Highly Chemoselective Synthesis of Novel 6- O -phosphorylated 6-Hydroxypyridazine-3(2H)-one

Article abstract of DOI:10.1080/10426507.2014.931395

6-O-Phosphorylated pyridazine-3(2H)-one derivatives were conveniently prepared by a facile method. Maleic hydrazide was prepared by the condensation of maleic anhydride with 85% hydrazine hydrate. It was then chemoselectively phosphorylated at the 6-O position using the Atherton-Todd reaction. An efficient, highly chemoselective method to synthesize 6-O-phosphorylated pyridazin-3(2H)-one derivatives is provided, and the approach has the merits of mild reaction conditions. GRAPHICAL ABSTRACT.

Full text of DOI:10.1080/10426507.2014.931395

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Phosphorus, Sulfur, and Silicon and the Related
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Highly Chemoselective Synthesis of Novel 6-O-
Phosphorylated 6-Hydroxypyridazine-3(2H)-one
Zhiyu Jua, Gongchun Lia, Mei Wanga, Fengling Yangb, Yong Yec & Yufen Zhaoc
a College of Chemistry and Chemical Engineering, Xuchang University, Xuchang 461000, P. R.
China
b College of Chemistry and Chemical Engineering, Pingdingshan University, Pingdingshan
467000, P. R. China
c Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department
of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052, P. R.
China
Accepted author version posted online: 26 Jun 2014.
To cite this article: Zhiyu Ju, Gongchun Li, Mei Wang, Fengling Yang, Yong Ye & Yufen Zhao (2014): Highly Chemoselective
Synthesis of Novel 6-O-Phosphorylated 6-Hydroxypyridazine-3(2H)-one, Phosphorus, Sulfur, and Silicon and the Related
Elements, DOI: 10.1080/10426507.2014.931395
To link to this article: http://dx.doi.org/10.1080/10426507.2014.931395
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Highly Chemoselective Synthesis of Novel 6-O-Phosphorylated 6-Hydroxypyridazine-
3(2H)-one
Zhiyu Jua, Gongchun Lia, Mei Wanga, Fengling Yangb, Yong Yec and Yufen Zhaoc
aCollege of Chemistry and Chemical Engineering, Xuchang University, Xuchang 461000, P. R.
China
bCollege of Chemistry and Chemical Engineering, Pingdingshan University, Pingdingshan
467000, P. R. China
cKey Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department of
Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052, P. R. China
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Abstract: 6-O-Phosphorylated pyridazine-3(2H)-one derivatives were conveniently prepared by
a facile method. Maleic hydrazide was prepared by the condensation of maleic anhydride with
85% hydrazine hydrate. It was then chemoselectively phosphorylated at the 6-O position using
the Atherton–Todd reaction. An efficient, highly chemoselective method to synthesize 6-O-
phosphorylated pyridazin-3(2H)-one derivatives is provided and the approach has the merits of
mild reaction conditions.
O
O
OH
O
HN
N
NH
N
N
O
OR
O
O
P
N
OR
O
OH
OH
Keywords: Maleic hydrazide; phosphorylation; chemoselective; Atherton–Todd reaction
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INTRODUCTION
Pyridazinone derivatives, a class of compounds containing the N-N bond, have been reported
to exhibit a wide variety of biological activities such as herbicide1, fungicidal2 and antibacterial3
activities well as to act as aldose reductase inhibitors4 and as hepatoprotective agents5. Recently
pyridazine-3(2H)-one was reported to be a stable and good leaving group and to show electron
withdrawing ability6,7. Also various organophosphorus compounds have been developed as
carboxylic acid activators. Pyridazine-3(2H)-one containing phosphate esters were synthesized
by the reaction of pyridazine-3(2H)-ones and O,O-dialkyl phosphorochloridates as carboxylic
acid activator.8
Pyridazinyl-substituted phosphorothioate esters are potent broad-spectrum insecticides. A
derivative of 6-hydroxy-3(2H)-pyridazinone, more commonly known as maleic hydrazide, is a
sparingly soluble, high melting monobasic acid, which has pKa 7.6 in 90 % ethanol.9 Substitution
at the (2H) position by alkyl or aryl groups does not affect the acidity appreciably, but the
solubility in organic solvents is improved. It was reported that these compounds react with O,O-
dialkyl phosphoro- chloridothioates similarly to phenols. O,O-Dialkyl phosphorochloridothioates
or O,O-dialkyl phosphorochloridates are highly reactive phosphoryl reagents, however, and a
regioselective phosphorylation of polyhydroxyphenols is difficult.10
The Atherton-Todd reaction is a powerful classical phosphorylation method, which is not only
widely used for the preparation of phosphates and related phosphorus compounds,11-14 but also
provides a method for the selective phosphorylation of different active groups. In a previous
paper we reported on the highly regioselective 4-O-phosphorylation of 2,4-
dihydroxyacetophotone with O,O-dialkyl phosphites.15 In addition the dialkylphosphite reagent
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showed also different chemoselectivities towards the different hydroxy functionalities in
puerarin.16 In this paper, we report on the effective and highly chemoselective O-phosphorylation
of maleic hydrazide with O,O-dialkyl phosphites by the Atherton–Todd reaction (Scheme 1).
