Synthesis and antimicrobial activity of novel 2-alkyl/arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihydro-2h-1, 3,2-benzoxazaphosphorine-2-oxides

Article abstract of DOI:10.1002/jhet.5570390529

Novel 2-alkyl/arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihydro-2H-1, 3,2-benzoxazaphosphorine-2-oxides (IV) have been synthesized from reactions of 2-cyclohexylaminomethyl-4-t-butylphenol I [8c] with various dichlorophosphinyl carbamates (III) [8a-b] in dry toluene in the presence of triethylamine at 40-50°C. All the title compounds (IVa-j) at reflux temperature are degraded to 2-amino-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihydro-2H-1,3, 2-benzoxazaphosphorine-2-oxide (IVk) exclusively. The structures are determined by ir, nmr and mass spectral studies. They were screened for antifungal activity against Penicillium notatum, Aspergillus niger and Helminthosporium sps, and antibacterial activity on Escherchia coli, Staphylococcus aureus and Pseudomonas aeruginosa. A few of them possess significant activity.

Full text of DOI:10.1002/jhet.5570390529

Sep-Oct 2002
Synthesis and Antimicrobial Activity of Novel
2-Alkyl/Arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-
dihydro-2H-1,3,2-benzoxazaphosphorine-2-Oxides
1039
Y. Hari Babu, P. Vasu Govardhana Reddy, C. Suresh Reddy*,
C. Devendranath Reddy and P. Uma Maheswari Devi^
*Department of Chemistry, Sri Venkateswara University, Tirupati - 517 502, India
^Department of Microbiology, Sri Padmavathi Mahila Viswavidyalayam, Tirupati, India
Received March 21, 2002
Novel 2-alkyl/arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihydro-2H-1,3,2-benzoxaza-
phosphorine-2-oxides (IV) have been synthesized from reactions of 2-cyclohexylaminomethyl-4-t-butylphenol
I [8c] with various dichlorophosphinyl carbamates (III) [8a-b] in dry toluene in the presence of triethylamine at
40-50 °C. All the title compounds (IVa-j) at reflux temperature are degraded to 2-amino-6-(1,1-dimethylethyl)-
3-cyclohexyl-3,4-dihydro-2H-1,3,2-benzoxazaphosphorine-2-oxide (IVk) exclusively. The structures are
determined by ir, nmr and mass spectral studies. They were screened for antifungal activity against Penicillium
notatum, Aspergillus niger and Helminthosporium sps, and antibacterial activity on Escherchia coli,
Staphylococcus aureus and Pseudomonas aeruginosa. A few of them possess significant activity.
J. Heterocyclic Chem., 39, 1039 (2002).
Introduction.
Cyclocondensation of IIIa-j in situ with 2-cyclohexyl-
aminomethyl-4-t-butylphenol (I) [8c] in the presence of
triethylamine at 40-50 °C, yielded the title compounds
(IVa-j). Thin layer chromatography was employed to fol-
low the progress of the reaction. Filtration of insoluble tri-
ethylamine hydrochloride followed by evaporation of the
solvent from the filtrate afforded crude compounds (IV)
which on recrystallization from ethanol gave analytically
pure samples. Primary and secondary alcohols reacted
readily with isocyanatophosphonic dichloride, but t-butyl
alcohol failed to react under the same conditions.
Large number of cyclophosphamide and its benzannu-
lated derivatives are found to possess significant antitu-
mour activity [1-6]. Certain carbamate derivatives are
highly anticholinergic and poison animals and insects
effectively. They exhibit direct effect on acetylcholine
receptors because of their pronounced structural resem-
blance to acetylcholine [7]. In view of the possible biolog-
ical and industrial potential for applications of substituted
carbamate heterocycles, the title compounds (IVa-j) were
synthesized.
All of the alkyl/arylcarbamato compounds (IVa-j) are
readily soluble in polar organic solvents and melt within
the 120-172 °C range. Interestingly on reflux in toluene,
they suffered thermal degradation to give only one prod-
uct, 2-amino-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-
dihydro-2H-1,3,2-benzoxazaphosphorine-2-oxide (IVk)
(Scheme 2).
Results and Discussion.
The synthetic route (Scheme-1) involves the addition of
isocyanatophosphonic dichloride (II) [8a] to various alco-
hols/thiols at -10 °C under inert, anhydrous
31
Reaction yields, elemental analysis, ir [9] and P nmr
Compd.
