Synthesis and antimicrobial activity of substituted phenophosphazines

Article abstract of DOI:10.1080/10426500801968144

Several Schiff base derivatives of phenophosphazines were synthesized by the reaction of amino phenophosphazines and aromatic aldehydes in equimolar ratio, using methanol as solvent. Possible structures have been proposed on the basis of elemental analysis, IR, and 1H NMR spectral studies. The antibacterial and antifungal activities of the above mentioned Schiff base derivatives have been evaluated against pathogens E. coli, S. typhi, S. aureus, B. subtilis, A. niger, and C. Albicans. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Synthesis and Antimicrobial
Activity of Substituted
Phenophosphazines
S. R. Lokhandwala a & K. R. Desai a
a Department of Chemistry , Veer Narmad South
Gujarat University , Surat, India
Published online: 07 Oct 2008.
To cite this article: S. R. Lokhandwala & K. R. Desai (2008) Synthesis and
Antimicrobial Activity of Substituted Phenophosphazines, Phosphorus, Sulfur, and
Silicon and the Related Elements, 183:11, 2678-2684
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Phosphorus, Sulfur, and Silicon, 183:2678–2684, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801968144
Synthesis and Antimicrobial Activity of Substituted
Phenophosphazines
S. R. Lokhandwala and K. R. Desai
Department of Chemistry, Veer Narmad South Gujarat University,
Surat, India
Several Schiff base derivatives of phenophosphazines were synthesized by the re-
action of amino phenophosphazines and aromatic aldehydes in equimolar ratio,
using methanol as solvent. Possible structures have been proposed on the basis of
elemental analysis, IR, and 1H NMR spectral studies. The antibacterial and anti-
fungal activities of the above mentioned Schiff base derivatives have been evaluated
against pathogens E. coli, S. typhi, S. aureus, B. subtilis, A. niger, and C. Albicans.
Keywords Antibacterial activity; antifungal activity; phenophosphazine; Schiff base
INTRODUCTION
Enzymatically catalyzed phosphate-transfer reactions are numerous
and vital in the metabolism of carbohydrate, lipid and protein, and a
proper concentration of the anion is of primary importance in assuring
an orderly biochemical sequence. Once phosphate gains access to the
body fluids and tissues, it exerts little pharmacological effect. If the ion
is introduced into the gastro-intestinal tract, the absorbed phosphate is
rapidly excreted. If large amounts are given by this route much of it may
escape absorption. This leads to cathartic action and therefore the phos-
phate salts are employed as mild laxatives.1 Owing to the fungicidal,2
antineoplastics,3 antiviral,4 antibacterial,5 and antiarthritic6 activity
of phosphorus and its salts, above phenophosphazine derivatives were
thought to be biologically active. Schiff bases also possess diversified
biological activities like tuberculostatic, fungicidal7 and bactericidal.8
The biological activity of Schiff base derivatives has been attributed
to azomethine linkage. A large number of Schiff bases are known to
Received 24 October 2007; accepted 31 January 2008.
The authors thank RSIC/CIL, Punjab University, Chandigarh for the spectral data
and N. V. Patel College, Vallabh Vidyanagar, for antimicrobial studies.
Address correspondence to S. R. Lokhandwala, Department of Chemistry, Veer Nar-
mad South Gujarat University, Surat 395 007, India. E-mail: snehal sl@yahoo.co.in
2678

Substituted Phenophosphazines
2679
possess useful biological activities like antimicrobial,9,10 fungicidal,11
and bactericidal.12,13
SCHEME 1
RESULTS AND DISCUSSION
10-oxo-5,10-dihydro-10λ5-phenophosphazine-10-ol14 was nitrated uti-
lizing nitric acid and acetic acid, which under pressure and in presence
of Palladium-Carbon catalyst was reduced to 2-amino-10-oxo-5,10-
dihydro-10λ5-phenophosphazin-10-ol. The amino derivative and substi-
tuted aromatic aldehydes were dissolved in methanol in 1:1 molar ratio
to yield 2-[(substitutedbenzylidene)-amino]-10-oxo-5,10-dihydro-10-λ5-
phenophosphazin-10-ol (Schiff base derivatives).The physical and ana-
lytical details of the compounds (01 to 10) are given in Table I.
IR Spectra
The formation of nitro derivative was identified by the appearance
of ν (C N) absorption band at 832−825 cm−1 which disappeared in
amino compound with the appearance of ν (C N) stretching vibra-
tion at 1345−1280 cm−1 present in monoamino derivative. The appear-
ance of strong absorption band of ν (C N) stretching vibration at 1710
cm−1 clearly indicated a Schiff base derivative. In phenophosphazine

