NO128976B - - Google Patents
Download PDFInfo
- Publication number
- NO128976B NO128976B NO410272A NO410272A NO128976B NO 128976 B NO128976 B NO 128976B NO 410272 A NO410272 A NO 410272A NO 410272 A NO410272 A NO 410272A NO 128976 B NO128976 B NO 128976B
- Authority
- NO
- Norway
- Prior art keywords
- oxo
- methyl
- hydroxy
- steroid
- acyloxy
- Prior art date
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000003431 steroids Chemical class 0.000 claims description 7
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- -1 methylmagnesium halide Chemical class 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 150000003128 pregnanes Chemical class 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000001195 anabolic effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims description 2
- 230000001548 androgenic effect Effects 0.000 claims 1
- 230000001072 progestational effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- VMNRNUNYBVFVQI-UHFFFAOYSA-N 10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2CC(=O)CCC2(C)C2C1C1CCCC1(C)CC2 VMNRNUNYBVFVQI-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229940117975 chromium trioxide Drugs 0.000 description 5
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 5
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 5
- LPMDCPLRVPBTRF-DAELLWKTSA-N (8r,9s,10r,13s,14s)-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound C([C@@]12C)CC(=O)C=C1C(C)=C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@H]21 LPMDCPLRVPBTRF-DAELLWKTSA-N 0.000 description 4
- JWMFYGXQPXQEEM-NUNROCCHSA-N 5β-pregnane Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](CC)[C@@]2(C)CC1 JWMFYGXQPXQEEM-NUNROCCHSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- DJOWTWWHMWQATC-KYHIUUMWSA-N Karpoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1(O)C(C)(C)CC(O)CC1(C)O)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C DJOWTWWHMWQATC-KYHIUUMWSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 239000000583 progesterone congener Substances 0.000 description 3
- DWJQHNJCKUWONS-NTNOATJHSA-N (8S,9S,10R,13S,14S,17S)-17-acetyl-6,10,13-trimethyl-1,2,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one Chemical compound CC(=O)[C@H]1CC[C@H]2[C@@H]3C=C(C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C DWJQHNJCKUWONS-NTNOATJHSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- CHNXZKVNWQUJIB-CEGNMAFCSA-N ethisterone Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 CHNXZKVNWQUJIB-CEGNMAFCSA-N 0.000 description 2
- 229960000445 ethisterone Drugs 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000003270 steroid hormone Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- GZSCFURMBHMSCE-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthrene-3,17-dione Chemical class C([C@@]12C)CC(=O)C=C1C(C)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@H]21 GZSCFURMBHMSCE-RTQNCGMRSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- GNFABWAPJFOZSF-KTORGGLSSA-N 6alpha-Methylprogesterone Chemical class C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](C(C)=O)CC[C@H]21 GNFABWAPJFOZSF-KTORGGLSSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 150000001441 androstanes Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 229950008604 mestanolone Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
- H05B3/00—Ohmic-resistance heating
- H05B3/68—Heating arrangements specially adapted for cooking plates or analogous hot-plates
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F24—HEATING; RANGES; VENTILATING
- F24C—DOMESTIC STOVES OR RANGES ; DETAILS OF DOMESTIC STOVES OR RANGES, OF GENERAL APPLICATION
- F24C15/00—Details
- F24C15/10—Tops, e.g. hot plates; Rings
- F24C15/102—Tops, e.g. hot plates; Rings electrically heated
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
- H05B3/00—Ohmic-resistance heating
- H05B3/68—Heating arrangements specially adapted for cooking plates or analogous hot-plates
- H05B3/72—Plates of sheet metal
Landscapes
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Combustion & Propulsion (AREA)
- Mechanical Engineering (AREA)
- General Engineering & Computer Science (AREA)
- Resistance Heating (AREA)
- Surface Heating Bodies (AREA)
- Central Heating Systems (AREA)
- Baking, Grill, Roasting (AREA)
- Steroid Compounds (AREA)
- Cookers (AREA)
- Electric Stoves And Ranges (AREA)
Description
Fremgangsmåte til fremstilling av 6-metyl-3-oxo-4,6-dien-steroider av androstan- og pregnanrekkene. Process for the production of 6-methyl-3-oxo-4,6-diene steroids of the androstane and pregnane series.
Foreliggende oppfinnelse angår fremstilling av nye 6-metyl-3-oxo-4,6-dien-steroider. The present invention relates to the production of new 6-methyl-3-oxo-4,6-diene steroids.
Oppfinnelsen skaffer nye forbindelser The invention provides new connections
av denne type, som er av verdi på grunn av deres biologiske egenskaper eller som mellomnrodukter ved fremstilling av andre 6-metylforbindelser med fordelaktige biologiske egenskaper, som f. eks. 6-metyl-androstanolon. of this type, which are of value because of their biological properties or as intermediate products in the production of other 6-methyl compounds with advantageous biological properties, such as e.g. 6-methyl-androstanolone.
Man har funnet det overraskende for-hold at 6-metyl-6-dehydro-derivatet av 3-oxo-A<4->steroidhormoner kan være mer aktivt med hensyn til hormonvirkning enn 3-oxo-4.6-dien-derivatene av androstan og pregnan og endog mer aktivt enn de tilsvarende 3-oxo-A<4->steroid-hormoner. The surprising fact has been found that the 6-methyl-6-dehydro-derivative of 3-oxo-A<4->steroid hormones can be more active with respect to hormonal action than the 3-oxo-4,6-diene derivatives of androstane and pregnane and even more active than the corresponding 3-oxo-A<4->steroid hormones.
