Synthesis and antiviral activities of α-aminophosphonate derivatives containing a pyridazine moiety

Article abstract of DOI:10.1080/10426507.2010.482543

The title compounds (4) were obtained by the reaction of 2-phenyl-4-chloro-5-(4-amin ophenyl)pyridazin-3(2H)-one, aldehydes, and O,O′-dialkyl phosphite under reflux conditions using dry toluene as a solvent. The preliminary bioassays indicate that the synthesized compounds have moderate to good against tobacco mosaic virus (TMV) activity. It was found that compound 4b had a good inactivation effect in vivo against TMV, with an inhibition rate of 81.0%. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.482543

Phosphorus, Sulfur, and Silicon, 186:81–87, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.482543
SYNTHESIS AND ANTIVIRAL ACTIVITIES
OF α-AMINOPHOSPHONATE DERIVATIVES CONTAINING
A PYRIDAZINE MOIETY
Jun Zhou, Hui-Tao Fan, Bao-An Song, Lin-Hong Jin,
Pinaki S. Bhadury, De-Yu Hu, and Song Yang
Center for Research and Development of Fine Chemicals, State Key Laboratory
Breeding Base of Green Pesticide and Agricultural Bioengineering and Key
Laboratory of Green Pesticide & Agricultural Bioengineering, Ministry of
Education, Guizhou University, Guiyang, People’s Republic of China
GRAPHICAL ABSTRACT
Abstract The title compounds (4) were obtained by the reaction of 2-phenyl-4-chloro-5-(4-
amin ophenyl)pyridazin-3(2H)-one, aldehydes, and O,Oꢁ-dialkyl phosphite under reflux con-
ditions using dry toluene as a solvent. The preliminary bioassays indicate that the synthesized
compounds have moderate to good against tobacco mosaic virus (TMV) activity. It was found
that compound 4b had a good inactivation effect in vivo against TMV, with an inhibition rate
of 81.0%.
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 derivatives; antiviral activity; pyridazine moiety; synthesis
INTRODUCTION
Pyridazine derivatives are known for their wide range of biological activities as in-
secticides,1 fungicides,2 plant virucides,3 and as cardiotonics.4 They also serve as important
Received 2 February 2010; accepted 20 March 2010.
We are grateful for the generous financial support received from the National Key Program for Basic
Research (No. 2010CB126105) and the National Natural Science Foundation of China (No 20872002).
Address correspondence to Bao-An Song, Center for Research and Development of Fine Chemicals, State
Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering and Key Laboratory of Green
Pesticide & Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, People’s
Republic of China. E-mail: songbaoan22@yahoo.com
81

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synthetic precursors to many active molecules due to the ease with which the four ring
carbons can be functionalized. Another important class of compounds that belongs to the
α-aminophosphonic acid group has been routinely employed as growth regulators,5 fungi-
cides,6 plant virucides7 and herbicides.8 A great deal of research has been conducted in
recent years on the development of suitable synthetic methodologies for biologically active
α-aminophosphonates and their derivatives.9–12 Among the various synthetic methods,13
catalytic hydrophosphonylation of preformed imine by dialkyl phosphite is of particular
interest, but this method suffers from lack of applicability to sensitive imines. To address the
latter issue, and in our pursuit to prepare fluorinated heterocyclic α-aminophosphonates with
potential antiviral activity against tobacco mosaic virus (TMV) in vivo, we had employed
in situ–generated imine in a three-component, one-pot, Mannich-type reaction involving
aldehyde, amine, and dialkyl phosphite.14 In this article, we report the preparation of new
pyridazin-3(2H)-one derivatives bearing α-aminophosphonate moiety and their subsequent
evaluation as anti-TMV agents.
RESULTS AND DISSUSSION
4,5-Dichloro-2-phenyl-3-pyridazone was synthesized by following a published re-
action of mucochloric acid with phenylhydrazine. The reaction of compound 2 with 4-
aminothiophenol and anhydrous potassium carbonate in acetone then afforded 2-phenyl-
4-chloro-5-(4-aminophenylthio) pyridazin-3(2H)-one 3, which was finally reacted in a
three-component reaction with different aldehydes and dialkyl phosphites to provide title
α-aminophosphonates 4 (Scheme 1). Synthesis of 4 was executed in different solvents
under varying conditions using Lewis acid catalysts, ionic liquids, microwave irradiation,
and conventional heating. Under optimized conditions, the best result was obtained when
the Mannich reaction was carried out for 7 h in dry toluene at its reflux temperature. The
products 4a–l were obtained in good to high chemical yield (51–79%).
