CH410931A - Process for the preparation of 5-oxy-dibenzocycloheptene derivatives - Google Patents

Description

  

  
 



  Process for the preparation of 5-oxy-dibenzocycloheptene derivatives
The invention relates to a process for the preparation of new 5-oxydibenzocycloheptene derivatives of the formula
EMI1.1
 where Rt and R2 each represent hydrogen, halogen or an alkyl group of 14 carbon atoms, but not both hydrogen atoms.



   The new compounds have a biocidal effect. They are also valuable as starting materials for the production of compounds of the formula
EMI1.2
 in which Y is a straight or branched one, optionally interrupted by an oxygen atom
Is a carbon chain with a maximum of 6 carbon atoms, and
Z represents a dialkylamino group in which one or both alkyl groups together with the nitrogen atom and optionally with the carbon chain Y can represent one or more heterocyclic rings in which, in addition to this nitrogen atom, a second heteroatom can also be contained.



   The last-mentioned substances have u. a. a strong antihistamine activity and antiacetylcholine effect.



   Halogen substituents are in particular chlorine and bromine and alkyl groups are particularly methyl, ethyl, propyl, isopropyl, butyl and tert.



  Butyl into consideration.



   The inventive method for the preparation of compounds of the formula list, characterized in that in a compound of the formula
EMI1.3
 in any order on the one hand the -CH2-CH2- bridge between the two phenyl rings is converted into a -CH = CH bridge and on the other hand it is reduced to the corresponding alcohol.



   A treatment with N-bromosuccinimide and subsequent removal of hydrogen bromide is particularly suitable for converting the saturated to an unsaturated bridge. This stage of the process, which is preferably carried out first, can advantageously be carried out in the presence of an inert organic solvent, e.g. B. carbon tetrachloride perform. The dehydrobromination also expediently takes place on the dissolved or dispersed monobromo product. It is advisable to use an organic base that is not only used as a solvent or



  Dispersant, but also can serve as an acceptor for the split off acid. Pyridine is best suited for this purpose.



   The reduction of the ketone can be carried out by the methods customary for this purpose.



   Compounds corresponding to the carbinols obtainable according to the invention, in which the phenyl nuclei are not substituted, were already known.



  Of these, dibenzo- (a, d) -1, 4-cycloheptadienol-5 from F. 90 C by H. J. Klinkhammer, dissertation, University of Leipzig (1951), and by W. Treibs and H. J. Klinkhammer, Ber. 84, 671 (1951).



     Dibenzo- (a, e) -1, 3, 5-cycloheptatrienol-5 was by Treibs and Klinkhammer, a. a. 0., which indicate as F. 980 C, and also by G. Berti, Gazz.



  Chim. Ital. 87, 293 (1957) and J. Org. Chem. 22, 230 (1957), which gives 1200 ° C. as the melting point.



   If the new compounds are used as medicaments, they can be mixed with suitable carriers and brought into the form suitable for administration.



   example 1
In a flask with a capacity of 500 ml, 160 g of P205 are added to 110 ml of an 850% phosphoric acid syrup at 80 ° C. while stirring. The temperature of the mixture is maintained at 1000 ° C. for a further hour, after which it is heated up to 1700 ° C.



  At this temperature 50 g of 1- (p-tolyl) -2- (o-carboxyphenyl) ethane are added in small portions with very vigorous stirring, after which the mixture is stirred for a further 4 hours at the same temperature.



   After cooling, the contents of the flask are poured onto ice water. The mass is stirred for a further t / 2 hour and extracted with ether. The ethereal solution is washed with a 2N soda solution and with water. After drying and evaporation of the ether, the residue is fractionally distilled in vacuo. 3-Methyl-dibenzo (a, d) -1,4-cycloheptadien-one- (5), boiling point = 165-1670 C / 2 mm, is obtained in a yield of 810%.



   A mixture of 6.7 g of 3-methyl-dibenzo- (a, d) -1, 4-cycloheptadienone- (5), 5.3 g of N-bromosuccinimide and 0.1 g is placed in a 100 ml flask Benzoyl peroxide d boiled under reflux for two hours in 25 ml of carbon tetrachloride. After cooling, the succinimide is filtered off and it is evaporated. The remaining monobromo compound can be crystallized from petroleum ether (boiling point 60-80 ° C.).



