CN1240436A - Method for producing 2-chloro-5-aminomethylthiazole - Google Patents
Method for producing 2-chloro-5-aminomethylthiazole Download PDFInfo
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- CN1240436A CN1240436A CN 97180716 CN97180716A CN1240436A CN 1240436 A CN1240436 A CN 1240436A CN 97180716 CN97180716 CN 97180716 CN 97180716 A CN97180716 A CN 97180716A CN 1240436 A CN1240436 A CN 1240436A
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- CN
- China
- Prior art keywords
- chloro
- aminomethylthiazole
- reaction
- ammonia
- radical
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- KCDQBIMJBRASQE-UHFFFAOYSA-N (2-chloro-1,3-thiazol-5-yl)methanamine Chemical compound NCC1=CN=C(Cl)S1 KCDQBIMJBRASQE-UHFFFAOYSA-N 0.000 title abstract description 4
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 13
- RTEUDRWHKUPKJB-UHFFFAOYSA-N 2-chloro-5-methyl-1,3-thiazole Chemical compound CC1=CN=C(Cl)S1 RTEUDRWHKUPKJB-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000002140 halogenating effect Effects 0.000 claims abstract description 6
- 239000011541 reaction mixture Substances 0.000 claims abstract description 6
- 150000003254 radicals Chemical group 0.000 claims description 10
- 230000026030 halogenation Effects 0.000 claims description 5
- 238000005658 halogenation reaction Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 abstract description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 abstract description 3
- 230000002225 anti-radical effect Effects 0.000 abstract 1
- 239000012320 chlorinating reagent Substances 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229950005499 carbon tetrachloride Drugs 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 2
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VZWOXDYRBDIHMA-UHFFFAOYSA-N 2-methyl-1,3-thiazole Chemical compound CC1=NC=CS1 VZWOXDYRBDIHMA-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- FSNCEEGOMTYXKY-JTQLQIEISA-N Lycoperodine 1 Natural products N1C2=CC=CC=C2C2=C1CN[C@H](C(=O)O)C2 FSNCEEGOMTYXKY-JTQLQIEISA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 229940074654 diuril Drugs 0.000 description 1
- -1 dodecyl superoxide Chemical compound 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010129 solution processing Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 229950009390 symclosene Drugs 0.000 description 1
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The present invention relates to a method for producing 2-chloro-5-aminomethylthiazole characterized in that 2-chloro-5-methylthiazole is made to react in a first stage with a radical chlorinating agent in the presence of a radical former and halogenated in the presence of a diluent that is stable in respect to anti-radical halogenating agents so as to yield 40 to 70 wt. %. Ammonia or an aqueous ammonia solution is added to the reaction mixture arising therefrom in a second stage and the 2-chloro-5-aminomethylthiazole is isolated in the usual manner.
Description
The present invention relates to the preparation method of 2-chloro-5-5-aminomethylthiazole.
By 2-chloro-5-5-chloromethyl thiazole and vulkacit H are reacted the method for preparing 2-chloro-5-5-aminomethylthiazole is that JP-A4021674 is known.But, reaction at this point, the vulkacit H adducts intermediate that necessary cracking forms, and must remove and remove the by product that in cracking process, produces.
Same known can passing through with 2-chloro-5-5-chloromethyl thiazole and ammonia soln reaction (EP-A446913).But the productive rate that this reaction obtains is unsatisfactory.
Found a kind of preparation method of 2-chloro-5-5-aminomethylthiazole, it is characterized in that, in the fs, radical form agent in the presence of and the thinner of stable free radical halogenating agent in the presence of, free radical chlorizating agent halogenation 2-chloro-5-methylthiazol, transformation efficiency is 40-70% (weight), then, in subordinate phase, ammonia or ammonia soln are added in the reaction mixture that obtains, and separate 2-chloro-5-5-aminomethylthiazole with customary way.
This reaction can following reaction formula representative.
Preferred free radical chlorination agent can be N-chloro-succinimide, 1,3 dichloro 5,5 dimethyl hydantoin and TCCA (Trichloroisocyanuric acid).
The consumption of chlorizating agent is the normal chlorine of 0.5-1.3 with respect to the thiazole amount, is preferably about equivalent.
It can be diamino superoxide and azo dialkyl group nitrile that radical forms agent, preferred Diisopropyl azodicarboxylate (=
Profor N), azo dicyclohexyl carbonization dintrile, superoxide is dodecyl superoxide and dibenzoyl peroxide for example.Radical formation agent is the 0.01-1 equivalent with respect to the consumption of chlorizating agent.Preferable amount is the 0.001-0.1 equivalent.
The thinner that is used for the stable free radical halogenating agent can comprise: halogenated aromatic hydrocarbon or aliphatic hydrocrbon, for example chlorobenzene, tetrachloromethane, 1,2-ethylene dichloride, ten chlorobutanes and oil of mirbane or acetonitrile.
This is reflected at heating and carries out down, and preferred room temperature to 150 ℃ is preferable over the boiling temperature of thinner especially.
This is reflected under the normal pressure and carries out, and still, also can depress (1-10 crust) and carry out adding.
The productive rate that halogenating reaction proceeds to 2-chloro-5-5-chloromethyl thiazole is 40-70% (weight), preferably obtains 50-60% (weight) productive rate.Termination reaction and the reaction of beginning subordinate phase then.
Be that it is no problem that the halogenation of 2-chloro-5-5-chloromethyl thiazole occurs in side chain astoundingly.For example, with chlorine element or SULPHURYL CHLORIDE, can not obtain required side chain halogenation.Be that required product can continue reaction without being further purified equally astoundingly.For example, known from J.Am.Chem.Soc.67p.400 (1945), for example 4-chloromethyl-rapid resinifying of 2-methylthiazol.As was expected equally, makes required 5-5-chloromethyl thiazole derivative carry out similar resinifying reaction, obtains impurity and reduced productive rate.
