Simple and high yielding synthesis of new α-aminophosphonates from imines

Article abstract of DOI:10.1080/10426500701681532

A simple and high yielding method was developed for the synthesis of novel α-aminophosphonates from imines, obtained from 2-chloroquinoline-3- carbaldehyde, by using triethylphosphite in the presence of chlorotrimethylsilane (TMSCl). This method developed for the synthesis of α-aminophosphonates gave excellent yields. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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Simple and High Yielding
Synthesis of New α-
Aminophosphonates from
Imines
Rajkumar U. Pokalwar a , Rajkumar V. Hangarge a
,
Balaji R. Madje a , Madhav N. Ware a & Murlidhar S.
Shingare a
a Department of Chemistry , Dr. Babasaheb
Ambedkar Marathwada University , Aurangabad,
India
Published online: 04 Jun 2008.
To cite this article: Rajkumar U. Pokalwar , Rajkumar V. Hangarge , Balaji R. Madje ,
Madhav N. Ware & Murlidhar S. Shingare (2008) Simple and High Yielding Synthesis
of New α-Aminophosphonates from Imines, Phosphorus, Sulfur, and Silicon and the
Related Elements, 183:6, 1461-1470, DOI: 10.1080/10426500701681532
To link to this article: http://dx.doi.org/10.1080/10426500701681532
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Phosphorus, Sulfur, and Silicon, 183:1461–1470, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701681532
Simple and High Yielding Synthesis of New
α-Aminophosphonates from Imines
Rajkumar U. Pokalwar, Rajkumar V. Hangarge,
Balaji R. Madje, Madhav N. Ware,
and Murlidhar S. Shingare
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad, India
A simple and high yielding method was developed for the synthesis of novel α-
aminophosphonates from imines, obtained from 2-chloroquinoline-3-carbaldehyde,
by using triethylphosphite in the presence of chlorotrimethylsilane (TMSCl). This
method developed for the synthesis of α-aminophosphonates gave excellent yields.
Keywords 2-Chloroquinoline-3-carbaldehyde; α-aminophosphonate; imines; TMSCl;
triethylphosphite
INTRODUCTION
Quinolines1 are an important class of heterocyclic compounds and
have been screened for biological activities such as bactericidal,2
antitumor,3 anti-inflammatory,4 antimalarial5 activities. Quinolines
such as 2-chloroquinoline-3-carbaldehyde occupy a prominent posi-
tion as they are key intermediates for further annelation and for
various functional group interconversions.6 It is also reported that
organophosphates are potent pesticides, which have wide variety of
application.7Recently, some new vinyl phosphates have been reported
as potent inhibitors of phosphatase8 and phosphodiesterase.9 There are
only few reports on the synthesis and bioactivity of their analogues
which have been found to have insecticidal10 and antifungal11 activities.
Also, phosphonates12 and α-aminophosphonates are important biologi-
cally active compounds13due to their structural analogy to amino acids,
Received 4 July 2007; accepted 20 July 2007.
Authors are thankful to the Head, Department of Chemistry, Dr. B. A. M. University,
Aurangabad for providing laboratory facilities and to A. Jadhav for providing spectral
data.
Address correspondence to S. Shingare, Department of Chemistry, Dr. Babasa-
heb Ambedkar Marathwada University, Aurangabad-431004 (MH.) India. E-mail:
msshingare11@rediffmail.com
1461

1462
R. U. Pokalwar et al.
and has been the subject of considerable current interest. They act as
peptide mimics,14 enzyme inhibitors,15antibiotics and pharmacological
agents.16
Generally, α-aminophosphonates are prepared in the presence of
Lewis acids or bases by the addition of phosphorous nucleophiles
to the imines. Lewis acids such as SnCl4, SnCl2, ZrCl4, ZnCl2
and MgBr2 have been used as catalysts for such reactions.17 Re-
cently, Lewis and Bronsted acids such as LiClO4,18 InCl3,19 lan-
thanide triflates,20 TaCl5-SiO2,21montmorillonite clay-MW,22Al2O3-
MW,23 CF3COOH24 were found to be effective in the preparation of
α-aminophosphonates. However, many of these procedures require ex-
pensive reagents, long reaction times and suffer from poor yields. These
reactions cannot be carried out in one-step by the reaction between a
carbonyl compounds, an amine and dialkylphosphite because the amine
and water present during imine formation can decompose or deactivate
the Lewis acid.25
RESULTS AND DISCUSSION
In continuation of our work related to phosphorus chemistry,26 we
were interested in the synthesis of α-aminophosphonates. We have
synthesized for the first time α-aminophosphonates containing highly
bioactive quinoline moiety in two steps. In the first step, imines of
TABLE I Synthesis of Imines of 2-Chloroquinoline-3-carbaldehydes
Reaction
time (min.)
Yield
(%)
m.p.
(0C).
