CN113248438A - Pyrazole compound and preparation method thereof - Google Patents

Pyrazole compound and preparation method thereof Download PDF

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CN113248438A
CN113248438A CN202110533936.0A CN202110533936A CN113248438A CN 113248438 A CN113248438 A CN 113248438A CN 202110533936 A CN202110533936 A CN 202110533936A CN 113248438 A CN113248438 A CN 113248438A
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phenyl
pyrazole
bromomethyl
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chloride
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CN113248438B (en
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祝华建
邵加安
张建康
吴兆晓
施涛
贾婷婷
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Hangzhou City University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Abstract

The invention discloses a pyrazole compound and a preparation method thereof, wherein the structural formula of the compound is as follows:
Figure DDA0003068978660000011
the R is1Is variously substituted phenyl, naphthyl, alkyl or heterocyclic aryl, R2Are variously substituted phenyl groups. The preparation method comprises the following steps: at a certain temperature, under the action of corresponding alkali, [3+2 ]]The aromatic cyclization reaction of (2) to synthesize the pyrazole compound containing the modifiable functional group. The preparation method provided by the invention has the advantages of simple operation, easily obtained raw materials, good tolerance of reacted functional groups, simultaneously introduced multiple substituent groups, easy separation of products and the like.

Description

Pyrazole compound and preparation method thereof
Technical Field
The invention belongs to a synthesis method of a compound, and particularly relates to a pyrazole compound and a preparation method thereof.
Background
Pyrazole and its derivatives are an important class of parent nucleus structures in many agricultural, material and pharmaceutical chemistries, for example, the most successful non-steroidal antidepressants celecoxib and teposalin are selective cyclooxygenase 2 (COX-2) inhibitors, which contain a pyrazole parent nucleus in their structure. Both the selective CB1 cannabinoid receptor inverse agonist Rimonabant (Rimonabant) for the treatment of obesity and the insecticidal drug Fipronil (Fipronil) also contain a pyrazole nucleus. The structural formula is as follows:
Figure RE-GDA0003140147490000011
the existing synthetic methods for pyrazole compounds mainly comprise: 1) synthesized by reacting 1,3 unsaturated carbonyl compound or analog with hydrazine or substituted hydrazine; 2) synthesized by a (3+2) cyclization reaction of a hydrazone or an analog thereof with an alkyne.
In the process of realizing the invention, the inventor finds that the pyrazole compounds synthesized by the existing synthesis method are basically substituted pyrazole, and cannot be used as a good synthon, so that the application of the pyrazole compounds in drug synthesis is limited.
The synthesis method comprises the following steps:
Figure RE-GDA0003140147490000021
in conclusion, the development of a novel, simple and efficient synthetic method and the synthesis of the pyrazole compound with a modifiable functional group have very important application values.
Disclosure of Invention
The invention aims to provide a pyrazole compound, which has a structural formula as follows:
Figure RE-GDA0003140147490000022
the R is1Is variously substituted phenyl, naphthyl, alkyl or heterocyclic aryl, R2Are variously substituted phenyl groups.
The invention also provides a pyrazole compound which comprises any one of the following components:
5- (bromomethyl) -1, 3-diphenyl-1H-pyrazole (example 1)
5- (bromomethyl) -1-phenyl-3- (p-tolyl) -1H-pyrazole (example 2)
5- (bromomethyl) -3- (4-methoxyphenyl) -1-phenyl-1H-pyrazole (example 3)
5- (bromomethyl) -3- (3-methoxyphenyl) -1-phenyl-1H-pyrazole (example 4)
5- (bromomethyl) -3- (2-methoxyphenyl) -1-phenyl-1H-pyrazole (example 5)
5- (bromomethyl) -3- (4-fluorophenyl) -1-phenyl-1H-pyrazole (example 6)
