CA1079290A

CA1079290A - Heterocyclic compounds

Info

Publication number: CA1079290A
Application number: CA324,131A
Authority: CA
Inventors: Henri Ramuz
Original assignee: F Hoffmann La Roche AG
Current assignee: F Hoffmann La Roche AG
Priority date: 1973-12-21
Filing date: 1979-03-26
Publication date: 1980-06-10
Also published as: DE2463173C2; IL52843A0; GB1489086A; PH13396A; CH611614A5; HK43380A; IE40788L; CA1072966A; SE434746B; AT350053B; ES451137A1; NL7416507A; ES451135A1; DE2460593A1; ZA747526B; GB1489088A; ES451136A1; ATA38778A; YU39311B; DD116829A5

Abstract

ABSTRACT OF THE DISCLOSURE

This invention relates to compounds of the general formula (I) or an acid addition salt thereof, or (II) in which n stands for 2 or 3, X represents a sulphur atom, SO or SO2, R
represents a group of the formula or (a) (b) in which R1, R2 and R3 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, aryl-(lower alkoxy), aryloxy, phenyl, nitro, trifluoro-methyl, hydroxy, cyano, di(lower alkyl)amino or lower alkanoyloxy group or two adjacent R1, R2 and R3 symbols together represent a methylenedioxy, ethylenedioxy or butadien-1,3-ylene-1,4-group, R4 represents a hydrogen atom or a lower alkyl group, R5, R6 and R7 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, hydroxy or benzyloxy group or two ad-jacent R5, R6 and R7 symbols together represent a methylenedioxy or ethylene-dioxy group, Y1, represents a straight-chain or branched chain, optionally hydroxy-substituted, aliphatic group containing 1 - 7 carbon atoms, of which 1 - 3 carbon atoms are present in the chain, Z represents a straight-chain or branched chain, optionally hydroxy-substituted, aliphatic group contain-ing 1 - 8 carbon atoms, or which 1 - 4 carbon atoms are present in the chain, m stands for zero or 1, Y represents a straight chain or branched-chain, optionally hydroxy-substituted, aliphatic group containing 2 - 8 carbon atoms, and T represents a group of the formula (i) (ii) (iii) or in which A represents the group in which R4 represents a hydrogen atom or an alkyl group containing 1 - 5 carbon atoms, R8 denotes a leaving atom or group, and Zm, R5, R6 and R7 have the above-mentioned meanings, or an acid addition salt of compound (II) in which T denotes the group (iii) The invention also relates to a process for preparing compounds of formula I and II which comprises either:
(a) when a compound of formula I is required, reacting an acid of the general formula (XVII) in which R, X, Y1 and n have the same meanings as above with an amine of the general formula (VIIa) wherein the various symbols are as defined above, and, if desired, the pro-duct is converted to its acid addition salt; or (b) when a compound of formula (II) is required, when T represents a radical (i), reacting a compound of the general formula (XIV) in which R and R8 have the same meanings as above, with a compound of the general formula (V) in which n has the same meaning as above, and oxidising the product if X in formula (II) is to denote SO or SO2, or when T represents a radical (ii), acylating a compound of the general formula in which R, X, Y, Z, R5, R6, R7, m and n have the same meanings as above, or when T represents a radical (iii), reacting a compound of the general formula (VIa) in which R, Y, X and n have the same meanings as above, with an amine of the general formula (XVI) in which R4 has the same meaning as above, and if desired, converting the product to its acid addition salt.
The compounds of the present invention are precursors in the pro-duction of sulphur-containing compounds claimed in our copending Canadian Patent Application Serial No. 216,313 filed December 18, 1974 which possess coronary dilating properties.

Description

~ ~0 7szsu This application is a divisional of our copending Canadian Patent Application Serial No. 216,313 flled December 18, 1974.

e present invention relates to sulphur-containing compounds~
According to the present in~ention there is provided a co~pound of the general formula ~(GH2)n 5 R - C - Yl CO - N~(Z)m ~ R6 (I) or an acid addition salt thereof, or X,--(CH2)n X
\ /
R - C Y T (II) 10 in which n stands for 2 or 3, X represents a sulphur atom, SO or S02, R

: represents a group of the formula ~1 R3 ~ or (a) (b) in which Rl, R2 and R3 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, aryl-(lower alkoxy), aryloxy, phenyl, nitro, trifluoro-methyl, hydroxy, cyano, di(lower alkyl)amino or lower alkanoloxy group or two adJacent Rl, R2 and R3 symbols together represent a methylenedioxy, ethylenedioxy or butadien-1,3-ylene-1,4-group, R4 represents a hydrogen atom or a lower alkyl group, R5, R6 and R7 each represent a hydrogen or halogen atom or a lower aIkyl, lower alkoxy, hydroxy or benzyloxy group ~ ::
- 1 - ~

~ , .
~,~...