The chemical structures of compounds 3 and 4a–l were confirmed by their spectral
data and elemental analysis. In the IR spectrum of 3, the characteristic stretching frequency
of N H appeared at 3437–3342 cm−1, whereas pyridazinone C&DBOND;O appeared at
1
1653 cm−1. The chemical shifts in H NMR spectrum showed a singlet at δ7.09 due to
the presence of an amino group and a multiplet in the region δ 6.65–7.53 for aromatic
protons. The products 4a–l exhibited in their IR spectra the characteristic absorption bands
1
at 3267–3300 cm−1 (N H) and at 1660–1670 cm−1 (C O). The H NMR spectral data
consisted of aromatic signals (δ 6.62–7.54) and chemical shifts near δ 4.72–4.78 appearing
as a doublet of doublets due to the CH moiety adjacent to a phosphorus atom. The 31P NMR
spectral data showed the presence of a phosphorus atom and appeared around δ19.85–23.39
as singlets or doublets.
EXPERIMENTAL
The melting points of the products were determined on a XT-4 binocular microscope
(Beijing Tech Instrument Co., China) and were not corrected. The IR spectra were recorded
1
on a Bruker Vector 22 spectrometer in KBr disks. H, 13C, 31P, and 19F NMR (solvent
CDCl3 or D3CCOCD3) spectra were performed on a JEOL-ECX 500 NMR spectrometer
at room temperature using TMS as internal standard. Elemental analysis was performed on
an Elementar Vario-III CHN analyzer. Analytical TLC was performed on silica gel GF254.
Column chromatographic purification was carried out using silica gel.

α-AMINOPHOSPHONATE DERIVATIVES
83
Scheme 1 Synthetic route to title compounds 4.
Dialkyl phosphites were prepared according to the method as described in the lit-
erature.15 Compound 2 was prepared according to the procedure in the literature.16 The
antiviral activity assay and data for compounds 4a–l can be found in the Supplemental
Materials (available online).
2-Phenyl-4-chloro-5-(4-aminophenylthio)pyridazin-3(2H)-one 3
A mixture of 2 (0.96 g, 4 mmol), 4-aminothiophenol (0.5 g, 4 mmol), and anhydrous
potassium carbonate (0.83 g, 6 mmol) in dry acetone (30 mL) was stirred for 2 h at room
temperature. After cooling, the reaction mixture was filtered. The solvent was evaporated
under reduced pressure. The crude product was purified by chromatography on silica gel
using a mixture of petroleum ether and ethyl acetate (V/V = 2:1) as the eluent to give the
compound 3 (0.94 g, 71%), mp 164–166 ◦C; IR (ν cm−1): 3437, 3342 (NH), 1653 (C O),
1593, 1560, 1490; 1H NMR (500 MHz, D3CCOCD3): δ 6.83–7.58 (m, 10H, Ar-H), 5.39 (s,
2H, NH2); 13C NMR (125 MHz, D3CCOCD3): δ 154.54, 151.58, 145.00, 141.85, 137.44,
132.40, 128.52, 128.12, 126.13, 125.55, 115.53, 109.94; Anal. Calcd. for C16H12ClN3OS:
C, 58.27; H, 3.67; N, 12.74. Found: C, 58.48; H, 3.51; N, 12.58.

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Preparation of Compound 4a–l
Compound 3 (0.20 g, 0.6 mmol) was first dissolved in dry toluene (10 mL). Aldehyde
(0.6 mmol) and dialkyl phosphite (0.72 mmol) were added to the above solution, and then
the mixture was refluxed for 7 h. The solvent was evaporated under reduced pressure. The
crude product was purified by chromatography on silica gel using a mixture of petroleum
ether and ethyl acetate (V/V = 2:1) as the eluent to afford the corresponding pure α-
aminophosphonates.
