Synthesis and in vitro antimicrobial activity of new α- aminophosphonates via tetrazolo [1,5-a] quinoline derivatives

Article abstract of DOI:10.1080/10426500903530867

A series of diethyl (4-fluorophenylamino) (substituted tetrazolo[1,5-a] quinolin-4-yl)methyl phosphonate derivatives has been synthesized for the first time from tetrazolo [1,5-a] quinoline derivatives. Elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data elucidated the structures of the all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and two fungi Candida albicans and Aspergillus niger in comparison with standard drugs. Significantly, microbiological behavior of these newly synthesized derivatives possesses significant antibacterial and antifungal activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903530867

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Synthesis and In Vitro Antimicrobial
Activity of New α-Aminophosphonates
via Tetrazolo [1,5-a] Quinoline
Derivatives
Amol H. Kategaonkar a , Swapnil S. Sonar a , Suryakant B. Sapkal a ,
Vaibhav U. Gawali b , Bapurao B. Shingate a & Murlidhar S. Shingare a
a Department of Chemistry , Dr. Babasaheb Ambedkar Marathwada
University , Aurangabad, Maharashtra, India
b Pharmacology Laboratory , Maharashtra Institute of Pharmacy ,
Pune, Maharashtra, India
Published online: 24 Sep 2010.
To cite this article: Amol H. Kategaonkar , Swapnil S. Sonar , Suryakant B. Sapkal , Vaibhav U.
Gawali , Bapurao B. Shingate & Murlidhar S. Shingare (2010) Synthesis and In Vitro Antimicrobial
Activity of New α-Aminophosphonates via Tetrazolo [1,5-a] Quinoline Derivatives, Phosphorus, Sulfur,
and Silicon and the Related Elements, 185:10, 2113-2121, DOI: 10.1080/10426500903530867
To link to this article: http://dx.doi.org/10.1080/10426500903530867
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Phosphorus, Sulfur, and Silicon, 185:2113–2121, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903530867
SYNTHESIS AND IN VITRO ANTIMICROBIAL ACTIVITY
OF NEW α-AMINOPHOSPHONATES VIA TETRAZOLO
[1,5-a] QUINOLINE DERIVATIVES
Amol H. Kategaonkar,1 Swapnil S. Sonar,1
Suryakant B. Sapkal,1 Vaibhav U. Gawali,2
Bapurao B. Shingate,1 and Murlidhar S. Shingare1
1Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, Maharashtra, India
2Pharmacology Laboratory, Maharashtra Institute of Pharmacy, Pune,
Maharashtra, India
A series of diethyl (4-fluorophenylamino) (substituted tetrazolo[1,5-a]quinolin-4-yl)methyl
phosphonate derivatives has been synthesized for the first time from tetrazolo [1,5-a] quino-
line derivatives. Elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data eluci-
dated the structures of the all newly synthesized compounds. In vitro antimicrobial activities
of synthesized compounds have been investigated against Gram-positive Bacillus subtilis,
Gram-negative Escherichia coli, and two fungi Candida albicans and Aspergillus niger
in comparison with standard drugs. Significantly, microbiological behavior of these newly
synthesized derivatives possesses significant antibacterial and antifungal activity.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords α-Aminophosphonate; antibacterial; antifungal; tetrazolo [1,5-a] quinoline
INTRODUCTION
The phosphonate (PO23−) moiety is a common structural fragment present in a wide
range of biologically active compounds. Such versatile biological activities1–8 as enzyme
inhibitory, antifungal, antioxidants, and herbicidal of α-aminophosphonates have given the
α-aminophosphonate moiety the status of a novel pharmacophore in the context of drug
design. Despite structural and electronic differences between phosphonate and carboxylic
functionalities (in terms of size, shape, acidity, and geometry), the phosphonate functional-
ity is regarded as a bioisostere of the carboxylic acids.9,10 Many of them can serve as haptens
Received 21 July 2009; accepted 27 November 2009.
The authors would like to thank the Head, Department of Chemistry, Dr. B. A. M. University, Aurangabad, for
constant encouragement and providing necessary facilities. A.H.K. is thankful to University Grants Commission,
New Delhi, India for a Research fellowship.
