CH224791A - Process for the preparation of calcium d-pantothenic acid. - Google Patents
Process for the preparation of calcium d-pantothenic acid.Info
- Publication number
- CH224791A CH224791A CH224791DA CH224791A CH 224791 A CH224791 A CH 224791A CH 224791D A CH224791D A CH 224791DA CH 224791 A CH224791 A CH 224791A
- Authority
- CH
- Switzerland
- Prior art keywords
- pantothenic acid
- sodium
- calcium
- parts
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 3
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 title description 8
- 235000005939 calcium D-pantothenic acid Nutrition 0.000 title description 6
- 239000011680 calcium D-pantothenic acid Substances 0.000 title description 6
- GHOKWGTUZJEAQD-UHFFFAOYSA-N pantothenic acid Chemical compound OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims description 16
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 229940055726 pantothenic acid Drugs 0.000 claims description 8
- 235000019161 pantothenic acid Nutrition 0.000 claims description 8
- 239000011713 pantothenic acid Substances 0.000 claims description 8
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 12
- 239000000243 solution Substances 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 229910000019 calcium carbonate Inorganic materials 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940000635 beta-alanine Drugs 0.000 description 2
- 229940043430 calcium compound Drugs 0.000 description 2
- 150000001674 calcium compounds Chemical class 0.000 description 2
- -1 d-pantothenic acid ester Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 2
- 229940039790 sodium oxalate Drugs 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- NPHAVLULUWJQAS-UHFFFAOYSA-N 5,5-dimethyloxolan-2-one Chemical compound CC1(C)CCC(=O)O1 NPHAVLULUWJQAS-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100034130 Tumor necrosis factor alpha-induced protein 8-like protein 1 Human genes 0.000 description 1
- 101710177305 Tumor necrosis factor alpha-induced protein 8-like protein 1 Proteins 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007273 lactonization reaction Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Darstellung von d-pantothensaur em Caleium. Zur Gewinnung von d-pantothensaurem Calcium hat man d-Pantothensäureester durch Bariumhydroxyd verseift, :
das Bariumsalz durch Zusatz von Schwefelsäure in die freie Panthothensäure übergeführt und diese mit Calciumcarbonat neutralisiert (The Journal of th.e American Chemical Society, B@d. 62 (19401, S. 1789). Dieses Verfahren ist recht umständlich, besonders deshalb, weil es von d-Pantothensäureester ausgeht, der in :grösse ren Mengen schwierig herzustellen ist.
In zwischen ist es gelungen, :d-pantothensaures Natrium in sehr reiner Form durch Kond:en- sation von ss-Alanin in Natriumalkoholaten mit d(-)-a-Oxy-,B,ss-,dimethyl-butyrolakton zu gewinnen. Wenn man nun dieses reine Natriumsalz und anorganische Säunen für die Herstellung des d-pantothensauren Cal ciums verwendet, so macht man die Erfah rung,
dass sich das gebildete Natriumsalz der anorganischen Säure .schwer entfernen lässt. Versetzt man z. B. eine Lösung von d-panto- thensaurem Natrium in absolutem Alkohol mit der berechneten Menge absoluter, alkoho lischer Salzsäure, so ,scheidet sich das gebil- dete Kochsalz nicht quantitativ ab, so dass das aus der freigemachten Pantothensäure gewonnene Calciumsalz stets etwa 1/.1 bis 1/2 Prozent Kochsalz enthält.
Ausserdem lässt sich die auf :diese Weise in Freiheit gesetzte Pantothensäure nie quantitativ durch Cal ciumcarbonat neutralisieren, :da sich ein Teil der freien Säure unter der Wirkung der Mineralsäure verestert oder laktonisiert.
Es wurde nun gefunden, :dass man ein. reines d-pantothensaures Calcium erhalten kann, wenn man aus einer alkoholischen Lö sung von d-pantothensaurem Natrium die Pantothensäure mittels einer organischen Säure, z. B. Oxalsäure, deren Natriumsalz in Alkohol unlöslich ist, in Freiheit .setzt und die so in Freiheit .gesetzte d-Pantothensäure mit einer Calciumverbindung neutralisiert.
Wie Versuche ergaben, kann man :dabei das Natrium fast quantitativ entfernen, so dass im d-pantothensauren Calcium höchstens noch Spuren davon vorhanden sind. Ausserdem ist so die Gefahr der Veresterung oder Laktoni- sierung :der freien Pantothensäure, wie sich zeigte, geringer, so dass eine fast quantitative Umsetzung der aus dem Natriumsalz frei gemachten d-Pantothensäure mit der Cal ciumverbindung, z. B. mit Calciumcarbonat, erzielt werden kann.
