CN111138429A - Synthesis method of 1,2, 4-triazole pyridine derivatives - Google Patents
Synthesis method of 1,2, 4-triazole pyridine derivatives Download PDFInfo
- Publication number
- CN111138429A CN111138429A CN201911406096.0A CN201911406096A CN111138429A CN 111138429 A CN111138429 A CN 111138429A CN 201911406096 A CN201911406096 A CN 201911406096A CN 111138429 A CN111138429 A CN 111138429A
- Authority
- CN
- China
- Prior art keywords
- synthesizing
- derivative according
- ethanol
- sodium hypochlorite
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention provides a new synthesis method of 1,2, 4-triazole pyridine derivatives. The 2-pyridine hydrazone derivative and sodium hypochlorite are used as main synthesis raw materials and react for 1-24 hours at 0-100 ℃ in an organic solvent to obtain the 1,2, 4-triazole pyridine derivative. The synthesis method of the derivative has the advantages of good atom economy, mild reaction conditions, simple and convenient operation and easy control.
Description
Technical Field
The invention relates to a synthesis method of 1,2, 4-triazole pyridine derivatives, belonging to the technical field of organic synthesis.
Background
The triazole heterocyclic compounds are important condensed ring heterocyclic compounds and are important raw materials of triazole pesticide bactericides and azole sterilizing and disinfecting drugs. The 1,2, 4-triazole pyridine derivative is an important one of the triazole heterocyclic derivatives, has good biocompatibility, and shows wide biological activity and pharmacological activity in the aspects of anti-inflammation, antithrombotic, antiproliferative, antidepressant, antibacterial and antiviral and the like, so the derivative is widely concerned by pharmaceutical chemistry experts.
The existing method for synthesizing the 1,2, 4-triazole pyridine derivatives mainly comprises: (1) 2-pyridylhydrazide as a raw material was subjected to microwave irradiation in an acetic acid solvent using a lawson reagent to synthesize a target compound (org. lett.2010,12, 792-795.； Tetrahedron Lett. 2006,47, 7591-7594.). (2) Taking 2-pyridylhydrazine as a raw material, and carrying out a series reaction with a carboxylic acid compound under the condition of phosphorus oxychloride/phosphorus pentachloride or 1, 1' -carbonyldiimidazole to synthesize a target compound; or with aryl iodides by Mo (CO)6The mediated carbonylation reaction synthesized the target compound (chem.2015,52, 75-79.; Org. Lett. 2016,18, 560-563.; Synth. Catal. 2016,358, 520-525.). (3) 2-pyridylhydrazone derivatives are used as a raw material, and an oxidizing agent such as high-valent iodine or N-bromosuccinimide is used to synthesize a target compound (RSC adv. 2015,5, 3781-3785.；RSC Adv. 2014,4, 34056-34064.). The method (1) and the method (2) have high yield, but the used reagent is sensitive or has high toxicity, the requirement on experimental equipment is high, and the reaction condition is harsh. The oxidant used in the method (3) has high toxicity, and the wide application of the reaction is limited.
Disclosure of Invention
The invention aims to provide a novel method for synthesizing 1,2, 4-triazole pyridine derivatives, which has the advantages of good atom economy, mild reaction conditions and simple and convenient operation.
The technical scheme of the invention is as follows:
a method for synthesizing 1,2, 4-triazole pyridine derivatives comprises the steps of using a compound (I) and sodium hypochlorite as raw materials, carrying out cyclization reaction in an organic solvent to obtain a target compound (II),
r is C1~C18Alkyl of (C)2~C18Alkenyl of, C2~C18Alkynyl of (A), C6～C40An aromatic substituent.
In the preparation method, R is C6～C30Aromatic compoundsThe substituent is preferably phenyl, naphthyl,
In the above preparation method, the organic solvent includes, but is not limited to, methanol, ethanol, isopropanol, dichloromethane, chloroform, acetonitrile, acetone, ethyl acetate, benzene, toluene, xylene, and the solvent is preferably ethanol;
in the preparation method, the reaction temperature is 0-100 ℃; the reaction time is 1-24 hours;
in the preparation method, the molar ratio of the compound (I) to the sodium hypochlorite is 1: 1-1: 10, and the optimal molar ratio is 1: 4.
