CN105017247A - [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione derivative preparation method - Google Patents
[1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione derivative preparation method Download PDFInfo
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- 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
Abstract
The present invention discloses a preparation method of a [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione derivative represented by a formula (I). The method comprises that 8-chloro-[1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione represented by a formula (II) is synthesized from 3-chloro-2-hydrazinopyridine and thiourea under microwave irradiation, and then the 8-chloro-[1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione and a halide are subjected to a microwave irradiation reaction in an alkali and an organic solution to prepare the compound represented by the formula (I), wherein in the formula (I), R is benzyl, 3,4-dichlorobenzyl, 2-(1-methoxyimino-2-methoxy-2-oxoethyl)benzyl, acetonitrile, 4-nitrile benzyl, 3-nitrile benzyl, (6-chloropyridine-3-yl)methyl, 3-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, or 2-chlorophenyl. The preparation method of the present invention has characteristics of simple operation, high product yield, short reaction time, low price of the reaction reagents used during the reaction process, and good application value.
Description
Technical field
The present invention relates to one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives.
Background technology
The mankind never stop exploring outfield from the beginning to the end, the initiative of new compound is also the emphasis that chemist studies all the time, in crisscross numerous and disorderly compound, nitrogen-containing heterocycle compound has excellent biological activity usually, such as, to the PAM activity, anti-convulsant activity, weeding activity etc. of mGlu2 acceptor.Equally, this compounds also shows good anti-microbial activity.Some of them have been developed becomes commercialization bactericide agricultural chemicals, such as, and azafenidin, prothioconazoles etc.Due to the multiple biological activity that nitrogen heterocyclic ring has, make [1,2,4] triazole [4,3-in new compound initiative
a] pyridine-3 (2
hthe preparation of)-40 thione derivatives is significant.
[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe synthesis of)-40 thione derivatives has been reported.As:
1989, Rama, R. report [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones and olefine reaction synthesize [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe method of)-40 thione derivatives:
1992, Sohda, Takashi report [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones and halide reaction synthesize [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe method of)-40 thione derivatives:
2012, Edlin, Chris D. reported synthesis [1,2,4] triazole [4,3-under DIPEA exists
a] pyridine-3 (2
hthe method of)-40 thione derivatives:
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of easy [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-40 thione derivatives preparation method.
A kind of [1,2,4] triazole [4,3-as shown in the formula (I)
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that comprising the steps: that under microwave radiation, carrying out ring closure reaction by 3-chloride-2-hydrazinopyridine and thiocarbamide synthesizes obtained 8-chloro-[1,2,4] triazole [4,3-as shown in formula II
a] pyridine-3 (2
h)-thioketones, then 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones and RCH2Cl microwave radiation in alkaline matter and organic solution as shown in the formula (III) react obtained product [1,2,4] triazole [4,3-shown in formula (I)
a] pyridine-3 (2
h)-40 thione derivatives;
R in formula (III) Chinese style (I) is identical with the R in formula (III), and R is phenyl, and 3,4-dichlorophenyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenyl, acetonitrile-base, 4-cyanophenyl, 3-cyanophenyl, 6-chloropyridine-3-base, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described recrystallization solvent is one or more in sherwood oil, ethyl acetate, normal hexane or ethanol.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described organic solvent is one or more in DMF, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane or acetone.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described alkaline matter is one or more in salt of wormwood, sodium bicarbonate, sodium hydroxide, potassium hydroxide or sodium hydride.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, it is characterized in that the molar ratio of described 3-chloride-2-hydrazinopyridine and thiocarbamide is 1:2.0 ~ 4.0, preferred molar ratio is 1:3.0.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones, the molar ratio of RCH2CL and alkaline matter is 1:1.0 ~ 1.5:1.0 ~ 2.0, and preferential molar ratio is 1:1.1:1.2.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, it is characterized in that the ring closure reaction temperature of described 3-chloride-2-hydrazinopyridine and thiocarbamide is 180 DEG C, the reaction times is 30min.
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe temperature of reaction of)-thioketones and RCH2Cl is 90 DEG C, and the reaction times is 15 min.
