Synthesis, spectral characterisation and anti-microbial activity of novel 3-substituted-2, 4-dihydro-12H-3λ5- tribenzo [f, j, n] [1,5,9, 12,3] dioxadiazaphosphacyclopentadecine-3-selones

Article abstract of DOI:10.3184/030823409X465358

Tris(bromomethyl)phosphineoxide and 2-[(2-[(Z)-1-(2-hydroxyphenyl) methyliden]aminophenyl)i mino]methylphenol have been utilised as precursors in the synthesis of novel pentaco-ordinate dioxadiazaphosphacyclopentadecines[e.g. 3-[(2-hydroxyethoxy)methyl]-2

Full text of DOI:10.3184/030823409X465358

410 RESEARCH PAPER
JULY, 410-413
JOURNAL OF CHEMICAL RESEARCH 2009
Synthesis, spectral characterisation and anti-microbial activity of
novel 3-substituted-2, 4-dihydro-12H-3A5- tribenzo [f, j, n] [1,5,9, 12,3]
dioxadiazaphosphacyclopentadecine-3-selones
S. Subba Reddy, V. Koteswara Rao, E. Dadapeer and C. Naga Raju*
Department of Chemistry, Sri Venkateswara University, Ttrupati - 517 502, India
Tris(bromomethyl )phos ph ineoxi de and 2-[ (2-[ (Z)-1-(2-hyd roxyphenyl) methyl ide nela min ophenyl)i min 0 Imethyl phen 01
have been utilised as precursors in the synthesis of novel pentaco-ordinate
3-[ (2-hydroxyethoxy)methyll-2.4-dihyd ro-12H-3'A 5-tribenzo[ f, j, nil 1,5,9, 12,31di oxadiazaphosphacyclopenta-deci
3-selonel in moderate (overall) yields. The synthesised
OR, lH, Be, 31p NMR and MS) studies and their anti-microbial
dioxadiazaphosphacyclopentadecines
[e.g.
ne-
compounds
were characterised
by elemental and spectral
activity was evaluated.
Keywords: tris (bromomethyl)phosphineoxide, 2-[(2-[(Z)-I-(2-hydroxyphenyl)methylidene] aminophenyl) imino] methylphenol,
dioxadiazaphosphacyclopentadecine, anti-microbial activity
Phosphorus containing macrocycles are interesting molecules
with potential applications in supra-molecular and synthetic
organic chemistry.1,2 They have been synthesised as
phosphineoxides, phosphines, phosphates, phosphonates and
phosphoranes.3 Crown ether analogues of this class have been
examined for their potential catalytic activity and ion carrying
properties. The design of host molecules capable of binding
neutral organic molecules and cations of metals as guests is
an area of rapidly expanding interest. This particular property
enables them to carry certain metal ion species and drug
molecules in the living system to their respective target sites.
Diederich and others have made significant advances in this
field of host-guest complexation.3-6 Increasing interest has
been paid to the chemistry of heterocyclic rings containing
phosphorus due to their unique properties, specific chemical
reactivity and their remarkable potential biological activity.7-12
In view of the various possible applications of phosphorus
heterocycles, macro-heterocycles containing phosphorus,
oxygen and nitrogen have been synthesised.
A strong absorption band in the region 1620-1628 em-I was
attributed to C=N stretching vibration. In IH NMR spectra
of 5a-j the chemical shifts of the aromatic hydrogens of the
phenyl rings were observed as multiplets16in the region i5 6.39-
7.90. The N-H hydrogen resonated as a multiplet at i5 4.72-
5.13. The imine carbons (C-8, C-13) resonated as singlets at
i5 163.5-165.1. Endocyclic methylene carbons (C-2, C-4)
which are directly linked to phosphorus gave doublets at
i5 61.5-62.5 (d, IJp_C = ~130 Hz).17The Exocyclic methylene
carbon (C-16) resonated as a doublet at i5 48.9 to 59.4 (d,
IJp_C = ~128 Hz). 13CNMR chemical shifts of the carbons
of compounds 5a-j were observed in the expected region.
