Preferential substitution

For substituted allylic systems, both a- and y-substitution can occur. Reaction conditions can influence the a- versus "/-selectivity. For example, the reaction of geranyl acetate with several butylcopper reagents was explored. Essentially complete a- or y-selectivity could be achieved by modification of conditions.28 In ether both CuCN and Cul led to preferential "/-substitution, whereas a-substitution was favored for all anions in THF. 

To discover which of the groups of a-H atoms would be expected to undergo preferential substitution in RCH2COCH3 requires comparison of the formation of the relevant enols, (105) and (106) ... 

Preferential substitution at the 4-position is much less pronounced in the reaction of 2,4,6-trichloropyrimidine with arylamines, so that the dichloropyrimidine dyes formed in this... 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

Line compounds. These are phases where sublattice occupation is restricted by particular combinations of atomic size, electronegativity, etc., and there is a well-defined stoichiometry with respect to the components. Many examples occur in transition metal borides and silicides, III-V compounds and a number of carbides. Although such phases are considered to be stoichiometric in the relevant binary systems, they can have partial or complete solubility of other components with preferential substitution for one of the binary elements. This can be demonstrated for the case of a compound such as the orthorhombic Cr2B-type boride which exists in a number or refractory metal-boride phase diagrams. Mixing then occurs by substitution on the metal sublattice. 

Reaction of 2-chloropyridine gives 2-chloro-6-fluoropyridine as the major product which arises from the preferential substitution of hydrogen over chlorine and would be unexpected on the basis of the nucleophilic substitution mechanism described above. The product obtained was suggested, therefore, to arise from the addition of fluorine to the most electron rich carbon-nitrogen double bond, followed by elimination of HF [155]. 

Leherte et al. (38-40) reported a series of MD calculations for water molecules adsorbed in the ferrierite framework. The ferrierite lattice is modeled with a Si/Al ratio of 8, with the siting for aluminum atoms taken from ab initio calculations. (The T4 site is preferentially substituted.) Four unit cells were included and the lattice and intramolecular water parameters kept rigid. Three different water concentrations were considered 23, 33, and 41 molecules in 4 unit cells. 

In contrast to thiophene, benzo[6]thiophene is preferentially substituted at the /3-position. The /3 a reactivity ratios and partial rate factors for the electrophilic substitutions of benzo[6]thiophene have been summarized. The reactivity ratio varies over a wide range, depending on the nature of the electrophile and the temperature of the reaction in the case of acetylation, the percentage of the a-substituted product increases with temperature. Also in contrast to thiophene, the extended selectivity treatment applied to the reactions at the a- and /3-positions of benzo[6]thiophene gives a non-linear plot. The effect of fusion of a benzene ring to thiophene is to decrease the reactivity of the a-position and increase the reactivity of the /3-position. 

If two different kinds of ligand are coordinated, the emission lifetime will be relatively short if that ligand which is preferentially substituted in the thermal reaction lies on the weak field axis of the complex. A recent illustration of the application of these rules is with [CrCN(NH3)5]2+, for which the emission lifetime of 22 (is is indeed relatively long.52... 

In the synthesis of D-tagatose from the more common D-fructose, 1-O-benzoyl-2,3-O-isopropylidene-P-D-fructopyranose afforded two products identified as l-O-benzoyl-5-0-benzyl-2,3-0-isopropylidene-P-D-fructopyranose (97%) and its 4-O-benzyl isomer (2.8%). The skew-boat 6S4(D) conformation with an oxygen atom at C-5 adopting a quasi-equatorial position is responsible for the unexpected regioselectivity observed [136]. Conformational equilibria may also be a reason for the non-exclusive, though preferential substitution at 0-3 of benzyl 4-0-benzyl-6-deoxy-a-L-talopyranoside (9) [142]. Even in this case, however, no tri-O-benzyl derivative was formed and no starting material 9 remained, the total isolated yield of 10 and 11 being 87%. 

In some cases arylthiazoles undergo preferential substitution in the 5-position of the thiazole ring. In the case of 2-phenyl-2-thiazoline, only the... 

Preferential substitution of a face-capping chloride ligand over a facecapping chalcogenide ligand can also be accomplished. Reactions between the... 

