CS274244B1 - Method of normethanephrine preparation - Google Patents
Method of normethanephrine preparation Download PDFInfo
- Publication number
- CS274244B1 CS274244B1 CS35489A CS35489A CS274244B1 CS 274244 B1 CS274244 B1 CS 274244B1 CS 35489 A CS35489 A CS 35489A CS 35489 A CS35489 A CS 35489A CS 274244 B1 CS274244 B1 CS 274244B1
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- CS
- Czechoslovakia
- Prior art keywords
- formula
- water
- methoxyphenyl
- hydroxy
- ethanone
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- ZYISHMORGJQMEO-UHFFFAOYSA-N 2-chloro-1-(4-hydroxy-3-methoxyphenyl)ethanone Chemical compound COC1=CC(C(=O)CCl)=CC=C1O ZYISHMORGJQMEO-UHFFFAOYSA-N 0.000 claims abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 5
- HDSZSHKKALYOPY-UHFFFAOYSA-N 2-azido-1-(4-hydroxy-3-methoxyphenyl)ethanone Chemical compound N(=[N+]=[N-])CC(=O)C1=CC(=C(C=C1)O)OC HDSZSHKKALYOPY-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 150000001298 alcohols Chemical class 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- YNYAYWLBAHXHLL-UHFFFAOYSA-N Normetanephrine Chemical compound COC1=CC(C(O)CN)=CC=C1O YNYAYWLBAHXHLL-UHFFFAOYSA-N 0.000 claims description 8
- YNYAYWLBAHXHLL-MRVPVSSYSA-N Normetanephrine Natural products COC1=CC([C@H](O)CN)=CC=C1O YNYAYWLBAHXHLL-MRVPVSSYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 4
- VQXINLNPICQTLR-UHFFFAOYSA-N carbonyl diazide Chemical compound [N-]=[N+]=NC(=O)N=[N+]=[N-] VQXINLNPICQTLR-UHFFFAOYSA-N 0.000 claims description 3
- 239000003245 coal Substances 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- VKFPRGQZWKTEON-UHFFFAOYSA-N 4-(2-amino-1-hydroxyethyl)-2-methoxyphenol;hydron;chloride Chemical compound Cl.COC1=CC(C(O)CN)=CC=C1O VKFPRGQZWKTEON-UHFFFAOYSA-N 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 1
- 150000001540 azides Chemical class 0.000 claims 1
- 238000000354 decomposition reaction Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 239000000377 silicon dioxide Substances 0.000 claims 1
- 229910052938 sodium sulfate Inorganic materials 0.000 claims 1
- 235000011152 sodium sulphate Nutrition 0.000 claims 1
- 238000004809 thin layer chromatography Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 4
- -1 4-hydroxy-3-methoxyphenyl Chemical group 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- VUZPGEIXNYGDJN-UHFFFAOYSA-N 1-nitroethanol Chemical class CC(O)[N+]([O-])=O VUZPGEIXNYGDJN-UHFFFAOYSA-N 0.000 description 1
- PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical class [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 1
- JSHLOPGSDZTEGQ-UHFFFAOYSA-N 3-methoxy-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCC1=CC=CC=C1 JSHLOPGSDZTEGQ-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012467 final product Substances 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
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- PZSJOBKRSVRODF-UHFFFAOYSA-N vanillin acetate Chemical compound COC1=CC(C=O)=CC=C1OC(C)=O PZSJOBKRSVRODF-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Způsob přípravy normetanephrinu (57) Způsob přípravy normetanepbrinu vzorce III spočívá v tom, že se na 2-chlor-l-(4-hydroxy-3-methoxyfenyl)-ethanon vzorce I působí alkalickým azidem sodným ve směsi vody a alkoholu s počtem atomů uhlíku 1 až 5 v objemovém poměru 1 : 1 až 10 za vzniku 2-azido-l-(4-bydroxy-3-methoxyfenyl)-ethanonu vzorce II, který se hydrogenuje v rozpouštědle mísitelném s vodou , například alkoholech s počtem uhlíků 1 až 5 nebo kyselině octové, za přítomnosti 1,0 až 1,3 molárních ekvivalentů kyseliny chlorovodíkové a 5 až 35 % hmot., katalyzátoru na bázi 5 až 10 % hmot. paladia na nosiči, například na uhlí nebo křemelině.Method for the preparation of normetanephrine (57) The process for the preparation of normetanepbrin of formula III consists in treating 2-chloro-1- (4-hydroxy-3-methoxyphenyl) -ethanone of formula I with an alkali sodium azide in a mixture of water and an alcohol having a carbon number of atoms 1 to 5 in a volume ratio of 1: 1 to 10 to give 2-azido-1- (4-hydroxy-3-methoxyphenyl) -ethanone of formula II, which is hydrogenated in a water-miscible solvent, for example alcohols having a carbon number of 1 to 5 or acetic acid, in the presence of 1.0 to 1.3 molar equivalents of hydrochloric acid and 5 to 35 wt.%, a catalyst based on 5 to 10 wt. palladium on a carrier, for example coal or diatomaceous earth.
