Patent GB-550479-A (GB)
Title: Manufacture of saturated and unsaturated pregnanepolycarbonyl compounds and substitution products thereof
IPC: C07J75/00
Filed: 1941-01-17
Abstract: 550,479. Pregnane polycarbonyl compounds. SOC. OF CHEMICAL INDUSTRY ] N BASLE. Jan. 17,1941. Nos. 661 and 662. Convention dates, Jan. 17, 1940 and Nov. 20, 1940. [Class 2 (iii)] Saturated or unsaturated pregnane polycarbonyl compounds are prepared by treating a pregnane-20-one containing in ring A or B a double linkage but no nuclear substituent with an oxidizing agent. In cases where the oxidizing agent used is one which would also oxidize the 21-methyl group in α-position to the 20-keto group, and when such an oxidation is not desired, the 20-keto group is preliminarily reduced to a carbinol group and if necessary protected by an esterification or etherification treatment. Oxidizing agents which are used include chromic acid, selenium dioxide, lead tetra-acylates, peroxides such as hydrogen peroxide in some cases in the presence of an alkali or metal oxide, per acids, halogen, metal oxides such as osmium tetroxide or vanadic acid, in some cases in presence of a chlorate, also permanganates, aryliodoso-acylates and a silver halide benzoate complex. Reducing agents which are used for the preliminary reduction step include mild reducing agents, especially nascent hydrogen which are suitable for converting the 20-keto group into a carbinol group. When it is necessary to convert the 20-carbinols into their corresponding esters or ethers they may be treated with an aliphatic acid such as formic, acetic, propionic, n-butyric, isobutyric, n-valeric, iso-valeric, caproic, capric, palmitic or stearic acids, or with the residue of an aromatic, fatty aromatic or inorganic acid, such as benzoic, cinnamic or a substituted. carbonic acid. For etherification there may be introduced the residue of an aliphatic or aliphatic-aromatic alcohol or phenol such as a methyl, ethyl, benzyl, or triarylmethyl residue. If it is desired after the oxidation to convert substituted hydroxyl groups or newly introduced oxide groups into hydroxyl groups, the product may be treated with a hydrolysing agent. A cautious hydrolysis will hydrolyse only the substituent in rings A or B, but not the substituted hydroxyl group in position 17. The hydrolysis product may if desired be re-acylated, treated with an agent which eliminates water or acid, or with an oxidizing or dehydrogenating agent. In examples (1) #<SP>4</SP>-pregnene -20 - one prepared according to Specification 550,478 is subjected to a preliminary reduction with hydrogen by the method of Rupe or Raney, and then oxidized by lead tetra-acetate in glacial acetic acid solution to give # <SP>4</SP>- pregnene- 3 : 20 - diol - 3 - acetate - 20 - propionate, which may be saponified to the corresponding diol. Oxidation of this diol forms #<SP>4</SP>- pregnene- 3 : 20 - dione. (2) #<SP>4</SP>- pregnene - 20 - one is oxidized with chromic acid in glacial acetic acid to form directly progesterone with also amounts of the corresponding 6-oxo-, and 3 : 6- dioxo - compounds. If instead of chromium trioxide there is used selenium dioxide or a lead tetracylate there are obtained primarily #<SP>4</SP>- 3 oxy- or #<SP>4</SP>-3-acyloxy-compounds, containing an aldehyde group in the 21 - position. (3) # <SP>3</SP>- pregnene - 20 - one is treated with osmium tetroxide in ether solution to give pregnane- 3 : 4 - diol - 20 - one. This compound may then be treated in known manner with an agent which eliminates water such as an alkali bisulphate to form pregnane- 3 : 20 - dione.