11. Nuclear Magnetic Resonance (NMR) Spectroscopy

Transcription

1 11. Nuler Mgneti Resonne (NMR) Spetrosopy A. Bsi Priniples Nuler mgneti resonne (NMR) spetrosopy is one of the most importnt nd widely used methods for determining the struture of orgni moleules. NMR llows one to dedue the ron-hydrogen onnetivity in moleule. The following experiment provides generl overview of NMR theory nd interprettion. For more extensive disussion, you should onsult your textook. The nuleus of hydrogen tom ( 1 ) s well s ertin other nulei ( 1 C, 15 N, 1 P, et.) possess property lled nuler spin. Any nuleus tht hs n odd mss numer nd/or n odd tomi numer hs nuler spin. Nuler spins re oriented rndomly in spe, however, in the presene of n externl mgneti field ( ) the spins lign. Some spins lign prllel to (α spin stte) while others lign ntiprllel to (β spin stte). The nuler spins tht lign prllel to re slightly lower in energy. (Figure 1) β-stte α-stte Figure 1. Nuler Spins in the Presene of When the nuler spins in the α nd β sttes re irrdited with eletromgneti energy from the rdio frequeny (RF), energy is sored nd some of the nuler spins in the α stte re spin-flipped to the higher energy β stte. At this stge, the nulei re sid to e in resonne with the pplied RF rdition. (Figure ) β-stte RF Rdition α-stte Nulei re in resonne with the RF rdition Figure. Nulei Irrdited with RF Rdition Experiment 11 NMR Spetrosopy Pge 1 of 11

2 ver time, the flipped spins slowly fll k down to the higher energy stte. The signl dey is deteted over time produing rw signl lled free indution dey (FID). A mthemtil funtion lled Fourier Trnsform onverts the FID into the NMR spetrum. (Figure ) Relxtion 1 NMR Spetrum Fourier Trnsform FID 1 Figure. Relxtion nd Genertion of the NMR Spetrum Every distint proton in moleule will require speifi RF frequeny to promote the spin-flip. Thus, the energy differene etween the α nd β sttes for eh proton is distint. Depending on the energy differene (ΔE), the sorption of eh proton on the NMR spetrum will pper t different lotions. B. The NMR Instrument The NMR spetrometer ontins very strong mgnet, whih genertes n extremely strong, uniform mgneti field. The mgnet poses no helth hzrd, however, you should not ring ertin items suh s wthes, redit rds, nd ellphones lose to it. The NMR instrument in our lortory is Mz instrument, whih orresponds to mgneti field of 9. Tesl. A higher mgneti field will produe higher resolution NMR spetrum, however, the instrument ost rises steeply with mgneti field strength. The smple is pled in n NMR tue, whih is inserted into the enter of the instrument. The tue is spun rpidly to improve homogeneity resulting in etter spetrum. A rdio frequeny (RF) onsole is tthed to the spetrometer; this onsole sends n intense pulse of RF energy to the smple. The RF pulse overs wide enough rnge to exite ll of the protons in the moleule. A omputer ollets the resulting FID nd onverts it to the NMR spetrum, whih n e printed nd nlyzed. NMR Spetrometer Experiment 11 NMR Spetrosopy Pge of 11

