Proton-Activated Reactivity

2 Activation of Reactant Molecules 4.2.1 Proton-Activated Reactivity 

When a molecule adsorbs on the siliceous part of the micropore of a zeolite, the main interaction it experiences is a dispersive van der Waals-type interaction. This is due to the dominant interaction with the large polarizable oxygen atoms that make up the zeolite framework. For example, the interaction between a hydrocarbon CH3 or CH2 group and the siliceous framework typically results in an interaction energy that is on the order of 5-10 kJ/mol. These electrostatic interactions are small. 

When an organic molecule approaches the zeolitic proton, in addition to the van der Waals dispersion forces, there is a weak additional interaction which is on the order of 5 kJ/mol. The large interaction energy of hydrocarbons with the sUiceous zeolite chaimel [e.g. hexane in silicalite (ZSM-5), 60 kJ/mol] is due to the fact that there are multiple contacts between the hydrocarbon and the zeolite channel which are additive in nature. This helps to illustrates the fact that the siliceous zeolite channel is quite hydrophobicl 1. 

The interaction of a zeolitic proton with a polar adsorbate is much stronger than with an apolar hydrocarbon. The heat of adsorption of CH3OH, for example, to the zeolitic proton is on the order of 80 kJ/mol. This is largely due to the strong interaction between the OH group on methanol and the zeohte proton. Its bonding features are well understood and sketched in Fig. 4.4l l. 

In zeolite catalysis, carbenium- or carbonium-ion intermediates are energetically located at the top of the reaction energy barriers. In contrast, in superacid solutions, these protonated intermediates are ground-state reactants. The zeolite carbonium- and carbenium-ion transition state concepts are illustrated for C-C activation and olefin isomerization reactions below.  

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For the purposes of this chapter, an arbitrary distinction is made between protonic and thermal activation, wherein protonic activation is caused by the action of acid at room temperature or lower, and thermal activation refers to the use of elevated temperatures with or without the addition of acid. In fact, in both cases, the initial steps in the postulated mechanisms are protonation of the C-2 oxygen atom followed by elimination of the aglycone to yield a ketohexofuranosyl or pyranosyl cation, which is the reactive intermediate in certain circumstances, this might be in equilibrium with the derived glycosyl fluoride. 

Therefore, if the excited-state lifetimes r0 and Tq are known, the plot of ( / 0)/( / ) versus [H30+] yields the rate constants k3 and k i. However, it should be emphasized that corrections have to be made (i) the proton concentration must be replaced by the proton activity (ii) the rate constant k 3 must be multiplied by a correction factor involving the ionic strength (if the reaction takes place between charged particles), because of the screening effect of the ionic atmosphere on the charged reactive species. 

The availability of protons is one of the most important properties of a medium by which it can influence an electrolytic reaction, especially a reduction. Anodic reactions are generally less susceptible to the proton activity, but both the stability of cation radicals and the reactivity of some nucleophiles in anodic substitution reactions depend on proton activity. 

Reactivation of immobilized HRP The immobilized HRP turns to inactive form by being protonated at the active site after reaction with H2O2. The inactivated HRP, however, is reactivated with alkaline imidazole solution by removing the proton from the protonated active site. This allows the immobilized HRP to maintain reactivity with H2O2 specimens. 

In the next step proton is transferred to the incoming monomer, which becomes ready to participate in chain growth. Propagation involves the most basic primary amino group and protonated (activated) monomer. After protonation of the monomer, the reactive intermediate is formed in which the proton may be located either on the exo-N-atom (A), endocyclic N-atoms (Q or on hydroxyl O-atom (B) ... 

Tertiary amines greatly accelerate the reactions. The effect is complex since the amines will bind iron as ligands and also decrease proton activity in the medium. That the latter effect must be of major significance is demonstrated by comparing the effects of pyridine and 2,6-lutidine. The latter exerts a more powerful catalysis effect despite the fact that steric hindrance weakens its ligand effect. Consequently, we infer that solvolysis to produce species such as FeCl(OCH3) and Fe( 00113)2 is extensive in the presence of bases and that the alkoxides must be more reactive than FeCb as substrates. The rate in the presence of 0.4M piperidine was immeasurably fast. The powerful acceleration is attributed to the high basicity of piperidine (pK = 2.80 in 50% ethanol) compared with pyridine (pK = 9.62) and 2,6-lutidine (pK, = 8.23). 

Proton-activating groups such as nitrile, ester, or p-nitrophenyl, on carbon atom 5 of the 7r-(penteno-4-lactonyl)cobalt tricarbonyl complexes make the compounds reactive toward bases. Bases cause the elimination of cobalt tricarbonyl anion and 5-substituted 2,4-pentadieno-4-lactones are produced 17). 

The relative independence of the elementary rate constant for proton-activated hydrocarbon conversion reactions carried out in different zeolite structures would indicate that the differences in the overall rate for different zeolites are not determined by the small differences in the reactivity of the protons (intrinsic acidity) but rather by a variation in the concentration of reactant molecules adsorbed on the zeolitic reaction centers. The higher apparent reactivity of the longer hydrocarbon chains in zeolite-catalyzed hydrocarbon conversion reactions can be likely ascribed to the increased concentration of hydrocarbon adsorbed at the reactive centers and not to a higher intrinsic reactivity of the hydrocarbon molecules. 

