Baixe Silverstein spectr...mistry nmr ftir ms - chapter5 13c nmr spectrometry e outras Manuais, Projetos, Pesquisas em PDF para Química, somente na Docsity! CHAPTER 5 BC NMR Spectrometry 5.1 Introduction* Faced with a choice during the early development of nuclear magnetic resonance spectrometry, most organic chemists would certainly have selected the carbon nu- cleus over the hydrogen nucleus for immediate investi- gation. After all, the carbon skeletons of rings and chains are central to organic chemistry. The problem, of course, is (hat the carbon skeleton consists almost completely of the !2C nucleus, which is not accessible to NMR spectrometry. The spcctrometrist is left to cope with the very small amount of the "C nucleus. There are enough differences between "PC and !H NMR spectrometry to justify separate chapters on ped- agogical grounds. With an understanding of the basic concepts of NMR spectrometry in Chapter 4, mastery of EC spectrometry will be rapid. The 12€ nucleus is not magnetically “active” (spin number, f, is zero), but the "C nucleus, like the 'H nu- cleus, has a spin number of3. However, since the natural abundance of !ºC is only 1.1% that of 2C, and its sen- sitivity is only about 1.6% that of 'H, the overall sensi- tivity of PC compared with !H is about 1/5700. The cartier, continuous-wave, slow-scan procedure requires a large sample and a prohibitivcly long time to obtain a C spectrum, but the availabitity of pulsed Fourier transform (FT) instrumentation, which permits simultaneous irradiation of all *C nuclei, has resulted in an increased activity in BC spectrometry, beginning in the early 1970s, comparable to the burst of activity in 'H spectrometry that began in the late 1950s. An important development was the use of broad- band decoupling (i.e., irradiation) of protons. Because of the large J values for LEC—H (— 110-320 Hz) and ap- preciable values for *C—C—HandPC—C—C—H, proton-coupled “C spectra usually show complex over- lapping multiplets that are difficult to interpret; but s. * Familiarity with Chapter 4 is assumed. 217 some proton-coupled spectra such as that of diethyl phthalate (Fig. 5.14) are quite simple. Irradiation (Fig. 5.1h) of the protons over a broad frequency range by means of a broadband generator removes these cou- plings. Figure 5.1c shows the effect of a delay between pulses (see Section 5.2). The result, in the absence of other coupling nuclei, such as “!P or 'ºF, is a single sharp peak? for cach chem- ically nonequivalent '3C atom except for the infrequent coincidence of 2C chemical shifts.i Furthermore, an in- crease in signal (up to 200%) acerues from the nuclear Overhauser effect (NOE) (see Section 4.20). This en- hancement results from an increase in population of the lower energy level of the 3C nuclei concomitant with the increase in population of the high-energy level of the !H nuclei on irradiation of the 'H nuclei, The net effect is a very large reduction in the time needed to obtain a broadband-decoupled spectrum (Fig. 5.1h) as compared with a coupled spectrum (Fig. 5.14). As described in Section 4.4 for pulsed Fourier trans- form spectrometry of protons, a short, powerful, rf pulse (on the order of a few microseconds) excites all of the !C nuclei simultaneously. At the same time, the broad- band decoupler is turned on in order to remove the 5C—!H coupling. Since the pulse frequencies are slightly oft resonance for alt of the nuclei, each nucleus shows a free induction decay (FID), which is an expo- nentially decaying sine wave with a frequency equal to the difference between the applied frequency and the resonance frequency for that nuclevs. Figure 5.24 shows the result for a single-carbon compound. The FID display for a compound containing more than onc *C nucleus consists of superimposed sine waves, each with its characteristic frequency, and an in- + Because of the low natural abundance of "ºC, the occurrence of adjacent "'C atoms has à low probability; thus we are free of the com- plication cf 8C—3C coupling. 3 But note the coincidenco of these '3C peaks in Figure 6.12. 218 ChapterS 13C NMR Spectrometry EAN Ss ooEMéMy coca 1 “ om SE NE Too TO do o ETR RR RE Re fa) FIGURE 5.1(a). The LC-NMR spectrum of diethyl phthalatc with the protons completely coupled. The solvent uscd was CDCI, at 25.2 MHz. Er Fer = EPIC ET o! T RE E 7 ve “Caldo ooênaHs 5 é , 2 1 “RS RE RO DO TO TE e (6) FIGURE 5.1(b). The "C-NMR spectrum of diethyl phthalate with the protons completely decoupled by the broadband decoupler. The solvent used was CDCI; at 25.2 MHz. Samples for 2C spectrometry are usually dissolved in CDCI,, and the "C peak of tetramethylsilane (TMS) is uscd as the internal reterence.