EP0000476B1 - Process for the preparation of cyclopentadecanolide - Google Patents
Process for the preparation of cyclopentadecanolide Download PDFInfo
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- EP0000476B1 EP0000476B1 EP78100237A EP78100237A EP0000476B1 EP 0000476 B1 EP0000476 B1 EP 0000476B1 EP 78100237 A EP78100237 A EP 78100237A EP 78100237 A EP78100237 A EP 78100237A EP 0000476 B1 EP0000476 B1 EP 0000476B1
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- acid
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- cyclopentadecanolide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D315/00—Heterocyclic compounds containing rings having one oxygen atom as the only ring hetero atom according to more than one of groups C07D303/00 - C07D313/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
Definitions
- the invention relates to a process for the preparation of cyclopentadecanolide.
- Cyclopentadecanolide is a natural musk fragrance.
- Various processes are known for its production, but they have a number of disadvantages, in particular that they only give low yields and that the starting materials are not easily accessible.
- 15-hydroxypentadecanoic acid is cyclized by vacuum distillation of its polyester [J. At the. Chem. Soc. 58, 654 (1936)].
- This process has the disadvantage that the starting materials for the preparation of 15-hydroxy-pentadecanoic acid, such as 9,10,16-trihydroxy-hexadecanecarboxylic acid (J. Chem. Soc. 1963, 3505), erucyl alcohol (J. Chem. Soc. 1962, 2348), Undec-10-enoic acid [Tetrahedron 19, 905 (1963); Japanese patent application 68 04 262] are too expensive for an economical process or are not available in sufficient quantities.
- the Russian inventor's certificate 521 274 describes a process in which 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] with butyl nitrite / NaHS0 3 is converted into the 12-keto-cyclopentadecanolide and this is followed Clemmensen is reduced to cyclopentadecanolide.
- the yield of cyclopentadecanolide in this process is only 36%, as can be seen from the examples.
- the reaction time of 90 hours spent on the Clemmensen reduction is technically unsustainable.
- the invention is therefore based on the object of developing a process which, starting from the easily accessible 13-oxa-bicyclo [10.4.0] hexadecene [1 (12)], gives cyclopentadecanolide in high purity and avoiding complex process steps .
- the process according to the invention although it opens the macrocycle, yields much better yields than the known processes, which likewise use 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] go out and in which the macrocycle is maintained in all reaction steps.
- cyclopentadecanolide of high purity is obtained in yields of 75 to 85% of theory, based on 13-oxa-bicyclo [10.4.0] hexadecene [1 (12)], with process steps which can be carried out without any technical effort.
- the hydrazone can be reduced according to Wolff-Kishner with sodium or a sodium alcoholate, the ketone according to Huang-Minlon with hydrazine in the presence of sodium or potassium hydroxide with simultaneous cleavage of the lactone ring to 15-hydroxypentadecanoic acid.
- the 12-oximino-cyclopentadecanolide is immediately, ie without saponifying to the ketone, reduced with an excess of hydrazine hydrate in the presence of alkali hydroxide with cleavage of the lactone ring to 15-hydroxypentadecanoic acid.
- the reducing cleavage is carried out by heating the mixture of oxime, hydrazine and alkali hydroxide in a higher-boiling organic solvent, such as ethylene or diethylene glycol, to temperatures of 150 to 200 ° C.
- the hydrazine: 12-oximinocyclopentadecanolide molar ratio should be between 1.5-3: 1.
- Hydrazine is preferably used in the form of 80% hydrazine hydrate.
- Sodium or potassium hydroxide is preferably used as the alkali hydroxide.
- the molar ratio of alkali metal hydroxide: 12-oximinocyclopentadecanolide is advantageously 3-5: 1.
- the 15-hydroxypentadecanoic acid can be cyclized by the customary processes known from the literature for the preparation of lactones from hydroxycarboxylic acids.
- the above-mentioned method by Spanagel and Carothers [J. At the. Chem. Soc. 58, 654 (1936)], in which a linear polyester is first prepared from 15-hydroxypentadecanoic acid, which is then depolymerized in the presence of a depolymerization catalyst such as magnesium chloride, magnesium oxide, lead dioxide, etc.