5- (bromomethyl) -3- (4-chlorophenyl) -1-phenyl-1H-pyrazole (example 7)
5- (bromomethyl) -3- (3-chlorophenyl) -1-phenyl-1H-pyrazole (example 8)
5- (bromomethyl) -3- (2-chlorophenyl) -1-phenyl-1H-pyrazole (example 9)
5- (bromomethyl) -3- (4-bromophenyl) -1-phenyl-1H-pyrazole (example 10)
5- (bromomethyl) -1-phenyl-3- (4- (trifluoromethyl) phenyl) -1H-pyrazole (example 11)
4- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) benzonitrile (example 12)
5- (bromomethyl) -3- (naphthalen-1-yl) -1-phenyl-1H-pyrazole (example 13)
2- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) pyridine (example 14)
5- (bromomethyl) -3- (furan-2-yl) -1-phenyl-1H-pyrazole (example 15)
5- (bromomethyl) -3- (tert-butyl) -1-phenyl-1H-pyrazole (example 16)
5- (bromomethyl) -3-phenyl-1- (p-tolyl) -1H-pyrazole (example 17)
5- (bromomethyl) -1- (4-methoxyphenyl) -3-phenyl-1H-pyrazole (example 18)
5- (bromomethyl) -1- (4-fluorophenyl) -3-phenyl-1H-pyrazole (example 19)
5- (bromomethyl) -1- (4-chlorophenyl) -3-phenyl-1H-pyrazole (example 20)
5- (bromomethyl) -1- (3-chlorophenyl) -3-phenyl-1H-pyrazole (example 21)
5- (bromomethyl) -1- (2-chlorophenyl) -3-phenyl-1H-pyrazole (example 22)
5- (bromomethyl) -1- (4-bromophenyl) -3-phenyl-1H-pyrazole (example 23)
5- (bromomethyl) -3-phenyl-1- (4- (trifluoromethyl) phenyl) -1H-pyrazole (example 24)
Another object of the present invention is to provide a method for preparing the pyrazole compound, which comprises:
completely dissolving 1.0 equivalent of chlorinated hydrazone, 0.5 to 5.0 equivalents of prop-2-alkynyl sulfate and 2.0 to 3.0 equivalents of alkali in an aprotic solvent, and stirring for reaction under the protection of nitrogen;
wherein the structural formula of the chlorinated hydrazone is as follows:
Figure RE-GDA0003140147490000041
the R is1Is variously substituted phenyl, naphthyl, alkyl or heterocyclic aryl, R2Is variously substituted phenyl;
the structural formula of the prop-2-alkynyl sulfur salt is as follows:
Figure RE-GDA0003140147490000042
and (2) filtering the reaction system obtained in the step (1), drying and concentrating the filtrate to obtain a residue, and performing silica gel column chromatography on the residue to obtain the pyrazole compound.
Further, in the step (1), the reaction temperature is 0 ℃, 10 ℃, or 25 ℃, preferably 0 ℃.
Further, in the step (1), the reaction time is 12 to 36 hours.
Further, the aprotic solvent is one or more selected from acetonitrile, dichloromethane, chloroform, acetone and 1, 2-dichloroethane, and is mixed in any ratio.
Further, the aprotic solvent is preferably chloroform.
Further, the alkali is selected from one or more of sodium acetate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium acetate and triethylamine which are mixed according to any ratio.
Further, the base is preferably potassium carbonate.
Further, the amount of the base used is preferably 2.0 equivalents of the chlorinated hydrazone.
The inventor obtains a pyrazole compound with multiple functional groups by dissolving a chloro hydrazone derivative and a propyl-2-alkynyl sulfur salt in chloroform and stirring for 12-36 hours at the temperature of 0 ℃. The synthesis method has the advantages of high yield, convenient post-treatment, no need of heavy/noble metal catalyst, mild reaction temperature and easily obtained reaction raw materials, and provides a simple, easy and efficient synthesis method for obtaining the polysubstituted pyrazole compound.
The synthesis method of the polysubstituted pyrazole compound provided by the invention has the following characteristics: 1. no heavy/noble metal catalyst is needed; 2. the reaction temperature is milder than that of the conventional synthetic method; 3. the substrate has wide applicability, and various substrate structures can bear the reaction conditions.
Detailed Description
The invention will now be further illustrated by the following examples.
Example 15- (bromomethyl) -1, 3-diphenyl-1H-pyrazole
Figure RE-GDA0003140147490000051
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 60%.
