Abstraction by base

Examine atomic charges and display the electrostatic potential map for 2,7-octadione. Are you able to say which hydrogens (at Ci or at C3) are more likely to be abstracted by base, and conclude which is the kinetically-favored enolate Which enolate (2,7-octadione, Cl enolate or C3 enolate) is the lower in energy What do you conclude is the thermodynamically-favored enolate Is this also the enolate in which the negative charge is better delocalized Compare electrostatic potential maps to tell. 

Another important feature of the Nef reaction is the possible use of a CH-NO2 function as an umpoled carbonyl function. A proton at a carbon a to a nitro group is acidic, and can be abstracted by base. The resulting anionic species has a nucleophilic carbon, and can react at that position with electrophiles. In contrast the carbon center of a carbonyl group is electrophilic, and thus reactive towards nucleophiles. 1,4-Diketones 4 can for example be prepared from a-acidic nitro compounds by a Michael additionfNef reaction sequence " ... 

If the starting ester has more than one acidic a hydrogen, the product /3-keto ester has a highly acidic, doubly activated hydrogen atom that can be abstracted by base. This deprotonation of the product requires that a full equivalent of base rather than a catalytic amount be used in the reaction. Furthermore, the... 

Although pyrrole is a much weaker base than most other amines, it is a much stronger acid (p/C, 15 tor the pyrrole versus 35 for diethylamine). The N—H proton is readily abstracted by base to yield the pyrrole anion,... 

In organic compounds having C—H bonds, the carbon atom being more electronegative will pull the bonding electron towards itself and so hydrogen can go out as a proton. Therefore, in presence of a base this H will be attracted by the base and a carbanion will be obtained. This acidic hydrogen will be abstracted by bases like NaOH, t-BuOe or alkyl lithium where the alkyl radical will behave like a base. 

The second substrate glyoxylate approaches from the other side of the molecule and condenses as is shown. Since any one of the three protons in either R or S chiral acetyl-CoA might have been abstracted by base B, several possible combinations of isotopes are possible in the L-malate formed. One of the results of the experiment using chiral (R) acetyl-CoA is illustrated in Eq. 13-43. The reader can easily tabulate the results of removal of the 2H or 3H. However, notice that if the base -B removes 2H (D) or 3H (T) the reaction will be much slower because of the kinetic isotope effects which are expected to be Hk/"k 7 and "k/ k = 16. A second important fact is that the pro-R hydrogen at C-3 in malate is specifically exchanged out into water by the action of fumarate hydratase. From the distribution of tritium in the malate and fumarate formed using the two chiral acetates, the inversion by malate synthase was established. See Kyte231 for a detailed discussion. 

In systems with a methine carbon in the azole ring, proton abstraction by base may lead to ring cleavage as observed in related thiadiazoles. This is a common reaction in isoxazole analogues. 

A methine proton in the thiadiazole ring is acidic and is readily abstracted by base. In fused 1,3,4-thiadiazoles proton abstraction may lead to cleavage of the N—N bonds as in the pyrimidinium salt (697) the thiocyanate (698) is formed (74KGS1660). From the isomeric oxo derivatives (699) and (700) having the same ring system, a common thiocyanate (701) is formed (74BCJ2813). 

It is unusual to think of a carbonyl compound as an acid, but the protons a to a carbonyl group can be removed by a strong base. Protons a to two carbonyl groups are even more acidic in some cases, acidity approaches that of phenols. This acidity is the basis for a-substitution reactions of compounds having carbonyl groups. Abstraction by base of an a proton produces a resonance-stabilized enolate anion that can be used in alkylations involving alkyl halides and tosylates. 

As carbon atoms with sp and sp2 configurations are more electronegative than sp3 carbon atoms, proton abstraction by bases from acetylenic, ethylenic, or aromatic CH bonds occurs more readily than from saturated aliphatic CH bonds. 

With the fluoride, we have predominant C—H bond-breaking, with little alkene character but considerable carbanion character to the transition state. A primary hydrogen is preferentially abstracted by base, since that permits the negative charge to develop on a primary carbon, to which there is attached only one electronreleasing alkyl group. Orientation is Hofmann. 

Alpha hydrogens are hydrogens on carbons directly attached to a carbonyl group. They are weakly acidic and can be abstracted by base to form a carbanion. The carbanion is called an enolate ion and is resonance stabilized. Neutralization of the enolate ion results in an enol, a compound in which an alcohol group is directly bonded to a carbon involved in a carbon-carbon double bond. The enol is in equilibrium with the original aldehyde or ketone in an equilibrium referred to as keto-enol tautomerism. The equilibrium usually favors the keto form. 

The NH proton of 3-aryl-3,4-dihydro-l,2,3-benzotriazin-4-imines is sufficiently acidic to be abstracted by base leading to opening of the triazine ring <1984CHEC(3)369>. A further example for this reactivity is the transformation of 54 (R = Ar) to the triazenes 209 in good yield (Equation 80) <1974J(P1)611>, but compare with Equations... 

Activation of the carboxyl group in itself is conducive to racemization. The otherwise chirally stable acylamino acids and peptides can lose chiral homogeneity once their free carboxyl group is converted into a reactive derivative. The electron-withdrawing effect of the activating group (X) renders the proton on the a-carbon atom slightly acidic and hence abstractable by base and chirality is, of course, lost in the carbanion. This simple mechanism, however, is operative only... 

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