Entry
R1
R2
R3
R4
R5
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
H
CH3
H
H
OCH3
H
OC2H5
H
H
CH3
H
H
H
H
CH3
H
H
OCH3
H
H
H
H
CH3
H
H
OCH3
H
H
H
H
H
CH3
H
H
H
C2H5
H
H
H
CH3
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
F
F
F
F
F
F
F
F
H
H
H
H
H
H
H
H
20
30
24
25
30
25
25
30
22
25
30
25
25
20
30
25
95.7
96.2
96.0
95.2
94.8
96.2
94.6
96.2
95.8
94.6
95.5
96.0
95.4
96.2
94.8
96.0
108–110
117–119
115–117
106–108
200–202
148–150
157–159
91–93
133–135
130–132
125–127
142–144
172–174
132–134
161–163
106–108
OCH3
H
OC2H5
H
C2H5

New α-Aminophosphonates from Imines
1463
SCHEME 1 Synthesis of α-aminophosphonates from Imines of 2-
Chloroquinoline-3-carbaldehyde.
2-chloroquinoline-3-carbaldehyde were synthesized and converted to
α-aminophosphonates using TMSCl and triethylphosphite in the next
step.
Imines (2a–p) (Scheme 1, Table I) were prepared at room tem-
perature from derivatives of 2-chloroquinoline-3-carbaldehyde and 3-
fluoroaniline or 2-methylaniline in ethanol using catalytic amount of
acetic acid in excellent yields and were characterized by mass spectra.
α-aminophosphonates (3a–p) (Scheme 1, Table II) were then prepared
in excellent yields by reacting imines (2a–p) with triethylphosphite
in the presence of TMSCl under reflux using acetonitrile as the sol-
vent. After completion of the reaction, the excess TMSCl was removed
using methanol. Sixteen new compounds were synthesized using this
methodology in excellent yields. All the compounds synthesized were
unequivocally characterized based on analytical data.27
CONCLUSION
In conclusion, a new methodology was developed for the synthesis of
new α-aminophosphonate derivatives from imines of 2-chloroquinoline-
3-carbaldehydes for first time using TMSCl. All the reactions were

1464
R. U. Pokalwar et al.
TABLE II TMSCl Facilitated Synthesis of α-Aminophosphonates
Reaction
time (min.)
Yield
(%)
m.p.
(0C).
Entry
R1
R2
R3
R4
R5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
H
CH3
H
H
OCH3
H
OC2H5
H
H
CH3
H
H
H
H
CH3
H
H
OCH3
H
H
H
H
CH3
H
H
OCH3
H
H
H
H
H
CH3
H
H
H
C2H5
H
H
H
CH3
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
F
F
F
F
F
F
F
F
H
H
H
H
H
H
H
H
60
55
60
60
50
60
60
70
50
60
55
60
65
60
50
60
92.1
90.1
92.5
89.2
91.0
93.3
91.0
92.2
90.0
89.5
92.0
92.0
90.0
92.0
90.5
91.2
146–148
136–138
163–165
113–115
153–155
155–157
160–162
159–161
139–141
104–106
143–145
160–162
98–100
OCH3
H
OC2H5
H
126–128
146–148
133–135
C2H5
performed under mild reaction conditions, shorter reaction time and
in quantitative yields (Table II). The methodology developed will be of
much use to combinatorial chemist.
EXPERIMENTAL
2-Chloroquinoline-3-carbaldehydes were prepared in the laboratory by
the reported procedure28and were purified by column chromatogra-
phy over silica gel (60–120 mesh). 3-fluoroaniline, 2-methylaniline,
triethylphosphite, TMSCl were procured from Lancaster. Acetoni-
trile, N, N-Dimethylformamide (DMF), absolute ethanol, acetic acid,
methanol and hexane were procured from S.D.Fine-chem. All melting
points were determined in open capillaries on Kumar’s melting point
apparatus. 1H NMR spectra were recorded on Mercury Plus Varian in
CDCl3at 400 MHz using TMS as an internal standard. IR spectra were
recorded on a Perkin-Elmer FTIR using KBr discs. Mass spectra were
recorded on Micromass Quatrro II using electrospray Ionization tech-
nique, showing (m+1) peak as a base peak. The test for the purity of
products and the progress of the reactions were accomplished by TLC
on Merck silica gel plates.

New α-Aminophosphonates from Imines
1465
General Procedure: (2a) N-((2-chloroquinolin-3-yl)
methylene)-3-fluorobenzenamine
To the stirred solution of 2-chloroquinoline-3-carbaldehyde (0.95 g, 5
mmol) in 10 ml absolute ethanol was added 3-fluoroaniline (0.68 g,
6 mmol) and 4 to 5 drops of acetic acid. The progress of reaction was
monitored on TLC (solvent system-Hexane: Ethyl acetate). After the
completion of the reaction (20 min), 20 ml of water was added and the
solid obtained was filtered and washed with water, dried in oven at 50◦C
for 5.0 h (1.35 g, yield 95.7 %). ES-MS: m/z 285 (m+1) and 287 (m+3)
3a) Diethyl (3-fluorophenylamino)(2-chloroquinolin-3-
yl)methylphosphonate:
To a mixture of N-((2-chloroquinolin-3-yl-methylene)-3-fluorobenze
namine (1.12 g, 4 mmol) and triethylphosphite (1.66 g, 10 mmol) in 10
ml acetonitrile under reflux was added TMSCl (1.08 g, 10 mmol). The
progress of the reaction was monitored on TLC using Hexane: Ethyl
acetate (8:2) as the solvent system. After the completion of the reac-
tion, the reaction mixture was concentrated under reduced pressure to
obtain an oily residue. The oily residue was dissolved in methanol and
was concentrated, and triturated with hexane. The solid obtained was
filtered, washed with hexane. The solid was further recrystallized from
DMF and water mixture, dried in oven at 50◦C for 8.0 h (dry wt. = 1.53
g, yield 92.1%).
