SN2-mechanism

The direct displacement or Sn2 mechanism occurs through a transition state in which bond breaking and bond making occur simultaneously. 

Classes of organic pollutants that hydrolyze via nucleophilic substitution reactions include the halogenated hydrocarbons, epoxides, and phosphorus esters. Further discussion of the factors affecting the reactivity of nucleophilic substitution reactions will be made as the hydrolysis mechanisms of these chemicals are examined in greater detail. 

We have seen above that in a vinyl carbon, the SN1 is not particularly favoured, while the SN2 mechanism is highly unlikely. 

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These reactions follow first-order kinetics and proceed with racemisalion if the reaction site is an optically active centre. For alkyl halides nucleophilic substitution proceeds easily primary halides favour Sn2 mechanisms and tertiary halides favour S 1 mechanisms. Aryl halides undergo nucleophilic substitution with difficulty and sometimes involve aryne intermediates. 

Reaction of Primary Alcohols with Hydrogen Halides The Sn2 Mechanism... 

REACTION OF PRIMARY ALCOHOLS WITH HYDROGEN HALIDES THE Sn2 MECHANISM... 

FIGURE 8 2 Hybrid orbital description of the bonding changes that take place at carbon during nucleophilic substitution by the Sn2 mechanism... 

Reactivity of Some Alkyl Bromides Toward Substitution by the Sn2 Mechanism ... 

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... 

The haloalkane dehydrogenase is believed to act by using one of its side chain carboxylates to dis place chloride by an Sn2 mechanism (Recall the reac tion of carboxylate ions with alkyl halides from Table 8 1 )... 

Having just learned that tertiary alkyl halides are practically inert to substitution by the Sn2 mechanism because of steric hindrance we might wonder whether they undergo nucleophilic substitution at all We 11 see m this section that they do but by a mecha nism different from 8 2... 

Section 8 13 When nucleophilic substitution is used for synthesis the competition between substitution and elimination must be favorable However the normal reaction of a secondary alkyl halide with a base as strong or stronger than hydroxide is elimination (E2) Substitution by the Sn2 mechanism predominates only when the base is weaker than hydroxide or the alkyl halide is primary Elimination predominates when tertiary alkyl halides react with any anion... 

Comparison of SnI and Sn2 Mechanisms of Nucleophilic Substitution in Alkyl Halides... 

The role of nitronium ion in the nitration of benzene was demonstrated by Sir Christo pher Ingold—the same per son who suggested the SnI and Sn2 mechanisms of nu cleophilic substitution and who collaborated with Cahn and Prelog on the R and S notational system... 

Aryl halides react too slowly to undergo substitution by the Sn2 mechanism with the sodium salt of diethyl malonate and so the phenyl substituent of phenobarbital cannot be introduced in the way that alkyl substituents can... 

Substitution nucleophilic bimolecular (Sn2) mechanism (Sec tions 4 12 and 8 3) Concerted mechanism for nucleophilic substitution in which the nucleophile attacks carbon from the side opposite the bond to the leaving group and assists the departure of the leaving group... 

Benzyl carbamates are readily cleaved under strongly acidic conditions HBr, AcOH 50% CF3COOH (25°, 14 days, partially cleaved) - 70% HF, pyridine CF3S03H FSOaH, or CHjSO.H.- In cleaving benzyl carbamates from peptides, 0.5 M 4-(methylmercapto)phenol in CF3CO2H has been recommended to suppress Bn additions to aromatic amino acids. To achieve deprotection via an Sn2 mechanism that also reduces the problem of Bn addition, HF-Me2S-p-cresol (25 65 10, v/v) has been recommended for peptide deprotection. 

SECTION 5.2. THE LIMITING CASES— SUBSTITUTION BY THE DIRECT DISPLACEMENT (Sn2) MECHANISM... 

Clearly, the tertiaiy nature of the chloride would make an Sn2 mechanism highly unlikely. Furthermore, the nitro substituent is essential to the success of these reactions. Cumyl chloride itself undergoes elimination of HCl on reaction with amines. 

The Sn2 mechanism is believed to describe most substitutions in which simple primary and secondary alkyl halides react with anionic nucleophiles. All the exanples cited in Table 8.1 proceed by the Sn2 mechanism (or a mechanism very much like Sn2— remember, mechanisms can never be established with certainty but represent only our best present explanations of experimental observations). We ll examine the Sn2 mechanism, particularly the stnacture of the transition state, in more detail in Section 8.5 after-first looking at some stereochemical studies cariied out by Hughes and Ingold. 

Because the SnI and Sn2 mechanisms are so different from each other, let s examine each one separately. 

As crowding at the carbon that bears the leaving group decreases, the rate of nucleophilic attack by the Lewis base increases. A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to predominate, and primary alkyl halides react with alkoxide bases by an Sn2 mechanism in preference to E2 ... 

As a practical matter, elimination can always be made to occur quantitatively. Strong bases, especially bulky ones such as terr-butoxide ion, react even with primary alkyl halides by an E2 process at elevated temperatures. The more difficult task is to find conditions that promote substitution. In general, the best approach is to choose conditions that favor the Sn2 mechanism—an unhindered substrate, a good nucleophile that is not strongly basic, and the lowest practical temperature consistent with reasonable reaction rates. 

Rate is governed by stability of car-bocation that is formed in ionization step. Tertiary alkyl halides can react only by the SnI mechanism they never react by the Sn2 mechanism. (Section 8.9) Rate is governed by steric effects (crowding in transition state). Methyl and primary alkyl halides can react only by the Sn2 mechanism they never react by the SnI mechanism. (Section 8.6)... 

Next, an alkyl halide (the alkylating agent) is added to the solution of sodium acetylide. Acetylide ion acts as a nucleophile, displacing halide from carbon and forming a new carbon-carbon bond. Substitution occurs by an Sn2 mechanism. 

Allyl chloride is quite reactive toward nucleophilic substitutions, especially those that proceed by the Sn2 mechanism, and is used as a starting material in the synthesis of a variety of drugs and agricultural and industrial chemicals. 

Alkylation occurs by an Sn2 mechanism in which the enolate ion acts as a nucleophile toward the alkyl halide. 

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