DK147019B - Analogifremgangsmaade til fremstilling af pyridyleddikesyrederivater - Google Patents

Analogifremgangsmaade til fremstilling af pyridyleddikesyrederivater Download PDF

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DK147019B
DK147019B DK268973AA DK268973A DK147019B DK 147019 B DK147019 B DK 147019B DK 268973A A DK268973A A DK 268973AA DK 268973 A DK268973 A DK 268973A DK 147019 B DK147019 B DK 147019B
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acetic acid
acid
pyridyl
acid derivatives
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DK147019C (da
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Ryozo Maeda
Katsumi Hirose
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Shionogi & Co
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C07D213/643—2-Phenoxypyridines; Derivatives thereof
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
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Description

i 147019
Den foreliggende opfindelse angår en analogifremgangsmide til fremstilling af hidtil ukendte pyridyleddikesyrederivater, der er nyttige som anti-inflammatoriske, anti-rheumatiske, analgetiske eller an-ti-pyretiske midler.
05 Mere specielt angår opfindelsen en analogifremgangsmide til fremstilling af forbindelser med den almene formel:
Q
Λ !
10 X-L -ή-CH-COOH
X
" 15
hvori X betegner hydrogen eller C^_galkyl, Y betegner hydrogen, halogen, C^galkyl, C^galkoxy, cyano eller C2_galkoxycarbonylami-no, Y1 betegner hydrogen eller C^_galkyl, R betegner hydrogen eller C^_^alkyl, A betegner et oxygenatom eller et svovlatom, og Q
20 betegner et eventuelt tilstedeværende oxygenatom, eller alkalimetal-eller jordalkaiimetalsalte deraf, hvilken fremgangsmåde er ejendommelig ved, at man hydrolyserer en forbindelse med den almene formel
Q
! R
25 X-C |-CHCOZ
--¾) (v'vi) 30 hvori Z betegner C^_galkoxy, Cy_^garalkyloxy eller anilino, og X, Y, Y1, Q, A og R har de ovenfor anførte betydninger, hvorefter en fremstillet forbindelse om ønsket omdannes til et alkalimetal- eller jordalkalimetalsalt deraf.
35 Fremstillingen af udgangsmaterialer og fremgangsmåden ifølge opfindelsen er nærmere belyst i følgende reaktion s skema: 2 147019
X-^ C0°H
A
Y1 (xx)
Trini Halogenering
X-ÉT ^4-COM
10
A
Y~=£il Y'-(III) 15 Trin 2 RCHN2
N R
x—C>~cotN2
A
2° I
γ^Φ <IV)
Trin 3 ^ ZH
N £ N R
25 X CHCOZ X p'I+j CHCOOH
\ Trin h \
A _^ A
30 Y^M (V) 2 >U (I,
Trin 5 Oxid.
4'
9 Q
- 3 U S i)
X--jj 0HCOZ X---01IUOOH
Trin 6 \
A A
r “2° Y^l Y (VI) γι^Οί (I) 147019 3 hvor M betegner et halogenatom (fx. chlor, brom), og Z betegner en alkoxygruppe med 1-8 carbonatomer (fx. methoxy, ethoxy, pro-poxy, n-butoxyj, en aralkyloxygruppe med 7-18 carbonatomer (fx. benzyloxy, phenethyloxy) eller en anilinogruppe, og X, Y, Y', Q, 05 R og A har hver især den ovenfor angivne betydning. Fremgangsmåden ifølge den foreliggende opfindelse omfatter trin 4 og 6.
Carboxyforbindelsen (II), hvorfra der udgås, kan fremstilles ved hydrolysering af esteren eller nitrilet, som svarer hertil, eller ved anvendelse af oxidation af en methylgruppe. Det er fx. kendt, 10 at 2-phenoxyisonikotinsyre fremstilles ved oxidation af 2-phenoxy-y--picolin.