REFERENCES
[1] (a) R. Elderfield, Heterocycl.Compd., 4, 1 (1952); (b) O. Meth-Cohn and B. Narine,
Tetrahedron, 19, 2045 (1978); (c) M. M. Ali, Tasneem, K. C. Rajanna, and P. K.
Saiprakash, Synlett, 2, 251–253 (2001), and references cited therein.
[2] H. V. Patel, K. V. Vyas, and P. S. Fernandes, Indian J. Chem., 29(B), 836 (1990).
[3] N. M. Sukhova, M. Lidak, A. Zidermane, I. S. Pelevina, and S. S. Voronia, Khim.
Farm. Zh. 23 1226, (1989).
[4] R. D. Dillard, D. E. Pavey, and D. N. Benslay, J. Med Chem., 16, 251 (1973).
[5] J. C. Craig and P. E. Person, J. Med. Chem., 14, 1221 (1971).
[6] (a) O. Meth-Cohn, Heterocycles, 35, 539 (1993), and references cited therein; (b)
Rajendran, S. P.; Manonmoni, M.; Vijaya-Lakshmi, S. Org. Prep. Proced. Int. , 26,
383 (1994).
[7] R. Engel, Phosphorus Containing Insecticides, Handbook of Organophosphorus
Chemistry (Marcel Dekker: New York, 1992), ch. 16.
[8] (a) S. B. Hang, T. S. Mullins, H. Shim, and F. M. Raushal, Biochemistry, 36, 9022
(1997); (b) M. M. Berggren, L. A. Burns, R. T. Abraham, and G. Powis, Cancer Res.,
53, 1862 (1993); (c) Cao, X. D.; Moran, E, J.; Siev, D.; Lio, A.; Ohashi, C.; Mjalli, A.
M. Bioorg. Med. Chem. Lett., 5, 2953 (1995).

1466
R. U. Pokalwar et al.
[9] (a) T. S. Widlanski, J. K. Myer, B. Stec, K. M. Holtz, and E. R. Kantroewitz, Chem.
Biol., 4, 489 (1997); (b) J. K. Stowell and T. S. Widlanski, J. Org. Chem., 60, 6930
(1995).
[10] F. Maurer, H. J. Riebel, I. Hammann, W. Behrenz, and B. Homeyer, Ger. Offen.
2533601, 1977.
[11] Z. V. Molodykh, I. A. Aleksandrova, R. U. Belyalov, T. K. Gazizor, and V. S. Reznik.
Khim.-Farm. Zh., 24, 136 (1990).
[12] G. L. Drake, and T. A. Calamari, Industrial Uses of Phosphonates (Review), R. L.
Hilder Brand,; Ed. (CRC Press. Boca Raton, 1983), Chap. 7.
[13] (a) S. C. Fields, Tetrahedron, 55, 12237 (1999); (b) T. Yokomatsu, Y. Yoshida, and S.
Shibuya, J. Org. Chem., 59, 7930 (1994).
[14] P. Kafarski, and B. Lejczak, Phosphorus, Sulfur, Silicon Relat. Elem., 63, 193 (1991).
[15] (a) M. C. Allen, W. Fuhrer, B. Tuck, R. Wade, and J. M. Wood, J. Med. Chem., 32,
1652 (1989); (b) P. P. Giannousis, and P. A. Bartlett, J. Med. Chem., 30, 1603 (1987).
[16] (a) F. R. Atherton, C. H. Hassal, and R. W. Lambert, J. Med. Chem., 29, 29 (1986);
(b) E. K. Baylis, C. D. Campbell, and J. Dingwall, J. Chem. Soc., Perkin Trans, 1,
2845 (1984).
[17] (a) Z. H. Kudzin, P. Lyzwa, J. Luczak, and G. Andrijewski, Synthesis, 44 (1997); (b)
J. S. Yadav and B. V. S. Reddy, K. Sarita Raj, K. Bhaskar Reddy, and A. R. Prasad,
Synthesis 2277 (2001); (c) S. G. Lee, J. H. Park, J. Kang, and J. K. Lee, Chem.
Commun., 1698 (2001).
[18] M. R. Saidi and N. Azizi, Synlett 1347 (2002).
[19] B. C. Ranu, A. Hajra, and U. Jana, Org. Lett., 1, 1141 (1999).
[20] C. Qian, and T. Huang, J. Org. Chem., 63, 4125 (1998).
[21] S. Chandrasekher, S. J. Prakash, V. Jagadeshwar and C. Narsihmulu, Tetrahedron
Lett., 42, 5561 (2001).
[22] J. S. Yadav, B. V. S. Reddy, and C. Madan, Synlett, 1131 (2001).
[23] B. Kaboudin and R. Nazari, Tetrahedron Lett., 42, 8211 (2001).
[24] T. Akiyama, M. Sanada, and K. Fuchibe, Synlett, 1463 (2003).
[25] J. Zon, Pol. J. Chem., 55, 643 (1981).
[26] (a) A. S. Mane, V. P. Chavan, B. K. Karale, R. V. Hangarge, M. S. Gaikwad, and M.
