SU512711A3 - Method for preparing benzo (4,5) -cyclohepta (1,2-b) -thiophene derivatives - Google Patents

Description

Ri is a hydrogen atom or a lower alkyl group unbranched at the a-carbon atom. Aminogrunna, expressed in formula II as X, can also be represented by a heterocyclic residue containing in some cases, in addition to the nitrogen atom, an oxygen atom, or sulfur, or nitrogen. The second nitrogen heteroatom may have a lower alkyl group as a substituent. Hydrolysis is carried out by heating Hri to 50-100 ° C in aqueous solutions of both inorganic acids, for example hydrochloric, sulfuric or phosphoric, and organic acids, for example, formic, acetic, fumaric, oxalic, etc. If the mixture consisting of If two substances of the formula II, which differ only in the position of the X-substituent, then the corresponding mixture of the desired α-products of the formula I, is formed, if necessary, -the next separation. Thus, the separation of the desired α-products of the formula I, differing only in the position of the carbonyl group at position 9 or 10, is carried out by fractional crystallization of their salts, for example fumarate. Example 1. 4- (1 - Methyl - 4-pi-peridylidene) -4H - benzo - (4,5) - cyclohepta 1,2-b thiophene-9 (10H) -one. A mixture of 24.6 g of crude 4- (methyl 4-1PI1 per-idilidene) -9-piperidino-4H-benzo - (4,5) - cyclohepta 1, 2- & tnofenovogo base and 4- (methyl 4-1 ni-neridiliden) - 10 - piperidino - 4Nbenzo - (4,5) - cyclohepta 1,2- /; the thiopheric base is dissolved in 250 cm 2 and. hydrochloric acid and heated under reflux for 1 hour. Then the crystals are cooled to 20-25 ° C, alkalinized with a concentrated solution of NaOH, and the base is extracted with 400 cm of chloroform. The combined extracts are washed three times with 30 cm of water, dissolved over sodium sulfate, and evaporated. The residue is dissolved in 50 cm of chloroform and adsorbed onto 1000 g of silica gel. Elute with chloroform containing 3% methanol. The first 6 l of the eluate is removed, the next 4 l are evaporated together. An oily substance is obtained, consisting mainly of both 4- (1-methyl-4-piperidylidene) -H-benzo (4,5) -cyclohexta 1 isomers , 2-b thiophene - 9 (10H) -one and i- (l-methyl - 4 - piperidylidene) - 4H-benzo (4,5) -: Cyclohepta 1,2 - & thiophene-10 (9P) -one. In order to separate, 19.7 g of the mixture is dissolved in 200 cm of isopropanol and boiled with 7 g of fumeic acid and allowed to crystallize; at room temperature. The product of kriugall-isation is filtered and crossed:; st11: yuyut from thirtyfold amount of etaiole (95%). In this way, a pure 4- (1-methyl-4 - -piperidylidene-4H-benzo- (4,5) -cyclohepta 1,2 - & 4- (1-Methyl-4-piperi1idene) -4H-benzo - (4,5-cyclohepta 1,2-6 thiophene-10 (9P) -one) is isolated from the isopropanoliooro stock solution (see Example 2). base excretions are added to 7.4 g of fumarate with 200 cm of water and alkalinized with a solution of 3N sodium hydroxide. The base is extracted with 150 cm of chloroform. The combined extracts are washed with 50 cm of water and dried over sodium sulfate. The solution is evaporated and boiled with 20 cm of vinegar but ethyl ether, then cooled at O – 5 ° C overnight and the crystalline precipitate filtered off. After drying, pure 4- (1-methyl-4-niperidylidene) -4H — beiso (4,5) -cyclohepta 1,2- L thiophene-9 (YUN) -ion base, melting at 148-149 ° C. The microanalysis corresponds to the CignigNOS formula. The structure is established using IR, NMR and mass spectra. Example 2. 4 - (1-Methyl-4 -piperidylidene) 4H-benzo- (4,5) - cyclohepta 1,2- & thiophene-10 (9P) -one. The isonopanol mother liquor (from example 1) is evaporated in vacuo. To the evaporated residue were added 100 cm of water and 6 g of the sweating and separated base was extracted in portions with 200 cm of chloroform. The chloroform extracts are washed with 50 cm of water and dissolved over sodium sulfate. After evaporation of the resulting solution, an oily residue is obtained, which is crystallized by heating the mixture with 20 cm of ethyl acetate. After cooling overnight at-5 ° C, filtration and drying, pure 4- (1-methyl-4-piperidylidene) -4P-benzo- (4.5) cyclohepta 1, 2- & thiophene-10 (9P) -one base, melted at 152-153 ° C. Microanalysis corresponds to the formula CignigNOS. The structure is determined by IR, NMR and mass spectra. To obtain fumarate, 8 g of pure base and 3.2 g of fumaric acid are dissolved in 100 cm of absolute ethanol at a kinen temperature and left to crystallize at night at-5 ° C. After filtering and drying, pure 4- (1-methyl-4-zineridylidene) -4P-benzo- (4,5) -cyclogeite 1,2- & thiophene-10 (9P) -onfumarate with t. PL. 192 ° C (with decomposition). Example 3. 4- (1-Ethyl-4-niperidylidene) 4H-benzo (4,5) - cyclohepta 1,2-6 thiophene-9 (10P) -one. A mixture of ns 43 g of crude 4- (I-ethyl-4-niperidylidene) -9-piperidino-4P-benzo- (4,5) -cyclohepta 1,2-b thiophenic base and 4- (1-ethyl-4piperidylidene) - 10-piperidino-4H-benzo (4,5) -cyclohepta 1,2-6 thiophene base is dissolved in 430 cm 3 n. hydrochloric acid and incubated for 30 minutes at 90 ° C. It is then cooled to 20-25 ° C, alkalinized with a concentrated solution of caustic soda, and the base is extracted in portions of 450 cm of chloroform. The combined extracts are washed twice with 50 cm of water, dried over sodium sulfate and evaporated.

