DE1181701B - Process for the preparation of basic dibenzo- [a, d] -cyclooctene derivatives and their salts - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY Internat. Class: C 07 c

GERMAN

PATENT OFFICE German class: 12 ο-25

EDITORIAL

LIBRARY

DES GERMAN
PATEHTdMTES

Number: 1181701

File number: B 66825 IV b / 12 ο

Filing date: April 14, 1962

Opening day: November 19, 1964

According to an older proposal, basic dibenzo- [a ^ -cyclooctene derivatives of the general Formula I.

(I)

CH-CH-CH ₂ -A

in which R is hydrogen or a lower alkyl radical and A is a basic group, their salts and quaternary ammonium compounds prepared by adding 5,6,7,12-tetrahydro-dibenzo- [a, d] -cycloocten-12-one of formula II

Process for the preparation of basic dibenzo- [a, d] -cyclooctene derivatives and their salts

Applicant:

C. F. Boehringer & Soehne G. m. B. H.,

Mannheim-Waldhof

Named as inventor:
Dr.-Ing. Kurt Stach, Mannheim,
Dr. rer. nat. Friedrich Bickelhaupt,
Neckarhausen near Mannheim

(II)

(R2 = lower alkyl radical) and from the resulting N-carbalkoxy compounds of the formula IV

with Grignard compounds of the formula

Hal-Mg-CH ₂ -CH (R) -CH ₂ -A

in which R and A have the meaning given at the beginning, and the reaction product with Treated dehydrating agents, whereupon the resulting alkylidene compounds (I), if desired converted into their salts or quaternary ammonium compounds. As basic residues A are preferably tertiary amino groups in question, z. B. dialkylamino groups or heterocyclic Residues such as piperidino, pyrrolidino, morpholino and piperazino radicals, which optionally can also be substituted.

It has now been found that compounds of the above formula I, which are the basic radical A carry a monoalkylamino group —NHRi, thereby producing them in a particularly advantageous manner let that one benzyl compounds of the formula III

(IV)

CH-CH-CH ₂ -N
R.

COOR ₂
Ri

CH-CH-CH ₂

-N

(III) / CH ₂ C ₆ H ₅

the carbalkoxy group is split off hydrolytically in a manner known per se.

The reaction of the benzyl compounds III with the haloformic acid esters (e.g. ethyl chloroformate) is made by heating in an inert solvent, ζ. Β. Benzene. the N-carbalkoxy compounds of the formula IV can be further processed without special isolation and purification will; the hydrolytic cleavage of the carbalkoxy group is preferably carried out with aqueous Hydrobromic acid made in glacial acetic acid. The obtained monoalkylaminoalkylidene compounds can, if desired, be converted into their salts in the customary manner.

The preparation of the starting compounds III takes place in 63% yield by reacting

in which R has the meaning given above and Ri is a lower alkyl group, with a haloformic acid ester Hai - COOR ₂ yf ^ y
with Grignard compounds of the formula

QMgCHaCHRCH ₂ N (Ri) CH ₂ C ₆ H ₅

in tetrahydrofuran and subsequent boiling of the reaction product with alcoholic hydrochloric acid (cf. Stach and Bickelhaupt, monthly journals für Chemie, 93 [1962], p. 896). 5,6,7,12-tetrahydrodibenzo- [a, d] -cycloocten-12-one you get through

409 728/485

Cyclization of 2- (3-phenylpropyl) -benzoic acid in 66% yield (see above, p. 889).

example

12- (3'-monomethylamino-propylidene) -5,6,7,12-tetrahydro-dibenzo- [a ^ j-cyclooctene

13 g (0.035MoI) 12- [3 '- (N-Benzyl-N-methyl) -aminopropylidene] -5,6,7,12-tetrahydro-dibenzo- [a, d] -cyclooctene and 10.8 g ( 0.105 mol) of ethyl chloroformate is heated to boiling in 60 ml of benzene for 6 hours and the volatile components are then removed in vacuo on a water bath. The resulting residue of crude 12- [3 '- (N-carbethoxy-N-methyl) aminopropylidene] -5,6,7,12-tetrahydrodibenzo [a, d] cyclooctene (yield 10.8 g = 88% of theory) is refluxed for 3 hours in 75 ml of glacial acetic acid and 75 ml of 48% hydrobromic acid, and the contents of the flask are concentrated to a small volume in vacuo. Water and ether are added, the aqueous acidic components are separated off, made alkaline with dilute sodium hydroxide solution and extracted with ether. The evaporation residue remaining after drying with sodium sulfate and removal of the solvent gives 5.3 g (= 54.7% of theory) of 12- (3'-monomethylamino-propylidene) -5,6,7,12-tetrahydro- dibenzo- [a, d] -cyclooctene from bp 0.15 163 to 171 ⁰ C; the hydrochloride has a melting point of 158 to 160 ° C. (from ether-isopropanol).

Claims (1)

Claim: Process for the preparation of basic dibenzo- [a, d] -cyclooctene derivatives of the general formula I. (D CH-CH-CH ₂ -A 40 R.
in which R is hydrogen or a lower alkyl radical and A is a monoalkylamino group of the formula - NH - Ri means, where Ri is a lower alkyl group presents, and their salts, characterized in that benzyl compounds of the formula III CH ₂ - N (HD
/ CH ₂ C ₆ H ₅ Ri in which R and Ri have the meaning given above, with a _{haloformic acid ester Hal - COOR 2} (R ₂ - = lower alkyl radical) and from the resulting N-carbalkoxy compounds of formula IV (IV) CH - CH - CH ₂ - N
R. COOR ₂
Ri in which R, Ri and R _{2 have} the meaning given above, the carbalkoxy group is hydrolytically split off in a manner known per se, whereupon the monoalkylaminoalkylidene compounds (I) obtained in this way are, if desired
their salts transferred. Considered publications:
"Methods of Organic Chemistry", 4th edition, Vol. 8 (1952), pp. 138/139. 409 728/485 11.64 @ Bundesdruckerei Berlin