CN103232404A - Preparation method of 4-methylthiazol - Google Patents
Preparation method of 4-methylthiazol Download PDFInfo
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- CN103232404A CN103232404A CN2013101527883A CN201310152788A CN103232404A CN 103232404 A CN103232404 A CN 103232404A CN 2013101527883 A CN2013101527883 A CN 2013101527883A CN 201310152788 A CN201310152788 A CN 201310152788A CN 103232404 A CN103232404 A CN 103232404A
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- methylthiazol
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- thioformamide
- thiophosphoric anhydride
- methane amide
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Abstract
The invention relates to a preparation method of 4-methylthiazol. The invention aims at solving the problem that in the existing method for preparing the methylthiazol, the reaction route is long, the reaction is complicated and not easy to control, the production cost of the used catalyst is high and the yield is high. The preparation method comprises the following steps of A, mixing formamide, anhydrous glycol dimethyl ether and phosphorus pentasulfide, heating the mixture to be reacted at the temperature of 45 to 50 DEG C, and filtering the mixture to obtain thioformamide; B, adding chloroacetone into the thioformamide to be reacted at the temperature of 50 to 60 DEG C, adjusting the pH value to 6 to 7, and cooling, filtering, washing and dehydrating the mixture to obtain the 4-methylthiazol. Raw materials are cheap and easy to obtain, the reaction condition is moderate, the synthesis step is simple, no catalyst is used, no pollution exists, the yield is high, operation is simple and convenient, and the solvent can be recycled. The preparation method is applied to the technical field of chemical industry.
Description
Technical field
The invention belongs to chemical technology field, be specifically related to the preparation method of 4-methylthiazol.
Background technology
In recent ten years, growth in the living standard along with people, people's quality of life requires also improving, the 4-methylthiazol is a kind of important medicine, agricultural chemicals and spices intermediate, because it has unique fragrance, so extensively it is used as in medicine, food, makeup and some daily necessitiess both at home and abroad.Because maintaining secrecy of foreign technology, its at home production application receive very big restriction.
[CN101870682] report,
, the reaction design is more reasonable, but reaction scheme is oversize, severe reaction conditions, and yield is 78%-82%, industrial production cost height.
According to [U.S.4111948],
In this reaction, because sulfydryl is very unstable, reduction ratio is difficult under the industrialized condition, and is only synthetic at laboratory condition at present.Next utilizes the potassium permanganate oxidation reaction more violent, wayward.
According to Pavlik, reports such as JamesW.,
This reacts complicated, and yield is 20%-22%, uses expensive catalysts, is unfavorable for industrial production.
Summary of the invention
The objective of the invention is to prepare in order to solve existing method that methylthiazol exists that reaction scheme is long, reaction complicated wayward, use Catalyst Production cost height and the high problem of yield, and provide the preparation method of 4-methylthiazol.
The preparation method of 4-methylthiazol of the present invention, carry out according to following steps:
One, the preparation of thioformamide: in solvent, add methane amide, under whipped state, room temperature condition, add thiophosphoric anhydride, finish, be warming up to 45～50 ℃, reaction 2h is cooled to room temperature again, filter, collect filtrate, obtain containing the mixing solutions of thioformamide; Wherein, the mass ratio of described solvent and methane amide is 1.5～4:1, the mass ratio of described thiophosphoric anhydride and methane amide is 1.0～1.1:1, described thiophosphoric anhydride is to add in batches, be specially: be that the ratio of 1.0～1.1:1 takes by weighing thiophosphoric anhydride in the mass ratio of thiophosphoric anhydride and methane amide, divide 8～10 batches of addings with the thiophosphoric anhydride that takes by weighing, per 20～30min adds a collection of thiophosphoric anhydride, every batch of add-on equalization is until adding thiophosphoric anhydride;
Two, the preparation of 4-methylthiazol: be that to the mixed solution and dripping monochloroacetone that contains thioformamide that step 1 obtains, the control temperature is lower than 20 ℃ under 5～10 ℃ the condition in temperature, after dropwising, under this temperature, react 1h, be warming up to 50～60 ℃ of reaction 6h then, behind the pH to 6 of regulator solution～7, be cooled to room temperature, filter, collect filtrate, steam solvent in the filtrate, wash again, namely get the 4-methylthiazol after dewatering; Wherein, describedly contain the mixing solutions of thioformamide and the molar ratio of monochloroacetone is 1:1.0～1.2.
