NO122644B - - Google Patents
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- NO122644B NO122644B NO146141A NO14614162A NO122644B NO 122644 B NO122644 B NO 122644B NO 146141 A NO146141 A NO 146141A NO 14614162 A NO14614162 A NO 14614162A NO 122644 B NO122644 B NO 122644B
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- Norway
- Prior art keywords
- bis
- benzoquinone
- starting materials
- acylamino
- benzoquinones
- Prior art date
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 7
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 claims description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- KKSCCSVQHNQDBX-UHFFFAOYSA-N n-[2,5-dichloro-3,6-dioxo-4-(propanoylamino)cyclohexa-1,4-dien-1-yl]propanamide Chemical compound CCC(=O)NC1=C(Cl)C(=O)C(NC(=O)CC)=C(Cl)C1=O KKSCCSVQHNQDBX-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- -1 ethylene imino group Chemical group 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QLHPOTDBWHTTBM-UHFFFAOYSA-N 2,5-diamino-3,6-dichlorocyclohexa-2,5-diene-1,4-dione Chemical compound NC1=C(Cl)C(=O)C(N)=C(Cl)C1=O QLHPOTDBWHTTBM-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- RCDDYOVHUCQAMN-UHFFFAOYSA-N N-[4-(butanoylamino)-2,5-dichloro-3,6-dioxocyclohexa-1,4-dien-1-yl]butanamide Chemical compound ClC=1C(C(=C(C(C1NC(CCC)=O)=O)Cl)NC(CCC)=O)=O RCDDYOVHUCQAMN-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- 150000004057 1,4-benzoquinones Chemical class 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000224432 Entamoeba histolytica Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000224421 Heterolobosea Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- RFUGMORVSDZBLC-UHFFFAOYSA-N [Na].CC(N)=O Chemical compound [Na].CC(N)=O RFUGMORVSDZBLC-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 210000003001 amoeba Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940007078 entamoeba histolytica Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- ZYWQUADTNKEZKA-UHFFFAOYSA-N n-(4-acetamido-2,5-dichloro-3,6-dioxocyclohexa-1,4-dien-1-yl)acetamide Chemical compound CC(=O)NC1=C(Cl)C(=O)C(NC(C)=O)=C(Cl)C1=O ZYWQUADTNKEZKA-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000004059 quinone derivatives Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 150000003388 sodium compounds Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
-
- A—HUMAN NECESSITIES
- A43—FOOTWEAR
- A43B—CHARACTERISTIC FEATURES OF FOOTWEAR; PARTS OF FOOTWEAR
- A43B3/00—Footwear characterised by the shape or the use
- A43B3/12—Sandals; Strap guides thereon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Phenolic Resins Or Amino Resins (AREA)
- Woven Fabrics (AREA)
- Manufacturing Of Printed Wiring (AREA)
Description
Fremgangsmåte til fremstilling av nye kinonderivater. Process for the production of new quinone derivatives.
Gjenstanden for foreliggende oppfin-nelse er fremstilling av 2,5-bis-etylen-imino-3,6-bis-acylamino-p-benzoekinoner. Acylaminogruppene inneholder særlig rester av alifatiske karbonsyrer med 2—6 kullstoffatomer, slik som f. eks. av eddiksyre, propionsyre eller smørsyre. Etylen-iminogruppen kan også være alkylert ved kullstoffatomene, fortrinnsvis med en metylgruppe. The object of the present invention is the preparation of 2,5-bis-ethylene-imino-3,6-bis-acylamino-p-benzoquinones. The acylamino groups in particular contain residues of aliphatic carboxylic acids with 2-6 carbon atoms, such as e.g. of acetic acid, propionic acid or butyric acid. The ethylene imino group can also be alkylated at the carbon atoms, preferably with a methyl group.