R
Compd.
R
1
13
data are given in Table 1. H, C nmr and mass spectral
data for some members of IV are presented in Tables 2, 3
and 4 respectively. Their proton nmr spectra (Table 2)
exhibited signals in the δ 6.72-7.36 range accounting for
the aromatic protons of benzoxazaphosphorine and
phenethyl moieties in III. In compounds IVa-j the 4(H)
protons resonated as two multiplets at δ 3.49-4.27 and δ
3.78-4.41 respectively. This indicates that the methylene
IVa
IVb
IVc
IVd
IVe
OCH
OCH CH
OCH CH Cl
OCH(CH )
IVf
IVg
IVh
IVi
OCH CH(CH )
2 3 2
3
OC H
2
3
6 11
OCH C H
2 6 5
OCH CH C H
SCH CH CH
2 2 3
2
2
3 2
2 2 6 5
OCH CH CH CH
IVj
2
2
2
3
Conditions, in dry toluene to afford the corresponding
dichlorophosphinyl carbamates (IIIa-j) [8b].

1040
Y. H. Babu, P. V. G. Reddy, C. S. Reddy, C. D. Reddy and P. U. M. Devi
Vol. 39
Table 1
31
Physical, IR and P NMR Spectral Data of 2-Alkyl/arylcarbamato-6-(1,1-dimethylethyl)-
3-cyclohexyl-3,4-dihydro-2H-1,3,2-benzoxazaphosphorine-2-oxides (IVa-j)
-1
31
Compd.
m.p
(°C)
Yield [a]
(%)
Molecular
Formula
Elemental Analysis
Found/(Calcd)
IR (cm )
C=O
P
P-NH
P=O
NMR
C
H
N
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
158-160
160-162
129-130
120-121
128-129
123-125
120-122
131.33
75.7
65.9
76.5
60.7
57.8
75.8
66.9
59.6
51
C
C
H
O N P
59.81 7.60
7.42
3075
3083
3170
3182
3085
3155
3195
3095
3167
3171
1727
1720
1763
1722
1725
1728
1724
1719
1720
1718
1270
1269
1261
1260
1260
1272
1260
1262
1263
1298
-1.11
-1.37
-1.99
-1.66
-1.56
-1.47
-1.34
-1.00
-1.23
-2.09
19 29
4 2
(60.0) (7.63) (7.36)
60.67 7.71 7.12
(60.9) (7.86) (7.08)
56.34 6.70 6.42
(56.0) (7.0) (6.53)
61.93 8.24 6.71
(61.7) (8.0) (6.86)
62.35 8.03 6.61
(62.5) (8.2) (6.63)
62.24 8.36 6.58
(62.5) (8.2) (6.63)
64.01 8.12 6.12
(64.2) (8.2) (6.25)
65.33 7.01 6.21
(65.7) (7.2) (6.41)
66.52 7.56 5.78
(66.3) (7.4) (5.95)
57.31 7.40 6.20
(57.2) (7.5) (6.36)
H
O N P
4 2
20 31
C
H O N PCl
20 30 4 2
C
H O N P
21 33 4 2
C
C
C
C
C
H O N P
22 35 4 2
H
O N P
4 2
22 35
H
O N P
4 2
24 37
H
O N P
4 2
25 33
140-141
170-172
H O N P
26 35 4 2
IVj
58.2
C H O N PS
21 33 3 2
[a] Recrystallized from ethanol.
3
protons at C-4 are magnetically non-equivalent due to their
axial and equatorial orientations in the six-membered chair
conformation of the benzoxazaphosphorine ring [10]
(Figure 1).
The singlet integrating for 9H in the region δ 1.17-1.25
is assigned to the t-butyl protons. The multiplates, in the δ
1.41-2.41 region, are attributed to the cyclohexyl protons.
The exocyclic P-NH-CO proton of IVb-j is observed in
the down field region as a broad signal at δ 8.90-9.94. But
the same proton in IVa resonated as a doublet at δ 9.26 (J =
region at δ 116.6 - 18.1 ( J = 7.2 - 7.8 Hz) is assigned to
C(8). Another doublet at δ 123.9-124.6 (J = 7.0-7.3 Hz) is
ascribed to C(10). The chemical shifts at δ 122.8-124.0,
145.8-147.2 and 125.2-128.7 are attributed to C(5), C(6)
and C(7) respectively. The C(4) resonating at δ 42.7-44.6.
