NO142669B - ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE, HETEROCYCLIC COMPOUNDS - Google Patents

Description

The present invention relates to an analogous method for the preparation of therapeutically active, heterocyclic compounds with the general formula

where R means a residue with the formula

wherein 1^, R2 and means hydrogen, halogen, lower alkyl, lower alkoxy, benzyloxy, phenyl, nitro, trifluoromethyl, hydroxy, cyano, di-lower alkylamino

or lower alkanoyloxy or two residues in a neighboring position together methylenedioxy, ethylenedioxy or butadiene-1,3-ylen-1,4,

R4 means hydrogen or lower alkyl,

R,., Rg and R7 mean hydrogen, halogen, lower alkyl, or lower alkoxy or two residues in a neighboring position together methylenedioxy or ethylenedioxy,

X means a sulfur atom, SO or SO,,,

Y means a straight chain or branched, optionally

with hydroxy substituted, alkylene residue with 2-5 carbon atoms, and

Z means a straight-chain or branched, optionally substituted with hydroxy, alkylene residue with 1-4 carbon atoms, and

m are the numbers 0 or 1 and

n the numbers 2 or 3, under which the "lower" residues contain 1-6 carbon atoms

and acid addition salts thereof.

Structurally related compounds are known from the German explanatory document no. 1,154,810 and DOS no. 2,000,435 which likewise have coronary dilatatory properties as calcium antagonists. However, these compounds are burdened with stronger and longer-lasting hypotensive and negative-ionotropic effects, i.e. with side effects, which can be clinically unfortunate. In contrast to these, the compounds produced according to the present invention do not have these negative properties, but on the contrary also have good anti-arrhythmic properties with good tolerability.

The term "lower alkyl" within the scope of the present invention means straight-chain or branched alkyl groups with 1-6 carbon atoms, such as e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert. butyl, amyl, hexyl.

"Lower alkoxy" means lower alkyl ether groups, where the term "lower alkyl" has the aforesaid meaning. "Halogen" includes the 4 halogen atoms fluorine, chlorine, bromine and iodine. "Lower alkanoyl" means alkanoyl groups with up to 6 carbon atoms, such as e.g. formyl, acetyl, propionyl, butyryl. "Aryl" means unsubstituted or substituted phenyl, the substituents being halogen, lower alkyl, lower alkoxy, nitro and amino. The term "leaving group" used in the following means, within the scope of the present invention, known groups such as e.g. halogen, preferably bromine or chlorine, arylsulphonyloxy, such as e.g. tosyloxy, alkylsulfonyloxy such as e.g. mesyloxy or also an epoxy group.,

The method according to the present invention for preparing the compounds of the above formula I and their salts is characterized by

a) reacts with a compound of the general formula

where R, X and n have the above meanings, with a compound of the general formula

where R ^ • - Ry, Yy Z and m have the aforementioned meanings, and

Rg means a leaving group such as halogen, arylsulfonyloxy or alkylsulfonyloxy

or

b) reacts with a compound of the general formula

where R, R4 - R7, Y, Z and m are previously indicated

importance,

with a compound of the general formula

where n has the above meaning,

or

c) reacts with a compound of the general formula

where R, Rg, X, Y and n have previously been specified

meanings,

with a compound of the general formula

where R^ - R7, Z and m have the previously stated meanings,

or

d) reacts with a compound of the general formula

where R, R^, X, Y and n have those indicated above

meanings,

with a compound of the general formula

where R, - - Rg, Z and m have those indicated above

meanings,

or

e) in a compound of the general formula

in which R, R4 -■R7, X, Y, Z, m and n have the previously stated meaning,

Y. and Z^ is a group corresponding to Y and respectively. Z at the time

at least one of the groups Y^ and Z^ contains a carbonyl group and R^ means hydrogen or an alkyl group with 1-5 carbon atoms,

reduces the carbonyl group

after which, if desired, a compound of formula I, in which X represents a sulfur atom, is oxidized to a compound of formula I, in which X represents. So or SO^, that one, if desired, N-lower-alkylates a compound of formula T,' in which R^ means hydrogen, that one, if desired, transfers a lower alkoxy- or benzyloxy- to a hydroxy group, that one, if desired, etherifying or esterifying a hydroxy group with a lower alkanecarboxylic acid and, if desired, transferring a base obtained to an -acid addition salt.

Preferred compounds falling under the preceding formula I are the compounds which are prepared according to claims 2-10 and whose special effect is evident from the later specified tables I and

II-

The reaction of a compound of formula II with a compound of formula III can be carried out in a manner known per se. Appropriately, the reaction takes place in an, under the reaction conditions inert, organic solvent and at a temperature between approx. -80°C and the reflux temperature of the reaction mixture, preferably between 0 and 50°C and in particular at room temperature. Ethers such as e.g. diethyl ether,

tetrahydrofuran, dioxane, aromatic hydrocarbons,

like for example. benzene, toluene, xylene or also dimethylformamide, dimethylsulphoxide. The reaction takes place in nsrvær

of a strong base such as butyllithium, a Grignard compound, sodium or sodium hydride, whereby, if X is a sulfur atom, suitably a particularly strong base such as butyllithium or a Grignard compound is used.

The compounds of the preceding formulas II and III used as starting materials are partly known and partly new. The new compounds are likewise subject to the invention. They can be produced in a manner known per se, i.e. in a manner analogous to the preparation of the known compounds.

The compounds of formula II, where X is a sulfur atom, can e.g. is obtained by reacting an aldehyde of the formula

where R has the preceding meaning,

with ethane or propane dithiol. The reaction conveniently takes place in an inert organic solvent, e.g. chloroform under room temperature.

The compounds of formula II, where X means SO or SO2, can be obtained by oxidation of corresponding compounds, where X is a sulfur atom. The oxidation can conveniently take place in a suitable solvent, using peracids such as peracetic acid, perphthalic acid, m-chloro-perbenzoic acid. Peracetic acid can e.g. is formed in situ from glacial acetic acid and hydrogen peroxide.

The reaction of a compound of formula IV with a compound of formula V can be carried out in a manner known per se. Appropriately, the reaction takes place in an, under the reaction conditions inert, organic solvent, preferably in a polar solvent such as halogenated hydrocarbons, e.g. chloroform, methylene chloride, or in ethylene glycol dimethyl-

ether, etc. The reaction also conveniently takes place in the presence of a water-splitting agent, such as e.g. sulfuric acid, hydrohalic acid, phosphoric acid and at a temperature between approx. 0°C and the reflux temperature of the reaction mixture, preferably at room temperature.

The compounds of formula V used as starting materials

are known and can be produced in a known manner.

The compounds of formula IV used as starting materials are new.

The compounds of formula IV can e.g. is produced by reacting a compound of the general formula

where R and Y have the preceding meanings, with a compound of the general formula

where R^ -Ry, Z and m have the above meanings..

The conversion conveniently takes place in the presence of an acid-binding agent, such as e.g. a tart. amine, e.g. N-ethyl-N,N-diisopropylamine, which also serves as a solvent. The reaction also suitably takes place at an elevated temperature, preferably at a temperature of up to approx. 130°C, depending on the boiling point of the solvent.

The compounds of formula XlVa used above are partly known and partly new. They can be produced in a manner known per se, i.e. in a manner analogous to the preparation of known compounds. The compounds of formula VII are known.

The reaction of a compound of formula VI with a compound of formula VII can be carried out in a manner known per se. Appropriately, the reaction takes place in an, under the reaction conditions inert, organic solvent, such as an ether, e.g. dibutyl ether, dioxane, tetrahydrofuran, an alkanol such as e.g. ethanol or propanol, an aromatic hydrocarbon such as benzene, toluene or xylene or also in acetonitrile, dimethylformamide, dimethylsulfoxide. The reaction can through-

carried out at a temperature between approx. room temperature and reaction

the reflux temperature of the mixture. Preferably, work is carried out at reflux temperature. If acid is split off during the reaction, this conveniently happens in the presence of a base, e.g. a tart. amine such as e.g. trimethylamine, N-ethyl-N,N-diisopropylamine or N,N-dimethylaniline.

The compounds of formula VII used as starting material

are known. However, the compounds of formula VI are new. The compounds of formula VI can e.g. is produced by reacting a compound of formula

where R, Rg and Y have the above meanings, with a compound of formula

where n has the above meaning,

and, if desired, transfers such an obtained compound of formula VI, where X means a sulfur atom, by oxidation to a compound of formula VI, where X means SO or SO2-

The reaction of a compound of formula XIV with a compound of formula V can be carried out in a manner known per se. Appropriately, the reaction takes place in an organic solvent that is inert under the reaction conditions, preferably in a polar solvent such as halogenated hydrocarbons, e.g. chloroform, methylene chloride or in ethylene glycol dimethyl ether. The reaction also conveniently takes place in the presence of a water-splitting agent, such as e.g. sulfuric acid, halogen-hydrogen acid, phosphoric acid and at a temperature between approx. 0°C and the reflux temperature of the reaction mixture, preferably at room temperature.

