NMRChemicalShiftsofCommonLaboratorySolventsasTraceImpurities
HugoE.Gottlieb,*VadimKotlyar,and
AbrahamNudelman*
DepartmentofChemistry,Bar-IlanUniversity,
Ramat-Gan52900,Israel
ReceivedJune27,1997
InthecourseoftheroutineuseofNMRasanaidfororganicchemistry,aday-to-dayproblemistheidentifica-tionofsignalsderivingfromcommoncontaminants(water,solvents,stabilizers,oils)inless-than-analyti-cally-puresamples.Thisdatamaybeavailableintheliterature,butthetimeinvolvedinsearchingforitmaybeconsiderable.Anotherissueistheconcentrationdependenceofchemicalshifts(especially1H);resultsobtainedtwoorthreedecadesagousuallyrefertomuchmoreconcentratedsamples,andrunatlowermagneticfields,thantoday’spractice.
Wethereforedecidedtocollect1Hand13Cchemicalshiftsofwhatare,inourexperience,themostpopularv6“extrapeaks”inavarietyofcommonlyusedNMR711solvents,inthehopethatthiswillbeofassistanceto79othepracticingchemist.
j/1201ExperimentalSection
.01: iNMRspectraweretakeninaBrukerDPX-300instrumentod(300.1and75.5MHzfor1Hand13C,respectively).Unless | 7otherwiseindicated,allwererunatroomtemperature(24(1991°C).Fortheexperimentsinthelastsectionofthispaper,probe ,7temperaturesweremeasuredwithacalibratedEurotherm840/T1 rdigitalthermometer,connectedtoathermocouplewhichwasebintroducedintoanNMRtubefilledwithmineraloiltoap-otcproximatelythesamelevelasatypicalsample.AteachO :temperature,theD2Osampleswerelefttoequilibrateforatleast)be10minbeforethedatawerecollected.
WInordertoavoidhavingtoobtainhundredsofspectra,we( etpreparedsevenstocksolutionscontainingapproximatelyequalaDamountsofseveralofourentries,choseninsuchawayasto npreventintermolecularinteractionsandpossibleambiguitiesiniotaassignment.Solution1:acetone,tert-butylmethylether,di-cilmethylformamide,ethanol,toluene.Solution2:benzene,di-bPumethylsulfoxide,ethylacetate,methanol.Solution3:acetic acid,chloroform,diethylether,2-propanol,tetrahydrofuran.Solution4:acetonitrile,dichloromethane,dioxane,n-hexane,HMPA.Solution5:1,2-dichloroethane,ethylmethylketone,n-pentane,pyridine.Solution6:tert-butylalcohol,BHT,cyclo-hexane,1,2-dimethoxyethane,nitromethane,siliconegrease,triethylamine.Solution7:diglyme,dimethylacetamide,ethyl-eneglycol,“grease”(engineoil).ForD2O.Solution1:acetone,tert-butylmethylether,dimethylformamide,ethanol,2-propanol.Solution2:dimethylsulfoxide,ethylacetate,ethyleneglycol,methanol.Solution3:acetonitrile,diglyme,dioxane,HMPA,pyridine.Solution4:1,2-dimethoxyethane,dimethylacetamide,ethylmethylketone,triethylamine.Solution5:aceticacid,tert-butylalcohol,diethylether,tetrahydrofuran.InD2OandCD3ODnitromethanewasrunseparately,astheprotonsexchangedwithdeuteriuminpresenceoftriethylamine.
Results
ProtonSpectra(Table1).Asampleof0.6mLofthesolvent,containing1µLofTMS,1wasfirstrunonitsown.Fromthisspectrumwedeterminedthechemicalshiftsofthesolventresidualpeak2andthewaterpeak.Itshouldbenotedthatthelatterisquitetemperature-(1)ForrecommendationsonthepublicationofNMRdata,see:IUPACCommissiononMolecularStructureandSpectroscopy.PureAppl.Chem.1972,29,627;1976,45,217.