- . : . . .. : . - , . . . . , ~ . . . : . . . . . .
,' ' , ~ :", ~ , ,"", ~,,,,, ", ", ;,~ ,, ,",: "

or two ad~acent R5, R6 and R7 sy~bols together represent a methylenedioxy or ethylenedioxy group, Yl represents:a straight-chain or branched-chain, optlonally hydroxy-substituted, aliphatic group containing 1 - 7 carbon atoms, of which 1 - 3 carbon ato~s are present in the chain, Z represents a straight-chain or branched-chain, optionally hydroxy-substituted, aliphatic group containing 1 - 8 carbon atoms, of which 1 - 4 carbon atoms are present in the chain, m stands for zero or 1, Y represents a straight-chain, or branched-chain, optionally hydroxy-substituted, aliphatic group containing

2 - 8 carbon atoms, of which 2 - 4 carbon atoms are present in the chàin and T represents a group of the formula 8 (i) A - (Z)m ~ (i~) or N H (iii) in which A represents the group R' - CO
- N

in which R4 represents a hydrogen atom or an aIkyl group containing 1 - 5 carbon atoms, R8 denotes a leaving atom or group and Z, m, R4, R5, R6 and R7 ~' ~....; ~, . .

~ .

, ' ' , .. : ~ .
.
..
. . . .. .

:` ~
. lQ79~g~

` have the above-mentioned meanings, F or an acid addition salt of compound ~II3 in which T denotes the group -N H (iii) -and a process for its productlon.
e compounds of the present invention are precursors in the production of sulphur-containing co~,pounds claimed in our copending C~nadian Patent Application Serial No. 216,313 filed December 18, 1974 which possess `~ coronary dilating properties.
As used in this description and in the accompanying claims, the term "lower alkyl" means straight-chain or branched-chain aIkyl groups con-taining 1 - 6 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, amyl, and hexyl). The term "lower alkoxy"
means lower aIkyl ether groups in which the "lower alkyl" moiety has the aforementioned significance. me term "halogen" means fluorine, chlorine, -~
bromine and iodine. me term "lower alkanoyl" means alkanoyl groups con-taining up to 6 carbon atoms (e.g. formyl, acetyl, pr~pionyl, and butyryl).
e term~"aryl" means unsubstituted or substituted phenyl, the substitutent(s) being selected from halogen, lower alkyl, lower alkoxy, nitro and amino.
The term l'leaving atom or group" used hereinafter means known atoms and groups such as, for example, halogen, preferably bromine or chlorine ary-; sulphonyloxy such as tosyloxy, aIkylsulphonyloxy such as mesyloxy or an epoxy group and the like.
This invention also relates to a process in which the compounds of fornLla (I) or (II) are prepared by either:
(a) when a compound of formula I is required,

- 3 -~ ~,.

, 10792gl~

reacting an acid cf the general form~la 2)n~X
/ ~ (XVII) R - C Yl C \
OH

in which R, X, Yl and _ have the same meanings as above with:an amine of the general formula R6 ,=j~
7 ~ (Z)m NH - R4 (VIIa) wherein the various symbols are as defined above, and, if desired, the pro-duct is converted to its acid addition salts; or (b) when a compound of formula (II) is required, when T represents a radical (i) reacting a compound of the general forn~la O
R--- C--Y--R8 (XrV) in which R and R8 have the same meanings as above, with a compound of the general formula ~ HS - (CH2)n SH (V) : in which n has the same meaning as above, and oxidising the product if X in formula (II) is to:denote SO or S02, or when T represents a radical (ii), acylating a compound of the general formula X \ 2 / X H R~
R - C - Y - N (Z~m l~
`~
's.'.......

