Patent GB-755537-A (GB)
Title: Xanthene derivatives and their production
IPC: C07D311/90
Filed: 1954-01-05
Abstract: The invention comprises 9-(b -piperidinoethyl) xanthene and its methobromide and 9-(b -pyrrolidinoethyl) xanthene, and a process for the preparation of derivatives of xanthene having a basic side chain in the 9-position wherein xanthene is treated in a non-polar organic solvent with sodium and an aromatic compound having a halogen atom attached directly to the aromatic nucleus whereby the sodium and the nuclear halogenated aromatic react to form a sodium donor which reacts, as formed, to donate sodium to the xanthene and the resultant xanthene sodium is reacted in a second stage with a halide of an organic base of the general formula <FORM:0755537/IV(a)/1> where R1 and R2 are either alkyl or alkenyl groups or together with the nitrogen atom form a hydroheterocyclic residue. Preferably the reaction is carried out by treating xanthene with sodium phenyl, produced in situ, the reaction being carried out in anisole at a temperature of not more than 45 DEG  C. and using an excess of, for example, three to four times the theoretical amount of sodium in finely divided form for the formation of the sodium phenyl. Specified aminoethyl halides which may be reacted with sodium xanthene according to the invention include di-n-butyl-amino-, methyl-butyl-amino-, diallyl-amino-, 2-methylpyrrolidino-, morpholino-, 2-methylpiperidino- and 2:6-dimethylpiperidino-, ethyl halides.  In examples: (1) finely divided sodium is reacted with chlorobenzene and xanthene in anisole and the product is treated with b -piperidinoethyl chloride to give 9-(b -piperidinoethyl) xanthene which is isolated by way of its hydrochloride; (2) 9-(b -pyrrolidinoethyl) xanthene and its hydrochloride are made by the method of (1); (3) 9 - (b  - di - isopropylaminoethyl) xanthene and its hydrochloride are made by the method of (1) and (4) 9-(b -piperidinoethyl) xanthene is converted into its methobromide.ALSO:Therapeutic preparations possessing spasmolytic and antihistaminic activity comprise as the active constituent derivatives of xanthene having in the 9-position a basic side chain of the formula R1(R2)N-CH2-CH2 wherein R1 and R2 are alkyl or alkenyl residues or form together with the nitrogen atom a heterocyclic residue and quaternary ammonium derivatives thereof (see Group IV(b)).  The compounds are preferably administered perorally in the form of liquid or solid preparations, for example by admixture with solid diluents such as sugar, lactose, talcum, starch, bolus alba and pectine and binding agents such as gelatine, gum arabic, methyl cellulose, yeast extract, agar and tragacanth, whereby tablets and pills may be formed.  By using water soluble diluents tablets may be formed which are water-soluble and may be used in the preparation of aqueous solutions.  Examples describe tablet preparations comprising (5) 9-(b -pyrrolidinoethyl) xanthene hydrochloride, potato starch, pectine, stearic acid, isopropyl alcohol, gelatine and water and (6) 9-(b -diisopropylamino ethyl) xanthene methobromide, vanillin, potato starch, lactose, gelatine, stearic acid, isopropyl alcohol, talcum and water.