TV-methyl groups

N-Methyl-E-cinnamide and p-chloro- -cinnamide were consequently tested as suitable additives. Both cause cinnamide crystals to grow as thin 100 plates (Figure 4c). In the presence of the former, the TV-methyl group of the additive molecule, which invariably adopts the synplanar conformation 3a (SO), prevents formation of the dimer, thus inhibiting the attachment of additional cinnamide molecules along a. The additive p-chloro-E-cinnamide inhibits the deposition of oncoming 100 layers, due to steric hindrance induced by the bulky chlorine atom. 

These systems have lower ring inversion barriers than their oxygen analogues. The 3,4-dimethyl derivative exists at low temperature in a preferred conformation with the 3-TV-methyl group axial (42 R = H). This preference is enhanced by the presence of an... 

Verapamil, a slow calcium channel antagonist used in treatment of angina, hypertension and superventricular tachycardia56,57, labelled with 13C in the 1-position of the phenethyl side chain, 61, and with 13C-labels in all four O-methyl groups, 62, and also containing 50% of 13C in the TV-methyl group, 62, has been prepared58 in multistep syntheses which involved, in the case of the synthesis of 61, the displacement of mesylate 63 with N-methyl-2-(3,4-dimethoxyphenyl)-l-[13C]-ethyl amine, 64 (equation 25). 

Several groups have examined the 13C spectra of the aporphine alkaloids (6, 7, 38-40) examples are found in Fig. 10. The chemical shift assignments (Table X) for the aliphatic carbon atoms of rings B and C were made by comparison to laudanosine (28) (6) and to the reduced proaporphines (41). In the case of caaverine (49) a comparison with (+)-lirmidine (50) revealed the P deshielding effect of the TV-methyl group on C-5 and C-6a and the shielding of C-7 by a y effect. 

Chemical shifts for aromatic azoles are recorded in Tables 17 and 18. Fast tautomerism renders two of the 13C chemical shifts equivalent for the NH derivatives (Table 17a), as in the proton spectra (Table 8a). However, data for the N-methyl derivatives (Table 17b) clearly indicate that the carbon adjacent to a pyridine-type nitrogen shows a chemical shift at lower field than that adjacent to a pyrrole-type TV-methyl group (in contrast to the H chemical shift behaviour). Solid-state studies on imidazole (and pyrazole) show there are three distinct signals for the annular carbon atoms (imidazole C(2), 136.3 C(4), 126.8 C(5), 115.3 ppm). Proton exchange does not occur in the solid, hence the spectra describe the structure in the crystal. Comparison with the corresponding chemical shifts for 1-methylimidazole (137.6, 129.3, 119.7 ppm) implies that tautomerism has been frozen in the solid state <1981CC1207>. Solid-state examination of 2,2/-bis-17/-imidazole also reveals frozen tautomerism. 

One of the major stumbling blocks in the clinical use of leurocristine (VCR) is the substantial difference in availability of this compound compared to vincaleukoblastine (VLB), itself a rare alkaloid. Clearly one of the ways to improve the yield of VCR is to oxidize the TV-methyl group to an TV-formyl group either chemically or microbiologically. Because the unit requiring refunctionalization is the vindoline portion, it was reasoned that initial work would be most effectively carried out with vindoline (101) as the model compound. 

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