.. .. .
,,: ' . - :

' . . ; ' . :

10'79Z90 in which R, X, Y, Z, R5, R6, R7, m and _ have the same meanings as above, to introduce a formyl or (Cl-C5 alkyl) carbonyl group, or when T represents a radical (iii), reacting a compound of the general formula / (CH2) ~
X\ /X
R C - Y - Cl (VIa) in which R, Y, X and n have the same meanings as above, with an amine of the general forn~la R4 NH2 (XVI) in which R4 has the same meaning as above, and if desired, converting the product to its acid addition salt.
me compounds of formula II in which T represents radical (i) can be prepared, for example, by reacting a compound of the general formula O
,. - .
R C Y - R8 (XIV) :
in which R, R8 and Y have the significance given earlier, with a compound of the general formula HS (CH ) - SH (V) in which n has the significance given earlier, and, if desired, converting a thus obtained compound of formula (II) in which X represents a sulphur atom into a compound of form~la II in which X represents S0 or S02 by oxidation.
The reaction of a compound of formula XIV with a compound of formula V can be carried out in a manner known per se. The reaction is expediently ~ ~., -~ .. .
. ... ,, ... , . , .... ,- . -, . : , . : . -: . -1(~79Z9~

carried out in an organic solvent which is inert under the reaction conditions, preferably in a polar solvent such as a halogenated hydrocarbon (e.g. chloroform or methylene chloride or the like) or ethyleneglycol dimethyl ether. The reaction is also expediently carried out in the presence of a water-cleaying agent (e.g. sulphuric acid, a hydrohalic acid3 or phosphoric acid) and at a temperature from 0C to the reflux temperature of the reaction mixture, preferably at room temperature.
The conversion of a thus obtained said compound of formula II in which X represents a sulphur atom into a compound of formula II in which X
represents SO or S02 can be carried out in a manner known per se; for exa~ple, by oxidation with a peracid such as, for example, peracetic acid, perph-thalic acid or m-chloroperbenzoic acid. Peracetic acid can, for example, be formed in situ from glacial acetic acid and hydrogen peroxide.
The a~ides of formula II in which T represents radical (ii) can be prepared in a m~nner known per se, for exa~,ple, by acylating a compound of general formula /(CH2)n~ 5 X \ / X H ~ R6 R _ C Y N- ( Z )m ~

The acylation can be carried out, for example, using a halide of a lower car-boxylic acid in a tertiary amine (e.g. pyridine) at a temperature of from 0C
to 30C, preferably at about room temperature.
The compounds of formula II in which T represents radical (ii~) can be prepared, for example, by reacting a compound of the general formula r~
.~
.... ~ , : ''~

10'79~9~

f (CH2)~
X~X
R C Y - Cl (VIa) in which R, X, Y and _ have the significance given earlier, with an amine of the general formula R4 N~I2 (XVI) in which R4 has the significance given earlier. Since, in carrying out this reaction, hydrogen chloride is cleaved off, the reaction is expediently carri-ed out in the presence of a base or using an excess of the amine of forn~la XVI .
me com~ounds (XVI) are known. me compounds of form~la (VIa) can be prepared in a manner analogous to the preparation of the compounds of forn~la (II) in which T represents radical (i).
Amides of formula I can be prepared, for example, by reacting an acid of the general formula Xf (CH2)~X ' .
\/ D ' R C - Yl C \ (XVII) OH
in which R, Yl, X and n have the sig~ificance given earlier, with an amine of the general formula R6 ~ ( )m HN R4 (VIIa) in which R4 - R7, Z and m have the significance given earlier.

~ . .
~_........................................................... .

., - , ' ,: .: ' ' '- ' ' - ' ~ 1079Z90 me reaction can be expediently carried out in the presence of a tertiary amine (e.g. triethylamine) and a halocarboxylic acid ester (e.g.
chloroformic acid isobutyl ester) mixed anhydride method) in an inert organic solvent (e.g. tetrahydrofuran) and at a temperature of from 0C to 30C.
The acids of formula XVII can be prepared in a manner analogous to that described hereinbefore for the preparation of co~lpounds of formula II
in ~hich T represents radical (i) starting from compounds of the general formula R C 1 OH (XVIII) in which R and Yl have the significance given earlier. me compounds of formula XVIII are known.
The ketones of formula I can be prepared in a manner known per se;
for example, by oxidising a corresponding alcohol. me oxidation can be car-ried out, for example, using chromiwm trioxide/pyridine in pyridine at a tem-perature of from -20C to about room temcerature, preferably at 0C.
me compounds of formula I and II in which T represents radical (iii) can be converted into acid addition salts, for example by treatment with an inorganic acid such as a hydroh~lic acid (e.g. hydrochloric acid or hydrobromic acid), sulphuric acid, phosphoric acid or with an organic acid such as oxalic acid, tartaric acid, citric acid or methanesulphonic acid. Of the acid addition salts of the mentioned con~pounds, the pharma-ceutically acceptable acid addition salts are preferred. If, in the course of the process of this invention, an acid addition salt of a compound of formula I or II is obtained, then such a salt can be converted into the free base in a known manner (e.g. by treatment with alkali) and the free .~
- - . . .
. , . ~ , ' ' '.; , , ~