S. Shingare, Synthetic Commun., 32, 2633 (2002); (b) V. P. Chavan, A. S. Mane, M.
S. Shingare, Indian J. Chem. 40B, 339 (2001); c) Pokalwar, R. U.; R. V. Hangarge,
P. V. Maske, M. S. Shingare, Arkivoc, (xi), 196 (2006).
[27] Spectral data for the all the compounds are as given as follows. 3a) Diethyl (3-
fluorophenylamino)(2-chloroquinolin-3-yl)methylphosphonate: IR (KBr):
3311 cm−1 (-NH) ; 1234 cm−1
( P ( P O
O ) ; 1032 cm−1 C ) 1H NMR (CDCl3,
δ ppm): 1.05 (t, 3H, O CH2 CH3, J = 8 Hz ); 1.35 (t, 3H, O CH2 CH3,
= 8 Hz); 3.7 (m, 1H, O CH2 CH3); 3.9 (m, 1H, O CH2 CH3); 4.2 (m, 2H,
CH2 CH3); 5.4 (d, 1H, NH CH
J
O
P
O, J = 24 Hz); 6.3–6.5 (m, 3H,
Ph-H, C2,C4,C6); 7.0 (dd, 1H, Ph H, C5,J = 8 Hz); 7.5 (t, 1H, Quinolin-H,
C5,J = 8 Hz); 7.69 (t, 1H, Quinolin-H, C6,J = 8 Hz); 7.75 (d,1H, Quinolin-H,
C7,J = 8 Hz); 7.99 (d, 1H, Quinolin-H, C8,J = 8 Hz); 8.34 (d, 1H, Quinolin-
H, C4,J = 8 Hz). ES-MS: m/z 423.1 (m+1) and 425.1 (m+3). Elemental
analysis: C20H21ClFN2O3P Calcd.: C: 56.81%, H: 5.01%, N: 6.63%; Found: C:
56.72%, H: 4.95%, N: 6.65%. 3b) Diethyl (3-fluorophenylamino)(2-chloro-
6-methylquinolin-3-yl)methylphosphonate: IR (KBr): 3305 cm−1
(
NH) ;
C ) 1H NMR (CDCl3, δ ppm):
Hz); 1.38 (t, 3H, CH2 CH3, 8
1230 cm−1
1.05 (t, 3H,
(
P
O
O ) ; 1022 cm−1
CH2 CH3,
( P O
J
=
8
O
J
=
Hz); 2.48 (s, 3H, Quinolin-CH3); 3.68 (m, 1H, O CH2 CH3); 3.88 (m, 1H,
CH2 CH3); 4.22 (m, 2H, O CH2 CH3); 5.16 (s, 1H, CH NH Ph); 5.35
O

New α-Aminophosphonates from Imines
1467
(d, 1H, NH CH
P
O, J = 24 Hz); 6.28–6.42 (m, 3H, Ph H, C2,C4,C6);
7.02 (dd, 1H, Ph H, C5,J = 8 Hz); 7.5 (d, 1H, Quinolin-H, C7,J = 8 Hz);
7.6 (s, 1H, Quinolin-H, C5); 7.9 (d,1H, Quinolin-H, C8,J = 8 Hz); 8.3 (d, 1H,
Quinolin-H, C4,J = 8 Hz). ES-MS: m/z 437.1 (m+1) and 439.2 (m+3). Elemen-
tal analysis: C21H23ClFN2O3P Calcd.: C: 57.74%, H: 5.31%, N: 6.41%; Found:
C: 57.62%, H: 5.21%, N: 6.35%. 3c) Diethyl (3-fluorophenylamino)(2-chloro-7-
methylquinolin-3-yl)methylphosphonate: IR (KBr): 3296 cm−1
(
NH) ; 1230
cm−1 O ) ; 1033 cm−1
(
P
( P O
C ) 1H NMR (CDCl3, δ ppm): 1.03 (t,
3H, O CH2 CH3,J = 8 Hz); 1.36 (t, 3H, O CH2 CH3,J = 8 Hz); 2.54 (s, 3H,
Quinolin-CH3); 3.66 (m, 1H, O CH2 CH3); 3.89 (m, 1H, O CH2-CH3); 4.22 (m,
2H, O CH2 CH3); 5.15 (s, 1H, CH NH Ph); 5.35 (d, 1H, NH CH
P O, J
= 24 Hz); 6.28–6.5 (m, 3H, Ph H, C2,C4,C6); 7.0 (dd, 1H, Ph H, C5,J = 8 Hz);
7.34 (d, 1H, Quinolin-H, C6,J = 4 Hz); 7.65 (d, 1H, Quinolin-H, C5,J = 8 Hz);
7.77 (s, 1H, Quinolin-H, C8); 8.27 (d, 1H, Quinolin-H, C4,J = 8 Hz). ES-MS: m/z
437.0 (m+1) and 439.1 (m+3). Elemental analysis: C21H23ClFN2O3P Calcd.: C:
