Deprotonation/reprotonation

It has been mentioned above that the pyrimidine radical cations are reasonably strong acids and rapidly deprotonate at a heteroatom. As all protonation/ deprotonation reactions at heteroatoms are reversible [e.g., equilibrium (22)], the radical cations are regenerated upon reprotonation. Deprotonation at carbon or reaction with water yield the final free-radical products. For the l,3Me2Thy system, where the deprotonation/reprotonation equilibria such as reaction (22) fall away, reactions (25)-(28) have been postulated to account for the fact that in the presence of 02 l,3Me25HOMeUra and l,3Me25(CHO)Ura [reaction (29)] are formed in a combined yield of 80% of primary S04 radicals (Rashid et al. 1991). The formation of these products has been taken as evidence that a free radical cation must be an intermediate. It is, however, also possible that the allylic radical is formed in a concerted reaction HS04 elimination. For such a process, a six-membered transition state can be written. 

The reason for the increased regioselectivity is that with tertiary alcohols as substrates there is no longer exclusively kinetic control. This is because the regioisomeric olefins are no longer formed irreversibly. Instead they can be reprotonated, deprotonated again, and thereby finally equilibrated. In this way, the greatest part of the initially formed Hofmann product is converted to the more stable Saytzeff isomer. Product formation is thus... 

Pulse radiolysis shows that the pyrimidine radical cations are fairly strong acids and rapidly deprotonate at a heteroatom [reaction (98)]. As protonation/deprotonation reactions at heteroatoms are easily reversible, the radical cations are regenerated upon reprotonation. Deprotonation at carbon or reaction with water yields the final free-radical products [reactions (99) - (101)]. It is noted that in thymidine [23] and 5 -thymidylic acid [104] the allylic thymine radical is observed by EPR and there is very little question that its precursor is the thymine radical cation. The identification of the C(6)-OH-5-yl radical by EPR supports the view [100] that reaction with water competes with the deprotonation at methyl. Due to the ready oxidation of the (reducing) C(5)-OH-6-yl by peroxodisulfate, this type of radical is only observed at low peroxodisulfate concentrations in these systems, i.e. the (oxidizing) C(6)-OH-5-yl radicals are correspondingly enriched under conditions favourable to a chain reaction [22]. In the case of 1,3-dimethyluracil the interesting characteristics of... 

K. G. Neoh, E. T. Kang, K. L. Tan, Structural study of polyaniline films in reprotonation/deprotonation cycles, Journal of Physical Chemistry 1991, 95, 10151. 

The mechanism of the first part of transamination is shown in Figure 29.14. The process begins with reaction between the a-amino acid and pyridoxal phosphate, which is covalently bonded to the aminotransferase by an iminc linkage between the side-chain -NTI2 group of a lysine residue and the PLP aldehyde group. Deprotonation/reprotonation of the PLP-amino acid imine in steps 2 and 3 effects tautomerization of the imine C=N bond, and hydrolysis of the tautomerized imine in step 4 gives an -keto acid plus pyridoxamine... 

Attempts to induce valence isomerization of 5W-dibcnz[c,e,]azepine (3) to dihydrophenanthro-[9,10-6]azirine under thermal conditions have failed.85 However, the aziridine 5 is formed, albeit in low yield (3 %), by irradiating the dibenzazepinc 3 in dichloromethane solution. Isomerization can also be achieved by deprotonation of SH-dibenzIr.eJazepine with lithium diiso-propylamide at — 78 "C, and then allowing the resulting anion 4 to reprotonate by heating the reaction mixture at 50°C.85... 

However, deprotonation of rc-rf-butyldimethylsilyl-protected products 2 (prepared according to the classical Henry conditions )22, and consecutive reprotonation, provides the silylated nitroaldols 2 with high (R, R ) selectivity. Deprotonation of 2 by treatment with lithium diisopropylamide in tetrahydrofuran at — 78 C furnishes nitronates which are stable against / -elimination at that temperature. Protonation of these intermediates is achieved with an acetic acid/tetrahydrofuran (1 1) solution at —100 C. To achieve maximum yields, the mixture should be warmed up slowly before aqueous workup. 

Deprotonation and then reprotonation of enantiomerically pure 1-alkenyl sulfoxide ( )-( +)-23 produces no double bond isomerization and no racemization, whereas similar treatment of (Z)-( —)-23 causes complete double bond isomerization and some racemization (equations 20 and 21)59d. 

The kinetic isotope effect of the protonation h/ d = 3.9 suggests that an in-nitrogen atom is protonated directly rather than conformational changes exposing the lone pair of a nitrogen atom to the outside prior to protonation. It is assumed that a protonated nitrogen does not invert. Inversion is only possible by a deprotonation-inversion-reprotonation sequence (Kjaer etal., 1979). 

