Patent GB-341402-A (GB)
Title: Process for the manufacture of alicyclic lactones of tetrahydronaphthalenes
IPC: C07D307/92
Filed: 1929-10-07
Abstract: Lactones of tetrahydronaphthalene, its Bz-homologues and Bz-substitution products.-Lactones of Bz-hydroxy-tetrahydronaphthalenes and their Bzhomologues are prepared by condensing a Bzalkoxy-a -tetralone or a Bz-homologue thereof (a -tetralone is 8-keto-5 : 6 : 7 : 8-tetrahydronaphthalene) with an oxalic acid ester, heating the resulting Bz-alkoxy-8-tetralone-7-ketocarboxylic acid ester to split off carbon monoxide, treating a metallic, preferably an alkali metal, compound of the Bz-alkoxy-8-tetralone-7-carboxylic acid ester formed with an a -halogen-acetic acid or alkylacetic acid ester, saponifying the condensation product with alkali, which simultaneously splits off carbon dioxide, eliminating the alkyl radicle from the alkoxy group by means of aluminium chloride to give Bz-hydroxy-8-tetralone-7-acetic acid or -alkylacetic acid, and finally reducing to the corresponding lactone.  The products possess therapeutic properties.  According to the example, 1 : 4-dimetyl-2-methoxy-8-tetralone is condensed with the diethyl ester of oxalic acid in the presence of sodium ethylate to give 1 : 4-dimethyl-2-methoxy-8-tetralone-7-ketocarboxylic acid ethyl ester, which by distillation in vacuo forms 1 : 4-dimethyl-2-methoxy-8-tetralone-7-carboxylic acid ethyl ester with elimination of carbon monoxide; the said tetralone derivative is converted into its potassium compound by treatment with metallic potassium and mixed with a -bromopropionic acid ethyl ester; the product is heated with caustic soda to form 1 : 4-dimethyl-2-methoxy-8-tetralone-7-a -propionic acid, from which 1 : 4-dimethyl-2-methoxy-5 : 6-dihydronaphthol-8 : 7-a -propionic acid lactone can be obtained by distillation; by treating the propionic acid in chlorobenzene solution with aluminium chloride, 1 : 4-dimethyl-2-hydroxy-8-tetralone-7 -a -propionic acid results and this, on reduction with sodium amalgam followed by acidification, yields the corresponding lactone which is identical with racemic desmotroposantonine.  The Specification as open to inspection under Sect. 91 (3) (a) describes also the treatment of a -tetralone itself, its Bz-homologues and Bz-substitution products.  In the case of a -tetralones which are not substituted by hydroxyl or alkoxyl in the benzene nucleus, it is stated that the process for the preparation of the lactones is simplified by the omission of the penultimate stage, viz. the treatment with aluminium chloride. This subject-matter does not appear in the Specification as accepted.  Bz-Alkoxy-tetralones are prepared by treating an hydroxy- or alkoxy-benzene or homologue thereof with succinic acid anhydride in the presence of aluminium chloride, reducing the resulting hydroxy-or alkoxy-benzoyl-propionic acid or Bz-homologue with amalgamated zinc and hydrochloric acid, condensing the hydroxy- or alkoxy-phenylbutyric acid or homologue-e.g. by melting preferably the hydroxy compound with zinc chloride or by treating the acid chloride, preferably of the alkoxy compound, in solution with aluminium chloride-and etherifying the resulting Bz-hydroxy-tetralone or Bz-homologue thereof in known manner.