CA1055881A - Electrolytic reduction of aromatic steroids - Google Patents
Electrolytic reduction of aromatic steroidsInfo
- Publication number
- CA1055881A CA1055881A CA204,982A CA204982A CA1055881A CA 1055881 A CA1055881 A CA 1055881A CA 204982 A CA204982 A CA 204982A CA 1055881 A CA1055881 A CA 1055881A
- Authority
- CA
- Canada
- Prior art keywords
- delta
- alkali metal
- methoxy
- process according
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/005—Ketals
- C07J21/008—Ketals at position 17
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
- C25B3/25—Reduction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Steroid Compounds (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
Abstract of the Disclosure .DELTA.2,5(10)-steroids, which are intermediates for the preparation of valuable pharmaceutical products, are produced from corresponding .DELTA.1,3,5(10)-steroids by electrolytically reducing the latter in liquid ammonia in a divided cell in the presence of an alkali metal salt of a strong acid having a pK
value of less than 5, or an undivided cell in the presence of an alkali metal salt of a weak acid having a pK value from 5 to 32. For example, oestrone methyl ether is electrolyti-cally reduced in ammonia in the presence of lithium perchlorate in a divided cell to produce 3-methoxy-.DELTA.2,5(10)-oestradien-17.beta.--ol.
value of less than 5, or an undivided cell in the presence of an alkali metal salt of a weak acid having a pK value from 5 to 32. For example, oestrone methyl ether is electrolyti-cally reduced in ammonia in the presence of lithium perchlorate in a divided cell to produce 3-methoxy-.DELTA.2,5(10)-oestradien-17.beta.--ol.
Description
~5~
; The invention relates to a process for producing ~ '5'(10)-steroids from corresponding ~1'3'5(10)-steroids by ; electrochemical reduction.
It is known that the electrolys:is of unsaturated aromatic steroids in liquid ammonia in an undivided cell in the presence of alkali or alkaline earth rnetal salts does ;~
indeed lead to the reduction of unsaturated ~roups, but the aromatic part of the steroid molecule is not attacked (see German Patent Publication No. 2,063llOl, published 22nd June 1972 to Dr. Klaus Junghans).
; The electrochemical reduction of aromatic steroids to form the corresponding Q2r5(10)-steroids is also known (see ' German Patent Specification No. 1,266,300). In such process, ;l the electrolysis is carried out in methylamine or in another alkylamine solvent. Ilowever, the process has the dlsadvantage that the amine used as the solvent must, after the electrolysis, ~ be separated from the product by distillation under reduced `~ pressure or precipitation with other liquids.
Because of the low conductivity of the reaction mix- `
- 20 ture, the consumption of current is very high, and there is a correspondingly strong evolution of heat. ~owever, in carrying .:
~' out the process on an industrial scaie the heat must be removed.
The present invention is based on the problem of dis-., .
;l covering a process for the electrochèmical reduction of aromatic steroids, in which the solvent can be separated from the product, ~;~
without great technical expenditure and less current consumption, and thus no great evolution of heat.
The above problem is solved by carrying out the elec-trolysis with a liquid ammonia solvent in a divided cell in the ,` l presence of an alkali metal salt of a strong acid having a pK
value of less than 5 as the conductive salt, or in an undivided ,, ~ .. . .
, , ,. . ~
,, -- 1 --~ .
! ~ ~ . , .
' ~
~S~;81!~
cell in the presence of an a]kali me-tal salt containing anions of a weak acid having a pK value of 5 to 32 as the con~uctive salts.
Electrochemical reduction in liquid ammonia is des-cribed for simple aromatic substances (see, Eor example, U.S. -Patents Nos. 3,493,477 and 3,488,266), but the smooth electrolysis of steroids having a complex structure and optionally substituted by functional groups could not have been expected~ Is is also surprising that the aromatic ring is reduced by working in accordance with the process of German ~atent Publication ~o.
; The invention relates to a process for producing ~ '5'(10)-steroids from corresponding ~1'3'5(10)-steroids by ; electrochemical reduction.
It is known that the electrolys:is of unsaturated aromatic steroids in liquid ammonia in an undivided cell in the presence of alkali or alkaline earth rnetal salts does ;~
indeed lead to the reduction of unsaturated ~roups, but the aromatic part of the steroid molecule is not attacked (see German Patent Publication No. 2,063llOl, published 22nd June 1972 to Dr. Klaus Junghans).