The transfer of a compound of formula VI obtained in this way, where X is a sulfur atom, to a compound where X is SO or SO 2 can take place in a manner known per se, e.g. by oxidation with a peracid such as e.g. peracetic acid, perphthalic acid, m-chloroperbenzoic acid. Peracetic acid can e.g. is formed in situ from glacial acetic acid and hydrogen peroxide.

The reaction of a compound of formula X with a compound of formula XI can be carried out in a manner known per se. Appropriately, the reaction takes place in an organic solvent that is inert under the reaction conditions, such as an ether, e.g. dibutyl ether, dioxane, tetrahydrofuran, an alkanol such as e.g. ethanol or propanol, an aromatic hydrocarbon such as e.g. benzene, toluene or xylene or also in acetonitrile, dimethylformamide, dimethylsulfoxide. The reaction can be carried out at a temperature between approx. room temperature and the reflux temperature of the reaction mixture. Preferably work at reflux temperature. If during the reaction the acid is split off, this conveniently happens in the presence of a base, e.g. a tertiary amine such as triethylamine, N-ethyl-N,N-diisopropylamine or N,N-dimethylaniline.

They used compounds of formula XI as starting materials

are known. However, the compounds of formula X are new.

The compounds of formula X can e.g. is produced by reacting a compound of formula

where R, X, Y and n have the above meanings,

with an amine of the formula

where R4 has the above meaning.

Since hydrogen chloride is split off by this, the reaction conveniently takes place in the presence of a base or using an excess of the amine of formula VI. Moreover, the reaction can be carried out in a manner analogous to the reaction of a compound of formula VI with a compound of formula VII.

The compounds of formula XVI are known. The compounds of formula Via, which are partly new, can be prepared in a manner analogous to the preparation of the compounds of formula VI.

The reduction of a carbonyl group or a group A to a compound of formula XII or XIII can be carried out on

in and of itself known manner.

Thus, an amide of formulas XII or XIII, i.e. a compound where the carbonyl group is bound directly to the nitrogen atom is reduced by treatment with metal hydrides such as lithium aluminum hydride, diisobutylaluminum hydride or with diborane. This conveniently takes place in an organic solvent that is inert under the reaction conditions, such as ether, e.g. diethyl ether, tetrahydrofuran or in di-

glyme and at a temperature between about 0°C and the reflux temperature of the reaction mixture, preferably at about room temperature.

The reduction of other carbonyl groups, i.e. those that are not bound directly to the nitrogen atom can likewise be carried out in a manner known per se. In particular, the reduction can be carried out so that it either leads to the corresponding hydroxymethylene group, which can then be further reduced to the methylene group, or directly to the methylene group.

The reduction to the hydroxymethylene group can be carried out by treatment with a complex metal hydride, such as an alkali metal aluminum hydride or an alkali metal borohydride.

The reduction using an alkali metal aluminum hydride or an alkali metal borohydride can conveniently be carried out at room temperature or at a temperature below or above room temperature and in an inert, organic solvent. Examples of suitable solvents for the reduction with an alkali metal aluminum hydride include anhydrous ether such as diethyl ether and tetrahydrofuran and for the reduction with an alkali metal borohydride, alkanols with 1-4 carbon atoms, such as methanol, ethanol or also dioxane. Lithium aluminum hydride is preferably used as alkali metal aluminum hydride and sodium borohydride is preferably used as alkali metal borohydride.

The further reduction of a hydroxymethylene group to the methylene group can be carried out in a manner known per se, in particular by conversion to the corresponding sulphonic acid esters or to halides and reduction of these with complex metal hydrides.

These reductions can be carried out in an analogous way to the described reduction of carbonyl groups.

The direct reduction of a carbonyl group to the methylene group can take place in a manner known per se, by means of a Wolff-Kishner reaction, i.e. by reacting the ketone with the help of

of hydrazine to the corresponding hydrazone and cleavage of the hydrazone under basic conditions.

They used as starting material compounds of the formulas XII

and XIII are new compounds.

Amides of the formula XII can e.g. is produced by reacting an acid of the formula

where R, Y, X and n have the above meanings, with an amine of the formula where R 1 - R 7 , Z and m have the above meanings. The reaction can conveniently take place in the presence of a tertiary amine such as triethylamine and a halocarboxylic acid ester such as chloroformate isobutyl ester (mixed anhydride method) in an inert, organic solvent, e.g. tetrahydrofuran and at a temperature of approx. 0°C to approx. 30°C. The compounds of formula XVII can be prepared in a method described above for the preparation of the compounds of formula XI, analogously by starting from compounds of the formula

The compounds of the formula XVIII belong to a known compound class.

The ketones of formula XII can be prepared in a manner known per se, e.g. by oxidation of the corresponding alcohols. The oxidation can e.g. happen with the chromium trioxide/pyridine complex in pyridine at a temperature of approx. -20°C to approx. room temperature, preferably at approx. 0°C.

The production of the amides of formula XIII can take place in a manner known per se, e.g. by acylation of a compound of formula I, where R 1 means hydrogen. The acylation can e.g. happen with a halide of a lower carboxylic acid in a tertiary amine, e.g. pyridine, wood. a temperature of approx. o°C to approx. 30°C, preferably at approx. room temperature.

The conversion of a compound of formula I, where X is a sulfur atom, to a compound where X means SO or SO2 can take place by oxidation in a suitable solvent, using peracids such as peracetic acid, perphthalic acid, m-chloroperbenzoic acid

Peracetic acid can e.g. is formed in situ from glacial acetic acid

and hydrogen peroxide.

Obtained compounds of formula I, where R 4 means hydrogen,

can be alkylated in a manner known per se, e.g. using lower alkyl halides. The compound in question is suitably reacted immediately with alkyl halides at low temperature.

The transfer of a lower alkoxy or aryl-lower alkoxy group to a hydroxy group can be carried out in a manner known per se, e.g. by heating with a concentrated hydrohalic acid, especially constantly boiling hydrobromic acid.

The reduction of a nitro group to the amino group can take place at i

and in a known manner, chemically or catalytically, e.g. using tin/hydrochloric acid or with hydrogen in the presence of a noble metal catalyst. The hydrogenation is preferably carried out in an alkanol, especially ethanol in the presence of palladium/charcoal or platinum oxide under normal pressure at room temperature.

The saponification of a cyano group can be carried out in a manner known per se, using an acid or a base.

The esterification or amidation of a carboxyl group can be carried out in a manner known per se, e.g. by treatment with a corresponding alcohol or a corresponding amine.

A present amino group: can, as mentioned above, be alkylated or, by treatment with an acid halide or acid anhydride, acylated in a manner known per se.

The esterification, as well as the esterification of a hydroxy group present, can take place in a manner known per se, e.g. by reaction with a corresponding halide, respectively with a corresponding acid halide or an acid anhydride.

The reduction of a carboxyl group can be carried out in a manner known per se, e.g. using diborane or lithium aluminum hydride in an inert organic solvent.

The oxidation of an alkylthio group can take place in a manner known per se, e.g. using hydrogen peroxide.

The compounds of formula I can be converted into acid addition salts, e.g. by treatment with an inorganic acid, such as a halogen-hydrogen acid, e.g. hydrochloric or hydrobromic acid, sulfuric acid, phosphoric acid or with an organic acid such as oxalic acid, tartaric acid, citric acid, methanesulfonic acid.

Of the acid addition salts of the compounds of formula I, the pharmaceutically usable ones are preferred. If an acid addition salt of a compound of formula I is obtained in the course of the method according to the invention, then such a salt can be transferred in a known manner, e.g. by treatment with alkali, to the free base and this can, if desired, be transferred to an acid addition salt.

The compounds of formula I, which contain an asymmetric carbon atom, can exist in racemic or optically active form and both the racemic and the optically active forms are the subject of the present invention. A race food. can, if desired, be split o'pp<r>in a manner known per se to the optical antipodes, e.g. by fractional crystallization of the corresponding salts with an optically active acid.

The compounds of formula I, as well as their acid addition salts, possess valuable coronary dilating properties and can thus i.a. find application for the treatment of angina pectoris.