Således har man f. eks. funnet at 6-metyl-6-dehydroderivatet av ethisteron som progestasjonalt middel er omtrent dobbelt så virkningsfullt som ethisteron når det gis oralt. Thus, one has e.g. found that the 6-methyl-6-dehydro derivative of ethisterone as a progestational agent is approximately twice as effective as ethisterone when given orally.
De 6-metyl-3-oxo-4,6-dien-derivater (I) av androstan og pregnan som fremstil-les ved fremgangsmåten ifølge oppfinnelsen, kan betraktes som 6-dehydro-derivater av 3-oxo-6-metyl-A<4->steroider som de kan overføres til ved hydrogenering. 3-oxo-6-metyl-A<4->derivatene av androstan og pregnan er, som kjent, av betydning på grunn av deres biologiske egenskaper. The 6-methyl-3-oxo-4,6-diene derivatives (I) of androstane and pregnane which are produced by the process according to the invention can be regarded as 6-dehydro derivatives of 3-oxo-6-methyl-A <4->steroids to which they can be transferred by hydrogenation. The 3-oxo-6-methyl-A<4->derivatives of androstane and pregnane are, as is known, of importance because of their biological properties.
Ved hjelp av oppfinnelsen skaffes der 6-metyl-3-oxo-4,6-dien-steroider av androstan- og pregnan-rekkene med den generelle formel: With the help of the invention, 6-methyl-3-oxo-4,6-diene steroids of the androstane and pregnane series are obtained with the general formula:
hvor R, er en oxogruppe, where R, is an oxo group,
en p-hydroxy- og en a-R,-gruppe, hvor R, er hydrogen, en alkyl-, a p-hydroxy and an a-R, group, where R, is hydrogen, an alkyl,
alkenyl- eller alkynylgruppe med høyst 5 carbonatomer, eller alkenyl or alkynyl group with no more than 5 carbon atoms, or
en p-(CH-R,-CR,-)- og en a-R-gruppe hvor R,, og R, er hydrogen, acyloxy-eller alkylgrupper med høyst 5 carbonatomer, og R3 er oxo, (5-hydroxy eller (3-acyloxy. a p-(CH-R,-CR,-)- and an a-R group where R,, and R, are hydrogen, acyloxy or alkyl groups with at most 5 carbon atoms, and R3 is oxo, (5-hydroxy or (3 -acyloxy.
Spesielt skaffes der ved oppfinnelsen de nye forbindelser: 6-metylandrosta-4,6-dien-3,17-dion, som er et dehydroderivat av 6-metyl-androstendion, og er av verdi som mellomprodukt ved f. eks. fremstillingen av 6-metyl-dehydrotestosteron. 17p-hydroxy-6,17a-dimetylandrosta-4,6-dien-3-on som er dehydroderivatet av 6a,17ct-dimetyl-testosteron og har anabol - iske egenskaper. 17p-hydroxy-17a-etynyl-6-metylandrosta-4,6-dien-3-on som er dehydroderivatet av 6a-metyl-ethisteron og er et virkningsfullt progestasjonalt middel når det gis oralt. In particular, the invention provides the new compounds: 6-methylandrosta-4,6-diene-3,17-dione, which is a dehydroderivative of 6-methyl-androstenedione, and is of value as an intermediate in e.g. the production of 6-methyl-dehydrotestosterone. 17p-hydroxy-6,17a-dimethylandrosta-4,6-dien-3-one which is the dehydroderivative of 6a,17ct-dimethyl-testosterone and has anabolic properties. 17p-hydroxy-17a-ethynyl-6-methylandrosta-4,6-dien-3-one which is the dehydro derivative of 6a-methyl-ethisterone and is an effective progestational agent when given orally.
6-metylpregna-4,6-dien-3,20-dion som er dehydroderivatet av 6a-metylprogeste-ron er et progestasjonalt middel og et ver-difullt utgangsstoff ved fremstillingen av de overraskende virkningsfulle 6-metyl-derivater av dehydrocortison. 6-methylpregna-4,6-dien-3,20-dione, which is the dehydroderivative of 6α-methylprogesterone, is a progestational agent and a valuable starting material in the production of the surprisingly effective 6-methyl derivatives of dehydrocortisone.
Oppfinnelsen skaffer en fremgangsmåte til fremstilling av 6-metyl-3-oxo-4,6-dien-steroider av androstan- og pregnan-seriene med den generelle formel (I). Denne fremgangsmåte er karakterisert ved at man omsetter det tilsvarende 3(3-hydroxy eller 3p-acyloxy-5a-hydroxy-6-oxo-steroid med den generelle formel: The invention provides a process for the production of 6-methyl-3-oxo-4,6-diene steroids of the androstane and pregnane series with the general formula (I). This method is characterized by reacting the corresponding 3(3-hydroxy or 3p-acyloxy-5a-hydroxy-6-oxo-steroid with the general formula:
hvor R er hydrogen eller acyl med et me-tylmagnesiumhalogenid så at der dannes et 6-metyl-3p,5a,6-trihydroxy- med den generelle formel: oxyderer dette steroid til det tilsvarende 5a,6-dihydroxy-6-metyl-3-oxo-steroid med den generelle formel: where R is hydrogen or acyl with a methylmagnesium halide so that a 6-methyl-3p,5a,6-trihydroxy- is formed with the general formula: this steroid oxidizes to the corresponding 5a,6-dihydroxy-6-methyl-3 -oxo-steroid with the general formula:
og dehydratiserer 5a,6-dihydroxy-6-metyl-3-oxo-steroidet. and dehydrates the 5α,6-dihydroxy-6-methyl-3-oxo-steroid.
