MXPA99005360A - Method for producing 2-chloro-5-aminomethylthiazole from 2-chloro-5-methylthiazole via 2-chloro-5-chloromethylthiazole - Google Patents
Method for producing 2-chloro-5-aminomethylthiazole from 2-chloro-5-methylthiazole via 2-chloro-5-chloromethylthiazoleInfo
- Publication number
- MXPA99005360A MXPA99005360A MXPA/A/1999/005360A MX9905360A MXPA99005360A MX PA99005360 A MXPA99005360 A MX PA99005360A MX 9905360 A MX9905360 A MX 9905360A MX PA99005360 A MXPA99005360 A MX PA99005360A
- Authority
- MX
- Mexico
- Prior art keywords
- chloro
- aminomethylthiazole
- radical
- methylthiazole
- ammonia
- Prior art date
Links
- KCDQBIMJBRASQE-UHFFFAOYSA-N (2-chloro-1,3-thiazol-5-yl)methanamine Chemical compound NCC1=CN=C(Cl)S1 KCDQBIMJBRASQE-UHFFFAOYSA-N 0.000 title claims abstract description 11
- RTEUDRWHKUPKJB-UHFFFAOYSA-N 2-chloro-5-methyl-1,3-thiazole Chemical compound CC1=CN=C(Cl)S1 RTEUDRWHKUPKJB-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- VRMUIVKEHJSADG-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=CN=C(Cl)S1 VRMUIVKEHJSADG-UHFFFAOYSA-N 0.000 title description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 10
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 7
- 239000003085 diluting agent Substances 0.000 claims abstract description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011541 reaction mixture Substances 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 3
- 230000002140 halogenating effect Effects 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 6
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 abstract description 5
- 230000002225 anti-radical effect Effects 0.000 abstract 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical class ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000005658 halogenation reaction Methods 0.000 description 6
- 230000026030 halogenation Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 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
- 238000004821 distillation Methods 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- -1 for example Chemical class 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 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
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical class ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- RKVAJLMJTGTGRC-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4,4-decachlorobutane Chemical class ClC(Cl)(Cl)C(Cl)(Cl)C(Cl)(Cl)C(Cl)(Cl)Cl RKVAJLMJTGTGRC-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AQBBZYVPKBIILN-UHFFFAOYSA-N 4-(chloromethyl)-2-methyl-1,3-thiazole Chemical compound CC1=NC(CCl)=CS1 AQBBZYVPKBIILN-UHFFFAOYSA-N 0.000 description 1
- UZAOOCPKYMGRHG-UHFFFAOYSA-N 5-(chloromethyl)-1,3-thiazole Chemical class ClCC1=CN=CS1 UZAOOCPKYMGRHG-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
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000002344 gold compounds Chemical class 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 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
- 230000009466 transformation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
PROCEDURE FOR THE OBTAINING OF 2-CHLORO-5-AMINOMETHYLSTAZOL FROM 2-CHLORO-5-METHYL-TEAZOL THROUGH 2-CHLORO-5-CHLOROMETHYLTYAZOLE.
FIELD OF THE INVENTION.
The present invention relates to a process for the preparation of 2-chloro-5-aminomethylthiazole.
DESCRIPTION OF THE PREVIOUS TECHNIQUE.
The preparation of 2-chloro-5-aminomethylthiazole by reaction of 2-chloro-5-chloromethylthiazole with hexamethylenetetraamine is known from JP-A 4 021 674. In this reaction, however, dissociation of the hexamethylenetetraamine adduct formed is required. in an intermediate manner and remove and eliminate the secondary products that are formed during the dissociation.
The reaction of 2-chloro-5-chloromethylthiazole with aqueous ammonia solution (EP-A 446) was also known.
913). Of course the yields obtained in this case Ref .: 30417 are unsatisfactory.
DETAILED DESCRIPTION OF THE INVENTION.
A process for obtaining 2-chloro-5-aminomethylthiazole has been found, characterized in that in a first step, 2-chloro-5-methyl-thiazole is halogen with a radical chlorinating agent in the presence of a radical former and in the presence of a stable diluent against the radical halogenating agents, up to a conversion of 40 to 70% by weight and then, in a second step, the reaction mixture formed is combined with ammonia or with aqueous ammonia solution and isolates 2-chloro-5-aminomethylthiazole in the usual way.
The reaction can be represented by means of the formula scheme:
As the radical chlorinating agents, preference may be given to N-chlorosuccinimide, 1,3-dichloro-5,5-dimethylhydantoin and trichloroisocyanuric acid.
The chlorinating agents are used in an amount of 0.5 to 1.3 equivalents of chlorine in relation to the thiazole. The approximately equivalent amount of chlorinating agent is preferred.
Diazylperoxides and azobisalkylnitriles, preferably azobisisobutyronitrile (= ®Profor N), azobiscyclohexylcarbonitrile, peroxides, such as, for example, lauroyl peroxide and dibenzoyl peroxide, may be mentioned as radical formers. The radical former is used in an amount of 0.01 to 1 equivalent, based on the chlorinating agent. An amount of 0.001 to 0.1 equivalents is preferred.
Suitable diluents which are stable to radical halogenation are: halogenated aromatic or aliphatic hydrocarbons, such as, for example, chlorobenzene, carbon tetrachloride, 1,2-di-chloroethane, decachlorobutane and also nitrobenzene or acetonitrile.