The coronary dilating effect can be measured according to the following method:

For the investigation, bastard dogs weighing between 20 and 20 kg are used

and 38 kg. The experimental animals are drugged with approx. 30 mg/kg i.v. pentobarbital and anesthesia is maintained with chloralose-urethane. Artificial respiration is maintained for the animals with room air. After opening the thorax, the heart and the Ramus circumflexus are exposed

In the left coronary artery, a pre-measured Flow probe of an electromagnetic flow meter is placed to measure the amount of blood flowing through. The arterial blood pressure is measured over a catheter in the femoral artery with a pressure transducer. Furthermore, a calibrated dilatation measuring strip is provided on the surface of the left ventricle for direct measurement of myocardial contraction force. The pulse wave for the blood pressure triggers a tachograph for measuring the heart rate. Water-soluble preparations are dissolved in isotonic sodium chloride solution, water-insoluble in propylene glycol, administered intravenously or as a suspension in gum arabic intraduodenal. The maximum effect of a substance is calculated after each dosage as a percentage of the initial value and displayed graphically. When measuring coronary blood flow, special consideration is given to the duration of action.

In the following table, the results obtained are compiled, where n means the number of animals used.

For the investigations, bastard dogs with weights in between were used

20 and 38 kg. The experimental animals were drugged with approx. 30 mg/kg i.v. pentobarbital and the anesthesia were maintained with chloralose-urethane. The animals received artificial respiration with room air. After opening the thorax, the heart was exposed and around the Ramus circumflexus of the left coronary artery a pre-calibrated flow sample of an electromagnetic flow meter was placed to measure the amount of blood flowing through. Water-soluble preparations were administered intravenously in isotonic saline solution, water-soluble ones dissolved in propylene glycol. The maximum effect of a substance was calculated as a result of each dosage as a percentage of the initial value and presented graphically.

The following table I shows the results obtained for

3 compounds, where n means the number of animals used. As can be seen from the table, when the dose is increased, a maximum effect is achieved, which will decrease again when the dose is increased further.

The following table II summarizes these action maxima for a representative number of compounds according to the present application.

The process products and their pharmaceutically usable acid addition salts can find use as drugs in the form of pharmaceutical preparations, which contain these products in admixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral or parenteral administration, such as e.g. water, gelatin, gum arabic, milk sugar, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycol, petroleum jelly. The pharmaceutical preparations can be in solid form, e.g. as tablets, dragées, capsules or in liquid form, e.g. in solutions, suspensions or emulsions. If necessary, they are also sterilized according to or contains auxiliary substances, such as preservatives, stabilisers, wetting or emulsifying agents, salts to change the osmotic pressure or buffers.

The daily dose for oral administration is between approx. 10-200 mg, by intravenous administration between approx. 1-20 mg.

However, the stated dosages are only to be understood as examples and can be changed according to the difficulty of the disease to be treated and according to the treating doctor's assessment.

EXAMPLE 1

74.7 g of 3,4-dimethoxybenzaldehyde is dissolved in 1250 ml of chloroform and 50 ml of 1,3-propanedithiol is added and cooled with stirring at 0°C. 20 ml of boron trifluoride etherate is added to this and the reaction mixture is allowed to stand for 18 hours in a refrigerator. It is then washed three times successively with 500 ml of a 7% KOK-

solution and 500 ml of a 10% NaCl solution. The organic extracts are combined, dried with magnesium sulfate and evaporated.

The residue is recrystallized twice with ether. You get 102.6

g 2-(3,4-dimethoxyphenyl)-m-dithiane with a melting point of 99 -

101°C.

In an analogous way, the following dithianes can be prepared: 2-(o-methoxyphenyl)-m-dithiane: melting point 126 - 127°C (from CH2C12/isopropyl ether)

2-phenyl-m-dithiane: melting point 72 - 73°C (from CH2C12/isopropyl-

ether )

2-(p-Chlorophenyl)-m-dithiane: melting point 87 - 88°C (from CH2C12/ in isopropyl ether)

2-(m-Methoxyphenyl)-m-dithiane: melting point 62 - 63°C (from isopropyl ether)

2-(3,4-,5-trimethoxyphenyl)rm-dithiane: melting point 88 - 89°C (from CH2C12/isopropyl ether)

2-(m-chlorophenyl)-m-dithiane: melting point 63 - 64°C (from cyclohexane) 2-(3,5-dimethoxyphenyl)-m-dithiane: melting point 90 - 91°C (from cyclohexane)

p-(m-dithian-2-yl)-N,N-dimethylaniline: melting point 118 - 119°C

(from cyclohexane)

2-(m-nitrophenyl)-m-dithiane: melting point 117 - 118°C (from CH2Cl2/methanol)

2-(3,4-methylenedioxyphenyl)-m-dithiane: melting point 86 - 87°C

(from cyclohexane)

2-p-tolyl-m-dithiane: melting point 89 - 90°C (from ether/hexane) 2-(m-bromophenyl)-m-dithiane: melting point 78 - 79°C (from cyclohexane) 2-(2-naphthyl )-m-dithiane: melting point 110 - 111°C (from cyclo-hexane) 2-(2,4,5-trimethoxyphenyl)-m-dithiane: melting point 156 - 157°C

(from CH2Cl2/methanol)

2-(p-fluorophenyl)-m-dithiane: melting point 105 - 106°C (from cyclohexane)

2-(4-biphenylyl)-m-dithiane: melting point 148 - 151°C (from tetrahydrofuran/cyclohexane)

2-(α,α,α-trifluoro-p-tolyl)-m-dithiane: melting point 103 - 104°C

(from cyclohexane)

2-(1-Naphthyl)-m-dithiane: melting point 147 - 148°C (from cyclohexane) 2-(3-benzyloxy-4-methoxyphenyl)-m-dithiane: melting point 168 - 170°C

(from cyclohexane)

2-(4-benzyloxy-3-methoxyphenyl)-m-dithiane: melting point 118 - 119°C

'from cyclohexane)

2-(2-thienyl)-m-dithiane: melting point 74 - 75°C (from cyclohexane) 2-(a , a ,cc-trifluoro-m-tolyl) -m-dithiane: melting point 69 - 71°C

(from heptane)

2-(p-isopropylphenyl)-m-dithiane': mp 58 - 59°C (from hexane) 2-(3,4-xylyl)-m-dithiane: m.p. 74 - 75°C (petroleum ether)

2-(3-butoxy-4-methoxyphenyl)-m-dithiane

2-(4-ethoxy-3-methoxyphenyl)-m-dithiane: m.p. 88 - 90°C (from methylene-

chloride + isopropyl ether)

m-(m-dithian-2-yl)-benzonitrile: m.p. 84 - 86°C (from isopropyl ether) 6-m-dithian-2-yl-1,4-benzodioxane: m.p. 140 - 142°C (from methylene-

chloride + isopropyl ether)

2-(4-Methoxy-m-thioyl)-m-dithiane: m.p. 75 77°C (from cyclohexane).

EXAMPLE. 2

60 g of 2-(3,4-dimethoxyphenyl)-m-dithiane (prepared according to example

1) dissolved in 470 ml of glacial acetic acid and added at room temperature

-'V:' rv'2-35 ml »3;0%' i'g H2b2- ,./hypcve'd~:.-tohp;5r^^réh'' - to .;opp3L;osningen* stfigéiS " '*..•" • ..';''' to approx. 40°C. The solution is allowed to stand overnight at room temperature.

temperature. It is then heated for 2 hours to 100°C. After cooling to room temperature, the crystalline base is

fall off, wash with some glacial acetic acid, dry in vacuum at 60°C

overnight and then recrystallized from acetonitrile. 57.1 g of 2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-

tetraoxide with a melting point of 243 - 245°C.