The reaction solution that the present invention fully reacts rear gained can obtain target product through simple conventional aftertreatment, described post-treating method can be: reaction terminates, reaction solution is directly concentrated to be obtained resistates or is poured into water by reaction solution, then extracts by ethyl acetate, merges organic layer, dry, concentrate and obtain resistates, then gained resistates currently known methods such as column chromatography or recrystallization method are carried out abstraction and purification and obtain target product [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-40 thione derivatives.Column chromatography or recrystallization solvent for use can be sherwood oil, ethyl acetate, normal hexane, ethanol or their mixed solution.
Compared with prior art, beneficial effect of the present invention is: the present invention is prepared under microwave condition by adopting, its preparation method is simple to operate, and product yield is high, the reaction times is short, reagent used in reaction process is all less expensive, has good using value.
Embodiment
Below in conjunction with embodiment, technical scheme of the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe synthesis of)-thioketones
By thiocarbamide (3mmol), 3-chloride-2-hydrazinopyridine (143 mg, 1mmol) joins in counteracting tank at the bottom of CEM Discovery single mold microwave synthesizer particular circle.Then Microwave-assisted synthesis instrument Radiation work under (180 ° of C, 30min) condition.Be poured into by mixture after end in 40ml water after forming precipitation and filter, thick product in ethanol recrystallization obtains 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones, yield 95%.
Embodiment 2 3-(benzylthio)-8-chloro-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), benzyl chlorine (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. 3-(benzylthio)-8-chloro-[1,2,4] triazole [4,3-
a] pyridine, productive rate 94%, m.p.140-141 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.29 (s, 2H, SCH
2), 6.62 (t,
j=7.0Hz, 1H, Py-H), 7.09-7.11 (m, 2H, Ar-H), 7.15-7.16 (m, 3H, Py-H and Ar-H), 7.27 (s, 1H, Ar-H), 7.62 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
13h
10clN
3s:found C 56.74, H 3.76, N 15.43; Calcd. C, 56.62; H, 3.66; N, 15.24.
The chloro-3-of embodiment 3 8-((3,4-dichloro benzyl) sulfenyl)-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), 1,2-bis-chloro-4-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.The i.e. chloro-3-of 8-((3,4-dichloro benzyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine, productive rate 93%, m.p.152-153 DEG C; 1H NMR (CDCl3,400 MHz), δ: 4.30 (s, 2H; SCH2), 6.75 (t, J=7.0Hz, 1H; Py-H), 7.02 (d, J=6.2Hz; 1H, Py-H), 7.33 (d; J=6.5Hz, 1H, Py-H);. Elemental analysis for C13H8Cl3N3S:found C 45.44, H 2.53, N 11.98; Calcd. C, 45.30; H, 2.34; N, 12.19.
Embodiment 4 (Z)-methyl 2-(2-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) phenyl) synthesis of-2-(methoxy imino) acetic ester
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), methyl (Z)-2-(2-(chloromethyl) phenyl)-2-(methoxy imino) acetic ester (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. (Z)-methyl 2-(2-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) phenyl)-2-(methoxy imino) acetic ester
,productive rate 93%, m.p.155-156 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 3.77 (s, 3H, OCH
3), 3.89 (s, 3H, OCH
3), 4.10 (s, 2H, SCH
2), 6.53 (t,
j=7.0Hz, 1H, Py-H), 6.66 (d,
j=7.0Hz, 1H, Ar-H), 6.90 (d,
j=7.5Hz, 1H, Ar-H), 7.13 (d,
j=7.5Hz, 1H, Ar-H), 7.19 (t,
j=7.5Hz, 1H, Ar-H), 7.25 (d,
j=7.0Hz, 1H, Py-H), 7.71 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
17h
15clN
4o
3s:found C 52.33, H 3.97, N 14.45; Calcd. C, 52.24; H, 3.87; N, 14.33
Embodiment 5 2-((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) synthesis of acetonitrile
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), 2-chloromethyl cyanide (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. 2-((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) acetonitrile
,productive rate 92%, m.p.200-201 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 3.90 (s, 2H, SCH
2), 7.00 (t,
j=7.0Hz, 1H, Py-H), 7.48 (d,
j=7.2Hz, 1H, Py-H), 7.24-7.28 (m, 2H, Ar-H), 7.31 (d,
j=6.5Hz, 1H, Py-H), 7.31 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
8h
5clN
4s:found C 42.97, H 2.31, N 24.99; Calcd. C, 42.77; H, 2.24; N, 24.94.
