核磁共振波譜分析11課件

1、1習(xí)題：習(xí)題：化合物化合物b的分子結(jié)構(gòu)如下，請根據(jù)其結(jié)構(gòu)及相應(yīng)的的分子結(jié)構(gòu)如下，請根據(jù)其結(jié)構(gòu)及相應(yīng)的的的2d nmr譜對譜對1h和和13c nmr進(jìn)行歸屬。進(jìn)行歸屬。1234567891023456784a8a28.16處的信號可被處的信號可被d2o交換交換: 8.16 ppm (oh)1h nmr譜譜h: 8.16; 7.65(d); 7.17; 7.04; 6.20(d); 5.31(t); 5.08; 3.36(d); 2.15(m); 2.10(m); 1.69; 1.66; 1.577.65 (d), 6.20 (d): 3-h, 4-h 7.17, 7.04: 5-h, 8-h1.

2、69 (s), 1.66 (s), 1.57(s): 4-h, 9-h, 10-h5.31 (t), 5.08: 2-h, 7-h3.36 (d), 2.15 (m), 2.10 (m): 1-h, 5-h, 6-h31h-1h cosy譜譜7.65 (d), 6.20 (d): h-3, h-45.31 (t), 3.36(d): h-2, h-15.31 (h-2), 3.36 (h-1)5.08, 2.15, 2.10: h-7, h-6, h-55.08 (h-7), 2.15 (h-6), 2.10 (h-5)4162.9; 158.8; 153.9; 138.1; 131.6; 1

3、26.2; 124.0; 120.9; 111.7; 112.013c-1h cosy的的dept譜譜144.7 (c) - 7.65 (h)128.1 (c) - 7.17 (h)103.0 (c) - 7.04 (h)39.6 (c) - 2.10 (h) 527.9 (c) - 3.36 (h) 126.4 (c) - 2.15 (h) 625.7 (c) - 1.66 (h)17.6 (c) - 1.57 (h)16.1 (c) - 1.69 (h)5coloc譜譜162.9 (c) - 7.65 (h)162.9 (c-2) 27.9 (c-1) - 7.17 (h)7.17 (h-

4、5), 128.1 (c-5)7.04 (h-8), 103.0 (c-8)7.17 (h-5) - 158.8, 153.9, 144.7, 128.1(c)144.7 (c-4), 7.65 (h-4)6.20 (h-3), 153.9 (c-8a or c-7)7.04 (h-8) - 126.2, 112.0, 103.0(c)112.0, 126.2 (c-4a, c-6)6.20 (h-3) - 111.7(c)111.7 (c-3)6coloc譜譜1.66 (h) - 17.6, 25.7, 131.6, 124.0(c)124.0 (c-7), 131.6 (c-8)17.6

5、(c-9), 1.57 (h-9)25.7 (c-10), 1.66 (h-10)1.69 (h-4), 16.1 (c-4)由于由于c-6的處于的處于c-9的順的順 式，式，-旁式效應(yīng)使旁式效應(yīng)使c-9位位于較高場于較高場(17.6), c-10位于位于較低場較低場(25.7)1.69 (h-4) - 16.1, 138.1 (c)138.1 (c-3), 120.9(c-2)7還沒有歸屬的氫有：還沒有歸屬的氫有：5.31 (t), 5.08: h-2, h-7比較比較2和和7所處的環(huán)境，由于取代基和空間位租效應(yīng)，所處的環(huán)境，由于取代基和空間位租效應(yīng)，2應(yīng)該比應(yīng)該比7處于更低場的位置。處于更

6、低場的位置。5.31(h-2), 5.08 (h-7)還沒有歸屬的碳有：還沒有歸屬的碳有：112.0, 126.2: c-4a, c-6158.8, 153.9: c-7, c-8a8coloc譜譜7.65 (h-4) - 162.9(c-2), 153.9, 144.7 (c-4), 128.1 (c-5)153.9 (c-8a), 158.8(c-7)6.20 (h-3) - 111.7(c-3), 111.2111.2 (c-4a), 126.2(c-6)91234567891023456784a8ah: 6.20 (d, h-3), 7.65 (d, h-4), 7.17 (h-5),

