PL741B1 - Method for the production of alkyl ortho derivatives of hydrocuprein. - Google Patents
Method for the production of alkyl ortho derivatives of hydrocuprein. Download PDFInfo
- Publication number
- PL741B1 PL741B1 PL741A PL74121A PL741B1 PL 741 B1 PL741 B1 PL 741B1 PL 741 A PL741 A PL 741A PL 74121 A PL74121 A PL 74121A PL 741 B1 PL741 B1 PL 741B1
- Authority
- PL
- Poland
- Prior art keywords
- hydrocuprein
- alkyl
- production
- parts
- alcohol
- Prior art date
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- 125000000217 alkyl group Chemical group 0.000 title description 10
- 238000000034 method Methods 0.000 title description 6
- 238000004519 manufacturing process Methods 0.000 title description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 101100519432 Rattus norvegicus Pdzd2 gene Proteins 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- KIWBPDUYBMNFTB-UHFFFAOYSA-M ethyl sulfate Chemical compound CCOS([O-])(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-M 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- -1 alkyl hydrocarbons Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- UTUNZTDXEIGXKD-UHFFFAOYSA-N ethoxyethane;sulfuric acid Chemical compound CCOCC.OS(O)(=O)=O UTUNZTDXEIGXKD-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- KSSNXJHPEFVKHY-UHFFFAOYSA-N phenol;hydrate Chemical group O.OC1=CC=CC=C1 KSSNXJHPEFVKHY-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
Description
Wynalazek dotyczy -wytwarzania alkilo¬ wych pochodnych hydr okupreiny, które, jak wiaidomio, sa poczescii wazneimi srodkami lecznicizemi i dotychczas byly wytwarzane w ten sposób, ze hydirokupreiny w zwykly sposób traktuje sie alkilujacemu srodkami (poirówn. opis pat. 'mierni. 254.712 i amg. p/ait. .16.619/1912). Nowy sposób poleca ma tern, ze tlenek hydrokupreiny, który mozna uzyskac, np., przeiz utlenienie hydrokuprei¬ ny, alkiluje sie, a otrzymane zalkilowiane tleinki hydrokupreiny przeprowadza, sie przez rediukcje w odpowiednie alkilowe hydroku¬ preiny.The invention relates to the preparation of alkyl derivatives of the hydrocuprein, which are known to be important therapeutic agents until now and have been produced in such a way that the hydirocupreins are treated in the usual way with an alkylating agent (see similarly Pat. No. 254,712 and amg). . p / ait. .16.619 / 1912). The new process recommends that the hydrocuprein oxide which can be obtained, for example, by the oxidation of hydrocuprein, is alkylated and the resulting alkylated hydrocuprein oxides are converted into the corresponding alkyl hydrocupreins by reduction.
Przy znanych sposobach nietylko jeden atom wodoru grupy fenolowo wodorotleno¬ wej hydrokupieimy zoistaije zastapiony ailki- leim, lecz przylacza sie alkil takze do atomu- azotu z!aaady, przez co powstaja zasaidy aimo- Jiowe, które 'zmniejszaja wydajnosc hydro¬ kupreiny. Przy nowym sposobie nie. tworza sie zasady amonowe, poLiiiewaiz atom azotu, do którego dolacza sie tylko alkil, chroniony jest przez polaczenie 'z jednym atomem tle¬ nu. Poniewaz tleinki alkilowe hydrokupireiny dadza sie latwo redukowac na alkilowe hy- drokupreiny, otrzymuje sie wedlug tego spo¬ sobu lepsza wydajnosc alkilowych hydto- k upre im.In the known processes, not only one hydrogen atom of the phenol hydroxide group is replaced by ailkylne, but alkyl also attaches to the aaad nitrogen atom, thereby forming an amo-ionic base which reduces the yield of hydrocuprein. Not with the new method. ammonium bases are formed, and the nitrogen atom to which only alkyl is attached is protected by linkage to one oxygen atom. Since the alkyl oxides of hydrocuprein can be easily reduced to alkyl hydrocupreins, a better yield of the alkyl hydrocarbons is obtained.
