Nucleophile of nucleophilicity

The probes and methods for determining the relative nucleophilicities of nucleophiles toward electrophilic olefins and toward vinyl cations were examined. Literature data were used in an attempt to construct a substrate-independent nucleophilicity scale toward vinylic carbon. 

Pseudo-first-order rate constants (k bs) for the reaction of anionic fV-hydrox-yphthaUmide (NHP) with HO increased by > 3-fold and 15-fold in the presence of inert monocations (LP, Na+, K+, and Cs+) and dication (Ba ), respectively, in aqueous solvent containing 2% v/v acetonitrile." Catalytic effects of these cations increased with the increase in the contents of acetonitrile in mixed aqueous solvents." The presence of anions such as CE and C03 did not show a kinetically detectable effect on for the alkaline hydrolysis of NHP-. The catalytic effects have been explained quantitatively in terms of an ion-pair mechanism in which cations produced a predominantly stabilizing effect on TS rather than on GS. The overall catalytic effect of inert cations is apparently the combined effect of ion-pair formation between cation and anionic reactants, which causes the increase in electrophilicity of carbonyl carbon of NHP for nucleophilic attack and decrease in the nucleophilicity of nucleophile (HO ). 

Nucleophilic substitution of benzene itself is not possible but the halogeno derivatives undergo nucleophilic displacement or elimination reactions (see arynes). Substituents located in the 1,2 positions are called ortho- 1,3 meta- and 1,4 para-. 

N,N,N, N -tetramethyl-l,8,-naph-thalenediamiDe M.P. 51 C. A remarkably strong mono-acidic base (pKg 12-3) which is almost completely non-nucleophilic and valuable for promoting organic elimination reactions (e.g. of alkyl halides to alkenes) without substitution. 

Methods of producing B —C bonds include hydroboration, nucleophilic displacement at a boron atom in BX., (X = halogens or B(0R>3) by e.g. a Grignard reagent, and a psewiio-Friedel-Crafts reaction with an aromatic hydrocarbon, BX3, and AICI3. 

Hase W L 1994 Simulations of gas-phase chemical reactions applications to S j2 nucleophilic substitution Science 266 998-1002... 

A more detailed classification of chemical reactions will give specifications on the mechanism of a reaction electrophilic aromatic substitution, nucleophilic aliphatic substitution, etc. Details on this mechanism can be included to various degrees thus, nucleophilic aliphatic substitutions can further be classified into Sf l and reactions. However, as reaction conditions such as a change in solvent can shift a mechanism from one type to another, such details are of interest in the discussion of reaction mechanism but less so in reaction classification. 

The attack by a reagent of a molecule might be hampered by the presence of other atoms near the reaction site. The larger these atoms and the more are there, the higher is the geometric restriction, the steric hindrance, on reactivity. Figure 3-6e illustrates this for the attack of a nucleophile on the substrate in a nucleophilic aliphatic substitution reaction. 

Thus, to name just a few examples, a nucleophilic aliphatic substitution such as the reaction of the bromide 3.5 with sodium iodide (Figure 3-21a) can lead to a range of stereochemical products, from a l l mbrture of 3.6 and 3.7 (racemization) to only 3.7 (inversion) depending on the groups a, b, and c that are bonded to the central carbon atom. The ring closure of the 1,3-butadiene, 3.8, to cyclobutene... 

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

Now we cany out the same reaction with thiolate as nucleophile, as shown in Figure 3-23. hlowever, we must now realize that the product has a parity of (+ 1) although we have the same mechanism as in Figure 3-22 with inversion of configuration. 

The Claisen condensation is initiated by deprotonation of an ester molecule by sodium ethanolate to give a carbanion that is stabilized, mostly by resonance, as an enolate. This carbanion makes a nucleophilic attack at the partially positively charged carbon atom of the e.ster group, leading to the formation of a C-C bond and the elimination ofan ethanolate ion, This Claisen condensation only proceeds in strongly basic conditions with a pH of about 14. 

