Nitrogen-substituted carbocations

Effects of nitrogen substitution can be predicted by quantum chemical calculations (42,43), or more qualitatively by examining the charge distribution in the relevant carbocations. When a carbocation is generated at C-l, the positive charge can be delocalized as shown below. 

The results of studies of the acid-catalyzed hydration of oxygen-, sulfur-, seleno-and nitrogen-substituted alkenes and the relevance of this work to partitioning of the corresponding carbocation intermediates (Chart 1) between deprotonation and nucleophile addition was reviewed in 1986.70. We present here a brief summary of this earlier review, along with additional discussion of recent literature. 

The intrinsic jr-donation capabilities of heavy element atoms (group 15 to group 17), compared to first-row atoms, has been investigated recently by Schleyer and coworkers63. The superior ability of nitrogen to act as a tr-donor in a-substituted carbocations... 

This section deals with addition reactions to cyclic N-acyliminium ions of type (69), locked in the s-trans conformation. Being unable to participate as a 47r-system in a Diels-Alder type reaction, (69) simply reacts as a nitrogen-stabilized carbocation with carbon-carbon multiple bonds. The products can be either the result of addition (70) or substitution (71 and 72), mainly dependent on the substitution pattern of the nucleophilic multiple bond (equation 37). 

Nucleophilic substitution reactions that occur imder conditions of amine diazotization often have significantly different stereochemisby, as compared with that in halide or sulfonate solvolysis. Diazotization generates an alkyl diazonium ion, which rapidly decomposes to a carbocation, molecular nitrogen, and water ... 

The first widely used intermediates for nucleophilic aromatic substitution were the aryl diazonium salts. Aryl diazonium ions are usually prepared by reaction of an aniline with nitrous acid, which is generated in situ from a nitrite salt.81 Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and a carbocation (see Part A, Section 4.1.5), aryl diazonium ions are stable enough to exist in solution at room temperature and below. They can also be isolated as salts with nonnucleophilic anions, such as tetrafluoroborate or trifluoroacetate.82 Salts prepared with 0-benzenedisulfonimidate also appear to have potential for synthetic application.83... 

If racemization were observed, it could only be due to a cleavage of one of die bonds to the chiral center prior to carbon-nitrogen bond formation or subsequent to it. This could occur by (a) enolization of the starting tridate, (b) an ionization of tridate to a carbocation and dien nucleophilic attack by die azide, or (c) enolization in the azido product. The fact that clean inversion occurs means not only that the substitution by azide occurs with inversion but also diat none of diese odier processes is signidcant under the reaction conditions since they would lead to racemized product. 

The intermediates resulting from the diazotization of primary, aliphatic amines are unstable they are rapidly converted into carbocations after loss of nitrogen, and yield products derived from substitution, elimination or rearrangement processes. 

Heteroatoms with higher electronegativity than carbon (e.g. nitrogen, oxygen, or the halogens) inductively destabilize carbocations at the /i position. Epoxides of the type shown in the last equation of Scheme 4.60 therefore react preferentially at the unsubstituted carbon atom. Only in the presence of certain Lewis acids, capable of chelate formation with simultaneous activation of the substituted carbon atom, is the alternative regiochemistry observed. 

Note that in ortho or para substitution the carbocation can be stabilized by delocalization of the positive charge to the nitrogen atom. This is not possible for meta substitution. Therefore, ortho and para substitution are preferred. 

Attack at C-3 gives a carbocation that is resonance-stabilized by a nonbonded pair of electrons on the adjacent nitrogen. Attack at C-2 gives a cation in which the positive charge is not adjacent to an atom bearing nonbonded electrons. Any additional resonance contributors disrupt the benzenoid structure in the left ring. Therefore, electrophilic aromatic substitution reactions of indole occur primarily at C-3. 

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