The residue is dissolved in 150 cm of chloroform containing 3% methanol and is adsorbed on 1000 g of silica gel. Elute with chloroform containing 3% methanol. The first 5 liters of eluate are removed, the next 4 liters are co-evaporated. An oily substance is obtained in the residue, mainly consisting of both isomers of 4- {1-ethyl-4-piperidylidene) -4H-benzo- (4,5) -cyclohepta 1,2-b thiophene-9 (10H) -one and 4- (1-ethyl-4-piperidylidene) -4H-benzo- (4,5) cyclohepta 1, 2- & thiophene-10 (9H) -one. In order to separate this mixture, 22 g of the residue in 80 cm of absolute ethanol is dissolved with heating and a hot solution of 8.3 g of fumaric acid in 140 cm of absolute ethanol is added. From the resulting solution, a crystalline product separates out on standing for 2 hours at room temperature, which is recrystallized from 750 cm of ethanol (90%). A pure 4- (1-ethyl-4-piperidylidene) -4H-benzo (4,5) cyclogen 1,2-b thiophene-9 (10H) -one fumarate is obtained, having a decomposition point of 231 ° C. To isolate the base, 7.5 g of fumarate is suspended in 30 cm of water and added to a 3N solution. caustic soda. The base is extracted with 60 cm of chloroform. The chloroform extract is washed with 25 cm of water, dried over sodium sulfate and evaporated. The oily residue is dissolved at boiling in 12 cm of ethyl acetate and left to crystallize overnight at a temperature of -5 ° C. The crystalline product is filtered and dried in vacuo. A pure 4- (1-ethyl-4-piperidylidene) -4Nbenzo- (4,5) -cyclohepta 1,2-Ytiofen-9- (YN) base is obtained with an mp. 128-130 ° C.

Microanalysis corresponds to the formula CBoHoiNOS. The structure is determined using infrared and nuclear magnetic resonance spectra.

4- (1-ethyl4-piperidylidene) -4H-benzo- (4,5) -cyclohepta 1,2-b thiophen-10 (9H) -one (see Example 4) is isolated from the mother liquor.