Analogously to what is described above, the following ditiano-

tetraoxides are produced:

2-(m-bromophenyl)-m-dithiane-1,1,3,4-tetraoxide: melting point 230 -

231 C (from acetonitrile)

2-(p-Fluorophenyl)-m-dithiane-1,1,3,3-tetraoxide: melting point 283 -

284 C (from acetonitrile

2-(m-nitrophenyl)-m-dithiane-1.1,3.3-tetraoxide: melting point 256 -

257 c (from acetonitrile)

2-(3,4,5-trimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide: melting

point >310 C (from acetonitrile)

2-(2-naphthyl)-m-dithiane-1,1,3,3-tetraoxide: melting point 277 - 278°C

(from acetone/acetonitrile)

2-p-tolyl-m-dithiane-1,1,3,3-tetraoxide: melting point 284 - 285°C

(from acetonitrile)

2-(4-Benzyloxy-3-methylxyphenyl)-m-dithiane-1,1,3,3-tetraoxide:

melting point 220 - 223 C (from acetone/aceton tril)

2-(3,4-dimethoxyphenyl)-1,3-dithiolane-1,1,3,3-tetraoxide: melt-

point 194 - 196 C (from acetone/acetonitrile)

2-(3,4-methylenedioxyphenyl)-m-dithiane-1,1,3,3-tetraoxide: melting

point >300 C (from acetone/acetonitrile)

2-(2<1->thienyl)-m-dithiane-1,1,3,3-tetraoxide: melting point >300°C

(from acetone/acetonitrile)

2-(3,4-dichlorophenyl)-m-dithiane-1,1,3,3-tetraoxide: melting point 254 - 255 C (from glacial acetic acid-water)

2-(α,α,α-triflupr-m-tolyl)-m-dithiane-1,1,3,3-tetraoxide: melt-

point 239 - 242 C (from glacial acetic acid-water)

2-(p-isopropylphenyl)-m-dithiane-1,1,3,3-tetraoxide: melting point 204 - 205 C (from acetonitrile-ethanol)

2-(3^,4-xylyl)-m-dithiane-1,1,3,3-tetraoxide: melting point 268 -

269 C (from acetonitrile + methanol)

2-(3-Butoxy-4-methoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide:

melting point 225 - 227 C (from glacial acetic acid-water)

2-(4-ethoxy-3-methoxy enyl)-m-dithian-1,1,.3} 3-tetraoxide:' melt-• . point,''.242 2'44 C (from Jaceton-acetoni tril.)'i : . • '. '" .' 'm-(m-dithian-2'-vi)-benzonitrile-1',1',3',31-tetraoxide:.melt-

point 259 - 260 C (from glacial acetic acid-water)

6-m-dithian-2'-y^-1,4-benzodioxane-1<1>,1',3',3'-tetraoxide:

melting point 232 C decomposition, (from glacial acetic acid-water)

2(4-methoxy-m-tolyl)-m-dithiane-1',1',3',3'-tetraoxide: melting

point 225 - 227 C (from glacial acetic acid-water).

EXAMPLE 3

In a sulfurization flask, under argon gassing, 19.2 g of 2-(3,4-dimethoxyphenyl)-m-dithane (prepared according to example 1) and 200 ml of tetrahydrofuran are cooled to -60°C and 33 ml of butyllithium in hexane are slowly added. The mixture is then stirred for 2 hours

-20°C. A solution of 18 g of N-(3-chloropropyl)-3,4-dimethoxy-N-methyl-phenethylamine in 200 ml of tetrahydrofuran is added dropwise to this

in increments of 15 minutes at -70°C. This is then allowed to stand for 18 hours at -20°C in a deep freezer and 3 hours at room-

temperature. The reaction solution is then poured onto water and ex-

triturated three times with ether. The ethereal extracts ex-

is triturated three times with 250 ml of 1 N KC1. 3 N sodium hydroxide is added to the acidic extracts until pH >12 and the separated oil is extracted with ether. The organic extracts are dried with magnesium sulfate and evaporated. The oil thus obtained (30 g) is dissolved in vinegar and ethereal HBr is added. The precipitate precipitated is recrystallized in ethanol. N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine hydrobromide with a melting point of 170 - 172°C is obtained.

Analysis for C2gH37N04S2-HBr

The N-(3-chloropropyl)-3,4-dimethoxy-N-methyl-phenethylamine used as starting material can be prepared as follows: 292.5 g of N-methylhomoveratrylamine are dissolved in 1000 ml of dimethylformamide and 415 g of anhydrous potassium carbonate are added. The mixture is stirred at 5°C, 237 g of 1.3 bromochloropropane in 500 ml of dimethylformamide are added, stirred for a further 4 hours at room temperature and then poured into 6 liters of water. The oil that is secreted extra- ■ here three times with each time 2 liters of ether. The organic extracts are dried with magnesium sulphate and evaporated in vacuo. The remaining oil is distilled with a mercury vapor diffusion pump at 0.005 mmHg between 69 and 70°C. You get 206.7

g N-(3-chloropropyl)-3,4-dimethoxy-N-methyl-phenethylamine: boiling point 69 - 70°C/0.005 mmHg.

Analogously to what was described above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-2-(m-methoxyphenyl)-N-mgtyl-m-dithian-2-propylamine hydrochloride: melting point 113 - 115 C (from acetone) N-(3,4-dimethoxyphenethyl-2-(3,4,5-trimethoxyphenyl)-N-methyl-m-dithian-2-propylamine hydrochloride: melting point 14 7 - 150 C

(of acetone)

N-(3,4-dimethoxyphenethyl)-2-(p-methoxyphenyl)-N-methyl-m-dithiane-2-propylamine hydrochloride: melting point 160 - 161 C (of acetone) N-(3,4-dimethoxyphenethyl) -2-(o-methoxyphenyl)-N-methyl-m-dithian-2-propylamine hydrochloride: melting point 151 - 152°C (of acetone) 2-(p-chlorophenyl)-N-(3,4-dimethoxyphenethyl) -N-methyl-m-dithian-2-propylamine hydrochloride: melting point 137 - 139 C (of acetone) N-(3,4-dimethoxyphenethyl)-N-methyl-2-phenyl-m-dithian-2-propylamine- hydrochloride: melting point 170 - 172 C (of acetone) N-(3,4-dimethoxyphenethyl)-N-methyl-2-(3,4-methylenedioxyphegyl)-m-dithiane-2-propylamine hydrochloride: melting point: 139 - 141 C

(of acetone)

N-(3,4-dimethoxyphenethyl)-N-methyl-2-(p-tolyl)-m-dithian-2-propylamine hydrochloride: melting point 139 - 141 C (from acetone) 2-(m-chlorophenyl)-N -(3,4-dimethoxyphenethyl)-N-methyl-m-dithian-2-propylamine hydrochloride: melting point 108 - 110 C (from acetone) N-(3,4-dimethoxyphenethyl)-2-(3,5 -dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine-oxalate (1:1): melting point 155 - 156 C

(of acetone)

N-(3,4-dimethoxyphenethyl)-2-(p-dimethylaminophenyl)-N-methyl-m-dithian-2-propylamine hydrochloride: melting point 183 - 184 C

(in acetone)

N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl)-m-dithian-2-propylamine hydrochloride: melting point 195 - 196 C (of acetone) N-(3,4-dimethoxyphenethyl) -N-methyl-2-(2,4,5-trimethoxyphenyl)-m-dithian-2-propylamine hydrochloride: melting point 156 - 158 C

(of acetone)

N-(3,4-dimethoxyphenethyl)-2-(p-fluorophenyl)-N-methyl-m-dithian-2-propylamine hydrochloride: melting point 138 - 139 C (from acetone) 2-(4-biphenylyl)-N - (3,4-dimethoxy enethyl)-N-methyl-ig-dithian-2-propylamine-oxalate (1:1): melting point 167 - 169 C (of acetone) v ■ . •. • N-(p-chlorophenethyl)-N-methyl-2-phenyl-g-dithian-2-propylamine-

hydrochloride: melting point 145 - 14 7 C (of acetone) starting from 2-phenyl-m-dithiane and N-(3-chloropropyl)-4-chloro-N-methyl-

phenethylamine

N-methyl-N-phenethyl-2-fgny1-m-dithiane-2-propylamine hydrochloride:

melting point 136 - 137 C (of acetone) starting from 2-phenyl-

m-dithiane and N-(3-chloropropyl)-N-methyl-phenethylamine (boiling point 78 - 80°C/0.001 mmHg)

N-(3,4-dimethoxyphenethyl)-N-methyl-2-phenyl-m-dithiane-2-ethylamine hydrochloride: melting point 172 - 174 C (of acetone) starting from 2-phenyl-m-dithiane and N-(2-chloroethyl)-3,4-dimethoxy-N-methyl-phenethylamine

N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-thienyl)-m-dithian-2-propylamine hydrochloride: melting point 138 - 140 C (from acetone) rac-N-(3,4- dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N,P-dimethyl-m-dithian-2-propylamine-oxalate (1:1) melting point 138 -

139 C (of acetone-acetic ester) starting from 2-(3,4-dimethoxyphenyl)-m-dithiane and N-(3-chloro-2-methylpropyl)-3,4-dimethoxy-N-methylphenethylamine

EXAMPLE 4

35.2 g of 2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide (prepared according to Example 2) was suspended in 180 ml of abs. dioxane and added with 2.53 g of sodium. The mixture is boiled under argon for 20 hours, whereby the sodium dissolves completely. Then 27.2 g of N-(3-chloropropyl)-3,4-dimethoxy-N-methyl-phenethylamine (prepared according to example 3) are added at room temperature, the dry solution is stirred for 1 hour at room temperature and boiled for 3 hours at reflux. The mixture is poured onto ice-water and extracted three times with vinegar. The acetic ester extracts are combined and extracted with 1 N HCl

three times. The acidic extracts are made alkaline and extracted with chloroform three times. The chloroform extracts are combined, washed with water, dried with magnesium sulfate and evaporated. The crystalline residue is recrystallized in methanol and crystals with a melting point of 143 - 145°C are obtained.