* A list of the common deuterated solvents is given in Appendix A. The scale is im ô units (ppm). The shifts in rontine "C spectra range over about 240 ppm from FMS — about 20 times that of routine 'H spectra (— 12 ppm). As a result of the large range and the sharpness of the decoupled peaks, impurities arc readity detected and mixlures may be readily analyzed. Even slercoisomers that are difficult ta analyze by means of 'H spectrometry usually show discrete 'C pcaks. An NMR instrument is often described in terms of the resonance frequency for a particular nucleus at a given magnetic field intensity. An instrument with a 7.05-T magnet is thus described at 300-MHz instrument for protons; an 11.7-T magnet corresponds to a 5(W- MHz instrument for protons. The resonance frequen- cies for 2C are about 1 thosc of !H (the ratio of the y values for these nuclides). Thus for a 7.05-T magnet, the 13C resonance frequency is about 75.5 MHz, and for an 11.7-T magnet, the resonance frequency is about 126.0 MHz. A routine BC spectrum at 75.5 MHz would require about 10 mg of sample in 0.4 mL of solvent in a 5-mm o.d. tube. Samples on the order of 100 ug can be han- dled in a concentric microcell with an inner tube of 40-100 uL capacity: the annular volume is left empty or is filled with solvent. A probe that accepts a 3-mm id. tube gives high sensitivity (Sec Section 4.6). Refer- ence to further details, collections of spectra, and spec- tra-structure correlations are appended at lhe end of the chapter. 5.2 Peak Assignments 5.2.1 Peak Intensity Tn pulsed Fourier transform 'H spectra, there is usually a satisfactory relationship between integrated peak ar- eas and the number of protons under thc areas because there is sufficient time between pulscs for relaxation to occur. In routine pulsed PC spectra, however, the 2C nuclei, whose relaxation times (71) vary over a wide range, are not equally relaxed between pulses, and the pcak areas do not integrate for the correct number of nuclei. Long delays between pulses can be used to ob- tain quantitative results, but the time needed may be prohibitive for routine work. Furthermore, the NOE re- + Wilh modern instrumentation, TMS is not actually added; instead. the € peak of the denterated solvent is used as à reference. The spectrum, however, is presented with the !3C: peak of TMS at à 0.00 at the righi-hand cdge of lhe scale. 52 Peak Assignments 221 sponse is not the same for ali 2C nuclci, resulting in further loss of quantitation (see Section 5.6). However, onc advantage does result. It is usually possible by inspection of a '*C spectrum to recognize the nuclei that do not bear protons by their low intensity (peaks 1 and 2 in Fig. 5.15). The common spin-lattice relaxation mechanism for !C results from dipole-dipole interaction with directly attached protons. Thus, non- protonated carbon atoms have longer 7, relaxation times, which together with little or no NOE, results in small peaks. It is therefore often possible to recognize carbonyl groups (except formyl), nitriles, nonproton- ated alkene and alkyne carbon atoms, and other qua- ternaryf carbon atoms readily. However, care must be taken to allow a sufficient number of pulses or a long enough interval between pulses (to compensate for the long Ti) so that these weak signals are not completely lost in the baseline noise. In Figure 5.1c, a 10-s interval (pulse delay) was used to increase the relative intensities of peaks 1 and 2). Í COCH,CH, GOCH.CH, Diethyl phthalate Tn the broadband-decoupled spectrum of diethyl phthalate (Fig. 5.1b), we can assign the small peak at 167.75 ppm to the two equivalent C=O groups, the small peak at 132,85 ppm to the equivalent substituted aromatic carbon atoms, the large peaks at 131.33 and 129.19 ppm to the remaining aromatic carbon atoms, the medium peak at 61.63 ppm to the two equivalent CH, groups, and the medium peak at 14.15 ppm to the two equivalent CH, groups. These assignments can be made on the basis of Appendices B and € and on the as- sumption that the quaternary carbon atoms are respon- sible for the weak peaks; their relative intensity can be increased by inserting a pulse delay (an interval be- tween the acquisition period and the next pulse) as in Figure S.1c. Note that the 10-s pulse delay nearly equal- izes the intensities of all the peaks except for those rep- resenting the quaternary carbon atoms. The most effective procedure for peak assignments is DEPT (Distortionless Enhancement by Polarization Transfer), whereby peaks can be classified as repre- senting CH,, CH,, CH (or €). This discussion is re- served for Section 5.5, 4 For want of a better general term, “quaternary" is used to describe any carbon atom without an attached hydrogen atom 222 Chapter5 “C NMR Spectrometry (CHa)ac-OH LL LIL Li ) J re wo 190 NO MO 190 O 130 120 mo 0 dO 5 70 80 4 40 3% 20 w O FIGURE 5.3. Decoupled “C-spectrum of i-butyl alcohol. Solvent, CDCLI, at 25.2 MHz; 5000-Hz sweepwidth. From Johnson and Jankowski (1972) spectrum No. 88, with permission. 