Aryl halides diarylamine reactions

Sjwyer and coworkers have developed an efficient alternative UUmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SnAt reaction. Phenol, thiophenol, or aniline reacts v/ith an appropriate aryl halide, In the presence of KF-aliunina and 18-crovm-6 In acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thio ether as shovm In Eqs. 9.6 and 9.7. ... 

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. 

A remarkable process was reported by Mori that forms aniline from dinitrogen (Equation (26)).106 Titanium nitrogen fixation complexes were generated from reactions of titanium tetrachloride or tetraisopropoxide, lithium metal, TMS chloride, and dinitrogen. These complexes generated a mixture of aryl and diarylamines in yields as high as 80% when treated with aryl halide and a palladium catalyst containing DPPF ... 

There has been a review of the effects of high pressure on the substitution reactions of amines with haloaromatic compounds, including polyhalobenzenes.17 Nucleophilic substitutions by amines often proceed readily in dimethyl sulfoxide (DMSO). The pAa values, in DMSO, have been reported for some ammonium ions derived from amines widely used as nucleophiles in, S Ar reactions.18 Correlations have been established19 between the oxidation potentials and the basicities of some arylamine and diarylamine anions and the rate constants for their reactions with aryl 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. 

Generally, reactions with anilines are slower than those with aliphatic amines, in part because anilines are less nucleophilic7. Condensation of aromatic amines with unactivated aryl halides usually requires the presence of copper catalysts. Reactions of diarylamines, such as diphenylamine and carbazole, are even slower. 

For the reactions of aryl halides with diarylamines (equation 17), the P(tol-o)3 ligand gives good yields in most cases, but catalyst loads of 5-10% were typically required99. In some cases, palladium complexes bearing DPPF as ligand are more effective catalysts for the formation of triarylamines, and can even produce unsymmetrical triarylamines in a one-step addition of two aryl halides sequentially to an aniline100. 

The isolated dimeric [ PdBrL 2] (L = P(l-Ad)(Bu-t)2, P(Bu-t)3) complex catalyzed the reactions of aryl halides with diarylamines with even faster rates, and these rates were similar to those of the aminations of aryl chlorides with cyclic or acyclic amines. For example, the amination of aryl chlorides with diphenylamine was complete within 15... 

The Buchwald-Hartwig reaction has been widely used in organic chemistry for the palladium-catalyzed cross-coupling of amines with aryl halides. In particular, it has been used in conjunction with benzothiophenes for arylamination of the thiophene. The final diarylamine product below demonstrated anti-fungal activity against dermatophytes, yeasts, and the Aspergillus species. ... 

The reactions of diarylamines with aryl halides is more straightforward than the reaction of secondary alkylamines because these substrates possess no hydrogens on the a carbon and cannot, therefore, nndergo /3-hydrogen elimination as palladium amides. However, competitive formation of arene by an nnknown mechanism remains one side prodnct. For the most part, the synthesis of triarylamines has focused on the preparation of discrete molecules and polymers that are important for electronic materials applications,... 

C.iii.c. Preparation of Small Molecules for Materials Science. Pd-catalyzed amination has also been used to prepare small molecules that are useful as hole-transport materials, selective metal-cation detection systems, and dyestuffs. As mentioned briefly in the section on reacting diarylamines with aryl halides, Marder and co-workers used palladium chemistry to form triarylamines, which are useful as hole-transport layers. Reactions of primary arylamines with aryl halides using DPPF-hgated palladium as catalyst allows for the selective addition of one aryl halide, followed by the addition of a second aryl halide to form mixed triarylamines, as shown in Eq. 42. This procedure has been used to generate unsymmetrical triarylamines that are analogs of TPD, as shown in Eq. 43. hi addition, they have used aminoferrocene as a substrate to conduct diarylations to form N, A-diarylaminoferrocenes. ... 

Another Ullmann synthesis is the syntheses of arylethers or diarylamines by the condensation reactions of aryl halides with phenols or arylamines. For example, reactions are shown in eqs. (22.16) [62] and (22.17) [63], and especially the former reaction is used for the production of polyphenylether type heat-resistant synthetic lubricants. 

Nitrosoarenes give unstable diaryl hydroxylamines with aryl Grignard reagents, which can be reduced directly to diarylamines.312 Since arylmagnesium halides reduce nitroarenes to nitroso compounds, readily available nitroarenes and nitrohetarenes can be involved in this reaction allowing a simple preparation of polyfunctionalized diaryl- and heteroarylamines (Scheme 108).313... 

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