Hydroformylation hydroaminomethylation

Abstract Today, the increasing global population and the rising consumption of fossil resources for energy and material use are important issues for research activities in the field of transformation of renewable resources. In petrochemistry, well-established reactions like hydroformylation are performed in multiton plants all over the world and are important examples for processing new resources beyond fossil feedstocks. This chapter deals with the application of three important reactions with carbon monoxide, specifically hydroformylation, hydroaminomethylation, and hydroesterification with renewables which have a C-C-double bond in the starting material. In these reactions, unsaturated oleocompounds and a variety of terpenes can be employed because of their naturally available double bonds. 

Hydroaminomethylation is hydroformylation coupled to amine-aldehyde condensation followed by hydrogenation. The hydroformylation reaction establishes... 

The hydroformylation reaction strategy has recently been extended, in a novel way, to the manufacture of primary amines by hydroaminomethylation of olefins with ammonia in a two-phase system. Thus, 1-pentene was reacted with ammonia here hydroformylation to an aldehyde, with CO and H2, with subsequent reductive amination occurs in a domino reaction. The catalyst was Rh/Ir/TPPS (Zimmermann et al., 1999). 

Hydroaminomethylation of Alkenes (Domino Hydroformylation-Reductive Ami nation) 439... 

Given the previous discussion on reductive amination, it is surprising that the potentially more complicated domino hydroformylation-reductive amination reactions have been more thoroughly developed. The first example of hydroaminomethylation was reported as early as 1943 [83]. The most synthetically useful procedures utilize rhodium [84-87], ruthenium [88], or dual-metal (Rh/Ir) catalysts [87, 89, 90]. This area was reviewed extensively by one of the leading research groups in 1999 [91], and so is only briefly outlined here as the second step in the domino process is reductive amination of aldehydes. Eilbrachfs group have shown that linear selective hydroaminomethylation of 1,2-disubstituted alkenes... 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Homogeneously catalyzed tandem reactions Hydroaminomethylation Hydroformylation... 

Secondary and tertiary amines can be obtained if the hydroformylation of olefins is conducted in the presence of primary and secondary amines under elevated hydrogen partial pressures. Here the rhodium catalyst is involved in both steps, the hydroformylation of an olefin as well as the hydrogenation of the imine or enamine resulting from a condensation of the oxo-aldehyde with the amine (Scheme 14). This combination of hydroformylation and reductive amination is also known as hydroaminomethylation and has been applied to the synthesis of various substrates of pharmaceutical interest [55-57] as well as to the synthesis of macrocycles [60-63] and dendrimers [64,65]. 

General Procedure for the Stepwise Hydroformylation/Reductive Amination on Allylated Hyperbranched Polyglycerols (PG). Synthesis of Hydroaminomethylated Hyperbranched PG-dendrimers. PG-Allyl, Rh(acac)(CO)2 and XANTPHOS were dissolved in dry toluene and placed in an autoclave. The autoclave was pressurized with CO/H2 (1 1, 30 bar), heated at 70 °C for 5d. After cooling, the amine was added to the crude PG-aldehyde (1H NMR was used to confirm full conversion) and stirred for 1-2 h. After stirring, Rh(acac)(CO)2 was added and the autoclave was pressurized with CO/H2 (1 6, 70 bar) and heated at 85 °C for 2-5 days. After cooling, the solvent was removed in vacuo and the crude mixture was purified by dialysis (benzoylated cellulose tubing) to give the re-... 

In a similar manner, polymers with unsaturated chains or side chains can be converted to polyamines [66-69]. Conjugated diolefins usually undergo hydroformylation with low selectivities [70]. Mostly hydrogenation of at least one double bond occurs and mixtures of various saturated and unsaturated amines and diamines are obtained [71]. Similar to alkenes also alkynes may serve as unsaturated compounds in hydro aminomethylation reaction sequences. Although synthetically attractive, only a few investigations towards hydroformylation and hydroaminomethylation of alkynes in the presence of N-nuclcophilcs are known. Usually a preferred transformation to furanonic derivatives is observed under hydroformylation conditions [27]. 

Hydroaminomethylation is a simple, efficient and atom-economic method to synthesize various amines. This one-pot reaction consists of three consecutive steps in the first step a hydroformylation of an olefin is performed followed by the reaction of the resulting aldehyde with a primary or secondary amine to give the corresponding enamine or imine. Lastly, this intermediate is hydrogenated to the desired secondary or tertiary amine (Fig. 11) [33-39]. In most cases rhodium salts or complexes are used as the homogeneous catalyst in the hydroaminomethylation. 

TMS systems, which were used in the isomerizing hydroformylation of frans-4-octene, should be apphcable to hydroaminomethylation as well because the hydroformylation is the first step of the reaction. For this reason similar TMS systems were apphed in a first series of investigations [40]. Propylene carbonate (PC) was chosen as the polar solvent si for the catalyst and alkanes (an isomeric mixture of dodecane or n-hexane) were used as non-polar component s2. 1.4-Dioxane, different pyrrohdones [N-methylpyr-rolidone (NMP), JV-ethylpyrrohdone (NEP), M-cyclohexylpyrrolidone (NCP) AT-benzylpyrrolidone (NBP) and N-octylpyrrohdone (NOP)] or esters of lactic acid (ethyllactate and butyllactate) served as mediator s3. As a test reaction the hydroaminomethylation of 1-octene with morphohne was investigated (Scheme 7). 