Første trin kan udføres ved behandling af udgangscarboxyfor-bindelsen (II) med halogeneringsmiddel. Eksempler på halogenerings-midler er thionylchlorid, phosphortrichlorid, phosphoroxychlorid, 15 phosphorpentachlorid og phosphortribromid. Omsætningen kan udføres under tilstedeværelse eller fravær af et inert opløsningsmiddel (fx. carbontetrachlorid, chloroform) ved stuetemperatur eller under opvarmning eller afkøling. En katalysator, såsom dimethylformamid, kan om nødvendigt tilsættes. Efter afslutning af omsætningen kan 20 reaktionsblandingen om ønsket behandles med en base (fx. pyridin, triethylamin, dimethylanilin).
Andet trin kan udføres ved omsætning af den ovenfor fremkomne carbonylhalogenidforbindelse (III) med en diazoalkan (fx. diazo-methan, diazoethan, diazopropan, diazoisobutan). Omsætningen kan 25 i almindelighed udføres under tilstedeværelse af et inert opløsningsmiddel, såsom en ether (fx. diethylether, tetrahydrofuran, diglym), et carbonhydrid (fx. benzen, toluen, n-hexan), et halogencarbonhy-drid (fx. chloroform, carbontetrachlorid, methylenchlorid), dimethylformamid eller en blanding heraf under afkøling eller ved stuetempe-30 ratur, eller om nødvendigt under forsigtig opvarmning.
Tredje trin kan udføres ved omsætning af den ovenfor fremkomne diazoalkanoylforbindelse (IV) med en alkohol (fx. methanol, etha-nol, isopropanol, n-amylal kohol, benzy lal kohol, phenethy lal kohol) eller anilin, Denne omsætning kan udføres under tilstedeværelse eller 35 fravær af en katalysator, såsom sølv (fx. som en kombination af sølvbenzoat og triethylamin) eller sølvoxid, eller under bestråling 4 147019 med uitra-violet lys og med eller uden et inert opløsningsmiddel (fx. γ-kollidin, dioxan, tetrahydrofuran, diglym, dimethylformamid, di-methylsulfoxid eller en blanding af to eller flere heraf) ved stuetemperatur eller under opvarmning.
05 Fjerde trin kan udføres ved hydrolysering af esteren eller ani- lidforbindelsen (V), som fremkom ovenfor. Hydrolysen kan udføres ved behandling med en syre, såsom en uorganisk syre (fx. saltsyre, svovlsyre, brombrinte) eller en organisk syre (fx. eddikesyre) eller et alkali (fx. alkalihydroxid, alkalicarbonat, alkalihydrogencarbonat), 10 fortrinsvis alkoholisk alkalihydroxid (fx. ethanol/kaliumhydroxid) ved stuetemperatur eller under opvarmning.
Femte trin kan udføres ved oxidation af esteren (V), som fremkom ved tredje trin, med hydrogenperoxid eller en persyre (fx. pereddikesyre, perbenzoesyre, m-chlorperbenzoesyre). Omsætningen 15 kan udføres i et inert opløsningsmiddel (fx. methanol, eddikesyre, chloroform, methylenchlorid) ved stuetemperatur eller under afkøling eller opvarmning. På denne mide fis N-oxidforbindelsen (VI).
Sjette trin kan udføres ved hydrolyse af N-oxidforbindelsen (VI), som fremkom ovenfor. Hydrolysen kan udføres ved behandling 20 med en syre, såsom en uorganisk syre (fx. saltsyre, svovlsyre, brombrinte) eller en organisk syre (fx. eddikesyre) eller et alkali (fx. alkalihydroxid, alkalicarbonat, alkalihydrogencarbonat), fortrinsvis alkoholisk alkalihydroxid (fx. ethanol/kaliumhydroxid) ved stuetemperatur eller under opvarmning.
