DE1047790B - Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids - Google Patents
Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acidsInfo
- Publication number
- DE1047790B DE1047790B DEF22728A DEF0022728A DE1047790B DE 1047790 B DE1047790 B DE 1047790B DE F22728 A DEF22728 A DE F22728A DE F0022728 A DEF0022728 A DE F0022728A DE 1047790 B DE1047790 B DE 1047790B
- Authority
- DE
- Germany
- Prior art keywords
- dioxyisophthalic
- halo
- acids
- acid
- salts
- 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.)
- Pending
Links
- 239000002253 acid Substances 0.000 title claims description 26
- 150000003839 salts Chemical class 0.000 title claims description 18
- 150000007513 acids Chemical class 0.000 title claims description 8
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- -1 alcohol amines Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 150000002336 glycosamine derivatives Chemical class 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
- C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
- C07C65/05—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring o-Hydroxy carboxylic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von therapeutisch wirksamen Salzen der 5-Halogen-4,6-dioxyisophthalsäuren Die 5-Chlor- und die 5-Brom-4,6-dioxyisophthalsäure sind bekannt. Zu ihrer Herstellung dient z. B. das Verfahren von F. Hemmelmayr und Rh. Meyer (Monatshefte für Chemie, 46, S. 143 [1925]). Eine pharmakologische oder andere medizinische bzw. biochemische Untersuchung dieser Verbindungen ist noch nicht bekanntgeworden. Process for the preparation of therapeutically effective salts of the 5-halo-4,6-dioxyisophthalic acids 5-chloro and 5-bromo-4,6-dioxyisophthalic acids are known. For their production z. B. the method of F. Hemmelmayr and Rh. Meyer (monthly magazine for chemistry, 46, p. 143 [1925]). A pharmacological or other medical or biochemical investigation of these compounds is still ongoing not known.
Es wurde nun überraschenderweise gefunden, daß man therapeutisch wirksame Salze der 5-Halogen-4,6-dioxqisophthalsäuren, welche den Fettsäurestoffwechsel stark hemmen, dadurch erhält, daß man eine 5-Halogen-4,6-dioxyisophthalsäure, deren Halogen ein Atomgewicht größer als 19 aufweist, oder deren Salze, gegebenenfalls in Gegenwart eines Lösungsmittels, mit einer nichttoxischen organischen Base oder deren Salzen umsetzt. It has now surprisingly been found that you can therapeutically effective salts of the 5-halo-4,6-dioxqisophthalic acids, which the fatty acid metabolism strongly inhibit, obtained by a 5-halo-4,6-dioxyisophthalic acid, whose Halogen has an atomic weight greater than 19, or its salts, optionally in the presence of a solvent, with a non-toxic organic base or converts their salts.
Die erhaltenen Salze weisen auch eine gute analgetische Wirkung auf und sind sehr gut verträglich. Am wirksamsten erwies sich hierbei die 5-Jod-4,6-dioxyisophthalsäure und deren Salze.The salts obtained also have a good analgesic effect and are very well tolerated. 5-iodo-4,6-dioxyisophthalic acid proved to be the most effective and their salts.
Die 5-Halogen-4,6-dioxyisophthalsäuren selbst besitzen zwar auch schon eine günstige pharmakologische Wirkung bei geringer Toxizität, jedoch sind sie als relativ starke organische Säuren schlecht magenverträglich. Die Alkalisalze dieser Säure besitzen zwar diese unangenehme Wirkung nicht, haben jedoch den Nachteil, daß bei ihrer längeren Anwendung dem Körper beträchtliche Mengen Na+- oder K+-Ionen zugeführt würden, was bei den zu behandelnden chronischen Stoffwechselerlkrankungen unvorteilhaft wäre. The 5-halo-4,6-dioxyisophthalic acids themselves also have already have a beneficial pharmacological effect with low toxicity, however as relatively strong organic acids, they are poorly tolerated by the stomach. The alkali salts this acid do not have this unpleasant effect, but have the disadvantage that with their prolonged use the body receives considerable amounts of Na + or K + ions would be supplied, what with the chronic metabolic diseases to be treated would be disadvantageous.