The invention has the advantages and positive effects that: compared with the existing synthesis method, the method selects sodium hypochlorite and the 2-pyridine hydrazone derivative (I) to carry out cyclization reaction to generate the 1,2, 4-triazole pyridine derivative (II), and the synthesis method has the advantages of mild conditions, good atom economy and simple and convenient operation. The raw materials of the synthetic method are easy to synthesize, the yield is high, and the synthetic method is suitable for mass production.
Drawings
FIG. 1 is a view of the structure of a single crystal of FIG. 6 a;
FIG. 2 is a graph of the fluorescence and absorption spectra of sodium hypochlorite and other inorganic salts, biological thiols, and oxidants on this reaction.
Detailed Description
Example 1:
1.0 mmol of 2-hydrazinopyridine and 0.7 mmol of benzaldehyde are dissolved in 10 mL of ethanol and refluxed for 1 h. After the solution was cooled to room temperature, it was stirred for an additional 2 hours. Filtered and washed with acetone and ethanol. Finally, benzaldehyde-2-pyridylhydrazone (1 a) was obtained as a starting material in a yield of 54%. The nuclear magnetic data for 1a are:1H NMR (400 MHz, CDCl3), δ ppm: 9.19 (s, 1H), 8.16(d,J= 4.0 Hz, 1H), 7.79 (s, 1H), 7.68 (d,J= 7.1 Hz, 2H), 7.63 (t,J= 8.3Hz, 1H), 7.39 (t,J= 8.0 Hz, 3H), 7.33 (t,J= 7.0 Hz, 1H), 6.79 (t,J= 5.6Hz, 1H);13C NMR (100 MHz, CDCl3), δ ppm: 157.3, 147.2, 139.2, 138.3, 135.2,128.9, 128.7, 126.5, 115.7, 107.8; HRMS (ESI) calcd. for C12H12N3[M+H]+:198.1026, found 198.1064。
1.0 mmol of benzaldehyde-2-pyridylhydrazone was dissolved in 20 mL of an ethanol solution, followed by addition of 4.0 mmol of sodium hypochlorite, reaction at room temperature for 3 hours, and solvent was distilled off. Separating and purifying by column chromatography to obtain 3-phenyl-1, 2, 4-triazole pyridine (1 b), with a yield of 54%. The nuclear magnetic data for 1b are:1H NMR (400 MHz, CDCl3), δ ppm: 8.16 (d,J= 7.0 Hz, 1H), 7.64-7.70 (m, 3H), 7.37-7.45 (m, 3H), 7.13-7.17 (m, 1H), 6.74-6.77 (m, 1H);13C NMR (100 MHz, CDCl3), δ ppm: 150.4, 146.6, 130.0, 129.1,128.0, 127.1, 126.5, 122.6, 116.5, 114.2; HRMS (ESI) calcd. for C12H10N3[M+H]+:196.0869, found 196.0891。
example 2:
