The site of nucleophilic attack

Two processes that are consistent with second order kinetics both involve hydrox ide ion as a nucleophile but differ in the site of nucleophilic attack One of these processes is an 8 2 reaction in which hydroxide displaces carboxylate from the alkyl group of the ester... 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

FIGURE 7.13 Molecular model of the pyrrolo [ 1,2-<2] i ndol e showing the site of nucleophile attack that provides a favorable stereoelectronic effect. The inset shows expected orbital interactions. 

In the envisaged titanium oxo complex, the Ti atom is side-bound to the peroxy moiety (02H), consistent with all the spectroscopic results mentioned in Section III in Scheme 27, between the two O atoms that are side-bound to Ti4+, the O atom attached to both the Ti and H atoms is expected to be more electrophilic than the O atom attached to only the Ti atom and is likely to be the site of nucleophilic attack by the alkene double bond. The formation of the Ti-OH group (and not the titanyl, Ti=0, as proposed by Khouw et al. (221)) after the epoxidation and its subsequent condensation with Si-OH to regenerate the Ti-O-Si links had been observed (Section III.B) by FTIR spectroscopy by Lin and Frei (133). Because this is a concerted heterolytic cleavage of the 0-0 bond, high epoxide selectivity and retention of stereochemistry may be expected, as indeed has been observed experimentally (204). 

Fully conjugated l,4-(oxa/thia)-2-azoles are electrophilic in character and this is mainly expressed by their tendency to react exclusively with nucleophiles. The site of nucleophilic attack is either the partly positively charged ring carbon atom of the azolylium cations, or the sp ring carbon of the exocyclic double bond. The other carbon atom of the ring seems to be unreactive. 

Investigation of the reaction of 3,3-disubstituted 1,2-dioxetanes with various heteroatom nucleophiles establishes the SN2 reactivity of these strained peroxides [134]. As reported in Sch. 80 for dioxetane 141, the sterically exposed oxygen of the peroxide bond becomes the site of nucleophilic attack to produce an anionic or zwitterionic adduct 142. Different reaction channels become available for the intermediate which depend on the chemical nature of the nucleophile. So epoxy alcohol 143, p-hydroxy hydroxylamine 144, diol 145, cyclic carbonate 146, and cyclic sulfite 147 can be obtained (Sch. 80) [134],... 

The reactions proceeded regioselectively, the less hindered oxygen being the site of nucleophilic attack by the enamine. 

An interesting feature of the kinetic data in Table VI is the relative insensitivity of the k0H/kHl0 ratio to substituent effects within a series of structurally related cations. Thus, for quinolinium and isoquinolinium cations, kOH/kH20 is within a factor of 2 of 2 x 107 M-1 for at least a 100-fold variation in each of k0H and kHl0. Similarly, km/kHl0 is the same within experimental error (2.4 x 105 M l) for the 10-methylacridinium cation and its 9-phenyl derivative despite a major structural variation at the site of nucleophilic attack and a resulting 400-fold difference in koH for these two cations. 

Fig. 4.11 LUMOs of some carbon electrophiles, and the sites of nucleophilic attack upon...

We are then left with the influence of the remaining ring fluorine atoms on the substitution process. In reality, halogen atoms that are at positions ortho, meta and para to the site of nucleophilic attack (Figure 9.25) have different effects these separate activating influences have been derived from the data contained in Table 9.5 [91, 94]. 

Electrostatic potential maps have been used to make predictions similar to these (Scrocco and Tomasi 1978). Such maps, however, do not in general reveal the location of the sites of nucleophilic attack (Politzer et al. 1982), as the maps are determined by only the classical part of the potential. The local virial theorem, eqn (7.4), determines the sign of the Laplacian of the charge density. The potential energy density -f (r) (eqn (6.30)) appearing in eqn (7.4) involves the full quantum potential. It contains the virial of the Ehrenfest force (eqn (6.29)), the force exerted on the electronic charge at a point in space (eqns (6.16) and (6.17)). The classical electrostatic force is one component of this total force. 

The stereoselectivity is high. For unsymmetrically substituted cyclopropanes, electrophilic attack by the Hg(II) species can occur with predominant retention or inversion, but there is always inversion of configuration at the site of nucleophilic attack". ... 

Ethyl rhenlumpentacarbonyl has been reacted with various metal hydrides in acetonitrile 158). The observed products were heterobimetallic compounds, although a solvated rheniumtetracarbonyl acyl complex was detected [Eq. (47)]. If the metal hydride is in excess, the rate-determining step is formation of the propionyl complex. The reaction was subsequently found to be first order in both the propionyl complex and the metal hydride. The second-order rate constants were measured and were found to be the reverse of the order of the acidities of the transition metal hydrides, which implies that the hydrides react as nucleophiles with the propionyl complex. In a separate experiment, [Re(COEt)(CO)j] was found to react with [Re(H)(CO)j] only after carbonyl dissociation, implying that the metal and not the acyl carbonyl is the site of nucleophilic attack by transition metal hydrides on acyl complexes. 

Sn2 goes via inversion at the site of nucleophilic attack, and S l usually goes by racemization. 

Recently, the regioselectivity of nucleophilic attack on (endo-dicyclopentadiene-PdCl2) has been used to confirm theoretical predictions concerning the mode of olefin activation by transition metals. Calculations suggest that olefin activation can occur by a lateral slipping of the olefin away from the symmetrical h geometry. The carbon most distant from the metal develops a partial positive charge and is predicted to be the site of nucleophilic attack . 

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