Ethylene hydroamination

While ethylene hydroamination with secondary amines was reported by Coulson using Rh as a catalyst in 1971 [86], unfortunately, despite decades of research in the area, there are no catalysts for this reaction across a broad range of substrates. Significant early work in d-block-metal-hydroamination catalysis took advantage of the controlled reactivity provided by mercurial salts. However, the toxicity and ensuing environmental problems of using Hg " " salts demanded an improvement in catalytic protocols. Indeed, steady advancement in the application... 

In 2004, Brunet and coworkers [112] disclosed platinum salts that can be used as catalysts for ethylene hydroamination with aniline to give N-ethylaniline at 150 °C with 25 bar of ethylene pressure. While the desired N-ethylaniline is the major product, N-diethylaniline and quinoline are obtained as accompanying side products (Scheme 15.19). 

Other Pt(II) catalysts in ionic solvent have been disclosed for alkene hydroamina-tion, including ethylene hydroamination (Section 15.3.2) by Brunet and coworkers [109, 112]. This same catalyst system can promote intermolecular hydroamination of unactivated 1-hexene to give a mixture of products, with the Markovnikov product being formed preferentially (Scheme 15.50) [109]. Even in this specialized reaction medium, elevated temperatures and long reaction times are required with these challenging unactivated substrates. 

Dub, P.A., Rodriguez-Zubiri, M., Daran, J.-C., Brunet, J.-J. and Poll, R., Platinum-catalyzed ethylene hydroamination with aniline Synthesis, characterization, and studies of intermediates, Organometallics 28 (16), 4764-4777 (2009). 

From a thermodynamic point of view, the addihon of NH3 and amines to olefins is feasible. For example, the free enthalpy for the addihon of NH3 to ethylene is AG° -4 kcal/mol [14]. Calculations showed that the enthalpies for the hydroamination of higher alkenes are in the range -7 to -16 kcal/mol and that the exothermicities of both hydrahon and hydroaminahon of alkenes are closely similar [15]. Such N-H addihons, however, are characterized by a high activation barrier which prevents the... 

The first example of a heterogeneously catalyzed hydroamination of an alkene appeared in a 1929 patent in which it is claimed that NHj reacts with ethylene (450°C, 20 bar) over a reduced ammonium molybdate to give EtNH2 [24]. An intriguing reaction was also reported by Bersworth, who reacted oleic acid with NH3 in the presence of catalysts like palladium or platinum black or copper chromite to give the hydroamination product in quantitative yields [25]. However, this result could not be reproduced [26]. 

It was thought that propionitrile came from dehydrogenation of the anti-Markovnikov hydroamination product, w-PrNHj. Propionitrile can break down to ethylene and HCN, the former reacting with NH3 to generate acetonitrile via ethyl-amine, the latter adding to propene to form the butyronitriles [26, 37]. 

PhNH2 reacts with ethylene in the presence of alkali metals, e.g., sodium deposited on alumina, to afford the hydroamination product in good yield but with a low turnover frequency (TOP = mol of product synthesized per mol of catalyst in 1 h) (Bq. 4.3) [44]. 

Last, McClain disclosed the gas phase hydroamination of ethylene and propene with NH3 over palladium on alumina (Eq. 4.4) [46]. 

This reaction is restricted to ethylene and to secondary amines of high basicity (nude-ophUicity) and low steric bulk (Me2NH, pyrrolidine, piperidine). No high molecular weight products are formed. However, the same catalysts [107,108] as well as PdQj [108] also exhibit some activity for the hydroamination of ethylene with PhNH2 (Eq. 4.9). 

Study of the mechanism of the rhodium-catalyzed hydroamination of ethylene with secondary amines indicated that the piperidine complex trans-RhCl(C2H4)(piperidine)2 can serve as a catalyst precursor [109, 110]. 

It was elegantly shown later that the hydroamination of ethylene with piperidine or Et2NH can be greatly improved using cationic rhodium complexes at room temperature and atmospheric pressure to afford a high yield of hydroaminated products (Eq. 4.10) [111]. However, possible deactivation of the catalyst can be questioned [17]. 

As shown in Eqs. (4.11) and (4.12), some dealkylation of the starting amine and redistribution of alkyl groups occur. Hydroamination of ethylene with PhNHj affords a low-yield mixture of N-ethylaniUne, N,N-diethylaniline, 2-methylquinoUne, 2-(l-butenyl)aniline, and N-ethyltoluidine [113, 114]. 

Using the above preformed catalysts, ethylene can be hydroaminated by primary and secondary amines under much lower pressures (3-55 atm) than those required for the reactions catalyzed by alkali metals (800-1200 atm). The example of N-ethyl-ation of piperidine has been described in full details in Organic Syntheses (Eq. 4.14) [120]. 