ch3o.ch 3 o.
H0^O^C0CH2Cl H0 ^ O ^ Cl 2 C0CH
IIII
CS 274244 BlCS 274244 Bl
Vynález ee týká způsobu přípravy normetanephrinu (l-(4-hydroxy-3-methoxyfenyl)-2-aminoetbanolu vzorce III), který se používá k stanovení katecholeminů v tělních tekutinách.The invention relates to a process for the preparation of normetanephrine (1- (4-hydroxy-3-methoxyphenyl) -2-aminoetbanol of formula III), which is used for the determination of catecholemines in body fluids.
Dosavadní postupy přípravy normetanephrinu vzorce III využívaly kondenzace nitromethanu s O-acetylvanilinem (Heacock R.A., Hutzinger 0.: Chem. and. Ind. 1961, 595), nebo O-benzylvanilinem (Axelrod J., Sonoh S., Witkop B.: J.Biol.Chem. 233, 697 (1958)) na derivát nitroethanolu, jehož redukcí získali žádaný produkt. Nevýhodou uvedených postupů jsou složitá reakčni podmínky a vznik vedlejšího produktu (nitrostyrenový derivát), který je nutno odstranit frakční krystalizací. Výtěžek nitroderivátu popisují autoři okolo 50 až 60 %, ale reakce je velmi špatně reprodukovatelná a skutečné výtěžky jsou mnohem nižší. Jiný postup využívá kondenzace bisulfitového aduktu 3-methoxy-4-hyčroxyfenylglyoxalu g benzylaminem a dvojí hydrogenace - nejprve na Raneyově niklu a potom na paladiu (Fodor G., Kovács 0., Mecher T.: Acta Chim.Acad.Sci.Hungar.l,395 (1951). Tento postup zahrnuje minimálně o dva reakčni stupně víc.Previous processes for the preparation of normetanephrine of formula III have utilized the condensation of nitromethane with O-acetylvanillin (Heacock RA, Hutzinger 0: Chem. And Ind. 1961, 595), or O-benzylvanillin (Axelrod J., Sonoh S., Witkop B .: J. Chem., 233, 697 (1958)) to the nitroethanol derivative, the reduction of which yields the desired product. The disadvantages of these processes are the complex reaction conditions and the formation of a by-product (nitrostyrene derivative) which must be removed by fractional crystallization. The yield of the nitro derivative is described by the authors at about 50 to 60%, but the reaction is very poorly reproducible and the actual yields are much lower. Another approach uses the condensation of the 3-methoxy-4-hydroxyphenylglyoxal bisulfite adduct with benzylamine and double hydrogenation - first on Raney nickel and then on palladium (Fodor G., Kovács 0, Mecher T .: Acta Chim.Acad.Sci.Hungar.l 395 (1951) This procedure involves at least two reaction steps more.