- reaction mixture was mixed with one liter of ice water and acidified to pH 2 with hydrochloric acid.
- the precipitated reaction product was extracted with ethyl acetate while hot. When the warm ethyl acetate solution cooled, the product crystallized again. The product is separated and dried.
- Example 4 50 g of 12-keto-cyclopentadecanolide (prepared according to Example 4) were treated with 36.6 g of 80% hydrazine hydrate and 54.7 g of potassium hydroxide in 150 ml of diethylene glycol among those in Example 3 implemented reaction conditions.
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Description
Die Erfindung betrifft ein Verfahren zur Herstellung von Cyclopentadecanolid.The invention relates to a process for the preparation of cyclopentadecanolide.
Cyclopentadecanolid ist ein natürlicher Moschus-Riechstoff. Zu seiner Herstellung sind verschiedene Verfahren bekannt, die jedoch eine Reihe von Nachteilen aufweisen, insbesondere, dass sie lediglich geringe Ausbeuten ergeben, und dass die Ausgangsmaterialien nicht leicht zugänglich sind.Cyclopentadecanolide is a natural musk fragrance. Various processes are known for its production, but they have a number of disadvantages, in particular that they only give low yields and that the starting materials are not easily accessible.
Von wirtschaftlichem Interesse sind lediglich zwei Verfahren. Bei dem in der DE-AS 2 026 056 beschriebenen Verfahren wird das gemäss DE-AS 2 136 496 aus Cyclododecanon leicht zugängliche 13-Oxa-bicyclo[10.4.0]-hexadecen-[1 (12)] mit Wasserstoffperoxid oder einem Alkylhydroperoxid in ein Peroxid überführt, dieses entweder thermisch oder durch Bestrahlung mit UV-Licht in ein Gemisch aus Cyclopentadecanolid und Cyclopentadecenolid gespalten und das Gemisch hydriert. Das Verfahren hat den Nachteil, dass das Arbeiten mit Peroxiden besondere Vorsichtsmassnahmen erfordert und dass die Ausbeute an Cyclopentadecanolid nur höchstens 57,9%, bezogen auf 13-Oxa-bicyclo[10.4.0]-hexa- decen-[1 (12)], beträgt.Only two processes are of economic interest. In the process described in DE-AS 2 026 056, 13-oxa-bicyclo [10.4.0] -hexadecen- [1 (12)], which is easily accessible according to DE-AS 2 136 496 from cyclododecanone, is reacted with hydrogen peroxide or an alkyl hydroperoxide transferred a peroxide, split it either thermally or by irradiation with UV light into a mixture of cyclopentadecanolide and cyclopentadecenolide and the mixture was hydrogenated. The process has the disadvantage that working with peroxides requires special precautionary measures and that the yield of cyclopentadecanolide is only at most 57.9%, based on 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] , is.
Bei dem zweiten Verfahren wird 15-Hydroxy- pentadecansäure durch Vakuumdestillation ihres Polyesters cyclisiert [J. Am. Chem. Soc. 58, 654 (1936)]. Dieses Verfahren hat den Nachteil, dass die Ausgangsmaterialien zur Herstellung der 15-Hydroxy-pentadecansäure, wie 9,10,16-Trihydroxy-hexadecancarbonsäure (J. Chem. Soc. 1963, 3505), Erucylalkohol (J.Chem. Soc. 1962, 2348), Undec-10-ensäure [Tetrahedron 19, 905 (1963); Japanische Patentanmeldung 68 04 262] für ein wirtschaftliches Verfahren zu teuer sind oder nicht in ausreichender Menge zur Verfügung stehen.In the second process, 15-hydroxypentadecanoic acid is cyclized by vacuum distillation of its polyester [J. At the. Chem. Soc. 58, 654 (1936)]. This process has the disadvantage that the starting materials for the preparation of 15-hydroxy-pentadecanoic acid, such as 9,10,16-trihydroxy-hexadecanecarboxylic acid (J. Chem. Soc. 1963, 3505), erucyl alcohol (J. Chem. Soc. 1962, 2348), Undec-10-enoic acid [Tetrahedron 19, 905 (1963); Japanese patent application 68 04 262] are too expensive for an economical process or are not available in sufficient quantities.
