Exchange hydrogen

Hydrogen-exchange rates as a function of level of hydration can be calculated from data such as those of Fig. 22. Results of this kind, for pH 2-10, are given in Fig. 23. The slope of the exchange rate-water 

Hydrogen Exchange.—Hydrogen-deuterium exchange in ethylbenzene is 

Hydrogen Exchange.—On the n.m.r. time-scale it is proton exchange with the water ligands rather than with the (protonated) azide ligands of [Cr(OH2)5(NsH)] + that can be observed. The rate law is  

The activation parameters for the two proton-exchange paths are AHt = 11.7 kcalmol and = + 3 cal deg- mol for the ki path, and = 3.2 kcal mol and AS = — 24 cal deg mol for the kz path. Proton exchange with the cobalt(m) complexes [Co(NH8)5(OHa)] and cis- and rfln -[Co(en)a(NH3)(OH2)] has been probed by determining the dependence of Co n.m.r. linewidths on pH. In fact, proton exchange with the aquo-ligands is fast, and it is only possible to establish lower limits to the rate constants. The forward and reverse rate constants for reaction (1) have been measured using the electric-field-jump relaxation 

The rate of proton transfer to the nickel(n)-triglycine complex is remarkably slow when the ligand is in its twice-deprotonated form, and considerably faster for the once-deprotonated form. Rates of protonation 

Hydrogen-deuterium exchange of alkanes catalysed by platinum(n) in AcOD and DgO is thought to involve hydrido(alkyl)platinum intermediates which in hydrogenation reactions may revert to the parent alkene. However, attempts to function- 

Electrophilic aromatic hydrogen exchange reactions fall into two classes, namely those reactions catalysed by acid and those reactions catalysed by base. Of these the former are by far the most common and have been subjected to the most extensive and intensive kinetic studies. 

The intermediacy of enols or enolate anions may be demonstrated by hydrogen exchange reactions (see Section 4.11.2). Both acid-catalysed and base-catalysed tautomerism mechanisms involve removal 

pentan-3-one can be deuteriated using a large excess of D2O, with either acid (DCl) or base (NaOD) catalyst the acid or base catalyst should also be deuteriated to minimize dilution of label. After 

Two mechanisms are shown above. The base-catalysed mechanism proceeds through the enolate anion. The acid-catalysed process would be formulated as involving an enol intermediate. Note that the terminal hydrogens in pentan-3-one are not exchanged, since they do not participate in the 

Altliough this section has been termed hydrogen exchange, it is important to realize that we could also visualize this simply as an enolate anion acting as a base. This is also true of the next section, and in some of the following sections we shall encounter enolate anions acting as nucleophiles. 

The process of hydrogen exchange shown above has implications if the a-carbon is chiral and has a hydrogen attached. Removal of the proton 

The pH and temperature dependences of linewidths and chemical shifts for aqueous solutions of [Ru(NH3)6] + have been discussed in terms of proton exchange between complex and solvent. This process is base-catalysed, with an activation enthalpy of 20 kcal mol and an activation entropy of +51 cal deg mol . These activation parameters are presumably composite quantities, as an activation enthalpy as high as 20 kcal mol is inconsistent with the very high rates observed. The formation of deprotonated species and ion pairs is proposed, to produce an appropriate multi-stage reaction whose overall activation parameters will include and S° terms for the relevant preequilibria.  

Chemical groups such as -NH or -OH (bul no/ - H). involving hydrogens attached to electronegative atoms, rapidly (and reversibly) exchange to -ND or -OD when exposed to DzO (heavy water). 

A typical experiment involves mixing of the protein solution with isotopically enriched solvent (usually D2O) under carefully controlled temperature and pH conditions, followed by sampling at timed intervals to monitor the extent of H-D exchange. Groups exposed to solvent at, or near, the surface of a globular protein will exchange rapidly, whereas those in more protected chemical environments will change more slowly. 

The mechanism of slow H D exchange in these systems is quite complicated, but one simple model relates it to the rate of transient conformational (unfolding) transitions of the protein. During such conformational changes, groups that are normally protected become briefly exposed to solvent and can undergo isotope exchange. 

Remember that proteins (and other biological macromolecules) are quite dynamic, flexible molecules. Even at equilibrium, and just like all chemical equilibrium processes, this equilibrium is dynamic, since thermal motion never stops. For a two-state process, the exchange kinetics may be described by  

Alternatively, ore might pre-equilibrate the protein mo rcul. in a D7O buffer, and then dilute into H.-XD to follow the releasi- of exchangeable dfHitenum atoms This can also be done using the radioactivity of tritium-labelled water 

Two reviews of catalytic transfer hydrogenation have appeared, The complex [Ru(Cl)(I (PPh3)3] not only functions as a useful hydrogenation catalyst as described in the previous section but also catalyses H2-D2 exchange in benzene solution. The Da-H2 exchange follows the rate law 

The rates are solvent-dependent and for cyclohexene in toluene at 80 C the rate law shown in equation (4) is obeyed. The zero-order dependence on olefin is ascribed to 

P = PPh3 S = olefin D = propan-2-ol A = acetone L = solvent, PPhj, or propan-2-ol 

Isotopic hydrogen exchange in both the side-chain and the aromatic ring of alkyl-benzenes catalysed by RhCls has several features in common with analogous reactions carried out in the presence of heterogeneous catalysts. This has led to the conclusion that a similar type of mechanism operates, i.e. the terminal abstraction 71-complex process. 

