DE1249852B

DE1249852B - Process for the production of carbam acid esters from a glycermathers

Info

Publication number: DE1249852B
Application number: DENDAT1249852D
Authority: DE
Original assignee: Dr Christian Brunnengraber Che mische Fabrik &. Co mbH Lübeck
Priority date: 1964-10-07
Publication date: 1967-09-14

Description

BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY

DEUTSCHESGERMAN

PATENTAMTPATENT OFFICE

AUSLEGESCHRIFTEDITORIAL

Int. Cl.: Int. Cl .:

C 07 cC 07 c

Deutsche Kl.: 12 ο-17/01 German class: 12 ο -17/01

Nummer: 1 249 852Number: 1 249 852

Aktenzeichen: B 78827 IV b/12 οFile number: B 78827 IV b / 12 ο

Anmeldetag: 7. Oktober 1964Filing date: October 7, 1964

Auslegetag: 14. September 1967Opened on September 14, 1967

Carbaminsäureester von (X-Guajacolglycerinäthern der allgemeinen FormelCarbamic acid esters of (X-guaiacol glycerol ethers the general formula

R __ O — CH₂ — CHOH — CH₂ — O — CO — NH₂ R __ O - CH ₂ - CHOH - CH ₂ - O - CO - NH ₂

haben als Muskelrelaxantien und Sedativa Bedeutung erlangt (vgl. USA.-Patentschriften 2 609 386 und 2 770 649). Derartige Carbaminsäureester wurden bisher hergestellt durch Umsetzung der Arylglycerinäther mit Phosgen zum Chlorameisensäureester der allgemeinen Formelhave gained importance as muscle relaxants and sedatives (cf. USA patents 2,609,386 and 2,770,649). Such carbamic acid esters have previously been produced by reacting the aryl glycerol ethers with phosgene to give the chloroformic acid ester of the general formula

R — O — CH₂ — CHOH — CH₂ — O — CO — ClR - O - CH ₂ - CHOH - CH ₂ - O - CO - Cl

der mit Ammoniak den entsprechenden Carbaminsäureester liefert. Doch erreichen einerseits die Ausbeuten kaum 6O°/o der Theorie, und zum anderen ist das Arbeiten mit Phosgen wegen dessen starker Giftigkeit und der korrodierenden Eigenschaften sehr gefährlich. which delivers the corresponding carbamic acid ester with ammonia. However, on the one hand, the yields reach hardly 60 per cent of theory, and on the other hand, working with phosgene is because of its high toxicity and its corrosive properties are very dangerous.

Eine andere Herstellungsweise geht aus vom cyclischen CarbonatAnother production method is based on the cyclic carbonate

R — O — CH₂ — CH — CH₂ R - O - CH ₂ - CH - CH ₂

Verfahren zur Herstellung von
Carbaminsäureestem von a-GlycerinäthernProcess for the production of
Carbamic acid esters of α-glycerol ethers

Anmelder:Applicant:

Dr. Christian Brunnengräber
Chemische Fabrik & Co. m. b. H.,
Lübeck, Ratzeburger Allee 106Dr. Christian well graves
Chemical Factory & Co. mb H.,
Lübeck, Ratzeburger Allee 106

das mit Phosgen oder leicht nach Meyer — Jacobsen: »Lehrbuch der organischen Chemie«, Bd. I, Teil 2, 1923, S. 1353, mit Kohlensäurediäthylester durch Umesterung gewonnen werden kann.that with phosgene or slightly according to Meyer - Jacobsen: "Textbook of Organic Chemistry", Vol. I, Part 2, 1923, p. 1353, with carbonic acid diethyl ester can be obtained by transesterification.

