DE1228619B - Process for the preparation of bis (dialkylaminoaethyl) thioethers - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07c

German class: 12 q-32/01

Number: 1228 619

File number: S 58448IV b / 12 q Filing date: May 31, 1958 Opening day: November 17, 1966

The invention relates to a new process for the preparation of bis (dialkylaminoethyl) thioethers the general formula

R R

N - CH ₂ -CH ₂ -S-CH ₂ - CH ₂ -N

RR _t

where R stands for identical or different low molecular weight alkyl radicals.

These compounds are intermediates in the manufacture of drugs.

The already known methods (K. J. M. Andrews, F. Bergel, A. L. Morrison, J. Chem. Soc. 1953, p. 2998; A. Fakstoro, J. Christiansen, Acta Chem. Scand., 8, 1954, p. 346; M. Borovicka, M. Protiva, 'Chem. Listy, 48, 1954, p. 1374,) for illustration these compounds have certain disadvantages when carried out industrially. As a starting material a 2-dialkylaminoethylisothiuronium chloride is used for this process - hydrochloride, which is decomposed by the action of a NaOH solution and converted into a 2-dialkylaminoethyl mercaptan and the sodium salt of which is then condensed with a 2-dialkylaminoethyl chloride.

The representation forms a very unpleasant step in the sequence of reactions just described of the free 2-dialkylaminoethyl mercaptans, which leads to only very low yields. These are likely due to the great volatility of this Caused compounds, partly of the amphoteric character, simultaneous presence of an acidic and a basic group in the molecule, partly in the presence of a sensitive one, due to atmospheric oxygen is ascribable to a disulfide group easily oxidizable sulfhydryl group.

For the same reason, the subsequent conversion of this mercaptan into the sulfide also proceeds with an unsatisfactory yield. So was z. B. the 2-dimethylaminoethyl mercaptan obtained only with a yield of 30 to 40% (Chem. Listy, 48, 1954, p. 1374), while the subsequent condensation to the sulfide proceeded with a yield of 60%. The Danish researchers (Acta Chem. Scand. 8, 1954, p. 346) produced the same mercaptan with a yield of 31% and their yield of the condensation product was 36.5%. The British authors (J. Chem. Soc, 1953, p. 2998) carried out the preparation of the mercaptan mentioned according to RO Clinton, UJ SaI method for the preparation of bis (dialkylaminoethyl) thioethers

Applicant:

Spofa, sdruzeni podnikü pro zdravotnickou

vyrobu, Prague

Representative:

Dipl.-Phys. Dr. W. Junius, patent attorney, Hanover, Abbestr. 20th Named as inventor: Dr.-Ing. Miroslav Protiva, RNDR. MiIoS Borovicka Prague Claimed priority: Czechoslovakia June 13, 1957 (PV 2116)

vador, S. C. Laskowski and CM. S u t e r (J. Am. Chem. Soc, 70, 1948, p. 950) with a yield of 22%. For the condensation was indicated a yield of 54%. From these results it can be seen that the sulfide is via the isothiuronium salt only obtainable with an overall yield of 11 to 21%, depending on the method of presentation is.

In the same work, the preparation of 2- (2-dialkylaminoethylmercapto) - described alkylamines, d. H. Compounds in which only one nitrogen atom of the molecule is substituted. To do this, either a substituted isothiuronium salt with a halogenated primary amine using Sodium ethylate reacted in absolute alcohol at -10 ° C., with satisfactory yields being obtained or it becomes an unsubstituted isothiuronium salt under the same conditions with reacted with a higher amine, the yields being unsatisfactory (18%). Symmetrically Substituted products can be built according to the process that involves the use of low temperature and the need to work in absolute alcohol does not have other disadvantages produce satisfactorily. In contrast, the present process, which also takes place at room temperature is being worked on, the first satisfactory way to produce symmetrically built substituted Aminoethyl mercapto compounds.

609 727/425

It has now been found that significantly higher yields can be achieved if the Isolation of the mercaptan leaves out.

