GB2109369A - Process for purifying guanine - Google Patents
Process for purifying guanine Download PDFInfo
- Publication number
- GB2109369A GB2109369A GB08227127A GB8227127A GB2109369A GB 2109369 A GB2109369 A GB 2109369A GB 08227127 A GB08227127 A GB 08227127A GB 8227127 A GB8227127 A GB 8227127A GB 2109369 A GB2109369 A GB 2109369A
- Authority
- GB
- United Kingdom
- Prior art keywords
- guanine
- solution
- purifying
- alkali metal
- crude
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
Abstract
A process for purifying guanine comprises dissolving crude guanine in a concentrated aqueous solution of an alkali metal hydroxide at an elevated temperature, cooling the resulting solution, thereby causing guanine to precipitate in the form of an alkali metal salt which is slightly soluble in the concentrated aqueous alkali solution, and neutralizing the metal salt with an acid.
Description
SPECIFICATION
Process for purifying guanine
The present invention relates to a process for purifying guanine which provides high quality guanine in high yield from crude guanine.
Guanine is one of the so-called nucleic acid bases and can be utilized in various fields, including production of pharmaceuticals. Guanine is prepared, for instance, by a process which comprises cyclizing 2,4,5-triamino-6oxy-pyrimidine with formic acid or the like as disclosed in Berichte, 33, 1371, 3035(1900), a process in which guanine is synthesized from an arylazocyanoacetyl derivative and urea, thiourea, formic acid or a derivative of formic acid as disclosed in Japanese Examined Patent Publication (Tokkyo Kokoku) No. 20067/1967, and a process in which a 2-arylazocyanoacetylguanidine is reacted with formic acid or a formic acid derivative under reducing conditions as disclosed in
Japanese Unexamined Patent Publication (Tokkyo Kokai) No. 141894/1976.However, in any of these known processes, the product contains a small amount of by-products as impurities and, therefore, must be further purified.
However, there has been no profitable process for purifying guanine and no pure product has been available on a commercial scale.
For guanine, there are no suitable solvents other than strong acids and strong bases.
Therefore, purification of guanine has been generally conducted by adsorption of impurities on an adsorbent such as active carbon in these solvents or recrystallization in the form of a mineral acid salt. However, an improved purity can be achieved only at the cost of a reduced yield and it has been impossible to
obtain high quality guanine at economical
cost.
It is an object of the present invention to provide a process for purifying guanine.
A further object of the invention is to provide a process for economically purifying guanine in high purities and high yields by
recovering guanine in the form of a metal salt from crude guanine.
These and other objects will become apparent from the description hereinafter.
The present inventors have found that gu
anine has a property to crystallize as a sparingly soluble salt from a highly concentrated aqueous alkali solution. On the basis of this finding, it has now been found that by dis
solving crude guanine in a concentrated aqueous alkali solution under heating and then cooling the solution, a metal salt of guanine
containing a far less amount of impurities than in a conventional purification process can
be precipitated as crystals to thereby achieve a purification of crude guanine.
In accordance with the present invention, there is provided a process for purifying guanine which comprises dissolving crude guanine in a concentrated aqueous solution of an alkali metal hydroxide at an elevated temperature, and cooling the resulting solution to precipitate a crystalline metal salt of guanine.
Pure guanine is obtained by, for instance, dissolving the alkali metal salt in water and neutralizing the solution with an inorganic or organic acid.
Bases which are effectively employed in the present invention are alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. It is desirable that the concentration of an aqueous solution of an alkali metal hydroxide used as a solvent is at least 1 5 % by weight. When the concentration is less than 15% by weight, the solubility of an alkali metal salt of guanine in the aqueous alkali solution increases and the yield is lowered.
Crude guanine is dissolved in an aqueous alkali solution at an elevated temperature, usually at a temperature of about 50 to about 90"C., preferably not less than about 60"C. The solution of guanine is then cooled to crystallize guanine in the form of the alkali metal salt.
