Synthesis and biological screening of octasubstituted-triphenodioxazines and its sulphur analogues with some novel intermediates

Article abstract of DOI:10.2478/s11532-009-0100-5

Attempts have been made to prepare for the first time the octasubstituted-triphenodioxazines and triphenodithiazines heterocycles by cyclisation of 3,6-dichloro-2,5-bis(2′,4′,5′-trichloroanilino)-1,4-benzoquinone and condensation. This wasfollowed by cycl

Full text of DOI:10.2478/s11532-009-0100-5

Cent. Eur. J. Chem. • 8(1) • 2010 • 51–57
DOI: 10.2478/s11532-009-0100-5
Central European Journal of Chemistry
Synthesis and biological screening of
octasubstituted-triphenodioxazines and
its sulphur analogues with some novel
intermediates
Research Article
Lalchand Heda, Chandresh Pareek*, Dushyant Pareek,
Sonraj Mosalpuri
P. G. Research Laboratories, Department of Chemistry,
S. D. Govt. College, 305901 Beawar, INDIA
Received 2 February 2009; Accepted 9 July 2009
Abstract: Attempts have been made to prepare for the first time the octasubstituted-triphenodioxazines and triphenodithiazines heterocycles by
cyclisation of 3,6-dichloro-2,5-bis(2’,4’,5’-trichloroanilino)-1,4-benzoquinone and condensation. This wasfollowed by cyclisation of
substituted 2-aminobenzenethiol respectively with chloranil and bromanil in ethanolic solution of fused sodium acetate in the presence
of benzoyl chloride in nitrobenzene. Their structures were confirmed on the basis of their chemical and spectral analyses.
Moreover, the biological activity of these compounds was evaluated against the test organisms viz - E.coli, S. aureus, B. subtilis,
M.luteus and C. albicans. These compounds synthesized from 2,4,5-trichloroaniline appeared to possess significant antimicrobial
activities and an explicit correlation between structure and biological activity was also observed.
Keywords: Triphenodioxazines • Triphenodithiazine • Benzoquinones • Antimicrobial activity
© Versita Warsaw and Springer-Verlag Berlin Heidelberg.
1. Introduction
prepare these new classes of heterocycles to study
their antimicrobial activities and determine their MICs
From the literature survey, it appears that the presence
of a halogen atom is crucial for significant activity in
compounds derived from both ‘Nature’ and ‘Chemical
Synthesis’.Theinfluenceofasubstituentsuchaschlorine
on the biological activity of a potential drug agent still has
to be established empirically in biological experiments
designed to detect desired activity. However, chlorinated
organic chemicals in the molecular weight between 200
and 600 constitute an important and indispensable
segment in the arsenal of existing biologically active
chemicals used as pharmaceutical agents [1].
(Minimum Inhibitory Concentrations), MBCs (Minimum
Bactericidal Concentrations) and MFCs (Minimum
Fungicidal Concentrations) against Escherichia coli
(causative for diarrhea), Staphylococcus aureus
(causative for wound infection), Bacillus subtilis,
Micrococcus luteus and Candida albicans (yeast).
The discovery and development of triphenodioxazine
(TPDO), triphenodithiazine (TPDT) and their derivatives
not only place them as a useful coloring materials in
the textile industry [2] for coloring plastics, varnishes,
viscose, rubber, paper [3-5], but also as potential
pharmaceutical agents [6,7]. These have been equally
useful as antibacterial, muscle-relaxant, and hypnotic
agents [8], antifungal [9,10], tranquillizers [11], anti-
inflammatory [12], antitumor [13,14], antipsychotics
A literature study also proposes that almost
no octasubstituted-triphenodioxazine (TPDO) and
triphenodithiazine (TPDT) derivatives have so far been
synthesized and studied. It was thought worthwhile to
* E-mail: pareekcd@yahoo.com
51

Synthesis and biological screening of
octasubstituted-triphenodioxazines and its sulphur
analogues with some novel intermediates
[15], antihistamines [16], and some recent applications in KBr pellets on FTIR 8201 PC spectrophotometer
1
regarding the preparation of nonlinear optical wave and H NMR spectra in DMSO solvent were run on
guiding polymer films [17-19], bearing
a unique 300 MHz FTNMR spectrometer using TMS as an internal
photovoltaic property also [20]. Thus, the industrial standard. The FAB MS were recorded on a JEOL SX
importance of these compounds lies in the fact that they 102/DA-6000 mass spectrometer whereas UV-vis
a find variety of applications in almost every field of life. spectra were recorded in Perkin-Elmer Lambda 15 UV-
A number of TPDO and TPDT compounds have vis spectrophotometer. Elemental analysis was carried
been reported for their multifaceted applications. out on Elemental Analyzer Vario EL 111 Carlo Erba 1108
Therefore, the present communication deals with for all the newly synthesized compounds. Spectral and
the synthesis of new class of octasubstituted TPDO elemental analysis was accomplished at SAIF - CDRI
and TPDT heterocycles with their utilitarian novel (Lucknow). All the reagents were used as obtained
intermediates. The octachlorotriphenodioxazine (1c) and commercially. The purity of the compounds in addition to
its bromo derivative (1d) were prepared by condensing spectral and elemental analyses was checked regularly
2,4,5-trichloroaniline with chloranil / bromanil (tetrahalo- in each step using TLC [60 mesh from Merck].