To prepare the hydrochloride, the base is dissolved in acetone

and added to an ice bath with 20 ml of dioxanic hydrogen chloride. The crystalline salt is filtered off and recrystallized from acetonitrile-acetone (1:3). The thus obtained N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride is dried overnight in high vacuum at 120°C. 38.9 g of substance with a melting point of 167 - 169°C are obtained. Analysis:

Analogous to what is described above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl)-m-dithiane-2-propylamig-1,1,3,3-tetraoxide -oxalate (1:1): melting point 190 - 191 C (of acetone-methanol) N-(3,4-dimethoxyphenethyl)-N-methyl-2-(3,4-trimethoxyphenyl)-m-dithian-2-propylamine -1,1,3,3-tetraoxide-oxalate (1:1): melting point 146 - 148°C (of acetone-acetic ester) 2-(m-bromophenyl)-N-(3,4-dimethoxyphenethyl)-N-methyl- m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: m.p. 158 - 160 C (of methanolic HCl and ethyl acetate) 2-(m-nitrophenyl)-N-(3,4-dimethoxyphenethyl)- N-methyl-m-dithiane-2-progylamine-1,1,3,3-tetraoxide hydrochloride: melting point 212 -

214 (of acetone)

N-(3,4-dimethoxyphenethyl)-2-(p-fluorophenyl)-N-methyl-m-dithiane-2-progylamine-1,1,3,3-tetraoxide hydrochloride: melting point 234 -

236 C (of methanol)

N-(3,4-dimethoxyphenethyl)-N-methyl-2-phenyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 149 C (decomposition)

(of methanol)

N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-ethyl-rn-dithian-2-pgopyramine-1,1,3,3-tetraoxide-oxalate (1:1): melting point 177 -

179 C (from methanol and acetone) [of 2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide and N-(3-chloropropyl)-3,4-dimethoxy-N- ethyl-phenethylamine]

N-(3,4-dimethoxyphenethyl)-2-(4-isopropylphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 225 -

227 C (of dioxanic HCl-acetic ester)

N-(3,4-dimethoxyphenethyl)-2-(3-trifluoromethyl-phenyl)-N-methyl-m-dithane-2-propylamine-1,1,3,3-tetraoxide-oxalate: melting point: 128 - 130 C (from acetone) N,2-bis-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide 2-(3,4-dimethoxyphenyl) -N-[4-(3,4-dimethoxyphenyl)-butyl]-m-dithian-2-propylamine-1,1,3,3-tetraoxide N-(3,4-dimethoxyphenethyl)-N-methyl-2- (3,4-xylyl)-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 176 - 178 C (from acetonitrile) 2-(3-butoxy-4-methoxy-phenyl)-N-(3,4-dimethoxy-phenyl)-N-methyl-m-dithian-2-propylamine-1,1,3, 3-tetraoxide: melting point: 84 - 85 C (from methanol-isopropyl ether)

N-{3[21-(3,4-dimethoxy-phenyl)-m-dithian-21-yl]-propyl-N-methyl-1,4-benzodioxane-6-ethylamine-1',1',3' , 3'-tetraoxide hydrochloride: melting point: 208 - 210 C (from acetonitrile)

N-[4-(3,4-dimethoxyphenyl)-butyl]-2-(p-isopropylphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point: 148 - 150 C (of acetic ester-dioxanic HCl) rac-2-(3,4-dimethoxyphenyl)-N-[3-(3,4-dimethoxyphenyl)-1-methyl-propyl]-N-methyl-m-dithiane -2-propylamine-1,1,3,3-tetraoxide: melting point: 115 - 117 C

N-(3,4-dimethoxyphenethyl)-2-(4-ethoxy-3-methoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point: 180 - 192 C (from acetonitrile) m-^2'-/3-[(3,4-dimethoxy-phenethyl)-methylamino]-propyl/-m-dithian-2'-yl-benzonitrile-1<1>,1' ,3',3<1->tetraoxide hydrochloride: melting point: 160°C decomposition

2-(1,4-benzodioxan-6-yl)-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melt -

point: 201 - 204 C N-(3,4-dimethoxyphenethyl)-2-(4-methoxy-m-tolyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide -hydrochloride: melt-

point 146°C decomposition (of acetone)

m-<^2' -/3-/[4-(3,4-dimethoxyphenyl)-butyl]-methylamino_/-propyl 1/m-dithian-2'-yl^-benzonitrile-1',1', 3",3<1->tetraoxide hydrochloride: melting point 120 - 122° (of water)

2-(3,4-dimethoxyphenyl)-N-methyl-N-(p-methylphenethyl)-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point:

169 - 171 C (of acetone and acetic acid).

EXAMPLE 5

6.08 g of 2-(3,4-methylenedioxyphenyl)-m-dithiane-1,1,3,3-tetraoxide (prepared according to example 2) is stirred under argon with 25 ml

abs. dimethylformamide and 0.8 g of a 55% sodium hydride suspension is added. The mixture is allowed to react for half an hour at room temperature and one hour at 40°C. After cooling to room temperature, 4.8 g of N-(3-chloropropyl)-3,4-dimethoxy-N-methyl-phenethylamine (prepared according to example 3) are added and the mixture is heated for 16 hours at 100°C. The cooled mixture is then poured onto ice and extracted three times with vinegar. The organic extracts are washed with water, dried with magnesium sulphate and evaporated in vacuo. The remaining oil is dissolved in acetone and 5 ml of a 6 N dioxanic hydrogen chloride solution is added. The precipitate that is scraped off is recrystallized in acetone. 7.5 g of N-3,4-dimethoxyphenethyl)-N-methyl-2-(3,4-methylenedioxyphenyl)-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride are obtained with a melting point of 24 7 - 248°C.

Analysis:

Analogously to what is described above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-N-methyl-2-p-tolyl-m-dithian-2-progylamine-1,1,3,3-tetraoxide hydrochloride : melting point 203 - 207 C (of acetonitrile-acetone)

2-(4-Benzyloxy)-3-methoxyphenyl-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithiane-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 220 - 221 °C (of ethanol)'

N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2'-thienyl)-m-dithian-2-progylamine-1,1,3,3-tetraoxide hydrochloride: melting point 179 - 182 C (off acetone) 2-(3,4-dichlorophenyl)-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 175 - 177 °C (of methanol) N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-ethylamine-1,1,3,3-tetraoxide-oxalate (1:1): melting point 202 - 204°C (of acetone).

EXAMPLE 6

10 g of 3',4'-dimethoxy-4-(methylveratrylamino)butyrophenone hydrochloride are dissolved in 50 ml of chloroform and 3.25 g of 1,3-propanedithiol are added. Hydrogen chloride is introduced into the mixture by

room temperature. After standing for 24 hours, the mixture is poured into water, made basic with 3 N caustic soda and extracted with ether. After drying and evaporation of the solvent, the oily residue is dissolved in acetone and added with the equivalent amount of anhydrous oxalic acid. The crystalline precipitate is recrystallized in acetone. One obtains 2-(3,4-dimethoxy-phenyl)-N-methyl-N-veratryl-m-dithian-2-propylene oxalate

(1:1) with a melting point of 133 - 136°C.

Analysis:

The 3<1>,4'-dimethoxy-4-(methyl-veratrylamino) butyrof enone used as starting material can be prepared as follows:

Add 500 g of polyphosphoric acid and

69 g of veratrol. To this, 61 g of 4-chlorobutyric acid is added in one portion, whereby the temperature rises continuously to 55°C. After an hour, the entire mass is poured over ice. Then extract with a mixture of ether-methylene chloride (3:1). The organic extracts are extracted with water, then with a saturated sodium bicarbonate solution and then once more with water, dried with magnesium sulfate and evaporated in vacuo. The remaining crystal grain is recrystallized from ether. You get 62.9

g 3,4-dimethoxy-γ-chloro-butyrophenone with a melting point of 91 - 92°C.