S0022-3263(97)01176-6CCC:$14.00Figure1.ChemicalshiftofHDOasafunctionoftempera-ture.
dependent(videinfra).Also,anypotentialhydrogen-bondacceptorwilltendtoshiftthewatersignaldown-field;thisisparticularlytruefornonpolarsolvents.Incontrast,ine.g.DMSOthewaterisalreadystronglyhydrogen-bondedtothesolvent,andsoluteshaveonlyanegligibleeffectonitschemicalshift.ThisisalsotrueforD2O;thechemicalshiftoftheresidualHDOisverytemperature-dependent(videinfra)but,maybecounter-intuitively,remarkablysolute(andpH)independent.Wethenadded3µLofoneofourstocksolutionstotheNMRtube.ThechemicalshiftswerereadandarepresentedinTable1.Exceptwhereindicated,thecouplingconstants,andthereforethepeakshapes,areessentiallysolvent-independentandarepresentedonlyonce.
ForD2Oasasolvent,theacceptedreferencepeak(δ)0)isthemethylsignalofthesodiumsaltof3-(trimeth-ylsilyl)propanesulfonicacid;onecrystalofthiswasaddedtoeachNMRtube.Thismaterialhasseveraldisadvan-tages,however:itisnotvolatile,soitcannotbereadilyeliminatedifthesamplehastoberecovered.Inaddition,unlessonepurchasesitintherelativelyexpensivedeuteratedform,itaddsthreemoresignalstothespectrum(methylenes1,2,and3appearat2.91,1.76,and0.63ppm,respectively).Wesuggestthatthere-sidualHDOpeakbeusedasasecondaryreference;wefindthatiftheeffectsoftemperaturearetakenintoaccount(videinfra),thisisveryreproducible.ForD2O,weusedadifferentsetofstocksolutions,sincemanyofthelesspolarsubstratesarenotsignificantlywater-soluble(seeTable1).Wealsoransodiumacetateandsodiumformate(chemicalshifts:1.90and8.44ppm,respectively).
CarbonSpectra(Table2).Toeachtube,50µLofthestocksolutionand3µLofTMS1wereadded.Thesolventchemicalshifts3wereobtainedfromthespectracontainingthesolutes,andtherangesofchemicalshifts
(2)I.e.,thesignaloftheprotonfortheisotopomerwithonelessdeuteriumthantheperdeuteratedmaterial,e.g.,CHCl3inCDCl3orC6D5HinC6D6.ExceptforCHCl3,thesplittingduetoJHDistypicallyobserved(toagoodapproximation,itis1/6.5ofthevalueofthecorrespondingJHH).ForCHD2groups(deuteratedacetone,DMSO,acetonitrile),thissignalisa1:2:3:2:1quintetwithasplittingofca.2Hz.
(3)Incontrasttowhatwassaidinnote2,inthe13Cspectrathesolventsignalisduetotheperdeuteratedisotopomer,andtheone-bondcouplingstodeuteriumarealwaysobservable(ca.20-30Hz).
©1997AmericanChemicalSociety
Downloaded by WUHAN UNIV on October 21, 2009 | http://pubs.acs.org Notes
Table1.
