CN101440065A - Mechanochemical preparation of 1,3,5-triaryl-2-pyrazoline compounds - Google Patents
Mechanochemical preparation of 1,3,5-triaryl-2-pyrazoline compounds Download PDFInfo
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- CN101440065A CN101440065A CNA2008101632516A CN200810163251A CN101440065A CN 101440065 A CN101440065 A CN 101440065A CN A2008101632516 A CNA2008101632516 A CN A2008101632516A CN 200810163251 A CN200810163251 A CN 200810163251A CN 101440065 A CN101440065 A CN 101440065A
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Abstract
The invention discloses a mechanochemical preparation method for a 1, 3, 5-triaryl-2-pyrazoline compound with a structure shown in a formula (III). The method comprises the following steps: a chalcone compound with a structure shown in a formula (I) and a phenyl hydrazine compound with a structure shown in a formula (II) are taken as raw materials, hydrosulfate is taken as a catalyst, and silica gel is taken as a grinding aid to perform a ball milling reaction in a closed ball milling tank; and after the reaction is finished, a reaction mixture is separated and purified to obtain the 1, 3, 5-triaryl-2-pyrazoline compound with the structure shown in the formula (III). The method has the advantages of safe and reliable production, simple and convenient operation, short reaction time, generally higher reaction yield, low production cost, simple post-treatment, small pollution and so on, and is the preparation method for the 1, 3, 5-triaryl-2-pyrazoline compound with better popularization and application prospects.
Description
(1) technical field
The present invention relates to a kind of 1,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds.
(2) background technology
Pyrazoline compounds has broad application prospect as medicinal application, and this compounds has tangible anti-inflammatory, pain relieving, antibiotic, sterilization, desinsection isoreactivity.In addition, some polysubstituted pyrazoline compounds have good optical character, can be used as fluorescent switch, rumbling compound and molecular probe etc.In numerous pyrazoline compounds, 1,3,5-triaryl-2-pyrazoline is a compounds of studying at most, its biological activity and preparation method are subjected to chemist's generally attention.
1,3, the existing quite long history of the preparation research of 5-triaryl-2-pyrazoline compounds, classic methods are to obtain target product by chalcone compound and the reaction of phenylhydrazine compounds.This method mostly is with AcOH, HCl, Et in solvent
3N, Ba (OH)
2Or strong acid such as NaOH or highly basic are finished reaction as reagent or catalyzer.These reactions generally need to carry out under reflux temperature, and the reaction times is longer.
In recent years, the people was also arranged with K
2CO
3Or SiO
2Deng as catalyzer, under ultrasonic or microwave condition, prepare pyrazoline compounds, but these methods still are in the research exploratory stage at present, concrete application also needs the regular hour perfect.
Mechanochemistry be a research material in the effect of high energy mechanical power with bring out the subject that issues living physicochemical change, be the advanced subject of Green Chemistry research.Chemical reaction under the mechanical force need not to use solvent, can avoid in the reaction process solvent to the pollution of environment, has reduced production cost simultaneously again; In addition, owing to there is not the intervention of solvent, the reaction system microenvironment is different from the solution, has caused the high local concentrations of reactive site, has both improved speed of reaction, has improved productive rate and selectivity again, also can make the separation purification of product become simple.Yet there are no the report that adopts the mechanochemistry method to prepare pyrazoline compounds.Therefore, finish the prepared in reaction 1,3 of phenyl styryl ketone and phenylhydrazine with the mechanochemistry method, 5-three aromatic bases-2-pyrazoline compounds are the important breakthroughs to traditional pyrazoline compounds preparation method.
(3) summary of the invention
The technical problem to be solved in the present invention provide a kind of easy and simple to handle, production safety is reliable, the reaction times is short, reaction yield is high, production cost is low, do not have substantially that the three wastes produce 1,3, the preparation method of 5-three aromatic bases-2-pyrazoline compounds.