Oppfinnelsen angår særlig 2,5-bis-etylenimmo-3,6-bis-acetylamino-p-benzoekinon med formelen The invention relates in particular to 2,5-bis-ethyleneimmo-3,6-bis-acetylamino-p-benzoquinone with the formula
De nye benzoekinonforbindelser er virk-somme mot amøber, slik som f. eks. mot Entamoeba histolytica, samt mot bakterier og dertil viser de en utpreget tumorhem-mende virkning. The new benzoquinone compounds are effective against amoebae, such as e.g. against Entamoeba histolytica, as well as against bacteria and in addition they show a distinct tumor-inhibiting effect.
De nye forbindelser fåes når man omsetter 2,5-dihalogen-3,6-bis-acylamino-p-benzoekinoner med etyleniminer eller lar en metallforbindelse, særlig alkalimetall, slik som natriumforbindelser av karbon-syreamider innvirke på 2,5-bis-etylenimino-3,6-dihalogen-p-benzoekinoner. Blant di-halogenforbindelsene er særlig diklor- og dibromforbindelsene egnet. The new compounds are obtained when 2,5-dihalogeno-3,6-bis-acylamino-p-benzoquinones are reacted with ethyleneimines or when a metal compound, especially an alkali metal, such as sodium compounds of carbonic acid amides act on 2,5-bis-ethyleneimino -3,6-dihalo-p-benzoquinones. Among the dihalogen compounds, the dichloro and dibromo compounds are particularly suitable.
Fortrinnsvis arbeider man i indifferente oppløsningsmidler, slik som dioksan, bensol og idet man går ut fra acylamino-benzoe-kinoner også i nærvær av alkoholer, slik som etyl-, isopropyl- eller butylalkohol eller isopropyleter. Preferably, one works in indifferent solvents, such as dioxane, benzene and, starting from acylamino-benzoe-quinones, also in the presence of alcohols, such as ethyl, isopropyl or butyl alcohol or isopropyl ether.
Ved den sistnevnte omsetning med etyleniminer kan man også anvende kon-densasjonsmidler, slik som tertiære baser. Reaksjonen lar seg utføre ved romtemperatur eller ved forhøyet temperatur. In the latter reaction with ethylene imines, condensing agents, such as tertiary bases, can also be used. The reaction can be carried out at room temperature or at an elevated temperature.
Utgangsstoffene er kjent eller kan fremstilles på i og for seg kjent måte. The starting materials are known or can be prepared in a manner known per se.
Kanonene som fåes ifølge fremgangs-måten kan anvendes som bakterisider samt som legemiddel, særlig ved kreftsykdommer eller sykdommer forårsaket av amøber, f. eks. i form av farmasøytiske preparater. Disse inneholder de nevnte forbindelser i blanding med et for enteral, parenteral eller lokal anvendelse egnet farmasøytisk organisk eller anorganisk bæremiddel. For dette kommer slike stoffer på tale som ikke reagerer med de nye forbindelser, slik som f. eks. gelatiner, melkesukker, stivelse, magnesiumstearat, talkum, vegetabilske oljer, benzylalkoholer, gummi, polyalkylen-glykoler, vaseliner, cholesterin eller andre kjente legemiddelbærere. De farmasøytiske preparater kan foreligge f. eks. som tab-letter, dragées, pulvere, salver, kremer, suppositorier eller i flytende form som opp-løsninger, suspensjoner eller emulsjoner. Eventuelt har de sterilisert og henholdsvis eller inneholder hjelpestoffer, slik som kon-serverings-, stabiliserings-, fukte- eller emulgeringsmiddel. De kan også inneholde andre terapeutisk verdifulle stoffer. The canons obtained according to the method can be used as bactericides as well as medicine, particularly in cancer or diseases caused by amoebas, e.g. in the form of pharmaceutical preparations. These contain the aforementioned compounds in admixture with a pharmaceutical organic or inorganic carrier suitable for enteral, parenteral or local application. For this, such substances come into question which do not react with the new compounds, such as e.g. gelatins, milk sugar, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, rubber, polyalkylene glycols, petroleum jelly, cholesterol or other known drug carriers. The pharmaceutical preparations may be present, e.g. as tablets, dragées, powders, ointments, creams, suppositories or in liquid form as solutions, suspensions or emulsions. If necessary, they have been sterilized and respectively or contain auxiliary substances, such as preservatives, stabilizers, wetting agents or emulsifiers. They may also contain other therapeutically valuable substances.
