Synthesis of new α aminophosphonate system bearing Indazole moiety and their biological activity

Article abstract of DOI:10.1016/j.ejmech.2012.01.024

We are reporting herein for the first time the synthesis of α-aminophosphonates containing Indazole moiety in two steps. In the first step, imines of substituted N-benzylidene-1-methyl-1H-indazole-3-carbohydrazide are synthesized and in the next step it h

Full text of DOI:10.1016/j.ejmech.2012.01.024

European Journal of Medicinal Chemistry 50 (2012) 39e43
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European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis of new
a
aminophosphonate system bearing Indazole moiety and their
biological activity
*
Nasir ali Shafakat Ali, Shaikh Zakir, Muqtadir Patel, Mazahar Farooqui
Post Graduate and Research Centre, Department of Chemistry, Maulana Azad College, Rauza Bagh, Aurangabad 431 001, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We are reporting herein for the first time the synthesis of a-aminophosphonates containing Indazole
Received 23 February 2011
Received in revised form
11 January 2012
Accepted 12 January 2012
Available online 30 January 2012
moiety in two steps. In the first step, imines of substituted N-benzylidene-1-methyl-1H-indazole-3-
carbohydrazide are synthesized and in the next step it has converted to -aminophosphonates using
chlorotrimethylsilane (TMSCl) and triethyl phosphite. Some of the synthesized derivatives are evaluated
for antibacterial activity against different bacterial strains.
a
Ó 2012 Elsevier Masson SAS. All rights reserved.
Keywords:
Indazole derivatives
Synthesis
a
-Aminophosphonates
Imines
Antibacterial
Biological active compounds
1. Introduction
antipyretic [23], dopamine antagonistic [24], anti-tumor [25], anti-
emetic [26], and anti-HIV activities [27].
Among the heterocyclic compounds, which are available for the
preparation of potentially valuable new building-blocks in medic-
inal chemistry, the Indazole nucleus is probably one of the least
studied. In contrast to the abundance of publications on its bio-
isosteres e.g., indole [1,2] or benzimidazole [3e5], there are limited
number of publications based on Indazole chemistry, may be due to
the fact that the Indazole moiety is rather scarce in natural products
[6e8]. Even though, a large number of synthetically prepared
compounds have displayed biological and pharmacological prop-
erties [9]. Bendazac, a non-steroidal anti-inflammatory agent, used
as an anti-cataract drug [10] and Granisetron, a serotonin 5-HT3
receptor antagonist used to treat and prevent nausea and vomiting
induced by cancer chemotherapy [11,12] this are the two examples
of bioactive molecules of current interest. Other compound of
interest isYC-I (a guanylyl cyclase activator) [13e15] used for the
treatment of cardiovascular diseases or erectile dysfunction and
lonidamine [16e18] drug used for treatment of cancer.
As natural amino acid analogues,
a-aminophosphonate
compounds has attracted the current interest in organic and
medicinal chemistry due to biological and pharmacological prop-
erties of this organophosphorus compounds [28]. As structure
analogues of amino acid (‘bioisosterism’) has received considerable
attention owing to their pronounced biological activities. These
entities has also been shown to serve as inhibitors of GABA-
receptors, inhibitors of various proteolytic enzymes, inhibitors of
dialkylglycine decarboxylase, peptide mimetic, antibiotics, and
pharmacological agent, including anti-tumor, antihypertensive
and antibacterial agents [29]. Apart from this, their potential as
herbicides [30], insecticides [31], fungicides [32], antiviral agents
[33], as well as their role for antibody generation [34] is well
known.
2. Result and discussion
Apart from this Indazoles constitute an important class of
heterocycles that displays an interesting biological properties [19],
such as anti-depressant [20], anti-inflammatory [21,22], analgesic,
Owing to their synthetic and biological values, the chemistry of
-aminophosphonates has stimulated increasing interest and the
development of new organophosphorus compounds are still
remains of great interests. Moreover literature survey has revealed
a
that compounds containing
moiety has not been reported so far.
a-aminophosphonates with Indazole
* Corresponding author. Tel./fax: þ91 240 2381102.
E-mail address: mazahar_64@rediffmail.com (M. Farooqui).