5.2.2 Deuterium Substitution Substitution of D for H on a carbon results in a dramatic diminution of the height of the C signal in a broad- band-decoupled spectrum for the [ollowing reasons. Since deuterium has a spin number of 1 and a magnetic moment 15% that of !H, it will split the 'ºC absorption into three lines (ratio 1:1:1) with a J value equal to 0.15 X Jow. Furthermore, T, for *C-—D is longer than that for *C—H because of decreased dipole-dipole re- laxation. Finally, the NOE is lost, since there is no ir- radiation of deuterium.* A separate peak may also be seen for any residual SC —H, since the isotope effect usually results in a slight upficld shift of the SC—D absorption (— 0.2 ppm per D atom). The isotope effect may also slightly shift the absorption of the carbon at- oms once removed from the deuterated carbon. 5.2.3 Chemical Shift Equivalence The definition of chemical shift equivalence given for protons also applies to carbon atoms: interchangeability by a symmetry operation or by a rapid mechanism. The presence of equivalent carbon atoms (or coincidence of shift) in a molecule results in a discrepancy between the apparent number of peaks and the actual number of carbon atoms in the molecule. * The same explanation also accounts for the relatively wcak signal shown by denterated solvents. In addition, small solvent molecules tumble rapidly; this rapid movement makes for a longer 7), hence for smaller peaks. Deuterated chloroform, CDCL,, shows a 1:1:1 triple, deuterated p-dioxane a 1:2:3:2:1 quinter, and deuterated DMSO (CDa:SO, a 1:3:6:7:6:3:1 septet in accordance with the 2n7 + 1 rule (Chapter 4). The chemical shifts, coupling constants, and muti- plicities of the ?C atoms of common NMR solvents are given in Ap- pendix A. Thus, !3C atoms of the methyl groups in t-buty] al- cohol (Fig. 5.3) are equivalent by rapid rotation in the same sense in which the protons of a methyl group are equivalent. The PC spectrum of +-butyl alcohol shows two peaks, one much larger than the other, but not nec- essarily exactly three times as large; the carbinyl carbon peak (quaternary) is much less than | the intensity of the peak representing the carbon atoms of the methyl groups. Ta the chiral molecule 2,2,4-trimethyl-1,3-pentane- diol (Fig. 5.4), we note that CH;a and CH,b are not equivalent, and two peaks are seen. Even though the two methy] groups labeled c are not equivalent, they coincidently show only one peak. Two peaks may be seen at higher resolution. In Section 4.12.3 we noted that the CH, protons of (CH;),NCH=0 gave separate peaks at room temper- ature, but became chemical shift equivalent at about 123º. Of course, the BC peaks show similar behavior. 5.3 Chemical Classes and Chemical Shifts In this section, chemical shifts will be discussed under the headings of the common chemical classes of organic compounds. As noted earlier, the range of shifts gen- erally encountered in routine SC studies is about 240 ppm. As a first reassuring statement, we can say that trends in chemical shifts of 2C are somewhat parallel to those of !H, so that some of the “feeling” for 'H spectra may carry over to '*C spectra. Furthermore, the concept of additivity of substituent effects (see Sections 4.7 and 5.3.6) is useful for both spectra. The SC shifts are re- lated mainly to hybridization and substituent electro- 53 Chemical Classes and Chemical Shifts 223 c oH H3€ Na f CH=— CH C—= cHo0H Hace” 8 cDcia c “lr Fa O A DS LIL TO SO HO NO O MO Wo 120 FIGURE 54, Decoupled “C-spectrum of 22, 4-trimethyl 5 NO 06 0 70 6 50 40 3 20 W O 1,3-pentanediol. Solvent used was CDC, at 25.2 MHz; 5000-Hz sweepwidth. From Johnson and Tankowski (1972), spectrum No. 324, with permission. negativity; solvent effects are important in both spectra. Chemical shifts for EC arc affected by substitutions as far removed as the ô position; in the benzene ring, pro- nounced shifts for '3C are caused by substituents at the ortho, meta, and para positions. The 3C chemical shifts are also moved significantly to the right by the y-gauche effect (see Section 3.5.1.1). Shifts to the right as much as several parts per million may occur on dilution. Hy- drogen-bonding effects with polar solvents may cause shifts to the left. Appendix B gives credence to the statement that 3C chemical shifts somcwhat parallel those of !H, but we note some divergences that are not readily explain- able and require development of another set of inter- pretive skills. In general, in comparison with 'H spectra, it seems more difficult to correlate BC shifts with sub- stituent electronegativity. Asin other types of spectrometry, peak assignments are made on the basis of reference compounds. Refer- ence material for many classes of compounds has ac- cumulated in the literature. The starting point is a gen- cral correlation chart for chemical shift regions of BC atoms in thc major chemical ctasses (see Appendices B and C); then, minor changes within these regions are correiated with structure variations in the particular chemical class. The chemical shift values in the follow- ing tables must not be taken too literally because of the use of various solvents and