Address correspondence to Murlidhar S. Shingare, Department of Chemistry, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad 431 004, Maharashtra, India. E-mail: prof msshingare@rediffmail.com
2113

2114
A. H. KATEGAONKAR ET AL.
in catalytic enzymes antibody generation and as transition state analogue inhibitors of dif-
ferent proteolytic enzymes that exhibit a wide spectrum of biological properties, including
antimicrobial, antitumor, antihypertensive, and antibacterial activities.11–16 It is well known
that inclusion of fluorine atoms and fluorine-containing substituents into molecules of or-
ganic substances results in profound changes of chemical and physicochemical properties,
and consequently, the biological activity of these substances. α-Aminophosphonates are
chief substrates in the synthesis of phosphonopeptides.17
Quinolines and their derivatives are important constituents of pharmacologically
active synthetic compounds. The quinoline nucleus can also be frequently recognized in
the structure of numerous, naturally occurring alkaloids. They have been associated with
a broad spectrum of biological activities.18, 19 The fusion of quinoline to the tetrazole ring
is known to increase the biological activity. The tetrazole group, which is considered to be
analogous to the carboxylic group as a pharmacore, possesses a wide range of biological
activities. Several substituted tetrazoles have been shown to possess anticonvulsant,20
anti-inflammatory,21 CNS dispersant,22 antimicrobial,23 anti-AIDS,24 and antifertility
agents.25, 26
By considering all the above aspects, for the first time we have synthesized the title
compounds to develop our ongoing research work.27–30
RESULTS AND DISCUSSION
Chemistry
The key intermediate tetrazolo [1,5-a] quinoline-4 carbaldehyde derivatives (2a–i)
were prepared by the reaction of 2-chloroquinoline-3-carbaldehyde derivatives (1a–i) with
sodium azide in a DMSO/AcOH mixture.31, 32 Furthermore, we have synthesized imines
(3a–i) by the reaction of tetrazolo [1,5-a] quinoline derivatives (2a–i) and 4-fluoroaniline
in ethanol at room temperature using a catalytic amount of acetic acid in excellent yields
(68–94%). The synthesized imines (3a–i), which were further treated with triethyl phosphite
in the presence of TMSCl at room temperature, afforded the compounds (4a–i), which are
outlined in Scheme 1. The time period required for this protocol is less than the previously
reported methods on tetrazolo [1,5-a] quinoline moiety.28
Structural Determination
Structures of the compounds (3a–i) and (4a–i) were elucidated on the basis of the
1
FT-IR, H NMR, 13C NMR, and mass spectroscopic analysis. Assignment of selected
characteristic IR band positions provide significant indication for the formation of di-
ethyl (4-fluorophenylamino) (substituted tetrazolo[1,5-a]quinolin-4-yl)methylphosphonate
derivatives. All the compounds (4a–i) showed intense bands in the region of 1607–1670
cm−1 corresponding to ν (C N) stretching, 1221–1251 cm−1 of the ν (P O) stretching
and 1021–1067 cm−1 of ν (P O C) stretching, which confirms the formation of desired
compounds (4a–i). All the compounds showed an additional sharp band in the region of
3251–3334 cm−1 assigned ν (NH) stretch. Further evidence for the formation of desired
1
compounds was confirmed from H NMR and 13C NMR spectra, which proved to be a
diagnostic tool for the positional elucidation of the proton and carbon, respectively. As-
signments of the signals are based on the chemical shift and intensity pattern. The proton at
(CH N) position of compounds (3a–i) was observed in the region of 9.12–9.27 ppm. The

SYNTHESIS OF NEW α-AMINOPHOSPHONATES
2115
Scheme 1 Synthesis of the compounds (4a–i).
aromatic protons of compounds (4a–i) are in the region of 6.57–8.71 ppm. A doublet due
to (CH-P) proton in all final compounds was observed in the range of 5.35–5.62 ppm. The
aromatic carbons of compounds (4a–i) are in the region of 114.5–159.0 ppm. The carbon
(CH-P) position showed a peak around the 52.0–53.0 ppm region. The mass spectrum of
compound 4a showed a molecular ion peak (m+1) at 430.3, compound 4b at 444.3 (m+1),
compound 4e at 460.3 (m+1), 4h at 474.3 (m+1), and compound 4i at 458.3 (m+1).