White solid, yield 65%. The melting point is 93.8-96.2 ℃.1H-NMR(400MHz,CDCl3):δ7.86(dd, J＝7.2,1.6Hz,2H),7.67-7.63(m,2H),7,54(t,J＝7.6Hz,2H)7.47(t,J＝7.2Hz, 1H),7.42(t,J＝7.2Hz,2H),7.34(t,J＝7.2Hz,1H),6.85(s,1H),4.51(s,2H)。13C NMR(100MHz,CDCl3):δ152.2,140.3,139.3,132.8,129.6,128.9,128.8,128.4, 126.0,125.4,106.2,21.3；HRMS calcd for C16H13BrN2+H+:313.0335,found: 313.0335。
Example 1 comparison of yield under different solvent conditions
Figure RE-GDA0003140147490000061
Figure RE-GDA0003140147490000062
Example 1 comparison of yield under different base conditions
Figure RE-GDA0003140147490000063
Figure RE-GDA0003140147490000064
Example 1 comparison of yields at different reaction temperatures and times
Figure RE-GDA0003140147490000065
Figure RE-GDA0003140147490000071
Example 1 comparison of yield under different equivalents of potassium carbonate
Figure RE-GDA0003140147490000072
Figure RE-GDA0003140147490000073
Example 1 comparison of yields for different equivalents of prop-2-ynylsulfonate
Figure RE-GDA0003140147490000074
Figure RE-GDA0003140147490000075
Comparative example 1: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and sodium acetate (2.0mmol,2.0 equiv.) were dissolved in 10mL acetonitrile and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder in a yield of 27%.
Comparative example 2: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and sodium acetate (2.0mmol,2.0 equiv.) were dissolved in 10mL of dichloromethane and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder in a yield of 33%.
Comparative example 3: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and sodium acetate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 41%.
Comparative example 4: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and sodium acetate (2.0mmol,2.0 equiv.) were dissolved in 10mL of 1, 2-dichloroethane, and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 37%.
Comparative example 6: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium acetate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 26%.
Comparative example 7: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and triethylamine (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 44%.
Comparative example 8: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 12 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder in a yield of 57%.
Comparative example 9: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 60%.
Comparative example 10: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 10 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 49%.
Comparative example 11: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 25 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 26%.
Comparative example 12: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (2.5mmol,2.5 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder in a yield of 51%.
Comparative example 13: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (2.0mmol,2.0 equiv.) and potassium carbonate (3.0mmol,3.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 55%.
Comparative example 14: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (0.5mmol,0.5 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 41%.
Comparative example 15: 5- (bromomethyl) -1, 3-diphenyl-1H-pyrazoles
N-Phenylphenylhydrazinecarbonyl chloride (1.0mmol,1.0 equiv.), prop-2-ynylsulfonate (5.0mmol,5.0 equiv.) and potassium carbonate (2.0mmol,2.0 equiv.) were dissolved in 10mL of chloroform and stirred at 0 ℃ for 24 hours under nitrogen. After the reaction was completed, the reaction system was filtered, the filtrate was evaporated and concentrated to give a residue, and the obtained residue was separated and purified by silica gel column chromatography (petroleum ether: ethyl acetate: 100:1) to give a white powder with a yield of 45%.
Example 25- (bromomethyl) -1-phenyl-3- (p-tolyl) -1H-pyrazole
Figure RE-GDA0003140147490000111
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-methoxy-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 64%.
White solid, yield 64%. The melting point is 96.5-100.1 ℃.1H-NMR(400MHz,CDCl3):δ7.76 (d,J＝8.0Hz,2H),7,65(t,J＝6.8Hz,2H),7.54(t,J＝7.6Hz,2H),7.46(t,J＝7.2 Hz,1H),7.23(d,J＝8.0Hz,2H),6.82(s,1H),4.50(s,2H)；13C NMR(100MHz, CDCl3):δ152.3,140.2,139.3,138.2,130.0,129.6,129.5,128.7,125.9,125.4,106.0, 21.5,21.4；HRMS calcd for C17H15BrN2+H+:327.0491,found:327.0488。
Example 35- (bromomethyl) -3- (4-methoxyphenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000121
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-methoxy-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 62%.
White solid, yield 62%. The melting point is 107.8-109.3 ℃.1H-NMR(400MHz,CDCl3):δ 7.81-7.78(m,2H),7.66-7.62(m,2H),7,55-7.51(m,2H),7.47-7.43(m,1H),6.95(d, J＝8.8Hz,2H),6.77(s,1H),4.50(s,2H),3.84(s,3H)；13C NMR(100MHz, CDCl3):δ159.9,152.0,140.20,139.4,129.6,128.7,127.3,125.7,125.4,114.3, 105.7,55.5,21.4；HRMS calcd for C17H15BrN2O+H+:343.0441,found:343.0443。
Example 45- (bromomethyl) -3- (3-methoxyphenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000122
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -3-methoxy-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 65%.