concentration. (Further- more, much of the early work used various reference compounds, and the values were corrected to give parts per million from TMS.) For example, the C=O ab- sorption of acetophenone in CDCI; appears at 2.4 ppm further to the left than in CCL; the effect on the other carbon atoms of acetophenone ranges from 0.0 to 11 ppm. A EC spectrum will often distinguish substitution patterns on an aromatic ring. If, for example, there are two identical (achiral) substituents, the symmetry ele- ments alone will distinguish among the para, ortho, and meta isomers if the chemical shifts of the ring carbon atoms arc sufficiently different. The para isomer has two simple axes and two planes. The ortho and meta isomers have one simple axis and one plane, but in the meta isomer, the elements pass through two carbon atoms. There is also a symmetry plane in the planc of the ring in each compound, which does not affect the ring carbon atoms. OCH; co, , OCH, , (3 Ct OCH, The aromatic region of the 2C spectrum for the para isomer shows two peaks; for the ortho isomer, three peaks; and for the meta isomer, four peaks. The quaternary carbon peaks are much less intense than the unsubstitutcd carbon peaks. The additivity of shift increments is demonstrated in Section 5.3.6. 5.3.1 Alkanes 5.3.1.1 Linear and Branched Alkanes We know from the general correlation chart (Appendix C) that alkane groups unsubstituted by heteroatoms absorb to about 60 ppm. (Methane absorbs at — 2.5 ppm). Within this range, we can predict the chemical shifts of individ- ual 3C atoms in a straight-chain or branched-chain hy- 226 Chapter5 “C NMR Spectrometry Table 5.4 Chemical Shifts of Cycloalkanes (ppm from TMS) ie CsHs -29 CH 284 Cats na Calha 269 CH 256 CH 261 CH 26.9 Coto 253 Each ring skeleton has its own set of shift parame- ters, but a detailed listing of these is beyond the scope of this text. Rough estimates for substituted rings can be made with the substitution increments in Table 5,3. One of the striking effects in rigid cyclohexane rings is the shift to the right caused by the y-gauche steric compression. Thus an axial methyl group at C-1 causes a shift to the right of several parts per million at C-3 and Cs, Table 5.5 presents chemical shifts [or several satu- rated heterocyclics. 5.3.4 Alkenes The sp? carbon atoms of alkenes substituted only by alkyl groups absorb in the range of about 110-150 ppm. Table 5.5 Chemical Shifls for Saturated Heterocyelics (ppm from TMS, neat) Unsubstituted H Q 8 N LS 6 Susa Lisa H Ri Ci 0 vol das 28161 190481 258 312 257 l ye l Va ( Jem o s N H us 266 259 n7 ns 28 695 291 “9 O Ss Y H Substitutcd o 244 Lars l 5 567 a13 CH, N 181 I CH, 480 The double bond has a rather small effect on the shifts of the sp? carbons in the molecule as the following com- parisons demonstrate. 254 Bs cH, cH—C— cH— C==CH, 316 w4 CH, s22 1437 1144 24 GH cH, cH—C— CH—CH—CH, 304 29 CH, 535 253 The methyl signal of propene is at 18.7 ppm, and of propane at 15.8 ppm. In (Z)-2-butene, the methyl sig- nals are at 12.1 ppm, compared with 17.6 ppm in (E)- 2-butene, because of the y effect. (For comparison, the methyl signals of butane are at 13.4 ppm). Note the y effect on one of the geminal methyl groups in 2-methyl- 2-butene (Table 5.6). In general, the terminal =CH, group absorbs to the right relative to an internal =CH— group, and Z —CH=CH-— signals are to the right from those of corresponding E groups. Calculations of approxi- mate shifts can be made from the following param- eters where «, 8, and y represent substitutents on the same end of the double bond as the alkene carbon of interest, and a”, B', and y' represent substituents on the far side. + 10.6 +72 -1,5 -—79 -1L8 , -1.5 ZÁcis) correction -11 2 e a wRr=s These parameters are added to 123.3 ppm, the shift for ethylene. Wc can calculate the values of €-3 and C-2 for (Z)-3-methyl-2-pentene as follows: CH des = 1233 +(2X 10.6) + (1X 72) +(1x-79)- 1.1 = 1427 ppm de 1=1233+(1xX10.6)+(2x —7.9) + (1X 1.8) — 11 = 115.2 ppm The measured values are C-3 = 137.2 and C-2 = 116.8. The agreement is fair. 53 Chemical Classes and Chemical Shifts 227 Table 56 Alkene and Cycloalkcne Chemical Shifts (ppm from TMS) — e me e e Ds Os Das mm — HC=CH, 136.2 113,3 12.1 1260 mo N No 187 1159 1402 1246 176 n43 140 1327 1232 133,3 1387 937 DA 126 NAM NANA — 1385 205 123 123.7 nas 26 1972 1244 57 353 1251 BL? 113 / NTENDO NAN 232 13170 177 175 115.9 144 129.5 116.5 1309 1264 180 1302 130 WA, WAY NWA 12 1372 1373 1378 132 º 132.5 128 1283 1274 1231 1093 169 1098 129 W 1316 A =. 