CN104672174A - Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole - Google Patents
Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole Download PDFInfo
- Publication number
- CN104672174A CN104672174A CN201510068556.9A CN201510068556A CN104672174A CN 104672174 A CN104672174 A CN 104672174A CN 201510068556 A CN201510068556 A CN 201510068556A CN 104672174 A CN104672174 A CN 104672174A
- Authority
- CN
- China
- Prior art keywords
- trichloromethyl
- chloro
- preparation
- thiadiazoles
- reaction
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
The invention discloses a preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole. The preparation method comprises the following steps: by taking trichloroacetonitrile as a raw material, firstly synthesizing trichloro-acetamidine, and then preparing thiadiazole to achieve continuous reaction. By adopting the preparation method disclosed by the invention, separation processes of an intermediate trichloro-acetamidine can be reduced; a single solvent is used in the whole reaction so as to ensure that continuous production of two-step reaction can be achieved; a liquid ammonia mode is changed into a production mode of introducing ammonia gas into the solvent, and the reaction temperature is improved to adapt to the industrial production; the trichloro-acetamidine intermediate does not need to be treated additionally, and can be directly applied to the next reaction to ensure that purification and refining processes can be reduced; the quality and yield of products can be significantly improved, and the production cost can be reduced; and greater industrial production values can be achieved.
Description
Technical field
The invention belongs to the field of chemical synthesis, particularly the preparation method of a kind of 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles.
Background technology
5-chloro-3-trichloromethyl-1,2,4-thiadiazoles (being called for short " thiadiazoles ") is a very important intermediate in medicine with Pesticidal products.
According to patent DE671785 and document Journal of Medicinal Chemistry, 1978, Vol. 21, No. 12, Trichloroacetonitrile is added dropwise in the liquefied ammonia of low temperature-40 DEG C by the synthesis of P1285 report trichlorine ethanamidine to react 7 hours, and remaining ammonia of rushing adds benzene filtering and concentrating hexane recrystallization yield again and only has 52%.The hydrogen chloride solution dripping ethanol again in ethyl acetate solution obtains trichlorine B amidine hydrochloric acid salt, and reaction needed is carried out under cold temperature source dry ice or liquid nitrogen cooling condition, and uses hypertoxic solvent benzol very unfavorable to production.
The synthesis of second step 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles uses trichlorine B amidine hydrochloric acid salt to react finally obtain product yield 56% for raw material adds liquid caustic soda and trichloromethyl sulfuryl chloride in methylene dichloride according to the method choice of patent US3260588.Two step total recoverys only have 29% and employ multiple different solvents, bring trouble in production operation.
Therefore, the preparation method being badly in need of a kind of 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles overcomes above-mentioned defect.
Summary of the invention
The object of this invention is to provide the preparation method of a kind of 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles, low to solve yield in prior art, and employ multiple different solvents, the problem of production process complexity.
For achieving the above object, the present invention is by the following technical solutions:
The preparation method of a kind of 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles, comprises the following steps:
Step one, in synthesis trichlorine ethanamidine process under the existence of solvent and catalyzer, ammonia is passed into state of saturation in-15 DEG C of cryosel water-baths, start to drip raw material Trichloroacetonitrile, control temperature of reaction at-10 DEG C, continue to pass into excess of ammonia gas until drip end, insulation reaction, until raw material Trichloroacetonitrile transformation efficiency is to more than 98%, is naturally warmed up to room temperature and leads to nitrogen bubble and drive excess of ammonia away;
Step 2, reaction solution is cooled to-5 DEG C, drip liquid caustic soda and adjust pH value to 9, then drip trichloromethyl sulfuryl chloride, keep pH value at 8-9, trichlorine ethanamidine is reacted completely, adds and be washed to layering, then deviate from solvent and obtain 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles.
Further, the solvent in described step one is halohydrocarbon.
Preferably, the solvent in described step one is 1,2-ethylene dichloride or methylene dichloride.