2680
S. R. Lokhandwala and K. R. Desai
TABLE I Analytical Data of 2-[(Substituted
Benzylidene)-amino]-10-oxo-5,10-dihydro-10-λ5-
phenophosphazin-10-OL Compounds
Analysis % found ( calcd.)
Comp.
no.
Molecular
formula
Yield M.p.
(%) (◦C)
Molecular
Weight (gm)
C
H
N
O
P
01
02
03
04
05
06
07
08
09
10
C20H17O3N2P
78.2 >300 65.91 4.68
7.68
13.18 8.51
364.334
368.753
413.200
360.346
379.306
426.404
394.360
380.334
334.308
410.360
(65.93) (4.70) (7.69) (13.17) (8.50)
C19H14O2N2PCl 81.0 >300 61.92 3.85
7.62
8.70 8.38
(8.69) (8.40)
7.73 7.51
(7.74) (7.50)
8.86 8.62
(8.88) (8.60)
16.88 8.15
(61.89) (3.83) (7.60)
C19H14O2N2PBr 75.1 298 55.22 3.41
6.77
(55.23) (3.42) (6.78)
83.0 280 70.20 4.78
(70.21) (4.76) (7.78)
63.5 >300 60.15 3.74 11.07
C21H17O2N2P
7.79
C19H14O4N3P
C25H19O3N2P
C21H19O4N2P
(60.16) (3.72) (11.08) (16.87) (8.17)
82.1 262 70.41 4.47 6.56 11.28 7.25
(70.42) (4.49) (6.57) (11.26) (7.26)
75.0 204 63.98 4.85 7.08 16.21 7.87
(63.96) (4.86) (7.10) (16.23) (7.85)
78.2 80 63.14 4.50 7.39 16.85 8.12
(63.16) (4.51) (7.37) (16.83) (8.14)
85.0 110 68.28 4.53
(68.26) (4.52) (8.38)
89.5 >300 61.48 4.68 6.85
C20H17O4N2P
C
19H15O2N2P
21H19O5N2P
8.40
9.58 9.28
(9.57) (9.27)
19.48 7.56
C
(61.46) (4.67) (6.83) (19.47) (7.55)
derivatives characteristic stretching vibration ν (P O)15appeared at
1240−1250 cm−1and ν (P OH)16appeared at 910−1040cm−1 (Table II).
NMR Spectra
1H NMR spectra of 2-amino-10-oxo-5,10-dihydro-10λ5-phenophos-
phazin-10-ol showed a proton signal at δ 4.0 as singlet which dis-
appeared in Schiff base derivative. Instead, a characteristic benzyli-
deneimine proton signal at δ 8.35 as singlet appeared showing the pres-
ence of N CH group. A proton signal at δ 2.0 was observed as singlet
in each compound confirming the presence of P OH. The other signals
were observed in accordance with the substituent groups and confirm-
ing their presence which are summarized in Table IV.
Antimicrobial Activity
The compounds were screened for their antibacterial and antifungal
activities using dry diffusion technique and cup-borer17,18 methods,

2681

2682
S. R. Lokhandwala and K. R. Desai
TABLE III Antimicrobial Screening Data of Imine Derivatives of
Phenophosphazine Compounds
Compound dose : 50 ppm
Zone of inhibition in mm
Comp.
no.
Molecular
formula
S Aureus B Subtilis E coli S typhi C Albicans A niger
01
02
03
04
05
06
07
08
09
10
C20H17O3N2P
7
10
6.5
8
12
7
9.5
11.5
6
6.5
30
9.5
9
10
13.5
17.5
11
6.5
9.5
6
7.5
6
6.5
9
11
5.5
6
7
4.5
4
5
8.5
12.5
16
7
11
9.5
3
6
9
5.5
7
5.5
6
8.5
10.5
5
C19H14O2N2PBr
6.5
7.5
11
C19H14O2N2PCl
C21H17O2N2P
C
19H14O4N3P
C25H19O3N2P
21H19O4N2P
15
8.5
9.5
18
12
5.5
30
C
12
C20H17O4N2P
C19H15O2N2P
C21H19O5N2P
20.5
14.5
8
5.5
—
Streptomycin
(Standard drug)
Streptomycin
Standard drug)
30
30
—
—
—
—
—
31
31
respectively, at concentration 10 mg/mL. Mueller-Hinton Agar and
Sabouraud Dextrose Agar were employed as culture media for these
activities respectively using DMF as solvent. The title compounds were
screened in vitro for their antibacterial activity against S aureus and
B Subtilis (gram positive bacteria) and E coli and S Typhi (gram neg-
ative bacteria) and antifungal activity against Candida albicans and
Aspergillus niger (fungus). The compounds showed potential antibac-
terial activity against B Subtilis. Compound SN-05 showed promising
activity against S Aureus (40%) and Compound SN-08 showed promis-
ing activity against B Subtilis (68.33%) , E coli (36.67%), S Typhi (60%),
A niger (35%), and compound SN-06 showed promising activity against
C albicans (41.67%), respectively, as compared to the standard drugs
(Table III ).
EXPERIMENTAL
All commercial reagents and solvents were dried and distilled by com-
mon methods before use. Melting points were determined by capillary
method and are uncorrected. The operations involving phosphorus com-
pounds were carried out in dry equipment in nitrogen atmosphere. IR
spectra were recorded on Perkin-Elmer 577 grating spectrometer in