149.3 1 v8.7 144.5 1449 126.6 253 107.1 1308 1273 149.7 260 126.1 71 u3s 36.2 145 1246 wa[ J> 326 25 289 23 21 ua 269 CH=C—CH, 748 2135 Carbon atoms directly attached to a (Z) C=C group are more shielded than those attached to Lhe ster- coisomeric (E) group by 4-6 ppm (Table 5.6). Alkene carbon atoms in polyenes are treated as though they were alkane carbon substituents on one of the double bonds. Thus, in calculating the shift of C2 in 14-pen- tadiene, C-4 is treated like a 8-spº carbon atom. Representative alkenes are presented in Table 5.6. There are no simple rules to handle polar substit- vents on an alkene carbon. The shifts for vinyl ethers can be rationalized on the basis of electron density of the contributor structures cH,=CH—0—CH, — CH, —CH=0"—CH, 842 1532 as can the shifts for a,B-unsaturated ketones. O CT 150.7 = Y The same rationalization applies to the proton shifts in these compounds. Shifis for several substituted alkenes arc presented in Table 5.7. The central carbon atom (===) of alkyl-substi- tuted allencs absorbs in the range of about 200- 215 ppm, whereas lhe terminal atoms (C=C=C) ab- sorb in the range of about 75-97 ppm. 5.3.5 Alkynes The sp carbon atoms of alkynes substituted only by al- kyl groups absorb in the range of approximately 65- 90 ppm (Table 5.8). The triple bond shifts the spº car- bon atoms, directly attached, about 515 ppm to the right relative to the corresponding alkane. The termi- nal==CH absorbs further to the right than the internal ==CR. Alkyne carbon atoms with a polar group di- rectly attached absorb from about 20 to 95 ppm. Polar resonance structures explain these shifts for alkynyl ethers, which are analogous to the shifts for vi- nyl ethers (Section 4.34). 232 S94 HC=C—OCH,CH; 280 884 cH,—C=C—O—CH, 228 Chapter5 “C NMR Speetrometry Table 5.7 Chemical Shifts of Substituted Alkenes (ppm from TMS) 1220 1337 cl 1261 153,2 1417 AN VAVÁ AN (srs n5o Br nas wa O 2 OCH, 64 Oia 202 O 1364 1385 1280 1287 1223 / 868 Jana A 1360 HO 1293 Gem, 119 COOH 299 COOCH, 4) COOCH, 92.1 o 153 107.7 Br H Br, CH, 1375 OH 1047 >=2<1327 108.9>—=C29,4 1378 EN > 1149 634 1175 H CH, H H o o 1338 1527 H 165.1 nos 1370 dp 1836 31507 1280 “o 5.3.6 Aromatic Compounds Benzene carbon atoms absorb at 128.5 ppm, neat or as a solution in CDC. Substituents shift the attached ar- omatic carbon atom as much as +35 ppm. Fuscd-ring absorptions are as follows: Naphthalene: C-1, 128.1; C-2, 125.9; C-4a, 133,7. Anthracene: C-1, 130.1; C-2, 125.4; C-4a, 132.2; €-9, 132.6. Phenanthrene: C-1, 128.3; €-2, 126.3; C-3, 126.3; C.4, 122.2; C-4a, 131.9*; C-9, 126,6, C-10a, 130,1.* Shilts of the aromatic carbon atom directly attached to the substituent have been correlated with substituent * Assignment uncertain. Table 5.8 Alkyne Chemical Shifts (ppm) ma Compond CI €C2 C3 C4 €5 cé 1-Butyne 670 847 2-Bulyne 736 i-Hexyne 681 845 181 307 29 135 2-Hexyne 27 937 7,69 196 216 121 3-Hexyne 154 130 809 electronegativity after correcting for magnetic aniso- tropy effects; shifts at the para aromatic carbon have been correlated with the Hammett « constant. Ortho shifts are not readily predictable and range over about 15 ppm. Meta shifts are generally small — up to several parts per million for a single substituent. The substituted aromatic carbon atoms can be dis- tinguished from the unsubstituted aromatic carbon atom by its decreased peak height; that is, it lacks a proton and thus suffers from a longer 7, and a dimin- ished NOE. Incremental shifts from the carbon atoms of ben- zene for the aromatic carbon atoms of representative monosubstituted benzene rings (and shifts from TMS of carbon-containing substituents) are given in Table 5.9. Shifts from benzene for polysubstituted benzene ring carbon atoms can be approximated by applying the principle of increment additivity. For example, the shift from benzene for C-2 of the disubstituted compound 4-chlorobenzonitrile is calculated by adding the effect for an ortho CN group (+ 3.6) to that for a meta Cl group (+ 1.0): CN CN d 1 4 2 2 3 is equivalent to + 3 2 4 % q a ci 53 Chemical Classes and Chemical Shifis 231 Table 5.11 Chemical Shifts of Alcohols (neat, ppm from TMS) é ; cH,0H vo SH 10. ÇA 21 13 AA 480 s70 258 oH 634 191 614 oH OH E a 670 297 oH 39. E 140 2» 194 723 2º oH E as OH nc 2s 37325 OH a no 8º ar" al To oH 234 259 350 ua 33 355 OH (69.5 oH Table 5.12 Chemical Shifts of Ethers, Acetals, and Epoxides (ppm from TMS) ETA Po BAAL AM er 76 4 AL) o. 146 s25, 1532 mo Na a Do aaa 712 a o (oa 5 23 A , 2 CS, n6 684 es - O RR 8 | 154 (3 o 99.6 0 109.9 < 199 07 665 ess) 659 o 0—— 26.6 Í o 232 Chapter5 13C NMR Spectrometry range of about 88-112 ppm. Oxirane (an cpoxide) ab- sorbs at 40.6 ppm. The alkyl carbon atoms of aralkyl ethers have shifts similar to those of dialky] cthers. Note the large shift to the right of the ring ortho carbon resulting from electron delocalization as in the vinyl ethers. 1295, 108 159.9. 