SI8012778A8

SI8012778A8 - Process for obtaining oxo compound

Info

Publication number: SI8012778A8
Application number: SI8012778A
Authority: SI
Inventors: Ernst Aufderhaar
Original assignee: Ciba Geigy Ag
Priority date: 1979-10-30
Filing date: 1980-10-30
Publication date: 1997-06-30
Also published as: HRP940093B1

Description

Obstajala je potreba, da bi razvili postopek za pripravo spojine III, ki bi imel manj reakcijskih stopenj, ki bi bil enostavnejši in bi nudil večje dobitke.There was a need to develop a process for the preparation of Compound III, which would have fewer reaction rates, was simpler and would yield greater yields.

Stanje tehnikeThe state of the art

Iz DE-OS 2 011 087 je znan postopek za pripravo 5karbamoil-10-okso-10,11-dihidro-5H-dibenz/b,f/azepina s hidrolizo 10-metoksi-5H-dibenz/b,f/azepin-5-karboksamida s'pomočjo vodnih mineralnih kislin. Dostopnost te izhodne snovi je navedena v BE-PS št. 597 793, po katerem npr. 5-acetil-5H-dibenz/b,f/azepin bromirajo v 5-acetil-10,11-dihidro-10,11-dibrom-5Hdibenz/b,f/azepin, tega pretvorijo v 5-acetil-10-brom-5H-dibenz/b,f/azepin in iz tega pripravijo 10-metoksi-5H-dibenz/b,f/azepin. Tega nato z obdelavo s fosgenom pretvorijo v ustrezni karbonilklorid, iz katerega s presnovo z amoniakom dobijo 10-metoksi-5H-dibenz/b,f/azepin-5-karboksamid. V primerjavi s tem postopkom priprave, ki je neugoden zato, ker ga je treba zelo dolgo izvajati zaradi razmeroma številnih vmesnih stopenj, in poleg tega zaradi velike porabe broma, ki služi le za intermediarno pretvorbo vmesnih proizvodov, obstoji postopek v smislu izuma iz le malo stopenj postopka, ki jih izvedemo na enostaven in pregleden način, pri čemer se izognemo dragim reagentom, in poleg tega vodi v visokem dobitku do končnega proizvoda s formulo III, ki ga dobimo z odlično čistoto.DE-OS 2 011 087 discloses a process for the preparation of 5carbamoyl-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine by hydrolysis of 10-methoxy-5H-dibenz / b, f / azepine-5 -carboxamide with the help of aqueous mineral acids. The availability of this starting material is indicated in BE-PS no. 597 793, according to which e.g. 5-acetyl-5H-dibenz / b, f / azepine brominated to 5-acetyl-10,11-dihydro-10,11-dibromo-5Hdibenz / b, f / azepine, converted to 5-acetyl-10-bromo- 5H-dibenz / b, f / azepine and from this, 10-methoxy-5H-dibenz / b, f / azepine is prepared. This is then treated with phosgene to the corresponding carbonyl chloride from which 10-methoxy-5H-dibenz / b, f / azepine-5-carboxamide is obtained by metabolism with ammonia. Compared to this preparation process, which is disadvantageous in that it has to be carried out for a very long time due to the relatively numerous intermediate stages, and in addition, due to the high consumption of bromine, which serves only the intermediate conversion of intermediate products, process steps, which are carried out in a simple and transparent manner, avoiding expensive reagents, and in addition lead in high yield to the finished product of Formula III, which is obtained with excellent purity.

Opis rešitve tehničnega problema z izvedbenimi primeriDescription of solution to a technical problem with implementation examples

Postopek v smislu izuma izvedemo tako dibenz/b,f/azepin s formulo da 5-ciano-5H/ v v \ ; 'j s .iThe process of the invention is carried out by dibenz / b, f / azepine of the formula that 5-cyano-5H / v in 1; 'j s .i

V ^X N 'V ^X N '

II

CN (I) nitriramo z obdelavo s solitrovo kislino, z didušikovim tetroksidom, v danem primeru v zmesi s kisikom, ali z didušikovim tetroksidom v inertnem topilu pri 0° do 120°C in dobljeni 5ciano-10-nitro-5H dibenz/b,f/azepin s formuloCN (I) is nitrated by treatment with nitric acid, with nitrous tetroxide, optionally in admixture with oxygen, or with nitrous tetroxide in an inert solvent at 0 ° to 120 ° C, to give 5cyano-10-nitro-5H dibenz / b, f / azepine of formula

NO (II) • · = · ·NO (II) • · = · ·

X \ z \ z • · ·X \ z \ z • · ·

I II III II II

bodisi z obdelavo z raztopino borovega trifluorida v nižjd·alkankarboksilni kislini ali halogenižjialkankarboksilni kislini in nato z vodo ali s kislo hidrolizo hidroliziramo v 5karbamoil-10-nitro-5H-dibenz/b,f/azepin s formuloeither by treatment with a solution of boron trifluoride in the lower alkanecarboxylic acid or halogenatedalkanecarboxylic acid and then hydrolyzed with water or acid hydrolysis to 5carbamoyl-10-nitro-5H-dibenz / b, f / azepine of the formula

NO (IV) / v vNO (IV) / v v

I II II • · ·I II II • · ·

CONH in tega s pomočjo katalitsko aktiviranega ali nascentnega vodi ka ob kislih pogojih reduciramo v 5-karbamoil-10-okso-10,11-di hidro-5H-dibenz/b,f/azepin (III) ali z obdelavo s katalitsko aktiviranim ali nascentnim vodikom ali kositrovimi II) kloridom ob kislih pogojih direktno reduciramo v 5-ciano-10-okso-10,11dihidro-5H-dibenz/b,f/azepin s formuloCONH, and this is reduced to acidic conditions by catalytically activated or nascent hydrogen to 5-carbamoyl-10-oxo-10,11-di hydro-5H-dibenz / b, f / azepine (III) or by treatment with catalytically activated or under acidic conditions, direct sulfuric acid or tin II) chloride is directly reduced to 5-cyano-10-oxo-10,11 dihydro-5H-dibenz / b, f / azepine of the formula

IIII

(V) oz. z obdelavo s katalitsko aktiviranim ali nascentnim vodikom najprej reduciramo v 5-ciano-10-izonitro-10,11 -diHdi?o-5H- dibenz/b,f/azepin s formulo(V) respectively. by treatment with catalytically activated or nascent hydrogen, it is first reduced to 5-cyano-10-isonitro-10,11-diHydro-5H-dibenz / b, f / azepine of the formula

NOH ll • a—· · / \ / \ / e · · ·NOH ll • a— · · / \ / \ / e · · ·

I II II I • · · · z \ „ / \ • N · (VI)I II II I • · · · z \ „/ \ • N · (VI)

II

CN tega nato ob kislih pogojih hidroliziramo v 5-ciano-t0-okso10,11-dihidro-5H-dibenz/b,f/azepin (V) in vsakokrat reakcijski proizvod s formulo V z obdelavo z raztopino borovega trifluorida v ocetni kislini in nato z vodo, s kislo hidrolizo ali z obdelavo z vodikovim peroksidom v prisotnosti alkalijskega ali zemeljskoalkalijskega hidroksida ali alkalijskega bikarbonata hidroliziramo v 5-karbamoil-10-okso-10,11-dihidro-5-dibenzazepin (III) ter dobljeni končni proizvod s formulo III izoliramo v čisti obliki.The CN is then hydrolyzed under acidic conditions to 5-cyano-t0-oxo10,11-dihydro-5H-dibenz / b, f / azepine (V) and, in each case, a reaction product of formula V is treated with a solution of boric trifluoride in acetic acid and then with water, acid hydrolysis or treatment with hydrogen peroxide in the presence of alkali or alkaline earth metal hydroxide or alkali bicarbonate is hydrolyzed to 5-carbamoyl-10-oxo-10,11-dihydro-5-dibenzazepine (III) and the resulting final product of formula III isolated in pure form.

Postopek v smislu izuma predstavlja naslednja reakcijska shema: _n The process of the invention is represented by the following reaction scheme: _n

ΧΟΗΧΟΗ

(V) ii i(V) ii i

I (III)I (III)

CONH,CONH,

Nitriranje spojine I v spojino s formulo II v smislu izuma poteče v inertnem topilu, t.j. takem, ki je ob pogojih nitriranja stabilno in ne vodi do neželenih reakcij z nitrirnim sredstvom. V prvi vrsti pridejo v poštev nižje alkankarboksilne ali halogennižjialkankarboksilne kisline z vsakokrat do 4 atomi ogljika, npr. ocetna, propionova, n-maslena ali izomaslena kislina, nadalje npr. trifluor- ali triklorocetna kislina, v danem primeru v zmesi z vodo, ali njihovi anhidridi, npr. anhidrid ocetne, propionove, n-maslene, izomaslene ali trifluorocetne kisline, ali zmesi takih karboksilnih kislin z ustreznimi anhidridi. Po prednostni izvedbeni obliki postopka v smislu izuma uporabimo kot topila anhidride navedenih nižjih alkahkarboksilnih kislin, npr. acetanhidrid, v danem primeru v zmesi z nižjdalkankarboksilno kislino, npr. ocetno kislino.The nitration of compound I to the compound of formula II of the invention proceeds in an inert solvent, i.e. one that is stable under nitriding conditions and does not lead to adverse reactions with the nitrating agent. In the first instance, lower alkanecarboxylic or halogen lower alkanecarboxylic acids with up to 4 carbon atoms, e.g. acetic, propionic, n-butyric or isobutyric acid, further e.g. trifluoro- or trichloroacetic acid, optionally in admixture with water, or their anhydrides, e.g. acetic, propionic, n-butyric, isobutyric or trifluoroacetic acid anhydride, or mixtures of such carboxylic acids with the corresponding anhydrides. According to a preferred embodiment of the process according to the invention, the solvents used for the anhydrides of the aforementioned lower carboxylic acids, e.g. acetanhydride, optionally in admixture with loweralkanecarboxylic acid, e.g. acetic acid.

Razmerje izhodne snovi glede na uporabljeno količino topila (teža/volumen) lahko variira v širokih mejah. S pridom uporabimo razmerje izhodne snovi proti topilu v območju od 1:3 do 1:3θ· Reakcijska temperatura je v območju od okoli 0 do 120°, zlasti 40 do 80°.The ratio of starting material to the amount of solvent used (weight / volume) can vary within wide limits. The ratio of starting material to solvent is advantageously used in the range from 1: 3 to 1: 3θ · The reaction temperature is in the range from about 0 to 120 °, in particular 40 to 80 °.

Po Chemical Revievs 36. (1945), str. 211 do 212, dobijo s presnovo stirola z dušikovim trioksidom zmes nitrozo in nitro spojin. Poleg tega vodi presnovni proizvod stirola z dušikovim trioksidom do 1-nitro-2-feniletilena, če reakcijski proizvod podvržejo destilaciji z vodno paro. Nadalje je tam navedeno, da vodi presnova stilbena z dušikovim tetroksidom do 1,2-dinitro-1,2-difeniletra. Po strani 218 iste literature daje presnova cikLoheksena s suhim dušikovim tetr- 6 oksidom v hladnem petroletru ustrezen bis-nitrozo-nitrofderivat in oljnate stranske proizvode.According to Chemical Revievs 36. (1945), p. 211 to 212 are obtained by the reaction of styrene with nitrogen trioxide a mixture of nitroso and nitro compounds. In addition, the metabolic product of styrene with nitrogen trioxide leads to 1-nitro-2-phenylethylene if the reaction product is distilled with water vapor. It is further stated that the metabolism of stilbene by nitrogen tetroxide leads to 1,2-dinitro-1,2-diphenylether. According to page 218 of the same literature, the metabolism of cyclohexene with dry nitrous tetr 6 oxide in cold petroleum ether gives the corresponding bis-nitroso-nitroferivate and oily by-products.

V J.Org.Chem. 28. (1963), str. 125 do 129, je navedeno da presnovni proizvod olefina z di dušikovim tetroksidom v bistvu vsebuje nitro in nitrozo skupine, katerega pretvorba v nitro-olefinsko spojino zahteva dodatek trietilamina. Tako npr. presnovijo ciklookten z di dušikovim tetroksidom in nato reakcijski proizvod obdelajo s tcie til aminom, nakar dobijo 1nitrociklookten.In J.Org.Chem. 28. (1963), p. 125 to 129, it is stated that the metabolite product of olefin with nitric oxide contains essentially nitro and nitroso of the group whose conversion to the nitro-olefin compound requires the addition of triethylamine. So e.g. they metabolise the cyclooctene with di-nitrogen tetroxide and then treat the reaction product with tcie tyl amine to give 1nitrocyclooctene.

V nasprotju s tem smo presenetljivo ugotovili, da pri nitriranju v smislu izuma odpadejo dodatne operacije, kot npr. destilacija z vodno paro ali obdelava reaM jska zmesi s trie til aminom, in da silno enostavna obdelava vodi do vseskozi dobrih dobitkov nitro spojine s formulo II. Ta spojina je nova in v literaturi ni opisana.In contrast, it has surprisingly been found that the nitration process of the invention does not require additional operations such as e.g. distillation with water vapor or treatment of a reaction mixture with triethyl amine, and that extremely simple treatment leads to all-time good yields of the nitro compound of formula II. This compound is novel and has not been described in the literature.

V smislu izuma nato spojino s formulo II pretvorimo v spojino s formulo III. Za to po eni varianti postopka v smislu predloženega izuma najprej ciano skupinoAccording to the invention, the compound of formula II is then converted to the compound of formula III. To do this, according to one variant of the process of the present invention, first a cyano group

I s pomočjo hidrolize presnovimo v karboksamidno skupino. Za to presnovo pridejo v poštev le take hidrolizne metode, ki ne vplivajo na 10-nitro skupino pri dvojni vezi. Snotmo hidroliziramo s pomočjo kislih sredstev, npr. mineralnih kislin, kot žveplove, solne, v danem primeru tudi mravljinčne ki slina. Prednostno uporabimo borov trifluorid v ekvimolski kni i gi ni ali v majhnem prebitku kot raztopino v nižjijklkanali halogennižjialkankarboksilni kislini, npr. v taki preje navedene vrste, kot ocetni ali trifluorocetni, pri čemer lahko uporabimo tudi definirane spojine borovega trifluorida z eno od navedenih karboksilnih kislin, kot z ocetno kislino npr. s formulo ΕΕ^’ζΟΗ^ΟΟΟΗ. V danem primeru dodatno za izved bo hidrolize reakcijski zmesi nadaljnje inertno topilo, npr.I is hydrolyzed to the carboxamide group. Only hydrolysis methods which do not affect the 10-nitro group on the double bond are considered for this metabolism. The whole is hydrolyzed by acidic agents, e.g. mineral acids such as sulfuric, hydrochloric, optionally also formic saliva. Preferably boron trifluoride is used in the equimolar knife or in a small excess, as a solution in a lower chloroalkyl carboxylic acid, e.g. in such yarns of the foregoing type, as acetic or trifluoroacetic, whereby defined compounds of boron trifluoride may also be used with one of the above carboxylic acids, such as acetic acid, e.g. with the formula ΕΕ ^ 'ζΟΗ ^ ΟΟΟΗ. In the present case, in addition to the embodiment, the hydrolysis of the reaction mixture will be a further inert solvent, e.g.

topilo aromatskega značaja, kot npr. benzol.a solvent of an aromatic character, such as e.g. benzene.

Nato reakcijsko zmes oz. nastalo in v danem primeru v čisti obliki izolirano adicijsko spojino spojine s formulo IV z obdelamo s hidrolizimimi sredstvi, npr. vodo, nakar dobimo 5-karbamil-10-nitro-5H-dibenz[b,f]azepin s formulo IV v čisti obliki.Then the reaction mixture or the resultant and optionally isolated pure addition compound of the compound of formula IV by treatment with hydrolysable agents, e.g. water, to give 5-carbamyl-10-nitro-5H-dibenz [b, f] azepine of formula IV in pure form.

Hidroliza nitrilne skupine v karboksamidno skupino s pomočjo borovega trifluorida v prisotnosti ocetne kisline je znana iz J.Org. Chemistry 20. (1955), 1448. Tam navedeni načini dela zahteva visoke temperature, velik prebitek borovega trifluorida in uporabo ocetne kisline, ki vsebuje vodo in ki skupaj z borovim trifluoridom tvori izredno korozivne raztopine, s čimer je zelo omejena njegova tehnična uporaba, zlasti pri visokih temperaturah, in je uporaben le ob speci«· nih pogojih v tehničnih aparaturah.Hydrolysis of the nitrile group to the carboxamide group by boron trifluoride in the presence of acetic acid is known from J.Org. Chemistry 20. (1955), 1448. The above methods require high temperatures, a large excess of boron trifluoride, and the use of acetic acid, which contains water, which, together with boron trifluoride, forms extremely corrosive solutions, which limits its technical use, in particular at high temperatures, and is only applicable under special conditions in technical appliances.