p-benzoquinone) respectively in the presence of fused
sodium acetate followed by oxidative cyclisation of 2.2. Experimental procedure for the preparation
resulting dianilino-p-benzoquinone (1a,1b). Whereas,
octachlorotriphenodithiazine (2c) and its bromo
derivative (2d) were synthesized in multi-steps through Title compounds 1c and 1d were synthesized in two
condensation followed by cyclisation of 2-amino-3,5,6- steps by a method described by Meister, Lucius and
trichlorobenzenethiol (2b) with chloranil and bromanil Bruning [21]. Some modifications were also employed
of octasubstituted triphenodioxazines 1c
and 1d
respectively.
to get a better yield. The general route for the synthesis
is shown in Scheme 1.
2. Experimental Procedure
2.2.1.Preparationofdianilino-p-benzoquinones1aand1b
2.2.1.1. General procedure
2.1. General
To
a
stirred suspension of chloranil/bromanil
All the melting points were determined by open capillary (0.01 mol) and anhydrous sodium acetate (0.82 g,
method and are uncorrected. IR spectra were recorded 0.01 mol) in ethanol (150 mL), an alcoholic solution
1c, 1d
Scheme 1. The synthetic route for triphenodioxazines (TPDO) and Intermediates
52

L.C. Heda et al.
2.2.2. Preparation of title compounds 1c and 1d
A mixture of dianilino-p-benzoquinone 1a, 1b (0.01 mol)
respectively with nitrobenzene (40 mL) and benzoyl
chloride (20 mL) was stirred under reflux at 800C for 10-
11 hours until the color of the reaction mixture turned
dark. The reaction mixture was cooled down overnight
to room temperature then filtered. The residue obtained
was first washed with 30% ethanol and finally with hot
water to give the desired products. After washing several
times with petroleum ether, products were re-crystallized
from DMF/nitrobenzene to give title compounds 1c and
1d.
of 2,4,5–trichloroaniline (3.93 g, 0.02 mol) was added.
The mixture was refluxed at 550C for 8 hours. The
residue obtained was filtered then washed first with hot
water and finally with 30% ethanol. Products were re-
crystallized from DMF to give the desired intermediates
1a and 1b respectively.
