Nucleophilicity order, for

The following overall nucleophilicity order for Sn2 mechanisms (in protic solvents) was given by Edwards and Pearson RS > ArS >1 >CN > OH > Nj > Br > ArO > Cl > pyridine > AcO > H2O. A quantitative relationship (the Swain-Scott equation) has been worked out similar to the linear free energy equations considered in Chapter 9 ... 

Nucleophilicity order for R3X, sign of AS " and existence of 7-coordinated vanadium carbonyls, are consistent with an A mechanism. 

For substitution at a carbonyl carbon, the nucleophilicity order is not the same as it is at a saturated carbon, but follows the basicity order more closely. The reason is presumably that the carbonyl carbon, with its partial positive charge, resembles a proton more than does the carbon at a saturated center. That is, a carbonyl carbon is a much harder acid than a saturated carbon. The following nucleophilicity order for these substrates has been de-termmined 321 Me2C=NO- > EtO" > MeO > OH" > OAr- > N-f > F" > H20 > Br" I". Soft bases are ineffective at a carbonyl carbon.322 In a reaction carried out in the gas phase with alkoxide nucleophiles OR solvated by only one molecule of an alcohol R OH, it was found that both RO and R O" attacked the formate substrate (HCOOR") about equally, though in the unsolvated case, the more basic alkoxide is the better nucleophile.323 In this study, the product ion R"0 was also solvated by one molecule of ROH or R OH. 

The term f (0, P) depends on the properties of the O and P atoms leading to a given nucleophilic order for these atoms in the nonconjugat-ed state as discussed in Section 2. 

The true nucleophilic order for halide ions was at one time nebulous. For example, in the displacement of /7-butyl brosylate, two series of halides display opposite reactivity BU4NCI > Bu4NBr > BU4NI but Lil > LiBr > LiCl. Winstein et al. (18) ascribed the noncorrespondence of lithium salt reactivity to the intrinsic strength and increasing dissociation of salts with larger anions. 

Table 1-4 gives some calculated reactivity indices free valence or Wheland atomic localization energies for radical, electrophilic, or nucleophilic substitution. For each set of data the order of decreasing reactivity is indicated. In practice this order is more reliable than the absolute values of the reactivity indices themselves. 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

For Sn2 reactions in solution, there are four main principles that govern the effect of the nucleophile on the rate, though the nucleophilicity order is not invariant but depends on substrate, solvent, leaving group, and so on. 

Carbonyl reactions are extremely important in chemistry and biochemistry, yet they are often given short shrift in textbooks on physical organic chemistry, partly because the subject was historically developed by the study of nucleophilic substitution at saturated carbon, and partly because carbonyl reactions are often more difhcult to study. They are generally reversible under usual conditions and involve complicated multistep mechanisms and general acid/base catalysis. In thinking about carbonyl reactions, 1 find it helpful to consider the carbonyl group as a (very) stabilized carbenium ion, with an O substituent. Then one can immediately draw on everything one has learned about carbenium ion reactivity and see that the reactivity order for carbonyl compounds ... 

Especially for large-scale work, esters may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents45 or with crown ether catalysts.46 The reactivity order for carboxylate salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due to both high solubility and minimal ion pairing with the anion 47 Acetone is a good solvent for reaction of carboxylate anions with alkyl iodides48 Cesium fluoride in DMF is another useful... 

Scheme 11.2 illustrates the conventional sequence for the manufacture of DAST brighteners. However, it is not always necessary and may not be desirable for DAS to be the nucleophile selected for the first step. In principle the three nucleophiles can be reacted in any order, but it is preferable for the most nucleophilic amine to react last in order to avoid forcing conditions during removal of the last remaining chloro substituents. Alkylamines react more readily than alcohols, thus ensuring that alkanolamines yield their hydroxyalkylaminotriazine derivatives. 

This trend is also observed in palladium chemistry where the general order for oxidative addition often correlates with that of nucleophilic substitution. Not only are 2-, 4- and 6-chloropyrimidines viable substrates for Pd-catalyzed reactions, but 4- and 6-chloropyrimidines react more readily than 2-chloropyrimidines. 

Fig. 11. Dependences of observed first-order rate constants on nucleophile concentration for thiocyanate susbtitution at dichlorobis(ethylmaltolato)meta-1(IV) complexes M(etmalt)2Cl2, and at a series of tin(IV) complexes SnL2Cl2 with L = the ligands whose formulae are shown against the thin line plots. The data refer to reactions in acetonitrile solution at 298.2 K (data from Refs. (264) and (265)).

A completely empirical LFER can also be constructed with recourse only to kinetic data. This has been the case in the setting up of a scale of nucleophilic power for ligands substituting in square-planar complexes based on the Swain-Scott approach. The second-order rate constants Ay for reactions in MeOH of nucleophiles Y with tra 5-Pt(py)2Cl2, chosen as the standard substrate... 

Fig. 4.8 Plots of pseudo first-order rate constants at 30 °C vs [nucleophile, Y] for reaction of trans-Pt(py)2Cl2 in methanol.

Concentrations of the nucleophile needed for good efficiency (quantum yield) are generally of the order of 10 -10 M. Quenchers have to be present in the same concentration range to be effective. Assuming the reactions to be diffusion controlled, this suggests that the excited aromatic species which reacts is short-lived (10 -10 sec.). We shall discuss in Section 2 the question whether we are dealing with a singlet or a triplet state. 

Direct metalation at the /8-carbon of azoles can also occur, although it is a much less facile process than that for the adjacent a-carbon, because of the greater charge density at what is normally a nucleophilic center in enamine-type reactions. Thus in order for reaction to occur, it is usually necessary to either block the a-position or activate the /3-site. If both factors are accommodated than /8-metalation occurs readily, and thus 3,4-disubstituted-2(3//)-thiazolethiones undergo direct lithiation with lithium diisopropylamide (LDA) at the 5-position, which is activated by the inductive effect of the adjacent sulfur (Scheme 4) (80S800). 

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