7、 7.04 (h-8), 3.36 (d, h-1), 5.31 (t, h-2), 1.69 (h-4), 2.10 (m, h-5), 2.15 (m, h-6), 5.08 (h-7), 1.57 (h-9), 1.66 (h-10), 8.16 (oh)c: 162.9 (c-2), 111.7 (c-3), 144.7 (c-4), 112.0 (c-4a), 128.1 (c-5), 126.2 (c-6), 158.8 (c-7), 103.0 (c-8), 153.9 (c-8a), 27.9 (c-1), 120.9 (c-2), 138.1 (c-3), 16.1 (c-4

8、), 39.6 (c-5), 26.4 (c-6), 124.0 (c-7), 131.6 (c-8), 17.6 (c-9), 25.7 (c-10)structure determination with nmrstrategies & tools in structure elucidation- the structure of taxol -pter sndorvarian deutschland gmbh11from sample to structure?12strategyinformation from nmr: # protons, 1h chemical shif

9、ts, 1h-1h couplings . 1h spectrum # magnetically nonequivalent carbons . 13c spectrum # nmr-detectable x nuclei (19f, 31p) . x spectrum 1h-13c direct correlation (one-bond) . hsqc (hetcor) identification if 1h spin systems . tocsy1h sequential assignment . cosy1h-x (13c, 15n, 19f, 31p.) long-range c

10、orrelation . hmbc stereochemistry, 3d structure . noesy, roesy13sample & instrumenttaxol sample: antineoplastic, anti-cancer drug c47h51no14 molar weight: 853.906 concentration: 5.2 mg in 0.6 ml cdcl3 = 10 mmolarinstrument:inova 500 mhz 4 channels (only 2 used here)1h,13c,15n triple resonance pr

11、obe pulsed field gradient unit waveform generators141h spectrum of taxolppm2345678ppm4.24.34.44.54.64.74.84.91h ppmexp. time 1 min 1513c spectrum of taxolppm20406080100120140160180200ppm128.0129.0130.0exp. time 14 h13c ppmcoaromaticch,ch2ch316chemical shifts1h shifts8.06 (2)7.67 (2)7.54 (1)7.44 (2)7

12、.43 (1)7.41 (2)7.35 (2)7.33 (2)7.28 (1)6.91 (1)6.21 (1)6.16 (1)5.72 (1)5.61 (1)4.87 (1)4.72 (1)4.33 (1)4.23 (1)4.13 (1)3.73 (1)3.48 (1)2.47 (1)2.38 (1)2.31 (3)2.29 (1)2.22 (1)2.17 (3)2.10 (imp.)1.81 (1)1.73 (1)1.72 (3)1.62 (3)1.53 (h2o)1.17 (3)1.08 (3)13c shifts203.61 172.72171.22170.35167.04167.011

13、41.95137.99133.71133.65133.23131.97130.21 (2)129.18129.03 (2)128.72 (2)128.70 (2)128.37127.04 (2)127.04 (2) 84.41 81.19 79.05 76.52 75.57 74.98 73.20 72.41 72.18 58.65 55.04 45.64 43.19 35.72 35.63 26.88 22.63 21.83 20.84 14.83 9.57(1h) = 51(13c) = 4717correlate protons and carbons2d hsqc: heteronuc

14、lear single quantum coherenceh1h3h4h2ac4 c1c2c31h chemical shiftcorrelate x-1h chemical shifts via one-bond 1j(x,h) couplingsch3cchhhch313c chemical shifth2b182d hsqc spectrum of taxolf1 (ppm)455055606570758085f2(ppm)4.04.24.44.64.85.05.25.45.65.86.06.2f1 (ppm)455055606570758085f2(ppm)4.04.24.44.64.