~ 10~9~90 base can, if desixed, be conYerted into another acid addition salt.
The following examples illustrate the process pro~ided by the present invention:
Example 1 74.7gof3,4-dimethoxybenzaldehyde are dissolved in 1250 ml of chloroform, treated with 50 ml of 1,3-propanedithiol and cooled at 0C with stirring. 20 ml of boron trifluoride etherate are added and the mixture is left to stand in a refrigerator for 18 hours. me mixture is then washed three times successively with 500 ml of a 7% potassium hydroxide solution and 500 ml of a 10% sodium chloride solution. The organic extracts are combined, dried over magnesium sulphate and evaporated. The residue is re-crystallised twice from ether. There are obtained 102.6 g of 2-(3,4-dimethoxyphenyl)-m-dithiane of melting point 99 - 101C.
The following dithiane can be manufactured in an analogous manner:
2-phenyl-m-dithiane of melting point 72 - 73C (from methylene chloride/isopropyl ether).

Exa~lple 2 60 g of 2-(3,4-dimethoxyphenyl)-m-dithiane (prepared as described in Example 1) are dissolved in 470 ml of glacial acetic acid and treated at room temperature with 235 ml of 30% h~drogen peroxide, the temperature of the solution rising to ca 40C. m e solution is left to stand overnight at room temperature. The solution is then heated for 2 hours at 100C.
After cooling to room temperature, the crystalline precipitate is filtered off under a vacuum, washed with some glacial acetic acid, dried in vacuo at 60C overnight and then recrystallised from acetonitrile. There are obtained 57.1 g of 2-(3,4-dimethoxyphenyl)-m}dithiane-1,1,3,3-tetraoxide of melting point 243 - 245C.
_ g _ ' .

, ,, , :

:.

1~7929~

~xample 3 292.5 g of N-methyl-homoveratrylamine are dissolved in 1000 ml of dimethylformamide and treated with 415 g of anhydrous potassium carbonate.
The mixture is stirred at 5C, treated with 237 g of 1,3-bromochloropropane in 500 ml of dimethylfornamide, stirred for a further 4 hours at room tem-perature and then poured into 6 litres of water. The separated oil is ex-tracted three times with 2 litres of ether each time. me organic extracts are dried with magnesium sulphate and evaporated in vacuo. The residual oil is distilled at between 60C and 70C with a mercury diffùsion pump at 0.005 Torr. There are obtained 206.7 g of N-(3-chloropropyl)-3,4-dimethoxy-N-methylphenethylamine of boiling point 69 - 70C/0.005 Torr.
Example 4 500 g of polyphosphoric acid and 69 g of veratrol are added to a 1 litre round-bottom flask. To this are added 61 g of L~chlorobutyric acid in one portion, the temperature rising steadily to 55C. After 1 hour, the entire mixture is poured on to ice. The mixture is then extracted with a mixture of ether/methylene chloride (3:1). The organic ~xtracts are extract-ed with water, then with a saturated sodium bicarbonate solution and finally again with water, dried over magnesium sulphate and evaporated in vacuo. me residual crystal mass is recrystallised from ether. There are obtained 62.9 g of 3,4-din~thoxy-~-chlorobutyrophenone of melting point 91 - 92c.
10.9 g of 3,4-dimethoxy-~-chlorobutyrophenone are dissolved in 120 ml of chloroform and treated with 5 ml of 1,3-propanedithiol and 1 ml of boron trifluoride etherate at room temperature. After 1 hour at room temperature, the chloroform solution is washed three times with water, three times with l-N sodium hydroxide and again three times with water. The organic phases ~ .