31pNMR resonances for the compounds 5a-j were observed
as singlets in the region i5 69.92-75.79.18
Experimental
Chemicals were obtained from Sigma-Aldrich, Merck and Lancaster,
and used as such without further purification. All solvents (AR or
extra pure grade) used for spectroscopic and other physical studies
were further purified by literature methods.17 All operations were
performed under a nitrogen atmosphere using standard glasswares.
Our present research has led to the synthesis of various 3-
substituted-2,4-dihydro-12H-3'A5-tribenzo [f,j, n] [I, 5,9,12,3]
dioxadiazaphosphacyclopentadecine-3-selones 5(a-j).
Melting points were determined using
a calibrated thermometer
using a Guna Digital Melting Point apparatus. Elemental analyses
were performed by the Central Drug Research Institute, Lucknow,
INDIA. IR Spectra were recorded in Environmental Engineering
Laboratory, Sri Venkateswara University, Tirupati as KEr discs on
a Nicolet 380 FT-IR spectrophotometer. IH and l3C NMR spectra
Results and discussion
The synthesis of various 3-substituted-2, 4-dihydro-12H-3'A5
-tribenzo [f, j, n] [I, 5, 9, 12, 3] dioxadiazaphosphacyclo-
pentadecine-3-selones 5a-j was accomplished in three steps.
Schiffs base (2) was prepared by reacting benzene-I,2-
diamine with two moles of salicylaldehyde in ethanol. It was
further reacted with tris(2-bromomethyl) phosphineoxide (1)
in the presence of triethylamine (TEA) in dry THF to give
3-[(2-bromomethyl-2, 4-dihydro-12H-3'A5 tribenzo[f, j, n][I,
5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-oxide (3).
This was then treated with ethylene glycol to form 3-[(2-
hydroxyethoxy] methy1-2,4,-dihydro-12H-14'A5-tribenzo[fJ, n]
[I, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-oxide
4(a). The compound 4(a) was converted to the corresponding
3-selone 5(a) by reacting with selenium (Se) in THF at 60-
65°C for about 5 h.13The same procedure was employed to
synthesise other members of the series 5b-j.
The characteristic IR, IH, 13C, 31p NMR, physical and
elemental analysis data of the compounds 5a-j are given in
the experimental. Compounds 5a-j exhibited P=Se stretching
frequencies13 in the region 593-610 em-I. Characteristic
absorption bands for P-C(aliphatic)N, -H and O-H stretching
vibrations were observed in the regions 739-757 em-I,
3380-3390 cm-1 and 3410-3471 cm-1 respectively. 14,15
were recorded as solutions in DMSO-d on a Bruker AMX 400 MHz
6
spectrometer operating at 400 MHz for IH, 100 MHz for l3C and
161.9 MHz for 3Ip. The IH and l3C chemical shifts were referenced
to tetramethylsilane and 3Ip chemical shifts to 85% H3P04• LC mass
spectra were recorded on a Jeol SX 102 DN600 Mass spectrometer.
Tris(bromomethyl)phosphine oxide (1) was prepared following the
literature procedure.20
Synthesis of 2-[(2-[(Z)-1-(2-hydroxyphenyl) methylidene} amino-
phenyl) imino}methylphenol (2): An ethanolic (25 mL) solution
of salicylaldehyde (11.0 g, 0.1 mole) was added dropwise to
a
cooled (10°C) and stirred solution of benzene-I, 2-diamine (5.3 g,
0.05 mole) in absolute ethanol (25 mL). The resulting mixture was
refluxed for 2 h. After cooling to room temperature, water (5 mL)
was added and the mixture was stirred for I h. The yellow precipitate
which formed was filtered, washed with water and dried. The progress
ofthe reaction was monitored by the TLC (ethyl acetate: hexane, 2 :8)
analysis. The product was recrystallised from chloroform to afford
yellow needles21 of(2), yield 10.68 g (73.2%), m.p. lSI-152°C.
Synthesis of 3-(2-bromomethyl)-2, 4-tetrahydro-12H-3'A5-tribenzo
[f,j, n} [1,5,9,12, 3] dioxadiazaphosphacyclopentadecine-3-oxide
(3): A solution of tris (bromo methyl) phosphine oxide (1, 1.11 g,
0.003 mole) in 10 mL of dry THF was added over a period of
20 minutes to a cooled (10°C) and stirred solution of 2-[(2-[(Z)-I-(2-
hydroxyphenyl)methylidene] aminophenyl) imino] methylphenol (2,
1.0 g, 0.003 mole) and triethyl amine (0.60 g, 0.006 mole) in 10 mL
of dry THF under nitrogen gas. After completion of the addition,
the temperature of the reaction mixture was raised to room
* Correspondent. E-mail: nagaJaju04@yahoo.co.in
temperature and stirred for
I h to form the intermediate (3).

