Electrophile-nucleophile acid-base

In each problem, identify the functional group to determine the general reaction type—substitution, elimination, or addition. Then, determine if the reagent is an electrophile, nucleophile, acid, base, and so forth. 

Look at the reagent and determine if it is an electrophile, nucleophile, acid, or base. 

Carbocations are strongly electrophilic (Lewis acids) and react with nucleophiles (Lewis bases)... 

The electrophilic character of boron is again evident when we consider the oxida tion of organoboranes In the oxidation phase of the hydroboration-oxidation sequence as presented m Figure 6 11 the conjugate base of hydrogen peroxide attacks boron Hydroperoxide ion is formed m an acid-base reaction m step 1 and attacks boron m step 2 The empty 2p orbital of boron makes it electrophilic and permits nucleophilic reagents such as HOO to add to it... 

Before beginning a detailed discussion of alkene reactions, let s review briefly some conclusions from the previous chapter. We said in Section 5.5 that alkenes behave as nucleophiles (Lewis bases) in polar reactions. The carbon-carbon double bond is electron-rich and can donate a pair of electrons to an electrophile (Lewis acid), for example, reaction of 2-methylpropene with HBr yields 2-bromo-2-methylpropane. A careful study of this and similar reactions by Christopher Ingold and others in the 1930s led to the generally accepted mechanism shown in Figure 6.7 for electrophilic addition reactions. 

A Grignard reaction begins with an acid-base complexation of Vfg2+ to the carbonyl oxygen atom of the aldehyde or ketone, thereby making the carbonyl group a better electrophile. Nucleophilic addition of R then produces a tetrahedral magnesium alkoxide intermediate, and protonation by addition of water... 

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. 

This electrophile/nucleophile dichotomy can be looked upon as a special case of the acid/base idea. The classical definition of acids and bases is that the former are proton donors, and the latter proton acceptors. This was made more general by Lewis, who defined acids as compounds prepared to accept electron pairs, and bases as substances that could provide such pairs. This would include a number of compounds not previously thought of as acids and bases, e.g. boron trifluoride (39),... 

It is Lewis complementarity, on the other hand, that is operative when the mating of the molecules is determined by acid-base interactions, one that is described and predicted by the complementary mating of the lumps with the holes in the two associated Laplacian distributions. A molecule s reactive surface is defined by the zero envelope of the Laplacian distribution, the envelope that separates the shells of charge concentration from those of charge depletion. The reactive surfaces make immediately clear the locations of the lumps, the nucleophilic sites, and the holes, the electrophilic sites, that are brought into juxtaposi-... 

Ring Opening by Acid, Base, Electrophiles or Nucleophiles.85... 

In this context, an avalanche of studies were devoted to acid-base reactions in their broadest sense (i.e., the Lewis picture), also involving complexation reactions, to the typical organic reactions of addition, substitution, and elimination types, involving nucleophilic and electrophilic reagents including the case of radicalar reactions and excited states (for a review see Ref. [11]) in which our group has... 

A first turning point in the dichotomy between radical and ionic chemistry is located at the level of the primary radical, usually an ion radical, formed upon single electron transfer to the substrate. If, for a reduction, the reaction medium is not too acidic (or electrophilic), and for an oxidation, not too basic (or nucleophilic), radical reactions involving the primary radical, such as self-coupling, have a first opportunity to compete successfully with acid-base reactions. In this competition, the acidity (for a reduction) or basicity (for an oxidation) of the substrate should also be taken into account insofar as they may lead to father-son acid-base reactions. It should also be taken into consideration that the primary radical may undergo spontaneous acid-base reactions such as expelling a base (or a nucleophile) after a reduction, and an acid (or an electrophile) after an oxidation. 

Schultz and coworkers (Jackson et a ., 1988) have generated an antibody which exhibits behaviour similar to the enzyme chorismate mutase. The enzyme catalyses the conversion of chorismate [49] to prephenate [50] as part of the shikimate pathway for the biosynthesis of aromatic amino acids in plants and micro-organisms (Haslam, 1974 Dixon and Webb, 1979). It is unusual for an enzyme in that it does not seem to employ acid-base chemistry, nucleophilic or electrophilic catalysis, metal ions, or redox chemistry. Rather, it binds the substrate and forces it into the appropriate conformation for reaction and stabilizes the transition state, without using distinct catalytic groups. 

To the extent that the N+ correlation is successful it means that the pattern of nucleophilic reactivity is not influenced by the nature of the electrophilic center at which substitution takes place. On the other hand, according to the concepts of the theory of hard and soft acids and bases (HSAB) as applied to nucleophilic substitution reactions (Pearson and Songstad, 1967) one would expect that a significant change in the HSAB character of the electrophilic center as an acid should lead to changes in the pattern of nucleophilic reactivity observed. Specifically, in substitutions occurring at soft electrophilic centers, soft-base nucleophiles should be more reactive relative to other nucleophiles than they are in substitutions at harder electrophilic centers, and in substitutions at hard electrophilic centers hard-base nucleophiles should appear relatively more reactive compared to other nucleophiles than they do in substitutions at softer electrophilic centers. 

As we have seen (Section 4, p. 191) the range of effective molarities associated with ring-closure reactions is very much greater than that characteristic of intramolecular general acid-base catalysis the main classification is therefore in terms of mechanism. By far the largest section (I, Tables A-D) gives EM s for intramolecular nucleophilic reactions. These can be concerted displacements (mostly at tetrahedral carbon), stepwise displacements (mostly addition-elimination reactions at trigonal carbon), or additions, and they have been classified in terms of the nucleophilic and electrophilic centres. 

The discussion and classification of reagents is masterful in identifying Ingold s new nomenclature and principles with more widely known oxidation-reduction and acid-base theory. The 1953 lectures at Cornell University, published as Structure and Mechanism in Organic Chemistry, follow this same strategy, showing how old classification schemes overlap with each other and how apparent inconsistencies disappear as old schemes are incorporated into the new one. Nineteenth-century Berzelian electrochemical dualism, revived by Lapworth and Robinson in the cationic/anionic schema, disappears into the electrophilic/nucleophilic language. 

One of the central mechanistic questions regarding ubiquitination has been whether the reaction utilizes general acid/base catalysis, possibly in a manner analogous to the catalysis of peptide-bond cleavage. For example, an acidic catalytic residue could deprotonate the substrate lysine and make it a better nucleophile for attacking the ubiquitin thioester bond. In addition, a basic catalytic residue could polarize the thioester bond making the carbonyl carbon a better electrophile, and... 

In order to clarify the different behavior of anion 2 and 3 (Scheme 4.10) toward DMC, various anions with different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) were compared with regard to nucleophilic substitutions on DMC, using different reaction conditions. Results were in good agreement with the hard-soft acid-base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first... 

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