CS267082B1 - Method of 5-bromo-6-amino-1-methyluracil preparation - Google Patents
Method of 5-bromo-6-amino-1-methyluracil preparation Download PDFInfo
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- CS267082B1 CS267082B1 CS872222A CS222287A CS267082B1 CS 267082 B1 CS267082 B1 CS 267082B1 CS 872222 A CS872222 A CS 872222A CS 222287 A CS222287 A CS 222287A CS 267082 B1 CS267082 B1 CS 267082B1
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Abstract
Riešenie sa týká spósobu pripravy 5- -bróm-6-amíno-l-metyluracilu z 6-amíno-l- -metyluracilu pósobením brómu vo vodnoalkalickom prostředí. Předmětná zlúčenina slúži ako medziprodukt na přípravu purínových báz. Reakcia sa uskutočňuje pri pH 9 až 13 a teplote 0 až 20 °C.The solution relates to the 5- -bromo-6-amino-1-methyluracil from 6-amino-l- - methyluracil by bromine action in aqueous alkali environment. The subject compound serves as an intermediate for the preparation of purine bases. The reaction is carried out at pH 9 to 13 and temperature 0 to 20 ° C.
Description
(57) Riešenie sa týká spósobu přípravy 5-bróm-6-amíno-l-metyluracilu z 6-amíno-l-metyluracilu pósobením brómu vo vodnoalkaliokom prostředí. Předmětná zlúčenina slúži ako medziprodukt na přípravu purínových báz. Reakcia sa uskutočňuje pri pH 9 až 13 a teplote 0 až 20 °C. CS 267082 Bl 2 CS 267 082 Bl
Predmetom vynálezu je spdsob přípravy 5-bróm-6-amíno-l-metyluracilu vzoroa I
(I) nh2 ch3
ktorý je medziproduktom pre pripravu purínovýoh báz. Doposial sa předmětná zlúčenina vzorca I připravovala reakciou brómu vo vodě (Barker, Luthy; J. Chem. Soc. 1956, 917-920) alebo v kyselině octovej (Wojoiechovski J.; Polský patent 42 976, Acta Polon. Pharm. 18, 409-13, 1961) z 6-amíno-l-metyluracilu vzorca II
O
(II)
Nevýhodou týchto postupov bolo pri použití vody vznik velkého množstva dibrómderivátu a jeho komplikované odstraňovanie, pri použití kyseliny octovej dlhá reakčná doba a používanie kyseliny octovej ako reakčného prostredia, v ktorom vznikali vedlajšie produkty v dósledku reakcie kyseliny a brómu. Spósobom podlá vynálezu sa předmětná zlúčenina připravuje pósobením brómu v alkalickom vodnom prostředí. Výhodou postupu je, že v alkalickom prostředí sa 6-amíno-l-metyluraoil rozpúšťa a bromácia prebieha velmi krátko v homogénnej fáze, alkalické prostredie znižuje obsah nežiadúceho dibrómderivátu. Reakčná teplota sa udržiava v rozmedzí 0 až 20 °C, s výhodou 5 až-15 °C, a alkalita roztoku sa udržuje v rozmedzí pH 9 až 13.
Molárny poměr brómu k uraoilu vzorca II je v rozmedzí 1:0,9 až 3:1. V dalšom je predmet vynálezu objasněný na příkladu bez toho že by sa na tento výlučné obmedzoval. Příklad 5-bróm-6-amíno-l-metyluracil 1 350 g (9,56 M) 6-amíno-l-metyluracilu sa suspenduje v 7 1 vody a k suspenzii sa za miešania pri teplote max. 20 °C přidá roztok 400 g (10 M) NaOH v 400 ml vody. K roztoku vzniklému rozpuštěním 6-amíno-l-metyluracilu sa z oddelovaoiého lievika za chladenia pri teplote 5 až 15 °C pod hladinu prikvapkáva za intenzívneho miešania 1,53 kg brómu (19,14 M) . Počas reakcie sa prídavkom roztoku NaOH udržuje pH roztoku v rozmedzí 9 až 13. Pridávanie brómu trvá v závislosti od chladenia 10 až 20 minút.
