Nucleophile solvent dependence

The order of enolate reactivity also depends on the metal cation which is present. The general order is BrMg < Li < Na < K. This order, too, is in the order of greater dissociation of the enolate-cation ion pairs and ion aggregates. Carbon-13 chemical shift data provide an indication of electron density at the nucleophilic caibon in enolates. These shifts have been found to be both cation-dependent and solvent-dependent. Apparent electron density increases in the order > Na > Li and THF/HMPA > DME > THF >ether. There is a good correlation with observed reactivity under the corresponding conditions. 

Most of these results have been obtained in methanol but some of them can be extrapolated to other solvents, if the following solvent effects are considered. Bromine bridging has been shown to be hardly solvent-dependent.2 Therefore, the selectivities related to this feature of bromination intermediates do not significantly depend on the solvent. When the intermediates are carbocations, the stereoselectivity can vary (ref. 23) widely with the solvent (ref. 24), insofar as the conformational equilibrium of these cations is solvent-dependent. Nevertheless, this equilibration can be locked in a nucleophilic solvent when it nucleophilically assists the formation of the intermediate. Therefore, as exemplified in methylstyrene bromination, a carbocation can react 100 % stereoselectivity. 

The exact behavior and mechanism of electrophilic additions to alkynes is clearly strongly dependent upon the reaction conditions. In a highly polar and strongly acidic but weakly nucleophilic solvent such as trifluoroacetic acid, addition via a vinyl cation intermediate is favored whereas in less polar, more nucleophilic solvents such as acetic acid, a different mechanism prevails. 

Belonging to group (i) are alkylmetal carbonyls and cyclopentadienylmetal alkyl carbonyls of formula RMn(CO)5, CpFe(CO)2R, and CpMo(CO)3R. Solvent dependence of the reaction of MeMn(CO)5 with CjHi,NH2 is illustrated also in Table I. The rate varies markedly with the dielectric constant and with the nucleophilic power of the solvent. For example, on going from dimethylformamide to mesitylene, the rate of insertion is reduced by 10. Similarly, the sequence MeCN > MejCO > THF > CHCI3 > CjHj was reported for the reaction of MeMn(CO)5 with P(0CH2)3CR (R = Me and Et) in various solvents (97). Analogous trends were observed for the insertion reactions of CpFe(CO)2R and CpMo(CO)3R (48, 80, 98). 

In the case of the hexacarbonyls, the rate-expression contains not only the same type of first-order term but in addition one second-order overall. For good entering groups (but not CO, for example) the rate expression contains a term strictly first-order in both the complex and the entering nucleophile. The first-order rates of CO exchange are practically identical with the rates of substitution in hydrocarbon solvents, but there is nevertheless some acceleration in ether (THF, dioxan) solutions. This solvent-dependence is not so well-marked ° as in the case of nickel tetracarbonyl. The second-order rate of substitution very strongly depends upon the basicity of the entering nucleophile... 

The solvent dependence of the reaction rate is also consistent with this mechanistic scheme. Comparison of the rate constants for isomerizations of PCMT in chloroform and in nitrobenzene shows a small (ca. 40%) rate enhancement in the latter solvent. Simple electrostatic theory predicts that nucleophilic substitutions in which neutral reactants are converted to ionic products should be accelerated in polar solvents (23), so that a rate increase in nitrobenzene is to be expected. In fact, this effect is often very small (24). For example, Parker and co-workers (25) report that the S 2 reaction of methyl bromide and dimethyl sulfide is accelerated by only 50% on changing the solvent from 88% (w/w) methanol-water to N,N-dimethylacetamide (DMAc) at low ionic strength this is a far greater change in solvent properties than that investigated in the present work. Thus a small, positive dependence of reaction rate on solvent polarity is implicit in the sulfonium ion mechanism. 

For the methyl-substituted ethylenes, i.e. in the absence of any steric effects, there is a roughly linear relationship between the chemoselectivity and the 13C nmr chemical shift of the most substituted carbon atom of the bromonium ions (Dubois and Chretien, 1978). This selectivity is therefore discussed in terms of the magnitude of the charge on the carbon atom and the relative hardness of the competing nucleophiles, according to Pearson s theory (Ho, 1977). However, this interpretation does not take into account the substituent dependence of the nucleophilic solvent assistance, which must play a role in determining this chemoselectivity. 

In the solvolysis of secondary alkyl sulfonates, competition between nucleophilic solvation and electron donation by the substituents results in a significantly solvent-dependent p, which varies from — 9 to — 1 on going from the non-nucleophilic hexafluoro-2-propanol to 80% aqueous ethanol (Bentley et al, 1981). In contrast, the p -invariance for alkene bromination in H20, M70, MeOH and AcOH [equations (22)-(25)] seems to imply a perfect balance between the two types of charge stabilization. However, this conclusion is probably risky since the nucleophilicities of the solvents implied in (22)-(25) do not vary markedly. Data in non-nucleophilic fluorinated solvents would therefore help to fill the gap in our knowledge. 

As illustrated in Scheme 5, ( )-31 directly gives cation 37 via phenyl participation, while (Z)-31 provides 38 more slowly via methyl participation. Cation 37 can further rearrange to more stable 38 by 1,2-hydride shift, but 38 cannot isomerize to less stable 37. As a result, ( )-31 can afford not only 33,35, and 36 but also 34, but (Z)-31 only gives 34 and 35 depending on the nucleophilicity of the solvent. The unrearranged product 32 is formed via inversion only from (Z)-3I in a more nucleophilic solvent. This must result directly from the SN2 reaction of (Z)-31. 

