Acid-base reactions carbanions + proton

The most common reaction of carbanions is combination with a positive species, usually a proton, or with another species that has an empty orbital in its outer shell (a Lewis acid-base reaction) ... 

Cleavage of a carbon-hydrogen bond to yield a carbanion and proton is a Bronsted acid-base reaction (Equations 5.24 and 5.25). The mechanism is not... 

The interposed acid-base reactions which are most frequently observed, belong to two categories acid-base reactions following a one-electron transfer, as observed for numerous carbonyl compounds at higher pH values and for some hydrocarbons and proton-transfer reactions involving the product of a two-electron reduction process, usually carbanions. 

The new carbanion abstracts a proton from an ammonia molecule in an acid-base reaction, leading to the formation of aniline. 

Because removal of a proton from a carbon bonded to phosphoms generates a resonance-stabilized carbanion (the ylide). this proton is somewhat more acidic than other protons on an alkyl group in the phosphonium salt. Very. strong bases are still needed, though, to favor the products of this acid—base reaction. Common bases used for this reaction are the organoUthium reagents such as butyllithium, CH3CH2CH2CH2Li, abbreviated as BuLi. 

We have, then, three acid-base reactions and a 1,2-alkyl shift all familiar reaction types. Step (1) involves formation of a carbanion step (3) involves intramolecular nucleophilic (8 2) attack by a carbanion-like alkyl group and step (4) involves attachment of a proton to a carbanion or a carbanion-Hke motely. 

Reagents such as n-butyllithium, methyllithium, and phenyllithium manufactured by this process are commercially available. Carbanions can also be formed by an acid-base reaction involving heterolytic dissociation of a carbon-hydrogen bond by a strong base. An example is the deprotonation of limonene (86) by -butyllithium complexed with tetramethylethylenedia-mine (TMEDA), as shown in equation 5.61. Note that there is more than one kind of allylic proton in 86, but the deprotonation preferentially produces the least-substituted carbanion. ... 

Because LDA is a non-nudeophilic base, it should react with a ketone to give an enolate anion. In an actual experiment, 2-pentanone (32) reacts first with LDA to form the enolate anion (not shown) and then with benzaldehyde (25) to form the aldol alkoxide product (also not shown). Subsequent mild acid hydrolysis gives 33 in 80% yield. Virtually no self-condensation of 32 is observed in this experiment, which suggests that the reaction is largely irreversible. Assume that 2-pentanone reacts with LDA to give enolate anion 34 (the two resonance forms are 34A and 34B). As in all of these reactions, the carbanion form of the enolate 34A is the nucleophile. To account for the observed lack of self-condensation, the equilibrium for this acid-base reaction must be pushed toward 34 (the reasons for this will be discussed in Section 22.4.2). If this statement is correct, it means that 32 has been converted almost entirely to 34, so there is little or no 43 available to react. Therefore, a different carbonyl compound may be added in a second chemical step to give 35. This is an overstatement of the facts, but it is a useful assumption that explains the results. Note that benzaldehyde is used, which has no a-protons and cannot form an enolate anion. 

In Section 1.7 (p. 41), we introduced acids and bases. Now we know quite a bit more about structure and can return to the important subject of acids and bases in greater depth. In particular, we know about carbocations and carbanions, which play an important role in acid—base chemistry in organic chemistry The Lewis definition of acids and bases is far more inclusive than the Bronsted definition, which focuses solely on proton donation (Breasted acid) and acceptance (Breasted base). The archetypal Brensted acid-base reaction is the reaction between KOH and HCl to transfer a proton from HCl to HO. This reaction is a competition between the hydroxide and the chloride for a proton. In this case, the stronger base hydroxide wins easily (Rg. 2.57). 

OrganoUthium compounds are used as bases to remove protons from very weak acids. The pA of methane is about 50, and the methyl carbanion is one of the strongest bases encountered in organic chemistry. OrganoUthium compounds, such as methyllithium, are used to prepare conjugate bases of a variety of organic compounds. For example, amines react with methyUithium in an acid—base reaction to form amide salts. The equiUbrium constant for the reaction of methyUithium with diisopropylamine is approximately 10 . ... 

The role of the base is apparently primarily that of a proton remover from the reactive methylene group thus if B represents the base, reaction (i) gives the carbanion, which then combines with the positive carbon of the carbonyl group (reaction ii) the product regains a proton from the piperidinium ion, and then by loss of water followed by mono-decarboxylation of the malonic acid residue gives the final acid. 