The present invention therefore relates to a process for the preparation of bis (dialkylaminoethyl) thioethers the general formula

N - CH ₂ -CH ₃ - S - CH ₂ -CH ₂ -N

where R stands for identical or different low molecular weight alkyl radicals, by decomposition of a dialkylaminoethyl isothiuronium chloride hydrochloride the general formula

®NH ₂

N-CH ₂ -CH ₂ -SC

NH ₂

N-CH ₂ - CH ₂ - Cl • HCl

Standing at night. The next day, a solution of 38 g of 2-dimethylaminoethyl chloride hydrochloride in 100 cm ^{3 of} methanol is added with stirring and the mixture is stirred at room temperature for 1 hour, then heated to reflux in a water bath and boiled for 5 hours with constant stirring . After standing overnight, the precipitated potassium chloride is filtered off with suction and washed several times with methanol. The combined filtrates are then concentrated to about 200 cm ^{3 under reduced pressure, 200 cm 3 of} water are added to the residue and the oily product is etherified. The essential extract is dried with solid potassium hydroxide and evaporated after filtration. The bis (2-dimethylaminoethyl) sulfide is obtained in a yield of g (53% of theory) by distilling the residue under reduced pressure; B.p. _i2 93 to 98 ° C.

Cl® · HCl

and reacting the mercaptan formed with a 2-dialkylaminoethyl halide hydrochloride the general formula

The essence of the process according to the invention is that the decomposition of the isothiuronium compound with 4 equivalents of alkali metal hydroxide in aqueous-alcoholic solution without isolation of the contained mercaptans and the solution of the mercaptan with 2-dialkylaminoethyl chloride hydrochloride initially at room temperature and then reacted at boiling temperature.

The hydrolysis with consumption of 2 alkali equivalents already takes place at room temperature, and the resulting mercaptan is directly replaced by the third alkali equivalent to form one Alkali salt neutralized. The resulting solution is then mixed with an alcoholic solution of Treated 2-dialkylaminoethyl chloride hydrochloride, wherein the base of the 2-dialkylaminoethyl chloride is set free by the action of the fourth alkali equivalent and the desired condensation to sulfide takes place. To end the condensation, the reaction mixture comes to the boil heated. By working up the reaction mixture, known per se, and by distilling the products the sulfide is obtained in pure form and in a yield greater than 50%; It means that the yields given in the literature are exceeded two to four times.

Example _go

57 g of 2-dimethylaminoethyl-isothiuronium chloride hydrochloride are added to a solution of 60 g of potassium hydroxide in 150 cm ^{3 of} methanol and 15 cm ^{3 of} water with stirring, the mixture is stirred for 3 hours at room temperature and then left over

Claims (1)

Claim: Process for the preparation of bis (dialkylaminoethyl) thioethers of the general formula N-CH ₂ -CH ₂ -S-CH ₂ -CH ₂ -N where R stands for identical or different low molecular weight alkyl radicals, by decomposition of a dialkylaminoethyl isothiuronium chloride hydrochloride of the general formula ®NH ₂ N-CH ₂ -CH ₂ -SC NH ₂ Cl® · HCl and reacting the mercaptan formed with a 2-dialkylaminoethyl halide hydrochloride the general formula N-CH ₂ - CH ₂ - Cl • HCl characterized in that the decomposition of the isothiuronium compound with 4 equivalents of alkali hydroxide in aqueous-alcoholic solution without isolation of the contained Mercaptans undertakes and the solution of the mercaptan with 2-dialkylaminoethyl chloride hydrochloride initially at room temperature and then reacted at boiling temperature. Considered publications:
German Patent No. 900 575;
Journal of the American Chemical Society, Vol. 70, 1948, p. 550; Journal of the Chemical Society, 1953, p. 2998; Acta Chem. Scand. Vol. 8, 1954, p. 346;
Chem. Listy, Vol. 48, 1954, p. 1374.