2.2.1.2. 3, 6-dichloro-2, 5-bis (2’, 4’, 5’-trichloroanilino)-1,
4-benzoquinone ‘1a’
It was obtained from chloranil (2.46 g 0.01 mol) in
42% yield; mp. did not melt below 3600C; UV (DMF)
λmax 370 nm; IR (νmax/cm-1): 3256 (NH str), 1655 (>C=O
str), 1576, 1496, 1384, 1353 1281, 1198, 1132, 1083,
1034, 963, 804, 757, 675, 638 cm-1; 1H NMR (DMSO, δ
ppm): 8.28 (s, 2NH), 7.55 (s, 2ArH), 7.27 (s, 2ArH); FAB
MS (2980C) m/z 565[ M+], 566 [M++1]; Anal.Calcd. for
C18H6Cl8N2O2 : C, 38.2; H,1.07; N, 4.95; found: C, 38.9;
H, 1.02; N, 4.99
2.2.2.1. 1, 3, 4, 6, 8, 10, 11, 13–octachlorotriphenodioxazine
‘1c’
It was obtained from ‘1a’ (5.6 g, 0.01 mol) as green
needles in 36% yield; mp. did not melt below 3600C; UV
(DMF) λmax 595 nm; IR (νmax/cm-1): 1655, 1573, 1490,
1424, 1360, 1287, 1195, 933, 872, 827, 666, 639 cm-1;
1H NMR (DMSO, δ ppm) 7.28 (s, 2ArH); FAB MS (2980C)
m/z 561 [M+]; 154(100%); Anal.Calcd. for C18H2Cl8N2O2 :
C, 38.48; H, .36; N, 4.99; found: C, 38.2; H, <1; N, 4.89
2.2.1.3. 3, 6-dibromo-2, 5-bis (2’, 4’, 5’,-trichloroanilino)-1,
4-benzoquinone ‘1b’
It was obtained from bromanil (4.246 g, 0.01 mol) in
36% yield; mp. did not melt below 3600C; UV (DMF) λmax
375 nm; IR (νmax/cm-1): 3238 (NH str), 1642 (>C=O str),
1560, 1475, 1380, 1375, 1285, 1281, 1190, 1195, 1080,
1030, 970, 810, 750, 680, 665 cm-1; 1H NMR (DMSO,δ
ppm): 8.25 (s, 2NH), 7.53 (s, 2ArH), 7.12 (s, 2ArH); FAB
MS (2980C) m/z 678[ M+], 679 [M++1]; Anal.Calcd. for
C18H6Br2Cl6N2O2 : C, 33.02; H, .31; N, 4.28; found: C,
32.08; H, <1; N, 4.32
2.2.2.2. 6, 13- dibromo
- 1, 3, 4, 8, 10, 11 –
hexachlorotriphenodioxazine, 1d
It was obtained from 1b (6.55 g, 0.01 mol) as shining
green colored crystals in 32% yield; mp. did not melt
below 3600C; UV (DMF) λmax 598 nm; IR (νmax/cm-1):
1640, 1565, 1498, 1420, 1360, 1290, 1200, 932, 865,
815, 640, 625 cm-1; 1H NMR (DMSO, δ ppm) : 7.12 (s, 2
Scheme 2. The synthetic route for triphenodithiazine (TPDT) and Intermediates
53

Synthesis and biological screening of
octasubstituted-triphenodioxazines and its sulphur
analogues with some novel intermediates
ArH); FAB MS (2980C) m/z 581 [M+]; 154(100%); Anal.
Calcd. for C18H2Br2Cl6N2O2 : C, 33.22; H, <1; N, 4.30;
found: C, 33.53; H, .24; N, 4.39
2.3.3. Preparation of title compounds [25] 2c and 2d
2.3.3.1. General procedure
To a stirred suspension of chloranil/bromanil (0.1 mol)
and 2-amino-3,5,6-trichlorobenzenethiol 2c (50.6 g,
0.2 mol) in ethanol (50 mL), anhydrous sodium acetate
(8.2 g, 0.1 mol) was added. The mixture was refluxed
at 550C for almost 100 hours, cooled overnight to room
temperature and the residue that precipitated was
filtered then washed with water followed by 30% ethanol
and further crystallized from DMF/acetone to give
the desired title products 2c and 2d. Structures were
determined from the FAB MS, 1H NMR and FTIR of the
respective compounds.
2.3. Experimental procedure for the preparation
of octasubstituted triphenodithiazines, 2c
and 2d
The general route for the synthesis of 2c and 2d is
shown in Scheme 2. Title compounds were synthesized
through following multi steps:
2.3.1. Preparation of 2– amino
trichlorobenzothiazole ‘2a’
-
4, 6, 7-
Compound 2a was synthesized by a method described
by Kaufmann and Kuchler [22], but some modifications
were also employed to reach the desired product with a
better yield.