Embodiment 6 4-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) synthesis of benzonitrile
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), CEM Discovery single mold microwave synthesizer 10ml rated pressure tank is added to chloromethyl benzonitrile (1.1 mmol) and NaOH (0.05 g, 1.2mmol).Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. 4-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) benzonitrile, productive rate 94%, m.p.194-195 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.50 (s, 2H, SCH
2), 6.89 (t,
j=7.0Hz, 1H, Py-H), 7.40 (d,
j=8.1Hz, 1H, Ar-H), 7.45 (d,
j=6.5Hz, 1H, Py-H), 7.54 (d,
j=8.1Hz, 1H, Ar-H), 7.82 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
14h
9clN
4s:found C 55.89, H 2.97, N 18.87; Calcd. C, 55.91; H, 3.02; N, 18.63.
The chloro-3-of embodiment 7 8-(((6-chloropyridine-3-base) methyl) sulfenyl)-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), CCMP (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.The i.e. chloro-3-of 8-(((6-chloropyridine-3-base) methyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine, productive rate 92%, m.p.150-151 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.40 (s, 2H, SCH
2), 6.81 (t,
j=7.0Hz, 1H, Py-H), 7.18 (d,
j=8.2Hz, 1H, Py-H), 7.34 (d,
j=7.2Hz, 1H, Py-H), 7.58 (dd,
j=2.5,2.5Hz, 1H, Py-H), 7.78 (d,
j=6.9Hz, 1H, Py-H), 8.31 (d,
j=2.3Hz, 1H, Py-H). Elemental analysis for C
12h
8cl
2n
4s:found C 46.42, H 2.75, N 17.96; Calcd. C, 46.32; H, 2.59; N, 18.00.
The chloro-3-of embodiment 8 8-((3-fluorophenyl) sulfenyl)-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), 1-chloromethyl-3-fluorobenzene (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.The i.e. chloro-3-of 8-((3-fluorophenyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine, productive rate 93%, m.p.99-100 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.30 (s, 2H, SCH
2), 6.69 (t,
j=7.0Hz, 1H, Py-H), 6.85-6.91 (m, 2H, Ar-H), 6.93 (d,
j=1.6Hz, 1H, Ar-H), 7.09-7.13 (m, 1H, Ar-H), 7.27 (d,
j=7.2Hz, 1H, Py-H), 7.71 (d,
j=7.5Hz, 1H, Py-H). Elemental analysis for C
13h
9clFN
3s:found C 53.22, H 2.97, N 14.51; Calcd. C, 53.15; H, 3.09; N, 14.30.
The chloro-3-of embodiment 9 8-((2-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe chloro-2-chloromethylbenzene of)-thioketones (1mmol), 1-(1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.The i.e. chloro-3-of 8-((2-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
,productive rate 95%, m.p.152-153 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.42 (s, 2H, SCH
2), 6.67 (t,
j=7.0Hz, 1H, Py-H), 6.97 (d,
j=4.0Hz, 2H, Ar-H), 7.13-7.17 (m, 1H, Ar-H), 7.27-7.29 (m, 1H, Ar-H), 7.34 (d,
j=7.9Hz, 1H, Py-H), 7.72 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
13h
9cl
2n
3s:found C 50.46, H 2.90, N 13.64; Calcd. C, 50.33; H, 2.92; N, 13.55.
Embodiment 10 3-((4-bromophenyl) sulfenyl)-8-chloro-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe bromo-4-chloromethylbenzene of)-thioketones (1mmol), 1-(1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. 3-((4-bromophenyl) sulfenyl)-8-chloro-[1,2,4] triazole [4,3-
a] pyridine, productive rate 96%, m.p.168-169 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.42 (s, 2H, SCH
2), 6.72 (t,
j=6.9Hz, 1H, Py-H), 7.04 (d,
j=7.8Hz, 2H, Ar-H), 7.28-7.33 (m, 3H, Ar-H and Py-H), 7.69 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
13h
9brClN
3s:found C 44.33, H2.61, N 11.68; Calcd. C, 44.03; H, 2.56; N, 11.85.