V nasprotju s tem pa lahko pri postopku v smislu izui * uporabimo borov trifluorid v le ekvimolskih ali rahlo prebi’ nih kol i čin ah v brezvočnih topilih pri sobni temperaturi. N; daljnja prednosti obstoji v tem, da lahko izoliramo definir; no adicijsko spojino borovega triklorida s hidroliznim proi vodom s formulo IV z veliko čisto to in skoraj kvantitativni] dobitkom tudi iz močno onečiščenih reakcijskih zmesi in z o' delavo z vodo prevedemo v čisti hidrolizni proizvod s foimu IV.In contrast, boron trifluoride can be used in the process in the sense of iso * in only equimolar or slightly excess amounts in silicone solvents at room temperature. N; a further advantage is that the definer can be isolated; The addition compound of boron trichloride with the hydrolysis pro- duct of formula IV with high purity and almost quantitative yields is also obtained from the heavily contaminated reaction mixtures and is converted into pure hydrolysis product with foam IV by o 'treatment with water.

Nato v smislu izuma nastali vmesni proizvod s formul IV, v danem primeru brez njegovega izoliranja v čisti oblik pretvorimo v končni proizvod s formulo III. Za to podvržemo spojino s formulo IV učinkovanju;Then, according to the invention, the resulting intermediate of formula IV is optionally converted into pure form without final isolation into a final product of formula III. To do this, the compound of formula IV is subjected to action;

katalitsko aktiviranega vodika, kot vodika v prisotnosti hidrimega katalizatorja, npr. nikljevega katalizatorja ali katalizatorja plemenite kovine, npr. Raneyevega niklja ali katalizatorja paladija na oglju, v primernem topilu, npr. nižjem alkanolu z do 4 atomi ogljika, kot metanolu ali etanolu, ♦ ’ t ....catalytically activated hydrogen, such as hydrogen in the presence of a hydride catalyst, e.g. Nickel or precious metal catalyst e.g. Raney nickel or palladium catalyst on charcoal, in a suitable solvent, e.g. lower alkanol with up to 4 carbon atoms, such as methanol or ethanol, .... 't ....

ali nascentnega vodika₇1 npr. s pomočjo primerne kovine, kot v danem primeru amalgamiranega cinka, zlasti železa v kislini, npr. v mineralni kislini, kot razredčeni žveplovi kislini ali karboksilni kislini, kot hižjijalkankarboksilni kislini, npr. eni od zgoraj navedenih, kot ocetni kislini, ali kemičnega redukcijskega sredstva, npr. kositrovega(II)fklorida. 21^,0, dobljeni redukcijski proizvod hidroliziramo v istem reakcijskem nastavku, npr. z vodo, in izoliramo končni proizvod s formulo III v čisti obliki. Tega dobimo z deloma zelo dobrim dobitkom in odličjao čisto to.or nascent hydrogen ₇ 1 e.g. using suitable metal, as in the case of amalgamated zinc, in particular iron in acid, e.g. in mineral acid, such as dilute sulfuric acid or carboxylic acid, such as hijalkalkanecarboxylic acid, e.g. one of the above, as acetic acid, or a chemical reducing agent, e.g. of tin (II) chloride. 21 ^, 0, the resulting reducing product is hydrolyzed in the same reaction sequence, e.g. with water, and isolate the final product of Formula III in pure form. We get this at a very good profit in part and did just that.

Lahko pa postopamo tudi tako, da spojino s formulo II hidroliziramo s pomočjo kislih sredstev, npr. kot so navedena, kot npr. z borovim trifluoridom v ocetni kislini, v danem primeru v prisotnosti nadaljnjega inertnega topila, npr. topila aromatskega značaja, kot klorbenzola, v prisotnosti vode, in spojino s formulo IV, ki jo vsebuje reakcijska zmes, nato, ne da bi jo izolirali, reduciramo ,tot je bilo npr. naveden^ npr. s pomočjo katalitsko aktiviranega vodika, kot vodika v prisofaosti hidrimega katalizatorja, kot nikljevega katalizatorja ali katalizatorja plemenite kovine, npr. Raneyevega niklja ali katalizatorja paladija na oglju, ali z nascentnim vodikom, npr. kot smo navedli, npr. z železom v kislini, npr. mineralni kislini, npr. vodni solni kislini, ali nižji alkaakarbokšilni kislini ali halogenuižjialkaukarboksilni kislini, npr. kot smo navedli, npr. ocetni kislini, ali z zmesjo Bl^-ocetna kislina-voda, ki je že prisotna v reakcijskem nastavku. Redukcijski proizvod, ki se nahaja v reakcijski zmesi, brez nadaljnjega izoliranja nato ali tudi istočasno hidroliziramo s pomočjo kislega sredstva, npr. kot smo navedli, npr. s pomočjo vodne kisline, npr. zmesi BR^-očetna kislina-voda, ki se nahaja v reakcijski zmesi-, in nastali končni proizvod s formulo III izoliramo v čisti obliki.Alternatively, the compound of formula II can be hydrolyzed by acidic agents, e.g. as listed, e.g. with boron trifluoride in acetic acid, optionally in the presence of a further inert solvent, e.g. solvents of an aromatic nature, such as chlorobenzene, in the presence of water, and the compound of formula IV contained in the reaction mixture is then reduced, without isolation, to the tot. stated ^ e.g. using catalytically activated hydrogen, such as hydrogen in the presence of a hydroimide catalyst, as a nickel catalyst or a precious metal catalyst, e.g. Raney nickel or palladium catalyst on charcoal, or with nascent hydrogen, e.g. as stated, e.g. with iron in acid, e.g. mineral acids, e.g. aqueous hydrochloric acid or lower alphaacarboxylic acid or halogenoalkylcarboxylic acid, e.g. as stated, e.g. acetic acid, or with a mixture of B1-acetic acid-water already present in the reaction sequence. The reduction product contained in the reaction mixture is subsequently or simultaneously hydrolyzed by an acidic agent, without further isolation, e.g. as stated, e.g. by means of aqueous acid, e.g. mixtures of BR ^ -acetic acid-water contained in the reaction mixture- and the resulting finished product of formula III is isolated in pure form.

Spojina s formulo IV in njen adukt z borovim trifluoridom sba nova in v literaturi nista opisana.The compound of formula IV and its adduct with boron trifluoride are novel and have not been described in the literature.

Druga varianta postopka za pripravo končnega proizvoda s formulo III v smislu izuma (obstoji s tem, da v spojini s formulo II reduciramo 10-nitroskupino, redukcijski proizvod hidroliziramo, dobljeni 5-ciano-10-okso-l0,11-dihidro5H-dibenz[b,f]azepin s formulo V hidroliziramo in dobljeni končni proizvod s formulo III izoliramo v čisti obliki.Another variant of the process for the preparation of the final product of Formula III of the invention (consisting in reducing the 10-nitro group in the compound of Formula II, reducing the reducing product to obtain 5-cyano-10-oxo-10,11-dihydro5H-dibenz [ b, f] azepine of formula V is hydrolyzed and the resulting finished product of formula III is isolated in pure form.

Po tej varianti postopka v smislu izuma spojino s formulo II pretvorimo v spojino s formulo V in iz tega pripravimo končni proizvod s formulo III. Torej v 5-ciano10-nitro-5H-dibenz[b,f]azepinu s formulo II nitro skupino reduciramo po eni od zgoraj opisanih metod in v reakcijski zmesi nastali vmesni proizvod s pomočjo hidrolize prevedemo v spojino s formulo V. Redukcijo lahko izvedemo, kot smo že prej navedli, na primer s pomočjo vodika v prisotnosti hidrimega katalizatorja, npr. nikljevega katalizatorja ali katalizatorja plemenite kovine, npr· Renejevega niklja ali katalizatorja paladija na oglju, v primernem topilu, npr. nižjem alkanolu z do 4 atomi ogljika, npr. metanolu ali etanolu, ali s pomočjo nase entne ga vodika, t. j. s pomočjo primerne kovine, kot v danem primeru amalgamiranega cinka ali zlasti železa v kislini, npr. mineralni kislini, kot razredčeni žveplovi ali koncentrirani solni kislini, ali nižjialkankarboksilni kislini, npr. eni od zgoraj navedenih, npr. ocetni kislini, ali s pomočjo kemičnega redukcijskega sredstva, kot npr. kositrovega(II) klorida.2^0. Pri tem lahko uporabimo dodatna topila, npr. nižji/alkanol z 1 do 4 atomi ogljika, npr. etanol, ali nižjialkoksinižjialkanol z vsakokrat do 4 atomi ogljika v nižjem alkoksilnem in nižjem alkanolnem delu, npr. 2-metoksiali 2-etoksietanol,in/ali topilo aromatskega značaja, npr. v danem primeru nižjialkiliran, kot metiliran, ali halogeniran, kot kloriran,benzol, kot benzol, toluol, ali klorbenzol. Reakcijska temperatura je v območju 10 do 100°, prednostno 30 do ?0°. Reakcijsko zmes nato, smotrno po odstranitvi netopnih deležev, podvržemo hifLolizi, npr. učinkovanju vode, in po obdelavi izoliramo 5-ciano-10-okso-10,11-r-dihidro-5H-dibenzCb,f3 azepin s formulo V v čisti obliki, ki ga dobimo z dobrim dobitkom in odlično čistoto. Ta spojina je nova in v literaturi ni opisana. Prednostna izvedbena oblika opisane pretvorbe spojine s formulo II v spojino s formulo V obstoji v tem, da za redukcijo s pomočjo kovine, npr. železa, kot je zgorajAccording to this variant of the process according to the invention, the compound of formula II is converted to the compound of formula V and a final product of formula III is prepared. Thus, in the 5-cyano10-nitro-5H-dibenz [b, f] azepine of formula II, the nitro group is reduced by one of the methods described above, and the resulting intermediate is converted by hydrolysis into a compound of formula V. The reduction can be carried out, as previously stated, for example by hydrogen in the presence of a hydride catalyst, e.g. Nickel or precious metal catalyst, eg · Raney nickel or palladium-on-carbon catalyst, in a suitable solvent, e.g. lower alkanol with up to 4 carbon atoms, e.g. methanol or ethanol, or by means of our own hydrogen, t. j. using suitable metal, such as in the case of amalgamated zinc, or in particular iron in acid, e.g. mineral acids, such as dilute sulfur or concentrated hydrochloric acid, or lower alkanecarboxylic acid, e.g. one of the above, e.g. acetic acid, or by means of a chemical reducing agent, such as e.g. of tin (II) chloride.2 ^ 0. Additional solvents may be used, e.g. lower / alkanol with 1 to 4 carbon atoms, e.g. ethanol, or lower alkoxysilane alcohol with up to 4 carbon atoms each in the lower alkoxyl and lower alkanol moieties, e.g. 2-methoxyali 2-ethoxyethanol, and / or an aromatic solvent, e.g. optionally lower alkylated, such as methylated or halogenated, such as chlorinated, benzene, such as benzene, toluene, or chlorobenzene. The reaction temperature is in the range of 10 to 100 °, preferably 30 to? 0 °. The reaction mixture is then subjected to hypholysis, e.g. after removal of insoluble particles. water, and after treatment, 5-cyano-10-oxo-10,11-r-dihydro-5H-dibenzCb, f3 azepine of formula V is isolated in pure form, obtained in good yield and excellent purity. This compound is novel and has not been described in the literature. A preferred embodiment of the described conversion of a compound of formula II into a compound of formula V is that for reduction by metal, e.g. iron as above

- .11 opisano, uporabimo topilo, ki nastale kovinske soli, npr. železove soli, topi in tako v veliki meri prepreči' nastanek težko filtrabilne oborine, npr. v obliki blata. Saka topila so npr. močno polarna organska topila, npr. nižjijalkiletri etilenglikola, kjer ima nižjijalkil do 4 atome ogljika in predstavlja npr. metil ali etil, in je torej npr. etilenglikol-monoetilester.- .11 described, use the solvent formed metal salts, e.g. iron salts, melts and thus largely prevents the formation of a difficult filtration precipitate, e.g. in the form of mud. Such solvents are e.g. strongly polar organic solvents, e.g. lower alkylethyl ethers of ethylene glycol, wherein the lower alkyl has up to 4 carbon atoms and represents e.g. methyl or ethyl, and is e.g. ethylene glycol monoethyl ester.

Nato cianojskupino v spojini s formulo V pretvorimo v karboksamidno skupino končnega proizvoda s formulo 111 s pomočjo hidrolize. To lahko izvedemo s pomočjo bazičnih ali kislih sredstev. Kot bazična sredstva pridejo za to v poštev ip?. r hidroksidi zemelj skoalkali j skih ali alkalijskih kovin, npr. magnezijev ali kalcijev hidroksid, nadalje npr. natrijev hidroksid, ' v prisotnosti peroksida, kot vodikovega peroksida, ali alkalijskega bikarbonata, kot natrijevega bikarbonata, v zmesi z vodikovim peroksidom, medtem ko kisla sredstva predstavljajo npr. mineralne kisline, kot žveplova ali polifosforjeva kislina, nadalje nižjejalkankarboksilne ali halogeunižjialkahkarboksilne kisline z do 4 atomi'ogljika, npr. mravljinčna ali ocetna kislina oz. triklor- ali trifluorocetna kislina v zmesi z mineralnimi kislinami, npr. koncentrirana žveplova kislina. Kisla sredstva so nadalje Lewisove kisline, npr. borov/brifluorid, ki je lahko raztopljen v nižji/alkankarboksilni kislini zgoraj opisane vrste, kot ocetni kislini, je pa lahko tudi definirana spojina, npr. s formulo BF_?.2 CH^COOH. V danem primeru dodamo reakcijski zmesi še nadaljnje topilo, npr. topilo aromatskegaThe cyano group in the compound of formula V is then converted to the carboxamide group of the final product of formula 111 by hydrolysis. This can be done using basic or acidic agents. As basic assets, ip? r hydroxides of earth alkaline or alkali metals, e.g. magnesium or calcium hydroxide, further e.g. sodium hydroxide, 'in the presence of peroxide, such as hydrogen peroxide, or alkali bicarbonate, such as sodium bicarbonate, in admixture with hydrogen peroxide, while the acidic agents are e.g. mineral acids, such as sulfuric or polyphosphoric acid, further lower the alkanecarboxylic or halogenated carboxylic acids of up to 4 carbon atoms, e.g. formic or acetic acid, respectively. trichloro- or trifluoroacetic acid in admixture with mineral acids, e.g. concentrated sulfuric acid. Acidic agents are further Lewis acids, e.g. boron / brifluoride, which may be dissolved in the lower / alkanecarboxylic acid of the species described above, as acetic acid, but may also be a defined compound, e.g. with the formula BF _? .2 CH ^ COOH. In the present case, a further solvent is added to the reaction mixture, e.g. aromatic solvent

- 12 značaja, kot npr. klorbenzol. Reakcijske temperature so v območju od -5 do +150°« prednostno 0 do 40°.- 12 characters, such as chlorobenzene. The reaction temperatures are in the range of -5 to + 150 °, preferably 0 to 40 °.

Varianta tega postopka obstoji v tem, da za pripravo vmesnega proizvoda s formulo V reduciramo 10-nitrojskupino v spojini s formulo II, dobljeni 5-ciano-10-izonitrozo-10,1ldihidro-5H-dibenz[b,f]azepin s formulo I izoliramo v čisti obliki, tega hidroliziramo v 5-ciano-'lO-okso-10,11-dibidro5H-dibenz[b,f3azepin s formulo V in tega izoliramo v čisti obliki. Ta varianta postopka je označena s tem, da nitro skupino v spojini s formulo II reduciramo v 10-izonitrozo spojino, ki ustreza formuli VI, npr. kot smo navedli, npr. s pomočjo cinkovega prahu v kislini'npr. nižjijalkankarboksilni kislini navedene vrste, kot ocetni kislini, v danem primeru v prisotnosti inertnega topila, kot nižjega alkanola navedene vrste, npr. etanolaj ali s pomočjo vodika v prisotnosti hidrimega katalizatorja, kot katalizatorja plemenite kovine, npr. katalizatorja paladija na oglju, v primernem topilu, npr. topilu aromatskega značaja, npr. piridinu, in dobljeni 5-ciano-10-izonitrozo-10,11-dihidro-5H~dibenz[b,f]azepin s formulo VI izoliramo v čisti obliki. Dobimo gaz dobrim dobitkom in odlično čistoto. Spojina je nova in v literaturi ni opisana. Spojino s formulo VI nato s pomočjo hidrolize hidroliziramo v spojino s formulo VI in dobljeni končni proizvod s formulo III izoliramo v čisti obliki. Pri tem v spojini s formulo VI v istem reakcijskem nastavku hidroliziramo 5-ciano skupino kot tudi 10-izonitrozo skupino. Tako lahko v spojini s formulo VI 10-izonitrozo skupino npr. s pomočjo mineralne kisline, kot solne kisline, prevedemo v 10okso skupino in nato reakcijsko zmes, npr. kot je opisano, hidroliziramo v prisotnosti vode s kislino, npr. mineralno kislino, kot žveplovo ali polifosforjevo kislino, ali s karboksilno kislino, npr. nižjo alkankarboksilno ali halogennižjialkankarboksilno kislino, kot ocetno ali trifluorocetno kislino, ali z borovim trifluoridom v prisotnosti karboksilne kisline, npr. ocetne kisline, ali zmesi takih kislin, v danem primeru v prisotnosti nadaljnjega inertnega topila, kot nižjega alkanola z do 5 atomi ogljika, kot metanola ali etanola, in končni proizvod s formulo III izoliramo v čisti obliki.An alternative to this process is that to prepare an intermediate of formula V, the 10-nitro group in the compound of formula II is reduced, to obtain 5-cyano-10-isonitroso-10,1-dihydro-5H-dibenz [b, f] azepine of formula I Isolated in pure form, hydrolyzed in 5-cyano-10-oxo-10,11-dibidro5H-dibenz [b, f3azepine of formula V and isolated in pure form. This variant of the process is characterized in that the nitro group in the compound of formula II is reduced to a 10-isonitrose compound corresponding to formula VI, e.g. as stated, e.g. using zinc powder in acid'npr. a lower alkanecarboxylic acid of said species, such as acetic acid, optionally in the presence of an inert solvent, such as a lower alkanol of said species, e.g. ethanol or by hydrogen in the presence of a hydride catalyst, such as a precious metal catalyst, e.g. a palladium catalyst on charcoal, in a suitable solvent, e.g. a solvent of an aromatic character, e.g. pyridine, and the resulting 5-cyano-10-isonitroso-10,11-dihydro-5H-dibenz [b, f] azepine of formula VI is isolated in pure form. We get gauze with good gains and excellent purity. The compound is novel and has not been described in the literature. The compound of formula VI is then hydrolyzed to the compound of formula VI, and the resulting finished product of formula III is isolated in pure form. In the same reaction sequence, the 5-cyano group is hydrolyzed in the compound of formula VI in the same reaction sequence as well as the 10-isonitrose group. Thus, in a compound of formula VI, a 10-isonitroso group may e.g. with a mineral acid, such as hydrochloric acid, is converted to the oxo group and then the reaction mixture, e.g. as described, hydrolysed in the presence of water with an acid, e.g. a mineral acid such as sulfuric or polyphosphoric acid, or with a carboxylic acid, e.g. a lower alkanecarboxylic or halogenated lower carbocarboxylic acid, such as acetic or trifluoroacetic acid, or with boron trifluoride in the presence of a carboxylic acid, e.g. acetic acids, or mixtures of such acids, optionally in the presence of a further inert solvent such as a lower alkanol of up to 5 carbon atoms, such as methanol or ethanol, and the final product of formula III is isolated in pure form.

