SU906380A3 - Method for preparing derivatives of 2,4,5,6-tetrahydro-1-n-pyrazino (3,2,1-jk) carbasoles or their acid additive salts - Google Patents

Description

using an excess of ammonia, which is, for example, 10-70 times, better than 20-50 times, with respect to the theoretically required amount. Ammonia is either used as a solution in water or in an organic solvent that is inert under the reaction conditions. Organic solvents suitable for ammonia are alcohols, for example methanol and ethanol. When using liquid ammonia, the reaction is carried out in an autoclave. Inorganic and organic acids such as hydrogen chloride, hydrogen bromide, naphthalene disulfonic (1.5), phosphoric, nitric, sulfuric, oxalic, lactic, tartaric, acetic, salicylic, benzoic, muraHat-dHg-CiH Kj-Og-O-CiH D V Halogen is chlorine, bromine or iodine, R. is alkyl, aryl or aralkyl. As 1,2-dihaloethanes and 1-hydroxy-2 sulfonic esters halogenoethanes are suitable as halogen containing chlorine, bromine or iodine eg 1,2-dichloroethane; 1,2-dibromoethane or 1,2-dilodethane. 1,2-dihaloethanes containing two different halogen atoms, for example 1-bromo-2-chloroethane, are also suitable. In the sulfonic acid esters of 1-hydroxy-2-bromoethane, 1-hydroxy-2-chloroethane or 1-hydroxy-2-iodoethane, the sulfonic acid ester group can occur from alkylsulfonic acid, especially with 1-4 C atoms, for example from methane, ethane or n-butanesulfonic acid1, from arylsulfonic acid, especially with 6-12 C atoms, for example benzene, O-, t- or p-tolyl, 2,3-, 2,4- or 3,5-xylene, 3L- or p -naphthylsulfonic acids, from aralkylsulfonic acids, especially with 7-8 C atoms, for example benzyl or phenethylsulfonic acids. Interaction of tetrahydrocarbons and formulas -toluene sulfonic, citric or adipic acid. Salts with acids are usually prepared by combining the components in a suitable diluent or dispersing agent. The 2,6-disubstituted 1,2,3,4-tetrahydrocarbazol-1-ones of formula JI used as starting materials are obtained by the interaction of the substituted Hbix in position six of 1,2,3,4-tetrahydrocarbazole-ones of formula 1I with 1, 2- dihalogenthanes or sulfonic acid 1-hydroxy-2-haloethanes. Hat Jlig-Hal Hal-CHg acids of 1-hydroxy-2-halogenoethanes are expediently carried out under conditions of catalysis of the phase transition. The reaction is carried out by stirring in a two-phase system of water and a water-immiscible organic solvent in the presence of a strong base and a phase transition catalyst. Non-miscible, inert solvents are suitable as organic solvents. Suitable solvents are, for example, aliphatic, cycloaliphatic or aromatic hydrocarbons and aromatic hypogenic hydrocarbons, for example benzene petroleum ether, toluene, 1,2-, 1,3- or}, 4-xylene, chlorobenzene. It is also possible to use mixtures of the indicated solvents; in addition to water-immiscible organic solvent, excess 1,2-dihaloethane can also be used. As a strong base, for example, sodium or potassium hydroxide is suitable. You can use the known catalysts for the phase transition. The known phase transition catalysts are quaternary ammonium or phosphonium salts, and the cation must have at least one hydrophobic residue with four carbon atoms or more. Such a residue is an alkyl, aryl, or aralkyl residue. Suitable compounds are, for example, tetrabutylammonium hydrogensulfate, benzyltrimethylammonium chloride and the like. Cations of other well-known phase transition catalysts are, for example, tetrapropylammonium, mathilmammammammammammammam, almetyangem almiramme, and alkydammammelemmeliymmeh Anions suitable for these cations are especially hydrogen sulfate, chloride and bromide. When carrying out the reaction, the reaction mixture is usually not heated. In most cases, a slight increase in temperature occurs at the beginning due to the starting reaction. The reaction time is about 1-40 at room temperature, often 20 hours, it can be reduced by increasing the reaction temperature, for example, to. Per mole of tetrahydrocarbazolone of formula III, usually 1–3 mole of preferably 1–2 mol of 1,2-dihalo genetane or sulfonic acid ester of 1-hydroxy-2-haloethane is usually used as the reaction component. If 2-dihaloethane is used not only as a reaction component, but also as a solvent, then it is necessary to use a higher 06 excess of it. In this case, for 1 mole of the tetrachloro carbazolone of formula III, for example, up to 15 mol, and if more is desired, up to 10 mol of 1-2 dihaloethane, are used. Per mole of tetrahydrocarbazolone of formula HI, 4-15 mol, preferably 5-10 mol, of a strong base are usually used, preferably in the form of an aqueous solution, the concentration of which is usually 10-40 wt.%, Preferably 20-40 wt.%. Per mole of tetrahydrocarbazolone of formula III, typically 0.005-0.05 mol, preferably 0.005-0.02 mol of catalyst is used. It is advisable to add a catalyst, dissolved 1st in a small amount of water. Large amounts of 1,2-dihaloethane or sulfonic acid ester of 1-hydroxy-2-haloethane, a strong base and a catalyst can also be used. But such an increase does not give advantages. Often, a reduction in the amount of a strong base and catalyst is also possible. But it is necessary to consider that. as the amount of catalyst decreases, the reaction time increases. The amount of catalyst is less than 5 mmol per 1 mol of the compound of formula III in most cases causes a long reaction time, which is unprofitable. The new esters of alkyl or aryl sulphonic acid of formula 11 used as starting materials are obtained by reacting I, 2,3,4-tetrahydroxycarbazol-1-ona of formula 111 with ethylene oxide to obtain a high yield of 9-hydroxyethyl-i, 2,3,4- tetrahydrocarbazole-1-BOTH of formula IV, followed by conversion to the alkyl or aryl sulfonic acid esters of formula f1 by known methods

