Abstraction of protons

On a purely statistical basis there are more hydrogens on the terminal methyl groups, i.e. six, than there are on the methylene units, which only have four in total. So, if all other things are equal, the hydrogens on the terminal methyl groups would be attacked in preference to those on the methylene carbons. Note also that, in this case, the effect is further enhanced because the resultant anion would be more stable if the charge were on the terminal carbon rather than on one of the middle carbons. 

The idea of accessibility may be taken further than a mere statistical effect. If there are two hydrogens that are equal in all respects except that one of them is partly hidden by some other part of the molecule, suggest what would be the difference in reactivity of these two hydrogens when treated with either a base that was small in size or one that was large. 

If the base is very small, such as the hydroxide anion, then it will be able to approach, and so react with, a hydrogen in almost any position, even if it is partly obscured by another part of the molecule. The converse is also true thus, if the base is very large, i.e. a hindered base which has a large steric demand, then such a base would be able to react only with hydrogens that are accessible. Hence, a degree of selectivity may be introduced by choosing the size of the base that will be used to abstract the proton. 

So far, we have only considered a single step reaction sequence. In many 

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More recently it has become apparent that proton equilibria and hence pH can be equally important in aprotic and other non-aqueous solvents. For example, the addition of a proton donor, such as phenol or water, to dimethylformamide has a marked effect on the i-E curve for the reduction of a polynuclear aromatic hydrocarbon (Peover, 1967). In the absence of a proton donor the curve shows two one-electron reduction waves. The first electron addition is reversible and leads to the formation of the anion radical while the second wave is irreversible owing to rapid abstraction of protons from the solvent by the dicarbanion. 

A simple example of such abstraction of proton is the formation of triphenylmethyl carbanion by NaNH2 in presence of liquid ammonia. 

Another important point deals with selectivity in the abstraction of -protons on equally substituted carbons. In a iyw-periplanar transition state as described above, the minimization of energy concept implies proton abstraction with a maximum of orbital overlap and a minimum of molecular deformation. Consequently, conformations possessing the more acute dihedral angles for bonds H —C—C—O wiU be favored (Scheme 2l/. 

Large heterocyclics offer a greater variety for ring opening, such as the abstraction of protons from not only the 2- but also the 3-position, leading to ring opening by (3-elimination and the formation of w-unsaturated compounds, such as 6-hydroxy-1-hexene from oxepane (CHEC 5.17.2.1.4). 

In continuation of the research on solid-phase synthesis of biologically interesting (3-lactam compounds towards the development of combinatorial libraries, Mata et al. [102] investigated use of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) as a key reagent for the construction of the (3-lactam ring in a stereoselective manner. The popular explanation involves the reaction of ketene B with the imine to form a zwitterionic intermediate D (Scheme 13). Alternatively, it is the activated acid A that acylates the imine to form the zwitterion D by abstraction of proton with... 

The neutral species formed by abstraction of protons located laterally at C3 and C5 in 1,2-type and at C2 of 1,3-type N-oxyazolium salts discussed in Section 1.5.2.1 are prone to react with nucleophiles in an allylic type substitution with elimination of -OR. The reaction is facilitated by the easy cleavage of the weak N-O bond (Scheme 19). The global reaction is displacement of specific lateral protons with a nucleophile. The entire sequence can be run in one pot. 

The UV photochemistry of phenol and related systems (such as indole, pyrrole, imidazole) is dominated by a hydrogen detachment reaction which is driven by repulsive 1ira states [33,35 10], For the isolated chromophores, the 1 mr -driven photodissociation has been explored in unprecedented detail by high-resolution photofragment translational spectroscopy [40], The OH (or NH) bond is broken homolytically, resulting in the formation of two radical species, the hydrogen atom and the phenoxy (or indolyl, etc.) radical. Ion pair formation (abstraction of protons) is energetically not feasible for isolated photoacids. 

Because abstraction of proton 2 gives the more highly substituted (therefore more stable) product, Zaitsev s rule predicts it will be the major product. Note that in other problems, however, you may be asked to propose mechanisms to explain unusual compounds that are only minor products. 