3 C. Smple Preprtion NMR smples re typilly prepred s dilute solution in deuterted solvent. A typil smple size is 5-1 mg of smple dissolved in.5 1. ml of deuterted solvent. Less thn 1 mg of smple n e used, however, this will neessitte longer NMR quisition time. Deuterted solvents re ones in whih ll of the hydrogen in the moleule hve een repled with the deuterium isotope. Deuterium does not show up in the rnge exmined for 1 NMR, thus the deuterted solvent is effetively NMR trnsprent. Some ommon NMR solvents re shown elow. The most ommonly used NMR solvent is hloroform-d, where the single hydrogen in hloroform is repled y deuterium. CD D C CD D hloroform-d etone-d 6 deuterium oxide D C D D C S CD methnol-d DMS-d 6 Common NMR Solvents Sometimes, n NMR solvent is spiked with tetrmethylsilne (TMS), whih provides referene signl tht n e used to lirte the spetrum. The TMS signl is set t extly ppm nd every other signl is sed off of tht referene point. NMR Tue NMR smples re pled inside speilly designed NMR tue, whih is 5 mm preision glss tue tht fits perfetly inside the instrument. ne inside the tue, the diluted smple should hve height of - m. NMR tues re reusle nd should e wshed out with etone nd left to dry thoroughly efore the next use. Gret re should e tken when inserting the smple tue into the spetrometer. If smple tue reks inside the instrument, gret del of time is required to remove the roken glss nd to get the instrument k up nd running. D. Interprettion of NMR Spetr 1. Bsis of the 1 NMR Spetrum The interprettion of 1 NMR spetr involves three si onepts: hemil shift, pek integrtion, nd oupling. Eh of these items provides importnt informtion regrding the moleulr struture. Comined, this informtion n e used to eluidte the struture of n unknown orgni moleule. Figure shows smple 1 NMR spetrum. The x-xis is the hemil shift (δ) expressed in prts per million (ppm). The typil hemil shift sle for proton NMR is -1 ppm. The hemil shift provides informtion regrding the hemil environment of the orresponding proton. The re under eh pek is know s the integrtion. The integrtion for signl is Experiment 11 NMR Spetrosopy Pge of 11

4 proportionl to the numer of hydrogen orresponding to tht prtiulr signl. Finlly, you will notie tht some peks re split ( nd, figure ). Pek splitting is lso known s oupling. The splitting for n individul signl provides informtion s to the numer of hydrogen present on the djent ron toms. C C Figure. Smple Proton NMR Spetrum. Chemilly Equivlent nd Distint ydrogen Every hemilly distint type of hydrogen in moleule gives rise to n individul signl in the proton NMR spetrum. This is in ontrst to hemilly equivlent hydrogen, whih nnot e differentited nd will e represented y single signl. For exmple, methne (figure 5A) hs four protons. These four protons nnot e distinguished nd re thus ll hemilly equivlent. Sine there is only one type of hydrogen in methne, only one proton NMR signl will result. In ethnol (figure 5B), there re three distint types of hydrogen: the proton, the C group, nd the C group. Note tht the two protons in the C group re equivlent nd the three protons in the C group re equivlent. When nlyzing moleule for hemilly equivlent or distint toms, py speil ttention to moleulr symmetry. Butne (figure 5D), for exmple, hs plne of symmetry, thus there re two equivlent ethyl (C C ) groups in the moleule. C C C C C C C C C C 1 type of 1 NMR Signl types of NMR Signls types of NMR Signls Figure 5. Exmples of Chemilly Equivlent nd Distint Protons types of NMR Signls (A) (B) (C) (D) Chirl Centers nd Distereotopi Protons In n hirl moleule, the two hydrogen in methylene -C - group re hemilly equivlent (see figure 5 B-D). If however, hirl enter (*) is present, the two methylene protons re no longer equivlent nd will eh hve its own seprte NMR signl. In this type of sitution, the methylene protons re sid to e distereotopi. For exmple, the moleule in figure 6A does not hve hirl enter nd the two highlighted hydrogen of the C group re hemilly equivlent. The moleule in figure 6B hs hirl enter, whih mkes the two hydrogen in the C group distereotopi nd hemilly distint. ne speil se is tht shown in figure 6C where there is not hirl enter, yet the two hydrogen in eh methylene group re distereotopi nd hemilly distint. This n e rtionlized y thinking three dimensionlly. Considering group Z s n out group on wedge, revels the sptil differene etween eh methylene hydrogen nd Z. ne hydrogen is out in loser sptil orienttion to Z, while the Experiment 11 NMR Spetrosopy Pge of 11

