Nucleophilic power

As a first approximation, within a given family of nucleophilic reagents, such as amines, basicity changes are mainly responsible for differences in nucleophilic power. The p values of some of the more familiar amines together with the rate constants for some of their reactions with chloroheteroaromatic compounds are shown... 

The most favorable coordination sites in thiophenes are the C2C3 and C4C5 double bonds ( -coordination, 38). This type of coordination greatly enhances the nucleophilic power of the sulfur atom, which then gives rise to two new modes of binding the metal atoms, as in the V, S-p.2-, 42, and V, S-p.3-species, 43. 

Since amines, unlike alcohols, do not react with dialkylzincs but may coordinatively bind to the zinc atom, the dilithio salt of 2,5-diisopropylpiperazine is a more potent catalyst than the piperazine itself, presumably due to the greater nucleophilic power of the dianion10. Dimethylzinc reacts rather slowly with aryl aldehydes and although the product is obtained in high enantiomeric excess, the chemical yield is low10. 

This is not the only equation that has been devised in an attempt to correlate nucleophilic reactivity. For reviews of attempts to express nucleophilic power quantitatively, see Ritchie, C.D. Pure Appl. Chem., 1978, 50, 1281 Duboc, C. in Chapman Shorter Correlation Analysis in Chemistry Recent Advances, Plenum NY, 1978, p. 313 Ibne-Rasa, K.M. J. Chem. Educ., 1967, 44, 89. See also Hoz, S. Speizman, D. J. Org. Chem., 1983, 48, 2904 Kawazoe, Y. Ninomiya, S. Kohda, K. Kimoto, H. Tetrahedron Lett., 1986, 27, 2897 Kevill, D.N. Fujimoto, E.K. J. Chem. Res. (S), 1988, 408. 

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). 

Tertiary amines too are found to produce cr-complexes 104 with 1,3,5-trinitrobenzene and related compounds. Complexes 104 are studied by spectroscopic and kinetic methods. In the case of l,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) and 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), the delocalization of the positive charge of the nucleophile moiety in the usaturated system of DBN and DBU enhances the stability of the zwitterionic complex 105 and, of course, the nucleophilic power of these bases, as well as their basicity244. 

Nevertheless, it can be observed that the significant values are in B, and these show a strong influence of the amine used. The author129 interpreted the results through a mechanism involving a molecular complex substrate, and calculated the values of and of the equilibrium constant K, shown in Table 15. Again, the significant values depend on the nucleophilic power of the amine. If such a molecular complex between... 

The measurement units of each parameter give a preliminary indication of the nature of these parameters, but for a more precise idea of their chemical and physical significance the reader is referred to the literature7-9. In the present context it is sufficient to bear in mind that most of these empirical parameters can be subdivided into parameters which measure the Lewis acidity (hence, the electrophilic power) and Lewis basicity (hence, the nucleophilic power) of a solvent. 

A completely empirical LFER can also be constructed with recourse only to kinetic data. This has been the case in the setting up of a scale of nucleophilic power for ligands substituting in square-planar complexes based on the Swain-Scott approach. The second-order rate constants Ay for reactions in MeOH of nucleophiles Y with tra 5-Pt(py)2Cl2, chosen as the standard substrate... 

The nucleophilic power of a sulfide group is greatly impaired by replacing the nickel ion by palladium. 

The tetradentate ligand forms monomeric square planar complexes. Synthetic and kinetic studies reveal that the coordinated mercapto group may be converted into the coordinated thioether function without breaking the metal-sulfur bond. The nucleophilic power of the coordinated mercapto group exceeds that of RSH, but depends on the metal atom. Bridging protects the sulfur atom from alkylation. In the case of nickel(ll), alkylation is accompanied by expansion of the coordination number of the nickel from 4 to 6. Ligand reactions have led to the synthesis of planar ligands completely cydized about the metal ion. 

The appropriate evaluation of the effect of the solvent change on the nucleophilic power of the water molecule is obtained by calculating the second-order rate constant, Arf2°/[H20] = The rate increase is found to be about a thousandfold. This factor may arise, at least in part, from a base-catalyzed attack of the water molecule whereby a molecule of DMSO, rather than a second molecule of water, acts as a catalyst. The transition state in such a case would be described by 194. 

In equation (10), Y is the ionizing power of the solvent and N its nucleophilic power with m and / measuring the sensitivity of the substrate to these factors. By selecting model compounds, e.g. t-butyl chloride, where only Y should be important and methyl chloride, where both N and Y would be important, then it is possible to obtain values of Y and N for various solvent mixtures. An examination of the variation of the rate of reaction of a given substrate in these solvents according to equation (10) would then reveal the relative importance of the associative and dissociative character to the reactions. 

The discussion of this mechanism is simplified in that the role of the ionizable zinc-bound water molecule as the catalytic group is now fairly generally accepted. The nucleophilic power... 

X-ray diffraction provides a structural analysis of the adduct obtained between acetone and triethylphosphine (155) in the presence of bromine. The process of obtaining 155 is an acid-catalysed process, while the adducts obtained in the presence of chlorotrimethylsilane may be ascribed to neutral attack of the nucleophile leading to the zwitterionic complex, as shown in Scheme 46. In Scheme 46 triethylphosphine may be substituted by trimethylphosphine. When triphenylphosphine or tributylphosphine were used, no reactions were observed, owing to the reduced nucleophilic power of the bulky phosphines and to the insolubility of the obtained adducts. 

The reagent triethylamine bishydrofluoride, which is prepared by mixing two equivalents of the known and stable reagent triethylamine trishydrolluoride with one equivalent of triethylamine, was recently introdueed as a new, efficient reagent for nucleophilic fluorine displacement reactions. Its nucleophilic power is even greater than that of triethylamine trishy-drofluoride, as can be seen from the reaction of 3. ... 

The rate coefficient x is dependent on the nucleophilic power of the halide ion according to the Swain—Scott relationship [155]... 

The empirical value of s = 0.43 indicates that the increase of x with growing nucleophilic power of X is relatively small which can be expected because N2 is a very good leaving group. An estimate of the rate coefficient for the A2 reaction with attack of water in the slow step may be computed from h2o- The experimental value of is lower than the computed value. Consequently, the reaction without participation of halide must follow an A2 mechanism, also. An A1 mechanism can be operative only if its reaction rate is faster than that of the competing A2 reaction. Furthermore, if the reaction pathway of the first term in rate eqn. (47) referred to an A1 mechanism with a carbonium ion intermediate it would lead to formation of additional halogenated product iP > ( h x /feh )[X ]), in contrast to the experimental findings. 

General acid-base catalysis. In general acid-base catalysis, a molecule other than water plays the role of a proton donor or acceptor. Chymotrypsin uses a histidine residue as a base catalyst to enhance the nucleophilic power of serine (Section 9.1.3). 

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