Antimicrobial Screening
Schrader33 proposed that organophosphorus compounds containing the general struc-
ture (A) may have significant biological activity. All organophosphorus compounds are
inherently good phosphorylating agents of enzymes by virtue of the group P-XYZ in
the general structure (A). Slight variation in structure can have very dramatic effects

2116
A. H. KATEGAONKAR ET AL.
on the efficiency of organophosphorus compounds in bi-activity. These chemically and
biologically variable parameters, which are hard to estimate, are involved in deciding
the structure–activity relationships of these compounds. (See the Supplemental Materials,
available online, for complete details.)
In conclusion, a series of new α-aminophosphonate derivatives was synthesized
and evaluated for antimicrobial activity. All the synthesized compounds showed good to
moderate antibacterial and antifungal activity. The importance of such work lies in the
possibility that the new compounds might be more efficacious drugs against bacteria and
fungi, which could be helpful in designing more potent antibacterial and antifungal agents
for therapeutic use.
EXPERIMENTAL
All chemicals and solvents were purchased from Merck, Spectrochem, and S. D.
Fine-chem (India). Melting points were determined in open capillaries on Kumar’s melting
point apparatus (India) and are uncorrected. IR spectra were recorded on a Jasco FT-IR 4100
(Japan) using KBr discs. 1H NMR and 13C NMR spectra were recorded on a Bruker DRK-
300 and NMR Spectrometer AC200. Mass spectra were recorded on Single-Quadrupole
Mass Detector 3100 (Waters). Elemental analyses were performed on a CHNS analyzer
Flash 1112 (Thermo Finnigan). The progress of the reactions was monitored by TLC on
Merck silica plates. Results are presented as chemical shift δ in ppm, multiplicity, J values
in Hertz (Hz), number of protons, and the proton’s position. Multiplicities are shown as
the abbreviations: s (singlet), brs (broad singlet), d (doublet), t (triplet), and m (multiplet).
Solvents were commercially available materials of reagent grade.
4-Fluoro-N-((tetrazolo[1,5-a]quinolin-4-yl)methylene)benzenamine (3a)
To a stirred solution of tetrazolo [1, 5-a] quinoline-4 carbaldehyde (5 mmol) in
absolute ethanol (10 mL), 4-fluoroaniline (6 mmol) was added with 4 to 5 drops of acetic
acid. The progress of the reaction was monitored by TLC (hexane:ethyl acetate solvent
system). After the completion of the reaction (15 min), 20 mL of water was added, and
the solid obtained was filtered, washed with water, and dried in an oven at 50◦C for 5 h.
Yield 94%, mp 180–182◦C. 1H NMR (400 MHz, CDCl3, Me4Si, δ ppm): 7.16 (t, 2H, J =
8 Hz, Ar H), 7.40 (t, 2H, J = 7.6 Hz, Ar H), 7.79 (t, 1H, J = 8 Hz, Ar H), 7.97 (t, 1H,
J = 8 Hz, Ar H), 8.18 (d, 1H, J = 7.6 Hz, Ar H), 8.73 (d, 1H, J = 8 Hz, Ar H), 8.80
(s, 1H, Ar H), 9.25 (s, 1H, CH N). 13C NMR (75 MHz, CDCl3, δ ppm): 116.0, 116.3,
116.9, 121.34, 122.9, 123.0, 123.7, 128.4, 130.3, 130.6, 131.1, 132.3, 146.6, 146.9, 151.8
(Ar C), 160.4 (C N). MS: m/z 292 (m+1). Elemental analysis: C16H10FN5 Calcd.: C:
65.97%; H: 3.46%; N: 24.04%. Found: C: 65.80%, H: 3.54%, N: 24.17%.