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Covalent. Formed by most of the non-metals and transition metals. This class includes such diverse compounds as methane, CH4 and iron carbonyl hydride, H2Fe(CO)4. In many compounds the hydrogen atoms act as bridges. Where there are more than one hydride sites there is often hydrogen exchange between the sites. Hydrogens may be inside metal clusters. 

Schnieder L, Seekamp-Rahn K, Wede E and Welge K H 1997 Experimental determination of quantum state resolved differential cross sections for the hydrogen exchange reaction H -r D2 -> HD -r D J. Chem. Phys. 107 6175-95... 

Truong T N 1997 Thermal rates of hydrogen exchange of methane with zeolite a direct ab initio dynamics study on the importance of quantum tunneling effects J. Rhys. Chem. B 101 2750... 

Neuhauser D, Baer M, Judson R S and Kouri D J 1989 Time-dependent three-dimensional body frame quantal wavepacket treatment of the atomic hydrogen + molecular hydrogen exchange reaction on the Liu-Siegbahn-Truhlar-Horowitz (LSTH) surfaced. Chem. Phys. 90 5882... 

The hydroxyl hydrogen exchanges but the hydrogen atoms of the CH3 (methyl) group do not. 

As a corollary to the above it should be pointed out that the exchange is in some instances stoichiometric and therefore the amount of cation in solution can be estimated by passage through a hydrogen exchanger as above and subsequent titration of the acid in the effluent. 

The cr-complexes (iv) are thus the intermediates corresponding to the substitution process of hydrogen exchange. Those for some other substitutions have also been isolated in particular, benzylidyne trifluoride reacts with nitryl fluoride and boron trifluoride at — ioo°C to give a yellow complex. Above — 50 °C the latter decomposes to hydrogen fluoride, boron trifluoride, and an almost quantitative yield of tn-nitrobenzylidyne trifluoride. The latter is the normal product of nitrating benzylidyne trifluoride, and the complex is formulated as... 

The solubility of hydrogen chloride in solutions of aromatic hydrocarbons in toluene and in w-heptane at —78-51 °C has been measured, and equilibrium constants for Tr-complex formation evaluated. Substituent effects follow the pattern outlined above (table 6.2). In contrast to (T-complexes, these 7r-complexes are colourless and non-conducting, and do not take part in hydrogen exchange. 

This genera] scheme could be used to explain hydrogen exchange in the 5-position, providing a new alternative for the reaction (466). This leads us also to ask whether some reactions described as typically electrophilic cannot also be rationalized by a preliminary hydration of the C2=N bond. The nitration reaction of 2-dialkylaminothiazoles could occur, for example, on the enamine-like intermediate (229) (Scheme 141). This scheme would explain why alkyl groups on the exocyclic nitrogen may drastically change the reaction pathway (see Section rV.l.A). Kinetic studies and careful analysis of by-products would enable a check of this hypothesis. 

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

Reactions at the a-carbons have been of considerable kiterest because it is at these positions that enzymatic oxidation, which is beheved to initiate the events leading to carcinogenic metaboUtes, generally occurs (5,7,8,73). The a-hydrogens exchange readily as shown in the following where D represents H. This exchange apparentiy results from stabilization of an anionic intermediate by electron delocalization (74,75). 

M. G. Reinecke, Tetrahedron 38, 427 (1982) R. Mumgan, Meta/Zation, Conformationa/Ana/ysis, Hydrogen Exchange and Rearrangement in Amides, Doctoral thesis. University of Plorida, Gainesville, 1987 A. Weissberger and E. C. Taylor, eds.. The Chemistry of Heteroyc/ic Compounds, in Ref. 11, pp. 448—449. 

A variant of the H2/NH2 chemical exchange process uses alkyl amines in place of ammonia. Hydrogen exchange catalyzed by NH2 is generaHy faster using alkyl amines than ammonia, and a dual-temperature flow sheet for a H2/CH2NH2 process has been developed (69). 

Acid-catalyzed hydrogen exchange Halogenation Acylation and alkylation Mercuration Diazo coupling Nitrosation... 

Hydrogen exchange at ring carbon in neutral azoles... 

Ring hydrogen atoms can be abstracted from the a-carbon atoms of azolium ions b strong bases, as demonstrated in base-catalyzed hydrogen exchange (Section 4.02.1.7.2... 

Acid-catalyzed hydrogen exchange is used as a measure of the comparative reactivity of different aromatic rings (see Table 5). These reactions take place on the neutral molecules or, at high acidities, on the cations. At the preferred positions the neutral isoxazole, isothiazole and pyrazole rings are all considerably more reactive than benzene. Although the 4-position of isothiazole is somewhat less reactive than the 4-position in thiophene, a similar situation does not exist with isoxazole-furan ring systems. 

Base-catalyzed hydrogen exchange has been summarized for five-membered rings (74AHC(l6)l). In many reactions of this type the protonated azole is attacked by hydroxide... 

Base-catalyzed hydrogen exchange occurs at the 3- and 5-positions of 1,2-dimethyl-pyrazolium salts. 2-Unsubstituted 1,3-dithiolylium salts are easily deprotonated by nucleophilic attack of hydrogen. The intermediate carbene easily undergoes dimerization. Hydrogen exchange can also occur (Scheme 23) (80AHC(27)15l). 

Isoxazoles are presently known to undergo hydrogen exchange, nitration, sulfonation, halogenation, chloroalkylation, hydroxymethylation, Vilsmeier-Haack formylation, and mercuration. The Friedel-Crafts reaction on the isoxazole nucleus has not yet been reported. 

Hammett and Taft constants, S, 107 homolytic substitution, S, 5 hydrogen exchange, S, 57, 69-70 hydroxy... 

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