DE895292C - Process for the preparation of 3-fluoro-tyrosine brominated or iodinated in the 5-position - Google Patents
Process for the preparation of 3-fluoro-tyrosine brominated or iodinated in the 5-positionInfo
- Publication number
- DE895292C DE895292C DEK3178D DEK0003178D DE895292C DE 895292 C DE895292 C DE 895292C DE K3178 D DEK3178 D DE K3178D DE K0003178 D DEK0003178 D DE K0003178D DE 895292 C DE895292 C DE 895292C
- Authority
- DE
- Germany
- Prior art keywords
- fluoro
- tyrosine
- brominated
- iodinated
- preparation
- 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.)
- Expired
Links
- VIIAUOZUUGXERI-ZETCQYMHSA-N 3-fluoro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(F)=C1 VIIAUOZUUGXERI-ZETCQYMHSA-N 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- DUZDIGZRRMKJFE-UHFFFAOYSA-N 2-amino-3-(3-bromo-5-fluoro-4-hydroxyphenyl)propanoic acid Chemical compound OC(=O)C(N)CC1=CC(F)=C(O)C(Br)=C1 DUZDIGZRRMKJFE-UHFFFAOYSA-N 0.000 description 1
- SBSBDTRZKUAPKP-UHFFFAOYSA-N 2-amino-3-(3-fluoro-4-hydroxy-5-iodophenyl)propanoic acid Chemical compound OC(=O)C(N)CC1=CC(F)=C(O)C(I)=C1 SBSBDTRZKUAPKP-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- XRRYGMTXOYFERK-UHFFFAOYSA-N [I].[K].[I] Chemical compound [I].[K].[I] XRRYGMTXOYFERK-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von in der 5-Stellung bromiertem oder jodiertem 3-Fluor-tyrosin Es ist bekannt, daß 3-Fluor-tyrosin auf die Schilddrüsenüberfunktion günstig einwirkt. Es wurde nun gefunden, daß durch Einführung eines Brom- oder ,Jodatoms in der 5-Stellung von 3-Fluor-tyrosin diese Verbindung weitgehend entgiftet wird bei gleichzeitiger Erhaltung der günstigen Wirkung auf die Schilddrüse. Außerdem besitzen die neuen Verbindungen eine günstige Wirkung auf den Kohlehydratstoffwechsel im Sinne einer Glykogenspeicherung.Process for the preparation of 5-position brominated or iodinated 3-fluoro-tyrosine It is known that 3-fluoro-tyrosine acts on hyperthyroidism acts favorably. It has now been found that by introducing a bromine or iodine atom in the 5-position of 3-fluoro-tyrosine this compound is largely detoxified while maintaining the beneficial effect on the thyroid gland. aside from that the new compounds have a beneficial effect on the carbohydrate metabolism in terms of glycogen storage.