4-Fluoro-N-((7-methyltetrazolo[1,5-a]quinolin-4-yl)methylene)benzenamine
(3b)
Yield 85%, mp 234–236◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 2.56 (s, 3H,
Ar CH3), 7.06 (d, 2H, J = 8 Hz, Ar H), 7.19 (d, 2H, J = 8 Hz, Ar H), 7.70 (d, 1H, J =
8 Hz, Ar H), 7.82 (s, 1H, Ar H), 8.55 (d, 1H, J = 10 Hz, Ar H), 8.65 (s, 1H, Ar H),
9.18 (s, 1H, CH N). MS: m/z 306.1 (m+1). Elemental analysis: C17H12FN5 Calcd.: C:
66.88%; H: 3.96%; N: 22.94%. Found: C: 66.72%, H: 3.78%, N: 22.76%.

SYNTHESIS OF NEW α-AMINOPHOSPHONATES
2117
4-Fluoro-N-((8-methyltetrazolo[1,5-a]quinolin-4-yl)methylene)benzenamine
(3c)
Yield 92%, mp 230–232◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 2.47 (s, 3H,
Ar CH3), 7.15 (d, 2H, J = 8 Hz, Ar H), 7.24 (d, 2H, J = 8 Hz, Ar H), 7.81 (d, 1H, J =
8 Hz, Ar H), 7.90 (s, 1H, Ar H), 8.57 (d, 1H, J = 10 Hz, Ar H), 8.65 (s, 1H, Ar H),
9.12 (s, 1H, CH N). MS: m/z 306.1 (m+1). Elemental analysis: C17H12FN5 Calcd.: C:
66.88%; H: 3.96%; N: 22.94%. Found: C: 66.81%, H: 3.73%, N: 22.67%.
4-Fluoro-N-((9-methyltetrazolo[1,5-a]quinolin-4-yl)methylene)benzenamine
(3d)
Yield 76%, mp 186–188◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 2.38 (s, 3H,
Ar CH3), 7.03 (d, 2H, J = 8 Hz, Ar H), 7.21 (d, 2H, J = 8 Hz, Ar H), 7.84 (d, 1H, J =
8 Hz, Ar H), 7.93 (s, 1H, Ar H), 8.63 (d, 1H, J = 10 Hz, Ar H), 8.79 (s, 1H, Ar H),
9.23 (s, 1H, CH N). MS: m/z 306.1 (m+1). Elemental analysis: C17H12FN5 Calcd.: C:
66.88%; H: 3.96%; N: 22.94%. Found: C: 66.93%, H: 3.81%, N: 22.69%.
4-Fluoro-N-((7-methoxytetrazolo[1,5-a]quinolin-4-yl)methylene)
benzenamine (3e)
Yield 82%, mp 240–242◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 4.01 (s, 3H,
Ar CH3), 7.16 (d, 2H, J = 8 Hz, Ar H), 7.49 (d, 2H, J = 8 Hz, Ar H), 8.56–8.76 (m,
4H, Ar H), 9.27 (s, 1H, CH N). MS: m/z 322.1 (m+1). Elemental analysis: C17H12FN5O
Calcd.: C: 63.55%; H: 3.76%; N: 21.80%. Found: C: 63.71%, H: 3.83%, N: 21.61%.
4-Fluoro-N-((8-methoxytetrazolo[1,5-a]quinolin-4-yl)methylene)
benzenamine (3f)
Yield 68%, mp 218–220◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 4.12 (s, 3H,
Ar CH3), 7.05 (d, 2H, J = 8 Hz, Ar H), 7.97 (d, 2H, J = 8 Hz, Ar H), 8.78–8.97 (m,
4H, Ar H), 9.26 (s, 1H, CH N). MS: m/z 322.1 (m+1). Elemental analysis: C17H12FN5O
Calcd.: C: 63.55%; H: 3.76%; N: 21.80%. Found: C: 63.67%, H: 3.64%, N: 21.73%.
4-Fluoro-N-((9-methoxytetrazolo[1,5-a]quinolin-4-yl)methylene)
benzenamine (3g)
Yield 82%, mp 238–240◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 4.04 (s, 3H,
Ar CH3), 7.13 (d, 2H, J = 8 Hz, Ar H), 7.76 (d, 2H, J = 8 Hz, Ar H), 8.68–8.77 (m,
4H, Ar H), 9.27 (s, 1H, CH N). MS: m/z 322.1 (m+1). Elemental analysis: C17H12FN5O
Calcd.: C: 63.55%; H: 3.76%; N: 21.80%. Found: C: 63.64%, H: 3.59%, N: 21.81%.