541 OCH, 114.1 5.3.10 Halides The effect of hatide substitution is complex. A single fluorine atom (in CH,F) causes a large shift to the left from CH, as electronegativity considerations would suggest. Successive geminal substitution by CI (CH,CI, CH,CL, CHCI,, CCl1,) results in increasing shifts to the left—again expected on the basis of electronegativity. But with Br and 1, the “heavy atom effect” supervenes, The carbon shifts of CH,Br and CH,Br, move progres- sively to the right. A strong progression to the right for 1 commences with CH4I, which is to the right of CH, . There is a progressive shift to the left at C-2 in the order 1>Br>F. Chlorine and Br show y-gauche shielding at C-3, but 1 does not, presumably because of the low Table 5,13 Shift Positions for Alkyl Halídes (neat, ppm from TMS) a Compound ca c2 c3 cH, -23 CH;F 754 CHI 24.9 CHCl, 540 cHCL, 75 cel, 96.5 CH,Br 10,0 CH,Br, 214 CHBr, 121 CBrs -285 CHI -207 CH, -540 cHI, —1399 cl, —292,5 CH.CH,F 79.3 146 CH.CH,CI E 187 CH,CH,Br 283 203 CH;CHI -02 216 CH.CH,CH,CI 467 265 115 CH,CH,CH,Br 357 268 132 CH,CH,CH,I 10.0 216 162 population of the hindered gauche rotamer. Table 5.13 shows these trends. I 1 H cH H H H H H H H cH, Halides may show large solvent effects; for exam- ple, €-1 for iodoethane is at — 6.6 in cyclohexane, and at —04in DMF. 5.3.11 Amines A terminal NH, group attached to an alkyl chain causcs a shift to the left of about 30 ppm at C-1, a shift to the lett of about 11 ppm at C-2, and a shift to the right of about 4.0 ppm at €-3, The NH;* group shows a some- what smaller effect. N-alkylation increases the shift to the left of the NH, group at C-1, Shift positions for se- lected acyclic and alicyclic amincs are given in Table 5.14A (see Table 5.5 for heterocyclic amines). 5.3.12 Thiols, Sulfides, and Disulfides Since the clectronegativity of sulfur is considerably less than that of oxygen, sulfur causes a correspondingly smaller chemical shift. Examples of thiols, sulfides, and disulfides are given in Table 5.14B. 8.3,13 Functional Groups Containing Carbon Carbon-13 NMR spectrometry permits direct observa- tion of carbon-containing functional groups; the shift ranges for these are given in Appendix A. With the ex- ception of CH=0, the presence of these groups could not be directly ascertained by 'H NMR. 5.3,13.1 Ketones and Aldehydes The R;C=0O and the RCH=O carbon atoms absorb in a characteristic region. Acetone absorbs at 203.8 ppm and acetaldehyde at 199.3 ppm. Alkyt substitution on the « carbon causes a shift to the left of the C==O absorption of 2-3 ppm until steric effects supervene. Replacement of the CH, of acetone or acetaldehyde by a phenyl group causes a shift to the right of the C=O absorption (ace- tophenone, 195.7 ppm; benzaldehyde, 190.7 ppm); sim- ilarly «,B-unsaturation causes shifts to the right (acro- lein, 192.1 ppm, compared with propionaldehyde, 201.5 ppm). Presumably, charge delocalization by the benzene ring or the double bond makes the carbonyt carbon less electron deficient. Of the cycloalkanones, eyclopentanone has a pronounced shift to the left, Table 5.15 presents chemical shifts of the C=O group of some 54 “CH Spin Coupling (J values) 233 Table 5.14A Shift Positions of Acyclic and Alicyclic Amines (neat, ppm from TMS) pa mm Compound c1 c2 c3 cs CH;NH, 26.9 CH;CH,NH, 35.9 179 CH,CH,CH;NH, 449 213 12 CH,CH.CH,CH,NH, 423 36.7 204 140 €CH5)aN 415 CH;CH.N(CH:) s82 138 Cyclohexylamine 50.4 367 257 251 N-Methyleyclohexylamine 58.6 333 251 263 (N—CH, 335) ketones and aldehydes. Because of rather large solvent effects, there arc differences of several parts per million from different literature sources. Replacement of CH, of alkanes by C—O causes a shift to the left at the a carbon (10-14 ppm) and a shift to the right at the 8 carbon (several ppm in acyclic compounds). 5,3.13.2 Carboxylic Acids, Esters, Chlorides, Anhy- drides, Amides, and Nitriles The €=0O groups of car- boxylic acids and derivatives are in the range of 150- 185 ppm. Dilution and solvent effects are marked for carboxylic acids; anions appear further to the left. The effects of substituents and electron delocalization are generally similar to those for kctones. Nitriles absorb in the range of 1185-125 ppm. Alkyl substituents on the nitrogen of amides cause a small (up to several ppm) shift to the right of the C=0 group (see Table 5.16). 53.133 Oximes The quaternary carbon atom ofsim- ple oximes absorb in the range of 145-165 ppm. Et is possible to distinguish betwecn E and Z isomers since the C==N shift is to the right in the sterically more com- pressed form, and the shift of the morc hindered sub- Table 5.14B Shift Positions of Thiois, Sulfides, and Disulfides (ppm from TMS) Do Compound ca cz c3 cH;SH 65 cH;CH,SH 19.8 173 CH;CH.CH,SH 26.4 26 126 CH;CH,CH,CH,SH 237 357 210 (CHS 193 (CH;CH,)S 255 148 (CH;CH.CH,),S 343 232 137 (CH;CH.CH,CH,)S 341 314 220 CH;SSCH, 220 CH;CH;SSCH,CH; 328 145 stituent (syn to the OH) is farther to the right than the less hindered. HO. oH Pá >N N | 1587 || Q. 1592 q HCO DcH—CH, HC” DCH—CH, 11.50 29.00 11.00 18.75 21.50 9.75 5.4 “C—H Spin Coupling (J values) Spin-coupling J values—at lcast as an initial consider- ation— are less important in 3C NMR than in 'H NMR. Since routine 3C spectra are usually decoupled, 3C—1H coupling values are discarded in the interest of obtaining a spectrum in a short time or on small sam- ples—a spectrum, furthermore, free of complex, over- lapping absorptions. *C—!H J values are given in ta- bles 5.17-5.19.