Substitution, electrophilic amination

Dichloronitrobenzene has been prepared by deamination of 3,5-dichloro-4-nitroaniline and of 2,4-dichloro-3-nitroaniline. This procedure is an example of the rather general oxidation of anilines to nitrobenzenes with peroxytrifluoroacetic acid. Use of this reagent is frequently the method of choice for carrying out this transformation, and it is particularly suitable for oxidation of negatively substituted aromatic amines. Conversely, those aromatic amines, such as />-anisidine and j8-naphthylamine, whose aromatic nuclei are unusually sensitive to electrophilic attack give intractable mixtures with this reagent. This is not... 

Substituted hydroxylamines 1-5 (R = R = H) and their A-mono- or A,A-disub-stituted derivatives 1-5 have been used extensively for electrophilic amination of both carbanions and enolates since the first report in 1938 on the use of 0-methylhydroxylamine 1 (R = Me) for conversion of Grignard reagents to primary amines. Oximes 7 (Z = H) have found limited applicability as amination reagents for carbon nucleophiles and then-use was first reported in 1907. Ketone 0-sulfonyloximes 7 (Z = SO2R) have recently been developed. 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

Recently, a direct kinetic study on the amination of substituted phenyhnagnesium bromides using Af,Af-dimethyl O-mesitylenesulfonyl hydroxylamine 3b as amination reagent has been reported by Erdik and Ate Ulkii . Rate data, the Hammett relationship and activation entropy support an Sn2 displacement of the carbon nucleophile on the electrophilic nitrogen. These results are consistent with the competition kinetics for electrophilic amination of substituted phenyl Grignard reagents with O-methylhydroxylamine In. ... 

There are a few reports on the use of oximes as electrophilic amination reagents. Since 1984, ketone O-sulfonyloxknes have found applicability as amino transfer reagents to car-banions. In the reaction of organometaUic compounds with oximes, carbanions attack the carbonyl carbon of the oxime, giving Af-substituted hydroxylamines as addition products (Scheme 53, path a). However, a number of scattered reports have been also published on the formation of aziridines by a-deprotonation, followed by addition (path b) or formation of azirines by a-deprotonation before addition (path c). Addition of carbanions to azirines also yields aziridines, which are hydrolyzed to a-aminoalcohols. 

In this chapter, C—N couplings, e.g. substitution reactions of carbanions on nitrogen atom of oximes to yield primary amines, have been reviewed. A list of oximes and 0-sulfonyloximes used for electrophilic amination is given in Table 6. These reagents aminate carbanions to A-organylimines as isolable intermediates which are hydrolyzed to primary amines (Scheme 53, path d Scheme 54). Depending on the organometaUic... 

The discussion in this chapter highlights the performance of O-substituted hydroxylamines and oximes as electrophilic amino transfer reagents. In conclusion, the scope of electrophilic amination will be greatly enhanced by developing new O-substituted hydroxylamines and oximes and further improvements in electrophilic amination would be of great synthetic interest. 

The reaction of 1,2-diazinamines with electrophiles is well studied while the substitution of amines-imines by nucleophiles is a highly nonstandard process. Nevertheless, even in the latter class new examples appeared since CHEC-II(1996) <1996CHEC-II(6)1>. A new section dealing with the so-called f-amino effect was added since many examples on 1,2-diazines have appeared since the mid-1990s. 

P. Beak, W.J. Zajdel u. D.B. Reitz, Chem. Rev. 84, 471 523 (1984) Metallation and Electrophilic Substitution of Amine Derivatives Adjacent to Nitrogen a-Metallo Amine Synthetic Equivalents". 

For reviews of metalalion and electrophilic substitution of amine derivatives adjacent to nitrogen, see Chem Rev 84 471 (1984)... 

Other Substituted Diazonium Ions. A series of aminodiazonium ions have been prepared under superacidic conditions [Eq. (4.141)]. Schmidt495 described the preparation and IR spectra of protonated hydrazoic acid 212 and methylazide as their hexachloroantimonate salts. Olah and co-workers496 have carried out a comprehensive study on aminodiazonium ions (protonated azides) by H, 13C, and 15N NMR spectroscopy. Even the electrophilic aminating ability of aromatics of 212 has been explored.496 The tetrachloroaluminate salt of 212 has also been prepared496... 

The free amino group strongly activates the aromatic ring towards electrophilic attack and aromatic substitution of amines often results in polysubstitution. For example, the bromination of aniline yields largely 2,4,6-tribromoaniline (Expt 6.59). 

The corresponding reactions are mostly ionic involving nucleophilic displacement by SnI, Sn2 or carbonyl substitution with amines, alcohols and thiols on carbon electrophiles. The normal polarity of the disconnection 1 will be a cationic carbon synthon 2 and an anionic heteroatom synthon 3 represented by acyl or alkyl halides 4 as electrophiles and amines, alcohol or thiols 5 as nucleophiles. 

Hydroxylation of arylamines with persulfate ion, or Boyland-Sims oxidation, gives ortho-substituted aminophenols in good yields [29]. As with the Elbs oxidation, the procedure is also carried out in two steps - first, treatment with the oxidant to obtain an aminophenyl sulfate ester and, second, hydrolysis to obtain the final product. Primary, secondary and tertiary amines can all be used in this reaction. The ortho product is formed, except when no ortho-positions are available, which leads to para-substitution. Electrophilic attack on the ipso-carbon is believed to be the most likely mechanism, although minor radical pathways also seem to be present. 

The diastereoselective electrophilic amination of ketone enolates in 2-substituted 2-acyl-1,3-dithiane 1-oxides 19 with di-/m-butyl azodicarboxylate (DBAD) was reported recently21. The un/i-isomcr, anti-19, led to the major isomer anti-20, while. vyn-19 gave predominantly. 9171-20. 

While the addition of organometallic reagents to acyclic or cyclic imines (43) is often compromised by poor imine reactivity, these reagents readily condense with structurally diverse, more electrophilic imini-um salts (44), bearing a positive charge on the nitrogen atom, to provide substituted tertiary amines (45 Scheme 6). A review of the literature describing additions to cyclic iminium salts prior to 1966 is avail-... 

To further extend fhe substitution pattern of fhese building blocks, benzarmelated N-amino-N-heterocycles were prepared Electrophilic amination of indole, 2-mefhylindole, or carbazole using hydroxylamine-O-sulfonic acid [25] yielded fhe corresponding N-amino-indole 17, -2-methyhndole 18, and -carbazole 19, respectively. However, attempting the same reaction with 2,7-dimethyhndole or dibenza-zepine (iminostilbene) failed, most likely due to steric hindrance. 

Under similar conditions, 5-phenyltetrazole is converted to a complex mixture containing amine 164 (42%), 3,5-diphenyl triazole, and different phenyl-substituted triazines and tetrazines (62LA146). Electrophilic amination of 1,2,4-triazole by HOSA [80JCR(M)514] or by DNPH (89S269) leads to l-amino- and 4-aminotriazole with the great dominance of the first. This is the only method to synthesize unsubstituted 1-amino-s-triazole. It is known as the nitrene amination of 1,2,4-triazoles [Eq. (46)] [74AHC (17)213]. 

Little work could be found on the electrophilic amination of simple nitrile-stabilized carbanions. The lithium anion of propionitrile reacts normally with an N-substituted oxaziridine (Eq. 141).158 The amination of nitriles with a camphor-derived N-unsubstituted oxaziridine was discussed earlier (Eq. II).151 Aminoma-lononitrile is formed from malononitrile anion and 0-(mesitylenesulfonyl)hydro-xylamine (Eq. 142).463... 

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