DE1620573B

DE1620573B - Process for the production of adenine

Info

Publication number: DE1620573B
Authority: DE
Inventors: Katsura Ikeda Ochiai Michihiko Suita Marumoto Ryuji Minoo Monta, (Japan)
Original assignee: Takeda Chemical Industries Ltd
Current assignee: Takeda Pharmaceutical Co Ltd

Description

den auf 110° C erhitzt. Durch Aufarbeitung des Reaktionsgemisches auf die im Beispiel 1 beschriebene Weise wird Adenin als weißes Pulver in einer Ausbeute von 9 Gewichtsteilen erhalten.heated to 110 ° C. By working up the reaction mixture to that described in Example 1 Thus, adenine is obtained as a white powder in a yield of 9 parts by weight.

Example 6

Ein Gemisch von 45 Raumteilen Formamid und 50 Gewichtsteilen Phosphorpentoxyd wird 5 Stunden auf 12O⁰C erhitzt. Durch Aufarbeitung des Reaktionsgemisches auf die im Beispiel 1 beschriebene Weise wird Adenin als weißes Pulver in einer Ausbeute von 8 Gewichtsteilen erhalten.A mixture of 45 parts by volume of formamide and 50 parts by weight of phosphorus pentoxide is heated for 5 hours at 12O ⁰ C. By working up the reaction mixture in the manner described in Example 1, adenine is obtained as a white powder in a yield of 8 parts by weight.

Example 7

Ein Gemisch von 45 Raumteilen Formamid und 100 Gewichtsteilen Polyphosphorsäure wird 24 Stunden auf 8O⁰C erhitzt. Durch Aufarbeitung des Reaktionsgemisches auf die im Beispiel 1 beschriebene Weise wird Adenin als weißes Pulver in einer Ausbeute von 7 Gewichtsteilen erhalten.A mixture of 45 parts by volume of formamide and 100 parts by weight of polyphosphoric acid is heated for 24 hours 8O ⁰ C. By working up the reaction mixture in the manner described in Example 1, adenine is obtained as a white powder in a yield of 7 parts by weight.

Example 8

Ein Gemisch von 45 Raumteilen Formamid und 120 Raumteilen Thionylchlorid wird 6 Stunden auf 125⁰C erhitzt. Durch Aufarbeitung des Reaktionsgemisches auf die im Beispiel 1 beschriebene Weise wird Adenin als weißes Pulver in einer Ausbeute vonA mixture of 45 parts by volume of formamide and 120 parts by volume of thionyl chloride is ^{heated to 125 °} C. for 6 hours. By working up the reaction mixture in the manner described in Example 1, adenine is obtained as a white powder in a yield of

7 Gewichtsteilen erhalten.7 parts by weight obtained.

Example 9

Ein Gemisch von 45 Raumteilen Formamid und 120 Raumteilen Chlorsulfonsäure wird 10 Stunden auf 100⁰C erhitzt. Durch Aufarbeitung des Reaktionsgemisches auf die im Beispiel 1 beschriebene Weise wird Adenin als weißes Pulver in einer Ausbeute vonA mixture of 45 parts by volume of formamide and 120 parts by volume of chlorosulfonic acid is ^{heated to 100 °} C. for 10 hours. By working up the reaction mixture in the manner described in Example 1, adenine is obtained as a white powder in a yield of

8 Gewichtsteilen erhalten.8 parts by weight obtained.

Claims

1 21 2

zene or toluene. The reaction is generally in

Claims: about 3 to 10 hours completed. ·

The adenine formed in the reaction can in an

1. Process for the preparation of adenine, indicated in a known manner from the reaction mixture characterized in that one separates 5, e.g. B. by narrowing the reaction formamide with an oxyacid or an anhy system, filtration and recrystallization. If Erdrid an oxyacid of phosphorus or sulfur, cleaning processes using or with their halides at temperatures of ion exchange resins or adsorption 70 up to 200 ° C. to isolate the adenine formed

2. The method according to claim 1, characterized in that it is applied.

draws that the formamide with Polyphos- The implementation of the claimed process

phosphoric acid, phosphorus pentoxide, phosphoroxychlo- is illustrated in the following examples in which

rid, phosphorus pentachloride, phosphorus trichloride, parts by weight to parts by volume such as grams

Pyrophosphoric acid tetrachloride, thionyl chloride, milliliters behave.