0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2012.01.024

40
N.aliS. Ali et al. / European Journal of Medicinal Chemistry 50 (2012) 39e43
Therefore, we have synthesized
a-aminophosphonates contain-
5. Materials & method
ing Indazole moiety in two steps. In the first step, imines of
substituted N-benzylidene-1-methyl-1H-indazole-3-carbohydrazide
are synthesized. Synthesis of these compounds proceeds through
the formation of methyl-1-methyl-1H-indazole-3-carboxylate, by
acidic esterification, and then it is converted into 1-methyl-1H-
indazole-3-hydrazideby using hydrazine hydrate in ethanol at
reflux temperature. The 1-methyl-1H-indazole-3-hydrazide was
condensed with different substituted benzaldehyde using catalytic
amount of conc. sulphuric acid in ethanol and in the next step it
ꢀ The bacterial strains are inoculated into fresh sterile MHB
(Muller Hinton Broth) media tube (4.5 ml) and were incubated
for 18e24 h at 37 ꢁC in a B. O. D. incubator
ꢀ Standard antibiotic Gentamycin and Kinamycin clear solutions
are prepared with final (1 mg/ml).
ꢀ The above antibiotic solutions are poured on sterile disc at
a final concentration of 40 mcg/disc for Gentamycin and Kin-
amycin drugs.
has finally converted to
trimethylsilane (TMSCl) and triethyl phosphite (Figs. 1 and 2).
a
-aminophosphonates using chloro-
ꢀ All discs were dried completely by incubating into hot air oven
in sterile Petri dishes.
ꢀ On MHA (Muller Hinton Agar) plates, the bacterial suspension
was poured and spread evenly with the help of glass spreader.
ꢀ After drying the plates completely, the antibiotic loaded discs
were kept on the plates.
3. Antimicrobial activity
Some of the synthesized derivatives are then assayed for their
in-vitro antibacterial activity against a panel of pathogenic as well
as standard bacterial strains such as Klebsiella pneumoniae, Staph-
ylococcus aureus, Salmonella typhimurium, Bacillus Subtilis,
P. auroginosa and Escherichia coli. Based on previous literature and
scope of the bacterial species are selected. Gentamycin and Kin-
amycin are procured from commercial sources. The purities and
potencies of the agents recovered from commercial preparations
were documented by showing that the MICs of antibacterial are-
within acceptable limits against the known strains.
ꢀ All plates were incubated at 37 ꢁC in a B.O.D. (Biological Oxygen
Demand) incubator for 24 h.
ꢀ Results were recorded and antibiotic activity had quantified by
measuring the zone of inhibition surrounded to the disc in
‘mm’ scale and presented in Table 1.
6. Conclusion
A new series of
a-aminophosphonate derivatives containing
highly bioactive Indazole moiety is synthesized in two steps. In the
first step, imines of Indazole moiety synthesized and in next step it
4. Determination of MIC in terms of zone of inhibition
has converted to a-aminophosphonates using TMSCl and triethyl
phosphite. Some of the synthesized derivatives are then evaluated
for antibacterial activity against different bacterial strains respect
to agar disc method. The fluoro groups 2b and 2c has improved
the antibacterial property as compared to the other derivatives of
series 2. The derivatives 2b and 2c has good killing properties for
The antibacterial activity has tested by agar disc diffusion
method. The killing or growth inhibition properties of the agents
are scored as clear zone of inhibition surrounding the disc and are
measured in mm scale.
O
O
OH
O
CH3
ii
O
NH
NH2
i
N
N
N
N
H3C
N
H3C
N
H3C
R3
R2
R1
iii
HO
R3
R2
R
O
O
R1
N
NH
R
N
N
H3C
1 (a-g)
Reagents and conditions: i) Methanol/H2SO4/Reflux ii) Hydrazine hydrate/Ethanol iii)
Ethanol/Acetic acid/Reflux
Fig. 1. Synthetic Scheme 1.

N.aliS. Ali et al. / European Journal of Medicinal Chemistry 50 (2012) 39e43
41
R3
O
R3
R2
R2
O
O
R1
R1
NH
O
N
NH
Et
NH
R
Et
R
i
P
N
N
O
N
N
H3C
H3C
2 (a-g)
1 (a-g)
Reagents and conditions: i) (EtO)3P, TMSCL/CH3CN/Reflux
Fig. 2. Synthetic Scheme 2.
K. pneumoniae in the group. The bactericidal properties of 2b and 2c
against the species of P. aeroginosa have improved over other
derivatives of the same group. But the overall killing or inhibiting
the growth of bacteria is inferior as compared to the standard
Gentamycin and Kinamycin drugs.