Embodiment 11 3-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) synthesis of benzonitrile
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones (1mmol), 3-chloromethyl benzonitrile (1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.I.e. 3-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) benzonitrile, productive rate 94%, m.p.186-187 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.44 (s, 2H, SCH
2), 6.82 (t,
j=6.9Hz, 1H, Py-H), 7.31-7.37 (m, 2H, Ar-H), 7.47 (d,
j=7.8Hz, 1H, Ar-H), 7.51 (d,
j=7.8Hz, 1H, Py-H), 7.61 (s, 1H, Ar-H), 7.80 (d,
j=6.7Hz, 1H, Py-H). Elemental analysis for C
14h
9clN
4s:found C 55.89, H 2.88, N 18.86; Calcd. C, 55.91; H, 3.02; N, 18.63.
The chloro-3-of embodiment 12 8-((4-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] synthesis of pyridine
By chloro-to DMF (5 mL), 8-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe chloro-4-chloromethylbenzene of)-thioketones (1mmol), 1-(1.1 mmol) and NaOH (0.05 g, 1.2mmol) are added to CEM Discovery single mold microwave synthesizer 10ml rated pressure tank.Then microwave radiation reaction under (90 ° of C, 15 minutes) condition.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.The i.e. chloro-3-of 8-((4-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine, productive rate 93%, m.p.162-163 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.28 (s, 2H, SCH
2), 6.69 (t,
j=7.0Hz, 1H, Py-H), 7.06 (d,
j=8.4Hz, 2H, Ar-H), 7.14 (d,
j=8.4Hz, 2H, Ar-H), 7.29 (d,
j=7.7Hz, 1H, Py-H), 7.67 (d,
j=7.4Hz, 1H, Py-H). Elemental analysis for C
13h
9cl
2n
3s:found C 50.13, H 3.05, N 13.71; Calcd. C, 50.33; H, 2.92; Cl, 22.86; N, 13.55.
Embodiment 13
Fungicidal activity is tested
Subjects: bacterial spot of tomato, cucumber fusarium axysporum, graw mold of tomato.
Test method: adopt pot experiment method.Respectively by cucumber seeds and tomato seeds after 50 DEG C are soaked, be seeded in after vernalization in pot for growing seedlings, wait to grow to 2 true leaves for test.
Medicament prepares: for reagent: get it filled and be made into 100ppm, get 89 kinds of each 5mg of compound, add 10% POLYSORBATE 80 again after adding acetone solution, finally adds water and fully dissolves.Because 100ppm is that 100mg/L is so amount of water=5mg*1000/100mg=50ml, because of final content≤1% of organic solvent so the amount=50ml*1%=0.5ml(adding acetone dissolves), be 0.1% so tween 0.05 ml should be had in 50 ml water because of the final content of tween, that is: 10% tween 0.05 ml. should be added
Contrast medicament: 3% Zhongshengmycin WP → 800 times liquid 0.01g medicine+8ml water
75% thiophanate methyl WP → 1000 times liquid 0.01g medicine+15ml water
50% cyprodinil water dispersible granule → 1000 times liquid 0.01g medicine+15ml water
Application method: bacterial spot of tomato and graw mold of tomato experiment in, when tomato seedling grows two panels compound leaf, with watering can by reagent agent with contrast medicament evenly spray confession try on plant.
In cucumber fusarium axysporum experiment, cucumber seeds is soaked in after respectively will processing 2h and carries out inoculation process.
Inoculation method:
Bacterial spot of tomato adopts the inoculation of bacteria suspension spray method: cultured bacterial spot of tomato bacterium is converted distilled water diluting and becomes 3 × 10
7cfu/ml bacteria suspension, uses watering can spray inoculation.After inoculation, moisturizing is cultivated.
Graw mold of tomato adopts plays mycelium inoculation inoculation: by filtered through gauze, liquid nutrient medium and bacterium block are separated, with crusher, the bacterium block of the substratum with a small amount of liquid is smashed, to mix with the bacterium block smashed with the liquid nutrient medium filtered again and be made into certain density solution, and with spectrophotometric determination solution transmittance (λ=630nm, OD=9.8).