; The electrochemical reduction of aromatic steroids to form the corresponding Q2r5(10)-steroids is also known (see ' German Patent Specification No. 1,266,300). In such process, ;l the electrolysis is carried out in methylamine or in another alkylamine solvent. Ilowever, the process has the dlsadvantage that the amine used as the solvent must, after the electrolysis, ~ be separated from the product by distillation under reduced `~ pressure or precipitation with other liquids.
Because of the low conductivity of the reaction mix- `
- 20 ture, the consumption of current is very high, and there is a correspondingly strong evolution of heat. ~owever, in carrying .:
~' out the process on an industrial scaie the heat must be removed.
The present invention is based on the problem of dis-., .
;l covering a process for the electrochèmical reduction of aromatic steroids, in which the solvent can be separated from the product, ~;~
without great technical expenditure and less current consumption, and thus no great evolution of heat.
The above problem is solved by carrying out the elec-trolysis with a liquid ammonia solvent in a divided cell in the ,` l presence of an alkali metal salt of a strong acid having a pK
value of less than 5 as the conductive salt, or in an undivided ,, ~ .. . .
, , ,. . ~
,, -- 1 --~ .
! ~ ~ . , .
' ~
~S~;81!~
cell in the presence of an a]kali me-tal salt containing anions of a weak acid having a pK value of 5 to 32 as the con~uctive salts.
Electrochemical reduction in liquid ammonia is des-cribed for simple aromatic substances (see, Eor example, U.S. -Patents Nos. 3,493,477 and 3,488,266), but the smooth electrolysis of steroids having a complex structure and optionally substituted by functional groups could not have been expected~ Is is also surprising that the aromatic ring is reduced by working in accordance with the process of German ~atent Publication ~o.
2/063,101, but in a divided cell ins-tead of an undivided cell, or by using in an undivided cell, as conductive salts, alkali metal salts having anions of acids that are weak acids in liquid ammonia, optionally with the addition of alkali metal salt of strong acids.
W'nen the elec-trolysis of the invention is carried out in a divided cell, there are used as conductive salts alkali metal salts, for example, lithium, sodium or potassium salts.
The anions necessary for charge equalization are derived from strong acids and are, for example, halides such as a chloride or bromide, or complex anions such as a tetrafluoborate, sulphate or perchlorate.
When the electrolysis is carried out in an undivided cell, there are used as conductive salts alkali salts of weak ` acids, for example, aniline, hydrazine~ alcohol or water in liquid ammonia, i.e. alkali metal anilides, hydrazides, alcohol- ;
ates, and hydroxides.
The concentration ratio of electrolyte salt to the steroid to be reduced has no influence on -the reduction and may vary within wide limits. The reduction is also not disturbed if ; a portion of the reactants is present as solid at the bottom :.
.'..... . .,,, , . , . , ,, , ., :
~55~
.
of the liquid (saturated solution).
In accordance with the invention, ammonia is used as solvent. Small amounts of other solvents may be added, provided they are inert with respect to the reac-tants. Such other sol-vents serve as a solubiliser between the ammonia and the steroid to be reduced. The other solvents include, for example, ethers such as diethyl ether, tetrahydrofuran and dioxane, acid deriva-- tives such as ethyl acetate, acetonitrile and dimethylformamide, and dimethyl sulphoxide.
The divided cell is of conventional construction, the electrode compartments being separated by porous m~terial, for example, glass frit, a clay diaphragm or asbestos wool, or by an ion-exchange membrane.
The electrolysis may be carried out with an~ type of current such as alternating current, rectified unsmoothed alter-nating current, direct current or modulated direct current. The ;, conditions of the electrolysis, such as voltage, amperage, cur-rent density, electrode area, pressure and temperature, can be varied widely. It is advantageous to operate at a current den-20 sity of 0.1 to 5 amperes/cm2 and a temperature of from -50C up to the boiling point of the reaction mixture. ~Iowever, it is also possible to operate under pressure. The nature of the electrode material is not critical. It only has to conduct the current and to be stable under the conditions of the electrolysis, as are, for example, gold, silver, mercury, platinum, aluminium, tungsten carbide and graphite. The process of electrolysis may be carried out in a continuous or discontinuous manner. -The starting compounds used in accordance with the invention are ~1~3~5(1)-3-hydroxy-trienes of oestrane, 18-methyl-30 oestrane, l9-nor-pregnane or l9-nor-cholestane in the form of
W'nen the elec-trolysis of the invention is carried out in a divided cell, there are used as conductive salts alkali metal salts, for example, lithium, sodium or potassium salts.
