Arylamines, tertiary

We learned m the preceding section that different reactions are observed when the var lous classes of alkylammes—primary secondary and tertiary—react with mtrosatmg agents Although no useful chemistry attends the nitrosation of tertiary alkylammes elec trophilic aromatic substitution by mtrosyl cation ( N=0 ) takes place with A A dialkyl arylamines... 

In the ketone method, the central carbon atom is derived from phosgene (qv). A diarylketone is prepared from phosgene and a tertiary arylamine and then condenses with another mole of a tertiary arylamine (same or different) in the presence of phosphoms oxychloride or zinc chloride. The dye is produced directly without an oxidation step. Thus, ethyl violet [2390-59-2] Cl Basic Violet 4 (15), is prepared from 4,4 -bis(diethylamino)benzophenone with diethylaruline in the presence of phosphoms oxychloride. This reaction is very useful for the preparation of unsymmetrical dyes. Condensation of 4,4 -bis(dimethylamino)benzophenone [90-94-8] (Michler s ketone) with AJ-phenjl-l-naphthylamine gives the Victoria Blue B [2580-56-5] Cl Basic Blue 26, which is used for coloring paper and producing ballpoint pen pastes and inks. 

Tertiary alkylamines illustrate no useful chemistry on nitrosation. Tertiary arylamines undergo nitrosation of the ring by electrophilic aromatic substitution. 

A different mode of reaction, however, is observed in photoreductions of nitroaromatics by aromatic tertiary amines. Irradiation of benzene solutions of N-methylated anilines and either m-chloronitrobenzene or 1-nitronaphthalene results in oxidative demethylation of the amines accompanied with reduction of the nitro compound to the corresponding arylamine 49). The authors suggest that hydrogen abstraction from the methyl group takes place as the primary chemical event. 

In general, EC reactions are typically observed according to the following general rank order (by relative ease of oxidation) o,p-quinol and o,p-aminophenol > tertiary amine > m-quinol rv phenol rv arylamine > secondary amine thiol > thioether primary amines, aliphatic alcohols. (HDVs) each redox active metabolite are obtained from the response across adjacent EC-Array sensors. These data are a reflection of the kinetic and thermodynamic components of electron transfer reactions. Since chemical structure is a critical determinant of an analyte s redox behavior, the intrinsic generation of an HDV with EC-Array provides qualitative information for each species. 

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. 

If three groups are present, the amine is tertiary. If the substituents are all alkyl groups, the amine is referred as being an alkylamine. If there is at least one aryl group directly attached to the nitrogen, then the amine is known as an arylamine. 

As discussed in more detail in Section 4.7, which reviews studies on the reaction mechanism, the major product that competes with the arylamine is the arene resulting from hy-drodehalogenation of the aryl halide. Hartwig showed that steric hindrance was crucial to minimize formation of this side product when monophosphines are used [135]. A second side product from reaction of a primary amine is diaryl alkyl tertiary amine, resulting from... 

The reductive alkylation of /V-alkylarylamines and diarylamine with ketones to give tertiary amines has been investigated by Greenfield and Malz, Jr.42 with platinum metal sulfides that had been shown to be excellent catalysts for the reductive alkylation of primary arylamines with ketones37 (see eq. 6.15). Good conversions to tertiary amines were obtained with relatively unhindered secondary arylamines and less hindered ketones. The relative ease in the reductive alkylation of diarylamines with ketones was in the following order cyclohexanone > acetone > ethyl methyl ketone > isoamyl methyl ketone > isobutyl methyl ketone. For example, 58% of diphenylamine was converted to iV-alkyldiphenylamine with cyclohexanone over rhodium sulfide at 150°C and 3.4-5.5 MPa H2 (eq. 6.19), while with isobutyl methyl ketone, a conversion of only 28% was obtained even at 235°C with in the same reaction time. 

Tertiary arylamines were prepared in good yields by hydrogenation of an alcoholic solution of a nitro compound and an aldehyde over Raney Ni in the presence of triethy-lamine hydrochloride or, better, over platinum oxide in the presence of acetic acid (eq. 6.22).48 Base metal and platinum metal sulfides are also effective to the reductive alkylation of nitro compounds with ketones36,37 as in an example shown in eq. 6.23. 