Indole, like benzothiophene, reacts with electrophiles to give preferentially -substituted products. Bromination241-243 in dioxane or pyridine, nitration by ethyl nitrate,244 chlorination by sulfuryl chloride,245 iodination in aqueous solution,246, 247 Vilsmeier and Reimer-Tiemann formylations,248-261 diazo coupling,252 thio-cyanation,263 and nitrosation254 all give the 3-substituted indoles, practically free from other isomers. 

The methylation or carboxymethylation of cellulose in DMSO-PF solution [215] resulted in preferential substitution at the 2-OH and 3-OH groups. This was attributed to the presence of methylol groups formed mainly at the C6 position during the cellulo.se dissolution process. 

Prodine presents a case where the 3-methyl substituent has a preferred axial orientation, and in this instance the (+)-3S,4S isomer is the more potent antipode.(44) Hence, in terms of equatorial 4-phenyl chairs, the Pro-4S edge is still the preferential substitution site (as in a-prodine) but the receptor is not as selective toward axial 3-methyl (13-fold antipodal activity difference) as it is toward equatorial groups (25-fold difference) (see 21). In addition, axial 3-methyl placed along the Pro-4S edge raises potency (4x) so its role is not passive as is a similarly positioned equatorial group. 

Fluorinated aromatic chlorides " or bromides are substrates for nucleophilic substitutions however, fluorine is preferentially substituted. This is demonstrated by the formation of compound 19j in good yield. - The trifluoromethyl and the trifluorometliylsulfonate groups are activating groups that are not readily displaced. Again, chlorine. - i5i.is4 bromine, or iodine are readily substituted by alcoholates. 

The related hydrazinopyridazines are prepared almost exclusively by halogen displacement, temperatures of about 100° being usually satisfactory to bring about this reaction. The relatively easier replacement of a halogen in halopyridazines with hydrazine as compared to ammonia is certainly due to the fact that the former is a better nucleophile than the latter. Besides the differences in reactivity of unsymmetrically substituted 3,6-dihalopyridazines (Section IV, B), the preferential substitution of the 3-chlorine atom as compared to... 

A particularly illuminating study involving isotopic substitution concerns the reaction of N-tritiated diethylamine with methyl benzoate (Kitamura et al., 1977). It was found that tritium was preferentially substituted into the p-position. There was also substantial substitution in the o-position but more surprising, the methyl group of the ester was labelled. It was proposed that reaction occurs as shown in Scheme 7 via radical ions [68] and [69]. 4-Cyano-benzyl-acetate, on irradiation in the presence of triethylamine is cleaved to give 4-cyanotoluene and 4,4 -dicyanobibenzyl (Ohashi et al., 1977d). When O-deuteriated methanol was used as solvent, deuterium was incorporated... 

The position of the preferentially substituted hydroxylic groups is not known. This is probably a matter of little importance, as is, perhaps, the presence of some non-l,6-glucosidic linkages. An unknown number of one-sided bound glycerol residues is also attached to the network. 

Alkanes and arenes can also be activated to other reactions by platinum complexes in aqueous solution (57,58). For arenes in the presence of H2PtCl5, reduction from Pt(IV) to Pt(II) occurs and the arene undergoes chlorination. The reaction is catalyzed by platinum(II) (59). Similarly, if a platinum(IV) catalyst such as HjPtClg is used, chloroalkanes are formed from alkanes. As an example, chloromethane is formed from methane (Eq. 23) (60-62). Linear alkanes preferentially substitute at the methyl... 

The reverse order of replacement of halogens, i.e. preferential substitution of chlorine rather than of bromine by hydrogen in bromochloro compounds, is possible if chlorine is activated by its position in the molecule. For example, 5-bromo-6-chloro-2,4-dimethylpyrimidine, in which chlorine is rendered labile by its a-position to one of the ring nitrogens, is reduced to 5-bromo-2,4-dimethylpyrimidine by refluxing with p-toluenesulfonylhydrazine in chloroform (equation 28). ... 

In benzimidazole, electrophiles preferentially substitute in the fused benzene ring in the 5(6)-position a powerful electron donor at C-5 will direct subsequent attack to C-4 electron-withdrawing groups lead to subsequent 4- or 6-substitution. Attack at C-2 is virtually unknown. 

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