Suitable thermomorphic solvent systems were appUed to the telomeriza-tion of butadiene with ethylene glycol or with carbon dioxide, to the isomer-izing hydroformylation of trans-4-octene and to the hydroaminomethylation of 1-octene with morpholine. Further investigations for the carboxytelomer-ization and for the synthesis of 4-nitrodiphenylamine were also carried out. In addition to common Ugands, PEG-modified ligands and fiuorous Ugands were used for the telomerization and the carboxytelomerization. 

One may improve efficiency of an o-DPPB directed hydroformylation by incorporating this reaction into sequential transformations (domino reactions) [16]. The hydroformylation itself should be ideally suited for such a purpose, since this reaction provides under fairly mild reaction conditions access to the synthetically valuable aldehyde functionality. The aldehyde itself should be ideally suited to allow for further skeleton-constructing reactions. One type of sequential transformations employing the hydroformylation reaction as a key step is the hydroaminomethylation of olefins originally discovered by Reppe [17]. However, efficient control of diastereoselectivity in the course of this hydroaminomethylation reaction was unknown [18, 19]. 

Keywords Carbon monoxide Hydroaminomethylation Hydroesterification Hydroformylation Renewable resources... 

Hydroaminomethylation is a promising reaction to functionalize unsaturated compounds with an amino group [13, 48, 49], The tandem reaction was discovered by Reppe in 1949 and has been further developed in recent years by Eilbracht and Beller. Hydroaminomethylation consists of three consecutive reactions which are carried out in the same reaction vessel [48], The first reaction is hydroformylation which is followed by the condensation with an amine. Hydrogenation of the generated enamine/imine to the amine is the last step. The conditions for hydroaminomethylation are related to the hydroformylation reaction but are not similar due to the two other reactions. The reaction is called an auto-tandem reaction because two of the three reactions need the same catalyst [9] (Scheme 16). 

This atom economic reaction, in which only water occurs as a by-product, is very attractive for forming various amines. Hydroaminomethylation includes three different mechanisms due to the three reactions involved. The mechanism of hydroaminomethylation is shown in Scheme 17. The first catalytic cycle is similar to hydroformylation, which is described above. 

A rhodium catalyst [Rh(cod)Cl]2 was applied at 140°C and 100 bar to achieve a yield of 99% in hydroaminomethylation of ethyl oleate and morpholine. Several amines were tested in the reaction with fatty compounds hexylamine, benzylamine, aspartic diethyl acid, valinol, and diisopropylamine are further amines which can be employed in hydroaminomethylation. The conversion with primary amines showed that hydroaminomethylation can proceed twice on the amine. The dimer fatty acid ester bridged with an amine is a highly functionalized molecule with various applications. An excess of the primary amine during the reaction prohibits the reaction of the hydroformylation product with a secondary amine which is the product of hydroaminomethylation with the primary amine (Scheme 19). 

The second double bond is not hydroaminomethylated because of the mild conditions at 80°C and 80 bar and due to steric hindrance [51]. Graebin describes seven different products of the hydroaminomethylation of limonene [52]. The reaction time was reduced to 10 h by optimization of the catalyst including stepwise hydroformylation for 5 h and hydrogenation with pure hydrogen gas for 5 h. Isomerization was reduced by adding triphenylphosphine as ligand. 

The applications of products from the hydroformylation and hydroesterilication of oleocompounds and terpenes are growing and may soon become of great interest for industry. In the future, more technically applicable processes must be developed to make an economic breakthrough. Hydroaminomethylation is a very promising reaction for oleocompounds and terpenes and can yield interesting amino compounds. 

An interesting variation of hydroformylation with a great potential for the industrial preparation of primary amines is hydroaminomethylation. In this process two catalytic reactions are combined, a hydroformylation and a reductive amination of the resulting aldehyde. Although first described more than 60 years ago a really successful procedure was only published recently [78]. To ensure the success of this sequence a rhodium catalyst for the hydroformylation was combined with an iridium catalyst for the imine reduction in a two-phase system, similar to the Ruhrchemie/Rhone-Poulenc process for the hydroformylation. It was demonstrated that less polar solvents such as toluene in combina-... 

Another one-step route to amines is hydroaminomethylation, which is a sequence of hydroformylation and reductive amination of the intermediate aldehyde in a one-pot reaction (Scheme 1). 

Aliphatic amines are amongst the most important bulk and fine chemicals in the chemical and pharmaceutical industry [13]. Hydroaminomethylation of alkenes to amines presents an atom-economic, efficient and elegant synthetic pathway towards this class of compounds. In hydroaminomethylation a reaction sequence of hydroformylation of an alkene to an aldehyde with subsequent reductive amina-tion proceeds in a domino reaction (see Eq. 4) [14]. Recently, the highly selective hydroamination of alkenes with ammonia to form linear primary and secondary aliphatic amines with a new Rh/Ir catalytic system (] Rh(cod)Cl 2], ] Ir(cod)Cl 2], aqueous TPPTS solution) has been described (see Scheme 2) [15]. The method is of particular importance for the production of industrially relevant, low molecular weight amines. 

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