O,O’-Diethyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phenyl
amino)-(phenyl)methylphosphonate (4a). Mp 192–194 ◦C; yield 63%; IR (ν
cm−1): 3288 (NH), 2980, 1660 (C O), 1593, 1519, 1490, 1234 (P O), 1020 (P-O-C); 1H
NMR (500 MHz, CDCl3): δ 6.65–7.53 (m, 15H, Ar-H), 5.21–5.25 (m, 1H, NH), 4.72 (dd,
J = 24 Hz, 7.45 Hz, 1H, CH), 3.61–4.18 (m, 4H, 2OCH2), 1.30 (t, J = 7.15 Hz, 3H, CH3),
1.09(t, J = 7.15 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ 16.24, 16.28, 16.50, 16.55,
55.19, 56.38, 63.35, 63.39, 63.73, 63.79, 113.20, 115.05, 125.18, 127.34, 127.78, 127.82,
128.36, 128.43, 128.45, 128.78, 128.93, 133.16, 135.07, 137.42, 141.38, 144.78, 148.59,
148.71, 155.29; 31P NMR (200 MHz, CDCl3): δ 22.48; Anal. Calcd for C27H27ClN3O4PS:
C, 58.32; H, 4.89; N, 7.56; Found: C, 58.08; H, 4.58; N, 7.27.
O,O’-Dipropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phen-
ylamino)-(phenyl)methylphosphonate (4b). Mp 196–199 ◦C; yield 58%; IR
(ν cm−1): 3292 (NH), 2968, 1664 (C O), 1593, 1560, 1510, 1492, 1454, 1228 (P O),
1004 (P-O-C); 1H NMR (500 MHz, CDCl3): δ 6.66–7.53 (m, 15H, Ar-H), 5.29–5.32 (m,
1H, NH), 4.74(dd, J = 24 Hz, 7.45 Hz, 1H, CH), 3.50–4.05 (m, 4H, 2OCH2), 1.64–1.71
(m, 2H, CH2), 1.44–1.51 (m, 2H, CH2), 0.91 (t, J = 7.45 Hz, 3H, CH3), 0.78 (t, J =
7.45 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ 9.94, 10.11, 23.74, 23.79, 23.95,
24.00, 68.79, 68.86, 69.02, 69.08, 112.97, 115.03, 125.19, 127.24, 127.82, 127.85, 128.37,
128.78, 128.90, 128.92, 133.18, 135.17, 137.40, 141.37, 144.86, 148.70, 148.80, 155.30;
31P NMR (200 MHz, CDCl3): δ 22.36; Anal. Calcd for C29H31ClN3O4PS: C, 59.64; H,
5.35; N, 7.19; Found: C, 59.68; H, 5.27; N, 7.38.
O,O’-Diisopropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-
one]}(phenylamino)-(phenyl)methylphosphonate (4c). Mp 182–184 ◦C; yield
57%; IR (ν cm−1): 3278 (NH), 2978, 1662 (C O), 1593, 1560, 1516, 1490, 1228(P O),
1
999 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.65–7.54(m, 15H, Ar-H), 5.23 (t, J = 8.3
Hz, 1H, NH), 4.66–4.72 (m, 2H, NCH+CH), 4.42–4.46 (m, 1H, CH), 1.33 (d, J = 6.3 Hz,
3H, CH3), 1.25 (d, J = 6.3 Hz, 3H, CH3), 1.24 (d, J = 6.3 Hz, 3H, CH3), 0.90 (d, J = 6.3
Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ 23.19, 23.24, 23.93, 23.96, 24.24, 24.27,
24.32, 24.34, 55.59, 56.80, 72.16, 72.22, 72.65, 72.70, 112.89, 114.99, 125.20, 127.25,
127.96, 128.01, 128.27, 128.38, 128.79, 133.20, 135.41, 137.41, 141.37, 144.87, 148.83,
148.93, 155.31; 31P NMR (200 MHz, CDCl3): δ 20.67; Anal. Calcd for C29H31ClN3O4PS:
C, 59.64; H, 5.35; N, 7.19; Found: C, 59.47; H, 5.17; N, 6.91.
