Patent GB-768269-A (GB)
Title: 11ª -hydroxy-4, 16-pregnadiene-3, 20-dione and its esters, and the production thereof
IPC: C07J5/00
Filed: 1954-08-25
Abstract: The invention comprises compounds of the general formula <FORM:0768269/IV(b)/1> wherein R represents hydrogen or an acyl radical of a carboxylic acid containing not more than 8 carbon atoms (which radical may contain substituents such as halo, mercapto, methoxy, ethoxy, hydroxy, carboxy or carbalkoxy), and the preparation thereof by reacting a 4 : 17a -dihalo - 11a  - acyloxypregnane - 3 : 20 - dione with an organic hydrazine to form the 3-hydrazone of an 11a -acyloxy-17a -halo-4-pregnene-3 : 20-dione, converting this by an exchange reaction with a ketone or aldehyde to the corresponding ketone, dehydrohalogenating this (e.g. by heating with an amine), and, if desired, hydrolysing the 11a -acyloxy group.  The ketone or aldehyde used for the exchange reaction is advantageously one in which the oxo group is attached to an electrophylic group, as in pyruvic acid, pyruvic aldehyde, and benzaldehydes such as o-, m- and p-hydroxy- and -carboxy-benzaldehydes.  In examples: (1) 4 : 17a -dibromo-11a -acetoxypregnane-3 : 20-dione is stirred with semicarbazide and sodium acetate in aqueous dioxan, the solution is then heated with pyruvic acid, and the resulting 11a -acetoxy-17a -bromo-4-pregnene-3 : 20-dione is refluxed with pyridine to produce 11a  - acetoxy - 4 : 16 - pregnadiene - 3 : 20-dione; (2) and (3) 4 : 17a -dichloro-11a -propionoxy- and -butyroxy - pregnane - 3 : 20 - dione are similarly converted to 11a  - propionoxy- and-butyroxy - 17a  - chloro - 4 - pregnene-3 : 20-dione and these to 11a -propionoxy- and -butyroxy - 4 : 16 - pregnadiene - 3 : 20 - dione; (4) and (5) 4 : 17a  - dibromo - 11a  - benzoyloxypregnane - 3 : 20 - dione is treated as in (1), or with 2 : 4-dinitrophenylhydrazine hydrochloride and sodium acetate in acetic acid followed by p-hydroxybenzaldehyde, to produce 11a  - benzoyloxy - 17a  - bromo - 4 - pregnene - 3 : 20-dione, which is heated with collidine to give 11a  - benzoyloxy - 4 : 16 - pregnadiene - 3 : 20-dione; the 2 : 4-dinitrophenylhydrazine in (5) may also be replaced by phenylhydrazine, p-nitro- or 3 : 5-dinitro-phenylhydrazine, semicarbazide or a - or b -naphthylsemicarbazide, and the p-hydroxybenzaldehyde by pyruvic acid, pyruvic aldehyde or carboxybenzaldehydes; (6) and (7) 4 : 17a -dibromo- and -dichloro-11a -(b  - cyclopentylpropionoxy) - pregnane - 3 : 20 - dione are converted as in (1) to 11a -(b -cyclopentylpropionoxy) - 4 : 6 - pregnadiene - 3 : 20 - dione; (8)-(12) the products of the previous examples are hydrolysed to 11a -hydroxy-4 : 16-pregnadiene-3 : 20-dione by means of sodium or potassium hydroxide in aqueous dioxan, methanol, ethanol or tert.-butanol.  Additional starting materials, intermediates and final products are listed.  Starting materials.  4 : 17a -Dihalo-11a -acyloxypregnane-3 : 20-diones are prepared by treating 11a -hydroxy- or an 11a -acyloxy-pregnane-3 : 20-dione with an acid anhydride to form the corresponding enol esters, 3 : 11a  : 20-triacyloxy-4 : 17(20)-pregnadienes, and treating these with a hypohalous acid. The preparation of 4 : 17a -dibromo- and -dichloro-11a -acetoxypregnane-3 : 20-dione is described in detail. Specification 668,533 is referred to.