2.3.3.2. 1, 3, 4, 6, 8, 10, 11, 13–octachlorotriphenodithiazine
‘2c’
It was obtained from chloranil (24.6 g, 0.1 mol) having
lavender colored crystals with 34% yield, mp: did not
melt below 3600C; UV λmax (DMF) 602 nm; IR (νmax/cm-1):
1652, 1564, 1329, 1236, 1113, 893, 742, 795, 679, 588
cm-1; 1H NMR (DMSO, δ ppm): 7.13 (s, 2ArH); FAB MS
(2980C) m/z 593 [M+]; Anal.Calcd for C18H2Cl8N2S2: C,
36.40; H, .34; N, 4.72; S, 10.8; found: C, 36.39; H, <1;
N, 4.71, S, 11.2
To a solution of 2,4,5–trichloroaniline (1.98 g,
0.01 mol) with glacial acetic acid (80 mL) and
ammonium thiocyanate (7.6 g, 0.1 mol), a solution of
cuprous chloride (9.9 g, 0.10mol) was added with 50 mL
of ethanol. The mixture was refluxed for one and half
hours with constant stirring at constant temperature
700C. Approximately 100 mL dilute hydrochloric acid
was added in and temperature was raised to 1000C
and heated again for the next half an hour, then cooled
and neutralized with saturated sodium carbonate. The
residue obtained was washed with water and further
re-crystallized from ethanol to give the product 2a with
42% yield, mp. 2700C; IR (νmax/cm-1): 3250, 1685, 1598,
1640, 1565, 1485, 1450, 1360, 1325, 1309, 1225, 918,
2.3.3.3. 6, 13- dibromo
- 1, 3, 4, 8, 10, 11 –
hexachlorotriphenodithiazine ‘2d’
It was obtained from bromanil (42.4 g, 0.1 mol) having
dark reddish-lavender colored crystals with 31% yield,
mp: did not melt below 3600C; UV λmax (DMF) 610 nm;
IR (νmax/cm-1): 1640, 1560, 1332, 1225, 1109, 1002, 902,
885, 790, 735, 728, 602, 590 cm-1; 1H NMR (DMSO, δ
ppm): 7.02 (s, 2ArH); FAB MS (2980C) m/z 681 [M+];
Anal.Calcd for C18H2Br2Cl6N2S2: C, 31.66; H, .30; N,
4.10; S, 9.39 found: C, 31.95; H, <1; N, 4.18; S, 9.70
1
955, 877, 815, 648, 671, 623 cm-1; H NMR (DMSO, δ
0
ppm) : 7.56 (s, 1ArH); 3.25 (s, 2NH); FAB MS (298 C)
m/z 252 [M+]; 253 [M++1]; Anal.Calcd. for C7H3Cl3N2S :
C, 33.16; H, 1.19; N, 11.05; found: C, 33.23; H, 1.04;
N, 4.39
2.4. Biological screening
2.4.1. Preliminary screening for antimicrobial activity
In the study of antimicrobial activity, the test organisms
used were: Gram negative bacillus (E. coli ATCC25922),
Gram positive bacillus (Bacillus subtilis ATCC6633)
and Gram positive cocci (Staphylococcus aureus
ATCC25923), Micrococcus luteus ‘NRRL B-1018’ and
Candida albicans ‘ATCC10231’ (yeast) collected from
the Microbiology lab of the All India Institute of Medical
Sciences [AIIMS].
2.3.2.Synthesisof2-amino-3,5,6-trichlorobenzenethiol
[23,24] ‘2b’
Compound 2a was refluxed with NaOH or KOH (each 10
times by weight) in water until the evolution of ammonia
ceased. The contents were diluted with ice-cold water,
which was further filtered and neutralized with 5N acetic
acid under vigorous stirring. The residue was extracted
with ether solvent. The ether layer was then evaporated.
After evaporation, the solid was re-crystallized
from ethanol to give 2b with 58% yields, mp. 3250C
(uncorrected); IR (νmax/cm-1) : 3229, 3190, 2330, 2230,
The sample [1a-2d] was dissolved in DMSO
(200 μg mL-1 concentration for bacterial and 200 μg
mL-1 for fungal strains). The test was performed by disc
diffusion assay as per NCCLS, 1997 [26]. The nutrient
agar plates containing an inoculum size of 106 cfu mL-1
for bacteria and RPMI 1640 supplemented with 1.5%
Bacto agar [containing 2×105 spores] for fungi were
1
1580, 1506, 1054, 1021, 928, 796, 711 cm-1; H NMR
(DMSO, δ ppm): 7.35 (s, 1ArH), 4.70 (s, 2NH), 1.39 (s,
1SH); FAB MS (2980C) m/z 227 (100%) [M+]; 228 [M++1];
Anal.Calcd. for C6H4Cl3NS: C, 31.53; H, 1.76; N, 6.13; S,
14.03; found: C, 31.45; H, 1.72; N, 6.12; S, 14.11
54

L.C. Heda et al.
used. Previously prepared impregnated discs (whatman’s 370C for 24 hours and 300C for 3 days respectively. After
filter paper of 6 mm in diameter) of strains were placed incubation, that concentration was noted as MBC (for
aseptically on sensitivity plates with appropriate controls. bacteria) or MFC (for fungi) at which no visible growth
Streptomycin (10 mcg) and Fluconazole (10 mcg) were was observed (Table 2) .
used as standard antibacterial and antifungal antibiotics
respectively. Plates were incubated at 370C for 24 hours
for bacteria and 300C for 3 days for fungal spores. 3. Results and discussion
Sensitivity was recorded by measuring the clean zone of
inhibition in millimeters on agar surface around the disc 3.1. Synthesis
(Table 1).