1.0 mmol of 2-hydrazinopyridine and 0.7 mmol of 2-naphthaldehyde are added to 10 mL of ethanol and refluxed for 2 h. After the solution was cooled to room temperature, it was stirred for an additional 2 hours. Filtered and washed with acetone and ethanol. Finally, 2-naphthaldehyde-2' -pyridylhydrazone (2 a) as a raw material was obtained in a yield of 88%. The nuclear magnetic data for 2a are:1H NMR (400 MHz, DMSO-d 6 ), δ ppm: 10.99 (s,1H), 8.20 (s, 1H), 8.13 (s,J= 4.9 Hz, 1H), 7.99-8.01 (m, 2H), 7.89-7.95 (m,3H), 7.64-7.69 (m, 1H), 7.48-7.54 (m, 2H), 7.32 (d,J= 8.4 Hz, 1H), 6.76-6.79 (m, 1H) ;13C NMR (100 MHz, DMSO-d 6 ), δ ppm: 157.0, 147.8, 138.8, 137.9,133.2, 133.1, 133.0, 128.3, 128.0, 127.7, 126.5, 126.3, 122.4, 115.0, 106.4;HRMS (ESI) calcd. for C16H14N3[M+H]+: 248.1182, found 248.1236。
1.0 mmol of 2-naphthaldehyde-2' -pyridylhydrazone was dissolved in 20 mL of an ethanol solution, followed by addition of 4.0 mmol of sodium hypochlorite, reaction at room temperature for 3 hours, and distillation to remove the solvent. Separating and purifying by column chromatography to obtain 2- (1, 2, 4-triazole pyridine-3) -naphthalene (2 b) with a yield of 50%. The nuclear magnetic data for 2b are:1H NMR (400 MHz, CDCl3), δ ppm: 8.37(d,J= 7.0 Hz, 1H), 8.28 (s, 1H), 8.00 (d,J= 8.5 Hz, 1H), 7.89-7.91 (m,3H), 7.82 (d,J= 9.3 Hz, 1H), 7.53-7.59 (m, 2H), 7.27-7.30 (m, 1H), 6.87-6.90 (m, 1H);13C NMR (100 MHz, DMSO-d 6 ), δ ppm: 150.1, 145.9, 133.2, 132.8,128.8, 128.5, 127.9, 127.7, 127.3, 127.1, 126.8, 125.3, 124.1, 124.0, 115.7,114.5; HRMS (ESI) calcd. for C16H12N3[M+H]+: 246.1026, found 246.1049。
example 3:
2.2 mmol of 2-hydrazinopyridine and 1.0 mmol of 7- (N, N-diethylamino) -coumarin-3-aldehyde were added to 15 mL of ethanol and refluxed for 3 h. After the solution was cooled to room temperature, the product was obtained by filtration, washed with acetone and ethanol. Finally, the starting material 7- (N, N-diethylamino) -coumarin-3-aldehyde-2' -pyridinehydrazone (3 a) was obtained in 82% yield. The nuclear magnetic data for 3a are: m.p. 233-;1H NMR (400 MHz, DMSO-d 6 ), δ ppm: 10.99 (s, 1H), 8.30 (s,1H), 8.10 (s, 1H), 8.05 (s, 1H), 7.62 (t,J= 6.9 Hz, 1H), 7.58 (d,J= 8.4Hz, 1H), 7.28 (d,J= 7.7 Hz, 1H), 6.76 (s, 2H), 6.56 (s, 1H), 3.45 (q,J=5.7 Hz, 4H), 1.13 (t,J= 7.2 Hz, 6H);13C NMR (100 MHz, DMSO-d 6 ), δ ppm:160.9, 156.9, 155.7, 150.4, 147.8, 137.8, 136.0, 133.2, 130.0, 114.9, 114.2,109.5, 108.3, 106.4, 96.4, 44.2, 12.4; HRMS (ESI) calcd. for C19H21N4O2[M+H]+:337.1659, found 337.1773。