57.74%, H: 5.31%, N: 6.41%; Found: C: 57.50%, H: 5.15%, N: 6.30%. 3d) Diethyl (3-
fluorophenylamino)(2-chloro-8-methylquinolin-3-yl) methylphosphonate:
IR (KBr): 3296 cm−1
(CDCl3, δ ppm): 1.05 (t, 3H, O CH2 CH3,J = 8 Hz); 1.36 (t, 3H, O CH2 CH3,
= 8 Hz); 2.5 (s, 3H, Quinolin CH3); 3.68 (m, 1H, O CH2 CH3); 3.9 (m, 1H,
CH2 CH3); 4.22 (m, 2H, O CH2 CH3); 5.18 (s, 1H, CH NH Ph); 5.35
(d, 1H, NH CH
(
NH) ; 1235 cm−1
(
P ( P O
O ) ; 1028 cm−1 C ) 1H NMR
J
O
P
O, J = 24 Hz); 6.2–6.5 (m, 3H, Ph H, C2,C4,C6); 7.0
(dd, 1H, Ph H, C5,J = 8 Hz); 7.33 (t, 1H, Quinolin-H, C6,J = 8 Hz); 7.5 (d,
1H, Quinolin-H, C7,J = 4 Hz); 7.6 (d, 1H, Quinolin-H, C5,J = 8 Hz); 8.22 (s,
1H, Quinolin-H, C4,J = 8 Hz). ES-MS: m/z 437.2 (m+1) and 439.1 (m+3). El-
emental analysis: C21H23ClFN2O3P Calcd.: C: 57.74%, H: 5.31%, N: 6.41%;
Found: C: 57.65%, H: 5.25%, N: 6.40%. 3e) Diethyl (3-fluorophenylamino)(2-
chloro-6-methoxyquinolin-3-yl) methylphosphonate: IR (KBr): 3305 cm−1
(
NH); 1224 cm−1
ppm): 1.05 (t, 3H, O CH2 CH3,J = 8 Hz); 1.35 (t, 3H, O CH2 CH3,J =
8 Hz); 3.68 (m, 1H, O CH2-CH3); 3.88 (s, 3H, Quinolin CH3); 3.9 (m,
1H, O CH2 CH3); 4.22 (m, 2H, O CH2 CH3); 5.16 (s, 1H, CH NH Ph);
5.35 (d, 1H, NH CH
(
P ( P O
O); 1033 cm−1 C) 1H NMR (CDCl3, δ
O
P
O, J = 24 Hz); 6.28–6.5 (m, 3H, Ph-H, C2,C4,C6);;
6.9 (s, 1H, Quinolin-H, C5); 7.0 (dd, 1H, Ph-H, C5,J = 8 Hz); 7.33 (d, 1H,
Quinolin-H, C7,J = 8 Hz); 7.88 (d, 1H, Quinolin-H, C8,J = 8 Hz); 8.22 (d, 1H,
Quinolin-H, C4,J = 8 Hz).ES-MS: m/z 453.1 (m+1) and 455.1 (m+3).Elemental
analysis: C21H23ClFN2O4P Calcd.: C: 55.70%, H: 5.12%, N: 6.19%; Found: C:
55.52%, H: 4.90%, N: 6.05%. 3f) Diethyl (3-fluorophenylamino)(2-chloro-7-
methoxyquinolin-3-yl) methylphosphonate: IR (KBr): 3296 cm−1
1230 cm−1 O ) ; 1024 cm−1
3H, O CH2 CH3,J = 8 Hz); 1.33 (t, 3H, O CH2 CH3,J = 8 Hz); 3.68 (m, 1H,
CH2 CH3); 3.86 (s, 3H, Quinolin CH3); 3.9 (m, 1H, O-CH2 CH3); 4.22
(m, 2H, O CH2 CH3); 5.16 (s, 1H, -CH-NH-Ph); 5.32 (d, 1H, NH CH O,
(
NH) ;
(
P
( P O
C ) 1H NMR (CDCl3, δ ppm): 1.05 (t,
O
O
P
J = 24 Hz); 6.3–6.5 (m, 3H, Ph-H, C2, C4,C6); 7.0 (dd, 1H, Ph H, C5,J = 8 Hz);
7.2 (d, 1H, Quinolin-H, C6,J = 8 Hz); 7.3 (s, 1H, Quinolin-H, C8); 7.62 (d,1H,
Quinolin-H, C5,J = 8 Hz); 8.22 (d, 1H, Quinolin-H, C4,J = 8 Hz). ES-MS: m/z
453.1 (m+1) and 455.0 (m+3). Elemental analysis: C21H23ClFN2O4P Calcd.: C:
55.70%, H: 5.12%, N: 6.19%; Found: C: 55.62%, H: 5.02%, N: 6.10%. 3g) Diethyl (3-
fluorophenylamino) (2-chloro-6-ethoxyquinolin-3-yl) methylphosphonate:
IR (KBr): 3302 cm−1
(
NH) ; 1232 cm−1
(
P ( P O C )
O ) ; 1035 cm−1
1H NMR (CDCl3, δ ppm): 1.03 (t, 3H, O CH2 CH3,J = 8 Hz); 1.35 (t, 3H,