The structures of the phosphorylated products were confirmed by electrospray ionization–mass
spectrometry (ESI–MS), nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy.
RESULTS AND DISCUSSION
Maleic hydrazide was synthesized by the condensation of maleic anhydride (1) with 85%
hydrazine hydrate. In order to obtain 6-O-phosphorylated maleic hydrazide, possible routes for
6-O-phosphorylation of maleic hydrazide are shown in Scheme 2.
Maleic hydrazide was phosphorylated with POCl3 or (RO)2P(O)Cl to yield the title
compounds with very low yields under harsh experimental conditions. When maleic hydrazide
was allowed to react with (RO)2P(O)H under Atherton–Todd reaction conditions, five 6-O-
phosphorylated maleic hydrazides were synthesized with good yields under mild reaction
conditions. It is well known that the rate of phosphorylation in an Atherton–Todd reaction
depends on the rate of nucleophilic attack. The Atherton–Todd reaction, under the present
experimental conditions, was found to proceed chemoselectively, favoring attack at 6-hydroxy
group of maleic hydrazide (2). Maleic hydrazide can, in principle, exist as equilibrium of two
tautomeric forms: the lactim and the lactam forms (Scheme 3). It has been reported that
spectroscopic studies of maleic hydrazide tautomers indicate the lactam form to be the most
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stable species in ethanol solution.17 This observation is in agreement with experimental and
theoretical data on the parent phthalhydrazide and its methyl isomers.17-20
The greater reactivity of the phenolic hydroxyl group in comparison to the amide function
results in a chemoselective reaction affording the O-phosphorylated maleic hydrazide. This
conclusion was also confirmed by 13C NMR and FT–IR spectra of compound 3a. For example,
the 13C NMR spectrum of compound 3a showed the signal of the carbon atom in 3-position at δ
= 161.3 ppm, which is in accord with the chemical shift of carbonyl carbon atom. In addition, the
infrared peaks in the region of 3300–3100 cm-1 and a broad band at 1680 cm-1 represented the
N–H stretching and bending modes, respectively. This indicates the presence of N-H and not O-
H functionality in the structure of compound 3a. The maleic hydrazide (2) reacts with various
dialkyl phosphites to form a series of 6-O-phosphorylated maleic hydrazide derivatives 3 (Table
1). The 1H, 13C and 31P NMR spectra of compound 3a are presented as an example in Figures
S1–S3 in the Supplemental Material.
Under the same experimental conditions dialkyl phosphites with different structures gave
different yields, as shown in Table 1. Compound 3a is obtained in 86 % isolated yield due to
small steric hindrance in the case of dimethyl phosphite. Diethyl phosphite, di-n-propyl
phosphite and di-n-butyl phosphite give the corresponding compound 3b, 3c and 3d in 84 %, 81
% and 80 % isolated yield, respectively. The compound 3e is obtained in only 76 % isolated
yield because of great steric hindrance in the case of di-i-butyl phosphite.
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In conclusion, a convenient procedure for the preparation of novel 6-O-phosphorylated maleic
hydrazide derivatives was reported using commercially available materials. These compounds
were synthesized by the condensation of maleic anhydride with 85% hydrazine hydrate and
subsequent Atherton–Todd reaction. Phosphorylation of maleic hydrazide was found to proceed
chemoselectively, favoring the attack at the oxygen atom in 6-position of maleic hydrazide.
EXPERIMENTAL
Maleic hydrazide (2) was synthesized according to the literature21 and was purified by
sublimation before use. Other starting materials were obtained from commercial sources and
used without further purification. Melting points were recorded with a microscopical
determinator XT4 (the thermometer was not calibrated). IR spectra were recorded with a
Shimadazu IR-408 spectrophotometer. 1H, 13C and 31P NMR spectra were obtained with a
Bruker Avance DPX-400 spectrometer; chemical shifts are given in ppm with positive values
downfield from internal tetramethylsilane (TMS) and external 85% H3PO4 (31P). Coupling
constants are in Hertz. ESI–MS spectra were recorded with a Bruker Esquire-3000 instrument.
