DD236312A1 - PROCESS FOR PREPARING SULFIDIC MORPHOLINIUM CHLORIDE - Google Patents

Abstract

The invention relates to a process for preparing sulfidic morpholinium compounds which can be used as biologically active compounds, as reagents in the film industry and as cationic compounds. The aim of the invention is the economically advantageous presentation of sulfidic morpholinium chlorides. The invention has for its object to develop a oeconomically favorable process for the preparation of these compounds. The object is achieved by the invention that Morpholiniumchloride the general formula 3 are prepared by ethoxylated amines of general formula 1 with thionyl chloride to a, v-dichloro compounds of general formula 2 and thiols in the presence of hydrogen chloride-binding substances at temperatures of 65 to 150C and Reaction times of 4-8 hours, wherein the thiols and the hydrogen chloride-binding substances in admixture or synchronously in a suitable solvent to the solutions of a, v-dichloro compounds in the molar ratio thiol: base: compound 2 of preferably 1: 2: 1 added become.

Description

-2- 752 51

R 'and R ^{2 represent} alkyl (1-20 C atoms), cycloalkyl, aryl, aralkyl or heteroaryl radicals.

The preparation of the compounds 3 takes place in such a manner that the mercapto compounds R ² SH and the hydrogen chloride-binding substances are added in a mixture or synchronously with the α, ω-dichloro compounds 2, the ratio thiol: base: compound 2 preferably = 1: 2: 1 amounts to. With an excess of base, the compounds 2 to 4-organyl-4- [2- (2-chloroethoxy) ethyl] morpholinium chlorides of the general formula 4 or with an excess of mercapto compound to α, ω-Diorganylthioverbindungen of the general formula. 5 react.

For the preparation of the morpholinium chlorides 3, it is not necessary to purify the α, ω-dichloro compounds 2; they can advantageously be used as crude products.

Suitable hydrogen chloride-binding substances are suitable inexpensive bases such as sodium or potassium hydroxide, optionally also alkali metal carbonates. The amines used as starting materials are preferably aliphatic amines such as methylamine, butylamine or tetradecylamine, but also other primary amines such as benzylamine or aniline.

As compounds with mercapto groups aliphatic thiols, such as. Methanethiol, butane-1-thiol, hexane-1-thiol or dodecane-1-thiol, aromatic thiols, such as. As thiophenol, thiocresols or 1 -Mercaptonaphthalen or heterocyclic thiols, such as

z. For example, 2-mercaptothiazole, 2-mercaptobenzothiazole, 2-mercaptobenzimidazole or similar compounds.

Alcohols, acetonitrile, nitromethane, dimethylformamide, dimethyl sulfoxide and other solvents or mixtures customary in nucleophilic substitution can be used as the solvent.

The reaction is carried out at temperatures of 65-150 ° C, preferably at temperatures of 80-120 ⁰ C; the reaction times are then 4-8 hours. In order to prevent oxidation of the thiols, inert gas, preferably nitrogen, is expediently passed through during the reaction. The resulting compounds 3 are crystalline compounds or highly viscous oils, some strongly hygroscopic and are obtained in the usual ways (crystallization, column chromatography) pure.

embodiment

The invention will be explained in more detail with reference to 8 examples:

Example 1: G-butyl-1H-dichloro-S, -dioxa-G-aza-undecane hydrochloride

To 17.6 g of e-butyl-S ^ dioxa-o-aza-undecane-IJI-diol in 20 cm ^{3 of} chloroform 19 g of thionyl chloride are added dropwise at 10-15 ⁰ C with stirring and cooling. The mixture is allowed to stand overnight and the solvent is removed in vacuo. The residue solidifies in the refrigerator. It is washed with absolute ether and recrystallized from absolute acetone. The substance is hygroscopic; the melting point is 81-82 ⁰ C; the yield is 80% d. th

C ₁₂ H ₂₆ Cl ₃ NO ₂ (MM: 322.7); calculated: C 44.66 / 44.34, H 8.12 / 7.69, N 4.34 / 4.55

Example 2: e-Dodecyl-I.H-dichloro-S.S-dioxa-B-aza-undecane hydrochloride

The preparation is carried out from 6-dodecyl-3,9-dioxa-6-aza-undecane-1,11-diol as in Example 1. The substance is obtained as an oil, which is dissolved in absolute ether for purification and precipitated with petroleum ether. The yield of reagent-free substance is 40% d. Th. C ₂₀ H ₄₂ Cl ₃ NO ₂ (MM: 434.9); c./gef .: C 55.23 / 55.20, H 9.73 / 9.66, N 3.22 / 3.21

Example 3: 4-Butyl-4- [2- (2-butylthio-ethoxy) ethyl] morpholinium chloride

A solution of 6.3 g of butane-1-thiol and 5.6 g of caustic soda in 30 cm ^{3 of} ethanol are added to a boiling solution of 22.5 g of e-Butyl-i-i-dichloro-S, -dioxa-o- aza undecane hydrochloride in 50 cm ^{3 of} ethanol with stirring and nitrogen purging slowly added dropwise. The mixture is then heated to boiling for 6 hours, separated from the sodium chloride and the solvent is distilled off in vacuo. The residue is oily and crystallizes slowly under absolute ether. The yield is 18 g, that is 76% d. Th. C ₁₆ H ₃₄ CINO ₂ S (MM: 340.0); calc .: N, 4.12 / 3.94, Cl, 10.1 / 10.2