Example 4. 4- (1-Ethyl-4-piperidylide; 04H - benzo - (4,5) - cyclohepta 1,2 - & thiophene-10 (9H) -one.

Ethanol mother liquor (from Nrmera 3) is evaporated in vacuo. 80 cm of water and a solution of 3 p. Of sodium hydroxide are added to the residue until alkaline. The base separated in portions was extracted with 80 cm of chloroform. The chloroform extracts are washed with 23 cm of water, dried over sodium sulfate and evaporated. The resulting residue is dissolved at boiling in 13 misopropanol and allowed to crystallize overnight at-5 ° C. The crystalline product is filtered off and the residue is obtained; pure 4- (1 - ethyl - 4 - piperidylidene) - 4H - bsnzo (4,5) - cyclogeite 1,2 - & thiophene-10 (9H) is an angular base, melting at 113-115 ° C.

Microanalysis corresponds to the formula C2oH2iNOS. The structure is determined by IR and NMR spectra.

Example 5. 4- (1-Methyl-4-piperidylylene) -4H-benzo (4,5) -cyclohepta 1,2- & thiophene9 (un) -one.

A mixture of 23.5 g of crude 9-g of g-butoxy-4- (1methyl - 4-pineridilidene) - 4H - beiso- (4.5) 5 cyclohepta 1,2- & thiophene base and 10-g, ogbutoxy-4- (1-methyl-4-piperidylidea) -4H-benzo- (4,5) -cyclohepta 1,2-t thiophene base is dissolved at 50 ° C in 235 cm 3 n. hydrochloric acid. Then, a solution of 10 at an oil bath temperature of 130 ° C for 0.5 hour is heated under reflux. Then cooled to room temperature and podsche.tachnut concentrated solution of caustic soda. The isolated precipitate is extracted with 300 cm of chloroform. The chloroform extract is washed with 100 ml of WATER, dried over sodium sulfate and evaporated. The residue obtained is dissolved in 200 cm3 of chloroform containing 3% methanol, and 20 are adsorbed onto 500 g of silica gel. The product is eluted with chloroform containing 3% methanol. The first 2 liters of eluate are removed, the next 1.5 liters are co-evaporated. An oily substance is obtained in the residue, which consists of 25 of both isomers of 4- (1-methyl-4-pinnernlidene) -4H-benzo- (4,5) -cyclohexa 1,2-b thiophene-9 (YUN) -one and 4- (1-methyl-4-nineridylidene) - 4H - benzo - (4,5) - cyclohepta 1,2 - b thiophene-10 (9H) -one. In order to separate the mixture, 15 g of the residue is dissolved in 45 cm of isopronanol and a hot solution of 5.65 g of fumaric acid is added, dissolved in 130 cm of isopropanol n, and crystallized at 40 ° C overnight. The crystalline product is recrystallized from a three-fold amount of absolute ethanol. A pure 4- (1-methyl-4-n -nneridylidene) 4H-benzo- (4,5) -cclogenate 1,2-6 thiophene-9 (10H) -onfumarate with a decomposition point is obtained. 197- 199 ° C.

4- (1-methyl-4-piperidylidene) -4H-benzo- (4,5) cyclohexta 1, 2- & thiophene-10 (9H) -one (see example 6).

5 EXAMPLE 6. 4 - (1 - Methyl - 4 - piperidylidene) - 4H - benzo - (4,5) - cyclohepta 1,2 - b thiophene-10 (9H) -one.

Isopropanol mother liquor (from solution 5) is evaporated in vacuo. 100 cm of water and a concentrated solution of caustic soda are added to the alkaline reaction to the residue obtained. The base that separated out was extracted with 90 cm of chloroform. The chloroform extract is washed with 30 cm of water, 5 is dissolved over sodium sulfate and unarned, an oily base is obtained, which is crystallized from 25 CM of isopropanol. Pure 4- (1-methyl-4-piperidylidene) -4H-benzo (4,5) -cyclohepta 1,2- & thiophene - U (9H) - it is the 0th base with m. pl. 152-153 ° C.