4-methylthiazol synthetic route of the present invention is as follows:
The present invention comprises following beneficial effect:
Synthetic method provided by the invention, synthetic route is simple, does not use catalyzer, and the solvent ethylene glycol dme conveniently recycles and reuses, avoid the pollution to environment, the reaction conditions gentleness, the reaction times is short, easy and simple to handle, yield is suitable for suitability for industrialized production greater than 94%.
Embodiment
Technical solution of the present invention is not limited to following cited embodiment, also comprises the arbitrary combination between each embodiment.
Embodiment one: the preparation method of the 4-methylthiazol of present embodiment carries out according to following steps:
One, the preparation of thioformamide: in solvent, add methane amide, under whipped state, room temperature condition, add thiophosphoric anhydride, finish, be warming up to 45～50 ℃, reaction 2h is cooled to room temperature again, filter, collect filtrate, obtain containing the mixing solutions of thioformamide; Wherein, the mass ratio of described solvent and methane amide is 1.5～4:1, the mass ratio of described thiophosphoric anhydride and methane amide is 1.0～1.1:1, described thiophosphoric anhydride is to add in batches, be specially: be that the ratio of 1.0～1.1:1 takes by weighing thiophosphoric anhydride in the mass ratio of thiophosphoric anhydride and methane amide, divide 8～10 batches of addings with the thiophosphoric anhydride that takes by weighing, per 20～30min adds a collection of thiophosphoric anhydride, every batch of add-on equalization is until adding thiophosphoric anhydride;
Two, the preparation of 4-methylthiazol: be that to the mixed solution and dripping monochloroacetone that contains thioformamide that step 1 obtains, the control temperature is lower than 20 ℃ under 5～10 ℃ the condition in temperature, after dropwising, under this temperature, react 1h, be warming up to 50～60 ℃ of reaction 6h then, behind the pH to 6 of regulator solution～7, be cooled to room temperature, filter, collect filtrate, steam solvent in the filtrate, wash again, namely get the 4-methylthiazol after dewatering; Wherein, describedly contain the mixing solutions of thioformamide and the molar ratio of monochloroacetone is 1:1.0～1.2.
Embodiment two: what present embodiment and embodiment one were different is: the solvent described in the step 1 is anhydrous glycol dimethyl ether or dioxane.Other step and parameter are identical with embodiment one.
The anhydrous glycol dimethyl ether of present embodiment is to adopt Vanadium Pentoxide in FLAKES to dewater, and obtains anhydrous glycol dimethyl ether.
Embodiment three: what present embodiment was different with embodiment one or two is: be warming up to 45～50 ℃ described in the step 1, reaction 2h.Other step and parameter are identical with embodiment one or two.
Embodiment four: what present embodiment was different with one of embodiment one to three is: the mass ratio of the solvent described in the step 1 and methane amide is 2～3:1.Other step and parameter are identical with one of embodiment one to three.
Embodiment five: what present embodiment was different with one of embodiment one to four is: the mass ratio of the solvent described in the step 1 and methane amide is 2.5:1.Other step and parameter are identical with one of embodiment one to four.
Embodiment six: what present embodiment was different with one of embodiment one to five is: the mass ratio of the thiophosphoric anhydride described in the step 1 and methane amide is 1.05:1.Other step and parameter are identical with one of embodiment one to five.
Embodiment seven: what present embodiment was different with one of embodiment one to six is: described in the step 2 under temperature is 6～8 ℃ condition, drip monochloroacetone in the thioformamide that obtains to step 1.Other step and parameter are identical with one of embodiment one to six.
Embodiment eight: what present embodiment was different with one of embodiment one to seven is: the thioformamide in the mixing solutions that contains thioformamide described in the step 2 is 1:1.2 with the theoretical molar of monochloroacetone ratio.Other step and parameter are identical with one of embodiment one to seven.
Embodiment nine: what present embodiment was different with one of embodiment one to eight is: described in the step 2 be warming up to then 55 ℃ the reaction 6h.Other step and parameter are identical with one of embodiment one to eight.
