Nucleophilicity electrostatic potential

There are ways to plot data with several pieces of data at each point in space. One example would be an isosurface of electron density that has been colorized to show the electrostatic potential value at each point on the surface (Figure 13.6). The shape of the surface shows one piece of information (i.e., the electron density), whereas the color indicates a different piece of data (i.e., the electrostatic potential). This example is often used to show the nucleophilic and electrophilic regions of a molecule. 

Examine the molecular model of ferrocene on Learning By Modeling Does ferrocene have a dipole moment Would you expect the cyclopentadienyl nngs of ferrocene to be more reactive toward nucleophiles or electrophiles Where is the region of highest electrostatic potential... 

An orbital hybridization description of bonding m methylamme is shown m Figure 22 2 Nitrogen and carbon are both sp hybridized and are joined by a ct bond The unshared electron pair on nitrogen occupies an sp hybridized orbital This lone parr IS involved m reactions m which amines act as bases or nucleophiles The graphic that opened this chapter is an electrostatic potential map that clearly shows the concentration of electron density at nitrogen m methylamme... 

Electron densities, bond densities, and spin densities, as well as particular molecular orbitals may be displayed as graphical surfaces. In addition, the value of the electrostatic potential or the absolute value of a particular molecular orbital may be mapped onto an electron density surface. These maps provide information about the environment around the accessible surface of a molecule. Electrostatic potential maps show overall charge distribution, while orbital maps reveal likely sites for electrophilic and/or nucleophilic attack. Surface displays may be combined with any type of model display. 

According to the resonance picture, where is the excess negative charge in azide anion Will the center nitrogen or a terminal nitrogen act as the nucleophilic site Examine atomic charges and the electrostatic potential map. Do they substantiate your conclusion Explain. 

Nucleophilic atoms can also be identified by inspection of electrostatic potential maps. Reactive sites appeal as negative electrostatic potentials. Examine electrostatic potential maps for trimethylamine, methyl fluoride, and phenol. Identify the most nucleophilic atom in each molecule. Are these the same as you identified above using Lewis structures Are all sides of the nucleophilic atoms equally electron rich, or only particular regions ... 

Enhanced nucleophilicity is often correlated with more negative electrostatic potential. Which of the three molecules listed above is most nucleophilic according to this criterion Which is least nucleophilic (The least nucleophilic molecule does not, in fact, undergo Sn2 reactions.)... 

Nucleophiles can also act as acids and bases, and this behavior substantially alters their nucleophilicity. At pH 5, trimethylamine exists mainly as its conjugate acid, trimethylammonium cation. First draw a Lewis structure, and then examine the electrostatic potential for trimethylammonium ion. On the basis of the map, which is the better nucleophile, the cation or the corresponding neutral amine At pH 12, phenol exists mainly as its conjugate base, phenoxide anion. First draw a Lewis structure (or series of Lewis structures), and then examine the electrostatic potential map for phenoxide anion. Which is the better nucleophile, phenoxide or phenol ... 

Examine atomic charges and the electrostatic potential nu for nitrite anion. Which atom(s) is most electron riel Which product would be obtained if this atom behav as a nucleophile in its reation with methyl bromide. 

Backside attack may be favored for electrostatic reasons. Examine electrostatic potential maps fox bromide + methyl bromide frontside attack and bromide + methyl bromide backside attack, transition states involving frontside and backside attack of Br (the nucleophile) onto CHsBr, respectively. Which atoms in the transition states are most electron-rich Which trajectory better minimizes electrostatic repulsion ... 

The molecule below has four stereoisomeric forms exoO exoCH2Br, exoO endoCH2Br, and so on. Examine electrostatic potential maps of the four ions and identify the most nucleophilic (electron-rich) atom in each. Examine the electron-acceptor orbital (the lowest-unoccuped molecular orbital or LUMO) in each and identify electrophilic sites that are in close proximity to the nucleophilic. Which isomers can undergo an intramolecular E2 reaction Draw the expected 8 2 and E2 products. Which isomers should not readily undergo intramolecular reactions Why are these inert ... 

Alcohol attack generates an unstable intermediate that undergoes nucleophilic attack by CL at carbon. Compare electrostatic potential maps of methanol, thionyl chloride intermediate, and phosphorus trichloride intermediate. What features of these maps are consistent with an electrophilic reactive intermediate ... 

In order to predict the structure of the product, you must identify the factors that will tend to favor selective ketal formation. Consider selective carbonyl protonation first. Obtain energies and atomic charges, and display electrostatic potential maps of the alternative protonated ketones (protonated ketone A, protonated ketone B). Identify the more stable isomer. Compare geometries and draw whatever Lewis structures are needed to account for your data. Why is one isomer more stable than the other Is the more stable isomer also that in which the positive charge is better delocalized Will the more stable isomer undergo nucleophilic attack more or less easily than the other Explain. 

The base may control some of this chemistry by selectively converting 2-mercaptoethanol into a stronger nucleophile. Display an electrostatic potential map for 2-mercaptoethanol. Which proton, that attached to oxygen or sulfur, is more acidic, that is, more likely to be removed by strong base Rationalize your result. 