1.0 mmol of 7- (N, N-diethylamino) -coumarin-3-aldehyde-2' -pyridylhydrazone was dissolved in 20 mL of an ethanol solution, followed by addition of 4.0 mmol of sodium hypochlorite, reaction at room temperature for 4 hours, and removal of the solvent by distillation. Separating and purifying by column chromatography to obtain 7- (N, N-diethylamino) -3- (1, 2, 4-triazolopyridine-3) -coumarin (3 b) with yield of 67%. The nuclear magnetic data for 3b are: m.p. 124-;1H NMR (400 MHz, DMSO-d 6 ), δ ppm: 8.38 (s, 1H), 8.32(d,J= 6.8 Hz, 1H), 7.83 (d,J= 8.7 Hz, 1H), 7.63(d,J= 8.8 Hz, 1H), 7.44(t,J= 7.2 Hz, 1H), 7.01 (t,J= 6.6 Hz, 1H), 6.82 (d,J= 8.5 Hz, 1H), 6.67(s, 1H), 3.50 (q,J= 6.0 Hz, 4H), 1.16 (t,J= 6.8 Hz, 6H);13C NMR (100 MHz,DMSO-d 6 ), δ ppm: 159.2, 156.7, 151.9, 146.8, 143.0, 130.3, 128.0, 126.0,115.0, 113.3, 109.7, 107.6, 106.2, 96.3, 78.9, 44.0, 12.3; HRMS (ESI) calcd.for C19H19N4O2[M+H]+:m/z335.1503, found 335.1568。
example 4:
2.2 mmol of 2-hydrazinopyridine and 1.0 mmol of 7- (hydroxy) -coumarin-3-aldehyde were added to 15 mL of ethanol and refluxed for 3 h. After the solution was cooled to room temperature, the product was obtained by filtration, washed with acetone and ethanol. Finally, the starting 7- (hydroxy) -coumarin-3-aldehyde-2' -pyridinehydrazone (4 a) was obtained in 73% yield. The nuclear magnetic data for 4a are:。1H NMR (400 MHz,DMSO-d 6 ), δ ppm: 11.11 (s, 1H), 10.67 (s, 1H), 8.39 (s, 1H), 8.12 (d,J= 3.9Hz, 1H), 8.06 (s, 1H), 7.68-7.63 (m, 2H), 7.31 (d,J= 8.36 Hz, 1H), 6.84-6.81 (m, 1H), 6.80-6.77 (m, 1H), 6.74 (d,J= 2.5 Hz, 1H);13C NMR (100 MHz,DMSO-d 6 ), δ ppm: 161.4, 160.3, 156.7, 154.8, 147.8, 137.9, 135.6, 132.4,130.1, 117.6, 115.2, 113.7, 111.9, 106.5, 102.0; HRMS (ESI) calcd. forC15H12N3O3[M+H]+: 282.0873, found 282.0870。
1.0 mmol of 7- (hydroxy) -coumarin-3-aldehyde-2' -pyridylhydrazone was dissolved in 20 mL of an ethanol solution, followed by addition of 4.0 mmol of sodium hypochlorite, reaction at room temperature for 4 hours, and removal of the solvent by distillation. Separating and purifying by column chromatography to obtain 7- (hydroxy) -3- (1, 2, 4-triazole pyridine-3) -coumarin (4 b) with a yield of 62%. The nuclear magnetic data for 4b are:1H NMR (400MHz, DMSO-d 6), δ ppm: 8.86 (s, 1H), 8.54 (s, 1H), 8.09-8.15 (m, 2H), 7.74 (s,1H), 7.51(s, 1H), 6.88 (s, 2H);13C NMR (100 MHz, DMSO-d 6+ drop of CF3COOD),δ ppm: 164.7, 157.2, 150.2, 145.6, 143.8, 137.5, 132.2, 128.8, 118.1, 115.0,112.3, 111.6, 107.1, 103.1; HRMS (ESI) calcd. for C15H10N3O3[M+H]+:280.0717,found 280.0752。
example 5:
2.2 mmol of 2-hydrazinopyridine and 1.0 mmol of 2,3,6, 7-tetrahydro-1H, 5H, 11H- [1]Benzopyrano [6,7,8-ij]Quinolizine-11-oxo-10-aldehyde was dissolved in 15 mL of ethanol and refluxed for 3 h. After the solution was cooled to room temperature, the product was obtained by filtration, washed with acetone and ethanol. Finally, the raw material 2,3,6, 7-tetrahydro-1H, 5H, 11H- [1 ] is obtained]Benzopyrano [6,7,8-ij]Quinolizine-11-oxo-10-aldehyde-2' -pyridylhydrazone (5 a) in 87% yield. The nuclear magnetic data for 5a are:1HNMR (400 MHz, CDCl3), δ ppm: 8.45 (s, 1H), 8.14 (d,J= 4.4 Hz, 1H), 8.11 (s,1H), 7.96 (s, 1H), 7.59 (t,J= 6.9 Hz, 1H), 7.31 (d,J= 8.4 Hz, 1H), 6.95(s, 1H), 6.76 (t,J= 6.5 Hz, 1H), 3.29 (q,J= 6.2 Hz, 4H), 2.90 (t,J= 6.3Hz, 2H), 2.78 (t,J= 6.2 Hz, 2H), 2.01-1.95 (m, 4H);13C NMR (100 MHz, DMSO-d 6 ), δ ppm: 161.0, 156.7, 150.8, 147.9, 145.9, 137.9, 135.9, 133.5, 125.7,118.6, 114.9, 112.5, 108.1, 106.3, 105.3, 49.4, 48.9, 26.9, 20.8, 19.9, 19.7;HRMS (ESI) calcd. for C21H21N4O2[M+H]+: 361.1659, found 361.1695。
1.0 mmol of 2,3,6, 7-tetrahydro-1H, 5H, 11H- [1]Benzopyrano [6,7,8-ij]Quinolizine-11-oxo-10-aldehyde-2' -pyridylhydrazone (5 a) was added to a 20 mL ethanol solution, followed by addition of 4.0 mmol of sodium hypochlorite, reaction at room temperature for 4 h, and solvent was distilled off. Separating and purifying by column chromatography to obtain 10- (1, 2, 4-triazolopyridine-3) -2,3,6, 7-tetrahydro-1H, 5H, 11H- [1]Benzopyrano [6,7,8-ij]Quinolizin-11-one (5 b) in 57% yield. The nuclear magnetic data for 5b are:1H NMR (400 MHz, DMSO-d 6 ), δ ppm: 8.25-8.30 (m, 2H), 7.82 (d,J=9.2 Hz, 1H), 7.42 (t,J= 6.8 Hz, 1H), 7.21 (s, 1H), 6.98 (t,J= 6.7 Hz,1H), 2.81 (t,J= 6.0 Hz, 2H), 2.74 (t,J= 6.0 Hz, 2H), 1.88-1.94 (m, 4H);13C NMR (100 MHz, DMSO-d 6 ), δ ppm: 159.3, 151.8, 149.8, 147.1, 146.6, 143.4,127.7, 126.3, 126.0, 118.9, 115.2, 113.1, 107.4, 105.1, 104.7, 49.4, 48.9,26.8, 20.7, 19.7; HRMS (ESI) calcd. for C21H19N4O2[M+H]+:m/z359.1503, found359.1540。
example 6:
0.1 mmol of 2-hydrazinopyridine and 0.07 mmol of 6 '- (N, N-diethylamino) -3' -hydroxy-3-oxospiro[ 2-benzofuran-1 (3H), 9' - (9H) -xanthene]-2' -aldehyde was dissolved in 2 mL of ethanol and refluxed for 22 h. After the solution was cooled to room temperature, it was stirred for a further 2 h, filtered and washed with acetone and ethanol. Finally, the starting material 6 ' - (N, N-diethylamino) -3 ' -hydroxy-3-oxospiro [ 2-benzofuran-1 (3H), 9 ' - (9H) -xanthene was obtained]-2' -aldehyde-2 "-pyridylhydrazone (6 a) in 57% yield. Followed by a solvent (CH)2Cl2:CH3OH = 3:1, v: v) volatilization method gave a single crystal of 6a, and the structure thereof was analyzed by single crystal diffractometer measurement (see fig. 1). The compound 6a has the molecular formula C30H26N4O4The crystal structure belongs to a triclinic system, the nuclear magnetic data of unit cell