Sodiumandbariumcation-templated - PDF document

Sodiumandbariumcation-templated synthesisandcation-inducedmolecular pirouettingofapyridine N -oxidecontaining [2]rotaxane SupplementaryInformation LauraM.HancockandPaulD.Beer* InorganicChemistryLaboratory,DepartmentofChemistry UniversityofOxford SouthParksRoad,Oxford,OX13QR(UK) Fax:(+44)01865-272690 E-mail: paul.beer@chem.ox.ac.uk S1 PARTI:SYNTHESISANDCHARACTERISATIONS1 ExperimentalDetailsS1 1 Hand 13 CSpectraofcompound2and4S5 Compound2 S5 Compound4 S6 PARTII:SULFATEABSTRACTIONOFBARIUMCATIONS S7 PARTIII:REFERENCES S7 PARTI:SYNTHESISANDCHARACTERISATION GeneralConsiderations .Commerciallyavailablesolventsandchemicalswereusedwithoutfurther purificationunlessstated.Wheredrysolventswereused,theyweredegassedwithnitrogen,driedby passingthroughanMBraunMPSP-800columnandthenusedimmediately.Waterwasdeionizedand microfilteredusingaMilli-QMilliporemachine. 1 Hand 13 CspectrawererecordedonaVarianMercury-VX300spectrometerandAVII500(for 13 Ccryoprobe).MassspectrometrywascarriedoutonaBrukermicrOTOFspectrometer. Thesynthesisofmacrocycle 1, 1 stopper 3, 1 S1( 5-(methoxycarbonyl)nicotinicacid), 2 andstopper S2 3 are reportedelsewhere.Compound S5 andpyridine N -oxideprecursorwerepreparedaccordingtoSchemes S1andS2respectively. ExperimentalDetails SchemeS1. SynthesisofCompound S5. S2 N O OMe OH O N O OMe HN O N O OH HN O NH O N O HN 40% (i)Oxalylchloride, cat.DMF,CH 2 Cl 2 (ii) S5 ,Et 3 N,CH 2 Cl 2 2KHSO 5 ·KHSO 4 ·K 2 SO 4 sat.NaHCO 3(aq) 1:12-butanone/H 2 O 97% (i)Oxalylchloride, cat.DMF,CH 2 Cl 2 (ii) S2 ,Et 3 N,CH 2 Cl 2 KOH 1:1THF/H 2 O N 3 NH O N O HN N 3 O 89%100% S1S3 S4 S6 2 H 2 N S2 SchemeS2. Synthesisofpyridine N -oxideprecursor 2. S3: 5-(methoxycarbonyl)nicotinicacid( S1) (0.2g,1.11mmol)wassuspendedindryCH 2 Cl 2 (30mL),oxalyl chloride(0.19mL,2.22mmol)andDMF(cat.)wereadded,andthemixturestirredunderN 2(g) for1h untilhomogenous.Thesolventwasremoved invacuo ,theresiduedissolvedindryCH 2 Cl 2 (20mL)and addeddropwiselytoasolutionof S2 (0.52g,1.16mmol),Et 3 N(0.28mL,2.0mmol)andDMAP(cat.)in dryCH 2 Cl 2 (30mL).Theresultingsolutionwasstirredfor1h,washedwith10%HCl (aq) (2×50mL)and H 2 O(2×50mL),driedoveranhydrousMgSO 4 andthesolventremoved invacuo .Theresultingbrown oilwaspurifiedbycolumnchromatography(silica;95:5CH 2 Cl 2 :MeOH)toyieldanoilycreamcoloured solid(0.60g,89%). 