PRI me R 7. 6 - Chlorine - 4 - (1 - methyl - 4 piperidne lidene) - 4H - benzo - (4,5) - cyclogen 1,2 - & thiophs-9 (un) -one.

A mixture of 47 g of 6-chloro-4- (1-methyl-4 - niperp5 diliden) -9 - pneridino - 4H - benzo- (4,5) 7

cyclohepta 1,2-6 thiopheic base n 6-chloro-4 - (I - methyl - 4 - pygleridylidene) -10 piperidino-4H - benzo - (4,5) - cyclohepta 1, 2-6 thiophene base at 50 ° C solution are in 470 cm 2 n. hydrochloric acid and incubated for 0.5 hour at 90 ° C. Then it is cooled and alkalinized with concentrated sodium hydroxide solution. The free base is extracted with 300 cm of chloroform. The extract obtained is washed with water, dried over sodium sulfate and evaporated. An oily base is obtained in the residue consisting of both isomers of 6-chloro-4- (l-Iethyl-4-pyridylidene) -4H-benzo- (4,5) cyclohepta 1, 2-6 thiophene-9 (10H) - she and 6-chloro-4 - (1 - methyl - 1 - piperidylidene) -4Nbenzo - (4,5) - cyclohepta 1,2 - 6 thiophene - 0 (9H) -one.

In order to separate the mixture, 48 g of an oily base is dissolved in 200 cm of boiling absolute ethanol, filtered and a hot solution of 13.3 g of fumaric acid in 200 cm of absolute ethanol is added. The crystalline product which separated out upon standing from the solution was suspended in 200 cm of dimethylformamide, filtered and washed with benzene, to obtain 6-chloro-4 - (1 - methyl 4-piperidylidene) - 4H - benzo - (4,5) - cyclohepta 1, 2 -6 thiophene - 9 - (UN) - on-fumarate. From the mother liquor, 6-chloro-4 (I-methyl-4-piperidylidene) -4H-beiso (4,5) -cyclogen 1,2-& thiopheas - 10 (9I) -oi (see example 8). 9 g of fumarate are suspended with 50 cm of water and alkalinized with a solution of 3 liters. caustic soda. The free base is extracted with chloroform. The extract obtained is washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is dissolved in chloroform and adsorbed onto 250 g of silica gel. Elute with chloroform containing 3% methanol. The first 2 L of eluate is removed, the remaining 0.5 L is evaporated. The resulting residue is recrystallized from twice the amount of ethyl acetate, to obtain pure 6 - chloro - 4 - (I - methyl - 4 - piperidylidene) - 4H - benzo - (4,5) cyclohepta 1, 2-b thiophene - 9 (UN) - one a base which melts at 152-153 ° C (with decomposition).

Microanalysis corresponds to the formula

CisHigClNOS.

The structure is determined by IR and NMR spectra.

Example 8. b- Chloro - 4 - (1 - methyl - 4lipridylidene) - 4H - benzo - (4,5) - hicloepta 1,2-6 thiophene-10 (9H) -one.

The ethanol mother liquor (from prime) and 7) is evaporated in vacuo. The resulting precipitate is suspended in water, alkalinized) with a solution of 3N. sodium hydroxide and free osuyvany several times extracted with chlorine feed. Chloroform extracts iromyayut water, dried over sulfate and Satr1: and soar p))) mind. The resulting residue was dissolved in chloroform, 250 g of silica gel was adsorbed, and eluted with chloroform containing 3% methiol. The first 900 cm of eluate is removed, the next 400 cm is evaporated. The residue is recrystallized from a six-fold amount of isopranol, to obtain pure 6 - chloro - 4 - (1 - methyl - 4) and 4H - benzo - (4,5) - iiclogite 1, 2-6 thiophene-10 (9H) - the base of Art. square 168-169 ° C.

Microanalysis corresponds to the formula

CigHClClNOS.

The structure is determined by PIK and

NMR spectrometry.

