Patent GB-515591-A (GB)
Title: Manufacture of ketones or their enol derivatives
IPC: C07J1/00
Filed: 1938-06-07
Abstract: 515,591. Cyclopentanophenanthrene ketones. SOC. OF CHEMICAL INDUSTRY IN BASLE. June 7, 1938, Nos. 16967, 16968 and 16969. Convention dates, June 5, 1937, Aug. 16,-1937, and April 22, 1938. [Class 2 (iii)] Ketones of the cyclopentanophenanthrene series or enol derivatives thereof are prepared by the action of agents known to be capable of removing water or acid on cyclopentanophenanthrene compounds which contain at the carbon atom 17 the grouping where X is an oxy or an acyloxy group and Y is a free or esterified or etherified hydroxyl group. Is desired the product may be hydrolysed. The reaction probably follows the course' It is stated that if Y is a free hydroxyl group the intermediate enol form is unstable and passes directly to the keto form, but if Y is an esterified or an etherified hydroxyl group a hydrolysis step by an acid or an alkaline agent is necessary for the formation of the keto form. In cases where Y is halogen it is preferred to proceed the hydrolysis step by a re-esterification step with a salt of carboxylic acid. Parent materials which possess at position 21 a free or esterified or etherified hydroxyl group Y yield a ketol of the formula or its enol derivative. As parent materials there may be used cyclopentanopolyhydrophenanthrene compounds of any steric configuration, which contain the required grouping in the 17-position, and which may be substituted in the nucleus by, for example, hydroxyl groups or substituted hydroxyl groups. Compounds specifically - mentioned include #<5>.<6>-3 oxy-, #<4>.<5>-3-keto-11 oxy-, #<5>.<6>-3:4- dioxy-, #<4>.<5>-3:6- dioxy-pregnenes ; also the 3:4:5- trioxy-, 3:4:6-trioxy-, 3:5:6-trioxy-, 4-, 5- or 6-oxy-3- keto-pregnanes or allo-pregnanes. Further there may be used compounds which yield parent materials for this invention under the conditions of working, such as oxygen addition products of 17-oxy-17 ethenyl compounds. Methods which may be used to split off water which are specifically mentioned include reaction with mineral acids in alcoholic or dioxane solution, with phosphorus oxychloride, a bisulphite, formic acid, oxalic acid, an acid anhydride such as acetic anhydride or phosphorus pentoxide, by the action of a catalyst such as iodine or a basic agent such as an alkali metal, an alkaline earth metal, a hydroxide or a carbonate thereof, a tertiary amine, or the salt of a carboxylic acid. The above processes may be combined with the use of a high temperature if desired in the presence of an indifferent gas or under diminished pressure. In addition to the elimination of water or acid in the side chain attached at the 17-position, an analogous reaction may occur at other points of the molecule. Thus nuclear hydroxyl groups may be eliminated as water, and ester groups in the form of acids. In examples, (1) A <4>.<6>-11:17:20: 21-tetroxy pregnenone-(3) is boiled under reflux in propyl alcohol solution with 30 per cent. sulphuric acid. Water is added followed by an ether extraction. After purification of the product by means of a carbonyl reagent there is obtained the required #<4>.<5>-11:21:dioxypregnenedione (3:20). Dioxane may be substituted for alcohol as the solvent and potassium bisulphate for sulphuric acid as the dehydrating agent. 'Instead of the 21-hydroxy compounds above there may be used 21-esters or ethers such as the acetate propionate, valerate, palmitate or benzoate. (2) The mixture of #<5>.<6>- and #<4>.<5>-3:4:17:20:21 pentoxy pregnenes obtained by the action of selenium dioxide on # <5>.<6>-3:17 dioxy-21-oxo-pregnene and subsequent reduction is treated with alcoholic hydrochloric acid to give #<4>.<5>-21-oxy-pregnendione-3:20. The same compound is obtained when 3:5:6:17:20:21 hexa-oxy pregnanes are treated in analogous manner. (3) 3-epi-allo-pregnone-trial-(3:17:20) is treated with boiling methyl alcoholic hydrochloric acid to give epi-allo-pregnanol-3-one-20. Similarly, treatment of 3-trans-allo-pregnanetriol-(3:17:20) with methyl alcoholic sulphuric acid gives allo-pregnanol-(3)-one-(20). (4) 5-17-20-trioxy-pregnanone-(3) is treated with sulphuric acid in propyl alcohol to give progesterone. Similarly from #<5>-3:17:20-trioxy pregnene there is obtained #<5>-pregnenol-(3)- one-(20).