.6, 128.9, 128.6, 128.1, 127.2, 125.2, 123.7, 123.3, 118.1, 116.8,
61.0, 42.9, 37.2, 33.1, 28.9, 26.3.
9,9-Dimethyl-12-(4-fluorophenyl)-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
◦
thione (6b). Purple crystals; yield: 84%; mp 120–122 C; IR: 3065, 2956, 2923, 2858,
1627, 1583, 1506, 1224; 1H NMR (400 MHz) δ: 8.19–6.34 (m, Ar-H, 10H), 3.01 (d, 1H,
J = 16.4 Hz), 2.85 (d, 1H, J = 16.8 Hz), 2.69 (d, 1H, J = 19.2 Hz), 2.63 (d, 1H, J =
20.0 Hz), 1.15 (s, 3H), 0.99 (s, 3H); 13C NMR (100 MHz) δ: 230.5, 162.3, 161.4, 159.9,
146.8, 140.0, 140.0, 131.6, 131.0, 130.8, 130.7, 129.0, 128.6, 127.2, 125.2, 123.9, 123.4,
118.4, 116.9, 114.9, 114.6, 61.1, 42.9, 37.0, 34.8, 33.1, 30.9, 28.9, 27.0,26.3.
9,9-Dimethyl-12-(4-methoxyphenyl)-8,9,10,12-tetrahydrobenzo[a]xanthene-11-
◦
thione (7b). Purple crystals; yield: 80%; mp 180–182 C; IR: 3073, 3024, 2956, 2925,
2860, 1607, 1579, 1508, 1250, 1220, 1183; 1H NMR (400 MHz) δ: 8.19–6.89 (m, Ar-H,
10H), 6.24 (s, 1H), 3.66 (s, 3H), 2.95 (d, 1H, J = 16.8 Hz), 2.81 (d, 1H, J = 16.8 Hz),
2.66 (d, 1H, J = 18.8 Hz), 2.59 (d, 1H, J = 17.6 Hz), 1.11 (s, 3H), 0.96 (s, 3H); 13C NMR
(125 MHz) δ: 230.6, 161.2, 157.7, 146.8, 136.5, 131.6, 131.1, 130.2, 128.6, 128.5, 127.0,
125.0, 124.3, 123.6, 118.9, 116.8, 113.3, 61.1, 55.0, 42.9, 36.9, 33.1, 28.9, 26.4.
9,9-Dimethyl-12-(4-tolyl)-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thione (8b).
Purple crystals; yield: 79%; mp 140–142 ◦C; IR: 3079, 3013, 2956, 2920, 2856, 1605, 1579,
1
1368, 1221, 1185; H NMR (500 MHz) δ: 8.18–6.66 (m, Ar-H, 10H), 6.28 (s, 1H), 2.97
(d, 1H, J = 16.5 Hz), 2.85 (d, 1H, J = 16.5 Hz), 2.69 (d, 1H, J = 20.0 Hz), 2.64 (d, 1H, J
= 16.5 Hz), 2.2 (s, 3H), 1.14 (s, 3H), 0.99 (s, 3H); 13C NMR (100 MHz) δ: 230.5, 161.2,
146.8, 141.2, 135.6, 131.6, 131.2, 129.1, 128.6, 128.5, 128.4, 126.9, 124.9, 124.3, 123.6,
118.9, 116.8, 61.1, 42.9, 37.3, 33.1, 29.2, 28.8, 26.5, 20.9.
9,9-Dimethyl-12-(4-hydroxy-3-methoxyphenyl)-8,9,10,12-tetrahydrobenzo[a]
◦
xanthene-11-thione (9b). Purple crystals; yield: 78%; mp 158–160 C; IR: 3501, 3063,
2923, 2853, 1612, 1578, 1512, 1371, 1268; 1H NMR (400 MHz) δ: 8.21–6.68 (m, Ar-H,
9H), 6.27 (s, 1H), 5.45 (s, 1H), 3.85 (s, 3H), 3.02 (d, 1H, J = 16.8 Hz), 2.84 (d, 1H, J =
16.8 Hz), 2.63 (d, 1H, J = 18.4 Hz), 2.58 (d, 1H, J = 18.4 Hz), 1.14 (s, 3H), 0.99 (s, 3H);
13C NMR (100 MHz) δ: 230.7, 161.3, 146.8, 145.8, 143.8, 136.4, 131.7, 131.2, 128.6,
128.5, 127.0, 125.1, 124.4, 123.6, 121.9, 118.8, 116.8, 113.9, 112.5, 61.2, 55.9, 42.9, 37.2,
33.1, 28.9, 26.3; MS (EI 70 eV): m/z 135.4 (100), 418.2 (M++2, 18).
9,9-Dimethyl-12-(3-ethoxy-4-hydroxyphenyl)-8,9,10,12-tetrahydrobenzo[a]
xanthene-11-thione (10b). Purple crystals; yield: 79%; mp 144–146 ◦C; IR: 3526, 3433,
3062, 2957, 2922, 2871, 1611, 1582, 1511, 1368, 1266, 1217, 1184; 1H NMR (500 MHz)
δ: 8.22–6.70 (m, Ar-H, 9H), 6.27 (s, 1H), 5.52 (s, 1H), 4.11–4.08 (m, 2H), 3.00 (d, 1H, J =
17.0 Hz), 2.85 (d, 1H, J = 17.0 Hz), 2.67 (d, 1H, J = 18.5 Hz), 2.62 (d, 1H, J = 18.5 Hz),
1.42 (t, 3H, J = 7 Hz), 1.14 (s, 3H), 1.00 (s, 3H); 13C NMR (100 MHz) δ: 230.7, 161.2,
146.8, 144.9, 143.9, 136.3, 131.7, 131.2, 128.6, 128.5, 126.9, 125.0, 124.5, 123.6, 121.7,

SPECTRAL ANALYSIS OF XANTHENES AND BENZOXANTHENES
1659
118.8, 116.8, 113.9, 113.5, 64.4, 61.2, 42.9, 37.2, 33.1, 28.9, 26.3, 14.8; MS (EI 70 eV):
m/z 146.9 (80), 429.5 (M+, 18).
Microbiological Screening
Antimicrobial activity tests were carried out against Bacillus cereus, Staphylococcus
aureus, Pseudomonas aeruginosa, and Salmonella typhi strains using the disc diffusion
method. The in vitro activities of the compounds were tested in Muller–Hinton agar (Hi-
Media, Mumbai) for bacteria by the zone of inhibition method.19 While this manuscript
was under review, Khurana et. al.20 reported the synthesis and biocidal evaluation of a
series of 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones. The antibacterial po-
tency of the tested compounds in 10 μg/mL was compared with the standard drug ampicillin
(10 μg/mL). Microbial suspensions were prepared in sterile saline (0.85% NaCl) with an
optical density conforming to the McFarland standard 0.5 [150 × 106 colony-forming
units (CFU)/mL)]. All stock solutions of the tested compounds were dissolved in dimethyl
sulfoxide (DMSO). It was found that DMSO at the final concentration had no influence on
the growth of the tested microorganisms.
Discs impregnated with known concentrations of the tested compounds were placed
on a Muller–Hinton agar plate that had been inoculated or seeded uniformly over the entire
plate with a culture of the bacterium to be tested. The plate was incubated for 18–24 h at
37 ◦C. Followed by incubation, the diameter of the zones of inhibition of growth (including
the 6-mm diameter of the disc itself) was measured and compared with the standard drug.
Supplementary Data
Figures 1–5 are available in the Supplemental Materials.
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