   6.4 g of the brominated product are heated with 20 ml of pyridine, after which the mixture is dissolved in 250 ml
2N hydrochloric acid is poured out. The precipitate is filtered off and crystallized from petroleum ether (melting point 60-80 ° C.). Yield of 3-methyl dibenzo- (a; e) -1,3,5-cycloheptatrienone- (5) 78 O / o.



  Melting point 80-81 C.



   10 g of 3-methyl-dibenzo- (a, e) -1, 3, 5-cycloheptatrienon- (5) are dissolved in 150 ml of 960% ethanol and added for 20 hours on the reflux condenser with 2 kg of 0.50 / above Sodium cooked on algam. The alcoholic solution is poured into ice water acidified with 3N acetic acid. The precipitate formed is filtered off, dried and crystallized from petroleum ether or gasoline. 7.5 g of 3-methyl-dibenzor (a, e) -1,3,5-cycloheptatrienol- (5) with a melting point of 18-119.50 ° C. are obtained. Yield 75%.



   Example 2
3-Bromo-dibentzo- [a, d] -1,, 4-cycloheptadien-one- (5) is prepared by adding 5.0 g of l- (p-bromophenyl) 2- (o-carboxyphenyl) -ethane dissolves in 5.7 g of thionyl chloride and the solution boils on the reflux condenser for 3 hours. The excess thionyl chloride is distilled off and the remaining oil is dissolved in 30 ml of CS.



   The solution is added to 4.3 g of A1 C13 in 50 ml of CS2. Hydrochloric acid gas develops. The reaction mixture is refluxed for 8 hours, then cooled and poured onto ice and hydrochloric acid. After addition of benzene, it is filtered, the organic layer is separated off, washed with sodium hydroxide solution and water and dried over Glauber's salt.



  The oil remaining after the solvent has been distilled off gives the 3-bromo dibenzo- [a, d] -1 4-cycloheptadiene 1 ', 4') - on- (5) as a crystalline mass when methanol is added.



   In a 100 ml flask, a mixture of 8.6 g of the 3-bromo-dibenzo- [a, d] -1,4-cyclo-heptadiene- (1 ', 4') - ons- (5), 5 , 3 g of N-bromosuccinimide and 0.1 g of benzoyl peroxide in 30 ml of carbon tetrachloride are boiled under reflux for 2 hours.



  After cooling to room temperature, the precipitated succinimide is filtered off and the solvent is distilled off. The dibromide formed can be recrystallized from petroleum ether. 9.1 g of the dibromide are heated with 30 ml of pyridine and the mixture is poured into 300 ml of 2N hydrochloric acid. The precipitate is filtered off and recrystallized from petroleum ether. 3-Bromo-dibenzo (a, e) -l, 3,5-cycloheptatrienone- (5) is obtained in 740% yield. Mp = 111 to 1120 C.



      8.5 g of 3-bromo-dibenzo (a, e) -1 1,3,5-cycloheptatrien- one- (5) are dissolved in 140 ml of ethanol and treated with 2 kg of sodium amalgam (0.5 O! O) for 20 Boiled under reflux for hours. The alcoholic solution is poured into ice water that has been acidified with 3N acetic acid. The precipitate formed is filtered off, dried and recrystallized from petroleum ether or gasoline.

 

Claims (1)

PATENT CLAIM Process for the preparation of 5-oxy-dibenzo cycloheptene derivatives of the formula EMI3.1 where Rt and R2 each denote hydrogen, halogen or an alkyl group of 1-4 carbon atoms, but Rj and R2 are not both hydrogen atoms, characterized in that one in a compound of the formula EMI3.2 on the one hand the -CH2-CH2-bridge between the two phenyl rings is converted into a -CH = CH-bridge, and on the other hand it is reduced to the corresponding alcohol. SUBCLAIMS 1. The method according to claim, characterized in that one in the -CH2-CH2 bridge of a compound of formula EMI3.3 first introducing a bromine atom by means of N-bromosuccinimide, then splitting off hydrogen bromide from the monobromo compound obtained and finally reducing the ketone obtained to the corresponding alcohol. 2. The method according to dependent claim 1, characterized in that the reaction with N-bromosuccinimide is carried out in the presence of an inert organic solvent.