In dem russischen Erfinderschein 521 274 wird ein Verfahren beschrieben, bei dem 13-Oxa-bicy- clo[10.4.0]-hexadecen-[1 (12)] mit Butylnitrit/ NaHS03 in das 12-Keto-cyclopentadecanolid übergeführt und dieses nach Clemmensen zum Cyclopentadecanolid reduziert wird. Die Ausbeute an Cyclopentadecanolid beträgt bei diesem Verfahren jedoch nur 36% wie aus den Beispielen hervorgeht. Ausserdem ist die für die Clemmensen-Reduktion aufgewendete Reaktionszeit von 90 Stunden technisch nicht tragbar.The Russian inventor's certificate 521 274 describes a process in which 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] with butyl nitrite / NaHS0 3 is converted into the 12-keto-cyclopentadecanolide and this is followed Clemmensen is reduced to cyclopentadecanolide. However, the yield of cyclopentadecanolide in this process is only 36%, as can be seen from the examples. In addition, the reaction time of 90 hours spent on the Clemmensen reduction is technically unsustainable.
Der Erfindung liegt daher die Aufgabe zugrunde, ein Verfahren zu entwickeln, das ausgehend vom leicht zugänglichen 13-Oxa-bicyclo[10.4.0]-hexadecen-[1(12)] in guten Ausbeuten und unter Vermeidung aufwendiger Verfahrensschritte Cyclopentadecanolid in hoher Reinheit liefert.The invention is therefore based on the object of developing a process which, starting from the easily accessible 13-oxa-bicyclo [10.4.0] hexadecene [1 (12)], gives cyclopentadecanolide in high purity and avoiding complex process steps .
Diese Aufgabe wird erfindungsgemäss dadurch gelöst, dass man 13-Oxa-bicyclo[10.4.0]-hexadecen-[1(12)] in an sich bekannter Weise in ein Lacton der allgemeinen Formel
- X ein Sauerstoffatom, die Gruppe = NOH oder =N-NH2 bedeutet,
- das Lacton der allgemeinen Formel I unter Öffnung des Lactonringes zur 15-Hydroxypentadecansäure reduziert und diese in an sich bekannter Weise zum Cyclopentadecanolid cyclisiert.
- X is an oxygen atom, the group = NOH or = N-NH 2 ,
- the lactone of the general formula I is reduced to 15-hydroxypentadecanoic acid while opening the lactone ring and cyclized to cyclopentadecanolide in a manner known per se.
Überraschenderweise werden bei dem erfindungsgemässen Verfahren, obwohl bei diesem eine Öffnung des Macrozyclus erfolgt, wesentlich bessere Ausbeuten erhalten als bei den bekannten Verfahren, die ebenfalls vom 13-Oxa-bi- cycio[10.4.0]-hexadecen-[1(12)] ausgehen und bei denen der Macrozyclus in allen Reaktionsschritten erhalten bleibt. Mit Hilfe des erfindungsgemässen Verfahrens wird mit technisch ohne Aufwand durchführbaren Verfahrensschritten Cyclopentadecanolid hoher Reinheit in Ausbeuten von 75 bis 85% der Theorie, bezogen auf 13-Oxa-bicyclo[10.4.0]-hexadecen-[1(12)] erhalten.Surprisingly, the process according to the invention, although it opens the macrocycle, yields much better yields than the known processes, which likewise use 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] go out and in which the macrocycle is maintained in all reaction steps. With the aid of the process according to the invention, cyclopentadecanolide of high purity is obtained in yields of 75 to 85% of theory, based on 13-oxa-bicyclo [10.4.0] hexadecene [1 (12)], with process steps which can be carried out without any technical effort.
