The Hydroformylation Reaction

Among all of the homogeneous processes catalyzed by transition metals, hydro-formylation stands out in three respects. It is the oldest process still in use today, it is responsible for producing the largest amount of material resulting from a homogeneous transition metal-catalyzed reaction,9 and it can be considered a green process because it proceeds with almost 100% atom economy. The hydroformylation reaction was outlined already in equation 9.5. 

Anastas and J. C. Warner, Green Chemistry Theory and Practice, Oxford University Press New York, 1998, p. 11. This book is an excellent resource for those new to the field of green chemistry. 

9In 2005, nearly 9.6 million metric tons (1 metric ton = 1000 kg or 1.1 U.S. tons) of hydroformylation products were produced worldwide S. Bizzari, M. Blagoev, and A. Kishi, Oxo Chemicals, in Chemical Economics Handbook, SRI Consulting Menlo Park, CA, 2006. 

Carbon Monoxide in Organic Synthesis, Springer Verlag New York, 1970. 

Kohlpaintner, Hydroformylation-Industrial, in Encyclopedia of Catalysis, Vol 3, I. Horvath, Ed Wiley Hoboken, NJ, 2003, p. 787. 

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Aliphatic Aldehyde Syntheses. Friedel-Crafts-type aUphatic aldehyde syntheses are considerably rarer than those of aromatic aldehydes. However, the hydroformylation reaction of olefins (185) and the related oxo synthesis are effected by strong acid catalysts, eg, tetracarbonylhydrocobalt, HCo(CO)4 (see Oxo process). 

The mechanism of the cobalt-cataly2ed oxo reaction has been studied extensively. The formation of a new C—C bond by the hydroformylation reaction proceeds through an organometaUic intermediate formed from cobalt hydrocarbonyl which is regenerated in the aldehyde-forrning stage. The mechanism (5,6) for the formation of propionaldehyde [123-38-6] from ethylene is illustrated in Figure 1. 

Meth5l-l,3-propanediol is produced as a by-product. The hydroformylation reaction employs a rhodium catalyst having a large excess of TPP (1) and an equimolar (to rhodium) amount of 1,4-diphenylphosphinobutane (DPPB) (4). Aqueous extraction/decantation is also used in this reaction as an alternative means of product/catalyst separation. 

The hydroformylation reaction is carried out in the Hquid phase using a metal carbonyl catalyst such as HCo(CO)4 (36), HCo(CO)2[P( -C4H2)] (37), or HRh(CO)2[P(CgH3)2]2 (38,39). The phosphine-substituted rhodium compound is the catalyst of choice for new commercial plants that can operate at 353—383 K and 0.7—2 MPa (7—20 atm) (39). The differences among the catalysts are found in their intrinsic activity, their selectivity to straight-chain product, their abiHty to isomerize the olefin feedstock and hydrogenate the product aldehyde to alcohol, and the ease with which they are separated from the reaction medium (36). 

With Unsaturated Compounds. The reaction of unsaturated organic compounds with carbon monoxide and molecules containing an active hydrogen atom leads to a variety of interesting organic products. The hydroformylation reaction is the most important member of this class of reactions. When the hydroformylation reaction of ethylene takes place in an aqueous medium, diethyl ketone [96-22-0] is obtained as the principal product instead of propionaldehyde [123-38-6] (59). Ethylene, carbon monoxide, and water also yield propionic acid [79-09-4] under mild conditions (448—468 K and 3—7 MPa or 30—70 atm) using cobalt or rhodium catalysts containing bromide or iodide (60,61). 

Garbonylation of Olefins. The carbonylation of olefins is a process of immense industrial importance. The process includes hydroformylation and hydrosdylation of an olefin. The hydroformylation reaction, or oxo process (qv), leads to the formation of aldehydes (qv) from olefins, carbon monoxide, hydrogen, and a transition-metal carbonyl. The hydro sdylation reaction involves addition of a sdane to an olefin (126,127). One of the most important processes in the carbonylation of olefins uses Co2(CO)g or its derivatives with phosphoms ligands as a catalyst. Propionaldehyde (128) and butyraldehyde (qv) (129) are synthesized industrially according to the following equation ... 

The nickel or cobalt catalyst causes isomerization of the double bond resulting in a mixture of C-19 isomers. The palladium complex catalyst produces only the 9-(10)-carboxystearic acid. The advantage of the hydrocarboxylation over the hydroformylation reaction is it produces the carboxyUc acids in a single step and obviates the oxidation of the aldehydes produced by hydroformylation. 

Since then, water has emerged as a useful solvent for organometallic catalysis. In addition to the hydroformylation reactions, several other industrial processes... 

Synthesis gas is an important intermediate. The mixture of carbon monoxide and hydrogen is used for producing methanol. It is also used to synthesize a wide variety of hydrocarbons ranging from gases to naphtha to gas oil using Fischer Tropsch technology. This process may offer an alternative future route for obtaining olefins and chemicals. The hydroformylation reaction (Oxo synthesis) is based on the reaction of synthesis gas with olefins for the production of Oxo aldehydes and alcohols (Chapters 5, 7, and 8). 

A simplified mechanism for the hydroformylation reaction using the rhodium complex starts by the addition of the olefin to the catalyst (A) to form complex (B). The latter rearranges, probably through a four-centered intermediate, to the alkyl complex (C). A carbon monoxide insertion gives the square-planar complex (D). Successive H2 and CO addition produces the original catalyst and the product ... 