White solid, yield 65%. The melting point is 101.2-104.5 ℃.1H NMR(400MHz,CDCl3)δ 7.67-7.63(m,2H),7.56-7.51(m,2H),7.49-7.46(m,1H),7.45-7.42(m,2H),7.33(t, J＝8.0Hz,1H),6.91-6.87(m,1H),6.83(s,1H),4.50(s,2H),3.87(s,3H)；13C NMR(100MHz,CDCl3):δ160.2,152.1,140.3,139.3,134.3,129.9,129.6,128.8, 125.5,118.6,114.5,111.0,106.4,55.6,21.3；HRMS calcd for C17H15BrN2O+H+: 343.0441,found:343.0444。
Example 55- (bromomethyl) -3- (2-methoxyphenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000131
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -2-methoxy-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 49%.
White solid, yield 49%. The melting point is 115.1-117.3 ℃.1H NMR(400MHz,CDCl3)δ 8.06(dd,J＝7.6,1.6Hz,1H),7.68-7.65(m,2H),7,55-7.51(m,2H),7.47-7.43(m, 1H),7.35-7.30(m,1H),7.12(d,J＝2.4Hz,1H),7.03(td,J＝7.6,1.2Hz,1H),7.00 (d,J＝8.0Hz,1H),4.59(s,2H),3.94(s,3H)；13C NMR(100MHz,CDCl3):δ 157.1,149.1,139.4,139.2,129.5,129.4,128.9,128.6,125.4,121.7,121.1,111.4, 110.2,55.7,21.7；HRMS calcd for C17H15BrN2O+H+:343.0441,found:343.0443。
Example 65- (bromomethyl) -3- (4-fluorophenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000132
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-fluoro-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 61%.
White solidYield 61%. The melting point is 106.5-111.4 ℃.1H NMR(400MHz,CDCl3)δ 7.85-7.81(m,2H),7,63(t,J＝7.2Hz,2H),7.56-7.52(m,2H),7.49-7.45(m,1H), 7.10(d,J＝8.8Hz,2H),6.79(s,1H),4.50(s,2H)；13C NMR(100MHz,CDCl3):δ 164.3,161.8.,151.3,140.5,139.2,129.7,129.1,128.9,127.7(d,J＝21.5Hz),125.4, 115.9,115.7,105.9,21.2；HRMS calcd for C16H12BrFN2+H+:331.0241,found: 331.0238。
Example 75- (bromomethyl) -3- (4-chlorophenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000141
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-chloro-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 66%.
White solid, yield 66%. The melting point is 100.2-104.0 ℃.1H NMR(400MHz,CDCl3)δ 7.79(d,J＝7.2Hz,2H),7,63(t,J＝6.4Hz,2H),7.54(t,J＝6.0Hz,2H),7.48(t,J＝6.0Hz,1H),7.38(d,J＝7.2Hz,2H),6.81(s,1H),4.49(s,2H)；13C NMR(100 MHz,CDCl3):δ151.1,140.6,139.1,134.2,131.4,129.7,129.1,129.0,127.2,125.4, 106.1,21.1；HRMS calcd for C16H12BrClN2+H+:346.9945,found:346.9941。
Example 85- (bromomethyl) -3- (3-chlorophenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000142
The synthesis procedure is the same as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -3-chloro-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 72%.
White solid, yield 72%. The melting point is 105.5-109.1 ℃.1H NMR(400MHz,CDCl3)δ 7.87(s,1H),7.72(d,J＝6.0Hz,1H),7,64(t,J＝7.8Hz,2H),7.55(t,J＝6.0Hz,2H), 7.49(t,J＝6.0Hz,1H),7.35-7.27(m,2H),6.83(s,1H),4.49(s,2H)；13C NMR (100MHz,CDCl3):δ150.9,140.6,139.1,134.9,134.7,130.2,129.7,129.0,128.44, 126.1,125.4,124.1,106.2,21.1；HRMS calcd for C16H12BrClN2+H+:346.9945, found:346.9944。
Example 95- (bromomethyl) -3- (2-chlorophenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000151
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -2-chloro-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 51%.