Reacts chlorosulfonic acid or tosyl chloride. 15th

3. Process according to Claims 1 and 2, thereby Example 1
characterized in that the reaction is carried out in the presence of a mixture of 45 parts by volume of formamide and of dioxane, tetrahydrofuran or chloroform 150 parts by volume of phosphorus oxychloride is carried out for 5 hours. heated to 12O ^{0 C.} After cooling down, the react

20 tion mixture with 1000 parts by volume of hot water

treated. The aqueous adenine solution thus obtained is

passed through a column filled with activated carbon. The adenine adsorbed on the activated carbon becomes

The invention relates to a new method with aqueous ammonia eluted. From the

for the production of adenine. In the narrow eluate, the adenine is converted into a white powder

Adenine can e.g. B. from pyrimidine derivatives obtained by a yield of 14 parts by weight.

Conversion of malononitrile and thiourea Analysis was by paper chromatography

or by converting malonic acid diamidine and using the one-dimensional ascending method

Formamide or carried out by reaction of formamidine, the solvent system being aqueous

and phenylazomalononitrile are obtained 30 ammonia and as a developer saturated with water

_{or butanol: 15n - NH 4} OH (100: 1) prepared from 4-amino-5-imidazole carbonamide were used,

will. i? / - values of 0.45 and 0.41 were determined.

These processes require several reaction steps

and the total yield based on easily accessible ultraviolet absorption:

borrowed starting materials is low. 35 _ληαχ _{= 2} 60 nrn (ε = 13.30 · 10 ³ ) at pH 4,

It is also known that adenine is produced by the reaction, _ _9i - _q <v _ η in. ifvn (, «nHin

-, ...... -IU, I ₁ , j Amax = -tv " ma (ε = iz, JU · iu) Dei pn. Iu.

of hydrogen cyanide with ammonia

can (Archives of Biochemistry and Biophysics, 94,.

[1961], p. 217). According to this procedure, each Example 2

but only low yields of adenine obtained, it 40 to a solution of 45 parts by volume of formamide in

Insoluble by-products are formed and the pure 200 parts by volume of dioxane become 190 parts by weight

The adenine obtained is very difficult to obtain. Given tosyl chloride. The mixture is 10 hours

According to the method according to the invention, the mixture is heated to 130.degree. The reaction mixture is on the

Adenine worked up in a one-stage reaction in good yield in the manner described in Example 1, wherein

manufactured. The formation of by-products that produce the 45 adenine as a white powder in a yield of

Make separation and purification of the adenine difficult, 9 parts by weight is obtained,

is largely suppressed. The procedure is.

characterized in that one formamide with example

of an oxyacid or an anhydride of an oxyacid To 200 parts by volume of tetrahydrofuran are 45

of phosphorus or sulfur or their halides 50 parts by volume of formamide and 200 parts by weight of phosphorus

at temperatures of 70 to 200 ° C. pentachloride given. The mixture is 6 hours

The heated as oxy acids or anhydrides of oxyacids to 12O ⁰ C. The reaction mixture is worked up in the manner described in phosphorus or sulfur or as their halides in Example 1, polyphosphoric acid, phosphorus pentoxide, phosphorus adenine being obtained as a white powder in a yield of phosphorus oxychloride, phosphorus pentachloride, phosphorus tri-55 9 parts by weight,
chloride, pyrophosphoric acid tetrachloride, thionylchlo-. .
rid, sulfuryl chloride, chlorosulfonic acid or tosyl example 4
suitable for chloride. The starting products are used in a mixture of 45 parts by volume of formamide and a molar ratio of 1: 1, but 140 parts by volume of phosphorus trichloride can also be used. One of the starting materials is used in excess for 7 hours and is heated to 130 ° C. By working up the reaction mixture in the manner described in Example 1

The starting materials are sealed in a adenine as a white powder in a yield of

Received vessel to about 70 to 200 ⁰ C, preferably to about 7 parts by weight.

120 to 150 ° C, heated. If necessary, an organ. .

Chemical solvents can be used to make the 65 example

Reaction is smoother. The organic solution is 45 parts by volume formamide and 63 parts by weight

medium are ethyl ether, tetramethylene oxide, pyrophosphoric acid tetrachloride in 200 room

Dissolved dioxane, chloroform, dichloroethane, ethyl acetate, part of chloroform. The mixture is 10 hours