The low intense signal at δ 34.0-34.6 and δ 31.1-31.8 are
for C(11) and C(12) respectively. The signal at δ 55.1-55.8
is assigned to C(1") for all compounds, except IVh, where
2
it resonates as a doublet with J = 4.4 Hz. C(4"), C(2") and
C(6"), C(3") and C(5") of cyclohexyl moiety exhibited sig-
nals in the expected range [13] which are given in Table 3.
The carbonyl carbon C(1') of the carbamate function res-
onated in the range of 146.3-159.0 ppm. The C(2') chemi-
cal shifts of the carbamate function appears downfield (-10
ppm) when compared to the signals of the corresponding
carbon chemical shifts in the respective free alcohols [11].
The resonances of other carbon atoms of the carbamate
9.6 Hz). The NH proton signals were confirmed by D O
2
exchange experiments. It is of interest to observe that the
protons of the carbamate function resonated downfield
when compared to those of the corresponding protons in
the free alcohols [11]. They are also not experiencing any
coupling with the phosphorus atom.
31
moiety appeared in the expected regions (Table 3). P nmr
signals [14] of these compounds (IVa-j) appeared in the
range -1.00 to -2.09 ppm (Table 1).
The EI mass spectra for IVa-j (Table 4) is rationalized in
+
the Scheme 3. Appearance of M at the appropriate molec-
+.
+
ular weights, [M-(R-OH)] at m/z 348, [M-(NHCOOR)]
+
at m/z 305, [M-(COOR)+H] at m/z 322 and [M-
(C H )] at m/z 325 with the benzoxazaphosphorine-2-
+
13
The proton-decoupled C nmr chemical shifts of IVa-j
6
11
oxide moiety conclusively establishes their proposed
structures [15,16] and these ions may be used as diagnostic
daughter ions of these compounds for their monitoring in
are given in Table 3. The oxygen-bearing carbon C(9) res-
onated as a doublets in the downfield region at δ 147.1-
2
153.6 ( J = 7.6-7.8 Hz) [12]. The doublet in the upfield

Sep-Oct 2002
Synthesis and Antimicrobial Activity
1041
Table 2
1
H NMR Chemical Shift (J in Hz) Data [a] of 2-Alkyl/arylcarbamato-6-(1,1-dimethyl-ethyl)-3-cyclohexyl-3,4-dihydro-2H-
1,3,2-benzoxazaphosphorine-2-oxides (IVa-j) [b]
Compound t-butyl-H Cyclohexyl-H Methylene-H
Ar-H
-NH-
OR-H
3.46 (s, 3H, OCH )
IVa
IVb
IVc
IVd
IVe
1.17
(s, 9H)
1.25
(s, 9H)
1.20
(s, 9H)
1.18
1.41-1.66
(m, 11H)
1.55-1.83
(m, 11H)
1.46-1.67
(m, 11H)
1.46-2.1
(m, 11H)
1.53-1.71
(m, 11H)
4.13-4.19 (m, H )
4.28-4.32 (m, H )
4.27-4.32 (m, H )
4.41-4.44 (m, H )
4.14-4.19 (m, H )
4.25-4.29 (m, H )
3.95-4.19 (m, H )
4.25-4.30 (m, H )
6.72-7.36
(m, 3H)
6.95-7.32
(m, 3H)
6.81-7.24
(m, 3H)
6.74-7.18
(m, 3H)
6.8-7.6
9.26
(d, J=9.6 Hz)
9.2
(brs, 1H)
9.18
(brs, 1H)
9.16
(brs, 1H)
9.66
(brs, 1H)
b
3
a
4.03 (q, 2H, OCH )
2
b
1.14 (t, 3H, CH )
a
3
4.64 (t, 2H, OCH )
2
