Electrophilic site

Iminothiobutyramide (30), containing four nucleophilic centers (only two of which might react with two electrophilic sites in phenacylbromide), undergoes the Hantzsch reaction preferentially, yielding the enamine (31) in dry dioxane or (4-phenylthiazol-2-yl)acetone (32) in isopropanol. Other enamines are obtainable from the ketone (32) by standard methods (626) (Scheme 15). 

The electrophilic site of an acyl cation is its acyl carbon An electrostatic poten tial map of the acyl cation from propanoyl chloride (Figure 12 8) illustrates nicely the concentration of positive charge at the acyl carbon as shown by the blue color The mechanism of the reaction between this cation and benzene is analogous to that of other electrophilic reagents (Figure 12 9)... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

The molecule below has four stereoisomeric forms exoO exoCH2Br, exoO endoCH2Br, and so on. Examine electrostatic potential maps of the four ions and identify the most nucleophilic (electron-rich) atom in each. Examine the electron-acceptor orbital (the lowest-unoccuped molecular orbital or LUMO) in each and identify electrophilic sites that are in close proximity to the nucleophilic. Which isomers can undergo an intramolecular E2 reaction Draw the expected 8 2 and E2 products. Which isomers should not readily undergo intramolecular reactions Why are these inert ... 

Electrostatic potential map for nitronium cation shows most positively-charged regions (in blue) as likely electrophilic sites. 

Next, consider the reactivity of phenyl diazonium ion. Are either of the reactions shown above consistent with nucleophilic attack at the ion s most electron-poor site Examine the lowest-unoccupied molecular orbital (LUMO) of phenyl diazonium ion. What electrophilic sites are identified by the LUMO Are either of the reactions shown above consistent with an orbital-controlled addition ... 

LUMO of phenyl diazonium ion reveals the most electrophilic sites. 

It is appropriate at this juncture to address some of the more useful transformations of 2,3-epoxy alcohols.913 A 2,3-epoxy alcohol such as compound 14 possesses two obvious electrophilic sites one at C-2, and the other at C-3. But in addition, C-l of a 2,3-epoxy alcohol also has latent electrophilic reactivity. For example, exposure of 14 to aqueous sodium hydroxide solution results in the formation of triol 19 in 79% yield (see Scheme 5). In this interesting transformation, hydroxide ion induces the establishment of an equilibrium between 2,3-epoxy-l-ol 14 and the isomeric 1,2-epoxy-3-ol 18. This reversible, base-induced epoxide migration reaction is a process known as the Payne rearrangement.14... 

Ketal 73 can be formed in a yield of about 60 % by refluxing a solution of tetronic acid (36), ethylene glycol, and a catalytic amount of para-toluenesulfonic acid in benzene for approximately 12 hours. With only one electrophilic site, 73 reacts smoothly with Dibal-H to give lactol 35 in 84% yield. Compound 35, a participant in a ring-chain tautomeric equilibrium process,18 should be regarded as a latent aldehyde. This substance can, in fact, serve as... 

The 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

Another significant method for generating the electrophilic site is acid-catalyzed epoxide ring opening.9 Lewis acids such as BF3, SnCl4, CH3A1C12, or TiCl3(0-i-Pr) can be used,10 as illustrated by Entries 4 to 7 in Scheme 10.1. 

In keeping with the anisotropic electrostatic potential model for the halogen atoms, halogens show an amphiphilic character and can work both as the electrophilic sites and the nucleophilic sites when involved in short contacts (Fig. 3). 

An amide anion will prefer substitution if its basicity is sufficiently lowered by resonance, and can be useful where the neutral nitrogen is unreactive or otherwise unsuitable. Quaterniza-tion cannot be prevented in the alkylation of even free neutral imidazole, but an imidazolide anion will match with only one of the electrophilic sites terminating dimethylene spacer on polystyrene. 

In a, P-unsaturated carbonyl compounds and related electron-deficient alkenes and alkynes, there exist two electrophilic sites and both are prone to be attacked by nucleophiles. However, the conjugated site is considerably softer compared with the unconjugated site, based on the Frontier Molecular Orbital analysis.27 Consequently, softer nucleophiles predominantly react with a, (i-unsaturated carbonyl compounds through conjugate addition (or Michael addition). Water is a hard solvent. This property of water has two significant implications for conjugate addition reactions (1) Such reactions can tolerate water since the nucleophiles and the electrophiles are softer whereas water is hard and (2) water will not compete with nucleophiles significantly in such... 

The most electrophilic site in the cationic dH Ru and Os arylcarbyne complexes is not the carbyne carbon, but the para position of the aryl ring. As noted in Section II, B,2, hydride reduction of these compounds affords zero-valent vinylidene species ... 