In this communication, we have synthesized eight new
polychlorinated heterocyclic compounds 1a-1d and
2.4.2. Determination of minimum inhibitory concentration 2a-2d. The synthesis of 1a-1b has been achieved by
(MIC), minimumbactericidalconcentration(MBC)and condensation of 2,4,5-trichloroaniline with chloranil and
minimum fungicidal concentration (MFC)
bromanil respectively, which upon further cyclisation
The MIC was determined by a tube dilution method for yielded the title compounds 1c and 1d respectively. The
each of the test organisms in triplicates. To 0.5 mL of structure of the product formed has been confirmed by
varying concentrations of sample (0 - 200 μg mL-1 for elemental analyses, NMR, IR and Mass spectral studies.
bacterial strains and 0-200 μg mL-1 for fungal strains),
The synthesis of 2c-2d has been achieved by applying
2 mL of nutrient broth was added. Then, a loopful of test a different approach through intermediates 2a and 2b.
organism (previously diluted to 0.5 McFarland turbidity Compound 2a was synthesized from thiocyanation
standards for Bacterial isolates and 106 cfu mL-1 for fungal of aniline with CuCl/NH4SCN in alcohol, which upon
strains) was introduced to the tubes. The procedure hydrolysis with KOH gave 2b. Cyclisation of 2b with
was repeated on the test organisms using standard chloranil/bromanil yielded the title products 2c and 2d
antibiotics streptomycin (for bacteria) and fluconazole respectively. The structures of the products have been
(for fungi). A tube (containing nutrient broth seeded with confirmed again by elemental analyses, NMR, IR and
test organisms) served as a control. The tubes containing Mass spectral studies.
bacterial cultures were then incubated at 370C for
AUVspectralstudyhasalsobeenaccomplishedfor1a-
24 hours for bacteria and 300C for 3 days for fungal 1d and 2c-2d. The λmax valuessuggest that a bathochromic
spores. After incubation the tubes were examined for shift is observed after substituting more electronegative
microbial growth.
Cl by relatively less electronegative Br. The similar
To determine the MBC [27] and MFC [28] for each impression is noticed after replacing oxygen (1c, 1d) by
set of test tubes in the MIC determination, a loopful of sulphur (2c, 2d). Although increments in λmax values are
broth was collected from those tubes which did not show reasonably less as the difference in electronegativity is
any growth and inoculated on sterile nutrient agar (for also less and some sort of conformational rigidity must be
bacteria) and RPMI 1640 (for fungi) by streaking. Plates present in the system.
inoculated with bacteria and fungi were incubated at
Table 1. Results of preliminary antimicrobial activity
Diameter of zone of inhibition (mm)
Compounds
E.coli
S.aureus
ATCC25923
17.44 ± 0.66
09.32 ± 0.42
14.56 ± 0.73
08.74 ± 0.45
06.14 ± 0.20
07.72 ± 0.43
12.63 ± 0.58
09.33 ± 0.67
20.83 ± 0.12
B.subtilis
M.luteus
NRRL B-1018
08.92 ± 0.03
19.35 ± 0.17
18.08 ± 0.14
07.33 ± 0.76
07.22 ± 0.19
09.41 ± 0.11
08.07 ± 0.53
07.61 ± 0.11
21.85 ± 0.05
C.albicans
ATCC10231
06.09 ± 0.12
05.26 ± 0.42
06.52 ± 0.53
05.04 ± 0.94
12.32 ± 0.08
10.55 ± 0.14
06.42 ± 0.29
06.77 ± 0.33
21.05b ± 0.08
ATCC25922
18.82 ± 0.32
16.05 ± 0.07
12.01 ± 0.86
06.42 ± 0.11
13.78 ± 0.53
09.26 ± 0.64
17.34 ± 0.14
05.82 ± -0.96
18.05a ± -0.07
ATCC6633
1a
1b
1c
1d
2a
2b
2c
2d
Ref
15.13 ± 0.49
12.52 ± 0.22
12.63 ± 0.46
08.72 ± 0.11
08.17 ± 0.05
06.38 ± 0.03
21.23 ± 0.69
09.21 ± 0.15
16.82 ± 0.20
a- Streptomycin, b- Fluconazole
55

Synthesis and biological screening of
octasubstituted-triphenodioxazines and its sulphur
analogues with some novel intermediates
-1
Table 2. Results of Minimum inhibitory concentration, MIC, MBC and MFC (µg mL )