Further, the catalyzer in described step one is quaternary ammonium salt phase transfer catalyst.
Preferably, the catalyzer in described step one is Tetrabutyl amonium bromide or triethyl benzyl ammonia chloride.
Further, the liquid caustic soda in described step 2 is the NaOH solution of 30%.
The present invention take Trichloroacetonitrile as raw material, first synthesizes trichlorine ethanamidine, then prepares thiadiazoles and realize successive reaction.
The invention has the beneficial effects as follows: the present invention is that raw material first synthesizes trichlorine ethanamidine with Trichloroacetonitrile, then prepares thiadiazoles, realizes successive reaction, decrease the process that intermediate trichlorine ethanamidine is separated; Whole reaction uses single solvent, makes two step reactions be able to continuous prodution; Changing liquefied ammonia is the mode of production passing into ammonia in solvent, and makes temperature of reaction obtain improvement to adapt to suitability for industrialized production; Trichlorine ethanamidine intermediate does not need other process, can be directly used in next step reaction, reduce purification refine process; Quality product yield is improved significantly, and reduces production cost; Have more industrial production value; It is 96%, two step total recoverys 68% that GC analyzes content.
Embodiment
The technique means realized for making the present invention, creation characteristic, reaching object and effect is easy to understand, below in conjunction with embodiment, setting forth the present invention further.
Terminological interpretation:
The chemical name of trichlorine ethanamidine: 2,2,2-trichlorine ethanamidine,
Structural formula:
No. CAS: 2533-68-8,
Molecular formula: C2H3CL3N2,
Molecular weight: 161.418,
Fusing point: 41 DEG C-43 DEG C,
Trichlorine ethanamidine is that white crystalline solid has ammonia taste, is soluble in organic solvent.
The preparation method of a kind of 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles, comprises the following steps:
Step one, in synthesis trichlorine ethanamidine process under the existence of solvent and catalyzer, ammonia is passed into state of saturation in-15 DEG C of cryosel water-baths, start to drip raw material Trichloroacetonitrile, control temperature of reaction at-10 DEG C, continue to pass into excess of ammonia gas until drip end, insulation reaction is until raw material Trichloroacetonitrile transformation efficiency is to more than 98%, i.e. raw material Trichloroacetonitrile residue less than 2%, is warmed up to room temperature naturally and logical nitrogen bubble drives excess of ammonia away;
Step 2, reaction solution is cooled to-5 DEG C, drip liquid caustic soda and adjust pH value to 9, then drip trichloromethyl sulfuryl chloride, keep pH value at 8-9, trichlorine ethanamidine is reacted completely, adds and be washed to layering, then deviate from solvent and obtain 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles.
Further, the solvent in described step one is halohydrocarbon.
Preferably, the solvent in described step one is 1,2-ethylene dichloride or methylene dichloride.
Further, the catalyzer in described step one is quaternary ammonium salt phase transfer catalyst.
Preferably, the catalyzer in described step one is Tetrabutyl amonium bromide or triethyl benzyl ammonia chloride.
Further, in described step 2, keep pH value at 8-9, use the NaOH solution of 30%.
Embodiment 1
In 500L still, add the ethylene dichloride of 350Kg and the Tetrabutyl amonium bromide of 1Kg, open and freezingly cool to-10 DEG C with stirring.Pass into ammonia and keep 4-5Kg per hour, temperature drops to-10 DEG C after rising to a certain degree again, starts to drip 100Kg Trichloroacetonitrile, drips Trichloroacetonitrile temperature and controls at-10 DEG C, dripped in 5 hours.Continue logical ammonia after dripping to sample, control starting material left less than 2%, after reaction terminates, stop logical ammonia and close coolant valve unlatching nitrogen valve making nature be warmed up to 20 DEG C
Material is forwarded in the cyclization still of 1000L.