Izum se nanaša zlasti na postopek, opisan v primerih. Naslednji primeri služijo za ilustracijo izuma; temperature so navedene v stopinjah Celzija.The invention relates in particular to the process described in the examples. The following examples serve to illustrate the invention; temperatures are given in degrees Celsius.

- - -.PRIMER 1- - -. EXAMPLE 1

6,0 δ (0,027 molov) 5-ciano-5P-dibenz[b,f]azepina raztopimo v zmesi 80 ml ac e t anhidrida in 20 ml ocetne kisline. Segrejemo na 50° in po kapljicah 1 1/2 ure dodajamo raztopine 5,6 g (0,08 molov) natrijevega nitrita v 10 ml vode, pri čemer ne pustimo, da hi temperatura narasla nad 55° · Še 2 uri držimo pri 50° in nato topilo oddestiliramo pri zmanjšanem pritisku in temperaturi kopeli 50°· Ostanek 2-krat digeriramo s po 100 ml ledene vode in prevzamemo v 80 ml etanola. Po večurnem stanju pri 0° odsesamo izločene rumene kristale in izperemo z malo etanola. Dobljeni 5-ciano-10-nitro-5H-dibenz[b,f]azepin se tali pri 175 do 176° oh razpadu.6.0 δ (0.027 mol) of 5-cyano-5P-dibenz [b, f] azepine was dissolved in a mixture of 80 ml of acetic acid anhydride and 20 ml of acetic acid. Heat to 50 ° C and add solutions of 5.6 g (0.08 moles) of sodium nitrite in 10 ml of water dropwise for 1 1/2 hours, leaving the temperature above 55 ° C for a further 2 hours. ° and then the solvent is distilled off under reduced pressure and a bath temperature of 50 °. The residue is digested twice with 100 ml of ice water each and taken up in 80 ml of ethanol. After an evening condition at 0 °, suction off the separated yellow crystals and wash with little ethanol. The resulting 5-cyano-10-nitro-5H-dibenz [b, f] azepine melts at 175 to 176 ° ohm decay.

Dobitek; 5,2 g, 72 % teor.Profit; 5.2 g, 72% of theory.

Analitski in spektroskopski podatki so v skladu z domnevano strukturo.The analytical and spectroscopic data are consistent with the assumed structure.

PRIMER 2EXAMPLE 2

6,5 g (0,05 mole) 5-ciano-5H-dibenz[b,f]azepina raztopimo v zmesi 100 ml ocetne kisline in 100 ml acetanhidrida. Segrejemo na 40° in 45 minut dodajamo 6,2 g (0,09 molov) natrijevega nitrita, pri čemer skozi raztopino vodimo počasen zračni tok. Temperatura naraste brez nadaljnjega segrevanja na 55° im jo po koncu dodajanja nitrita še 1 uro držimo na 55°.6.5 g (0.05 mol) of 5-cyano-5H-dibenz [b, f] azepine were dissolved in a mixture of 100 ml of acetic acid and 100 ml of acetanhydride. Heat to 40 ° C and add 6.2 g (0.09 mol) of sodium nitrite for 45 minutes, allowing a slow air flow through the solution. The temperature rises without further heating to 55 ° and is maintained at 55 ° for 1 hour after the end of nitrite addition.

: 1.5 '-r.': 1.5 '-r.'

Topilo oddestiliramo v vakuumu pri temperaturi kopeliThe solvent was distilled off in vacuo at bath temperature

50°, prevzamemo ostanek v 300 ml toluola, stresamo za odstranitev anorganskih sestavin večkrat z vodo in toluol oddestiliramo v vakuumu do 40 ml. Izločeni rumeni proizvod odsesamo in izperemo z malo toluola; identičen je s 5-ciano-1O-nitro5H-dibenz[b,f]azepinom po primeru 1.50 °, the residue is taken up in 300 ml of toluene, shaken to remove inorganic constituents several times with water and the toluene distilled off in vacuo to 40 ml. The extracted yellow product is sucked off and washed with a little toluene; it is identical to 5-cyano-10-nitro5H-dibenz [b, f] azepine according to Example 1.

Dobitek: 6,1 g; 77,5 % teor.Yield: 6.1 g; 77.5% of theory.

PRIMER 3EXAMPLE 3

19,6 g (0,09 molov) 5-ciano-5H-dibenz[b,f]azepina presnovimo kot v primeru 2 v 300 ml ocetne kisline in 3θθ ml acetanhidrida z 18,6 g (0,2? molov) natrijevega nitrita .Bdeče rumeni sirup, dobljen po odparjenju topila, premešavamo s 300 ml vode do popolne strditve. Odsesamo, izperemo z vodo do nevtralne reakcije filtrata in posušimo v vakuumu.19.6 g (0.09 mol) of 5-cyano-5H-dibenz [b, f] azepine are reacted as in Example 2 in 300 ml of acetic acid and 3θθ ml of acetanhydride with 18.6 g (0.2 mol) of sodium nitrite .Also yellow syrup obtained after evaporation of the solvent is stirred with 300 ml of water until complete solidification. Suction off, rinse with water to neutralize the filtrate and dry in vacuo.

Isti surovi proizvod dobimo, če gornjo presnovo izvedemo pri temperaturi 80 do 85°.The same crude product is obtained if the above metabolism is carried out at a temperature of 80 to 85 °.

Dobljeni surovi proizvod je primeren za nadaljnje presnove, lahko pa ga očistimo tudi takole:The obtained crude product is suitable for further metabolism, but can also be purified as follows:

1. 23,7 g surovega proizvoda prekristaliziramo iz izopropanola in dobimo rumen kristalni material, ki je identičen s 5-ciano-1Q-nitro-5B-dibenz[b,f]azepinom po primeru 1. Dobitek 18,0 g, 76,2 % teor.1. 23.7 g of the crude product are recrystallized from isopropanol to give a yellow crystalline material identical to 5-cyano-1Q-nitro-5B-dibenz [b, f] azepine according to Example 1. Yield 18.0 g, 76. 2% theor.

2. Končni proizvod, ki je enak glede na dobitek in kvaliteto, dobimo z digeriranjem surovega proizvoda z ocetno kislino.2. The final product, which is the same in terms of yield and quality, is obtained by digesting the crude product with acetic acid.

PRIMER 4EXAMPLE 4

V buči proizvedemo s počasnim dokapavanjem 20 %-ne žveplove kisline v koncentrirano vodno raztopino 40,0 g (0,58 molov) natrijevega nitrita nitrozne pline (RgO^), ki jih s počasnim zračnim tokom uvedemo v raztopino 10,9 g (0,05 molov) 5-ciano-5H-dibenz[b,f]azepina v 100 ml toluola, segreto na 55°. Koncentracijo dovedenega zračnega kisika pri tem vzdržujemo tako nizko, da se ne morejo tvoriti eksplozijske zmesi toluolne pare-kisika. Uvajamo do popolne presnove izhodnega materiala (kontrola s tenkoslojno kromatografijo), prebitek preženemo z živahnim tokom dušika in toluol odparimo pod zmanjšanim pritiskom pri temperaturi 40°. Dobljeni rdeči sirup prevzamemo v 100 ml izopropanola. Po večurnem stanju pri 5° kristalizat odsesamo in izperemo z malo izopropanola. Dobljeni 5-ciano-10-nitro-5H-dibenz[b, fjazepin je identičen s proizvodom po primeru 1.The flask is produced by slow dropwise addition of 20% sulfuric acid to a concentrated aqueous solution of 40.0 g (0.58 mol) of sodium nitrite nitrous gas (RgO ^), which is introduced into a solution of 10.9 g (0 by slow air flow). , 05 mol) of 5-cyano-5H-dibenz [b, f] azepine in 100 ml of toluene, heated to 55 °. At the same time, the concentration of the supplied air oxygen is kept so low that no explosive mixtures of toluene vapor-oxygen can form. Introduce to complete metabolism of starting material (control by thin layer chromatography), digest the excess with a vigorous stream of nitrogen and evaporate the toluene under reduced pressure at 40 ° C. The resulting red syrup is taken up in 100 ml of isopropanol. After an evening condition at 5 °, the crystallizate is sucked off and washed with a little isopropanol. The 5-cyano-10-nitro-5H-dibenz [b, fjazepine obtained is identical to the product of Example 1.

Dobitek: 9,4- g, 71,7 % teor.Yield: 9.4 g, 71.7% of theory.

PRIMER 5EXAMPLE 5

Analogno načinu dela, opisanemu v primeru 4, proizvedemo v buči iz 55,o g (0,8 molov) natrijevega nitrita nitroz ne pline in jih vodimo s pomočjo počasnega zračnega toka v raztopino 10^9 g (0,05 molov) 5-ciano-5H-dibenz[b,f]azepina v 110 ml ocetne, kisline in 110 ml acetanhidrida, ki jo držimo pri 50°. Po 3 urah je presnova končana; nato topilo pod vakuumom oddestiliramo pri temperaturi kopeli 5θ°, ostanekAnalogous to the mode of operation described in Example 4, sodium nitrite gas is produced in a flask of 55 g (0.8 mol) of sodium nitrite and guided by a slow air stream into a solution of 10 ^ 9 g (0.05 mol) of 5-cyano -5H-Dibenz [b, f] azepine in 110 ml of acetic acid and 110 ml of acetanhydride kept at 50 °. After 3 hours the metabolism is complete; the solvent was then distilled off under vacuum at a bath temperature of 5θ °, the residue

- ΑΓ*- ΑΓ *

- »/- τ.- »/ - τ.

prevzamemo ν 50 ml izopropanola in izkristalizirani material odsesamo po večurnem stanju pri 20°. Dobimo 5-ciano-lO-nitro5H-dibenz[b,f]azepin, ki Je identičen s proizvodom, dobljenim po primeru 1.50 ml of isopropanol is taken up and the crystallized material is sucked off at 20 ° in the evening. 5-cyano-10-nitro5H-dibenz [b, f] azepine is obtained which is identical to the product obtained according to Example 1.

Dobitek: 9,5 g, 72,5 % teor.Yield: 9.5 g, 72.5% of theory.

PRIMER 6EXAMPLE 6

Analogno načinu dela, opisanem v primeru 4, proizvedemo v buči iz $0,0 g (0,45 molov) natrijevega nitrita nit rožne pline in Jih vodimo s pomočjo počasnega zračnega toka v raztopino 10,9 g (0,05 molov) 5-ciano-5H-dibenz[b,f]azepina v 110 ml acetanhidrida, ki Jo držimo pri 55°. Po končani presnovi (kontrola s tenkoslojno kromatografijo) reakcijsko zmes uparimo pod vakuumom pri temperaturi kopeli 50° in ostanek prevzamemo z 20 ml ocetne kisline. Pustimo ste ti 2 uri pri 20°, kristalizat odsesamo in ga izperemo z malo ocetne kisline. Dobimo 5-ciano-10-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 1.Analogous to the mode of operation described in Example 4, a barrel of $ 0.0 g (0.45 mol) of sodium nitrite is produced by a filament of corrosive gas and guided by a slow air stream into a solution of 10.9 g (0.05 mol) of 5- cyano-5H-dibenz [b, f] azepine in 110 ml of acetanhydride, kept at 55 °. After complete digestion (control by thin layer chromatography), the reaction mixture was evaporated under vacuum at a bath temperature of 50 ° and the residue was taken up with 20 ml of acetic acid. Leave it for 2 hours at 20 °, suction off and wash it with a little acetic acid. 5-cyano-10-nitro-5H-dibenz [b, f] azepine is obtained which is identical to the product obtained according to Example 1.

Dobitek: 9,1 g» 69,4 % teor.Yield: 9.1 g »69.4% of theory.

PRIMER 7EXAMPLE 7

10,0 g (0,046 molov) 5-ciano-5H-dibenz[b,f3azepina raztopimo v 100 ml toluola pri 55°· Iz tlačne steklenice počasi uvedemo v raztopino ob mešanju 5,0 g (0,054 molov) ^K2⁰4’ ^pri č®¹¹⁶¹ temperatura naraste do 60°, nato držimo reakcijsko zmes pri tej temperaturi, dokler ves izhodni material ni presnovljen (kontrola s tenkoslojno kromatografijo), potem ohladimo na 20° in toluolno fazo posušimo nad natrijevim sulfatom. Po uparjenju v vakuumu dobimo rdeče olje, ki ga prevzamemo v 50 ml izopropanola. Po večurnem stanju pri 20° kristale odsesamo in izperemo z malo izopropanola. Dobljeni 5-ciano-10-nitro-5H-dibenz[b,f]azepin je identičen s proizvodom, dobljenim po primeru 1.10.0 g (0.046 mol) of 5-cyano-5H-dibenz [b, f3azepine are dissolved in 100 ml of toluene at 55 °. · From the pressure bottle, slowly introduce into the solution with stirring 5.0 g (0.054 mol) of ^K 2 ⁰ 4 ' ^at č ^{1161, the} temperature rises to 60 °, then the reaction mixture is held at this temperature until all starting material is digested (control by thin layer chromatography), then cooled to 20 ° and the toluene phase is dried over sodium sulfate. Evaporation in vacuo gave a red oil which was taken up in 50 ml of isopropanol. After an evening condition at 20 °, the crystals were aspirated and washed with a little isopropanol. The 5-cyano-10-nitro-5H-dibenz [b, f] azepine obtained is identical to the product obtained in Example 1.

Dobitek: 6,7 g, 56 % teor.Yield: 6.7 g, 56% of theory.

PRIMER 8EXAMPLE 8

45,6 g (0,2 mola) 5-ciano-5H-dibenz[b,f]azepina raztopimo v 250 ml ocetne kisline pri 55° in iz tlačne stekbmoe v 2 1/2 ure v raztopino uvedemo ob mešanju NgO^, pri čemer z občasnim hlajenjem vzdržujemo temperaturo pri 55°. Konec reakcije spoznamo po zelenem obarvanju raztopine (prebitek Ng V kot tudi s kontrolo s tenkoslojno kromatografijo Pustimo ohladiti, mešamo še več ur pri sobni temperaturi in nato izločeno oborino odfiltriramo ter jo izperemo z malo ocetne kisline. Z up ar j en jem filtrata in raztapljanjem z acetonitrilom dobimo drugi kristalizat 5-ciano-10-nitro-5Hdibenz[b,fjazepina, ki je identičen s proizvodom, dobljenim po primeru 1.45.6 g (0.2 mol) of 5-cyano-5H-dibenz [b, f] azepine were dissolved in 250 ml of acetic acid at 55 ° and introduced into the solution with stirring of NgO 2 for 2 1/2 hours. keeping the temperature at 55 ° by occasional cooling. The end of the reaction is known by the green coloration of the solution (excess Ng V as well as control by thin layer chromatography. Allow to cool, stir for several hours at room temperature and then filter the precipitate off and wash it with a little acetic acid. Using the filtrate and dissolving it. acetonitrile yields a second crystallisate of 5-cyano-10-nitro-5Hdibenz [b, fjazepine, identical to the product obtained in Example 1.

Celoten dobitek: 19,5 g, 57 % teor.Overall yield: 19.5 g, 57% of theory.