b
4.14 (t, 2H, CH Cl)
a
2
4.64 (m, 1H, OCH)
b
(s, 9H)
1.21
1.02 (d, 6H, 2CH )
a
3
3.78 (brs, 2H)
3.85 (m, 2H, OCH )
2
(s, 9H)
(m, 3H)
1.93 (m, 2H, CH )
2
1.15 (m, 2H, CH )
2
0.86 (brs, 3H, CH )
3
IVf
1.22
(s, 9H)
1.42-1.69
(m, 11H)
3.96-4.21 (m, H )
6.79-7.23
(m, 3H)
9.20
(brs, 1H)
3.61 (d, 2H, OCH )
1.66-1.69 (m, 1H, CH)
b
2
4.21-4.30 (m, H )
a
0.85 (d, 6H, 2CH )
3
IVg
IVh
IVi
1.23
(s, 9H)
1.23
(s, 9H)
1.21
(s, 9H)
1.25
1.43-1.73
(m, 11H)
1.44-1.76
(m, 11H)
1.41-1.72
(m, 11H)
1.42-1.77
(m, 11H)
4.01-4.13 (m, H )
6.87-7.24
(m, 3H)
6.9-7.3
(m, 8H)
6.8-7.2
(m, 8H)
7.0-7.2
(m, 3H)
9.48
(brs, 1H)
9.55
(brs, 1H)
9.03
(brs, 1H)
9.78
4.87 (s, 1H, CH)
1.21-1.60 (m, 10H, C H )
5.06 (s, OCH )
2
b
4.20-4.29 (m, H )
a
6 10
3.40-3.49 (m, H )
b
3.95-4.05 (m, H )
a
3.92-3.96 (m, H )
4.8 (t, 2H, OCH )
2
b
3.98-4.02 (m, H )
2.78 (t, 2H, CH )
a
2
IVj
4.00-4.10 (m, H )
2.65 (m, 2H,SCH )
2
1.52-1.59 (m, 2H, CH )
b
(s, 9H)
4.15-4.26 (m, H )
(brs, 1H)
a
2
0.94 (t, 3H,CH )
3
[a] Data in parentheses are coupling constants, J in Hz; [b] Recorded in DMSO-d .
6
Table 3
13
C NMR Chemical Shift Data [a] of Compounds 2-Alkyl/arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihydro-2H-1,3,2-benzoxazaphosphorine-
2-oxides (IVa-j) [b]
Com-
pound
Carbon Number
C C-1' C-2" C-3" C-4" C-1' C-2' C-3' C-4' C-5' & 7' C-6
11 12
C
C
C
C
C
C
C
C
4
5
6
7
8
9
10
& C-6" & C-5"
& 8'
IVa
43.4 123.8 146.4 125.4
117.7
148.2
124.5 34.4 32 55.2 31.0 25.9
25.2 155.1 52.5
(d, 5.2)
-
-
-
-
-
-
-
-
-
-
-
-
-
(d, J = 7.2 Hz) (d, 7.7) (d, 7.3)
IVb 43.3 123.9 146.3 125.3
IVc 43.5 124 146.5 125.2
IVd 43.3 123.9 146.3 125.3
117.7
(d, 7.3)
117.7
(d, 7.3)
117.7
(d, 7.2)
117.8
(d, 7.3)
117.6
(d, 7.3)
117.6
(d, 7.2)
118.1
(d, 7.3)
116.8
(d, 7.5)
116.7
148.1
(d, 7.6)
148.2
(d, 7.6)
148.2
124.4 34.4 32 55.1 31.5 25.8
124.5 34.4 32 55.6 31.5 25.8
124.4 34.4 32 55.1 31.5 25.8
25.2 154.5 55.1 14.4
25.2 154.3 63.2 21.8
25.2 146.3 61.3 14.4
-
-
-
(d, 7.7) (d, 7.3)
IVe
IVf
43.3 123.6 146.3 125.4
43.7 123.6 146.5 128.5
148.3
(d, 7.6)
147.6
(d, 7.7)
153.6
(d, 7.8) (d, 7.2)
148.5
(d, 7.8) (d, 7.0)
145.9
123.9 34.3 32 55.3 31.4 25.7
25.3 146.3 68.8 43.4 21.8
24.3 146.4 68.7 44.8 24.1
-
-
124.6 34.5 31 55.5 31.1 24.4
124.6 34.3 31 55.4 31.1 29.7
IVg 44.6 122.8 146.2 128.7
IVh 44.2 123.5 147.2 125.7
28.8
159 60.2 48.8 30.3
(d, 5.2)
28.9
124.3 34.3 32 55.8 31.2 25.8
25.2 154.5 67.9 135.8 128.7 127.7 127.3
(d, 4.6)
24.7 152.8 65.3 34.0 136.2 127.8 127.4
(d, 4.4)
IVi
IVj
42.7 122.9 145.9 125.6
43.9 123.6 145.8 125.6
124.3
34 32 54.4 31.4 24.9
125 (C ')
7
148.7
124.3 34.6 32 55.5 31.3 25.8
25.0 154.3 29.3 25.0 14.1
-
-
(d, 7.6)
(d, 7.7)
[a] Data in parentheses are coupling constants, J in Hz; [b] Recorded in DMSO-d .