Elemental analyses of the new compounds were performed with a Vario EL III 0 serial no.
11024054 instrument. Sample 1H, 13C and 31P NMR spectra for 3a are presented in the
Supplemental Materials (Figures S 1 – S 3)
General Experimental Procedure for the Synthesis of Compounds 3a-e
A solution of dialkyl phosphonite (2.2 mmol) in CCl4 (0.6 mL) was added dropwise to the
solution of maleic hydrazide (2 mmol) in a mixture of Et3N (0.3 mL) and the corresponding
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alcohol (1 mL) at 0 °C during 30 min. Then the reaction mixture was stirred at room temperature
for approximately 8-10 h. After water (5 mL) was added to the solution it was extracted with 3 ×
5 mL of ethyl acetate. The ethyl acetate solution was dried over anhydrous magnesium sulfate.
From the resulting solution the solvent was evaporated under reduced pressure to yield
compound 3. Finally the residue was purified by column chromatography on silica gel with ethyl
acetate / corresponding alcohol (5:1) as eluent to yield pure compounds 3.
Dimethyl (6-Oxo-1,6-dihydropyridazin-3-yl) Phosphate (3a)
Colorless liquid. 1H NMR (CDCl3, 400 MHz):  = 11.83 (b s, 1H, NH), 7.19 (d, J = 8.0 Hz,
1H, CH=CH), 7.04 (d, J = 8.0 Hz, 1H, CH=CH), 3.93 (d, J = 11.6 Hz, 6H, OCH3); 13C NMR
(CDCl3, 100 MHz):  = 161.3 (C-3), 147.6 (d, 2JPC = 6.4 Hz, C-6), 133.9 (C-4), 128.5 (d, 3JPC
=
6.0 Hz, C-5), 55.5 (d, 2JPC = 6.0 Hz, -OCH3); 31P NMR (CDCl3, 162 MHz)  = -5.3; IR (KBr): ν
= 3180 (N-H), 1685 (C=O), 1277 (P=O), 3085 (=C-H), 2975, 2880, 1600 cm−1. ESI–MS, m/z:
221.2 [M+H]+. Anal. Calcd. for C6H9N2O5P: C, 32.74; H, 4.12; N, 12.73. Found: C, 32.91; H,
4.22; N, 12.53 %.
Diethyl (6-Oxo-1,6-dihydropyridazin-3-yl) Phosphate (3b)
Colorless liquid. 1H NMR (CDCl3, 400 MHz):  = 11.69 (b s, 1H, NH), 7.12 (d, J = 8.0 Hz,
1H, CH=CH), 6.96 (d, J = 8.0 Hz, 1H, CH=CH), 4.18 (dq, 3JPH = 11.6 Hz, J = 7.2 Hz, 4H,
OCH2), 1.25 (t, J = 7.1 Hz, 6H, CH3); 13C NMR (CDCl3, 100 MHz):  = 161.3 (C-3), 147.6 (d,
2JPC = 6.3 Hz, C-6), 133.7 (C-4), 128.5 (d, 3JPC = 5.6 Hz, C-5), 65.4 (d, 2JPC = 6.0 Hz, OCH2),
15.9 (d, 3JPC = 6.7 Hz, CH3); 31P NMR (CDCl3, 162 MHz):  = -7.8; IR (KBr): ν = 3168 (N-H),
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1680 (C=O), 1277 (P=O), 3080 (=C-H), 2970, 2880, 1600 cm−1. ESI–MS, m/z: 249.2 [M+H]+.
Anal. Calcd. for C8H13N2O5P: C, 38.72; H, 5.28; N, 11.29. Found: C, 38.90; H, 5.16; N, 11.20
%.
Dipropyl (6-Oxo-1,6-dihydropyridazin-3-yl) Phosphate (3c)
White solid. 1H NMR (CDCl3, 400 MHz):  = 11.54 (b s, 1H, NH), 7.18 (d, J = 9.9 Hz, 1H,
CH=CH), 7.01 (d, J = 9.9 Hz, 1H, CH=CH), 4.14 (dt, 3JPH = 11.5 Hz, J = 6.7 Hz, 4H, OCH2),
1.70 (m, 4H, CH2), 0.94 (t, J = 7.2 Hz, 6H, CH3); 13C NMR (CDCl3, 100 MHz):  = 161.3 (C-3),
147.7 (d, 2JPC = 6.0 Hz, C-6), 133.7 (C-4), 128.6 (d, 3JPC = 5.4 Hz, C-5), 70.8 (d, 2JPC = 6.3 Hz,
OCH2), 23.5 (d, 3JPC = 7.1 Hz, CH2), 9.9 (CH3); 31P NMR (CDCl3, 162 MHz):  = -7.5; IR
(KBr): ν = 3170 (N-H), 1682 (C=O), 1275 (P=O), 3080 (=C-H), 2975, 2881, 1602 cm−1. ESI–
MS, m/z: 277.2 [M+H]+. Anal. Calcd. for C10H17N2O5P: C, 43.48; H, 6.20; N, 10.14. Found: C,
43.67; H, 6.41; N, 10.02 %.