Recently, Muha (83) has found that the concentration of cation radicals is a rather complex function of the half-wave potential the concentration goes through a maximum at a half-wave potential of about 0.7 V. The results were obtained for an amorphous silica-alumina catalyst where the steric problem would not be significant. To explain the observed dependence, the presence of dipositive ions and carbonium ions along with a distribution in the oxidizing strengths of the surface electrophilic sites must be taken into account. The interaction between the different species present is explained by assuming that a chemical equilibrium exists on the surface. 

The use of an electron-rich trivalent phosphorus center for addition to or substitution at an electrophilic site is a long-established approach to the formation of carbon-phosphorus bonds. The classical studies of the Michaelis-Arbuzov, Michaelis-Becker, Abramov, Pudovik, and related reactions and their mechanisms and synthetic utilities have been thoroughly reviewed. In this chapter, we present only a brief introduction to these reactions and provide several examples of their more facile uses from the older literature. More attention is given to relatively recent developments regarding such reactions that are seen as improvements in their general utility. 

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-... 

Screening of over 66,000 compounds from the MLSMR by scientists at the PCMD for inhibitors of Cathepsin B resulted in the identification and characterization of an alternate substrate, SID 16952359 [29]. This study also describes issues relating to the nucleophilicity of dithiothreitol (DTT) and cysteine, reductants frequently used in HTS protocols, and the potential for reactivity with electrophilic sites of probe molecules. 

The phosphonium cationic center is well known for its ability to stabilize adjacent anionic centers (i.e. Wittig reagents), however we have shown it to be capable of activating (or destabilizing) cationic electrophilic sites.15 As noted... 

Parry (344) determined the infrared spectrum of pyridine adsorbed on rj-alumina dehydrated at 450°. Characteristic differences in the 1400-1700 cm region exist in the spectra of pyridine adsorbed via hydrogen bonds, pyridinium ions, and pyridine coordinately bonded to electrophilic sites. Pyridinium ions are characterized by a strong band at 1540 cm and a very strong band at 1485-1500 cm" coordinately bonded pj ridine has a strong absorption at 1447-1460 cm". No evidence was found for the existence of Bronsted sites on the alumina surface. 

Electrophilic site for Schiff base formation with reactive amines such as a-amino acids. Corresponding transaminated species, pyridoxamine, reacts with electrophilic carbonyl compounds... 

C1CH2CH2CHZ [Z = C(0)H, CCH, or CN] to cyclopropane derivatives. In each case the cyclization barrier is lower than the 5n2 barrier of an analogous acyclic system, despite the cyclization being over 25kcal moP less exothermic. The surprisingly small enthalpic barrier to the cyclizations is due to the nucleophile being held in close proximity to the electrophilic site in the substrate, and this destabilizes the ground state. 

Typically, the most common precursors to new Si-N-P systems are simple silylaminophosphines (eq 1). The difunctional character of these compounds, which is due to the nucleophilic site at phosphorus and a complementary electrophilic site at silicon, makes them very versatile reagents. They have been used in a new synthesis of alkyl and/or phenyl substituted phospha-zenes (R2PN)jj ( ) and have led to the preparation of promising precursors to potentially electrically conducting polymer systems of general formula (RPN)n>... 

In an extensive review on abiotic catalysis, Huang (2000) noted that the reactivity of hydrolyzable organic contaminants arises from the presence of electron-deficient (electrophilic) sites within the molecules. Figures 14.2 and 14.3 show the patterns of reactivity in two cases of nucleophihc substitution and monomolecular nucleophilic substitution. The Sj 2 mechanism (nucleophilic substitution) involves attack of the electrophilic sites by OH" or H O, generation of a higher coordination nnmber intermediate, subsequent elimination of the leaving group, and the formation of an hydrolysis product (Fig. 14.2). 

Besides the classical additions of carbon-centered nucleophiles to the electrophilic sites of the cumulenic chain, transition-metal allenyhdenes are able to promote... 

The relatively high yield of vinblastine from Catharanthus extracts and the remarkable biological activity of this alkaloid render this compound a natural choice for structural modification. Vinblastine is subject to attack by electrophilic reagents at a number of sites (Fig. 6), but by careful selection of reagents and conditions it is possible to operate in this structurally complex theater with considerable selectivity. Potentially electrophilic sites are, in some cases, immune from electrophilic attack. 

Dibenzothiophene derivatives have been used as co-catalysts in the addition polymerization of vinyl and diene monomers. Dibenzothiophene itself, in conjunction with vanadium oxychloride, is effective in initiating the polymerization of isobutylene, - although when incorporated in a Ziegler catalyst system, competition between donor and monomer for the most electrophilic sites results in deactivation of the catalyst. Despite the fact that 2-vinyl- - - and 4-vinyldibenzothiophene - readily undergo thermal polymerization,... 

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