The anions necessary for charge equalization are derived from strong acids and are, for example, halides such as a chloride or bromide, or complex anions such as a tetrafluoborate, sulphate or perchlorate.
When the electrolysis is carried out in an undivided cell, there are used as conductive salts alkali salts of weak ` acids, for example, aniline, hydrazine~ alcohol or water in liquid ammonia, i.e. alkali metal anilides, hydrazides, alcohol- ;
ates, and hydroxides.
The concentration ratio of electrolyte salt to the steroid to be reduced has no influence on -the reduction and may vary within wide limits. The reduction is also not disturbed if ; a portion of the reactants is present as solid at the bottom :.
.'..... . .,,, , . , . , ,, , ., :
~55~
.
of the liquid (saturated solution).
In accordance with the invention, ammonia is used as solvent. Small amounts of other solvents may be added, provided they are inert with respect to the reac-tants. Such other sol-vents serve as a solubiliser between the ammonia and the steroid to be reduced. The other solvents include, for example, ethers such as diethyl ether, tetrahydrofuran and dioxane, acid deriva-- tives such as ethyl acetate, acetonitrile and dimethylformamide, and dimethyl sulphoxide.
The divided cell is of conventional construction, the electrode compartments being separated by porous m~terial, for example, glass frit, a clay diaphragm or asbestos wool, or by an ion-exchange membrane.
The electrolysis may be carried out with an~ type of current such as alternating current, rectified unsmoothed alter-nating current, direct current or modulated direct current. The ;, conditions of the electrolysis, such as voltage, amperage, cur-rent density, electrode area, pressure and temperature, can be varied widely. It is advantageous to operate at a current den-20 sity of 0.1 to 5 amperes/cm2 and a temperature of from -50C up to the boiling point of the reaction mixture. ~Iowever, it is also possible to operate under pressure. The nature of the electrode material is not critical. It only has to conduct the current and to be stable under the conditions of the electrolysis, as are, for example, gold, silver, mercury, platinum, aluminium, tungsten carbide and graphite. The process of electrolysis may be carried out in a continuous or discontinuous manner. -The starting compounds used in accordance with the invention are ~1~3~5(1)-3-hydroxy-trienes of oestrane, 18-methyl-30 oestrane, l9-nor-pregnane or l9-nor-cholestane in the form of
-3-.. ''' .
5B8~
their 3-alkyl, 3-cycloalkyl or 3-aralkyl ethers. They may con-tain, in addition -to the double bonds in the aromatic A-ring, one or more conjugated carbon-to-carbon bonds such as, for example, ~6_, ~8_, or a9 (11)_ and/or other reducible groupings, for example, carbonyl groups in the 6-, 11- or 20-position, nitro or imino groups ~C=N~, wherein R represents hydrogen, hydroxyl, alkyl, aryl or aralkyl. The double bonds are co-reduced during the process of the invention, and an exo-cyclic multiple bond, such as the 17~-ethinyl group, is reduced to a double bond. Such an isolated carbon-to-carbon double bond is not further reduced. The steroid structure may contain addi-tional alkyl groups, for example, methyl in the 1-, 6-, 7- or 16-position, and free or functionally convertedhydroxyl groups in the 1-, 3-, 6-, 7-, 11-, 15-, 16-, 17-, or 21-position. A
17-alkyl group may be ~-or ~-positioned.