Electrostatic potential map for penicillin model shows positively-charged regions (in blue) as likely sites for nucleophilic attack. 

Examine the structure of penicillin model (R=H), a model for the active compounds. What, if anything, distinguishes it from a typical amide (N,N-dimethylacetamide, for example) What is responsible for the differences Compare electrostatic potential maps for penicilhn model and dimethylacetamide. Which compound is more likely to undergo nucleophilic attack Explain. 

Nucleophilicity is determined by HOMO energy the higher the energy the more reactive the nucleophile. HOMO energies (in au) for these nucleophiles are -0.275 (enamine), -0.266 (lidiium enolate), -0.337 (silyl enol ether), and -0.339 (enol). Rank the nucleophiles from most reactive to least reactive. How does this ranking compare to that based on electrostatic potential ... 

Electrostatic potential map for amine-amide shows negatively-charged regions (in red) as likely nucleophilic sites. 

Examine the highest-occupied molecular orbital (HOMO) of singlet methylene. Where is the pair of electrons, inplane or perpendicular to the plane Next, examine the electrostatic potential map. Where is the molecule most electron rich, in the o or the 7t system Where is the most electron poor Next, display the corresponding map for triplet methylene. Which molecule would you expect to be the better nucleophile The better electrophile Explain. Experimentally, one state of methylene shows both electrophilic and nucleophilic chemistry, while the other state exhibits chemistry typical of radicals. Which state does which Elaborate. 

Figure 5.1 Some nucleophiles and electrophiles. Electrostatic potential maps identify the nucleophilic (red negative) and electrophilic (blue positive) atoms.

An electrostatic potential map of boron trifluoride is shown. Is BF3 likely to be a nucleophile or an electrophile Draw a Lewis structure for BF3, and explain your answer. 

Electrostatic potential maps of (a) formaldehyde (CH20) and (b) methanethiol (CH3SH) are shown. Is the formaldehyde carbon atom likely to be electrophilic or nucleophilic What about the methanethiol sulfur atom Explain. 

Judging from the following electrostatic potential maps, which kind of carbonyl compound has the more electrophilic carbonyl carbon atom, a ketone or an acid chloride Which has the more nucleophilic carbonyl oxygen atom Explain. 

One further comparison aromatic aldehydes, such as benzaldehyde, are less reactive in nucleophilic addition reactions than aliphatic aldehydes because the electron-donating resonance effect of the aromatic ring makes the carbonyl group less electrophilic. Comparing electrostatic potential maps of formaldehyde and benzaldehyde, for example, shows that the carbonyl carbon atom is less positive (less blue) in the aromatic aldehyde. 

Electrostatic potential maps of a typical amide (acetamide) and an acyl azide (acetyl azide) are shown. Which of the two do you think is more reactive in nucleophilic acyl substitution reactions Explain. 

What kind of chemistry do enols have Because their double bonds are electron-rich, enols behave as nucleophiles and react with electrophiles in much the same way that aikenes do. But because of resonance electron dona lion of a lone-pair of electrons on the neighboring oxygen, enols are more electron-rich and correspondingly more reactive than aikenes. Notice in the following electrostatic potential map of ethenol (BbC CHOH) how there is a substantial amount of electron density (yellow-red) on the a carbon. 

As the following resonance structures indicate, enamines are electronically similar to enolate ions. Overlap of the nitrogen lone-pair orbital with the double-bond p orbitals leads to an increase in electron density on the a carbon atom, making that carbon nucleophilic. An electrostatic potential map of N,N-6imethyl-aminoethvlene shows this shift of electron density (red) toward the a position. 

The chemistry of amines ts dominated by the lone pair of electrons on nitrogen, which makes amines both basic and nucleophilic. They react with acids to form acid-base salts, and they react with electrophiles in many of the polar reactions seen in past chapters. Note in the following electrostatic potential map of trimethylamine how the negative (red) region corresponds to the lone-pair of electrons on nitrogen. 

In contrast with amines, amides (RCONH ) are nonbasic. Amides don t undergo substantial protonation by aqueous acids, and they are poor nucleophiles. The main reason for this difference in basicity between amines and amides is that an amide is stabilized by delocalization of the nitrogen lone-pair electrons through orbital overlap with the carbonyl group. In resonance terms, amides are more stable and less reactive than amines because they are hybrids of two resonance forms. This amide resonance stabilization is lost when the nitrogen atom is protonated, so protonation is disfavored. Electrostatic potential maps show clearly the decreased electron density on the amide nitrogen. 

Amine bases in nucleic acids can react with alkylating agents in typical Sjsj2 reactions. Look at the following electrostatic potential maps, and tell which is the better nucleophile, guanine or adenine. The reactive positions in each are indicated. 

Walden, Paul, 360 Walden inversion. 359-360 Wang resin, solid-phase peptide synthesis and. 1037 Water, acid-base behavior of, 50 dipole moment of, 39 electrostatic potential map of. 53 nucleophilic addition reactions of, 705-706 pKaof, 51-52... 

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