Patent GB-1061869-A (GB)
Title: Ethanoanthracene derivatives and processes for their production
IPC: C07D243/08
Filed: 1964-10-20
Abstract: Novel compounds of the Formula I, wherein each of X and Y represents hydrogen or a halogen atom up to the atomic number 35; Z represents hydrogen or a methyl group; A represents a straight or branched C1- 5 alkylene or C1- 5 alkylidene chain; and each of R1 and R2 represents hydrogen or a C1- 4 alkyl group, or R1\t and R2 together with the adjacent nitrogen atom and optionally with the inclusion of an oxygen atom, or an imino or C1- 4 alkylimino, C1- 4 hydroxyalkylimino or C3- 9 alkanoyloxyalkyl-imino group as a ring member, represent a saturated heterocyclic radical of 5 to 7 ring members, but R1 and R2 cannot both represent hydrogen atoms when X, Y and Z represent hydrogen atoms and A represents a methylene group, and inorganic and organic acid addition salts thereof, are prepared by reducing with a complex metal hydride a compound of the Formula II wherein A1, R11 and R12 have the same meanings as A, R1 and R2 except that in at least one of them a methylene group bound to the nitrogen atom is replaced by a carbonyl group, or R11 represents a C2- 5 alkoxycarbonyl group and A1 and R12 have the same meanings as A and R2 or in the group represented by A1 a methylene group bound to the nitrogen atom is replaced by a carbonyl group if R11 and R12\t together with the nitrogen atom and optionally with the inclusion of an oxygen atom or an imino, C1- 4 alkylimino or C1- 4 hydroxyalkylamino group as ring member, represent a saturated heterocyclic radical of 5 to 7 ring members, the reduction being carried out in an organic solvent, and, if desired, acylating so obtained compounds containing hydroxyalkylimino groups; by reacting a compound of the Formula V with a C1- 5 saturated, aliphatic oxo compound and reducing the reaction product either subsequently or simultaneously; by reacting with a reducing agent a compound of the Formula VI wherein Z1 represents a straight or branched chained cyanoalkyl, cyanoalkylidene, hydroxyiminoalkyl, or hydroxyiminoalkylidene radical of up to 5 carbon atoms, or a cyano group provided that at least one of X, Y and Z is different from hydrogen, to convert the cyano group or the hydroxylimino group into an aminoethyl or amino group respectively by hydrogenation; or by hydrolysing or thermolysing into acid and secondary amine a compound of the Formula VIII wherein R4 represents a carboxylic acyl radical or the radical of a monofunctional derivative of carbonic acid or a sulphonic acid radical, or R1 and R4 together with the adjacent nitrogen atom represent a phthalimido radical, or with the inclusion of an imino group substituted by an acyl radical as ring member, form a saturated heterocyclic radical of 5 to 7 ring members, whereby A cannot represent a methylene group when X, Y, Z and R1 represent hydrogen atoms; and, if desired, forming acid addition salts with organic or inorganic acids.  <FORM:1061869/C2/1> <FORM:1061869/C2/2> <FORM:1061869/C2/3> <FORM:1061869/C2/4> <FORM:1061869/C2/5> <FORM:1061869/C2/6> <FORM:1061869/C2/7> <FORM:1061869/C2/8> <FORM:1061869/C2/9> Carboxylic acid amides of the Formula II wherein the group A contains a carbonyl group may be prepared from 9,10-dihydro-9,10-ethanoanthracen -11-yl-acetic acids which may be, if desired, a -alkylated or from a - and/or b -alkylated 9,10-dihydro-9,10 - ethanoanthracen - 11 - yl-propionic acids by conversion to the acid chlorides with thionyl chloride and reacting these with amines of the formula HNR1R2, into the corresponding amides.  Carboxylic acid amides of the Formula II wherein the group R11 contains a carbonyl group or represents an alkoxycarbonyl group, A1 has the same meaning as A and R21 represents a hydrogen atom, may be prepared by reacting 11 - amino - 9,10 - dihydro -9,10 - ethanoanthracene or amines of the Formula IV, where A11 represents a straight or branched chained C2- 5 alkylene group with reactive functional derivatives of alkanoic acids or with haloformic acid alkyl esters or dialkyl carbonates.  Carboxylic acid amides of the Formula II wherein A1 and R1 each contain a carbonyl group, may be prepared by reacting 9,10-dihydro -9,10-ethanoanthracene - 11 - carbonyl chloride, 9,10 - dihydro - 9,10 - ethanoanthracen -11-yl acetyl chloride, its a -alkylated derivatives, 9,10 - dihydro -9,10 - ethanoanthracen - 11 -yl propionyl and its a - and/or b -alkylated derivatives with alkali metal derivatives of alkylcarboxylic acid amides.  Optionally b -alkylated 11-(2-aminoethyl)-9,10-dihydro - 9,10 - ethanoanthracenes of the Formula IV may be prepared by reducing optionally a  - alkylated 9,10 - dihydro - 9,10 - ethanoanthracen -11-yl acetonitriles.  Optionally b - and/or g -alkylated 11-(31-aminopropyl) -9,10 - dihydro - 9,10 - ethanoanthracenes of the Formula IV may be prepared by reacting the appropriate 9,10-dihydro-9,10-ethanoanthracen -11-yl propionyl chloride with ammonia and reducing the amide so produced. Ethanoanthracenes of the Formula VI where Z1 represents a cyano group may be prepared by reacting anthracenes of the Formula VII, optionally substituted in rings A** and C**, with acrylonitrile or with methacrylonitrile.  Ethanoanthracenes of the Formula VI where Z1 represents a branched or straight C2- 5 cyanoalkyl chain may be prepared by reacting reactive esters of 9,10 - dihydro - 9,10 - ethanoanthracen -11-yl alkanols with sodium cyanide in an inert solvent.  Ethanoanthracenes of the Formula VI wherein Z1 represents a C1- 5 hydroxyliminoalkyl group may be prepared by refluxing substituted or unsubstituted 9.10-dihydro-9,10-ethanoanthracene - 11 - carboxaldehyde or 11 - oxoalkyl - 9,10 - dihydro - 9,10 - ethanoanthracene with hydroxylamine hydrochloride in the presence of pyridine.  Ethanoanthracenes of the Formula VIII as defined above may be prepared by alkylating the sodium derivatives of 11-acylaminoalkyl-9,10 - dihydro - 9,10 - ethanoanthracenes of the Formula II wherein A1 has the same meaning as A, R21 represents a hydrogen atom and R11 represents an acyl group, or by reacting reactive esters of hydroxy compounds of the Formula XI with carboxylic acid amides of the Formula X where R1 and R4 are defined as for Formula VIII.  9,10 - Dihydro - 9,10 - ethanoanthracen - 11 - yl -methyl-p-toluene sulphonate may be prepared by reacting p-toluene sulphochloride with the appropriately substituted methanol.  9,10 - Dihydro - 9,10 - ethanoanthracen - 11 -yl-acetic acid may be prepared by hydrolysing the corresponding acetonitrile.  9,10 - Dihydro - 9,10 - ethanoanthracen - 11 - yl-propionic acid may be prepared by decarboxylating the product of the reaction of malonic acid diethyl ester with 9,10-dihydro-9,10-ethanoanthracen - 11 - yl - methyl p - toluene sulphonate and sodium hydride.  Therapeutic compositions with spasmolytic, antiemetic and anesthesia-potentiating properties, which antagonize reserpine, tetrabenzine and tremorine and potentiate the action of noradrenaline, comprise compounds of the Formula I and a pharmaceutically acceptable carrier.