/ H

bNg- bNg

Sh

B- OgS11

The ethoxylation of 1,2,3,4-tetrahydrocarbazol-1-gum (formula IV) is carried out in the presence of alkaline catalysts, for example sodium hydroxide, potassium hydroxide, etc., in solutions that are inert to the reagents. The most suitable solvents are dipolar aprotic solvents, for example dimethylformamide and dimethyl sulfoxide. In this case, the presence of water is beneficial, since the formation of by-products is reduced. For the transition of 9-OXYETHYL-1,2,3,4-tetrahydrocarbazol-1-ones of formula IV to the sulfonic esters of formula II are suitable. Lactically, all aromatic or ali-phatic sulfonate sulfonic acids. Preferably, methanesulfonyl chloride is used. They work in inert solvents, especially in hydrocarbons, such as toluene or benzene, and in the presence of tertiary bases, such as triethylamine or pyridine. Used as starting materials. 1, 2, 3, 4-tetrahydrocabrazol-1-15, they are of formula 1I, substituted at position 6 with alkyl, alkoxy, or halogen, if they are not known to be easily synthesized by methods known for producing 1,2,3, 4-tetrahydrocarbon-20 basolones. . . The compounds of general formula 1 and their pharmaceutically acceptable salts with Acids possess valuable pharmaceutical properties. First of all, they have a pronounced psychotropic, especially antidepressant effect. The proposed compounds of formula 1 and their pharmaceutically acceptable salts of acids with acids are used on humans separately in mixtures with one another or in pharmaceutical preparations as psychotropic substances, especially as antidepressants, which contain an effective amount of at least one active substance. of the proposed compounds of formula 1 or its salt with acids other than the usual pharmaceutically acceptable carriers and additives. Suitable carriers are, for example, water, vegetable oils. starch, gelatin, lactose, magnesium stearate, vrski, vaseline, etc. In the The use of additives, for example, wetting agents, swelling agents, preservatives, etc., Pharmacist prepare the form of drugs, for example, as. tablets, capsules, aqueous or oily solutions or suspensions, emulsions, injecting aqueous or oily solutions or suspensions, dispersible powders or mixtures of aerosols. In addition to the compounds of formula 1, the preparations may contain one more. or more other pharmaceutically active substances: tranquilizers, for example, meprobamate, chlorpromazine v 08 and benzodiazepine-based sedatives, for example, diaeepam or chlordiazepoxide, cardiovascular agents and vasodilating agents, for example, /) - blockers, glycerol nitrite, pentaerythritol tetras, for example, /) - blockers. , molsidomine and carbocromen. The proposed compounds of formula 1 are superior to known compounds of this type as antidepressants. In addition, they are valuable intermediates for the preparation of other, also pharmacologically active compounds. The pharmacological superiority of the proposed compounds over the known compound, similar in structure and action, is shown in the table below, li p and meper I. 306 g (1 mol7 of 6-methyl-9 (2-bromoethyl) -1,2,3,4-tetrahydrocarbazol-α-it, 1500 ml (60 mol) of liquid ammonia are heated in a V2 A autoclave for 20 hours at. After evaporation excess ammonia, the remaining crude product is suspended in a mixture of 2000 ml of ethyl acetate and 1 POP ml of water, and sodium hydroxide solution is added to alkaline the aqueous layer. Shake vigorously, the organic layer is washed with water, dried with sodium sulfate and precipitated with hydrochloride gas. 8-methyl-2,4,5,6-tetrahydro-1H-pyrazino {s, 2, carbazole The mixture is sucked off and recrystallized from a mixture of ethyl acetate (1: 1). Melting point: 274-276 ° C, yield: 87% of theory, molar weight: 260.5%: C, 68.7; H, 6.9; N , 4;: C1 13.1 C, 5H, 6 HC1 Calculated (1)%: C 69.2; H 6.5; N 10.7; C1 13.6. Instead of liquid ammonia, you can also use solutions of ammonia in organic solvents which, under the reaction conditions, are inert to ammonia, are solutions of ammonia in water. If the reaction is