Cucumber fusarium axysporum adopts the inoculation of Baconic method for soaking seed: will in PD substratum cultured cucumber fusarium axysporum filtered through gauze mycelia, regulate spore concentration to 1 × 10
6cfu/ml soaks seed.
After clear water is fully fallen ill, carry out Disease investigation, and calculate disease index and prevention effect.
In formula: EF: prevention effect relatively; CK: the final average disease index in check plot; PT: the final average disease index in treatment zone.
Fungicidal activity testing experiment result is as shown in table 1.
the fungicidal activity (% preventive effect) of each compound under table 1 100ppm
。
Claims (8)
1. [1,2,4] triazole [4,3-as shown in the formula (I)
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that comprising the steps: that under microwave radiation, carrying out ring closure reaction by 3-chloride-2-hydrazinopyridine and thiocarbamide synthesizes obtained 8-chloro-[1,2,4] triazole [4,3-as shown in formula II
a] pyridine-3 (2
h)-thioketones, then 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones and RCH2Cl microwave radiation in alkaline matter and organic solution as shown in the formula (III) react obtained product [1,2,4] triazole [4,3-shown in formula (I)
a] pyridine-3 (2
h)-40 thione derivatives;
R in formula (III) Chinese style (I) is identical with the R in formula (III), and R is phenyl, and 3,4-dichlorophenyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenyl, acetonitrile-base, 4-cyanophenyl, 3-cyanophenyl, 6-chloropyridine-3-base, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
2. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described recrystallization solvent is one or more in sherwood oil, ethyl acetate, normal hexane or ethanol.
3. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described organic solvent is one or more in DMF, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane or acetone.
4. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described alkaline matter is one or more in salt of wormwood, sodium bicarbonate, sodium hydroxide, potassium hydroxide or sodium hydride.
5. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, it is characterized in that the molar ratio of described 3-chloride-2-hydrazinopyridine and thiocarbamide is 1:2.0 ~ 4.0, preferred molar ratio is 1:3.0.
6. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketones, the molar ratio of RCH2CL and alkaline matter is 1:1.0 ~ 1.5:1.0 ~ 2.0, and preferential molar ratio is 1:1.1:1.2.
7. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, it is characterized in that the ring closure reaction temperature of described 3-chloride-2-hydrazinopyridine and thiocarbamide is 180 DEG C, the reaction times is 30min.
8. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
hthe preparation method of)-40 thione derivatives, is characterized in that described 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe temperature of reaction of)-thioketones and RCH2Cl is 90 DEG C, and the reaction times is 15 min.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6043369A (en) * | 1993-08-10 | 2000-03-28 | Basf Aktiengesellschaft | [1,3,4] Triazolo [1,5-A] pyridines |
| DE10038019A1 (en) * | 2000-08-04 | 2002-02-14 | Bayer Ag | Substituted triazolopyride (az) ine |
| CN102669121A (en) * | 2012-04-20 | 2012-09-19 | 浙江工业大学 | Application of triazolopyrimidine derivative in preparation of medicine for resisting agricultural fungi |
| CN103626737A (en) * | 2013-12-10 | 2014-03-12 | 浙江工业大学 | Application of triazole compound containing pyridine as bactericide |
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2015
- 2015-06-16 CN CN201510332161.5A patent/CN105017247B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6043369A (en) * | 1993-08-10 | 2000-03-28 | Basf Aktiengesellschaft | [1,3,4] Triazolo [1,5-A] pyridines |
| DE10038019A1 (en) * | 2000-08-04 | 2002-02-14 | Bayer Ag | Substituted triazolopyride (az) ine |
| CN102669121A (en) * | 2012-04-20 | 2012-09-19 | 浙江工业大学 | Application of triazolopyrimidine derivative in preparation of medicine for resisting agricultural fungi |
| CN103626737A (en) * | 2013-12-10 | 2014-03-12 | 浙江工业大学 | Application of triazole compound containing pyridine as bactericide |
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| J. A. HASSANIN ET AL.: "Synthesis of functionalized 7-chloro-1,2,4-triazolo [4, 3-a]quinoline", 《HETEROCYCLIC COMMUNCATIONS》 * |
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