* One-bond “C—!H coupling ('/cn) ranges from about 110 to 320 Hz, increasing with increased s char- acter of the LC—!H bond, with substitution on the car- bon atom of clectron-withdrawing groups, and with angular distortion. Appreciable *C—!H coupling also extends over two or more (4) bonds (Jc). Table 5.17 gives some representativo 'Jcy values. Table 5.18 gives some representative 2/cy values, which range from about —5 to 60 Hz. The 3/m values are roughly comparable to Ycy values for sp' carbon atoms. In aromatic rings, however, the 3cw values are characteristically larger than 2 values. In benzene itself, Jon = 74 Hz and cu — 1.0 Hz. Coupling ot “C to several other nuclei, the most + CNC coupling is not observed in a routine “C. spectrum, except in compounds that have been deliberately enriched with VC, because of the low probability of two adjacent VC atoms in a molecule. 236 Chapter5 13C NMR Spectrometry Table 5.16 (Continued) DO SR sm e e e es ms 1 e º 108 à H Huso2 H CHsCN 1096 En e 101.2 De=CQGms 77 1208 H CN HC CN 76 173 nes a a e e 1187 CN 1123 1327 1320 1294 a à In CHOI; (50%). » Saturated aqueous solution of CH;COONa. « Neat or saturated solution, “In D,O. * In DMSO. * In dioxane (--50%). trum). So-called off-resonance decoupling* is obsolete for this purpose and has been completely replaced by DEPT (Section 5.5). Beyond the number of protons attached to a BC atom, it would be nice to know which protons are at- tached to each 3C atom. In other words, what are the correlations? Chapter 6 deals with both 'H—!H and 1H— RC correlations, 5.5 DEPT: We mentioned in Section 5.4 that a DEPT spectrum distinguishes between a CH, group, a CH; group, and a CH group. No attempt will be made here to discuss the com- plex multipulse sequence for DEPT; some of the sim- pler multipulse sequences will be described in Chapter 6. The novel feature in the DEPT sequence is a variable proton pulse that is set at 45º, 90º, or 135º in three sep- arate experiments. The signal intensity at a particular time for each of the three different pulses depends on the number of protons attached to a particular carbon * The broadband decoupler is moved several thousand Hz from the proton frequency of TMS: this results in “residual” (i.e.. reduced) cou- pling by directly attached proton, thus reducing overlap of signals. However, overlap remains a serious problem. + Distortionless Enhancement by Polarization Transfer. As the name implies, sensitivity is increased by polarization transfer from the more sensitive coupled proton(s) to the less sensitive '3C atom. The APT (Attached Proton Test; see Sanders (1993)) gives similar information but lacks the sensitivity of DEPT. atom. A separate subspectrum is recorded for each of the CH. CH;,, and CH groups. The broadband- decoupled "ºC spectrum is also acquired. The presentation of subspectra can be condensed to two lines as shown in Figure 5.6 and in Chapter 6. One line (B subspectrum) shows peaks CH, and CH up, and CH, down. The other line (A subspectrum) shows the CH peaks up. Quaternary carbon atoms are not te- corded in a subspectrum since there is no attachcd pro- ton, but of course the main (conventional 2C) spectrum does show these peaks. In many laboratories, a DEPT spectrum is considered part of a routine "C spectrum. The DEPT spectrum of 2-methyl-6-methylene-7- octen-4-ol (ipsenol) is shown in Figure 5.6; the !H spec- trum has been discussed (Figure 4.49). The DEPT spec- trum labels the €, CH, CH, and CH, peaks. From lcft to right in the ºC (main) spectrum, they are as follows: €, CH, CH,, CH,, CH, CH,, CH,, CH, CH,, CH,. The triplet at à 77.0 is the solvent peak. The peaks to lhe left of the solvent peak are olefinic, and those to the right are aliphatic. At this point, we cannot assign all of the peaks: this can be done through the correlation spectra in Chapter 6. However, somc reasonable assumptions can be made. From left to right: C-6, C-7, C-8 or the CH, group on €-6; €-4,C3 or €-5; €-2,C-l or the CH; group on C-2. Since C-4 is a CH group, we are dealing with a secondary alcohol. 5.6 Quantitative Analysis Quantitative BC NMR is desirable in two situations. First, in structural determinations, it is clearly useful to Table 5.17 Some !/cy Values 5.6 Quantitative Analysis 237 = me a a — — Compound J (Hz) J(Hz) spº CH.CH; 1249 -—45 cH,CH,CH, 1192 59 (CH9.CH 142 26.7 CH;NH, 13309 cH;OH 141.0 -24 cH.CI 159.0 55 CH.CL 1780 269 CHCI, 209.0 10 1230 49.3 1340 [> H 1280 H Db 161.0 205.0 156.2 148.4 172.4 188.3 1590 cH=CH 249.0 CHC=CH 281.0 HC==N 269.0 know whether a signal results from more than onc shift- equivalent carbon. Second, quantitative analysis of a mixture of two or more components requires that the area of a signal be proportional to the number of carbon atoms causing that signal, There are four reasons that broadband-decoupled 5C spectra are usually not susceptible to quantitative analysis. 