carried out not at 80 ° C, but at 20 ° C, which increases the reaction time to 72 hours, then using the same procedure, the same product is obtained with a yield of 83%. The reaction can be carried out using the same method at 120 ° C for 6 hours, and the yield is 87-89%. Preparation of the starting material 6-methyl-9- (2-bromoethyl) -1,2,3,4-tetra hydrocarbazol-1-one. Starting from 199 g (1 mol) of 6-methyl-1, 2,3,4-tetrahydrocarbazol-1-one (mp. 199 ° C), 1520 g (8.1 mol) of 1,2-dibromoethane and 1000 ml ( 7.5 mol of an aqueous solution of sodium hydroxide (30%) with stirring at room temperature was added 4.25 g (12.5) of tetrabutylammonium hydrogensulfate dissolved in 25 ml of water. The reaction starts with a slow rise in temperature and ends with a constant stirring after 7 hours. For processing, the aqueous alkaline layer is extracted / separated, the organic layer is washed with water and the excess dibromoethane is distilled in vacuum. The residue is recrystallized from 200 m ethanol to yield 281 g, which is 92% of 6-methyl-9- (2-bromoethyl) -1,2,3,4-tetrahydrocarbazol-1-one theory (mp. 103 C) Amount used as tetrabutylammonium hydrogensulfate catalyst can reduce ijo 5 mmol per 1 mole of carbolone used. At the same time, the reaction time is doubled. Instead of excess dibromoethane, you can also use other water-immiscible and inert solvents, under reaction conditions, such as toluene, benzene or chlorobenzene 199 g (| mol) b-methyl-1, 4-tetrahydrocarbazol-1-one and 376 g (2 mol) of 1,2-dibromoethane are dissolved in 1000 ml of toluene and mixed with 1000 ml of sodium hydroxide solution and 4.25 And 2.5 mmol) of hydrodisulfate tetrabutyl ammonium for JO h at bOS After separation of the aqueous layer, nepero cation of the solvent and recrystallization of the remaining crude product, 275 g of 6-methyl-9- (2-bromo7 ethyl) -1,2,3,4-tetrahydrocarbazole-1- are obtained it (90% of theory) (m.p. 102 UZS) .H {BrNO} molar weight 306. Found,%: C 59.0; H 5.4; Br 25.5; N 4,6; About 5.6. Calculated,%: C 58.8; H 5.2; Br 26.1; N 4,6; About 5.2. Instead of 6-metsh-9- (2-bromoethyl) -1, 2J 3,4-tetrahydrocarbazol-1-it can also be used 262 g of 6-met11P-9- (2-chloroethyl) -1,2,3,4- tetrahydrocarbazol-1-one, which is obtained as follows. 100 g (0.5 mol) b-metsh1-1,2,3,4-tetrahydrocarbazol-1-one, 500 ml (4 mol) of ethylene chloride is mixed with 500 ml of sodium hydroxide solution (30%) and 4.25 g ( 12.5 mmol) hydrogensulfate tetra-iammonium for 20 h at. before . Process as described in example 1 to obtain 112 g (86% of theory) of 6-methyl-8- (2-chloroethyl) -1,2,3,4-tetrahydrocarbazol-1-one (m.p.). C-E-H ClNO: molar weight 261.5. Z: C 69.4; H 6.1; C1 13, G; N 5.5, O 6.3. Ymmisleno,%: C 68.9; H 6.1; C 13.6; N 5.4; About 6.1. Instead of 1,2-dihaloethanes, the sulLoacid esters of 1-hydroxy-2-halogenoethanes can be used as starting materials, which are prepared as follows. 100 g (9.5 mol) of 6-methyl-1,2,3,4-tetrahydrocarbazol-1-oia and 234.5 g (1 mol) of p-toluenesulfonic acid chloroethyl ester are dissolved in 700 ml of toluene and mixed with a solution of 4.25 g (12.5 mmol) of tetrabutylammonium 1hydrogen sulfate in 500 ml of an aqueous solution of sodium hydroxide (30%) at room temperature for 10 hours. The organic layer is separated, washed with water and evaporated to give 108 g (83% of theory ) 6-methyl-9- (2-chloroethyl) -1,2,3,4-tetrahydro-. carbazble-1-it (m.p. 106-107 C) P p and. meper 2. 6-methoxy-9- (2-bromoethyl) -1,2,3,4-tetrahydrocarbazol-1-one is reacted as described in Example 1 to obtain 8-methoxy-2,4,5,6-tetrahydro- 1H-pyrazinoSZ, 2.1- and 3-carbazole hydrochloride (mp), yield 86% of theory; molar weight C H M 276.5. g Found,%: C 65.3; H 6.1; O 5.7; N 10.2; Ct 12.8. Calculated. %: C 65.2: P 6.1; O 5.8; N 10.0; Ci 12.9. Receiving precursors. 6-methoxy-1,2,3,4-tetrahydrocarbazol-1-one. 123 g (} mol) of p-methoxyaniline is dissolved in 600 ml of water with the addition of 260 g of concentrated hydrochloric acid. After cooling to 0 ° C, 69 g of sodium nitrite dissolved in I30 ml of water is added dropwise.