Example 4: 4-Butyl-4- [2- (2-dodecylthio-ethoxy) ethyl] morpholinium chloride

Dodecan-1-thiol is reacted with 6-butyl-1,11-dichloro-S ^ -dioxa-e-aza-undecane hydrochloride as in Example 3. After recrystallization from absolute acetone, the substance melts at 73 ° C. The yield is 67% d. Th C ₂₄ H ₅₀ CINO ₂ S (MM: 452.2);. calc .: 7.84 / 8.01

Example 5: 4-Butyl-4- [2- [2- (benzthiazol-2-yl-thio) ethoxy] ethyl] morpholinium chloride 2-Mercaptobenzothiazole is treated with 6-butyl-1,11-dichloro-S-dioxa -e-aza-undecane hydrochloride as implemented in Example 3. The purification is carried out by recrystallization from acetone and a little ethanol. The pure substance melts at 156 ° C and the yield is 86% d. th

C ₁₉ H ₂₉ CIN ₂ O ₂ S ₂ (MM: 417.0); C / V .: C 54.72 / 54.75 H 7.01 / 7.01 N 6.72 / 6.74

Example 6: 4-Dodecyl-4- [2- (2-butylthio-ethoxy) ethyl] morpholinium chloride

Butane-1-thiol is reacted with 6-dodecyl-1,11-dichloro-S ^ -dioxa-B-aza-undecane hydrochloride (crude product) as in Example 3. The substance is a viscous sticky mass and is dissolved in absolute ether for purification and precipitated with petroleum ether. The yield is 40-50% d. th

C ₂₄ H ₅₀ CINO ₂ S (MM: 452.2); calc .: 7.84 / 7.38

Example 7: 4-Butyl-4- [2- (2-chloroethoxy) ethyl] morpholinium chloride

15 g of δ-butyl-S-dioxa-e-aza-undecane-UI-diol in 30 cm ^{3 of} chloroform are added with cooling at 10-15 ° C with 15.5 g of thionyl chloride. It is allowed to stand overnight, poured into the same volume of water and makes with sodium hydroxide slightly alkaline (ρμ8). After about 5 minutes, the formation of the morpholinium compound can already be detected by thin-layer chromatography. The mixture is allowed to stand for a few hours, the chloroform layer is separated off and the aqueous phase is shaken out again with chloroform. The solvent is distilled off and the residue is recrystallized from absolute acetone. From the mother liquor can be precipitated with ether more substance. The yield is 80% d. Th., The melting point is 124 ⁰ C.

C ₁₂ H ₂₅ Cl ₂ NO ₂ (MM: 286.2); c./f .: C 50.35 / 49.89 H 8.80 / 8.73 N 4.89 / 4.81

Example: 8: H-Butyl-e.i ^ dioxa-B.i-dithia-H-aza-heneicosan

A solution of 45.2 g of e-Butyl-UI-dichloro-S ^ -dioxa-e-aza-undecane-hydro-chloride is dissolved in 100 cm ³ of ethanol to a boiling

Solution of 28 g of butane-1-thiol and 16.8 g of caustic soda in 80 cm ^{3 of} ethanol was added dropwise with stirring and nitrogen purge. The mixture is heated for 7 hours at reflux, the ethanol is distilled off and fractionated in vacuo. K _p = 183 ° C / 6 Pa; n _D ²⁰ = 1.4851

The yield is 32 g, which is 58% d. Th.

C ₂₀ H ₄₃ NO ₂ S ₂ (MM: 393.7); C / C .: C 61.02 / 61.04 H 11.01 / 10.67 N 3.56 / 3.50

Claims (1)

Invention claim: Process for the preparation of sulfidic morpholinium chlorides of the general formula 3, Cl where R ¹ and R ² = alkyl (1-20 C atoms), cycloalkyl, aryl, aralkyl or heteroaryl, characterized in that ethoxylated amines of general formula 1 with thionyl chloride to α, ω-dichloro compounds of general formula 2 'H Cl and these are reacted with thiols in the presence of hydrogen chloride-binding substances at temperatures of 65 to 150 ° C and reaction times of 4 to 8 hours by the thiols and the hydrogen chloride-binding substances in a mixture or synchronously in a suitable solvent to the solutions of α, ω-dichloro in the molar ratio of thiol: base: compound 2 of preferably = 1: 2: 1 are added. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of sulfidic Morpholiniumchloride, z as biologically active compounds. As in crop protection, as a corrosion inhibitor, in the modification of photographic developers and can be used as cationic compounds. Characteristic of the known technical solutions Compounds of this type are not yet known. Their preparation is possible in principle analogous to known morpholinium, z. B. by quaternization of the corresponding 4-substituted morpholines (either of 4-Organylmorpholinen with 2- (2-organylthio-ethoxy) ethyl-chlorides or 4- [2- (2-organylthio-ethoxy) ethyl] morpholines with chloroalkanes) or by reacting secondary N-substituted 2- (2-organylthio-ethoxy) ethylamines with 2,2'-dichlorodiethyl ether. However, these processes have the disadvantage that starting materials must be used whose preparation proceeds over a larger number of intermediates, sometimes with poor yields. Object of the invention The aim of the invention is the economically advantageous presentation of sulfidic morpholinium chlorides. Explanation of the essence of the invention The invention has for its object to develop an economically favorable process for the preparation of sulfidic Morpholiniumchloride. The object is achieved in that tertiary amines of the structure 1, which can be in a known manner from primary amines R ¹ NH ₂ and the resulting in Ethyienchlorhydrinsynthese 2-chloroethoxyethanol or in the homolog mixture of primary amine and ethylene oxide, with thionyl chloride usual way to compounds of structure 2 and these thiol-containing substances R ² SH in the presence of hydrogen chloride-binding substances in suitable solvents to compounds of structure 3 are implemented. τ +