The process of the present invention can be practiced by conducting dissolution of crude guanine and cooling of the solution in a batchwise operation. It is also possible to conduct the process of the invention in a continuous operation. When the dissolution and the precipitation are conducted by a multi-stage recrystallation process, high quality guanine can be obtained in a very high yield without using any other purification aids such as active carbon.
It is also possible to practice the present invention in combination with a known purification procedure involving the use of an adsorbent such as active carbon. Thus, depending on the quality grade of crude guanine, these procedures can be used in various combinations.
The metal salts of guanine can be easily converted into guanine, for instance, by dissolving the salts in water or a low concentration of an aqueous alkali solution and neutral
izing with an acid, e.g. mineral acids such as sulfuric acid, and organic acids such as acetic acid.
In accordance with the process of the present invention, high purity guanine can be obtained in a high yield. The purified guanine
has a high whiteness. Since the solvent used
in the invention is an aqueous alkali solutiion, the equipment may be made of common
metal materials and this is also an advantage
in industrial application of the process.
The present invention is more specifically
described and explained by means of the
following Examples. It is to be understood
that the present invention is not limited to the
Examples and various changes and modifications may be made in the invention without departing from the spirit and scope thereof.
Example I {Synthesis of guanine)
In 200 g. of formamide, 80 g. of 2,4,5 triamino-6-oxy-pyrimidine sulfate was cyclized by heating at 160"C. for 8 hours to give 49 g. of crude guanine having a purity of 98 % (measured by liquid chromatography) and a whiteness of 70 %.
(Purification of guanine)
To 100 ml. of a 20 % by weight aqueous solution of sodium hydroxide was added 10 g. of the crude guanine synthesized above and was dissolved by heating at 70"C. The solution was then gradually cooled to a temperature below 15"C. to precipitate the sodium salt of guanine (hereinafter referred to as ''guanine salt"). After separation of the crystals by filtration, the filtrate contained 0.4 g.
of guanine. This filtrate was discarded. The above procedure is referred to as the first crystallization.
The guanine salt separated in the first crystallization was dissolved again in a 20 % by weight aqueous solution of sodium hydroxide under heating and the solution was cooled to give crystals of the guanine salt (the second crystallization). The crystals were separated and the filtrate was used as a solvent for the first crystallization.
A third crystallization was carried out in the same manner as above, and the filtrate was used as a solvent for the second crystallization. The above crystallization procedures were carried out in six stages in total. The guanine salt recovered in the 6th crystallization stage was neutralized with 30 % sulfuric acid to give pure guanine.
When the above recrystallization procedure in six stages was repeated several times, the composition of the crystallization solvent in each stage became a steady state. The sixstage crystallization conducted in the steady state yielded 9.1 g. of the pure guanine. The yield was 92 %. The purified guanine had a purity of 99.6 % (measured by liquid chromatography) and a whiteness of 94 % (measured by a spectrophotometer at 480 nm).
Example 2
In 100 ml. of a 20 % by weight aqueous solution of sodium hydroxide was dissolved under heating 10 g. of crude guanine synthesized in the same manner as Example 1, and the solution was cooled to give crystals of the guanine salt. The guanine salt crystals were recovered by filtration and dissolved in 200 ml. of a 1 % by weight aqueous solution of sodium hydroxide. The solution was decolorized by addition of 0.3 g. of activated carbon and the carbon was filtered off. The filtrate was neutralized with an acid to give 8.4 g. of pure guanine. The purity was 99.5 % and the whiteness was 89 %. The yield was 85 %.
Comparative Example
In 200 ml. of a 1 % by weight aqueous solution of sodium hydroxide was dissolved 10 g. of crude guanine synthesized in the same manner as in Example 1, and the solution was decolorized with 1 g. of activated carbon with stirring. The activated carbon was removed and the solution was neutralized with an acid to give 7.5 g. of purified guanine. The yield was 76 %. The purity was 99.3 % and the whiteness was 81 %.