JOURNAL OF CHEMICAL RESEARCH 2009 411
Se
THF
4(a-j)
Compound
R
Compound
R
17
19
/O~
5f
5a
/O~OH
18
H
I
5b
5g
/N~OH
5h
5c
5d
5i
~
2
r
OH
-N ~20
19
/ \
5j
5e
- N
'--./ N H
Scheme
1
The progress ofthe reaction was monitored by the TLC (ethyl acetate:
hexane, 2:6) analysis. After completion of the reaction, the solution
was filtered to remove triethylamine hydro bromide. The filtrate was
used for the next step of the reaction.
8.42 (s, 2H, -N=CH-), 6.40-7.82 (m, 12H, ArH), 5.45 (m, 4H, P-
CHrO,rom), 4.35 (m, 2H, P-CHrO,liph), 3.61 (t, J = 7.4 Hz, 2H,
-O-CH2-CH2), 3.82 (t, J = 7.4 Hz, 2H, -CH2-CH2-OH), 4.27 (s,
lH, -CHrOl:!), l3C NMR (DMSO-d6) 0 (ppm) 61.5 (d, 'Jp.c= 126Hz,
C-2, C-4), 153.8 (C-6, C-15), 118.2(C-7, C-14), 164.7 (C-8, C-13), 162.7
(C-IO, C-II), 114.2 (C- 6', C-17'), 131.5 (s, C-7', C-16'), 121.2 (C-8',
C-15'), 130.5 (C-9', CoW), 122.6 (C-IO', C-13'), 128.9 (C-II', C-
12'),59.4 (d, 'Jp.c = 131 Hz, C-16), 72.5 (C-18), 61.4 (C-19); 3'p NMR
(DMSO-d6) 070.82; LCMS m/z (%) 527[28, M+'], 482(19), 452(100),
326 (37), 138(15). Anal. Calcd for C2sH2SN204PSe: C, 56.93; H, 4.78;
N, 5.31. Found: C, 56.89; H, 4.76; N, 5.30%.
Synthesis
of 3-[(2-hydroxyethoxy)
methylj-2,
4-dihydro-12H-3"A5-
tribenzo [f,j, n] [1,5,9,12, 3]dioxadiazaphosphacyclopentadecine-
3-selone (Sa): Ethylene glycol (0.18 g, 0.003 mole) was added
at 10°C in the presence of TEA under nitrogen atmosphere
to the intermediate (3) in dry THF (20 mL). After completion
of the addition, the temperature of the reaction mixture was
raised to room temperature and stirred for I h to form the 3-(2-
3- [(2-hydroxyamino
)methylj-2,4-dihydro-12H-3"A5
-tribenzo[f, j, n]
hydroxyethoxy)-2, 4-dihydro-12H-3"A5-tribenzo[f,j,
n] [1,5,9,12,3]
[1, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
(5b):
dioxadiazaphosphacyc1opentadecine-3-oxide
(4a). The progress of
Yield: 59%; m.p. 172-173 °C; IR (KEr) em" 3471 (OH), 3390 (NH),
1627 (C=N), 603 (P=Se), 739 (P-C'lip); 'H NMR (DMSO-d6):
o (ppm) 8.72 (s, 2H, -N=CH-), 6.40-7.82 (m, 12H, ArH), 5.45 (m,
4H, P-CH2-O"om)' 3.35 (m, 2H, P-CH2-NH), 5.13 (m, H, P-CH2-
NH), 3.64 (t, J = 7.2 Hz, 2H, -NH-Q.;G-CH2), 3.84 (t, J = 7.2 Hz,
2H, -CHrQ.;G-OH), 4.30 (s, lH, -CHrOH), l3C NMR (DMSO-d6)
o(ppm)61.8(d, 'Jp.c = 133Hz,C-2,C-4), 153.8(C-6,C-15), 1I8.2(C-7,
C-14), 164.5(C-8,C-13), 162.7(C-IO,C-II), 114.2(C-6' ,C-17'), 131.5
the reaction was monitored by the TLC (ethyl acetate: hexane, 2: 8)
analysis. After completion of the reaction, the solution was filtered
under a nitrogen atmosphere to remove triethylamine hydrobromide.
