DE2418085A1 - 2-(Iodoethyl)-1,3-dioxolan-4-methanol prepn. - from glycerol and iodine, useful as mucolytic and expectorant - Google Patents

2-(Iodoethyl)-1,3-dioxolan-4-methanol prepn. - from glycerol and iodine, useful as mucolytic and expectorant

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Publication number
DE2418085A1
DE2418085A1 DE2418085A DE2418085A DE2418085A1 DE 2418085 A1 DE2418085 A1 DE 2418085A1 DE 2418085 A DE2418085 A DE 2418085A DE 2418085 A DE2418085 A DE 2418085A DE 2418085 A1 DE2418085 A1 DE 2418085A1
Authority
DE
Germany
Prior art keywords
iodine
iodoethyl
methanol
glycerol
reaction
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
Application number
DE2418085A
Other languages
German (de)
Inventor
Estruch Marcelo Fosalba
Montardit Pujol
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Diagnostics GmbH
Original Assignee
Roche Diagnostics GmbH
Boehringer Mannheim GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Roche Diagnostics GmbH, Boehringer Mannheim GmbH filed Critical Roche Diagnostics GmbH
Publication of DE2418085A1 publication Critical patent/DE2418085A1/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
    • C07D317/20—Free hydroxyl or mercaptan

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

2-(Iodoethyl)-1,3-dioxolan-4-methanol (I) is prepd. by reacting glycerol and iodine in an organic solvent capable of forming an azeotrope with the H2O liberated in the reaction; and extracting the prodt. (I) has a mucolytic and expectorant activity much stronger than that of glyceryl guaiacolate, and can be administered in doses 20-25 times lower than conventional inorganic iodine cpds. since it accumulates pref. in the fatty tissues.

Description

Verfahren zur Herstellung von 2-(Jodäthyl)-1,3-dioxolan-4-methanol Eine sehr große Zahl organischer und anorganischer Jodverbindungen wird in'der Therapie verwendet. Alle diese Verbindungen können in zwei verschiedene Gruppen eingeteilt werden: 1. Jodverbindungen, deren Jodion stark ionisiert ist; dies sind die anorganischen Jodide und gewisse organische Jodverbindungen, die selbst oder in Form ihrer Stoffwechselprodukte die Wirkungen eines dissoziierten Jodidions aufweisen.Process for the preparation of 2- (iodoethyl) -1,3-dioxolane-4-methanol A very large number of organic and inorganic iodine compounds are used in therapy used. All of these compounds can be divided into two different groups become: 1. Iodine compounds, the iodine ion of which is strongly ionized; these are the inorganic ones Iodides and certain organic iodine compounds, either by themselves or in the form of their metabolic products exhibit the effects of a dissociated iodide ion.

2. Jodverbindungen, in denen das Jodatom fest an das Kohlenstoffatom gebunden ist und im System nicht frei wird.2. Iodine compounds in which the iodine atom is firmly attached to the carbon atom is bound and does not become free in the system.

Die erste Gruppe von Verbindungen weist den therapeutischen Effect des Jodidions auf. Die Verbindungen der zweiten Gruppe werden in diagnostischen Arbeiten als Kontrastmittel verwendet, wobei eine wesentliche Konzentration der Jodverbindung insbesondere in einem Organ oder Gewebe erzeugt wird. Das Produkt, dessen Herstellungsverfahren Gegenstand der Erfindung ist, gehört zur ersten Gruppe.The first group of compounds has the therapeutic effect of iodide ion. The compounds of the second group are used in diagnostic Working as a contrast agent, being a substantial concentration of the used Iodine compound is generated in particular in an organ or tissue. The product, the manufacturing process of which is the subject of the invention belongs to the first group.

2-(Jodäthyl) -1,3-dioxolan-4-methanol, auch als Jodpropylidenglycerin bezeichnet, hat eine starke schleimlösende (mukolytische) Wirkung und Expektorationswirkung, die viermal stärker ist als die von Glycerylguajakolat und wird in einer Dosis verabreicht, die 20- bis 25mal geringer ist als die der Ublichen anorganischen Jodpräparate.2- (iodoethyl) -1,3-dioxolane-4-methanol, also as iodopropylidene glycerine has a strong expectorant (mucolytic) and expectorant effect, which is four times stronger than that of glyceryl guaiacolate and is given in a dose which is 20 to 25 times less than that of the usual inorganic iodine preparations.