1. “O nuclci with long 7, relaxation times may not returm to the equilibrium Boltzmann distribution betwcen pulses. Thus the signals do not achieve full amplitude. 2. The nuclear Overhauser enhancement (NOE, see s27=76 (21) Section 5.1) varies among the “C nuclei, and the signal intensíties vary accordingly. 3. “The number of data points used to record the peak may not be sufficient to record the proper shape and area of the peak. 4. The pulse consists of a central frequency (») of maximum amplitude with frequencies of decreasing amplitude on both sides. Peaks resulting from these different pulse amplitudes vary in amplitude, The first problem—a long T,—can often be re- solved by inserting a pulse delay after the acquisition period to reestablish equilibrium. However, the length of time required may be prohibitive, especially for qua- ternary PC nuclei. To deal with the NOE variations, “inverse gated decoupling” (Fig. 5.7) is useful (compare “gated decou- pling,” Section 5.4). Briefly, the !H broadband decou- pler is “gated” (switched) on only during the “C pulse and the acquisition period: it is gated off during the pulse delay period. The NOE, a slow process, builds up only slightly during the pulse and acquisition period. Decoupling. a fast process, is established almost im- mediately on irradiating with the 'H broadband decou- pler, so that the end result is a number of singlets whose intensities are proportional to the number of carbon at- oms they represent. Of course, loss of part of the NOE means many repetitions to build up the signal intensity. The time required can be shortened by addition of a paramag- netic relaxation reagent, such as the metal-organic complex Cr(acac). to reduce all of the 7, and T; relax- ations. The remaining problems, which are instrumental in nature, are more difficult to deal with but are usually less important. 238 Chapter5 € NMR Spectrometry Table 5.19 Coupling Constants for “F, “P, and D Coupled to “C SS Compound 1J (Hz) 23 (Hz) 37 (Hz) “F (Hz) CH.CE, am cr, 235 CF;cCO,H 284 437 CHF 245 210 71 33 (CH,CH.CH,CH;)P 10.9 117 125 (CH;CHo)aP* Bro 49 43 (CH)sP+CH, I- 88 (CH; 52) 109 CH CBGa(OCHrCHs) 143 71 Vc0r69) — JIccor62 (CoHs)P 124 196 67 00 CDC 31.5 CDiÇCD, 19.5 (CD5)SO 20 Db 25 D D D D D 160 140 120 100 so 80 “o 20 pem FIGURE 56. DEPT spectrum of ipsenol in CDCI, at 75.6 MHz. Subspectrum A, CH up. Subspectrum B, CH, and CH up, CH, down. The conventional 2C spectrum is at the bottom of the figure. Problem 5.7 Compound B, CO. Problems 241 T T T l l 1 L L 190 180 10 160 50 40 Problem 5.7 Compound €, C, HO. 130 120 no L T j l l T l L 190 180 vo 180 150 HO 130 120 no 242 Chapter5 2C NMR Spectrometry Problem 5.7 Compound D, CHLO. T T” T T T 1 T 1 T T 1 T T T T T T l l l 1 1 l l L l j 1 l J L | 1 , j l l mo 180 170 160 150 140 130 120 110 100 90 BO TO 60 50 40 30 20 10 06. 18) Problem 5.7 Compound E, CsH,jBr. T T T y T T T T T T T T T T T T T T T 1 L Ii L L l l 1 j J j L 1 1 l l L L 190 180 170 160 150 140 130 120 110 100 90 BO 70 60 SO do 30 20 10 08. tey Problems 243 Problem 5.7 Componnd F, CJH,CIO. T T T T T T T T T T T T T T T T T T a a 5 a j L j Ii L Ii l l Ii l 1 l L L 1 | L 1 1 L 190 180 10 180 150 140 130 120 10 100 90 ao 70 so 50 a) 30 20 1 o& 11 Problem 5.7 Compound G, Cy. T T T T T T T T 1 T T T T T T T T T T T a d n | Ii l Í l Ii l 1 L l l L l J L 1 Ii L ! j L 10 180 170 160 150 140 130 120 110 "100 90 80 70 6 50 40 30 20 10 ta) 246 ChapterS “VC NMR Spectrometry Appendix B Comparison of 'H and “C Chemical Shifts "200 “o do "mo o “o do "Tê “T% 20 5% MZ Aischycies [O RMEZZ727777 NS A romotic Conjugated Alkene 777777774 VZZZIZZZA Terminal Methylena BC Shirt Range Alhkene DI “H Shirt Range Za Overiap Region DD UZZZ2272088 >eu-0 o — -cu,-o t 13, A Cru 0 cu Hand CC Chemical » Shifts DCH-NS-CH-N$ CH; NS [2227777700 -ccH TT—"um TO >en-CÊ-cHr CÊ cur CU Z7777— *CHy-Cc! "= Hu 30 -'cu-ct DAS cm-cg ZA “o “oo z0 “o z0 co so so EX) 20 se ou pH! i 1 ; (cha, 6xo1 / - .. A | th ue ATOS iso Mp do ogmame PMO Gee cHens Cho ta tcH)pc=o legend: 'H-— "E — Appendix C The BC Correlation Chart for Chemical Classes R = H or alkyl subsituents Y = polar substituemts o 180 180 140 120 Acyelic hydrocarbons —CHs ' -CH, | -CH ' ( -c- t Alicyclic hydrocarbons CaMa CsHa to CroHag Alkenes Aromaties Ar-R AY Hetergaromaties Aleohols C-OH Ethers C-0-C Acetals, Ketals o-c-o Halides C-Aus C-Cha C-Brs C-ha Amines C-NA, Nitro C-NO, Mercaptans, Sulfides === = =-—4 c-s-R Sulfoxides, Sulfones c-so-r, C-sa,-R Aldenydes, sat. RCHO Aldehydes, a, B--unsar. R-C=C-CH=0 Ketones, a, f-unsat. R-C=c-C=0 Carboxylic acids, sat RCOOH Saits RCOO” Carboxylie acids, a, f-unsar. A-C=C-COOH Esters, sat R-COOR' Esters, q, j-unsat. R-C=C-COOR' (continued) 248 Chapter5 "ºC NMR Spectrometry Appendix C (Continued) 220 200 180 Anhydrides (RCO,)0 Amides RCONH Nitriles R-CEN Oximes Rp C=NOH Carbarmates RANCOOR' Isocyanates R-N=C=0 Cyanates R-O-CSN Isothiocyanates R-N=C=S ——— Thiocyanates R-S-C2N [===—| ==