Check that by continuous gas-chromatography this reaction mixture monitors the halogenating reaction process.Behind the required productive rate that obtains 2-chloro-5-5-chloromethyl thiazole, from solvent, steam reaction mixture by distillation.Optional inert solvent for example ether in the presence of, with the crude product that obtains directly and ammonia react without being further purified.Preferred especially and 65% NH
3(residue for water) is under 20-150 ℃ of temperature and the adding to depress and carry out of 2-100 crust.2-chloro-5-5-chloromethyl thiazole: NH
3Mol ratio be 1: 10-60.Reaction times is 0.5-6 hour.
Also can handle this crude product with concentrated ammonia solution.Also can not remove in advance under the situation of desolvating with the reaction mixture after ammonia or the ammonia solution processing halogenation.
Under-40-150 ℃ temperature, react with ammonia.This step reaction can be carried out at normal pressure or adding to depress.If carry out this step reaction, carry out in the preferred autoclave under the ammonia vapour pressure of reaction with liquefied ammonia.
After reaction is finished, remove excess of ammonia, for example by distillation or with aqueous acid hydrochloric acid neutral method for example.
Distillation remove excessive solvent and the 2-chloro-5-amino methyl thiazole that will obtain and 2-chloro-5-methylthiazol mixture with method commonly used for example chromatography separates, distill or remove amine by salifiable method.
Embodiment 1
To reflux 6 hours at the 2-chloro-5-methylthiazol of the 2g in the 15ml tetrachloromethane (0.015mol) and N-chlorosuccinimide and the 200mg Diisopropyl azodicarboxylate (AiBN) of 2.4g (0.019mol).After this mixture cooling, add the 50ml methylene dichloride and filter this mixture, and wash filtrate with water twice.Dry and under reduced pressure stripping remove and desolvate, obtain being dispersed with the solid yellow liquid.Check that by GC transformation efficiency is 50.5%, the muriate of ring and the concentration of polychloride＜2%.
Embodiment 2
To at room temperature heat 6 hours at the 2-chloro-5-methylthiazol of the 1.5g in the 10ml tetrachloromethane (0.011mol) and 1,3 dichloro 5,5 dimethyl hydantoin and the 150mg AiBN of 1.7g.Obtain crude product through similar last handling process, contain 48.5% 2-chloro-5-5-chloromethyl thiazole.
Embodiment 3
In autoclave, crude mixture and 10mL liquid NH that embodiment 1 is obtained
3With 50ml tert-pentyl-methyl ether reaction.This mixture is placed to room temperature, then room temperature restir 16 hours.After boiling off solvent and excess of ammonia, add 50ml 5%HCl, with this mixture of dichloromethane extraction three times, and with dense NaOH adjusting water to pH7 with extract again.After the extraction, regulate pH to 11-12, and obtain product by reextraction with dense NaOH.Obtain 1.18g 5-amino methyl-2-diuril azoles, contain 95.3% by GC mensuration.
Embodiment 4
In 70 ℃ autoclave and under the pressure of 30 crust, the crude mixture that embodiment 2 is obtained and the NH of 30mL65% concentration
3Reacted 1.5 hours.With this mixture cooling and step-down.After this mixture pressurization degassing, regulate pH to 7 with the HCl aqueous solution (5%) and 10ml water.Obtain the required product of 0.74g through embodiment 3 described aftertreatments separation.
Claims (1)
1.2-the preparation method of chloro-5-5-aminomethylthiazole, it is characterized in that, in the fs, radical form agent in the presence of and thinner that can the stable free radical halogenating agent in the presence of, free radical chlorizating agent halogenation 2-chloro-5-methylthiazol, transformation efficiency is 40-70% (weight), then, in subordinate phase, with ammonia or ammonia soln, at random in thinner, be added in the reaction mixture that obtains, at random after removing thinner in advance, separate 2-chloro-5-5-aminomethylthiazole with customary way.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 97180716 CN1240436A (en) | 1996-12-20 | 1997-12-08 | Method for producing 2-chloro-5-aminomethylthiazole |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19653586.7 | 1996-12-20 | ||
| CN 97180716 CN1240436A (en) | 1996-12-20 | 1997-12-08 | Method for producing 2-chloro-5-aminomethylthiazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1240436A true CN1240436A (en) | 2000-01-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 97180716 Pending CN1240436A (en) | 1996-12-20 | 1997-12-08 | Method for producing 2-chloro-5-aminomethylthiazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1240436A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111036158A (en) * | 2019-12-28 | 2020-04-21 | 邯郸市瑞田农药有限公司 | 2 chlorine-5 chloromethyl thiazole synthesis reaction system |
| CN114555568A (en) * | 2019-10-04 | 2022-05-27 | 巴斯夫欧洲公司 | Preparation of 2-chloro-1- (2-chlorothiazol-5-yl) ethanone |
-
1997
- 1997-12-08 CN CN 97180716 patent/CN1240436A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114555568A (en) * | 2019-10-04 | 2022-05-27 | 巴斯夫欧洲公司 | Preparation of 2-chloro-1- (2-chlorothiazol-5-yl) ethanone |
| CN111036158A (en) * | 2019-12-28 | 2020-04-21 | 邯郸市瑞田农药有限公司 | 2 chlorine-5 chloromethyl thiazole synthesis reaction system |
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| PB01 | Publication | ||
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
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