http://www.chemistrymag.org/cji/2003/059074ne.htm

  Sep. 1, 2003  Vol.5 No.9 P.74 Copyright cij17logo.gif (917 bytes)

A rapid synthesis of 6-hydroxy-2-phenylpyridazin-3-one under microwave irradiation

Li Baozhi, Zhang Jinsong, Lu Yufeng
(College of Chemistry & Environmental Science, Hebei University, Baoding 071002, China)

Received June 4, 2003; Supported by the National Science Pre-research Foundation of Hebei University, China (No.2003Q04)

Abstract A rapid and efficient synthesis of 6-hydroxyl-2-phenylpyridazin-3-one in excellent yields from maleic anhydride with phenylhydrazine hydrochloride under microwave irradiation is described. The effects of different factors on this condensation reaction have been discussed.
Keywords microwave irradiation; synthesis; pyridazinone; condensation reaction

1 INTRODUCTION
There is considerable current interest in organic reactions under microwave irradiation [1]. Some reactions that needed a long time to complete (i.e. several hours or several days) could be carried out in several minutes under microwave promotion [2,3]. Pyridazine-derivatives represent one of the most active classes of compounds processing a wide spectrum of biological activity. They were widely used in pharmaceuticals and agrochemicals [4,5]. Rohm-Haas Company had reported that pyridazines exhibit useful plant growth regulating effects [6,7]. It was reported that diacylhydrazines exhibit excellent insecticides [8-10]. Though microwave irradiation its application has been applied to accelerate some condensation reactions [11-13],  in the synthesis of pyridazinone has not been reported. Herein we wish to report a fast and efficient procedure to synthesize pyridazinone under microwave irradiation. The results show microwave irradiation can enhance this condensation reaction (Scheme 1).

Scheme 1

2 EXPERIMENTAL
Melting points were uncorrected and were measured with micro-melting point apparatus. IR spectra (KBr) were obtained on a Perkin-Elmer 983G spectrometer. 1H NMR spectra were determined on a Bruker AC-80 spectrometer using CDCl3 as solvent and tetramethylsilane (TMS) as internal reference. Mass spectra were determined on a VG7070E spectrometer (EI, 70ev). Microwave irradiation was carried out with commercial microwave oven (650W, 2450MHz). The products were characterized by 1H NMR spectra and their melting points were compared with the literature values.
General procedure. A mixture of maleic anhydride 0.5883g (6.00mmol), phenylhydrazine hydrochloride 0.4338g (3.00mmol) and dense hydrochloric acid 0.5ml (about 6.08mmol), in a cone bottle was introduced into the microwave oven and irradiated for 0.5-8min (output power at 100%). The progress of the reaction was monitored by TLC. Then, H2O (10ml) was added to the reaction mixture and the solution's pH value was adjusted to 7 with saturated Na2CO3. After cooling, the solution was filtrated to give a white solid. The crude products were recrystallized from N, N-dimethylformamide in 22.1-98.0% yields.

3 RESULTS AND DISCUSSION
This condensation reaction has been investigated at various mole ratio of phenylhydrazine hydrochloride (1) and maleic anhydride (2) when the power of microwave irradiation and the reaction time were kept unchanged. The results were showed in Table 1.The yields were increased with the mole ratio of reactant 1 and 2 up to 1:2 and then leveled off. When the other reaction conditions were invariable, the effect of different microwave power on the reaction was shown in Table 2. This may be due to the fact that the more molecules absorbs microwave energy in short time the better the results are as microwave radiation intensity increases. When the other reaction conditions were invariable, the effect of different reaction time on the condensation reaction was shown in Table 3. As summarized in Table 3, the yields were increased with the longer reaction time before 4 minutes, after it the yields were reduced because of the increase of side reaction. In order to prevent from producing the emergence of boiling phenomenon, we installed the reflux device while reacting in the microwave oven. We also tried this reaction in water bath, but very low yield (35%) was obtained. In addition, we substituted 2,4-dinitrophenylhydrazine for reactant 1 and the satisfied results were obtained. The yield was up to 88.4% at first, the melt point agrees with document value (Found:196-197ºC; Reported [14]: 196-197ºC). Secondly, the structure of the product is confirmed through element analysis and H1NMR, IR, MS, consistent with the document report. Finally, the reaction time was largely shortened compared with reported 4 hours under classical heating [14] and the 40mmHg pressure was avoided.