25 De således fremkomne substituerede eddikesyrederivater (I) kan omdannes til deres passende alkalimetalsalt (fx. natriumsalt, kaliumsalt) eller jordal kalimetalsalt (fx. calciumsalt, magnesiumsalt, bariumsalt) på normal vis i overensstemmelse med de krav, der stilles til separation, rensning eller formulering.
30 Disse substituerede eddikesyrederivater (I) eller deres salte er nyttige som anti-inflammatoriske, anti-rheumatiske, analgetiske eller anti-pyretiske midler. For visse af de omhandlede substituerede eddikesyrederivater (I) vises i den efterfølgende tabel I den anti-ery-tematiske aktivitet (ED5Q mg/kg), anti-ødem aktiviteten (ED3q mg/ 35 kg) og den akutte toxicitet (LD50 mg/kg): 5 147019
Tabel I
Forbindelse Anti-erytematisk Anti-ødem Akut toxicitet aktivitet aktivitet (marsvin oralt) (rotter oralt) (mus oralt) 05 ED50 mg/kg ED5Q mg/kg LDgg mg/kg
Aspirin 79 48 1998
Phenylbutazon 26 48 1414
Calcium bis[2-(2- phenoxy-5-pyridyl)- 21 8 1645 10 propionat]
Calcium bis[2-(2- phenoxy-4-pyridyl)~ 47 16 2248 propionat] 2-(2-p-chlorphenoxy- 19 6,5 1153 15 5-pyridyl)-propionsyre
Fodnote: Den anti-erytematiske aktivitet konstateredes med Wilhelmis fremgangsmåde (Wilhelmi, G., (1949), Schweiz. Med.
Wehnschr., 79, 577). Anti-ødem aktiviteten konstateredes med Benitz fremgangsmåde (Benitz, K.F. et al., (1963), 20 Arch. Int. Pharmacodyn., 144, 185-195). Toxiciteten af prøvedes ved oral administrering af forsøgsforbindelsen til mus.
Endvidere viser tabel II den anti-inflammatoriske aktivitet og 25 den akutte toxicitet for en række forbindelser fremstillet ifølge opfindelsen sammenlignet med phenylbutazon. Den anti-inflammatoriske aktivitet blev bestemt som anti-ødem aktiviteten ved anvendelse af en vandig opløsning af 1% carrageenin (0,05 ml) som et phlogistisk middel. 30 minutter efter oral administrering af hhv. 10 mg/kg, 25 30 mg/kg og 50 mg/kg af en testforbindelse injiceredes det phlogistiske middel subkutant i plantar-delen af en rottepote. Opsvulmningsvolu-minet miltes 3 timer efter carrageenin og inhiberingsprocenten bestemtes ved at beregne forholdet mellem ødemvoluminet af den behandlede fod i forhold til den ubehandlede fod. Den akutte toxicitet 35 bestemtes ved anvendelse af en gruppe pi 10 mus af DS-stamme for hver dosis. LD^g-værdien efter 72 timer fra oral administrering af en testforbindelse bestemtes.