6

1042
Y. H. Babu, P. V. G. Reddy, C. S. Reddy, C. D. Reddy and P. U. M. Devi
EXPERIMENTAL
Vol. 39
bio and eco systems.
The melting points were determined on a Mel-Temp apparatus
and are uncorrected. Elemental analyses were performed at the
Central Drug Research Institute, Lucknow, India. IR spectra were
recorded as KBr pellets and Nujol mulls on a Perkin-Elmer 283
1
13
31
unit. The H, C, and P NMR spectra were taken on AMX 400
1
MHz spectrometer operating at 400 MHz for H, 100 MHz for
C and 161.9 MHz for P. Compounds were dissolved in
13
31
1
DMSO-d , and chemical shifts were referenced to TMS ( H and
6
13
31
C) and 85% H PO ( P). Mass spectral data (EI) were col-
3
4
lected on a JEOL JMSD-300 instrument at 70 eV.
Synthesis of 2-Isopropylcarbamato-6-(1,1,-dimethylethyl)-3-
cyclohexyl-3,4-dihydro-2H-1,3,2-benzoxazaphosphorine-2-
oxide (IVd).
A solution of isopropyl alcohol (0.60 g, 0.01 mole) in 20 ml
dry toluene is added drop wise during 30 minutes to a cold solu-
tion (-10 °C) of dichloro isocyanatophosphine oxide (II, 1.6 g,
0.01 mole) in 20 ml of dry toluene. After the addition, the tem-
perature of the reaction mixture is slowly raised to room temper-
ature and stirring is continued for another 2 hours. This reaction
Table 4
Mass Spectral Data of Important Ions of IVd, IVh and IVj
Compound
m/z (Relative Abundance)
+
IVd
IVh
IVj
408 (25, M ), 348 (14), 325 (9), 322 (3), 305 (60), 279 (15), 265 (34), 243 (18), 239 (49), 228 (18), 147 (21) 91 (76), 79 (90).
+
456 (9, M ), 348 (25), 325 (7), 305 (80), 323 (14), 280 (41), 279 (15) 265 (37), 243 (29), 239 (28), 228 (36), 108 (57), 91 (70), 79 (92).
440 (3, M ), 348 (11), 323 (8), 305 (40), 280 (42), 279 (14), 261 (38), 243 (16), 228 (14), 163 (60), 108 (51), 91 (67), 56 (78).
+
Antimicrobial Activity.
mixture is added drop wise to a cold (0 °C) solution of I (2.61 g,
0.01 mole) and triethylamine (2.02 g, 0.02 mole) in 30 ml of dry
toluene. After the addition, the temperature of the reaction mix-
ture is slowly raised to 40-50 °C and stirring is continued for an
additional five hours. The completion of the reaction is moni-
tored by thin layer chromatography (TLC) in the 1:6 mixture of
ethyl acetate and n-hexane as mobile solvent. The triethylamine
hydrochloride is filtered and the solvent from the filtrate is evap-
orated under reduced pressure. The residue is washed with water
followed by chilled 2-propanol and recrystallized from ethanol to
afford IVd, yield 2.47 g (60.7%), mp: 120-121 °C. Other mem-
bers of IV are prepared by this procedure. Physical and spectral
data of IVa-j are provided in Tables 1-4.
The compounds IVa-j and IVk (Table 5) were screened
for their antinfungal activity against Penicillium,
Helmenthosporium and Aspergillus niger by comparing
with standard antibiotics Griseofulvin-30, 25 and Nystatin-
31 mm respectively. Agar-well method [17] was followed
for screening the compounds at three different concentra-
tions (60, 80, 100 µg/disc). Their antibacterial activity was
evaluated according the disc-diffusion method [18,19] at
three different concentrations against Escherchia coli,
Pseudomonas aeruginosa and Staphylococcus aureus by
comparing with standards Tetracyclin-13 mm,
Gentamycin-14 mm and Vancomcyin-12 mm respectively.
The title compounds showed more antifungal activity when
compared with antibacterial activity.