The filtrate was reacted with selenium's in THF at 60-65 °C for 4 h to
afford the corresponding 13-selone (Sa). The progress of the reaction
was monitored by TLC (ethyl acetate: hexane, 2:8) analysis. After
completion of the reaction, solvent was removed in a rota-evaporator
to obtain crude product. It was recrystallised from 2-propanol to get
pure compound 5(a). The same experimental procedure was adopted
for the preparation of the remaining title compounds 5b-j.
(C-7', CoW),
(C-IO', C-13'), 128.9 (C-Il', C-12'), 55.4 (d, 'Jp.
121.2 (C-8', C-15'), 130.5 (C-9', C-14'), 122.6
130 Hz, C-
c
=
16),74.5 (C-18), 41.4 (C-19); 3'p NMR (DMSO-d6) 0 72.38; LCMS
m/z (%) 526[47, M+'],480(46), 452(100), 326 (18), 138(15),104(37).
Anal. Ca1cd C2sH26NP3PSe: C, 57.04; H, 4.98; N, 7.98. Found: C,
57.01; H, 4.95; N, 7.95%.
3-[(2-hydroxyethoxy
[1, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
Yield: 60%; m.p. 152-153°C; IR (KEr) cm" 3428 (O-H), 1625
(C=N), 596 (p=Se), 742 (P-C'lip); 'H NMR (DMSO-d6): 0 (ppm)
)methylj-2,
4-dihydro-12H-3"A5 -tribenzo [f,j, n]
(Sa):

412 JOURNAL OF CHEMICAL RESEARCH 2009
(DMSO-d6) 0 73.72; Anal. Calcd C27H29N203PSe: C, 60.11; H, 5.42;
N, 5.19. Found: C, 60.08; H, 5.40; N, 5.16%.
3-[(2-aminoethyl)amino]methyl-2,4-dihydro-12H-3A5 -tribenzo[f,j, n]
[1, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
(Sc):
3-(sec-butoxymethyl)-2,4-dihydro-12H-3A5-tribenzo[f,
j, n] [1, 5,
Yield: 60%; m.p. 154-156°C; IR (KEr) cm-' 3385 (NH), 1626
(C=N), 596 (p=Se), 750 (P-C'lip); 'H NMR (DMSO-d6): 0 (ppm)
8.72 (s, 2H, -N=C.!:!-), 6.40-7.82 (m, 12H, ArH), 5.50 (m, 4H,
P-CH2-O,rom)' 4.72 (m, lH, P-CH2-NH) 3.20 (m, 2H, P-CH2-NH),
9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
(Sg): Yield:
58%; m.p. 165-167°C; IR (KEr) cm-' 1625 (C=N), 609 (p=Se),
739 (P-C'lip); 'H NMR (DMSO-d6): 0 (ppm) 8.72 (s, 2H, -N=C.!:!-),
6.40-7.82 (m, 12H, ArH), 5.45 (m, 4H, P-CHrO,rom), 4.31 (m, 2H,
3.24 (t, J = 7.6 Hz, 2H, -NH-CHrCH2),
-CHr Cl:b-NH2), 3.12 (t, J= 7.9 Hz 2H, -CHr~l:b),
3.14 (t, J = 7.6 Hz, 2H,
l3C NMR
P-CHrO-),
2.30 (m, lH, -O-CH-CH2), 1.41 (m, 2H, -CH- CHr
CH3), 0.97 (t, J = 6.4 Hz, 3H, -CHrQh),
1.2 (d, J = 7.1 Hz, 3H,
(DMSO-d6) 0 (ppm) 61.5 (d, 'Jp_c = 130 Hz, C-2, C-4), 153.8 (C-6,
C-15), 118.2 (C-7, C-14), 164.4 (C-8, C-13), 162.7 (C-10, C-11), 114.2
(C- 6', C-17'), 131.5 (C-7', C-16'), 121.2 (C-8', C-15'), 130.5
-CH-CH3), l3C NMR (DMSO-d6) 0 (ppm) 61.5 (d, 'Jp_c = 130 Hz,
C-2, C-4), 153.8 (C-6, C-15), 118.2(C-7, C-14), 164.6 (C-8, C-13), 162.7
(C-10, C-11), 114.2 (C- 6', C-17'), 131.5 (C-7', C-16'), 121.2 (C-8',
C-15'), 130.5 (C-9', C-J41), 122.6 (C-10', C-13'), 128.9 (C-11', C-12'),
59.2 (d, 'Jp_c = 127 Hz, C-16), 76.5 (C-18), 21.4 (C-19), 40.9 (C-20),
17.1 (C-21), 15.4 (C-22); 3'p NMR (DMSO-d6) 0 71.25; Anal. Calcd
C27H29N203PSe: C, 60.11; H, 5.42; N, 5.19. Found: C, 60.08; H,
5.40; N, 5.16%.
