Patent GB-1211697-A (GB)
Title: Method for preparing acetylenic compounds
Inventor: ESCHENMOSER ALBERT
IPC: C07C47/21
Filed: 1967-10-30
Abstract: 1,211,697. Acetylenic compounds. A. ESCHENMOSER. 30 Oct., 1967 [1 Nov., 1966; 23 Dec., 1966; 10 Feb., 1967 (2); 9 March, 1967], No. 49203/67. Headings C2C and C2U. [Also in Division C5] Acetylenic compounds of the Formula (I) are prepared by fragmentation of compounds of the Formula (II) with loss of molecular nitrogen (R 1  and R 2  and/or R 3  and R 4  are directly bonded to each other, and, if desired, R 2  and R 3  and/or R 1  and R 4  are also directly bonded to each other; R 1 , R 2 , R 3  and R 4  are each organic radicals, mono-, di- or tri-valent, or, when singly bonded, may also be H; X<SP>1</SP> is N = R 5  in which R 5  is ethyleneimino, free, esterified or etherified hydroxy, or amino substituted by a nucleofuge, particularly tosyl; and X is a reactive esterified hydroxyl group and Y is a free hydroxyl group, or X and Y together are an oxido group). Fragmentation can occur under the very conditions under which the starting oximes and hydrazones are formed, e.g. when the corresponding carbonyl compounds are reacted with a substituted hydrazine or with a reactive ether or ester of hydroxylamine. Preferred starting compounds include (a) carbocyclic or heterocyclic compounds with the double bond in a ring but not having either of its carbon atoms common to 2 rings and the conjugated carbonyl group in a side-chain, e.g. 1 - propionyl - cyclohexa - 1,4 - diene; (b) carbocyclic or heterocyclic compounds with both the keto group and the double bond in the same ring, the carbon atoms belonging to the double bond not being involved in any other ring, e.g. 2,3 - dimethyl - cyclopent - 2 - en - 1 - one; (c) an at least bicyclic carbocyclic or heterocyclic compound with the double bond forming the fusion face of 2 rings and the keto group being in one of these rings, e.g. bicyclo [10.3.0] pentadec - 1(12) - en - 13 - one; (d) cyclic ketones with a double bond between a carbon atom alpha to the keto group and a carbon atom common to two rings, e.g. 6-methyl-bicyclo [4-4-0] dec-1(2)-en-3-one; and (e) as (a) but having the carbon atom of the double bond more remote from the side chain common to 2 rings, e.g. 10,10-dimethyl-4-acetyl-tricyclo [7.1.1.0<SP>3.8</SP>] undec-3(4)-ene; and these lead respectively to (a) open chain compounds with a carbonyl group and a triple bond or cyclic compounds with the carbonyl group and the triple bond in 2 different side-chains; (b) as (a), but when cyclic having the carbonyl group and triple bond not necessarily in different sidechains; (c) mono or poly-cyclic compounds with the carbonyl group and triple bond in the same ring; (d) substituted cyclic compounds in which the carbonyl group is in a ring and the triple bond is in a side-chain to this ring; and (e) similar to (d). Steroids with a nuclear double bond and a nuclear or side-chain, e.g. 20, keto group are especially preferred starting materials. Hydrazones carrying a nucleofuge may be fragmented by acidic reagents, inorganic or organic bases, or sodium hydride in DMS, or thermally or photochemically, or by contact with polar adsorption agents, e.g. silica gel, or ion exchange resins. In the spontaneous decomposition of hydrazones referred