Embodiment ten: what present embodiment was different with one of embodiment one to nine is: the pH to 6.5 of the conditioned reaction liquid described in the step 2.Other step and parameter are identical with one of embodiment one to nine.
Verify beneficial effect of the present invention by following examples:
Embodiment 1
The preparation method of the 4-methylthiazol of present embodiment carries out according to following steps:
The first step: the preparation of thioformamide
In the 500mL four-hole bottle, add anhydrous glycol dimethyl ether 300g, under agitation condition, add methane amide 105g, then at room temperature, the 110g thiophosphoric anhydride is added (thiophosphoric anhydride that every 20min adds 30g) in batches, finish, be warming up to 45～50 ℃, reacted 2 hours, be cooled to room temperature, adopt aperture 0.45um filter paper filtering, collect filtrate and put in the four-hole bottle of another 500mL, obtain containing the mixing solutions of thioformamide, standby;
Second step: the preparation of 4-methylthiazol
Be to drip the 250g monochloroacetone in the thioformamide solution in the above-mentioned four-hole bottle under 5～10 ℃ the condition in temperature, the control temperature is lower than 20 ℃, after dropwising, reacted 1 hour, be warming up to 50～60 ℃ of reactions 6 hours again, regulate pH to 6～7, be cooled to room temperature, adopt aperture 0.45um qualitative filter paper to filter, collect filtrate and steam monochloroacetone, obtain the sturdy product of oily, wash 3 times, dewater 3 times with anhydrous magnesium sulfate, aperture 0.45um filter paper filtering obtains 4-methylthiazol 225g.
The yield of the 4-methylthiazol of present embodiment preparation is 95%.
Embodiment 2
The preparation method of the 4-methylthiazol of present embodiment carries out according to following steps:
The first step: the preparation of thioformamide
In the 1000mL four-hole bottle, add anhydrous glycol dimethyl ether 400g, under agitation condition, add methane amide 200g, at ambient temperature, the 210g thiophosphoric anhydride is added (thiophosphoric anhydride that every 20min adds the 50g amount) in batches, finish, be warming up to 5～50 ℃, reacted 2 hours, be cooled to room temperature, adopt aperture 0.45um filter paper filtering, collect filtrate and put in the four-hole bottle of another 1000mL, obtain containing the mixing solutions of thioformamide, standby;
Second step: the preparation of 4-methylthiazol
Be to drip the 490g monochloroacetone in the thioformamide solution in the above-mentioned four-hole bottle under 5～10 ℃ the condition in temperature, the control temperature is lower than 20 ℃, after dropwising, down, reacted 1 hour, be warming up to 50～60 ℃ of reactions 6 hours again, conditioned reaction liquid pH to 6～7, be cooled to room temperature, adopt aperture 0.45um qualitative filter paper to filter, collect filtrate and steam monochloroacetone, obtain the sturdy product of oily, wash 3 times, dewater 3 times with anhydrous magnesium sulfate, aperture 0.45um filter paper filtering obtains 4-methylthiazol 415g.
The yield of the 4-methylthiazol of present embodiment preparation is 94.5%.
Claims (10)
1.4-the preparation method of methylthiazol is characterized in that the preparation method of described 4-methylthiazol carries out according to following steps:
One, the preparation of thioformamide: in solvent, add methane amide, under whipped state, room temperature condition, add thiophosphoric anhydride, finish, be warming up to 45～50 ℃, reaction 2h is cooled to room temperature again, filter, collect filtrate, obtain containing the mixing solutions of thioformamide; Wherein, the mass ratio of described solvent and methane amide is 1.5～4:1, the mass ratio of described thiophosphoric anhydride and methane amide is 1.0～1.1:1, described thiophosphoric anhydride is to add in batches, be specially: be that the ratio of 1.0～1.1:1 takes by weighing thiophosphoric anhydride in the mass ratio of thiophosphoric anhydride and methane amide, divide 8～10 batches of addings with the thiophosphoric anhydride that takes by weighing, per 20～30min adds a collection of thiophosphoric anhydride, every batch of add-on equalization is until adding thiophosphoric anhydride;
Two, the preparation of 4-methylthiazol: be that to the mixed solution and dripping monochloroacetone that contains thioformamide that step 1 obtains, the control temperature is lower than 20 ℃ under 5～10 ℃ the condition in temperature, after dropwising, under this temperature, react 1h, be warming up to 50～60 ℃ of reaction 6h then, behind the pH to 6 of regulator solution～7, be cooled to room temperature, filter, collect filtrate, steam solvent in the filtrate, wash again, namely get the 4-methylthiazol after dewatering; Wherein, describedly contain the mixing solutions of thioformamide and the molar ratio of monochloroacetone is 1:1.0～1.2.