Alle diese Nachteile können vermieden werden, wenn man die Salze der 5-Halogen-4,6-dioxyisophthalsäuren mit nichttoxischen organischen Basen verwendet. Diese zeigen bei sehr guter Wirkung eine ausgezeichnete Verträglichkeit. Einige dieser Salze haben darüber hinaus den Vorteil einer verzögerten Ausscheidung. Dies bedeutet, daß ein therapeutisch wirksamer Blutspiegel über eine längere Zeit eingehalten wird. All of these disadvantages can be avoided by using the salts of 5-halo-4,6-dioxyisophthalic acids with non-toxic organic bases are used. These show excellent tolerability with a very good effect. Some these salts also have the advantage of delayed excretion. this means that a therapeutically effective blood level is maintained over a longer period of time will.
Als nichttoxische Basen eignen sich insbesondere die Alkoholamine, wie Äthanolamin, Diäthanolamin, Aminozuckerderivate, wie Glukosamin, Methylglukamin, oder cyclische Basen, wie Morpholin und Piperazin. The alcohol amines are particularly suitable as non-toxic bases, such as ethanolamine, diethanolamine, amino sugar derivatives such as glucosamine, methylglucamine, or cyclic bases such as morpholine and piperazine.
Die Herstellung der Salze der 5-Halogen-4,6-dioxyisophthalsäuren erfolgt entweder durch inniges Vermischen der Komponenten, gegebenenfalls in Gegenwart eines Lösungsmittels, oder durch doppelte Umsetzung eines Salzes der 5-Halogen-4,6-dioxyisophthalsäuren mit Salzen der Basen. Als Lösungsmittel wählt man vorteilhaft ein solches, aus dem das Salz auch umkristallisiert werden kann. The preparation of the salts of 5-halo-4,6-dioxyisophthalic acids takes place either by intimate mixing of the components, optionally in the presence a solvent, or by double reaction of a salt of 5-halo-4,6-dioxyisophthalic acids with salts of bases. The solvent chosen is advantageously one from which the salt can also be recrystallized.
Man verwendet bevorzugt 2 Mol einer monobasischen oder 1 Mol einer dibasischen Verbindung auf 1 Mol der 5-Halogen-4,6-dioxyisophthalsäure. Man kann aber auch Salze aus 1 Mol Base und 1 Mol 5-Halogen-4,6-dioxyiso- phthalsäure herstellen; diese haben jedoch den Nachteil, in wäßriger Lösung zu disproportionieren. It is preferred to use 2 moles of a monobasic or 1 mole of a monobasic dibasic compound to 1 mole of 5-halo-4,6-dioxyisophthalic acid. One can but also salts of 1 mole of base and 1 mole of 5-halogen-4,6-dioxyiso- make phthalic acid; however, these have the disadvantage that they are disproportionate in aqueous solution.
Die bisher in der Literatur noch nicht beschriebene 5-Jod-4,6-dioxyisophthalsäure kann z. B. auf folgende Weise gewonnen werden: 19,8 g 4,6-Dioxvisophthalsäure werden mit 8 g Natriumhydroxyd in 500 ccm Wasser gelöst. Hierauf wird unter Rühren eine Lösung von 26 g Jod und 20 g Kaliumjodid in 100 ccm Wasser zugetropft. The 5-iodo-4,6-dioxyisophthalic acid which has not yet been described in the literature can e.g. B. be obtained in the following way: 19.8 g of 4,6-dioxvisophthalic acid dissolved with 8 g of sodium hydroxide in 500 ccm of water. Then a Solution of 26 g of iodine and 20 g of potassium iodide in 100 ccm of water were added dropwise.