1 HNMR (300MHz,CDCl 3 H 2 & H 6 ),8.78(1H,t, 4 J =2.1Hz,pyridine H 4 ),8.05(1H,brs,ArN H ),7.55(2H,d, 3 J =8.9Hz,Ar H NH),7.11–7.28(17H,m,Ar H ),4.02(3H,s, C H 3 ),1.31(18H,s, t Bu); 13 CNMR (300MHz,CDCl 3 143.5,135.9,134.9,131.9,131.1,130.6,127.3,125.8,124.3,119.3,63.8,34.3,33.3; HRMS(ESI): m/z calc.forC 41 H 42 N 2 O 3 [M+Na] + :633.3088;found633.3091. S3 S4: S3 (1.81g,2.96mmol)wasdissolvedin1:1THF/H 2 O(50mL),KOH(0.196g,3.5mmol)wasadded, andthesolutionstirredfor16h.10%citricacid (aq) wasaddeduntilthesolutionwaspH=7,andthe aqueousmixtureextractedwithCH 2 Cl 2 (3x50mL).Thecombinedorganiclayersweredriedover anhydrousMgSO 4 ,andthesolventremoved invacuo .Theresultingstickybrownsolidwasrecrystallized fromCHCl 3 togiveanoff-whitesolid(1.77g,100%). 1 HNMR (300MHz, d 6 H ),10.63(1H,s,ArN H ),9.27(1H,d, 4 J =2.0Hz, pyridine H 2 ),9.21(1H,d, 4 J =2Hz,pyridine H 6 ),8.74(1H,t, 4 J =2Hz,pyridine H 4 ),7.68(2H,d, 3 J = 8.8Hz,Ar H NH),7.10–7.34(17H,m,Ar H ),1.26(18H,s, t Bu); 13 CNMR (300MHz, d 6 165.8,163.1,152.3,147.9,146.9,143.6,142.5,136.4,136.0,130.7,130.4,130.1,127.7,126.4,125.8, 124.5,119.6,34.9,31.1; HRMS(ESI): m/z calc.forC 40 H 40 N 2 O 3 + :596.2966;found:595.2980. S5: 4,4'-bis(azidomethyl)biphenyl( S5 ) (300mg,1.14mmol)wasdissolvedin1:1Et 2 O/EtOAc(10mL),5% HCl (aq) (20mL)wasaddedandthebiphasicmixturecooledto0ºC.AsolutionofPh 3 P(295mg, 1.13mmol)in1:1Et 2 O/EtOAc(10mL)wasaddeddropwiseover30min,andthesolutionstirredfor18 hatRT.Theprecipitatewascollectedbyvacuumfiltrationandwashedwith1:1Et 2 O/EtOAc(2×50 mL).TheresultingsolidwassuspendedinCH 2 Cl 2 ,10%NaOH (aq) addedandthebiphasicmixturestirred for30minuntilallsolidhaddissolved.Theorganiclayerwasseparated,washedwithH 2 O(2×50mL), driedoverMgSO 4 ,andthesolventremoved invacuo togiveawhitewaxysolid(100mg,37%). 1 HNMR (300MHz,CD 3 H ),7.42(4H,d, 3 J =8.2Hz,Ar H ),4.40(2H,s, C H 2 N 3 ),3.83(2H,s,C H 2 NH 2 ); 13 CNMR (75.5MHz,CD 3 128.9,128.1,128.0,55.1,46.2. HRMS(ProbeFI) calculatedforC 14 H 14 N 4 [M] ·+ :238.1218;found 238.1212. S6: S4 (192mg,1.06mmol)wassuspendedindryCH 2 Cl 2 (20mL),thenoxalylchloride(0.190mL,2.12 mmol)andDMF(cat.)wereadded.Themixturewasstirredfor1huntilallsolidhaddissolved.The solventwasremoved invacuo ,thenredissolvedindryCH 2 Cl 2 (15mL)andaddeddropwisetoasolution ofcompound S5 (253mg,1.06mmol)andEt 3 N(0.42mL,3mmol)inCH 2 Cl 2 (20mL).Theresulting solutionwasstirredfor1h,washedwith10%HCl (aq) (2x50mL)andH 2 O(2x50mL),driedover anhydrousMgSO 4 ,andthesolventremoved invacuo .Theresultingbrownoilwaspurifiedbycolumn chromatography(silica;95:5CH 2 Cl 2 /MeOH)givinganoilyorangesolid(306mg,72%). 1 HNMR (300MHz,CDCl 3 H 2 ),9.26(1H,s,pyridine H 6 ),8.69(1H,s,pyridine H 4 ),7.61(4H,d, 3 J =8.2Hz,Ar H ),7.47(2H,d, 3 J =8.2Hz,Ar H ),7.41(2H,d, 3 J =8.2Hz,Ar H ),6.61 (1H,brs,N H ),4.72(2H,d, 3 J =5.9Hz,NHC H 2 ),4.40(2H,s,C H 2 N 3 ),3.99(3H,s,OC H 3 ); 13 CNMR S4 (75.5MHz,CDCl 3 127.6,127.5,125.9,54.5,52.7,44.0; HRMS(ESI) m/z calc.forC 54 H 52 N 6 O 2 [M+Na] + :839.4044;found: 839.4038. Pyridine N- oxideaxleprecursor(2): Compound S5 (0.198g,0.24mmol)andNaHCO 3 (1.03g,7.26mmol)weredissolvedin1:12- butanone/H 2 O(50mL)andasaturatedsolutionofOxone ® (0.446g,0.726mmol)inH 2 O(3mL)was addeddropwisely.Thesolutionwasstirredvigorouslyfor2hbeforeadditionofNaCl(1.70g,29.0 mmol)andextractionwithCHCl 3 (3×50mL).TheorganiclayerwasdriedoveranhydrousMgSO 4 and thesolventremoved invacuo togiveawhitesolid(0.196g,97%). 1 HNMR (300MHz,CDCl 3 H ),8.88(1H,s,pyridineH 6 ),8.84(1H,s, pyridineH 2 ),8.38(2H,brs,CH 2 N H &pyridine H 4 ),7.63(2H,d, 3 J =8.8Hz,Ar H NH),7.55(2H,d, 3 J = 8.2Hz,biphenylArH),7.49(2H,d, 3 J =8.2Hz,biphenylArH),7.15–7.35(19H,m,stopperAr H ),4.53 (2H,d, 3 J =4.7Hz,C H 2 NH),4.35(2H,s,C H 2 N 3 ),1.36(18H,s, t Bu H ) 13 CNMR (75.5MHz,CDCl 3 ) 130.6,128.6,128.3,127.4,127.3,127.2,125.8,124.3,119.5,63.8,54.4,44.0,34.3,31.3. HRMS(ESI): m/z calc.forC 54 H 52 N 6 O 3 [M+Na] + :855.3993;found:855.3994. Calixdiquinone N- oxiderotaxane(4): Generalprocedure:calixdiquinonemacrocycle 1 (30mg,0.0285mmol),compound 2 (24mg,0.0285 mmol),andstopper 3 (14mg,0.0285mmol)weredissolvedindegassedCH 2 Cl 2 (20mL),(asolutionof M(ClO 4 ) x (0.0285mmol)in)CH 3 CN(0.25mL)wasaddedandthesolutionstirredfor15min.DIPEA(5 3 CN) 4 PF 6 (2mg,0.0054mmol)wereaddedandthesolutionstirredunder N 2 for16h.Thesolventwasremoved invacuo andthecrudematerialpurifiedbypreparativeTLC (silica;1:1acetone/hexane&CH 3 3 CN/MeOH)toobtainayellowsolid. Withoutcation:NeatCH 3 CNaddedi.e.noM(ClO 4 ) x ,givingayieldof10%(7mg). WithBarium:M=Bax=2,givingayieldof28%(18mg).N.B.Ba(ClO 4 ) 2 mostlysuspended throughoutreaction WithSodium:M=Na,x=1,givingayieldof50%(34mg). 