Synthetic Studies in the Santonin Series

Tulloch, Alexander P (1954) Synthetic Studies in the Santonin Series. PhD thesis, University of Glasgow.

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Part I. A study of some synthetic routes to santonin. Mukherjee's preparation of ethyl alpha-(4-methyl-3-oxo-cyclohexyl)propionate has been shortened and the overall yield raised considerably. The preparation of the hitherto unknown 1-chloro- and l-diethylaminopent-1-en-3-one is described. Attempts to condense these compounds with 2-methylcyclohexanone and with ethyl alpha-(4-methyl-3-oxo-cyclohexyl)propionate were unsuccessful. Condensation of the latter with l-diethylaminopentan-3-one affords ethyl alpha-(2:3:4:5:6:7:8:10-octahydro-1:10-dimethyl-2-oxo-7-naphthyl)propionate: the best conditions for the reaction have been determined. The bromination-dehydrobromination of ethyl alpha-(2:3:4:5:6:7:8:10-octahydro-1:10-dimethyl-2-oxo-7-naphthyl)-propionate has been studied - ethyl alpha-(2:3:4:5:6:10-hexa-hydro-1:10-dimethyl-2-oxo-7-naphthyl)propionate is the product in all cases. An attempt to convert the latter to dihydrosantonin was not successful. Several other approaches to the santonin structure have been studied, but a satisfactory synthesis has not been found. Part II. The synthesis of some compounds analogous to santonin. Methyl 4-methyl-3-oxocyclohexyl acetate has been prepared for the first time by a modification of Mukherjee's procedure. Condensation with 1-diethylamino-pentan-3-one followed by hydrolysis gives 2:3:4:5:6:7:8 :10-octahydro-1:10-dimethyl-2-oxo-7-naphthylacetic acid which yields 3:8-dibromo-2:3:4:5:6:7:8:10-octahydro-1:10-di-methyl-2-oxo-7-naphthylacetic acid on bromination. Dehydrobromination and lactonisation then give the gamma lactone of 2:5:6:7:8:10-hexahydro-8-hydroxy-1:10-dimethyl-2-oxo-7-naphthylacetic acid which is similar in structure to santonin, but lacks the methyl group at C11. Chemical and spectrographic evidence for this structure are provided. In the hope of preparing a second analogue, the gamma lactone of 2:5:6:7:8:10-hexahydro-8-hydroxy-10-methyl-2-oxo-7-naphthylacetic acid, 2:3:4:5:6:7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid has been prepared. 3 :8-Dibromo-2:3 :4:5:6:7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid and the gamma lactone of 2:3:4:5:6:-7:8:10-octahydro-8-hydroxy-10-methyl-2-oxo-7-naphthyl-acetic acid have been obtained from this acid, but could not be converted to the second analogue. The second isomer of 2:3:4:5:6 :7:8:10-octahydro-10-methyl-2-oxo-7-naphthylacetic acid has also been prepared by a shorter route from 2-methylcyclohexanone.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1954
Depositing User: Enlighten Team
Unique ID: glathesis:1954-79108
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 Mar 2020 09:09
Last Modified: 31 Mar 2020 09:09

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