Nucleophilic attack substitution

It also makes the carbon atom even more positive (because -OH2+ is more electron withdrawing than -OH) => the carbon atom is more susceptible to nucleophilic attack => Substitution reactions become possible (Sn2 or SnI, depending on the class of alcohol). 

Activated Esters. Mixed anhydrides may be prepared by reaction of carboxylic acids with trifluoroacetic anhydride. The method has been used widely as a means of activating carboxyl groups to nucleophilic attack. The method has also been highly useful in Friedel-Crafts acylation of arenes (eqs 1 and 2). Sulfonic acids are also activated to nucleophilic attack substituted sulfones result. Intramolecular Friedel-Crafts reactions are also facilitated, but only for formation of six-membered rings. ... 

The attack by a reagent of a molecule might be hampered by the presence of other atoms near the reaction site. The larger these atoms and the more are there, the higher is the geometric restriction, the steric hindrance, on reactivity. Figure 3-6e illustrates this for the attack of a nucleophile on the substrate in a nucleophilic aliphatic substitution reaction. 

Charge diagrams suggest that the 2-amino-5-halothiazoles are less sensitive to nucleophilic attack on 5-position than their thiazole counterpart. Recent kinetic data on this reactivity however, show, that this expectation is not fulfilled (67) the ratio fc.. bron.c.-2-am.noih.azoie/ -biomoth.azoie O"" (reaction with sodium methoxide) emphasizes the very unusual amino activation to nucleophilic substitution. The reason of this activation could lie in the protomeric equilibrium, the reactive species being either under protomeric form 2 or 3 (General Introduction to Protomeric Thiazoles). The reactivity of halothiazoles should, however, be reinvestigated under the point of view of the mechanism (1690). 

Ilvespaa (98) has demonstrated that, using some amines, the 2-chloro-5-nitrothiazole undergoes an opening reaction in a competitive reaction parallel to the normal substitution process. This confirms the sensitivity of position 4 to nucleophilic attack when a nitro group is present in position 5 (Scheme 16). 

In a second possibility illustrated in Figure 8 Ih the nucleophile attacks the sub state from the side opposite the bond to the leaving group This is called back side dis placement or substitution with inversion of configuration... 

FIGURE 8 1 Two contrast mg stereochemical pathways for substitution of a leaving group (red) by a nucleophile (blue) In (a) the nucleophile attacks carbon at the same side from which the leaving group departs In (b) nude ophilic attack occurs at the side opposite the bond to the leaving group... 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

Tertiary alkyl halides are so sterically hindered to nucleophilic attack that the pres ence of any anionic Lewis base favors elimination Usually substitution predominates over elimination m tertiary alkyl halides only when anionic Lewis bases are absent In the solvolysis of the tertiary bromide 2 bromo 2 methylbutane for example the ratio of substitution to elimination is 64 36 m pure ethanol but falls to 1 99 m the presence of 2 M sodium ethoxide... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

The sp hybridized carbon of an acyl chloride is less sterically hindered than the sp hybridized carbon of an alkyl chloride making an acyl chloride more open toward nude ophilic attack Also unlike the 8 2 transition state or a carbocation intermediate m an Stvfl reaction the tetrahedral intermediate m nucleophilic acyl substitution has a stable arrangement of bonds and can be formed via a lower energy transition state... 

The other process is a nucleophilic acyl substitution triggered by hydroxide attack at the carbonyl group... 

A nitro group behaves the same way m both reactions it attracts electrons Reaction is retarded when electrons flow from the aromatic ring to the attacking species (electrophilic aromatic substitution) Reaction is facilitated when electrons flow from the attacking species to the aromatic ring (nucleophilic aromatic substitution) By being aware of the connection between reactivity and substituent effects you will sharpen your appreciation of how chemical reactions occur... 

Attack by the halide nucleophile at the sp hybridized carbon of the alkyl group is anal ogous to what takes place in the cleavage of dialkyl ethers Attack at the sp hybridized carbon of the aromatic nng is much slower Indeed nucleophilic aromatic substitution does not occur at all under these conditions... 

The 7 glutamyl phosphate formed m this step is a mixed anhydride of glutamic acid and phosphoric acid It is activated toward nucleophilic acyl substitution and gives glutamine when attacked by ammonia... 

Nucleophilic Reactions. The strong electronegativity of fluorine results in the facile reaction of perfluoroepoxides with nucleophiles. These reactions comprise the majority of the reported reactions of this class of compounds. Nucleophilic attack on the epoxide ring takes place at the more highly substituted carbon atom to give ring-opened products. Fluorinated alkoxides are intermediates in these reactions and are in equiUbrium with fluoride ion and a perfluorocarbonyl compound. The process is illustrated by the reaction of methanol and HFPO to form methyl 2,3,3,3-tetrafluoro-2-methoxypropanoate (eq. 4). 

Toluene itself does not undergo substitution by nucleophilic attack of anions but requires substitution by strongly electronegative groups, such as nitro groups, before the ring becomes sufftciendy electrophilic to react with anions. 

Virtually all of the organo derivatives of CA are produced by reactions characteristic of a cycHc imide, wherein isocyanurate nitrogen (frequendy as the anion) nucleophilically attacks a positively polarized carbon of the second reactant. Cyanuric acid and ethylene oxide react neady quantitatively at 100°C to form tris(2-hydroxyethyl)isocyanurate [839-90-7] (THEIC) (48—52). Substitution of propylene oxide yields the hydroxypropyl analogue (48,49). At elevated temperatures (- 200° C). CA and alkylene oxides react in inert solvent to give A/-hydroxyalkyloxazohdones in approximately 70% yield (53). Alternatively, THEIC can be prepared by reaction of CA and 2-chloroethanol in aqueous caustic (52). THEIC can react further via its hydroxyl fiinctionahty to form esters, ethers, urethanes, phosphites, etc (54). Reaction of CA with epichlorohydrin in alkaline dioxane solution gives... 

In contrast to electrophilic reagents, the highly -tt-deficient character of the pteridine nucleus is responsible for its vulnerability towards nucleophilic attack by a wide variety of reagents. The direct nucleophilic substitution of pteridine itself in a Chichibabin-type reaction with sodamide in diethylaniline, however, was unsuccessful (51JCS474). Pteridin-6-one, on the other hand, yielded pteridine-6,7-dione under the same conditions, via a still unknown reaction mechanism. 

The high chemical stability of pterins towards aqueous base is due to anion formation suppressing nucleophilic attack at a ring carbon atom by electrostatic repulsion. Substitution... 

Pyrrole, furan or thiophene do not react with nucleophilic reagents by substitution or addition but only by proton transfer. However, it should be noted that protonated pyrroles are susceptible to nucleophilic attack (see Section 3.02.2.4.5). 

The TT-electron density refers to the electron density at a given carbon atom obtained by summing the contributions from all the filled molecular orbitals. Electrophilic attack occurs where this density is highest, and nucleophilic attack where it is lowest tt-electron densities are not dominant in determining the orientation of homolytic substitution. 

Iodide and thiocyanate ion are effective catalysts for inducing a related rearrangement (62AG(E)S28). This reaction can be envisioned as proceeding by nucleophilic attack on the lesser substituted aziridinyl carbon atom by iodide ion to give an iodoethyl intermediate such as (132) which is subsequently converted to the final product. 

---