Man kann bei der er- findungsgemässen Umwandlung des d-panto- thensauren Natriums in das d-pantothensaune Calcium von isoliertem d-pantothensauren Natrium ausgehen, ebensogut aber auch von einer Lösung, die aus ss-Alanin, Natrium- alkoholaten und d(-)-a-Oxy-ss,
ss-dimethyl- butyrolakton durch Kondensation entstande nes d-pantothensaures Natrium enthält.
Nach dem neuen Verfahren kann ein d-pantothensaures Calcium erhalten werden, das , eine Drehung von
EMI0002.0024
zeigt, in Nadeln kristallisiert und nicht hy- groskopisch ist, während das bisher bekannte Cal'ciumsalz eine Drehung von + 24' zeigt und ein microkristallines Pulver darstellt.
Das Verfahrenserzeugnis soll als Arznei mittel verwendet werden. <I>Beispiel 1:</I> Zu einer Lösung von d-pantothensaumm Natrium (welches durch Umsetzung einer Lösung von 356 Teilen ss-Alanin in der be rechneten Menge Natriummethylat durch ge lindes Erwärmen mit 520 Teilen d(-)-a- Oxy-ss,ss-dimethylbutyrolakton bei einer Tem peratur von<B>25-30'</B> nach ein- bis zweitägi gem Stehen und Abdampfen des Methylalko hols im Vakuum erhalten wurde)
in 3000 Tei len absolutem Alkohol gibt man eine Lösung von 190 Teilen wasserfreier Oxalsäure in 2000 Teilen absolutem Alkohol hinzu. Das ausgefallene Natriumoxalat wird entfernt und die alkohol-isehe Lösung der freien Pan- tothensäure mit 3000 Teilen Wasser und 250 Teilen Calciumcarbonat versetzt.
Man dampft den Alkohol im Vakuum bei einer Badtemperatur von 50 ab und entfernt das überschüssige Calciumcarbonat nach Beendi gung der Unisetzung durch Filtration. Ver braucht werden 193 Teile = 98 % der Theo rie. Die wässerige Lösung des d-pantothen- sauren Calciums wird im Vakuum zum dicken Sirup eingedampft.
Dieser Sirup wird in 8000 Teilen absolutem Alkohol aufgenom- men und die Lösung schwach erwärmt, -wor auf d-pantothensaures Caleium macrokristal- linisch ausfällt. Man saugt ab, wäscht mit Alkohol und trocknet das Salz: Die Ausbeute beträgt 814 Teile = 85,4% der Theorie; in Wasser. Aua der Mutter
EMI0002.0072
lauge können noch weitere Mengen des Cal ciumsalzes enthalten werden.
<I>Beispiel 2:</I> Man löst 48,2 Teile d-pantothensaures Na trium durch gelindes Erwärmen in 200 Tei len absolutem Alkohol auf und fällt das Na trium durch Zusatz einer Lösung von 10 Tei len wasserfreier Oxalsäure in 50 Teilen abso lutem Alkohol aus. Nach der Entfernung des Natriumoxalates versetzt man das Filtrat mit Wasser und neutralisiert die Pantothensäure durch Zusatz von <RTI
ID="0002.0090"> Caleiumearbonat. So wie die Umsetzung beendet ist, wird das überschüs sige Caleiumearbonat erbfiltriert und die wäs- serige Lösung im Vakuum eingedampft.
Das zurückbleibende sirupartige Salz wird in 300 Teilen absolutem Alkohol bei<B>50'</B> ge löst und angeimpft, worauf rasche Kristalli- sation eintritt: Man erhält das im Beispiel 1 beschriebene Salz. Die Ausbeute beträgt 40,4 Teile - 84;9 i' o der Theorie;
EMI0002.0112
EMI0002.0113
in Wasser.
Method for the preparation of d-pantothensaur em Caleium. To obtain calcium d-pantothenic acid, d-pantothenic acid ester was saponified with barium hydroxide:
the barium salt is converted into the free pantothenic acid by adding sulfuric acid and this is neutralized with calcium carbonate (The Journal of the American Chemical Society, B @ d. 62 (19401, p. 1789). This process is quite cumbersome, especially because it starts from d-pantothenic acid ester, which is difficult to manufacture in larger quantities.