6 147019
Tabel II R
, CHCOOH
r^<“ 05 «>
Forb. Inhiberingsprocent
Nr. ' Dosis (mg/kg) LD5Q
X a R A Y_V__(mg/kg) 10 50 25 10 P.B. 35,9 10,8 1413,5
1 H 4 H 2-0 4-CI H 40,8 30,7 >1500P
2 H 4 Me 2-0 4-CI H 60,7 40,3 1000P
3 H 4 Me 2-0 Η H 57,0 37,4 XI500P
15 4 H 4 H 2-0 3-CI H 36,5 12,9 >1500P
5 H 4 Me 2-0 2-CI H 41,2 2,6 >1500P
6 H 4 Me 2-0 3-CI ' H 42,6 28,5 1150P
7 H 5 Me 2-0 Η H 74,1 40,4 >1500P
8 H 5 Me 2-0 4-CI H 56 56,2 30,6 750P
20 9 H 6 Me 2-0 Η H 36,7 12,3 1250P
10 H 6 Me 2-0 4-CI H 41,9 16,9 >1500P
11 H 4 Me 2-0 4-Me H 46,3 31 23,4 >1500P
12 H 5 Me 2-S Η H 69,8 41,6 21,9 1000P
13 H 5 Me 2-0 4-Me H 51,5 19,7 1250P
25 14 H 4 Me 2-S 4-CI H 42,6 20,0 1500P
15 H 4 Me 2-S Η H 39,0 10,0 1500P
16 H 4 Et 2-0 4-CI H 34,0 14,7 1250P
17 H 5 H 2-0 4-CI H 57,0 9,5 750P
18 H 5 Me 2-0 3-CI H 40,3 3,4 >1500P
30 19 H 4 Me 2-0 4-CN H 49,5 17,1 >1500P
20 H 5 H 2-0 Η Η H 48,7 36,1 14,1 1000P
21 H 4 Me 2-0 4-NHCOOEt H 46,8 0 >1500P
22 H 5 Me 2-0 4-Br H 52,7 12,2 1500P
23 H 5 Me 3-0 Η H 66,0 36,4 750P
35 24 4-ME 5 Me 2-0 Η H 42,0 20,5 >1500P
25 6-Me 5 Me 2-0 Η H 53,4 20,8 1250P
26 H 5 Me 2-0 2-Me 3-Me '54,3 26 1250P
27 H 5 Me 2-0 2-CI H 39,2 27,2 >1500P
7 147019
28 Η 5 Me 2-0 2-Me Η 65,8 36,9 >1500P
29 Η 5 Me 2-0 3-Me Η 48,1 22,4 >1500Ρ 30 Η 5 Me 2-0 3-Me 4-Me41,8 34,6 8,0 >1500Ρ 31 Η 3 Me 4-0 Η Η 42,2 05 32* Η 5 Me 2-0 Η Η 34,2 39,4 26,2 >1500 33 Η 5 Me 2-0 3-MeO Η 36,7 30,9 1250
Note: a: den med eddikesyreresten substituerede stilling af ' pyridinringen 10 P.B.: phenylbutazon *: forbindelsen er N-oxid P: formodet LD^Q-værdi
Produkterne (I) er nyttige ved behandling af forskellige rheu-15 matiske lidelser, inflammationer, feber og smertefulde tilstande i ren form eller i kombination med en fast eller flydende farmaceutisk exci-pient. Praktiske eksempler på egnede farmaceutiske præparater af produkterne (I) er tabletter, kapsler, piller, granulater, pulvere eller suppositorier. I almindelighed er doseringen for disse produk-20 ter (I) mellem 1 og 1/10 af den praktiske dosering for phenylbutazon. Præparater indeholdende produkterne (I) kan doseres i enheder egnet til en enkelt daglig terapeutisk dosis i mindre enheder til flere doser eller i større enheder til opdeling i enkelte doser.
Fremgangsmåden ifølge opfindelsen belyses nærmere i de følgen-25 de eksempler.
Eksempel 1-4
Til 5% kaliumhydroxid/ethanol opløsning sættes det nedenfor angivne udgangsmateriale (V), og den resulterende blanding omrøres 30 ved stuetemperatur i 2 timer. Reaktionsblandingen inddampes under reduceret tryk til fjernelse af opløsningsmidlet. Remanensen opløses i en lille smule vand, gøres sur med saltsyre og de udfældede krystaller filtreres til opnåelse af det tilsvarende, angivne produkt. De side 2 angivne udgangsmaterialer og mellemprodukter er tilsvarende 35 betegnet (II), (III), (IV) og (V)
Ch2coz ch2cooh ^ 6-o_^ —> o~°-^' 147019 8
Eksempel II III IV V I
nr. Y smp. smp.(IR) Smp. Z Smp.(IR) smp. IR
1 H 248 69-70 87-88d Eto 58-59 93-94d 1730 2 4-CI 236-7 46-47 129-130d Eto 50-51 152-153d 1730 Nu 05 3 3-CI 235 1773 64-65d Bzo 1745 CCI 123-124d 1720 Chl 4 2-Ci 232-4 1770 CCI 84-85d Bzo 1745 CCI 133-134d 1720 Chl
Fodnote: Betegnelserne har følgende betydning: smp., (°C); IR infrarødt absorptionsspektrum (cm ); Eto. ethoxygruppe; 10 Bzo, benzyloxygruppe; Nu, Nujol; CCI, carbontetrachlorid;
Chl, chloroform; d, dekomponeringspunkt (hver tegn har i det følgende samme betydning som ovenfor).