Oppfinnelsen beskrives i de følgende eksempler. Temperaturene er angitt i C-grader. The invention is described in the following examples. The temperatures are indicated in degrees C.
Eksempel 1: Example 1:
43,65 g 2,5-diklor-3,6-bis-acetamino-p-benzoekinon suspenderes i 500 cm<3> dioksan. Under omrøring tildryppes en blanding av 33,5 g trietylamin og 25,5 cm<3> etylenimin i 100 cm<3> dioksan. Den innvendige temperatur stiger derved litt etter litt til 35°. Om-setningen er avsluttet etter 9 timers om-røring i vannbad ved 50°. Man skiller bunn-fallet fra, vasker det med etanol og oppløser de deri inneholdte krystaller av trietylaminhydroklorid ved omrystning med 200 cm<3> vann. Man suger på ny fra, vasker med vann og etanol, og tørker det således erholdte 2,5-bis-etylenimino-3,6-bis-acet-amino-p-benzoekinon. Dette danner røde krystaller med spaltningspunkt 203° og har formelen: 43.65 g of 2,5-dichloro-3,6-bis-acetamino-p-benzoquinone are suspended in 500 cm<3> of dioxane. While stirring, a mixture of 33.5 g of triethylamine and 25.5 cm<3> of ethyleneimine in 100 cm<3> of dioxane is added dropwise. The internal temperature thereby rises little by little to 35°. The reaction is finished after 9 hours of stirring in a water bath at 50°. The precipitate is separated, washed with ethanol and the crystals of triethylamine hydrochloride contained therein are dissolved by shaking with 200 cm<3> of water. The mixture is sucked off again, washed with water and ethanol, and the 2,5-bis-ethyleneimino-3,6-bis-acet-amino-p-benzoquinone thus obtained is dried. This forms red crystals with a cleavage point of 203° and has the formula:
Eksempel 2: Example 2:
31,92 g 2,5-diklor-3,6-bis-propionylamino-p-benzoekinon suspenderes i 340 cm<3 >dioksan. Under god omrøring tildryppes ved romtemperatur en blanding av 16,9 cm<3 >etylenimin og 22,25 g trietylamin i 65 cm<3 >dioksan innen 15—20 minutter. Temperaturen stiger litt etter litt til 40° og holdes etter at den eksoterme reaksjon er avsluttet videre i 7 timer på 45°. De gule krystaller av bis-propionylamino-diklorkinon er etter denne tid forsvunnet og i stedet er det oppstått en grøt av røde krystaller. Disse suges fra, vaskes med dioksan og suspenderes i 150 cm vann, for å skille fra det dannede trietylaminhydroklorid. De suspenderte krystaller isoleres igjen ved frasugning og vaskes med etanol. Det således erholdte 2,5-bis-etylenimino-3,6-bis-propionylamino-p-benzoekinon med formelen 31.92 g of 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone are suspended in 340 cm<3 >dioxane. With good stirring, a mixture of 16.9 cm<3 >ethylenimine and 22.25 g of triethylamine in 65 cm<3 >dioxane is added dropwise at room temperature within 15-20 minutes. The temperature rises little by little to 40° and is kept after the exothermic reaction has ended for a further 7 hours at 45°. The yellow crystals of bis-propionylamino-dichloroquinone have disappeared after this time and instead a slurry of red crystals has formed. These are sucked off, washed with dioxane and suspended in 150 cm of water, to separate from the formed triethylamine hydrochloride. The suspended crystals are isolated again by suction and washed with ethanol. The thus obtained 2,5-bis-ethyleneimino-3,6-bis-propionylamino-p-benzoquinone with the formula
smelter ved 213° under rask dekomponering. melts at 213° with rapid decomposition.