De 3p-acyloxy eller 3|3-hydroxy-5a-hydroxy-6-oxo-steroider som danner ut-gangsmaterialet i ovennevnte fremgangsmåte, kan fåes på forskjellige måter, f. eks. ved oxydasjon av de tilsvarende 3|3-acyloxy- The 3p-acyloxy or 3|3-hydroxy-5a-hydroxy-6-oxo steroids which form the starting material in the above-mentioned process can be obtained in various ways, e.g. by oxidation of the corresponding 3|3-acyloxy-
5a,6p-dihydroxy-steroider som kan frem-stilles av 3p-acyloxy-5,6-epoxy-steroider ved hydrolytisk spaltning av epoxyd-rin-gen. Slike reaksjoner er velkjente og be-skrevet i litteraturen. 5a,6p-dihydroxy steroids which can be produced from 3p-acyloxy-5,6-epoxy steroids by hydrolytic cleavage of the epoxy ring gene. Such reactions are well known and described in the literature.
Ved utførelsen av fremgangsmåten ifølge oppfinnelsen blir 3p-acyloxy- eller 3p-hydroxy-5a-hydroxy-6-oxosteroidet (II) overført til 6-metyl-3p,5a,6-trihydroxy-steroidet (III), hensiktsmessig ved at en opp-løsning av forbindelsen (II) (hvor R er hydrogen eller en acyl-gruppe), hvor oppløs-ningsmidlet f. eks. kan være eter, butyleter eller en blanding av benzen og eter, tilsettes til et overskudd av metylmagnesiumhalo-genid. fortrinnsvis bromidet eller jodidet, og reaksjonsblandingen deretter kokes under tilbakeløpskjøling eller man lar den stå ved romtemperatur i flere timer. Derpå spaltes det dannede kompleks, og steroidet ekstraheres. Det således erholdte 6-metyl-3p,5a,6-trihydroxy-steroid (III) kan blandes med dets 3p-acyloxy-derivat i mengder som avhenger av den anvendte reaksjonstid for Grignard-reaksjonen og øvrige betingelser. Det er derfor tilrådelig å forsåpe reaksjo-nens sluttprodukt for å overføre det tilsatte 3p-acyloxy-5a, 6-dihydroxy-6-metyl-steroid til det ønskede 6-metyl-3p,5a,6-trihydroxy-steroid (III). When carrying out the method according to the invention, the 3p-acyloxy- or 3p-hydroxy-5a-hydroxy-6-oxosteroid (II) is transferred to the 6-methyl-3p,5a,6-trihydroxy-steroid (III), conveniently by -solution of the compound (II) (where R is hydrogen or an acyl group), where the solvent e.g. can be ether, butyl ether or a mixture of benzene and ether, is added to an excess of methylmagnesium halide. preferably the bromide or the iodide, and the reaction mixture is then boiled under reflux or allowed to stand at room temperature for several hours. The complex formed is then cleaved, and the steroid is extracted. The thus obtained 6-methyl-3p,5a,6-trihydroxy-steroid (III) can be mixed with its 3p-acyloxy derivative in amounts that depend on the reaction time used for the Grignard reaction and other conditions. It is therefore advisable to saponify the end product of the reaction in order to transfer the added 3p-acyloxy-5a,6-dihydroxy-6-methyl-steroid to the desired 6-methyl-3p,5a,6-trihydroxy-steroid (III).
Overføringen av 6-metyl-3p,5a,6-tri-hydroxy-steroidet (III) til det tilsvarende 3-oxo-steroid (IV) kan utføres ved oxyda-sjonsmidler som vanlig brukes ved oxydasjon av sekundære alkoholer til de tilsvarende ketoner. Kromtrioxyd oppløst i eddik-syre eller i pyridin er således godt egnet, imidlertid må man ved valg av oxydasjons-middel ta hensyn til arten av eventuelle ytterligere substituenter som måtte være til stede i 6-metyl-3p,5a,6-trihydroxy-steroidet (III). The transfer of the 6-methyl-3p,5a,6-tri-hydroxy-steroid (III) to the corresponding 3-oxo-steroid (IV) can be carried out by oxidizing agents which are commonly used in the oxidation of secondary alcohols to the corresponding ketones. Chromium trioxide dissolved in acetic acid or in pyridine is thus well suited, however, when choosing an oxidizing agent, account must be taken of the nature of any additional substituents that may be present in the 6-methyl-3p,5a,6-trihydroxy steroid (III).