PRIMER 9EXAMPLE 9

45,θ g (0,2 mola) 5-ciano-5H-dibenz[b,f]azepina raztopimo v 25θ ml ocetne kisline pri 55°. K temu dokapavamo45, θ g (0.2 mol) of 5-cyano-5H-dibenz [b, f] azepine was dissolved in 25θ ml of acetic acid at 55 °. We get to the topic

-19,.-19 ,.

ml vode, dokler se ne začne pojavljati motnost,in nato iz tlačne steklenice počasi uvedemo dokler se v tenko slojnem k roma to gramu ne da več dokazati izhodne snovi. Ohladimo na 5° in 2 uri mešamo pri tej temperaturi, nato kristalizat filtriramo in ga izperemo z 80 %-no ocetno kislino. Dobimo 5-ciano-lO-nitro-5H-dibenz[b,f3azepin, ki je identičen s proizvodom, dobljenim po primeru Λ.ml of water until turbidity begins to appear and then slowly introduce from the pressure bottle until the gram substance can no longer prove the starting material. The mixture was cooled to 5 [deg.] And stirred at this temperature for 2 hours, then the crystallizate was filtered off and washed with 80% acetic acid. 5-cyano-10-nitro-5H-dibenz [b, f3azepine is obtained which is identical to the product obtained by Example Λ.

Dobitek: 42,1 g, 80 % teor.Yield: 42.1 g, 80% of theory.

PRIMER 10EXAMPLE 10

43,6 g (0,2 mola) 5-ciano-5H-dibenzCb,f]azepina raztopimo v 173 ml ocetne kisline pri 33°. V raztopino uvajamo pri tej temperaturi Ή^θ4 steklenice toliko časa, dokler vsa izhodna snov ni presnovljena (kontrola s tenkoslojno kromatografijo) in se proizvod obori . Nato ob občasnem hlajenju po deležih dodamo 16,4 g (0,2 mola) natrije vega acetata in vzdržujemo temperaturo pri 5θ do 33°. Nato 3 ure mešamo pri sobni temperaturi, filtriramo in kristalizat nato izperemo z ocetno kislino in vodo. Dobimo 5-ciano10-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom dobljenim po primeru 1.43.6 g (0.2 mol) of 5-cyano-5H-dibenzCb, f] azepine were dissolved in 173 ml of acetic acid at 33 °. Introduce into the solution at this temperature ^ θ4 bottles until all starting material has been digested (control by thin layer chromatography) and the product precipitated. Then, with occasional cooling, 16.4 g (0.2 mol) of sodium acetate are added portionwise and the temperature is maintained at 5θ to 33 °. The mixture was then stirred at room temperature for 3 hours, filtered and the crystallizate was then washed with acetic acid and water. 5-cyano10-nitro-5H-dibenz [b, f] azepine is obtained which is identical to the product obtained in Example 1.

Dobitek: 3θ»1 8» 68,6 % teor.Yield: 3θ »1 8» 68.6% Theor.

PRIMER 11EXAMPLE 11

21,8 g (0,1 mol) 3-ciano-5H-dibenz[b,f]azepina razto pimo v 110 ml acetahhidrida pri 35°. V to raztopino uvajamo iz tlačne steklenice 10,0 g (0,1 mol) ^0^ tako počasi, da21.8 g (0.1 mol) of 3-cyano-5H-dibenz [b, f] azepine were dissolved in 110 ml of acetic anhydride at 35 °. 10.0 g (0.1 mol) ^ 0 ^ is introduced into the solution from the pressure bottle so slowly that

-2α-ne izhajajo temnorjavi plini, in temperaturo vzdržujemo z občasnim hlajenjem pri 55°. Po koncu reakcije 1 uro prevajamo močan tok dušika, nato ohladimo na -20° in 2 uri držimo pri tej temperaturi. Nato rumeni kristalizat odsesamo in ga izperemo z malo acetonitrila, nakar dobimo 5-ciano10-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 1. Filtrat uparimo pri vakuumu pri temperaturi kopeli 50° v rdeče olje. Prevzamemo z 10 ml acetonitrila, pustimo 2 uri stati pri 5° in drugi kristalizat odsesamo.-2α-does not produce dark brown gases, and the temperature is maintained by periodic cooling at 55 °. At the end of the reaction, a strong stream of nitrogen was transferred for 1 hour, then cooled to -20 ° and kept at this temperature for 2 hours. The yellow crystallizate is then sucked off and washed with a little acetonitrile to give 5-cyano10-nitro-5H-dibenz [b, f] azepine, which is identical to the product obtained in Example 1. The filtrate was evaporated under vacuum at a bath temperature of 50 ° C. red oil. Take up with 10 ml of acetonitrile, allow to stand at 5 ° for 2 hours, and suck off the second crystallisate.

Celoten dobitek: 19,5 g 74,1 % teor.Overall yield: 19.5 g 74.1% of theory.

PRIMER 12EXAMPLE 12

21,8 g (0,1 mol) 5-ciano-5H-dibenz[b,f]azepina raztopimo v 140 ml acetanhidrida pri 50°. V to raztopino počasi uvedemo ob mešanju iz tlačne steklenice 12,0 g (0,13 molov) ^2θ4’ čemer držimo temperaturo s hlajenjem med 50 in 55°. Pustimo še 1 uro reagirati, nato skozi raztopino vodimo močan tok dušika in počasi dodamo 60 ml vode, pri čemer s hlajenjem vzdržujemo temperaturo pri 50 do 55°· Nato ohladimo na 5°, pustimo kristalizirati 1 uro in odfiltriramo. dobimo 5-ciano1O-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 1.21.8 g (0.1 mol) of 5-cyano-5H-dibenz [b, f] azepine were dissolved in 140 ml of acetanhydride at 50 °. 12.0 g (0.13 mol) ^ 2θ4 'is slowly introduced into this solution with stirring from a pressure bottle while keeping the temperature at cooling between 50 and 55 °. Allow to react for 1 hour, then run a strong stream of nitrogen through the solution and slowly add 60 ml of water, keeping the temperature at 50 to 55 ° C by cooling. Then cool to 5 °, allow to crystallize for 1 hour and filter. 5-cyano10-nitro-5H-dibenz [b, f] azepine is obtained which is identical to the product obtained according to Example 1.

Filtrat uparimo pod vakuumom in po prevzemu ostanka v 40 ml 80-%-ne ocetne kisline cdobimo drugi kristalizat. Celoten dobitek: 21,5 g, 81,7 % teor.The filtrate was evaporated in vacuo and, after the residue was taken up in 40 ml of 80% acetic acid, the second crystallizate was obtained. Overall yield: 21.5 g, 81.7% of theory.

--21 .+ ·- 21. + ·

PRIMER 13EXAMPLE 13

43,6 S (θ»2 mola) 5-ciano-5H-dibenz[b,f]azepina raztopimo v 43O ml acetanbidrida. V to raztopino uvajamo ob mešanju in občasnem hlajenju iz tlačne steklenice 19,0 g (0,206 molov) tako počasi, da temperatura ne naraste nad 25°. Ro koncu presnove se raztopina obarva zeleno in proizvod se obori v kristalih. Mešamo 1 uro ob hlajenju z ledom in prevajanju močnega toka dušika, nato odfiltriramo in izperemo z malo etilestra ocetne kisline. Dobimo 5-ciano10-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 1. Iz filtrata dobimo po uparjenju v vakuumu in prevzemu z etilestrom ocetne kisline drugi kristalizat.43.6 S (θ »2 moles) of 5-cyano-5H-dibenz [b, f] azepine was dissolved in 43O ml of acetanhydride. 19.0 g (0.206 mol) was slowly introduced into the solution under stirring and occasional cooling from a pressure bottle so that the temperature did not rise above 25 °. At the end of the metabolism, the solution turns green and the product precipitates in crystals. The mixture was stirred for 1 hour under ice-cooling and a strong stream of nitrogen was then filtered and washed with a little of ethyl acetic acid. 5-Cyano10-nitro-5H-dibenz [b, f] azepine is obtained, which is identical to the product obtained in example 1. The filtrate is obtained after evaporation in vacuo and the second crystallisate is taken up with ethyl acetate.

Celotni dobitek: 42,3 g» 80,4 % teor.Total Yield: 42.3 g »80.4% of theory.

PRIMER 14EXAMPLE 14

35»θ g (0,16 molov) 5-ciano-5H-dibenz[b,f]azepina suspendiramo v 160 ml acetanbidrida pri 20°. K temu pustimo ob mešanju 5 ur počasi dokapavati raztopino 14,7 g (0,16 molov) ^2θ4 ^v ml acetanbidrida, pri čemer držimo temperaturo med 20 in 25°. Po popolni presnovi izhodne snovi (kontrola s tenko slojno kromatografijo) ohladimo z 1-urnim prevajanjem močnega toka dušika na 0 do 5° in. kristalni proizvod odsesamo. Dobimo 5-ciano-10-nitro-5H-dibenz(b,f)azepin, ki je iden tičen s proizvodom, dobljenim po primeru 1.35 »θ g (0.16 moles) of 5-cyano-5H-dibenz [b, f] azepine was suspended in 160 ml of acetanhydride at 20 °. To this, a solution of 14.7 g (0.16 mol) ^ 2θ4 ⁱⁿ ml of acetanhydride was slowly added dropwise over 5 hours while maintaining the temperature between 20 and 25 °. After complete digestion of the starting material (control by thin layer chromatography), it is cooled by translating a strong stream of nitrogen to 0 to 5 ° in 1 hour. the crystalline product is filtered off. 5-cyano-10-nitro-5H-dibenz (b, f) azepine is obtained which is identical to the product obtained according to example 1.

Iz filtrata dobimo po uparjenju v vakuumu na 50 ml drugi kristalizat.The filtrate was obtained after evaporation in vacuo to 50 ml of the second crystallizate.

.......- 22 Celoten dobitek; 34,6 g, 80 % teor........- 22 Total Profit; 34.6 g, 80% of theory.

PRIMER 15EXAMPLE 15

43,θ g (°,2 mola) 5-ciano-5H-dibenz[b,f]azepina raztopimo v 175 ml anhidrida ocetne kisline pri 50°. Iz tlačne steklenice uvedemo v 2 urah v to raztopino toliko N^O^, da se izhodna snov popolnoma presnovi in v odpadnem plinu ugotovimo rahel prebitek ^0^. Pustimo, da se proizvod izkristalizira pri 5θ°; in nato po deležih dodamo 16,5 g (0,2 mola) natrijevega acetata. So se toplota neha razvijati, mešamo še 30 minut pri 5θ°, nato pa še več ur pri sobni temperaturi.43, θ g (°, 2 mol) of 5-cyano-5H-dibenz [b, f] azepine is dissolved in 175 ml of acetic anhydride at 50 °. Introduce from the pressure bottle within 2 hours into this solution so much N ^ O ^ that the starting material is completely metabolized and a slight excess ^ 0 ^ is found in the waste gas. Let the product crystallize at 5θ °; and then 16.5 g (0.2 mol) of sodium acetate were added portionwise. The heat ceases to develop, stirring for another 30 minutes at 5θ ° and then continuing for another hour at room temperature.

Po filtriranju in spiranju kri stali za ta z ocetno kislino in vodo dobimo 5-ciano-10-nitro-5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 1. Z obdelavo matične lužnice lahko dobimo nadaljnje 3 g spojine.After filtering and washing the blood, standing with acetic acid and water gave 5-cyano-10-nitro-5H-dibenz [b, f] azepine, which is identical to the product obtained in Example 1. Further treatment of the mother liquor can give further 3 g of compound.

Celoten dobitek; 44,1 g, 83,8 % teor.Total profit; 44.1 g, 83.8% of theory.

PRIMER 16EXAMPLE 16

K raztopini 2,0 g 5-ciano-5H-dibenz[b,f3azepina v 20 ml acetanhidrida ocetne kisline dokapavamo pri 20° ob mešanju 5 ml konc. solitrove kisline (okoli 64 %-ne), pri čemer poteče eksotermna reakcija ob spremembi barve do temnofrumene. Pustimo še 1 uro reagirati pri 20°, dokapamo nato pri 5θ° ml vode in prevzamemo oborjeno mast v etil estru ocetne kisline. Iz ostanka, ki ga dobimo po izpiranju in uparjenju organske faze, dobimo z acetonitrilom pri daljšem stanju 0,6 g rumenih kristalov, ki po kontroli s tekočinsko kro-25matografijo vsebujmo 7θ % 5-ciano-10-nitro-5H-dibenz[b,f]azepina.To a solution of 2.0 g of 5-cyano-5H-dibenz [b, f3azepine in 20 ml of acetic acid acetanhydride was added dropwise at 20 ° while stirring 5 ml of conc. hydrochloric acid (about 64%), the exothermic reaction proceeds when the color changes to darkfruity. Allow to react for another 1 hour at 20 °, then dropwise at 5θ ° ml of water and take up the precipitated fat in acetic acid ethyl ester. From the residue obtained after washing and evaporation of the organic phase, 0.6 g of yellow crystals are obtained with the acetonitrile at a longer state which, after control by liquid chromatography, contains 7θ% 5-cyano-10-nitro-5H-dibenz [b , f] azepine.

PRIMER 17EXAMPLE 17

Suspenziji 26,5 S (0,1 mola) 5-ciano-10-nitro-5H-dibenz[b,f]azepina v 100 ml ocetne kisline dodamo pri sobni temperaturi 50 ml raztopine 15 utež.% BF^ v ocetni kislini (= 0,11 molov). Pri tem temperatura naraste počasi na 54° ob popolnem raztapljanju izhodne snovi. Pri 5θ° 5 minut dodajamo 5θ ml vode, kar vodi do ponovnega porasta temperature na 57°. Pri tej temperaturi v 20 minutah po deležih vnesemo 40 g železovega prahu, pri čemer vzdržujemo temperaturo z občasnim hlajenjem na 65 do 7θ°· Po prenehanju eksotermne reakcije mešamo še 15 minut in nato odfiltriramo anorganski material, ki ga nato 5-krat izperemo z malo ocetne kisline. Celoten filtrat dokapamo ob dobrem mešanju v 1 1/2 1 vode, nastalo oborino odfiltriramo po 2-umem mešanju in z vodo izperemo do nevtralnega. Po sušenju pri 60° v vakuumu dobimo 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom. Dobitek: 23,® S, 91,2% teor.To a suspension of 26.5 S (0.1 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine in 100 ml of acetic acid was added at room temperature 50 ml of a solution of 15 wt% BF ^ in acetic acid ( = 0.11 moles). The temperature rises slowly to 54 ° with complete dissolution of the starting material. At 5θ ° for 5 minutes, 5θ ml of water is added, causing the temperature to rise to 57 ° again. At this temperature, 40 g of ferrous powder is injected at 20 minutes, maintaining the temperature with occasional cooling to 65 to 7θ °. After the exothermic reaction is stopped, the mixture is stirred for another 15 minutes and then the inorganic material is filtered off and then washed 5 times with a little acetic acids. The whole filtrate was added dropwise with good stirring into 1 1/2 l of water, the resulting precipitate was filtered off after 2 ml stirring and washed with water until neutral. After drying at 60 ° in vacuo, 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is obtained, which is identical to the authentic material on the basis of the IR spectrum. Yield: 23, ® S, 91.2% of theory.

PRIMER 18EXAMPLE 18

K suspenziji 26,5 g (θ,1 mola ) +5-ciano-10-nitro5H-dibenz[b,f]azepina v zmesi 260 ml klorbenzola in 150 ml Ocetne kisline hitro dodamo 50 ml raztopine 15 #tež.% BF^To a suspension of 26.5 g (θ, 1 mole) + 5-cyano-10-nitro5H-dibenz [b, f] azepine in a mixture of 260 ml of chlorobenzene and 150 ml of acetic acid, quickly add 50 ml of a solution of 15 # wt.% BF ^

.......^-*24· - -* v ocetni kislini in dobimo ob šibkem ugrevanju bistro rumeno raztopino. Reakcijsko zmes mešamo 10 minut in nato v enem deležu dodamo 40 g železovega prahu. Ob dobrem mešanju 5θ minut dokapavamo 100 ml vode, pri čemer naraste temperatura na 65°........ ^ - * 24 · - - * in acetic acid and a clear yellow solution is obtained by weak heating. The reaction mixture was stirred for 10 minutes and then 40 g of iron powder was added in one portion. With good stirring for 5θ minutes, add 100 ml of water, increasing the temperature to 65 °.

Z zunanjim segrevanjem držimo temperaturo 2 uri na 60 do 65°, anorganski del odfiltriramo in ga speremo še s klorbenzolom in ocetno kislino. Po odločen ju klorbenzolne faze le-to izperemo z vodo, dokler se ne začne kristalizacija proizvoda. Uparimo v vakuumu in ostanek prevzamemo s 100 ml metanola. Fo odsesanju in izpiranju z malo metanola dobimo 5-karbamil-10okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki je na osnovi IRspektra identičen z avtentičnim materialom.With external heating, the temperature is kept at 60-65 ° C for 2 hours, the inorganic part is filtered off and washed with chlorobenzene and acetic acid. After a determined chlorobenzene phase, they are washed with water until crystallization of the product begins. Evaporate in vacuo and take up the residue with 100 ml of methanol. Suction and rinsing with a little methanol yielded 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine, which is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 21,4 g, 85 # teor.Yield: 21.4 g, 85 # of theory.

