DE273323C - - Google Patents

Description

IMPERIAL

PATENT OFFICE.

There is much in the chemical literature up to now on the preparation of aminoalkyl ethers little known. The only simpler representatives are described by Knorr (Ber. 37 [1904], P. 3494 ff. And p. 3504 to 3507 as well as Ber. 38 [1905], p.3129ff.), Namely dimethylaminodiethyl ether and its parent substance, amino diethyl ether. Knorr gained this body through interaction between dimethylamine and iodine ethyl ether or by reacting chloroethylamine with sodium ethylate.

To represent the lower homologues of this body class, i.e. the amino derivatives, which are derived from the common dimethyl ether, separates the second of the above Methods from the beginning, as the chloromethylamine as well as the alcohol on which it is based, the aminomethanol, is currently are unknown and probably also because of their expected instability for technical Purposes are unlikely to be usable.

But it was by no means to be expected that the first method, consisting in the implementation of iodine ethers with ammonia or substituted ammonia would lead to the goal. There is a huge difference in the resistance of iodine ethyl ether to the halogen derivatives of the ordinary Dimethyl ether. While the former is a relatively stable body, it disintegrates known to be chloromethyl ether when standing alone, faster even when present of moisture or of basic or acidic compounds in formaldehyde and trioxymethylene. This is particularly easy Decomposition in the presence of ammonia, as already WedeTdnd (Ber. 36 [1903], p. 1385) and found others before him (Bull, de la soc. chim. Nouv. ser. 28 [1877], pp. 171/172).

Litterscheid (Annalen 334 [1904], p. 49 ff.) Was already exposed to chloromethyl ether studied on bases. He stood up, perhaps with considerations similar to those given above the implementation of chloromethyl ether with tertiary bases, such as pyridine and quinoline, is limited and only get addition products. In the few cases where chloromethyl ether on secondary bases, such as dimethylamine or cytisine, were acted upon Addition products of a complicated type are obtained, while the reaction with aniline is only Hydrochloric aniline supplied (cf. loc. cit., p. 56 bis 62).

With regard to the existing literature cited above, it was the same less to expect that the halomethyl alkyl ethers will under appropriate conditions quite smoothly with primary or secondary amines of the aliphatic or fatty aromatic Row in the sense of the equation:

■ zNH-.

Cl-CH ₂ -OCH ₃ , R ₁

CH ₃ + Nh

\ HCl

(where R _{1 is} alkyl or aralkyl, R _{2 is} hydrogen or alkyl) would convert to alkyl or aralkylaminomethylalkyl ethers. While Litterscheid (loc. Cit.) Allowed dimethylamine and chloromethyl ether to act on one another in molecular amounts, according to the present process, 2 mol of base are brought into action for every 1 mol of chloromethyl alkyl ether. The hydrochloric acid formed during the reaction is immediately bound by the second base molecule. If an ethereal or benzene solution is used, the hydrochloric acid salt usually precipitates in crystalline form. Its weight is almost exactly the calculated one.

The action of chloromethyl alkyl ether on aniline and monomethylaniline proceeds apparently quite smooth in the first phase, only during work-up condensation appears prevent the extraction of pure products.

Examples.

i. N-methoxymethylallylamine.

38 g of aylamine are dissolved in about 200 ecm of benzene and a solution of 27 g of chloromethyl ether in 100 ecm of benzene is slowly added dropwise while stirring and cooling with ice water. The allylamine chlorohydrate formed in the reaction, which separates out in an oily form, is shaken out with water after a while, the benzene is dried with sodium sulfate and distilled off in vacuo. The residue boils at a pressure of 7.5 mm at 113 ^0th The distillate is a colorless oil with a very unpleasant odor; it dissolves easily in dilute hydrochloric acid and is separated out again from the solution by means of sodium hydroxide solution. When the hydrochloric acid solution is heated, the pungent odor of formaldehyde occurs immediately.

2. N-methoxymethyl diethylamine.

36.5 g of diethylamine are removed in 150 ecm

dissolved in solid ether and, while cooling with ice, 20.2 g of chloromethyl ether in 80 ecm of ether were slowly added dropwise. The mixture is then stirred for a further ¹ Z ₂ hours while cooling. The hydrochloric acid diethylamine which has precipitated out is filtered. Its weight is 27 g, while ² 7.35 g is calculated. The filtrate is freed from the ether and the residue is fractionated. The fraction passing over at a pressure of 76 mm at 64 to 71 ° shows a nitrogen content of 12.30 percent, while for the formula: (C ₂ HJ ₂ N-CH ₂ O-CH ₃ 11.96 percent N can be calculated. At Repeated fractionation, the main part boils under a pressure of 68 mm at 53 °. The colorless, slightly liquid base has a very pungent, tear-irritating odor. It dissolves in water and in hydrochloric acid; the base is precipitated from the odorless hydrochloric acid solution .

3. N-methoxymethylhomopiperonyl-

amine.

35 g homopiperonylamine are in 200 ecm Dissolved benzene and, while stirring and cooling with ice water, a solution of 9 g of chloromethyl ether added dropwise in benzene. Hydrochloric acid homopiperonylamine immediately separates out in the form of fine white crystals. After finished In the reaction, the hydrochloric acid salt is filtered off, washed with benzene and the filtrate is removed freed from benzene in vacuo. The residue is a colorless, very viscous oil, which shows the same properties as the product of the previous example.

4. N-ethoxymethyl homopironylamine.

This base is exactly like that described in Example 3, replacing the chloromethyl ether represented by chloromethyl ethyl ether. It resembles that in appearance and properties.

5. N-methyl methoxymethyl homopipe-

ronylamine.

44 g of N-methylhomopiperonylamine are in Dissolve 220 ecm of benzene and mix 10.5 g of chloromethyl ether in 50 ecm of benzene added slowly. When the reaction has ended, the hydrochloric acid becomes methyl homopiperonylamine suctioned off and the filtrate freed from benzene in vacuo. The residue forms a colorless, mobile oil that cannot be distilled without decomposition.

6. N-methoxymethylethyl homopipe-

ronylamine

is made from N-ethyl homopiperonylamine (colorless oil with a boiling point of 125 to 126 ° below a Pressure of 4 mm) and chloromethyl ether obtained in the manner described. The base shows the same properties as those described under 3, 4 and 5.

7. N-methoxymethyl-a-methyl homo-

pironylamine

becomes from a-methylhomopiperonylamine (CH ₂ O ₂ ) -C ₆ H ₃ -CH ₂ -CH (CH ₃ ) -NH ₂

and chloromethyl ether obtained. The base is even more viscous than the one previously described, but otherwise shows the same properties. The new bodies are well characterized Compounds of mostly oily nature, of which the lower molecular ones distill in vacuo without decomposition. They have a strongly basic character and

form permanent salts. Since the alkyl or aralkylaminomethylalkyl ethers as intermediates for the synthesis of important drugs, especially hydrastinine, use can find, the present process represents a significant step forward and a valuable asset to technology.

Claims (1)

Patent claim: ίο Process for the representation of alkyl and aralkylaminomethylalkyl ethers of the general formula: Alkyl-O , R ₁ (.R ₁ = alkyl or aralkyl, R ₂ = hydrogen or alkyl), consisting in that one mol. Of a halomethylalkyl ether (halogen · CH ₂ - O · alkyl) to 2 mol. Of a primary or secondary amine of the ali- 20 phatic or fatty aromatic series, expediently in the presence of an inert organic solvent, can act.