7.2. Synthesis of 1-methyl-1H-indazole-3-hydrazide
To the suspension of 1-methyl-1H-indazole-3-carboxylate (10 g,
0.52 mol) in ethanol 20 ml were added hydrazine hydrate (5.2 g,
0.10 mol) and 1 ml of glycial acetic acid. The reaction mass was
heated at reflux temp for 4e6 h. After completion of reaction,
reaction mixture was cooled to room temperature separated solid
was filtered and washed with chilled 5 ml ethanol and dried at 50-
60 ꢁC. Yield. 89%
7. Experimental
Melting points are taken on a precision melting point apparatus
(DBK) instrument and are uncorrected. IR spectra are obtained in
potassium bromide (KBr)disks on a Bruker IR spectrometere, and
1H NMR spectra were obtained on deuteriochlroform (CDCL3) on
a Varian 400 MHz spectrometer. Mass spectra were recorded on
a MicroMass spectrometer by Waters. The yields unless otherwise
mentioned are for pure product. All the raw materials, reagents and
solvents used were of commercial grade only.
7.3. Synthesis of 1-methyl N-(4-(trifluoromethyl) benzylidene) 1H-
indazole-3-carbohydrazide (1b)
Tothestirredsolutionof1-methyl-1H-indazole-3-carbohydrazide
(2.0 g, 0.010 mol) in 20 ml of absolute ethanol added 4-(trifluoro
methyl) benzaldehyde (1.8 g, 0.010 mol) and 1 ml of conc. sulphuric
acid. The reaction mixture was heated to reflux for 6 h. After the
completion of the reaction, 60 ml of water was added to the reaction
mixture and stirred for 1 h. The solid obtained was filtered and
washed with water, dried at 45e50 ꢁC.
7.1. Synthesis of methyl 1-methyl-1H-indazole-3-carboxylate
To the stirred suspension of N-methyl indazolic acid (10 g,
0.056 mol) in 100 ml methanol added 10 ml sulphuric acid drop-
wise. The reaction mixture heated to reflux for 4 h. After comple-
tion of reaction, reaction mass concentrated and neutralized with
saturated sodium bicarbonate solution and extracted with 100 ml
ethyl acetate, ethyl acetate layer wash with 50 ml water, dried over
anhydrous sodium sulphate and concentrate on Rotavapor solid
obtained was filtered, washed with chilled ethyl acetate (10 ml),
Yield. 85%
7.4. Synthesis of diethyl (2-(1-methyl-1-H-indazole-3 carbonyl)
hydrazinyl (phenyl) methyl phophonate (2b)
To the mixture of 1-methyl-N-(4-(trifluoromethyl) benzyli-
dene)-1H-indazole-3-carbohydrazide (1 g, 0.0028 mol) and trie-
thylphosphite (1.40 g, 0.0084 mol) in 20 ml acetonitrile, added
chlorotrimethylsilane (TMSCl)(0.90 g, 0.0084 mol) The reaction
mixture was heated to reflux for 12 h. The progress of the reaction
Table 1
Antibacterial data of substituted diethyl (2-(1-methyl-1-H-indazole-3 carbonyl) hydrazinyl (phenyl) methyl phophonate (2aed).
Antibacterial activity in terms of zone of inhibition (mm) when tested at 40 mcg/disc)
Entry
R
R1
R2
R3
K. pneumonia
S. typhy
P. auroginosa
B, Subtilis
E. coli
S. auerues
2a
2b
2c
2d
H
H
H
Br
H
H
F
H
CF3
H
H
H
H
H
3
7
8
2
13
18
2
5
4
3
11
14
1
6
7
4
17
21
5
4
4
7
15
15
0
3
5
1
11
13
2
5
3
1
7
9
H
H
Gentamicin(40 mcg/disc)
Kanamycin(40 mcg/disc)

42
N.aliS. Ali et al. / European Journal of Medicinal Chemistry 50 (2012) 39e43
was monitored by TLC. After completion of the reaction, reaction
mixture was concentrated under reduced pressure to obtain an oily
residue. The oily residue was dissolved in methanol and again
concentrated, and then triturated with hexane. It was recrystallised
by N-N-dimethylformide and water till compound has obtained in
semi solid state.