5 other hydrogen is k nd is further wy from Z. These two hydrogen reside in different hemil environments nd will hve different NMR shifts. Distereotopi hydrogen give rise to omplex NMR signls tht n often e diffiult to interpret. Chemilly Equivlent C protons * Chemilly Distint C protons Chemilly Distint C protons (A) (B) (C) Z Z Figure 6. Exmples of Distereotopi Protons. Chemil Shift The hemil shift of proton gives us insight into the hemil environment of tht proton i.e. wht type of groups re nery. Chemil shift inreses from right to left on the NMR spetrum. The right end of the spetrum is onsidered upfieled nd protons in this region re sid to e shielded. The left end of the spetrum is onsidered downfield nd protons in this region re sid to e deshielded. (Figure 7) downfield deshielded protons upfield shielded protons ppm Figure 7. Chemil Shift Terminology All proton NMR hemil shifts re reltive to the signl produed y tetrmethylsilne (TMS), whih hs hemil shift tht is defined t δ = ppm. TMS is often used s n internl stndrd nd the spetrum n e referened to the hemil shift of this stndrd. Chemil shifts re remrkly preditle nd knowing few se vlues long with some simple trends will llow you nlyze vriety of NMR spetr. Some typil proton NMR regions re shown in figure 8. Alohol - / Amine -N roxyli id ldehyde romti vinyl X Z Z=,C C sp - R-C ~.9 ~1. ~1.7 X =, N, hlogen sturted Figure 8. Typil 1 NMR Chemil Shift Regions Experiment 11 NMR Spetrosopy Pge 5 of 11

6 Chemil Shift rigin Exmintion of figure 8 revels tht protons in different hemil environments disply NMR resonnes (signls) t different hemil shifts. The protons in moleule re eh shielded y the nery eletrons. In the presene of n externl mgneti field ( ) the moleule s eletrons produe smll lol mgneti fields (B lol ) tht opposes the pplied field from the instrument. In effet, the proton is shielded from the externl mgneti field y the opposing lol mgneti field. The overll mgneti field experiened y n individul proton is the effetive mgneti field (B effetive ) A smller B effetive, mens tht due to shielding, proton experienes less of the externl mgneti field resulting in lower hemil shift. B effetive = - B lol Protons in more eletron defiient environments re less shielded from the externl mgneti field nd resonte t higher hemil shifts. Protons t higher hemil shifts re sid to e deshielded. Chemil Shift Preditions Chemil shift vlues re typilly dditive. Strting with se vlue, hemil shift vlue n e pproximted y inrementlly dding the hemil shift effet from eh tthed group. Bse vlues for the methyl, methylene, nd methine groups re shown elow. Methyl Methylene Methine C C C ~.9 ppm ~1. ppm ~1.7 ppm For exmple, dding n eletronegtive hlorine inreses proton s hemil shift y ~. ppm. Thus, hloromethne hs proton NMR signl t.9 +. =.1 ppm. Chloroethne, on the other hnd, hs proton NMR signl t =. ppm orresponding to the methylene group. C C C.1 ppm. ppm The presene of one or more eletronegtive toms will deshield nery proton y the indutive effet. The more eletronegtive the tthed tom, the stronger the deshielding effet nd the higher the hemil shift. Some representtive exmples re shown elow. C C Br C I C N C δ ~. ppm.1 ppm.7 ppm. ppm. ppm e- neg.5. Br.8 I.7 N. Additionlly, s the numer of eletronegtive toms ner prtiulr proton inreses, the hemil shift lso inreses. C C C C C.9 ppm.1 ppm 5. ppm 7. ppm Experiment 11 NMR Spetrosopy Pge 6 of 11

