NO833755L - PROCEDURE FOR THE PREPARATION OF DIBENZAZEPINKAR BOXAMIDES - Google Patents

Description

The invention relates to a process for the production of new 5H-dibenz/b,f7azepine-5-carboxamides of the general formula I

wherein R.j and independently of each other means hydrogen or lower alkyl or interconnected lower alkylene or ethyleneoxyethylene, one of the symbols X^ and X^ means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, lower alkoxy, halogen, atomic number up to and including 35 or cyano and the other means hydrogen , lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl or both symbols X^

and X2 means hydrogen, X^ means lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, halogen of atomic numbers up to and including 35, cyano or dilower alkylsulfamoyl or X^ can also mean hydrogen if at least one of the radicals X^ and X^ is different from hydrogen and simultaneously with halogen or cyano as X^ resp. X^ and hydrogen as X^resp. X^ means hydrogen or lower alkyl and R 2 means lower alkyl or R^ together with R 2 means lower alkylene or ethyleneoxyethylene and simultaneously with lower alkoxy as X^resp. X- and hydrogen as X^ resp. X^R^ together with R^ means lower alkylene or ethyleneoxyethylene, X^ means hydrogen or together with lower alkyl or halogen which X^ can also mean one of these residues and the symbols Y. and Y~ each mean hydrogen, if one of the symbols X^ and X^ means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and the other means hydrogen or both means hydrogen or and Y2 together means an extra bond if

at least one of the radicals R 1 , R 2 , X 1 and X 2 is different from hydrogen or X 2 is different from cyano or at least one of the radicals X 2 and X 2 is different from halogen, or in which R 2 and R 2 together mean lower alkylene or ethyleneoxyethylene and X^ together with Y means oxo and X2 together with Y2 means hydrogen or X^ means hydroxy and X2, Y^ together with Y2 means hydrogen or R^ and R2 independently of each other means lower alkyl or together lower alkylene or ethyleneoxyethylene, X^ together with X2 means epoxy or epimethylene and Y^ and Y2 each means hydrogen, X^ means hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, halogen of atomic number up to and including 35, cyano or dilower alkylsulfamoyl, and X^ means hydrogen or simultaneously with lower alkyl or halogen which X^ likewise means one of these residues.

These compounds manage to reduce the amnesiogenic effect of electroshock as the convulsions triggered by the electroshock completely or considerably, e.g. to 50% corresponding to anticonvulsant ED^q which also partly still in lower dosages to at least a similar or even stronger degree than piracetam.

The findings summarized above can be established in the following one-step learning test on mice: The test device consists of a large box (35 x 20 x 10 cm), which is connected by means of a sliding door to a smaller box (10 x 10 x 18 cm). While the small box is illuminated clearly from above using a 100 Watt lamp, the large box is dark. The bottoms in both compartments consist of an electrifiable grid.

For training, the mice are placed individually in the brightly lit small box. Since mice have a spontaneous preference for the dark, they walk in the dark part for at least 30 seconds. As soon as they have entered it completely, the sliding door closes and a foot shock is given (1 mA, 5 seconds). The animals are then immediately removed from the facility.

To investigate the learning effect (retest), after 24 hours, the mice are placed individually again in the bright compartment and the latency until they are completely in the dark is measured. Usually, most animals now remain in the bright part throughout the observation time of 150 seconds.

The learning effect is strongly canceled resp. the memory of the foot shock is partially erased when, as an amnesiogenic treatment immediately connected to the foot shock of exercise reviews, a temporal electroshock treatment is connected. Parameters of the electroshock: 50 mA, 0.4 seconds, 50 Hz, 0.6 msec pulse width.

To test and compare their protective effect against the amnesiogenic effect of the electroshock, the test substances are each time 30 minutes before training intra-peritoneally administered as a suspension in methocel and the animals immediately after training were subjected to the electroshock treatment. 24 hours later, the degree of residual learning effect still retained is measured using the residence time in the lighted box and compared to that of the other test substances as well as of control animals with only methocel administration and training without, as also with subsequent electroshock treatment. As according to the Mann-Whitney U-test still significantly effective doses, i.e. DE . was it e.g. for 10-methylthio-min

5H-dibenz/b,f7azepine-5-carboxamide determined 0.1 mg/kg i.p. and for 3-methylsulfonyl-5H-dibenz/b,f7azepine-5-carboxamide likewise established 0.1 mg/kg i.p.

As literature on similar experiments, mention should be made of: S.J. Sara and D.Lefevre, Psychopharmacologia 2_5 , 32-40 (1 972) Hypoxia-induced amnesia in one-trial learning and pharma-cological protection by piracetam; and Boggan, W.O., and Schlesinger, K. , in Behavioral Biology 1_2, 1 27-1 34 (1 974).

Compounds of the general formula I in which R₂ and R₂ are hydrogen or lower alkyl, X₂ in X₂ and X₂ are each hydrogen and Y₂ and Y₂ together are an additional bond, are described in Swiss Patent No. 500,196 as intermediates, in particular 10-methoxy-5H-dibenz-/b,f7azepine-5-carboxamide, N-methyl-, N,N-dimethyl-, N-butyl-and N,N-dibutyl-10-methoxy-5H-dibenz/b ,f7~azepine-5-carboxamide.

Furthermore, in Swiss patents 325 662, 403 767, 500 101 and 501 196, British patent 906 452, European Offen-legungsschrift 50 589 as well as in Belgian patent 892 882 compounds of formula I are described as anticonvulsants, in which R., and R2 have given meanings, X., and X_ mean hydrogen or lower alkyl respectively, if R^ and R2 mean hydrogen or lower alkyl, X^ and X2 mean hydrogen, X^ and X^ mean hydrogen or if X^ and/or X2 mean hydrogen or lower alkyl, is X^ halogen, lower alkyl or lower alkoxy and X^ halogen or lower alkyl, wherein and Y 2 each means hydrogen or together an additional bond. Furthermore, US patent 3,842,091 and Japanese application 7308631 describe as anticonvulsants compounds of formula I in which R^ means lower alkyl, X^ together with X2 means epoxy or epimethylene and R2, X^, X^, Y^ and Y2 mean hydrogen. Furthermore, in US patent 4 235 895, Belgian patent 833 852 and European patent application 50 589 compounds of formula I are mentioned as anticonvulsants in which R^ and R2, X^ and X^ mean hydrogen, X^ means cyano or hydroxy and X2 means hydrogen resp. . X^ means halogen and X2hydrogen or halogen resp. X^ and X 2 hydrogen and X^ cyano and Y^ and Y 2 together mean an extra bond or, if X^ is hydroxy, Y^ and Y 2 mean hydrogen, and some of these are in the previously unpublished Belgian patent 892 882 proposed as nootropics.

The compounds of formula I can be used for the prophylaxis or therapy of cerebral insufficiency, in particular of memory disorders of various genesis, such as senile dementia, multi-infarct dementia or dementia of the Alzheimer type, further of sequelae of brain trauma or apoplexy.