Die Überführung des 13-Oxa-bicyclo[10.4.0]-hexadecen-[1 (12)] in ein Lacton der allgemeinen Formel I, in der X für ein Sauerstoffatom steht, kann wie in der DE-OS 2 410 859 beschrieben durch Ozonolyse der Doppelbindung oder entsprechend J.Org.Chem. 37, 581 (1972) mit einem Überschuss einer Persäure erfolgen.The conversion of 13-oxa-bicyclo [10.4.0] hexadecen- [1 (12)] into a lactone of the general formula I, in which X represents an oxygen atom, can be carried out as described in DE-OS 2 410 859 Ozonolysis of the double bond or according to J.Org.Chem. 37, 581 (1972) with an excess of a peracid.
Zur Überführung des 13-Oxa-bicyclo[10.4.0]-hexadecen-[1 (12)] in ein Lacton der allgemeinen Formel 1, in der X für die Gruppe =NOH steht, hat es sich als vorteilhaft erwiesen, 13-Oxa-bicy- clo[10.4.0]-hexadecen-[1(12)] gemäss J.C.S. Chem. Comm. 1972, 1078 mit Nitrosylchlorid oder mit unter den Reaktionsbedingungen Nitrosyl-Ionen bildenden Stickstoffverbindungen, wie Alkylnitriten oderAlkalinitriten, umzusetzen.For the conversion of 13-oxa-bicyclo [10.4.0] -hexadecen- [1 (12)] into a lactone of the general formula 1, in which X represents the group = NOH, it has proven advantageous to use 13-oxa -bicy- clo [10.4.0] -hexadecen- [1 (12)] according to JCS Chem. Comm. 1972, 1078 with nitrosyl chloride or with nitrogen compounds forming nitrosyl ions under the reaction conditions, such as alkyl nitrites or alkali nitrites.
Das entstandene 12-Oximinocyclopentadecanolid kann anschliessend in an sich bekannter Weise, z.B. mit Natriumhydrogensulfit, zum 12-Ketocyclopentadecanolid, d.h. einer Verbindung der allgemeinen Formel I, in der X für das Sauerstoffatom steht, hydrolisiert werden oder mit Hydrazinhydrat in das entsprechende Hydrazon, d.h. eine Verbindung der allgemeinen Formel I, in der X für die =NNH2-Gruppe steht, umgewandelt werden. Das Hydrazon lässt sich nach Wolff-Kishner mit Natrium oder einem Natriumalkoholat, das Keton nach Huang-Minlon mit Hydrazin in Gegenwart von Natrium- oder Kaliumhydroxid unter gleichzeitiger Spaltung des Lactonringes zur 15-Hydroxypentadecansäure reduzieren.The resulting 12-oximinocyclopentadecanolide can then be hydrolyzed in a manner known per se, for example with sodium hydrogen sulfite, to give 12-ketocyclopentadecanolide, ie a compound of the general formula I in which X represents the oxygen atom, or with hydrazine hydrate in the corresponding hydrazone, ie one Compound of the general formula I in which X represents the = NNH 2 group are converted. The hydrazone can be reduced according to Wolff-Kishner with sodium or a sodium alcoholate, the ketone according to Huang-Minlon with hydrazine in the presence of sodium or potassium hydroxide with simultaneous cleavage of the lactone ring to 15-hydroxypentadecanoic acid.
In einer besonders bevorzugten Ausführungsform des erfindungsgemässen Verfahrens wird jedoch das 12-Oximino-cyclopentadecanolid unmittelbar, d.h. ohne es zum Keton zu verseifen, mit einem Überschuss an Hydrazinhydrat in Gegenwart von Alkalihydroxid unter Spaltung des Lactonringes zur 15-Hydroxypentadecansäure reduziert. Die reduzierende Spaltung erfolgt durch Erwärmen der Mischung von Oxim, Hydrazin und Alkalihydroxid in einem höher siedenden organischen Lösungsmittel, wie Äthylen- oder Diäthylenglykol, auf Temperaturen von 150 bis 200°C.In a particularly preferred embodiment of the process according to the invention, however, the 12-oximino-cyclopentadecanolide is immediately, ie without saponifying to the ketone, reduced with an excess of hydrazine hydrate in the presence of alkali hydroxide with cleavage of the lactone ring to 15-hydroxypentadecanoic acid. The reducing cleavage is carried out by heating the mixture of oxime, hydrazine and alkali hydroxide in a higher-boiling organic solvent, such as ethylene or diethylene glycol, to temperatures of 150 to 200 ° C.