Przyklad 1. 328 czesci tlenku hydrokupireiny (1 Mol.), który mozna otrzymac przez traktowanie hy¬ drokupreiny woda utleniona w ten sposób, ze mieisflaniiine równych czesci hydrokuprei¬ ny, alkoholu i 30%-towej wody utlenionej pozostawia sie az do rozpuszczenia sie przy temperaturach,' mieprzekraczaljacych 40°, po-czem (p«o dlodalniu woldly, alzi dlo zmetnienia; tlen¬ ku hydrokupireiiny, wydzielaja sie krysztaly w postaci listfcówi o punkt, topi. 199°, rozpu-. siziciza sie w 1600 czesciaich alkoholu datkiem 40 czesci wodizianu sodowego (1 Mol.) i izadaije sie 154 czesciaimi siarcziainu etylowe-; go (1 Miol.). Po dwudniowam odstaniu w teim- peraturzie pokojowej (przy ogrzaniu wystar¬ cza krótszy ez,ais) 'ziaikwiasizia sie kwaisem siar¬ kowym i dodaje sie tyle amoinjiaiku, taz oranz metylowy wlasnie zostaje zmieniony. Pod¬ czas stania wydziela sie siarczan tlenku ety¬ lowego hydrokupreiny, który zostaje odssa- ny i zmyty alkoholem i woda. Tworza sie bezbarwne, mocno gorzkie igielki, które w" al¬ koholu i wodzie sa trudno rozpuszczalne.Example 1. 328 parts of hydrocuprein oxide (1 mol.) Which can be obtained by treating hydrocuprein with hydrogen peroxide in such a way that the mieisflaniin of equal parts of hydrocuprein, alcohol and 30% hydrogen peroxide is allowed to dissolve at temperatures, exceeding 40 ° C, during the course of a long period of time woldly, as well as to become cloudy; hydrocupirein oxide, crystals in the form of leaflets are released by a point, melts 199 °, dissolves in 1600 parts of alcohol with an addition 40 parts of sodium hydroxide (1 mol.) And made of 154 parts of ethyl sulphate (1 mol.). After two days of standing in room temperature (shorter wire, ais is enough for heating), it becomes acidified with sulfur acid. As much amoinic acid is added, the methyl orange is just changed. As it stands, the ethyl oxide sulphate of hydrocuprein is released, which is sucked off and washed away with alcohol and water. Colorless, strongly bitter needles are formed, which are sparingly soluble in alcohol and water.
W celu przeprowadzenia tego zwiazku w hy- drokupreine etylu ogrzewa sie z nadmiarem kwasu siarkowego trzy godziny w kociolku Papina do 80°. Po oziebieniu wstrzasa sie z nadmiarem lugu sodowego i eteru. Po od- destylowainiu, zmytego woda eiterycziniego roztworu, poizbstaje hydrokupreima etylu, która sie skutecznie oczysizcza przez zamiane na obojetny siarczan.To convert this compound into ethyl hydrocuprein, it is heated with excess sulfuric acid for three hours in a Papin kettle to 80 °. After cooling it, it is shaken with an excess of sodium hydroxide and ether. After distilling the washed water of the eiteric solution, an ethyl hydrocupreim is obtained, which is effectively purified by conversion to inert sulfate.