Material in cyclization still is cooled to the alkali lye of-5 DEG C of droppings 30%, makes reacting system PH value arrive 9, then start the trichloromethyl sulfuryl chloride dripping 135.5Kg simultaneously, then drip trichloromethyl sulfuryl chloride, regulate pH value, and keep pH value 8.Drip and terminate insulation 1h sampling, raw material is all transformed, reaction end adds 500L and washes static layering again, organic layer concentrating under reduced pressure recycling design, obtains 116.8Kg brown liquid GC content 95.5%.
Embodiment 2
In 500L still, add the methylene dichloride of 350Kg and the triethyl benzyl ammonia chloride of 1Kg, open and freezingly cool to-10 DEG C with stirring.Pass into ammonia and keep 4-5Kg per hour, temperature drops to-10 DEG C after rising to a certain degree again, starts to drip 100Kg Trichloroacetonitrile, drips Trichloroacetonitrile temperature and controls at-10 DEG C, dripped in 5 hours.Continue logical ammonia after dripping to sample, control starting material left less than 2%, after reaction terminates, stop logical ammonia and close coolant valve unlatching nitrogen valve making nature be warmed up to 20 DEG C
Material is forwarded in the cyclization still of 1000L.
Material in cyclization still is cooled to the alkali lye of-5 DEG C of droppings 30%, makes reacting system PH value arrival 9 start to drip the trichloromethyl sulfuryl chloride of 135.5Kg more simultaneously, then drip trichloromethyl sulfuryl chloride, regulate pH value, and keep pH value 9.Drip and terminate insulation 1h sampling, raw material is all transformed, reaction end adds 500L and washes static layering again, organic layer concentration and recovery solvent, obtains 118.2Kg tawny liquid, GC content 96.3%.
Embodiment 3
In 500L still, add the methylene dichloride of 350Kg and the Tetrabutyl amonium bromide of 1Kg, open and freezingly cool to-10 DEG C with stirring.Pass into ammonia and keep 4-5Kg per hour, temperature drops to-10 DEG C after rising to a certain degree again, starts to drip 100Kg Trichloroacetonitrile, drips Trichloroacetonitrile temperature and controls at-10 DEG C, dripped in 5 hours.Continue logical ammonia after dripping to sample, control starting material left below 2%, after reaction terminates, stop logical ammonia and close coolant valve unlatching nitrogen valve making nature be warmed up to 20 DEG C
Material is forwarded in the cyclization still of 1000L.
Material in cyclization still is cooled to the alkali lye of-5 DEG C of droppings 30%, makes reacting system PH value arrive 9, then drip trichloromethyl sulfuryl chloride, regulate pH value, and keep pH value 8.5.Drip and terminate insulation 1h sampling, raw material is all transformed, reaction end adds 500L and washes static layering again, organic layer concentrating under reduced pressure recycling design, obtains 116.8Kg brown liquid GC content 96.1%.
Embodiment 4
In 500L still, add 1, the 2-ethylene dichloride of 350Kg and the triethyl benzyl ammonia chloride of 1Kg, open and freezingly cool to-10 DEG C with stirring.Pass into ammonia and keep 4-5Kg per hour, temperature drops to-10 DEG C after rising to a certain degree again, starts to drip 100Kg Trichloroacetonitrile, drips Trichloroacetonitrile temperature and controls at-10 DEG C, dripped in 5 hours.Continue logical ammonia after dripping to sample, control starting material left below 2%, after reaction terminates, stop logical ammonia and close coolant valve unlatching nitrogen valve making nature be warmed up to 20 DEG C
Material is forwarded in the cyclization still of 1000L.
Material in cyclization still is cooled to the alkali lye of-5 DEG C of droppings 30%, makes reacting system PH value arrive 9, then drip trichloromethyl sulfuryl chloride, regulate pH value, keep pH value 9.Drip and terminate insulation 1h sampling, raw material is all transformed, reaction end adds 500L and washes static layering again, and organic layer concentrating under reduced pressure recycling design, obtains 116.8Kg brown liquid, GC content 95.8%.
