Alpha effects

Another significant structural effect that inrparts high nucleophilicity is the alpha effect. It is observed that atoms which are directly bonded to an atom with one or rhore unshared pairs of electrons tend to be stronger nucleophiles than would othermse be expected. Examples in Table 5.7 include H02, which is more nucleophilic than HO , and... 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

The rationale behind this choice of bond integrals is that the radical stabilizing alpha effect of such radicals are explained not by the usual "resonance form" arguments, but by invoking frontier orbital interactions between the singly occupied molecular orbital of the localized carbon radical and the highest occupied molecular orbital (the non-bonding electrons atomic orbital) of the heteroatom (6). For free radicals the result of the SOMO-HOMO interaction Ts a net "one-half" pi bond (a pi bond plus a one-half... 

Electrophysiological effects Extracts of hypericum were examined for their electrophysiological effects in animals. The onset of effects occurred 3-4 hours after administration. Frequencies affected first were in the alpha range and were maximal in the frontal cortex (Dimpfel and Hofmann 1995). Another study examined the EEG effects for two hypericum extracts in rats one extract high in hyperforin and lacking naphthodi-anthrones (C02), and another extract (LI 160) low in hyperforin. Both extracts showed similar early alpha effects, but only LI 160 had a late effect of increased delta frequencies. The alpha effects are comparable to... 

Although oximes are ambident nucleophiles, a neat regioselectivity allows the formation of oxazolinones. The alpha effect, which is especially relevant for the substimtion of R2C=NO anions at a carbonyl carbon, may offer a good explanation for the Bac2/Bai2 sequence ((9-methoxycarbonylation and A-methylation... 

Enhanced nucleophilicity of an attacking nucleophile attributable to one or more unshared pairs of electrons on an atom that lies immediately adjacent to the nucleophilic group ". The increased nucleophihcity of hydrazines and hydroxylamines is due to an alpha effect, as is the increased nucleophilicity of H02 compared to HO in solution. This effect on nuclephile reactivity can... 

As is also true for ambident anions, substances exhibiting alpha effects in their reactions consistently deviate from the anticipated structure-reactivity correlations known for simple nucleophiles. 

One explanation for the alpha effect is ground-state de-stabilization Repulsive electronic interactions between the alpha atom s lone-pair and the nucleophile occur in the ground-state, and such destabilization is expected to be relieved as a covalent bond is forming in the transition-state of a nucleophilic substitution reaction. Reduced solvation in molecules exhibiting the alpha effect may also play a role in the increased nucleophilicity for example, OH2 displays no effect in the gas phase, but a substantial effect is observed in solution. Another factor may be the abihty of the alpha lone-pair to stabilize any partially positive group formed in the transition state. 

RITCHIE EQUATION ELECTROPHILE NUGLEOPHILIC GATALYSIS NUCLEOPHILIC COMPETITION NUCLEOPHILICITY ALPHA EFFECT ELECTROPHILICITY... 

Substitution reactions at a saturated carbon, ALPHA EFFECT SUBSTRATE... 

This is an example of what John Edwards and I call the alpha effect. I think it is valuable because it does enable us to generate quite easily a very powerful nucleophilic reagent in water, this hydrogen peroxide anion. 

If, adjacent to the attacking atom on the nucleophile, there is an atom containing one or more unshared pairs, the nucleophilicity is enhanced. Examples of such nucleophiles are H02, Me2C=NO", NH2NH2, etc. This is called the alpha effect,324 and the reasons for it... 

Allylic rearrangement 527,712 with condensation 527 Allysine 429 Alpha-carbon plot 64 Alpha effect on reaction rates 590 Alpha helix See a Helix Alport disease 438 Alternan 175... 

For the vinyl cation, using the isodesmic reaction shown in equation 12b, it was found that CH3 and SiH3 were 27 and 24 kcalmol-1 more stabilizing than H, respectively28. In this case the alpha effect of silicon is comparable to that of carbon. 

When lone pairs exist on neighboring atoms, w e call this the alpha effect. The lone pairs are repelling each other, and this is a destabilizing effect. 

The alpha effect in the SN2 reactions of methyl substrates with three different nucleophiles was shown to correlate with Koopman s theorem ionization potentials for the leaving group.128 This was taken as evidence that (1) the size of the alpha effect in Sn2 reactions depends on the ability of the nucleophile and the leaving group to donate an electron to the methyl group and (2) these transition states have some SET character. The results support the Hoz model129 for the alpha effect. 

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