Diameter of zone of inhibition (mm)
Compounds
E.coli
S.aureus
B.subtilis M.luteus
C.albicans
MICa
MBCb
28.4
MIC
MBC
11.8
MIC
MBC
15.5
MIC
MBC
>100
2.8
MIC
MBCc
>100
>100
>100
>100
7.4
1a
1b
1c
1d
2a
2b
2c
2d
Ref
30.5**
35.2
12.5
15.8
17.3
22.1
>100
3.6
>100
>100
>100
>100
8.2
33.1
13.2
20.5
45.1
43.6
14.4
12.3
23.3
21.8
9.2
7.6
>100
>100
69.5
>100
>100
66.5
>100
>100
>100
58.4
>100
>100
>100
56.3
>100
>100
>100
12.3*
>100
15.8
>100
>100
>100
11.78
>100
8.5
>100
>100
>100
>100
>100
1.9
>100
>100
>100
>100
>100
0.9
12.6
9.8
33.8
32.2
>100
>100
3.9e
>100
>100
<0.1
>100
31.2d
>100
30.6
>100
0.9
>100
<0.1
a MIC, minimum inhibitory concentration (the lowest concentration that inhibited the bacterial or fungal growth);
b MBC, minimum Bactericidal concentration (the lowest concentration at which no bacterial growth was observed);
c MFC, minimum fungicidal concentration (the lowest concentration at which no fungal growth was observed);
d- Streptomycin;
e- Fluconazole;
* - significant activity.
benzoquinones, aminobenzenethiol and benzothiazole,
as intermediates. Biological screening and values of
MICs for the newly synthesized compounds suggest that
the presence of a Cl atom (like any other substituent) on
these compounds serves as a modulator of activity and
replacing Cl by Br astoundingly diminishes the biological
activity. Hence, it can be stipulated that there is a definite
correlation between structure and biological activity.
Compounds 1a and 2c have significant antimicrobial
activity against E.coli and B. subtilis. Therefore, these
active compounds can be exploited as antibacterial
agents for the production of new drugs. Moreover, λmax
values for TPDO and TPDT heterocycles also make
them good chromogenic compounds.
3.2. Biological screening
One of the purposes for preparing these new classes
of compounds was to evaluate their antimicrobial
activity. The preliminary antimicrobial activities for all the
products have been shown in Table 1. In the terms of
the zone of inhibition, the maximum activity was shown
by 1a against E. coli; 1b, 1c against M. luteus and 2c
against E. coli, S. aureus and B. subtilis whereas the
minimum zone of inhibition was observed by 1d and 2d
against all strains.
Significant activity of 2c was shown against B. subtilis
in comparison to standard antibiotic Streptomycin,
whereas the almost similar zone of inhibition was
depicted by 1a against E. coli and B. subtilis. The
results of MICs and MBCs are summarized in Table 2.
The results revealed that compound 2c was highly
active against B. subtilis and almost similar to moderate
sensitivity was shown by 1b and 1c against M. luteus.
Only compounds 2a and 2b expressed moderate
sensitivity against C. albicans with respect to standard
antibiotic Fluconazole.
Acknowledgements
The authors express their sincere thanks to Dr.
K. G. Ojha, Professor of Applied Chemistry M.D.S.
University, Ajmer (Rajasthan) INDIA for his valuable
criticism and helpful discussions and authors extend
their gratitude to Microbiology Department, J.L.N.
Medical College,Ajmer for providing biological screening
facility. One of the authors Chandresh Pareek is thankful
to SAIF, CDRI Lucknow for the spectral and chemical
analyses and to UGC-CSIR for granting TRF to him.
Based upon the above findings in our study, we can
establish a correlation between structure and biological
activity, where the activity is significantly decreased by
replacing Cl with Br on the title compounds.
4. Conclusion
Four new polychlorinated triphenodioxazine (TPDO) and
triphenodithiazine(TPDT)heterocyclesweresynthesized
from 2,4,5-trichloroaniline with two newly reported
56

L.C. Heda et al.
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