The reaction is carried out at an elevated temperature, preferably from room temperature to 150 ° C, particularly preferably at the boiling point of the diluent.
The reaction was carried out at normal pressure. However, it is also possible to work at elevated pressure of 1 to 10 bar.
The halogenation reaction is carried out until a yield in 2-chloro-5-chloromethylthiazole of 40 to 70% by weight, preferably 50 to 60% by weight, is reached. The reaction is then interrupted and the second stage of the reaction is started
It was surprising that the halogenation of 2-chloro-5-methylthiazole occurred in the side chain without problems. In this way, a specific halogenation of the side chains could not be achieved with elemental chlorine or sulfuryl chloride. It was also surprising that the desired product could then be reacted without further purification. Thus it was known from the publication J. Am. Chem. Soc. 67, page 400 (1945) that, for example, 4-chloromethyl-2-methylthiazole is rapidly transformed into a resin. Similar reactions of transformation to resin and therefore coalescence and yield reductions of the desired 5-chloromethylthiazole derivative were also expected.
The development of the halogenation is controlled by means of assay by continuous gas chromatography of the reaction mixture. Once the desired yield has been reached in 2-chloro-5-chloromethylthiazole, the reaction mixture is freed from the solvent by distillation. The raw product obtained in this way is combined, without further purification, with ammonia, if appropriate in the presence of an inert solvent such as, for example, ether. Particularly preferred is the reaction with 65% NH3 (residue H20) at temperatures of 20 to 150 ° C and at high pressure of 2 to 100 bar. The molar ratio 2-chloro-5-chloromethylthiazole: NÍÍ5 amounts to 1: 10-60. The reaction time is between 0.5 and 6 hours.
The crude product can also be combined with concentrated aqueous ammonia solution. It is also possible to combine the reaction mixture from the halogenation, without prior elimination of the solvent, with ammonia or with ammonia solution.
The reaction with ammonia is carried out at temperatures of -40 ° C to 150 ° C. It can be operated at normal pressure as well as at high pressure. If working with liquid ammonia, the reaction will preferably be carried out in the autoclave at the vapor pressure of the ammonia.
After completion of the reaction, excess ammonia is removed, for example by distillation or by neutralization with an aqueous acid, for example hydrochloric acid.
The excess solvent is removed by distillation and the mixture formed, consisting of 2-chloro-5-amino-methylthiazole, is removed in the usual manner, for example by chromatography, distillation or removal of the amine by salt formation.
Example 1
Combine 2 g (0.015 mol) of 2-chloro-5-methylthiazole in 15 ml of carbon tetrachloride, with 2.4 g
(0.019 moles) of N-chlorosuccinimide and 200 mg of azobisisobutyronitrile (AiBN) and heated for 6 hours under reflux. After cooling, it is combined with 50 ml of CH2C12, filtered, washed twice with water. After drying and removal of the solvent in vacuo, a yellow colored liquid is obtained, which is mixed with solid product. The conversion is, according to gaseous chromatography, of 50.0%, the gold compounds in the nucleus and polychlorinated compounds are present in a concentration of < 2 %.
Example 2
At room temperature for 1.5 hours, 1.5 g (0.011 mol) of 2-chloro-5-methylthiazole and 10 ml of carbon tetrachloride are heated with 1.7 g of 1,3-dichloro-5,5-dimethylhydantoin and 150 mg of carbon tetrachloride. AiBN. After analogous processing a crude product is obtained, which is constituted, in 48.5%, by 2-chloro-5-chloromethylthiazl.
Example 3
The crude mixture obtained in example 1 is reacted in an autoclave with 10 ml of liquid NH3 and 50 ml of tere. -amil-ethyl ether. It is allowed to reach room temperature and is stirred for a further 16 hours at room temperature additionally. After evaporation of the solvent and excess ammonia, 50 ml of 5% HCl are added, the mixture is extracted three times with CH 2 Cl 2, the aqueous phase is adjusted to pH 7 with concentrated NaOH and then extracted again. The extraction is adjusted to pH 11-12 with concentrated NaOH and the product is obtained by re-extraction. 1.18 g of 5-aminomethyl-2-chlorothiazole are isolated with a content of 95.3% according to gas chromatography.
Example 4
The crude mixture, obtained in example 2, is reacted in an autoclave with 30 ml of 65% NH3 at 70 ° C and at a pressure of 30 bar for 1.5 hours. The mixture was refrigerated and decompressed. After degassing in a vacuum, the pH is adjusted to 7 with aqueous HCl (5%) and with 10 ml of H20. After working-up, as described in example 3, 0.74 g of the desired product are isolated.
It is noted that in relation to this date, the best method known to the applicant, to carry out the aforementioned invention, is that which is clear from the present description of the invention.
Having described the invention as above, property is claimed as contained in the following:
Claims (1)
1. Process for obtaining 2-chloro-5-aminomethylthiazole, characterized in that, in a first step, 2-chloro-5-methylthiazole is halogen with a radical chlorinating agent in the presence of a radical former and in the presence of a stable diluent against the radical halogenating agents up to a conversion of 40 to 70% by weight and then, in a second step, the reaction mixture obtained, if necessary after prior elimination of the diluent, is combined with ammonia or aqueous solution of ammonia, if appropriate in a diluent and 2-chloro-5-aminomethylthiazole is isolated in the usual manner.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19653586.7 | 1996-12-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99005360A true MXPA99005360A (en) | 2000-02-02 |
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