Hydroformylation side reaction

Propylene-Based Routes. The strong acid-catalyzed carbonylation of propylene [115-07-1] to isobutyric acid (Koch reaction) followed by oxidative dehydration to methacrylic acid has been extensively studied since the 1960s. The principal side reaction in the Koch reaction is the formation of oligomers of propylene. Increasing yields of methacrylic acid in the oxydehydration step is the current focus of research. Isobutyric acid may also be obtained via the oxidation of isobutyraldehyde, which is available from the hydroformylation of propylene. The -butyraldehyde isomer that is formed in the hydroformylation must be separated. 

Hydroformylation of a range of 1,1-di- and 1,1,2-trisubstituted unsatur-ated esters yields quaternary aldehydes (Table 1, entries 1-8). Hence, the regiochemistry-directing influence of the electron-withdrawing ester function overcompensates Keuleman s rifle. Furthermore, hydroformylation of 1,2-disubstituted unsaturated esters occurred with high a-selectivity and chemoselectivity (Table 1, entries 9 and 10). As a side reaction hydrogenation of the alkene has been observed [41]. 

A wide variety of new approaches to the problem of product separation in homogeneous catalysis has been discussed in the preceding chapters. Few of the new approaches has so far been commercialised, with the exceptions of a the use of aqueous biphasic systems for propene hydroformylation (Chapter 5) and the use of a phosphonium based ionic liquid for the Lewis acid catalysed isomerisation of butadiene monoxide to dihydrofuran (see Equation 9.1). This process has been operated by Eastman for the last 8 years without any loss or replenishment of ionic liquid [1], It has the advantage that the product is sufficiently volatile to be distilled from the reactor at the reaction temperature so the process can be run continuously with built in product catalyst separation. Production of lower volatility products by such a process would be more problematic. A side reaction leads to the conversion of butadiene oxide to high molecular weight oligomers. The ionic liquid has been designed to facilitate their separation from the catalyst (see Section 9.7)... 

Interception of the reaction sequence at the alkylcobalt carbonyl stage before carbonyl insertion, and hydrogenation of this intermediate, produces an alkane. This undesired side reaction is only minor (1-3%) in cobalt-catalyzed hydroformylation of a nonfunctional olefin, but may become predominant with phenyl- or acyl-substituted olefins. Ethylbenzene has been obtained in >50% yield from styrene (37), and even more alkane was obtained from a-methylstyrene (35). 

Non-corrin cobalt has a number of interesting applications in the chemical industry, for example in the hydroformylation (OXO) reaction between CO, H2 and olefins. A number of non-corrin Co-containing enzymes have been described, including methionine aminopep-tidase, prolidase, nitrile hydratase and glucose isomerase. We describe the best characterized of these, namely the E. coli methionine aminopeptidase, a ubiquitous enzyme, which cleaves N-terminal methionine from newly translated polypeptide chains. The active site of the enzyme (Figure 15.13) contains two Co(II) ions that are coordinated by the side-chain atoms of five amino acid residues. The distance between the two Co2+ is similar to that between the two Zn2+ atoms in leucine aminopeptidase, and indeed the catalytic mechanism of methionine aminopeptidase shares many features with other metalloproteases, in particular leucine aminopeptidases. 

A fundamental topic in hydroformylation research is the control of regio-selectivity and the suppression of side-reactions like the hydrogenation reac-... 

As mentioned earlier, in the Ruhrchemie-Rhone Poulenc process for propene hydroformylation the pH of the aqueous phase is kept between 5 and 6. This seems to be an optimum in order to avoid acid- and base-catalyzed side reactions of aldehydes and degradation of TPPTS. Nevertheless, it has been observed in this [93] and in many other cases [38,94-96,104,128,131] that the [RhH(CO)(P)3] (P = water-soluble phosphine) catalysts work more actively at higher pH. This is unusual for a reaction in which (seemingly) no charged species are involved. For example, in 1-octene hydroformylation with [ RhCl(COD) 2] + TPPTS catalyst in a biphasic medium the rates increased by two- to five-fold when the pH was changed from 7 to 10 [93,96]. In the same detailed kinetic studies [93,96] it was also established that the rate of 1-octene hydroformylation was a significantly different function of reaction parameters such as catalyst concentration, CO and hydrogen pressure at pH 7 than at pH 10. 

Hydroformylation of phenylacetylene 97 in the presence of -hexylamine 98 catalyzed by (1,5-cyclooctadienyl)-rhodium tetraphenylboronate, [Rh(l,5-COD)] [(7] -C6HsBPh3)], gave the corresponding 2-pyrrolidone 101 (Scheme 16). However, the reaction suffered from competing side-reactions such as hydrogenation of allylamine intermediate 100. ... 