Die neuen Verbindungen können durch Einführung des Halogenatoms in das 3-Fluor-tyrosin. nach den üblichen Methoden der Bromierung oder Jodierung gewonnen werden. Beispiel z 20 g 3-Fluor-tyrosin werden zusammen mit 88 g Soda in 16o ccm Wasser durch gelindes Erwärmen gelöst. Hierauf wird auf 5° abgekühlt und tropfenweise mit einer gekühlten Jod-Jodkalium-Lösung versetzt, die in 8o ccm 25,5 g Jod enthält. Die erste Hälfte der Jodlösung wird verhältnismäßig rasch, die zweite nur langsam entfärbt. Die erhaltene Lösung wird 14 Stunden im Eisschrank stehengelassen und dann unter Eiskühlung Schwefeldioxyd eingeleitet, worauf die Lösung bald zu einer Kristallmasse erstarrt, die abgesaugt und mit Wasser gewaschen wird. Nach dem Trocknen erhält man zusammen mit einer weiteren Kristallisation aus den eingeengten Mutterlaugen 25 g 3-Fluor-5-jodtyrosin = 76 °/o der Theorie: Nach ein- bis zweimaligem Llmkristallisieren aus 2o ccm Alkohol erhält man farblose Kristalle vom F. 19o bis 1g3°.The new compounds can be obtained by introducing the halogen atom into the 3-fluoro-tyrosine. can be obtained by the usual methods of bromination or iodination. Example z 20 g of 3-fluoro-tyrosine are dissolved together with 88 g of soda in 160 cc of water by gentle heating. It is then cooled to 5 ° and a cooled iodine-iodine potassium solution is added dropwise, which contains 25.5 g of iodine in 80 ccm. The first half of the iodine solution is decolorized relatively quickly, the second only slowly. The solution obtained is left to stand in the refrigerator for 14 hours and then sulfur dioxide is passed in while cooling with ice, whereupon the solution soon solidifies to a crystal mass, which is filtered off with suction and washed with water. After drying, together with a further crystallization from the concentrated mother liquors, 25 g of 3-fluoro-5-iodotyrosine = 76% of theory: after one or two crystallizations from 20 cc of alcohol, colorless crystals with a melting point of 19o to are obtained 1g3 °.
Beispiel 2 10 g 3-Fluor-tyrosin werden in 300 ccm Eisessig aufgeschwemmt, und es wird bei Zimmertemperatur eine Lösung von 8 g Brom in Eisessig allmählich zugetropft. Man läßt die Reaktionsmischung über Nacht stehen und erwärmt schließlich noch kurze Zeit auf 40°. Das 3-Fluor-tyrosin ist danach vollständig in Lösung gegangen. Eisessig und Bromwasserstoff werden im Vakuum auf dem Wasserbad entfernt, der kristalline Rückstand wird in Wasser gelöst und mit Alkali auf ein pH von 4 bis 4,5 eingestellt. Nach Stehen in der Kälte scheiden sich farblose Kristalle aus, die aus Wasser umkristallisiert werden, und man erhält so 10,7 g 3-Fluor-5-bromtyrosin = 76 % der Theorie.Example 2 10 g of 3-fluoro-tyrosine are suspended in 300 cc of glacial acetic acid, and a solution of 8 g of bromine in glacial acetic acid is gradually added dropwise at room temperature. The reaction mixture is left to stand overnight and finally heated to 40 ° for a short time. The 3-fluoro-tyrosine then completely dissolved. Glacial acetic acid and hydrogen bromide are removed in vacuo on the water bath, the crystalline residue is dissolved in water and adjusted to a pH of 4 to 4.5 with alkali. After standing in the cold, colorless crystals separate out and are recrystallized from water, giving 10.7 g of 3-fluoro-5-bromotyrosine = 76 % of theory.
Die Verbindung tritt in zwei ineinander überführbaren Formen auf, schollenförmige Kristalle (aus Wasser) vom F. 22o° (Mikro) und voluminöse, feine haarförmige Nadeln (aus Alkohol) vom F.226° (Mikro).The connection occurs in two forms that can be converted into one another, Lump-shaped crystals (from water) with a temperature of 22o ° (micro) and voluminous, fine hair-like needles (made of alcohol) from F.226 ° (micro).
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK3178D DE895292C (en) | 1944-12-06 | 1944-12-06 | Process for the preparation of 3-fluoro-tyrosine brominated or iodinated in the 5-position |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK3178D DE895292C (en) | 1944-12-06 | 1944-12-06 | Process for the preparation of 3-fluoro-tyrosine brominated or iodinated in the 5-position |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE895292C true DE895292C (en) | 1953-11-02 |
Family
ID=7209758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK3178D Expired DE895292C (en) | 1944-12-06 | 1944-12-06 | Process for the preparation of 3-fluoro-tyrosine brominated or iodinated in the 5-position |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE895292C (en) |
-
1944
- 1944-12-06 DE DEK3178D patent/DE895292C/en not_active Expired
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