After termination of the diazotirovine, 350 ml of methanol and 148 g (1 mol) of sodium salt of 1-hydroxymethyl dyslohexanop are added and, with ice, the temperature is kept below -4-3 ° C. After 5 to 5%, 33.5 g of anhydrous sodium carbonate and 250 g of crystallized acetate sodium is adjusted to pH 5-6. After completion of the reaction (at 10–12 h at 7 o'clock) with the addition of 10 g, approximately 250 g of a concentrated solution of sodium hydroxide is adjusted to a pH of 9–9.5, stirred for 3 more hours at room temperature, then the product is sucked off and washed with water 15 to neutral state. Yield 202 g (87% of theory) of cshslogeksadion monop-methoxyphenylhydrazone (so pl. 177 “C).

Found,%: C 67, J; H 6.7; 20 M 11.9; About 13.9.

Calculated,%: C 67.2; H 6.9, N 12.1; About 13.8.

232 g (1 mol) of cyclohexanedione-mono-p-methoxyphenylhydrazone, 25 1200 ml of water, 350 g of sulfuric acid (65 degrees Bome), 100 ml of ethanol are boiled at reflux temperature. After cooling, it is filtered off with suction and washed with water until neutral. zo 6-methoxy-1,2,3,4-tetrahydrocarbase is obtained. (m.p. 222 C) 193 g (90% of theory).

Found,%: C 72.1; H 5.9; N 14.3; O.,) 5

Calculated,%: C, 72.6; H 6.0; N 14.9; About 6.5.

By the specified 1-1M procedures using otherwise substituted anilines, other substituted 40 at position 6 1,2,3,4-tetrahydro-., Carbazole 1 ones can be obtained,

6-methoxy-9- (2-bromoethyl) -1,2,3,4-tetrahydrocarbazol-1-one.

215 g (1 mol) of b-methoxy-1,2,3,4- 45 -tetrahydrocar5azol-1-one. (Mp.), 50Qrl, 2-dibromoethane, 1000 ml of an aqueous solution of caustic soda (30%) and 2 g of tetrabutylammonium hydrogensulfate are stirred at room temperature 50 for 20 hours and processed as described in Example 1 to give 286 g (89% of theory) of 6-methoxy-9- (2-bromoethyl) -1,2,3,4- tezrag1edrokarazol-1-one so pl. A9 C Molar js weight 322.

Found,% J C 56.1; And 5.0; W. 24.5; N 4.5; About 9.5. C.sH.eBrNOi

Calculated,%: C 55.9; H 5.0; Br 24.8; N 4.3; About 9.9.

