Aryl halides arylamine synthesis

Aryl halides cannot be converted to arylamines by the Gabriel synthesis because they do not undergo nucleophilic substitution with /V-potassiophthalimide in the first step of the procedure. 

Hartwig, J.F., Transition metal catalysed synthesis of arylamines and aryl ethers from aryl halides and triflates scope and mechanism, Angew. Chem., Int. Ed. Engl, 1998, 37, 2047-2067. 

The Sandmeyer procedure for the synthesis of aryl halides from arylamines has been applied, with modification, to the conversion of 5- and 8-aminoquinolines to the iodo and bromo derivative. 8-Aminoquinoline is converted to 8-bromoquinoline in good yield on treatment with /-butyl nitrite in the presence of CuBr in acetonitrile at 60 °C <2003JOC5123> and 5-amino-6-nitroquinoline is converted to the 5-iodo derivative under equally mild conditions using potassium nitrite and copper iodide in DMSO at 60 °C <2005JOC2445>. 

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. 

This review covers palladium-catalyzed amination of aryl halides and sulfonates. The nickel-catalyzed process [82-85] requires much higher catalyst loads and has a narrower substrate scope. Thus, it is not reviewed. Sections 4.2 to 4.5 cover the development of different palladium catalysts for the synthesis of arylamines and related structures. This work has... 

A new method of synthesis of A-alkylphthalimides (79) via alkylation of phthalim-ide in dry media under microwave irradiation was carried out by Bodgal et al. (1996). The reactions were performed by simply mixing phthalimide with an alkyl halide adsorbed on potassium carbonate to give a good yield of the product. Yadav and Subba Reddy (2000) reported a novel and efficient synthesis of A-arylamines (80) by the reaction of activated aryl halides with secondary amines in the presence of... 

J. F. Hartwig, Transition Metal Catalyzed Synthesis of Arylamines and Aryl Ethers from Aryl Halides and Triflates Scope and Mechanism, Angew. Chem. Int. Ed. 1998,37,2047. P. G. Jessop, T. Ikariya, and R. Noyori, Homogeneous Catalysis in Supercritical C02, Chem. Rev. 1995, 95, 259. 

Louie, J., Hartwig, J. F. Palladium-catalyzed synthesis of arylamines from aryl halides. Mechanistic studies lead to coupling in the absence of tin reagents. Tetrahedron Lett. 1995, 36, 3609-3612. 

The synthesis of W-arylamines 474 by amination of aryl halides with morpholine (469) was carried out in the presence of basic alumina under MWI. This required 4-5 min of irradiation to give 88-89% yields (Scheme 92). Conventional heating at 120 °C required 8h for completion to give 65-69% yields (00MI3). 

Some of the optimized procedures for Stille and Sonogashira reactions involve the addition of copper cocatalysts to accelerate the cross-coupling procedures. A word of caution should be provided on the role of these additives in Pd-catalyzed amination procedures. Beletskaya and Davydov have reported the arylation of benzotriazole and of diary-lamines in polar organic or aqueous organic solvents using a combination of palladium and copper as catalyst.The arylation of amino acids has been reported under similar conditions.However, these reaction conditions are similar to classic Ullmann procedures for the synthesis of arylamines, except for the addition of palladium to the reaction mixture. In one case, subsequent work showed that the palladium species was not an essential component and that copper alone was the true catalyst in their reactions. An unusual accelerating effect of amino acid coordination to copper was used to explain the low-temperature Ullmann conditions. Beletskaya, however, showed that lower yields and a mixture of N1 and N2 arylation products were observed from the reactions of benzotriazole in the absence of copper and no reaction was observed in the absence of palladium. The conditions for this chemistry are, however, distinct enough from those of the majority of the aryl halide aminations to support the idea that a different mechanism may operate. 

With the development of Buchwald-Hartwig amination reactions, the amine component of these indoles can also be introduced into these precursors via palladium catalysis [8]. As shown by Ackermann, this can be coupled with aryl halide alkynylation and cyclization to provide a one-pot, three-component synthesis of substituted indoles (Scheme 6.6) [9]. In this case, simple ortho-dihaloarene derivatives S were employed as starting materials, with Sonogashira coupling occurring at the more activated aryl-iodide bond, followed by selective coupling of various alkyl or arylamines. Alternatively, Zhao has recently demonstrated that amination can be performed on both bromoalkyne 6, followed by the aryl-bromide bond, to provide a route to 2-amidoindoles (Scheme 6.7) [10]. 

Transition Metal Catalyzed Synthesis of Arylamines and Aryl Ethers from Aryl Halides and Tri-flates Scope and Mechanism. 

Reaction of Arylamines Copper-catalyzed C—N coupling affords powerful tool for the synthesis of nitrogenated compounds [33]. In 1987, Paine reported soluble cuprous ion as the active catalytic species in Ullmann coupling [34]. Soluble air-stable copper(I) complex, Cu(PPh3)jBr, has been used for the synthesis of functionalized diaryl and triaryl amines (Scheme 20.17) [35]. Copper(I) complexes 7-8 and CuI-PBu have been employed for the coupling of aryl halides with aiyl amines [36, 37]. The catalyst with PBu could be used for the coupling of less reactive aiyl chlorides in the presence of KOTlu. 

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. 

Discrete copper compounds can also be used as catalysts for the synthesis of arylamines (Scheme 3.52) [58]. Venkataraman used a neocuproine-ligated copper(I) species to promote the coupling of aryl halides with secondary amines. A practical advantage to this chemistry was that only air-stable materials were needed to construct the catalyst needed for the cross-coupling. A base was needed to promote the reaction, and potassium tert-butoxide was found to be more effective in the cross-coupling than other common bases including potassium phosphate, sodium methoxide, or cesium carbonate. Curiously, cesium carbonate was not as active in this chemistry, but it was quite effective in the preparation of diaryl ethers. Several aryl halides were screened for activity, and aryl bromides and iodides afforded moderate to good yields of the arylamines. It should be noted that an electron-neutral aryl chloride was converted into the triarylamine, albeit in lower yield (49%). 

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