The dosage is then based on the type of disturbance, the individual condition, age and weight of the patient and the duration of the treatment and is particularly between approx.

0.2 and approx. 17 mg/kg per day or about. 15 to 1200 mg per day for adults of normal weight of approx. 70 kg.

The invention relates, for example, to a method for preparing compounds of formula I, in which R1 and R2 independently of each other mean hydrogen or lower alkyl or connected to each other lower alkylene or ethyleneoxyethylene, one of the two symbols X^ and X and/or the symbol X^ means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and X^ also means halogen up to atomic number 35, dilower alkylsulfamoyl, lower alkyl, cyano or lower alkoxy and a resp. the remaining two of the symbols X.j , X.sub.2 and X.sub.^ mean hydrogen. however, X^ or X^ can if at least one of the residues R 1 and R 2 is different from hydrogen or lower alkyl and one of the residues X^ and X^ is different from hydrogen and Y. and Y means an extra bond, also means lower alkoxy and X^ resp . X^ can mean hydrogen, X^ means hydrogen or together with halogen or lower alkyl which X^ can also mean one of these residues, Y. and Y2 together mean an extra bond or together with hydrogen like X^

and X2 can also each mean hydrogen, or if at least one of the residues R^ and R2 is different from hydrogen and X^ and X^ means hydrogen, X^ can also mean halogen up to atomic number 35 or cyano, X2 means hydrogen and Y^ and Y2 together an additional binding.

The invention primarily means a method for preparing such compounds of formula I, in which R 1 and R 2 independently of each other mean hydrogen or lower alkyl or associated with each other lower alkylene or ethyleneoxyethylene, one of the two symbols X 1 and X 2 means lower alkyl thio, lower alkyl sulfinyl, lower alkyl sulfonyl or trifluoromethyl and the other hydrogen, X^ means hydrogen, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano, halogen up to atomic number 35, di-lower alkyl sulfamoyl, lower alkyl or lower alkoxy, X^ means hydrogen or together with halogen or lower alkyl as X^ can likewise means one of these residues and Y^ and Y2 together mean an additional bond or each hydrogen.

The invention primarily also relates to the preparation of compounds of formula I, in which R^ and R2 independently of each other mean hydrogen or lower alkyl or associated with each other lower alkylene or ethyleneoxyethylene, X^ and X2 mean hydrogen, X^ means halogen with atomic number up to and including 35, lower alkyl , lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or dilower alkylsulfamoyl, X^means hydrogen or simultaneously with halogen or lower alkyl which X^may also mean one of these residues and Y. and Y2 each means hydrogen or if at least one of the residues R- and R2 are different from hydrogen or X^ is different from cyano or X^ is different from halogen, Y^ and Y^ together can mean an additional bond.

The invention primarily relates to further preparation of compounds of formula I, in which one of the symbols R^ and R2 means lower alkyl and the other hydrogen or both means lower alkyl or together lower alkylene or ethyleneoxyethylene, one of the symbols X^ and X ? means halogen of atomic number 35 or cyano and the other similarly as X^ and X^ means hydrogen, with Y^ and Y2 together meaning an extra bond.

The invention primarily also relates to the preparation of compounds of formula I, in which R^ and R2 independently of each other mean hydrogen or lower alkyl or connected to each other lower alkylene or ethyleneoxyethylene, X^ and Y^ together mean oxo and X2 and Y2 each mean hydrogen or X^lower oxy or hydroxy and X2, Y^ and Y2 are each hydrogen, X^ means halogen of atomic number up to and including 35, lower alkyl, lower alkoxy, further lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or diloweralkylsulfamoyl, or if R 1 and R2 together means lower alkylene or ethyleneoxyethylene means hydrogen and X^ means hydrogen or simultaneously with halogen or lower alkyl which X^ can also mean one of these residues.

The invention relates above all to the preparation of compounds of formula I, in which on the one hand R^ , R 2 , X^

and X2 means hydrogen, X3 means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each time up to and including 4 C atoms such as methylthio or methylsulfonyl, diloweralkylsulfamoyl with up to and including 4 C atoms in each alkyl moiety, such as dimethylsulfamoyl, lower alkyl or lower alkoxy with up to and with 4 C atoms, such as methyl or methoxy, halogen of atomic number up to and including 35, such as chlorine or trifluoromethyl, X^ means

hydrogen together with lower alkyl or halogen such as X., can also mean lower alkyl and Y. and Y2 each means hydrogen or together an extra bond or in which on the other hand and R2 independently of each other means hydrogen or lower alkyl each having up to 4 C atoms and e.g. means methyl,

one of the radicals X^ and X2 means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each time up to and including 4 C atoms such as methylthio or methylsulfonyl, trifluoromethyl or, if at least one of the radicals R^ and R2 means lower alkyl, means halogen of atomic number up to and including 35, as chlorine or bromine or cyano and the other as X^ and X^ are hydrogen and Y^ and Y2 together form an additional bond.

The invention relates in particular to the preparation of compounds of formula I in which five of the symbols R^, R2, X^, X2, X^ and X^ mean hydrogen and a different residue R^ and/or R2 means lower alkyl with up to and including 4 C atoms as methyl or butyl, a different residue X₂ or X₂ means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl with each time up to and including 4 C atoms such as methylthio or methylsulfonyl, or trifluoromethyl resp. a residue different from it X^means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each time up to and including 4 C atoms such as methylthio, or methylsulfonyl, diloweralkylsulfamoyl with up to and including 4 C atoms in each alkyl part, such as dimethylsulfamoyl, lower alkyl or lower alkoxy with up to and . with 4 C atoms such as methyl or methoxy, halogen of atomic number up to and including 35, such as chlorine, or trifluoromethyl and Y^ and Y2 together mean an additional bond.

The invention relates in particular to the production of the new compounds mentioned in the production examples.

The above and the following are understood to mean lower residues or compounds preferably those with a maximum of 7, especially a maximum of 4 carbon atoms. In the compounds with the general formula I, the general terms used can for example be indicated by the residues mentioned below: Lower alkyl is e.g. propyl, butyl, isobutyl, pentyl, isopentyl, neo-pentyl, hexyl, heptyl and above all methyl and especially as X^ next to hydrogen son X^ is ethyl, the lower alkylene e.g. 4- to 6-membered and consequently forms, together with the adjacent nitrogen atom, e.g. 1-pyrrolidinyl, 2,5- and 3,4-dimethyl-1-pyrrolidinyl, 1-piperidinyl, 4-methyl-, 2,6-dimethyl- or 4,4-dimethyl-1-piperidinyl or hexahydro-1H -azepin-1-yl. Low-area coke is e.g. ethoxy, pro<p>oxy, iso-propoxy, butoxy, isobutoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, heptyloxy and above all methoxy. Lower alkylthio is e.g. ethylthio, propylthio, isopropylthio, butylthio or isobutylthio and above all methylthio, lower-alkylsulfinyl, e.g. methylsulfinyl or ethylsulfinyl and lower alkylsulfonyl, e.g. ethylsulfonyl, <p>ropylsulfonyl, iso<p>ropylsulfonyl, butylsulfonyl or isobutylsulfonyl and above all methylsulfonyl. Halogen up to atomic number 35 is fluorine, bromine and above all chlorine, and dilave alkylsulfamoyl e.g. dimethylsulfamoyl or diethylsulfamoyl. A substituent X is, for example, in the 2-position or especially in the 3-position. If X 4 as X 3 means lower alkyl or halogen, X 3 is preferably at the same distance from the nitrogen atom of the middle ring, i.e. e.g. the methyl group or the chlorine atoms X^ and X^ are located in the 2,8- or preferably in the 3,7-position of the tricycle.