N-((7-Ethoxytetrazolo[1,5-a]quinolin-4-yl)methylene)-4-fluorobenzenamine
(3h)
Yield 94%, mp 176–178◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm):1.51 (t, 3H,
J = 6Hz, CH2-CH3), 4.17 (q, 2H, J = 6 Hz, CH2-CH3), 7.17 (d, 2H, J = 8 Hz, Ar H), 7.48
(d, 2H, J = 8 Hz, Ar H), 7.94 (d, 2H, J = 6Hz, Ar H), 8.64 (s, 1H, Ar H), 8.92 (s, 1H,

2118
A. H. KATEGAONKAR ET AL.
Ar H), 9.20 (s, 1H, CH = N). MS: m/z 336.1 (m+1). Elemental analysis: C18H14FN5O
Calcd.: C: 64.47%; H: 4.21%; N: 20.88%. Found: C: 64.53%, H: 4.06%, N: 20.93%.
4-Fluoro-N-((9-methyltetrazolo[1,5-a]quinolin-4-yl)methylene)benzenamine
(3i)
Yield 89%, mp 102–104◦C. 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.36 (t, 3H,
J = 8 Hz, CH2-CH3), 2.89 (q, 2H, J = 8 Hz, CH2-CH3), 7.14 (d, 2H, J = 8 Hz, Ar H),
7.21 (d, 2H, J = 8 Hz, Ar H), 7.72 (d, 1H, J = 8 Hz, Ar H), 7.81 (s, 1H, Ar H), 8.58
(d, 1H, J = 10 Hz, Ar H), 8.67 (s, 1H, Ar H), 9.24 (s, 1H, CH N). MS: m/z 320.1
(m+1). Elemental analysis: C18H14FN5 Calcd.: C: 67.70%; H: 4.42%; N: 21.93%. Found:
C: 67.64%, H: 4.54%, N: 21.78%.
Diethyl(4-fluorophenylamino)(tetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4a)
A mixture of 4-fluoro-N-{(tetrazolo[1,5-a]quinolin-4-yl)methylene}benzenamine
(3a, 4 mmol), triethylphosphite (10 mmol), and TMSCl (10 mmol) was stirred magnetically
at room temperature. The progress of the reaction was monitored by TLC. After completion
of the reaction (5 min), the reaction mixture was poured onto crushed ice. The solid
obtained was extracted with chloroform (2 × 50 mL), washed with water (2 × 10 mL) and
brine (2 × 20 mL), and the separated organic layer was dried over anhydrous Na2SO4. The
solvent was removed under reduced pressure. The obtained crude product was purified
by column chromatography on silica gel by hexane:ethyl acetate (8:2) as an eluent. Yield
95%, mp 162–164◦C. IR (KBr, νmax/cm−1): 3286 (N H), 1612 (C N), 1230 (P O),
1
1051 (P O C). H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.06 (t, 3H, J = 6 and
8 Hz, CH3), 1.38 (t, 3H, J = 6 and 8 Hz, CH3), 2.79 (brs, 1H, NH), 4.01 (m, 2H, OCH2),
4.32 (m, 2H, OCH2), 5.62 (d, 1H, J = 26 Hz, CHP), 6.66 (d, 2H, J = 6 Hz, Ar H), 6.80
(t, 2H, J = 8 Hz, Ar H), 7.69 (d, 1H, J = 8 Hz, Ar H), 7.87 (m, 2H, Ar H), 8.09 (s,
1H, Ar H), 8.71(d, 1H, J = 8 Hz, Ar H).13C NMR (75 MHz, CDCl3, δ ppm): 16.0
(CH3), 16.4 (CH3), 52.7 (CH-P), 63.5 (OCH2), 64.2 (OCH2), 114.9, 115.7, 116.0, 116.7,
122.8, 123.9, 128.0, 129.0, 130.1, 131.1, 141.5, 141.7, 147.1, 155.0, 158.1 (Ar C). MS:
m/z 430.3 (m+1). Elemental analysis: C20H21FN5O3P Calcd.: C: 55.94%; H: 4.93%; N:
16.31%. Found: C: 56.20%, H: 5.12%, N: 16.24%.