More than show and describe ultimate principle of the present invention and principal character and advantage of the present invention.The technician of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and specification sheets just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (6)
1. the preparation method of 5-chloro-3-trichloromethyl-1,2, a 4-thiadiazoles, is characterized in that, comprise the following steps:
Step one, in synthesis trichlorine ethanamidine process under the existence of solvent and catalyzer, ammonia is passed into state of saturation in-15 DEG C of cryosel water-baths, start to drip raw material Trichloroacetonitrile, control temperature of reaction at-10 DEG C, continue to pass into excess of ammonia gas until drip end, insulation reaction, until raw material Trichloroacetonitrile transformation efficiency is to more than 98%, is naturally warmed up to room temperature and leads to nitrogen bubble and drive excess of ammonia away;
Step 2, reaction solution is cooled to-5 DEG C, drip liquid caustic soda and adjust pH value to 9, then drip trichloromethyl sulfuryl chloride, keep pH value at 8-9, trichlorine ethanamidine is reacted completely, adds and be washed to layering, then deviate from solvent and obtain 5-chloro-3-trichloromethyl-1,2,4-thiadiazoles.
2. the preparation method of 5-according to claim 1 chloro-3-trichloromethyl-1,2,4-thiadiazoles, is characterized in that, the solvent in described step one is halohydrocarbon.
3. the preparation method of 5-according to claim 1 chloro-3-trichloromethyl-1,2,4-thiadiazoles, is characterized in that, the solvent in described step one is 1,2-ethylene dichloride or methylene dichloride.
4. the preparation method of 5-according to claim 1 chloro-3-trichloromethyl-1,2,4-thiadiazoles, is characterized in that, the catalyzer in described step one is quaternary ammonium salt phase transfer catalyst.
5. the preparation method of 5-according to claim 1 chloro-3-trichloromethyl-1,2,4-thiadiazoles, is characterized in that, the catalyzer in described step one is Tetrabutyl amonium bromide or triethyl benzyl ammonia chloride.
6. the preparation method of 5-according to claim 1 chloro-3-trichloromethyl-1,2,4-thiadiazoles, is characterized in that, keeps pH value at 8-9 in described step 2, uses the NaOH solution of 30%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510068556.9A CN104672174A (en) | 2015-02-10 | 2015-02-10 | Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510068556.9A CN104672174A (en) | 2015-02-10 | 2015-02-10 | Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104672174A true CN104672174A (en) | 2015-06-03 |
Family
ID=53307816
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510068556.9A Pending CN104672174A (en) | 2015-02-10 | 2015-02-10 | Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104672174A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105001097A (en) * | 2015-06-11 | 2015-10-28 | 安徽东至广信农化有限公司 | O-phenylenediamine mother solution deaminizing and ammonia gas removal method |
| CN106278906A (en) * | 2016-08-13 | 2017-01-04 | 安徽东至广信农化有限公司 | A kind of circulation ammonolysis process for o-phenylenediamine mother solution |
| CN112661667A (en) * | 2020-12-28 | 2021-04-16 | 浦拉司科技（上海）有限责任公司 | Preparation method of trifluoroacetamidine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE671785C (en) * | 1936-03-22 | 1939-02-14 | I G Farbenindustrie Akt Ges | Process for the preparation of trichloroacetamidine and its derivatives |
| US3260588A (en) * | 1961-03-15 | 1966-07-12 | Olin Mathieson | Method for controlling pests |
| US3979403A (en) * | 1974-05-01 | 1976-09-07 | Olin Corporation | Process for the preparation of 3-trichloromethyl-5-chloro-1,2,4-thiadiazole |