1 HNMR (300MHz,CDCl 3 H ),8.68(2H,s,pyridine H 6 & isophthalamide H 2 ),8.54(1H,s,pyridine H 2 ),8.52(1H,t, 3 J =5.6Hz,axleCH 2 N H ),8.39(2H,brs, macrocycleNH),8.23(2H,dd, 3 J =7.9Hz, 4 J =1.9Hz,isophthalamide H 4 & H 6 ),8.03(1H,s,pyridine H 4 ),7.92(2H,d, 3 J =8.8Hz,Ar H NH),7.64(1H,s,triazole,C H ),7.59(2H,d, 3 J =7.5Hz,biphenyl Ar H ),7.50(2H,d, 3 J =8.2Hz,biphenylAr H ),7.37–7.41(4H,m,biphenylAr H ),7.06–7.29(31H,m, isophthalamide H 5 &stopperAr H ),6.85(2H,d, 3 J =8.8Hz,Ar H OCH 2 ),6.55–6.56(4H,m,calixAr H ), 6.50(4H,d, 3 J =9.1Hz,hydroquinoneAr H ),6.32–6.37(8H,m,calix&hydroquinoneAr H ),5.60(2H, S5 s,axleOC H 2 ),5.17(2H,s,C H 2 N),4.59(2H,d, 3 J =5.6Hz,axleC H 2 NH),4.29(2H,d, 2 J =12.9Hz, calixC H 2 ),4.21(2H,t, 3 J =8.7Hz,macrcocycleC H 2 ),4.09(2H,d, 2 J =12.9Hz,calixC H 2 )3.96–3.99 (2H,m,macrocycleC H 2 ),3.89–3.94(6H,m,macrocycleC H 2 ),3.82–3.85(2H,m,macrocycleC H 2 ), 3.71–3.77(4H,m,macrocycleC H 2 ),2.92(2H, 2 J =12.9Hz,calixC H 2 ),2.73(2H, 2 J =12.9Hz,calix C H 2 ),1.32(18H,s,axle t Bu),1.29(18H,s,axle t Bu),0.95(18H,s,calix t Bu); 13 CNMR (125MHz, CDCl 3 148.7,148.2,148.0,147.5,147.3,147.0,145.0,144.4,144.1,143.5,141.3,140.9,140.3,140.2,139.7, 137.9,136.2,134.1,134.0,132.5,132.2,132.1,131.8,131.4,131.2,130.9,130.8,129.5,129.4,129.2, 129.0,128.0,127.7,127.7,127.5,127.0,126.3,125.9,125.4,125.3,124.9,124.7,124.5,124.4,122.9, 118.7,115.4,114.2,113.5,74.4,67.7,67.0,634.0,63.7,62.3,54.2,53.7,43.4,41.0,34.6,34.5,34.2, 31.6,31.6,31.4. HRMS(ESI): m/z calc.forC 154 H 154 N 8 O 16 [M+Na] + :2395.1414;found2395.1450 1 Hand 13 CspectraofCompounds2and4 Compound2 FigureS1. 1 HNMRspectrumof 2 (CDCl 3 , 300MHz,293K) S6 FigureS2. 13 CNMRspectrumof 2 (CDCl 3 , 75.5MHz,293K) Compound4 FigureS3. 1 HNMRspectrumof 4 (CDCl 3 , 300MHz,293K) S7 FigureS4. 13 CNMRspectrumof 4 (CDCl 3 , 125MHz,293K) PARTII:SULFATEABSTRACTIONOFBARIUMCATION FigureS5. Partial 1 HNMRspectrain5:1CDCl 3 /CD 3 CNof(a)rotaxane 4 ,(b)rotaxane 4 +1eq.Ba(ClO 4 ) 2 and(c)rotaxane 4 +1eq.Ba(ClO 4 ) 2 +1eq.(TBA) 2 SO 4 . PARTIII:REFERENCES 1.A.V.Leontiev,C.A.JemmettandP.D.Beer, Chem.Eur.J. ,2011, 17 ,816-825. 