20101213第五讲氮杂环化合物核磁共振谱

2.52 (1H, q, J 8.6 Hz), 2.96 (1H, dt, J 2.2, 8.6 Hz), 2.10 (1H, ddd, 2.4, 8.6, 12.6 Hz), 2.75 (1H, td, 8.6, 12.6 Hz),
3.77 (1H, m), 3.88 (2H, m), 4.04 (1H, ddd, J 3.5, 5.9, 10.8 Hz)
Piperazine dihydrochloride salt
65
32
B. Qin et al. / Spectrochimica Acta Part A 61 (2005) 665–671
B. Qin et al. / Spectrochimica Acta Part A 61 (2005) 665–671
L. Fielding, Magn. Reson. Chem., 36, 387-397 (1998)
Z. Dega-Szafran et al. / Journal of Molecular Structure 651–653 (2003) 635–644
哌嗪类化合物
伊曲康唑
E. Inkmann, U. Holzgrabe :J. Pharm. Biomed. Anal. 20 (1999) 297–307
Isoxazolidines
SA Ali et al. ARKIVOC 2008 (xvi) 255-267
Isoxazolidines
SA Ali et al. ARKIVOC 2008 (xvi) 255-267
Azacyclohexanes
Proton spectrum of N-(2-hydroxyethyl)-morpholinium chloride in DMSO-d6. Ring inversion results in line broadening
Isoxazolidines
life times of the major specie
NI
1H NMR spectra of C5 CH3 in CD3OD
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Isoxazolidines
373K
298K +D2O
9
7 976 532 6352
李 茜, 沈文斌, 邹巧根，药学学报 2003 ,38(10) :767 - 770 李 茜, 沈文斌, 邹巧根，药学学报 2003 ,38(10) :767 - 770
盐酸西替利嗪
李 茜, 沈文斌, 邹巧根，药学学报 2003 ,38(10) :767 - 770
哌嗪衍生物
两边的取代基相同
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
哌嗪衍生物
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
哌嗪衍生物
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
盐酸洛美利嗪
297K+4 drop H2O 297K+2 drop H2O 297K+1 drop H2O 297K+1 drop H2O
297K+4 drop H2O
322K
317K
322K 307K
297K
297K
张尊建, 李
茜, 沈文斌, 徐云根，中国药科大学学报 2003 ,38(10) :767 - 770
哌嗪衍生物
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
哌嗪衍生物
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
哌嗪衍生物
两边的取代基相同
L.H. Gan et al. J. Colloid Interface Sci. 183, 329–338 (1996)
kaspar
15
Z. Chilmonczyk et al. J. Mol. Struct. 385, 195–207 (1996)
Buspirone analogues
Z. Dega-Szafran et al. / Journal of Molecular Structure 651–653 (2003) 635–644
4
R1 R
4
+ R2 N X- R3
enantiomers that can be resolved 对映体可以能拆分开
胺类化合物的手性
在环状化合物中，氮原子的翻转速度大大降低，在室 温下就可以区分对映体。
Azacyclohexanes
There is a conformational change in the ring as well as inversion at the pyramidal nitrogen. Therefore it is difficult to say whether the axial-equatorial equilibrium is achieved by ring inversion, or by nitrogen inversion
哌嗪类化合物
加入不同摩尔比的DCl之后，各个位置化学位移的变化
E. Inkmann, U. Holzgrabe :J. Pharm. Biomed. Anal. 20 (1999) 297–307
哌嗪类化合物
加入不同摩尔比的DCl之后，各个位置化学位移的变化
E. Inkmann, U. Holzgrabe :J. Pharm. Biomed. Anal. 20 (1999) 297–307
Favorable pseudoequatorial orientation
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Isoxazolidines
SA Ali et al. ARKIVOC 2008 (xvi) 255-267
Isoxazolidines
Synthesis of isoxazolidines
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Isoxazolidines
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Buspirone analogues
Z. Dega-Szafran et al. / Journal of Molecular Structure 651–653 (2003) 635–644
Isoxazolidines
NI
1H NMR spectra in CDCl3
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Isoxazolidines
NI
75:25
1H & 13C NMR spectra in CDCl3
SA Ali et al. Can. J. Anal. Sci. Spectrosc. 53, 66-74,2008
Buspirone analogues
kaspar
Z. Chilmonczyk et al. J. Mol. Struct. 385, 195–207 (1996)
Freebase in CD2Cl2+CFCl3
kaspar
Hydrochloride in CDCl3
18
21,21’
15
15
Z. Chilmonczyk et al. J. Mol. Struct. 385, 195–207 (1996)
Z. Dega-Szafran et al. Journal of Molecular Structure 704 (2004) 129–137
Steroidal Neuromuscular Blocking Drugs
L. Fielding, Magn. Reson. Chem., 36, 387-397 (1998)
Piperazine dihydrochloride salt
5 2 6 3
B. Qin et al. / Spectrochimica Acta Part A 61 (2005) 665–671
Piperazine dihydrochloride salt
65
32
B. Qin et al. / Spectrochimica Acta Part A 61 (2005) 665–671
L. Fielding, Magn. Reson. Chem., 36, 387-397 (1998)
Steroidal Neuromuscular Blocking Drugs
400 MHz 1H NMR spectra of (a) 1 in CDCl, (b) 2 in CDCl3, (c) 3 in DMSOd6 and (d) 4 in CDCl3. Sample: 10 mg ml/m1, 52C
L. Fielding, Magn. Reson. Chem., 36, 387-397 (1998)
Steroidal Neuromuscular Blocking Drugs
Expansion of the 400 MHz 1H NMR spectrum of 1 (10 mg ml/ml) showing the signals from protons b to N+. (a) CDCl3 at 22C; (b) CDCl3 at 52C; (c) CDCl3-toluene-d (30 : 70) at 52C.
盐酸西替利嗪
298K
Hydrochloride 298K
333K
353K
当加入4 滴D2O 后,所有质子和碳信号均变为 尖锐的峰形。此结果表明当加入适量的重水 (亦即氮上的质子与D 原子交换) 后, 哌嗪环以 稳定的椅式构象存在。这是由于当加入 D2O 后,H 质子被D 原子所交换,而形成N-D 键。由 于后者的键能为前者的6～8 倍,因此哌嗪环的 椅式构象要产生翻转的活化能大为增加 ,其构 象翻转不再容易,仅以稳定的椅式构象存在,因 而仅能观察到其稳定构象的核磁共振信号。
Steroidal Neuromuscular Blocking Drugs
invisible in 13C NMR spectra
Nitrogen inversion occurs at a similar rate to ring reversal in saturated six-membered heterocycles, which allows an N-alkyl group to remain equatorial.
氮杂环化合物的核磁共振谱
Structure of Amines
H
N H H H sp3 hybridized
N H H H
X
ammonia 氨
ammonium salts 铵盐
amine 胺
R'
R"" N H H R' N H R'' R' N R''' R'' R' N R''' R''
primary amine
secondary amine
tertiary amine
quaternary ammonium salts季铵盐
胺类化合物的手性
胺类化合物的手性
R1 R2 R
3
6 kcal mol-1Βιβλιοθήκη BaiduN
R1 R2 R3
N
极快速的翻转使得我们不能区分对映体的存在。
胺类化合物的手性
R1 R2 R3 + N XR