The pharmaceutical preparations can be single-dose pharmaceutical forms, i.e. dosage unit forms for oral administration such as tablets, dragees or capsules or for rectal administration such as suppositories or non-single-dose pharmaceutical forms for oral administration, such as syrups. Dosage unit forms contain a compound of the general formula I in an amount suitable for intake of the above-mentioned daily dose in a one- or several-time, preferably maximum three-time, especially two-time administration of each time preferably one or two dosage units, i.e. the total respective one third or in particular half of a daily dose respectively half, one sixth or one quarter corresponding to approx. 2.5 to approx. 600 mg, preferably approx. 5 to approx. 300 mg. Instead of a single compound of the general formula I, several can also be administered at the same time, as the total doses and quantities likewise remain in the range indicated above for individual compounds.

Divisible dosage units such as breakable tablets and those with delayed active substance release can also contain higher amounts of active substance and, on the other hand, dosage unit forms for administration to children also contain correspondingly lower amounts of active substance.

Non-single-dose oral medicinal forms such as syrups contain those of individual dosage units corresponding amounts of active substances in suitable amounts or volume units e.g. of 2.5, 5 or 10 ml.

The pharmaceutical preparations contain one or possibly more compounds of the general formula I preferably together with inorganic or organic solid or liquid pharmaceutically usable carriers which are suitable for enteral use, e.g. oral administration. For the production of tablets or dragon cores, the active substances are combined, e.g. with solid powdered carriers such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine, optionally with the addition of lubricants and lubricants, e.g. silicon dioxide, talc, stearic acid or salts thereof, such as magnesium or calcium stearate and/or polyethylene glycol, optionally with the addition of binders such as magnesium aluminum silicate, starches such as corn, wheat, rice or arrowroot starch, gelatins, tragent, methyl cellulose, sodium carboxymethyl cellulose and /or polyvinylpyrrolidone and, if desired, explosives, e.g. again starches, agar, alginic acid or salts thereof, such as sodium alginate and/or fizzy mixes, or adsorbents, colourings, flavorings and sweeteners. The dragon cores are coated, for example, with concentrated sugar solutions such as may also contain gum arabic, talc and/or titanium dioxide or a varnish dissolved in a slightly volatile organic solvent or solvent mixture. Dyes can be added to these covers, e.g. for the characterization of different active substance doses.

As additional oral dosage unit forms, injectable capsules made of gelatin as well as soft, closed capsules made of gelatin and a plasticizer such as glycerol are suitable. The capsules contain the active substance preferably as granules, e.g. in a mixture with fillers, such as corn starch and/or lubricants such as talc or magnesium stearate and possibly a stabilizer such as e.g. ascorbic acid. In soft capsules, the active substance is preferably dissolved or suspended in suitable liquids such as liquid polyethylene glycols, as they may also have added stabilizers.

As non-single-dose pharmaceutical forms, commonly produced syrups which contain an active substance of the general formula I, preferably in suspended form, come into consideration in particular.

The pharmaceutical preparations may be sterilized and/or contain excipients, e.g. preservatives, stabilisers, wetting and/or emulsifying agents, solvents, salts for regulating the osmotic pressure and/or buffers. The present pharmaceutical preparations which, if desired, can contain further pharmacologically active substances are prepared in a manner known per se, e.g. by usual mixing, granulating, coating or dissolving methods and contains from approx. 5% to 10%, especially from approx. 10% to approx. 80% of one or possibly more compounds with the general formula I.

The method according to the invention is characterized by

a) a compound of the general formula II

wherein Z represents a halogen atom, is reacted with a compound of the general formula III b) a compound of the general formula IV

in which R^ , R 2 , X^ and X^ has the meaning given under formula I, is reacted with a lower alkyl mercaptan or an alkali metal lower alkyl mercaptide to a compound of the general formula I, in which X. or X 2 means lower alkyl thio, X 2 resp. X^ means hydrogen and and Y2 together means an additional bond and , R2, X^ and X^ have the meaning given under formula I, or

c) in a connection with formula

in which Z 2 means a voretred mercapto group and Z 2 means a group of formula n = NR. , /=NHR.,_7%e or /=N(R,)(R„)7 ^K^ (C) I-l *- 12—' where A^ means an acid anion, Z^-C(=Z2) is hydrolyzed - the group

to the corresponding 0=C(NR.R. 1 -aruDDen oa if øinsk<p>t hvrtrn-

is lysed a compound with the general formula I in which resp. X2 means lower alkoxy and Y 1 and Y« together means an extra bond, to the corresponding compound in which X^ is hydroxy, resp. to the tautomeric oxo compound and this, if desired, is reduced to the corresponding compound with hydroxy X^ and hydrogen Y^, X^ and Y2 or a compound of the general formula I in which X^, X2 and/or X^ means lower alkylthio, oxidized to the corresponding compound of the general formula I with lower alkylsulfonyl or lower alkylsulfinyl as X 1 , X 2 and/or X 2 .

The reaction according to a) is preferably carried out in an organic solvent, e.g. in a lower alkanol such as ethanol, isopropanol or butanol, or in an ethereal liquid such as tetrahydrofuran or dioxane or a hydrocarbon such as benzene or toluene, at room temperature or preferably warm, e.g. at the boiling temperature of the solvent used. The ammonia and other gaseous starting substances with the general formula III, which may be required as starting material, can be introduced at the beginning or during the entire duration of the reaction or, when using a water-miscible solvent, also be used as a concentrated aqueous solution. However, you can also use liquid ammonia or methylamine and carry out the reaction if necessary in a closed vessel.

Starting substances with the general formula II are obtained, for example, by reacting the corresponding 5-unsubstituted 5H-dibenz-/b,f7azepine with phosgene or carbonic acid dibromide in an inert organic solvent such as e.g. benzene or especially toluene at room temperature or slightly elevated temperature, e.g. until the boiling temperature of the said solvent. Of the 5H-dibenz-/b,f7azepines necessary for this reaction, some and others can be prepared in a manner known per se.