O,O’-Diethyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phenyl
◦
amino)-(2-fluorophenyl)methylphosphonate (4d). Mp 206–208 C; yield 66%;
IR (ν cm−1): 3298 (NH), 2978, 1668 (C O), 1635, 1593, 1558, 1512, 1490, 1456,
1
1246 (P O), 1026 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.69–7.53 (m, 14H, Ar-H),
5.31–5.38 (m, 1H, NH), 5.15 (dd, J = 24 Hz, 8.6 Hz, 1H, CH), 3.68–4.26 (m, 4H, 2OCH2),
1.33 (t, J = 7.15 Hz, 3H, CH3), 1.08 (t, J = 6.85 Hz, 3H, CH3); 13C NMR (125 MHz,
CDCl3): δ 16.16, 16.21, 16.51, 16.56, 47.31, 48.52, 63.58, 63.63, 63.80, 63.86, 113.50,
114.79, 115.44, 115.62, 122.77, 122.88, 124.92, 125.19, 127.35, 128.38, 128.79, 130.05,

α-AMINOPHOSPHONATE DERIVATIVES
85
130.07, 130.12, 130.13, 133.15, 137.52, 141.36, 144.74, 148.18, 148.30, 155.30; 31P NMR
(200 MHz, CDCl3): δ 21.79 (J = 4.6 Hz); 19F NMR (470 MHz, CDCl3): δ –118.04; Anal.
Calcd for C27H26ClFN3O4PS: C, 56.50; H, 4.57; N, 7.32; Found: C, 56.81; H, 4.21; N,
7.14.
O,O’-Dipropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phen-
ylamino)-(2-fluorophenyl)methylphosphonate (4e). Mp 201–203 ◦C; yield 67%;
IR (ν cm−1): 3286 (NH), 2968, 1668 (C O), 1595, 1560, 1512, 1490, 1456, 1228 (P O),
1004 (P-O-C); 1H NMR (500 MHz, CDCl3): δ 6.67–7.52 (m, 14H, Ar-H), 5.32–5.35 (m,
1H, NH), 5.15 (dd, J = 24.6 Hz, 8.55 Hz, 1H, CH), 3.55–4.11 (m, 4H, 2OCH2), 1.41–1.72
(m, 4H, 2CH2), 0.91 (t, J = 7.45 Hz, 3H, CH3), 0.75 (t, J = 7.45 Hz, 3H, CH3); 13C NMR
(125 MHz, CDCl3): δ 9.84, 10.09, 23.70, 23.74, 23.95, 24.00, 47.17, 48.41, 69.04, 69.10,
113.38, 114.78, 115.41, 115.58. 122.91, 123.02, 124.90, 125.19, 127.32, 128.37, 128.79,
130.02, 130.07, 133.16, 137.50, 141.36, 144.78, 148.26, 148.38, 155.30, 159.82, 161.73;
31P NMR (200 MHz, CDCl3): δ 21.74 (J = 4.6 Hz); 19F NMR (470 MHz, CDCl3) δ:
-118.17; Anal. Calcd for C29H30ClFN3O4PS: C, 57.85; H, 5.02; N, 6.98; Found: C, 57.78;
H, 5.02; N, 6.49.
O,O’-Diisopropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-
one]}(phenylamino)-(2-fluorophenyl)methylphosphonate (4f). Mp 228–230
◦C; yield 59%; IR (ν cm−1): 3284 (NH), 2978, 1668 (C O), 1595, 1560, 1508, 1490,
1
1456, 1228 (P O), 993 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.68–7.51 (m, 14H,
Ar-H), 5.23–5.38 (m, 1H, NH), 5.07 (dd, J = 24.6 Hz, J = 8.6Hz, H, CH), 4.77–4.80(m,
1H, CH), 4.41–4.45 (m, 1H, CH), 1.34 (d, J = 6.3 Hz, 3H, CH3), 1.29 (d, J = 6.3 Hz, 3H,
CH3), 1.23 (d, J = 6.3 Hz, 3H, CH3), 0.85 (d, J = 6.3 Hz, 3H, CH3); 13C NMR (125 MHz,
CDCl3): δ 23.05, 23.10, 23.96, 24.00, 24.26, 47.57, 48.80, 72.38, 72.44, 72.76, 72.82,
113.18, 114.71, 115.33, 115.51, 123.23, 123.34, 124.80, 125.20, 127.29, 128.38, 128.79,
129.85, 129.90, 133.18, 137.50, 141.37, 144.81, 148.44, 148.55, 155.30, 159.89, 161.91;
31P NMR (200 MHz, CDCl3): δ 19.99 (J = 4.58 Hz); 19F NMR (470 MHz, CDCl3): δ
-118.01; Anal. Calcd for C29H30ClFN3O4PS: C, 57.85; H, 5.02; N, 6.98; Found: C, 57.98;
H, 5.24; N, 6.72.
