Patent GB-1328979-A (GB)
Title: Dicarbonyl dicyano and carbonylcyano compounds
IPC: C07C49/185
Filed: 1970-09-15
Abstract: 1328979 Dicarbonyl, dicyano and carbonylcyano compounds CIBA-GEIGY AG 15 Sept 1970 [18 Sept 1969 3 Oct 1969 3 Nov 1969 24 Dec 1969 6 March 1970] 44010/70 Headings C2C and C2U Compounds of the formula (wherein R<SP>1</SP> is -CO-R 1  or -C=N; R<SP>11</SP> is -CO-R 2 , -CO-OR 3  or -C=N; R 1 , R 2 , R 4 , R 5 , R 6 , R 7  and R 8  are each H or a saturated or unsaturated, optionally substituted acyclic or alicyclic hydrocarbon radical, or an optionally substituted aromatic hydrocarbon, aralkyl, aralkenyl or heteroaromatic radical any 2 or more of which may be linked together to form a ring or rings of at least 4 ring members; R 3  has any of the values for R 1  except H; and n 1  and n 2  are each zero, 1 or 2) are prepared by reaction of compounds of the formula or their tautomers, with a base which is sufficiently strong to deprotonize the S-carrying methylene group, optionally in the presence of a thiophilic compound. Suitable bases are alkali and alkaline earth metal alcoholates and aliphatic amines, the latter being used in the presence of lithium salts of strong inorganic acids. Specified thiophilic compounds are organic derivatives of trivalent phosphorus. The reaction is effected at room temperature or a raised temperature, generally in an organic solvent. Preferred starting materials are those derived from steroids, and novel products have the formula (wherein R 1  is an optionally substituted hydrocarbon radical; R 2  is H or free or esterified OH; R 3  is H or α- or #-(free or esterified OH) or CH 3 ; R 2  + R 3  is alkylidene- or cycloalkylidene-dioxy ; R 4  is H, Cl or free or esterified OH; R 5  is H or together with R 4  is oxo; R 6  is H or halogen or together with R 4  is a double bond or α,α- or #,#-epoxy group; R 7  is H, CH 3  or halogen; #<SP>1</SP> and #<SP>6</SP> double bonds are optional; and R 8  is H, or, in #<SP>1</SP> compounds, it may also be Cl), these being derived from corresponding steroids containing a 21-SCOR, grouping, or are corresponding 19-nor compounds saturated in the 1,2-position or corresponding #<SP>1,3,5(10)</SP>-steroid trienes containing a free, esterified or etherified OH group in the 3-position. Examples describe the preparation of steroids of the above formula and also of 1-(p-bromophenyl)-1,3-dioxo-hexane 3,5-dioxo-octane; cyclopenta-1,3-dione; 2-acetyl 17#-acetoxy-3-oxo-#<SP>4</SP>-androstene; 2-acetyl-3- oxo-#<SP>4</SP>-cholestene; 2-acetyl-3-oxo-17#-propionyloxy-#<SP>4,6</SP>-androstadiene; 1-ethoxy-1,3- dioxo-hexane; 1-ethoxy-1,3-dioxo-2-methylhexane; 2,4-dioxo-3-methyl-heptane; and α- methyl-#-oxo-butyraldehyde. 2 - (Para - bromophenyl) - 2 - oxo - ethylbutyryl-sulphide is preapred from p-bromophenacyl bromide and the N-ethyl-diisopropylammonium salt of thiobutyric acid. Butyryl-2- oxo-butyl-sulphide is prepared similarly. 2- Ethoxy-2-oxo-ethyl-butyryl-sulphide is prepared from thiobutyric acid and bromoethyl acetate in the presence of triethylamine. 1-theMyl-2- ethoxy-2-oxo-ethyl-butyryl-sulphide and 1-methyl- 2-oxo-propyl-butyryl-sulphide are prepared similarly. 1-Methyl-2-oxo-propyl-formyl-sulphide is prepared from 1-bromoethylmethyl-ketone and sodium thioformate. Steroid starting materials of the formula are obtained by reacting the corresponding 21- halides, -mesylates or -tosylates with mercapto compounds e.g. thio-acids, or by acylating the corresponding free 21-mercapto compounds. The novel steroids are stated to possess thymolytic, suprarenal-inhibiting, anti-inflammatory and anti-leukaemic action and they may be made up into pharmaceutical or veterinary compositions with suitable carriers.