INDEX ring formation

Whereas small alkyl substituents such as methyl are tolerated at the C2 carbon, larger substituents (i.e., R = phenyl) that restrict the free rotation decrease neuroleptic potency. Additionally, if rotation is restricted through ring formation as in (4), the chlorpromazine index is greatly reduced (295). Rotation restriction through ring formation at the 3-posi-... 

The most interesting studies included the evaluation of the reactivity of the same radicals for two different reaction paths, 16 and 17. The computational studies correctly selected path 16 as the most reactive one. However, the question remains is there sufficient selectivity to accomplish only transformation 16. The computed selectivity index was 0.0336 (0.1216-0.0980). These values assured the formation of products only through a five-memebered ring formation. This was in full agreement with experimenal results [128]. It is well known that a secondary radical is more stable than a primary radical. The calculations supported this by favoring the cyclohexyl radical by 7.7 kcal/mol over the cyclopentylmethyl radical. Therefore, formation of the six-membered ring product was thermodynamically controlled. 

The authors justified their result considering that the bond index [Br = (coefficient r LUMO) (coefficient s LUMO) ] on the LUMO accounted for the formation of the Dewar isomer on the central ring of the trithiazole. By contrast, calculations show that the Dewar isomer should be formed on the third ring of the trithiazole (Fig. 17) (99MI233). 

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

Sulfur. Thiophene and benzo[ >] thiophene are both aromatic heterocycles, as discussed earlier in this review. Isothiazole is a planar molecule with an aromaticity comparable with those of thiazole and pyrazole, and higher than those of isoxazole and oxazole,122 140 as evaluated on the basis of Bird s aromaticity index A, based upon the statistical degree of uniformity of the bond orders of the ring periphery. Theoretical calculations and experimental data in connection with the aromaticity of isothiazole have been reviewed.141 Thiazole is also viewed as an aromatic molecule, similar to thiophene. It lacks an experimental aromaticity value, but the heat of formation together with bond lengths and angles have been calculated by various computational meth-... 

The important field of ionic liquids, in most cases 1,3-dimidazolium salts (143) has been studied by IR and Raman spectroscopies supported by B3LYP calculations. Additionally, calculations of the heteroaromaticity (HOMA index) showed that cation formation causes a decrease of the aromaticity of the imidazole ring. However, when the R groups at positions 1,3 are benzyl or adamantyl, the aromatic nature of the heterocyclic moiety increases. Moreover, the electron distribution performed using the GAPT method indicated the positive charge delocalization in the imidazolium ring [143],... 

Pyrazine A-oxides have continued to attract much attention in recent years, perhaps because the presence of an A-oxide entity can substantially modify the properties of the whole system, especially in respect of activities at other positions on the ring. For example, the aromaticity index for 2-methoxypyrazine is decreased by 23% on formation of its 4-oxide 383 and formation of an A-oxide activates adjacent positions toward direct bromination,782deuteration,1457 and other electrophilic attack.1078... 

The aromaticity index of the ring system (20) has been calculated and compared with related systems <87T4725>. Quantum chemical calculation for the formation of some derivatives of ring system (24) (e.g., (130), see 8.17.6.5.2) suggested that the cyclization is quite asynchronous and can be regarded as a Diels-Alder reaction of inverse electron demand <90JCS(P2)1943>. 

Assuming =0 in equations (8) and (l)-(6) we obtain the auxiliary problem for the function 0, = T Y, + qZ, where index i=l denotes temperature in cemented area and i=2 - temperature in the rock formation. Introducing the mean temperature of the cemented ring with internal radius r=ro and external radius r=l as... 

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