(C-9', C-14'), 122.6 (C-10', C-13'), 128.9 (C-11', C-12'), 36.9 (d, 'Jp_
126 Hz, C-16), 55.6 (C-18), 41.2 (C-19); 3'p NMR (DMSO-d6)
c
=
o 70.43; LCMS m/z (%) 525[23, M+'], 480(24), 452(100), 326(37),
138(15), 104(19). Anal. Calcd C2sH27N402PSe: C, 57.15; H, 5.18; N,
10.66. Found: C, 57.13; H, 5.16; N, 10.64%.
3-[ (2-aminoethyl)suljanyl]methyl-2, 4-dihydro-12H-3A5 -tribenzo
[f, j, n}[l, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-
selone (Sd): Yie1d:58%; m.p. 167-168°C; IR (KEr) cm-' 3380
(NH), 1628(C=N), 593 (p=Se), 749 (P-C'lip); 'H NMR (DMSO-d6):
o (ppm) 8.72 (s, 2H, -N=C.!:!-), 6.40-7.82 (m, 12H, ArH), 5.45 (m,
4H, P-Q.:b-O"om), 2.80 (m, 2H, P--Qb-S-), 2.40 (t, J= 7.4 Hz, 2H,
-S--Qb-CH2), 2.60 (t, J = 7.4 Hz, 2H, -CHr CHrNH2), 3.80 (t,
J = 7.8 Hz 2H, - C H r m ) , l3C NMR (DMSO-d6) 0 (ppm) 61.5 (d,
'Jp_c = 128 Hz, C-2, C-4), 153.8 (C-6, C-15), 118.2 (C-7, C-14), 164.5
(C-8, C-13), 162.7(C-10, C-11), 114.2(C- 6', C-17'), 131.5(C-7', C-16'),
121.2 (C-8', C-15'), 130.5 (C-9', C-14'), 122.6 (C-IO', C-13'), 128.9
(C-ll', C-12'), 48.9 (d, 'Jp_c = 130 Hz, C-16), 36.2 (C-18), 38.4 (C-19);
3'p NMR (DMSO-d6) 0 69.92; LCMS m/z (%) 542[33, M+'], 498(100),
452(17),326 (37), 138(15), 104(62). Anal. Calcd C2sH26NP2PSSe: C,
55.35; H, 4.83; N, 7.75. Found: C, 55.33; H, 4.82; N, 7.73%.