The technical solution adopted in the present invention is:
A kind of structure is suc as formula 1 shown in (III), 3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds, described method comprises: is raw material suc as formula chalcone compound shown in (I) and structure suc as formula the phenylhydrazine compounds shown in (II) with structure, with the hydrosulfate is catalyzer, with silica gel is grinding aid, ball-milling reaction in the closed ball milling jar; Reaction finishes the afterreaction mixture and obtains structure suc as formula 1,3 shown in (III) through separation and purification, 5-triaryl-2-pyrazoline compounds.Reaction formula is as follows:
In formula (I), formula (II), the formula (III), R
1～R
15Independent separately is H, Cl, OCH
3Or NO
2
The present invention's suggestion usually reacts under the state of high speed ball milling, and the high speed ball milling of indication is often referred to rotating speed between 1290～2220rpm.
Hydrosulfate of the present invention can be selected from the combination of following one or more arbitrary proportions: sal enixum, sodium pyrosulfate, magnesium hydrogen sulfate, calcium bisulfate, aluminium hydrogen sulfate, hydrogen sulfate zinc, hydrogen sulfate iron; Contain or do not contain crystal water in the structural formula of described hydrosulfate.Further, described hydrosulfate is preferably the combination of following one or more arbitrary proportions: sulfuric acid monohydrate hydrogen sodium, sal enixum, magnesium hydrogen sulfate.
The present invention recommends the amount of substance that feeds intake of each material than chalcone compound: the phenylhydrazine compounds: hydrosulfate is 1:1～5:0.05～0.5, and the amount of substance that preferably feeds intake is than being 1:2～4:0.05～0.2.
The silica gel quality that is added can be 2～20 times of chalcone compound quality, is preferably 5～10 times.
The described reaction times was generally 2～20 minutes, was preferably 5～10 minutes.
Described separation purification method carries out according to following steps: the solvent with heat washes complete reaction mixture, filters, and filtrate is steamed under boiling state and fallen partial solvent to saturated, be cooled to room temperature, separate out solid, drying, obtain 1,3,5-triaryl-2-pyrazoline compounds.
Described solvent is recommended as the combination of following one or more arbitrary proportions: ethanol, methyl alcohol, ethyl acetate, acetone, methylene dichloride, further, described solvent most preferably is ethanol.
Comparatively concrete, described method recommends to carry out according to following steps: in ball grinder by the chalcone compound: the phenylhydrazine compounds: hydrosulfate is that 1:2～4:0.05～0.2 feeds intake, and described hydrosulfate is the combination of one or more arbitrary proportions in sulfuric acid monohydrate hydrogen sodium, sal enixum, the magnesium hydrogen sulfate; The silica gel that adds 5～10 times of chalcone compound qualities.To place ball mill in the ball grinder with the rotating speed ball-milling reaction of 1290～1920rpm 5～10 minutes.After reaction finishes, with hot ethanol complete reaction mixture is washed, filter, filtrate is steamed under boiling state and is fallen part ethanol to saturated, is cooled to room temperature, separates out solid, and drying obtains 1,3,5-triaryl-2-pyrazoline compounds.
Beneficial effect of the present invention is embodied in: (1) is compared with original method, and reaction process of the present invention need not to use solvent, has got rid of easily equipment is produced corrosive strongly-acid or strong basicity reagent and environment produced the solvent of pollution; (2) original method reaction generally all is to carry out under heating, and the inventive method need not heating; (3) original time in method reaction times mostly longer, the inventive method has shortened the reaction times greatly; (4) the inventive method yield height not only, but also make reaction substrate select face to widen greatly, for the phenyl styryl ketone and the phenylhydrazine derivant of different substituents, yield changes problem greatly before having solved;
To sum up, that the present invention has is easy and simple to handle, production safety is reliable, the reaction times is short, reaction yield is generally higher, production cost is low, aftertreatment is simple and pollute advantages such as few, be a kind of 1,3 of better popularizing application prospect that has, the preparation method of 5-triaryl-2-pyrazoline compounds.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1:1,3, the preparation of 5-triphenyl-2-pyrazoline
In the 75mL ball grinder, add phenyl styryl ketone (2.08g, 10mmol), phenylhydrazine (1.08g, 10mmol), (0.14g 1mmol) and silica gel (10g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.After reaction finishes, with hot dehydrated alcohol reaction mixture is washed, filter, filtrate is steamed under boiling state and is fallen part ethanol to saturated, is cooled to room temperature, separates out solid, and drying obtains 1,3,5-triphenyl-2-pyrazoline 2.72g, yield 91%.