På analog måde opnås følgende forbindelser: 15 2-(2-p-chIorphenoxy-5-pyridyl)eddikesyre, smp. 116-117°C; 2-(2-phenoxy-5-pyridyl)eddikesyre, smp. 83,5-85°C, og 2-[2-(2,3-xylyioxy)-5-pyridyl]eddikesyre, smp. 120-121°C.
Eksempel 5-21 20 Det nedenfor angivne materiale opløses i en blanding af 30% vandig kaliumhydroxid (18 ml) og methanol (18 ml) og opløsningen henstår ved stuetemperatur i 1 time. Reaktionsblandingen inddampes til fjernelse af methanol. Remanensen opløses i en lille smule vand.
Det vandige lag indstilles på pH 3 med saltsyre og rystes med ether.
25 Etherlaget afdampes til fjernelse af opløsningsmidlet og til dannelse af det tilsvarende, angivne produkt. De side 2 angivne udgangsmaterialer og mellemprodukter er tilsvarende betegnet (11), (III) og (IV).
30 ch„ CH3
^CHC00CH2_^~^ _ "^CHCOOH
i-^Y > 35 9 147019
Eks. il til IV I
nr. Stilling A Y smp. smp. smp. smp. IR
af COOH eller IR eller IR
05 5 4 2-0 4-CI 236-237 46-47 117-8d 1l9-120d 1720 CHI
6 4 2-0 3-CI 233-235 1773 CCI 2070, 84-85d 1735 Nu
1633 CCI
7 4 2-0 2-CI 232-234 90-91 78 107,5 1720Chl -75,5d -108,5d 10 8 4 2-0 H 248 69-70 47-49d 98-99d 1720 Chl 9 3 2-0 H 181-182 89-91 104d 94-95 1715 -1720 Nu 10 3 2-0 4-CI 157-158 63-65 2060 110-111 1720 Nu
1615 CCI
15 11 3 6-0 H 166-167 1777 CCI 2070 CCI 92-93 1698 Nu 12 3 6-0 4-CI 170-171 1781 CCI 75-76d 114-115 1715 Nu 13 2 6-0 H 103-104 1770 CCI 80-80,5d 135-136 1590 Nu
Ca 14 2 6-0 4-CI 117-118 67-70 65-66d 80-81d 1765 20 1720 Nu 15 4 2-0 4-Met 235-236 1775 CCI 103-103,5d 129-130d 1715 Nu 16 4 2-0 4-Me 256-257 60-62 105,5 101-102d 1725 Nu -106,5d 17 4 2-S H 255 1775 CCI 2070 140-141 1570 Nu 25 1630 CCI Ca 18 4 2-S 4-CI 254-255 1770 CCI 80-81d 64-65 Al 1590 Nu 19 3 6-0 4-Met 174-175 1778 CCI 2060 155 Ca 1585 N.u
1630 1615 CCI
30 20 3 6-0 4-Me 158-160 1178 CCI 2060 98-99 1700 Nu
1630 1615 CCI
21 3 6-S H 162-163 76-77 2060 114,5- 1697 Nu 1625 1610 115,5
35 CCI
Fodnote: d, dekomponeringspunkt (°C); Al, aluminiumsalt; Ca, calciumsalt; Met, methoxygruppe; Me, methylgruppe.