7 Alohol nd Amine Protons The group of n lohol nd N/N group of n mine typilly gives rod singlet in the -5 ppm rnge. In most ses, nd N protons re not split y protons on neighoring toms. Alkene nd Aromti Protons Protons with nery π-eletrons, speifilly vinyl nd ryl protons, hve unusully high hemil shifts. This is due to n effet known s mgneti nisotropy. In these systems, the lol mgneti field ligns with the externl mgneti field, using the proton to hve lrger thn expeted effetive mgneti field. Vinyli protons typilly pper in the ppm region. Terminl lkene protons tend to hve slightly lower hemil shift thn n internl lkene proton (.9 vs 5. ppm). Aryl protons typilly pper in the ppm region. A phenyl group C 6 5 hs three distint types of protons, however, the signls for these protons frequently overlp nd show up s single line orresponding to 5 hydrogen or messy grouping of peks orresponding to 5 hydrogen. When the romti ring is di or tri sustituted, the ryl proton signls re typilly etter resolved, espeilly when one of the sustituents is n eletronegtive tom or eletron withdrwing group.. Integrtion It is importnt to reognize tht the re under n NMR signl is proportionl to the numer of protons orresponding to tht prtiulr signl. Modern NMR spetrometers hve the ility to utomtilly integrte eh signl providing reltive pek res with ese. For exmple, the integrted NMR spetrum of -utnone is shown in figure 9. The re under eh integrl is proportionl to the numer of represented y tht prtiulr signl. Methyl group, hs three equivlent hydrogen. This is represented in the NMR spetrum y n integrtion for. The methylene group hs two equivlent hydrogen nd therefore integrtes for. Finlly, methyl group hs three equivlent hydrogen nd integrtes for. 1 Figure 9. NMR Spetrum of -Butnone In some ses, you will hve integrtion vlues tht need to e normlized sed on the smllest integrtion vlue. This proess is further explored in pre-l question. Experiment 11 NMR Spetrosopy Pge 7 of 11

8 5. Spin-Spin Splitting (Coupling) The signl orresponding to prtiulr proton will split s result of the protons on neighoring ron toms. Bsi splitting follows the n+1 rule where n is the numer of protons on the djent ron. Looking t the NMR spetrum of -utnone (figure 9), you will see tht signl is split into four lines nd signl is split into three lines. The reson for this oserved splitting is due to oupling with the protons on the djent ron toms. Figure 1 shows -utnone long with the oserved splitting for eh proton in the moleule. The signl orresponding to ppers s single line (singlet). This is euse it is not oupled to ny other hydrogen. The djent ron does not hve ny hydrogen for to ouple with. The signl orresponding to on the other hnd is split into four lines (qurtet). This is due to one of the djent rons hving three protons tthed. Following the n + 1 rule, with n =, + 1 = (qurtet). Finlly, the signl orresponding to is triplet euse the djent ron hs two protons ( + 1 = ). No on the djent C No splitting Single Line = singlet on the djent C n + 1 = + 1 = Split into four lines = qurtet Figure 1. Splitting in -Butnone on the djent C n + 1 = + 1 = Split into three lines = triplet The most ommon splitting ptterns, lso known s multipliities, re shown in figure 11. ne pek is split into more thn seven lines, it is ommonly referred to s multiplet, m. Singlet Doulet Triplet Qurtet Quintet Sextet Septet s d t q quin. sex. sep. Figure 11. Common Multipliities Complex Splitting When proton is oupled to two or more sets of not equivlent hydrogen, the splitting eomes more omplex nd follows the (m + 1)(n + 1) splitting pttern. Consider for exmple the lkene shown in figure 1. The ron highlighted in the green ox is oupled with two different types of hydrogen. Coupling with the lkene, splits the signl into doulet. Coupling with the C hydrogens further splits the signl into triplet providing doulet of triplets. A splitting tree Experiment 11 NMR Spetrosopy Pge 8 of 11

