CH262429A - Process for the production of an optically active acid. - Google Patents
Process for the production of an optically active acid.Info
- Publication number
- CH262429A CH262429A CH262429DA CH262429A CH 262429 A CH262429 A CH 262429A CH 262429D A CH262429D A CH 262429DA CH 262429 A CH262429 A CH 262429A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- sep
- ester
- optically active
- bisdehydro
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 17
- 238000000034 method Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000002148 esters Chemical class 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- -1 (-) -Menthyl Chemical group 0.000 claims description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims 1
- 239000000344 soap Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- PDRGHUMCVRDZLQ-UHFFFAOYSA-N d-equilenin Natural products OC1=CC=C2C(CCC3(C4CCC3=O)C)=C4C=CC2=C1 PDRGHUMCVRDZLQ-UHFFFAOYSA-N 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- PDRGHUMCVRDZLQ-WMZOPIPTSA-N equilenin Chemical compound OC1=CC=C2C(CC[C@]3([C@H]4CCC3=O)C)=C4C=CC2=C1 PDRGHUMCVRDZLQ-WMZOPIPTSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
- C07C51/493—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification whereby carboxylic acid esters are formed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung einer optisch aktiven Säure. Es wurde gefunden, dass man. zu einer optisch aktiven Säure gelangen kann, wenn man raceniisclie ri-7-Metliy 1-bisdeliydro-doisy - nolsäure bzw. ein Säurederivat derselben durch Behandlung mit einem optisch aktiven Alko hol bzw. einem Ester eines solchen verestert, die so erhaltenen Ester in die beiden Diastereo isomeren trennt und anschliessend im Ester der (-)-n-7-Methyl-bisdeliydro-doisynolsäiire die veresterte Carboxy lgruppe verseift.
Die Veresterung wird beispielsweise < luiTh I@rliitzen des Säureehlorids, -bromids oder -jodids mit einem optisch aktiven Alkohol, wie z. B. d- oder 1-Menthol, Borneol oder Ter- pineol, durchgeführt. Die dabei gebildeten beiden diastereoineren optisch aktiven Ester lassen sich z. B. durch fraktionierte Kristalli sation oder Chromatographie rein gewinnen.
Die Hydrolyse der veresterten Carboxyl- gruppe kann in üblicher Weise mittels Alka- lien oder Säuren durchgeführt werden.
Die so erhaltene (-)-n-7-Methyl-bisdehy- dro-doisynolsäure vom F. 2l_7-219 und der Drehung
EMI0001.0032
ist schon be kannt und soll als Heilmittel Verwendung finden.
Beispiel: 8 Gewichtsteile raeemisches n-7-Methyil- bisdehydro - doisynolsäure - Chlorid (erhalten z. B. aus dein bei 228-2300 schmelzenden Methyläther der racemisclien n-Bisdehydro- doisynolsäure vom F. 2040 und Oxally lchlorid) werden mit der Bleiehen Menge 1-Mentliol einige Stunden unter Stiekstoff auf 100-1100 erhitzt.
Der entstehende Chlorwasserstoff wird durch den Stickstoffstrom aus dem Reak- tionsgemiseh entfernt.
Die erkaltete Schmelze kristallisiert beim Anreiben mit Methanol sofort. Sie wird fein pulverisiert und zwecks Entfernung von über schüssigem Menthol mit wenig Methanol ge waschen. Hierauf löst man in möglichst wenig heissem absolutem Aeeton und lässt bei 200 kristallisieren.
Die so erhaltene erste Kristall fraktion besteht: aus fast reinem (-)-1Tent.hyl- (-f-) -11 - 7 - methy 1- bisdehydro - doisy nolsäure- ester.Aus den auf 30 Volumenteile eingeengten Mutterlaugen ergibt sieh eine .zweite Kristall fraktion von annähernd gleicher Zusammen- set.#ruii_#- wie das erste Kristallisat. Beide Frak tionen werden zusammen erneut aus absolu tem Aceton umkristallisiert.