The starting steroids include, for example, oestrone methyl ether; 3-methoxy-~1'3'5(1)'3-oestratetraen-17~-ol; 3-methoxy-18-methyl-~1'3'5(1)'3-oestratetraen-17-one; 3-methoxy-~ '3'5(1)-pregnatrien-17~-ol-20-ethylene-ketal; 3-methoxy-~1~3'5'(10)'9(11)-oestratetraen-17~-ol; 3-ethoxy-17a-methyl-oestra-~1'3'5(1)-trien-17~-ol; 3-cyclohexyloxy-17~-vinyl-~1'3'5(1)-oestratrien-173-ol; 3-methoxy-19-nor-~1'3'5(1)-chloestatriene; 3-methoxy-1-methyl-19-nor-20-cycloethylenedioxy-'3'5(10)-pregnatriene; 3-methoxy-17~,20;20,21-bis-methylene-dioxy-pregna-l9-nor-~1'3'5(10)-pregnatriene; 3-methoxy-17-ethylene-diOxy-~1'3'5(10)-oestratriene and 3-methoxy-17~-t-b t ~1,3,5(10),9(11)_Oestratetraene.
The compounds obtained by the process of the present invention are often intermediate products fot the preparation of i 30 valuable pharmaceutical products.
~"'"' . ~
~, -ds ~
~3S5~8~L `
The present invention will be further illustrated by way of the followiny Examples in which Examples 1, 4, 6, and 7 relate to divided cells.
Example 1 1.0 g of oestrone methyl ether is dissolved in 50 ml of tetrahydrofuran and 200 ml of liquid ammonia, and the solution is electrolyzed in the presence of 2.5 g of lithium perchlorate in a cell divided by a glass frit for 1.5 hours at 1 ampere (cathode of stainless steel and anode of graphite). After evaporating the solvent, water is added, and the mixture is filtered. There is thus obtained 0.9 g of 3-methoxy-~ ' (1)-oestradien-17~--ol melt-ing at 114-116C (methanol~.
Example 2 2.0 g of 3-methoxy-~1'3'5(1)'3-oestratetraene-17~-ol are eleckrolyzed in 200 ml of liquid ammonia and 20 ml of ethanol in the presence of 2 g of lithium ethylate and 0.5 g of lithium C
anilide for 3 hours in an undivided cell between an aluminium cathode and a platinum anode at a current density of 2.5 amperes/
cm . After working up, there are isolated 1.8 g of 3-methoxy-~ '5(1~-oestradien-17~-ol melting at 110C.
Example 3 l~
0-5 g of d~l-3-methoxy-lg-methyl-~l~3~5(lo)~8 oest ; tetraen-17-one in 250 ml of liquid ammonia is electrolyzed in an autoclave at 30C between a stainless steel cathode and a graphite anode in the presence of 2.0 g of sodium chloride and ` 2.0 g of sodium ethylate at 2 amperes. When the reaction has ;, terminated, the solvent is evaporated by cautious pressure equilization, water is added to the residue, and the mixture is L
filtered. There is thus obtained 0.4 g of _,1-3-methoxy-18-methyl-h ' (1)-oestradien-17~-ol melting at 98-100C.
Example 4 - 1.0 g of 3-methoxy-hl'3'5(1)-pregnatrien-17a-ol-20-ethylene-ketal is electrolyzed in a cell divided by a cation exchange membrane in 200 ml of liquid ammonia in the presence of 2.5 g of sodium perchlorate with an aluminium cathode. After ; working up, 1.0 g of 3-methoxy-Q2'5(1)-pregnadien-17~-ol-20- -ethylene-ketal melting at 172-175C.
Example 5 1.0 g of 3-methoxy-~l~3~5(lO)~9(ll)-oestratetraen-17~--ol is dissolved in 25 ml of dioxane, and the solution is intro-duced into a decolorized mixture of 0.5 g of lithium in 200 ml of liquid ammonia, 5 g of lithium chloride, 15 ml of ethanol and 5 ml of aniline. When electrolysis at 1 ampere between two platinum electrodes has terminated and the ammonia has been evaporated, a large amount of water is added, and the mixture ; is filtered. 0.8 g of 3-methoxy-~2'5(1)-oestradien-173-ol melting at 108-112C is isolated.
Example 6 1.0 g oE 3-methoxy-17-ethylene-dioxy-~1'3'5(1)-oestra-triene in 10 ml of ethanol is added to 200 ml of liquid ammonia and 2 g of lithium chloride, and electrolyzed for 1 hour at 1 ampere with a tungsten carbide electrode in a cell divided by - 20 a cation exchange membrane. After working up, 0.9 g of 3-methoxy-17-ethylene-dioxy-~2'5(1)-oestradiene melting at 115-120C is obtained.
