Reprotonation

The relatively low pX values seen for the benzoyl acetanilides, especiaHy as two-equivalent couplers, minimize concerns over slow ionization rates and contribute to the couplers overaH reactivity. But this same property often results in slow reprotonation in the acidic bleach, where developer carried over from the previous step can be oxidized and react with the stiH ionized coupler to produce unwanted dye in a nonimage related fashion. This problem can be eliminated by an acidic stop bath between the developer and the bleach steps or minimized by careful choice of coupling-off group, coupler solvent, or dispersion additives. 

The dienol is unstable, and two separate processes have been identified for ketonization. These are a 1,5-sigmatropic shift of hydrogen leading back to the enone and a base-catalyzed proton transfer which leads to the / ,y-enone. The deconjugated enone is formed because of the kinetic preference for reprotonation of the dienolate at the a carbon. Photochemical deconjugation is a synthetically useful way of effecting isomerization of a,) -unsaturated ketones and esters to the j ,y-isomers. 

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. 

In the case of the ketone (12), a racemic mixture was converted to an optically active mixture (optical yield 46%) by treatment with the chiral base (13). This happened beeause 13 reacted with one enantiomer of 12 faster than with the other (an example of kinetic resolution). The enolate (14) must remain coordinated with the chiral amine, and it is the amine that reprotonates 14, not an added proton donor. 

Reprotonation of Ru(CO)2(CNR)(PPhj)2 gives Ru(CO)j(CNR)(PPhj)2-, which is an isomer of the previously described compound. The probable structures of the original isomer (XXV) and the second isomer (XXVI) are shown above. 

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... 

Method B In contrast, reprotonation of the tert-butyldimethylsilyl-protected nitronate anions gives awh-isomers selectively (41 9-19 1). 

P-gp substrates are in general either neutral or cationic at physiological pH (weak bases). Weak bases can cross the lipid membrane in the uncharged form and reprotonate in the negatively charged cytosolic leaflet of the membrane. With a few exceptions (e.g., the tetraphenyl phosphonium ion, which can reach the cytosolic membrane leaflet due to charge delocalization [70]), permanently charged cations do not cross the cell membrane and therefore cannot interact with P-gp in intact cells. They can, however, insert into the cytosolic leaflet in inside-out cellular vesicles and are then transported by P-gp [42, 71]. 

The main extra species that forms upon acidification of paratungstate was identified as a -[(H)Wi204o]7, which is internally protonated and forms at higher pH than a -[(H2)Wi204o]6 (141). This monoproto-nated species, a-[(H)Wi204o]7, was previously only obtained by reduction and reoxidation (154). It is slowly reprotonated to o -[(H2) Wi2O40]6-, the half-life of the reaction being 1 day at room tempera-... 

Extension of this research was then delayed until two of us had returned to New Zealand. One of the first jobs of Tasker, a PhD student from Brisbane, was to use 3H-labeling methods to examine epimerization. At that time we were under the impression that reprotonation of carbanion intermediates would be diffusion controlled, as was subsequently reported for phenylglycine in phosphate buffers (18), so that no isotopic discrimination against 3H would be present. But then Wautier et al. reported (6) the complete loss of chirality in [Co(tren)(AA-(S)-AA OMe)]3+, prepared by treating [Co(tren)((S)-AAOMe)]3+ (AA = Ala, Leu) generated in situ in MeOH with (S)-AA OMe (AA = Leu, His, Ala, Val), although their reaction times and temperatures (1-15 h sometimes 35-50°C) and other experimental conditions ([Co(III)] —0.1 M L/V-ethylmorpholine salt of p-toluene sul-... 

This equilibrium value is the same as that found for the chelated acid (Kk = 1.0) (17) so it is likely that the dipeptide carbanion, like 15 (Scheme 15), shows less kinetic discrimination for reprotonation (k-i/ k-2) than does the ester carbanion 18. In D20 H-exchange and epi-merization occur at the same rate, kohs = 6.4 X 10 4 s 1 (pD = 8.4, 34°C), to give the same equilibrium distribution of A-S-S and A-R-S products (24). 

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