Dibutyl (6-Oxo-1,6-dihydropyridazin-3-yl) Phosphate (3d)
White solid. 1H NMR (CDCl3, 400 MHz):  = 11.48 (b s, 1H, NH), 7.16 (d, J = 8.0 Hz, 1H,
CH=CH), 7.00 (d, J = 8.0 Hz, 1H, CH=CH), 4.15 (dt, 3JPH = 11.5 Hz, J = 7.0 Hz, 4H, OCH2),
1.64 (m, 4H, CH2), 1.34 (m, 4H, CH2), 0.87 (t, J = 7.4 Hz, 6H, CH3); 13C NMR (CDCl3, 100
MHz):  = 161.3 (C-3), 147.7 (d, 2JPC = 6.0 Hz, C-6), 133.6 (C-4), 128.5 (d, 3JPC = 5.6 Hz, C-5),
69.0 (d, 2JPC = 6.4 Hz, OCH2), 32.0 (d, 3JPC = 6.9 Hz, CH2), 18.5 (CH2), 13.4 (CH3); 31P NMR
(CDCl3, 162 MHz):  = -7.5; IR (KBr): ν = 3172 (N-H), 1681 (C=O), 1270 (P=O), 3082 (=C-H),
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2970, 2880, 1600 cm−1. ESI–MS, m/z: 305.2 [M+H]+. Anal. Calcd. for C12H21N2O5P: C, 47.37;
H, 6.96; N, 9.21. Found: C, 47.56; H, 7.05; N, 9.08 %.
Diisobutyl (6-Oxo-1,6-dihydropyridazin-3-yl) Phosphate (3e)
White solid. 1H NMR (CDCl3, 400 MHz):  = 11.41 (b s, 1H, NH), 7.22 (d, J = 9.9 Hz, 1H,
CH=CH), 7.03 (d, J = 9.9 Hz, 1H, CH=CH), 4.00 (dd, 3JPH = 11.5 Hz, J = 7.2 Hz, 4H, OCH2),
2.01 (m, 2H, CH), 0.98 (d, J = 6.7 Hz, 12H, CH3); 13C NMR (CDCl3, 100 MHz):  = 160.8 (C-
3), 147.7 (d, 2JPC = 6.0 Hz, C-6), 133.8 (C-4), 128.7 (d, 3JPC = 5.6 Hz, C-5), 75.1 (d, 2JPC = 6.6
Hz, OCH2), 29.0 (d, 3JPC = 7.2 Hz, CH), 18.6 (CH3); 31P NMR (CDCl3, 162 MHz):  = -7.5; IR
(KBr): ν = 3169 (N-H), 1680 (C=O), 1276 (P=O), 3084 (=C-H), 2971, 2880, 1601 cm−1. ESI–
MS, m/z: 305.2 [M+H]+. Anal. Calcd. for C12H21N2O5P: C, 47.37; H, 6.96; N, 9.21. Found: C,
47.58; H, 7.08; N, 9.04 %.
Supplemental data for this article can be accessed on the publisher's website. <TQ> Please
make the words "publisher's website" a live DOI link. </TQ>
FUNDING
We are grateful to the National Natural Science Foundation of China (Nos. 20972143 and
20972130), Technology Research and Development Program of Henan province (No.
122102210426), and Science and Technology Major Project of Henan Province Educational
Committee (No. 14B150060) for financial support.
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REFERENCES
1. Xu, H.; Zou, X. M.; Zhu, Y. Q.; Liu, B.; Tao, H. L.; Hu, X. H.; Sang, H. B.; Hu, F. Z.;
Wang, Y.; Yang, H. Z. Pest Manag. Sci. 2006, 62, 522-530.
2. Zou, X. J.; Lai, L. H.; Jin, G. Y.; Zhany, Z. X. J. Agric. Food. Chem. 2002, 50, 3757-3760.
3.