Example 9. (4- (1 - Isoyl propyl - 4 - piperidylidene) - 4H - benzo - (4,5) - cycloheite 1,2-6 thiophene-9 (YN) -one. A mixture of 99 g of crude 4- (1 - iso-iroyl - 4 piperidylideas) - 9 - piperidino - 4H - beiso (4,5) - cyclohepta 1,2-6 thiophenic based and 4- (1 - isoylpropyl - 4 - iiideridide) U - iiideridio - 4H - benzo - (4, 5) - cyclogeite 1,2-6 thiopheic osovioi during

half an hour kin t under reflux with 990 cm 2 n. hydrochloric acid. The solution is left at 10 ° -5 ° C, the hydrochloride is taken out, and the latter is filtered on a filter and suspended in 500 cm of water. The suspension is alkalinized with a co-caustic solution of sodium hydroxide and the free axis is extracted with 600 cm of chloroform. After washing with water and drying the solution with sodium sulfate and chloroform, the 1st solution is evaporated in vacuo. In the residue, a crude, oil-based, basement is obtained, and from both isomers 4- (1-isopropyl-4-iii-iridylidene) -4H-beiso (4,5) -cyclogeite 1.2-6 tiofei-9 (YN) -one and 4- (1 - iso-iroyl - 4 - piperidilidei) - 4Nbenzo - (4,5) - cyclogeite 1,2 - 6 thiophene - 10 (9H) -opa. For the separation of both isomers, 85.7 g of crude axis was dissolved at boiling in 700 cm of isopropanol and a hot solution of 29 g of fumaric acid in

500 cm of isopropanol. The crystalline fumarate is filtered off and finally spiked with 200 cm of isoiroyanol. From the mother liquor, 4- (1 - isopropyl - 4 - and imidylidei) - 4H - benzo - 4,5) - cyclogen 1, 2- / are separated; t; ofei - Yu (9H) -one (see Irpmer Yu).

Fumarate is recrystallized from od: Iiadi .atp multiple of this iola / water

8: 1. Get pure 4- (1 - nzopropyl - 4p: -perpdpl1 den) - 4H - benzo - (4,5) -cyclohepta 1, 2-6 tpophen - 9 (10H) - it is fumarate, which melts at 214-216 ° С (with decomposition).

In order to isolate the base, 27 g of fumarate is suspended in 100 cm of water and alkalized. ammonia. The free base is extracted with 200 cm of chloroform. The extract adsorb 500 g of silica gel. Elute with chloroform containing 5% methanol. Perzyo 0.9 L eluate is removed, the following

0.9 l at 1 aryut. The oily residue is recrystallized from a double amount of uxuspoethyl ether / petroleum ether 1: 1, to obtain pure 4- (1 - isopropyl - 4-piperidylidene) - 4H - benzo - (4,5) -cnclohepta 1.2-6 thiophene - 9 ( 10H) —New base with a decomposition point of 117-119 ° C. Microalysis according to the formula

CziHssNOS.

The structure is degraded by IR and NMR spectra.

Example 10. 4- (1 - Isopropyl - 4 - iiiridilidei) - 4Ii-6e: 30- (4,5) - cyclohepta 1, 2nd tpofen - 10 (9H) - op.

The isopropanol mother liquor (from example 9) is evaporated in vacuo. The residue is suspended in 300 cm-water and made alkaline with a acetone-free caustic soda solution, and the base is taken up in portions and extracted with 800 cm of chloroform. The extract is washed with water, dried over sodium sulfate and evaporated in vacuo, the resulting residue is dissolved in chloroform and adsorbed on 1000 g of silc gel. The product is eluted with chloroform, containing porridge, 5% methanol. The first 2.4 L of the eluate is removed, the remaining 1.5 L is harvested to give an oily base. In order to produce fumarate, 16.9 g of base and G, 1 g of fumaric acid is dissolved in 85 cm of absolute ethanol and crystallized overnight at about-5 ° C. The fumarate is filtered off and recrystallized from a sixteenfold amount of 95% ethanol to give 4- {1-iso-propyl-4-piperidylidene) -4H-benzo (4,5) cyclohepta 1, 2- & thiophene - 10 (9H) - op - fumarate, which melts at 225-226 ° C (with decomposition).

Microanalysis corresponds to the formula

C2lH23NOS-C4H404.

