Bases nucleophile basicity

From the pATa values shown, there is relatively little difference in basicities for diethylamine, pyrrolidine, or piperidine. Note, however, that morpholine and piperazine are weaker bases than piperidine. This is the result of an electron-withdrawing inductive effect from the second heteroatom, making the nitrogen atom both less basic and also less nucleophilic. This makes morpholine a useful base with basicity between that of piperidine and pyridine pK 5.2) (see Section 4.6). The second pK value for the diamine piperazine is substantially lower than the first, since the inductive effect from the protonated amine will withdraw electrons away from the unprotonated amine (see Section 4.7). 

The thermodynamic tendency of a substance to act as a Lewis base. The strength of a Lewis base depends on the nature of the acid with which the Lewis base forms a Lewis adduct. Hence, comparative measures of Lewis basicities are given by equilibrium constants for the formation of the adducts by a common reference acid. See Lewis Base Nucleophilicity Hard Bases Soft Bases Donor Number... 

MEISENHEIMER ADDUCT LEWIS BASICITY DONOR NUMBER HARD BASES LEWIS BASE NUCLEOPHILICITY SOFT BASES L HOPITAL S RULE L Hospital s rule L HOPITAL S RULE... 

Nucleophilicity. A distinction is usually made between nucleophilicity and Lowry-Bronsted basicity [213]. The latter involves specifically reaction at a proton which is complexed to a Lewis base (usually H2O), while the former refers to reactivity at centers other than H. Linear correlations have been shown for gas-phase basicity (proton affinity) and nucleophilicity of nitrogen bases toward CH3I in solution [214] where the solvent is not strongly involved in charge dispersal. In each case, reaction of the base/nucleophile... 

The general base catalysis mechanism, (b) in Scheme 11.4, has a More O Ferrall-Jencks diagram (Fig. 11.4B) which shows that decreasing the nucleophilicity/basicity of the nucleophile (decreasing the energy, , of just the top-left corner) would cause movement of the transition structure coordinates towards the top-left. Resolving this into its components indicates an increase in /9. The value of /3 is related to that of a by a = ft — 1, so that the value of a should become less negative, which is not consistent with the observed results. 

In contrast, oxidations always involve the most nucleophilic (basic, negative-charge density) center (substrate or substrate-base combination) that produces... 

In this chapter, the concepts of organic bases and basicity were presented. These discussions were expanded to define nucleophiles and nucleophilicity. Trends associated with conjugate bases of acids and nucleophilicity were presented and translated to define the concept of leaving groups. As discussions continue, all of these concepts will play important roles in the various organic reaction mechanistic types presented in the following chapters. 

We are going to look at these compounds briefly here. Pyrimidine is more important than either of the others because of its involvement in DNA and RNA—you will find this in Chapter 49. All three compounds are very weak bases—hardly basic at all in fact. Pyridazine is slightly more basic than the other two because the two adjacent lone pairs repel each other and make the molecule more nucleophilic (the a effect again see p. 588 of Chapter 23). 

A cationic C- and S-coordinated mercaptocarbene complex undergoes deprotonation when treated with proton-acceptor bases or basic nucleophiles to give a neutral mercaptocarbyne complex ... 

Stronger Acids Have Lower pKg Values Species vs. pH Graph Media pH Crosscheck Acidic Media Contain Powerful Electrophiles and Weak Nucleophiles Basic Media Contain Excellent Nucleophiles and Weak Electrophiles No Medium Can Be Both Strongly Acidic and Strongly Basic Common Acids and Their pKg Values Common Bases and Their pKapH Values... 

There is no leaving group other than the original nucleophile (kicking out NH2 with a p TaHL = 35 from a tetrahedral intermediate 22 p Ta units less basic is not an option), so we should examine the possibilities for proton transfer. Hydroxide is a good base. In basic water, the most common proton source is neutral water. 

The HSAB-principle may be criticized as being too opportunistic the qualitative hard and soft assignments for reacting centers are used to explain rather small regio preferences, which reflect energy differences of only a few tenths of a Kcal/mol. However, the HSAB-principle is soundly based [41]. Basicity and polarisability may be used (with care) to predict qualitatively relative reactivities of a series of nucleophilic species. 

Scheme 2.2. Proposed mechanism for the aromatisation of the 19-aldehyde intermediate via a hydroperoxy acetal, (a) Enolization step (b) enzyme-assisted nucleophilic attack by hydroperoxyl intermediate. AH A, acidic amino-acid residue and conjugate base. BjBH, basic amino-acid residue and...

Carbon-based nucleophiles are generally regarded as soft bases, and Li is a hard acid. From this perspective alone, it would be difficult to rationalize that this reaction heavily favors the products, since the softness of the bases n-butyl and phenyl carbanions is similar. The significantly higher Br0nsted-Lowry basicity of the n-butyl carbanion (pK of n-butane is 50) relative to the phenyl carbanion (pKa of benzene is 43) plays a vital role in rationalizing the formation of phenyllithium. 

As shown in Figure 8.37, a reasonably linear correlation of log fca versus log Ky, was obtained for this series of nucleophiles. Basicity alone cannot explain nucleophilicity, however, as evidenced by reactions in which the nucleophilic atom is different. For example, phenoxide is more than 10 times more basic than thiophenoxide, but thiophenoxide is more than 10 times more nucleophilic than phenoxide. Uggerud concluded that strong bases have large intrinsic barriers for nucleophilic reaction but stabilize the products relative to reactants, so basicity and nucleophilicity are strongly correlated only for highly exothermic reactions. ... 

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