The, if desired, to the reaction according to a) ending hydrolysis of compounds with lower alkoxy such as X 1 and X 2 takes place according to the enol ether character of these compounds, for example by heating in an aqueous or aqueous organic mineral acid, e.g. in diluted e.g. 2-normal hydrochloric acid or dilute sulfuric acid at slightly elevated temperatures to the boiling temperature, i.e. approximately at 60 to approx. above 100°C. However, the hydrolysis can e.g. also carried out in an aqueous organic medium, e.g. a mixture of water with a lower alkanol or dioxane, in the presence of an acidic ion exchanger, e.g. "Amberlite" (^R)IR-100 (market product from the company Rohm

(R)

and Haas, Philadelphia) or "Dowex" ^ (commercial product of Dow Chemical Co., Midland, Michigan).

The reaction according to b) is preferably carried out in the presence of an alkaline condensing agent such as an alkali metal lower alkoxide or the lower alkyl mercaptan is used in the form of an alkali metal mercaptide, e.g. sodium mercaptide. The turnover takes place e.g. in a lower alkanol, such as ethanol, at room temperature to slightly elevated temperature, e.g. up to 100°C or boiling point of the solvent used. Of the starting substances with the general formula IV, 1 a,10b-dihydro-6H-dibenz-/b,f7oxireno/d7azepine-6-carboxamide is known and further can be prepared analogously to this compound.

In the reaction according to c), for example, a compound of formula V is used in which the etherified mercapto group Z is aliphatically etherified mercapto as lower alkylthio, e.g. methylthio, and the acid anion A ® is, for example, the anion of a strong protonic acid, for example a halohydrogen acid, as a halide, e.g. the iodide ion. The hydrolysis preferably takes place in an alkaline medium, e.g. in an aqueous alkaline solution such as caustic soda or potassium hydroxide, preferably in the temperature range from

about. 60 to approx. 100°C preferably during boiling.

The hydrolysis of lower alkoxy to hydroxy takes place e.g. by treatment with an aqueous mineral acid, the reduction of the double bond and also other compounds of formula I in which Y.sub.1 and Y.sub.2 are a bond are available by catalytic hydrogenation, e.g. in the presence of copper chromite. The oxidation of lower alkylthio to lower alkylsulfinyl resp. -sulfonyl takes place, for example, by means of hydrogen peroxide in an inert organic or inorganic aqueous solvent, e.g. in possibly aqueous acetic acid or in the mixture formed by glacial acetic acid and aqueous hydrogen peroxide solution, at a slightly elevated temperature between approx. 60 and 100°C, when a compound substituted with lower alkylsulfonyl is to be obtained as an oxidation product. The oxidation of the lower alkylthio to lower alkylsulfinyl group is carried out e.g. either according to the above procedure in the temperature range from approx. 20 to 60°C, or especially using alkali metal, especially sodium or potassium periodate, such as sodium metaperiodate in organic aqueous, e.g. lower alkanol-aqueous, especially ethanolic-aqueous medium in the cold, e.g.

at 0°C to room temperature, compare here also GB-PS

1 114 970. The starting materials for these oxidations can e.g. is prepared according to method a) or, if X. or X2 is lower alkylthio, also according to method b).

The invention also relates to the embodiments of the method where one proceeds from one or the other desirable process step as an intermediate formed compound and carries out the missing process steps or forms a starting material under the reaction conditions or uses it in the form of a derivative. Preferably, such starting materials are used which lead to the new compounds highlighted above, as new starting materials and methods for their production are also covered by the invention.

In the following examples 1 to 13, the preparation according to the invention of the compounds of the general formula I is explained in more detail and in the further examples the preparation of pharmaceutical preparations.

Example_1_

A solution of 19.8 g (0.2 mol) phosgene in 300 ml abs. toluene. The mixture is boiled for 20 hours under reflux. It is then evaporated completely in a rotary evaporator, the crude 3-methylsulfonyl-5H-dibenz-/b,f7azepine-5-carbonyl chloride remaining with a melting point of 160-162°C.

The above-mentioned crude product is dissolved with stirring at 70°C in 600 ml abs. ethanol. Ammonia gas is introduced into this solution over the course of 2 hours, with the reaction solution constantly boiling under reflux. The reaction mixture is then evaporated in a rotary evaporator, the residue is washed with water and 3-methylsulfonyl-5H-dibenz/b,f/-azepine-5-carboxamide is recrystallized after drying from acetonitrile. Melting point 195-197°C.

The starting material can be prepared as follows:

a) To a solution of 27.3 g (0.1 mol) 10,11-dihydro-3-methylsulfonyl-5H-dibenz/b,f/azepine (compare GB-PS 1 000 191) in 100 ml of toluene is allowed while stirring, add 9 g (0.115 mol) of acetyl chloride dropwise over the course of 30 minutes, keeping the temperature between 20 and 50°C. The reaction mixture is then boiled for 5 hours under reflux and then cooled to 5°C, after which 5-acetyl-10,11-dihydro-3-methylsulfonyl-5H-dibenz/b,fJazepine crystallizes out. It is suctioned off, washed well with water and dried in a vacuum cabinet at 80°C. Melting point then 157-159°C. b) 31.5 g (0.1 mol) of 5-acetyl-10,11-dihydro-3-methylsulfonyl-5H-dibenz/b,f7azepine are dissolved in 2000 ml of carbon tetrachloride and the solution is mixed with 17.8 g (0.1 mol) N-bromosuccinimide. While stirring and in a nitrogen atmosphere, the mixture is heated to boiling under illumination with a UV lamp. It is kept boiling until N-bromosuccinimide, which is at the bottom of the vessel, has transformed into succinimide which floats on the solution, which lasts approximately 1 hour. The reaction mixture is then cooled to 20°C and washed in a separatory funnel with water. After drying over sodium sulphate, the solvent is distilled off in a rotary evaporator, and the oily residue is dissolved in 60 ml abs. ethanol. This solution is mixed with a solution of 60 g of potassium hydroxide in 240 ml of abs. ethanol and boil for 1 hour under reflux. After the reaction mixture has cooled to 20°C, 200 ml of water is added, the precipitated crystals of 3-methylsulfonyl-5H-di-benz/b,f/azepine are sucked off, washed with water, then with diethyl ether and dried in a vacuum cabinet at 80°C. Melting point then 141-143°C.

Example_el_2

Analogously to example 1, 23.9 g (0.1 mol) of 3-methylthio-5H-dibenz/b,f7azepine and 19.8 g (0.2 mol) of phosgene are prepared in 300 ml of abs. toluene 3-methylthio-5H-dibenz/b,f7azepine-5-carbonyl chloride as an oily crude product and from this with ammonia gas in 600 ml abs. ethanol 3-methylthio-5H-dibenz/b,f7azepine-5-carb-oxamide, melting point 179-180°C (from methanol).