In the meantime we have succeeded in obtaining: d-pantothenic acid sodium in a very pure form by condensing ss-alanine in sodium alcoholates with d (-) - a-oxy-, B, ss-, dimethyl-butyrolactone. If one now uses this pure sodium salt and inorganic acids for the production of d-pantothenic acid calcium, one has the experience
that the formed sodium salt of the inorganic acid is difficult to remove. If you move z. B. a solution of sodium d-pantothenic acid in absolute alcohol with the calculated amount of absolute, alcoholic hydrochloric acid, the formed salt does not separate quantitatively, so that the calcium salt obtained from the liberated pantothenic acid always about 1 / . Contains 1 to 1/2 percent table salt.
In addition, the pantothenic acid released in this way can never be quantitatively neutralized by calcium carbonate, because part of the free acid is esterified or lactonized under the action of the mineral acid.
It has now been found: that one. pure calcium d-pantothenic acid can be obtained if the pantothenic acid is obtained from an alcoholic solution of sodium d-pantothenic acid by means of an organic acid, e.g. B. releases oxalic acid, the sodium salt of which is insoluble in alcohol, and neutralizes the d-pantothenic acid released in this way with a calcium compound.
Experiments have shown that you can: remove the sodium almost quantitatively, so that at most traces of it are still present in the d-pantothenic acid calcium. In addition, the risk of esterification or lactonization: the free pantothenic acid, as has been shown, is lower, so that an almost quantitative conversion of the d-pantothenic acid released from the sodium salt with the calcium compound, e.g. B. with calcium carbonate can be achieved.
In the case of the conversion of sodium d-pantothenic acid into calcium d-pantothenic acid according to the invention, one can start from isolated sodium d-pantothenic acid, but just as well from a solution consisting of .s-alanine, sodium alcoholates and d -a-Oxy-ss,
contains ss-dimethylbutyrolactone produced by condensation of d-pantothenic acid sodium.
According to the new process, a calcium d-pantothenic acid can be obtained that, a rotation of
EMI0002.0024
shows, is crystallized in needles and is not hygroscopic, while the calcium salt known up to now shows a rotation of + 24 'and is a microcrystalline powder.
The process product should be used as a medicinal product. <I> Example 1: </I> To a solution of d-pantothensaumm sodium (which is obtained by reacting a solution of 356 parts of ss-alanine in the calculated amount of sodium methylate by gentle heating with 520 parts of d (-) - a- Oxy-ss, ss-dimethylbutyrolactone at a temperature of <B> 25-30 '</B> after one to two days standing and evaporation of the methyl alcohol in a vacuum)
in 3000 parts of absolute alcohol are added a solution of 190 parts of anhydrous oxalic acid in 2000 parts of absolute alcohol. The precipitated sodium oxalate is removed and 3000 parts of water and 250 parts of calcium carbonate are added to the alcoholic solution of the free pantothenic acid.
The alcohol is evaporated off in vacuo at a bath temperature of 50 and the excess calcium carbonate is removed by filtration after completion of the dissolution. 193 parts are used = 98% of the theory. The aqueous solution of calcium d-pantothenic acid is evaporated to a thick syrup in vacuo.
This syrup is taken up in 8000 parts of absolute alcohol and the solution is warmed up slightly, which precipitates macrocrystalline on d-pantothenic acid Caleium. It is filtered off with suction, washed with alcohol and the salt is dried: the yield is 814 parts = 85.4% of theory; in water. Ouch the mother
EMI0002.0072
lye can also contain additional amounts of the calcium salt.
<I> Example 2: </I> 48.2 parts of sodium d-pantothenic acid are dissolved by gentle heating in 200 parts of absolute alcohol and the sodium is precipitated by adding a solution of 10 parts of anhydrous oxalic acid in 50 parts of absolute pure alcohol. After the sodium oxalate has been removed, water is added to the filtrate and the pantothenic acid is neutralized by adding <RTI
ID = "0002.0090"> Caleium carbonate. As soon as the reaction has ended, the excess calcium carbonate is filtered off and the aqueous solution is evaporated in vacuo.
The remaining syrupy salt is dissolved in 300 parts of absolute alcohol at <B> 50 '</B> and inoculated, whereupon rapid crystallization occurs: The salt described in Example 1 is obtained. The yield is 40.4 parts - 84; 9 i 'o of theory;
EMI0002.0112
EMI0002.0113
in water.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH224791T | 1941-09-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH224791A true CH224791A (en) | 1942-12-15 |
Family
ID=4453723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH224791D CH224791A (en) | 1941-09-01 | 1941-09-01 | Process for the preparation of calcium d-pantothenic acid. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH224791A (en) |
-
1941
- 1941-09-01 CH CH224791D patent/CH224791A/en unknown
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