Diethyl(4-fluorophenylamino)(7-methyltetrazolo[1,5-a]quinolin-
4-yl)methylphosphonate (4b)
Yield 86%, mp 158–160◦C. IR (KBr, νmax/cm−1): 3316 (N H), 1623 (C N), 1221
(P O), 1025 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.04 (t, 3H, J = 6
and 8 Hz, CH3), 1.37 (t, 3H, J = 6 and 8 Hz, CH3), 2.54 (s, 3H, Ar CH3), 3.73 (brs, 1H,
NH), 3.85–4.0 (m, 2H, OCH2), 4.04–4.35 (m, 2H, OCH2), 5.60 (d, 1H, J = 26 Hz, CHP),
6.65 (d, 2H, J = 4 Hz, Ar H), 6.77 (t, 2H, J = 8 Hz, Ar H), 7.65 (d, 2H, J = 8 Hz,
Ar H), 8.03 (s, 1H, Ar H), 8.54 (d, 1H, J = 8 Hz, Ar H).13C NMR (75 MHz, CDCl3,
δ ppm): 16.1 (CH3), 16.4 (CH3), 21.3 (CH3), 52.7 (CH-P), 63.5 (OCH2), 64.3 (OCH2),
115.0, 115.7, 116.0, 116.5, 122.6, 124.0, 128.3, 128.6, 131.0, 132.5, 138.4, 141.7, 147.0,

SYNTHESIS OF NEW α-AMINOPHOSPHONATES
2119
155.0, 158.2 (Ar C). MS: m/z 444.3 (m+1). Elemental analysis: C21H23FN5O3P Calcd.:
C: 56.88%; H: 5.23%; N: 15.79%. Found: C: 56.96%, H: 5.32%, N: 15.90%.
Diethyl(4-fluorophenylamino)(8-methyltetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4c)
Yield 87%, mp 152–154◦C. IR (KBr, νmax/cm−1): 3327 (N H), 1612 (C N), 1228
1
(P O), 1043 (P O C). H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.21 (t, 3H, J =
6 and 8 Hz, CH3), 1.45 (t, 3H, J = 6 and 8 Hz, CH3), 2.38 (s, 3H, Ar CH3), 3.62 (brs,
1H, NH), 3.88–4.11 (m, 2H, OCH2), 4.27–4.43 (m, 2H, OCH2), 5.48 (d, 1H, J = 26 Hz,
CHP), 6.74 (d, 2H, J = 4 Hz, Ar H), 6.86 (t, 2H, J = 8 Hz, Ar H), 7.68 (d, 2H, J =
8 Hz, Ar H), 8.21 (s, 1H, Ar H), 8.47 (d, 1H, J = 8 Hz, Ar H). MS: m/z 444.3 (m+1).
Elemental analysis: C21H23FN5O3P Calcd.: C: 56.88%; H: 5.23%; N: 15.79%. Found: C:
56.74%, H: 5.34%, N: 15.86%.
Diethyl(4-fluorophenylamino)(9-methyltetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4d)
Yield 78%, mp 208–210◦C. IR (KBr, νmax/cm−1): 3334 (N H), 1626 (C N), 1225
1
(P O), 1036 (P O C). H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.13 (t, 3H, J =
6 and 8 Hz, CH3), 1.38 (t, 3H, J = 6 and 8 Hz, CH3), 2.47 (s, 3H, Ar CH3), 3.74 (brs,
1H, NH), 3.87–4.10 (m, 2H, OCH2), 4.34–4.47 (m, 2H, OCH2), 5.54 (d, 1H, J = 26 Hz,
CHP), 6.78 (d, 2H, J = 4 Hz, Ar H), 6.89 (t, 2H, J = 8 Hz, Ar H), 7.71 (d, 2H, J =
8 Hz, Ar H), 8.20 (s, 1H, Ar H), 8.46 (d, 1H, J = 8 Hz, Ar H). MS: m/z 444.3 (m+1).
Elemental analysis: C21H23FN5O3P Calcd.: C: 56.88%; H: 5.23%; N: 15.79%. Found: C:
56.73%, H: 5.31%, N: 15.90%.