12 g of 3,4-dimethoxy-γ-chlorobutyrophenone are added with 40 ml of N-ethyl-N,N-diisopropylamine and 9 g of N-methylhomoveratrylamine and stirred for 6 hours at 120°C. After evaporation of the solvent in a vacuum, the viscous mass is treated with ether and caustic soda. The organic extracts are washed with water and extracted with 1 N HCl. The acidic extracts are then made alkaline and extracted with ether. The ether extracts are combined, dried with sodium sulphate and evaporated. The thus obtained, and by thin-layer chromatography almost pure, 3',4'-dimethoxy-4-(methyl-veratrylamino)-butyrophenone can be used without further purification.

Analogously to what was described above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-odithian-2-butylamine oxalate (1:1) with melting point 134 - 136 C

of acetone;

by proceeding from

1,3-propanedithiol and 5-[(3,4-dimethoxyphenethyl)-methylamino]-3',4'-dimethoxyvalerophenone (m.p. for the hydrochloride 165 -

166°C)

obtained by

3.4-dimethoxy-6-chlorovalerophenone and N-methylhomoveratrylamine. N-(3,4-dimethoxy-phenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-odithian-2-pentylamine-oxalate (1:1) m.p. 109 - 111 C of acetone;

by proceeding from

1,3-propanedithiol and 6-[(3,4-dimethoxyphenethyl)-methylamigo]-3 1,4'-dimethoxyhexanophenone (m.p. of the hydrochloride 128 - 129 C) obtained by

6-chloro-3',4'-dimethoxyhexanophenone and N-methylhomoveratrylamine. 2-(3,4-dimethoxyphenyl)-N-| 3-(3,4-dimethoxyphenyl)-propylj-N-methyl-m-dithian-2-propylamine oxalate (1:1) with melting point 116 - 118 C of acetone;

by proceeding from

1,3-propanedithiol and 3',4'-dimethoxy-4-<'[3,4-dimethoxyphenyl)-propyljmethylaminojbutyrophenone,

obtained by

3,4-dimethoxy-y-chlorobutyrophenone and 3-(3,4-dimethoxyphenyl)-N-methylpropylamine.

2-(3,4-dimethoxyphenyl)-N-methyl-N-(a-methyl-phenetal)-m-dithian-2-propylamine-oxalate (1:1): melting point 131 - 132 C (of acetone-acetic ester) ;

by proceeding from

1, 3-propanedithiol and 4-[(3,4-dimethoxy-oc-methylphenethyl)-methylamino]-3',4'-dimethoxybutyrophenone,

obtained by

3,4-dimethoxy-γ-chlorobutyrophenone and N,α-dimethyl-(3-phenylethylamine) (boiling point = 130 - 140°/20 mmHg);

N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-1,3-dithiolane-2-propylamine oxalate (1:1) with melting point 150 - 152 of acetone

by proceeding from

4-[(3,4-dimethoxyphenethyl)-methylamino]-3',4',-dimethoxybutyro-phenone and 1,2-ethanedithiol.

EXAMPLE 7

10.4 g of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide are added with 5.11 g of N-methylhomoveratrylamine, 30 ml of N-ethyl -N,N-diisopropylamine and 70 ml of dimethylformamide• The solution is heated at 120°C during 6 hours. After evaporation, the residue is further processed analogously to example 5.

N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride is obtained with a melting point of 167 - 169°C.

Analogous to the above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-N-methyl-2-phenyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 149 C ( cleavage) of methanol

N-(p-chlorophenethyl)-N-methyl-2-phenyl-m-dithian-2-gropyramine-1,1,3,3-tetraoxide hydrochloride: melting point 246 - 249 C (decomposition)

of methanol-methylene chloride

N-methyl-N-phenethyl-2-phenyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride: melting point 165 - 167°C, of acetone 2-(3,4-dime ' :oxyphenyl)-N-methyl-N-veratryl-m-dithian-2-propylamine^ 1,1,3,3-tetraoxide: melting point 137 - 139 C of acetone-ethanol. N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithian-2-progylamine-1,1,3,3-tetraoxide hydrochloride: melting point 130 - 132 C of acetone.

The 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide used in the foregoing as starting material can be prepared as follows: 10.9 g 3,4 -dimethoxy-γ-chlorobutyrophenone (prepared according to example 6) is dissolved in 120 ml of chloroform and 5 ml of 1,3-propanedithiol and 1 ml of boron trifluoride etherate are added at room temperature. After one hour at room temperature, the chloroform solution is washed

three times with water, three times with 1 N caustic soda and again

three times with water. The organic phases are dried with magnesium sulphate and evaporated in vacuo. The oily residue is immediately dissolved in 500 ml of chloroform at 0 - 5°C and 45.7 g of solid m-chloroperbenzoic acid is added, so that the reaction temperature does not exceed 5°C. The mixture is then allowed to rest for 64 hours in a refrigerator. The organic phase is washed three times with 1 N caustic soda and three times with water, dried with magnesium sulphate and evaporated in vacuo. The residue is recrystallized in methylene chloride/isopropyl ether. 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithian-1,1,3,3-tetraoxide with a melting point of 183 - 184°C is obtained.

The 2-(3-chloropropyl)-2-phenyl-m-dithiane-1,1,3,3-tetraoxide used in the above as starting material can be prepared as follows: 19.63 g of 2-phenyl-m-dithiane is dissolved in 300 ml of tetrahydrofuran.• At -70°C, 43.5 ml of a solution of butyllithium in hexane is slowly added dropwise under argon gassing. The mixture is stirred for a total of 1 1/2 hours at -20°C. A solution of 15.74 g of 1,3-bromochloropropane in 250 ml of abs is added to the red solution obtained. tetrahydrofuran at -70°C. The solution thus obtained is allowed to stand for one hour at -20°C and one hour at room temperature. The solvent is evaporated in vacuo and the oily residue is taken up in ether. The ether-containing phase is washed with 1 N sodium hydroxide solution and with water, dried with magnesium sulphate and evaporated in vacuo. The 2-(3-chloropropyl)-2-phenyl-m-dithiane thus obtained is peroxidized, as indicated in the previous section, with m-chloroperbenzoic acid in chloroform at 0 - 5°C. After recrystallization in acetic ester, 2-(3-chloropropyl)-2-phenyl-m-dithiane-1,1,3,3-tetraoxide with a melting point of 182°C is obtained.

EXAMPLE 8

3.76 g 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithian-

1,1,3,3-tetraoxide is heated with 50 ml of ethanol, 30 ml of chloroform and 1.95 g of N-methylhomovaratrylamine for 18 hours under argon at reflux. After evaporation of the solvent, the residue is chromatographed on silica gel with chloroform-ethanol (98:2). The oil obtained is dissolved in acetone and equivalent amounts of anhydrous oxalic acid are added. The precipitate is filtered off and recrystallized with methanol-acetone. There was obtained rac.-α-[(3,4-dimethoxyphenethyl)-methylamino]-methyl-2-(3,4-dimethoxyphenyl)-m-dithiane-2-ethanol-1,1,3,3-tetraoxide-oxalate (1:1) crystallizes with 1 mol of acetone and melts at 162 - 164°C.

Analysis:

The 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane-1,1,3,3-tetraoxide used as starting material can produce

set as follows:

9.6 g of 2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide (prepared according to example 2) is dissolved in 35 ml of dimethylformamide

and added with stirring under argon, at room temperature with 1.2 g of sodium hydride. The suspension is stirred for another 1/2

hour at 40°C, then it is cooled and 2.8 g of epichlorohydrin are added. The mixture is then heated for 16 hours

100°C. After cooling to room temperature, the suspension is poured onto water and the oily material is extracted with chloroform. After evaporation of the solvent, the residue is chromatographed

on silica gel with chloroform-ethanol (98:2). The obtained 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane-1,1,3,3-

tetraoxide is recrystallized from methylene chloride-ethanol and has a melting point of 175 - 176°C.

EXAMPLE 9

3.65 g of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,3-dioxide, 7.8 g of N-methylhomoveratrylamine and 20 ml of dimethylsulfoxide are heated under argon for 16 hours on 50°C. The solution is then poured into 200 ml of water and made strongly alkaline.

The excess N-methylhomoveratrylamine is extracted with ether.

The alkaline solution is then extracted with methylene chloride. The methylene chloride extracts are dried over magnesium sulfate. After evaporation of the solvent, the residue is taken up in acetone and dioxanic hydrogen chloride is added (to pH 2). The crystalline residue is recrystallized from acetone-acetonitrile and N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine-1,3-dioxide hydrochloride is obtained : melting point 148 - 14 9°C. (mixture of diastereomers).

