Nucleophiles relative reaction rates

When comparing the hydrolysis of methyl bromide with its reaction with Cl under the same conditions (i.e., [Cl-] = 100 mM, see Illustrative Example 13.2), we see that from a thermodynamic point of view, the hydrolysis reaction is heavily favored (compare ArG° values). This does not mean that the methyl bromide present is primarily transformed into methanol instead of methyl chloride (which it would be, if the reaction were to be thermodynamically controlled). In fact, in this and all other cases discussed in this chapter, we will assume that the reactions considered will be kinetically controlled that is, the relative importance of the various transformation pathways of a given compound will be determined by the relative reaction rates and not by the respective ArG° values. Thus, in our example, because CE is about a 103 times better nucleophile as compared to water (see Section 13.2) and because its concentration is about 103 times smaller than that of water (0.05 M versus 55.3 M), the two reactions would be of about equal importance under the conditions prevailing in this groundwater. Note that the product methyl chloride would subsequently also hydrolyze to yield methanol, though at a much slower rate. We will come back to this problem in Section 13.2 (Illustrative Example 13.2). 

The nucleophilicity of a particular reagent ( Y, Y0, or HY) can be defined as its ability to donate an electron pair to another atom (see Section 8-1). In fact, the Sn2 reactivity of a reagent toward a methyl derivative can be taken to measure its nucleophilicity toward carbon. The relative reaction rates of some nucleophiles toward methyl bromide are listed in order of increasing nucleophilicity in Table 8-4, together with their basicities as measured by Kb. Important generalizations can be made from these data provided that one recognizes that they may apply only to hydroxylic solvents. 

As mentioned in the organic section (Section II), adjusting the electronegativity of the leaving group will affect the relative reaction rates of both nucleophilic substitution as well... 

Another type of reaction allowed us to study the philicity of silylene 4. As we have shown earlier, 4 adds smoothly to a variety of alkynes giving way to the silacyclopropene framework (Eq. 4) [10], Varying the / ara-substituents of diphenylacetylene offers us the possibility to tune the electron density of the triple bond, and we now studied the rates of the reaction of 3 with diphenylacetylenes lOa-c. The absolute reaction rates of these three first-order reactions are identical (Ai = 6.3 0.2 10 4s-l) this result is in accordance with a mechanism, in which the formation of silylene 4 from cyclotrisilane 3 is the rate determining step [6], However, the relative reaction rates of the addition of 4 to the triple bond of lOa-c, which were determined by competition experiments, turned out to differ appreciably from each other. Electron withdrawing substituents favor the addition of 4 to the alkyne, whereas electron donating substituents, such as a methyl group, slow down the reaction rate. As shown in Fig. 5, the relative reactions rates correlate well with the [Pg.62]

It is widely accepted that the carbonyl reactivity toward nucleophiles increases in the order aldehyde>ketone>ester>amide [6]. This reactivity order is simply based on the extent to which each carbonyl carbon is sterically and electronically activated. However, reactivities might change when these carbonyl substrates are subjected to a Lewis acid. It is generally assumed that the coordination capability of the carbonyl oxygen to Lewis acids is the means by which Lewis acids activate carbonyl substrates. Thus, in some re.spects, the reaction rate parallels the Lewis basicity of the carbonyls. Furthermore, the reactivity of a carbonyl substrate depends on the reaction type as well as the Lewis acid employed. Special care must be taken in assessing the relationship between the relative reaction rate, the relative Lewis basicity, and the inherent carbonyl reactivity of each substrate. It is instructive to take a look at the following example (Schemes 2-2 and 2-3 Fig. 2-1). 

As expected, N-, 0-, S- and C-nucleophiles attack the ring C-atoms of pyridine. Addition of the nucleophile and elimination of a pyridine substituent as leaving group occur in a two-step process, i.e. in an S Ar reaction with regeneration of the heterarene system. S Ar reactions in pyridine occur preferably in the 2- and 4-positions and less readily in the 3-position, as indicated by studies of relative reactivity of halopyridines (e.g. chloropyridine + NaOEt in EtOH at 20°C relative reaction rates 2-Cl 0.2, 4-C1=1,3-C1 10-5). 