7.10. N-(2-Chlorobenzylidene)-1-methyl-1H-indazole-3-
carbohydrazide (1f)
IR (KBr) cmꢂ1:- 3211(eNH), 2940 and 2814 (Ar-CH stretching &
bending), 1654(CONH) 1H NMR CDCl3:-
protons), d 7.15e8.19 (8H, Ar-H), d
d
3.93 (s, 3H, N-CH3
8.28 (s, 1H, N]CHimine proton),
9.89(s, 1H, CONH proton, exchangeable with D2O). 13C
NMR(CDCl3):- 41.8, 108.4, 119.1, 120.2, 122.6, 124.1, 125.8, 127.9,
Similarly the other derivatives of this series are prepared. Their
d
structures have been confirmed by IR, 1HNMR and Mass spectra.
d
129.9, 130.8, 132.6, 138.2, 140.7, 141.9, 143.5, 155.2, Mass (m/z):-
313(Mþ1) M.P. 237-39 ꢁC., Yield 84%
7.5. N-(4-benzylidene-1-methyl-1H-indazole-3-carbo hydrazide
(1a)
7.11. Diethyl(2-(1-methyl-1H-indazole-3-carbonyl)
hydrazinyl)(phenyl)methyl phosphonate (2a)
IR (KBr) cmꢂ1:- 3213(eNH), 2944 and 2816 (Ar-CH stretching &
bending), 1656(CONH). 1H NMR CDCl3:-
d
4.14 (s,3H, N-CH3
8.46 (s, 1H, N]CH imine proton),
10.15 (s, 1H, CONH proton, exchangeable with D2O)., 13C
NMR(CDCl3):- 41.8, 108.4, 119.6, 120.1, 122.8, 125.5, 127.5, 127.9,
IR (KBr) cmꢂ1:- 3423 (NH), 2977 and 2911 (Ar-CH streching &
protons), d 7.21e8.41 (9H, Ar-H), d
bending), 1636(C]N), 1227(eP]O), 968 (ePeOeC). 1H NMR
d
CDCI3:-
OeCH2eCH3),
NHeNHeCH, proton, exchangeable with D2O),
OeCH2eCH3methylene protons),
O), 6.63e8.32 (9H, aromatic protons),
proton, exchangeablewithD2O), 13C NMR(CDCl3):-
d
1.16e1.20 (t, 3H, OeCH2eCH3),
d 1.23-0.1.34 (t, 3H,
d
d
3.82 (s, 3H, N-CH3 proton),
d
3.84e3.89 (t, 1H,
4.14e4.22 (q, 4H,
128.5, 129.2, 130.3, 133.1, 138.5, 140.1, 145.4, 155.9, Mass (m/z):- 279
d
(Mþ1) M.P. 190-92 ꢁC., Yield 88%
d
4.78e4.83 (d, 1H, eNHeCHeP]
8.54e8.60(d, 1H, CONH
16.7, 16.7, 42.1,
d
d
7.6. 1-Methyl-N-(4-(trifluoromethyl)benzylidene)-1H-indazole-3-
carbo hydrazide (1b)
d
61.9., 61.9, 67.5, 108.5, 119.6, 120.4, 123.4, 125.5, 126.4, 127.5,
127.5.127.9, 128.5, 135.5, 138.6, 141.2, 160.3. Mass (m/z):- 416 (Mþ1)
Yield 83%
IR (KBr) cmꢂ1:- 3203(eNH), 2940 and 2806 (Ar-CH stretching &
bending), 1652(CONH) 1HNMR CDCl3:-
d
4.1 (s, 3H, N-CH3 protons),
8.42 (s,1H, N]CH imine proton), 10.21(s,
1H, CONH proton, exchangeable with D2O)., 13C NMR(CDCl3):-
42.1, 108.9, 120.1, 120.6, 123.2, 123.9, 125.8, 127.9, 128.2, 128.8,
d
7.25e8.46 (8H, Ar-H),
d
d
7.12. Diethyl(2-(1-methyl-1H-indazole-3-carbonyl)hydrazinyl)(4-
(trifluoro) phenyl)methylphosphonate (2b)
d
IR (KBr) cmꢂ1:- 3417 (NH), 2985 and 2907 (CH streching &
129.8, 130.7, 133.5, 138.9, 140.6, 145.8, 156.4., Mass (m/z):- 347
(Mþ1) M.P. 197-199 ꢁC Yield 90%.