The starting material is prepared analogously to examples 1a) and 1b): a) From 24.1 g (0.1 mol) 10,11-dihydro-3-methylthio-5H-di-benz/b,f7azepine (GB-PS 1 114 970) and 9 g (0.115 mol) of acetyl chloride in 100 ml of toluene gives 5-acetyl-10,11-dihydro-3-methylthio-5H-dibenz/b,f7azepine, melting point 69-74°C (from petroleum ether). b) From 28.3 g of 5-acetyl-3-10,11-dihydro-10,11-dihydro-3-methylthio-5H-dibenz/b,f7azepine and 17.8 g (0.1 mol) N-bromo -succinimide in 2000 ml of carbon tetrachloride and subsequent treatment with 60 g of potassium hydroxide in 300 ml of abs. ethanol gives 3-methylthio-5H-dibenz/b,f7azepine, melting point 167-169°C (from ethanol).

Example_el_3

Analogously to example 1, 22.3 g (0.1 mol) of 3-methoxy-5H-dibenz/b,f7azepine and 19.8 g (0.2 mol) of phosgene in 300 ml abs. toluene 3-methoxy-5H-dibenz/b,f7azepine-5-carbonyl chloride as an oily crude product and from this with ammonia gas in 600 ml abs. ethanol 3-methoxy-5H-dibenz/b,f7azepine-5-carboxamide, mp 154-156°C (from benzene).

The starting material is prepared analogously to examples 1a) and 1b) from 10,11-dihydro-3-methoxy-5H-dibenz/b,f7azepine (compare GB-PS 926 816) by acetylation, bromination and hydrogen bromide removal.

Example_el_4

Analogously to example 1, 30 g (0.1 mol) of 3-(dimethylsulfamoyl)-5H-dibenz/b,f/azepine (compare Swiss PS 408 927) and 19.8 g (0.2 mol) of phosgene in 300 ml abs. toluene 3-(dimethylsulfamoyl)-5H-dibenz/b,f7azepine-5-carbonyl chloride as an oily crude product and therefrom with ammonia gas in 600 ml abs. ethanol 3-(Dimethylsulfamoyl)-5H-dibenz/b,f7azepine-5-carboxamide, mp 215-217°C (from methanol).

Example_el_5

Analogously to example 1, 21.8 g (0.1 mol) of 5H-dibenz/b,f7azepine-3-carbonitrile and 19.8 g (0.2 mol) of phosgene in 300 ml abs. toluene 3-cyano-5H-dibenz/b,f7azepine-5-carbonyl chloride, melting point 168-170°C (crude product) and therefrom with ammonia gas in 600 ml abs. ethanol 3-cyano-5H-dibenz/b,f7_ azepine-5-carboxamide, mp 269-272°C (from chloroform).

The starting material is produced as follows:

a) Analogous to example 1a), 27.2 g (0.1 mol) of 3-bromo-10,11-dihydro-5H-dibenz/b,f7azepine and 9 g (0.115 mol) of acetyl chloride in 300 ml of abs. toluene 5-acetyl-3-bromo-10,11-dihydro-5H-dibenz/b,f7azepine (crude product). (Compare US-PS 3,056,774).

b) Analogous to example 1b), 31.4 g (0.1 mol) of 5-acetyl-3-bromo-10,11-dihydro-5H-dibenz/b,f7azepine (crude product) is obtained

and 17.8 g (0.1 mol) of N-bromosuccinimide in 350 ml of carbon tetrachloride and subsequent treatment with 60 g of potassium hydroxide in 300 ml of abs. ethanol 3-bromo-5H-dibenz/b,f7azepine, melting point 218-220°C (from toluene).

c) 27.2 g (0.1 mol) 3-bromo-5H-dibenz/b,f7azepine, 10.7 g (0.12 mol) copper cyanide and 50 ml dimethylformamide are boiled under

stirring 4 hours under reflux. The reaction mixture is then cooled to 40°C and stirred vigorously with 200 ml of a 50% aqueous ethylenediamine solution and 200 ml of methylene chloride. The organic phase is then cooled and the aqueous phase is extracted twice more with methylene chloride. The combined organic solutions are washed with water, dried over sodium sulphate and evaporated to a small volume whereupon 5H-dibenz/b,f7azepine-3-carbonitrile of melting point 181-182°C crystallizes out on cooling.

Example<p_>el_6

Analogously to example 1, 21.8 g (0.1 mol) of 5H-dibenz/b,f7azepine-2-carbonitrile and 19.8 g (0.2 mol) of phosgene in 300 ml abs. toluene 2-cyano-5H-dibenz/b,f7azepine-5-carbonyl chloride, melting point 208-209°C (crude product) and from this with ammonia gas in 600 ml abs. ethanol 2-cyano-5H-dibenz/b,f/- azepine-5-carboxamide, melting point from 284°C under decomposition (from methylene chloride).

The starting material is produced as follows:

a) Analogous to example 1a), 27.2 g (0.1 mol) of 2-bromo-10,11-dihydro-5H-dibenz/b,f/azepine and 9 g of acetyl chloride are obtained

in 300 ml abs. toluene 5-acetyl-2-bromo-10,11-dihydro-5H-dibenz-/b,f_7azepine, melting point 1 36-1 42°C (crude product).

b) Analogous to example 1b), 31.4 g (0.1 mol) of 5-acetyl-2-bromo-10,11-dihydro-5H-dibenz/b,f7azepine and 17.8 g

(0.1 mol) of N-bromosuccinimide in 350 ml of carbon tetrachloride and subsequent treatment with 60 g of potassium hydroxide in 300 ml of abs. ethanol 2-bromo-5H-dibenz/b,f7azepine, mp 111-113°C (from hexane).

c) Analogous to example 5c), 10.7 g (0.12 mol) of copper cyanide is obtained from 27.2 g (0.1 mol) of 2-bromo-5H-dibenz/b,f7azepine

and 50 ml of dimethylformamide 5H-dibenz/b,f7azepine-2-carbonitrile, melting point 171-173°C (from methylene chloride).

Example_el_7

25.6 g (0.1 mol) of 5H-dibenz/b,f7azepine-5-carbonyl chloride (compare GB-PS 906 452) are dissolved with stirring at 70°C in 600 ml of abs. ethanol. Gaseous methylamine is introduced into this solution over the course of 2 hours, the reaction solution being constantly boiled under reflux. The reaction mixture is then evaporated in a rotary evaporator and the residue is stirred with water. The product is suctioned off, washed thoroughly with water and then dried in a vacuum cabinet at 70°C. After recrystallization from ethanol, N-methyl-5H-dibenz/b,f7azepine-5-carboxamide is obtained, melting point 210-212°C.

In an analogous manner, using 27.0 g (0.1 mol) of 10-methyl-5H-dibenz/b,f7azepine-5-carbonyl chloride

(compare Swiss PS 403 767) obtain N,10-dimethyl-5H-dibenz-/b,f7aze<p>yne-5-carboxamide.