Example 7 1.0 g of 3-methoxy-17 -t-butoxy-~1~3~5(10)~9(11) oe t t~traen:i~sdissolved in 4 ml of aniline and 3 ml of ethanol, added to 150 ml of liquid ammonia and 5 g of lithium perchlor~
.:
ate, and electrolyzed for 2 hours at 1 ampere with a merecury ~ electrode in a cell divided by a glass frit. After working up, ;, the crude product (1.1 g) is dissolved in ethanol and heat~d -~ 30 with 3 ml of concentrated hydrochloric acid. By the cautious .`~'''. .
:' .: :
';, ' : addition of water and after cooling, 0.~ y of nor-testosterone ;:
is obtained which, after recrystallization from isopropyl ether, ;~
melts at 108-110C.
,. ~'.
.. . .
.-, .~, .':
. .
'....... , 10 .
;j"
... ,~
,,, ~
. D, ' :
.' . .
;~'.' ' ' ~
" ,"' '~ ' .~J
:i~
.. ''.',' ` ..
.. . .
.: .
.. . .
.,i ~
., ~
:- ....................................................................... .
.''` ~: ` .
:. 30 : . .
.,:;
~., -7-:.
,
5B8~
their 3-alkyl, 3-cycloalkyl or 3-aralkyl ethers. They may con-tain, in addition -to the double bonds in the aromatic A-ring, one or more conjugated carbon-to-carbon bonds such as, for example, ~6_, ~8_, or a9 (11)_ and/or other reducible groupings, for example, carbonyl groups in the 6-, 11- or 20-position, nitro or imino groups ~C=N~, wherein R represents hydrogen, hydroxyl, alkyl, aryl or aralkyl. The double bonds are co-reduced during the process of the invention, and an exo-cyclic multiple bond, such as the 17~-ethinyl group, is reduced to a double bond. Such an isolated carbon-to-carbon double bond is not further reduced. The steroid structure may contain addi-tional alkyl groups, for example, methyl in the 1-, 6-, 7- or 16-position, and free or functionally convertedhydroxyl groups in the 1-, 3-, 6-, 7-, 11-, 15-, 16-, 17-, or 21-position. A
17-alkyl group may be ~-or ~-positioned.
The starting steroids include, for example, oestrone methyl ether; 3-methoxy-~1'3'5(1)'3-oestratetraen-17~-ol; 3-methoxy-18-methyl-~1'3'5(1)'3-oestratetraen-17-one; 3-methoxy-~ '3'5(1)-pregnatrien-17~-ol-20-ethylene-ketal; 3-methoxy-~1~3'5'(10)'9(11)-oestratetraen-17~-ol; 3-ethoxy-17a-methyl-oestra-~1'3'5(1)-trien-17~-ol; 3-cyclohexyloxy-17~-vinyl-~1'3'5(1)-oestratrien-173-ol; 3-methoxy-19-nor-~1'3'5(1)-chloestatriene; 3-methoxy-1-methyl-19-nor-20-cycloethylenedioxy-'3'5(10)-pregnatriene; 3-methoxy-17~,20;20,21-bis-methylene-dioxy-pregna-l9-nor-~1'3'5(10)-pregnatriene; 3-methoxy-17-ethylene-diOxy-~1'3'5(10)-oestratriene and 3-methoxy-17~-t-b t ~1,3,5(10),9(11)_Oestratetraene.
The compounds obtained by the process of the present invention are often intermediate products fot the preparation of i 30 valuable pharmaceutical products.
~"'"' . ~
~, -ds ~
~3S5~8~L `
The present invention will be further illustrated by way of the followiny Examples in which Examples 1, 4, 6, and 7 relate to divided cells.
Example 1 1.0 g of oestrone methyl ether is dissolved in 50 ml of tetrahydrofuran and 200 ml of liquid ammonia, and the solution is electrolyzed in the presence of 2.5 g of lithium perchlorate in a cell divided by a glass frit for 1.5 hours at 1 ampere (cathode of stainless steel and anode of graphite). After evaporating the solvent, water is added, and the mixture is filtered. There is thus obtained 0.9 g of 3-methoxy-~ ' (1)-oestradien-17~--ol melt-ing at 114-116C (methanol~.
