Formal protonation reactions

Many organic reactions involve acid concentrations considerably higher than can be accurately measured on the pH scale, which applies to relatively dilute aqueous solutions. It is not difficult to prepare solutions in which the formal proton concentration is 10 M or more, but these formal concentrations are not a suitable measure of the activity of protons in such solutions. For this reason, it has been necessaiy to develop acidity functions to measure the proton-donating strength of concentrated acidic solutions. The activity of the hydrogen ion (solvated proton) can be related to the extent of protonation of a series of bases by the equilibrium expression for the protonation reaction. 

The carbomethoxy cycle starts with the attack of a methoxy group at a coordinated carbonyl group or a migratory insertion of CO in a palladium methoxy bond. Any type of methoxy species will have a low concentration in the acidic medium of the reaction. In Figure 12.20 many details of these reactions, discussed above in section 12.2, have been omitted and only a shorthand notation is presented. Subsequently insertion of ethene takes place. It is known from stoichiometric experiments that both reactions are relatively slow. In the final step a formal protonation takes place, which as we saw before, may actually involve enolate species. 

The etherification of a,(jJ-bis (hydroxyphenyl)PSU with C1MS was demonstrated to be quantitative (for all procedures A, B and C), based on FTIR and 200 MHz H-NMR analyses (6). A careful analysis of the 200 MHz -H-NMR spectra of a,w-bis(vinylbenzyl)PSU prepared according to procedures A and B shows a signal assigned to aromatic formal protons (-OCH2O-, 6=5.64 ppm). This is due to a chain extension reaction of the q,U)-bis(hydroxyphenyl)PSU with methylene chloride. 

Of these four reactions (ii) and (iv) involve simple proton transfers to and from oxygen atoms, and experience shows that such equilibria will be set up very rapidly. The rate-limiting steps then become (i) and (iii), which involve greater structural changes and are likely to be slow. They are both formally termolecular reactions, and it is of interest to enquire whether either of them can be split up into consecutive bimolecular processes, one of which is rate-limiting. The only possibilities are as follows ... 

Figure 5.15 Cyclic voltammograms obtained for a mercury electrode immersed in a 5 mM solution of 2,7-AQDS as the pH of the unbuffered contacting electrolyte solution (0.1 M UCIO4) is varied by using either HCIO4 or NaOH. The pH values, from left to right, are 2.8, 3.5, 4.8 and 6.1. The scan rate is 0.1 V s, with an initial potential of —1.000 V. The inset shows the dependence of the formal potential on the solution pH in unbuffered solution. Reprinted from. Electroanal. Chem., 498, R. J. Forster and J. P. O Kelly, Protonation reactions of anthroquinone-2,7-disulfonic acid in solution and within monolayers, 127-135, Copyright (2001), with permission of Elsevier Science...

It was found that 7,8- and 7,9-dicarbollide dianions, formed on abstraction of a bridging endo proton from the corresponding dicarba-nzrfo-undecaborate monoanion with sodium metal solution or sodium amide in liquid ammonia or butyl lithium in THF, very easily interact with alkyl halides to yield B-alkyl-7,8- and -7,9-dicarba-nz[Pg.205]

To study the stereochemistry of protonation reactions, substituted indenes have been cathodically reduced in DMF/TBAP with added water or phenol [170b,173,174]. In the presence of water, a formal anti addition of protons was observed, whereas addition of phenol led to the prevalent formation of products, formally deriving from syn protonation. Obviously, steric effects and/or acidities of proton donor and the dihydroproduct play an important role. A detailed discussion of stereochemical aspects is found in Chapter 26. 

We have already seen in the chapter on nucleophilic substitution that carbon/ carbon double bonds, e.g. vinyl compounds, do not readily undergo the simple addition of a nucleophile so as to form a tetrahedral intermediate. This is because, in such a case, the negative charge would have to reside on a carbon atom. However, if there are sufficient electron withdrawing groups attached to this carbon, then it is possible to form this intermediate. Once formed, it could then eliminate another group so as to re-form the carbon/carbon double bond, resulting in an overall substitution reaction. However, in practice this pathway is rarely observed. Instead, it is found that an alternative pathway is followed, in which the anionic intermediate that is formed initially picks up a proton, which results in a formal addition reaction as the first step. 

Although the reaction requires no external catalyst, carbon dioxide is activated by the interaction of its electrophilic carbon atom and the negatively polarized carbon in the ortho (or para) position of the phenolate ring. This mechanism is supported by the fact that even under high CO2 pressure no salicylic acid is formed from phenol. The product is stabilized via an a > y proton migration. The free acid is obtained from the sodium salt in reaction with an external proton (usually from sulfuric acid). Formally, this reaction can be regarded as the insertion of CO2 into an aromatic C-H bond however, the above mechanism disproves this idea. 

The higher kinetic acidity of H2 complexes requires that the reverse reaction, protonation of a metal hydride, occur at H rather than at M, for which there is ample evidence. Actually protonation at the hydride is misleading because it is really the M-H bond that is protonated to form M-j/2-H2, as pointed out in a review by Kuhlman that addresses site selectivity of protonation of hydride-halide complexes, MH(X).64 Formal protonation of a hydride ligand would give M-ff -H2, which is not known to be stable. Proton transfer to halide ligands is quite rare because an add with a lower than the coordinated HX produced is necessary. One example is protonation of trens-PtHX(P Bu3)2 with triflic acid, which gives trans-[Pffl( f2-H2)(P Bu3)2][OTf] for X = H and an unstable spedes claimed to be... 

The preceding equilibrium of alkylallenes shows a formal analogy with the initial reaction slep of an acidic hydrolysis of saturated carboxylic acid esters R (RO)C—O or protonation reactions of carbonyl compounds RiR2C=0. This similarity concerns the position of the attack of the proton relative to the positions of the substituents and the kinds of atoms involved in that reactions. In both the cases (C and O) the attacked atoms have perpendicular p AOs in the LCAO expansions of their two outermost occupied orbitals. 

The reactions of benzyne complexes of zirconium " also occur by electrophilic attack at an M-C bond. The isolated phosphine adduct of a zironocraie-benzyne complex reacts with ketones to imdergo insertion into one of the M-C bonds and with alcohol to make an aryl alkoxo complex, as shown in Equation 12.67. An electron-rich ruthenium-benzyne complex also reacts with electrophiles, such as borzaldehyde or carbon dioxide, to form products from insertion, as shown at the top of Equation 12.68. It also reacts with weak acids, such as aniline, to form products from formal protonation at the Ru-C bond, as shown at the bottom of Equation 12.68. - This reaction with aniline could occur by initial protonation at the metal, followed by C-H bond-forming reductive elimination, or by direct protonation of the M-C bond. Initial protonation of the metal center was proposed. 

After studying the mechanism by which hydrogen bond donors catalyze electron transfer, the authors developed a novel oxidative lactonization reaction to demonstrate the synthetic utility of hydrogen-bond coupled electron transfer (Fig. 40). Importantly, this work extends the current understanding of how hydrogen bonding can promote electron transfer events in synthetic contexts, even in the absence of a formal proton transfer event. 

Interestingly, photolysis of fluorenylidenesilene 588 is reported to give insertion of the Si=C bond in one of the ortho methyl groups of the fluorenylidene substituent yielding the polycyclic compound 647 (equation 214). This product has the opposite regiochranistiy in respect to the formal addition of a C—H bond across the Si=C double bond of the 1-silaaUene moiety than that found in the protonation reaction. ... 

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