The structure is identified with the help of K and NMR spectra.

Example 11. 4- (1-n-butyl-4-piperidylidene) -4H-beiso- (4,5) -cyclohepta 1, 2-6 thiofep-9 (10K) -one.

A mixture of 47 g of crude 4- (1 - to-butyl - 4 - iperidylidees) - 9 - iperidipo-4H-benzo- (4.5) 1 and 1-heheptol 1, 2- & thiophene base and 4 (1 - "- butyl-4 - ipperidylideas) - 10 - iISRIDIO-4H - bizo - (4,5) - n parathogeite 1,2 - & Thiofep osipopia iri 40 ° C is dissolved in 470 cm-2 and. hydrochloric acid and stirred for 30 min at 90 ° C. The mixture is then cooled to room tagging and pressurized with copious sodium hydroxide solution. The base that is isolated is extracted with 600 cm of chloroform, the extract is washed with water, dried over sodium sulfate and ynapi; In the residue; you get a mixture of 4- (1- -butyl4-iiperidylgtden) -4H-benzo- (4,5) -pclohepta 1, 2nd tnofsn-9 (10K) -one base and 4- (1- K - Outil - 4 - Nineridylidene) 4P - benzo - (4,5) - t. sylohepta, 2-6 tiofei 10 (9H) -Hono base. For the purpose of separating the odonch nosomers, 43 g of a kinky raw base is dissolved in 150 cm of isonro-anol and a hot solution of 15 g of fumaric acid in 750 cm of iso-iropanol is added. After two hours at room temperature, the separated crude fumarate is filtered off. From the mother liquor, 4- (1-n-butyl-4-p; peridpl 1den) -4P-benzo (4,5) -cyclogeite 1,2-h tiufen-10 (9P) -oi

(see example 12).

Crude fumarate suspend in 200 cm of WATER and iodilase 3 and. ammonia solution. Free osirovanie extracted with 200 cm x:, oroform, the extract is washed with water, dried over sodium sulfate and evaporated in vacuum. The residue is dissolved in chloroform and adsorbed onto 500 g of silica gel. The product is eluted with chloroform containing 2.5% methanol. The first 1000 cm of eluate

removed, the next 600 cm. evaporated; an oily residue is obtained. 8 g of the residue and 3.2 g of malic acid are dissolved in 60 cm of syrup of isopyropanol. The solution is left overnight at a temperature of -5 ° C. The product is filtered and

dried in vacuum iri 70-80 ° C, and 4- (1 - n - butyl - 4-piperidylidene) -4P-beiso (4,5) - cyclohepta 1,2-b thiophene - 9 (10H) - onmalat is obtained, with m.p. 188-190 ° С (with decomposition). Microanalysis corresponds to the formula

C, .P, .SL1b05.

The structure is determined; 1, eaten with an NMR NMR spectroscopy.

Example 12. 4- (1 - n - butyl - 4 - piperidylidene) - 4H - benzo - (4,5) - cyclohepta 1, 2- & thiophene-10 (9P) -one.

The isonopanol mother liquor (from Example 11) is evaporated in vacuo. The residue is suspended in 300 cm WATER 1 and made alkaline with a solution of 3N. ammonia. The free base of G 1e is extracted with 300 cm of chloroform, washed with water, dried over evaporated. The residue obtained is chromatographed on 500 g of C 1lpkagel, eluted with chloroform containing 2% methanol. 2.2 L of the eluate is removed, the remaining 0.6 L is evaporated and the residue is twice recrystallized from 13 propanol. 4- (1- "- - 4 - piperidylpdei) - 4P - benzo - (4,5) cycloepta 1, 2- & p1: ofen - 10 (9H) - oiovoe with t. pl. 104-105 C.

Mpcroalysis corresponds to the formula

CojHasNOS.

 determined by IR and NMR spectra.

Example 13. 7 - Chlorine - 4 - (1 - methyl 4piper 1D lideden) - 4H - benzo - (4,5) - Z clogepta 1,2-b tpofep-10 (9H) -one.