Example 2 2.0 g of 3-methoxy-~1'3'5(1)'3-oestratetraene-17~-ol are eleckrolyzed in 200 ml of liquid ammonia and 20 ml of ethanol in the presence of 2 g of lithium ethylate and 0.5 g of lithium C
anilide for 3 hours in an undivided cell between an aluminium cathode and a platinum anode at a current density of 2.5 amperes/
cm . After working up, there are isolated 1.8 g of 3-methoxy-~ '5(1~-oestradien-17~-ol melting at 110C.
Example 3 l~
0-5 g of d~l-3-methoxy-lg-methyl-~l~3~5(lo)~8 oest ; tetraen-17-one in 250 ml of liquid ammonia is electrolyzed in an autoclave at 30C between a stainless steel cathode and a graphite anode in the presence of 2.0 g of sodium chloride and ` 2.0 g of sodium ethylate at 2 amperes. When the reaction has ;, terminated, the solvent is evaporated by cautious pressure equilization, water is added to the residue, and the mixture is L
filtered. There is thus obtained 0.4 g of _,1-3-methoxy-18-methyl-h ' (1)-oestradien-17~-ol melting at 98-100C.
Example 4 - 1.0 g of 3-methoxy-hl'3'5(1)-pregnatrien-17a-ol-20-ethylene-ketal is electrolyzed in a cell divided by a cation exchange membrane in 200 ml of liquid ammonia in the presence of 2.5 g of sodium perchlorate with an aluminium cathode. After ; working up, 1.0 g of 3-methoxy-Q2'5(1)-pregnadien-17~-ol-20- -ethylene-ketal melting at 172-175C.
Example 5 1.0 g of 3-methoxy-~l~3~5(lO)~9(ll)-oestratetraen-17~--ol is dissolved in 25 ml of dioxane, and the solution is intro-duced into a decolorized mixture of 0.5 g of lithium in 200 ml of liquid ammonia, 5 g of lithium chloride, 15 ml of ethanol and 5 ml of aniline. When electrolysis at 1 ampere between two platinum electrodes has terminated and the ammonia has been evaporated, a large amount of water is added, and the mixture ; is filtered. 0.8 g of 3-methoxy-~2'5(1)-oestradien-173-ol melting at 108-112C is isolated.
Example 6 1.0 g oE 3-methoxy-17-ethylene-dioxy-~1'3'5(1)-oestra-triene in 10 ml of ethanol is added to 200 ml of liquid ammonia and 2 g of lithium chloride, and electrolyzed for 1 hour at 1 ampere with a tungsten carbide electrode in a cell divided by - 20 a cation exchange membrane. After working up, 0.9 g of 3-methoxy-17-ethylene-dioxy-~2'5(1)-oestradiene melting at 115-120C is obtained.
Example 7 1.0 g of 3-methoxy-17 -t-butoxy-~1~3~5(10)~9(11) oe t t~traen:i~sdissolved in 4 ml of aniline and 3 ml of ethanol, added to 150 ml of liquid ammonia and 5 g of lithium perchlor~
.:
ate, and electrolyzed for 2 hours at 1 ampere with a merecury ~ electrode in a cell divided by a glass frit. After working up, ;, the crude product (1.1 g) is dissolved in ethanol and heat~d -~ 30 with 3 ml of concentrated hydrochloric acid. By the cautious .`~'''. .
:' .: :
';, ' : addition of water and after cooling, 0.~ y of nor-testosterone ;:
is obtained which, after recrystallization from isopropyl ether, ;~
melts at 108-110C.
,. ~'.
.. . .
.-, .~, .':
. .
'....... , 10 .
;j"
... ,~
,,, ~
. D, ' :
.' . .
;~'.' ' ' ~
" ,"' '~ ' .~J
:i~
.. ''.',' ` ..
.. . .
.: .
.. . .
.,i ~
., ~
:- ....................................................................... .
.''` ~: ` .
:. 30 : . .
.,:;
~., -7-:.
,
Claims (12)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for producing a .DELTA.2,5(10)-steroid compris-ing the step of reducing a corresponding .DELTA.1,3,5(10)-steroid by electrolysis in liquid ammonia in a cell in the presence of an alkali metal salt of an acid, provided that when said cell is a divided cell the acid is a strong acid having a pK value of less than 5 and when said cell is an undivided cell the acid is a weak acid having a pK value from 5 to 32.