1468
R. U. Pokalwar et al.
O
O
CH2-CH3,J = 8 Hz); 1.45 (t, 3H, Quinolin
CH2 CH3); 3.89 (m, 1H, O CH2-CH3); 4.06 (m, 2H, Quinolin
O, J = 24 Hz); 6.28–6.5
(m, 3H, Ph-H, C2,C4,C6); 6.99 (d,1H, Quinolin-H, C5,J = 8 Hz); 7.02 (dd, 1H, Ph-H,
O
CH2 CH3,J = 4 Hz); 3.66 (m, 1H,
O
CH2 CH3);
4.22 (m, 2H, O CH2-CH3); 5.34 (d, 1H, NH CH
P
C5,J = 8 Hz); 7.32 (d, 1H, Quinolin-H, C7,J = 4 Hz); 7.87 (d,1H, Quinolin-H, C8,
J
= 8 Hz); 8.2 (s, 1H, Quinolin-H, C4,J = 4 Hz).ES-MS: m/z 467.2 (m+1) and 469.2
(m+3). Elemental analysis: C22H25ClFN2O4P Calcd.: C: 56.60%, H: 5.40%, N:
6.00%; Found: C: 56.72%, H: 5.30%, N: 6.02%. 3h) Diethyl (3-fluorophenylamino)
(2-chloro-8-ethylquinolin-3-yl) methylphosphonate: IR (KBr): 3297 cm−1
(
NH); 1237 cm−1
( P ( P O
O); 1028 cm−1 C) 1H NMR (CDCl3, δ ppm): 1.04
(t, 3H, O CH2 CH3,J = 8 Hz); 1.35 (t, 3H, O CH2 CH3,J = 7 Hz); 1.38 (t,
3H, Quinolin CH2 CH3,J = 8 Hz); 3.22 (m, 2H, Quinolin CH2 CH3); 3.7 (m,
1H, O CH2 CH3); 3.9 (m, 1H, O CH2 CH3); 4.2 (m, 2H, O CH2 CH3); 5.37
(d, 1H, NH CH
P
O, J = 24 Hz); 6.28–6.40 (m, 3H, Ph H, C2,C4,C6); 7.02
(dd, 1H, Ph H, C5,J = 8 Hz); 7.42 (t, 1H, Quinolin-H, C6,J = 8 Hz); 7.54 (d,
1H, Quinolin-H, C7, J = 8 Hz; 7.59 (d,1H, Quinolin-H, C5,J = 8 Hz); 8.28 (d, 1H,
Quinolin-H, C4,J = 4 Hz).ES-MS: m/z 451.3 (m+1) and 453.2 (m+3). Elemen-
tal analysis: C22H25ClFN2O3P Calcd.: C: 58.61%, H: 5.59%, N: 6.21%; Found: C:
58.52%, H: 5.46%, N: 6.12%. 3i) Diethyl (o-tolylamino) (2-chloroquinolin-3-
yl) methylphosphonate: IR (KBr): 3395 cm−1
(
NH); 1236 cm−1
(
P O);
1024 cm−1
(
P
O
C) 1H NMR (CDCl3, δ ppm): 1.0 (t, 3H, O CH2 CH3,J =
8 Hz); 1.3 (t, 3H, O CH2 CH3,J = 8 Hz); 2.3 (s, 3H, Ph CH3,); 3.7 (m, 1H,
O
CH2-CH3); 3.9 (m, 1H, O CH2 CH3); 4.2 (m, 2H, O CH2-CH3); 4.9 (s, 1H,
CH NH Ph); 5.4 (d, 1H, NH CH
O, J = 24 Hz); 6.4 (d, 1H, Ph H, C6);
P
6.6 (t, 1H, Ph H, C4); 6.9 (t, 1H, Ph H, C5,J = 8 Hz); 7.0 (d, 1H, Ph H, C3,
J
= 8 Hz); 7.5 (t, 1H, Quinolin H, C6,J = 8 Hz); 7.7 (t, 1H, Quinolin-H, C7,J = 8
Hz); 7.8 (d,1H, Quinolin-H, C5); 8.0 (d, 1H, Quinolin-H, C8,J = 8 Hz); 8.3 (d, 1H,
Quinolin-H, C4,J = 8 Hz).ES-MS: m/z 419.1 (m+1) and 421.1 (m+3).Elemental
analysis: C21H24ClN2O3P Calcd.: C: 60.22%, H: 5.78%, N: 6.69%; Found: C: 60.12%,
H: 5.65%, N: 6.61%. 3j) Diethyl (o-tolylamino) (2-chloro-6-methylquinolin-
3-yl) methylphosphonate: IR (KBr): 3392 cm−1
( ( P O);
NH); 1232 cm−1
1033 cm−1
(
P
O
C) 1H NMR (CDCl3,δ ppm): 1.1 (t, 3H, O CH2 CH3,J =
8 Hz); 1.3 (t, 3H, O CH2 CH3,J = 8 Hz); 2.3 (s, 3H, Ph CH3,); 2.5 (s, 3H,
Quinolin CH3,); 3.7 (m, 1H, O CH2 CH3); 3.9 (m, 1H, O CH2 CH3); 4.2 (m,
2H, O CH2 CH3); 4.88 (s, 1H, CH NH Ph); 5.38 (d, 1H, NH CH
P O,
J = 24 Hz); 6.4 (d, 1H, Ph H, C6,J = 8 Hz); 6.6 (t, 1H, Ph H, C4,J = 8 Hz);
6.9 (t, 1H, Ph H, C5); 7.0 (d, 1H, Ph H, C3); 7.5 (d, 1H, Quinolin-H, C7,J =