2.K.M.BroadusandS.R.Kass, J.Am.Chem.Soc. ,2000, 122 ,9014-9018. 3.H.W.Gibson,S.-H.Lee,P.T.Engen,P.Lecavalier,J.Sze,Y.X.ShenandM.Bheda, J.Org. Chem. ,1993, 58 ,3748-3756. S1PARTI:SYNTHESISANDCHARACTERISATIONS1 ExperimentalDetailsS1 1 Hand 13 CSpectraofcompound2and4S5 Compound2S5 Compound4S6 PARTII:SULFATEABSTRACTIONOFBARIUMCATIONSS7 PARTIII:REFERENCESS7 PARTI:SYNTHESISANDCHARACTERISATIONGeneralConsiderations.Commerciallyavailablesolventsandchemicalswereusedwithoutfurtherpurificationunlessstated.Wheredrysolventswereused,theyweredegassedwithnitrogen,driedbypassingthroughanMBraunMPSP-800columnandthenusedimmediately.WaterwasdeionizedandmicrofilteredusingaMilli-QMilliporemachine.Hand13CspectrawererecordedonaVarianMercury-VX300spectrometerandAVII500(for13Ccryoprobe).MassspectrometrywascarriedoutonaBrukermicrOTOFspectrometer.ThesynthesisofmacrocyclestopperS1(5-(methoxycarbonyl)nicotinicacid),andstopperS2arereportedelsewhere.CompoundS5andpyridine-oxideprecursorwerepreparedaccordingtoSchemesS1andS2respectively.ExperimentalDetails SchemeS1.SynthesisofCompoundS5. S3S4:S3(1.81g,2.96mmol)wasdissolvedin1:1THF/HO(50mL),KOH(0.196g,3.5mmol)wasadded,andthesolutionstirredfor16h.10%citricacid(aq)wasaddeduntilthesolutionwaspH=7,andtheaqueousmixtureextractedwithCHCl(3x50mL).ThecombinedorganiclayersweredriedoveranhydrousMgSO,andthesolventremovedinvacuo.TheresultingstickybrownsolidwasrecrystallizedfromCHCltogiveanoff-whitesolid(1.77g,100%).HNMR(300MHz,),10.63(1H,s,ArN),9.27(1H,d,=2.0Hz,pyridine),9.21(1H,d,=2Hz,pyridine),8.74(1H,t,=2Hz,pyridine),7.68(2H,d,8.8Hz,ArNH),7.10–7.34(17H,m,Ar),1.26(18H,s,Bu);13CNMR(300MHz,165.8,163.1,152.3,147.9,146.9,143.6,142.5,136.4,136.0,130.7,130.4,130.1,127.7,126.4,125.8,124.5,119.6,34.9,31.1;HRMS(ESI):m/zcalc.forC4040:596.2966;found:595.2980.S5:4,4'-bis(azidomethyl)biphenyl(S5(300mg,1.14mmol)wasdissolvedin1:1EtO/EtOAc(10mL),5%HCl(aq)(20mL)wasaddedandthebiphasicmixturecooledto0ºC.AsolutionofPhP(295mg,1.13mmol)in1:1EtO/EtOAc(10mL)wasaddeddropwiseover30min,andthesolutionstirredfor18hatRT.Theprecipitatewascollectedbyvacuumfiltrationandwashedwith1:1EtO/EtOAc(2×50mL).TheresultingsolidwassuspendedinCHCl,10%NaOH(aq)addedandthebiphasicmixturestirredfor30minuntilallsolidhaddissolved.Theorganiclayerwasseparated,washedwithHO(2×50mL),driedoverMgSO,andthesolventremovedinvacuotogiveawhitewaxysolid(100mg,37%).HNMR(300MHz,CD),7.42(4H,d,=8.2Hz,Ar),4.40(2H,s,),3.83(2H,s,CNH);13CNMR(75.5MHz,CD128.9,128.1,128.0,55.1,46.2.HRMS(ProbeFI)calculatedforC1414[M]·+:238.1218;foundS6:S4(192mg,1.06mmol)wassuspendedindryCHCl(20mL),thenoxalylchloride(0.190mL,2.12mmol)andDMF(cat.)wereadded.Themixturewasstirredfor1huntilallsolidhaddissolved.Thesolventwasremovedinvacuo,thenredissolvedindryCHCl(15mL)andaddeddropwisetoasolutionofcompoundS5(253mg,1.06mmol)andEtN(0.42mL,3mmol)inCHCl(20mL).Theresultingsolutionwasstirredfor1h,washedwith10%HCl(aq)(2x50mL)andHO(2x50mL),driedoveranhydrousMgSO,andthesolventremovedinvacuo.Theresultingbrownoilwaspurifiedbycolumnchromatography(silica;95:5CHCl/MeOH)givinganoilyorangesolid(306mg,72%).HNMR(300MHz,CDCl),9.26(1H,s,pyridine),8.69(1H,s,pyridine),7.61(4H,d,=8.2Hz,Ar),7.47(2H,d,=8.2Hz,Ar),7.41(2H,d,=8.2Hz,Ar),6.61(1H,brs,N),4.72(2H,d,=5.9Hz,NHC),4.40(2H,s,C),3.99(3H,s,OC);13CNMR S5s,axleOC),5.17(2H,s,CN),4.59(2H,d,=5.6Hz,axleCNH),4.29(2H,d,=12.9Hz,calixC),4.21(2H,t,=8.7Hz,macrcocycleC),4.09(2H,d,=12.9Hz,calixC)3.96–3.99(2H,m,macrocycleC),3.89–3.94(6H,m,macrocycleC),3.82–3.85(2H,m,macrocycleC),3.71–3.77(4H,m,macrocycleC),2.92(2H,=12.9Hz,calixC),2.73(2H,=12.9Hz,calix),1.32(18H,s,axleBu),1.29(18H,s,axleBu),0.95(18H,s,calixBu);13CNMR(125MHz,CDCl148.7,148.2,148.0,147.5,147.3,147.0,145.0,144.4,144.1,143.5,141.3,140.9,140.3,140.2,139.7,137.9,136.2,134.1,134.0,132.5,132.2,132.1,131.8,131.4,131.2,130.9,130.8,129.5,129.4,129.2,129.0,128.0,127.7,127.7,127.5,127.0,126.3,125.9,125.4,125.3,124.9,124.7,124.5,124.4,122.9,118.7,115.4,114.2,113.5,74.4,67.7,67.0,634.0,63.7,62.3,54.2,53.7,43.4,41.0,34.6,34.5,34.2,31.6,31.6,31.4.HRMS(ESI):m/zcalc.forC15415416[M+Na]:2395.1414;found2395.1450Hand13CspectraofCompounds2and4Compound2 FigureS1.HNMRspectrumof(CDCl300MHz,293K) S7 FigureS4.CNMRspectrumof(CDCl125MHz,293K)PARTII:SULFATEABSTRACTIONOFBARIUMCATION FigureS5.PartialHNMRspectrain5:1CDCl/CDCNof(a)rotaxane,(b)rotaxane+1eq.Ba(ClOand(c)rotaxane+1eq.Ba(ClO+1eq.(TBA)SOPARTIII:REFERENCES1.A.V.Leontiev,C.A.JemmettandP.D.Beer,Chem.Eur.J.,2011,,816-825.2.K.M.BroadusandS.R.Kass,J.Am.Chem.Soc.,2000,,9014-9018.3.H.W.Gibson,S.-H.Lee,P.T.Engen,P.Lecavalier,J.Sze,Y.X.ShenandM.Bheda,J.Org.Chem.,1993,,3748-3756.