Table 1 Changing the mole ratio of phenylhydrazine hydrochloride/ maleic anhydride

Entry

Mole ratio a

Power (%)

Time (min)

Yield (%)

1

1:1

100

7

72.2

2

1:1.5

100

7

73.4

3

1:1.7

100

7

93.2

4

1:2

100

7

95.5

5

1:2.5

100

7

93.5

6

1:3

100

7

89.8

a The mole ratio is phenylhydrazine hydrochloride / maleic anhydride

Table 2 changing the power of microwave irradiation

Entry

Mole ratio a

Power (%)

Time (min)

Yield (%)

1

1:1.7

100

8

93.0

2

1:1.7

50

8

82.9

3

1:1.7

10

8

79.2

4

1:2

100

8

93.8

5

1:2

50

8

85.7

6

1:2

10

8

80.1

Table 3 changing the reaction time of synthesizing pyridazinone

Entry

Mole ratio a

Power (%)

Time (min)

Yield (%)

1

1:2

100

30s

22.1

2

1:2

100

50s

35.6

3

1:2

100

2min

58.3

4

1:2

100

3min

88.5

5

1:2

100

4min

98.0

6

1:2

100

5min

97.2

7

1:2

100

8min

93.8

4 CONCLUSIONS
We concluded the best synthetical conditions of the pyridazinone were the mole ratio of phenylhydrazine hydrochloride and maleic anhydride is 1:2, the power of microwave irradiation was 100%(2450MHz), reaction time was 4 min., and the yield of pyridazinone was up to 98.0%. In conclusion, a rapid and efficient method for the preparation of 6-hydroxyl-2-phenylpyridazin-3-one has been provided, which has the characteristics such as its operational simplicity, high yields, short reaction time and low cost. This method will be better than the existing one.

REFERENCES
[1] Micheal D, Mingos P, et al. Chem. Soc. Rev., 1991, 20: 1.
[2] Bram G, Majdoub A, et al. Tetrahedron, 1990, 46: 5167.
[3] Yuan Y C, Gao D B, et al. Synth. Commun., 1990, 20: 925.
[4] (a) Heinisch G, Koplent F H. Prog. Med. Chem., 1992, 29:141.
     (b) Heinisch G, Koplent F H. Prog. Med. Chem., 1990, 27:1.
[5] Sha J J. Foreign New Pesticide Handbook. Beijing: Chemical Industry Press. 1993, 10: 130 (in Chinese).
[6] Fujimoto T T. (Rohm and Haas Company). Ger offen 2 808 795, 1978.
[7] Fujimoto T T. (Rohm and Haas Company). US 4 344 934, 1982.
[8] Hsu Adan Chi-Tung. (Rohm and Haas Company). EP 0 232 075, 1987.
[9] Hsu Adan Chi-Tung. (Rohm and Haas Company). EP 0 245 950, 1987.
[10] Hsu Adan Chi-Tung. (Rohm and Haas Company). EP 0 253 468, 1987.
[11] Li Z M, Zou X J, Yao E Y, et al. Yingyong Huaxue of China, 1993,10 (6): 86.
[12] Fan X J, You J M, Tan G Z, et al. Progress in. chem. 1998, 10 (3): 285.
[13] Li H Z, Zhang J S, et al. Synth. Commun., 2002, 32 (6): 927.
[14] Zhang X G. Fine organic compound technique handbook. 1. Beijing: Science and Technology Press, 1992 (in Chinese).

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