Solche Glycolcarbonate können (vgl. Liebigs Annalen der Chemie, Bd. 562,1949, S. 219/220) mit Ammoniak oder Aminen leicht zu Carbaminsäureestem aufgespalten werden. Es muß jedoch damit gerechnet werden, daß die beiden IsomerenSuch glycol carbonates can (cf. Liebigs Annalen der Chemie, Vol. 562, 1949, pp. 219/220) with ammonia or amines are easily split into carbamic acid esters. However, it must be expected be that the two isomers

R — O — CH₂ — CHOH — CH₂ — O — CO — NH₂ R - O - CH ₂ - CHOH - CH ₂ - O - CO - NH ₂

. CH₂OH. CH ₂ OH

R —O —CH,-CH:R —O —CH, -CH:

O — CO-NH, O - CO-NH,

nebeneinander entstehen, deren Trennung schwierig und verlustreich ist (vgl. The Journal of Organic Chemistry, Bd. 24, 1959, S. 1088).arise side by side, the separation of which is difficult and costly (cf. The Journal of Organic Chemistry, Vol. 24, 1959, p. 1088).

So sollen die Carbaminsäureester des Guajacolglycerinäthers und des 3-o-Toloxy-l,2-propandiols nach der kanadischen Patentschrift 589 331 mit Hilfe von Diäthylcarbonat auf zwei Wegen gewonnen werden können.The carbamic acid esters of guaiacol glycerol ether and 3-o-toloxy-1,2-propanediol are said to be according to the Canadian patent 589 331 can be obtained in two ways with the aid of diethyl carbonate can.

Einmal wird die Umesterung so frühzeitig unterbrochen, daß sich neben nur wenig cyclischem Carbonat vorwiegend der gemischte EsterOnce the transesterification is interrupted so early that there is only a little cyclic carbonate predominantly the mixed ester

R-O-CH₂-CHOH-CH₂-O-CO-O-C₂H₅ RO-CH ₂ -CHOH-CH ₂ -O-CO-OC ₂ H ₅

ao gebildet hat, der dann mit Ammoniak den gewünschten primären Carbaminsäureester liefert, jedoch nur in einer Ausbeute von etwa 25 ⁰J₀, so daß sich die Hauptmenge der Ausgangsstoffe der Umsetzung entzogen hat und aufgearbeitet werden muß.ao has formed, which then gives the desired primary carbamic acid ester with ammonia, but only in a yield of about 25 ⁰ I ₀ , so that the majority of the starting materials have withdrawn from the reaction and must be worked up.

Zum anderen wird die Umesterung weitergeführt bis zur mehr oder weniger vollständigen Bildung des cyclischen Carbonats, das dann mit wäßrigem Ammoniak allein oder vorzugsweise mit wasserfreiem Ammoniak, gelöst in einem organischen Lösungsmittel, wie Äthanol, Isopropanol, Benzol, Toluol, oder in einem mischbaren organischen Lösungsmittelpaar, wie Toluol—Isopropanol, zum Carbaminsäureester umgesetzt wird. Doch wird in keinem Fall die Bildung erheblicher Mengen des störenden sekundären Carbaminsäureesters vermieden (vgl. die deutsche Auslegeschrift 1176 123), so daß auch nur Ausbeuten von 48,7 bis 63,2 % der Theorie erhalten werden.On the other hand, the transesterification is continued until the more or less complete formation of the cyclic carbonate, which then with aqueous ammonia alone or preferably with anhydrous ammonia, dissolved in an organic solvent such as ethanol, isopropanol, benzene, toluene, or in one miscible organic solvent pair, such as toluene-isopropanol, is converted to the carbamic acid ester. But in no case does education become more significant Avoid quantities of the interfering secondary carbamic acid ester (cf. the German Auslegeschrift 1176 123), so that only yields of 48.7 to 63.2% of theory are obtained.

Es wurde nun ein Verfahren zur Herstellung von Carbaminsäureestem von a-Glycerinäthern der allgemeinen FormelThere has now been a method for the preparation of carbamic acid esters of α-glycerol ethers of the general formula

in der R eine gegebenenfalls einfach substituierte Phenylgruppe, eine gegebenenfalls substituierte Cycloalkylgruppe oder eine heterocyclische Gruppe bedeutet, gefunden durch Umsetzen eines Glycerinäthers der allgemeinen Formelin which R is an optionally monosubstituted phenyl group, an optionally substituted cycloalkyl group or represents a heterocyclic group found by reacting a glycerin ether of general formula