Example Solvation can have a profound effect on the potential energy profile for a reaction. Jorgensen s research group provided important insights into the role of solvation. Consider the nucleophilic addition of the hydroxide anion to formaldehyde ... 

Fig. 11.37 Free energy profile for the nucleophilic attack of water on CO2 (a) in aqueous solution and (b) in the enzyme carbonic anhydrase. (Graphs redrawn from Aqvist J, M Fothergill and A Warshel 1993. Computer Simulai of the COj/HCOf Interconversion Step in Human Carbonic Anhydrase I. Journal of the American Chemical Society 115 631-635.)...

The purpose of this eornpuLer project is Lo examine several polynuclear aromatic hydrocarbons and to relate their electron density patterns to their carcinogenic activity. If nucleophilic binding to DN.A is a significant step in blocking the normal transcription process of DN.A, electron density in the hydrocarbon should be positively correlated to its carcinogenic potency. To begin with, we shall rely on clinical evidence that benzene, naphthalene, and phenanthrene... 

The Grignard reagent RMgX is nucleophilic by virtue of the potential car banion (alkyl anion) R. It will react with the electrophilic carbonyl group as follows ... 

The mechanism of the aromatic substitution may involve the attack of the dectrophilic NOj" " ion upon the nucleophilic aromatic nucleus to produce the carboniiim ion (I) the latter transfers a proton to the bisulphate ion, the most basic substance in the reaction mixture... 

In the strongly basic medium, the reactant is the phenoxide ion high nucleophilic activity at the ortho and para positions is provided through the electromeric shifts indicated. The above scheme indicates theorpara substitution is similar. The intermediate o-hydroxybenzal chloride anion (I) may react either with a hydroxide ion or with water to give the anion of salicyl-aldehyde (II), or with phenoxide ion or with phenol to give the anion of the diphenylacetal of salicylaldehyde (III). Both these anions are stable in basic solution. Upon acidification (III) is hydrolysed to salicylaldehyde and phenol this probably accounts for the recovery of much unreacted phenol from the reaction. 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

This thesis has been completely devoted to catalysis by relatively hard catalysts. When aiming at the catalysis of Diels-Alder reactions, soft catalysts are not an option. Soft catalysts tend to coordinate directly to the carbon - carbon double bonds of diene and dienophile, leading to an activation towards nucleophilic attack rather than to a Diels-Alder reaction . This is unfortunate, since in water, catalysis by hard catalysts suffers from a number of intrinsic disadvantages, which are absent for soft catalysts. 

Over a decade of research, we were able to show that practically all conceivable carbocations could be prepared under what became known as stable ion conditions using various very strong acid systems (see discussion of superacids) and low nucleophilicity solvents (SO2, SO2CIF, SO2F2, etc.). A variety of precursors could be used under appropriate conditions, as shown, for example, in the preparation of the methylcyclopentyl cation. 

The high acidity of superacids makes them extremely effective pro-tonating agents and catalysts. They also can activate a wide variety of extremely weakly basic compounds (nucleophiles) that previously could not be considered reactive in any practical way. Superacids such as fluoroantimonic or magic acid are capable of protonating not only TT-donor systems (aromatics, olefins, and acetylenes) but also what are called (T-donors, such as saturated hydrocarbons, including methane (CH4), the simplest parent saturated hydrocarbon. 

The formation of the (X-delocalized norbornyl cation via ionization of 2-norbornyl precusors in low-nucleophilicity, superacidic media, as mentioned, can be considered an analog of an intramolecnlar Friedel-Crafts alkylation in a saturated system. Indeed, deprotonation gives nortricyclane,... 

This realization led me to study related possible intermolecular electrophilic reactions of saturated hydrocarbons, Not only protolytic reactions but also a broad scope of reactions with varied electrophiles (alkylation, formylation, nitration, halogenation, oxygenation, etc.) were found to be feasible when using snperacidic, low-nucleophilicity reaction conditions. 

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