The compounds IVb-d, IVg, IVh, IVj and IVk were
more effective against S. aureus and the compound IVh,
IVi and IVj were effective against E. coli and the com-
pounds IVe, IVf, IVg, IVh, IVi and IVj showed more
antibacterial activity against Pseudomonas aeruginosa.
However all these compounds exhibited more antifungal
activity against Penicillium notatum, Aspergillus niger and
Helminthosporium sps.
Preparation of 2-Amino-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-
dihydro-2H-1,3,2-benzoxazaphosphorine-2-oxide (IVk).
A solution of IVd (4.08 g, 0.01 mole) in 30 ml of dry toluene
was pyrolised vigorously for 1 hour, the solution was cooled
immediately and solid product is collected by filtration. The solid
was washed with water and recrystallized from 2-propanol-
methanol (3:1) to afford pure compound IVk, yield 2.01 g
-1
(62.5%), mp 130-132 °C; ν
(nujol) cm : 1261 (P=O), 3179
max
1
(P-NH), H NMR: 4.06 (d, H J = 7.9 Hz, CH ), 3.89 (d, H , J =
a
2
b
20 Hz, CH ), 7.0-7.35. (m, 3H, Ar-H), 9.5 (d, 2H, J = 9.8 Hz,
2
31
NH ); P NMR: -1.01.
2
Anal. Calcd. for C H O N P: C, 63.35; H, 8.38; N, 8.69.
17 27
2 2
Found: C, 63.19; H, 8.34; N, 8.66.

Sep-Oct 2002
Synthesis and Antimicrobial Activity
1043
Table 5
Antimicrobial Activity of 2-Alkyl/Arylcarbamato-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-
dihydro-2H-1,3,2-benzoxazaphosphorine-2-oxides
Zone of Inhibition (mm) [b]
Compound
Concen-
tration
µg/disc
Fungi
Helmentho-
sporium
Bacteria
Escherchia
coli
Penicillium
Aspergillus
niger
Staphylococcus
aureus
Pseudomonas
aeruginosa
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
60
80
100
60
80
100
60
80
100
60
80
100
60
80
100
60
80
100
60
80
100
60
80
100
60
1
2
4
-
4
6
9
11
15
4
6
10
7
10
12
-
3
5
-
7
5
7
9
2
4
6
2
7
10
5
7
11
5
6
8
1
2
4
4
6
10
3
5
7
4
6
8
1
3
4
4
6
3
5
7
5
7
10
3
4
7
5
6
9
7
9
13
6
9
10
3
4
6
3
5
7
3
6
7
5
7
9
4
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
7
-
4
6
-
3
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
3
6
-
-
5
-
3
6
8
2
4
6
1
3
5
0
-
7
-
-
-
3
8
15
2
4
6
-
-
-
1
2
5
-
-
10
6
1
4
6
10
-
2
3
-
-
-
3
6
8
10
12
10
11
12
-
10
12
6
80
100
60
80
100
60
IVj
IVk
80
100
10
14
-
-
9
8
[a] standards
30
25
31
12
13
14
[a] Griseofulvin (30 µg/disc) for Penicillium and Helminthosporium, Nystatin (25 µg/disc) for Aspergillus niger, Vancomycin (10 µg /
disc) for Staphylococcus aureus, Tetracyclin (15 µg/disc) for Escherichia coli and Gentamycin (10 µg/disc) for Pseudomonas aerugionsa;
[b] diameter of filter paper is 16 mm, compounds 4a-d tested in 20% ethanol, 4e-k tested in 30% of ethanol;"-" indicates no activity.
[5] H. Arnold and F. Bourseaux, Angew. Chem., 70, 539
(1958).
[6a] S. M. Ludeman, G. Zon and W. Egan, J. Med. Chem., 22,
151 (1979); [b] P. B. Farmer and P. J. Cox, J. Med. Chem., 18, 1106
(1975).
Acknowledgements.
The authors express their thanks to Dr. C. Nagaraju and Dr. M.
Venugopal for helpful discussions and the Directors of SIF, IISC
Bangalore and CDRI, Lucknow, for the analytical and spectral
data.
[7] Robert White Stevens, Pesticides in the Environment
Marcel Dekker, Inc, New York, Vol. 1, 1971.
[8a] Z. B. Papanastasiou and T. J. Bardos, J. Med. Chem., 5,
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C. Naga Raju, Heterocyclic Communications, 6, 431 (2000); [c] W. J.
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Spectrometric Identification of organic compounds, (John Wiley &
Sons, New York), 208, 1981.
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