White solid, yield 51%. The melting point is 114.8-120.1 ℃.1H NMR(500MHz,CDCl3)δ 7.91(dd,J＝7.6,2.4Hz,1H),7.68-7.64(m,2H),7,56-7.52(m,2H),7.49-7.45(m, 2H),7.33-7.27(m,2H),7.10(s,1H),4.53(s,2H)；13C NMR(100MHz,CDCl3):δ 149.8,139.5,139.2,132.5,131.8,130.8,130.6,129.6,129.4,128.9,127.1,125.4, 110.1,21.3；HRMS calcd for C16H12BrClN2+H+:346.9945,found:346.9941。
Example 105- (bromomethyl) -3- (4-bromophenyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000152
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-bromo-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 61%.
White solid, yield 61%. The melting point is 99.8-103.2 ℃.1H NMR(400MHz,CDCl3)δ7.73 (d,J＝8.4Hz,2H),7,63(t,J＝7.2Hz,2H),7.54(t,J＝7.6Hz,4H),7.47(t,J＝7.2 Hz,1H),6.82(s,1H),4.50(s,2H)；13C NMR(100MHz,CDCl3):δ151.1,140.6, 139.1,132.0,131.9,129.7,129.0,127.5,125.4,122.3,106.0,21.1；HRMS calcd for C16H12Br2N2+H+:390.9440,found:390.9435。
Example 115- (bromomethyl) -1-phenyl-3- (4- (trifluoromethyl) phenyl) -1H-pyrazole
Figure RE-GDA0003140147490000161
The synthesis procedure is as in example 1 except that N-phenyl phenylhydrazinecarbonyl chloride is replaced by (Z) -N' -phenyl-4- (trifluoromethyl) phenylhydrazinecarbonyl chloride to give a white solid in 67% yield.
White solid, yield 67%. The melting point is 111.2-115.7 ℃.1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.0Hz,2H),7,66(t,J＝7.2Hz,4H),7.58-7.54(m,2H),7.51-7.47(m, 1H),6.89(s,1H),4.51(s,2H)；13C NMR(100MHz,CDCl3):δ150.8,140.8.,139.1, 129.7,129.1,126.1,125.9(q,J＝7.9Hz),125.5,106.4,21.0；HRMS calcd for C17H12BrF3N2+H+:381.0209,found:381.0207。
Example 124- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) benzonitrile
Figure RE-GDA0003140147490000162
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -4-cyano-N' -phenylbenzenecarbazoyl chloride to give a white solid with a yield of 65%.
White solid, yield 65%. The melting point is 134.5-138.0 ℃.1H NMR(400MHz,CDCl3)δ 7.95(d,J＝7.6Hz,2H),7,69(d,J＝8.0Hz,2H),7.63(t,J＝7.2Hz,2H),7.56(t,J＝ 7.2Hz,2H),7.52-7.48(m,1H),6.89(s,1H),4.50(s,2H)；13C NMR(100MHz, CDCl3):δ150.2,141.1,138.9,137.3,132.8,129.8,129.3,126.3,125.4,119.2,111.7, 106.6,20.8；HRMS calcd for C17H12BrN3+H+:338.0287,found:338.0288。
Example 135- (bromomethyl) -3- (naphthalen-1-yl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000163
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' -phenyl-1-naphthylcarboximoyl chloride to give a white solid with a yield of 41%.
White solid, yield 41%. The melting point is 95.8-98.3 ℃.1H NMR(400MHz,CDCl3)δ8.60 (dd,J＝7.2,1.6Hz,1H),7,92-7.88(m,2H),7.78(dd,J＝7.2,1.2Hz,1H),7.75-7.71 (m,2H),7.59-7.52(m,5H),7.50-7.46(m,1H),6.87(s,1H),4.59(s,2H)；13C NMR (100MHz,CDCl3):δ152.1,139.6,139.3,134.2,131.5,130.9,129.6,128.9,128.8, 128.6,127.5,126.7,126.2,126.1,125.6,125.4,110.0,21.3；HRMS calcd for C20H15BrN2+H+:363.0491,found:363.0489。
Example 142- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) pyridine
Figure RE-GDA0003140147490000171
The synthesis procedure is as in example 1 except that N-phenyl phenylhydrazinecarboxylic acid chloride is replaced by (Z) -N' -phenyl methyl pyridine hydrazinecarboxylic acid chloride to give a white solid with a yield of 32%.