, . , 1~79Z91~

are dried over magnesium sulphate and evaporated in vacuo. The oily residue is immediately dissolved in 500 ml of chloroform at 0 - 5C and treated with 45/7 g of solid m-chloroperbenzoic acid in such a manner that the temperature does not exceed 5C. me mdxture is subsequently left in a refrigerator for 64 hours. The organic phase is washed three times with -l-N sodium hydroxide and three times with water, dried over magnesium sulphate and evaporated in vacuo. The residue is recrystallised from methylene chloride/isopropyl ether. There is obtained 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide of melting point 183 - 184C.

Example 5 19.63 g of 2-phenyl-m-dithiane are dissolved in 300 ml of tetra-hydrofuran. 43.5 ml of a solution of butyl lithium in hexane are slowly added drop wise at -70C while gassing with argon. me mixture is stirred for a total of 1.5 hours at -20C. me red solution obtained is added to a solution of 15.74 g of 1,3-bromochloropropane in 250 ml of absolute tetrahydrofuran at -70~C. me thus-obtained solution is left to stand for 1 hour at -20C and for 1 hour at room temperature. me solvent is evaporat-ed in vacuo and the oily residue taken up in ether. me ethereal phase is washed with l-N sodium hydroxide and with water, dried over magnesium sulphate and evaporated in vacuo. m e thus-obtained 2-(3-chloropropyl)-2-phenyl-m-dithiane is peroxidised at 0 - 5C with m-chloroperbenzoic acid in chloro-form as described in the previous example. After recrystallisation from ethyl acetate, there is obtained 2-(3-chloropropyl)-2-phenyl-m-dithiane-1,1, 3,3-tetraoxide of melting point 182C.

Example 6 9.6 g of 2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide (pre-~..., ~, , . ~ i . .
. .. ' , .

1079ZgO

pared as described in Exa~lple 2) are dissolved in 35 ml of dimethylformamide and, with stirring under argon, treated with 1,2 g of sodium hydride at room temperature. The suspension is stirred at 40C for a further 0.5 hours, then cooled and treated with 2.8 g of epichlorohydrin. The mixture is then heated at 100C for 16 hours. A~ter cooling to room temperature, the suspension is poured on to water and the oily material extracted with chloroform. After evaporation of the solvent, the residue is chromato-graphed on silica gel with chloroform/ethanol (98:2). The 2-(3,4-dimethoxy-phenyl)-2-(2,3-epoxypropyl)-m-dithiane-1,1,3,3-tetraox~de obtained is re-crystallised from methylene chloride/ethanol and has a melting point of 175 - 176C.

Example 7 76.9 g of 2-(3,4-dimethoxyphenyl)-m}dithiane(prepared as described in Exanple 1) are dissolved in 900 ml of absolute tetrahydrofuran, the solution is cooled to -70C and treated with 128 ml of a butyl lithium solution in such a manner that the temperature does not exceed -60C. me mixture is then held for 2 hours at -20C, a precipitate forming. me mixture is again cooled to -70C and 47.3 g of 1,3-bromochloropropane in 750 ml of absolute tetrahydrofuran are added. The mixture is then held for 1 hour at -20C and for 1 hour at room temperature. The tetrahydro-furan is then evaporated, the residue taken up in ether and extracted. After evaporation of the solvent, there is obtained 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane.
me 2-(3,4-dimethoxyphenyl)-2-(2,3-epoxypropyl)-m-dithiane can be prepared in an analogous manner starting from 2-(3,4-dimethoxyphenyl)-m-dithiane (prepared as described in Example 1) using epichlorohydrin instead of 1,3-bromochloropropane.

~' .
~.. ., ~, '' ', '' : `

.
- . . . . .

- . : , . . ..
.
,,:: : ,, .: :' , . . . :