Substituted Phenophosphazines
2683
TABLE IV 1H NMR Data of Imine Derivatives of Phenophosphazine
Compounds
Comp. no.
01
Assignments (δ)
1.8(s,1H,P OH);
8.35(s,1H,N CH);3.8(s,1H,N H);3.72(t,3H,C OCH3);6.4−7.6
(m,11H,Aromatic)
02
03
04
2.1(s,1H,P OH);8.36(s,1H,N CH);3.7(s,1H,N H);6.5−7.7(m,11H,Aromatic)
1.9(s,1H,P OH);8.38(s,1H,N CH);3.9(s,1H,N H);6.4−7.7(m,11H,Aromatic)
2.0(s,1H,P OH);7.52(s,1H,N CH);4.1(s,1H,N H); 5.5(s,1H,C H);
6.7(s,1H,C H); 6.5−7.3(m,12H,Aromatic)
05
06
07
1.7(s,1H,P OH);8.38(s,1H,N CH);4.0(s,1H,N H);6.4−8.2(m,11H,Aromatic)
1.9(s,1H,P OH);8.39(s,1H,N CH);4.0(s,1H,N H);6.4−7.3(m,16H,Aromatic)
1.9(s,1H,P OH);8.38(s,1H,N CH);3.9(s,1H,N H);
1.33(t,3H,C OCH3);3.97(d,2H,C CH2);
4.9(s,1H,C-OH);6.4−7.0(m,10H,Aromatic)
08
2.0(s,1H,P OH);8.34(s,1H,N CH);3.92(s,1H,N H);
3.74(t,3H,C OCH3);5.1(s,1H,C OH); 6.5−7.1(m,10H,Aromatic)
1.8(s,1H,P OH);8.36(s,1H,N CH);4.0(s,1H,N H);6.4−7.6(m,12H,Aromatic)
1.9(s,1H,P OH);8.40(s,1H,N CH);3.93(s,1H,N H);
09
10
3.72(t,3H,C OCH3);5.0(s,1H,C OH); 6.5−7.0(m,9H,Aromatic)
KBr discs in the region of 4000–200 cm−1.NMR were recorded on JEOL
FX-90Q spectrophotometer using CDCl3 as solvent.
Synthesis of 2-Nitro-10-oxo-5,10-dihydro-
10λ5-phenophosphazin-10-ol
10-oxo-5,10-dihydro-10λ5-phenophosphazine-10-ol (4.92 g, 20 mmol)
was dissolved in acetic acid (127 mL, 2000 mmol ) at 100◦C. The so-
lution was cooled to room temperature and a mixture of nitric acid (50
mL, 600 mmol) and acetic acid (12.3 mL, 2000 mmol) were added at
such a rate that the temperature of the reaction mixture did not rise
above 20◦C. The reaction mixture was stirred overnight at 15−20◦C,
and the mixture was poured in 1 liter of ice cold water. The reaction
mixture was filtered out and recrystallized from acetic acid (50 mL).
Synthesis of 2-Amino-10-oxo-5,10-dihydro-10λ5-
phenophosphazin-10-ol
2-nitro-10-oxo-5,10-dihydro-10λ5-phenophosphazin-10-ol (5.52 g,
20 mmol) was suspended in methanol and the pH was adjusted to
7.2 using methanolic KOH (10%). The reaction mixture was refluxed
for 6 h at room temperature under pressure in presence of 5% Pd/C

2684
S. R. Lokhandwala and K. R. Desai
(748 mg). The catalyst and the solvent were removed to give solid
which was dissolved in 150 mL of water. The solution was stirred with
charcoal at 60◦C for 45 min and filtered to remove charcoal. The filtrate
was then acidified to pH = 6 using 2N HCl, and the precipitates were
collected over water.
Synthesis of 2-[(4ꢀ-Methoxy-benzylidene)-amino]-10-oxo-5,10-
dihydro-10-λ5-phenophosphazin-10-ol
2-amino-10-oxo-5,10-dihydro-10λ5-phenophosphazin-10-ol ( 4.92 g, 20
mmol) and p-methoxy benzaldehyde (2.4 mL, 20 mmol) were dissolved
in methanol. The reaction was refluxed for 6−8 h in presence of acid cat-
alyst. The reaction mixture was then filtered, washed, dried, and recrys-
tallized from hot methanol (35 mL). The process was repeated using dif-
ferent substituted aldehydes (20 mmol) to obtain different compounds.
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