White solid, yield 32%. The melting point is 91.2-95.4 ℃.1H NMR(400MHz,CDCl3)δ8.64 (d,J＝4.8Hz,1H),8.03(d,J＝8.0Hz,1H),7.73(td,J＝8.0,1.6Hz,1H),7.67-7.63 (m,2H),7.56-7.51(m,2H),7.49-7.46(m,1H),7.25-7.22(m,1H),7.19(s,1H),4.51 (s,2H)；13C NMR(100MHz,CDCl3):δ152.4,151.8,149.6,140.7,139.2,136.9, 129.7,129.0,125.6,123.1,120.4,107.6,21.2；HRMS calcd for C15H12BrN3+H+: 314.0287,found:314.0288。
Example 155- (bromomethyl) -3- (furan-2-yl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000172
The synthesis procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' -phenylfuran-2-carbohydrazide oyl chloride to give a white solid with a yield of 40%.
White solid, yield 40% and melting point 72.6-76.8 ℃.1H NMR(400MHz,CDCl3)δ 7.63-7.60(m,2H),7.53(t,J＝7.6Hz,2H),7.47-7.44(m,2H),6.77(s,1H),6.75(d,J ＝2.8Hz,1H),6.48-6.47(m,1H),4.47(s,2H)；13C NMR(100MHz,CDCl3):δ 148.3,144.8,142.4,140.2,139.0,129.6,129.0,125.6,111.6,106.7,105.8,21.0； HRMS calcd for C14H11BrN2+H+:303.0128,found:303.0122。
Example 165- (bromomethyl) -3- (tert-butyl) -1-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000181
The synthesis procedure is as in example 1 except that N-phenyl phenylhydrazinecarbonyl chloride is replaced by (Z) -N' -phenyl pivaloyl chloride to give a white solid with a yield of 65%.
White solid, yield 65%. The melting point is 68.9-72.4 ℃.1H NMR(400MHz,CDCl3)δ7.57 (d,J＝7.2Hz,2H),7.49(t,J＝8.0Hz,2H),7.40(t,J＝7.2Hz,1H),6.39(s,1H), 4.46(s,2H),1.35(s,9H)；13C NMR(100MHz,CDCl3):δ162.8,139.6,138.9,129.5, 128.3,125.3,105.7,32.4,30.7,21.9；HRMS calcd for C14H17BrN2+H+:293.0648, found:293.0644。
Example 175- (bromomethyl) -3-phenyl-1- (p-tolyl) -1H-pyrazole
Figure RE-GDA0003140147490000182
The procedure was as in example 1 except that N-phenylbenzenecarbazoyl chloride was replaced with (Z) -N' - (p-tolyl) phenylcarbazoyl chloride to give a white solid in 57% yield.
White solid, yield 57%. The melting point is 85.0-88.3 ℃.1H NMR(400MHz,CDCl3)δ7.86 (dd,J＝7.2,1.6Hz,2H),7,53-7.49(m,2H),7.41(t,J＝7.6Hz,2H),7.35-7.43(m, 3H),6.83(s,1H),4.49(s,2H)；13C NMR(100MHz,CDCl3):δ152.0,140.3,138.9, 136.8,132.9,130.2,128.9,128.3,126.0,125.4,105.9,21.4,21.3；HRMS calcd for C17H15BrN2+H+:327.0491,found:327.0487。
Example 185- (bromomethyl) -1- (4-methoxyphenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000191
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' - (4-methoxyphenyl) phenylcarbazoyl chloride to give a white solid in 47% yield.
White solid, yield 47%. The melting point is 114.4-118.2 ℃.1H NMR(400MHz,CDCl3)δ 7.85(d,J＝6.8Hz,2H),7,54(t,J＝8.0Hz,2H),7.41(t,J＝7.2Hz,2H),7.33(t,J＝ 6.8Hz,1H),7.03(d,J＝8.4Hz,2H),6.81(s,1H),4.46(s,2H),3.88(s,3H)；13C NMR(100MHz,CDCl3):δ160.0,151.9,140.4,133.0,132.2,128.9,128.3,127.1, 125.9,114.7,105.6,55.8,21.3；HRMS calcd for C17H15BrN2O+H+:343.0441, found:343.0443。
Example 195- (bromomethyl) -1- (4-fluorophenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000192
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' - (4-fluorophenyl) phenylcarbazoyl chloride to give a white solid in 75% yield.