PRIMER 19EXAMPLE 19

K suspenziji 26,5 g (0,1 mola) 5-ciano-10-nitro-5H-dibenz [b,f]azepina v 200 ml ocetne kisline pustimo hitro dotekati 50 ml raztopine 15 utež.% BF^ v ocetni kislini. Mešamo 45 minut do popolnega raztapljanja in do prenehanja zmerno eksotermne reakcije. Pri 5θ° nato dodamo 40 g železovega prahu in 50 minut počasi dokapavamo 100 ml vode, pri čemer temperatura naraste na 65°. 15 nr mešamo pri sobni temperaturi, ponovno segrejemo na 60°, neraztopljeno odfiltriramo in še 5-hrat izperemo z ocetno kislino. Filtrat uparimo v vakuumu na volumen okoli 100 ml in po kapljicah dodamo 400 ml vode. Smeš mešamo še 2 uri, odfiltriramo in filtrsko pogačo izperemo z vodo do nevtralnegaJPo sušenju pri 50° v vakuumu dobimo 25,8 g (94,4 % teor.) surovega proizvoda, ki ga prekristaliziramo iz 200 ml ocetne kisline/vode (8:2). Dobimo čist 5-karbamil- 25 10-okso-10,11-dihidro-5H-dibenz[b,f3azepin, ki je na osnovi IR-spektra identičen z avteutičnim materialom.To a suspension of 26.5 g (0.1 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine in 200 ml of acetic acid, 50 ml of a solution of 15 wt% BF ^ in acetic acid were rapidly added. Stir for 45 minutes until complete dissolution and until moderately exothermic reaction ceases. At 5θ ° 40 g of ferrous powder are then added and 50 ml of water are slowly added dropwise over 50 minutes, increasing the temperature to 65 °. The mixture was stirred at room temperature, warmed again to 60 °, filtered undissolved and washed with acetic acid for 5 hours. The filtrate was evaporated in vacuo to a volume of about 100 ml and 400 ml of water was added dropwise. The mixture was stirred for a further 2 hours, filtered off and the filter cake washed with water to neutral. After drying at 50 ° in vacuo, 25.8 g (94.4% of theory) of the crude product was recrystallized from 200 ml of acetic acid / water (8: 2). Pure 5-carbamyl-25 10-oxo-10,11-dihydro-5H-dibenz [b, f3azepine is obtained, which is identical to that of the autoreutic material on the basis of IR spectrum.

Dobitek: 19,7 g» 78 % teor.Yield: 19.7 g »78% of theory.

PRIMER 20EXAMPLE 20

51,5 g (0,12 molov) 5-ciano-10-nitro~5H-dibenz[b,f] azepina suspendiramo v 540 ml klorbenzola in hitro dodamo 98 ml raztopine 10 utež.% BF^ v ocetni kislini. Ob segrevanju na 30° nastopi raztapljanje, takoj nato pa se začne izločati BFj-adukt 5-karbamil-10-nitro-5H-dibenz[b,£]azepina. Pustimo 2 uri kristalizirati v ledeni kopeli, odsesamo in izperemo z bencinom. Suhi vmesni proizvod, raztopimo v zmesi 200 ml ocetne kisline in 55 ml vode. 5° minut po deležih dodajamo 50 g železovega prahu in temperaturo držimo s hlajenjem pri okoli 60°. Mešamo še 1 uro pri 50°, filtriramo in izperemo z ocetno kislino. Filtrat uparimo v vakuumu in ostanek prevzamemo s 500 ml vode. Izločeni proizvod odsesamo, z vodo izperemo do nevtralnega in v vakuumu posušimo pri 50°. Dobimo 5-karbamill0-okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki je na osnovi IE-spektra identičen z avtentičnim materialom.51.5 g (0.12 mol) of 5-cyano-10-nitro ~ 5H-dibenz [b, f] azepine are suspended in 540 ml of chlorobenzene and 98 ml of a solution of 10 wt% BF ^ in acetic acid are quickly added. Upon heating to 30 °, dissolution occurs and immediately the 5-carbamyl-10-nitro-5H-dibenz [b, l] azepine BFj adduct is eliminated. Allow to crystallize in an ice bath for 2 hours, vacuum and rinse with gasoline. The dry intermediate is dissolved in a mixture of 200 ml of acetic acid and 55 ml of water. 5 g of iron powder were added 5% in portions and kept at 60 ° C by cooling. The mixture was stirred at 50 ° for 1 hour, filtered and washed with acetic acid. The filtrate was evaporated in vacuo and the residue was taken up with 500 ml of water. The separated product is sucked off, washed with water to neutral and dried in vacuo at 50 °. 5-Carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is obtained, which is identical to the authentic material on the basis of the IE spectrum.

Dobitek: 26,0 g, 86 % teor.Yield: 26.0 g, 86% of theory.

PRIMER 21EXAMPLE 21

K suspenziji 4,0 (0,015 molov) 5-ciano-10-nitro-5Hdibenz[b,f]azepina v 40 ml ocetne kisline po kapljicah dodamo 2 ml konc. žveplove kisline in še 15 ur mešamo pri sobni temperaturi. Bistri raztopini polagamo dodamo 100 ml vode, izločeni material prevzamemo v kloroformu, kloroformski sloj izperemo z vodo in uparimo do suhega. Po prekristaliziranju ostanka iz izopropanola dobimo čisti 5-karbamil-1O-nitro-5Hdibenz[b,f]azepin; tal. 208 do 212°, dobitek 2,2 g, 52,4 % teor. Analitski in spektroskopski podatki so v skladu z navedeno strukturo.To a suspension of 4.0 (0.015 mol) of 5-cyano-10-nitro-5Hdibenz [b, f] azepine in 40 ml of acetic acid was added dropwise 2 ml of conc. of sulfuric acid and stirred at room temperature for another 15 hours. To the clear solution was added 100 ml of water, the precipitated material was taken up in chloroform, the chloroform layer was washed with water and evaporated to dryness. Recrystallization of the residue from isopropanol yields pure 5-carbamyl-10-nitro-5Hdibenz [b, f] azepine; m.p. 208 to 212 °, yield 2.2 g, 52.4% of theory. The analytical and spectroscopic data are in accordance with that structure.

PRIMER 22 g (0,038 molov) 5-ciano-10-nitro-5H-dibenz[b,f]azepina segrevamo 5 ur na 9θ do 100° v 100 ml 98 %-ne mravljinčne kisline. Pustimo nhladiti na sobno temperaturo in nato dodajamo 90 ml vode, dokler se ne začne pojavljati motnost, pustimo kristalizirati 15 ur, filtriramo, izperemo kristale z vodo in posušimo pri 40° v vakuumu. Dobimo 5-karbamil10-nitro-5H-dibenz[b,f)azepin, ki je identičen s proizvodom, dobljenim po primeru 21.EXAMPLE 22 g (0.038 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine was heated for 9 hours at 9θ to 100 ° in 100 ml of 98% formic acid. The mixture was allowed to cool to room temperature and then 90 ml of water was added until turbidity began to appear, crystallized for 15 hours, filtered, the crystals were washed with water and dried at 40 ° in vacuo. 5-Carbamyl10-nitro-5H-dibenz [b, f) azepine is obtained which is identical to the product obtained according to Example 21.

Dobitek: 9,1 g» 85,% teor.Yield: 9.1 g »85% theory.

PRIMER 23EXAMPLE 23

K suspenziji 13,1 g (0,05 molov) 5-ciano-10-nitro-5Hdibenz[b,f)azepina v 130 ml klorbenzola pustimo ob mešanju hitro dotekati 25 ml raztopine 15 utež.% BP^ v ocetni kislini in dobimo bistro rjavkasto raztopino, katere temperatura naraste na 35°. Kristalizacija, ki se začne po nekaj minutah, je dokončana z 1-urnim mešanjem v ledeni kopeli. Odsesamo, izpere- 27 mo s klorbenzolom in sušimo v vakuumu pri 40°, nakar dobimoTo a suspension of 13.1 g (0.05 mol) of 5-cyano-10-nitro-5Hdibenz [b, f) azepine in 130 ml of chlorobenzene was allowed to rapidly stir with 25 ml of a solution of 15 wt% BP ^ in acetic acid while stirring. a clear brownish solution, the temperature of which rises to 35 °. The crystallization, which begins after a few minutes, is completed by stirring for 1 hour in an ice bath. It is sucked off, washed with chlorobenzene and dried in vacuo at 40 ° to give

19,2 g 5-karbamil-10-nitro-5H-dibenz[b,f]azepina kot BR^adukt. Za sprostitev končnega proizvoda suspendiramo BR^adukt v 150 ml vode, mešamo 15 ur, odsesamo in z vodo izperemo do nevtralnega. Po sušenju dobimo 5-karbamil-10-nitro5H-dibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 21.19.2 g of 5-carbamyl-10-nitro-5H-dibenz [b, f] azepine as a BR ^ adduct. To release the final product, suspend the BR ^ adduct in 150 ml of water, stir for 15 hours, vacuum and rinse with water until neutral. After drying, 5-carbamyl-10-nitro5H-dibenz [b, f] azepine is obtained which is identical to the product obtained in Example 21.

Dobitek: 15,5 6» 95»7 % teor.Yield: 15.5 6 »95» 7% Theor.

PRIMER 24EXAMPLE 24

E suspenziji 26,5 g (0,1 mola) 5-ciano-10-nitro-5Hdibenz[b,£]azepina v 40 ml ocetne kisline pustimo dotekati 50 ml raztopine 15 utež.% BR^ v ocetni kislini in mešamo, dokler ne pride do popolnega raztapljanja ob spautanaa ugrevanju na 40°. Nato 10 minut dokapavamo 10 ml vode, pri čemer se raztopina segreje na 50°, držimo 10 minut na tej temperaturi in nato počasi dokapamo nadaljnjih 500 ml vode. Nastalo suspenzijo kristalov 1 uro mešamo pri sobni temperatu ri, odsesamo in z vodo speremo do nevtralnega. Po sušenju pri 60° v vakuumu dobimo 5-karbamil-10-nitro-5H-dibenz[b,f3azepin, ki je identičen s proizvodom, dobljenim po primeru 21.To a suspension of 26.5 g (0.1 mol) of 5-cyano-10-nitro-5Hdibenz [b, S] azepine in 40 ml of acetic acid, 50 ml of a solution of 15 wt% BR ^ in acetic acid are added and stirred until no complete dissolution occurs with spautanaa heating at 40 °. Then 10 ml of water is added dropwise for 10 minutes, the solution is heated to 50 °, kept at this temperature for 10 minutes and then a further 500 ml of water is added slowly. The resulting crystalline suspension was stirred at room temperature for 1 hour, filtered off with suction and washed with water until neutral. After drying at 60 [deg.] In vacuo, 5-carbamyl-10-nitro-5H-dibenz [b, f3azepine is obtained, which is identical to the product obtained in Example 21.

Dobitek: 27,4 g, 97»5 % teor.Yield: 27.4 g, 97 »5% theory.

PRIMER 25EXAMPLE 25

1θ,θ g (0,055 molov) 5-karbamil-lO-nitro-5H-dibenz[b,f]azepina raztopimo v zmesi 100 ml ocetne kisline in 501θ, θ g (0.055 mol) of 5-carbamyl-10-nitro-5H-dibenz [b, f] azepine are dissolved in a mixture of 100 ml of acetic acid and 50

- 28 ml konc. solne kisline in hičLriramo po dodatku 1,0 g paladija na oglju (5 %-nega) pri sobni temperaturi in normalnem pritisku. Po navzemu 1700 ml (109 % teor.) vodika hidriranje prekinemo, katalizator odfiltriramo in filtrat v vakuumu uparimo na okoli 1/4 volumna. Po dodatku 400 ml vode pustimo kristalizirati nekaj ur pri 5°, odsesamo in z vodo izperemo do nevtralnega, nakar dobimo 5-karbamil-10-okso-10,11dihidro-5H-dibenz[b,f3azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom.- 28 ml conc. of hydrochloric acid and hydrochloride after the addition of 1.0 g of palladium on charcoal (5%) at room temperature and normal pressure. After 1700 ml (109% of theory) of hydrogen was removed, the hydrogenation was discontinued, the catalyst was filtered off and the filtrate was evaporated in vacuo to about 1/4 volume. After addition of 400 ml of water, it was allowed to crystallize for a few hours at 5 °, sucked off and washed with water to neutral, to give 5-carbamyl-10-oxo-10,11 dihydro-5H-dibenz [b, f3azepine, based on the IR spectrum identical with authentic material.

Dobitek: 7»θ g» 78,6 % teor.Yield: 7 »θ g» 78.6% theory.

Do podobnega rezultata pridemo ob uporabi platine na oglju (5 %-ne) kot katalizatorja.A similar result is obtained using platinum on charcoal (5%) as a catalyst.

PRIMER 26EXAMPLE 26

7,0 g (0,025 molov) 5-harbamil-10-nitro-5H-dibenz[b,f3azepina raztopimo v zmesi 100 ml ocetne kisline in 50 ml konc solne kisline. Ob mešanju 15 minut dodajamo pri temperaturi 30 do 40° 12 g železovega prahu, mešamo še 1 uro pri 40°, neraztopljeno odfiltriramo v toplem in še 3-krat izperemo z ocetno kislino. Piltrat popolnoma uparimo v vakuumu, ostanek prevzamemo s 100 ml vode in mešamo več ur. Odfiltriramo, izperemo z vodo do nevtralnega in v vakuumu posušimo pri 60°. Dobimo 5-karbamil-10-okso-10,1l-dihidro-5H-dibenz[b,f3azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom. Dobitek: 5,5 g, 88,6 % teor.7.0 g (0.025 mol) of 5-harbamyl-10-nitro-5H-dibenz [b, f3azepine were dissolved in a mixture of 100 ml of acetic acid and 50 ml of hydrochloric acid conc. After stirring for 15 minutes, 12 g of iron powder are added at 30 to 40 ° C, stirred for another 1 hour at 40 °, filtered undissolved in warm and washed 3 times with acetic acid. The filtrate was completely evaporated in vacuo, the residue taken up with 100 ml of water and stirred for several hours. It was filtered off, washed with water to neutral and dried in vacuo at 60 °. 5-Carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f3azepine is obtained, which is identical to the authentic material on the basis of the IR spectrum. Yield: 5.5 g, 88.6% of theory.

PRIMER 27EXAMPLE 27

7)9 δ (0,03 mole) 5-c iano-10-nit ro-5H-dibenz [b, f]azepina suspendiramo v 150 ml etanola in dodamo 50 ml konc. solne kisline. Pri temperaturi 40° 15 minut dodajamo 15 g železovega prahu oh živahnem mešanju, pri čemer temperatura naraste na 55°. Pustimo še 1 uro mešati pri 55°, neraztopljen material odfiltrirano v toplem in še 5-krat izperemo s po 25 ml etanola. Filtrat uparimo na volumen 80 ml in oh mešanju počasi dodamo 400 ml ledene vode. Odsesamo sivo/belo ohorino, z vodo izperemo do nevtralnega in posušimo v vakuumu pri 80°. Dobimo 5-ciano-10-okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki se po pretapljanju iz etanola tali pri 154 do 156°.7) 9 δ (0.03 mol) of 5-c iano-10-nit ro-5H-dibenz [b, f] azepine was suspended in 150 ml of ethanol and 50 ml of conc. hydrochloric acids. At a temperature of 40 ° for 15 minutes, 15 g of iron powder are added for vigorous stirring, bringing the temperature to 55 °. The mixture is allowed to stir at 55 ° for 1 hour, the insoluble material is filtered off in warm form and washed 5 times with 25 ml of ethanol each. Evaporate the filtrate to a volume of 80 ml and slowly add 400 ml of ice water to the stirring. Suction off the gray / white ohorina, rinse with water and neutral under vacuum at 80 °. 5-cyano-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is obtained, which melts at 154 to 156 ° C after melting from ethanol.

Dobitek: 4,8 g, 68,4 % teor.Yield: 4.8 g, 68.4% of theory.

PRIMER 28EXAMPLE 28

52,6 g (0,2 mola) 5-ciano-10-nitro-5H-dibenz[b,f J azepina suspendiramo v zmesi 400 ml toluola in 200 ml etanola.52.6 g (0.2 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were suspended in a mixture of 400 ml of toluene and 200 ml of ethanol.

Pri dodatku 130 ml konc. solne kisline se material raztopi ob šibkem ugrevanju. Segrejemo na 40° in nato 10 minut dodajamo raztopino 113 S (0,5 molov) SnCl^ · 2 H^O v 90 ml konc. solne kisline. Temperatura naraste na 55° in jo nato še 20 minut držimo na 55°. Pustimo ohladiti, organsko fazo odločimo in vodno fazo še večkrat ekstrahiramo s toluolom. Združene toluolne ekstrakte izperemo z vodo do nevtralnega, posušimo nad natrijevim sulfatom in uparimo v vakuumu. Dobije- 50 ni surovi proizvod suspendiramo s 100 ml izopropanola, odsesamo in hladno izperemo z malo izopropanola. Dobimo 5ciano-10-okso-10,11-dihidro-5H-dibenz[b,f3azepin, ki je identičen s proizvodom, dobljenim po primeru 2?.With the addition of 130 ml conc. hydrochloric acids dissolve the material under weak heating. Heat to 40 ° and then add a solution of 113 S (0.5 mol) SnCl 2 · 2 H 2 O in 90 ml conc. hydrochloric acids. The temperature rises to 55 ° and is then kept at 55 ° for 20 minutes. Allow to cool, decompose the organic phase and extract the aqueous phase several more times with toluene. The combined toluene extracts were washed with water to neutral, dried over sodium sulfate and evaporated in vacuo. The resulting crude product was suspended with 100 ml of isopropanol, filtered off with suction and washed with cold isopropanol. 5cyano-10-oxo-10,11-dihydro-5H-dibenz [b, f3azepine is obtained which is identical to the product obtained from Example 2 ?.

