Substitution at a Saturated Carbon

In a carbon centre that is involved in four covalent single bonds, how many electrons are there around the carbon atom Demonstrate your answer by focusing on the carbon atom in a molecule of methane, CH4, and drawing a dot and cross structure for it. 

The answer is, of course, eight a full octet of electrons is accommodated around the carbon atom in this molecule. What is the maximum number of electrons that a carbon atom may normally accommodate in its outermost, that is its valence, shell of orbitals  

As carbon is a second row element, the maximum number of electrons that it may normally accommodate in its valence shell is eight. 

Now let us turn our attention to the electronic characteristics of the incoming nucleophile. Give two examples of typical nucleophiles. 

The incoming nucleophile is electron rich, and so your examples may have included such anionic species as hydroxide, halide, hydride or cyanide anions or may have included such neutral species as ammonia or water molecules. Note that in all cases, whether the species in question was anionic or neutral, there was always a lone pair of electrons. Nucleophiles are (almost) never positive species, because the positive charge on a cation indicates that it is electron poor, which is the opposite electrical property to that of a typical nucleophile. 

Full theoretical treatments have been carried out at many levels of theory, and they agree that the inversion pathway has the lower energy. The solvent, which is invariably present in everyday chemistry, is not 

2 The Se2 Reaction. In electrophilic substitution, the substrate is usually an organometallic reagent, for which we can use methyllithium as the simplest version. We saw the low-energy orbitals of methyl-lithium with and without hybridisation in Fig. 1.64. The frontier orbitals for the SE2 reaction will be the HOMO of the nucleophile (the rCLi orbital strongly associated with C—M bonding) and the LUMO of the electrophile, modelled in Fig. 5.3 by an empty p orbital. In this case,457 the frontier orbital interaction (Fig. 5.3) can be bonding for attack on either side of the carbon atom. 

In agreement, electrophilic substitution at a saturated carbon atom sometimes takes place with retention of configuration 5.18 — 5.19461 and 5.21 — 5.22462,463 when it is called SE2ret,464 and sometimes, but more rarely, with inversion of configuration 5.18 — 5.20 and 5.21 — 5.23, when it is called SE2inv. 

Retention of configuration is the more usual pattern for electrophilic attack on a C—M bond, especially, but not invariably, for carbon electrophiles. This may simply be because electrophiles are attracted to the site of highest electron population, but explanations for changes from retention to inversion in going from one 

We can also explain inversion of configuration in the Sn2 reaction by looking at the frontier orbitals, but it is a much weaker explanation. The appropriate frontier orbitals will be the HOMO of the nucleophile and the LUMO of the electrophile. Taking the orbitals of methyl chloride in Figs 1.45 and 1.47, we can see the LUMO is the r cx orbital. The overlap is bonding when the nucleophile approaches the electrophile from the rear, but would be both bonding and antibonding of the nucleophile were to approach from the front. 

In the absence of solvent, the gas-phase SN2 reaction is different, but it still takes place with inversion of stereochemistry. There is a double well in the energy surface the nucleophile and the alkyl halide combine exothermically with no energy barrier to give an ion-molecule complex. In a sense the naked nucleophile is solvated by the only solvent available, the alkyl halide. The Sn2 reaction then takes place with a low barrier, and the product ion-molecule complex dissociates endothermically to give the products. 

It has only recently become possible for synthetic chemists to use the stereochemistry that reactions like this possess, as seen with the reagent 5.10 created using butyllithium and (-)-sparteine. The explanation offered in this case is that reactive electrophiles, those not requiring Lewis acid catalysis, are apt to react with inversion of configuration, while those that need to coordinate to the metal to experience some Lewis acid catalysis, are apt to react with retention of configuration, because the electrophile is necessarily being held on the same side as the metal. 

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C. A. Bunion, Nucleophilic Substitution at a Saturated Carbon Atom, Elsevier, New Vbrk, 1963. 

Volume 8 Volume 9 Volume 10 Volume 12 Volume 13 Proton Transfer Addition and Elimination Reactions of Aliphatic Compounds Ester Formation and Hydrolysis and Related Reactions Electrophilic Substitution at a Saturated Carbon Atom Reactions of Aromatic Compounds Section 5. POLYMERISATION REACTIONS (3 volumes)... 

Sneen et al. formulated an intermediate-mechanism theory. The formulation is in fact very broad and applies not only to borderline behavior but to all nucleophilic substitutions at a saturated carbon. According to Sneen, all SnI and Sn2 reactions can be accommodated by one basic mechanism (the ion-pair mechanism). The substrate first ionizes to an intermediate ion pair that is then converted to products ... 

The cleavage of C—S bonds in C—SO2R anion radicals plays an important role in SrnI tyP processes ". Kornblum and coworkers described a photostimulated electron transfer chain substitution at a saturated carbon where the leaving group is PhSOj ... 

A type of reaction that has probably received more detailed study than any other—largely due to the monumental work of Ingold and his school—is nucleophilic substitution at a saturated carbon atom the classical displacement reaction exemplified by the conversion of an alkyl halide into an alcohol by the action of aqueous base ... 

Nucleophilic substitution at a saturated carbon atom 4.3 EFFECT OF STRUCTURE... 

He is, in contrast to H , a very poor leaving group indeed, with the result that in simple aromatic nucleophilic substitution ipso attack (cf. p. 161) is the rule rather than the exception. Cl , Bre, N2, S03, NR2, etc., are found to be among the more effective leaving groups and, with them, certain analogies to nucleophilic substitution at a saturated carbon atom (p. 77) may now be observed. 

From Ingold, Structure and Mechanism in Organic Chemistry, 315. See Ingold, with L. C. Bateman, K. A. Cooper, and E. D. Hughes, "Mechanism of Substitution at a Saturated Carbon Atom. Pt. XIII. Mechanism Operative in the Hydrolysis of Methyl, Ethyl, Isopropyl, and Tert.-Butyl Bromides in Aqueous Solutions," JCS... 

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