The relative reaction rates of RsSiH are also consistent with electrophilic attack by ozone. Ozone has been regarded as an electrophile or a nucleophile (i), but the fact that electron-withdrawing groups decrease the rate of reaction would indicate that electrophilic attack is involved. 

As with nucleophilic substitution reactions, rates of dehydrohalogenation reactions will be dependent on the strength of the C-X bond being broken in the elimination process. Accordingly, it is expected that the ease of elimination of X will follow the series Br>Cl>F. The relative reactivities of Br and Cl toward elimination is evident from the hydrolysis product studies of 1,2-dibromo-3-chloropropane (DBCP Burlinson et al., 1982). DBCP has been used widely in this country as a soil fumigant for nematode control and has been detected in groundwaters (Mason et al., 1981) and subsoils (Nelson, et al., 1981). Hydrolysis kinetic studies demonstrated that the hydrolysis of DBCP is first order both in DBCP and hydroxide ion concentration above pH 7. Below pH 7, hydrolysis occurs via neutral hydrolysis however, the base-catalyzed reaction will contribute to the overall rate of hydrolysis as low as pH 5. Product studies performed at pH 9 indicate that transformation of DBCP occurs initially by E2 elimination of HBr and HCl (Figure 2.4). 

This contrasts markedly with most electrophihc additions to carbon—carbon double bonds and with nucleophilic substitutions at saturated carbon atoms. The latter reactions are essentially irreversible, and overall results are a function of relative reaction rates. 

The two identical leaving groups (X = Y) in phosgene substitutes 1002 can be consecutively replaced to prepare both symmetrical and unsymmetrical ureas. The selectivity toward the unsymmetrical N,N -disubstituted ureas is critically dependent on the relative reaction rates of the two consecutive nucleophilic substitutions. If the second step is much slower than the first one, the formation of the symmetrical urea is minimized [726]. 

Nucleophile e.g., Electrophile—LG e g., (CHslsC—Br Relative Reaction Rate... 

As for various catalytic activity of alkali metal hydroxides, it should be noted that this effect is not unique for this reaction and is observed in almost all base-catalytic processes involving alkalis, for example, vinylation reaction [5,6,109,152,166], nucleophilic substitution and elimination [153], Favorsky reaction [167], synthesis of divinyl sulfide from acetylene and alkali metal sulfides [168], and cyclization of cyanoacetylenic alcohols [169]. For instance, in vinylation of 2-ethoxyethanol with acetylene in the presence of different hydroxides, the following relative reaction rates are observed [109,152] ... 

The term nucleophilicity refers to the effect of a Lewis base on the rate of a nucleophilic substitution reaction and may be contrasted with basicity, which is defined in terms of the position of an equilibrium reaction with a proton or some other acid. Nucleophilicity is used to describe trends in the kinetic aspects of substitution reactions. The relative nucleophilicity of a given species may be different toward various reactants, and it has not been possible to devise an absolute scale of nucleophilicity. We need to gain some impression of the structural features that govern nucleophilicity and to understand the relationship between nucleophilicity and basicity. ... 

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. ... 

Halopyridines undergo self-quaternization on standing while the less reactive 2-halo isomers do not. However, more is involved here than the relative reactivity at the ring-positions. The reaction rate will depend on the relative riucleophilicity of the attack-ing pyridine-nitrogens (4-chloropyridine is more basic) and on the much lower steric hindrance at the 4-position. Related to this self-quatemization are the reactions of pyridine and picolines as nucleophiles with 4-chloro- and 2-chloro-3-nitropyridines. The 4-isomer (289) is. again the more reactive by 10-30-fold (Table VII, p. 276). 

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

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