Det som utgangsstoff anvendte 2,5-diklor-3,6-bis-propionylamino-p-benzoekinon kan fremstilles som følger: 62,1 g 2,5-diklor-3,6-diamino-p-benzoekinon suspenderes i 260 cm<3> propionsyre-anhydrid og tilsettes dråpevis 1,75 cm<3 >konsentrert svovelsyre. Temperaturen stiger ca. 5—10°. Deretter rører man 5 timer i vannbad ved 45° og lar stå natten over. Under isavkjøling tilsettes langsomt 200 cm<3> etanol og de dannede gule krystaller suges fra, vaskes grundig med etanol og omkrystalliseres av iseddik. Man får gule nåler av 2,5-diklor-3,6-bis-propionylamino-p-benzoekinon med smeltepunkt 253° (dekomponering). The 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone used as starting material can be prepared as follows: 62.1 g of 2,5-dichloro-3,6-diamino-p-benzoquinone is suspended in 260 cm< 3> propionic anhydride and add dropwise 1.75 cm<3 >concentrated sulfuric acid. The temperature rises approx. 5-10°. The mixture is then stirred for 5 hours in a water bath at 45° and left overnight. Under ice-cooling, slowly add 200 cm<3> of ethanol and the yellow crystals formed are sucked off, washed thoroughly with ethanol and recrystallized from glacial acetic acid. Yellow needles of 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone with a melting point of 253° (decomposition) are obtained.
Eksempel 3: Example 3:
31,25 g 2,5-diklor-3,6-bis butyrylamino-p-benzoekinon suspenderes i 300 cm<3> dioksan.. Ved romtemperatur tildryppes en blanding av 15,3 cm<3> etylenimin og 20,33 g trietylamin i 60 cm<3> dioksan under om-røring i 20 minutter. Temperaturen stiger av seg selv til 35°. Deretter røres videre under oppvarming til 45° i ennå 7 timer. Det opparbeides som i eksemplene 1 og 2. Man får således røde krystaller av 2,5-bis-etylenimino -3,6 -bis -butyrylamino -p - benzoekinon med formelen 31.25 g of 2,5-dichloro-3,6-bis butyrylamino-p-benzoquinone are suspended in 300 cm<3> dioxane. At room temperature, a mixture of 15.3 cm<3> ethyleneimine and 20.33 g of triethylamine is added dropwise in 60 cm<3> dioxane with stirring for 20 minutes. The temperature rises by itself to 35°. The mixture is then stirred under heating to 45° for a further 7 hours. It is worked up as in examples 1 and 2. You thus get red crystals of 2,5-bis-ethyleneimino-3,6-bis-butyrylamino -p - benzoquinone with the formula
med smeltepunkt 214° (dekomponering). with melting point 214° (decomposition).
Fremstillingen av det som utgangsstoff anvendte 2,5-diklor-3,6-bis-butyrylamino-p-benzoekinon som består av okergule krystaller med smeltepunkt 251—252° skjer idet man går ut fra 2,5-diklor-3,6-diamino-p-benzoekinon og smørsyreanhydrid analogt med fremstillingen av 2,5-diklor-3,6-bis-propionylamino-p-benzoekinon, som er beskrevet i eksempel 2. The preparation of the 2,5-dichloro-3,6-bis-butyrylamino-p-benzoquinone used as starting material, which consists of ochre-yellow crystals with a melting point of 251-252°, takes place starting from 2,5-dichloro-3,6- diamino-p-benzoquinone and butyric anhydride analogously to the preparation of 2,5-dichloro-3,6-bis-propionylamino-p-benzoquinone, which is described in example 2.