8 Hz); 7.55 (s, 1H, Quinolin-H, C5); 7.9 (d,1H, Quinolin-H, C8,J = 8 Hz); 8.3 (s,
1H, Quinolin-H, C4).ES-MS: m/z 433.2 (m+1) and 435.1 (m+3). Elemental anal-
ysis: C22H26ClN2O3P Calcd.: C: 61.04%, H: 6.05%, N: 6.47%; Found: C: 60.92%,
H: 5.94%, N: 6.35%. 3k) Diethyl (o-tolylamino) (2-chloro-7-methylquinolin-
3-yl) methylphosphonate: IR (KBr): 3354 cm−1
( ( P O);
NH); 1235 cm−1
1035 cm−1
(
P
O
C) 1H NMR (CDCl3,δ ppm): 1.05 (t, 3H, O CH2 CH3,J =
8 Hz); 1.35 (t, 3H, O CH2 CH3,J = 8 Hz); 2.33 (s, 3H, Ph CH3,); 2.52 (s, 3H,
Quinolin-CH3,); 3.73 (m, 1H, O CH2 CH3); 3.94 (m, 1H, O CH2-CH3); 4.26 (m,
2H, O CH2 CH3); 4.92 (s, 1H, CH NH-Ph); 5.49 (d, 1H, NH CH
P
O, J =
24 Hz); 6.36 (d, 1H, Ph H, C6,J = 8 Hz); 6.63 (t, 1H, Ph H, C4,J = 8 Hz); 6.94 (t,
1H, Ph H, C5,J = 8 Hz); 7.04 (d, 1H, Ph H, C3,J = 8 Hz); 7.33 (d, 1H, Quinolin-H,
C6,J = 8 Hz); 7.64 (d, 1H, Quinolin-H, C5,J = 8 Hz); 7.76 (s,1H, Quinolin-H, C8);
8.26 (s, 1H, Quinolin-H, C4).ES-MS: m/z 433.3 (m+1) and 435.2 (m+3). Elemental
analysis: C22H26ClN2O3P Calcd.: C: 61.04%, H: 6.05%, N: 6.47%; Found: C: 60.86%,

New α-Aminophosphonates from Imines
1469
H: 5.90%, N: 6.30%. 3l) Diethyl (o-tolylamino) (2-chloro-8-methylquinolin-3-
yl) methylphosphonate: IR (KBr): 3418 cm−1
( ( P O); 1024
NH); 1238 cm−1
cm−1
(
P
O
C) 1H NMR (CDCl3,δ ppm): 1.0 (t, 3H, O CH2 CH3,J = 8 Hz); 1.3
(t, 3H, O CH2 CH3,J = 8 Hz); 2.3 (s, 3H, Ph CH3,); 3.7 (m, 1H, O CH2 CH3);
3.9 (m, 1H, O CH2-CH3); 4.2 (m, 2H, O CH2 CH3); 4.88 (s, 1H, CH NH-Ph);
5.3 (d, 1H, NH CH
P
O, J = 24 Hz); 6.4 (d, 1H, Ph-H, C6,J = 8 Hz); 6.6 (d, 1H,
Ph H, C4,J = 8 Hz); 6.9 (t, 1H, Ph H, C5); 7.0 (d, 1H, Ph H, C3,J = 8 Hz); 7.3 (t,
1H, Quinolin-H, C6); 7.4 (d, 1H, Quinolin-H, C7); 7.6 (d,1H, Quinolin-H, C5); 8.22 (d,
1H, Quinolin-H, C4,J = 8 Hz). ES-MS: m/z 433.3 (m+1) and 435.2 (m+3).Elemental
analysis: C22H26ClN2O3P Calcd.: C: 61.04%, H: 6.05%, N: 6.47%; Found: C: 60.96%,
H: 5.99%, N: 6.40%. 3m) Diethyl (o-tolylamino) (2-chloro-6-methoxyquinolin-
3-yl) methylphosphonate: IR (KBr): 3341 cm−1 (-NH); 1237 cm−1
( P O);
1032 cm−1
(
P
O
C) 1H NMR (CDCl3,δ ppm): 1.05 (t, 3H, O CH2 CH3,J =
8 Hz); 1.35 (t, 3H, O CH2 CH3,J = 8 Hz); 2.34 (s, 3H, Ph CH3,); 3.69 (m, 1H,
O
CH2 CH3); 3.87 (s, 3H, Quinolin
O
CH3); 4.0 (m, 1H, O CH2 CH3); 4.22
O, J = 24 Hz); 6.35 (d, 1H, Ph H,
(m, 2H, O CH2 CH3); 5.4 (d, 1H, NH CH
P
C6,J = 8 Hz); 6.63 (t, 1H, Ph H, C4,J = 8 Hz); 6.94 (t, 1H, Ph H, C5,J = 8 Hz);
7.0 (s, 1H, Quinolin H, C5,J = 4 Hz); 7.05 (d, 1H, Ph H, C3,J = 8 Hz); 7.31 (d,
1H, Quinolin-H, C7,J = 4 Hz); 7.87 (d,1H, Quinolin-H, C8,J = 8 Hz); 8.21 (d, 1H,
Quinolin-H, C4,J = 4 Hz).ES-MS: m/z 449.2 (m+1) and 451.1 (m+3). Elemental
analysis: C22H26ClN2O4P Calcd.: C: 58.86%, H: 5.84%, N: 6.24%; Found: C: 58.72%,