R _ o — CH₂ — CHOH — CH₂OHR _ o - CH ₂ - CHOH - CH ₂ OH

worin R die vorstehend angegebene Bedeutung besitzt, mit Diäthylcarbonat in Anwesenheit eines Umesterungskatalysators, weiteres Umsetzen des erhal-wherein R has the meaning given above, with diethyl carbonate in the presence of a transesterification catalyst, further implementation of the

■ . :■ . ■■- ■ ■. : ■. ■■ - ■ 709 647/570709 647/570

Claims

ten cyclic carbonates of the general formula R - O - CH ₂ - CH - CH ₂

wherein R has the meaning given above, with aqueous ammonia, which is characterized is that the cyclic carbonate still containing the catalyst is still hot with a Solvents which are indifferent to all reactants, especially toluene or xylene, are mixed and suspended in crystalline form in the solvent by subsequent cooling and then Reacts below about 20 to 25 ° C with more than about 3 mol of aqueous ammonia to form the carbamic acid ester.

The method of the invention avoids the disadvantages of the known methods and has the advantage that The desired primary carbamic acid ester is formed by far predominantly, which is formed after a single recrystallization is obtained pure in a yield of about 90%.

The reaction is preferably carried out with 4 moles of ammonia, working in xylene.

In particular, 3- (o-methoxyphenoxy) -2-oxy-propyl carbamate can be obtained by the process of the invention will.

The following examples illustrate the process of the invention.

B e i s ρ i e 1 1

198 parts of 3- (o-methoxyphenoxy) -l, 2-propanediol (guaiacol glycerol ether), 236 parts of diethyl carbonate and 2.2 parts of 30% strength sodium methylate solutions are heated to the boil with mechanical stirring. The alcohol which forms is distilled off using a fractionation column. When the internal temperature Has reached 130 ° C, the excess carbonic acid diethyl ester under reduced pressure distilled off and the remaining catalyst-containing carbonic acid ester of guaiacol glycerol ether 500 parts of toluene were added while still hot and the mixture was cooled to 20 ° C., the majority of which crystallized out. In 280 parts of concentrated aqueous ammonia are stirred into this suspension. After 12 hours the 3- (o-methoxyphenoxy) -2-oxy-propylcarbamate is filtered off, dried below 50 ° C and removed Recrystallized ethyl acetate. 203 parts with a melting point of 96 ° C. are obtained.

Example 2

198 parts of 3- (o-methoxyphenoxy) -l, 2-propanediol (guaiacol glycerol ether), 236 parts of diethyl carbonate and 0.4 part of sodium are heated to the boil with mechanical stirring. The alcohol which forms is distilled off using a fractionation column. When the internal temperature reached 13O ⁰ C, the excess Kohlensäurediäthylester is distilled off under reduced pressure and the remaining catalyst-containing carbonate ester of Guajacolglycerinäthers still hot mixed with 500 parts of xylene and cooled to 2O ⁰ C, with the largest

ίο Part crystallized out. Parts of concentrated aqueous ammonia are stirred into this suspension. After 12 hours under reduced pressure below 50 ⁰ C, ammonia and water by means of a water azeotropically distilled off. The xylene is then removed under reduced pressure and the residue is recrystallized from isopropanol. There are 200 parts of pure 3- (o-methoxy-phenoxy) -2-oxy-propyl carbamate obtained, mp = 96 ⁰ C.

^Extra patent claim:

Process for the preparation of carbamic acid esters of α-glycerol ethers of the general formula

RO-Ch ₂ -CHOH-CH ₂ -O-CO-NH ₂

in which R is an optionally monosubstituted phenyl group, an optionally substituted one Cycloalkyl group or a heterocyclic group means by reacting a glycerin ether of general formula

RO-CH ₂ -CHOH-CH ₂ OH

wherein R has the meaning given above, with diethyl carbonate in the presence of a Transesterification catalyst, further reaction of the resulting cyclic carbonate of the general formula

R - O - CH ₂ - CH - CH ₂

wherein R has the meaning given above, with aqueous ammonia, characterized in that the cyclic carbonate still containing the catalyst is mixed while still hot with a solvent which is inert to all reactants, especially toluene or xylene, and is crystallized in the solvent by subsequent cooling suspended and then reacted below about 20 to 25 ⁰ C with more than about 3 mol of aqueous ammonia to the carbamic acid ester.