Eksempel i: Example in:
I en suspensjon av 29,11 g 2,5-diklor-3,6-bis-acetamino-p-benzoekinon i 340 cm<3 >dioksan inndryppes en blanding av 23,3 cm<3 >C-metyl-etylenimin og 25,30 g trietylamin i 65 cm<3> dioksan. Temperaturen stiger derved eksotermt fra 25 til 50° C. Man holder deretter 9 timer under omrøring i vannbad på 45°. Opparbeidelsen er analogt med den som er angitt i eksemplene 1 og 2. Man får lyserød krystaller av 2,5-bis-(metyl-etylen-imino)-3,6-bis-acetamino-p-benzoekinon med formelen A mixture of 23.3 cm<3 >C-methyl-ethyleneimine and 25 .30 g triethylamine in 65 cm<3> dioxane. The temperature thereby rises exothermically from 25 to 50° C. It is then kept for 9 hours with stirring in a water bath at 45°. The preparation is analogous to that indicated in examples 1 and 2. Pink crystals of 2,5-bis-(methyl-ethylene-imino)-3,6-bis-acetamino-p-benzoquinone are obtained with the formula
med smeltepunkt 199—202° (dekomponering). with melting point 199—202° (decomposition).
Eksempel 5: Example 5:
Til en suspensjon av 15,96 g av det ifølge eksempel 2 fremstillbare 2,5-diklor-3,6-bis-propionylamino-p-benzoekinon i 200 cm<3 >dioksan tildryppes en blanding av 11,65 cm<3 >C-metyletylenimin og 12,65 g trietylamin i 35 cm<3> dioksan. Temperaturen stiger litt etter litt til 35° og holdes deretter med et vannbad i 9 timer ved 45°. Man opparbeider slik som i eksemplene 1 og 2 og får således lyserøde krystaller av 2,5-bis-( metyl-etylen-imino)-3,6-bis-propionylamino-p-benzoekinon med formelen A mixture of 11.65 cm<3 >C -methylethylenimine and 12.65 g of triethylamine in 35 cm<3> dioxane. The temperature rises little by little to 35° and is then kept with a water bath for 9 hours at 45°. Work-up as in examples 1 and 2 and thus obtain pink crystals of 2,5-bis-(methyl-ethylene-imino)-3,6-bis-propionylamino-p-benzoquinone with the formula
med smeltepunkt 209°. with melting point 209°.
Eksempel 6: Example 6:
25,9 g 3,6-diklor-2,5-bis-etylenimino-p-benzoekinon suspenderes i 250 cm3 abso-lutt dioksan. I den godt omrørte suspensjon innføres ved en temperatur mellom 10 og 25° 16,2 g acetamid-natrium langsomt. Man omrører 18 timer ved romtemperatur, suger fra det krystallinske reaksjonsprodukt og vasker det grundig med vann for fjernelse av det dannede natriumklorid. Til slutt vaskes med alkohol og tørkes. Man får således 2,6-bis-acetamino-2,5-bis-etylen-imino-p-benzoekinon. 25.9 g of 3,6-dichloro-2,5-bis-ethyleneimino-p-benzoquinone are suspended in 250 cm 3 of absolute dioxane. At a temperature between 10 and 25°, 16.2 g of acetamide sodium are slowly introduced into the well-stirred suspension. The mixture is stirred for 18 hours at room temperature, the crystalline reaction product is sucked off and washed thoroughly with water to remove the sodium chloride formed. Finally, wash with alcohol and dry. 2,6-bis-acetamino-2,5-bis-ethylene-imino-p-benzoquinone is thus obtained.