15、85.05.25.45.65.86.06.21h ppm13c ppmexpansion of the gradient 1h-13c hsqc spectrum 1 scan per increment 256 increments in f1 exp. time 15 min191h-15n hsqc of taxolf2 (ppm)2345678f1(ppm)110.5111.0111.5112.0112.5113.0113.5f2 (ppm)6.846.886.926.967.00f1(ppm)111.6111.8112.0112.2112.4112.6112.8113.0xnhox6

16、.9115n ppm1h ppmgradient 1h-15n hsqc spectrum 8 scans per increment 64 increments in f1 exp. time 30 min20conclusions from hsqc cross peaks in 13c hsqc: assigned 26 1h-13c pairs cross peaks in 15n hsqc: assigned 1 1h-15n pair positive peaks, integrals 1 & 3 in 1h 1d: 17 ch & 6 ch3 groups neg

17、ative peaks, two shifts in 1h dimension: 3 ch2 groups absent in 13c hsqc but present in 13c 1d: 15 quaternary carbons absent in 13c hsqc but present in 1h 1d: 1 exchangeable nh proton21determine coupling networks2d tocsy: total correlation spectroscopyxh1r2or1oh2h3h4h1h2h3h4xxxxxxxidentify protons b

18、elonging to the same scalar coupling network / spin system1h chemical shift1h chemical shift22f1 (ppm)7.37.47.57.67.77.87.98.08.1f2(ppm)7.47.57.67.77.87.98.08.12d tocsy spectrum of taxolexpansion of the tocsy spectrum 2 scans per increment 256 increments in f1 exp. time 32 min7.37.47.57.67.77.87.98.

19、08.1f2(ppm)7.47.57.67.77.87.98.08.17.41, 7.35, 7.287.67, 7.43, 7.338.06, 7.54, 7.44f1 (ppm)1h ppm1h ppm23sequential assignment2d cosy: correlation spectroscopyh1h2h3h4h1h2h3h4h4h4h3h3h1h1h2h2correlate scalar coupled protonsxh1r2or1oh2h3h4h1h2h3h4xxxxxxx24f2 (ppm)2.02.53.03.54.04.5f1(ppm)2.02.53.03.5

20、4.04.52d dqcosy spectrum of taxoloo hhhhh2.384.332.471.814.8784.4135.6372.18xxxsequential assignment of spin system spin system known from tocsy geminal pairs known from hsqcexpansion of the dq-cosy spectrum 1 scan per increment 640 increments in f1 exp. time 40 min1h ppm1h ppm25substructures of tax

21、olaxbxcxxnhoo hhhxxoch3hhhxxxxohhxxxohhxxc h3c h3xxoohhhhhxxx9 substructures assigned26long range couplingsch3cchhhch3c5c3c4c11h chemical shifth5h4h2bh1h2a13c chemical shift2d hmbc: heteronuclear multiple bond coherencecorrelate 13c-1h chemical shifts via long-range 2,3j(x,h) couplings1235c4oc2272d

22、hmbc spectrum of taxolf1 (ppm)20406080100120140160180200f2(ppm)2345678f1 (ppm)20406080100120140160180200f2(ppm)2345678gradient hmbc spectrum 4 scans per increment 1024 increments in f1 optimized for 6 hz coupling exp. time 2 h13c ppm1h ppmcoarom.ch,ch2ch328connect substructuresf1 (ppm)16016116216316

23、4165166167168169170171172173174f2(ppm)5.86.06.26.46.66.87.05.72167.016.91f1 (ppm)60708090100110120130140150160f2(ppm)7.57.67.77.87.98.08.1167.048.067.677.41167.0155.04expansions of the gradient hmbc spectrumaxo167.01127.04128.72131.97133.237.677.337.42nhoooohhh6.915.723.484.7255.0473.20x167.01xxb7.4

24、17.35128.37129.03127.04137.997.28x29full assignment of taxolbcanhoooooooooohooch3ohohch3ch3ch3ch3ch3hhhhhhhhhhhhhh167.01127.04128.72131.97133.237.677.337.427.417.357.28128.37129.03127.04137.99129.18130.21133.71128.70167.048.067.447.546.915.723.484.726.162.292.221.731.725.611.171.082.176.213.731.622.384.332.471.814.874.234.132.3155.0473.20172.7214.83141.95133.2372.4135.7279.0543.19171.2228.8475.5726.8821.83203.619.5758.6545.6481.19170.3576.5222.6384.4135.6372.1874.9830stereochemistrynhoooooooooohooch3ohohch3ch3ch3ch3ch3hhhhhhhhhhhhasym