Hydroformylation product linearity

Several synthetic approaches toward 3,3-diarylpropyl- or 4,4-diarylbutylamines (Figure 12.2) comprise hydroformylation as the key step. One possible route involves the reaction of the (D.co-diarylalkylhalide, obtained in a few steps from the hydroformylation product linear aldehyde, with an appropriate amine [19]. On the contrary, the aldehydes can be converted directly into the amines via a transition metal catalyzed reductive amination reaction [20]. Although these methods have heen employed efficiently for the synthesis of compounds 10,11 [19], and 12 [20], the most elegant solution is the direct hydroaminomethylation where the initial hydroformylation of the alkene is followed by the condensation of the intermediate aldehyde with the amine present in the reaction mixture and a final hydrogenation to give a saturated secondary or tertiary amine. 

The 0x0 process is employed to produce higher alcohols from linear and branched higher olefins. Using a catalyst that is highly selective for hydroformylation of linear olefins at the terminal carbon atom. Shell converts olefins from the Shell higher olefin process (SHOP) to alcohols. This results in a product that is up to 75—85% linear when a linear feedstock is employed. Other 0x0 processes, such as those employed by ICI, Exxon, and BASE (all in Europe), produce oxo-alcohols from a-olefin feedstocks such alcohols have a linearity of about 60%. Enichem, on the other hand, produces... 

The asymmetric hydroformylation of aryl ethenes such as substituted styrene or naphthylethene is of industrial interest because the hydroformylation products of these substrates are precursors to important nonsteroidal antiinflammatory drugs such as (S )-ibuprofen and (S )-naproxen. Strong efforts have been made to improve the branched/linear ratio, as well as the enantioselectivity of the product. 

The additional presence of 1-nonanal serves as model for the formation of the linear hydroformylation product of 1-octene and its influence on catalyst solubility. The aldehyde lowers the complex solubility further (Fig. 19) as compared to the mixture with olefln only. 

A key issue in the hydroformylation reaction is the ratio of normal to iso product (linear and branched product) produced. Figure 6.1 explains this colloquial expression. The linear product is the desired product, since the value of butanal is higher also because this is the product which can be converted to... 

The linearity of the aldehyde product increases with the concentration of triphenyl phosphine. This is being exploited in the Union Carbide process for the hydroformylation of propene in which linearities >90% are obtained. The rate, however, drops to lower values and the most likely explanation for the higher linearities in this system would seem to be the steric congestion around the rhodium atom at high phosphine concentrations, which kinetically and thermodynamically favours the formation of linear alkyl rhodium complexes relative to branched alkyl rhodium complexes. Product linearity decreases with the number of triphenyl phosphines present in the series of precursor complexes ... 

Scheme 4.2 Rationalisation for the formation of linear over branched hydroformylation products...

Multiatomic [6] as well as cationic [7] rhodium catalysts also display a high preference for linear hydroformylation products. However, a catalyst system which generally yields branched hydroformylation products has not yet been found. Vinylarenes, such as styrene (16), form preferentially the (.vo-aldehyde 20 and not the n-aldehydes. The possibility to form a relatively stable Rh- -allyl complex 18 is most likely the decisive factor for this result [8]. Subsequent oxidation of 20 leads to 2-arylpropionic acids 21, of which some derivatives like 22-24 are of great importance as non-steroidal inflammatory drugs (NSID) (Scheme 3) [9]. For their synthesis by the hydroformylation of styrenes, not only a regioselective but also an enantioselective reaction process is... 

Figure 12 Isomerization of cobalt alkyls leading to linear and branched hydroformylation products.

The regioselectivity in the hydroformylation of monohydroxyben-zenes was the same for the host catalyst and a triphenylphosphine complex of rhodium (with a molar product ratio linear branched = 2 1) (35). No isomerization was observed. Rates of the conversion of monohydrox-ybenzenes when host-guest catalysis is employed are lower than when a triphenylphosphine complex of rhodium is used. In contrast, dihydroxy substrates, which are more strongly boimd to the host, react at higher rates, with an initial increase by a factor of 4 relative to catalysis by the bare rhodium complex. Dihydroxybenzenes also gave the selectivities to linear products (linear branched molar product ratio > 20 1, see below). At 30% conversion, product inhibition took place. 

It is this exothermic step that probably is the source of the preference for linear hydroformylation products over branched ones. The structure of the comparable 18-electron branched intermediate 7 is about 2 kcal/mol less stable than 7, according to Jiao s calculations. This difference leads ultimately to the anti-Markovnikov, linear aldehyde over the branched-chain isomer. Although -elimination is possible now, the high partial pressure of CO present in the reaction vessel tends to stabilize 7 and prevent loss of CO that would generate the vacant site necessary for elimination to occur. 

S25.1 In the case of cyclohexene, only one hydroformylation product is possible cyclohexanecarboxaldehyde. Unlike the unsaturated compounds mentioned in the text and in Example 25.1, cyclohexene, due to its cyclic structure, cannot produce linear and branched isomers. 

The importance of substrate steric effects on hydroformylation rate and product linearity is shown by the results in Table 12. There is essentially no difference in product linearity for the normal alkenes longer than propylene, or for 4-methyl-1-pentene the linearity with propylene is a little lower due to the slightly reduced crowding in its R Rh intermediate. (The lower rate with propylene is no doubt due to the reduced solubility... 

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