CN104370844A - Synthesis method of 3-thione-5-mercaptomethyl-1,2,4-triazole - Google Patents
Synthesis method of 3-thione-5-mercaptomethyl-1,2,4-triazole Download PDFInfo
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- CN104370844A CN104370844A CN201410593715.2A CN201410593715A CN104370844A CN 104370844 A CN104370844 A CN 104370844A CN 201410593715 A CN201410593715 A CN 201410593715A CN 104370844 A CN104370844 A CN 104370844A
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- reactant
- triazole
- synthetic method
- mercaptomethyl
- thione
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- PFUCDWWOYLRZFX-UHFFFAOYSA-N NNC(NC(CS)=O)=S Chemical compound NNC(NC(CS)=O)=S PFUCDWWOYLRZFX-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of 3-thione-5-mercaptomethyl-1,2,4-triazole, which comprises the following steps: by using thiosemicarbazide and thioglycolic acid as raw materials and water as a solvent, carrying out amidation reaction under heating conditions to obtain a reaction product A, regulating the pH value to an alkaline state, refluxing to react completely to obtain a reaction product B, regulating the pH value of the reaction product B to an acidic state to precipitate out, and separating out the precipitate, thereby obtaining the 3-thione-5-mercaptomethyl-1,2,4-triazole. The 3-thione-5-mercaptomethyl-1,2,4-triazole is prepared from the thiosemicarbazide and thioglycolic acid by using the water as the solvent; and compared with the prior art, the method is simple and easy to operate, and has the advantages of mild reaction conditions, simple and accessible raw materials, high product yield (higher than 62%) and high product purity (higher than 98%).
Description
Technical field
The present invention relates to medical art, be specifically related to a kind of synthetic method of 3-thioketones-5-mercapto methyl-1,2,4-triazole.
Background technology
1,2,4-triazole derivative the present age many fields have important application, as in coordination supramolecule chemistry for molecular assemblies provides the weak interaction such as hydrogen bond or pi-pi accumulation to play the keying action of molecular recognition or self-assembly; At field of medicaments as antifungal drug; At pesticide field for the synthesis of sterilant etc.; In Materials science, as novel organic luminescent device, molecular based material, constructs magneticsubstance, is widely used in actual life.
3-thioketones-5-mercapto methyl-1,2,4-triazole is a kind of very important pharmaceutical intermediate, its synthetic method (Ukrainskii Khimicheskii Zhurnal, 1971,37 (2) are reported in prior art, 172-9), concrete synthetic route is as follows:
Reagent wherein and condition are: step I, N
2h
4h
2o, solvent is methyl alcohol ,-10 DEG C; Step III: Na
2cO
3solution boils.The yield of aforesaid method is lower, is only 33%, and reaction conditions is wayward.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of synthetic method of new 3-thioketones-5-mercapto methyl-1,2,4-triazole.The method is simple to operation, and reaction conditions is gentle, and products therefrom yield is high.
The synthetic method of 3-thioketones-5-mercapto methyl-1,2,4-triazole of the present invention is: with thiosemicarbazide and Thiovanic acid for raw material, water is solvent, carries out amidate action, obtain reactant A under heating condition, regulate its pH to alkalescence, back flow reaction, to completely, obtains reactant B, regulate the pH of reactant B to acid, there is Precipitation, isolate precipitation, namely obtain 3-thioketones-5-mercapto methyl-1,2,4-triazole.
In above-mentioned synthetic method, carrying out refluxing and then namely having target product to generate reaction system acidifying as long as the pH of reactant A to be adjusted to alkalescence, preferably, is pH >=7.5 regulating reactant A again; More preferably, be regulate the pH of reactant A to be 8 ~ 10.Specifically can regulating the pH value of reactant A with alkali conventional in prior art, as regulated with alkaline matters such as sodium hydroxide, potassium hydroxide, sodium carbonate or sodium bicarbonates, preferably adopting sodium hydroxide to regulate the pH value of reactant A.When regulating the pH value of reactant A, normally regulate after alkaline matter water wiring solution-forming again.
In above-mentioned synthetic method, amidate action normally carries out back flow reaction in a heated condition, and the temperature of back flow reaction is generally 80 ~ 140 DEG C, is preferably 100 ~ 140 DEG C; Whether amidate action is complete in thin-layer chromatography tracing detection, and under above-mentioned qualifications, reaction is to completely usually needing 1 ~ 5h.