Die mit dieser Verbindung erzielte Konzentration im Blut läßt sich leicht konstant halten. Dies ist auf die Speicherwirkung des Fettgewebes zurückzuführen, in dem Jodpropylidenglycerin vortibergehend eingelagert wird.The concentration in the blood achieved with this compound can be easy to keep constant. This is due to the storage effect of the adipose tissue, in which iodopropylidene glycerine is temporarily stored.

Zur Herstellung vcn 2-(Jodäthyl)-l,jr-dioxolan-4-methanol nach dem Verfahren gemäß der Erfindung wird Glycerin mit elementarem Jod in Gegenwart eines organischen Lösungsmittels, das ein azeotropes Gemisch mit dem frei werdenden Wasser zu bilden vermag, umgesetzt. Das Reaktionsprodukt besteht aus einem Gemisch verschiedener Substanzen, unter denen sich das Produkt gemäß der Erfindung befindet.For the preparation of 2- (iodoethyl) -l, jr-dioxolane-4-methanol according to the Process according to the invention is glycerol with elemental iodine in the presence of a organic solvent, which is an azeotropic mixture with the released water able to form, implemented. The reaction product consists of a mixture of different Substances among which the product according to the invention is located.

Die Reaktionsteilnehmer werden in einem Verhältnis von 1000 Teilen Glycerin zu 200 bis 450 Teilen Jod umgesetzt.The reactants are in a ratio of 1000 parts Glycerin converted to 200 to 450 parts of iodine.

Das Gemisch wird unter RUhren auf 11 bis 1400C erhitzt.The mixture is heated to 11 to 1400 ° C. with stirring.

Die Reaktionszeit beträgt 15 bis 30 Stunden. Das bei der Reaktion frei werdende Wasser wird mit einem Lösungsmittel, z.B. Toluol, entfernt.The reaction time is 15 to 30 hours. That with the reaction Any water released is removed with a solvent, e.g. toluene.

Bei der Synthese dieser Verbindung werden zwei stellungsisomere Jodderivate, nämlich 2-Jodpropylidenglycerin und 3-Jodpropylidenglycerin, gebildet, die die folgenden Strukturformeln haben (beide Isomere haben die gleichen therapeuthischen Eigenschaften und unterscheiden sich in ihrer Abbaugeschwindigkeit): Da einige der gebildeten Produkte Jodverbindungen sind, ermöglicht eine Bestimmung des organischen Jods keine spezifische Bestimmung des 2-(Jodäthyl)-i,3-dioxolan-4-methanols, wenn hierbei nicht gleichzeitig gewisse Reinheitsmerkmale festgestellt werden, wie es durch Chromatographie oder Aufnahme des kernmagnetischen Resonanzspektrums möglich ist.During the synthesis of this compound, two positionally isomeric iodine derivatives, namely 2-iodopropylidene glycerol and 3-iodopropylidene glycerol, are formed, which have the following structural formulas (both isomers have the same therapeutic properties and differ in their rate of degradation): Since some of the products formed are iodine compounds, a determination of the organic iodine does not allow a specific determination of 2- (iodoethyl) -i, 3-dioxolane-4-methanol if certain purity features are not determined at the same time, as can be determined by chromatography or recording of the nuclear magnetic resonance spectrum is possible.

Aus diesen Gründen muß der gewUnschte Wirkstoff nach beendeter Reaktion extrahiert werden, wobei in kontinuierlicher Arbeitsweise nacheinander Athylacetat und Benzol verwendet werden. Die Reinheit des erfindungsgemäßen Produkts mit den genannten schleimlösenden Eigenschaften und Expektorationseigenschaften erfordert die Anwendung des nachstehend beschriebenen Extraktionsverfahrens.For these reasons, the desired active ingredient must be used after the reaction has ended extracted, with ethyl acetate successively in continuous operation and benzene can be used. The purity of the product according to the invention with the called expectorant properties and expectoration properties the use of the extraction procedure described below.

Beispiel 1 1000 Teile Glycerin, 350 Teile Jod und 20 Teile Toluol werden in einen mit Wasserabscheider versehenen Reaktor eingeführt. Das Gemisch wird 25 Stunden bei 1150C gehalten. Example 1 1000 parts of glycerine, 350 parts of iodine and 20 parts of toluene are introduced into a reactor equipped with a water separator. The mixture is kept at 1150C for 25 hours.