Name and draw amines, and classify amines as primary, secondary, tertiary, quaternary, arylamines, or heterocyclic amines. 

N-oxidation can occur in a number of ways to give either hydroxylamines from primary and secondary amines [Eqs. (11) and (12)], hydroxamic acids from amides, or N-oxides from tertiary amines [Eq. (13)]. The enzyme systems involved are either cytochrome P450 or a flavoprotein oxygenase. Hydroxylamines may be further oxidized to a nitro compound via a nitroso intermediate [Eq. (11)]. Oximes can be formed by rearrangement of the nitroso intermediate or N-hydroxylation of an imine, that could in turn be derived by dehydration of a hydroxylamine [Eq. (11)]. N-Oxides may be formed from both tertiary arylamines and alkylamines and from nitrogen in heterocyclic aromatic systems, such as a pyridine ring. 

Diaryl sulfamides (201) produced in the condensation of Grignard (primary, tertiary or aryl) and ( -ga-nolithium (primary or aryl) reagents with sulfamylimines (200) can, however, be hydrolyzed in refluxing aqueous pyridine to afford arylamines (202) in good (75-95%) overall yield (Scheme 38). ... 

The Skraup synthesis can be used with a number of substituted arylamines. p-Toluidine forms 6-methylquinoline and o-toluidine 8-methylquinoline. Both quinoline and pyridine are cyclic tertiary amines and react with acid to form salts (pyridinium and quino-linium salts) and with alkyl halides to form quaternary salts. 

Tricyanovinyl-N,N-dimethylaniline has been prepared by adding hydrogen cyanide to -dimethylaminobenzalmalono-nitrile and oxidizing the adduct.3 The present procedure, an adaptation of one that has been published,3 is the more convenient preparative method. It can be applied to a wide variety of secondary and tertiary aromatic amines to give />-tricyanovinyl-arylamines that, like the present one, are dyes.3 Other types of aromatic compounds also condense with tetracyanoethylene in this manner. Thus one can obtain 4-tricyano vinyl-2,6-dimethyl-phenol from 2,6-dimethylphenol, 2-tricyanovinylpyrrole from pyrrole, and 9-tricyanovinylphenanthrene from phenanthrene.4... 

Reduction of hindered imides. Hindered tertiary amines such 2,6-disubstituted arylamines can be prepared by reduction of the corresponding imides with borane. 

Arylamines. Primary," secondary, and tertiary arylamines have been prepared by Pd(0)-catalyzed IV-arylation methods. The most common and effective catalytic system contains (dbaljPd, r-BuONa, and a tertiary phosphine such as BINAP. The nucleophilic species for the synthesis of primary anilines is a Ti-N complex formed from (i-PrO) Ti, Li, and McjSiCl in THF under nitrogen at room temperature (8 h). N-Arylation of chiral secondary amines proceeds without affecting the stereocenters. Arylation with Arl is facile because it can be carried out at room temperature. More recent development indicates that employment of 2-dimethylamino-2 -dicyclohexylphosphinobiphenyl as ligand in the amination of unactivated chloroarenes under mild conditions is also possible. 

As summarized in Table I, this strategy is applicable to the synthesis of many secondary or tertiary amines. It must, however, be noted that some arylamines are not sufficiently nucleophilic to be used in this synthesis. For example, anilines do not react under these conditions, although 2-aminopyridine does. The functionality in some... 

Meisenheimer found that when oxides of tertiary derivatives of arylamines are heated at 100° allyl and benzyl groups can migrate from nitrogen to oxygen whereby 0-substituted hydroxylamines are formed 55... 

Of the many nitrogen functional groups in xenobiotics, only secondary and tertiary acyclic, cyclic, and arylamines as well as hydroxylamines and hydrazines are oxidized by FMO and excreted in the urine (Fig. 10.17). The tertiary amines form stable amine oxides, and secondary amines are sequentially oxidized to hydroxylamines, nitrones, and a complex mixture of products. Secondary N-alkylarylamines can be N-oxygenated to reactive N-hydroxylated metabolites, which are responsible for the toxic, mutagenic, and... 

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