In contrast, in protic solvents and at low bromine concentration, the addition process is characterized by a second order rate law (first order in bromine), Scheme 2, path b. In this case, due to the ability of the solvent to provide a specific electrophilic solvation to the leaving bromide ion, the reaction occurs via an SN1 -like unimolecular ionization of the 1 1 it complex to form a bromonium or P-bromocarbenium bromide ion pair. It is worth noting that protic solvents can also give nucleophilic assistance, depending on their specific solvent properties. 

The unusual rate enhancement of nucleophiles in micelles is a function of two interdependent effects, the enhanced nucleophilicity of the bound anion and the concentration of the reactants. In bimolecular reactions, it is not always easy to estimate the true reactivity of the bound anion separately. Unimolecular reactions would be better probes of the environmental effect on the anionic reactivity than bimolecular reactions, since one need not take the proximity term into account. The decarboxylation of carboxylic acids would meet this requirement, for it is unimolecular, almost free from acid and base catalysis, and the rate constants are extremely solvent dependent (Straub and Bender, 1972). 

A solvent-dependent chemoselectivity, pointing to a dependence of the relative reactivities of the 1,2- and 1,1-disubstituted double bonds on solvent polarity and nucleophilicity, has been observed in the reaction of benzeneselenenyl chloride with 2-methylenebicyclo[2.2.1]hept-5-ene (159) which gives products 160-163140. In methylene chloride the reaction occurs with a moderate chemoselectivity, attack on the endocyclic bond being preferred over that on the exocyclic one in a 60 40 ratio. In methanol, the addition is completely chemoselective and the attack occurs exclusively on the endocyclic double bond (equation 132). It may be further noted that 162 and 163 isomerize and solvolyze at high temperatures, leading to the homoallylic products 160 and 161. 

Ionic hydrogenation of the same bicyclic diene 382 by Et3SiH in the presence of CF3COOH at room temperature or at 80 °C via ions 387 and 388 is accompanied by transannular cyclizations (equation 139)192. The behavior of diene 382 under Ritter reaction conditions (MeCN, H2SO4) reveals new possibilities to control the transannular cyclizations (equation 140)193. Depending on the sulfuric acid concentration, the reaction temperature and the presence of a nucleophilic solvent, these transformations can be directed to the formation of either the bicyclic amides 389 and 390 having the precursor structure or the tricyclic products 391193. 

The catalysed alkylation of l//,4//-pyrazol-5-ones is solvent dependent. In benzene, bis-alkylation occurs at the 4-position whereas, in a carbon disulphide benzene mixture, O-alkylation is observed, although the major product (4, Scheme 5.22) results from nucleophilic attack by the pyrazolone on the carbon disulphide, followed by alkylation of the dithiolate dianion [92]. The catalysed reaction of 2-thiono-3-aryl-thiazolidin-4-ones with alkylating agents under soliddiquid two-phase conditions results in alkylation at the 5-position (60-80%) [93]. The aldol condensation of the thiazolidinones with aryl aldehydes is also catalysed by quaternary ammonium salts. 

An anodic azacyclization, producing tropane-related 11-substituted dibenzo[a,d]cycloheptimines 123, was recently developed by Karady et al. [136, 137]. This two-electron process is initiated by anodic oxidation of the O-substituted hydroxylamine 119 in nucleophilic solvent. It is proposed that the first one-electron oxidation leads to the aminium radical cation 120 which adds rapidly to the double bond. The electron-rich carbon radical 121 is readily oxidized to the carbocation 122. Selective nucleophilic attack on 122 from the less hindered exo-side yields the 11- substituted product 123. Depending on the... 

With counteranions of lower nucleophilicity the " Sn NMR chemical resonance of solutions of tributyl tin salts is further shifted to lower field. Lambert and Kuhlmann reported for the tiibutylstarmyl borate Bu3SnB(C6F5)3H 8" Sn = 360 in benzene and Kira and co-workers found for the related BusSnTFPB 8 Sn = 356 in CD2Cl2. In the latter case, F NMR spectroscopy indicates no cation-anion interaction. Finally, for Bu3SnTPFPB in toluene at —60 °C 5" Sn = 434.2 was reported by Piers et The solvent dependence of the Sn NMR chemical shift suggests... 

The development of these various solvent parameters and scales has been accompanied by the realization that there are uncertainties in the physical property of the solvent that is correlated by a particular parameter in cases where systematic changes in solvent structure affect several solvent properties. Consider a reaction that shows no rate dependence on the basicity of hydroxylic solvents, and a second reaction that proceeds through a transition state in which there is a small transition state stabilization from a nucleophilic interaction with the hydroxyl group. The rate constants for the latter reaction will increase more sharply with changing solvent nucleophilicity than those for the former, and they should show a correlation with some solvent nucleophilicity parameter. This trend was observed in a comparison of the effects of solvent on the rate constants for solvolysis of 1-adamantyl and ferf-butyl halides, and is consistent with a greater stabilization of the transition state for reaction of the latter by interaction with nucleophilic solvents. ... 

Effect of nucleophile R reacts with nucleophilic solvents rather than with Nu" (solvolysis), except when R is relatively stable Rate depends on nucleophilicity r >Br >Cr RS. >RO Equilibrium lies towards weaker Bronsted base... 

Cyclobutanes were also obtained from metallacyclopentanes by simple thermal decomposition, by treatment with other nucleophiles (rather than alkenes) such as phosphanes, nucleophilic solvents or by reaction with oxygen. Byproducts of these reactions are the respective alkenes or linear dimers. The extent of the formation of byproducts depends on the temperature of the decomposition, on the solvent and the nucleophile and on the coordination number of the metal. 

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