The catalyst reported by Grotjahn and Lev (11-13) for alkyne hydration (2) is capable of isomerizing alkenes, but veiy slowly. Because we knew that the rate of alkyne hydration was unchanged in the presence of excess phosphine ligand, we thought that like alkyne hydration, alkene isomerization would require loss of acetonitrile ligand (14) and alkene binding. Subsequent deprotonation at an allylic position would make an q -allyl intermediate which when reprotonated at the other... 

Under basic conditions, obviously only one isomerization step takes place and thus a terminal alkyne will deliver 1,2-dienes selectively. With internal alkynes, on the other hand, selectivity can only be achieved when the alkyne is either symmetrical as in 14 [34] (Scheme 1.6) or has a tertiary center on one side as in 16 [35, 36] (Scheme 1.7). So, unlike potassium 3-aminopropylamide in 1,3-diaminopropane, where the Jt-bonds can migrate over a long distance by a sequence of deprotonations and reprotonations, here the stoichiometric deprotonation delivers one specific anion which is then reprotonated (in 16 after transmetalation). 

Substrates with carbamate-protected [81, 82] and even free hydroxyl groups [69] reacted similarly in a deprotonation-reprotonation sequence, the latter even with retention of the -configuration of an alkene such as 46 (Scheme 1.19). The analogous (E)-alkene also delivers only E-product. 

An unusual approach is the isomerization of a methyl-substituted 1,2,3-buta-triene to a vinylallene by stoichiometric deprotonation with wBuLi-TMEDA and reprotonation [83]. With an ether substituent on the butatriene a similar reaction is possible with KOtBu in DMSO [84], while a phenyl-substituted butatriene reacted spontaneously in CHC13 [85]. 

Let us consider the possible events following excitation of an acid AH that is stronger in the excited state than in the ground state (pK < pK). In the simplest case, where there is no geminate proton recombination, the processes are presented in Scheme 4.6, where t0 and Tq are the excited-state lifetimes of the acidic (AH ) and basic (A- ) forms, respectively, and ki and k i are the rate constants for deprotonation and reprotonation, respectively, kj is a pseudo-first order rate constant, whereas k i is a second-order rate constant. The excited-state equilibrium constant is K = k /k 7 ... 

The acido-basic properties of water molecules are greatly affected in restricted media such as the active sites of enzymes, reverse micelles, etc. The ability of water to accept or yield a proton is indeed related to its H-bonded structure which is, in a confined environment, different from that of bulk water. Water acidity is then best described by the concept of proton-transfer efficiency -characterized by the rate constants of deprotonation and reprotonation of solutes - instead of the classical concept of pH. Such rate constants can be determined by means of fluorescent acidic or basic probes. 

The pK of tyrosine explains the absence of measurable excited-state proton transfer in water. The pK is the negative logarithm of the ratio of the deprotonation and the bimolecular reprotonation rates. Since reprotonation is diffusion-controlled, this rate will be the same for tyrosine and 2-naphthol. The difference of nearly two in their respective pK values means that the excited-state deprotonation rate of tyrosine is nearly two orders of magnitude slower than that of 2-naphthol.(26) This means that the rate of excited-state proton transfer by tyrosine to water is on the order of 105s 1. With a fluorescence lifetime near 3 ns for tyrosine, the combined rates for radiative and nonradiative processes approach 109s-1. Thus, the proton transfer reaction is too slow to compete effectively with the other deactivation pathways. 

The kinetics and thermodynamics of the act-nitro equilibrium of picrylacetone (105) in 50 50 and 30 70 (v/v) H20-MC2S0 mixtures have been reported. Rate of general base-catalysed deprotonation of (105) and general acid-catalysed reprotonation of the resulting anion (106) have been monitored at low pH a fast equilibrium protonation of (106) to give a directly observable short-lived nitronic acid species (107) has been found to precede conversion to (105). The constants pAf and pATj,... 

The Brpnsted coefficient /3b = 0.52 for deprotonation of 3-phenylcoumaran-2-one (108) by a series of bases in 50% (v/v) water-dioxane, and q bh = 0.48 for reprotonation by the conjugate acid of the buffer, are indicative of a fairly symmetrical transition state for proton transfer, although the primary KE, ku/ku = 3.81, found for proton abstraction by HO is lower than expected. " The moderate intrinsic rate constant for deprotonation of (108) suggests that generation of the charge in the transition state is accompanied by only a small amount of molecular and solvent reorganization. In acidic solution, below pH 5, O-protonation of (110) occurs initially to form (109)... 

---