Utarbeidelse av N-(2-alkoxyvinyl) sulfonamides N- tosyl-1,2,3-triazoles og påfølgende konvertering til erstattet Phthalans og fenetylaminer
Summary
Representant eksperimentelle prosedyrer for syntese av N-(2-alkoxyvinyl) sulfonamides og påfølgende konvertering til phthalan og phenethylamine derivater er presentert i detalj.
Abstract
Nedbryting av N– tosyl-1,2,3-triazoles med rhodium(II) acetate dimer i nærvær av alkoholer danner syntetisk allsidig N-(2-alkoxyvinyl) sulfonamides, som reagerer under en rekke forhold råd til nyttig N– og Oinneholder forbindelser. Acid-katalysert tillegg av alkoholer eller thiols til N-(2-alkoxyvinyl) sulfonamide inneholder phthalans gir tilgang til ketals og thioketals, henholdsvis. Selektiv reduksjon av vinylgruppe i N-(2-alkoxyvinyl) sulfonamide inneholder phthalans via hydrogenering gir den tilsvarende phthalan i god avkastning, mens reduksjon med natrium bis (2-methoxyethoxy) aluminumhydride genererer en Ring åpnet phenethylamine analog. Fordi N-(2-alkoxyvinyl) sulfonamide funksjonsgruppe er syntetisk allsidig, men ofte hydrolytically ustabil, denne protokollen understreker sentrale teknikker i forbereder, håndtere og reagere disse sentrale virkemidler underlag i flere nyttig transformasjoner.
Introduction
Rhodium (II)-azavinyl carbenoids har nylig dukket opp som en svært allsidig reaktive mellomliggende vei til mange verdifulle produkter. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 særlig mange romanen bruk av disse mellomprodukter for produksjon av heterocycles10 har gitt kjemikere med ny og effektiv syntetisk strategier. Mot dette formål, vår gruppe startet utviklingen av en ny protokoll for syntese av phthalans11 som vil utnytte siste fremskritt i den inter- og intramolekylære tillegg av oksygen-baserte nucleophiles til Rh (II)-azavinyl carbenoids avledet fra N-sulfonyl-1,2,3-triazoles. 12 , 13 , 14 , 15 , 16 , 17 vår tilnærming har en enkel to-trinns protokoll for å konvertere terminal alkynes som 1 til N-sulfonyl-1,2,3-triazoles 2 bærer en hengende alkohol (figur 1). Deretter en Rh II-katalysert denitrogenation / 1,3-OH innsetting kaskade 2 inneholder phthalans 3 har en reaktiv N-(2-alkoxyvinyl) sulfonamide funksjonsgruppe.
Siden N-(2-alkoxyvinyl) sulfonamide moiety er en potensielt allsidig, men relativt underexplored N– og O-som inneholder synthon,16,17,18, 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 vi ble interessert i å studere reaktivitet av smeltet enol-Eter/ene-sulfonamide systemet under en rekke forhold (figur 2). Etter screening ulike redusere protokoller, to metoder ble identifisert som førte til stabile phthalan og/eller phenethylamine inneholder produkter (figur 2, 3 → 4/5). Først, det ble oppdaget at en standard hydrogenering n-(2-alkoxyvinyl) sulfonamide 3a med katalytisk palladium på karbon (Pd/C) selektivt reduserer C = C bånd å gi phthalan 4. Alternativt gir behandling av 3a med natrium bis (2-methoxyethoxy) aluminium hydrid i diethyl Eter/toluen unikt substituerte phenethylamine avledede 5. Vi tror at begge disse transformasjoner er verdifull, som de føre til klasser med potensielle biologiske aktivitet inkludert neuroactive egenskaper som oppstår fra innebygde phenethylamine og ved 4, metall-chelation via den cis– orientert N– og O-atomer.
Mens han etterforsker syre forfremmet tillegg utnytte rikt C = C bånd 3a, det ble funnet at behandlingen av denne sammensatte med katalytiske trimethylsilyl chloride i nærvær av alkoholer eller en thiol gitt ketals 6a-c og thioketal 6e, henholdsvis, mens beholder bisyklisk phthalan rammen. Alternativt, røring 3a i en 1:1 eddiksyre/vann løsning gir stabil hemiketal 6 d.
Protocol
Representative Results
Discussion
Triazoles 2a-b rent kan fås via en Cu (I)-katalysert azide-alkyne [3 + 2] cycloaddition (CuAAC) bruker CuTC som katalysator. Spesielt genereres triazole 2a mest effektivt ved høy temperatur via en standard reflux i kloroform 3t eller oppvarming 100 ° c i 15 min i en mikrobølgeovn reaktor (Merk at kan variere avhengig av mikrobølgeovn effektivitet); triazole 2b forberedes imidlertid mest effektivt via en CuAAC ved romtemperatur. Derfor må innsats tas å identifisere…
Disclosures
The authors have nothing to disclose.
Acknowledgements
Dette arbeidet ble finansiert av Hamilton College og Edward og Virginia Taylor Fund for Student/avdeling forskning i kjemi.
Materials
| 2-Ethynylbenzyl alcohol, 95% | Sigma Aldrich | 520039 | |
| Copper (I) thiophene-2-carboxylate | Sigma Aldrich | 682500 | |
| Chloroform, ≥99% | Sigma Aldrich | 372978 | |
| Toluenesulfonylazide, 99.24% | Chem-Impex International | 26107 | Potentially explosive |
| Dichloromethane, ≥99.5% | Sigma Aldrich | 320269 | |
| Rhodium (II) acetate dimer, 99% | Strem Chemicals | 45-1730 | |
| Silica Gel, 32-63, 60A | MP Biomedicals Inc. | 2826 | For silica gel plugs |
| Hexanes | Sigma Aldrich | 178918 | |
| Ethyl acetate | Sigma Aldrich | 439169 | |
| Chlorofom-D | Sigma Aldrich | 151823 | |
| Ethylene glycol | Sigma Aldrich | 293237 | |
| Chlorotrimethylsilane, 98% | Acros | 11012 | |
| Sodium bicarbonate | Sigma Aldrich | S6014 | Dissolved in deionized water to prepare a saturated aqueous solution |
| Sodium sulfate | Fisher Scientific | S429 | |
| Ethyl alcohol, absolute – 200 proof | Aaper Alcohol and Chemical Co. | 82304 | |
| 10 wt% Palladium on carbon | Sigma Aldrich | 520888 | Can ignite in the presence of air, hydrogen gas, and/or a flammable solvent |
| Hydrogen gas | Praxair | UN1049 | |
| Diethyl ether | Sigma Aldrich | 309966 | |
| 60 wt% sodium bis(2-methoxyethoxy)aluminum hydride solution in toluene | Sigma Aldrich | 196193 | Reacts violently with water |
| Methanol | Sigma Aldrich | 34966 | |
| Ammonium chloride | Fisher Scientific | A661 | Dissolved in deionized water to prepare a saturated aqueous solution |
| Hydrochloric acid, 37% | Sigma Aldrich | 258148 | Dissolved in deionized water to prepare a 1M solution |
| Sodium Chloride | Sigma Aldrich | S25541 | Dissolved in deionized water to prepare a saturated aqueous solution |
| 2-5 mL Microwave vials | Biotage | 355630 | |
| Microwave vial caps | Biotage | 352298 | |
| RediSep Rf Gold Normal Phase, Silica Columns, 20 – 40 micron | Teledyne Isco | 69-2203-345 | For column chromatography |
| Balloons | CTI Industries Corp. | 912100 | For hydrogenation |
| Biotage Initiator+ Microwave Reactor | Biotage | 356007 |
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