US650408A - Process of making acidyl morphin esters. - Google Patents

Description

"UNITED STATES ERNST ll/I EN-NEL, OF DARMSTADT,

PROCESS OF MAKlNG ,ACIDYL MORPHIN ESTERS'.

SPEOIFIOATIOR forming part of Letters Patent No. 650,408, dated. May 29, 1900.

:lppllcation filed August 9, 1899- Serle11i'o. 726,698. (No specimens-l i v i i To allwhom itimaty concern.-

- Be it known that I, ERNST MENNEL, a subjeet of the Emperor of Germany, residing at Darmstadt, Germany, have invented a certain new and useful- Chemical Process, of which the following is a vfu'll, clear, and exact description. Carboxy-alkylic esters of morphin prepared according to Ottos process'possess but little to stability and little tendency to crystallize.

Their acidyl compounds, on the other hand,

exhibit decided crystallizability and comparaponnds can be obtained from the simple alx 5 pha-acidyl-morphins of the fatty-acid seriesas,-for instance, aeetyl-mprphin, propionylmorphin, &c.'by treating the same with .chlorocarboxylie esters and'alkali, preferably in molecular proportions,

' Carboxy-alkylic esters of morphin, as mentioned by Otto, are represented by this general typical formula:

OH ocoon' in which, Rsignifies anyfunivalent alcohol radical, (or alkyl'.)

' The carboxy-alkylic esters of acidyl-mor- 3o phins, which form the subject of my'invention, are represented by this general typical formula: j

" in which R'signifie's as before, and A signifies any'acid radical (or acidyl) of the fatty series. 4 p

Thereaction by which the carboxy-alkylic esters of acidyl-morphin's are formed in my process is represented by the-following equation:

0,,n,,no

wer

-0 in which R' and t signify as before rand 1n" GERMANY, AssIeNoR'To Louls' unnoie' E. A'. MERCK, WILLY MERGE; AND 0. E. MERCK, or SAME PLACE,

net in its other side chain.

signifies an alkali metal, (univalent in the instance here'shown or (the above equation being translated into common language) An acidyl-morphin an alkali hy- :J it? vdrate-la chlorocarbo'xylic alkyl ester 5 5 a carboxv alkylic ester of an aci'dyLmor l phin an alkali ehlorid -water. Takingan actual specific example, in which? ,0,

A shall signify acetyl and R shall signifye' ethyl and M shall signify potassium,th ef above e nation takes the followin 'forinz tive stability. Ihave'found that such comv q I otassinm. chlorocarboxylic ACBAWI'mOXphII} hydroxid' ethyl ester I acetyl-rnorphin In a similar double decomposition,"onlyiising: other chloroearboxylic esters instead of" the ethyl ester, as above, we-obtain, for instanc carboxy-inethylic ester of acetyl morphin o. .oo0oH, '1" so or carboxy-propylic ester of acetyl-inorphin:

Q17Hfi v 0.0000,, 7 35 & c. Also by using other acidyl-morphins---v as, for instance, propionylmorphin or bu- CH H . tyr'y'l morphin-instead of the acetyl mor ph in we can vary the composition of the prod Other alkalies go as, for instance, sodiuin hydroxid--can also be substituted for the potassium hydroxid as the agent for inducing the above-recited reaction; but this will not yield a different 4 product, but is merely a variation possibly hearing on the convenience of manipulation or the economy of the process.-

As an example of my process, a, suitable acidyl-morphin, being suspended in benzene,

is shakena'tordinary temperatures with the ce.

' successive small portions,

mg into solution with the benzene, while the alkali chlorid formed as a by-product is found dissolved in the aqueous liquor. The reaction being completed, the benzene solution is siphoned off, washed, and dried. On evaporating the-solvent herefrom the acidyl-mcrphin carboxy-alkylic ester in a nearly-pure state is found as the residue.

Example of manufacture.-Aeetyl mow phin carboxyethylic esfer..0ne thousand grams of alpha-acetyl-morphin, finely powdered, is suspended in twelve kilograms of benzene and three hundred and thirty grams of chlorocarboxylic ethyl ester is added. Into this mixture one hundred and sixtyone grains of potassa in about ten-per-ceut. solution is allowed to flow in small portions,while the mixture is vigorously shaken. When the alkaline solution has all been added, the previously-prevailing odor of the chlorocarboxylic ethyl ester disappears. After the settling of the liquids the beuzenic stratum is siphoned off. This part having been washed with water and then dried, the benzene is distilled ofi. The desired ester in nearly a pure state remains as a solid crystalline mass. By recrystallizing it from three to four times its bulk of absolute alcohol it is obtained in beautiful glass-like needles or prisms, which melt at 150 centigrade. By treating the prod- .uct, finely powdered,with its exact molecular equivalent of titrated hydrochloric acidthehy- I drochlorate of the product is obtained in small colorless needles, which melt at 185 centigrade under evolution of gas. These needles, in combination with platinic chlorid, yield a platinum double salt, which crystallizes in orange-colored little needles and whose melting-point is about 210 centigrade.

'Aetyl-morphin carboxy-methylic ester is It will be obvious that many changes maybe made in thedisclosure herein without departing froin the spirit of my invention.

What I claim is-- v 1. The process of preparing a carhoxy-al kylic ester of an acidyl-inorphin, which consists in treating an alpha-mono-acidyl compound ofi morphin, whose acidyl constituent, is ofi the fatty-acid series, with a chlorocarboxyl'ic ester and an alkali.

2. The process of preparing a carboxy-alkylic ester of an acidyl-morphin, which consists in treating an alpha-mono-acidyl compound of morphin, whose acidyl constituent is of the fatty-acid series, with a chlorocarboxylic ester and an alkali, the same being used in molecular"proportions.

3'. The process of treating alpha-monoacetyl-morphin with chlorocarboxylic ethyl ester and an alkali, thereby producing the carboxy-ethylic ester of acetyl-morphiu.

Signed at Darmstadt, Germany, this 20th dayof July, 1899.

ERNST MENNEL.

Witnesses JEAN GRUN-D, RICHARD GUENTIIER.