parameters of α =86.019 deg, β = 81.897 deg and gamma = 75.425 deg.6 a are as follows:1H NMR (400 MHz,DMSO-d 6 ), δ ppm: 11.16 (s, 1H), 10.85 (s, 1H), 8.10 (d,J= 6.0 Hz, 2H), 8.04(d,J= 7.0 Hz, 1H), 7.81 (t,J= 7.0 Hz, 1H), 7.75 (t,J= 6.9 Hz, 1H), 7.58(t,J= 6.8 Hz, 1H), 7.33 (d,J= 7.0 Hz, 1H), 6.96 (s, 1H), 6.81 (s, 1H),6.71 (t,J= 9.0 Hz, 2H), 6.48 (s, 3H), 3.36 (s, 4H), 1.08 (s, 6H);13C NMR(100 MHz, DMSO-d 6 ), δ ppm: 169.0, 157.7, 156.2, 152.4, 152.2, 152.0, 149.2,148.0, 138.0, 137.0, 135.6, 130.1, 128.8, 126.4, 126.2, 124.6, 124.2, 118.0,115.0, 111.2, 108.7, 105.7, 104.5, 102.8, 97.0, 83.5, 43.8, 12.4; HRMS (ESI)calcd. for C30H27N4O4[M+H]+: 507.2027, found 507.2112; FT-IR (KBr, cm-1): 2971,1744, 1600, 1622, 1441, 1216, 1166, 1108, 868, 766, 697, 522。
0.1 mmol of 6 ' - (N, N-diethylamino) -3 ' -hydroxy-3-oxospiro [ 2-benzofuran-1 (3H), 9 ' (9H) -xanthene]-2 ' -aldehyde-2 ' ' -pyridylhydrazone (6 a) was added to a 5 mL ethanol solution, followed by addition of 0.4 mmol sodium hypochlorite, reaction at room temperature for 4 h, and solvent was distilled off. Separating and purifying by column chromatography to obtain 2 '- (1, 2, 4-triazole pyridine-3) -6' - (N, N-diethylamino) -3 '-hydroxy spiro [ 2-benzofuran-1 (3H), 9' (9H) -xanthene]-3-ketone (6 b) in 13% yield. Nuclear magnetism of 6bThe data are as follows:1H NMR (400 MHz, DMSO-d 6+ drop of CF3COOD ), δ ppm:8.40 (d,J= 6.7 Hz, 1H), 8.03-8.17 (m, 4H), 7.64-7.76 (m, 2H), 7.38-7.46 (m,3H), 7.01 (d,J= 8.3 Hz, 3H), 3.63 (d,J= 6.3 Hz, 4H), 1.19 (s, 6H);13C NMR(100 MHz, DMSO-d 6+ drop of CF3COOD), δ ppm: 199.0, 167.5, 167.3, 165.2,157.0, 154.0, 149.8, 145.1, 140.8, 137.2, 134.8, 133.6, 132.4, 131.2, 130.3,129.8, 128.2, 121.5, 115.5, 110.2, 104.5, 103.4, 100.2, 97.1, 47.0, 44.7,12.7; HRMS (ESI) calcd. for C30H25N4O4[M+H]+:505.1870, found 505.1918。
example 7: comparative experiment
Example 6 starting material 6a is non-fluorescent and when reacted with sodium hypochlorite, produces compound 6b (λ em = 563 nm) which has yellow fluorescence. The inventors conducted comparative experimental studies using 6a as an example. The effect of other inorganic salts, biological thiols and oxidants, in addition to sodium hypochlorite, on the reaction was investigated by fluorescence and absorption spectroscopy (see figure 2). The results show that only sodium hypochlorite can cause a significant change in the spectroscopic properties of the 6a system and produce a signal peak consistent with 6b (see fig. 2c and 2d), indicating that sodium hypochlorite can specifically convert 6a to 6 b.