3-[(2-hydroxyethyl)suljanyl]methyl-2,4-dihydro-12H-3A5
-tribenzo
[f, j, n] [1, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
(Sh): Yield: 57%; m.p. 147-149°C; IR (KEr) cm-' 3428 (OH),
1620 (C=N), 594(p=Se), 755 (P-C'lip); 'H NMR (DMSO-d6):
o (ppm) 8.72 (s, 2H, -N=C.!:!-), 6.40-7.82 (m, 12H, ArH), 5.45 (m,
4H, P-CH2-O,rom)' 2.80 (m, 2H, P-CH2-S-), 2.40 (t, J = 7.4 Hz, 2H,
-S-CH2-CH2), 2.60 (t, J = 7.4 Hz, 2H, -CHr CHrOH), 4.28 (s,
lH, -CH2-OH), l3C NMR (DMSO-~) 0 (ppm) 62.5 (d, 'Jp_c= 126Hz,
C-2, C-4), 153.8 (C-6, C-15), 118.2 (C-7, C-14), 164.4 (C-8, C-13),
165.0 (C-10, C-11), 114.2 (C- 6', C-17'), 131.5 (C-7', C-16'), 121.2
(C-8', C-15'), 130.5 (C-9', C-J41), 122.6 (C-10', C-13'), 128.9 (C-11',
C-12'), 58.1 (d, 'Jp-c = 129 Hz, C-16), 61.3 (C-18), 70.6 (C-19); 3'p
NMR (DMSO-d6) 0 65.25; Anal. Calcd C2sH2SN203PSSe: C, 55.25;
H, 4.64; N, 5.15. Found: C, 55.21; H, 4.61; N, 5.12%.
3-[(1-ethyl-2-hydroxyamino)methylj-2,
4-dihydro-12H-3 105_
3-(piperazinomethyl)-2,4-dihydro-12H-3A5 -tribenzo[f, j, n}[l, 5,
tribenzo[f, j, n}[l, 5, 9, 12, 3] dioxadiazaphosphacyclopentadecine-
3-selone (51): Yield: 58%; m.p. 152-154°C; IR (KEr) cm-' 3410
(OH), 3390 (NH), 1625 (C=N), 595 (p=Se), 757 (P-C'lip); 'H NMR
(DMSO-d6): 0 (ppm) 8.72 (s, 2H, -N=C.!:!-), 6.40-7.82 (m, 12H,
ArH), 5.45 (m, 4H, P-Q.:b-O,rom), 3.35 (m, 2H, P-Q.:b-NH), 3.13
9, 12, 3] dioxadiazaphosphacyclopentadecine-3-selone
(Se): Yield:
62%; m.p. 158-160°C; IR (KEr) cm-' 3389 (NH) 1628 (C=N), 610
(p=Se), 753(P-C'lip); 'H NMR (DMSO-d6): 0 (ppm) 8.72 (s, 2H,
-N=C.!:!-), 6.40-7.82 (m, 12H, ArH), 5.45 (m, 4H, P--Qb-O,rom),
3.40 (m, 2H, P-Q.:b-N), 2.53 (t, J = 6.7 Hz, 4H, -N-Q.:b-CH2),
(m, lH, -NH-CH-(CH2h),
3H, J = 6.8 Hz, -CHrCfu),
4.30 (s, lH, -CHrOH),
= 131 Hz, C-2, C-4), 153.8 (C-6, C-15), 118.2 (C-7, C-14), 163.5 (C-8,
C-13), 162.7 (C-10, C-11), 114.2 (C- 6', C-17'), 131.5 (C-7', C-16'),
121.2 (C-8', C-15'), 130.5 (C-9', C-J41), 122.6 (C-10', C-13'), 128.9
(C-ll', C-12'), 48.9 (d, J = 128Hz,C-16), 61.5 (C-18), 26.7 (C-19), 11.4
(C-20), 67.4 (C-21); Anal. Calcd C27H30N303PSe: C, 58.49; H, 5.45;
N, 7.58. Found: C, 58.45; H, 5.43; N, 7.56%.
1.54 (m, 2H, -CH-CH2-CH3), 1.10 (t,
2.71 (d, J= 7.2 Hz, 2H, -CH--Qb-OH),
l3C NMR (DMSO-d6) 0 (ppm) 62.5 (d, 'Jp_c
2.30 (m, 4H, -CHr CHrNH), 3.70 (m, lH, -CHrNH-CH2),
l3C
NMR (DMSO-d6) 0 (ppm) 61.5 (d, 'Jp_c = 129 Hz, C-2, C-4), 153.8
(C-6, C-15), 118.2 (C-7, C-14), 164.6 (C-8, C-13), 162.7 (C-10, C-11),
114.2 (C-6', C-17'), 131.5 (C-7', C-16'), 121.2 (C-8', C-15'), 130.5
(C-9', C-14'), 122.6 (C-10', C-13'), 128.9 (C-11', C-12'), 59.4 (d,
'Jp_c = 131 Hz, C-16), 72.5 (C-18, C-22), 61.4 (C-19, C-21); 3'p NMR
(DMSO-d6) 0 71.92; Anal. Calcd C27H29N402PSe: C, 58.80; H, 5.30;
N, 10.16. Found: C, 58.76; H, 5.27; N, 10.14%.