Man gewinnt auf diese Weise den reinen (-)-Menthyl-(-(-)-n- 7-methyl-bisdehydro-doisynolsä.ure-ester vom F. 163-16.1 Und der Drehung
EMI0001.0068
--
EMI0001.0069
(Essigester, e = 1,18).
Zur Gewinnung des (-)-Menthyl-(-)-n- 7 - inethyl - bisdehydro - doisynolsäure - esters wird die Mutterlauge der zweiten Kristallisa tion zur Trockne eingedampft und der Rück stand aus 450 Volumenteilen Methanol um gelöst. Man erhält farblose Kristalle vom F. 112" und der Drehung
EMI0001.0077
1,5 .
Die beiden diaster eoisomeren Menthyl- ester vom F. 163-1640 bzw. 1120 können z. B. durch einstündiges Erhitzen auf 1650 in einer Schmelze, die auf 1. Gewiehtsteil Ester, 2,5 Gewichtsteile Kaliumhydroxyd und 8 Volu menteile Propylalkohol enthält, verseift wer den. Es tritt dabei keine Racemisierung auf.
Auch ausgehend von weitgehend angereicher ten Säuren, die durch Verseifung nicht völ lig reiner Menthylester erhalten werden, kön nen durch ein- bis dreimalige Rekristallisa- tion aus Methanol-Wasser-Gemischen die rei nen Antipoden gewonnen werden. Die so gebildeten (-[-)-n-7-Methyl-bisdehydro-doisy- nolsäure und (-)-n-7-Methyl-bisdehydro- doisynolsäure haben die folgenden.
Eigen schaften
EMI0002.0013
rechtsdrehende <SEP> Säure <SEP> linksdrehende <SEP> Säure
<tb> Schmelzpunkt <SEP> 218-220 <SEP> 217-219
<tb> 22
<tb> 100,"0 <SEP> -f- <SEP> 1,5 <SEP> Alkohol <SEP> c <SEP> 1, <SEP> 13 <SEP> - <SEP> <B>99>5<U>+</U></B> <SEP> 1,5
<tb> = <SEP> Alkohol <SEP> c <SEP> = <SEP> 0,92
<tb> 5280 <SEP> + <SEP> 138 <SEP> <SEP> 1,5 <SEP> - <SEP> 135 <SEP> <SEP> 2,0
<tb> [a]
<tb> Schwellenwert <SEP> ca. <SEP> 15 <SEP> <I>r</I> <SEP> ca.
<SEP> 0,05 <SEP> <I>r</I> Die linksdrehende Säure ergibt keine Schmelz- piuikterniedrigLuig im Gemisch mit dem Methyläther der durch Kalischmelze von d-Equilenin gewonnenen n-Bisdehydro-doisy- nolsäure.
Process for the production of an optically active acid. It was found that one. can arrive at an optically active acid if one raceniisclie ri-7-Metliy 1-bisdeliydro-doisy - nolic acid or an acid derivative thereof by treatment with an optically active alcohol or an ester of such esterified the ester thus obtained into the separates the two diastereoisomers and then saponifies the esterified carboxyl group in the ester of (-) - n-7-methyl-bisdeliydro-doisynolic acid.
The esterification is carried out, for example, of the acid chloride, bromide or iodide with an optically active alcohol, such as. B. d- or 1-menthol, borneol or terpeneol performed. The two diastereoisomeric optically active esters formed can be z. B. win pure by fractional crystallization or chromatography.
The hydrolysis of the esterified carboxyl group can be carried out in the customary manner by means of alkalies or acids.
The (-) - n-7-methyl-bisdehydro-doiso-nolic acid obtained in this way from F. 2l_7-219 and the rotation
EMI0001.0032
is already known and should be used as a remedy.