Dehydratiseringen av 3-oxo-steroidet (IV) tid det ønskede 6-metyl-3-oxo-4,6-dien-derivat (I) kan utføres ved at forbindelsen (IV) i et oppløsningsmiddel behand-les med en kilde for hydrogenioner, hensiktsmessig saltsyre. Reaksjonen kan utfø-res f. eks. ved at hydrogenklorid ledes inn i en oppløsning av 3-oxo-steroidet (IV) ved en temperatur omkring 0° C. Alternativt kan dehydratiseringen gjennomføres ved at en oppløsning av 3-oxo-steroidet (IV) i en lavere alifatisk alkohol med opptil 5 kullstoffatomer, som metanol eller etanol, tilsatt litt konsentrert saltsyre, oppvarmes under tilbakeløpskjøling. The dehydration of the 3-oxo-steroid (IV) and the desired 6-methyl-3-oxo-4,6-diene derivative (I) can be carried out by treating the compound (IV) in a solvent with a source of hydrogen ions , suitable hydrochloric acid. The reaction can be carried out e.g. by introducing hydrogen chloride into a solution of the 3-oxo-steroid (IV) at a temperature around 0° C. Alternatively, the dehydration can be carried out by dissolving the 3-oxo-steroid (IV) in a lower aliphatic alcohol with up to 5 carbon atoms, such as methanol or ethanol, with a little concentrated hydrochloric acid added, are heated under reflux.
Fremgangsmåten ifølge oppfinnelsen kan anvendes for 3p-acyloxy- eller 3p-hydroxy-5a-hydroxy-6-oxo-steroider av androstan- og pregnantypen. Således kan fremgangsmåten anvendes for de følgende forbindelser: 3|3-acyloxy-5ct-hydroxyandro-stan-6-on som ved C-atomet i 17-stillingen kan ha hydroxylgrupper med eller uten alkyl-, alkenyl- eller alkynylgrupper som ikke inneholder mer enn 5 kullstoffatomer, som ytterligere substituenter, 3p-acyloxy-5a-hydroxypregnan-6-on, som ved C-atomet i 20-stillingen kan være ytterligere substi-tuert med en acyloxy -eller hydroxy-gruppe med eller uten acyloxy- eller alkyl-grupper, som ikke inneholder mer enn 5 kullstoffatomer ved C-atomet i 17- eller 21-stillingen. The method according to the invention can be used for 3p-acyloxy or 3p-hydroxy-5a-hydroxy-6-oxo steroids of the androstane and pregnane type. Thus, the method can be used for the following compounds: 3|3-acyloxy-5ct-hydroxyandro-stan-6-one which at the C atom in the 17 position can have hydroxyl groups with or without alkyl, alkenyl or alkynyl groups which contain no more than 5 carbon atoms, as additional substituents, 3p-acyloxy-5a-hydroxypregnan-6-one, which at the C atom in the 20 position can be further substituted with an acyloxy or hydroxy group with or without acyloxy or alkyl -groups, which do not contain more than 5 carbon atoms at the C atom in the 17 or 21 position.
I det følgende beskrives som eksempler noen utførelsesformer for fremgangsmåten ifølge oppfinnelsen: Eksempel 1: 17a- etynyl- 17$- hydroxy- metylandrosta-4, 6- dien- 3- on ( V). In the following, some embodiments of the method according to the invention are described as examples: Example 1: 17a-ethynyl-17$-hydroxy-methylandrosta-4, 6-dien-3-one (V).
3p-acetoxy-17a-etynylandrostan-5a, 3p-acetoxy-17a-ethynylandrostane-5a,
17p-diol-6-on (sm.p. 245—247° C, [a] q = 103° i kloroform) (10,5 g) i en blanding av tørr tetrahydrofuran (100 ml) og eter (100 ml) ble tilsatt til en Grignard-reagens som var fremstillet av magnesium (5,4 g), metyljodid (15 ml) og eter (190 ml). Blandingen ble omrørt i 2 timer ved romtemperatur, hvorpå man lot den stå i ytterligere 18 timer. Etter behandling med for-tynnet svovelsyre ble det organiske skikt vasket inntil det var nøytralt og derpå tør-ret, og oppløsningsmidlene ble fjernet. Residuet ble oppvarmet med metanolisk kali-umhydroxyd (100 ml 2 %'s) i 30 minutter under tilbakeløpskjøling. Etter tilsetning av vann fikk man et produkt som fra vandig metanol krystalliserte i nåler, 17a-etynyl-6-metylandrostan-3p,5a,6-17p-tetrol, sm.p. 254—255° C, [a] ^° 51° (c, 17p-diol-6-one (m.p. 245-247° C, [a] q = 103° in chloroform) (10.5 g) in a mixture of dry tetrahydrofuran (100 ml) and ether (100 ml) was added to a Grignard reagent prepared from magnesium (5.4 g), methyl iodide (15 ml) and ether (190 ml). The mixture was stirred for 2 hours at room temperature, after which it was allowed to stand for a further 18 hours. After treatment with dilute sulfuric acid, the organic layer was washed until it was neutral and then dried, and the solvents were removed. The residue was heated with methanolic potassium hydroxide (100 ml 2%'s) for 30 minutes under reflux. After addition of water, a product was obtained which crystallized from aqueous methanol in needles, 17a-ethynyl-6-methylandrostane-3p,5a,6-17p-tetrol, m.p. 254—255° C, [a] ^° 51° (c,
1,01 i etanol). 1.01 in ethanol).