proton
solventresidualpeakH2O
aceticacidacetoneacetonitrilebenzene
tert-butylalcoholtert-butylmethyletherBHTb
multssssssssssssssssst,7q,7mmssssssssssst,7q,7dsc,dsq,7t,7sq,7t,7sembrstmd,9.5shsc,hst,7md,6sep,6mmmsmmsmmt,7q,7
CDCl37.261.562.102.172.107.361.281.193.226.985.012.271.437.261.433.735.301.213.483.653.573.393.403.552.093.022.948.022.962.882.623.711.253.721.322.054.121.262.142.461.063.760.861.260.881.262.653.491.094.330.881.271.224.048.627.297.680.071.853.762.367.177.251.032.53
1H
J.Org.Chem.,Vol.62,No.21,19977513
NMRData
(CD3)2SO2.503.33a1.912.092.077.371.114.191.113.086.876.652.181.368.321.403.905.761.093.383.513.383.243.243.431.962.942.787.952.892.732.543.571.063.444.631.994.031.172.072.430.913.340.861.252.533.164.014.420.861.271.043.788.587.397.791.763.602.307.187.250.932.43
C6D67.160.401.551.551.557.151.051.551.073.047.054.792.241.386.151.402.904.271.113.263.463.343.113.123.331.602.572.057.632.361.861.683.350.963.341.653.890.921.581.810.853.410.921.360.891.242.403.072.940.871.230.953.678.536.666.980.291.403.572.117.027.130.962.40
CD3CN1.942.131.962.081.967.371.162.181.143.136.975.202.221.397.581.443.815.441.123.423.533.453.293.283.451.972.962.837.922.892.772.503.601.123.542.471.974.061.202.062.430.963.510.861.270.891.282.573.282.164.310.891.291.093.878.577.337.730.081.803.642.337.1-7.37.1-7.30.962.45
CD3OD3.314.871.992.152.037.331.401.153.206.922.211.407.901.453.785.491.183.493.613.583.353.353.522.073.312.927.972.992.862.653.661.193.602.014.091.242.122.501.013.590.881.290.901.292.643.344.340.901.291.503.928.537.447.850.101.873.712.327.167.161.052.58
D2O4.792.082.222.061.241.213.22
(CD3)2CO2.052.84a1.962.092.057.361.181.133.136.962.221.418.021.433.875.631.113.413.563.473.283.283.461.973.002.837.962.942.782.523.591.123.573.391.974.051.202.072.450.963.280.871.290.881.282.593.313.124.430.881.271.103.908.587.357.760.131.793.632.327.1-7.27.1-7.20.962.45
chloroformcyclohexane
1,2-dichloroethanedichloromethanediethyletherdiglyme
1,2-dimethoxyethanedimethylacetamidedimethylformamidedimethylsulfoxidedioxaneethanolethylacetateethylmethylketoneethyleneglycol“grease”fn-hexaneHMPAgmethanolnitromethanen-pentane2-propanolpyridinesiliconegreaseitetrahydrofurantoluenetriethylamine
a
CH3CH3CH3CHCH3OHcCCH3OCH3ArHOHcArCH3
ArC(CH3)3CHCH2CH2CH2CH3CH2CH2CH2OCH3CH3CH2
CH3CONCH3NCH3CHCH3CH3CH3CH2CH3CH2OHCH3COCH2CH3CH2CH3CH3COCH2CH3CH2CH3CHCH3CH2CH3CH2CH3CH3OHCH3CH3CH2CH3CHCH(2)CH(3)CH(4)CH3CH2CH2OCH3
CH(o/p)CH(m)CH3CH2
Downloaded by WUHAN UNIV on October 21, 2009 | http://pubs.acs.org Publication Date (Web): October 17, 1997 | doi: 10.1021/jo971176v1.173.563.673.613.373.373.602.083.062.907.923.012.852.713.751.173.652.074.141.242.193.181.263.65
2.613.344.401.174.028.527.457.871.883.74
0.992.57
InthesesolventstheintermolecularrateofexchangeisslowenoughthatapeakduetoHDOisusuallyalsoobserved;itappearsat2.81and3.30ppminacetoneandDMSO,respectively.Intheformersolvent,itisoftenseenasa1:1:1triplet,with2JH,D)1Hz.b2,6-Dimethyl-4-tert-butylphenol.cThesignalsfromexchangeableprotonswerenotalwaysidentified.dInsomecases(seenotea),thecouplinginteractionbetweentheCH2andtheOHprotonsmaybeobserved(J)5Hz).eInCD3CN,theOHprotonwasseenasamultipletatδ2.69,andextracouplingwasalsoapparentonthemethylenepeak.fLong-chain,linearaliphatichydrocarbons.TheirsolubilityinDMSOwastoolowtogivevisiblepeaks.gHexamethylphosphoramide.hInsomecases(seenotesa,d),thecouplinginteractionbetweentheCH3andtheOHprotonsmaybeobserved(J)5.5Hz).iPoly(dimethylsiloxane).ItssolubilityinDMSOwastoolowtogivevisiblepeaks.
showtheirdegreeofvariability.Occasionally,inordertodistinguishbetweenpeakswhoseassignmentwasambiguous,afurther1-2µLofaspecificsubstratewereaddedandthespectrarunagain.