Example_el_8

11.5 g (0.5 mol) of sodium are dissolved in 2000 ml of abs. ethanol with stirring. 24 g (0.5 mol) of gaseous methylmercaptan are introduced into this solution at 20-40°C. Then 25.1 g (0.1 mol) of 1α,10b-dihydro-6H-dibenz/b,f 1-oxireno/d7aze<p>yne-6-carboxamide (compare DE-OS 2 246 842) are added and the mixture boiled for 12 hours under reflux. The reaction mixture is then evaporated in vacuo and the residue is stirred with 1500 ml of water and 300 ml of diethyl ether for 3 hours at 2-5°C. The suspension is suctioned off and washed with water and diethyl ether. The moist 10-methylthio-5H-dibenz/b,f7azepine-5-carboxamide is dried in vacuum at 80°C and melts after recrystallization from methanol at 175-177°C.

Example_el_9

28.2 g (0.1 mol) of 10-methylthio-5H-dibenz/b,f7azepine-5-carboxamide, 100 ml of glacial acetic acid and 42 ml of 30% aqueous hydrogen peroxide solution are heated with stirring for 1 hour at 85°C. The reaction mixture is then cooled to 5°C, 10-methylsulfonyl-5H-dibenz/b,f7azepine-5-carboxamide crystallising out. The product is suctioned off, washed with 2n-acetic acid, then with water and finally with acetone. After drying in a vacuum cabinet at 100°C, the substance melts at 275-278°C during decomposition.

Example_1_0

26.3 g (0.1 mol) of 10-trifluoromethyl-10,11-dihydro-5H-dibenz/b,f7azepine are introduced with stirring into a solution of 19.8 g (0.2 mol) of phosgene in 350 ml of toluene. The mixture is heated under continuous introduction of phosgene for 20 hours under reflux. It is then evaporated to dryness on a rotary evaporator, 50 ml of petroleum ether/ether (2:1) is added and cooled with stirring to 5°C. The crystallized 10-trifluoromethyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carbonyl chloride is filtered off

then and dried, melting point 154-158°C.

The above-mentioned product is dissolved with stirring at 70°C in 400 ml of 95% ethanol. Ammonia gas is introduced into this solution for 5 hours, the reaction solution being constantly kept under reflux. The reaction mixture is then evaporated to dryness on a rotary evaporator and the residue is stirred with water and a little ice-cold ether. The crystallized 10-trifluoromethyl-11-dihydro-5H-dibenz/b,f7~azepine-5-carboxamide is filtered off with suction, washed with a little water and cold ether and dried. Melting point 172-174°C.

The starting material can e.g. is prepared as follows: a) 31.3 g (0.1 mol) of 10-bromo-5-acetyl-5H-dibenz/b , f ~ l-azepine is stirred in an autoclave with 83.2 g (0.42 mol) trifluoromethyl iodide and 31.6 g (0.5 mol) of copper powder in 250 ml of dimethylformamide for 70 hours at 150°C. 200 ml of dimethylformamide is then distilled off on a rotary evaporator, and the residue is extracted four times with 800 ml of ether each time. The combined ether extracts are washed three times with water and dried over sodium sulfate. After clarification with diatomaceous earth and charcoal, the ether solution is reduced to 50 ml and cooled to 5°C. The crystallized 10-trifluoromethyl-5acetyl-5H-dibenz/b,f7-azepine is suctioned off and dried. Melting point 144-147°C. b) 30.3 g (0.1 mol) of 10-trifluoromethyl-5-acetyl-5H-dibenz-/b,f7azepine are heated in a solution of 30 g of potassium hydroxide lozenges (85%) in 120 ml of ethanol with stirring for 2 \ hours during reflux. The reaction mixture is then poured on

900 ml of water and extracted three times with 300 ml of ether each time. The combined ether extracts are washed twice with water and then dried over sodium sulfate. The solvent is distilled off in rotary evaporators. The oily residue is dissolved in 90 ml of hexane and 10 ml of ether. 10-trifluoromethyl-5H-dibenz/b,f7aze<p>ine crystallizes on cooling to 20°C and is filtered off with suction and dried. Melting point 123-126°C.

c) 26.1 g (0.1 mol) of 10-trifluoromethyl-5H-dibenz/b, f ~ l-azepine is hydrogenated in 500 ml of acetic acid with 4.4 g of 10% Pd/C

at 20-22°C at normal pressure for 40 hours. The catalyst is then filtered off and the filtrate is evaporated in a rotary evaporator.

The oily residue is purified by chromatography

400 g silica gel. 10-trifluoromethyl-10,11-dihydro-5H-dibenz-[b,f/azepine is eluted with petroleum ether/toluene (4:1); melting point 57-59°C.

Example_el_11_

Analogous example 1 is prepared from 26.1 g (0.1 mol) 10-trifluoromethyl-5H-dibenz/b,f/azepine and 19.8 g (0.2 mol) phosgene in 350 ml toluene 10-trifluoro-5H- dibenz/b,f/azepine-5-carbonyl chloride; melting point 140-144°C. This is likewise transferred according to example 1 with ammonia gas in 400 ml of ethanol to 10-trifluoromethyl-5H-dibenz/b,f/azepine-5-carboxamide; melting point 194-196°C.

Example_el_12

28.2 g (0.1 mol) of 10-methylthio-5H-dibenz/b,f/azepine-5-carboxamide are heated with 130 ml of 30% hydrogen peroxide in 600 ml of ethanol for 3 hours under reflux. The reaction mixture is then evaporated to dryness in a rotary evaporator. The residue is dissolved in 100 ml of acetone and mixed with 500 ml of abs. ether. 10-methylsulfinyl-5H-dibenz/b,f/azepine-5-carboxamide is filtered off with suction and dried; melting point 242-247°C.

Example_1_3

Analogous to examples 1-12, the following can also be prepared: 10-methoxy-11-methyl-5H-dibenz/b,f/azepine-5-carboxamide, 10-cyano-11-methoxy-5H-dibenz/b,f/azepine- 5-carboxamide, 10-bromo-5H-dibenz/b,f/azepine-5(N-methyl)carboxamide, 10-cyano-5H-dibenz/b,f/azepine-5(N-methyl)carboxamide, 3, 7-dichloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide, 3.7-dimethyl-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide,

2.8-Dimethyl-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide,

3-methylthio-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide,

3-dimethylsulfamoyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide,

5-(1-piperidinyl)carbonyl7~10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine,

5-((1-piperidinyl)-carbonyl/-10,11-dihydro-10-oxo-5H-di-benz/b,f/azepine,

3-Methylsulfony1-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide.