bending), 1624(C]N), 1231 (eP]O), 978 (-P-O-C). 1H NMR CDCI3:-
d
1.21e1.27 (t, 3H, OeCH2eCH3),
3.94 (s, 3H, N-CH3 proton),
d
1.3e0.1.42 (t, 3H, OeCH2eCH3),
3.96e3.99 (t, 1H, NHeNHeCH,
d
d
7.7. N-(3-Fluorobenzylidene)-1-methyl-1H-indazole-3-
carbohydrazide (1c)
proton, exchangeable with D2O),
methylene protons), 0.85e4.93 (d, 1H, eNHeCHeP]O),
6.6e7.9 (8H, aromatic protons), 8.59 (s, 1H, CONH proton,
exchangeable with D2O, 13C NMR(CDCl3):-
16.6, 16.6, 42.7, 62.4,
d 4.14e4.29 (q, 4H, OeCH2eCH3
d
IR (KBr) cmꢂ1:- 3222(eNH), 2945 and 2816 (Ar-CH stretching &
d
d
bending), 1659(CONH) 1H NMR CDCl3:-
d
3.98 (s, 3H, NeCH3
8.46 (s, 1H, N]CH imine
9.98 (s, 1H, CONH proton, exchangeable with D2O). 13C
NMR(CDCl3):- 42.6, 109.4, 113.5.118.6, 124.2, 124.8, 126.2, 128.6,
d
62.4, 68.1, 108.9, 119.9, 120.6, 123.8, 124.5, 124.5, 125.2, 126.2,
127.8, 127.8, 128.9, 138.5, 138.8, 141.8, 160.9. Mass (m/z):- 485
(Mþ1) Yield 86%
protons),
proton),
d 7.11e8.32 (8H, Ar-H), d
d
d
128.9, 129.8, 130.9, 133.9, 139.8146.2, 157.4, 162.3, Mass (m/z):- 297
(Mþ1) M.P. 200-02 ꢁC, Yield 86%.
7.13. Diethyl(3-fluorophenyl)(2-(1-methyl-1H-indazole-3-
carbonyl) hydrazinyl) methyl phosphonate (3c)
7.8. N-(2-Bromobenzylidene)-1-methyl-1H-indazole-3-
carbohydrazide (1d)
IR (KBr) cmꢂ1:- 3444 (NH), 2989 and 2934 (CH streching
& bending), 1649 (C]N), 1236 (eP¼O), 981 (-P-O-C). 1H NMR
CDCI3:-
OeCH2eCH3),
NHeNHeCH, proton exchangeable with D2O),
OeCH2eCH3methyleneprotons),
O), 6.68e8.39(8H, aromatic protons),
proton, exchangeable with D2O). 13C NMR(CDCl3):
d
1.19e1.27 (t, 3H, OeCH2eCH3),
d
1.31e1.39 (t, 3H,
3.95e3.99(t, 1H,
4.18e4.29 (q, 4H,
IR (KBr) cmꢂ1:-3200(eNH), 2934 and 2800 (Ar-CH stretching &
d
3.92(s, 3H, N-CH3protons),
d
d
bending), 1645(CONH).1H NMR CDCl3:-
protons), d 7.15e8.37 (8H, Ar-H), d
d
3.94 (s, 3H, N-CH3
8.32 (s, 1H, N]CH imine proton),
9.90 (s, 1H, CONH proton, exchangeable with D2O). 13C
NMR(CDCl3):- 42.6, 109.4, 119.4, 120.5, 121.4, 124.8, 125.5, 126.9,
d
4.84e4.90(d, 1H, eNHeCHeP]
8.87 (s, 1H, CONH,
16.4, 16.4, 42.5,
d
d
d
d
d
129.6, 130.2, 131.9, 133.9, 139.8, 140.5, 141.2, 145.5, 156.2, Mass (m/
62.7, 62.7, 67.5, 109.4, 114.1, 114.1, 120.1, 120.4, 123.5, 123.8,
125.8, 125.9, 129.8, 137.4, 138.9, 141.9, 161.1., Mass (m/z):- 435
(Mþ1) Yield 77%.
