Patent GB-514516-A (GB)
Title: Improvements in and relating to the manufacture of cyclic ketones
Filed: 1938-05-05
Abstract: 514,516. Cyclic ketones. ROBINSON, R. May 5, 1938, No. 13476. [Class 2 (iii)] Cyclic ketones containing a cyclopentano or cyclopenteno ring are prepared by the action of a condensing agent which is a strong mineral acid or is an anhydride derived from an acid which is stable in the anhydrous condition at 18‹C. and 760 mm. pressure on compounds of the general formula where R is a substituted or unsubstituted phenyl group or a #-polynuclear-aromatic group, particularly a #-naphthyl group. The condensation effects the removal of water between the carboxyl group and the group R producing ring closure with the formation of a diketone or a hydroxy ketone depending on whether the starting material is of the saturated form or the unsaturated form above. In the case of the unsaturated starting material end formation occurs. In the case of saturated starting materials suitable condensing agents are phosphoric anhydride in benzene, phosphoric anhydride in syrupy phosphoric . acid, and concentrated sulphuric acid. In the case of unsaturated starting materials condensation may be effected by the use of sulphuric acid or an aliphatic anhydride such as acetic or propionic anhydride. In the latter case the product appears as the acetyl derivitive, due to esterification of the enolic hydroxyl group. The group R in the formulae above may be substituted, for instance by hydroxy group, by alkoxy group or by halogen. The starting materials may be prepared by the action of dilute aqueous caustic alkali or diketonic acids of the general formula R-CO-CH,-CH,-COCH2-CH2-COOH. In the case where R is a naphthyl group or a substituted naphthyl group the production is described in Specification 514,592. In examples (1) #-phenyl-gamma-#- diketoheptoic acid is treated with 2 per cent. aqueous potassium hydroxide to give 3-phenyl- #<2>-cyclopenten-1-one-2-acetic acid, and this is then treated with concentrated sulphuric acid at 95‹C. for 10 minutes. The reaction mixture is slowly diluted with water and the 4-hydroxy- 3<1>-keto-1 : 2-cyclopenteno naphthalene which separates is crystallized from alcohol. / (2) #-#-naphthyl-gamma-#-diketoheptoic acid is converted into 3-#-naphthyl-#<2>-cyclopenten-1-one-2-acetic acid as above and this is then treated with acetic anhydride under reflux to give the acetyl derivative of 4-hydroxy-3<1>-keto-1 : 2-cyclopentenophenanthrene which may be hydrolysed with hot alcoholic soda. (3) 3-(6-methoxy-#- naphthyl)-A <2>-cyclopenten-1-one-2-acetic acid prepared as described in specification 514,592 is treated as described in example (2) to give the acetyl derivative which may be hydrolysed to the free -7methoxy-4-hydroxy-3<1>-keto-1 :2- cyclopentenophenanthrene. (4) 8-chloro-7- methoxy-4-hydroxy-3<1>-keto-1 : 2-cyclopentenophenanthrene is prepared in a similar manner to that described in examples (2) and (3) from 3-( 5-chloro-6-methoxy-#-naphthyl)-#<2>-cyclopenten-1-one-2-acetic acid, which may itself be obtained from #-(5-chloro-6-methoxy-#-naphthyl)-gamma-#-diketoheptoic acid. (5) 3-#-naphthyloxyclopentan-1-one-2-acetic acid prepared by reducing the corresponding #<2>-cyclopentanone acid with hydrogen in the presence of methyl alcohol and palladised strontium carbonate is treated with a solution of phosphoric anhydride in syrupy phosphoric acid to give 3<1>: 4-diketo- 1 : 2 : 3 : 4-tetrahydro-1 : 2-cyclopentenophenanthrene. (6) 3-(6-methoxy-#-naphthyl)- cyclopentan-1-one-2-acetic acid prepared by reduction from the corresponding #<2>-cyclopentenone acid as described in example (5) is treated with a condensing agent also as described in example (5) to give 3<1> : 4-diketo-7-methoxy- 1 : 2 : 3 : 4-tetrahydro-1 : 2-cyclopentanophenanthrene. The diketo-heptoic acid used in example (1) is prepared by heating furfurylideneacetophenone with concentrated hydrochloric acid in alcohol solution. Corresponding methods are used to prepare the heptoic acids in examples 2,3 and 4. Thus #-#-naphthyl-gamma-#-diketoheptoic acid is prepared by condensing 2-acetyl naphthalene and furfuraldehyde in alcohol solution in the presence of sodium to give furfurylidene-2- acetyl-naphthalene which is condensed by hydrochloric acid to the required heptoic acid. # - (6 -methoxy- #-naphthyl)-gamma-#- diketoheptoic acid is prepared in a similar manner from 6-acetyl-2-methoxynaphthalene. In this case a certain amount of dimethylation takes place with the formation of #-(6-hydroxy-#-naphthyl)- gamma-#-diketoheptoic acid. Halogenated compounds may be formed in similar manner. Thus by the action of acetyl chloride on 1- chloro-2-methoxy naphthalene in nitrobenzene solution in the presence of aluminium chloride there is obtained 1-chloro-2-methoxy-6-acetylnaphthalene which can be converted into its furfurylidene derivative as described above using, however, larger amounts of acetic acid.