In above-mentioned synthetic method, as long as regulate the pH of reactant B namely to have Precipitation to acidity, start to occur more Precipitation successively when regulating pH≤6.5 of reactant B, when the pH value of reactant B has a large amount of Precipitations 5 ~ 6 time; In order to improve productive rate further, the pH value of reactant B can also be adjusted toward lower acidity further, be 1 ~ 5 as being adjusted to pH value.Acid conventional in usual prior art regulates the pH value of reactant B, as adopted the acid such as hydrochloric acid, sulfuric acid, nitric acid, formic acid or acetic acid to regulate, also can be in reactant B, pass into hydrogen chloride gas, to form the pH value of hydrochloric acid and then adjustment reactant B.
In above-mentioned synthetic method, after reactant A is adjusted to alkalescence, normally under 80 ~ 140 DEG C of conditions, carry out back flow reaction, be preferably 100 ~ 140 DEG C; Whether back flow reaction is complete in thin-layer chromatography tracing detection, and under above-mentioned qualifications, reaction is to completely usually needing 0.5 ~ 3h.
In above-mentioned synthetic method, the mol ratio of thiosemicarbazide and Thiovanic acid is stoichiometric ratio, preferably adopts the Thiovanic acid little over amount, and more preferably thiosemicarbazide and Thiovanic acid mole is 1:1.2 ~ 1.5.In method, the consumption of water can be determined as required, is usually advisable can dissolve the raw material participating in reaction.
Compared with prior art, the present invention with thiosemicarbazide and Thiovanic acid for raw material, water is that solvent synthesis obtains 3-thioketones-5-mercapto methyl-1,2,4-triazole, the method is simple to operation, reaction conditions is gentle, and raw material is simple and easy to get, and products therefrom yield is high, can more than 62% be reached, the purity (survey of HPLC method) more than 98% of products therefrom.
Embodiment
With specific embodiment, the invention will be further described below, but the present invention is not limited to these embodiments.
Embodiment 1
1) by raw material thiosemicarbazide (compound 1) amidation:
By raw material thiosemicarbazide (91.14) (5.5g, 0.06mol) join in 250mL round-bottomed flask, and add 70mL deionized water, stir 30min, add Thiovanic acid (92.12) (5mL, 0.72mol), be warming up to 140 DEG C, stir 30min and make material dissolution; Keep 140 DEG C of return stirring reaction 3h, obtain reactant A (solution namely containing thiosemicarbazide amidated products (compound 2));
2) by thiosemicarbazide amidated products (compound 2) cyclization:
Reactant A is placed in 250mL flask, be cooled to room temperature, and the pH value of reactant A is adjusted to 9, be warming up to 120 DEG C, insulated and stirred back flow reaction 1h, obtain lightpink solution, filter, collect filtrate, obtain lightpink clear solution, be reactant B (solution namely containing compound 3);
3) ring product (compound 3) acidifying will be closed after thiosemicarbazide amidation:
In reactant B, slowly instill concentrated hydrochloric acid, and constantly stir, control the pH=6 of reactant B, have a large amount of white precipitate to separate out, suction filtration, washing, collecting precipitation, dry, obtain light pink solid 4 (purity 98%, HPLC method), yield 82.6%.
Detect the present embodiment gained light pink solid 4, result is as follows:
FT-IR(KBr，cm
-1)：3088(s),2893(s),2477(m),1577(s),1393(s),1332(m),1270(w),1257(w),1190(m),1025(s),993(s),807(m),759(w),731(w),664(m),493(m),425(w).
1HNMR(500MHz,(CD
3)
2SO-d6)δ(ppm)7.12(s,1H),2.83(s,2H),2.03(s,1H),1.56(s,1H).
Therefore, can determine that above-mentioned light pink solid 4 is 3-thioketones-5-mercapto methyl-1,2,4-triazole, its structural formula is shown below, and molecular formula is C
3h
5n
3s
2.
Embodiment 2
Repeat embodiment 1, unlike:
Step 2) in, the pH value of reactant A is adjusted to 8, is warming up to 100 DEG C of insulated and stirred back flow reaction 2h;
Step 3) in, regulate the pH=6 of reactant B with sulfuric acid, have a large amount of white precipitate to separate out, suction filtration, washing, collecting precipitation, precipitation use water recrystallization 1 ~ 2 time, dry, obtain light pink solid (purity 98%, HPLC method), yield 78.4%.