7514J.Org.Chem.,Vol.62,No.21,1997
Table2.
CDCl3
solventsignals
13C
Notes
NMRDataa(CD3)2SO
C6D6
CD3CN1.32(0.02118.26(0.02CD3OD49.00(0.01D2O
(CD3)2CO29.84(0.01206.26(0.1377.16(0.0639.52(0.06128.06(0.02aceticacid
CO175.99172.31171.93CH3
20.8120.5120.95acetoneCO
207.07205.87206.31CH3
30.9230.6030.56acetonitrileCN
116.43117.60117.91CH3
1.891.121.03benzeneCH128.37129.15128.30tert-butylalcoholC
69.1568.1366.88CH3
31.2530.7230.38tert-butylmethyletherOCH3
49.4549.3548.70C72.8772.8172.04CCH3
26.9927.2426.79BHTC(1)
151.55152.51151.47C(2)135.87138.19139.12CH(3)125.55129.05127.97C(4)128.27126.03124.85CH3Ar21.2021.3120.97CH3C30.3331.6131.25C
34.2535.0034.33chloroformCH77.3679.1979.16cyclohexaneCH226.9427.5126.331,2-dichloroethaneCH243.5045.2545.02vdichloromethaneCH253.5254.9554.8467diethyletherCH3
15.2015.7815.1211CH2
65.9166.1262.0579diglymeCH3
59.0158.7757.98oj/CH270.5171.0369.54120CH2
71.9072.6371.251.1,2-dimethoxyethaneCH3
59.0858.4558.0101CH2
71.8472.4717.07: iodimethylacetamideCH3
21.5321.5121.29d | CO171.07170.61169.5479NCH335.2834.8937.3891 NCH3
38.1337.9234.42,71dimethylformamideCH
162.62162.79162.29 reCH336.5036.1535.73boCH3
31.4531.0330.73tcOdimethylsulfoxideCH340.7641.2340.45 :)dioxaneCH267.1467.6066.36beethanolCH3
18.4118.8918.51W(CH2
58.2857.7256.07 etethylacetateCH3CO
21.0420.8320.68aDCO171.36170.96170.31 nCH260.4960.5659.74iotaCH3
14.1914.5014.40cilbethylmethylketoneCH3CO
29.4929.3029.26PuCO
209.56208.30208.72 CH2CH336.8936.7535.83CH2CH3
7.868.037.61ethyleneglycolCH263.7964.2662.76“grease”CH229.7630.7329.20n-hexaneCH3
14.1414.3413.88CH2(2)22.7023.2822.05CH2(3)
31.6432.3030.95HMPAbCH3
36.8737.0436.42methanolCH350.4149.7748.59nitromethaneCH362.5063.2163.28n-pentaneCH3
14.0814.2913.28CH2(2)22.3822.9821.70CH2(3)
34.1634.8333.482-propanolCH3
25.1425.6725.43CH
64.5063.8564.92pyridineCH(2)
149.90150.67149.58CH(3)123.75124.57123.84CH(4)
135.96136.56136.05siliconegreaseCH31.041.40tetrahydrofuranCH2
25.6226.1525.14CH2O
67.9768.0767.03tolueneCH3
21.4621.4620.99C(i)137.89138.48137.35CH(o)129.07129.76128.88CH(m)128.26129.03128.18CH(p)
125.33126.12125.29triethylamineCH3
11.6112.4911.74CH2
46.25
47.07
45.74
a
SeefootnotesforTable1.b2JPC)3Hz.cReferencematerial;seetext.