Man läßt noch über Nacht rühren und säuert dann mit Salzsäure an. Die ausgefallene 5-Jod-4,6-dioxyisophthalsäure wird abgesaugt und aus 500/,dem Alkohol umkristallisiert. Sie zersetzt sich unter Jodabspaltung ab 250"C.The mixture is left to stir overnight and then acidified with hydrochloric acid. The precipitated 5-iodo-4,6-dioxyisophthalic acid is suctioned off and from 500 /, the alcohol recrystallized. It decomposes with elimination of iodine from 250 "C.
Die Herstellung der 5-Jod-4,6-dioxyisophthalsäure ist jedoch nicht Gegenstand vorliegender Erfindung. However, the production of 5-iodo-4,6-dioxyisophthalic acid is not Subject of the present invention.
Beispiel 1 27 g 5-Brom-4,6-dioxyisophthalsäure werden in 200 ccm Alkohol gelöst und unter Rühren zu einer Lösung von 20 g Morpholin in 100 ccm Alkohol zulaufen gelassen. Example 1 27 g of 5-bromo-4,6-dioxyisophthalic acid are in 200 ccm Dissolve alcohol and stir into a solution of 20 g of morpholine in 100 cc of alcohol allowed to run.
Man kühlt hierauf ab, saugt das ausgefallene Bis-morpholinsalz der 5-Brom4,6-dioxyisophthalsäure ab und wäscht mit Alkohol nach. Das Salz schmilzt bei 199"C unter Zersetzung.It is then cooled and the bis-morpholine salt which has precipitated is filtered off with suction 5-bromo-4,6-dioxyisophthalic acid and washes with alcohol. The salt melts at 199 "C with decomposition.
Beispiel 2 32 g 5-Jod-4,6-dioxyisophthalsäure werden in 100 ccm Isopropylalkohol gelöst und mit einer Lösung von 14 g Äthanolamin in 50 ccm Isopropylalkohol versetzt. Das ausgefallene Bis-äthanolaminsalz der 5-Jod-4,6-dioxyisophthalsäure wird nach Abkühlen abgesaugt und mit Isopropylalkohol nachgewaschen. Es schmilzt bei 1530. Example 2 32 g of 5-iodo-4,6-dioxyisophthalic acid are dissolved in 100 cc of isopropyl alcohol dissolved and mixed with a solution of 14 g of ethanolamine in 50 cc of isopropyl alcohol. The precipitated bis-ethanolamine salt of 5-iodo-4,6-dioxyisophthalic acid will Sucked off after cooling and washed with isopropyl alcohol. It melts at 1530.
Beispiel 3 32 g 5-Jod-4,6-dioxyisophthalsäure werden in 100 ccm Isopropylalkohol gelöst und mit einer Lösung von 23 g Diäthanolamin in 50 ccm Isopropylalkohol versetzt. Das ausgefallene Bis-diäthanolaminsalz der 5-Jod4,6-dioxyisophthalsäure wird nach Abkühlen abgesaugt und mit Isopropylalkohol nachgewaschen. Es schmilzt bei 117°C. Example 3 32 g of 5-iodo-4,6-dioxyisophthalic acid are dissolved in 100 cc of isopropyl alcohol dissolved and mixed with a solution of 23 g of diethanolamine in 50 cc of isopropyl alcohol. The precipitated bis-diethanolamine salt of 5-iodo-4,6-dioxyisophthalic acid is after Sucked off cooling and washed with isopropyl alcohol. It melts at 117 ° C.
Beispiel 4 32 g 5-Jod-4,6-dioxyisophthalsäure werden in 320 ccm Alkohol gelöst und unter Rühren in eine Lösung von 20 g Morpholin in 100 ccm Alkohol gegossen. Nach Erkalten wird abgesaugt und mit Alkohol nachgewaschen. Example 4 32 g of 5-iodo-4,6-dioxyisophthalic acid are dissolved in 320 cc of alcohol dissolved and with stirring in a solution of 20 g of morpholine poured into 100 cc of alcohol. After cooling, it is suctioned off and washed with alcohol.
