DE233069C - - Google Patents

Description

KAISFR

PATENT OFFICE.

PATENT LETTERING

- ΛΓί 233069 CLASS 12 #. GROUP

Patented in the German Empire on January 9, 1910.

A few years ago Xeger (Chem. Centralbl. 1906, I, p. 565; 1906, II, p. 889; 1907, I, p. 483, p. 1054, p. 1434) and independently from him Gaebel (Chem. Centralbl. 1907, I, p. 52) deposited a new alkaloid from the dry malt germs of the barley, which they the constitution of a p-oxyphenylethyldimethylamms due to its chemical behavior

- CH ₉ · CH ₉

OiT-

to speak. This constitution is by no means to be regarded as secure until now all known chemical transformations of hordenine (Hofmann's degradation of methylhordenine methyl hydroxide to trimethylamine and p-vinyl anisole, oxidation of the methyl or Acethylhordenins to p-methoxy or p-acetoxybenzoic acid) just as well with the formula

OH-

CH,

, -CH-Ni

get reconciled. It was only through the present synthesis of hordenine that so by no means foreseen is the proof of the correctness of the assumption of Leger and Gaebel have been delivered.

Since the horde is a relatively non-toxic body (cf. Camus, Chem. Centralbl. 1906, I, p. 566, p. 693, p. 863) and due to its special effect on it Cholera, dysentery, and diarrhea are valuable medicines, so comes the synthetic one Representation of the Hordenine is of considerable technical importance.

If one tries to obtain the hordenine by direct alkylation of p-oxyphenylethylamine To represent, then in addition to smaller amounts of mono- and dimethylated products, the halogen salt of the quaternary is preferred Get ammonium base. Accordingly, in the Journal of the former soc. Vol. 95 [1909], p. 1127, p. 2193/94, p. 2197 only the representation of the hordenine iodine methylate from the primary amine, but not that of the base mentioned himself.

It has now been found that the quaternary halogen salts of hordenine are easily in this can be converted if it is subjected to distillation in vacuo. This reaction is easy and almost quantitative. This behavior was based on previous observations not foreseeable about the cleavage of quaternary ammonium salts. Already Lossen (Ann. D. Ch. 181, p. 382) found that mixed substituted compounds, the methyl contain, methyl halogen is not always split off. Claus (Ber. 17 [1884], p. 1324 and 19 [1886], p. 2785) even set up the law that precisely the most carbon-rich Radically separates. W e d e kind (Ber. 35 [1902], p. 766) obtained from benzylmethylallylphenylammonium iodide benzyl iodide in the distillation.

In a similar way to methyl, other radicals (such as benzyl, etc.) can also be incorporated into the Amino group of p-oxyphenylethylamine or its positional isomers, e.g. B. the isomer

Ό- or m - oxyphenylethylamine, introduce. Instead of the oxyphenylethylamines, their homologues in the core or in the side chain can be used Derivatives are subjected to the same reaction. In some cases it is also beneficial to alkylate their ethers instead of the free phenols, e.g. if, after adding 3 molecules of a gaseous alkylating agent, like chloromethyl, and the corresponding amount of alkali wants to alkylate to the end in one operation in the pressure vessel. In this procedure you would use the free Oxyphenyläthylamine a Mixtures of derivatives alkylated on oxygen and nitrogen are obtained. Here can then the ethers obtained by distilling the quaternary salts in vacuo in turn saponify to the phenols by boiling with mineral acids.

Example i.

13.7 parts of p-oxyphenylethylamine are in Dissolved 100 parts of alcohol, boiled with 14.2 parts of methyl iodine until a neutral reaction was reached.

Then 2.3 parts of sodium dissolved in alcohol are added and a further 14.2 parts of iodomethyl are added, the mixture is boiled again until neutral and this is repeated a third time. Upon concentration of the alcoholic solution of the sparingly soluble Hordeninjodmethylat crystallized (melting point 230 ⁰⁾ from which can be removed by recrystallization from hot water from the last traces of sodium iodide. It can either be subjected to distillation as such or it can also be converted into the chloromethylate by treatment with silver chlorine or lead chlorine and then distilled in vacuo. The completely colorless distillate is freed from some of the chloromethylate which has formed back with the aid of ether and converted into the nicely crystallized hordenine chlorohydrate (melting point 175 ^° ). This turns out to be identical to the hordenine chlorohydrate described in the literature. The base deposited from the salts melts at 118 °. The above-mentioned chloromethylate of hordenine is easily soluble in water, moderately soluble in hot alcohol, hardly soluble in cold alcohol, and insoluble in ether. It

5.0 melts at 285 ^° with decomposition.

Instead of the quaternary salts of p-oxyphenylethylamine in the above example, the quaternary salts of o-oxyphenylethylamine, e.g. o-oxyphenylethyltrimethylammonium iodide (Ber. 38 [1905], p. 2076), be subjected to the same reaction.

Example 2.

201.5 parts of hydrochloric acid m-ethoxyphenylethylamine (melting point 160 to 165 ⁰ , represented for example by the action of sodium hypochlorite solution on m-ethoxyphenylpropionic acid amide), 168 parts of caustic potash, 1000 parts of alcohol and 160 parts of chloromethyl are stirred in a pressure vessel for a few hours up to Disappearance of the alkaline reaction heated to 100 °. The potassium chloride is then nitrated, evaporated to dryness, the m-Ätoxyphenyläthyltrimethylammoniumchlorid extracted with alcohol and crystallized it 'from acetone. This body melts at 130 °, is easily soluble in water and alcohol, less soluble in acetone and insoluble in ether. In aqueous solution, it provides with the corresponding potassium iodide Jodmethylat in the form of shiny white needles melting at 185-190 ^0th The chloromethylate is almost quantitatively cleaved in methylene chloride and m-Äthoxyphenyläthyldimethylamin by double distillation under vacuum, a colorless liquid of boiling point 130 to 133 ⁰ mm at 15 pressure. 20 parts of m-Ätoxyphenyläthyldimethylamin are refluxed with 100 parts of constant boiling hydriodic acid decolorized by prior boiling with phosphorus in a stream of _{carbonic acid V for 2 hours.} Then ethyl iodine and hydrogen iodide are distilled off in vacuo and the base is separated in a known manner from the remaining hydrogen iodic acid m-oxyphenylethyldimethylamine. This is sparingly soluble in water, somewhat more easily in alcohol, easily soluble in chloroform and melts at

Claims (1)

Patent claim: Process for the preparation of Oxyphenyläthyldialkylaminen, consisting therein that the by the action of alkyl halides on Oxyphenyläthylamine or their o-ether obtainable quaternary ammonium salts by distillation in vacuo and then, if necessary, the ethers by boiling with mineral acids to give the corresponding free phenols saponified.