If cobalt carbonylpyridine catalyst systems are used, the formation of unbranched carboxylic acids is strongly favored not only by reaction of a-olefins but also by reaction of olefins with internal double bonds ( contrathermo-dynamic double-bond isomerization) [59]. The cobalt carbonylpyridine catalyst of the hydrocarboxylation reaction resembles the cobalt carbonyl-terf-phos-phine catalysts of the hydroformylation reaction. The reactivity of the cobalt-pyridine system in the hydrocarboxylation reaction is remarkable higher than the cobalt-phosphine system in the hydroformylation reaction, especially in the case of olefins with internal double bonds. This reaction had not found an industrial application until now. 

Figure 24 Phosphine-based dendrimers prepared from T8[CH = CH2]8 and used in the hydroformylation reaction.

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

The adoption of a second liquid phase has also proved useful in the hydroformylation reaction of propylene for which Ruhrchemie and Rhone-Poulenc have used Rh based water... 

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). 

Hydroformylation is the oldest and in production volume the largest homogeneously catalyzed industrial process. The hydroformylation reaction was discovered by Otto Roelen in 1938 the reaction is also called oxosynthesis and Roden s reaction [1-13]. 

The steps in the hydroformylation reaction are closely related to those that occur in the Fischer-Tropsch process, which is the reductive conversion of carbon monoxide to alkanes and occurs by a repetitive series of carbonylation, migration, and reduction... 

B and C respectively. The contents of units A , B1 or C1 depend on the reaction conditions employed in the hydroformylation step. One of the most important factors for the selectivity for the formation of A, B, or C is the nature of the 0X0 catalyst employed to carry out the hydroformylation reaction. 

Other metal complexes containing Pd, Ru, Co, or Pt have also been used.176 The hydroformylation reaction can also be performed by using methyl formate instead of carbon monoxide and hydrogen.177... 

Many chiral diphosphine ligands have been evaluated with regard to inducing enantioselectivity in the course of the hydroformylation reaction [25,26]. However, a real breakthrough occurred in 1993 with the discovery of the BI-NAPHOS ligand by Takaya and Nozaki [65]. This was the first efficient and rather general catalyst for the enantioselective hydroformylation of several classes of alkenes, such as aryl alkenes, 1-heteroatom-functionalized alkenes, and substituted 1,3-dienes, and is still a benchmark in this area [66,67]. But still a major problem in this field is the simultaneous control of enantio-... 

Mono and binuclear platinum(II) complexes with diphosphines have been reported as catalysts in the hydroformylation reaction. Dppp and related diphosphines are used as ligands in platinum/Sn systems for the hydroformylation of different substrates.99-107... 

An important feature of biphasic hydroformylation is the separability due to density differences. Because of the differences in density of the polar compound water (1.0 gem"1) and the hydrophobic oxo products (average 0.8), no problems occur. Additionally, the hydroformylation products are not sensitive to water. Another important question is to what extent water and the reactants are mixed. Therefore, the reactor in Figure 5.3 b), a continuously stirred tank reactor (CSTR) [22], normally contains usual installations to guarantee excellent mixing. For the lower alkenes with their significant water solubility (propene, butene) this is no problem. In these cases, the hydroformylation reaction takes place at the interfacial region [23]. 

The hydroformylation reaction is highly exothermic, which makes temperature control and the use of the reaction heat potentially productive and profitable (e.g, steam generation). The standard installation of Ruhrchemie/Rhone-Poulenc s aqueous-phase processes is heat recovery by heat exchangers done in a way that the reboiler of the distillation column for work-up of the oxo products is a falling film evaporator... 

The hydroformylation reactions were carried out in a number of different solvent systems, Table 2, at 50-60°C and 40 bar CO/H2 (1 1) using the (S,R)-1 m-C6F13(CH2)3]2-BINAPHOS ligand, Figure 6.11. After 18 hours in the PFMC/toluene system, 100% conversion was achieved with 100% selectivity to aldehydes of which 92% were... 

The ionic liquid investment could be further reduced if future research enables the application of ammonium based alkylsulfate or arylsulfonate ionic liquids. For these systems bulk prices around 15 /kg are expected. Ammonium based alkylsulfate or arylsulfonate ionic liquids usually show melting points slightly above room temperature but clearly below the operating temperature of the hydroformylation reaction. Therefore these systems may be less suitable for the liquid-liquid biphasic process in which the ionic liquid may be involved in process steps at ambient temperature (e.g. phase separation or liquid storage). In contrast, for the SILP catalyst a room temperature ionic liquid is not necessarily required as long as the film becomes a liquid under the reaction conditions. Assuming an ammonium based SILP catalyst, the capital investment for the ionic liquid for the industrial SILP catalyst would add up to 105,000 . 

The hydroformylation reaction was discovered by Otto Roelen in 1938 (2,3) while investigating the influence of olefins on the Fischer-Tropsch reaction (/). Particularly in commercial publications, it has been termed the oxo reaction the more proper term, hydroformylation, was proposed by Adkins (4). 

The hydroformylation reaction has been the subject of excellent reviews (for example I, 6-8) therefore, the object of this particular treatise is not to provide comprehensive coverage of all aspects. The basic chemistry is presented, along with recent developments of interest as reported in the literature, although not in chronological order. Stereochemical studies (6) are included only when pertinent to another point under consideration. Carbonylations or hydrocarboxylation reactions which produce ketones, esters, acids, esters, or amides are not included (/). Also not included is the so-called Reppe" synthesis, which is represented by Eq. (1). 

After it was recognized that the hydroformylation reaction is catalyzed by a soluble species, HCo(CO)4 was proposed as the catalyst (//). Sub-... 

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