Exchange under Basic Conditions

Stoichiometric C-deprotonation of a compound results in a carbanion which can be quenched by addition of tritiated water or another tritium source, either in situ or after some manipulation of the deprotonated substrate. This method can have advantages over thermodynamic exchange procedures, including greater chemo- or regioselectivity, the achievement of higher specific activity or economy in the use of tritium. 

When LDA (or to a lesser extent LiHMDS) is used as the base to deprotonate a substrate, isotope incorporation from added tritium or deuterium can be considerably less than 

---

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions. It has been reported that even weak bases such as phenolate can extract the proton at the 5-position of 4-phenyl-l,2,3-thiadiazole <1999J(P1)1473>. 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions, yet to date there have been no published estimates or experiments to determine the pA of these protons. Few attempts have even been made to metalate and alkylate this heterocycle. One study <85S945> found that metalation of 5-phenyl-1,2,3-thiadiazole (25) with methyllithium gives 4-lithio-5-phenyl-l,2,3-thiadiazole, which is stable and reacts with aldehydes and ketones in high yields (Equation (11)). Also, treatment of 4-phenyl-1,2,3-thiadiazole with lithium diisopropylamide, in the presence of TMS-Cl, affords 4-phenyl-5-trimethylsilyl-1,2,3-thiadiazole. 

The chemist can adopt a variety of procedures to simplify complex spectra to make them more amenable to first-order analysis or analysis by inspection. A simple example is deuterium exchange which was described in the previous section. Acidic protons attached to carbon may also be exchanged under basic conditions. 

The vinyl ether in the latter part of the equation is copolymetized with tetrafluoroethylene, and then the sulfonyl fluoride group is hydrolyzed under basic conditions in order to produce the ion-exchange membrane (44—46). 

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

The intermediate tricyclic ketones 495 and 496 have been transformed to the methoxy-substituted derivative 97284,285) latter ketone is subject to hydrogen-deuterium exchange only under basic conditions and appears to exist entirely in the keto form despite the ready formation of its anion and successful methylation on oxygen . In agreement with the aromatic nature of 490, the hydrocarbon undergoes electrophilic substitution reactions... 

Metal-free corrin is stable only in the protonated form and reversibly deprotonates at C-8 and C-l 3 in neutral or basic media (pX mcs 8.6 in dimethyicellosolve- water, 1 l).250 Therefore, deutera-tion under basic conditions (Na0D-KCN/Bul0D-D2O (1 1), r.t., M = H2, CoHI(CN)2, Ni2+) occurs at those positions. The electrophilic proton-deuterium exchange (TFA/Bu 0D-D20 (1 1), r.t., M = H2, Coih(CN)2, Ni2+) is more facile at C-5 and C-15 than at C-10 as predicted from MO calculations.239,250... 

Contrary to the recyclizations in alkaline medium, the transformations of either the salt 184 and the diketone 205 in acidic oxygen-labelled aqueous solutions lead only to the labelled a-naphthol 204. These facts are evidence that the rate of isotopic exchange in the carbonyl group in this case is higher than the enolization rate under basic conditions. The conversions 204 = 204 under acidic conditions also do not occur. 

Application of the principle of stereoelectronic control to the hydrolysis of esters under basic conditions leads to the following predictions Z esters are allowed to undergo carbonyl-oxygen exchange but E esters cannot. 

Exchange Rate Coefficients and Partial Rate Factors for Detritiation of Indoles under Basic Conditions at 25°C... 

Under basic conditions, hypoxanthin (8.108), its 1- and 3-methyl derivatives, and 5-chloro-l-methylhypoxanthin,3 all underwent exchange at the... 

In the preparation of dynamic nitroaldol systems, different aldehydes and nitroalkanes were first evaluated for reversible nitroaldol reactions in the presence of base to avoid any side- or competitive reactions, and to investigate the rate of the reactions. 1H-NMR spectroscopy was used to follow the reactions by comparison of the ratios of aldehyde and the nitroalcohols. Among various bases, triethylamine was chosen as catalyst because its reactions provided the fastest exchange reaction and proved compatible with the enzymatic reactions. Then, five benzaldehydes 18A-E and 2-nitropropane 19 (Scheme 9) were chosen to study dynamic nitroaldol system (CDS-2) generation, because of their similar individual reactivity and product stabilities in the nitroaldol reaction. Ten nitroaldol adducts ( )-20A-E were generated under basic conditions under thermodynamic control, showing... 

---