Claims (1)

A mixture of 35 g of raw. Insto7-chloro-4- (1-met | tl-4-piperid1tl de) -9-piperndio-4-benzo- (4,5) -C1 cloghepta 1,2- / t ofeno base and 7-chloro-4- ( 1-meth 1L-4-tsiper 1diliden) - 10 - ppper 11 D 1H - 4H - benzo (4,5) - tscllohepta 1,2- & The thiophenic osvanium is dissolved at 40 ° C in 350 cm 2 and. hydrochloric acid and stirred for 0.5 hour at a temperature of 90 ° C. When cooled, the mixture is made alkaline with a caustic sodium solution of sodium hydroxide at 20 ° C and the free base is extracted with 400 cm of chloroform. The extracts are washed with water, and the mixture saturated with sodium sulfate is evaporated. An oily osovapie is obtained in the residue consisting of both isomers: 7-chloro-4- (1-methyl-4-iiperidylidene) -4H-beiso- (4,5) -cyclohepta 1,2-b thiophene - 9 (YUN ) - oia and 7 - chloro-4- (methyl - 4 - pinidylidene) - 4H - benzo - 4,5 cycloheite 1, 2-6 thiophene - 10 (9H) - it. For the separated isomers, the resulting residue is dissolved in 200 cm of boiling absolute ethanol and a hot solution of 9 g of alkali salt in 200 cm of absolute ethanol is slowly added by stirring. The viscous crystalline precipitate of oxalate is filtered off after soaking in tea 3 tea at-5 ° C. 7-chloro-4 (1-methyl-4-yiperpdylpdep) -4H-beiso (4,5) -cyclohepta 1,2-6 thiophene-9 (10H) -he is isolated from the mother liquor (see example 14). The crude oxalate is suspended in 150 cm of water and made alkaline with a copolymer caustic solution. Loose precipitate extracted with 50 cm of chloroform. Chloroform solution is adsorbed on 500 g of snickel. The product is eluted with chloroform containing 3% methanol. The first 1000 smulyuat removed, next not 1400 cm evaporated. The residue obtained is recrystallized twice from four-isopropyl amounts of isopropanol. 7-chloro-4- (1-methpl-4-npneridpliden) -4H-benzo- (4,5) -cyclohepta 1,2-b thiofen-10 (9H) -oopen-axled with t. Il is obtained. 150-151 ° C. Microaialysis corresponds to the formula CisHigClNOS. The structure is determined by IR, NMR and mass spectra. Example 14. 7 - Chlorine - 4 - (1 - methyl-4-pnperidylpden) - 4H - benzo - (4,5) -cyclogenate 1,2-b thiophene-9 (10H) -op. The ethanol mother liquor (nz irimer 13) is evaporated in vacuo. The residue is suspended in 100 cm of water and alkalinized with a concentrated solution of caustic soda. The free base is extracted with 50 cm of chloroform. Organic phase adsorb PA 250 g of silica gel. The product is eluted with chloroform containing 3% methanol. The first 1400 cm of eluate is removed, the next 600 cm is evaporated and the residue is recrystallized from fivefold amounts, sms ethyl ethyl acetate / ethyl ether 1: 1. This gives 7 - chloro - 4 - (1 - methyl - 4 - pyper1: d11L le | 0 - 411 - benzo - (4,5) - cyclohepta, 2-6 tpoffe: 1-9 (10H) -one base, i. : the second melts at 192-194 ° C. (with decomposition). The microanalysis corresponds to the formula CigHisClNOS. The structure is determined by IR and NMR spectra. Measure 15 is 15. 6 - Bromo - 4 - (1-methyl-4-piperidylidene) - 4H - benzo - (4,5) - cyclohepta 1, 2-b tofen-10 (9H) -op. C 1 mixture of 15.4 g of crude 6-bromo-4- (1-methyl-4 piperidylidene) - 9 - piperndino - 4H - benzo (4,5) - tsplogept 1,2-6 tofenovogo based and 6-bromo - 4 - (1 - methyl - 4 - ipperidilidei) -10 - niperidppo - 4P - benzo- (4,5) -cyclohexite 1 2-6 tiofei Dissolve the base in 155 cm 2N hydrochloric acid and hold for 0.5 hour at 90 ° C. The solution is then alkalified with cooling 3 and a solution of sodium hydroxide and the free base is extracted with 320 cm of beisol. In the residue, an oil