Nucleophilicity and hydrogen bonding

There is a wealth of information on gas phase ion thermodynamics because of the power of mass spectrometry and ion cyclotron resonance techniques. Before we discuss carboca-tion, and subsequently carbanion, stabilities, keep in mind that ionic structures are much more sensitive to environmental influences than radicals. The polarity, nucleophilicity, and hydrogen bonding ability of the solvent are important influences, as are the nature of the counterion. As such, thermodynamic information is a less reliable predictor of reactivity for carbocations and carbanions than it is for radicals. Nevertheless, gas phase thermodynamics is an excellent starting point, defining the intrinsic stabilities of ions. Any deviation in trends between gas phase and solution studies is likely a consequence of solvation effects, a theme we will visit many times throughout this book. 

The second class contains dual parameters, which occur in pairs of complementary attribntes cationic and anionic charge, Lewis or Brpnsted acidity and basicity (and refinements such as hard or soft acidity and basicity), electrophi-licity and nucleophilicity, and hydrogen-bonding tendency as donor and as acceptor (Table A.2b). A number of the entries in the table are incomplete in that only one of a potential pair of complementary parameters has been investigated. A table of values of most of the listed parameters for selected solvents forms Table A. 3. 

The reactivity of a nucleophilic reagent may also depend on stereochemical conformation, degree of solvation and hydrogen-bonding,... 

The nucleophilic substitution of quinoline as affected by cationiza-tion and hydrogen bonding is discussed in Section II, C, by the leaving group and other substituents in Sections II, D and II, E, respectively, and in Section III, A, 2, and by the nucleophile in Section II, F. 

The downward curvature observed in this and other systems could be easily explained in terms of a mixed aggregate between the catalyst and the nucleophile. A hydrogen-bond donation to the amide catalyst would render the amine a better nucleophile, up to a value of saturation , after which increasing amounts of catalysts should have no further effect. The results in Table 15 can be easily explained in the same terms, where K measures the equilibrium of the association between the amine and the catalyst. 

In the addition-elimination routes, either via a carbanionic intermediate (I) or via a neutral adduct (II), the anionic nucleophile Nu or the neutral nucleophile NuH attacks the /3-carbon with the expulsion of X. In the a,/8-route (IV), the /9,/3-route (VI) and the /8, y- elimination-addition routes (VII), HX is eliminated in the initial step, and the nucleophile and hydrogen are then added to the intermediates. Substitution occurs also by heterolytic C—X bond cleavage in an SN1 process (X). Initial prototropy followed by substitution can also give vinylic substitution products (XII, XIV), as well as two consecutive Sn2 reactions (XV) where the leaving group leaves from an allylic position. 

The SN1 mechanism is specially favoured when the polar protic solvent is also a non-basic nucleophile. Therefore, it is most likely to take place when an alkyl halide is dissolved in water or alcohol. Protic solvents are bad for the SN2 mechanism because they solvate the nucleophile, but they are good for the SN1 mechanism. This is because polar protic solvents can solvate and stabilise the carbocation intermediate. If the carbocation is stabilised, the transition state leading to it will also be stabilised and this determines whether the SN1 reaction is favoured or not. Protic solvents will also solvate the nucleophile by hydrogen bonding, but unlike the SN2 reaction, this does not affect the reaction rate since the rate of reaction is independent of the nucleophile. 

Polar protic solvents (curve 1) stabilize the charged transition state by solvation and also stabilize the nucleophile by hydrogen bonding. 

With phenolic ethers (16) and certain pyrroles (17), carbon disulfide (1) will insert into the nucleophilic carbon-hydrogen bond by a Friedel-Crafts-type reaction (Scheme 9). 

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