2. A process according to claim 1, wherein the alkali metal salt of a strong acid is an alkali metal halide, tetrafluo-borate, sulphate or perchlorate.
3. A process according to claim 2, wherein the alkali metal is lithium, sodium or potassium.
4. A process according to claim 1, wherein the alkali metal salt of a weak acid is an alkali metal salt of aniline, hydrazine or alcohol or an alkali metal hydroxide.
5. A process according to claim 4, wherein the alkali metal is lithium, sodium or potassium.
6. A process according to claim 1, wherein the elec-trolysis is carried out in an undivided cell in the presence of an alkali metal salt of a strong acid, having a pK value of less than 5 and an alkali metal salt of a weak acid having a pK value from 5 to 32.
7. A process according to claim 6, wherein the alkali metal salt of a strong acid is an alkali metal halide, tetrafluo-borate, sulphate or perchlorate.
8. A process according to claim 7, wherein the alkali metal is lithium, sodium or potassium.
9. A process according to claim 1, 2 or 3, wherein the electrode compartments in the divided cell are separated by porous material or an ion-exchange membrane.
10. A process according to claim 1, 2 or 3, wherein the electrolysis is operated at a current density within the range of from 0.1 to 5 amperes/cm2.
11. A process according to claim 1, 2 or 3, wherein the .DELTA.1,3,5(10)-steroid is a 3-alkyl, -cycloalkyl or -aralkyl ether of a .DELTA.1,3,5(10)-3-hydroxy-triene of the oestrane, 18-methyl oestrane, 19-nor-pregnane or 19-nor-cholestane series.
12. A process according to claim 1 or 2, wherein the .DELTA.1,3,5(10)-steroid is oestrone methyl ether; 3-methoxy-.DELTA.1,3,5(10),8-oestratetraen-17.beta.-ol; 3-methoxy-18-methyl-.DELTA.1,3,5(10),8-oestratetraen-17-one; 3-methoxy-.DELTA.1,3,5(10)-pregnatrien-17.alpha.-ol-20-ethylene-ketal; 3-methoxy-.DELTA.1,3,5(10),9(11)-oestratetraen-17.beta.-ol; 3-ethoxy-17.alpha.-methyl-.DELTA.1,3,5(10)-oestratrien-17.beta.-ol; 3-cyclohexyloxy-17.alpha.-vinyl-.DELTA.1,3,5(10)-oestratrien-17.beta.-ol; 3-methoxy-19-nor-.DELTA.1,3,5(10)-cholestatriene; 3-methoxy-1-methoxy-19-nor-20-cycloethylenedioxy-.DELTA.1,3,5(10)-pregnatriene; 3-methoxy-17.alpha.,20; 20,21-bis-methylenedioxy-19-nor-.DELTA.1,3,5(10)-pregnatriene;
3-methoxy-17-ethylenedioxy-.DELTA.1,3,5(10)-oestratriene or 3-methoxy-17.beta.-t-butoxy-.DELTA.1,3,5(10),9(11)-oestratetraene.