Diethyl(4-fluorophenylamino)(7-methoxytetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4e)
Yield 91%, mp 172–174◦C. IR (KBr, νmax/cm−1): 3288 (N H), 1650 (C N), 1251
(P O), 1021 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.04 (t, 3H, J = 6
and 8 Hz, CH3), 1.37 (t, 3H, J = 6 and 8 Hz, CH3), 3.91 (s, 3H, OCH3), 3.93–4.07 (m,
3H, OCH2 and NH), 4.28–4.35 (m, 2H, OCH2), 5.60 (d, 1H, J = 26 Hz, CHP), 6.63 (dd,
2H, J = 4, 6 Hz, Ar H), 6.77 (t, 2H, J = 8 Hz, Ar H), 7.25 (d, 1H, J = 8 Hz, Ar H),
7.40 (dd, 1H, J = 2, 6 Hz, Ar H), 8.02 (d, 1H, J = 0.4 Hz, Ar H), 8.56 (d, 1H, J =
10 Hz, Ar H).13C NMR (75 MHz, CDCl3, δ ppm): 16.0 (CH3), 16.4 (CH3), 52.7 (CH-P),
55.8 (OCH3), 63.6 (OCH2), 64.2 (OCH2), 109.5, 114.8, 115.7, 116.0, 118.1, 120.7, 123.1,
124.7, 125.3, 130.7, 141.6, 146.5, 155.0, 158.2, 159.0 (Ar C). MS: m/z 460.3 (m+1).
Elemental analysis: C21H23FN5O4P Calcd.: C: 54.90%; H: 5.05%; N: 15.24%. Found: C:
54.96%, H: 5.20%, N: 15.30%.
Diethyl(4-fluorophenylamino)(8-methoxytetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4f)
Yield 84%, mp 160–162◦C. IR (KBr, νmax/cm−1): 3267 (N H), 1670 (C N), 1243
(P O), 1067 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.04 (t, 3H, J = 6
and 8 Hz, CH3), 1.41 (t, 3H, J = 6 and 8 Hz, CH3), 3.86 (s, 3H, OCH3), 3.91–4.11 (m, 3H,

2120
A. H. KATEGAONKAR ET AL.
OCH2 and NH), 4.21–4.38 (m, 2H, OCH2), 5.58 (d, 1H, J = 26 Hz, CHP), 6.65 (dd, 2H,
J = 4, 6 Hz, Ar H), 6.84 (t, 2H, J = 8 Hz, Ar H), 7.23 (d, 1H, J = 8 Hz, Ar H), 7.38
(dd, 1H, J = 2, 6 Hz, Ar H), 8.14 (d, 1H, J = 0.4 Hz, Ar H), 8.61 (d, 1H, J = 10 Hz,
Ar H). MS: m/z 460.3 (m+1). Elemental analysis: C21H23FN5O4P Calcd.: C: 54.90%; H:
5.05%; N: 15.24%. Found: C: 54.78%, H: 5.16%, N: 15.10%.
Diethyl(4-fluorophenylamino)(9-methoxytetrazolo[1,5-a]quinolin-4-
yl)methylphosphonate (4g)
Yield 78%, mp 176–178◦C. IR (KBr, νmax/cm−1): 3251 (N H), 1668 (C N), 1241
(P O), 1060 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.07 (t, 3H, J = 6
and 8 Hz, CH3), 1.37 (t, 3H, J = 6 and 8 Hz, CH3), 3.78 (s, 3H, OCH3), 3.86–4.10 (m, 3H,
OCH2 and NH), 4.22–4.37 (m, 2H, OCH2), 5.62 (d, 1H, J = 26 Hz, CHP), 6.58 (dd, 2H,
J = 4, 6 Hz, Ar H), 6.81 (t, 2H, J = 8 Hz, Ar H), 7.16 (d, 1H, J = 8 Hz, Ar H), 7.35
(dd, 1H, J = 2, 6 Hz, Ar H), 8.17 (d, 1H, J = 0.4 Hz, Ar H), 8.68 (d, 1H, J = 10 Hz,
Ar H). MS: m/z 460.3 (m+1). Elemental analysis: C21H23FN5O4P Calcd.: C: 54.90%; H:
5.05%; N: 15.24%. Found: C: 54.81%, H: 5.18%, N: 15.34%.