O,O’-Diethyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phenyl
amino)-(2-methoxyphenyl)methylphosphonate (4g). Mp 205–207 ◦C; yield
79%; IR (ν cm−1): 3280 (NH), 2980, 1664 (C O), 1635, 1593, 1558, 1514, 1490, 1458,
1
1246 (P O), 1026 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.67–7.53 (m, 14H, Ar-H),
5.36–5.42 (m, 2H, NCH+NH), 3.56–4.22 (m, 7H, 2OCH2+OCH3), 1.32 (t, J = 7.45 Hz,
3H, CH3), 1.02 (t, J = 7.45 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ 16.19, 16.24,
16.55, 16.60, 47.08, 48.31, 55.87, 63.16, 63.21, 63.59, 63.64, 110.61, 112.53, 114.77,
121.25, 123.60, 125.19, 127.12, 128.16, 128.36, 128.78, 129.50, 133.25, 137.40, 141.36,
145.03, 148.69, 148.80, 155.32, 157.18, 157.23; 31P NMR (200 MHz, CDCl3): δ 23.39;
Anal. Calcd for C28H29ClN3O5PS: C, 57.39; H, 4.99; N, 7.17; Found: C, 57.68; H, 5.01;
N, 7.00.
O,O’-Dipropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phen-
ylamino)-(2-methoxyphenyl)methylphosphonate (4h). Mp 193–195 ◦C; yield
72%; IR (ν cm−1): 3296 (NH), 2966, 1670 (C O), 1635, 1593, 1560, 1519, 1490, 1456,
1
1230 (P O), 997 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.67–7.53 (m, 14H, Ar-H),
5.37–5.43 (m, 1H, NCH+NH), 3.43–4.10 (m, 7H, 2OCH2+OCH3), 1.36–1.73 (m, 4H,
2CH2), 0.92 (t, J = 7.45 Hz, 3H, CH3), 0.73 (t, J = 7.45 Hz, 3H, CH3); 13C NMR (125
MHz, CDCl3): δ 9.88, 10.14, 23.69, 23.73, 23.96, 24.01, 47.00, 48.23, 55.81, 68.60, 68.66,

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J. ZHOU ET AL.
68.86, 68.92, 110.55, 112.49, 114.74, 121.24, 123.71, 125.19, 127.12, 128.20, 128.24,
128.36, 128.78, 129.45, 133.24, 137.40, 137.40, 141.37, 145.03, 148.70, 148.81, 155.32,
157.11, 157.16; 31P NMR (200 MHz, CDCl3): δ 23.35; Anal. Calcd for C30H33ClN3O5PS:
C, 58.68; H, 5.42; N, 6.84; Found: C, 58.71; H, 5.22; N, 6.82.
O,O’-Diisopropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-
one]}(phenylamino)-(2-methoxyphenyl)methylphosphonate (4i). Mp 222–224
◦C; yield 51%; IR (ν cm−1): 3300 (NH), 2976, 1664 (C O), 1595, 1560, 1519, 1490,
1
1458, 1228 (P O), 1002 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.67–7.53(m, 14H,
Ar-H), 5.29–5.35 (m, 1H, NCH+NH), 4.74–4.80 (m, 1H, OCH), 4.34–4.40 (m, 1H, OCH),
3.93 (s, 3H, OCH3), 1.34 (d, J = 6.3 Hz, 3H, CH3), 1.28 (d, J = 6.3 Hz, 3H, CH3), 1.21
(d, J = 6.3 Hz, 6H, 2CH3), 0.76 (d, J = 6.3 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3):
δ 22.92, 22.97, 23.99, 24.03, 24.25, 24.28, 24.39, 24.41, 47.39, 48.63, 55.78, 71.83, 71.88,
72.37, 72.43, 110.57, 112.36, 114.70, 121.19, 124.13, 125.20, 127.14, 128.17, 128.21,
128.34, 128.78, 129.28, 133.25, 137.39, 141.39, 145.04, 148.87, 148.97, 155.32, 157.28;
31P NMR (200 MHz, CDCl3): δ 21.78; Anal. Calcd for C30H33ClN3O5PS: C, 58.68; H,
5.42; N, 6.84; Found: C, 58.85; H, 5.12; N, 6.60.