Równiez korzystny rezultat mo-zna osia¬ gnac, nie wydzielajac siarczanu etylowego 'tlenku hydrokupreiny, lecz ogrzewajac pro¬ dukt reakcji, zakwaszony kwasem siarko¬ wym z nadmiarem kwasu kilka godzin do 80°; produkt ten po oddestylowaniu alko¬ holu i po oziebieniu wstrzasa sie z nadmia¬ rem lugu sodowego i eteru. Po oddestylowa- •niu przemytego woda eterycznego roztworu pazostaijtef hydrokupreiM etylu, która otozy- sz.oziai sie prze/pfowadjzeindeimj n'al dboijetiny siiairozan.Also, a favorable result can be obtained by not releasing the ethyl sulphate of hydrocuprein oxide but by heating the reaction product acidified with sulfuric acid with an excess of acid for several hours to 80 °; this product, after the alcohol has been distilled off and cooled down, is shaken with an excess of sodium liquor and ether. After distilling off the washed water of an ethereal solution of hydrocuppressant ethyl, which was obtained and transformed into the induction of Siiairosan.
' Przykliad 2. 4 czesci tlenku hydrokupreiny, 20 czesci alkoholu i 1 czesc potazu zraiczego i 2 czesci chlorku etylenowego ogrzewa sie w kociol¬ ku Papina 20 godzin do 105°. Nastepnie do¬ daje sie 6 czesci siarczanu sodowego, za¬ kwasza sie kwasem siarkowym i ogrzewa sie w kociolku Papina dalsze 3 godziny do 80°.Example 2. 4 parts of hydrocuprein oxide, 20 parts of alcohol and 1 part of traumatic potassium and 2 parts of ethylene chloride are heated in a Papin kettle for 20 hours to 105 °. Then 6 parts of sodium sulphate are added, acidified with sulfuric acid and heated in a Papin kettle for a further 3 hours to 80 °.
Po oddestylowaniu alkoholu i ostudzeniu do¬ daje sie lugu sodowego w nadmiarze i wy¬ ciaga eterem. Po zgeszczeniu eterycznego roztworu wydziela sie 'chlorek etylu hydro¬ kupreiny w delikatnych bezbarwnych igiel¬ kach; jest on latwo rozpuszczalny w alko¬ holu, chloroformie i rozcienczonych kwasach, trudniej w eterze, nierozpusizozainy w ben¬ zynie i wodzie; punkt toplliwosci lezy przy 164°.After the alcohol has been distilled off and cooled down, excess sodium hydroxide is added and extracted with ether. After concentrating the ethereal solution, hydrocuprein ethyl chloride is separated in fine colorless needles; it is easily soluble in alcohol, chloroform and dilute acids, more difficult in ether, non-ossozaines in gasoline and water; the melting point is at 164 °.
Wytwarzanie innych alkilowych hydrto- kuprein odbywa sie w analogiczny sposób* Z as tr ze ¦¦ zernie patentowe.The production of other alkyl hydrotacreins is carried out in an analogous manner * With the exception of patent no.
Sposób wytwarzania alkilowych ortopo- chodnych hydrokupreiny, tern znamienny, ze tlenek hydrokrmpreiny, który mp., moizinia uzy¬ skac przez utlenienie hydrokupreiny, alki¬ luje sie zwyklem! metodami, a zalkilowane produkty zostaja przeprowadzone zapomoca odtleniajacych srodków w alkilowe pochod¬ ne hydrokupreiny.The method for the preparation of alkyl ortho-derivatives of hydrocuprein, characterized by the fact that hydrocrmprein oxide, which, for example, can be obtained by the oxidation of hydrocuprein, is customary! by methods, and the alkylated products are converted by deoxidizing agents into the alkyl derivatives of hydrocuprein.
Vereinigte Chininfabriken Zimmer & Cc., Ges. mit beschrankter Haftung.Vereinigte Chininfabriken Zimmer & Cc., Ges. mit beschrankter Haftung.
Zastepca: M. Kryz an, rzecmik patenitowy. ?ik* RRAF.KOZIANSKICH W KRAKBW4Deputy: M. Kryzan, patenite artist. ? ik * KOZIANSKICH RRAF. IN KRAKBW4
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL741B1 true PL741B1 (en) | 1924-10-31 |
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