Das so gewonnene Bis-morpholinsalz der 5-Jod-4,6 dioxyisophthalsäure schmilzt bei 175"C unter Zersetzung.The bis-morpholine salt of 5-iodo-4,6 dioxyisophthalic acid obtained in this way melts at 175 "C with decomposition.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF22728A DE1047790B (en) | 1957-04-03 | 1957-04-03 | Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF22728A DE1047790B (en) | 1957-04-03 | 1957-04-03 | Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1047790B true DE1047790B (en) | 1958-12-31 |
Family
ID=7090554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF22728A Pending DE1047790B (en) | 1957-04-03 | 1957-04-03 | Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1047790B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118084627A (en) * | 2024-01-12 | 2024-05-28 | 厦门沃克沃德医药科技有限公司 | Preparation method of cannabigerol and analogues thereof |
-
1957
- 1957-04-03 DE DEF22728A patent/DE1047790B/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118084627A (en) * | 2024-01-12 | 2024-05-28 | 厦门沃克沃德医药科技有限公司 | Preparation method of cannabigerol and analogues thereof |
| CN118084627B (en) * | 2024-01-12 | 2024-09-24 | 厦门沃克沃德医药科技有限公司 | Preparation method of cannabigerol and analogues thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1445186C3 (en) | 3,3'-di-2-imidazolin-2-yl-carbanilide | |
| DE1047790B (en) | Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids | |
| DE1210865B (en) | Process for the preparation of the 2,6-dioxo-tetrahydropyrimidine-4-carboxylic acid salt of 4-amino-5-imidazolecarboxamide | |
| DE604228C (en) | Process for the preparation of easily soluble in water preparations of the salts of the china alkaloids which are difficult to dissolve or insoluble in water or of their aqueous solutions | |
| AT203000B (en) | Process for the preparation of new salts of 4,6-dioxyisophthalic acid and 5-halogen (especially 5-iodine) - 4,6-dioxyisophthalic acid | |
| AT100211B (en) | Process for the preparation of new organic arsenic compounds. | |
| DE1068271B (en) | Process for the preparation of therapeutically active salts of 5-halo-4,6-dioxyisophthalic acids | |
| DE829166C (en) | Process for the preparation of N- (p-arsenosobenzyl) glycine amide and its salts | |
| DE963515C (en) | Process for the production of poorly soluble, crystallized streptomycin and dihydrostreptomycin salts | |
| DE938249C (en) | Process for the preparation of dihydrocodeine hydrorhodanide | |
| DE613125C (en) | Process for the preparation of water-soluble compounds of the oxydiphenyl ethers and their substitution products | |
| DE556368C (en) | Process for the preparation of readily soluble sodium salts of acylaminophenolar acids | |
| DE444970C (en) | Process for the preparation of salts of the aminobenzoic acid alkyl esters with aromatic sulfonic acids | |
| AT112730B (en) | Method of making medicinal products. | |
| DE955060C (en) | Process for the preparation of penicillin salts | |
| DE965405C (en) | Process for the production of drugs with an oxytocic and sympatholytic effect by reacting the diaethylamide of diaethylamino-acetic acid with physiologically compatible acids | |
| DE2156056C3 (en) | 3-tf ', 2'-diphenylethyl) -5- (2piperidino-ethyl) -1,2,4-oxadiazole-4-hydroxybenzoylbenzoate- (2), its preparation and preparations containing these compounds | |
| DE703879C (en) | Process for the preparation of organic mercury compounds | |
| DE629841C (en) | Process for the preparation of an aqueous quinine solution for injection purposes | |
| DE953344C (en) | Process for the preparation of a new isonicotinoyl hydrazone | |
| DE853794C (en) | Process for the preparation of penicillin compounds with extended action | |
| DE216267C (en) | ||
| DE859518C (en) | Process for the production of the sodium or calcium salt of penicillin, optionally in dissolved form, from the potassium salt | |
| DE1035155B (en) | Process for the preparation of therapeutically useful salts of 4,6-dioxyisophthalic acid | |
| AT153203B (en) | Process for the preparation of water-soluble mercury compounds. |