of 1I1-base is obtained, which consists of the pz of both isomers 6 - bromo - 4 - (1-methyl - 4 - ipperndplpdep) - 4P - benzo - (4,5) - tcclohepta 1,2-6 tnof | en-9 (10H) -one n 6 - bromo - 4 - (1metnl - 4 - piperidylidene) - 4P - benzo- (4,5) incohepta 1, 2-b tofen - 10 (9H) - it. In order to separate the isomers, the effluent residue is dissolved in a small amount of chloroform and adsorb 500 g of silica gel. The product is eluted with chloroform containing 2% methanol. The first 4 l of the eluate is removed, from the next nerve fraction (0.4 l) of the eluate, 6 - chlorine - 4 - (1 - metpl-4pippdiliidep) - 4p - beiso - (4,5) - cyclogeite 1, 2-b Tpofei - 9 (10P) -one (see pref. 16). The next second fraction (1.4 l) of the eluate is evaporated and the residue is recrystallized twice from a six-fold amount of iso-iropanol. 6 - bromo - 4 - (1 - methyl - 4 - iperidylidene) - 4H - benzo - (4,5) -cyclogeite 1,2-b tpophene - 10 (9H) - is obtained on the base with m. Pl. 172-173 ° C. Microanalysis corresponds to the formula CigHisBrNOS. The structure is determined by IR and NMR spectra. Example 16. 6 - Bromo - 4 - (1-methyl-4-ppiperidpliden) - 4P - beiso - (4,5) - cyclohepta 1,2-6 tiofetz-9 (10) -op. The first elution fraction (from example 15) is partially evaporated and adsorbed onto a vadstype with a multiple amount of splicel. The product is eluted with chloroform containing 2% metaiol. The first 300 cm of eluate is removed, the next 80 cm is evaporated. The resulting residue is recrystallized from a repeated amount of ethyl acetate. 6 - bromo - 4 - (1 - methyl 4-ipidine) - 111 - benzo - (4,5) - cyclohepta 1,2-thiophen-9 (10H) -one base is obtained, which melts at 143-146 ° C with decomposition). Microanalysis complies with the formula CigHisBrNOS. The structure is determined by IR and NMR spectra. The method of obtaining benzo- (4,5) cyclohepta 1, 2-b thiophep derivatives of the general formula 5 10 15 20 where RI and R2 have the indicated meanings; X is a substituent in the 9 or 10 position and is a lower alkoxy group or amino group of the formula N (CH 2 R 3) R 4 in which Rs is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom or a lower alkyl group that is branched at the a-carbon atom, or Ra and R4 together form a heterocyclic residue, which may include a second hetero atom, for example an oxygen atom, a sulfur atom of the nitrogen atom unsubstituted by a lower alkyl residue, or a mixture of compounds of formula II with a different the position of the X group is subjected to acid hydrolysis, followed by isolation of the target product by a known technique in the form of a free base or salt. where RI is a hydrogen atom, a halogen or a lower alkoxy group containing 1-4 carbon atoms; R2 is a lower alkyl group containing 1-4 carbon atoms; -A-B means -CH2-CO- or -CO-CH2-group, as well as salts of the said derivatives, o t, and that the compounds of the general formula Priority featured: 11.03.70, if RI is a hydrogen atom, a halide or lower alkoxy group containing 1 to 4 carbon atoms, Rs is a lower alkyl group containing 1-4 carbon atoms, -A-B - means -CHa-CO- or -CO-CHa-primer, X is an amino group of the formula NR3R4, which is B position 9 or 10, in which Rs is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom — a lower alkyl group not branched on the a-carbon atom; RS and R4 together form a heterocyclic residue, which may include a second hetero atom, such as an oxygen atom, sulfur, or a nitrogen atom unsubstituted or substituted by a lower alkyl residue. 07/31/70, if X is a lower alkoxy group, standing at position 9 or 10.