CH207721A - Process for preparing 2-methyl-5-chloromethyl-6-aminopyrimidine hydrochloride. - Google Patents
Process for preparing 2-methyl-5-chloromethyl-6-aminopyrimidine hydrochloride.Info
- Publication number
- CH207721A CH207721A CH207721DA CH207721A CH 207721 A CH207721 A CH 207721A CH 207721D A CH207721D A CH 207721DA CH 207721 A CH207721 A CH 207721A
- Authority
- CH
- Switzerland
- Prior art keywords
- methyl
- aminopyrimidine
- chloromethyl
- hydrochloride
- hydrochloric acid
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- IUICOFBIOJSLTA-UHFFFAOYSA-N 5-(chloromethyl)-2-methylpyrimidin-4-amine;hydrochloride Chemical compound Cl.CC1=NC=C(CCl)C(N)=N1 IUICOFBIOJSLTA-UHFFFAOYSA-N 0.000 title description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- KEYFHYRXUHGMLW-UHFFFAOYSA-N 5-(ethoxymethyl)-2-methylpyrimidin-4-amine Chemical compound CCOCC1=CN=C(C)N=C1N KEYFHYRXUHGMLW-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- -1 2-methyl-6-chloromethyl-6-aminopyrimidine hydrochloride Chemical compound 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 1
- FAXPFVAQBCHONX-UHFFFAOYSA-N 5-ethoxy-2,6-dimethylpyrimidin-4-amine Chemical compound CC1=NC(=C(C(=N1)C)OCC)N FAXPFVAQBCHONX-UHFFFAOYSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Procédé de préparation<B>du</B> chlorhydrate de 2-méthyl-6-chlorométhyl-6-aminopyrimidine. La présente invention a pour objet la pré paration avec un bon rendement et sous une pression pratiquement non supérieure à la pression atmosphérique du chlorhydrate de 2-méthyl-5=chlorométhyl-6 - aminopyrimidine.
Il est connu qu'on ne peut préparer ce chlorhydrate par réaction entre une 2-méthyl- 5-alcoxyméthyl-6-aminopyrimidine et l'acide chlorhydrique en présence d'acide acétique glacial qu'à des pressions supérieures à la pression atmosphérique et à des températures au-dessus de 100 C.
On a trouvé qu'il est possible de préparer le chlorhydrate de 2-méthyl-5-chlorométhyl- 6-aminopyrimidine, ayant un point de fusion de<B>213</B> à 214 " C, en faisant réagir une 2- méthyl - 5 - alcoxyméthyl - 6 -aminopyrimidine avec l'acide chlorhydrique en présence d'un alcool aliphatique, de préférence d'un alcool n'ayant pas plus de 10 atomes de carbone. La réaction s'effectue à la pression atmosphé rique.
Cette réaction peut s'exprimer par la formule suivante:
EMI0001.0017
dans laquelle R représente un groupe alcoxy. Le produit obtenu par le procédé selon l'invention sert à différents usages, par exemple comme produit intermédiaire pour la fabrication de la vitamine Bi. Cette der- nière peut être obtenue en chauffant le chlorhydrate de 2-méthyl-5-chlorométhyl-6- aminopyrimidin e avec du 4 - méthyl - 5 - hydroxyéthylthiazol pendant environ 5 mi nutes .à 115 <RTI
ID="0001.0029"> C. Les exemples suivants. donnés à titre nul lement limitatifs, illustrent le procédé de fa brication selon l'invention.
<I>Exemple 1:</I> 7.0 gr de 2-méthyl-5-éthoxyniéthyl-6- aminopyrimidine sont dissous dans 100 cm' de butanol et la solution est chauffée au bain- marie pendant. environ 6 heures tout en fai sant passer au travers un courant d'acide chlorhydrique sec. Le chlorhydrate de ?- méthyl - 5 - chlorométhyl - 6 - aminopyrimidine cristallise peu à. peu. On refroidit. alors la, masse, on ajoute un à deux volumes d'éther et filtre.
On lave les cristaux à l'éther et les sèche à .10-50 C environ. Rendement brut: environ 10 -r, soit 86 % de la théorie.
Exemple <I>2:</I> On dissout 10 gr de 2-méthyl-5-éthoxy- méthyl-6-aminopyrimidine dans 50 cm'' de butanol et chauffe la solution au bain-marie pendant environ 6 heures en faisant passer dans la solution un courant d'acide chlorhy drique sec. On filtre la masse et sèche le chlorhydrate de 2-méthyl-5-chlorométhyl-6- aminopy rimidine à 40-50' C environ. Le rendement brut est de 11 gr, soit 95 % de la théorie.
