Aromatic solvent-induced shifts

Convincing evidence was found that the majority of acyclic aldo-nitrones exist in the Z-form, by investigating the ASIS-effect (aromatic solvent induced shift effect) (399). However, in some cases, specified by structural factors and solvent, the presence of both isomers has been revealed. Thus, in C -acyl-nitrones the existence of Z -and -isomers was detected. Their ratio appears to be heavily dependant on the solvent polar solvents stabilize Z-isomers and nonpolar, E-isomers (399). A similar situation was observed in a- methoxy-A-tert-butylnitrones. In acetone, the more polar Z-isomer was observed, whereas in chloroform, the less polar E-isomer prevailed. The isomer assignments were made on the basis of the Nuclear Overhauser Effect (NOE) (398). /Z-Isomerization of acylnitrones can occur upon treatment with Lewis acids, such as, MgBr2 (397). Another reason for isomerization is free rotation with respect to the C-N bond in adduct (218) resulting from the reversible addition of MeOH to the C=N bond (Scheme 2.74). The increase of the electron acceptor character of the substituent contributes to the process (135). 

In this context, it should be pointed out that the correlation between aromatic solvent-induced shifts (ASIS) and the axial or equatorial orientation of protons in cyclic sulfoxides and sulfites is quite distinct (211-213) and may be utilized in the assignment of configurations. For instance, the absolute configuration at sulfur was assigned to the penicillin sulfoxide 202 based on analysis of the effect of aromatic solvents on the chemical shifts of protons of the thiazolidine ring (214,215). 

Generally solvents chosen for NMR spectroscopy do not associate with the solute. However, solvents which are capable of both association and inducing differential chemical shifts in the solute are sometimes deliberately used to remove accidental chemical equivalence. The most useful solvents for the purpose of inducing solvent-shifts are aromatic solvents, in particular hexadeuterobenzene (CgDg), and the effect is called aromatic solvent induced shift (ASIS). The numerieal values of ASIS are usually of the order of 0.1 - 0.5 ppm and they vary with the moleeule studied depending mainly on the geometry of the complexation. 

This aromatic solvent induced shift (ASIS) is explained by the formation of preferential collision complexes or clusters of aromatic solvent molecules in the vicinity of the polar groups of the solute, so that the effect of the solvent magnetic anisotropy within the space occupied... 

In addition, aromatic solvent induced shifts (ASIS, see Section 4.1.1.4.) can be useful for structural assignments in this class of compounds 286. 

Lanthanide shift reagents have been used to differentiate diastereomeric oximes, dinitrophenyl-hydrazones 304,305, and nitrones 306. A collision complex model to rationalize aromatic solvent induced shifts in the spectra of oximes and hydrazones has been developed305,307. 

Aromatic solvent induced shifts assisted in the stereochemical assignment of highly substituted cyclobutanes470. NMR measurements in the presence of lanthanide shift reagents are useful for azetidines471 and cis- and rra ,v-2-ethenylcyclobutanecarbonitrile472. 

There are marked solvent effects as illustrated in Table 12. Especially the ASIS (aromatic solvent induced shift, 5CDC 3 — 8< d6) f°r H(l) is large. Besides, concen-... 

Compared with the pronounced solvent-induced chemical shifts observed with ionic and dipolar solutes, the corresponding shifts of nonpolar solutes such as tetrame-thylsilane are rather small cf. Table 6-6. A careful investigation of chemical shifts of unsubstituted aromatic, as well as alternant and nonalternant, unsaturated hydrocarbons in aliphatic and aromatic non-HBD solvents by Abboud et al. has shown that the differential solvent-induced chemical shift range (relative to benzene as reference) is of the order of only —1.4...+1.0 ppm (positive values representing downfield shifts) [405]. The NMR spectra of these aromatic compounds have been shown to be sensitive to solvent dipolarity and polarizability, except in aromatic solvents, for which an additional specific aromatic solvent-induced shift (ASIS see later) has been found. There is no simple relationship between the solvent-induced chemical shifts and the calculated charge distribution of the aromatic solute molecules. This demonstrates the importance of quadrupoles and higher multipoles in solute/solvent interactions involving aromatic solutes [405]. 