Claims (5)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB37618/61A GB1041279A (en) | 1961-10-19 | 1961-10-19 | 13-alkyl steroid ketones |
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| Publication Number | Publication Date |
|---|---|
| NO122644B true NO122644B (en) | 1971-07-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| NO146142A NO122645B (en) | 1961-10-19 | 1962-10-18 | |
| NO146140A NO122643B (en) | 1961-10-19 | 1962-10-18 | |
| NO146141A NO122644B (en) | 1961-10-19 | 1962-10-18 | |
| NO146143A NO122646B (en) | 1961-10-19 | 1962-10-18 |
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| NO146140A NO122643B (en) | 1961-10-19 | 1962-10-18 |
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| CH (5) | CH450407A (en) |
| CY (1) | CY429A (en) |
| DE (4) | DE1793608B1 (en) |
| DK (6) | DK113641B (en) |
| ES (1) | ES281669A1 (en) |
| FI (4) | FI41026B (en) |
| FR (1) | FR2796M (en) |
| GB (2) | GB1041279A (en) |
| MY (1) | MY6800075A (en) |
| NO (4) | NO122645B (en) |
| SE (6) | SE313809B (en) |
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| DE2636404C2 (en) * | 1976-08-12 | 1983-12-08 | Schering AG, 1000 Berlin und 4709 Bergkamen | ?? 1?? 5? -17? -Ethynyl steroids of the estran series, processes for their preparation and pharmaceutical preparations containing them |
| US8617597B2 (en) | 2006-07-06 | 2013-12-31 | Bayer Intellectual Property Gmbh | Pharmaceutical composition containing a tetrahydrofolic acid |
| CN104926906B (en) * | 2015-06-04 | 2016-02-10 | 保定北瑞甾体生物有限公司 | A kind of preparation method of 17 Alpha-hydroxy Progesterone |
-
1961
- 1961-10-19 GB GB37618/61A patent/GB1041279A/en not_active Expired
- 1961-10-19 GB GB37617/61A patent/GB1041278A/en not_active Expired
-
1962
- 1962-10-15 SE SE11026/62A patent/SE313809B/xx unknown
- 1962-10-15 SE SE11024/62A patent/SE312552B/xx unknown
- 1962-10-15 SE SE11023/62A patent/SE312551B/xx unknown
- 1962-10-15 SE SE01423/67A patent/SE335526B/xx unknown
- 1962-10-15 SE SE11025/62A patent/SE312553B/xx unknown
- 1962-10-17 DK DK448162AA patent/DK113641B/en unknown
- 1962-10-17 CH CH1217162A patent/CH450407A/en unknown
- 1962-10-17 CH CH1275267A patent/CH459195A/en unknown
- 1962-10-17 CH CH1562766A patent/CH432509A/en unknown
- 1962-10-17 CH CH1562666A patent/CH450408A/en unknown
- 1962-10-17 CH CH1562566A patent/CH455763A/en unknown
- 1962-10-18 FI FI1878/62A patent/FI41026B/fi active
- 1962-10-18 NO NO146142A patent/NO122645B/no unknown
- 1962-10-18 ES ES281669A patent/ES281669A1/en not_active Expired
- 1962-10-18 DK DK449562AA patent/DK121228B/en unknown
- 1962-10-18 DK DK449762AA patent/DK115621B/en unknown
- 1962-10-18 DE DE19621793608 patent/DE1793608B1/en active Pending
- 1962-10-18 NO NO146140A patent/NO122643B/no unknown
- 1962-10-18 DE DE1962S0111837 patent/DE1617818B2/en active Granted
- 1962-10-18 NO NO146141A patent/NO122644B/no unknown
- 1962-10-18 FI FI1877/62A patent/FI41025B/fi active
- 1962-10-18 DK DK449662AA patent/DK115549B/en unknown
- 1962-10-18 DE DE1962S0082099 patent/DE1468604C2/en not_active Expired
- 1962-10-18 FI FI1879/62A patent/FI41027B/fi active
- 1962-10-18 DE DE19621618855 patent/DE1618855B2/en active Granted
- 1962-10-18 AT AT822762A patent/AT264730B/en active
- 1962-10-18 NO NO146143A patent/NO122646B/no unknown
- 1962-10-18 FI FI1876/62A patent/FI41024B/fi active
- 1962-10-19 AT AT825662A patent/AT256354B/en active
- 1962-10-19 AT AT825862A patent/AT256356B/en active
- 1962-10-19 AT AT825762A patent/AT256355B/en active
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1963
- 1963-01-16 FR FR921556A patent/FR2796M/en not_active Expired
-
1966
- 1966-05-02 SE SE05984/66A patent/SE340619B/xx unknown
-
1968
- 1968-01-15 CY CY42968A patent/CY429A/en unknown
- 1968-12-31 MY MY196875A patent/MY6800075A/en unknown
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1969
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1970
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