White solid, Mp:134 ℃ of .IR (KBr): 3129,1490,1400cm
-1.
1H NMR (400MHz, DMSO-d
6): δ (ppm)=7.76-6.71 (m, 15H, ArH), 5.48 (dd, J=5.2,9.6Hz1H, ArCHN), 3.93 (dd, J=9.6,14.0Hz1H, CH
2C=N), 3.11 (dd, J=5.2,14.0Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=147.13,144.22,142.52,132.23,128.94,128.81,128.59,127.35,125.80,125.64,118.56,112.91,63.12,42.95.m/z (EI) 298 (M
+, 100), 221 (38), 206 (5), 194 (11), 91 (14).
Embodiment 2:1,3, the preparation of 5-triphenyl-2-pyrazoline
In the 75mL ball grinder, add phenyl styryl ketone (2.08g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.07g 0.5mmol) and silica gel (10g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1,3 with embodiment 1,5-triphenyl-2-pyrazoline 2.77g, and yield 93%, physical data is with embodiment 1.
Embodiment 3:1,3, the preparation of 5-triphenyl-2-pyrazoline
In the 75mL ball grinder, add phenyl styryl ketone (2.08g, 10mmol), phenylhydrazine (5.41g, 50mmol), (0.27g 2mmol) and silica gel (21g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1,3 with embodiment 1,5-triphenyl-2-pyrazoline 2.69g, and yield 90%, physical data is with embodiment 1.
Embodiment 4:1,3, the preparation of 5-triphenyl-2-pyrazoline
In the 75mL ball grinder, add phenyl styryl ketone (2.08g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.68g 5mmol) and silica gel (21g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 2min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1,3 with embodiment 1,5-triphenyl-2-pyrazoline 2.63g, and yield 88%, physical data is with embodiment 1.
Embodiment 5:1-(4-chloro-phenyl-)-3, the preparation of 5-phenylbenzene-2-pyrazoline
In the 75mL ball grinder, add phenyl styryl ketone (2.43g, 10mmol), the 4-chlorophenyl hydrazine (2.85g, 20mmol), (0.12g 1mmol) and silica gel (4.17g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1-(4-chloro-phenyl-)-3 with embodiment 1,5-phenylbenzene-2-pyrazoline 2.93g, yield 88%.
Faint yellow solid, Mp:160-161 ℃ of .IR (KBr): 3132,1489,1398cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.77-6.97 (m, 14H, ArH), 5.50 (dd, J=5.6,12.0Hz1H, ArCHN), 3.94 (dd, J=12.0,17.6Hz1H, CH
2C=N), 3.14 (dd, J=6.0,17.6Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=148.05,142.97,141.99,131.98,129.00,128.86,128.61,127.47,125.77,122.10,114.29,63.00,43.06.m/z (EI) 332 (M
+, 100), 255 (31), 125 (22).
Embodiment 6:1, the preparation of 3-phenylbenzene-5-(4-chloro-phenyl-)-2-pyrazoline
In the 75mL ball grinder, add 4-chlorine phenyl styryl ketone (2.43g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.12g 1mmol) and silica gel (49g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,3-phenylbenzene-5-(4-chloro-phenyl-)-2-pyrazoline 2.96g, yield 89%.