The 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,3-dioxide used as starting material can be prepared as follows: 76.9 g of 2-(3,4-dimethoxyphenyl) -m-dithiane (prepared according to example 1) is dissolved in 900 ml abs. tetrahydrofuran, the solution is cooled to -70°C and then added with 128 ml of a butyllithium solution so that the temperature does not exceed -60°C. The mixture is then kept for 2 hours at -20°C, whereby a precipitate is formed. It is then cooled again at -70°C and 47.3 g of 1,3-bromochloropropane in 750 ml abs is added. tetrahydrofuran. The mixture is then kept for 1 hour at -20°C and one hour at room temperature. The tetrahydrofuran is then evaporated, the residue taken up in ether and extracted. After evaporation of the solvent, 2-(3-chloropropyl)-2-(3-dimethoxyphenyl)-m-dithiane is obtained.

Dissolve 55.25 g of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane in 500 ml of glacial acetic acid. While stirring at 5°C, a solution of 34 g of 30% hydrogen peroxide in 300 ml of glacial acetic acid is added dropwise over the course of 2 hours. The mixture is allowed to stand for 60 hours at room temperature and is then concentrated in vacuo at 40°C.

The oil obtained is chromatographed on 1.5 kg of silica gel with chloroform-ethanol, first 98:2, and then 95:5. It is obtained after recrystallization in acetonitrile 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,3-dioxide: melting point 163 - 164°C, (mixture of diastereomers).

EXAMPLE 10

Analogous to example 8, by starting from 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane and N-methylhomoveratrylamine

rac. -ct-[(3,4-dimethoxyphenethyl)-methylamino]-methyl-2-(3,4-dimethoxyphenyl)-m-dithian-2-ethanol is prepared. The corresponding hydrobromide crystallizes from acetonitrile-acetic ester and melts at 97 - 99°C.

The 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane used as starting material can, analogously to example 9, by

starting from 2-(3,4-dimethoxyphenyl)-m-dithiane (prepared according to example 1), using epichlorohydrin instead of 1,3-bromochloropropane, is obtained.

EXAMPLE 11

3.4 g of lithium aluminum hydride in 60 ml of tetrahydrofuran are heated to reflux. 14.7 g of N-(3,4-dimethylphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-2-propionamide in 80 ml of tetrahydrofuran are then added dropwise. The resulting suspension is heated for a further 3 hours at reflux, then cooled to 0°C and carefully added with 50 ml of saturated sodium sulphate solution. The whole is filtered off, the solution is diluted with water and extracted with ether. The ethereal extracts are washed with 1 N caustic soda,

so with water, dried with magnesium sulphate and evaporated. The oily residue is chromatographed on silica gel with chloroform-ethanol (95:5). The base obtained is dissolved in acetone and equivalent amounts of anhydrous oxalic acid are added. The precipitate formed is recrystallized from methanol-acetone. The N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithian-2-propylamine oxalate (1:1) thus obtained melts at 186 - 188°C.

Analysis:

The N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithian-2-propionamide used as starting material can be prepared as follows: 50 g of 3-veratroylpropionic acid in 400 ml of chloroform and 22.7 g 1,3-propanedithiol is added while stirring until saturation with hydrogen chloride. After 3 hours at room temperature, evaporated the solution to 50 ml and dilute with ether. The corresponding solution is extracted three times with 5% sodium carbonate.

The basic phases are combined, made acidic with concentrated hydrochloric acid. The precipitated product is extracted with ether-methylene chloride 1:3. The organic extracts are dried and evaporated.

The residue is recrystallized from ethanol and 2-(3,4-dimethoxyphenyl)-m-dithian-2-propionic acid with a melting point of 134 - 135°c is obtained.

13.2 g of 2-(3,4-dimethoxyphenyl)-m-dithian-2-propionic acid, 4 g of triethylamine and 180 ml of tetrahydrofuran are cooled at 0°C and 5.44 g of chloroformate isobutyl ester in 80 ml of tetrahydrofuran are added dropwise over the course of 10 minutes. The mixture is then kept for 3 hours at room temperature and 7.25 g of homoveratrylamine in 40 ml of tetrahydrofuran are then added at 0°C. The suspension is allowed to stand for 48 hours at 3°C, then evaporated, water is added and extracted with ether-methylene chloride 3:1. The ethereal extracts are washed with water, sodium bicarbonate,

1 N tartaric acid and water. The organic phase is dried with magnesium sulphate and evaporated. The residue is crystallized from methylene chloride-ether at 0°C. One obtains N-(3,4-dimethyloxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithian-2-propionamide with a melting point of

135 - 136°C.

Analogously to what was described above, N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine hydrobromide can be prepared. Melting point 170 - 172°C of ethanol.

EXAMPLE 12

0.5 g 2-;/3-[2"-(3,4-dimethoxyphenyl)-m-dithian-2"-yl]-propyl7-methylaminoj-31,4'-dimethoxyacetophenone-1",1",3 ",3"-tetraoxide is dissolved in 15 ml of ethanol and 30 ml of tetrahydrofuran and 50 mg of sodium borohydride is added. After stirring for 16 hours, 15 ml of 1 N HCl and then 12 ml of 1 N NaOH are added to the mixture. The tetrahydrofuran is evaporated and the residue extracted with methylene chloride.

The organic extracts are washed with water, dried with magnesium sulphate and evaporated in vacuo. The crystals obtained are recrystallized in methanol and 0.3 g of a-r^//3-[ 2'-(3,4-dimethoxyphenyl)-m-dithian-2'-yl]propyl/methylamineq7methyl^ veratryl-

alcohol 1',1',3',3'-tetraoxide. Melting point: 132.- 133°C.

The starting material used 2-'/3-[2"-(3,4-dimethoxyphenyl)-m-dithian-2"-yl]-propyl/-methylaminoj-3',4'-dimethoxyacetophenone-1",1" ,3",3"-tetraoxide can be obtained by reacting 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide and tu-methylamino-3 ,4-dimethoxyacetophenone: melting point: 140°C decomposition (of acetone).

EXAMPLE 13

10 g of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-pentylamine (prepared according to example 6) are dissolved in 50 ml of glacial acetic acid and treated at room temperature with 20 ml of 30% hydrogen peroxide. After 3 hours, the mixture is heated for 3 hours at 35°C and then for 18 hours at 40°C. The solution is then poured into water, made basic with sodium hydroxide and extracted with methylene chloride. After removal of the solvent, the residue is chromatographed on silica gel with a mixture of chloroform-methanol-saturated ammonia (97:3). The product obtained is dissolved in acetone and the equivalent amount of oxalic acid is added. The precipitate formed is recrystallized from acetone-methanol. N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-pentylamine-1,1,3,3-tetraoxide-oxalate (1:1) is obtained with a melting point of 189 - 191°C.

Analysis:

Analogous to the above, the following compounds can be prepared: N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-butylamine-1,1,3,3-tetraoxide- oxalate with a melting point of 161 - 163 C (from acetone-methanol), (base 123 - 126°C from ethanol),

vsd to proceed from

N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-butylamine (prepared according to Example 6) 2-(3,4-dimethoxyphenyl)-N- [3-(3,4-dimethoxyphenyl)-propyl]-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrobromide, with a melting point of 138 - 140 C of acetonitrile-acetic ester , by starting from

2-(3,4-dimethoxyphenyl)-N-[3-(3,4-dimethoxyphenyl)-propyl]-N-methyl-m-dithian-2-propylamine (prepared according to Example 6), rac. -N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N,(3-dimethyl-m-dithian-2-propylamine-1^1,3,3-tetraoxide hydrochloride with a melting point of 183 - 185 C (of acetone-acetic ester),

by proceeding from

rac. -N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N,(3-dimethyl-m-dithian-2-propylamine (prepared according to example 3). 2-(3,4-dimethoxyphenyl )-N-methyl-N-(α-methyl-phenethyl)-m-dithian-2-propylamine-1,1,3,3-tetraoxide hydrochloride with a melting point of 185 - 187 C (of acetone-acetic ester),

by proceeding from

2-(3,4-dimethoxyphenyl)-N-methyl-N-(α-methyl-phenethyl)-m-dithian-2-propylamine (prepared according to Example 6).

EXAMPLE 14

11.2 g of 2-[4-(benzyloxy)-3-methoxyphenyl]-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide ( prepared according to example 5) is heated with 100 ml of 48% hydrobromic acid for 2 minutes in the steam bath. The aqueous solution is then extracted with ether, evaporated in vacuo and distilled azeotropically with ethanol-benzene three times. The residue is crystallized from acetone. The crystalline mass thus obtained is recrystallized three times from methanol-acetonitrile and 4-{21-[3-<(3,4-dimethoxyphenethyl)-methylamino propyl]-m-dithian-2'-ylj-2-methoxyphenol-1 is obtained ',1',3',3'-tetraoxide hydrobromide with a melting point of 192°C (decomposition).

