Amination reactions diarylamines

Diarylamines are manufactured by the self-condensation of a primary aromatic amine in the presence of an acid, or the reaction of an arylamine with a phenol, at high temperatures. 

Good yields of 10-aryl-3,6-dinitroacridones were obtained merely by heating 2,2, 4,4 -tetranitrobenzophenone (419) with an excess of the corresponding aryl amines at 125°C. For example, aniline provided 420 in 80% yield (Eq. 38). The reaction is fairly general for meta- and para-substituted anilines, though it proceeds less readily with orf/io-substituted compounds (79JCS(P1)1364). A method of isolation of the intermediate diarylamine in the synthesis of certain 10-aryl-3,6-dinitroacridones from 2,2, 4,4 -tetranitrobenzophenone has also been described (93JCR(M)2779). 

Diarylamines couple with considerably more difficulty than alkylarylamines. In contrast to primary aromatic amines and alkylarylamines, dialkylarylamines are substituted by diazonium ions only in the 4-, not in the 2-position. This is due to the considerable sensitivity of azo coupling reactions to steric hindrance. 

Therefore in this section we will focus first on the reactions of arenediazonium ions with secondary amines such as A-alkylanilines and dialkylamines. Reactions with primary amines will be discussed later in this section. Most diarylamines do not undergo Af-azo coupling to a significant extent, as they are weaker nucleophiles. 

In addition, complexes of P(/-Bu)3 have been shown to catalyze the formation of diaryl heteroarylamines from bromothiophenes.224 Aminations of five-membered heterocyclic halides such as furans and thiophenes are limited because their electron-rich character makes oxidative addition of the heteroaryl halide and reductive elimination of amine slower than it is for simple aryl halides. Reactions of diarylamines with 3-bromothiophenes occurred in higher yields than did reactions of 2-bromothiophene, but reactions of substituted bromothiophenes occurred in more variable yields. The yields for reactions of these substrates in the presence of catalysts bearing P(/-Bu)3 as ligand were much higher than those in the presence of catalysts ligated by arylphosphines. 

Aromatic amines RNH2 (R = Ph, 2-MeCgH4 or 4-MeOCgH4) are phenylated by triphenylbismuth in the presence of 0.5 equivalent of copper(II) acetate to yield diarylamines RNHPh. Butylamine yields a mixture of TV-butylaniline and N-butyldiphenylamine in this reaction and piperidine gives TV-phenylpiperidine36. A similar alkylation of the secondary amines pyrrolidine, piperidine and morpholine with trimethylbismuth or tris(2-phenylethyl)bismuth in the presence of copper(II) acetate affords tertiary amines, e.g. 14. The reaction proceeds by way of transient pentavalent bismuth compounds37. 

Fagnou et al. reported the synthesis of mukonine (11) starting from methyl vanillate (644). This synthesis uses both a palladium(0)-catalyzed intermolecular direct arylation and an intramolecular cyclization reaction. Triflation of methyl vanillate (644) afforded the aryl triflate 645. Using a Buchwald-Flartwig amination protocol, the latter was subjected to direct arylation with 2-chloroaniline (646) to furnish the corresponding diarylamine 647. Finally, intramolecular cyclization of 647 afforded mukonine (11). To date, this is the best synthesis (three steps, 75% overall yield) available for mukonine based on commercially available methyl vanillate (644) (582) (Scheme 5.45). 

Ar Nj — ArNHAr. 148 Diarylamines are also obtained by the reaction of N-arylhydroxyl-amines with aromatic compounds (benzene, toluene, anisole) in the presence of F3CCOOH ArH + Ar NHOH - ArNHAr. 149... 

There has been a review of die effects of high pressure on the substitution reactions of amines witii haloaromatic compounds, including polyhalobenzenes.17 Nucleophilic substiditions by amines often proceed readily hi dimethyl sulfoxide (DMSO). The pKa values, hi DMSO, have been reported for some ammonium ions derived from amines widely used as nucleophiles in 5nAt reactions.18 Correlations have been established19 between die oxidation potentials and the basicities of some arylamhie and diarylamine anions and die rate constants for dieir reactions with aiyl halides in DMSO. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Aminations of five-membered heterocyclic halides, such as furans and thiophenes, are limited. These substrates are particularly electron-rich. As a result, oxidative addition of the heteroaryl halide and reductive elimination of the amine are slower than for simple aryl halides (see Sections 4.7.1 and 4.7.3). In addition, the amine products can be air-sensitive and require special conditions for their isolation. Nevertheless, Watanabe has reported examples of successful couplings between diarylamines and bromothiophenes [126]. Triaryl-amines are important for materials applications because of their redox properties, and these particular triarylamines should be especially susceptible to electrochemical oxidation. Chart 1 shows the products formed from the amination of bromothiophenes and the associated yields. As can be seen, 3-bromothiophene reacted in higher yields than 2-bromothiophene, but the yields were more variable with substituted bromothiophenes. In some cases, acceptable yields for double additions to dibromothiophenes were achieved. These reactions all employed a third-generation catalyst (vide infra), containing a combination of Pd(OAc)2 and P(tBu)3. The yields for reactions of these substrates were much higher in the presence of this catalyst than they were in the presence of arylphosphine ligands. 

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. 

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