The compounds with a reactive germanium-nitrogen bond readily undergo transamination and substitution reactions with compounds having proton-active hydrogen atoms. In particular the transamination reaction offers a route to many other germanium derivatives. It may be expected, therefore, that the digermazanes will prove to be very suitable intermediates for the preparation of many new compounds. 

Finally, Mukaiyama-Mannich-type reactions can also be induced and mediated by proton activation of the imine component, which thereby obtains a sufficient degree of reactivity to be attacked by highly nucleophilic silicon enolates. Thus, Wenzel and Jacobsen have shown that the specific protection by N-aryl substituents with a pendant ortho-hydioxy or ortho-methoxy chelating group is not required, if the acetate-derived sHyl ketene acetals 362 are reacted with simply BOC-protected aryl and hetaryl imines 361. Thus, P-amino esters 364 are obtained in excellent enantiomeric excess, if the reaction is catalyzed by the chiral urea derivative 363 that is assumedto act by activation through hydrogen bonding (Scheme 5.95) [181]. 

I 6 Dioxygen Binding and Activation Reactive Intermediates 6.1.2.3 Flow of Electrons and Protons... 

The second aspect, predicting reaction dynamics, including the quantum behaviour of protons, still has some way to go There are really two separate problems the simulation of a slow activated event, and the quantum-dynamical aspects of a reactive transition. Only fast reactions, occurring on the pico- to nanosecond time scale, can be probed by direct simulation an interesting example is the simulation by ab initio MD of metallocene-catalysed ethylene polymerisation by Meier et al. [93]. 

While the classical approach to simulation of slow activated events, as described above, has received extensive attention in the literature and the methods are in general well established, the methods for quantum-dynamical simulation of reactive processes in complex systems in the condensed phase are still under development. We briefly consider electron and proton quantum dynamics. 

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. 

This reaction sequence is much less prone to difficulties with isomerizations since the pyridine-like carbons of dipyrromethenes do not add protons. Yields are often low, however, since the intermediates do not survive the high temperatures. The more reactive, faster but less reliable system is certainly provided by the dipyrromethanes, in which the reactivity of the pyrrole units is comparable to activated benzene derivatives such as phenol or aniline. The situation is comparable with that found in peptide synthesis where the slow azide method gives cleaner products than the fast DCC-promoted condensations (see p. 234). 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

Thiazolium derivatives unsubstituted at the 2-position (35) are potentially interesting precursors of A-4-thiazoline-2-thiones and A-4-thiazoline-2-ones. Compound 35 in basic medium undergoes proton abstraction leading to the very active nucleophilic species 36a and 36b (Scheme 16) (43-46). Special interest has been focused upon the reactivity of 36a and 36b because they are considered as the reactive species of the thiamine action in some biochemical reaction, and as catalysts for several condensation reactions (47-50). 

One reason for the low reactivity of pyridine is that its nitrogen atom because it IS more electronegative than a CH in benzene causes the rr electrons to be held more tightly and raises the activation energy for attack by an electrophile Another is that the nitrogen of pyridine is protonated in sulfuric acid and the resulting pyndinium ion is even more deactivated than pyndine itself... 

Complexation of the initiator and/or modification with cocatalysts or activators affords greater polymerization activity (11). Many of the patented processes for commercially available polymers such as poly(MVE) employ BE etherate (12), although vinyl ethers can be polymerized with a variety of acidic compounds, even those unable to initiate other cationic polymerizations of less reactive monomers such as isobutene. Examples are protonic acids (13), Ziegler-Natta catalysts (14), and actinic radiation (15,16). 

In theory two carbanions, (189) and (190), can be formed by deprotonation of 3,5-dimethylisoxazole with a strong base. On the basis of MINDO/2 calculations for these two carbanions, the heat of formation of (189) is calculated to be about 33 kJ moF smaller than that of (190), and the carbanion (189) is thermodynamically more stable than the carbanion (190). The calculation is supported by the deuterium exchange reaction of 3,5-dimethylisoxazole with sodium methoxide in deuterated methanol. The rate of deuterium exchange of the 5-methyl protons is about 280 times faster than that of the 3-methyl protons (AAF = 13.0 kJ moF at room temperature) and its activation energy is about 121 kJ moF These results indicate that the methyl groups of 3,5-dimethylisoxazole are much less reactive than the methyl group of 2-methylpyridine and 2-methylquinoline, whose activation energies under the same reaction conditions were reported to be 105 and 88 kJ moF respectively (79H(12)1343). 

The enzyme provides a general base, a His residue, that can accept the proton from the hydroxyl group of the reactive Ser thus facilitating formation of the covalent tetrahedral transition state. This His residue is part of a catalytic triad consisting of three side chains from Asp, His, and Ser, tvhich are close to each other in the active site, although they are far apart in the amino acid sequence of the polypeptide chain (Figure 11.6). 

The same arguments can be applied to other energetically facile interconversions of two potential reactants. For example, many organic molecules undergo rapid proton shifts (tautomerism), and the chemical reactivity of the two isomers may be quite different It is not valid, however, to deduce the ratio of two tautomers on the basis of subsequent reactions that have activation energies greater than that of the tautomerism. Just as in the case of conformational isomerism, the ratio of products formed in subsequent reactions will not be controlled by the position of the facile equilibrium. 

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