Nucleophilic aliphatic substitution nitrogen

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. 

Another attempt to use the host-guest complexation of simple cyclophanes has been reported by Schneider They take the easily accessible host 7, an analogue of which had been demonstrated by Koga to bind aromatic guest molecules by inclusion into its molecular cavity, and study its rate effects on nucleophilic aliphatic substitutions of ambident anions (NOf, CN, SCN ) on 2-bromomethylnaphthalene 8 and benzylbromide. Similar bimolecular reactions are well known in cyclodextrin chemistry and other artificial host systems . In addition to the rather poor accelerations observed (see Table 3) the product ratio is changed in the case of nitrite favouring attack of the ambident nucleophile via its nitrogen atom. 

The process can continue to give one other nitrogen-based product, the quaternary ammonium salt. The final composition of the reaction will consist of varying ratios of RNHg, RgNH, R3N, and R4N C1 . Because the ratio of products is difficult to control or predict, we avoid using an amine (or ammonia) as a nucleophile in nucleophilic aliphatic substitution reactions. 

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... 

Reaction with Nitrogen Nucleophiles. The acid-catalyzed reaction of primary, secondary, and tertiary amines with ethyleneimine yields asymmetrically substituted ethylenediamines (71). Steric effects dominate basicity in the relative reactivity of various amines in the ring-opening reaction with ethyleneimine (72). The use of carbon dioxide as catalyst in the aminoethylation of aliphatic amines, for which a patent application has been filed (73), has two advantages. First, the corrosive salts produced when mineral acids are used as catalysts (74,75) are no longer formed, and second, the reaction proceeds with good yields under atmospheric pressure. 

A series of 3-amino (or 3-N-substituted amino)-l,2,4-oxadiazoles 108 can be obtained in moderate to high yields by the photoinduced rearrangement of 3-acylamino-l,2,5-oxadiazoles (furazans) 106 irradiated in the presence of an excess of ammonia or aliphatic amines [64—66]. The reaction follows a fragmentation-cycloaddition route, with the initial formation of a nitrile and a nitrile-oxide the latter is attacked by a nitrogen nucleophilic reagent (ZH in Scheme 12.29), and the open-chain interme-... 

Enantioselective allylic substitutions of cyclic allylic esters have been more challenging to develop than enantioselective reactions of symmetrical, acyclic allylic esters. In one set of reactions, racemic allylic esters react to form non-racemic products by addition of carbon or nitrogen nucleophiles in the presence of palladium catalysts. In these cases, attack at the two termini of the allylic intermediate generates the two enantiomers. Only a handful of ligands have generated catalysts that form products from the substitution of aliphatic. 

The chemistry of amines is dominated by the lone-pair electrons on nitrogen, which makes amines both basic and nucleophilic. The base strength of arylamines is generally lower than that of aliphatic amines because the nitrogen lone-pair electrons are delocalized by interaction with the aromatic tt system. Electron-withdrawing substituents on the aromatic ring further weaken the basicity of a substituted aniline, while electron-donating substituents increase basicity. 

Only the diaza-18-crown-6 was observed when R was a benzylic or aliphatic group. When R was a 4-substituted phenyl (e.g., 4-OCH3), only the 1 1 adduct, aza-9-crown-3, was isolated. The authors suggested that since the aniline nitrogen atom is less nucleophilic than an aliphatic amine nitrogen atom. 

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