Faint yellow solid, Mp:129-132 ℃ of .IR (KBr): 3133,1492,1395cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.76-6.71 (m, 14H, ArH), 5.52 (dd, J=6.0,12.0Hz1H, ArCHN), 3.92 (dd, J=12.0,17.6Hz1H, CH
2C=N), 3.12 (dd, J=7.2,17.2Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=147.27,144.03,141.42,132.12,131.86,128.93,128.88,128.73,128.60,127.83,125.69,118.73,112.94,62.37,42.71.m/z (EI) 332 (M
+, 100), 221 (21), 194 (12), 91 (14).
Embodiment 7:1, the preparation of 5-two (4-chloro-phenyl-)-3-phenyl-2-pyrazoline
In the 75mL ball grinder, add 4-chlorine phenyl styryl ketone (2.43g, 10mmol), the 4-chlorophenyl hydrazine (2.85g, 20mmol), (0.12g 1mmol) and silica gel (12g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 10min with the operation of the rotating speed of 1920rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,5-two (4-chloro-phenyl-)-3-phenyl-2-pyrazoline 3.31g, yield 90%.
Faint yellow solid, Mp:139-140 ℃ of .IR (KBr): 3134,1490,1400cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.77-6.67 (m, 13H, ArH), 5.54 (dd, J=6.4,12.2Hz1H, ArCHN), 3.92 (dd, J=12.0,17.8Hz1H, CH
2C=N), 3.14 (dd, J=6.4,17.8Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=148.15,142.79,140.86,131.98,131.86,128.96,128.65,128.59,127.78,125.79,122.26,114.32,62.26,42.81.m/z (EI) 366 (M
+, 72), 255 (37), 125 (100), 90 (100), 90 (34).
Embodiment 8:1, the preparation of 5-phenylbenzene-3-(4-chloro-phenyl-)-2-pyrazoline
In the 75mL ball grinder, add 4 '-the chlorine phenyl styryl ketone (2.43g, 10mmol), phenylhydrazine (2.16g, 20mmol) ,-(0.14g 1mmol) and silica gel (12g), adds abrading-ball to the hydration sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 20min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,5-phenylbenzene-3-(4-chloro-phenyl-)-2-pyrazoline 3.00g, yield 90%.
Faint yellow solid, Mp:150-152 ℃ of .IR (KBr): 3154,1491,1386cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.77-6.71 (m, 14H, ArH), 5.50 (dd, J=6.4,12.0Hz1H, ArCHN), 3.91 (dd, J=12.8,17.6Hz1H, CH
2C=N), 3.13 (dd, J=6.4,17.2Hz1H, CH2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=146.10,144.03,142.36,133.05,131.18,128.93,128.84,128.66,127.42,127.29,125.82,118.81,113.03,63.33,42.80.m/z (EI) 332 (M
+, 100), 255 (41), 91 (14), 59 (11).
Embodiment 9:1, the preparation of 3-two (4-chloro-phenyl-)-5-phenyl-2-pyrazoline
In the 75mL ball grinder, add 4 '-the chlorine phenyl styryl ketone (2.43g, 10mmol), the 4-chlorophenyl hydrazine (2.85g, 20mmol), (0.12g 1mmol) and silica gel (12g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,3-two (4-chloro-phenyl-)-5-phenyl-2-pyrazoline 3.27g, yield 89%.
White solid, Mp:154-155 ℃ of .IR (KBr): 3133,1488,1385cm
-1.
1H NMR (400MHz, DMSO-d
6): δ (ppm)=6.97-7.78 (m, 13H, ArH), 5.52 (dd, J=6.4,12.4Hz1H, ArCHN), 3.92 (dd, J=12.4,17.6Hz1H, CH
2C=N), 3.13 (dd, J=6.4,18.0Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=146.98,142.76,141.83,133.28,130.90,129.01,128.62,127.52,127.41,125.77,122.34,114.38,63.17,42.89.m/z (EI) 366 (M
+, 100), 289 (31), 125 (23).