Dobitek: 29,0 g, 62 % teor.Yield: 29.0 g, 62% of theory.

PRIMER 29EXAMPLE 29

5,0 g (0,02 mola) 5-ciano-10-nitro-5H-dibenz[b,f]azepina raztopimo pri 60° v zmesi 80 ml etanola in 80 ml ocente kisline. Ob mešanju 10 minut dodajamo po deležih 10 g cinkovega prahu, pri čemer temperatura naraste na 80°. Po prenehanju reakcije dodamo pri sobni temperaturi 40 ml konc. solne kisline. Reakcijsko zmes mešamo 5 ur, neraztopljeno filtriramo, filtrat uparimo do suhega in ostanek prevzamemo s 50 ml vode. Po večkratnem prekristaliziraaju izločenega ^surovega proizvoda dobimo čist 5-ciano-10-okso-l0,H-dihii?o--5Hdibenz[b,f]azepin, ki je identičen s proizvodom, dobljenim po primeru 27.5.0 g (0.02 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were dissolved at 60 ° in a mixture of 80 ml of ethanol and 80 ml of acetic acid. After stirring for 10 minutes, 10 g of zinc powder are added in portions, increasing the temperature to 80 °. After completion of the reaction, 40 ml of conc. hydrochloric acids. The reaction mixture was stirred for 5 hours, filtered undissolved, the filtrate was evaporated to dryness and the residue was taken up with 50 ml of water. Recrystallisation of the recovered crude product repeatedly yields pure 5-cyano-10-oxo-10, H-dihydro-5Hdibenz [b, f] azepine, which is identical to the product of Example 27.

Dobitek: 2,5 g,5° % teor.Yield: 2.5 g, 5% theory.

PRIMER 50EXAMPLE 50

26,5 g (0,1 mol) 5-ciano-10-nitro-5H-dibenz[b,fjazepina suspendiramo v zmesi 15θ ml ocetne kisline in 100 ml konc. solne kisline. Pri 50° dodajamo ob mešanju po deležih 50 minut 40 g železovega prahu in ob hlajenju držimo temperaturo pri 60°. Še 50 minut mešamo pri 50 do 60°, neraztopljeno odfiltriramo in izperemo z ocetno kislino. Filtratu dodamo26.5 g (0.1 mol) of 5-cyano-10-nitro-5H-dibenz [b, phiazepine were suspended in a mixture of 15θ ml of acetic acid and 100 ml of conc. hydrochloric acids. At 50 °, 40 g of iron powder are added with stirring for 50 minutes and kept at 60 ° C during cooling. The mixture was stirred at 50-60 ° C for another 50 minutes, filtered undissolved and washed with acetic acid. The filtrate was added

- 31' dvojni volumen vode in 3-krat ekstrahiramo s po 100 ml metilenklorida. Združene organske faze izperemo z vodo, posušimo nad. natrijevim sulfatom in uparimo. Kristalni ostanek suspendiramo v 100 ml izopropanola in odsesamo. Tako dobljeni 5ciano-10-okso-l0,11-dihidro-5H-dibenz[b,f]azepin je identičen s proizvodom, dobljenim po primeru 27.- 31 'double the volume of water and extract 3 times with 100 ml of methylene chloride each. The combined organic phases are washed with water, dried over. sodium sulfate and evaporated. The crystalline residue was suspended in 100 ml of isopropanol and aspirated. The thus obtained 5cyano-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is identical to the product obtained from Example 27.

Dobitek: 21,8 g, 95»2 % teor.Yield: 21.8 g, 95 »2% of theory.

PPTMTTR 51PPTMTTR 51

5,2 g (0,02 mola) 5-ciano-10-nitro-5H-dibenz[b,f]azepina suspendiramo v zmesi 100 ml klorbenzola in 50 ml etanola. Pri sledečem dodatku 50 ml konc. solne kisline se segreje zmes na 35°. Pni tej temperaturi dodamo ob živahnem mešanju po deležih v 5 minutah 20 g železovega prahu, pri čemer se reakcijska zmes v nekaj minutah segreje na 60°. Nato pustimo še 3 ure mešati in v tem času ohladiti na 25°, železovo blato odfiltriramo in večkrat izperemo z etanolom in vodo. Iz organske faze filtrata dobimo po izpiranju z vodo, sušenju in uparjenju kristalni surovi proizvod, ki ga prekristaliziramo iz izopropanola. Tako dobljeni 5-ciano-10-okso-10,ndihidro-5H-dibenz[b,f]azepin je identičen s proizvodom, dobljenim po primeru 27·5.2 g (0.02 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were suspended in a mixture of 100 ml of chlorobenzene and 50 ml of ethanol. For the next addition, 50 ml conc. the hydrochloric acid is heated to 35 ° C. At this temperature, 20 g of ferrous iron was added, stirring vigorously, for 5 minutes, with the reaction mixture heated to 60 ° C in a few minutes. It is then allowed to stir for a further 3 hours and cooled to 25 ° in the meanwhile, the sludge filtered off and washed several times with ethanol and water. From the organic phase of the filtrate, crystalline crude product is obtained after washing with water, drying and evaporation, which is recrystallized from isopropanol. The 5-cyano-10-oxo-10, dihydro-5H-dibenz [b, f] azepine thus obtained is identical to the product obtained from Example 27 ·

Dobitek: 3,8 g, 81 % teor.Yield: 3.8 g, 81% of theory.

Z reakcijskim nastavkom, ki smo ga izvedli analogno s toluolom namesto klorbenzolom kot topilom, dobimo 84 % dobitka navedenega končnega proizvoda.The reaction mixture, which was carried out analogously to toluene instead of chlorobenzene as solvent, gave 84% yield of said final product.

PRIMER 52EXAMPLE 52

26,5 g (0,1 mol) 5-ciano-10-nitro-5H-dibenz[b,f]azepina suspendiramo skupaj s 40 g železovega prahu v zmesi 250 ml toluola in 125 ml etanola. Pustimo 75 minut dokapavati 100 ml konc. solne kisline ob intenzivnem mešanju, pri čemer temperatura naraste na 60°. Po 10-urnem mešanju pri sobni tem peraturi reakcijsko zmes obdelamo analogno primeru 5*1« nakar dobimo 5-ciano-10-okso-l0,H-dihidro-5H-dibenz[b,f]azepin, ki je identičen s piuizvoto, dobi jenim po primeru 27·26.5 g (0.1 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were suspended together with 40 g of iron powder in a mixture of 250 ml of toluene and 125 ml of ethanol. Leave to boil for 75 minutes with 100 ml of conc. of hydrochloric acid under vigorous stirring, bringing the temperature to 60 °. After stirring at room temperature for 10 hours, the reaction mixture was treated analogously to Example 5 * 1 'and then 5-cyano-10-oxo-10, H-dihydro-5H-dibenz [b, f] azepine identical to the pyroisote is obtained. obtained by example 27 ·

Dobitek: 19,8 g, 84,6 % teor.Yield: 19.8 g, 84.6% of theory.

PRIMER 55EXAMPLE 55

Ob hlajenju z ledom pustimo 2,0 g (0,0085 molov) 5ciano-10-okso-10,11-dihidro-5H-dibenz[b,f]azepina v 10 ml konc. žveplove kisline stati 50 minut pri 0 do 5° in nato raz topino dokapamo v 200 ml ledene vode. Kosmičasto oborino odsesamo, z vodo izperemo do nevtralnega, posušimo in prekristaliziramo iz izopropanola. Dobimo 5-karbamil-10-okso-10,11dihidro-5H-dibenz[b,f]azepin, ki je na osnovi. IR-spektra identičen z avtentičnim materialom.Allowing 2.0 g (0.0085 mol) of 5cyano-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine in 10 ml conc. The sulfuric acid was allowed to stand at 0 to 5 ° for 50 minutes and then the solution was added to 200 ml of ice water. The hairy precipitate was filtered off with suction, washed with water until neutral, dried and recrystallized from isopropanol. 5-Carbamyl-10-oxo-10,11 dihydro-5H-dibenz [b, f] azepine is obtained. IR spectrum identical to authentic material.

Dobitek: 1,4 g, 65 % teor.Yield: 1.4 g, 65% theory.

PRIMER 54EXAMPLE 54

Zmes 1,0 g (0,0045 molov) 5-ciano-10-okso-10,11dihidro-5H-dibenz[b,f]azepina, 8 ml ocetne kisline in 2 ml konc. žveplove kisline mešamo 48 ur do popolnega raztapljanja. Dobljeno raztopino dokapamo ob mešanju v 100 ml ledene vode, kosmičasto oborino odfiltriramo, z vodo izperemo do ne- - -33-vtralnega in posušimo pri 50° v vakuumu, nakar dobimo 5karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom. Dobitek: 0,9 g, 84 % teor.A mixture of 1.0 g (0.0045 mol) of 5-cyano-10-oxo-10,11 dihydro-5H-dibenz [b, f] azepine, 8 ml of acetic acid and 2 ml of conc. The sulfuric acid was stirred for 48 hours until complete dissolution. The resulting solution was added dropwise with stirring in 100 ml of ice water, the hairy precipitate was filtered off, washed with water until non- - -33-vented and dried at 50 ° in vacuo to give 5carbamyl-10-oxo-10,11-dihydro-5H- dibenz [b, f] azepine, which is identical to the authentic material on the basis of the IR spectrum. Yield: 0.9 g, 84% theory.

PRIMER 35EXAMPLE 35

Raztopino 2,0 g (0,0085 molov) 5-ciano-1Q-okso-10,11dihidro-5H-dibenz[b,f]azepina v 20 ml 98 %-ne mravljinčne kisline 8 ur segrevamo v kopeli 110 do 120°. Kato raztopino vnesemo v 100 ml ledene vode, filtriramo, izperemo z vodo do nevtralnega in sušimo pri 50° v vakuumu. Dobljeni 5-karbamil10-okso-10,11-dihidro-5H-dibenz[b,f]azepin je na osnovi IR-spektra identičen z avtentičnim materialom.A solution of 2.0 g (0.0085 mol) of 5-cyano-1Q-oxo-10,11 dihydro-5H-dibenz [b, f] azepine in 20 ml of 98% formic acid was heated in a bath 110 to 120 ° for 8 hours . The solution was introduced into 100 ml of ice water, filtered, washed with water to neutral and dried at 50 ° in vacuo. The resulting 5-carbamyl10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is identical on the basis of the IR spectrum with the authentic material.

Dobitek: 1,8 g, 84 % teor.Yield: 1.8 g, 84% theory.

PRIMER 36EXAMPLE 36

1,0 g (0,0043 molov) 5-ciano-10(1l)-okso-10,11-dihidro 5H-dibenz[b,f]azepina zdrgnemo z 20 gpolifosforjeve kisline in za popolno raztapljanje več dni pustimo stati pri sobni temperaturi. Nato v majhnih deležih dodamo prebitek vode, odsesamo rumenkasto belo oborino in z vodo izperemo do nevtralnega. Po prekristaliziranju iz klorbenzola dobimo 5-karbamil10-okso-10,11-dihidro-5H-dibenz[b,f]azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom.1.0 g (0.0043 mol) of 5-cyano-10 (1 l) -oxo-10,11-dihydro 5H-dibenz [b, f] azepine are triturated with 20 g of polyphosphoric acid and allowed to stand at room temperature for several days temperature. Then in small portions add the excess water, suction off a yellowish white precipitate and rinse with water until neutral. Recrystallization from chlorobenzene yields 5-carbamyl10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine, which is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 0,75 g, 70 % teor.Yield: 0.75 g, 70% of theory.

- — 34PRIMER 37- - 34 EXAMPLE 37

K suspenziji 1,0 g (0,0043 mole) 5-ciano-10-okso10,11-dihidro-5H-dibenz[b,f]azepina v 20 ml metanola pustimo dotekati ob mešanju pri sobni temperaturi 5,θ ml HgOg (30 %nega) in po 3θ minutah dodamo 5,0 g natrijevega hidrogenkarbonata. Po 3-urnem mešanju neraztopljeno odfiltriramo in 1-krat izperemo z metanolom kot tudi večkrat z vodo, nakar dobimo 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f]azepin ki je na osnovi IR-spektra identičen z avtentičnim,materialom Dobitek: 0,6 g, 55 % teor.To a suspension of 1.0 g (0.0043 mol) of 5-cyano-10-oxo10,11-dihydro-5H-dibenz [b, f] azepine in 20 ml of methanol was allowed to stir while stirring at room temperature 5, θ ml of HgOg ( 30%) and 5.0 g of sodium hydrogen carbonate are added after 3θ minutes. After stirring for 3 hours, the solution is filtered off and washed once with methanol as well as repeatedly with water, to give 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine, which is based on IR -spectrum identical to authentic material Yield: 0.6 g, 55% theory.

PRIMER 38EXAMPLE 38

V suspenzijo 3,° g (0,013 molov) 5-ciano-10-okso-10,11dihidro-5H-dibenz[b,f]azepina v znesi 30 ml ocetne kisline in 3 ml vode toliko časa ob mešanju uvajamo plinski BP^, dokler ne poneha najprej močno eksotermna reakcija, in držimo temperaturo z zunanjim hlajenjem na 5θ°· Pustimo ohladiti in k bistri reakcijski raztopini ob hlajenju z ledom dokapamo 100 ml vode, odfiltriramo brezbarvno oborino, odstanek na filtru izperemo z vodo do nevtralnega in prekristaliziramo iz acetonitrila. Dobljeni 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f]azepin je na osnovi IR-spektra identičen z avtentič nim materialom.To the suspension of 3, ° g (0.013 mol) of 5-cyano-10-oxo-10,11 dihydro-5H-dibenz [b, f] azepine in the amount of 30 ml of acetic acid and 3 ml of water, gas BP is introduced while stirring. until the exothermic reaction is strong, keeping the temperature with external cooling at 5θ °. Allow to cool and add 100 ml of water to the clear reaction solution under ice-cooling, filter the colorless precipitate, wash the filter residue with water to neutralize and recrystallize . The resulting 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 2,3 g, 71 % teor.Yield: 2.3 g, 71% of theory.

PRIMER 39EXAMPLE 39

2,0 g (0,0085 molov) 5-cian.o-10-okso-10,11-dihidro-5Hdibenz[b,fjazepina vnesemo po deležih ob mešanju v 40 ml raz--35- topine 10 utež.% BP^ v ocetni kislini, nakar v 15 minutah pri 20° dobimo bistro raztopino. Po 3-umem stanju dodamo ob hlajenju z ledom 100 ml vode in raztopino z dodatkom raztopine natrijevega : hidroksida naravnamo na pH 6. Izločeni suro vi 5-karbamil-10-okso-10,11 -dihidro-5H-dibenz [b, f 3 a zepin odsesamo, izperemo z vodo in posušimo. Ha osnovi IR-spektra je identičen z avtentičnim materialom.2.0 g (0.0085 mol) of 5-cyan.-10-oxo-10,11-dihydro-5Hdibenz [b, phiazepine are introduced by proportions while stirring in 40 ml of a solution of 35-solids of 10 wt.% BP ^ in acetic acid, then a clear solution is obtained within 20 minutes at 20 °. After 3 ml, 100 ml of water were added under ice-cooling and the solution was adjusted to pH 6 with the addition of sodium hydroxide solution. The crude vi 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f 3 a The zepin is sucked off, washed with water and dried. The Ha-based IR spectrum is identical to the authentic material.

Dobitek: 1,6 g, 74,8 % teor.Yield: 1.6 g, 74.8% of theory.

PRIMER 40EXAMPLE 40

K suspenziji 11,7 δ (0,05 molov) 5-ciano-10-okso-10,11 dihidro-5H-dibenz[b,f]azepina v 60 ml ocetne kisline dodamoTo a suspension of 11.7 δ (0.05 mol) of 5-cyano-10-oxo-10,11 dihydro-5H-dibenz [b, f] azepine in 60 ml of acetic acid

10,3 δ (θ»θ55 molov) kompleksa BP^ . 2 CH^COOH in pustimo, da temperatura brez zunanjega hlajenja naraste na 35°, pri čemer se izhodna snov počasi raztopi. Po okoli 1 uri se začne kristalizirati BP^-adukt. 4 ure mešamo pri sobni temperaturi, odfiltriramo in izperemo z ocetno kislino. Vmesni proizvod suspendiramo v 100 ml vode in po dodatku natrijevega acetata do pH 6 mešamo 1 uro. Po odsesanju iz izpiranju z vodo dobimo 9,0 g 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f]azepina, ki je na osnovi IR-spektra identičen z avtentičnim materialom Iz filtrata vmesnega proizvoda lahko po uparjenju s frakcioni rano kristalizacijo iz metanola/vode dobimo nadaljnja 1,2 g proizvoda.10.3 δ (θ »θ55 moles) of the BP ^ complex. 2 CH ^ COOH and allow the temperature to rise to 35 ° without external cooling, slowly dissolving the starting material. After about 1 hour the BP ^ -duct begins to crystallize. The mixture was stirred at room temperature for 4 hours, filtered off and washed with acetic acid. The intermediate was suspended in 100 ml of water and stirred for 1 hour after addition of sodium acetate to pH 6. Suction extraction with water gave 9.0 g of 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine, which is identical on the basis of the IR spectrum with authentic material. a further 1.2 g of product can be obtained after evaporation by fractional crystallization from methanol / water.