2. the preparation method of 4-methylthiazol according to claim 1 is characterized in that the solvent described in step 1 and two is anhydrous glycol dimethyl ether or dioxane.
3. the preparation method of 4-methylthiazol according to claim 1 is characterized in that be warming up to 47 ℃ described in the step 1, reaction 2h.
4. the preparation method of 4-methylthiazol according to claim 1 and 2, the mass ratio that it is characterized in that the solvent described in the step 1 and methane amide is 2～3:1.
5. the preparation method of 4-methylthiazol according to claim 4, the mass ratio that it is characterized in that the solvent described in the step 1 and methane amide is 2.5:1.
6. the preparation method of 4-methylthiazol according to claim 1, the mass ratio that it is characterized in that the thiophosphoric anhydride described in the step 1 and methane amide is 1.05:1.
7. the preparation method of 4-methylthiazol according to claim 1, it is characterized in that described in the step 2 under temperature is 7～8 ℃ condition, the mixed solution and dripping monochloroacetone that contains thioformamide that step 1 obtains.
8. the preparation method of 4-methylthiazol according to claim 1 is characterized in that the mol ratio 1:1.2 of thioformamide and monochloroacetone in the mixing solutions that contains thioformamide described in the step 2.
9. the preparation method of 4-methylthiazol according to claim 1 is characterized in that being warming up to 55 ℃ of reaction 6h then described in the step 2.
10. the preparation method of 4-methylthiazol according to claim 1 is characterized in that the pH described in the step 2 is 6.5.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105130924A (en) * | 2015-07-22 | 2015-12-09 | 蚌埠中实化学技术有限公司 | Preparation method of 4-methylthiazole-5-ethyl formate |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4111948A (en) * | 1975-06-27 | 1978-09-05 | Merck & Co., Inc. | Process for the preparation of 4-methylthiazole |
| JPH01305072A (en) * | 1988-06-01 | 1989-12-08 | Nippon Kayaku Co Ltd | Production of thiazoles |
| CN101870682A (en) * | 2009-04-24 | 2010-10-27 | 成都市考恩斯科技有限责任公司 | Preparation method of 4-methylthiazolaldehyde-5 |
| CN102363616A (en) * | 2011-10-18 | 2012-02-29 | 山东美罗福农化有限公司 | Probenazole low-toxicity bactericide and preparation method thereof |
-
2013
- 2013-04-27 CN CN2013101527883A patent/CN103232404A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4111948A (en) * | 1975-06-27 | 1978-09-05 | Merck & Co., Inc. | Process for the preparation of 4-methylthiazole |
| JPH01305072A (en) * | 1988-06-01 | 1989-12-08 | Nippon Kayaku Co Ltd | Production of thiazoles |
| CN101870682A (en) * | 2009-04-24 | 2010-10-27 | 成都市考恩斯科技有限责任公司 | Preparation method of 4-methylthiazolaldehyde-5 |
| CN102363616A (en) * | 2011-10-18 | 2012-02-29 | 山东美罗福农化有限公司 | Probenazole low-toxicity bactericide and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| RAYMONPD. K URKJY 等: "The Preparation of Methylthiazoles", 《J. AM. CHEM. SOC.》 * |
| 张荣华 等: "噻唑环衍生物的合成", 《化学研究与应用》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105130924A (en) * | 2015-07-22 | 2015-12-09 | 蚌埠中实化学技术有限公司 | Preparation method of 4-methylthiazole-5-ethyl formate |
| CN105130924B (en) * | 2015-07-22 | 2017-03-15 | 蚌埠中实化学技术有限公司 | A kind of method for preparing 4 methylthiazol, 5 Ethyl formate |
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Application publication date: 20130807 |