Lehmkuhl et al. demonstrated the beneficial effect of TMEDA (N,N,N, N -tetram-ethylethylenediamine) on the addition of n-BuNHj to ethylene catalyzed by n-BuNHIi (from n-BuNH2 and EtLi) [121]. This is also tme for secondary amines. The efficiency of this system is exemplified by the hydroamination of ethylene with EtjNH (Eq. 4.15). 

Scheme 4-2 General scheme for the base-catalyzed hydroamination of ethylene with Et2NH...

Attempts to hydroaminate ethylene, aUylbenzene, and norbornene with ArNH2 in the presence of zirconium bisamides Cp2Zr(NHAr)2 (Ar = 2,6-Me2CsH3, o-MeQH4) at temperatures up to 160°C have been unsuccessful [126]. 

Nevertheless, hydroamination of ethylene, propene, 1-butene, and the like with NH3, primary and secondary amines using Cp 2Sm(thf)2 (0.5-1%) has been claimed in a patent [128]. 

The feasibility of acid-catalyzed direct hydroamination has been demonstrated. Acidic zeolites afford, at low conversions, highly selective formation of ethyla-mine,297,298 isopropylamine,298 and ferf-butylamine,298-301 in the reaction of ammonia with ethylene, propylene, and isobutylene, respectively. Amine formation is explained as a reaction of surface carbocation intermediates with adsorbed or... 

A few examples are known using homogeneous transition-metal-catalyzed additions. Rhodium(III) and iridium(III) salts catalyze the addition of dialkylamines to ethylene.302 These complexes are believed to activate the alkene, thus promoting hydroamination. A cationic iridium(I) complex, in turn, catalyzes the addition of aniline to norbornene through the activation of the H—N bond.303 For the sake of comparison it is of interest to note that dimethylamino derivatives of Nb, Ta, and Zr can be used to promote the reaction of dialkylamines with terminal alkenes.304 In this case, however, C-alkylation instead of /V-alkylation occurs. 

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

Similarly, hydroamination of ethylene with aniline and PtBr2 was achieved.1 421 The influence of a number of parameters such as reaction time, temperature, ethylene pressure and aniline/catalyst ratio have been investigated. It was found that the catalyst is gradually poisoned by the formed TV-alkylated aniline. Accordingly, a biphasic system with [(C4)4P]Br and decane as the organic phase afforded higher turnover numbers, see Scheme 9.37. 

Alkali metals, their hydrides, and amides have been proven as catalysts for the hydroamination of olefins under various conditions. Some typical examples for the hydroamination of ethylene as the fundamental reaction, being also of considerable industrial interest, are given in Table 2. 

The amides of rubidium or cesium have been proven as the best catalysts for the hydroamination of ethylene with ammonia. In liquid ammonia below the critical temperature (132.5 °C) at 100 °C and an initial pressure of only 11 MPa a turnover number (TON) of about 4 mol C2H4/(mol CSNH2) per h could be reached [6]. 

Table 2. Catalyst systems containing alkali metals for the hydroamination of ethylene. 

Iron pentacarbonyl and some ruthenium(III) complexes, such as RuCls 3 H2O or Ru(NH3)4(OH)Cl2, are claimed in a patent as catalysts for the hydroamination of ethylene and higher olefins in homogeneous solution [13]. 

As the first transition metal-based homogeneous catalysis of hydroamination, in the early 1970s Coulson from the Du Pont laboratories had described the addition of secondary aliphatic amines to ethylene in the presence of various rhodium compounds [15, 16]. Definite results were reported with RhCl3 3 H2O as pre-catalyst in tetrahydrofuran as solvent under starting ethylene pressures of 5-14 MPa at 180-200 °C for different secondary amines (Table 3). 

Table 3. Hydroamination of ethylene with secondary amines in tetrahydrofuran with RhCb H2O as pre-catalyst at 200 C. ...

Quite stable catalytic reaction solutions were obtained in THF with the starting pressure for ethylene of 6-6.5 MPa at a reaction temperature of 120 °C. Under these conditions and with the ratios piperidine/rhodium of 100 1 and 1000 1 in 36 and 72 h, yields of 70 and 50 % ethylpiperidine were reached, which correspond to TONs of 2 and 7 mol amine/(mol Rh) per h, respectively. Total conversion is also possible if the reaction time is prolonged further. As a side reaction, ethylene dimerization to butene was observed. This indicates the formation of a hydrido rhodium(III) complex in the hydroamination reaction, as formulated in Scheme 3, route (b). Hydrido rhodium(III) complexes are known as catalysts for ethylene dimerization [19], and if the reductive elimination of ethylpiperidine from the hydrido-y9-aminoethyl rhodium(III) complex is the rate-limiting step in the catalytic cycle of hydroamination, a competitive catalysis of the ethylene dimerization seems possible. In the context of these mechanistic considerations, an increase of the catalytic activity for hydroamination requires as much facilitation of the reductive elimination step as possible. 

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