Dette tetrol (4 g) i pyridin (40 ml) ble tilsatt til en oppløsning av kromtrioxyd (4 g) i pyridin (40 ml), og man lot blandingen stå natten over. Produktet ble ekstrahert med eter og krystallisert fra vandig etanol, hvorved man fikk nåler av 17a-etynyl-6-metylandrostan-5a,6,17p-triol-3-22 This tetrol (4 g) in pyridine (40 ml) was added to a solution of chromium trioxide (4 g) in pyridine (40 ml) and the mixture was allowed to stand overnight. The product was extracted with ether and crystallized from aqueous ethanol, yielding needles of 17α-ethynyl-6-methylandrostane-5α,6,17β-triol-3-22
on, sm.p. 246—248° C, [a] D = 36° (c, on, sm.p. 246—248° C, [a] D = 36° (c,
1.02 i etanol). 1.02 in ethanol).
Denne forbindelse (1 g) i etanol (25 ml) inneholdende 2 dråper konsentrert saltsyre ble oppvarmet i 30 minutter under tilbakeløpskjøling. Produktet ble ekstrahert med eter og krystallisert fra vandig metanol, hvorved man fikk nåler av 17a-etynyl-17p-hydroxy-6-metylandrosta-4,6-dien-3-20 This compound (1 g) in ethanol (25 ml) containing 2 drops of concentrated hydrochloric acid was heated for 30 minutes under reflux. The product was extracted with ether and crystallized from aqueous methanol, yielding needles of 17α-ethynyl-17β-hydroxy-6-methylandrosta-4,6-diene-3-20
on, sm.p. 200—201° C, [a] D = — 58°, (c, on, sm.p. 200—201° C, [a] D = — 58°, (c,
1.03 i kloroform), XmaUs 290 m|x (log e = 4,36). 1.03 in chloroform), XmaUs 290 m|x (log e = 4.36).
Eksempel 2: Example 2:
6- metylpregna- 4, 6- dien- 3, 20- dion ( VI). 6- methylpregna- 4, 6- diene- 3, 20-dione (VI).
3p,20-diacetoxypregnan-5a-ol-6-on 3β,20-diacetoxypregnan-5α-ol-6-one
20 20
(sm.p. 224—225° C, [a] D = 48° i kloroform) (4,3 g) i benzen (200 ml) ble under omrøring tilsatt til en oppløsning av metyl-magnesiumjodid som var fremstillet ut fra magnesium (4,3 g) og metyljodid (12 ml) i tørr eter (100 ml). Blandingen ble oppvarmet i 3 timer under tilbakeløpskjøling, av-kjølt og behandlet med iskold ammonium-kloridoppløsning. Det utskilte faste stoff ble krystallisert fra en blanding av aceton og hexan, hvorved man fikk nåler av 6-me-tylpregnan-3p,5a,6,20-tetrol, sm.p. 220— (m.p. 224-225° C, [a] D = 48° in chloroform) (4.3 g) in benzene (200 ml) was added with stirring to a solution of methylmagnesium iodide which had been prepared from magnesium (4.3 g) and methyl iodide (12 ml) in dry ether (100 ml). The mixture was heated for 3 hours under reflux, cooled and treated with ice-cold ammonium chloride solution. The separated solid was crystallized from a mixture of acetone and hexane to give needles of 6-methylpregnan-3β,5α,6,20-tetrol, m.p. 220—
224° C, [a] D°= — 17° (c, 0,24 i kloroform). 224° C, [a] D°= — 17° (c, 0.24 in chloroform).
Dette tetrol (1,5 g) i pyridin (15 ml) ble tilsatt til kromtrioxyd (3 g) i pyridin (30 ml), og man lot blandingen stå natten over. Der ble så filtrert under anvendelse av hjelpefilter, og den faste rest ble vasket med varm benzen (600 ml). Filtratet med vaskevæsken ble i sin tur vasket med for-tynnet saltsyre, vandig natriumkarbonat og vann, derpå tørret og sendt gjennom en kort kolonne av aluminiumoxyd. Ved elue-ring med eter fikk man 6-metylpregnan-5a, 6-diol-3.20-dion, som fra en blanding av aceton og hexan krystalliserte i nåler, sm.p. This tetrol (1.5 g) in pyridine (15 ml) was added to chromium trioxide (3 g) in pyridine (30 ml) and the mixture was allowed to stand overnight. It was then filtered using an auxiliary filter, and the solid residue was washed with hot benzene (600 ml). The filtrate with the washing liquid was in turn washed with dilute hydrochloric acid, aqueous sodium carbonate and water, then dried and passed through a short column of aluminum oxide. Elution with ether gave 6-methylpregnan-5a, 6-diol-3,20-dione, which crystallized from a mixture of acetone and hexane in needles, m.p.
22 22
247—249° C [a] D = + 69° (c, 0,39 i kloroform). 247—249° C [a] D = + 69° (c, 0.39 in chloroform).
Denne forbindelse (300 mg) i metanol (50 ml) inneholdende 2 dråper konsentrert saltsyre ble oppvarmet i 30 minutter under tilbakeløpskjøling. Blandingen ble helt over i en forholdsvis stor mengde vann, og de faste utskilte stoffer ble samlet, vasket og tørret. Ved krystallisasjon fra heksan fikk man plater av 6-metylpregna-4,6-dien-22 3,20-dion, sm.p. 152—154° C, [a] D = + This compound (300 mg) in methanol (50 ml) containing 2 drops of concentrated hydrochloric acid was heated for 30 minutes under reflux. The mixture was poured into a relatively large amount of water, and the solid separated substances were collected, washed and dried. Crystallization from hexane gave slabs of 6-methylpregna-4,6-diene-22 3,20-dione, m.p. 152-154° C, [a] D = +
176° (c, 0,56 i kloroform, Xm.lks 288,5 m^ (log = 4,37). 176° (c, 0.56 in chloroform, Xm.lks 288.5 m^ (log = 4.37).