1~92~1~

Example 8 50 g of 3-veratroylpropionic acid in 400 ml of chloroform and 22.7 g of 1,3-propanedithiol are treated with hydrogen chloride up to saturation while stirring. After 3 hours at room temperature, the solution is evaporated to 50 ml and diluted with ether. m e resultine solution is extracted three times with 5% sodium carbonate. The basic phases are combined and made acidic with concentrated hydrochloric acid. me precipitated product lS
extracted with ether/methylene chloride (1:3). me organic extracts are dried and evaporated. The residue is recrystallised from ethanol, there being obtained 2-(3,4-dimethoxypheny1)-m-dithiane-2-propionic acid Or melt-ing point 134 - 135C.
13.2 g of 2-(3,4-dimethoxyphenyl)-m-dith~a~e-2-propionic acid, 4 g of triethylamine and 180 ml of tetrahydrofuran are cooled to 0C and treated dropwise within 10 minutes with ~.44 g of chloroformic acid isobutyl ester in 80 ml of tetrahydrofuran. me mixture is then held at room te~lperature for 3 hours and treated with 0C with 7.25 g of homoveratrylamine in 40 ml of tetrahydrofuran. The suspension is left to stand at 3C for 48 hours, then evaporated, treated with water and extracted with ether/methylene chloride (3:1). me ethereal extracts are washed-with water, sodium bicarbonate sol-2Q ution, l-N tartaric acid and water. m e organic phase is dried over magnesium sulphate and evaporated. me residue is crystallised from methy-lene chloride/ether at 0C. mere is obtained N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-2-propionamide of melting point 135 -136C.

Example 9 3.95 g of 2-(3-chloropropyl~-2-(3,4-dimethoxyphenyl)-m-dithiane ~, ' . .- .- , , ~ : ' : .
.
-. , ' ~ :
'' " ' . . " ' ' ' ~" :, " ;', . ' ', . :' ,, : ' " ,' ': . "''' ; ' ' . ' . ' :~0~9290 1,1,3,3-tetraoxide are dissolYed~in sa nl of dimethylformamide. The solution is cooled to 0C and treated with 15 g of methylamine. me mixture is heated at 40C under pressure for 18 hours. The solution is then concentrated and the crystalline residue recrystallised from a sm~ll amount of methanol.
mere is thus obtained the desired starting material of melting point 164C.

r ~ :
.. .. . . . .

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for the preparation of a compound of the general formula (I) or an acid addition salt thereof, or (II) in which n stands for 2 or 3, X represents a sulphur atom, SO or SO2, R
represents a group of the formula or (a) (b) in which R1, R2 and R3 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, aryl-(lower alkoxy), aryloxy, phenyl, nitro, tri-fluoromethyl, hydroxy, cyano, di(lower alkyl)amino or lower alkanoyloxy group or two adjacent R1, R2 and R3 symbols together represent a methylene-dioxy, ethylenedioxy or butadien-1,3-ylene-1,4-group, R4 represents a hydrogen atom or a lower alkyl group, R5, R6 and R7 each represent a hydro-gen or halogen atom or a lower alkyl, lower alkoxy, hydroxy or benzyloxy group or two adjacent R5, R6 and R7 symbols together represent a methylene-dioxy or ethylenedioxy group, Y1 represents a straight-chain or branched-chain, optionally hydroxy-substituted, aliphatic group containing 1 - 7 carbon atoms, of which 1 - 3 carbon atoms are present in the chain, Z represents a straight-chain or branched chain, optionally hydroxy-substituted, aliphatic group containing 1 - 8 carbon atoms, of which 1 - 4 carbon atoms are present in the chain, m stands for zero or 1, Y represents a straight-chain or branched chain, optionally hydroxy-substituted, aliphatic group containing 2 - 8 carbon atoms, of which 2 - 4 carbon atoms are present in the chain and T represents a group of the formula -R8 (i) (ii) or (iii) in which A represents the group in which R4 represents a hydrogen atom or an alkyl group containing 1 - 5 carbon atoms, R8 denotes a leaving atom or group and Z, m, R4, R5, R6 and R7 have the above-mentioned meanings, or an acid addition salt of compound (II) in which T denotes the group , (iii) either:
(a) when a compound of formula I is required, reacting an acid of the general formula (XVII) in which R, X, Y1 and n have the same meanings as above, with an amine of the general formula (VIIa) wherein the various symbols are as defined above, and, if desired, the product is converted to its acid addition salt; or (b) when a compound of formula (II) is required, when T represents a radical (i) reacting a compound of the general formula (XIV) in which R and R8 have the same meanings as above, with a compound of the general formula (V) in which n has the same meaning as above, and oxidising the product if X in formula (II) is to denote SO or SO2, or when T represents a radical (ii), acylating a compound of the general formula in which R, X, Y, Z, R5, R6, R7, m and n have the same meanings as above to introduce a formyl or (C1-C5 alkyl) carbonyl group, or when T represents a radical (iii), reacting a compound of the general formula (VIa) in which R, Y, X and n have the same meanings as above, with an amine of the general formula (XVI) in which R4 has the same meaning as above, and if desired, converting the product to its acid addition salt.