Example 3 (Synthesis of guanine)
To 550 g. of formamide were added 93 g.
of 2-phenylazocyanoacetylguanine, a Raney nickel catalyst prepared from 14 g. of an alloy containing 48 % of nickel and 14 g. of activated carbon. In an autoclave with a hydrogen pressure of 30 kg/cm2., the reaction was conducted at 150"C. for 5 hours. The formamide was distilled away under reduced pressure and the residue was treated with an alkali to give 52 g. of crude guanine.
(Purification of guanine)
Ten grams of the obtained crude guanine was subjecfed to 8 stages of crystallization under the same conditions as in Example 1 to give 8.0 g. of pure guanine. The purity was 99.6 % and the whiteness was 87 %.
In addition to the ingredients used in the
Examples, other ingredients can be used in the Examples as set forth in the specification to obtain substantially the same results.
Claims (3)
1. A process for purifying guanine which comprises dissolving crude guanine in a concentrated aqueous solution of an alkali metal hydroxide at an elevated temperature, and cooling the resulting solution to precipitate a crystalline metal salt of guanine.
2. The process of Claim 1, wherein the concentration of the aqueous solution of an alkali metal hydroxide is at least 1 5 % by weight.
3. A process for purifying guanine substantially as described in any one of the examples disclosed herein.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15215581A JPS5855485A (en) | 1981-09-28 | 1981-09-28 | Purification of guanine |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2109369A true GB2109369A (en) | 1983-06-02 |
GB2109369B GB2109369B (en) | 1985-06-12 |
Family
ID=15534220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08227127A Expired GB2109369B (en) | 1981-09-28 | 1982-09-23 | Process for purifying guanine |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS5855485A (en) |
CH (1) | CH651834A5 (en) |
DE (1) | DE3235372A1 (en) |
GB (1) | GB2109369B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207650B1 (en) * | 1989-05-15 | 2001-03-27 | Bristol-Myers Squibb Company | Antiviral, highly water soluble, stable, crystalline salts of 2′, 3′-dideoxyinosine, 2′, 3′-dideoxy-2′, 3′-didehydrothymidine and 2′, 3′-dideoxy-2′-fluoroinosine |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3727508A1 (en) * | 1987-08-18 | 1989-03-02 | Boehringer Ingelheim Kg | METHOD FOR PRODUCING SODIUM PURINE |
DE3729471A1 (en) * | 1987-09-03 | 1989-03-16 | Huels Troisdorf | Process for the preparation of guanine |
DE3928365A1 (en) * | 1989-08-28 | 1991-03-07 | Huels Chemische Werke Ag | METHOD FOR PRODUCING PURE GUANINE |
DE4022314A1 (en) * | 1990-07-13 | 1992-01-16 | Boehringer Ingelheim Kg | METHOD FOR PRODUCING 2-CHLORINE-1,7-DIHYDROPURIN-6-ON AND METHOD FOR CLEANING IT |
DE4136114C2 (en) * | 1991-11-02 | 1995-05-24 | Boehringer Ingelheim Kg | Improved process for the production of guanine and its alkali metal salts |
DE4422587C2 (en) * | 1994-06-28 | 2000-11-30 | Sueddeutsche Kalkstickstoff | Process for the production of purines |
-
1981
- 1981-09-28 JP JP15215581A patent/JPS5855485A/en active Pending
-
1982
- 1982-09-23 GB GB08227127A patent/GB2109369B/en not_active Expired
- 1982-09-24 CH CH565682A patent/CH651834A5/en not_active IP Right Cessation
- 1982-09-24 DE DE19823235372 patent/DE3235372A1/en active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207650B1 (en) * | 1989-05-15 | 2001-03-27 | Bristol-Myers Squibb Company | Antiviral, highly water soluble, stable, crystalline salts of 2′, 3′-dideoxyinosine, 2′, 3′-dideoxy-2′, 3′-didehydrothymidine and 2′, 3′-dideoxy-2′-fluoroinosine |
Also Published As
Publication number | Publication date |
---|---|
GB2109369B (en) | 1985-06-12 |
DE3235372C2 (en) | 1990-09-06 |
CH651834A5 (en) | 1985-10-15 |
JPS5855485A (en) | 1983-04-01 |
DE3235372A1 (en) | 1983-04-14 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19950923 |