O,O’-Diethyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phen-
◦
ylamino)-(4-chlorophenyl)methylphosphonate (4j). Mp 206–208 C; yield 58%;
IR (ν cm−1): 3282 (NH), 2983, 1662 (C O), 1593, 1521, 1489, 1234 (P O), 1016
1
(P-O-C); H NMR (500 MHz, CDCl3): δ 6.62–7.53 (m, 14H, Ar-H), 5.24–4.27 (m, 1H,
NH), 4.70 (dd, J = 24 Hz, 6.85 Hz, 1H, NCH), 3.71–4.81 (m, 4H, 2OCH2), 1.15 (t, J =
6.9 Hz, 3H, CH3), 1.30 (t, J = 6.9 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3): δ 16.32,
16.37, 16.52, 16.57, 54.61, 55.83, 63.57, 63.62, 63.80, 63.84, 113.56, 115.04, 125.18,
127.39, 128.41, 128.81, 129. 09, 129.12, 129.16, 133.15, 133.72, 134.29, 137.48, 141.34,
144.70, 148.33, 148.45, 155.30; 31P NMR (200 MHz, CDCl3): δ 21.80; Anal. Calcd for
C27H26Cl2N3O4PS: C, 54.92; H, 4.44; N, 7.12; Found: C, 55.07; H, 4.44; N, 7.08.
O,O’-Dipropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-one]}(phen-
ylamino)-(4-chlorophenyl phenyl)methylphosphonate (4k). Mp 156–158 ◦C;
yield 67%; IR (ν cm−1): 3288 (NH), 2970, 1666 (C O), 1593, 1516, 1489, 1232 (P O),
1
999 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.63–7.53 (m, 14H, Ar-H), 5.20–4.39 (m,
1H, NH), 4.70 (dd, J = 24 Hz, 6.85 Hz, 1H, NCH), 3.60–4.08 (m, 4H, 2OCH2), 1.49–1.56
(m, 4H, 2CH2), 0.91 (t, J = 7.45 Hz, 3H, CH3), 0.81 (t, J = 7.45 Hz, 3H, CH3); 13C NMR
(125 MHz, CDCl3): δ 9.96, 10.09, 23.80, 23.84, 23.95, 24.00, 54.57, 55.78, 68.98, 69.05,
69.12, 113.50, 115.02, 125.18, 127.37, 128.40, 128.80, 129.13, 133.14, 133.86, 134.25,
137.47, 141.35, 144.71, 148.39, 148.49, 155.29; 31P NMR (200 MHz, CDCl3): δ 21.70;
Anal. Calcd for C29H30Cl2N3O4PS: C, 56.31; H, 4.89; N, 6.79; Found: C, 56.39; H, 4.52;
N, 6.49.
O,O’-Diisopropyl-4{[(2-phenyl-4-chloro-5-thio)pyridazin-3(2H)-
one]}(phenylamino)-(4-chlorophenyl phenyl)methylphosphonate (4l). Mp
198–200 ◦C; yield 63%; IR (ν cm−1): 3267 (NH), 2978, 1664 (C O), 1593, 1516, 1489,
1
1234 (P O), 993 (P-O-C); H NMR (500 MHz, CDCl3): δ 6.62–7.53 (m, 14H, Ar-H),
5.21–5.22 (m, 1H, NH), 4.48–4.74 (m, 3H, NCH+2CH), 1.33 (d, J = 6.3 Hz, 3H, CH3),
1.28 (d, J = 6.3 Hz, 3H, CH3), 1.24 (d, J = 6.3 Hz, 3H, CH3), 0.98 (d, J = 6.3 Hz,
3H, CH3); 13C NMR (125 MHz, CDCl3): δ 23.40, 23.44, 23.93, 23.96, 24.26, 55.08,
56.29, 72.42, 72.48, 72.66, 72.72, 113.31, 114.98, 125.19, 127.34, 128.40, 128.80, 128.96,
129.25, 129.29, 133.16, 134.07, 134.15, 137.46, 141.35, 144.76, 148.59, 148.70, 155.30;
31P NMR (200 MHz, CDCl3): δ 19.85; Anal. Calcd for C29H30Cl2N3O4PS: C, 56.31; H,
4.89; N, 6.79; Found: C, 56.18; H, 4.72; N, 6.67.

α-AMINOPHOSPHONATE DERIVATIVES
87
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