Eksempel 3: Example 3:
6, 17a- dimetyl- 17if- hydroxyandrosta-4, 6- dien- 3- on ( VII). 6, 17α-dimethyl-17α-hydroxyandrosta-4, 6-dien-3-one (VII).
3|3-acetoxy-5a,17|3-dihydroxy-17a-me-tylandrostan-6-on (sm.p. 207—208° C, 3|3-acetoxy-5a,17|3-dihydroxy-17a-methylandrostan-6-one (m.p. 207-208° C,
24 24
[a] D - — 98° i kloroform) (6,5 g) i eter (300 ml) ble tilsatt til en Grignard-reagens som var fremstillet av magnesium (6,5 g) og metyljodid (42 g) i en blanding av eter (300 ml) og benzen (200 ml). Blandingen ble oppvarmet i 3y2 time under tilbakeløps-kjøling, avkjølet og behandlet med en vandig ammoniumkloridoppløsning. Utskilte faste stoffer ble oppsamlet, vasket og deretter forsåpet ved oppvarmning med kaliumkarbonat (4 g) i metanol (180 ml) og vann (20 ml) i en time under tilbakeløps-kjøling. Oppløsningsmidlene ble fjernet og residuet ekstrahert med varm aceton. Ved tilsetning av heksan fikk man nåler av 6,17a-dimetylandrostan-3(3,5a,6,17p-tetrol, [a] D - — 98° in chloroform) (6.5 g) in ether (300 ml) was added to a Grignard reagent prepared from magnesium (6.5 g) and methyl iodide (42 g) in a mixture of ether (300 ml) and benzene (200 ml). The mixture was heated for 3y2 hours under reflux, cooled and treated with an aqueous ammonium chloride solution. Separated solids were collected, washed and then saponified by heating with potassium carbonate (4 g) in methanol (180 ml) and water (20 ml) for one hour under reflux. The solvents were removed and the residue extracted with hot acetone. By adding hexane, needles of 6,17a-dimethylandrostane-3(3,5a,6,17p-tetrol,
20 20
sm.p. 233—234° C, [a] D = —24° (c, 0,55 sm.p. 233—234° C, [a] D = —24° (c, 0.55
i etanol). in ethanol).
Denne tetrol (1,8 g) i pyridin (18 ml) ble tilsatt til en oppløsning av kromtrioxyd (1,8 g) i pyridin (18 ml), og man lot blandingen stå natten over. Produktet ble ekstrahert med benzen og krystallisert fra en blanding av aceton og heksan, hvorved man This tetrol (1.8 g) in pyridine (18 ml) was added to a solution of chromium trioxide (1.8 g) in pyridine (18 ml) and the mixture was allowed to stand overnight. The product was extracted with benzene and crystallized from a mixture of acetone and hexane, whereby
fikk nåler av 6,17a-dimetylandrostan 5a,6, got needles of 6,17a-dimethylandrostane 5a,6,
23 17p-triol-3-on, sm.p. 223—224° C, [a] D 23 17p-triol-3-one, m.p. 223—224° C, [a] D
= —25°, (c, 0,53 i kloroform): = —25°, (c, 0.53 in chloroform):
Denne forbindelse (1,85 g) i metanol (20 ml) inneholdende konsentrert saltsyre (0,3 ml) ble oppvarmet i en time under til-bakeløpskjøling. Produktet ble ekstrahert med eter og omkrystallisert fra en blanding av aceton og heksan, hvorved man fikk 6,17a-dimetyl-17p-hydroxyandrosta-4,6-23 dien-3-on, sm.p. 157—158° C, [a] D = +38° This compound (1.85 g) in methanol (20 ml) containing concentrated hydrochloric acid (0.3 ml) was heated for one hour under reflux. The product was extracted with ether and recrystallized from a mixture of acetone and hexane to give 6,17α-dimethyl-17β-hydroxyandrosta-4,6-23dien-3-one, m.p. 157—158° C, [a] D = +38°
(c, 0,52 i kloroform) lnnU 290 m^i (log e= 4,37). (c, 0.52 in chloroform) lnnU 290 m^i (log e= 4.37).