Po přidaní celého brómu sa reakčná zmes okyslí prídavkom 800 až 850 ml 36 %-nej HC1 tak, aby pH roztoku bolo 5 až 6. Vylúčený 5-bróm-6-amíno-l-metyluraoil sa odsaje na frite, premyje 2 až 3 1 vody a nakoniec 1 1 etanolu a vysuší. Získá sa 1 900 g surového (90,3 %) 5-bróm-6-amíno-l-metyluraoilu s obsahom brómu 36,5 % (Br vypočítané 36,32) teplota topenia 280 až 285 °C (prekryštalizované z vody). CS 267 082 Bl 3
(57) The present invention relates to a process for preparing 5-bromo-6-amino-1-methyluracil from 6-amino-1-methyluracil by the action of bromine in an aqueous alkali medium. The present compound serves as an intermediate for the preparation of purine bases. The reaction is carried out at a pH of 9 to 13 and a temperature of 0 to 20 ° C. CS 267082 Bl 2 EN 267 082 Bl
The present invention provides a process for the preparation of 5-bromo-6-amino-1-methyluracil of formula I
(I) nh2 ch3
which is an intermediate for the preparation of purine bases. So far, the subject compound of formula I has been prepared by the bromine in water reaction (Barker, Luthy; J. Chem. Soc. 1956, 917-920) or in acetic acid (Wojoiechovski J .; Polish Patent 42,976, Acta Polon. Pharm. 18, 409 -13, 1961) from 6-amino-1-methyluracil of formula II
O
(II)
The disadvantage of these processes was the use of water to produce a large amount of the dibromo derivative and its complicated removal, using a long reaction time with acetic acid and the use of acetic acid as a reaction medium in which by-products were formed due to the reaction of acid and bromine. According to the present invention, the subject compound is prepared by the action of bromine in an alkaline aqueous medium. The advantage of the process is that in an alkaline environment, 6-amino-1-methylureail dissolves and the bromination proceeds very briefly in a homogeneous phase, the alkaline medium decreasing the content of the undesired dibromo derivative. The reaction temperature is maintained between 0 ° C and 20 ° C, preferably between 5 ° C and 15 ° C, and the alkalinity of the solution is maintained between pH 9 and 13.
The molar ratio of bromine to uraoil of formula II is in the range of 1: 0.9 to 3: 1. In the following, the invention is illustrated by way of example without limiting it to this exclusive. Example 5-Bromo-6-amino-1-methyluracil 1350 g (9.56 M) 6-amino-1-methyluracil is suspended in 7 L of water and a solution of 400 g is added to the suspension with stirring at max. (10 M) NaOH in 400 mL water. To the solution formed by dissolving 6-amino-1-methyluracil, 1.53 kg of bromine (19.14 M) are added dropwise from the separating funnel under cooling at 5 to 15 ° C below the surface with vigorous stirring. During the reaction, the pH of the solution is maintained between 9 and 13 by the addition of NaOH solution. The addition of bromine takes 10 to 20 minutes depending on the cooling.
After the addition of the whole bromine, the reaction mixture is acidified by the addition of 800-850 ml of 36% HCl to bring the pH of the solution to 5-6. The precipitated 5-bromo-6-amino-1-methyluraoil is suctioned off on a frit, washing 2 to 3 l. water and finally 1 l of ethanol and dried. 1 900 g of crude (90.3%) 5-bromo-6-amino-1-methyluraoil having a bromine content of 36.5% (Br calculated 36.32) are obtained, m.p. 280 DEG-285 DEG C. (recrystallized from water). CS 267 082 B1 3
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS872222A CS267082B1 (en) | 1987-03-31 | 1987-03-31 | Method of 5-bromo-6-amino-1-methyluracil preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS872222A CS267082B1 (en) | 1987-03-31 | 1987-03-31 | Method of 5-bromo-6-amino-1-methyluracil preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS222287A1 CS222287A1 (en) | 1989-05-12 |
| CS267082B1 true CS267082B1 (en) | 1990-02-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS872222A CS267082B1 (en) | 1987-03-31 | 1987-03-31 | Method of 5-bromo-6-amino-1-methyluracil preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS267082B1 (en) |
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1987
- 1987-03-31 CS CS872222A patent/CS267082B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS222287A1 (en) | 1989-05-12 |
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