3-methoxy-17-ethylenedioxy-.DELTA.1,3,5(10)-oestratriene or 3-methoxy-17.beta.-t-butoxy-.DELTA.1,3,5(10),9(11)-oestratetraene.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732337155 DE2337155A1 (en) | 1973-07-18 | 1973-07-18 | ELECTROLYTIC REDUCTION OF AROMATIC STEROIDS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1055881A true CA1055881A (en) | 1979-06-05 |
Family
ID=5887618
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA204,982A Expired CA1055881A (en) | 1973-07-18 | 1974-07-18 | Electrolytic reduction of aromatic steroids |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5032158A (en) |
| CA (1) | CA1055881A (en) |
| CH (1) | CH601493A5 (en) |
| DD (1) | DD112996A5 (en) |
| DE (1) | DE2337155A1 (en) |
| DK (1) | DK131434B (en) |
| FR (1) | FR2237981B1 (en) |
| GB (1) | GB1478679A (en) |
| HU (1) | HU169278B (en) |
| NL (1) | NL7409717A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2814500C3 (en) * | 1978-03-31 | 1981-07-30 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Process for making? 5 (10) -7 unsaturated steroids |
-
1973
- 1973-07-18 DE DE19732337155 patent/DE2337155A1/en not_active Withdrawn
-
1974
- 1974-07-12 DK DK376874AA patent/DK131434B/en unknown
- 1974-07-16 DD DD179944A patent/DD112996A5/xx unknown
- 1974-07-17 GB GB31660/74A patent/GB1478679A/en not_active Expired
- 1974-07-17 HU HUSC484A patent/HU169278B/hu unknown
- 1974-07-18 CH CH2337155A patent/CH601493A5/xx not_active IP Right Cessation
- 1974-07-18 NL NL7409717A patent/NL7409717A/en not_active Application Discontinuation
- 1974-07-18 JP JP49082670A patent/JPS5032158A/ja active Pending
- 1974-07-18 CA CA204,982A patent/CA1055881A/en not_active Expired
- 1974-07-18 FR FR7424992A patent/FR2237981B1/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB1478679A (en) | 1977-07-06 |
| HU169278B (en) | 1976-10-28 |
| DD112996A5 (en) | 1975-05-12 |
| FR2237981A1 (en) | 1975-02-14 |
| JPS5032158A (en) | 1975-03-28 |
| DK131434B (en) | 1975-07-14 |
| FR2237981B1 (en) | 1977-07-01 |
| DK131434C (en) | 1975-12-08 |
| DE2337155A1 (en) | 1975-02-20 |
| NL7409717A (en) | 1975-01-21 |
| DK376874A (en) | 1975-03-17 |
| CH601493A5 (en) | 1978-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ogumi et al. | Application of the spe method to organic electrochemistry—II. Electrochemical hydrogenation of olefinic double bonds | |
| EP1963354B1 (en) | HIGH PURITY 17alfa-CYANOMETHYL-17beta-HYDROXY-ESTRA-4,9-DIENE-3-ONE AND PROCESS FOR THE SYNTHESIS THEREOF | |
| Heintz et al. | Electrosynthesis of aryl-carboxylic acids from chlorobenzene derivatives and carbon dioxide | |
| CA1055881A (en) | Electrolytic reduction of aromatic steroids | |
| CA1181717A (en) | Electrochemical dehydrogenation of steroidal .delta. su3,5 xx enol ethers under basic conditions to provide steroidal .delta. su4,6 xx dienones | |
| US4193850A (en) | Alkanoyloxylation of beta-ionone | |
| US3925173A (en) | Electrocatalytic hydrogenation process | |
| US4050998A (en) | Electrolytic reduction of aromatic steroids | |
| US3444059A (en) | Electrolytic reduction of cyclopentanophenanthrene derivatives | |
| Medici et al. | Anodic electrochemical oxidation of cholic acid | |
| US3444057A (en) | Electrolytic reduction of aromatic steroids | |
| Lamoureux et al. | An electrolysis cell with close consecutive flow-through porous electrodes for particular organic electrosynthesis | |
| US3843499A (en) | Production of 4-endotricyclo(5,2,1,02,6-endo)decylamine | |
| US4029648A (en) | Process of making gona-1,3,5(10),9(11)-tetraenes | |
| US2770588A (en) | Method of recovering fatty acid and alkali by the electrolysis of an aqueous solution of an alkali metal salt of a fatty acid | |
| CA1052319A (en) | ELECTROCHEMICAL REDUCTION OF .alpha.,.beta.-UNSATURATED KETO-STEROIDS | |
| US3250690A (en) | Electrolytic reductive coupling of cyano compounds | |
| JPS6237386A (en) | Electric synthesis of ketone | |
| Mengoli et al. | Anodic ethylation of lead by cathodically produced diethylcadmium | |
| DE1593501C3 (en) | 15,16 beta-methylene steroids of the 19-nor-androstane series, processes for their preparation and agents containing them | |
| US3720694A (en) | Partial electrochemical reduction of 19-nor-delta 1,3,5(10)-steroids | |
| Udupa et al. | A comparative study of the reduction of aromatic aldehydes at stationary and rotating amalgamated cathodes | |
| US4448650A (en) | Process for the preparation of cyclopentadec-4-ynone and of its 3-methyl homologue | |
| US4057586A (en) | Process for the manufacture of hydroquinone dimethyl ethers | |
| Maekawa et al. | Selective Dimerization by Paired Electrolysis of Enol Acetate. |