Embodiment 10:1-phenyl 3, the preparation of 5-two (4-chloro-phenyl-)-2-pyrazoline
In the 75mL ball grinder, add 4,4 '-the dichloro phenyl styryl ketone (2.77g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.22g 1mmol) and silica gel (14g), adds abrading-ball to magnesium hydrogen sulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1-phenyl 3 with embodiment 1,5-two (4-chloro-phenyl-)-2-pyrazoline 3.38g, yield 92%.
Faint yellow solid, Mp:148-149 ℃ of .IR (KBr): 3159,1635,1400cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.76-6.72 (m, 13H, ArH), 5.54 (dd, J=6.0,8.2Hz1H, ArCHN), 3.90 (dd, J=12.0,13.6Hz1H, CH
2C=N), 3.12 (dd, J=6.4,17.6Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=146.19,143.81,141.21,133.11,131.92,131.03,128.91,128.86,128.62,127.78,127.29,118.93,113.01,62.56,42.53.m/z (EI) 366 (M
+, 77), 255 (52), 91 (100), 77 (50), 64 (23).
Embodiment 11:1,3, the preparation of 5-three (4-chloro-phenyl-)-2-pyrazoline
In the 75mL ball grinder, add 4,4 '-the dichloro phenyl styryl ketone (2.77g, 10mmol), the 4-chlorophenyl hydrazine (2.85g, 20mmol), (0.26g 1mmol) and silica gel (14g), adds abrading-ball to hydrogen sulfate zinc again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1,3 with embodiment 1,5-three (4-chloro-phenyl-)-2-pyrazoline 3.66g, yield 91%.
Faint yellow solid, Mp:146-147 ℃ of .IR (KBr): 3145,1488,1405cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.77-6.68 (m, 12H, ArH), 5.69 (dd, J=6.0,12.2Hz1H, ArCHN), 3.92 (dd, J=12.0,17.8Hz1H, CH
2C=N), 3.14 (dd, J=6.0,17.6Hz 1H, CH
2C=N).
13C NMR (100MHz, DMSO-d
6): δ (ppm)=147.12,142.63,140.74,133.42,132.11,130.82,129.02,128.70,127.81,127.47,122.57,114.46,62.51,42.71.m/z (EI) 400 (M
+, 73), 289 (26), 127 (31), 125 (100), 90 (26), 75 (17).
The preparation of embodiment 12:1-phenyl-3-(4-chloro-phenyl-)-5 (4-p-methoxy-phenyl)-2-pyrazolines
In the 75mL ball grinder, add 4-methoxyl group-4 '-the chlorine phenyl styryl ketone (2.73g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.12g 1mmol) and silica gel (14g), adds abrading-ball to sodium pyrosulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1-phenyl-3-(4-chloro-phenyl-)-5 (4-p-methoxy-phenyl)-2-pyrazoline 2.27g, yield 90% with embodiment 1.
Faint yellow solid, Mp:154-155 ℃ of .IR (KBr): 3128,1491,1383cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=7.76-6.70 (m, 13H, ArH), 5.45 (dd, J=6.4,12.4Hz1H, ArCHN), 3.87 (dd, J=12.4,17.6Hz1H, CH
2C=N), 3.71 (s, 3H, CH
3), 3.08 (dd, J=6.0,17.2Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d
6): δ (ppm)=158.47,146.06,144.01,134.24,132.94,131.27,128.79,128.65,127.25,127.06,118.71,114.32,113.06,62.80,54.99,42.78.m/z (EI) 362 (M
+, 100), 255 (16), 228 (10), 91 (15).
Embodiment 13:1, the preparation of 5-phenylbenzene-3-(4-p-methoxy-phenyl)-2-pyrazoline
In the 75mL ball grinder, add 4 '-the methoxyl group phenyl styryl ketone (2.43g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.23g 1mmol) and silica gel (12g), adds abrading-ball to calcium bisulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,5-phenylbenzene-3-(4-p-methoxy-phenyl)-2-pyrazoline 2.99g, yield 91%.
