Substitution, SNi

Similar qualitative relationships between reaction mechanism and the stability of the putative reactive intermediates have been observed for a variety of organic reactions, including alkene-forming elimination reactions, and nucleophilic substitution at vinylic" and at carbonyl carbon. The nomenclature for reaction mechanisms has evolved through the years and we will adopt the International Union of Pure and Applied Chemistry (lUPAC) nomenclature and refer to stepwise substitution (SnI) as Dn + An (Scheme 2.1 A) and concerted bimolecular substitution (Sn2) as AnDn (Scheme 2.IB), except when we want to emphasize that the distinction in reaction mechanism is based solely upon the experimentally determined kinetic order of the reaction with respect to the nucleophile. 

A study of the reaction between 4-dimelhylamino-butanone and N-deuterated ar-ylamines indicates the presence of both direct substitution (Sni or Sn ) and climina-tion/addition the nature of the arylamine is decisive in establishing the predominant mechani.sm. 

Elimination reactions introduce n bonds into organic compounds, so they can be used to synthesize alkenes and alkynes—hydrocarbons that contain one and two n bonds, respectively. Like nucleophilic substitution, elimination reactions can occur by two different pathways, depending on the conditions. By the end of Chapter 8, therefore, you will have learned four different organic mechanisms, two for nucleophilic substitution (SnI and Sn2) and two for elimination (El and E2). 

The reaction between an alcohol and thionyl chloride proceeds via an internal nucleophilic substitution, SNi, in which retention is also observed at the substituted carbon. 

Our electron sink also presents two alternative routes, substitution or elimination. With a p abH of 10.7 and a soft carbon anion, this is a good nucleophile and a moderate base. Our 1-bromobutane presents a primary unhindered site so the decision is clearly in the substitution quadrant (Section 9.5). There are two possible substitutions, SnI ... 

EXAMPLE As an example of a molecular inversion, in a T order nucleophilic substitution (SnI reaction) the chirahty of a carbon can be flipped from S to R configuration (or vice versa) 50% of the time. This is due to the chiral carbon having only sp hybridization of its electrons in the intermediate state, which creates a carbon center that is flat and thus subject to nucleophilic attack from either the top or the bottom. If inversion occurs then it is considered to be proof that the reaction indeed is SnI and therefore has an intermediate molecule in its transition state. 

Carbocations, however formed, are very electrophilic. They react readily with nucleophiles, as shown in reaction (5.18). These reactions are important as steps in electrophilic addition to double bonds and unimolecular nucleophilic substitution (SnI) reactions. 

The mechanism of the Ramberg-Backlund reaction is rather straightforward. When a-halosulfone 1 is treated with a strong base, deprotonation rapidly takes place to give a-anion 3, which undergoes a backside displacement (intramolecular nucleophilic substitution, SNi) to provide thiirane dioxide 4 (also known as episulfone) as the key intermediate.10 The Swi reaction with loss of halide is the rate-limiting step. Finally, the unstable 4 releases sulfur dioxide and the ring strain to deliver alkene 2. 

Clearly, the NEt2 group is involved. The nitrogen is a nucleophile and can do an internal nucleophilic substitution (SNi), a very fast reaction for entropy reasons because two different molecules do not have to come together. 

Substitution (SnI or Sn2) is the major reaction of nucleophiles in which one functional group is replaced by another (nucleophilic aliphatic substitution). Nucleophiles can also form a new bond to an acyl carbon (nucleophilic acyl addition). Both of these retrosynthetic transforms are represented by the C-Nuc species, where Nuc = CN , AcQ-, RO , N3-, CO2-, etc. and X = Cl, Br, I, OAc, OSO2R, and so on for Sn2 reactions. In nucleophilic acyl substitutions, the nucleophile is usually a carbon, nitrogen or oxygen species. 

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