Nucleophilicity and basicity

The low reactivity of phosphite 3 has been explained as follows [44], During the reaction of phosphite 3 with an electrophile (E), efficient electron transfer from the lone pairs of oxygen to the incipient antibonding orbital of the P-E bond is not pos- 

The orientation of the unshared electron pairs of oxygen in compounds containing P-O bonds also modulates the gas-phase basicity [45, 46] and oxidation potentials [47] of these compounds. 

---

The connection between basicity and nucleophilicity holds when compaiing atoms in the same row of the periodic table. Thus, HO is more basic and more nucleophilic than F , and H3N is more basic and more nucleophilic than H2O. It does not hold when proceeding down a column in the periodic table. For exanple, I is the least basic of the halide ions but is the most nucleophilic. F is the most basic halide ion but the least nucleophilic. 

Amines are organic derivatives of ammonia in the same way that alcohols and ethers are organic derivatives of water. Like ammonia, amines contain a nitrogen atom with a lone pair of electrons, making amines both basic and nucleophilic. We ll soon see, in fact, that most of the chemistry of amines depends on the presence of this lone-pair of electrons. 

The chemistry of amines ts dominated by the lone pair of electrons on nitrogen, which makes amines both basic and nucleophilic. They react with acids to form acid-base salts, and they react with electrophiles in many of the polar reactions seen in past chapters. Note in the following electrostatic potential map of trimethylamine how the negative (red) region corresponds to the lone-pair of electrons on nitrogen. 

As can be seen in Figure 6.12, penicillin G contains two amide functionalities, of which the (Madam linkage is extremely susceptible to basic and nucleophilic attack. Therefore, deavage of the phenylacetyl side chain could not be performed using classical base hydrolysis. The problem of selectivity was resolved by taking advantage of the fad that the amide bond to be hydrolysed is secondary rather than tertiary. 

Both the basic and nucleophilic reactions within the cage are totally inhibited by the presence of one equivalent of Na + PFg in THF. Double ion exchange between the two ion pairs is favored which removes superoxide from the cage Eq. (10) ... 

If relatively basic and nucleophilic aromatic amines are diazotized in nitrosylsul-furic acid, C- instead of TV-nitrosation takes place as shown by Blangey (1938) for 1-naphthylamine, which gave in this system 4-nitroso-l-naphthylamine. A possible mechanistic explanation of Blangey s observation is given in Section 3.2. 

The difference between basicity and nucleophilicity is a difference of function. In other words, the hydroxide ion can function in two ways as a base (which means it is pulling off a proton and then running away with that proton) or as a nucleophile (latching onto a compound). In some cases, the hydroxide ion might function mostly as a base while in other situations, the hydroxide ion might function mostly as a nucleophile. To understand mechanisms weU, it is important to be able to distinguish between the two roles. Let s see an example. 

When comparing atoms in the same row of the periodic table, basicity and nucleophilicity do parallel each other ... 

Organomagnesium and organolithium compounds are strongly basic and nucleophilic. Despite their potential to react as nucleophiles in SN2 substitution reactions, this reaction is of limited utility in synthesis. One limitation on alkylation reactions is competition from electron transfer processes, which can lead to radical reactions. Methyl and other primary iodides usually give the best results in alkylation reactions. 

N-Silylation causes a significant lowering of the basicity and nucleophilicity at the nitrogen of unsaturated amines, thus enabling their utilization in [2+1]- and [4+2]-cycloaddition reactions [1,2]. 

The electron pairs on the oxygen atom make it both basic and nucleophilic. i) In the presence of strong acids, alcohols act as bases and accept protons ... 

The first silicon-organophosphorus betaine with a thiolate center (15a) was synthesized by the reaction of stable silanethione (14) with trimethyl-methylenephosphorane (Scheme 8) and characterized by multinuclear NMR spectroscopy.14 Compound 15a is formed under kinetic control and is transformed, under the thermodynamically controlled conditions, into the silaacenaphthene salt (16). The processes presented in this scheme reflect the competition of the basicity and nucleophilicity of phosphorus ylides. Betaine 15b prepared from less nucleophilic and less basic ylide with phenyl substituents at the phosphorus atom is much less resistant toward retro-decomposition compared to the alkyl analog. Its equilibrium concentration does not exceed 6%. 

Compound LII, on the other hand, can be made readily. It can have either the planar tricovalent boron structure or the "triptych tetra-covalent structure. In the latter structure the nitrogen is attached to boron and should be considerably less basic and nucleophilic than usual. It does in fact react unusually slowly with methyl iodide and with acids. The neutralization reaction with acids in water is not only slow but of zero order with respect to the acid. It is believed to have a rate-determining transformation from the triptych to the more basic form as the first step. 

Besides the applications of the electrophilicity index mentioned in the review article [40], following recent applications and developments have been observed, including relationship between basicity and nucleophilicity [64], 3D-quantitative structure activity analysis [65], Quantitative Structure-Toxicity Relationship (QSTR) [66], redox potential [67,68], Woodward-Hoffmann rules [69], Michael-type reactions [70], Sn2 reactions [71], multiphilic descriptions [72], etc. Molecular systems include silylenes [73], heterocyclohexanones [74], pyrido-di-indoles [65], bipyridine [75], aromatic and heterocyclic sulfonamides [76], substituted nitrenes and phosphi-nidenes [77], first-row transition metal ions [67], triruthenium ring core structures [78], benzhydryl derivatives [79], multivalent superatoms [80], nitrobenzodifuroxan [70], dialkylpyridinium ions [81], dioxins [82], arsenosugars and thioarsenicals [83], dynamic properties of clusters and nanostructures [84], porphyrin compounds [85-87], and so on. 

Cyclohexyl halides may undergo elimination or substitution reactions. They are usually more prone to elimination, but the acetate anion MeCC>2 is not particularly basic, and nucleophiles are particularly nucleophilic in the polar aprotic solvent DMF. More cyclohexyl acetate (substitution) than cyclohexene (elimination) is likely to form. 

The more basic and nucleophilic fluorous phosphine 5b was similarly studied, and gave even better results. As siunmarized in Fig. 3 (entries 6 and 7), high yields of 4a,c were obtained with much shorter rim times (1 h vs 8 h). In the case of 4c, the data were much improved over those with catalyst 5a (entries 7 vs 3). The relative rates of these two reactions are compared in the inset in Fig. 4 (5b 5 > 5a). 

---