White solid, yield 75%. The melting point is 101.7-104.3 ℃.1H NMR(400MHz,CDCl3)δ 7.84(dd,J＝7.2,1.6Hz,2H),7,65-7.60(m,2H),7.42(t,J＝7.2Hz,2H),7.34(t,J＝ 7.2Hz,1H),7.25-7.20(m,2H),6.83(s,1H),4.47(s,2H)；13C NMR(100MHz, CDCl3):δ162.7(d,J＝247Hz),152.3,140.5,135.4,132.7,128.9,128.5,127.5(d,J＝9Hz),126.0,116.6(d,J＝23Hz),106.1,21.1；HRMS calcd for C16H12BrFN2+H+: 331.0241,found:331.0244。
Example 205- (bromomethyl) -1- (4-chlorophenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000201
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced with (Z) -N' - (4-chlorophenyl) phenylcarbazoyl chloride to give a white solid in 63% yield.
White solid, yield 63%. The melting point is 88.6-93.4 ℃.1H NMR(400MHz,CDCl3)δ7.84 (d,J＝7.2Hz,2H),7,61(t,J＝8.0Hz,2H),7.51(d,J＝8.4Hz,2H),7.42(t,J＝7.2 Hz,2H),7.35(t,J＝7.2Hz,1H),6.84(s,1H),4.49(s,2H)；13C NMR(100MHz, CDCl3):δ152.5,140.4,137.8,134.6,132.6,129.8,128.9,128.6,126.6,126.0,106.5, 21.1；HRMS calcd for C16H12BrClN2+H+:346.9945,found:346.9941。
Example 215- (bromomethyl) -1- (3-chlorophenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000202
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced with (Z) -N' - (3-chlorophenyl) phenylcarbazoyl chloride to give a white solid in 78% yield.
White solid, yield 78%. The melting point is 77.2-79.5 ℃.1H NMR(400MHz,CDCl3)δ7.85 (d,J＝6.0Hz,2H),7,71(s,1H),7.58(t,J＝6.4Hz,1H),7.47-7.41(m,4H),7.38-7.33 (m,1H),6.85(s,1H),4.51(s,2H)；13C NMR(100MHz,CDCl3):δ152.6,140.4, 140.3,135.4,132.6,130.6,129.0,128.9,128.6,126.0,125.7,123.2,106.7,21.0；HRMS calcd for C16H12BrClN2+H+:346.9945,found:346.9939。
Example 225- (bromomethyl) -1- (2-chlorophenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000211
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' - (2-chlorophenyl) phenylcarbazoyl chloride, the yield is 47%.
White solid, yield 47%. The melting point is 96.3-99.2 ℃.1H NMR(400MHz,CDCl3)δ7.85 (d,J＝7.2Hz,2H),7,62(dd,J＝7.2,1.6Hz,1H),7.58(dd,J＝6.4,1.6Hz,1H), 7.51-7.46(m,2H),7.41(t,J＝7.6Hz,2H),7.33(t,J＝7.2Hz,1H),6.83(s,1H),4.36 (s,2H)；13C NMR(100MHz,CDCl3):δ152.6,141.6,136.7,132.8,132.7,131.3, 130.7,130.5,128.9,128.5,128.0,126.1,105.1,20.5；HRMS calcd for C16H12BrClN2+H+:346.9945,found:346.9944。
Example 235- (bromomethyl) -1- (4-bromophenyl) -3-phenyl-1H-pyrazole
Figure RE-GDA0003140147490000212
The procedure was as in example 1 except that N-phenylbenzenecarbazoyl chloride was replaced with (Z) -N' - (4-bromophenyl) phenylcarbazoyl chloride to give a white solid in 66% yield.
White solid, yield 66%. The melting point is 82.6-85.4 ℃.1H NMR(400MHz,CDCl3)δ7.84 (d,J＝6.8Hz,2H),7,67(d,J＝7.6Hz,2H),7.56(d,J＝7.2Hz,2H),7.42(t,J＝6.4 Hz,2H),7.37-7.32(m,1H),6.84(s,1H),4.49(s,2H)；13C NMR(100MHz,CDCl3): δ152.6,140.4,138.3,132.8,132.6,129.0,128.6,126.8,126.0,122.6,106.6,21.1； HRMS calcd for C16H12Br2N2+H+:390.9440,found:390.9447。
Example 245- (bromomethyl) -3-phenyl-1- (4- (trifluoromethyl) phenyl) -1H-pyrazole
Figure RE-GDA0003140147490000221
The procedure is as in example 1 except that N-phenylbenzenecarbazoyl chloride is replaced by (Z) -N' - (4- (trifluoromethyl) phenyl) phenylcarbazoyl chloride to give a white solid in 70% yield.