Base-catalyzed hydrocarbon conversions, although generally less common than acid-catalyzed reactions, also play a significant role in hydrocarbon chemistry. They proceed through proton abstraction giving intermediate carbanions 92A 94... 

The one-base mechanism is characterized by the retention of the substrate-derived proton in the product (internal retum).30) With this criterion, reactions catalyzed by a-amino-c-caprolactam racemase,323 amino acid racemase of broad specificity from Pseudomonas striata333 have been considered to proceed through the one-base mechanism. However, such internal returns were not observed in the reactions of alanine racemases from K coli B,33) B. stearothermophilus,263 and S. typhirmaium (DadB and /1/r).263 The internal return should not be observed in the two-base mechanism, because the base catalyzing the protonation to the intermediate probably obtains the proton from the solvent. But the failure of the observation of the internal return can be also explained by the single-base mechanism in which exchange of the proton abstracted from the substrate a-carbon with the solvent is much faster than its transfer to the a-carbanion. Therefore, lack of the internal return does not directly indicate the two-base mechanism of the alanine racemase reaction. 

The interest in proton transfer to and from carbon arises partly because this process occurs as an elementary step in the mechanisms of a number of important reactions. Acid and base catalysed reactions often occur through intermediate carbonium ions or carbanions which are produced by reactions (1) and (2). A knowledge of the acid—base properties of carbonium ions or carbanions may also help in understanding reactions in which these species are present as reactive intermediates, even when they are generated by processes other than proton transfer. Kinetic studies of simple reactions such as proton transfer are also important in the development of theories of kinetics. Since both rates and equilibrium constants can often be measured for (1) and (2) these reactions have been useful in the investigation of correlations between rate coefficients and equilibrium constants (linear free energy relations). 

This reaction type is called the ElcB mechanism, which stands for unimolecular elimination conjugate base reaction, because the conjugate base of the starting material is being formed as the reactive intermediate. It is sometimes called the carbanion mechanism. As this mechanism results from the removal of a proton, it is not surprising that it is favoured by those substrates that possess an acidic hydrogen atom. Thus, would you expect the ElcB mechanism to be more prevalent in reactions that result in a carbon/carbon double bond or in reactions that result in a carbon/carbon triple bond ... 

Which electrophile is lost from the amino acid residue is, of course, controlled by the enzyme. One way this may occur is by the enzyme binding the PLP imine so that the electrophile is in close proximity to a suitable or base to aid abstraction and also so that the a orbital of the bond to be broken is periplanar with the p r acceptor system, i.e. orthogonal to the plane of the pyridine ring (XXXI). Maximal orbital overlap, stereoelectronic control, will lower the activation energy for the reaction. Aldol-type reactions can also occur with PLP as in the laboratory the key to making carbon-carbon bonds is the formation of a stabilised carbanion. Proton abstraction from the initially formed imine gives a masked carbanion which can nucleophili-... 

In the formation of the first synthetic intermediate in Sequence D, the very effective Verley-Doebner modification of the fundamental Knoevenagel condensation is used. This modification uses malonic acid in place of the conventional ester to promote enoUzation. In addition, the heterocyclic amine, pyridine, functions as both the base catalyst and the solvent. A cocatalyst, P-alanine (an amino acid), is also introduced. Mechanistically, the reaction closely resembles the aldol condensation in that in both cases a carbanion is generated by abstraction, by base, of a proton alpha to a carbonyl group. The resulting carbanion is stabilized as an enolate anion (see below). 

Substitution processes focused around the carbonyl group as well as at the carbonyl group are, of course, also possible. Consider the case depicted in item 7 of Table 9.9. As noted immediately above for the intermolecular and intramolecular versions of the Claisen condensation, success depends upon generation of an anion a- to the carbon of the carbonyl. Generation of such anions, particularly at fairly high dilution (where reaction between esters is less likely) with hindered bases, followed by addition of an electrophilic species to the reaction medium, results in overall substitution of the electrophilic species for the proton that was removed. In item 7 of Table 9.9, as shown in Scheme 9.147, the methyl ester of cyclohexanecar-boxylic acid (methyl cyclohexanecarboxylate) does not react with the hindered base (LDA) at the carbon of the carbonyl. Rather, the base removes the proton on the carbon a- to the carbonyl and the carbanion so formed then acts as a nucleophile toward methyl iodide (CH3I). Substitution yields methyl 1-methylcyclohexanecarboxylate, lithium iodide, and recovered base, diisopropylamine [(CH3)2CH]2NH. ... 

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