Das Molverhältnis Hydrazin:12-Oximinocyclopentadecanolid sollte zwischen 1,5-3:1 liegen. Hydrazin wird vorzugsweise in Form von 80%igem Hydrazinhydrat eingesetzt. Als Alkalihydroxid werden vorzugsweise Natrium- oder Kaliumhydroxid verwendet. Das Molverhältnis Alkalihydroxid: 12-Oximinocyclopentadecanolid beträgt vorteilhaft 3-5:1.The hydrazine: 12-oximinocyclopentadecanolide molar ratio should be between 1.5-3: 1. Hydrazine is preferably used in the form of 80% hydrazine hydrate. Sodium or potassium hydroxide is preferably used as the alkali hydroxide. The molar ratio of alkali metal hydroxide: 12-oximinocyclopentadecanolide is advantageously 3-5: 1.
Grundsätzlich ist es möglich, ausser Oxim und Hydrazon auch andere Azomethinderivate des 12-Ketocyclopentadecanolids, z.B. das Semicarbazon oder substituiertes Phenylhydrazone nach Wolff-Kishner oder Huang-Minlon zur 15-Hydroxypentadecansäure zu reduzieren. Diese Derivate bieten jedoch keine Vorteile gegenüber Oxim oder Hydrazon, sondern erfordern lediglich einen zusätzlichen Verfahrensschritt.In principle, it is possible, in addition to oxime and hydrazone, to use other azomethine derivatives of 12-ketocyclopentadecanolide, e.g. to reduce the semicarbazone or substituted phenylhydrazone according to Wolff-Kishner or Huang-Minlon to 15-hydroxypentadecanoic acid. However, these derivatives offer no advantages over oxime or hydrazone, but only require an additional process step.
Die Cyclisierung der 15-Hydroxypentadecansäure kann nach den üblichen, aus der Literatur bekannten Verfahren zur Herstellung von Lactonen aus Hydroxycarbonsäuren erfolgen. Als besonders vorteilhaft hat sich die vorstehend genannte Methode von Spanagel und Carothers [J. Am. Chem. Soc. 58, 654 (1936)] erwiesen, bei der zunächst aus 15-Hydroxypentadecansäure ein linearer Polyester hergestellt wird, der dann in Gegenwart eines Depolymerisationskatalysators, wie Magnesiumchlorid, Magnesiumoxid, Bleidioxid usw. depolymerisiertwird.The 15-hydroxypentadecanoic acid can be cyclized by the customary processes known from the literature for the preparation of lactones from hydroxycarboxylic acids. The above-mentioned method by Spanagel and Carothers [J. At the. Chem. Soc. 58, 654 (1936)], in which a linear polyester is first prepared from 15-hydroxypentadecanoic acid, which is then depolymerized in the presence of a depolymerization catalyst such as magnesium chloride, magnesium oxide, lead dioxide, etc.
Da in dem erfindungsgemässen Verfahren praktisch alle Zwischenprodukte und das Endprodukt kristallin anfallen, ist eine Reinigung auf jeder Stufe möglich. Auf diese Weise wird das Endprodukt in hoher Reinheit erhalten und eine spezielle Reinigung entfällt.Since virtually all intermediates and the end product are obtained in crystalline form in the process according to the invention, cleaning is possible at any stage. In this way, the end product is obtained in high purity and no special cleaning is required.