White solid, yield 70%. The melting point is 97.7-101.3 ℃.1H NMR(400MHz,CDCl3)δ 7.86-7.80(m,6H),7,43(t,J＝7.2Hz,2H),7.36(t,J＝7.2Hz,1H),6.88(s,1H),4.54 (s,2H)；13C NMR(100MHz,CDCl3):δ153.0,142.2(d,J＝1.6Hz),140.5,132.4, 129.0,128.7,126.9(q,J＝3.6Hz),126.0,125.2,123.8(d,J＝240.0Hz),107.2,21.0； HRMS calcd for C17H12BrF3N2+H+:381.0209,found:381.0204。
Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the application being indicated by the following claims.
It will be understood that the present application is not limited to the precise arrangements that have been described above and that various modifications and changes may be made without departing from the scope thereof. The scope of the application is limited only by the appended claims.

Claims (10)

1. A pyrazole compound is characterized in that the structural formula is as follows:
Figure FDA0003068978640000011
the R is1Is variously substituted phenyl, naphthyl, alkyl or heterocyclic aryl, R2Are variously substituted phenyl groups.
2. The pyrazole compound according to claim 1, which is any one of the following compounds:
5- (bromomethyl) -1, 3-diphenyl-1H-pyrazole;
5- (bromomethyl) -1-phenyl-3- (p-tolyl) -1H-pyrazole;
5- (bromomethyl) -3- (4-methoxyphenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (3-methoxyphenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (2-methoxyphenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (4-fluorophenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (4-chlorophenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (3-chlorophenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (2-chlorophenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (4-bromophenyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -1-phenyl-3- (4- (trifluoromethyl) phenyl) -1H-pyrazole;
4- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) benzonitrile;
2- (5- (bromomethyl) -1-phenyl-1H-pyrazol-3-yl) pyridine;
5- (bromomethyl) -3- (furan-2-yl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3- (tert-butyl) -1-phenyl-1H-pyrazole;
5- (bromomethyl) -3-phenyl-1- (p-tolyl) -1H-pyrazole;
5- (bromomethyl) -1- (4-methoxyphenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -1- (4-fluorophenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -1- (4-chlorophenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -1- (3-chlorophenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -1- (2-chlorophenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -1- (4-bromophenyl) -3-phenyl-1H-pyrazole;
5- (bromomethyl) -3-phenyl-1- (4- (trifluoromethyl) phenyl) -1H-pyrazole.
3. A preparation method of a pyrazole compound is characterized by comprising the following steps:
completely dissolving 1.0 equivalent of chlorinated hydrazone, 0.5 to 5.0 equivalents of prop-2-alkynyl sulfate and 2.0 to 3.0 equivalents of alkali in an aprotic solvent, and stirring for reaction under the protection of nitrogen;
wherein the structural formula of the chlorinated hydrazone is as follows:
Figure FDA0003068978640000021
the R is1Is variously substituted phenyl, naphthyl, alkyl or heterocyclic aryl, R2Is variously substituted phenyl;
the structural formula of the prop-2-alkynyl sulfur salt is as follows:
Figure FDA0003068978640000022
and (2) filtering the reaction system obtained in the step (1), drying and concentrating the filtrate to obtain a residue, and performing silica gel column chromatography on the residue to obtain the pyrazole compound.
4. The method according to claim 3, wherein the reaction temperature in the step (1) is 0 ℃, 10 ℃, or 25 ℃, preferably 0 ℃.
5. The method according to claim 3, wherein the reaction time in the step (1) is 12 to 36 hours.
6. The method according to claim 3, wherein the aprotic solvent is one or more selected from acetonitrile, dichloromethane, chloroform, acetone, and 1, 2-dichloroethane, and is mixed in an arbitrary ratio.
7. The method according to claim 3, wherein the aprotic solvent is preferably chloroform.
8. The method according to claim 3, wherein the base is one or more selected from the group consisting of sodium acetate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium acetate, and triethylamine, in any ratio.
9. The process of claim 3, wherein the base is potassium carbonate.
10. The method according to claim 3, wherein the base is used in an amount of 2.0 equivalents of the chlorinated hydrazone.
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