z):- 357 (Mþ1), M.P. 230-32 ꢁC, Yield 84%
7.9. 1-Methyl-N-(2-nitrobenzylidene)-1H-indazole-3-
carbohydrazide (1e)
7.14. Diethyl(2-bromophenyl)(2-(1-methyl-1H-indazole-3-
carbonyl)hydrazinyl methyl phosphonate (2d)
IR (KBr) cmꢂ1:-3200(eNH), 2934 and 2800 (Ar-CH stretching &
bending), 1645(CONH). 1H NMR CDCl3:-
d
3.90 (s, 3H, N-CH3
8.26 (s, 1H, N]CH imine proton),
9.84 (s, 1H, CONH proton, exchangeable with D2O). 13C
NMR(CDCl3):- 42.2, 108.7, 119.9, 120.7, 123.2, 124.8, 126.8, 128.3,
IR (KBr) cmꢂ1:- 3421 (NH), 2989 and 2932 (CH streching &
protons),
d
7.05e8.11 (8H, Ar-H),
d
bending), 1643(C]N), 1231 (eP]O), 977 (ePeOeC). 1H NMR
d
CDCI3:-
OeCH2eCH3),
NHeNHeCH, proton, exchangeable with D2O),
OeCH2eCH3 methylene protons),
d
1.11e1.20 (t, 3H, OeCH2eCH3),
d 1.23-0.1.30 (t, 3H,
d
d
3.81 (s, 3H, N-CH3 proton),
d
3.91e3.97 (t, 1H,
129.5, 130.5, 131.3, 138.9, 140.1, 141.2, 142.5, 155.9, Mass (m/z)
d 4.11e4.21 (q, 4H,
324(Mþ1), M.P. 237-39 ꢁC, Yield 79%.
d
4.80 (d, 1H, eNHeCHeP¼O),

N.aliS. Ali et al. / European Journal of Medicinal Chemistry 50 (2012) 39e43
43
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6.61e8.23 (8H, aromatic protons),
d
8.51 (s, 1H, CONH proton,
16.3, 16.3, 42.6, 62.8,
exchangeable with D2O). 13C NMR(CDCl3):-
d
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511e520.
IR (KBr)cmꢂ1:- 3412 (NH), 2965 and 2913 (CH streching &
bending), 1634 (NO2), 1651(C]N), 1239 (eP¼O), 988 (ePeOeC). 1H
NMR CDCI3:-
d 1.14e1.22 (t, 3H, OeCH2eCH3), d 1.26e0.1.34 (t, 3H,
OeCH2eCH3), dd 3.86 (s, 3H, N-CH3 proton),
1H, NHeNHeCH, proton, exchangeable with D2O),
(q, 4H, OeCH2eCH3 methylene protons), 4.83e4.88e4.93(d,
1H,eNHeCHeP¼O), 6.67e8.27(8H, aromatic protons), 8.47
(s, 1H, CONH, proton, exchangeable withD2O)., 13C NMR(CDCl3):-
16.1, 16.1, 42.3, 62.2, 62.2, 63.5, 109.2, 120.3, 120.8, 123.5, 124.4,
d
3.94e3.99 (t,
d
4.15e4.24
d
d
d
d
126.1, 127.3, 128.1, 133.4, 136.7, 139.2, 142.1, 146.9, 160.8., Mass (m/
z):- 462 (Mþ1), Yield 75%.
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F. Rossi, Farmaco 47 (1992) 567e584.
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10699e10706.
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(1997) 5627e5629.
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(b) F.R. Atherton, C.H. Hassel, R.W. Lambert, J. Med. Chem. 29 (1986) 29;
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(1994) 234;
7.16. Diethyl(2-chlorophenyl)(2-(1-methyl-1H-indazole-3-
carbonyl)hydrazinyl) methylphosphonate (2f)
IR (KBr) cmꢂ1:- 3454 (NH), 2956 and 2910 (CH streching &
bending), 1654(C]N), 1226 (eP]O), 971 (-P-O-C). 1H NMR CDCI3:-
d
1.17e1.26 (t, 3H, OeCH2eCH3),
3.89 (s, 3H, N-CH3 proton),
d
1.29-0.1.38 (t, 3H, OeCH2eCH3),
3.92e3.95 (t, 1H, NHeNHeCH,
d
d
proton, exchangeable withD2O),
methylene protons), 4.87e4.95 (d, 1H, eNHeCHeP]O),
6.60e8.21 (8H, aromatic protons), 8.41 (s, 1H, CONH proton
exchangeable with D2O). 13C NMR(CDCl3):-
15.9, 15.9, 41.7, 61.6,
d 4.17e4.28 (q, 4H, OeCH2eCH3
d
d
d
d
61.6, 63.1, 108.7, 119.8, 120.1, 123.2, 126.2, 126.5, 127.8, 128.2, 128.6,
131.7, 139.5, 141.7, 142.4, 161.1., Mass (m/z)451 (Mþ1), Yield 80%.
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