Eksempel 4: Example 4:
6- metylandrosta- 4, 6- dien- 3, 17- dion ( VIII) 6- methylandrosta- 4, 6- diene- 3, 17-dione (VIII)
3p.l7p-diacetoxy-5a-hydroxyandrostan-6-on (4 g) i benzen (250 ml) ble tilsatt til en Grignard-reagens som var fremstillet av magnesium (4 g) og metyljodid (25 ml) i eter (50 ml). Blandingen ble oppvarmet i 2 timer under tilbakelønskjøling, avkjølet og behandlet med vandig ammoniumklorid. Det utskilte faste stoff ble forsåDet med kaliumkarbonat i vann og metanol, hvorved man fikk 6-metylandrostan-36.5a 617p-tetrol, som fra aceton krystalliserte i form av nåler, sm.p. 195—205° C (mykner) [a] D 21 3β,17β-diacetoxy-5α-hydroxyandrostan-6-one (4 g) in benzene (250 mL) was added to a Grignard reagent prepared from magnesium (4 g) and methyl iodide (25 mL) in ether (50 mL ). The mixture was heated for 2 hours under reflux, cooled and treated with aqueous ammonium chloride. The separated solid was treated with potassium carbonate in water and methanol, whereby 6-methylandrostane-36.5a 617p-tetrol was obtained, which crystallized from acetone in the form of needles, m.p. 195—205° C (softens) [a] D 21
= 24° (c, 0,25 i etanol). = 24° (c, 0.25 in ethanol).
Denne forbindelse (3.3 g) i pyridin (33 ml) ble tilsatt til en oppløsning av kromtrioxyd (6,6 g) i pyridin (66 ml) og man lot blandingen stå natten over. Produktet ble ekstrahert med benzen, renset kromatogra-fisk og krystallisert fra vandig aceton. Det erholdte 5a.6-dihydroxy-6-metylandrostan-3,17-dion dannet nåler, sm.p. 242—244° C, This compound (3.3 g) in pyridine (33 ml) was added to a solution of chromium trioxide (6.6 g) in pyridine (66 ml) and the mixture was allowed to stand overnight. The product was extracted with benzene, purified chromatographically and crystallized from aqueous acetone. The obtained 5α,6-dihydroxy-6-methylandrostane-3,17-dione formed needles, m.p. 242—244° C,
21 21
[a] D = + 65° (c, 0,57 i kloroform). [a] D = + 65° (c, 0.57 in chloroform).
Dette stoff (0,5 g) i metanol (20 ml) inneholdende 2 dråper konsentrert saltsyre ble oppvarmet i en time under tilbakeløps-kjøling. Det faste stoff som man fikk etter tilsetning av vann, ble vasket, tørret og krystallisert fra en blanding av aceton og heksan. 6-metylandrosta-4,6-dien-3,17-dion krystalliserte i nåler, sm.p. 164° C, This substance (0.5 g) in methanol (20 ml) containing 2 drops of concentrated hydrochloric acid was heated for one hour under reflux. The solid obtained after addition of water was washed, dried and crystallized from a mixture of acetone and hexane. 6-methylandrosta-4,6-diene-3,17-dione crystallized in needles, m.p. 164°C,
21 21
[a] D = + 139° (c, 0,51 i kloroform), [a] D = + 139° (c, 0.51 in chloroform),
Xmak, 287 mji (log 6 = 4,37). Xmax, 287 mji (log 6 = 4.37).
Claims (1)
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO410272A NO128976B (en) | 1972-11-13 | 1972-11-13 | |
NL7314753A NL160698C (en) | 1972-11-13 | 1973-10-26 | ELECTRIC STOVE. |
DE19732355345 DE2355345C3 (en) | 1972-11-13 | 1973-11-06 | Heating device, in particular stove or hot plate |
SE7315175A SE394785B (en) | 1972-11-13 | 1973-11-08 | HEATING DEVICE WITH HEATING ZONES SURROUNDED BY COLDER ZONES |
IT5358873A IT996417B (en) | 1972-11-13 | 1973-11-09 | ELECTRIC HEATING DEVICE PARTICULARLY FOR KITCHENS |
GB5247073A GB1418819A (en) | 1972-11-13 | 1973-11-12 | Heating appliance |
CH1585673A CH563098A5 (en) | 1972-11-13 | 1973-11-12 | |
FR7340335A FR2206643B1 (en) | 1972-11-13 | 1973-11-13 | |
BE137685A BE807248A (en) | 1972-11-13 | 1973-11-13 | HEATING DEVICE |
JP12762473A JPS559794B2 (en) | 1972-11-13 | 1973-11-13 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO410272A NO128976B (en) | 1972-11-13 | 1972-11-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
NO128976B true NO128976B (en) | 1974-02-04 |
Family
ID=19880073
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO410272A NO128976B (en) | 1972-11-13 | 1972-11-13 |
Country Status (10)
Country | Link |
---|---|
JP (1) | JPS559794B2 (en) |
BE (1) | BE807248A (en) |
CH (1) | CH563098A5 (en) |
DE (1) | DE2355345C3 (en) |
FR (1) | FR2206643B1 (en) |
GB (1) | GB1418819A (en) |
IT (1) | IT996417B (en) |
NL (1) | NL160698C (en) |
NO (1) | NO128976B (en) |
SE (1) | SE394785B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4045654A (en) * | 1975-09-02 | 1977-08-30 | A/S Ardal Og Sunndal Verk | Electric hotplate with thermostat |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS562379Y2 (en) * | 1976-04-28 | 1981-01-20 | ||
DE3033828A1 (en) * | 1980-09-09 | 1982-04-29 | Fischer, Karl, 7519 Oberderdingen | ELECTRIC COOKING PLATE |