White solid, Mp:134-135 ℃ of .IR (KBr): 3135,1498,1386cm
-1.
1H NMR (400MHz, DMSO-d
6): δ (ppm)=7.70-6.67 (m, 14H, ArH), 5.41 (dd, J=6.4,12.0Hz1H, ArCHN), 3.89 (dd, J=12.0,17.6Hz1H, CH
2C=N), 3.79 (s, 3H, CH
3), 3.07 (dd, J=6.0,17.6Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d
6): δ (ppm)=159.80,147.20,144.55,142.68,128.92,128.77,127.30,127.23,125.82,124.86,118.21,114.10,112.75,63.07,55.21,43.22.m/z (EI) 328 (M
+, 100), 251 (31), 91 (6).
Embodiment 14:1-phenyl-3, the preparation of 5-two (4-p-methoxy-phenyl)-2-pyrazoline
In the 75mL ball grinder, add 4,4 '-the dimethoxy phenyl styryl ketone (2.68g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.32g 1mmol) and silica gel (13g), adds abrading-ball to aluminium hydrogen sulfate again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1290rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1-phenyl-3 with embodiment 1,5-two (4-p-methoxy-phenyl)-2-pyrazoline 3.33g, yield 93%.
White solid, Mp:141-142 ℃ of .IR (KBr): 3131,1499,1399cm
-1.
1H NMR (400MHz, DMSO-d
6): δ (ppm)=7.70-6.67 (m, 13H, ArH), 5.36 (dd, J=6.4,12.0Hz1H, ArCHN), 3.85 (dd, J=12.4,17.6Hz1H, CH
2C=N), 3.79 (s, 3H, CH
3), 3.71 (s, 3H, CH
3), 3.04 (dd, J=6.4,17.2Hz1H, CH
2C=N).
13CNMR (100MHz, DMSO-d
6): δ (ppm)=159.76,158.39,147.14,144.58,134.52,128.68,127.15,127.00,124.95,118.14,114.25,114.07,112.82,62.61,55.17,54.95,43.21.m/z (EI) 358 (M
+, 100), 251 (21), 224 (19), 179 (17), 121 (19), 91 (61), 77 (18), 64 (14).
Embodiment 15:1, the preparation of 3-phenylbenzene-5-(4-nitrophenyl)-2-pyrazoline
In the 75mL ball grinder, add 4-nitro phenyl styryl ketone (2.53g, 10mmol), phenylhydrazine (2.16g, 20mmol), sodium pyrosulfate (0.12g, 1mmol), (0.14g 1mmol) and silica gel (13g), adds abrading-ball to sal enixum again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,3-phenylbenzene-5-(4-nitrophenyl)-2-pyrazoline 3.06g, yield 89%.
The light red solid, Mp:130-132 ℃ of .IR (KBr): 3132,1501,1400cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=8.24-6.78 (m, 14H, ArH), 5.78 (dd, J=6.4,12.8Hz1H, ArCHN), 4.03 (dd, J=12.8,17.6Hz1H, CH
2C=N), 3.25 (dd, J=6.0,17.6Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=148.14,147.54,144.64,143.94,132.62,131.97,130.67,129.02,128.89,128.63,125.80,122.46,120.84,119.00,112.98,62.24,42.62.m/z (EI) 343 (M
+, 20), 313 (100), 221 (61), 194 (9), 91 (15).
Embodiment 16:1, the preparation of 5-phenylbenzene-3-(4-nitrophenyl)-2-pyrazoline
In the 75mL ball grinder, add 4 '-the nitro phenyl styryl ketone (2.53g, 10mmol), phenylhydrazine (2.16g, 20mmol), (0.35g 1mmol) and silica gel (13g), adds abrading-ball to hydrogen sulfate iron again, tightens cover.Ball grinder is put into ball mill make mixture reaction 5min with the operation of the rotating speed of 1820rpm, TLC (sampling is dissolved in ethyl acetate) follows the tracks of extent of reaction.Purification procedures obtains 1 with embodiment 1,5-phenylbenzene-3-(4-nitrophenyl)-2-pyrazoline 3.08g, yield 90%.