Die Mischung von 221 g (1,85 Mol) Isoamylnitrit, 378 g (1,7 Mol) 13-Oxa-bicyclo[10.4.0]-hexa- decen-[1(12)], 850 ml Äthanol und 850 ml Wasser wurde auf -5°C abgekühlt und innerhalb von 75 Minuten tropfenweise mit 129 ml 10%iger Salzsäure versetzt. Die Reaktionsmischung wurde 2 Stunden bei 0 bis +5°C gerührt, anschliessend mit 1000 ml Wasser versetzt. Das ausgefallene Kristallisat wurde abgetrennt, neutral gewaschen und getrocknet.The mixture of 221 g (1.85 mol) of isoamyl nitrite, 378 g (1.7 mol) of 13-oxa-bicyclo [10.4.0] -hexadecen- [1 (12)], 850 ml of ethanol and 850 ml of water The mixture was cooled to -5 ° C. and 129 ml of 10% hydrochloric acid were added dropwise over the course of 75 minutes. The reaction mixture was stirred at 0 to + 5 ° C for 2 hours, then 1000 ml of water were added. The precipitated crystals were separated, washed neutral and dried.
Ausbeute: 448,3 g (= 97% der Theorie) 12-OximinocyclopentadecanolidYield: 448.3 g (= 97% of theory) of 12-oximinocyclopentadecanolide
Die Mischung von 379,5 g (5,5 Mol) Natriumnitrit, 1110 g (5 Mol) 13-Oxa-bicyclo[10.4.0]-hexa- decen-[1(12)], 2520 ml Isopropanol und 2520 ml Wasser wurde auf eine Temperatur zwischen 0 bis +5°C abgekühlt und in diesem Temperaturbereich innerhalb von 2 Stunden tropfenweise mit 420 g 38%iger Salzsäure versetzt. Anschliessend wurden 138 g 38%ige Salzsäure innerhalb von 20 Minuten unter besonders intensiver Kühlung zugegeben. Die Reaktionsmischung wurde 2 Stunden bei 0 bis +5°C gerührt, anschliessend innerhalb von 2,5 Stunden mit Eiswasser versetzt. Das ausgefallene Kristallisat wurde abgetrennt, neutral gewaschen und getrocknet.The mixture of 379.5 g (5.5 mol) sodium nitrite, 1110 g (5 mol) 13-oxa-bicyclo [10.4.0] -hexadecen- [1 (12)], 2520 ml isopropanol and 2520 ml water was cooled to a temperature between 0 to + 5 ° C. and 420 g of 38% hydrochloric acid were added dropwise in this temperature range over the course of 2 hours. 138 g of 38% hydrochloric acid were then added over the course of 20 minutes with particularly intensive cooling. The reaction mixture was stirred at 0 to + 5 ° C for 2 hours, then ice water was added within 2.5 hours. The precipitated crystals were separated, washed neutral and dried.
Ausbeute: 1299 g (= 95,7% der Theorie) 12-OximinocyclopentadecanolidYield: 1299 g (= 95.7% of theory) of 12-oximinocyclopentadecanolide
In einem mit Innenthermometer, Rückflusskühler und Rührer versehenen 4-I-Dreihalskolben wurden 1000 ml Diäthylenglykol vorgelegt. Anschliessend wurden unter Kühlen nacheinander 280 g (5 Mol) Kaliumhydroxid, 269 g (1 Mol) 12-Oximinocyclopentadecanolid und 187,5 g 80%iges Hydrazinhydrat zugegeben. Dann wurde die Apparatur mit Stickstoff gespült und das Reaktionsgemisch 2 Stunden auf Rückflusstemperatur erhitzt. Danach wurde das überschüssige Hydrazinhydrat im Gemisch mit Wasser abdestilliert. Dabei wurde die Sumpftemperatur auf 185 bis 195°C gesteigert. Diese Temperatur wurde solange gehalten, bis die Stickstoffentwicklung beendet war (etwa 9 Stunden). Das Reaktionsgemisch wurde mit einem Liter Eiswasser versetzt und mit Salzsäure auf einen pH-Wert von 2 angesäuert. Das ausgefallene Reaktionsprodukt wurde in der Wärme mit Essigester extrahiert. Beim Abkühlen der warmen Essigesterlösung kristallisierte das Produkt wieder aus. Das Produkt wird abgetrennt und getrocknet.1000 ml of diethylene glycol were placed in a 4-liter three-necked flask equipped with an internal thermometer, reflux condenser and stirrer. 280 g (5 mol) of potassium hydroxide, 269 g (1 mol) of 12-oximinocyclopentadecanolide and 187.5 g of 80% hydrazine hydrate were then added in succession while cooling. The apparatus was then flushed with nitrogen and the reaction mixture was heated to reflux for 2 hours. The excess hydrazine hydrate was then distilled off in a mixture with water. The bottom temperature was increased to 185 to 195 ° C. This temperature was maintained until nitrogen evolution ceased (about 9 hours). The reaction mixture was mixed with one liter of ice water and acidified to pH 2 with hydrochloric acid. The precipitated reaction product was extracted with ethyl acetate while hot. When the warm ethyl acetate solution cooled, the product crystallized again. The product is separated and dried.