Uvedené nevýhody odstraňuje způsob přípravy normetanephrinu vzorce III podle vynálezu, jehož podstata spočívá v tom, že se na 2-chlor-l-(4-hydroxy-3-methoxyfenyl)-ethanon vzorce I působí alkalickým azidem sodným ve směsi vody a alkoholu s počtem atomů uhlíku 1 až 5 v objemovém poměru 1 : 1 až 10 za vzniku 2-azido-l-(4-hydroxy-3-methoxyfenyl)-ethanonu vzorce II, který se hydrogenuje v rozpouštědle mísitelném s vodou, například alkoholech s počtem uhlíků 1 až 5 nebo kyselině octové, za přítomnosti 1,0 až 1,3 molárních ekvivalentů kyseliny chlorovodíkové a 5 až 35 % hmot. katalyzátoru na bázi 5 až 10 % hmot. paladia na nosiči, například na uhlí nebo křemelině.The above-mentioned disadvantages are overcome by the process for the preparation of the normetanephrine of formula III according to the invention, which comprises treating 2-chloro-1- (4-hydroxy-3-methoxyphenyl) -ethanone of formula I with an alkali sodium azide in a mixture of carbon atoms 1 to 5 in a volume ratio of 1: 1 to 10 to give 2-azido-1- (4-hydroxy-3-methoxyphenyl) -ethanone of formula II, which is hydrogenated in a water-miscible solvent, e.g. % to 5 or acetic acid, in the presence of 1.0 to 1.3 molar equivalents of hydrochloric acid and 5 to 35 wt. % of a catalyst based on 5 to 10 wt. palladium on a carrier, for example coal or diatomaceous earth.
Při hydrogenaoi dochází k redukci ketoskupiny a azidoskupiny současně a s přítomným chlorovodíkem vzniká jako konečný produkt hydrochlorid normetanephrinu. Výcho zí surovina 2-chlor-l-(4-bydroxy-3-methoxyfenyl)-ethanonu vzorce I je snadno dostupná. (Pratt D.D. Robinson R.: J.Chem.Soc. 123, 753 (1923)).In hydrogenation, the keto and azido groups are reduced at the same time and normethephrine hydrochloride is formed as the final product with hydrogen chloride present. The starting material of 2-chloro-1- (4-hydroxy-3-methoxyphenyl) -ethanone of formula I is readily available. (Pratt, D. D. Robinson, R .: J. Chem. Soc. 123, 753 (1923)).
Výhoda způsobu přípravy podle vynálezu spočívá v tom, že z chlorketonu vzorce I se jednoduchým způsobem připraví ve výtěžku 68 až 77 % izolovatelný azidoketon vzorce II. Jeho katalytickou hydrogenaoi za obvyklých podmínek se, opět v dobrém výtěžku 83 až 88 %, získá žádaný normetanephrin vzorce III. Obě reakce jsou jednoznačné, nedochází ke vzniku žádných vedlejších produktů. Při izolaci není třeba používat ohromatografii nebo frakční krystalizaci, čistý produkt vzorce III i meziprodukt vzorce II se získávají jedinou krystalizací.An advantage of the process according to the invention is that from the chloroketone of the formula I, an isolatable azidoketone of the formula II can be prepared in a simple manner in a yield of 68 to 77%. Its catalytic hydrogenation under conventional conditions, again in good yields of 83-88%, yields the desired normetanephrine of formula III. Both reactions are unambiguous, no by-products are formed. No isolation or fractional crystallization is required in the isolation, both pure product III and intermediate II are obtained by a single crystallization.
Příklady provedeníExamples
Příklad 1Example 1
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS35489A CS274244B1 (en) | 1989-01-19 | 1989-01-19 | Method of normethanephrine preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS35489A CS274244B1 (en) | 1989-01-19 | 1989-01-19 | Method of normethanephrine preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS35489A1 CS35489A1 (en) | 1990-09-12 |
| CS274244B1 true CS274244B1 (en) | 1991-04-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS35489A CS274244B1 (en) | 1989-01-19 | 1989-01-19 | Method of normethanephrine preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS274244B1 (en) |
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1989
- 1989-01-19 CS CS35489A patent/CS274244B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS35489A1 (en) | 1990-09-12 |
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