9 (figure 1) is used to show how the signl splits into doule of triplets. Think of the initil signl first splitting into two (doulet) then eh of these two lines further splitting into three lines (triplet). In relity, the peks often overlp whih results in the oservtion of fewer thn expeted peks (figure 1). C C doulet n = = C C m = C + 1 = ()() = doulet of triplets triplets Idel: Well seprted d of t Figure 1: Complex Splitting Relity: peks often overlp () () () Coupling Summry Severl importnt fetures regrding oupling re listed elow. 1. The most ommon oupling ours etween non-equivlent protons tht re seprted y three onds. Br Br. Coupling will e oserved etween protons seprted y two onds if the two protons re hemilly distint. Eh lkene hydrogen ppers s doulet euse they re hemilly distint nd oupled to one nother.. Coupling is typilly not oserved through heterotoms suh s oxygen nd nitrogen. Singlet Singlet. Chemilly equivlent protons do not ouple. Both C groups re hemilly equivlent. They show up s singlet integrting for The Coupling Constnt (J Vlues) The oupling onstnt (k J - vlue) is the distne etween two peks in split signl. If two protons re oupled to one nother, they will hve identil oupling onstnts. When nlyzing omplex spetr, the oupling onstnt is onvenient piee of dt to help determine whether or not two signls re oupled to one nother. The oupling onstnt for prtiulr signl is lulted y sutrting the hemil shift of two neighoring peks in signl nd multiplying tht numer y the frequeny of the spetrometer. The NMR elow ws tken on Mz instrument. The oupling onstnt of the qurtet t ~. ppm is: (.8.5) x = 9 z. Now Experiment 11 NMR Spetrosopy Pge 9 of 11

10 prove tht this qurtet is oupled to the triplet y lulting its oupling onstnt. Tles of ommon oupling onstnts n e found in most orgni textooks nd online. 1.9 ppm C C.5 ppm. ppm 1.5 ppm 1.6 ppm.8 ppm.9 ppm 1 E. Experimentl Proedure A set of unknown IR nd NMR spetr for vriety of orgni ompounds will e ville in the lortory. A list of possile strutures will e provided seprtely. Your TA will ssign you two of the numered unknowns. You will nlyze the IR nd NMR dt nd mth your spetr to one of the possile strutures. In your lortory noteook, you will identify eh of your unknowns. You should inlude list of the IR sorptions nd NMR signls long with the identity of the group tht eh signl orresponds to. You should lso inlude rief explntion of how you identified your unknown sed on pieing together this dt. F. Pre-L Questions 1. The struture of morphine is shown elow. ow mny hemilly distint types of hydrogen re present in this moleule? N. Predit the expeted multipliity (singlet, doulet, et.) for every distint set of hydrogen in eh moleule elow. C C C C C C C C C C C C C C C C C C C C C. Consider the NMR spetrum shown elow. The integrtion vlues re not normlized. Normlize eh integrtion y dividing eh integrtion vlue y the lowest integrtion vlue. Do your vlues dd up for the orret numer of hydrogen? If not, multiply eh vlue y ommon numer to get the orret totl numer of hydrogen represented. Experiment 11 NMR Spetrosopy Pge 1 of 11

11 C Clulte the oupling onstnt (J) for the NMR signl t δ 6. ppm shown elow. A 5 Mz instrument ws used to reord the spetrum. You will find tht this is typil oupling onstnt for trns-lkenes G. Post-L Questions 1. A reless student mistkenly dissolved his smple in non-deuterted hloroform (C ). Wht do you think resulted in the orresponding NMR spetrum tht he reorded?. For eh ompound shown elow, predit the expeted IR nd NMR dt. Reord the NMR dt in the form (hemil shift, multipliity, integrtion). You hemil shift vlues nd IR sorption vlues only need to e rough pproximtion. The first moleule is lredy ssigned to provide n exmple.. ppm, q, 1. ppm, t,.9 ppm, s, 9 1. ppm, t,. ppm, t, IR Dt: C=, 17 m -1 Csp -, 9-99 m -1 Csp -, 15 m -1 Csp -, 15 m -1 Experiment 11 NMR Spetrosopy Pge 11 of 11