Nach beendeter Reaktion wird mit Athylacetat extrahiert, zur Trockene eingedampft, mit Benzol extrahiert und zur Trockene eingedampft.After the reaction has ended, it is extracted with ethyl acetate to dryness evaporated, extracted with benzene and evaporated to dryness.

Beispiel 2 1000 Teile Glycerin, 450 Teile Jod und 20 Teile Toluol werden in einen mit Wasserabscheider versehenen Reaktor eingeführt. Das Gemisch wird 25 Stunden bei 1350C gehalten. Nach beendeter Reaktion wird mit Xthylacetat extrahiert, zur Trockene eingedampft, mit Benzol extrahiert und zur Trockene eingedampft. Example 2 1000 parts of glycerol, 450 parts of iodine and 20 parts of toluene are introduced into a reactor provided with a water separator. The mixture is kept at 1350 ° C. for 25 hours. After the reaction has ended, it is extracted with ethyl acetate, evaporated to dryness, extracted with benzene and evaporated to dryness.

Claims (4)

P a t e n t a n s p r ü c h eP a t e n t a n s p r ü c h e 1. Verfahren zur Herstellung von 2-(Jodäthyl)-1,3-dioxolan-4-methanol, dadurch gekennzeichnet, daß man Glycerin und Jod in Gegenwart eines organischen Lösungsmittel-s, das ein azeotropes Gemisch mit dem freiwerdenden Wasser zu bilden vermag, umsetzt und das gewünschte Produkt durch Extraktion isoliert.1. Process for the preparation of 2- (iodoethyl) -1,3-dioxolane-4-methanol, characterized in that glycerol and iodine in the presence of an organic Solvent-s that form an azeotropic mixture with the released water capable of converting and isolating the desired product by extraction. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man 250 bis 450 Teile Jod pro 1000 Teile Glycerin verwendet.2. The method according to claim 1, characterized in that 250 up to 450 parts of iodine per 1000 parts of glycerin used. 3. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man die Reaktion bei einer Temperatur zwischen 1100 und 1400C durchführt und das bei der Reaktion freiwerdende Wasser mit einem organischen Lösungsmittel, mit dem es ein azeotropes Gemisch bildet, entfernt.3. The method according to claim 1 and 2, characterized in that one the reaction is carried out at a temperature between 1100 and 1400C and that at the reaction released water with an organic solvent with which it forms an azeotropic mixture is removed. 4. Verfahren nach Anspruch 1 bis 3, dadurch gekennzeichnet, daß man das bei der Reaktion gebildete 2-(Jodäthyl)-1,3-dioxolan-4-methanol isoliert, indem man das Reaktionsgemisch zuerst mit Athylacetat und dann mit Benzol extrahiert.4. The method according to claim 1 to 3, characterized in that one the 2- (iodoethyl) -1,3-dioxolane-4-methanol formed in the reaction is isolated by the reaction mixture is extracted first with ethyl acetate and then with benzene.
DE2418085A 1973-08-03 1974-04-13 2-(Iodoethyl)-1,3-dioxolan-4-methanol prepn. - from glycerol and iodine, useful as mucolytic and expectorant Pending DE2418085A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES417572A ES417572A1 (en) 1973-08-03 1973-08-03 Procedure for the obtaining 2- (iodoethyl) -1,3-dioxolan-4-methanol. (Machine-translation by Google Translate, not legally binding)

Publications (1)

Publication Number Publication Date
DE2418085A1 true DE2418085A1 (en) 1975-02-27

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DE2418085A Pending DE2418085A1 (en) 1973-08-03 1974-04-13 2-(Iodoethyl)-1,3-dioxolan-4-methanol prepn. - from glycerol and iodine, useful as mucolytic and expectorant

Country Status (2)

Country Link
DE (1) DE2418085A1 (en)
ES (1) ES417572A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51122065A (en) * 1975-04-01 1976-10-25 Maggioni & C Spa Preparation and use of halogenated 1*33 dioxorane derivatives
US4111959A (en) * 1976-03-03 1978-09-05 American Cyanamid Company 15,16-Dioxy prostenoic acids and esters and intermediates in their preparation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51122065A (en) * 1975-04-01 1976-10-25 Maggioni & C Spa Preparation and use of halogenated 1*33 dioxorane derivatives
US4111959A (en) * 1976-03-03 1978-09-05 American Cyanamid Company 15,16-Dioxy prostenoic acids and esters and intermediates in their preparation

Also Published As

Publication number Publication date
ES417572A1 (en) 1976-03-16

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