Celoten dobitek: 10,2 g, 81 % teor.Overall yield: 10.2 g, 81% of theory.

- 36 PRIMER 41- 36 EXAMPLE 41

K suspenziji 23,4 g (0,1 mola) 5-ciano-10-okso-10,11dihidro-5H-dibenz[b,f )azepina v 40 ml ocetne kisline dodamo 50 ml raztopine 15 utež.% BF^ v ocetni kislini in mešamo, dokler ne poneba šibko razbijanje toplote. Z dodajanjem 15 ml vode po kapljicah ob porastu temperature na 40 do 45° dobimo bistro temnomodro raztopino. Držimo 15 minut na 40° in nato počasi dodamo nadaljnjih 135 ml vode. Dobljeno kristalno obo-* rino več ur mešamo pri sobni temperaturi, nato odsesamo in izperemo z vodo do nevtralnega. Po sušenju pri 5θ° v vakuumu dobimo 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,fJazepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom.To a suspension of 23.4 g (0.1 mol) of 5-cyano-10-oxo-10,11 dihydro-5H-dibenz [b, f) azepine in 40 ml of acetic acid was added 50 ml of a solution of 15 wt% BF ^ in acetic acid acid and stir until a weak heat dissipates. Adding 15 ml of water dropwise, increasing the temperature to 40 to 45 °, gives a clear dark blue solution. Hold for 40 minutes at 40 ° and then slowly add a further 135 ml of water. The resulting crystalline precipitate was stirred at room temperature for several hours, then sucked off and washed with water until neutral. Drying at 5θ ° in vacuo gave 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine, which is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 24,2 g, 96,0 % teor.Yield: 24.2 g, 96.0% of theory.

PRIMER 42EXAMPLE 42

V suspenzijo 23,4 g (0,1 mola) 5-ciano-10-okso-10,11dihidro-5H-dibenz[b,f]az'epina v 230 ml klorbenzol a pustimo pri sobni temperaturi ob mešanju hitro dotekati zmes 15,4 ml (0,11 molov) kompleksa BF^ . 2 CH^COOH z 38 ml ocetne kisline. Ob rahlem ugrevanju nastane bistra rjavkasta raztopina, iz katere se po okoli 10 minutah obori krisfsLen BF^-adukt. Držimo 3θ minut na 5°, odfiltriramo in izperemo s klorbenzol om. Suhi vmesni proizvod suspendiramo v 200 ml vode, mešamo 3θ minut, odsesamo in z vodo izperemo do nevtralnega. Po sušenju v vakuumu pri 60° dobimo 5-karbamil-10-okso-10,11-dihidro-5Hdibenz[b,f]azepin , ki je na osnovi IR-spektra identičen z avtentičnim materialom.A suspension of 23.4 g (0.1 mol) of 5-cyano-10-oxo-10,11 dihydro-5H-dibenz [b, f] azepine in 230 ml of chlorobenzene was allowed to stir rapidly at room temperature with stirring 15 , 4 ml (0.11 moles) of the BF ^ complex. 2 CH ^ COOH with 38 ml acetic acid. A slight warming results in a clear brownish solution from which the crystalline BF4-adduct precipitates after about 10 minutes. Hold for 3θ minutes at 5 °, filter and wash with chlorobenzene. The dry intermediate was suspended in 200 ml of water, stirred for 3θ minutes, filtered off with suction and washed with water until neutral. Drying in vacuo at 60 ° yields 5-carbamyl-10-oxo-10,11-dihydro-5Hdibenz [b, f] azepine, which is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 24^1 g, 93,6 % teor.Yield: 24 ^ 1 g, 93.6% of theory.

-ΎΓPKIMER 43-ΎΓPKIMER 43

1,0 g (0,004 mole) 5-ciano-10-nitro-5H-dibenz[b,f]azepina raztopimo pri 60° v zmesi 40 ml etanola in 20 ml ocetne kisline in ob živahnem mešanju v teku 10 minut dodamo 2,0 g cinkovega prahu. Pustimo 15 minut mešati, neraztopljeno filtriramo v toplem ter izperemo z etanolom in vodo. Filtrat uparimo do suhega in prevzamemo v 50 ml vode. Po odsesanju, izpiranju z vodo in sušenju dobimo surov 5-ciano-10izonitrozo-10,11-dihidro-5H-dibenz[b,f]azepin,ki se po prekristaliziranju iz etanola tali pri 185° ob razpadu. Analitski in spektroskopski podatki so v skladu z domnevano strukturo. Dobitek: 0,9 g, 95 % teor.1.0 g (0.004 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine are dissolved at 60 ° in a mixture of 40 ml of ethanol and 20 ml of acetic acid and stirring vigorously for 10 minutes, 2. 0 g of zinc powder. The mixture is allowed to stir for 15 minutes, filtered undissolved in warm water and washed with ethanol and water. The filtrate was evaporated to dryness and taken up in 50 ml of water. After suction, washing with water and drying, crude 5-cyano-10isonitroso-10,11-dihydro-5H-dibenz [b, f] azepine is obtained which, after crystallization from ethanol, melts at 185 ° on decay. The analytical and spectroscopic data are consistent with the assumed structure. Yield: 0.9 g, 95% theory.

PRIMER 44 g (0,19 ,molov) 5-ciano-10-nitro-5H-dibenz[b,f]azepina raztopimo v 500 ml piridina in po dodatku 10 g paladija na oglju (5 %-nega) hidriramo pri sobni temperaturi in normalnem pritisku. Po 2 urah je navzem vodika 7960 ml (93 % teor) in hidriranje poneha. Katalizator odfiltriramo, topilo odparimo v vakuumu in dobljeni surovi proizvod prekristaliziramo iz metanola/vode, nakar dobimo 5-ciano-10-izonitrozo10,11-dihidro-5H-dibenz[b,f]azepin, ki je identičen s proizvo dom, dobljenim po primeru 43.EXAMPLE 44 g (0.19 mol) of 5-cyano-10-nitro-5H-dibenz [b, f] azepine were dissolved in 500 ml of pyridine and, after the addition of 10 g of palladium on carbon (5%), was hydrogenated at room temperature. and normal pressure. After 2 hours, the hydrogen uptake was 7960 ml (93% of theory) and the hydrogenation was gone. The catalyst was filtered off, the solvent was evaporated in vacuo and the crude product obtained was recrystallized from methanol / water to give 5-cyano-10-isonitroso 10,11-dihydro-5H-dibenz [b, f] azepine identical to the product obtained by Case 43.

Dobitek: 35,6 g, 75,2 % teor.Yield: 35.6 g, 75.2% of theory.

PRIMER 45EXAMPLE 45

2,5 g (0,01 mol) 5-ciano-10-izonitrozo-10,11-dihidro- 385H-dibenz[b,f3azepina suspendiramo v zmesi 25 ml toluola, ml etanola in 10 ml konc. solne kisline. Suspenzijo 30 minut mešamo pri 50°, odločimo toluolno fazo in jo v vakuumu uparimo do suhega. Kristalni ostanek suspendiramo v 10 ml izo< propanola, odsesamo in 2-krat izperemo z izopropanolom, nakar dobimo 5-c i ano -10-ok so -10,11 -dihi dro- 5H-dibenz [ b, f 3 a z epin, ki je identičen s proizvodom, dobljenim po primeru 27. Dobitek: 0,8 g, 35 % teor.2.5 g (0.01 mol) of 5-cyano-10-isonitroso-10,11-dihydro-385H-dibenz [b, 3azepine were suspended in a mixture of 25 ml of toluene, ml of ethanol and 10 ml of conc. hydrochloric acids. The suspension was stirred at 50 ° for 30 minutes, the toluene phase was decided and evaporated to dryness in vacuo. The crystalline residue was suspended in 10 ml of iso <propanol, filtered off with suction and washed twice with isopropanol, to give 5-ano-10-ok are -10,11 -dihydro-5H-dibenz [b, f 3 az epine, which is identical to the product obtained from Example 27. Yield: 0.8 g, 35% of theory.

PRIMER 46EXAMPLE 46

26,3 g (mol) 5-ciano-10-nitro-5H-dibenz[b,f3azepina suspendiramo v zmesi 265 ml etilenglikol-monoetiletra in 75 ml konc. solne kisline. Pri 40° v 40 minutah dodamo v majhnih deležih 40 g železovega prahu in temperaturo držimo z zunanjim hlajenjem pri 40°. Mešamo še 2 uri pri sobni temperaturi, nato segrejemo na 80°, pri čemer se izločeni proizvod spet topi, in filtriramo skozi segreto nučo, ki jo nato izperemo z etilenglikol-monoetiletrom. Kristalizacijo, ki se začne v filtratu, dokončamo z dodatkom 200 ml vode. Po 1-urnem hlajenju na ledeni kopeli filtriramo in izperemo z zmesjo etilenglikol-monoetiletra in vode v razmerju 1:1. Dobimo 5-ciano-10-okso-10,11-dihidro-5H-dibenz-Ib,f3azepin, ki ga s primerjavo IR-spektrov identificiramo z materialom iz primera 27.26.3 g (mol) of 5-cyano-10-nitro-5H-dibenz [b, 3azepine were suspended in a mixture of 265 ml of ethylene glycol monoethyl ether and 75 ml of conc. hydrochloric acids. 40 g of iron powder are added in small portions at 40 ° for 40 minutes and the temperature is maintained by external cooling at 40 °. The mixture was stirred for 2 hours at room temperature, then warmed to 80 °, whereupon the recovered product was melted again, and filtered through a heated flask, which was then washed with ethylene glycol monoethyl ether. The crystallization starting in the filtrate was completed by the addition of 200 ml of water. After cooling for 1 hour in an ice bath, it was filtered and washed with a mixture of ethylene glycol monoethyl ether and water in a 1: 1 ratio. 5-cyano-10-oxo-10,11-dihydro-5H-dibenz-Ib, f3azepine was obtained, which was identified by the material of Example 27 by comparison of the IR spectra.

Dobitek: 19,0 g, 81,2 % teor.Yield: 19.0 g, 81.2% of theory.

Najboljši način za gospodarsko izkoriščanje izumaThe best way to make economic use of the invention

6,0 g (0,027 molov) 5-ciano-5H-dibenz[b,f3azepina raztopimo v zmesi 80 ml acetanbidrida in 20 ml ocetne kisline. Segrejemo na 5θ° im po kapljicah Ί 1/2 ure dodajamo raztopine 5,6 g (0,08 molov) natrijevega nitrita v 10 ml vode, pri čemer ne pustimo, da bi temperatura narasla nad 55° · Še 2 uri držimo pri 5θ° im mato topilo oddestiliramo pri zmanjšanem pritisku in temperaturi kopeli 5θ°· Ostanek 2-krat digeriramo s po 100 ml ledene vode in prevzamemo v 80 ml etanola. Po večurnem stanju pri 0° odsesamo izločene rumene kristale in izperemo z malo etanola. Dobljeni 5-ciano-10-nitro-5H-dibenz[b,f3azepin se tali pri 175 do 17θ° oh razpadu.6.0 g (0.027 moles) of 5-cyano-5H-dibenz [b, f3azepine were dissolved in a mixture of 80 ml of acetanhydride and 20 ml of acetic acid. Heat to 5θ ° im dropwise Ί 1/2 hour add solutions of 5.6 g (0.08 mol) of sodium nitrite in 10 ml of water, without allowing the temperature to rise above 55 ° · Hold for another 2 hours The mate solvent was distilled off under reduced pressure and a bath temperature of 5θ °. The residue was digested twice with 100 ml of ice water each and taken up in 80 ml of ethanol. After an evening condition at 0 °, suction off the separated yellow crystals and wash with little ethanol. The resulting 5-cyano-10-nitro-5H-dibenz [b, f3azepine melts at 175 to 17θ ° ohm decay.

Dobitek: 5»2 g, 72 % teor.Yield: 5 »2 g, 72% theory.

Suspenziji 26,3 g (0,1 mola) 5-ciano-10-nitro-5H-dibenz[b,flazepina v 100 ml ocetne kisline dodamo pri sobni temperaturi 50 ml raztopine 15 utež.% BP^ v ocetni kislini (= 0,11 molov). Pri tem temperatura naraste počasi na 34° ob popolnem raztapljanju izhodne snovi. Pri 3θ° 5 minut dodajamo 3θ ml vode, kar vodi do ponovnega porasta temperature na 37°. Rri tej temperaturi v 20 minutah, po deležih vnesemo 40 g železovega prahu, pri čemer vzdržujemo temperaturo z občasnim hlajenjem na 65 do 7θ°. Ro prenehanju eksotermne reakcije mešamo še 15 minut in nato odfiltriramo anorganski material, ki ga nato 3-krat izperemo z malo ocetne kisline.To a suspension of 26.3 g (0.1 mol) of 5-cyano-10-nitro-5H-dibenz [b, flazepine in 100 ml of acetic acid was added at room temperature 50 ml of a solution of 15% by weight BP ^ in acetic acid (= 0 , 11 moles). The temperature rises slowly to 34 ° with complete dissolution of the starting material. At 3θ ° for 5 minutes, 3θ ml of water is added, causing the temperature to rise again to 37 °. At this temperature within 20 minutes, 40 g of iron powder is introduced in portions, maintaining the temperature with occasional cooling to 65 to 7θ °. After the exothermic reaction was stopped, the mixture was stirred for a further 15 minutes and then the inorganic material was filtered off, which was then washed 3 times with a little acetic acid.

—Αύ ——Αύ -

Celoten filtrat dokapamo ob dobrem mešanju v 1 1/2 1 vode, nastalo oborino odfiltriramo po 2-umem mešanju in z vodo izperemo do nevtralnega. Po sušenju pri 60° v vakuumu dobimo 5-karbamil-10-okso-10,11-dihidro-5H-dibenz[b,f] azepin, ki je na osnovi IR-spektra identičen z avtentičnim materialom.The whole filtrate was added dropwise with good stirring into 1 1/2 l of water, the resulting precipitate was filtered off after 2 ml stirring and washed with water until neutral. After drying at 60 ° in vacuo, 5-carbamyl-10-oxo-10,11-dihydro-5H-dibenz [b, f] azepine is obtained, which is identical to the authentic material on the basis of the IR spectrum.

Dobitek: 23,0 g, 91,2% teor.Yield: 23.0 g, 91.2% of theory.

Claims

1. Postopek za pripravo okso spojine s formulo III λ' Λ · * i u h i \ A _N / V (III)1. A process for the preparation of an oxo compound of formula III λ 'Λ · * iuhi \ A _N / V (III)

CONH, označen s tem, da 5-ciano-5H-dibenz/b,f/azepin s formulo • *⁼* / v v \ i n i’ i \^/X N ^ZlCONH, characterized in that 5-cyano-5H-dibenz / b, f / azepine of the formula • * ⁼ * / vv \ in i 'i \ ^{/ X} N ^Z l

CN (I) nitriramo z obdelavo s solitrovo kislino, z dušikovim tetroksidom, v danem primeru v zmesi s kisikom, ali z didušikovim tetroksidom v inertnem topilu pri 0° do 120° in dobljeni 5-ciano10-nitro-5H dibenz/b,f/azepin s formulo tCN (I) is nitrated by treatment with nitric acid, with nitrogen tetroxide, optionally in admixture with oxygen, or with nitrous tetroxide in an inert solvent at 0 ° to 120 °, to give 5-cyano10-nitro-5H dibenz / b, f / azepine of formula t

• · = · · ^\/ \/ \• · = · · ^ \ / \ / \

I H 11 I (II)I H 11 I (II)

V ^X N / VIn ^X N / V

II

CN bodisi z obdelavo z raztopino borovega trifluorida v nižjialkankarboksilni kislini ali halogenižjialkankarboksilni kislini in nato z vodo ali s kislo hidrolizo hidroliziramo v 5karbamoil-10-nitro-5H-dibenz/b,f/azepin s formuloCN, either by treatment with a solution of boron trifluoride in a lower alkanecarboxylic acid or a halogenoalkanecarboxylic acid and then hydrolyzed with water or acid hydrolysis to 5carbamoyl-10-nitro-5H-dibenz / b, f / azepine of the formula

N0_ . ² * · = · / V \/N0_. ² * · = · / V \ /

I II II J (IV)I II II J (IV)

V ^X _N / V’V ^X _N / V '

II

C0NH₂ C0NH ₂

42- in tega s pomočjo katalitsko aktiviranega ali nascentnega vodika ob kislih pogojih reduciramo v 5-karbamoil-10-okso-10,11-dihidro-5H-dibenz/b,f/azepin (III) ali z obdelavo s katalitsko aktiviranim ali nascentnim vodikom ali kositrovimiII) kloridom ob kislih pogojih direktno reduciramo v 5-ciano-10-okso-10,11dihidro-5H-dibenz/b,f/azepin s formulo42, and this is reduced to 5-carbamoyl-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine (III) by catalytically activated or nascent hydrogen under acidic conditions or by treatment with catalytically activated or nascent under acidic conditions, hydrogen or tin II) chloride is directly reduced to 5-cyano-10-oxo-10,11 dihydro-5H-dibenz / b, f / azepine of the formula

II /’ *\ /\ i ll II 1 (V)II / '* \ / \ i ll II 1 (V) |

·. · · ··. · · ·

II

CN oz. z obdelavo s katalitsko aktiviranim ali nascentnim vodikom najprej reduciramo v 5-ciano-10-izonitro-10,11-dihidro-5H- dibenz/b , f /azepin s formulo NOHCN oz. by treatment with catalytically activated or nascent hydrogen, it is first reduced to 5-cyano-10-isonitro-10,11-dihydro-5H-dibenz / b, f / azepine of the formula NOH

II • · — · · /\/ \/ XII • · - · · / \ / \ / X

I Γι ιί Ϊ (VI) • · · · „ / \ • N ·I Γι ιί Ϊ (VI) • · · · „/ \ • N ·

II

CN z*.CN with *.

tega nato ob kislih pogojih hidroliziramo v 5-ciano-10-okso10,11-dihidro-5H-dibenz/b,f/azepin (V) in vsakokrat reakcijski proizvod s formulo V z obdelavo z raztopino borovega trifluorida v ocetni kislini in nato z vodo, s kislo hidrolizo ali z obdelavo z vodikovim peroksidom v prisotnosti alkalijskega ali zemeljskoalkalijskega hidroksida ali alkalijskega bikarbonata hidroliziramo v 5-karbamoil-10-okso-10,11-dihidro-5-dibenzazepin (III),this is then hydrolyzed under acidic conditions to 5-cyano-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine (V), and each time a reaction product of formula V is treated with a solution of boric trifluoride in acetic acid and then with water, by acid hydrolysis or by treatment with hydrogen peroxide in the presence of alkali or alkaline earth metal hydroxide or alkali bicarbonate, is hydrolyzed to 5-carbamoyl-10-oxo-10,11-dihydro-5-dibenzazepine (III),

- 43- 43

2l Postopek po zahtevku 1, označen s tem, da za nitriranje 5-ciano-5H-dibenz/b,f/azepina kot topilo uporabimo nižje alkankarboksilne ali halogennižjialkankarboksilne kisline z vsakokrat do 4 atomi ogljika ali njihove anhidride ali zmesi takih karboksilnih kislin z ustreznimi anhidridi.2l A process according to claim 1, characterized in that the lower alkanecarboxylic or halogenatedalkanecarboxylic acids of up to 4 carbon atoms or their anhydrides or mixtures of such carboxylic acids are used as the solvent for the nitration of 5-cyano-5H-dibenz / b, f / azepine anhydrides.