A relatively weak rate enhancement was observed in the biphasic hydroformylation of 1-octene using Rh/tppts catalysts in the presence of cosolvents such as ethanol to enhance the solubility of the olefin in the aqueous phase and with addition of buffers (Na2C03/NaHC03) to eliminate side reactions such as the formation of acetals.31,365,366 Similarly, addition of ethanol improved the yields in the hydroformylation of 1-octene catalysed by Rh2(p-S-tBu)2(CO)2(tppts)2 species in an aqueous/organic two phase system.367 However, the high selectivity to linear aldehyde observed for neat olefin in the biphasic system (97%) decreased (to 83%) in the presence of the cosolvent.367... 

The hydroformylation of trflns-3-octene at room temperature using the (non-encapsulated) rhodium catalyst based on tris(weta-pyridyl)phosphine afforded 2-ethylheptana] and 2-propylhexanal in exactly a 1 1 ratio. The encapsulated catalyst provided an unprecedented selectivity for 2-propylhexanal of 75% (Scheme 8.3). Again the selectivity is largely retained at 40 °C whereas at 80 °C the isomerization side reaction prohibits the selective formation of aldehydes. Similar regioselectivities were obtained in the hydroformylation of frflns-2-hexene, trans-2-nonene and trans-3-nonene at 25 °C. 

In 1961 Heck and Breslow presented a multistep reaction pathway to interpret basic observations in the cobalt-catalyzed hydroformylation.28 Later modifications and refinements aimed at including alternative routes and interpreting side reactions.6 Although not all the fine details of hydroformylation are equally well understood, the Heck-Breslow mechanism is still the generally accepted basic mechanism of hydroformylation.6,17,19,29 Whereas differences in mechanisms using different metal catalysts do exist,30 all basic steps are essentially the same in the phosphine-modified cobalt- and rhodium-catalyzed transformations as well. 

A number of side-reactions may be observed during hydroformylation. Doublebond migration51 resulting in the formation of more than two aldehydes may be significant ... 

Another side reaction of hydroformylation is formate ester formation (11). The 4% yield of formates did not change in the temperature range examined or with lower CO partial pressure. 

The other common elimination is the /3-elimination (equation 7). This is a vital step in many palladium-catalyzed reactions, such as alkene arylation, and occurs as a side reaction leading to isomerization in other alkene reactions such as hydrogenation and hydroformylation. 

The discovery and development of highly efficient Rh-catalysts with chiral diphosphites and phosphine-phosphites have dramatically improved the enantioselectivity of asymmetric hydro-formylation to >90% ee in the first half of the 1990s. It appears that the success of the chiral Rh-catalyzed process has replaced the chiral Pt-catalyzed process used extensively in 1980s, which often suffer from side reactions, such as hydrogenation and isomerization, as well as low selectivity to branched aldehydes. It can be said that the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation and... 

Hydroformylation of acrylonitrile (75) and of fluoroolefins (133) also suffer from hydrogenation as a serious side reaction. 

The isomerization of epoxides is discussed in Section II, D,l. The isomerizations of olefins and of alkyl- and acylcobalt carbonyls have been considered as side reactions to hydroformylation but studies dealing principally with these reactions will now receive attention. 

An interesting side reaction is the isomerization of the C=C-double bond in the molecule, which changes the regioselectivity of hydroformylation. Depending on the products, isomerization in this reaction is either suppressed or enhanced to use the isomerization. In the case of a terminal olefin and a desired linear product, isomerization is hindered for better selectivity for the n-aldehvde. In the case of internal double bonds and desired linear products, isomerization is used to bring the unsaturated site to the end of the molecule to conduct the reaction on the terminal end [10, 11]. 

Recently a new approach towards MMA was proposed. Starting from acrylamide, a Rh-catalyzed hydroformylation yielded, with high selectivity, the desired branched aldehyde. Given the many possible side reaction this is an achievement in its own right. Addition of Raney Ni allowed a sequential reduction of the aldehyde [86]. The alcohol obtained in this manner can then be converted via standard reactions into MMA (Scheme 5.47). Whether this approach does not involve, once again, too many steps remains to be seen. 

In addition to the hydroformylation reactions, side reactions of the product alcohols and aldehydes occur to form heavy ends, particularly at higher reaction temperatures, and usually account for 9% of the product distribution. Industrial reactors usually start using high boiling solvents, but after a while these heavy ends become the solvents. 

Catalyst decomposition is, overall, receiving little attention in academic work on homogeneous catalysis, and only in recent years has research on decomposition and stabilization of organometallic catalysts started to expand (116), with emphasis on reactions of significant commercial interest such as hydroformylation (117), metathesis 118), crosscoupling, and polymerization 119). Ligand decomposition seems to be a key issue for industrial application, because it affects the total number of turnovers, TON. Phosphine decomposition is an unavoidable side reaction in metal-phosphine complex-catalyzed reactions and the main barrier for commercial application of homogeneous catalysts. There are a few exceptions to this statement for example, the rhodium tppts-catalyzed hydroformylation of propene, a process developed by Ruhrchemie-Rhone Poulenc (now Celanese). 

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