Chemical shifts heterocyclic rings

Carbon-13 NMR is often a more useful tool than H NMR for the elucidation of heterocyclic structures in which there are few or no ring protons. For symmetrically substituted 1,2,3-thiadiazoles, the carbon adjacent to the nitrogen atom is expected to have a lower field chemical shift than the carbon atom adjacent to the sulfur atom, as exemplified in CHEC-II(1996) <1996CHEC-II(4)289>. Several examples that follow this rule are illustrated in Table 5. There is now a more extensive body of data available and it is possible to more accurately predict the chemical shift of ring carbons. In the case of monosubstituted 1,2,3-thiadiazoles, the substituted carbon usually has a lower field chemical shift than the unsubstituted carbon. 

Magnetic criteria have received wide application mainly as a qualitative test for aromaticity and antiaromaticity. The values of the exaltation of diamagnetic susceptibility (in 10-6A cm-3 mol-1), and therefore aromaticity, decrease in the sequence thiazole (17.0) > pyrazole (15.5) > sydnone (14.1). The relative aromaticity of heterocycles with a similar type of heteroatom can be judged from values of the chemical shifts of ring protons. The latter reveals paramagnetic shifts when Tr-electron delocalization is weakened. For example, in the series of isomeric naphthoimidazoles aromaticity decreases in the sequence naphthof 1,2-djimidazole (8 = 7.7-8.7 ppm) > naphtho[2,3- perimidine (8 = 6.1-7.2 ppm). This sequence agrees with other estimates, in particular with energetic criteria. 

Table 2 H Chemical Shifts of Protons on the Heterocyclic Rings of Simple Benzazines cf. naphthalene, column 1)...

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

This effect allows one to monitor the perturbation of the tt-c lection system by interaction of the electrophilic phosphorus atom with a Lewis base. Following the same rationale, the still larger chemical shifts of neutral 1,3,2-diazaphospholes and 1,3,2-diazaphospholide anions are considered to reflect predominantly a reduction in n-n transition energy due to destabilization of the n(P) orbital with an increasing number of lone-pairs on the NPN-moiety rather than differences in the charge densities or n-electron distribution in the heterocyclic ring [16]. 

Rings incorporating [4 +2] rt-electrons are aromatic according to the Hiickel definition and on this basis 1,2,3-thiadiazoles can be considered as aromatic. This is supported by 13C and 111 NMR chemical shifts. In 1990, the aromaticities of some five- and six-membered ring heterocycles including 1,2,3-thiadiazole were studied by computational methods and found to correlate well with their chemical natures <1990JPR885>. 

Structure elucidation of three related derivatives of ring system 2 ( temozolomide 9a, mitozolomide 9b, and the related acid derivative 9c) has been carried out by 13C and 15N NMR spectroscopy <1995J(P1)249> (Scheme 2). The 1SN NMR chemical shifts measured in dimethyl sulfoxide (DMSO) solutions are listed in Table 1. For compound 9a, Lowdin charges of the nitrogen atoms have also been calculated and found to have a linear relationship with the experimentally determined chemical shifts of these atoms. The NMR data of 9a have been correlated with those of a series of heterocycles of related structure by the same team <2002MRC300>. 

H-NMR chemical shifts of the heterocyclic rings of selected substances are listed in Table 5 (bicyclic compounds). Table 6 (azepino[2,l-fl]isoqui-nolines). Table 7 (several pyridobenzazepines), and Table 8 (several homo-berbine-type isoquinobenzazepines). 

C-NMR chemical shifts of the heterocyclic rings of selected bicyclic compounds and of homoberbine-type isoquinobenzazepines (including the alkaloid saulatine, 11) are listed in Tables 9 and 10, respectively. Shifts of a-olefinic and (at higher field) )S-olefinic carbon atoms of enamines 77a, 288, and 292-294 and of the iminium group carbon atom in bicyclic salt 60 are found in the respective regions reported in the literature to be typical of such compounds (82T1975, p. 1986). 

The effects of the 1,2,3-triazole and 1-amino-1,2,3-triazole heterocycles on the chemical shift of the carbon atoms in the phenyl ring of compounds (40) and (41) (X = H) are compared with the value for benzene. With regard to the effects of substituent X para and meta) on the 1,2,3-triazole carbons, C(4) is deshielded by electron-withdrawing groups, whereas C(5) is shielded. Reasonable correlations with Hammett a values are observed for the chemical shifts of both C(4) and C(5) of (41) <86MRC53>. The chemical shifts of C(4) and C(5) in 5-amino-l-aryl-l,2,3-triazoles are shifted upheld by 2-5 ppm compared with the corresponding 5-anilino-1,2,3-triazoles. In 5-anilino-... 

The circulating electrons in the 7t-system of aromatic hydrocarbons and heterocycles generate a ring current and this in turn affects the chemical shifts of protons bonded to the periphery of the ring. This shift is usually greater (downfield from TMS) than that expected for the proton resonances of alkenes thus NMR spectroscopy can be used as a test for aromaticity . The chemical shift for the proton resonance of benzene is 7.2 ppm, whereas that of the C-1 proton of cyclohexene is 5.7 ppm, and the resonances of the protons of pyridine and pyrrole exhibit the chemical shifts shown in Box 1.12. 

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