3. Postopek po zahtevku 2, označen s tem, da kot topilo uporabimo ocetno kislino, acetannidrid ali njune zmesi.Process according to claim 2, characterized in that acetic acid, acetannidride or mixtures thereof are used as the solvent.

4. Postopek po enem od zahtevkov 1 do 3, označen s tem, da uporabimo razmerje izhodne snovi 5-ciano-5H-dibenz/b,f/diazepina proti topilu (teža/volumen) 1:3 do 1:30.Process according to one of Claims 1 to 3, characterized in that a 5-cyano-5H-dibenz / b, f / diazepine to solvent ratio (weight / volume) of 1: 3 to 1:30 is used.

5. Postopek po enem od zahtevkov 1 do 4, označen s tem, da nitriranje izvedemo v temperaturnem območju okoli 0 do 120°C zlasti 40 do 80°C.Process according to one of Claims 1 to 4, characterized in that the nitriding is carried out in a temperature range of about 0 to 120 ° C, in particular 40 to 80 ° C.

6. Postopek po zahtevku 1, označen s tem, da izvedemo kislo hidrolizo 5-ciano-10-nitro-5H-dibenz/b,f/azepina s pomočjo mineralnih kislin ali mravljinčne kisline in vode.Process according to claim 1, characterized in that the acid hydrolysis of 5-cyano-10-nitro-5H-dibenz / b, f / azepine is carried out with the help of mineral acids or formic acid and water.

7. Postopek po zahtevku 1, označen s tem, da izvedemo obdelavo 5-ciano-10-nitro-5H-dibenz/b,f/azepina s pomočjo borovega trifluorida v ekvimolski količini ali v majhnem prebitku in z ocetno kislino.Process according to claim 1, characterized in that the treatment of 5-cyano-10-nitro-5H-dibenz / b, f / azepine is carried out with boron trifluoride in an equimolar amount or in a small excess and with acetic acid.

8. Postopek po zahtevku 7, označen s tem, da nastalo definirano BF^-adicijsko spojino 5-karbamoil-10-nitro-5H-dibenz/b,f/azepina izoliramo v čisti obliki in z obdelavo z vodo prevedemo v 5-karbamoil-10-nitro-5H-dibenz/b,f/azepin s formulo IV.Process according to claim 7, characterized in that the resulting defined BF ^ -addition compound 5-carbamoyl-10-nitro-5H-dibenz / b, f / azepine is isolated in pure form and converted to 5-carbamoyl by treatment with water -10-nitro-5H-dibenz / b, f / azepine of formula IV.

9. Postopek po enem od zahtevkov 6 do 8, označen s tem, da hidrolizo izvedemo v prisotnosti nadaljnjega inertnega tonila .Process according to one of Claims 6 to 8, characterized in that the hydrolysis is carried out in the presence of further inert tonnage.

- 4ti 10. Postopek po zahtevku 9, označen s tem, da uporabimo topilo aromatskega značaja.Process according to claim 9, characterized in that a solvent of an aromatic character is used.

11. Postopek po zahtevku 10, označen s tem, da kot nadaljnje topilo uporabimo klorbenzol.Process according to claim 10, characterized in that chlorobenzene is used as a further solvent.

12. Postopek po zahtevku 1, označen s tem, da redukcijo 5-ciano-10-nitro-5H-dibenz/b,f/azepina II v 5-karbamoil-10nitro-5H-dibenz/b,f/azepin izvedemo s pomočjo vodika v prisotnosti katalizatorja plemenite kovine.Process according to claim 1, characterized in that the reduction of 5-cyano-10-nitro-5H-dibenz / b, f / azepine II to 5-carbamoyl-10nitro-5H-dibenz / b, f / azepine is carried out by hydrogen in the presence of a precious metal catalyst.

13. Postopek po zahtevku 12, označen s tem, da uporabimo katalizator paladij na oglju.Process according to claim 12, characterized in that a charcoal palladium catalyst is used.

14. Postopek po zahtevku 12, označen s tem, da redukcijo 5-ciano-10-nitro-5H dibenz/b,f/azepina II v 5-karbamoil-10nitro-5H-dibenz/b,f/azepin izvedemo s pomočjo nascentnega vodika z obdelavo primerne kovine v kislini.Process according to claim 12, characterized in that the reduction of 5-cyano-10-nitro-5H dibenz / b, f / azepine II to 5-carbamoyl-10nitro-5H-dibenz / b, f / azepine is carried out by nascent hydrogen by treating suitable metal in acid.

15. Postopek po zahtevku 14, označen s tem, da reduciramo s pomočjo železa v mineralni kislini ali nižji alkankarboksilni kislini z do 4 atomi ogljika ali njunih mešanicah.A process according to claim 14, characterized in that it is reduced by iron in the mineral acid or lower alkanecarboxylic acid with up to 4 carbon atoms or mixtures thereof.

16. Postopek po zahtevku 15, označen s tem, da reduciramo s pomočjo železa v zmesi ocetne in solne kisline.16. A process according to claim 15, characterized in that it is reduced by iron in a mixture of acetic and hydrochloric acid.

17. Postopek po enem od zahtevkov 1 do 16, označen s tem, da za pretvorbo spojine s formulo II v spojino s formulo III potrebne redukcijske in hidrolizne ukrepe izvedemo v istem reakcijskem nastavku brez izoliranja vmesnega proizvoda s formulo IV.Process according to one of Claims 1 to 16, characterized in that for the conversion of the compound of formula II into the compound of formula III, the necessary reduction and hydrolysis steps are carried out in the same reaction sequence without isolating the intermediate of formula IV.

18. Postopek po zahtevku 1, označen s tem, da redukcijo 5-ciano-10-nitro-5H dibenz/b,f/azepina v 5-ciano-10-okso10,11-dihidro-5H-dibenz/b,f/azepin izvedemo s pomočjo nascent- Umnega vodika z obdelavo primerne kovine v kislini.Process according to claim 1, characterized in that the reduction of 5-cyano-10-nitro-5H dibenz / b, f / azepine to 5-cyano-10-oxo 10,11-dihydro-5H-dibenz / b, f / azepine is carried out with the aid of nascent hydrochloric acid by treatment of a suitable metal in acid.

19. Postopek po zahtevku 18, označen s tem, da reduciramo s pomočjo železa ali cinka v mineralni kislini.A process according to claim 18, characterized in that it is reduced by the use of iron or zinc in a mineral acid.

20. Postopek po zahtevku 1, označen s tem, da za redukcijo 5-ciano-10-nitro-5H dibenz/b,f/azepina ^v 5-ciano-10okso-10,11-dihidro-5H-dibenz/b,f/azepin uporabimo SnCl^^H^O21. Postopek po enem od zahtevkov 18 do 20, označen s tem, da redukcijo izvedemo ·ν prisotnosti nižjega alkanola zProcess according to claim 1, characterized in that for the reduction of 5-cyano-10-nitro-5H dibenz / b, f / azepine ^to 5-cyano-10oxo-10,11-dihydro-5H-dibenz / b, f / azepine SnCl ^^ H ^ O21 is used. Process according to one of Claims 18 to 20, characterized in that the reduction is carried out in the presence of lower alkanol by

1 do 4 atomi ogljika, nižjialkoksinižjialkanola z vsakokrat do 4 atomi ogljika v nižjem alkoksilnem in nižjem alkanolnem delu in/ali topila aromatskega značaja kot dodatnega topila.1 to 4 carbon atoms, lower alkoxysilanes of ethanol with up to 4 carbon atoms each in lower alkoxyl and lower alkanol moieties and / or solvents of an aromatic nature as an additional solvent.

22. Postopek po enem od zahtevkov 18 do 21, označen s tem, da redukcijo izvedemo v prisotnosti nižjega alkiletra etilenglikola, kjer ima nižji alkil do 4 atome ogljika.Process according to one of Claims 18 to 21, characterized in that the reduction is carried out in the presence of a lower alkylether of ethylene glycol, where the lower alkyl has up to 4 carbon atoms.

23. Postopek po enem od zahtevkov 18 do 22, označen s tem, da redukcijo izvedemo v temperaturnem območju od 10 do 100°C, prednostno 30 do 70°C.Process according to one of Claims 18 to 22, characterized in that the reduction is carried out in the temperature range from 10 to 100 ° C, preferably from 30 to 70 ° C.

24. Postopek po zahtevku 1, označen s tem, da v 5ciano-10-okso-10,11-dihidro-5H-dibenz/b,f/azepinu s formulo VProcess according to claim 1, characterized in that in 5cyano-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine of formula V

5-ciano skupino hidroliziramo s pomočjo natrijevega bikarbonata v prisotnost vodikovega peroksida.The 5-cyano group is hydrolyzed with sodium bicarbonate in the presence of hydrogen peroxide.

25. Postopek po zahtevku 1, označen s tem, da v 5ciano-10-okso-10,11-dihidro-5H-dibenz/b,f/azepinu s formulo VA process according to claim 1, characterized in that in 5cyano-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine of formula V

5-ciano skupino hidroliziramo s pomočjo solne, žveplove, polifosforjeve, mravljinčne, ocetne kisline, borovega trifluorida ali definirane adicijske spojine borovega trifluorida z ocetno kislino in sledečo obdelavo z vodo.The 5-cyano group is hydrolyzed by hydrochloric, sulfuric, polyphosphoric, formic, acetic acid, boron trifluoride, or a defined boronic trifluoride addition compound with acetic acid and subsequent treatment with water.

- 40 26. Postopek po enem od zahtevkov 24 in 25, označen s tem, da hidrolizo izvedemo v prisotnosti nadaljnjega topila.Process according to one of Claims 24 and 25, characterized in that the hydrolysis is carried out in the presence of a further solvent.

27. Postopek po zahtevku 26, označen s tem, da kot nadaljnje topilo uporabimo topilo aromatskega značaja.Process according to claim 26, characterized in that a solvent of an aromatic character is used as a further solvent.

28. Postopek po enem od zahtevkov 24 do 27, označen s tem, da izvedemo hidrolizo v temperaturnem območju od -5 do +150°C, prednostno od 0 do 40°C.Process according to one of claims 24 to 27, characterized in that the hydrolysis is carried out in the temperature range from -5 to + 150 ° C, preferably from 0 to 40 ° C.

29. Postopek po zahtevku 1, označen s tem, da redukcijo 5-ciano-10-nitro-5H dibenz/b,f/azepina (II) v 5-ciano-10-izonitrozo-10,11-dihidro-5H-dibenz/b,f/azepin (VI) izvedemo s pomočjo cinkovega prahu v kislini ali s pomočjo vodika v prisotnosti katalizatorja paladija na oglju v primernem topilu.Process according to claim 1, characterized in that the reduction of 5-cyano-10-nitro-5H dibenz / b, f / azepine (II) to 5-cyano-10-isonitroso-10,11-dihydro-5H-dibenz / b, f / azepine (VI) is carried out with the help of zinc powder in acid or with hydrogen in the presence of a palladium catalyst on charcoal in a suitable solvent.

30. 30. Postopek po Procedure after zahtevku request 29, 29, označen marked s s tem, so, da Yes kot as topilo solvent uporabimo topilo we use a solvent aromatskega aromatic značaja. character. 31 - 31 - Postopek po Procedure after zahtevku request 30, 30, označen marked s s tem, so, da Yes kot as topilo solvent uporabimo piridin pyridine is used • • 32. 32. Postopek po Procedure after zahtevku request 29, 29, označen marked s s tem, so, da Yes 5-ciano- 5-cyano-

10-izonitrozo-10,11-dihidro-5H-dibenz/b,f/azepin (VI) s pomočjo mineralne kisline hidroliziramo v 5-ciano-10-okso-10,11-dihidro-5H-dibenz/b,f/azepin (V), tega izoliramo in nadalje hidroliziramo .10-Isonitroso-10,11-dihydro-5H-dibenz / b, f / azepine (VI) is hydrolyzed by mineral acid to 5-cyano-10-oxo-10,11-dihydro-5H-dibenz / b, f / azepine (V), this is isolated and further hydrolyzed.

33· Postopek po zahtevku 32, označen s tem, da hidroliziramo s pomočjo solne kisline.33 A process according to claim 32, characterized in that it is hydrolyzed by hydrochloric acid.

34. Postopek po enem od zahtevkov 32 in 33,. označen s tem, da hidrolizo izvedemo v prisotnosti aromatskega topila ali nižjega alkanola z do 4 atomi ogljika ali njunih mešanicah.A method according to one of claims 32 and 33. characterized in that the hydrolysis is carried out in the presence of an aromatic solvent or lower alkanol of up to 4 carbon atoms or mixtures thereof.

35. Postopek po zahtevku 34, označen s tem, da hidrolizo izvedemo v prisotnosti zmesi toluola-etanola.35. The process of claim 34, wherein the hydrolysis is carried out in the presence of a toluene-ethanol mixture.

36. Modifikacija postopka po zahtevku 1, označena s tem, da v 5-ciano-10-izonitrozo-10,11-dihidro-5H-dibenz/b, f/azepinu s formulo VI hidroliziramo 5-ciano skupino v karbamil kot tudi 10-izonitrozo skupino v istem reakcijskem nastavku.A process modification according to claim 1, characterized in that in 5-cyano-10-isonitroso-10,11-dihydro-5H-dibenz / b, f / azepine of formula VI, the 5-cyano group is hydrolyzed to carbamyl as well as 10 -isonitrose group in the same reaction sequence.

37- Postopek po zahtevku 36, označen s tem, da hidroliziramo s pomočjo kislih sredstev.37- Process according to claim 36, characterized in that it is hydrolyzed by acidic means.

38. Postopek po zahtevku 37, označen s tem, da hidroliziramo s pomočjo mineralne kisline, nižje alkankarboksilne ali haloeennižjialkankarboksilne kisline ali Lewisove kisline v prisotnosti vode.38. A process according to claim 37, characterized in that it is hydrolyzed with the help of a mineral acid, lower alkanecarboxylic or haloenic acid or carboxylic acid or Lewis acid in the presence of water.

39- Postopek po zathevku 38, označen s tem, da hidroliziramo s pomočjo borovega trifluorida v ocetni kislini in s sledečo obdelavo z vodo.39- Process according to claim 38, characterized in that it is hydrolyzed by boron trifluoride in acetic acid and subsequent treatment with water.

40. Postopek po enem od zahtevkov 36 do 39, označen s tem, da hidroliziramo v prisotnosti nadaljnjega inertnega topila.A process according to any one of claims 36 to 39, characterized in that it is hydrolyzed in the presence of a further inert solvent.

41. Postopek po zahtevku 40, označen s tem, da kot na inertno topilo uporabimo nižji alkanol z do 5 atomi ogljika.41. A process according to claim 40, characterized in that a lower alkanol of up to 5 carbon atoms is used as the inert solvent.