EP0162620A3 (en) * | 1984-05-11 | 1987-05-13 | THORN EMI Patents Limited | A cooking arrangement |
JPS61120674U (en) * | 1985-01-18 | 1986-07-30 | ||
DE3545442A1 (en) * | 1985-12-20 | 1987-06-25 | Bosch Siemens Hausgeraete | HEATING ELEMENT FOR THERMAL HOME APPLIANCES, ESPECIALLY FOR COOKING POINTS |
DE8717025U1 (en) * | 1987-12-28 | 1988-06-23 | Jaksch, Adolf, 8000 München | Built-in electric frying plate |
DE102004013045B4 (en) * | 2004-03-10 | 2006-06-29 | Alfred Kärcher Gmbh & Co. Kg | Device for preparing food, in particular as a mobile field kitchen |
DE102013021356A1 (en) | 2012-12-29 | 2015-08-20 | Labetherm Limited Zweigniederlassung Deutschland | Design of a crucible bottom of the cooking appliance and method for operating such a device |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS442126Y1 (en) * | 1965-02-05 | 1969-01-27 | ||
DE1579652A1 (en) * | 1966-01-26 | 1970-10-29 | Stumpp & Schuele Kg | Electrically heated cooking, roasting and baking equipment |
DE2030558A1 (en) * | 1970-06-20 | 1971-12-30 | Blanc & Co | Hotplate |
-
1972
- 1972-11-13 NO NO410272A patent/NO128976B/no unknown
-
1973
- 1973-10-26 NL NL7314753A patent/NL160698C/en not_active IP Right Cessation
- 1973-11-06 DE DE19732355345 patent/DE2355345C3/en not_active Expired
- 1973-11-08 SE SE7315175A patent/SE394785B/en unknown
- 1973-11-09 IT IT5358873A patent/IT996417B/en active
- 1973-11-12 GB GB5247073A patent/GB1418819A/en not_active Expired
- 1973-11-12 CH CH1585673A patent/CH563098A5/xx not_active IP Right Cessation
- 1973-11-13 JP JP12762473A patent/JPS559794B2/ja not_active Expired
- 1973-11-13 FR FR7340335A patent/FR2206643B1/fr not_active Expired
- 1973-11-13 BE BE137685A patent/BE807248A/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4045654A (en) * | 1975-09-02 | 1977-08-30 | A/S Ardal Og Sunndal Verk | Electric hotplate with thermostat |
Also Published As
Publication number | Publication date |
---|---|
NL160698C (en) | 1979-11-15 |
DE2355345A1 (en) | 1974-06-06 |
IT996417B (en) | 1975-12-10 |
NL160698B (en) | 1979-06-15 |
GB1418819A (en) | 1975-12-24 |
NL7314753A (en) | 1974-05-15 |
FR2206643A1 (en) | 1974-06-07 |
FR2206643B1 (en) | 1977-06-03 |
JPS559794B2 (en) | 1980-03-12 |
BE807248A (en) | 1974-03-01 |
DE2355345C3 (en) | 1979-06-21 |
SE394785B (en) | 1977-07-04 |
DE2355345B2 (en) | 1978-10-19 |
JPS49108653A (en) | 1974-10-16 |
CH563098A5 (en) | 1975-06-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE1618830C3 (en) | 11 beta-OB-13beta-C-gona-1,3,5 (10) -trienes containing oxygen in the 3 and 17 positions and process for their preparation | |
NO148662B (en) | Conditioning shampoos. | |
US3357973A (en) | 7alpha-mono-and dihalomethyl steroids | |
US3262949A (en) | 7-methyl androstane compounds | |
DJERASSI et al. | STEROIDAL SAPOGENINS. VII. 1 Experiments in the hecogenin series (Part 1) | |
NO128976B (en) | ||
US2768189A (en) | Method of producing alpha-brominated keto steroid compounds | |
DE1468035A1 (en) | Process for the preparation of 19-alkyl steroids | |
US2678932A (en) | Process for iodinating ketosteroids and products produced thereby | |
DE1468410A1 (en) | Process for the preparation of 16-methylene steroids | |
US3032552A (en) | 1-methyl steroids of the androstane series | |
US2326756A (en) | Ketones of the cyclopentano-poly-hydrophenanthrene series and a method of producing the same | |
DE1518980C3 (en) | Process for the production of 3-keto-Delta high 4 - or Delta high 1,4 -9 beta, 10 alpha-steroids of the androstane or pregnane series | |
US3254098A (en) | Process for the production of 19 norandrostanes and 19 nor-pregnanes | |
US3170936A (en) | Process for the preparation of 6, 17alpha-dimethyl-4, 6-pregnadiene-3, 20-dione | |
US3159643A (en) | 6-methylene-3-oxo-delta4 steroids and process for preparation of same | |
US3062844A (en) | 6-methyl-3-oxo-4:6-dienic steroids | |
US3177206A (en) | Selective bromination of a-ring aromatic 17-ketalized steroids | |
US3133913A (en) | 17alpha-methyl steroids and process to make same | |
US3151134A (en) | Delta9(11)-dehydro-estrone, estradiol, derivatives thereof and process for preparation | |
US2358808A (en) | Valuable compounds of the pregnane series and a method of producing the same | |
US3062845A (en) | Process for the conversion of alpha-acetyl steroids to beta-acetyl steroids and intermediates therein | |
US3148185A (en) | Process for the preparation of 3-hydroxy-6-keto-5beta, 10alpha-steroids | |
US3077485A (en) | 2-formyl-delta2-androstenes | |
US3082219A (en) | Method for the preparation of delta16-20-keto steroids |