Ausbeute: 239 g (= 92,6% der Theorie) 15-Hydroxypentadecansäure:
- (Schmelzpunkt: 84°C).
- (Melting point: 84 ° C).
Bei Verwendung von jeweils 5 Mol Lithiumhydroxid, Natriumhydroxid oder Natriumäthylat anstelle von 5 Mol Kaliumhydroxid betrugen die Ausbeuten an 15-Hydroxypentadecansäure 87 bis 91,6% der Theorie.When 5 mol of lithium hydroxide, sodium hydroxide or sodium ethylate were used instead of 5 mol of potassium hydroxide, the yields of 15-hydroxypentadecanoic acid were 87 to 91.6% of theory.
403 g (1,5 Mol) 12-Oximinocyclopentadecanolid (hergestellt gemäss Beispiel) wurden in einem Gemisch aus 2 I Äthanol und 2 I 40%iger Natriumbisulfitlösung 2,5 Stunden auf Rückflusstemperatur erhitzt. Dann wurde die Reaktionsmischung mit 3 1 Wasser versetzt und mit Äther extrahiert. Die organische Phase wurde abgetrennt, neutral gewaschen und getrocknet. Anschliessend wurde das Lösungsmittel abdestilliert und der Rückstand im Vakuum destilliert (Kp: 150-153°C/1,73 Pa). Ausbeute: 332 g (= 87% der Theorie) 12-Keto-cyclopentadecanolid.403 g (1.5 mol) of 12-oximinocyclopentadecanolide (prepared according to example) were heated to reflux temperature in a mixture of 2 l of ethanol and 2 l of 40% sodium bisulfite solution for 2.5 hours. Then the reaction mixture was mixed with 3 1 of water and extracted with ether. The organic phase was separated, washed neutral and dried. The solvent was then distilled off and the residue was distilled in vacuo (bp: 150-153 ° C./1.73 Pa). Yield: 332 g (= 87% of theory) of 12-keto-cyclopentadecanolide.
50 g 12-Keto-cyclopentadecanolid (hergestellt gemäss Beispiel 4) wurden mit 36,6 g 80%igem Hydrazinhydrat und 54,7 g Kaliumhydroxid in 150 ml Diäthylenglykol unter den in Beispiel 3 beschriebenen Reaktionsbedingungen umgesetzt.50 g of 12-keto-cyclopentadecanolide (prepared according to Example 4) were treated with 36.6 g of 80% hydrazine hydrate and 54.7 g of potassium hydroxide in 150 ml of diethylene glycol among those in Example 3 implemented reaction conditions.
Ausbeute: 48 g (94,4% der Theorie) 15-Hydroxy- pentadecansäure.Yield: 48 g (94.4% of theory) of 15-hydroxypentadecanoic acid.
385 g (1,49 Mol) 15-Hydroxypentadecansäure wurden in einer Destillationsapparatur 3 Stunden auf 160°C erhitzt. Dann wurde Wasserstrahlvakuum angelegt, um das Restwasser zu entfernen. Der Rückstand wurde mit 23 g Magnesiumchlorid gemischt und unter Rühren und einem Vakuum von 66,5 Pa in eine auf 280°C vorgeheizte Destillationsapparatur getropft. Bei 140°C/66,5 Pa gingen 330 g (93,2% der Theorie, bezogen auf eingesetzte 15-Hydroxypentadecansäure) Cyclopentadecanolid über.385 g (1.49 mol) of 15-hydroxypentadecanoic acid were heated to 160 ° C. in a distillation apparatus for 3 hours. Then water jet vacuum was applied to remove the residual water. The residue was mixed with 23 g of magnesium chloride and added dropwise to a distillation apparatus preheated to 280 ° C. with stirring and a vacuum of 66.5 Pa. At 140 ° C / 66.5 Pa 330 g (93.2% of theory, based on the 15-hydroxypentadecanoic acid used) cyclopentadecanolide passed over.