<I>Exemple 3:</I> On procède comme pour l'exemple 1 en remplaçant le butanol par du méthanol. Le rendement est légèrement inférieur à celui de l'exemple 1.
La réaction peut être conduite à tempé rature ordinaire ou à température élevée. Une température élevée, mais inférieure à 100 " C, est préférable à cause du meilleur rendement en produit et de la moindre durée de la réaction.
Le groupe éthoxy de la matière première peut être remplacé par d'autres groupes alcoxy et on peut remplacer l'acide chlorhydrique gazeux par de l'acide chlorhydrique en solu tion concentrée. Lorsqu'on emploie de l'acide chlorhydrique concentré, il faut éviter que le groupe amino ne soit remplacé par un groupe hydroxy. On peut prévenir cette substitution de différentes façons, par exemple en limitant la durée du chauffage du mélange de réaction a Mie demi-heure.
A process for the preparation of <B> </B> 2-methyl-6-chloromethyl-6-aminopyrimidine hydrochloride. The object of the present invention is the preparation with a good yield and at a pressure substantially not higher than atmospheric pressure of 2-methyl-5 = chloromethyl-6-aminopyrimidine hydrochloride.
It is known that this hydrochloride can be prepared by reaction between a 2-methyl-5-alkoxymethyl-6-aminopyrimidine and hydrochloric acid in the presence of glacial acetic acid only at pressures above atmospheric pressure and at temperatures above 100 C.
It has been found that it is possible to prepare 2-methyl-5-chloromethyl-6-aminopyrimidine hydrochloride, having a melting point of <B> 213 </B> at 214 ° C, by reacting a 2- methyl - 5 - alkoxymethyl - 6 -aminopyrimidine with hydrochloric acid in the presence of an aliphatic alcohol, preferably an alcohol having not more than 10 carbon atoms The reaction is carried out at atmospheric pressure.
This reaction can be expressed by the following formula:
EMI0001.0017
in which R represents an alkoxy group. The product obtained by the process according to the invention is used for various uses, for example as an intermediate product for the manufacture of vitamin Bi. The latter can be obtained by heating 2-methyl-5-chloromethyl-6-aminopyrimidin hydrochloride with 4 - methyl - 5 - hydroxyethylthiazol for about 5 minutes to 115 <RTI.
ID = "0001.0029"> C. The following examples. given in no way limiting, illustrate the manufacturing process according to the invention.
<I> Example 1: </I> 7.0 g of 2-methyl-5-ethoxyniethyl-6-aminopyrimidine are dissolved in 100 cm 3 of butanol and the solution is heated in a water bath for. approximately 6 hours while passing through a stream of dry hydrochloric acid. The hydrochloride of? - methyl - 5 - chloromethyl - 6 - aminopyrimidine crystallizes little by little. little. We cool down. then the mass, one to two volumes of ether is added and filtered.
The crystals are washed with ether and dried at approximately 10-50 C. Gross yield: about 10 -r, or 86% of theory.
Example <I> 2: </I> 10 g of 2-methyl-5-ethoxy-methyl-6-aminopyrimidine are dissolved in 50 cm '' of butanol and the solution is heated in a water bath for about 6 hours while passing a stream of dry hydrochloric acid in the solution. The mass is filtered and 2-methyl-5-chloromethyl-6-aminopy rimidine hydrochloride is dried at about 40-50 ° C. The gross yield is 11 gr, or 95% of theory.
<I> Example 3: </I> The procedure is as for Example 1, replacing the butanol with methanol. The yield is slightly lower than that of Example 1.
The reaction can be carried out at room temperature or at elevated temperature. A high temperature, but less than 100 ° C, is preferable because of the better product yield and shorter reaction time.
The ethoxy group of the raw material can be replaced by other alkoxy groups, and the gaseous hydrochloric acid can be replaced by hydrochloric acid in concentrated solution. When using concentrated hydrochloric acid, care must be taken to prevent the amino group from being replaced by a hydroxy group. This substitution can be prevented in various ways, for example by limiting the heating time of the reaction mixture to half an hour.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US207721XA | 1937-12-14 | 1937-12-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH207721A true CH207721A (en) | 1939-11-30 |
Family
ID=21800483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH207721D CH207721A (en) | 1937-12-14 | 1938-12-13 | Process for preparing 2-methyl-5-chloromethyl-6-aminopyrimidine hydrochloride. |
Country Status (2)
| Country | Link |
|---|---|
| CH (1) | CH207721A (en) |
| FR (1) | FR868802A (en) |
-
1938
- 1938-12-12 FR FR868802D patent/FR868802A/en not_active Expired
- 1938-12-13 CH CH207721D patent/CH207721A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FR868802A (en) | 1942-01-17 |
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