4. Costantino, L.; Rastelli, G.; Cignarella, G.; Barlocco, D. Il Farmaco 2000, 55, 544-552.
5. Kwon, S. K.; Moon, A. Arch. Pharm. Res. 2005, 28, 391-394.
Sonmez, M.; Borber, I.; Akbas, E. Eur. J. Med. Chem. 2006, 41, 101-105.
6. Kim, J. J.; Kweon, D. H.; Cho, S. D.; Kim, H. K.; Jung, E. Y.; Lee, S. G.; Falck, J. R.;
Yoon, Y. J. Tetrahedron 2005, 61, 5889-5894.
7. Kim, J. J.; Park, Y. D.; Lee, W. S.; Cho, S. D.; Yoon, Y. J. Synthesis 2003, 1517-1520.
7. Kim, J. J.; Park, Y. D.; Lee, W. S.; Cho, S. D.; Yoon, Y. J. Synthesis
2003, 1517-1520.
8. Won, J. E.; Kim, H. K.; Kim, J. J.; Yim, H. S.; Kim, M. J.; Kang, S. B.; Chung, H. A.; Lee,
S. G.; Yoon, Y. J. Tetrahedron 2007, 63, 12720-12730.
9.
Albert, A.; Phillips, J. N. J. Chem. Soc. 1956, 1294-1304.
Breuil, S. D. J. Org. Chem. 1961, 26, 3382–3386.
10.
11.
12.
Atherton, F. R.; Openshaw, H. T.; Todd, A. R. J. Chem. Soc. 1945, 660-663.
Jones, S.; Selitsianos, D. A. Org. Lett. 2002, 4, 3671-3673.
13. Jones, S.; Selitsianos, D.; Thompson, K. J.; Toms, S. M. J. Org. Chem. 2003, 68, 5211-
5216.
14. Cao, S.; Guo, Y.; Wang, J.; Qi, L.; Gao, P.; Zhao, H.; Zhao, Y. F. Tetrahedron Lett. 2012,
53, 6302-6305.
10
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15. Ju, Z. Y.; Li, G. C.; Wang, J.; Ye, Y.; Yang, F. L.; Zhao. Y. F. Phosphorus, Sulfur Silicon
Relat. Elem. 2012, 187, 859-863.
16. Chen, X. L.; Qu, L. B.; Yuan, J. W.; Zhao. Y. F. J. Chin. Chem. Soc. 2007, 54, 583–585.
17. Suárez, M.; Lehn, J. M.; Zimmerman, S. C.; Skoulios, A.; Heinrich, B. J. Am. Chem. Soc.
1998, 120, 9526-9532.
18. Burton, N. A.; Green, D. V. S.; Hiller, L. H.; Taylor, P. J.; Vincent, M. A.; Woodcock, S. J.
Chem. Soc., Perkin Trans. 2 1993, 3, 331-335.
19.
Elvidge, J. A.; Redman, A. P. J. Chem. Soc. 1960, 1710-1714.
20. Zhou, Z. Y.; Wu, X.; Su, Z. M.; Xie, Y. Z.; Pan, X. M.; Ding, W. B. Acta Chim. Sin. 2004,
62, 2244-2252.
21. Mizzoni, R. H.; Spoerri, P. E. J. Am. Chem. Soc. 1951, 73, 1873-1874.
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O
O
OH
O
HN
N
a
NH
N
b
N
O
O
O
P
OR
N
OR
O
OH
OH
1
3a-e
2
Scheme 1 Synthesis of the title compounds. Reagents and reaction conditions: (a) 85%
hydrazine hydrate (1 equiv.), anhydrous ethanol, reflux 6 h; (b) Dialkyl phosphite (1.1 equiv.),
Et3N (1.1 equiv.), CCl4 (2 equiv.), ice bath 0.5 h, room temperature 8–10 h.
1) POCl3; 2)ROH
O
OH
O
HN
N
NH
N
N
2) (RO)2P(O)Cl
3) (RO)2P(O)H
O
O
P
OR
N
OR
OH
OH
3a-e
2
Scheme 2 Possible routes for the 6-O-phosphorylation of maleic hydrazide.
OH
O
3
3
2
N 2
N1
4
5
4
5
NH
N1
6
6
OH
lactim
OH
lactam
Scheme 3 Maleic hydrazide tautomer equilibrium: lactim and lactam tautomer.
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Table 1 The 6-O-phosphorylated maleic hydrazide derivatives prepared
R
Yield (%)
86%
3
a
b
c
CH3
CH3CH2
84%
CH3CH2CH2
CH3CH2CH2CH2
(CH3)2CHCH2
81%
80%
d
e
76%
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