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2731543A DE2731543C3 (en) | 1977-07-13 | 1977-07-13 | Process for the preparation of cyclopentadecanolide |
| DE2731543 | 1977-07-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0000476A1 EP0000476A1 (en) | 1979-02-07 |
| EP0000476B1 true EP0000476B1 (en) | 1981-10-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP78100237A Expired EP0000476B1 (en) | 1977-07-13 | 1978-06-26 | Process for the preparation of cyclopentadecanolide |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4187222A (en) |
| EP (1) | EP0000476B1 (en) |
| JP (1) | JPS5419989A (en) |
| DE (2) | DE2731543C3 (en) |
| IT (1) | IT1105097B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0626291B2 (en) * | 1985-03-15 | 1994-04-06 | 株式会社東芝 | Gain control device |
| DE4115182A1 (en) * | 1991-05-09 | 1992-11-12 | Haarmann & Reimer Gmbh | NEW DERIVATIVES OF CYCLIC LACTONES, METHOD FOR THE PRODUCTION THEREOF AND METHOD FOR THE PRODUCTION OF 15-PENTADECANOLIDE AND ITS HOMOLOGOS |
| DE10041198B4 (en) | 2000-08-23 | 2004-01-15 | Symrise Gmbh & Co. Kg | Process for the preparation of macrocyclic esters |
| GB2423986A (en) * | 2004-12-24 | 2006-09-13 | Givaudan Sa | Fragrance Compound |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2092031A (en) * | 1937-09-07 | Process of preparing cycijc esters | ||
| US3890353A (en) * | 1969-05-29 | 1975-06-17 | Firmenich & Cie | Process for preparing lactones |
| JPS5125033B2 (en) * | 1971-08-18 | 1976-07-28 | ||
| DE2410859A1 (en) * | 1974-03-07 | 1975-09-18 | Haarmann & Reimer Gmbh | Macrocyclic ketolactone musk perfume prepn. - from oxa- bicycloalkenes by ozonolysis |
| SU521274A1 (en) * | 1974-03-29 | 1976-07-15 | Ордена Ленина Институт Элементоорганических Соединений Ан Ссср | The method of obtaining cyclopentadecanolide or its methyl derivative |
| DE2511410C2 (en) * | 1975-03-15 | 1983-10-20 | Basf Ag, 6700 Ludwigshafen | 12-Oxo-15-hydroxy-tetradecanecarboxylic acid lactones and process for their preparation |
-
1977
- 1977-07-13 DE DE2731543A patent/DE2731543C3/en not_active Expired
-
1978
- 1978-06-26 DE DE7878100237T patent/DE2861130D1/en not_active Expired
- 1978-06-26 EP EP78100237A patent/EP0000476B1/en not_active Expired
- 1978-06-30 US US05/921,158 patent/US4187222A/en not_active Expired - Lifetime
- 1978-07-11 IT IT50241/78A patent/IT1105097B/en active
- 1978-07-12 JP JP8415678A patent/JPS5419989A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| IT7850241A0 (en) | 1978-07-11 |
| DE2861130D1 (en) | 1981-12-17 |
| IT1105097B (en) | 1985-10-28 |
| US4187222A (en) | 1980-02-05 |
| JPS5419989A (en) | 1979-02-15 |
| DE2731543C3 (en) | 1980-07-31 |
| DE2731543A1 (en) | 1979-01-18 |
| DE2731543B2 (en) | 1979-11-22 |
| JPS6121474B2 (en) | 1986-05-27 |
| EP0000476A1 (en) | 1979-02-07 |
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