Fig. 7-12. Reactions of phenolic /8-aryl ether and a-ether structures (1) during neutral sulfite pulping (Gierer, 1970). R = H, alkyl, or aryl group. The quinone methide intermediate (2) is sulfonated to structure (3). The negative charge of the a-sulfonic acid group facilitates the nucleophilic attack of the sulfite ion, resulting in /8-aryl ether bond cleavage and sulfonation. Structure (4) reacts further with elimination of the sulfonic acid group from a-position to form intermediate (5) which finally after abstraction of proton from /8-position is stabilized to a styrene-/8-sulfonic acid structure (6). Note that only the free phenolic structures are cleaved, whereas the nonphenolic units remain essentially unaffected.

While the abstraction of protons adjacent to the carbon-nitrogen double bond of imines/imine derivatives has been utilized for tiie regioselective generation of azaallyl anions (which are useful in asymmetric ketone synthesis), it competes with and often prevents the addition of nucleophiles to imines. For this reason, imine additions often involve azomethines (e.g. benzylidineanilines) which are not capable of enolization. Many potentially useful additions, however, involve substrates capable of proton abstraction. By avoiding in certain instances some of the structural features of imines/imine derivatives and the reaction conditions responsible for proton abstraction, products resulting from this serious side reaction can be minimized. 

When it is considered that the base-catalysed reaction starts with the formation of carboanion on the methylenic group by the abstraction of proton, the acid dissociation constant (pKa) would be one of the indexes for the difficulty of the reaction. Although there are no good relationship between the product yield and the pKa value, it is clear that this catalyst could not promote the reaction with reactant 2 of high pKa value. The tendency of catalytic property for these four condensations (entry 1-4) is similar to that over 3-aminopropyl-functionalised silica gel catalyst prepared through silylation [18]. 

The oxidative coupling of isobutene can be performed in two separate steps, coimected with reduction of catalyst and reoxidation of the reduced catalyst afterwards. The two step process leads to an improvement of DMH selectivity as compared to the conventional process. The formation of carbon dioxide requires surface lattice oxygen from tbe catalyst, while formation of DMH occurs by abstraction of protons and electrons at the catalyst surface. They are absorbed on the catalyst bulk and, finally, react to water there. Thus, the rate of carbon dioxide formation is more affected by catalyst reduction than the rate of DMH formation. 

Equilibrium Molecular Parameters. Polyelectrolyte effects, evidenced by increased solution viscosity and reduced scattering intensity at very low concentrations, were observed for polyamic acid solutions in NMP which had not been redistilled over P2O5. We attribute this effect to the abstraction of protons from the amic acid by amine impurities in the NMP. This is discussed in more detail in an earlier study (6). Measurements reported by other workers in other amide solvents such as dimethylacetamide, have been made with LiBr added to suppress the polyelectrolyte affect (3). Measurements described here were made on solutions in NMP which had been redistilled over P2O5 > and no polyelectrolyte effects were observed. 

There are related reactions involving the addition to, or abstraction of protons from the organic group. Thus acetonyl and other oxoalkyl compounds give olefin-coordinated ions in which the enol forms, e.g., of acetone, are stabilized by bonding to the metal atom ... 

Regioselective formation of the tosylhydrazone dianion was observed in tosylhydrazones of the type 111 derived from unsymmetrical ketones such as 2-butanone. Abstraction of protons from the less hindered side of 111 and subsequent reaction with acetone gave a / -hydroxytosylhydrazone, which on treatment with alkyllithium gave the homoallylic alcohol 112 in good yield as shown in equation 58s 3. Another example is shown in equation 59. 

The specific exchange at C-2 in the azoles in neutral solution, via an ylide, has already been discussed (section 21.1.2.1). In strongly basic solution, deprotonation takes place by direct abstraction of proton from the neutral heterocycle at the positions adjacent to the oxygen and the sulfur in oxazole and thiazole and, less easily, at C-5 in 7f-methylimidazole. ... 

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