175.82173.2120.3720.73204.43207.4330.1430.91116.02118.260.201.79128.62129.3268.1968.7430.4730.6849.1949.5272.4073.1727.0927.28152.05152.42136.08138.13128.52129.61125.83126.3821.4021.2331.3431.5034.3535.0577.7979.1727.2327.6343.5945.5453.4655.3215.4615.6365.9466.3258.6658.9070.8770.9972.3572.6358.6858.8972.2172.4721.1621.76169.95171.3134.6735.1737.0338.26162.13163.3135.2536.5730.7231.3240.0341.3167.1667.7218.7218.8057.8657.9620.5621.16170.44171.6860.2160.9814.1914.5428.5629.60206.55209.8836.3637.097.918.1464.3464.2230.2130.8614.3214.4323.0423.4031.9632.3636.8837.1049.9749.9061.1663.6614.2514.3722.7223.0834.4534.8925.1825.5564.2364.30150.27150.76123.58127.76135.28136.891.3825.7226.2767.8068.3321.1021.50137.91138.90129.33129.94128.56129.23125.68126.2812.3512.3846.77
47.10
175.11177.2120.5621.03209.67215.9430.6730.89118.06119.680.851.47129.3469.4070.3630.9130.2949.6649.3774.3275.6227.2226.60152.85139.09129.49126.1121.3831.1535.3679.4427.9645.1154.7815.4614.7766.8866.4259.0658.6771.3370.0572.9271.6359.0658.6772.7271.4921.3221.09173.32174.5735.5035.0338.4338.76164.73165.5336.8937.5431.6132.0340.4539.3968.1167.1918.4017.4758.2658.0520.8821.15172.89175.2661.5062.3214.4913.9229.3929.49212.16218.4337.3437.278.097.8764.3063.17
31.2914.4523.6832.7337.0036.4649.8649.50c63.0863.22
14.3923.3835.3025.2724.3864.7164.88150.07149.18125.53125.12138.35138.272.1026.4825.6768.8368.68
21.50138.85129.91129.20126.2911.099.0746.96
47.19
Downloaded by WUHAN UNIV on October 21, 2009 | http://pubs.acs.org NotesForD2Osolutionsthereisnoacceptedreferenceforcarbonchemicalshifts.Wesuggesttheadditionofadropofmethanol,andthepositionofitssignaltobedefinedas49.50ppm;onthisbasis,theentriesinTable2wererecorded.Thechemicalshiftsthusobtainedare,onthewhole,verysimilartothosefortheothersolvents.Alternatively,wesuggesttheuseofdioxanewhenthemethanolpeakisexpectedtofallinacrowdedareaofthespectrum.Wealsoreportthechemicalshiftsofsodiumformate(171.67ppm),sodiumacetate(182.02and23.97ppm),sodiumcarbonate(168.88ppm),sodiumbicarbonate(161.08ppm),andsodium3-(trimethylsilyl)-propanesulfonate[54.90,19.66,15.56(methylenes1,2,and3,respectively),and-2.04ppm(methyls)],inD2O.TemperatureDependenceofHDOChemicalShifts.Werecordedthe1HspectrumofasampleofD2O,containingacrystalofsodium3-(trimethylsilyl)propane-sulfonateasreference,asafunctionoftemperature.The
v671179oj/1201.01: iod | 7991 ,71 rebotcO :)beW( etaD niotacilbPu J.Org.Chem.,Vol.62,No.21,19977515
dataareshowninFigure1.Thesolidlineconnectingtheexperimentalpointscorrespondstotheequation
δ)5.060-0.0122T+(2.11×10-5)T2
(1)
whichreproducesthemeasuredvaluestobetterthan1ppb.Forthe0-50oCrange,thesimpler
δ)5.051-0.0111T(2)
givesvaluescorrectto10ppb.Forbothequations,Tisthetemperaturein°C.
Acknowledgment.GeneroussupportforthisworkbytheMinervaFoundationandtheOttoMayerhoffCenterfortheStudyofDrug-ReceptorInteractionsatBar-IlanUniversityisgratefullyacknowledged.
JO971176V
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