Factor 4—The Solvent

25 Using your answers to the last six problems, which of the six compounds above would you expect to be most likely to undergo an S l reaction  

So far, we have looked at the substrate, the nucleophile, and the leaving group. This takes care of all of the parts of the compounds that are reacting with each other. Let s summarize substitution reactions in a way that allows us to see this  

by talking about the substrate, the nucleophile, and the leaving group, we have covered almost everything. But there is one more thing to take into account. What solvent are these compounds dissolved in It can make a difference. Let s see how. 

There is a really strong solvent effect that greatly affects the competition between SnjI and S ]2, and here it is polar aprotic solvents favor Sjsj2 reactions. So, what are polar aprotic solvents, and why do they favor S 2 reactions  

Let s break it down into two parts polar and aprotic. Hopefully, you remember from general chemistry what the term polar means, and you should also remember that like dissolves like (so polar solvents dissolve polar compounds, and nonpolar solvents dissolve nonpolar compounds). Therefore, we really need a polar solvent to run substitution reactions. S 1 desperately needs the polar solvent to stabilize the carbocation, and Sn2 needs a polar solvent to dissolve the nucleophile. S il certainly needs the polar solvent more than Sn2 does, but you will rarely see a substitution reaction in a nonpolar solvent. So, let s focus on the term aprotic. 

Let s break it down into two parts polar and aprotic. Hopefully, you remember from general chemistry what the term polar means, and you should also 

Aprotic means that the solvent does not have a proton on an electronegative atom. The solvent can still have hydrogen atoms, but none of them are connected to electronegative atoms. The most common examples of polar aprotic solvents are acetone, DMSO, DME, and DMF  

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A pKa of 4.5 for the carboxyl group of indomethacin was calculated from aqueous solubility data(30). Potentiometric titration data for indomethacin in 50% methanol-water yielded pKa of 4.5 using a correction factor for the solvent(31). 

Solvent time-correlation functions. We next consider the solvent time-correlation functions appearing in Eq. (5.185). As we have clarified in Sec. 5.4.1, these time-correlation functions describe, within the linear response regime and the factorization approximation, the solvent response to the solute perturbation. We summarize here main features of and Fzz k,t) in the small-A region where... 

Four factors have an impact on whether a particular reaction will occur via an S],j2 or an S],jl mechanism (1) the substrate, (2) the leaving group, (3) the nucleophile, and (4) the solvent (Figure 7.25). We must learn to look at aU four factors, one by one, and to determine whether the factors favor Sjsjl or Si,j2. 

There are four factors that impact the competition between the n2 mechanism and Sfgl (1) the substrate, (2) the nucleophile, (3) the leaving group, and (4) the solvent. 

The mechanism that the reaction follows depends, among other factors, on the solvent and the temperature. PhenyUithium in tetrahydrofuran favors 1,2 polymers, whereas lithium dispersion or phenylUthium in paraflinic hydrocarbons such as heptane as a solvent favors 1,4 polymers. A higher temperature favors... 

Viscosity of Resin Solutions. The viscosity of coatings must be adjusted to the appHcation method to be used. It is usually between 50 and 1000 mPa-s(=cP), at the shear rate involved in the appHcation method used. The viscosity of the coating is controUed by the viscosity of the resin solution, which is in turn controUed mainly by the free volume (4). The factors controlling free volume are temperature, resin stmcture, solvent stmcture, concentration, and solvent-resin interactions. 

The strength of the complexation is a function of both the donor atom and the metal ion. The solvent medium is also an important factor because solvent molecules that are potential electron donors can compete for the Lewis acid. Qualitative predictions about the strength of donor-acceptor complexation can be made on the basis of the hard-soft-acid-base concept (see Section 1.2.3). The better matched the donor and acceptor, the stronger is the complexation. Scheme 4.3 gives an ordering of hardness and softness for some neutral and ionic Lewis acids and bases. 

Thus, a 2-D separation can be seen as 1-D displacement operating in two dimensions. The 2-D TLC separation is of no interest if selection of the two mobile phases is not appropriate. With this in mind, displacement in either direction can be either selective or non-selective. A combination of two selective displacements in 2-D TLC will lead to the application of different separating mechanisms in each direction. As an extreme, if the solvent combinations are the same (5ti = 5t2 5vi = va) or very similar (5ti 5vi 5ya), the compounds to be separated will be poorly resolved or even unresolved, and as a result a diagonal pattern will be obtained. In such circumstances, a slight increase in resolution might occur, because of an increase by a factor of V2 in the distance of migration of the zone (4). 

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