Diethyl(7-ethoxytetrazolo[1,5-a]quinolin-4-yl)(4-
fluorophenylamino)methylphosphonate (4h)
Yield 84%, mp 134–136◦C. IR (KBr, νmax/cm−1): 3301 (N H), 1628 (C N), 1233
(P O), 1043 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.08 (t, 3H, J = 6
and 8 Hz, CH3), 1.36–1.50 (m, 6H, 2 × CH3), 3.61–4.04 (m, 4H, 2 × OCH2), 4.25–4.32
(m, 2H, OCH2), 4.73 (brs, 1H, NH), 5.35 (d, 1H, J = 26 Hz, CHP), 6.57 (dd, 2H, J = 6 and
8 Hz, Ar H), 6.82 (d, 2H, J = 8 Hz, Ar H), 6.95 (s, 1H, Ar H), 7.30 (d, 1H, J = 8 Hz,
Ar H), 7.94 (d, 1H, J = 10 Hz, Ar H), 8.30 (s, 1H, Ar H).13C NMR (75 MHz, CDCl3, δ
ppm): 14.5 (CH3), 16.0 (CH3), 16.4 (CH3), 51.3 (CH-P), 53.3 (OCH2), 63.6 (OCH2), 64.0
(OCH2), 105.6, 114.6, 115.6, 115.9, 123.9, 128.3, 128.7, 129.4, 136.3, 141.7, 143.0, 147.3,
154.8, 157.5, 157.9 (Ar C). MS: m/z 474.3 (m+1). Elemental analysis: C22H25FN5O4P
Calcd.: C: 55.81%; H: 5.32%; N: 14.79%. Found: C: 55.95%, H: 5.45%, N: 14.85%.
Diethyl(9-ethyltetrazolo[1,5-a]quinolin-4-yl)(4-fluorophenylamino)
methylphosphonate (4i)
Yield 88%, mp 124–126◦C. IR (KBr, νmax/cm−1): 3306 (N H), 1607 (C N), 1225
(P O), 1052 (P O C). 1H NMR (200 MHz, CDCl3, Me4Si, δ ppm): 1.05 (t, 3H, J = 6
and 8 Hz, CH3), 1.34–1.45 (m, 6H, 2 × CH3), 3.26 (q, 2H, J = 8 Hz, Ar CH2), 3.68–4.19
(m, 3H, OCH2 and NH), 4.24–4.31 (m, 2H, OCH2), 5.39 (d, 1H, J = 24 Hz, CHP), 6.61
(dd, 2H, J = 4, 8 Hz, Ar H), 6.82 (t, 2H, J = 8 Hz, Ar H), 7.46 (d, 1H, J = 8 Hz, Ar H),
7.51–7.75 (m, 2H, Ar H), 8.33 (d, 1H, J = 4 Hz, Ar H).13C NMR (75 MHz, CDCl3, δ
ppm): 14.7 (CH3), 16.0 (CH3), 16.4 (CH3), 24.1 (Ar CH2) 51.3 (CH-P), 63.5 (OCH2), 64.2
(OCH2), 114.5, 114.9, 115.8, 125.6, 127.3, 128.2, 129.0, 132.6, 137.8, 141.8, 142.2, 145.7,
149.0, 149.1, 154.8 (Ar C). MS: m/z 458.3 (m+1). Elemental analysis: C22H25FN5O3P
Calcd.: C: 57.76%; H: 5.51%; N: 15.31%. Found: C: 57.95%, H: 5.45%, N: 15.60%.

SYNTHESIS OF NEW α-AMINOPHOSPHONATES
2121
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