3-(propoxymethyl)-2,4-dihydro-12H-3A5tribenzo[f,j, n}[l,5, 9,12,3]
3-[(1-phenylethoxy )methyl]-2, 4-dihydro-12H-3A5 -tribenzo[f,j, n]
dioxadiazaphosphacyclopentadecine-3-selone
(Sf): Yield: 63%;
[1,5,9,12,3] dioxadiazaphosphacyclopentadecine-3-selone(Sj):
Yield:
m.p. 156-158°C; IR (KEr) cm-' 1625 (C=N), 598 (p=Se), 752
(P-C'lip); 'H NMR (DMSO-d6): 0 (ppm) 8.72 (s, 2H, -N=C.!:!-),
6.40-7.82 (m, 12H, ArH), 5.45 (m, 4H, P-Q.:b-O"om), 4.34 (m, 2H,
P-Q.:b-O-), 2.18 (t, J = 7.4 Hz, 2H, -O-Q.:b-CH2), 1.61 (m, 2H,
64%; m.p. 138-140°C; IR (KEr) cm-' 3420 (OH), 1625 (C=N), 596
(p=Se), 753 (P-C'lip); 'H NMR (DMSO-d6): 0 (ppm) 8.72 (s, 2H,
-N=C.!:!-), 6.39-7.82 (m, 17H, ArH), 5.45 (m, 4H, P-CHrO,rom)'
4.34 (m, 2H, P-CHrO'liph), 4.14 (t, J= 7.4 Hz, lH, -O-CH-C'rom)'
1.98 (d, J = 6.8 Hz, 3H, -CH--Qh), l3C NMR (DMSO-d6) 0 (ppm)
61.5 (d, 'Jp_c = 132 Hz,C-2, C-4), 153.8 (C-6, C-15), 118.2 (C-7,
C-14), 164.4(C-8,C-13), 162.7(C-10,C-11), 114.2(C-6',C-17'), 131.5
(C-7', C-16'), 121.2 (C-8', C-15'), 130.5 (C-9', C-J41), 122.6 (C-10',
C-13'), 128.9 (C-11', C-12'), 59.4 (d, 'Jp_c = 130Hz, C-16), 72.5 (C-18),
-CHrQ.:b-CH2),
1.10 (t, J = 6.2 Hz, 3H, -CHd:Jh),
l3C NMR
(DMSO-d6) 0 (ppm) 61.6 (d, 'Jp_c = 128 Hz, C-2, C-4), 153.8 (C-6,
C-15), 118.2 (C-7, C-14), 164.7 (C-8, C-13), 162.7 (C-10, C-11), 114.2
(C- 6', C-17'), 131.5 (C-7', C-16'), 121.2 (C-8', C-15'), 130.5 (C-9',
C-J41), 122.6(C-10' ,C-13'), 128.9(C-1J1, C-12'), 59.4 (d, 'Jp_c = 131Hz,
C-16), 72.5 (C-18), 35.4 (C-19) 19.4 (C-20), 14.6 (C-21); 3'p NMR
Table 1 Antibacterial activity of the title compounds 5a-j
Compd
Zone of inhibition/mm
Staphylococcus
aureus
Escherichia coli
100 ppm"
50 ppm"
25 ppm"
100 ppm"
50 ppm"
25 ppm"
5a
5b
5c
5d
5e
5f
5g
5h
11
8
10
6
14
13
7
10
12
11
9
8
6
8
6
12
10
12
12
14
13
9
10
10
12
12
8
7
8
4
5
4
6
6
4
5
8
5
6
9
11
4
8
10
8
12
11
8
8
7
4
5
4
6
5
8
5
6
5i
5j
6
8
8
Penicillinh
6
"In DMF.
hReferencecompound.

JOURNAL OF CHEMICAL RESEARCH 2009 413
Table 2 Antifungal activity" of the title compounds 5a-j
Compd.