Example: 8 parts by weight of chemical n-7-methyl bisdehydro doisynolic acid chloride (obtained, for example, from the methyl ether of racemisclien n-bisdehydro doisynolic acid of F. 2040 and oxallyl chloride, which melts at 228-2300) with the lead amount 1-Mentliol heated to 100-1100 under nitrogen for a few hours.
The hydrogen chloride formed is removed from the reaction mixture by the stream of nitrogen.
The cooled melt crystallizes immediately when rubbed with methanol. It is finely pulverized and washed with a little methanol to remove excess menthol. Then dissolve in as little hot absolute aeetone as possible and allow to crystallize at 200.
The first crystal fraction obtained in this way consists of almost pure (-) - 1Tent.hyl- (-f-) -11 - 7 - methy 1- bisdehydro - doisy nolsäure- ester. From the mother liquors, concentrated to 30 parts by volume, you get one. second crystal fraction of approximately the same composition. # ruii _ # - like the first crystallizate. Both fractions are recrystallized together again from absolute acetone.
In this way the pure (-) - menthyl - (- (-) - n- 7-methyl-bisdehydro-dooisynolic acid ester of F. 163-16.1 and the rotation
EMI0001.0068
-
EMI0001.0069
(Ethyl acetate, e = 1.18).
To obtain the (-) - menthyl - (-) - n- 7 - ynethyl - bisdehydro - doisynolic acid - ester, the mother liquor from the second crystallization is evaporated to dryness and the residue is dissolved from 450 parts by volume of methanol. Colorless crystals from F. 112 "and the rotation are obtained
EMI0001.0077
1.5.
The two diaster eoisomeric menthyl esters of F. 163-1640 and 1120 can, for. B. by one hour heating to 1650 in a melt containing the 1st part by weight of ester, 2.5 parts by weight of potassium hydroxide and 8 parts by volume of propyl alcohol, saponified who the. There is no racemization.
Even starting from largely enriched acids, which are not completely pure menthyl esters obtained by saponification, the pure antipodes can be obtained by recrystallizing one to three times from a methanol-water mixture. The thus formed (- [-) - n-7-methyl-bisdehydro-doisynolic acid and (-) - n-7-methyl-bisdehydro-dooisynolic acid have the following.
Characteristics
EMI0002.0013
clockwise <SEP> acid <SEP> counter-clockwise <SEP> acid
<tb> Melting point <SEP> 218-220 <SEP> 217-219
<tb> 22
<tb> 100, "0 <SEP> -f- <SEP> 1,5 <SEP> alcohol <SEP> c <SEP> 1, <SEP> 13 <SEP> - <SEP> <B> 99> 5 < U> + </U> </B> <SEP> 1.5
<tb> = <SEP> alcohol <SEP> c <SEP> = <SEP> 0.92
<tb> 5280 <SEP> + <SEP> 138 <SEP> <SEP> 1.5 <SEP> - <SEP> 135 <SEP> <SEP> 2.0
<tb> [a]
<tb> Threshold value <SEP> approx. <SEP> 15 <SEP> <I> r </I> <SEP> approx.
<SEP> 0.05 <SEP> <I> r </I> The levorotatory acid does not result in a melting point low in the mixture with the methyl ether of the n-bisdehydro-doisynolic acid obtained by potash melting of d-equilenin.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH262429T | 1946-04-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH262429A true CH262429A (en) | 1949-06-30 |
Family
ID=4474356
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH262429D CH262429A (en) | 1946-04-30 | 1946-04-30 | Process for the production of an optically active acid. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH262429A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5113048A (en) * | 1989-12-15 | 1992-05-12 | Crest Electronics | Pneumatically actuated hospital signaling device |
-
1946
- 1946-04-30 CH CH262429D patent/CH262429A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5113048A (en) * | 1989-12-15 | 1992-05-12 | Crest Electronics | Pneumatically actuated hospital signaling device |
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