Infrared spectra and nuclear-magnetism detection are carried out to gained light pink solid, determines that this light pink solid is 3-thioketones-5-mercapto methyl-1,2,4-triazole.
Embodiment 3
Repeat embodiment 1, unlike:
Step 2) in, the pH value of reactant A is adjusted to 10, is warming up to 80 DEG C of insulated and stirred back flow reaction 3h;
Step 3) in, regulate the pH=6.5 of reactant B with sulfuric acid, have a large amount of white precipitate to separate out, suction filtration, washing, collecting precipitation, precipitation use water recrystallization 1 ~ 2 time, dry, obtain light pink solid (purity 98%, HPLC method), yield 72.5%.
Infrared spectra and nuclear-magnetism detection are carried out to gained light pink solid, determines that this light pink solid is 3-thioketones-5-mercapto methyl-1,2,4-triazole.
Embodiment 4
Repeat embodiment 1, unlike:
Step 2) in, the pH value of reactant A is adjusted to 7.5, is warming up to 120 DEG C of insulated and stirred back flow reaction 2h;
Step 3) in, regulate the pH=3 of reactant B with sulfuric acid, have a large amount of white precipitate to separate out, suction filtration, washing, collecting precipitation, precipitation use water recrystallization 1 ~ 2 time, dry, obtain light pink solid (purity 98%, HPLC method), yield 62%.
Infrared spectra and nuclear-magnetism detection are carried out to gained light pink solid, determines that this light pink solid is 3-thioketones-5-mercapto methyl-1,2,4-triazole.
Claims (7)
- The synthetic method of 1.3-thioketones-5-mercapto methyl-1,2,4-triazole, it is characterized in that: with thiosemicarbazide and Thiovanic acid for raw material, water is solvent, carries out amidate action under heating condition, obtain reactant A, regulate its pH to alkalescence, back flow reaction is to complete, obtain reactant B, regulate the pH of reactant B to acid, have Precipitation, isolate precipitation, namely 3-thioketones-5-mercapto methyl-1,2,4-triazole is obtained.
- 2. synthetic method according to claim 1, is characterized in that: pH >=7.5 regulating reactant A.
- 3. synthetic method according to claim 1, is characterized in that: the pH regulating reactant A is 8 ~ 10.
- 4. synthetic method according to claim 1, is characterized in that: amidate action refluxes under 80 ~ 140 DEG C of conditions.
- 5. synthetic method according to claim 1, is characterized in that: pH≤6.5 regulating reactant B.
- 6. synthetic method according to claim 1, is characterized in that: the pH regulating reactant B is 3 ~ 6.
- 7. synthetic method according to claim 1, is characterized in that: after reactant A is adjusted to alkalescence, under 80 ~ 140 DEG C of conditions, carry out back flow reaction.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410593715.2A CN104370844A (en) | 2014-10-29 | 2014-10-29 | Synthesis method of 3-thione-5-mercaptomethyl-1,2,4-triazole |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1617859A (en) * | 2001-11-28 | 2005-05-18 | 科学研究和应用咨询公司 | 5-sulfanyl-4h-1,2,4-triazole derivatives and their use as a medicament |
-
2014
- 2014-10-29 CN CN201410593715.2A patent/CN104370844A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1617859A (en) * | 2001-11-28 | 2005-05-18 | 科学研究和应用咨询公司 | 5-sulfanyl-4h-1,2,4-triazole derivatives and their use as a medicament |
Non-Patent Citations (3)
| Title |
|---|
| HAMED A. EAD,ET AL.: "Synthesis and Reactions of New 1,2,4-Triazoles and Their Biological Activities", 《ARCH. PHARM.》 * |
| SHVAIKA, O. P.，ET AL.: "Formation and recyclization reactions for heterocycles. IV. Reaction of thiocyanates with hydrazine", 《UKRAINSKII KHIMICHESKII ZHURNAL》 * |
| SHVAIKA, O. P.，ET AL.: "Recyclization of azolidones under the influence of hydrazine", 《DOKLADY AKADEMII NAUK SSSR》 * |
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