PRI me R 3. 6-chloro-9- (2-bromoethyl) -1,2,3,4-tetrahydrocarbazol-1, it is subjected to interaction, as described in example I, to obtain 8 chloro-2,4, 5,6-tetrahydro-1H-lirazino 3,2,1 - j carbazole hydrochloride (mp. 295-305 s) theory output; molar weight 231.

Found,%: C59.8; H5.1; N 9.6; C, 24.6; C1 P 9.

C, vH ,, N / HCl

Calculated,%: C 9.8; H 5.0; N 10.0; cr 25.2; From 12.6.

The starting material 6-chloro-9- (2-broethyl) -1,2,3,4-tetrahydrocarbazol-1-one is obtained by reacting 6-chloro, 2,3,4-tetrahydrocarbazol-1-one (mp. 226C as described in Example 1 for the preparation of the starting materials, 6-chloro-9- (2-bromoethyl) -5,2,3,4-tetrahydrocarbazole-1-one has a mp. and it is obtained with a yield of 86% of theory; molar weight С Н Вг С1 326

. Found,%: C51.9; H4.0; Br 23.9; CE 11.2; N 4.3; O 5.3 Calculated,%: C 51.5; H 4.0; Br 24.4; All 10.9; N 4.3; About 4.9.

PRI me R 4. 6-bromo-9- (2-bromoethyl) -1,2,3,4-tetrahydrocarbaeol-1-one is reacted as indicated in Example 1 to give 8-bromo-2, 4,5,6-tetrahydro-1H-pyrazino {3, 2, - jk carbazol hydrochloride, (mp. 298-300 ° C) yield 85% of theory, molar weight 325.5.

Found,%: C 51.7; H 4.3; N 8.4; BG 24.2; C1 10.1. .

CiyH.

Calculated,%: C, 51.8; H 4.3; N 8.6; Br 24.6; se-10.9.

Utilized as starting material, 6-bromo-9- (2-bromoethyl) -1, 2,3,4-tetrahydrocarbazol-1-one is obtained from 6-bromo-1,2,3,4-tetraparidrocarbazoJ-J-one ( mp 227 c) as indicated in the example for the preparation of precursors; and yield 88% of theory, molar weight (Br.j.NO 371.

Found,%: C 45,, 0; H 3.4; Br 42.8; M 3.6; About 4.5.

N1,%: C 45.2; H 3.5; Br 43, 1; N 3.8; About 4.3.