C25 H35 N08 S2-HBr

In an analogous way, starting from 2-[3-(benzyloxy)-3-methoxy-phenyl j-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithian-2-propylamine-1,1,3 ,3-tetraoxide 5-^2' -/3-[(3,4-dimethoxyphenethyl)-methylamino]-propyl7-m-dithian-2'-yl]--2-methoxyphenyl-1' ,1' ,3' ,3'-tetraoxide hydrobromide is prepared: melting point: 201°C decomposition (of acetonitrile).

EXAMPLE 15

2 g 5-[2'-[3-[(3,4-dimethoxyphenethyl)methylamino]propyl[-m-dithian-2'-yl]-2-methoxyphenol-1',1',3',3'-tetraoxide dissolved in absolute pyridine and added with an excess of acetic anhydride. After 16 hours at room temperature, the solvent is evaporated and the residue is chromatographed on silica gel. 5-^2'-/3-[3,[(3,4-dimethoxyphenethyl)methylamino]propyl/-m-dithian-2'-yl-2-methophenylacetate-1',11,3',3'-tetraoxide a thick oil is obtained.

Analysis:

EXAMPLE 16

0.3 g of 2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide is added to 0.16 g of 3,4-dimethoxy-j3-f phenylethyl chloride, 5 ml of N,N-diisopropyl-N-ethylamine and 1.5 ml of dimethylformamide and heated for 16 hours at 130°C. The solution is then distributed between water and vinegar. The residue is chromatographed on silica gel and N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide is obtained: melting point : 144°C (of methanol).

The 2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine-1,1,3,3-tetraoxide used as starting material can be prepared as follows.

3.95 g of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide are dissolved in 50 ml of dimethylformamide. The solution is cooled to 0°C and 15 g of methylamine are added. It is heated for 18 hours at 40°C under pressure. The solution is then concentrated and the crystal grain is recrystallized from a little methanol. The above-mentioned product with a melting point of 164°C is obtained.

EXAMPLE 17

1 g of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithian-2-propylamine (prepared according to example 11) is dissolved in 20 ml abs. pyridine and 200 ml of acetic anhydride are added. After 18 hours, the solvent is concentrated, the residue is distributed between ether and sodium carbonate (5%). After evaporation of the solvent, an oil (1.2 g) is obtained, which is dissolved in 20 ml abs. tetrahydrofuran. This reading is infused slowly

to a suspension of 0.4 g of lithium aluminum hydride and 20 ml of abs. tetrahydrofuran. The blanéing is added with a concentrated, aqueous sodium sulphate solution and then removed. After evaporation of the solvent, the residue is distributed between ether and water and the organic extracts are worked up. The oily residue is treated with oxalic acid in acetone-acetic ester, whereby N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-ethyl-m-dithian-2-propylamine-1,1,3, 3-Tetraoxyoxalate crystallizes out: melting point 126 - 127°C.

EXAMPLE 18

Dissolve 1 g homoveratric acid in 15 ml abs. tetrahydrofuran and add 0.15 g of triethylamine. At 0 - 5°C, 0.72 g of chloroformic acid isobutyl ester is slowly added dropwise and the mixture is stirred for one hour at 5 - 10°C. A solution of 1.63 g of 2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine [prepared analogously to example 16 from 2-(γ-chloropropyl)-2- (3,4-dimethoxyphenyl)-m-dithiane and methylamine in 5 ml of tetrahydrofuran. The mixture is allowed to stand overnight at room temperature. After evaporation of the solvent, the residue is distributed between 1 N hydrochloric acid and ether. The organic extracts are washed with 5% sodium carbonate solution and water. After drying with magnesium sulfate, the solvent is concentrated. The oily residue (1.5 g) is dissolved in 15 ml of tetrahydrofuran and a suspension of 0.15 g of lithium aluminum hydride is added dropwise under reflux and argon. The mixture is boiled for 2 hours and then added slowly with a concentrated sodium sulphate solution in water and then with 10 ml of methylene chloride. The mixture is decanted and the solution is concentrated. The residue is chromatographed on silica gel and N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithian-2-propylamine is obtained in the form of a thick oil.

Claims (10)

1. Analogy method for the preparation of therapeutically active, heterocyclic compounds of the general formula where R means a residue of the formula wherein R^, and R^ means hydrogen, halogen, lower alkyl, lower alkoxy, benzyloxy, phenyl, nitro, trifluoromethyl, hydroxy, cyano, di-lower alkylamino or lower alkanoyloxy or two residues in neighboring position together methylenedioxy, ethylenedioxy or butadiene-1,3-ylene-1,4, R. means hydrogen or lower alkyl, R,., Rg and R^ mean hydrogen, halogen, lower alkyl, or lower alkoxy or two adjacent residues '' .' together, methylenedioxy or'ethylenedioxy, X means a sulfur atom, SO or SO2, Y means a straight-chain or branched, optionally substituted with hydroxy, alkylene residue with 2-5 carbon atoms, and Z means a straight-chain or branched, possibly hydroxy-substituted alkylene residue with 1-4 carbon atoms, and m are the numbers 0 or 1 and n the numbers 2 or 3, under which the "lower" residues contain 1-6 carbon atoms and acid addition salts thereof, characterized by a) reacting a compound with the general formula in which R, X and n have the above meaning, with a connection with-the general formula in which R 4 - R 4 , Y, Z and m have the meanings indicated above and Rg means a leaving group such as halogen, arylsulfonyloxy or alkylsulfonyloxy, or b) reacts with a compound of the general formula in which R, R^ - R^, Y, Z and m have the above meaning, with a compound of the general formula in which n has the above meaning, or c) reacts with a compound of the general formula where R, Rg, X, Y and n have the above meaning, with a compound of the general formula in which R. - R^, Z and m have the above meaning, or v d) reacts a compound with the general formula in which R, R^, X, Y and n have the above meaning, with a compound of the general formula in which R^ - Rg, Z and m have the above meaning, or e) in connection with the general formula <K>7 in which R, R4 - R?, X, Y, Z, m and n have the above meaning, Y-L and Z1 are a group corresponding to Y respectively. Z in that at least one of the groups Y1 and Z1 contains a carbonyl group and R4 means hydrogen or an alkyl group with 1-5 carbon atoms, reduces the carbonyl group after which, if desired, one oxidizes a compound of formula I, in which X represents a sulfur atom, to a compound of formula 1. in which X represents SO or SO2, that one, if desired, N-lower-alkylates a compound of formula I, in which R-4 means hydrogen, that one, if desired, transfers a lower alkoxy- or benzyloxy- to a hydroxy group, that one, if desired, etherifies or esterifies a hydroxy group with a lower alkanecarboxylic acid and, that, if desired, a base obtained is transferred to an acid addition salt. 2. Process according to claim 1, characterized in that one prepares N-(3,4-dimethoxyphenethyl)-2-(p-methoxyphenyl)-N-methyl-m-dithian-2-propylamine or an acid addition salt thereof. 3. Method according to claim 1, characterized in that one prepares N-(3,4-dimethoxyphenethyl)-N-methyl-2-phenyl-m-dithian-2-propylamine or an acid addition salt thereof. 4. Process according to claim 1, characterized in that one prepares N-(p-chlorophenethyl)-N-methyl-2-phenyl-m-dithian-2-propylamine or an acid addition salt thereof. 5. Process according to claim 1, characterized in that one prepares N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl)-m-dithiane-2-propylamine or an acid addition salt thereof. 6. Method according to claim 1, characterized in that one prepares N-(3,4-dimethoxyphenethyl)-N-methyl-2-(p-tolyl)-m-dithian-2-propylamine-1,1,3,3- tetraoxide or an acid addition salt thereof. 7. Method according to claim 1, characterized in that 2-(m-nitrophenyl)-N-(3,4-dimethoxyphenethyl)-N-methyl-m-dithiane-2-propylamine-1,1,3,3- tetraoxide. j. or .an acid addition salt thereof.., . '• ••• -'■ .. 8. Method according to claim 1, character, characterized in that one prepares N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-pentylamine or an acid addition salt thereof. 9. Process according to claim 1, characterized in that N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-ethyl-m-dithian-2-propylamine-1,1,3 ,3-tetraoxide or an acid addition salt thereof. 10. Method according to claim 1, characterized in that N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-N-methyl-m-dithiane-2-propylamine-1,1,3,3- tetraoxide or an acid addition salt thereof is prepared.