-
2015
- 2015-02-10 CN CN201510068556.9A patent/CN104672174A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE671785C (en) * | 1936-03-22 | 1939-02-14 | I G Farbenindustrie Akt Ges | Process for the preparation of trichloroacetamidine and its derivatives |
| US3260588A (en) * | 1961-03-15 | 1966-07-12 | Olin Mathieson | Method for controlling pests |
| US3979403A (en) * | 1974-05-01 | 1976-09-07 | Olin Corporation | Process for the preparation of 3-trichloromethyl-5-chloro-1,2,4-thiadiazole |
Non-Patent Citations (1)
| Title |
|---|
| ELSLAGER, EDWARD F.，等: "Synthesis of 5,5"-[[3-(dimethylamino)propyl]imino]bis[3-(trichloromethyl)-1,2,4-thiadiazole] and related thiadiazoles as antimalarial agent", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105001097A (en) * | 2015-06-11 | 2015-10-28 | 安徽东至广信农化有限公司 | O-phenylenediamine mother solution deaminizing and ammonia gas removal method |
| CN106278906A (en) * | 2016-08-13 | 2017-01-04 | 安徽东至广信农化有限公司 | A kind of circulation ammonolysis process for o-phenylenediamine mother solution |
| CN112661667A (en) * | 2020-12-28 | 2021-04-16 | 浦拉司科技（上海）有限责任公司 | Preparation method of trifluoroacetamidine |
| CN112661667B (en) * | 2020-12-28 | 2023-02-03 | 浦拉司科技（上海）有限责任公司 | Preparation method of trifluoroacetamidine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104672174A (en) | Preparation method of 5-chloro-3-trichloromethyl-1,2,4-thiadiazole | |
| CN102153494B (en) | Synthesis technology for N,N-diethylamino group ethanethiol | |
| CN107286086B (en) | Preparation method of N-cyanomethyl bis (trifluoromethyl) nicotinamide and application of N-cyanomethyl bis (trifluoromethyl) nicotinamide | |
| CN101607892B (en) | Method for producing sodium citrate | |
| CN102127068B (en) | Method for synthesizing aztreonam compound | |
| CN101723773B (en) | Method for preparing high purity N-acetyl-DL-amino acid | |
| CN103396292B (en) | Method for industrially producing A,A'-dihydroxy-1,3-diisobutylbenzene | |
| CN107935842A (en) | A kind of preparation method of 2 chlorine, 4 bromine, 6 methyl benzoic acid | |
| CN111777568A (en) | Clean and environment-friendly production process of 2-chloro-5-chloromethyl thiazole | |
| CN110483498A (en) | A kind of preparation method of Tazobactam Sodium intermediate | |
| CN103145645A (en) | Preparation technology of mercapto-5-methyl-1,3,4-thiadiazole | |
| EP1832593A1 (en) | Direct process for the production of sterile Cefepime dihydrochloride monohydrate | |
| CN103360337B (en) | A kind of 2-sulfydryl-5-methyl isophthalic acid, the preparation method of 3,4-thiadiazoles | |
| CN101580456B (en) | Kettle type crystallization process of paradichlorobenzene in solid waste benzene chloride tar | |
| CN112851543A (en) | Preparation method of methoxyamine hydrochloride and preparation method of N-methoxyacetamide | |
| CN110872242B (en) | Synthesis method of celecoxib intermediate p-hydrazino benzenesulfonamide hydrochloride | |
| CN105949051A (en) | Crystalizing process of chloroacetic acid | |
| CN110885284A (en) | Synthesis method of 2-bromomalondialdehyde | |
| CN115784978B (en) | Method for synthesizing 2-amino-6-bromopyridine | |
| CN109280011A (en) | The synthetic method of OLED intermediate 2- bromine pyrene | |
| CN112661727B (en) | Purification method of 7- (2, 2-trichloroethyl oxycarbonyl) taxol | |
| CN102532117B (en) | Method for preparing 1-(4,5-dihydrothiazol-2-yl)-3-hydroxyl-azetidine hydrochloride | |
| CN113698448B (en) | Preparation method of amcinonide | |
| CN112979570B (en) | Method for synthesizing hexazinone by continuous solvent-free reaction | |
| CN101565369B (en) | Method for preparing 3-bromine-5-trifluoromethylbenzoic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150603 |