2. A compound of the general formula (I) or an acid addition salt thereof, or (II) in which n stands for 2 or 3, X represents a sulphur atom, SO or SO2, R
represents a group of the formula or (a) (b) in which R1, R2 and R3 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, aryl-(lower alkoxy), aryloxy, phenyl, nitro, trifluoro-methyl, hydroxy, cyano, di(lower alkyl)amino or lower alkanoyloxy group or two adjacent R1, R2 and R3 symbols together represent a methylenedioxy, ethylenedioxy or butadien-1,3-ylene-1,4-group, R4 represents a hydrogen atom or a lower alkyl group, R5, R6 and R7 each represent a hydrogen or halogen atom or a lower alkyl, lower alkoxy, hydroxy or benzyloxy group or two adjacent R5, R6 and R7 symbols together represent a methylenedioxy or ethy-lenedioxy group, Y1 represents a straight-chain or branched-chain, optionally hydroxy-substituted, aliphatic group containing 1 - 7 carbon atoms, of which 1 - 3 carbon atoms are present in the chain Z represents a straight-chain or branched chain, optionally hydroxy-substituted, aliphatic group containing 1 - 8 carbon atoms, of which 1 - 4 carbon atoms are present in the chain, m stands for zero or 1, Y represents a straight-chain or branched-chain, optionally hydroxy-substituted, aliphatic group containing 2 - 8 carbon atoms, of which 2 - 4 carbon atoms are present in the chain and T represents a group of the formula -R8 (i) (ii) (iii) in which A represents the group in which R4 represents a hydrogen atom or an alkyl group containing 1 - 5 carbon atoms, R8 denotes a leaving atom or group, and Z, m, R4, R5, R6 and R7 have the above-mentioned meanings or an acid addition salt of compound (II) in which T denotes the group (iii) when prepared by a process according to claim 1 or by an obvious chemical equivalent thereof.

3. A process for the production of a compound of formula (I), as defined in claim 1, in which an acid of general formula (XVII) in which R, X, Y1 and n have the same meanings as in claim 1, is reacted with an amine of the general formula (VIIa) and, if desired, the product is converted to its acid addition salt.

4. A process for the preparation of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-2-propionamide which comprises reacting 2-(3,4-dimethoxyphenyl)-m-dithiane-2-propionic acid with homoveratrylamine.

5. N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-2-propionamide whenever prepared by the process of claim 4 or by an obvious chemical equivalent thereof.

6. A process for the production of a compound of formula (II), as defined in claim 1, in which, when T represents a radical (i) reacting a compound of the general formula (XIV) in which R and R8 have the same meanings as in claim 1, with a compound of the general formula (V) in which n has the same meaning as in claim 1, and oxidising the product if X in formula (II) is to denote SO or SO2, or when T represents a radical (ii), acylating a compound of the general formula in which R, X, Y, Z, R5, R6, R7, m and n have the same meanings as in claim 1, to introduce a formyl of (C1-C5 alkyl)carbonyl group, or when T represents a radical (iii), reacting a compound of the general formula (VIa) in which R, Y, X and n have the same meanings as in claim 1, with an amine of the general formula (XVI) in which R4 has the same meaning as in claim 1, and if desired, converting the product to its acid addition salt.

7. A process for the preparation of 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide which comprises reacting 3,4-dimethoxy-y-chlorobutyrophenone with 1,3-propanedithiol, and subsequent-ly oxidizing with m-chloroperbenzoic acid.

8. 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide whenever prepared by the process of claim 7 or by an obvious chemical equivalent thereof.

9. A process for the preparation of N-methyl-2-(3,4-dimethoxyphenyl) -m-dithiane-2-propylamine-1,1,3,3-tetraoxide which comprises reacting 2-(3-chloropropyl)-2-(3,4-dimethoxyphenyl)-m-dithiane-1,1,3,3-tetraoxide with methylamine.

10. N-methy1-2-(3,4-dimethoxypheny1)-m-dithiane-2-proppylamine-1,1,3, 3-tetraoxide whenever prepared by the process of claim 9 or by an obvious chemical equivalent thereof.