Example_1_4

Tablets containing each 25 mg of 3-methylsulfonyl-5H-dibenz/b,f/azepine-5-carboxamide may be prepared as follows:

Composition (for 1000 tablets)

The active substance is mixed with the lactose and 146 g of potato starch, the mixture is moistened with an alcoholic solution of the gelatin and granulated through a sieve. After drying, the rest of the potato starch, talc, magnesium stearate and the highly dispersed silicon dioxide are mixed in and the mixture is pressed into tablets of 73.0 mg weight each and the active substance content stated above and which, if desired, can be equipped with breaking drills for finer adjustment of the dosage.

Instead of the above-mentioned active substance, it can e.g. the same amount of 10-methylthio-5H-dibenz/b,f/azepine-5-carboxamide is also used.

In an analogous way, you can also get tablets containing another of those in the examples or specifically the compounds mentioned in the description with the general formula I.

Claims (35)

1. Process for the preparation of new 5H-dibenz-/b,f7azepine-5-carboxamides of the general formula I wherein R 1 and R 2 independently of each other mean hydrogen or lower alkyl or associated with each other lower alkylene or ethyleneoxyethylene, one of the symbols X. and X_ means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, lower alkoxy, halogen of atomic numbers up to and including 35 or cyano and the other means hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl or both symbols X^ and X^ means hydrogen, X^ means lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, halogen of atomic number up to and including 35, cyano or dilaverealkylsulfamoyl or, if at least one of the residues X^ and X2 is different from hydrogen and at the same time with halogen or cyano as X^ resp. X^ and hydrogen as X^ resp. X^, R^ means hydrogen or lower alkyl and R2 means lower alkyl or R^ together with R2 means lower alkylene or ethyleneoxyethylene and at the same time with lower alkoxy as X^ resp. X2 and hydrogen as X2 resp. X^ means R^ together with R2 the lower alkylene or ethyleneoxyethylene, X^ can also mean hydrogen, X^ means hydrogen or together with lower alkyl or halogen which X^ can likewise mean one of these residues, and the symbols Y^ and Y2 each time mean hydrogen, if one of the symbols X^ and X2 means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and the other means hydrogen or both means hydrogen or, if at least one of the radicals R^ , R2 , X^ and X2 is different from hydrogen or X^ is different from cyano and at least one of the residues X^ and X^ are different from halogen, Y.. and Y2 together mean an extra bond, or in which R 1 and R2 together mean lower alkylene or ethyleneoxyethylene and X^ together with Y^ means oxo and X2 as well as Y2 means hydrogen or X^ means hydroxy and X2 , Y^ as well as Y2 means hydrogen or R^ and R2 independently of each other means lower alkyl or together lower alkylene or ethyleneoxyethylene, X^ together with X2 means epoxy or epimethylene and Y^ and Y2 each time means hydrogen, X^ means hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, halogen of atomic number up to and including 35, cyano or dilower alkylsulfamoyl and X^ means hydrogen or together with lower alkyl or halogen as X^ likewise one of these residues, characterized by ata) a connection with the general formula II in which Z represents a halogen atom, is reacted with a compound of the general formula III or b) a compound of the general formula IV in which R^ , , X^ and X^ have the meaning given under formula I, is reacted with a lower alkyl mercaptan or an alkali metal lower alkyl mercaptide to a compound of the general formula I, in which X^ or X_ means lower alkylthio, X^ or X^ means hydrogen and Y. and Y_ together mean an additional bond and R^ , R2, X^ and X^ have the meaning given under formula I, or c) in a connection with formula wherein an etherified mercapto group and Z2 means a group of formula n = NR1 , ^NHR.,7 or /^N(R ) (R J ) <QP> , (-) where Aw means an acid anion, the Z^ - C(=Z2 ) group is hydrolyzed to the corresponding O=C(NR^ R2 ) group, and if desired, hydrolyze a compound of the general formula I in which X^ resp. X2 means lower alkoxy and Y1 and Y2 together means an extra bond to, a corresponding compound in which X^ means hydroxy resp. to the tautomeric oxo compound, and this is reduced if desired to a corresponding compound with hydroxy X^ and hydrogen Y^ , X2 and Y2 or a compound of the general formula I, in which X^ , X2 and/or X^ means lower alkylthio, oxidise the corresponding compound of the general formula I with lower alkylsulfonyl or lower alkylsulfinyl as , X2 and/or X^ • 2. Process according to claim 1 for the production of new 5H-dibenz/b,f/azepine-5-carboxamide with the general formula T in which R. and R.sub.2 independently of each other mean hydrogen or lower alkyl or connected to each other lower alkylene or ethyleneoxyethylene, one of the two symbols X^ and X2 and/or the symbol X^ means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and X^ also means halogen until atomic number 35, lower alkylsulfamoyl, lower alkyl, cyano or lower alkoxy and the resp. the remaining two of the symbols X^ , X2 and X^ mean hydrogen, however, X^ or X2 can also mean lower alkoxy and X2 resp. X^ hydrogen if at least one of the residues R^ and R2 is different from hydrogen and lower alkyl and one of the residues X^ and X^ is different from hydrogen and and Y2 means an extra bond, X^ means hydrogen or at the same time co- halogen or lower alkyl which X3 can X^ also mean one of these residues, Y^ and Y2 together mean an extra bond or together with hydrogen as X^ and X2, Y^ and Y2 can also each mean hydrogen or if at least one of the residues R^ and R2 is different from hydrogen and X^ and X^ means hydrogen, X^ can also mean halogen up to atomic number 35 or cyano, X2 hydrogen and Y^ and Y2 together an extra bond, characterized by a) a compound of the general formula II in which Z means a halogen atom , is reacted with a compound of the general formula III orb) a compound of the general formula IV in which R^ , R2 , X^ and X^ have the meaning given under formula I is reacted with lower alkyl mercaptan or an alkali metal lower alkyl mercaptide to a compound of the general formula I, in which X^ or X2 means lower alkylthio, X2 resp. X^ means hydrogen and Y- and Y2 together mean an extra bond and R^ , R2 , X3 and X^ have the meaning given under formula I, and if desired, a compound of the general formula I in which X^ , X2 and/or X^ means lower alkylthio is oxidized to a corresponding compound of the general formula I with lower alkylsulfonyl or lower alkylsulfinyl as X1 , X2 and/or X3 . 3. Method according to claim 2, characterized in that compounds of the general formula I are prepared in which X^ is different from cyano and/or R2 is different from hydrogen or at least one of the residues X3 and X3 is different from halogen, when and X2 means hydrogen and Y... and Y2 means an extra bond. 4. Method according to claim 1, characterized in that compounds of the general formula I are prepared, in which R 1 and R 2 independently of each other mean hydrogen or lower alkyl or connected to each other mean lower alkylene or ethyleneoxyethylene, one of the two symbols X 1 and X 2 means lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and the other means hydrogen, X^ means hydrogen, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano, halogen up to atomic number 35, diloweralkylsulfamoyl, lower alkyl or lower alkoxy, X^ means hydrogen or simultaneously with halogen or lower alkyl as X^ may likewise mean one of these residues and Y^ and Y 2 together mean an extra bond or each hydrogen. 