The light red solid, Mp:118-119 ℃ of .IR (KBr): 3139,1501,1395cm
-1.
1HNMR (400MHz, DMSO-d
6): δ (ppm)=8.27-6.77 (m, 14H, ArH), 5.62 (dd, J=6.4,12.8Hz1H, ArCHN), 3.98 (dd, J=12.4,17.2Hz1H, CH
2C=N), 3.19 (dd, J=6.4,17.6Hz1H, CH
2C=N).
13C NMR (100MHz, DMSO-d6): δ (ppm)=146.48,145.00,143.16,141.94,138.62,129.00,128.91,127.53,126.21,125.77,123.88,119.61,113.41,63.59,42.24.m/z (EI) 343 (M
+, 100), 226 (47), 220 (17), 91 (70), 77 (46), 64 (31).
Claims (10)
1, a kind of structure is suc as formula 1 shown in (III), 3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds, described method comprises: is raw material suc as formula chalcone compound shown in (I) and structure suc as formula the phenylhydrazine compounds shown in (II) with structure, with the hydrosulfate is catalyzer, is grinding aid ball-milling reaction in the closed ball milling jar with silica gel; Reaction finishes the afterreaction mixture and obtains structure suc as formula 1,3 shown in (III) through separation and purification, 5-triaryl-2-pyrazoline compounds; Feed intake amount of substance than chalcone compound: the phenylhydrazine compounds: hydrosulfate is 1:1～5:0.05～0.5;
Formula (I), formula (II)) in, in the formula (III), R
1～R
15Independent separately is H, Cl, OCH
3Or NO
2
2, as claimed in claim 11,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described hydrosulfate is one of following or the combination of two or more arbitrary proportions: sal enixum, sodium pyrosulfate, magnesium hydrogen sulfate, calcium bisulfate, aluminium hydrogen sulfate, hydrogen sulfate zinc, hydrogen sulfate iron; Contain or do not contain crystal water in the structural formula of described hydrosulfate.
3, as claimed in claim 21,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described hydrosulfate is the combination of following one or more arbitrary proportions: sulfuric acid monohydrate hydrogen sodium, sal enixum, magnesium hydrogen sulfate.
4, as one of claim 1～3 described 1,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds, it is characterized in that the described amount of substance that feeds intake is than chalcone compound: the phenylhydrazine compounds: hydrosulfate is 1:2～4:0.05～0.2.
5, described 1,3 as one of claim 1～3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described silica gel quality is 2～20 times of chalcone compound quality.
6, described 1,3 as one of claim 1～3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described drum's speed of rotation is 1290～2220rpm.
7, as claimed in claim 61,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that the described reaction times is 2～20 minutes.
8, as claimed in claim 71,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that the described reaction times is 5～10 minutes.
9, as claimed in claim 11,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described separation purification method is as follows: the solvent with heat washes complete reaction mixture, filter, filtrate is steamed under boiling state and is fallen partial solvent to saturated, is cooled to room temperature, separates out solid, dry, obtain 1,3,5-triaryl-2-pyrazoline compounds; Described solvent is the combination of following one or more arbitrary proportions: ethanol, methyl alcohol, ethyl acetate, acetone, methylene dichloride.
10, as claimed in claim 91,3, the Mechanochemical preparation of 5-triaryl-2-pyrazoline compounds is characterized in that described solvent is an ethanol.
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| CN102660253A (en) * | 2012-03-07 | 2012-09-12 | 泰山医学院 | Pyrazoline derivative Ni<2+> fluorescence probe and application thereof |
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