Zone of inhibition/mm
Aspergillus niger
Helminthosporium
oryzae
100 ppm"
50 ppm"
25 ppm"
100 ppm"
50 ppm"
25 ppm"
5a
5b
5c
5d
5e
5f
5g
5h
10
11
12
13
10
9
10
9
14
8
7
8
9
10
7
5
6
8
11
9
10
5
4
6
8
5
3
4
6
9
6
5
11
11
12
14
12
12
9
11
13
9
6
9
10
10
8
10
8
9
5
5
7
4
7
9
4
5
8
5i
5j
12
7
10
4
5
Griseofulvnb
12
12
"In DMF.
bReference compound.
21.3 (C-19), 81.3 (C-20), 127.1 (C-21,C-25), 128.9 (C-22, C-24), 128.4
(C-23); 31p NMR (DMSO-d6) i575.79; Anal. Calcd C31H29N203PSe:
C, 63.38; H, 4.98; N, 4.77. Found: C, 63.35; H, 4.96; N, 4.75%.
with that of the reference compound. The majority of the compounds
exhibited high activity against fungi. The compounds 5d and 5i
showed higher activity against H oryzae and A. niger respectively,
when compared with that of the standard and warrants further testing
to determine their minimum inhibitory concentrations as well as their
cytotoxicity.
Antibacterial activity
Antibacterial activity of all the compounds 5a-j was assayed22
against Staphylococcus aureus ATCC-25923 (Gram positive)
and Escherichia coli ATCC-25922 (Gram-negative) at three
different concentrations (100, 50 and 25 ppm) in DMF (Table 1).
The compounds were diluted in DMF for bioassay. Solvent control
was included although no antibacterial activity has been noted in the
solvent employed. Penicillin G (Hi-media) controls (20 flg mL-I)
were included to compare with compounds 5a-j. All samples were
tested in triplicate and average results were recorded.
We thank Dr P. Chandra Mohan Reddy, Deptartment of
Microbiology, S.V. College ofP.G Studies, Kadapa. India, for
the anti-microbial studies.
Received 14 March; accepted 16 June 2009
Paper 09/0495 doi: 10.3184/030823409X465358
Published online: 14 July 2009
Disc diffusion bioassay
For the bioassay a suspension of approximately 1.5 x lOS bacterial
cells per mL was used. The bacterial suspension 1.5 mL was
uniformly spread on nutrient agar (Hi-media) in 12 x 1.2 cm glass
Petri dishes, left aside for 15 min and excess of suspension was then
drained and discarded. For the agar disc diffusion method, the test
compound was introduced onto the disc and then allowed to dry.
The disc was completely saturated with the test compound. Then the
disc was introduced onto the upper layer of the medium seeded with
bacteria. The Petri dishes were incubated at 35°C for 24 h. Bioactivity
was determined by measuring the diameters of the inhibition zones
in mm. The compounds 5a-j were made up at 25, 50 and 100 flg
mL-I concentrations for bio-activity screening by the disc diffusion
method. Each test was done in triplicate and the mean diameter of the
inhibition zones was calculated. Controls included the use of solvent
without test compounds although antibacterial activity was not
noted for the solvent employed in the test. The minimum inhibitory
concentration (MIC) was determined for the compounds 5a-j
used at concentrations of 0.1-5.6 mg mL-I. Specifically 0.1 mL of
standardised inoculum (1-2 x 107CFU mL-I) was added to each tube.
The tubes were incubated aerobically at 35°C for 24 h. Two control
tubes were maintained for each test batch. These included antibiotic
control (tube containing the growth medium without inoculum) and
organism control (tube containing the growth medium, physiological
saline and the inoculum). The lowest concentration (highest dilution)
of the compounds 5a-j that produced no visible bacterial growth
(no turbidity) when compared with the control tubes was considered
as MIC. The highlight is that majority of the compounds exhibited
high activity against both bacteria and two compounds (5e and Sf)
were more effective than the standard compound. Penicillin was
tested as a standard reference to compare the activities of these
compounds.
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Antifungal activity
The compounds 5a-j were screened for their antifungal activity
(Table 2) against Aspergillus niger and Helminthosporium oryzae
along with standard fungicide griseofulvin at three different
concentrations (100, 50 and 25 ppm) in DMF23. All the compounds
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