5. Process according to one of claims 1 to 3, characterized in that compounds of the general formula I are prepared, in which R 1 and R 2 independently of each other mean hydrogen or lower alkyl or associated with each other lower alkylene or ethyleneoxyethylene, X 1 and X 2 mean hydrogen, X^ means halogen of atomic number up to and including 35, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or dilower alkylsulfamoyl, X^ means hydrogen or together with halogen or lower alkyl which X^ can likewise mean one of these residues and Y^ and Y 2 each means hydrogen or if at least one of the residues R 1 and R 2 is different from hydrogen or X 2 is different from cyano or X 2 is different from hydrogen, Y 2 and Y 2 together can mean an extra bond. 6. Process according to one of claims 1 to 3, characterized in that compounds of the general formula I are prepared, in which one of the symbols R.j and means lower alkyl and the other hydrogen or both means lower alkyl or together means lower alkylene or ethyleneoxyethylene, one of the symbols X .and X means halogen of atomic number up to and including 35 or cyano and the other similarly as X^ and X^ .means hydrogen, since and Y together form an additional bond. 7. Process according to one of claims 1 to 3, characterized in that compounds of the general formula I are prepared, in which R., and R.sup. independently of each other means hydrogen or lower alkyl or connected to each other means lower alkylene or ethyleneoxyethylene, X^ and Y ^ together mean oxo and X^ and Y^ mean hydrogen resp. X^ means lower alkoxy or hydroxy and X2 , Y^ and Y^ each means hydrogen, X^ means halogen of atomic number up to and including 35, lower alkyl, lower alkoxy, further lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or diloweralkylsulfamoyl or, if R^ and R^ together means lower alkylene or ethyleneoxyethylene means X^ hydrogen and X^ means hydrogen or simultaneously with halogen or lower alkyl which X^ can likewise mean one of these residues. 8. Process according to claim 1, characterized in that compounds of the general formula I are prepared, in which R^ , R 2 , X^ and X^ mean hydrogen, X^ means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each with up to 4 C atoms, dilower alkylsulfamoyl with up to 4 C atoms in each alkyl part, lower alkyl or lower alkoxy with up to 4 C atoms, halogen of atomic number up to and including 35, or trifluoromethyl, X^ means hydrogen or at the same time as lower alkyl or halogen as X^, X^ can also mean lower alkyl and Y^ and Y2 each mean hydrogen or together an extra bond. 9. Method according to claim 1, characterized in that compounds of the general formula I are prepared, in which R 1 and R 2 independently of each other mean hydrogen or lower alkyl, each of which has up to and including 4 C atoms, one of the residues X. and X means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each time up to and including 4 C atoms or trifluoromethyl, or if at least one of the residues and R2 means lower alkyl means one of the residues X^ and X2 halogen of atomic number up to and including 35 or cyano, and the other as well as X^ and X^ means hydrogen and Y^ and Y2 together mean an additional bond. 10. Method according to claim 1, characterized in that compounds of the general formula I are prepared, in which 5 of the symbols R^ , R2 , X^ , X2 , X^ and X^ mean hydrogen and a different residue thereof R^ and/or R 2 means lower alkyl with up to and including 4 C atoms, a residue different from this X 2 or X 2 means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl with each time up to and including 4 C atoms or trifluoromethyl resp. a residue different from this X^ means lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each with up to and including 4 C atoms, dilower alkylsulfamoyl with up to and including 4 C atoms in each alkyl part, lower alkyl or lower alkoxy with up to and including 4 C atoms, halogen of atomic number up to and including 35 or trifluoromethyl and Y 1 and Y 2 together mean an additional bond. 11. Method according to one of claims 1 to 3, characterized in that 3-methylsulfonyl-5H-dibenz/b,f/azepine-5-carboxamide is produced. 12. Method according to one of claims 1 to 3, characterized in that 3-methylthio-5H-dibenz/b,f7azepine-5-carboxamide is produced. 13. Method according to one of claims 1 to 3, characterized in that 3-methoxy-5H-dibenz/b,f/azepine-5-carboxamide is produced. 14. Method according to one of claims 1 to 3, characterized in that 3-(dimethylsulfamoyl)-5H-dibenz/b,f/azepine-5-carboxamide is produced. 15. Method according to one of claims 1 to 3, characterized in that 3-cyano-5H-dibenz/b,f/azepine-5-carboxamide is produced. 16. Method according to one of claims 1 to 3, characterized in that 2-cyano-5H-dibenz/b,f7azepine-5-carboxamide is produced. 17. Method according to one of claims 1 to 3, characterized in that N-methyl-5H-dibenz/b,f/azepine-5-carboxamide is produced. 18. Method according to one of claims 1 to 3, characterized in that N,10-dimethyl-5H-dibenz/b,f7azepine-5-carboxamide is produced. 19. Method according to one of claims 1 to 3, characterized in that 10-methylthio-5H-dibenz/b,f7azepine-5-carboxamide is produced. 20. Method according to one of claims 1 to 3, characterized in that 10-methylsulfonyl-5H-dibenz/b,f7azepine-5-carboxamide is produced. 21. Process according to claim 1, characterized in that 10-trifluoromethyl-5H-dibenz/b,f7azepine-5-carboxamide is produced. 22. Process according to claim 1, characterized in that 10-trifluoromethyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 23. Process according to claim 1, characterized in that 10-methoxy-11-methyl-5H-dibenz/b,f7azepine-5-carboxamide is produced. 24. Process according to claim 1, characterized in that 10-cyano-5H-dibenz-/b,f7azepine-5-(N-methyl)carboxamide is produced. 25. Process according to claim 1, characterized in that 3,7-dichloro-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 26. Method according to claim 1, characterized in that 3,7-dimethyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 27. Method according to claim 1, characterized in that 2,8-dimethyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 28. Process according to claim 1, characterized in that 3-methylthio-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 29. Method according to claim 1, characterized in that 3-dimethylsulfamoyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 30. Process according to claim 1, characterized in that 10-methylsulfinyl-5H-dibenz/b,f7azepine-5-carboxamide is produced. 31. Method according to claim 1, characterized in that 3-chloro-5H-dibenz/b,f7-azepine-5-carboxamide is produced. 32. Process according to claim 1, characterized in that 5-(((1-piperidinyl)-carbonyl)-10,11-dihydro-10-oxo-5H-dibenz/b,f7azepine is produced. 33. Process according to claim 1, characterized in that 5-(1-piperidinyl)-carbonyl 7-10,11-dihydro-10-hydroxy-5H-dibenz/b,f7azepine is produced. 34. Process according to claim 1, characterized in that 3-methylsulphonyl-10,11-dihydro-5H-dibenz/b,f7azepine-5-carboxamide is produced. 35. Process according to claim 1, characterized in that 10-cyano-11-methoxy-5H-dibenz/b,f7azepine-5-carboxamide is produced.