Figure 2 (a) fluorescence at 563 nm of compound 6a in ethanol-phosphate buffered solution (1:4 v/v, 20 mM, pH = 7.4) after addition of various controls. Inset is the change in fluorescence colour under 365nm UV (λ ex = 505 nm, λ em = 563 nm, slit: 2.5 nm/5 nm). The concentration of 6a is 10 mu M, and the concentrations of inorganic salt, nucleophilic reagent and oxidizing agent are 20 mu M. Blank 1: blank, sodium hydrosulfide 2: 3: sodium fluoride 4: sodium chloride 5: sodium bromide 6: sodium iodide 7: sodium thiosulfate 8: sodium acetate 9: sodium sulfate 10: sodium nitrite 11: sodium nitrate 12: sodium cyanide 13: sodium thiocyanate 14: sodium phosphate 15: sodium dihydrogen phosphate 16: disodium hydrogen phosphate 17: sodium bicarbonate 18: sodium hydrogen sulfate 19: sodium bisulfite 20: sodium sulfate 21: sodium carbonate 22: cysteine 23: homocysteine 24: glutathione 25: hydrogen peroxide 26: superoxide anion 27: hydroxyl radical 28: singlet oxygen 29: nitric oxide radical 30: tert-butanol peroxide, 31, tert-butyl peroxy-butanol radical, 32, nitrous peroxide and 33, sodium hypochlorite. (b) Compound 6a was added to ethanol-phosphate buffer solution (1:4 v/v, 20 mM, pH = 7.4) with the absorption spectra of various controls. (c) Compound 6a + NaOCl and 6b normalized fluorescence spectra. (d) Normalized absorption spectra for compounds 6a + NaOCl and 6 b.
Claims (8)
1. A method for synthesizing 1,2, 4-triazole pyridine derivatives is characterized by comprising the following steps: the target compound (II) is prepared by using a compound (I) and sodium hypochlorite as raw materials through cyclization reaction in an organic solvent,
r is C1~C18Alkyl of (C)2~C18Alkenyl of, C2~C18Alkynyl of (A), C6～C40An aromatic substituent.
2. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 1, characterized in that: r is C6～C30An aromatic substituent.
3. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 2, characterized in that: r is phenyl, naphthyl,
、
、
Or (b).
4. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 1, characterized in that: the organic solvent is selected from methanol, ethanol, isopropanol, dichloromethane, chloroform, acetonitrile, acetone, ethyl acetate, benzene, toluene and xylene.
5. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 4, wherein the method comprises the following steps: the organic solvent is ethanol.
6. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 1, characterized in that: the reaction temperature is 0-100 ℃; the reaction time is 1-24 hours.
7. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 1, characterized in that: the molar ratio of the compound (I) to sodium hypochlorite is 1: 1-1: 10.
8. The method for synthesizing the 1,2, 4-triazolopyridine derivative according to claim 7, wherein the method comprises the following steps: the molar ratio of compound (I) to sodium hypochlorite was 1: 4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911406096.0A CN111138429A (en) | 2019-12-31 | 2019-12-31 | Synthesis method of 1,2, 4-triazole pyridine derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911406096.0A CN111138429A (en) | 2019-12-31 | 2019-12-31 | Synthesis method of 1,2, 4-triazole pyridine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111138429A true CN111138429A (en) | 2020-05-12 |
Family
ID=70522679
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911406096.0A Pending CN111138429A (en) | 2019-12-31 | 2019-12-31 | Synthesis method of 1,2, 4-triazole pyridine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111138429A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112341472A (en) * | 2020-11-20 | 2021-02-09 | 济南大学 | Tyrosinase activated double-quenching diagnosis and treatment prodrug and preparation thereof |
| CN114349764A (en) * | 2022-01-12 | 2022-04-15 | 沈阳感光化工研究院有限公司 | Fluorane compounds, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102186851A (en) * | 2008-08-19 | 2011-09-14 | 阵列生物制药公司 | Triazolopyridine compounds as pim kinase inhibitors |
| US20160039813A1 (en) * | 2014-08-06 | 2016-02-11 | Bristol-Myers Squibb Company | Process for the preparation of 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates therefor |