to above the product may itself be converted to a hydrazone if excess of hydrazine reagent is present; these hydrazones may then be cleaved to the free ketones. Aldehyde products formed in the presence of alcohols may be isolated as acetals or hemi-acetals. The oximes are fragmented in a basic medium with reactive esters of hydroxylamine. The products of the process, many of which are new, may be converted to known odiferous compounds and flavours, e.g. by catalytic hydrogenation or partial hydrogenation. The seco-steroid products may be converted to biologically active steroids. Examples describe the preparation of the following starting materials and intermediates, products of the process of the invention and compounds into which these products are converted: 1,12 - epoxy - bicyclo [10.3.0] pentadecan - 13 - one and its tosyl hydrazone, cyclopentadec - 4 - yn - 1 - one, cyclopentadec - 4 - en- 1 - one, cyclopentadecanone, 3 - methyl - cyclopentadec - 4 - yn - 1 - one, 3 - methylcyclopentadec - cis - 4 - en - 1 - one, 3 - methyl - cyclopentadecan - 1 - one, 2 - ethyl - 2,3 - epoxy - cyclopentanone, hept - 4 - yn - 1 - al, cis - hept - 4 - en- 1 - al, epoxy -jasmone, undec - 8 - en - 5 - yn-2- one, undecan - 2 - one, 2 - methyl - 2,3 - oxidocyclohexan - 1 - one, hept - 5 - yn - 1 - al, cis - hept- 5 - en - 1 - al, the tosyl hydrazone of epoxy-isophorone, 4,4 - dimethylhept - 6 - yn - 2 - one, 4,4 - dimethylhept - 6 - en - 2 - one, 4,4 - dimethyl heptan - 2 - one, 2,3 - dihydroxy - 3,5,5- trimethyl - cyclohexanone - (1) and its 3-mesylate and the oxime of the last-named, the epoxide of cedranal, 1 - formylmethyl - 3 - ethynyl - 4,4,8- trimethyl - bicyclo [3.3.0] octane, 4 - acetoxy-4- cyano - 10,10 - dimethyl - tricyclo [7.1.1.0<SP>3.8</SP>]- undec - 7 - ene, 10,10 - dimethyl - tricyclo [7.1.1.0<SP>3.8</SP>] undec - 3(8) - en - 4 - one and its epoxide, 10,10 - dimethyl - bicyclo [7.1.1]- undec - 6 - yn - 2 - one, the epoxide of piperitone, 3 - isopropylhept - 1 - yn - 6 - one, 3 - isopropylheptan - 6 - one, the epoxide of 2 - n - pentylcyclopent - 2 - en - 1 - one, dec - 4 - yn - 1 - al, 3 - methyl - 2,3 - oxido - cyclohexan - 1 - one, hept - 6 - yn - 2 - one, hept - 6 - en - 2 - one, heptan - 2 - one, 1,2 - epoxy - 6 - methylbicyclo [4.4.0] decan - 3 - one, 2 - methyl - 2 - (but - 3 - yn - 1 - yl) - cyclohexan - 1 - one, 1 - propionylcyclohexa - 1,4 - diene, 1,2 - epoxy - 1 - propionylcyclohex - 4 - ene and its tosyl hydrazone, cisnon - 3 - en - 6 - yn - 1 - al, cis,cis - nona - 3 6 - dien - 1 - al, the tosyl hydrazone of 14 - methylbicyclo [10.3.0] pentadec - 1(12) - en - 13 - one, 1,7 - epoxybicyclo [5.3.0] decan - 2 - one, cyclodec - 5 - yn - 1 - one, 1,6 - epoxy - bicyclo [4.4.0]- decan - 2 - one, cyclodec - 5 - yn - 1 - one, 7,7- dimethyl - 1 - hydroxyticyclo [4.4.0] decan - 3 - one and its epoxide, 3,3-dimethyl-2-(but-3-yn-1-yl)- cyclohexan - 1 - one, bicyclo [9.4.0] pentadec- 1(11)-en- 12-one and its epoxide, cyclopentadec-5- yn - 1 - one, cyclopentadec - 5 - en - 1 - one, 14- methylbicyclo [10.3.0] pentadec - 13 - ol, 14- methyl - bicyclo [10.3.0] pentadec - 1(12) - ene, 3- methyl - cyclopentadecane - 1,5 - dione, 14- methylbicyclo [9.4.0] pentadec - 1(11) - en - 12-one and its epoxide, 3 - methylcyclopentadec - 5 - yn - 1 - one, 3 - methylcyclopentadec - 5 - en-l-one, bicyclo [9.4.0] pentadec - 1(11) - en - 12 - one and its tosyl hydrazone, bicyclo [9.4.0] pentadecan- 12 - ol, bicyclo [9.4.0] pentadec - 1(11) - ene, cyclopentadecane - 1,6 - d 7 one, bicyclo [10.3.0] pentadec - 1(12) - en - 2 - one and its epoxide, cyclopentadec - 5 - yn - 1 - one, bicyclo [10.4.0] hexadec - 1(12) - en - 13 - one and its epoxide, cyclohexadec - 5 - yn - 1 - one, cis - cyclohexadec- 5 - en - 1 - one, cyclohexadecanone; cycloheptadec - 4 - yn - 1 - one, cycloheptadec-5-yn-1-one, cycloheptadec - 6 - yn - 1 - one, and the corresponding cycloheptadecenones; undec-5-yn-2- one, undec - 5 - en - 2 - one, 1,2 - epoxy - 2 - hexylcyclopentanone, undec - 4 - yn - 1 - al, cis-undec- 4 - en - 1 - al, 2 - butyl - 2,3 - epoxycyclopentan-1- one, non - 4 - yn - 1 - al, cis - non - 4 - en - 1 - al, 2 - heptyl - 2,3 - epoxycyclopentan - 1 - one, dodec- 4 - yn - 1 - al, cis - dodec - 4 - en - 1 - al, 2-decyl- 2,3 - epoxycyclopentan - 1 - one, pentadec - 4 - yn- 1 - al, cis - pentadec - 4 - en - 1 - al, 2,3 - epoxy-2- ethyl - cyclopentan - 1 - one, hept - 4 - yn - 1 - al, undeca - 4,8 - dien - 2 - one, dec - 4 - yn - 1 - al, cis - dec - 4 - en - 1 - al, 1,2 - epoxy - 1 - propionylcyclopentane, hept - 5 - yn - 1 - al, 1 - oxo - 17#- acetoxy - 1,2 - seco - 5α - androst - 2 - yne, 5-oxo- 11# - hydroxy - 17α,20; 20,21 - bismethylenedioxy-4,5-seco-pregn-3-yne and the corresponding 19 - nor - compound, 5,20 - dioxo-11#, 17α - 21 - trihydroxy - 4,5 - secopregn - 3 - yne, 3# - acetoxy - 16 - oxo - 16,17 - seco - #<SP>5</SP>-pregnen - 17(20) - yne and its diethyl acetal, 5- oxo - 17# - acetoxy - 4,5 - seco - androst - 3 - yne and the corresponding 19-nor compound, 5,20- dioxo - 21 - hydroxy - 4,5 - seco - pregn - 3 - yne and its 21-acetate and 20-ethylene ketal, the tosyl hydrazone of 3#-acetoxy-16-oxo- 16,17- seco - #<SP>5</SP> - pregnen - 17(20) - yne, 3 - methoxy- 16 - oxo - 16,17 - seco - #<SP>1,3,5(10)</SP> - 19 - norpregnatrien - 17(20) - yne and its dimethyl and diethyl acetals, 5-oxo-17α-ethynyl-17#-hydroxy- 4,5 - seco - 19 - norandrost - 3 - yne, 3#,17#- diacetoxy - 5 - oxo - 5,6 - seco - androst - 6 - yne, 5,17 - dioxo - 4,5 - seco - estr - 3 - yne, 5,20- dioxo - 4,5 - seco - pregn - 3 - yne, 3# - hydroxy- 9 - oxo - 9,11 - seco - 5α - spirost - 11 - yne, 4- methyl - 5 - oxo - 17# - acetoxy - 4,5 - secoandrost - 3 - yne, 3# - acetoxy - 16 - oxo - 16- methyl - 16,17 - seco - #<SP>5</SP> pregn -17(20) - yne, 3 - oxo 17# - acetoxy - 2,3 - seco - 5α - androst- 1 - yne, 3,3,17,17 - bisethylenedioxy - 10 - oxo- 5,10 - seco - estr - 5(6) - yne and the corresponding 17-one, 5 - oxo - 17# - carbomethoxy- 4,5 - seco - androst - 3 - yne and 5 - oxo - 4,5- seco-cholest-3-yne. Steroid starting materials prepared are 3-oxo- 4,5 - oxido - 20,20 - ethylenedioxy - 21 - hydroxypregnane (by ketalizing 3,21-dihydroxy-20-oxo- #<SP>5</SP> - pregnane, Oppenauer oxidation and epoxidation of the #<SP>4</SP> double bond); 3-oxo-4#,5-oxido- 17# - hydroxy - 17α - ethynyl - 19 - nor - androstane; 3 - methoxy - 16α,17α - oxido - 20 - oxo- #<SP>1,3,5(10)</SP> - 19 - norpregnatriene; 3#,17# - diacetoxy - 5,6 - oxido - 7 - oxo - androstane (mixture of epimers) and its tosyl hydrazone; the oximes of 17α,20,20,21 - bismethylenedioxy - 3 - oxo - 4#,5#- and 4α,5α - epoxy - 11# - hydroxypregnanes, 3 - oxo