10 1-47019
Eksempel 22-46
Omsætningerne udføres som i eksempel 5-21, hvorved der fås følgende produkter: 05 CH3 ? 10
Eks. Produkt nr. Stilling af X A Y Y' smp. (°C)
CHgCHCOOH
15 22 3 H 6-0 3-CI H 106-7 23 4 H 2-0 4-CN H 105-6d 24 3 H 6-S 4-CI H 150 Ca 25 4 H 2-0 4-NH- H 136-7d cooc2h5 20 26 3 H 6-0 4-Br H 119-120 27 3 H 6-0 4-CN H 120-1 28 3 H 5-0 Η H 135-135,5 29 3 4-Me 6-0 Η H 135-6 30 3 2-Me 6-0 Η H 92-3 25 31 3 H S-0 2-Me 3-Me 116-7 32 3 H 6-0 2-CI H 96-7 33 3 H 6-0 2-Me H 65-7 34 3 H 6-0 3-Me H 81-2 35 3 H 6-0 3-Me 5-Me 120-1
30 36 3 H 6-0 3-Me 4-Me 90-I
37 3 H 4-0 Η H 145-6 38 3 H 6-0 4-i-Bu H 77-8 39 4 H 2-0 2-Me 3-Me 86-7d 40 3 5-Me 6-0 Η H 107-8 35 41 3 H 6-0 2-Me 5-Me 195 def.
42 3 H 6-0 2-Me 4-Me 189 def. Ca 43 3 H 6-0 2-Me 6-Me 202 def. Ca U7.019 11 44 4 Η 2-0 3-Me 4-Me 123-4d 45 4 H 2-0 3-Me 5-Me 103-4d 46 3 H 6-0 3-Met H 69,5-70,5 05 Fodnote: def. betyder "deformation".
Eksempel 47-48 På samme måde som i eksempel 5-21 fås følgende produkter: 10 2-(2-p-chlorphenoxy-4-pyridyl)-n-smørsyre, smp. 92-93°C; 2-(2-p-chlorphenoxy-5-pyridyl)-n-smørsyre, aluminiumkompleks, smp. 236°C.
Eksempel 49 15 Ved behandling af ethyl 2-(2-phenoxy-4-pyridyl)propionat-N- oxid med en blanding af 20% vandig kaliumhydroxid og 95% ethanol ved stuetemperatur i 2 timer fås 2-(2-phenoxy-4-pyridyl)propion-syre-N-oxid, smp. 100-101°C (dekomponering).
e
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DK154074C (da) * 1974-10-17 1989-02-27 Ishihara Sangyo Kaisha Alfa-(4-(5 eller 3,5 substitueret pyridyl-2-oxy)-phenoxy)-alkan-carboxylsyrer eller derivater deraf til anvendelse som herbicider, herbicidt middel samt fremgangsmaader til bekaempelse af ukrudt
US4083714A (en) * 1974-10-17 1978-04-11 Ishihara Sangyo Kaisha, Ltd. Alkoxyalkyl esters of substituted pyridyloxyphenoxy-2-propanoic acids, herbicidal composition containing the same and method of use thereof
US4133675A (en) * 1976-07-23 1979-01-09 Ciba-Geigy Corporation Pyridyloxy-phenoxy-alkanecarboxylic acid derivatives which are effective as herbicides and as agents regulating plant growth
GB9005965D0 (en) * 1990-03-16 1990-05-09 Shell Int Research Herbicidal carboxamide derivatives
WO1998029391A1 (en) * 1996-12-26 1998-07-09 Kureha Kagaku Kogyo Kabushiki Kaisha 6-(nonsubstituted or substituted) phenoxypicolinic acids, process of preparing the same, and agricultural/horticultural germicides containing the same
US11591289B2 (en) 2017-02-24 2023-02-28 Xeniopro GmbH Aromatic compounds
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