| CN108299426A (en) * | 2018-03-20 | 2018-07-20 | 宝鸡文理学院 | One kind [1,2,4]-triazol [4,3-a] pyridine compounds and their and its synthetic method |
-
2019
- 2019-12-31 CN CN201911406096.0A patent/CN111138429A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102186851A (en) * | 2008-08-19 | 2011-09-14 | 阵列生物制药公司 | Triazolopyridine compounds as pim kinase inhibitors |
| US20160039813A1 (en) * | 2014-08-06 | 2016-02-11 | Bristol-Myers Squibb Company | Process for the preparation of 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates therefor |
| CN108299426A (en) * | 2018-03-20 | 2018-07-20 | 宝鸡文理学院 | One kind [1,2,4]-triazol [4,3-a] pyridine compounds and their and its synthetic method |
Non-Patent Citations (3)
| Title |
|---|
| BLAUVELT, MARISA L.: "5-Thianthrenyl-5-ylium Perchlorate", 《E-EROS ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS》 * |
| HOON YOUNG SON等: "A Convenient Synthesis of New 3,7-Diphenylthieno[3,2-e]bis[1,2,4]triazolo[4,3-a:4’,3’-c]pyrimidine Derivatives by Oxidative Cyclization Using Alumina-supported Calcium Hypochlorite", 《BULL. KOREAN CHEM. SOC.》 * |
| 张艳辉: "反应型次氯酸荧光探针的设计、合成及生物应用研究", 《中国优秀博硕士学位论文数据库（硕士）工程科技I辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112341472A (en) * | 2020-11-20 | 2021-02-09 | 济南大学 | Tyrosinase activated double-quenching diagnosis and treatment prodrug and preparation thereof |
| CN114349764A (en) * | 2022-01-12 | 2022-04-15 | 沈阳感光化工研究院有限公司 | Fluorane compounds, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO331656B1 (en) | Process for synthesizing camptothesin related compounds | |
| CN111138429A (en) | Synthesis method of 1,2, 4-triazole pyridine derivatives | |
| JP2011140494A (en) | New vinca-alkaloid derivative and method for preparing the same | |
| EP0000092B1 (en) | Method of preparing ascorbic acid and intermediates specially adapted for use therein | |
| Katritzky et al. | Preparation of nitropyridines by nitration of pyridines with nitric acid | |
| WO2013168693A1 (en) | Method for producing sepiapterin and tetrahydrolactoylpterin | |
| Enders et al. | Asymmetric Synthesis of Thiadecalins via an Organocatalytic Triple Cascade/Sulfa-Michael Sequence | |
| Móczár et al. | Synthesis and fluorescence studies of novel bis (azacrown ether) type chemosensors containing an acridinone unit | |
| JP2599610B2 (en) | Process for producing 2β-substituted methylpenicillin derivatives | |
| Nikolaeva et al. | Synthesis of novel iono-and photochromic spiropyrans derived from 6, 7-dihydroxy-8-formyl-4-methyl-2H-chromene-2-one | |
| CN113717037B (en) | Green synthesis method of 2, 5-dimethoxy benzaldehyde | |
| US4421923A (en) | Ring substituted crown ethers and method of producing same | |
| Dyachenko et al. | Ethyl 3-amino-3-selenoxopropanoate as a new reagent for the synthesis of selenium-containing heterocycles | |
| HJEDS et al. | Synthesis of Some 4-Aminoalkyl-5-methyl-3-isoxazolols Structurally Related to Muscimol and y-Aminobutyric Acid (GABA) | |
| Soni et al. | Reactions of coumarin-3-carboxylate, its crystallographic study and antimicrobial activity | |
| CN114539197B (en) | Synthesis method of 3-fluoroalkyl substituted chromone derivative | |
| JP3290172B1 (en) | Method for producing 2-aminophenoxazin-3-one derivative or 3-aminophenoxazin-2-one derivative | |
| Almtorp et al. | Synthesis of flavonoids via the isoxazoline route | |
| CN110229056B (en) | Novel curcumin analogue and preparation method and application thereof | |
| JPS58225093A (en) | Benzothiazinorifamycin derivative and its preparation | |
| Golubev et al. | Synthesis of 4-trifluoromethyl-2 H-chromenes via the reaction of 2-(trifluoroacetyl) phenols with vinyltriphenylphosphonium chloride | |
| KR100911720B1 (en) | A process for preparing crystal foam of sarpogrelate hcl | |
| KR950005737B1 (en) | Separating method of component from gingkolide complex | |
| Mack et al. | A novel 3 (2H)-furanone-2 (5H)-furanone rearrangement | |
| JPS6113712B2 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200512 |
|
| WD01 | Invention patent application deemed withdrawn after publication |