EXAMPLE 54 6-fluoro-9- (2-bromo-tetyl) -1,2-, 3,4-tetrahydrocarbazol-1-am is reacted as indicated in Example 1 to give 8-fluoro-2 , 4,5,6-tetrahydro-1H-1raznno.3.2,2,1 j carbazol-hydrochloride a (t, mp. ZOZ-ZOZ C) output 81% of theory, molar weight 264.5. Found,%: C 62.8; H 5.5; F 6.8; N 10.3; C1 13.9. C, vH, iFN.j-HCl Calculated,%: C 63.5; H 5.3; F 7.2; N 10.6; ,four. The 6-fluoro-U-β-brbm-ethyl) -1,2,3,4-tetrahydrocarbazole-1 used as the starting material is obtained from 6-fluoro-1,2,3,4-tetragide rokarbazol-l-one (t. mp 210 ° C) as indicated in example 1 to obtain starting materials, mp. 131 ° C and a yield of 76% of theory, molar weight 310. Found,%: C, 52.1; H, 4.1; Br 25.8; F 6.1; N 4.9, C, v Н liBrFNO Calculated,%: C 54.2; H 4.2; Br 25.8; F 6; N 4.5. PRI me R 6. 122 g (0.38 mol) of 6-methyl-9- (| -methylsulfonyloxy) -1,2,3,4-tetrahydrocarbazol-1-it is heated n 650 ml (26 mol) of liquid ammonia in an autoclave for 20 hours. The remaining evaporation of the ammonia is suspended in a mixture of 1000 ml of acetic ether and 500 ml of water and a dilute sodium hydroxide solution is added until noticeable Gel-ing reaction of the layer. Shake and shake, wash the organic layer with water, dry with sulphate on ri, and add 8-methyl-2,4,5,6-tetrahydro-1H-pyrazino hydrochloride 3, 2, 1-jk to the addition of suc-cic hydrogen chloride gas. vehicle base. Filtered and recrystallized from a mixture of acetic ether - ethanol (1: 1) (t, pl. 274-276 ° C), yield 79.2 (80% of theory), molar weight 260.5 C H N N HC1 The same results can be obtained if, instead of using 6-methyl-9- ({L-methylsulfonyl-OXYETSH1-1, 2,3,4-tetrahydrocarbazole -1-it) used in the example, either 6-methyl-9- (pr-phenylsulfonyloxyethyl) I is used , 2,3,4-tetrahydrocarbazol-1-one or 151 g of 6-methyl-9- (p-Tosilethyl) -1, 2,3,4-tetrahydrocarbazol-1-one and carry out the process. Preparation of the starting material-methyl -9- (2-hydroxyethyl) -1,2,3,4-thetahydrocarbazol-1-he Exodus from 199 g (1 mol) .6-methyl-1, 3,4-tetrahydrocabazol-1-one, dissolved in 2000 ml of dimethylformide, 5.6 g (0.1 mol) of potassium hydroxide, dissolved in 200 ml of water, are added Then, 66.1 g of 74.2 ml (1.5 mol) of ethylene oxide is added at room temperature and heated to 50 ° C for 30 mun. A pressure of at most 0.2-0.5 bar occurs. 50 ° C, the solvent. Distilled under vacuum, the remainder mixed with a mixture of 800 ml of water and 10 ml of glacial acetic acid, the crystallized product is sucked off, washed with 500 ml of water and dried under vacuum. Yield 39.5 g (98.6% of theory); m.p..113116C molar weight 243. С Н N0 6-methyl-9- (fV methyl-sulfonyl Jotoxyl-ethyl) -1,2,3,4-mctr.lhydrocarbazole-l -on 239.5 g (0.98 mol) of 6-methyl-9- (2-hydroxyethyl) -, 2,3,4-tetrahydrocarbazol-1-it is dissolved in ml of toluene, 109.6 g (1.08 mol ) triethylamine and doO. dropwise 124.3 g (|, 08 mol) of methanesulfonyl chloride within 15 minutes. Cooling temperature is maintained at 25-30 C. Then another is stirred for 30 minutes at a falling temperature. After addition of 3000 ml of toluene, 500 ml of water and 15 ml of concentrated hydrochloric acid, the mixture is heated to 55 ° C, the toluene phase is separated, washed with 500 ml of water and evaporated. The residue is recrystallized from 5 liters of isopropanol. Output 280 g (89% of theory), tggs. 131-1 with decomposition of C ,, BUT S molar weight 321. If methanesulfonyl chloride is replaced by an equivalent amount of benzenesulfonyl chloride or p-toluenesulfonyl chloride (tosyl chloride), then 6-methyl-9- () 5-phenylsulfonyloxyethyl) -1, 2,3,4 -tetrahydrocarbazol-1-one (mp. 9193 0) C2 tH2iQ4 S molecular weight 383, or 6-methyl-9 - ((L-p-toluenesulfonyloxyethyl) -1,2,3,4-tetrahydrocarbazole- 1 - it (mp. 129-131 s) C, 2. molecular weight 397.

8-Methyl-2,4,5,6-tetrahydro-1H-hydroxazio 3,2,1-j k carbazole hydrochloride

8 Methoxy 2,4,5,6-tetrahydro-1I-pyrazino 3, 2, -jk Kap6a3on ri-schrochloride

8-Methyl-2,3, Za, A, 5,6-hexahydro-1 H-pyrazino 3,2,1-J 1 3 carbazol hydrochloride, (known)

Claims (3)

Claim 1. a method for producing a derivative; 2,4,5,6-tetrahydro-1 NTyrazino L3j2, l-jk carbazoles of the general formula R ,TO where R is methyl or methoxy, or fluoro, chloro, bromo or their acid addition salts, characterized in that 1, 2,3,4-tetrahydrocarbazole of the general formula B 72 18.0 37 18.5 14 8.7 122 where R has the indicated meanings: X is a bromine atom, chlorine or. the remainder of the formula - OS02.R where R is methyl, phenyl or tolyl is subjected to cyclization under the action of ammonia. 2. A method according to claim 1, characterized in that liquid ammonia is used. 3. A method according to claim 1 or 2, characterized in that the process is carried out at 50-100 ° C with stirring. Sources of information taken into account in the examination 1. Heterocyclic Compounds, Ed. R, Elderfield, Ts., I.L1960, v. 6, p. 318. 2. Published for the Federal Republic of Germany) P2 and 4230, cl. 12 p 10/10, publ. 1972.