Specific solvent effects on the resonance positions of the nuclei of dissolved compounds consist mainly of hydrogen-bonding effects and aromatic solvent-induced shifts (ASIS effects). The interactions between the solute and the surrounding solvent molecules lead, in these cases, to molecular species which are more or less definable entities. If the... 

When a dipolar molecule is dissolved in a magnetically anisotropic solvent consisting of disc-shaped molecules, e.g. benzene, the NMR signals of the solute H-atoms are usually shifted upheld with respect to their positions in an isotropic solvent such as 2,2-dimethylpropane (neopentane) or tetraehloromethane cf. the preceding discussion of (Ta in Eq. (6-21). The specific solvent-induced H NMR chemical shift of a solute H-atom signal when the solvent is changed from a reference aliphatic solvent to an aromatic solvent is called aromatic solvent-induced shift (ASIS) and is defined according to Eq. (6-24) [278, 279],... 

Manumycin A (52) was the first metabolite isolated from Streptomyces parvulus (strain Tii 64) [110] and its structure and absolute configuration have been described [111]. Other minor components such as manumycin B (53), C (54) and D (55) have similar structural moieties indicating their close structural and biosynthetic relationship [112]. These other compounds differ in the polyketide assembly of the acylamino side chain and in the stereochemistry at C-4. Manumycin D (55) is the first of the manumycin type compounds without an oxirane ring in the mC7N unit. Their structural elucidation has been recently carried out [112] by H NMR spectroscopy using aromatic solvent induced shift (ASIS) effects at the olefinic 3-H and circular dichroism (CD) spectroscopy has been used to determine the absolute stereochemistry of the mC7N unit. 

Solvation and Shift Reagents.—The solvation parameters for a series of alcohols have been determined using the n.m.r. chemical shift of tris-n-butylphosphine oxide. Ion pair association between tetraphenylboron and cationic centres was used to study the electronic structure of aminonaphthylphosphonium salts (24 X = Ph4B ). Shift reagents have been used in the conformational analysis of adenosine phosphates and aromatic solvent induced shifts to probe the stereochemistry of butadienylphosphonates and their polymers. The geometries of difluorophosphine derivatives were evaluated from liquid crystal n.m.r. studies with the aid of electron diffraction. ... 

Factor (c) appears to depend on complex interacting effects and deserves detailed discussion. When the proton nmr spectrum of a polar substance, typically but not always a ketone (83), dissolved in an aromatic hydrocarbon is compared with that obtained in a saturated hydrocarbon, large shifts of up to 1.5 ppm are frequently observed. These shifts are either upfield or downfield, depending on the stereochemistry of each proton-bearing group (84). This general behavior, known as ASIS (aromatic solvent-induced shifts), has been reviewed by Foster and Lazio (85). 

After the feasibility study on strychnine, the bis-alkaloid vinblastine 19 was investigated by C-N HSQC-HMBC obtained again from H-C HSQC and H-N HMBC [27]. For the prediction and recognition of artefacts from spectra overlap, Martin et al. applied the approach based on indirect covariance of the parent HSQC, and aromatic solvent induced shift, which proved successful. The authors stated that no new information was created by UIC but a favourable visualization scheme was used. Figure 5.16 presents an example of a C-N correlation. 

Some spectral data, including PMR and UV, that have recently become available include the three examples cited below. In PMR experiments, when the solvent is changed from deuteriochloroform to the aromatic and anisotropic benzene-de or pyridine-dg which are capable of forming collision complexes, it is found that protons ortho to a phenolic hydroxyl show larger deshielding than protons in the meta or para positions. This phenomenon, commonly called aromatic solvent induced shifts (ASIS), has been used to locate the site of the phenolic function in the new alkaloid protothalipine found in Thalictrum rugosum Ait. (T. glaucum Desf.) (Ranunculaceae). ... 

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