H: 5.72%, N: 6.15%. 3n) Diethyl (o-tolylamino)(2-chloro-7-methoxyquinolin-
3-yl) methylphosphonate: IR (KBr): 3386 cm-1 ( NH); 1236 cm-1 (
P O);
1026 cm-1 (
P
O
C) 1H NMR (CDCl3,δ ppm): 1.06 (t, 3H, O CH2 CH3,J =
8 Hz); 1.33 (t, 3H, O CH2 CH3,J = 8 Hz); 2.3 (s, 3H, Ph CH3,); 3.7 (m, 1H,
O
CH2 CH3); 3.85 (s, 3H, Quinolin
O
CH3); 3.92 (m, 1H, O CH2 CH3); 4.22
O,
(m, 2H, O CH2 CH3); 4.88 (s, 1H, CH NH Ph); 5.38 (d, 1H, NH CH
P
J = 24 Hz); 6.4 (d, 1H, Ph H, C6,J = 8 Hz); 6.6 (t, 1H, Ph H, C4,J = 8 Hz); 6.9 (t,
1H, Ph H, C5,J = 4 Hz); 7.0 (d, 1H, Ph H, C3,J = 8 Hz); 7.2 (d, 1H, Quinolin H,
C6,J = 8 Hz);7.3 (s, 1H, Quinolin-H, C8); 7.6 (d,1H, Quinolin-H, C5); 8.2 (d, 1H,
Quinolin-H, C4,J = 8 Hz).ES-MS: m/z 449.0 (m+1) and 451.1 (m+3). Elemental
analysis: C22H26ClN2O4P Calcd.: C: 58.86%, H: 5.84%, N: 6.24%; Found: C: 58.79%,
H: 5.76%, N: 6.10%. 3o) Diethyl (o-tolylamino) (2-chloro-6-ethoxyquinolin-3-
yl) methylphosphonate: IR (KBr): 3341 cm-1 ( NH); 1237 cm-1 (
P O); 1032
cm-1 (
P
O
C) 1H NMR (CDCl3,δ ppm): 1.05 (t, 3H, O CH2-CH3,J = 8 Hz);
1.35 (t, 3H, O CH2 CH3,J = 8 Hz); 1.44 (t, 3H, Quinolin
O
CH2 CH3,J = 8
Hz); 2.33 (s, 3H, Ph CH3,); 3.7 (m, 1H, O CH2 CH3); 3.9 (m, 1H, O-CH2 CH3);
4.05 (q, 2H, Quinolin CH2 CH3); 4.22 (m, 2H, O CH2 CH3); 5.39 (d, 1H,
NH CH
O
P
O, J = 24 Hz); 6.36 (d, 1H, Ph H, C6,J = 8 Hz); 6.63 (t, 1H, Ph H,
C4,J = 8 Hz); 6.94 (t, 1H, Ph H, C5,J = 8 Hz); 6.96 (d, 1H, Quinolin-H, C5,J = 4
Hz); 7.05 (d, 1H, Ph H, C3,J = 8 Hz); 7.33 (d, 1H, Quinolin H, C7.J = 8 Hz); 7.86
(d,1H, Quinolin-H, C8,J = 8 Hz); 8.2 (d, 1H, Quinolin-H, C4,J = 8 Hz).ES-MS: m/z
463.3 (m+1) and 465.3 (m+3). Elemental analysis: C23H28ClN2O4P Calcd.: C:
59.68%, H: 6.10%, N: 6.05%; Found: C: 59.72%, H: 5.96%, N: 6.00%. 3p) Diethyl (o-
tolylamino) (2-chloro-8-ethylquinolin-3-yl) methylphosphonate: IR (KBr):
3323 cm−1
(
NH) ; 1238 cm−1 O ) ; 1030 cm−1 C ) 1H NMR (CDCl3,δ
( P ( P O
ppm): 1.06 (t, 3H, O CH2 CH3,J = 8 Hz); 1.32 (t, 3H, O CH2 CH3,J = 8 Hz);
1.4 (t, 3H, Quinolin CH2 CH3,J = 8 Hz); 2.34 (s, 3H, Ph CH3,); 3.2 (q, 2H, Quino-
lin -CH2-CH3); 3.7 (m, 1H, O CH2 CH3); 3.9 (m, 1H, O CH2 CH3); 4.2 (m, 2H,
O
CH2 CH3); 4.9 (s, 1H, CH NH-Ph); 5.36 (d, 1H, NH CH
P
O, J = 24
Hz); 6.4 (d, 1H, Ph-H, C6,J = 8 Hz); 6.6 (t, 1H, Ph H, C4,J = 8 Hz); 6.9 (t, 1H,

1470
R. U. Pokalwar et al.
Ph H, C5,J = 4 Hz); 7.04 (d, 1H, Ph H, C3,J = 8 Hz); 7.42 (t,1H, Quinolin-H, C6,
J
= 8 Hz); 7.5 (d, 1H, Quinolin-H, C7.J = 8 Hz); 7.67 (d, 1H, Quinolin-H, C5,J = 8 Hz);
8.3 (d, 1H, Quinolin-H, C4,J = 8 Hz).ES-MS: m/z 447.1 (m+1) and 449.2 (m+3). El-
emental analysis: C23H28ClN2O3P Calcd.: C: 61.81%, H: 6.32%, N: 6.27%; Found:
C: 61.70%, H: 6.21%, N: 6.18%.
[28] O. Meth-Cohn, B. Narine, and B Tarnowski,. J. Chem. Soc., Perkin Trans-1, 1520
(1981).