Aldehydes, via hydroformylation

The synthesis of aldehydes via hydroformylation of alkenes is an important industrial process used to produce in the region of 6 million tonnes a year of aldehydes. These compounds are used as intermediates in the manufacture of plasticizers, soaps, detergents and pharmaceutical products [7], While the majority of aldehydes prepared from alkene hydroformylation are done so in organic solvents, some research in 1975 showed that rhodium complexes with sulfonated phosphine ligands immobilized in water were able to hydroformylate propene with virtually complete retention of rhodium in the aqueous phase [8], Since catalyst loss is a major problem in the production of bulk chemicals of this nature, the process was scaled up, culminating in the Ruhrchemie-Rhone-Poulenc process for hydroformylation of propene, initially on a 120000 tonne per year scale [9], The development of this biphasic process represents one of the major transitions since the discovery of the hydroformylation reaction. The key transitions in this field include [10] ... 

A special concern is the purity of the gas feed. Poisons may have a remarkable influence on the long-time stability of the hydroformylation catalysts and, consequently, the degree of conversion and selectivity is influenced. In smaller companies, the production of aldehydes via hydroformylation may become a serious problem due to the significantly higher price of CO in comparison to This... 

A recent example where Co2(CO)8 serves as a precatalyst is in the preparation of linear and branched aldehydes via propylene hydroformylation in supercritical C02 (93-186 bar 66-108 °C). Cyclohexane carbaldehyde is produced from cyclohexene using Co2(CO)8 and an acid RCOOH, or else is successful with another established Co catalyst, Co(OOCR)2, assumed to form in situ in the former case. Oligomerization of aldehydes such as n-butanal is achieved with Co2(CO)6L2 as catalyst (L = CO, PR3).1364... 

Additional C,C-Bond Formation of Aldehydes Obtained via Hydroformylation... 

Metal-catalysed hydrocarboxylation of olefins (Equation 3) is the poor relative of the more famous hydroformylation. It generally requires forcing reaction conditions and suffers from mediocre activities and selectivities (n/i ratio). Moreover, the same products can be made via hydroformylation and oxidation of the aldehyde product.431 Consequently, there are few industrial applications of hydrocarboxylation e.g. Ni(CO)4-catalysed production of propionic acid by hydrocarboxylation of ethylene.432,433... 

Similarly, preparation of a,a-difluorohomoallylic alcohols has been achieved by zinc-mediated addition of CH2=CHCF2Br to carbonyl compounds.29 The reaction is successful with dialkyl ketones as well as aliphatic and aromatic aldehydes (Equation 4.12). The allylation products are particularly useful since the alkene may be oxidized to an aldehyde,32 epoxide,33 or converted to a 8-lactone34 via hydroformylation. 

Another route to carboxylic acids from aldehyde products (once again, generally produced via hydroformylation catalysis) was discovered by Wakamatsu and coworkers. They reported the carbonylation of aldehydes and primary organic amides to produce A-acylamino acids (equation 16). The reaction is efficiently catalyzed by HCo(CO)4 at 100 °C and 140 bar of 3 2 H2/CO (hydrogen is needed to help stabilize HCo(CO)4). Yields of over 90% of the appropriate... 

Optically active 3-ser-butylfuran, -thiophene, and -pyrrole are obtained via hydroformylation of an a,/ -unsaturated aldehyde acetal in the presence of RhC1(CO)(PPh3)2. Hydroformylation... 

Asymmetric hydroformylation of acetylenes such as 2-butyne, 1-octyne or phenylacetylene can yield chiral saturated aldehydes via prior or subsequent hydrogenation22. Results of this variant, mainly investigated for mechanistic reasons22, are compiled in Table 8. 

Other alternative reaction pathways to AA or MAA via hydroformylation of 7-octenoic acid or the respective ester and consecutive oxidation of the formed aldehydic group may fail due to the poor accessibility of the C8 compound needed as starting material. This is unfortunate because recent development in the selective hydroformylation to linear aldehydes using sophisticated phosphite ligands [134,135] may enable such reaction sequence. 

Since its discovery by Roelen in 1938, hydroformylation or the oxo process has become one of the most important methods for the synthesis of aldehydes. Aldehydes produced via hydroformylation are critical feedstock and synthetic precursors in both basic research and industrial applications. The significance of this reaction in chemical industry has drawn much attention in both basic and applied research, leading to the development of more efficient and versatile reaction processes. 

Chain elongation and chain branching of aldehydes via C-C bond formation reactions initiated with a hydroformylation step are of huge synthetic value for the construction of bulk and fine chemicals. Especially in the last years, the total synthesis of natural products and pharmaceutically important compounds has benefited from these approaches. Different methodologies will be discussed in detail here. 

In a patent by Mitsubishi, it is available via hydroformylation of limonene and subsequent acid-catalyzed intramolecular cyclization of the aldehyde [1]. The alcohol can also be produced in one step by Pt/Sn-catalyzed hydroformylation, suggested by a protocol of Gusevskaya and coworkers (Scheme 5.123) [2, 3]. Platinum and tin are essential for the cychzation in the last step. Alternatively, the tandem reaction has been investigated in detail with rhodium complexes based on PPhg, P[0(o-fBu)Ph]3, or PPTS (pyridinium / -toluenesulfonate)... 

Scheme 6.1 Classes of organic compounds relevant to flavoring chemistry accessible via hydroformylation and alternative venues to aldehydes.

Hydroxy aldehydes can be prepared via hydroformylation of corresponding unsaturated alcohols. In particular, tertiary hydroxy olefins have seen broad application as substrates. For example, IFF claimed the reaction of 2-methyldodec-ll-en-2-ol with syngas at 700 psi ( 48 bar) and 120-140 C (Scheme 6.40) [132]. Under these conditions, preferentially the terminal aldehyde was formed. 

After the first interpretations by O. Roelen, W. Reppe et al. H. Kroper, A. R. Martin and G. Natta et it is the merit of M. Orchin et aL [30-33], I. Wender et aL [34], R. F. Heck and D. S. Breslow [35, 36, 759], L. Marko et aL [37], P. Pino et aL [89] and F. Piacenti et aL [919] to have carried out the essential experiments which allow a deeper insight into the complicated reaction sequence in which olefins are converted into aldehydes via a number of organometallic intermediates in the hydroformylation reaction. 

For instance, in the case of hydroformylation of ot-olefins in the presence of simple carbonyl catalysts, both branched and linear aldehydes are formed, whereas with some substituted carbonyl catalysts essentially linear aldehydes are obtained (9/, 92). Branched aJdehydes are believed to be formed via secondary insertion of the olefin into a linear aldehydes via primary insertion ... 

The preparation of aldehydes by dehydration is useful because the aldehydes are easily accessible via hydroformylation of olefins. 

In contrast to triphenylphosphine-modified rhodium catalysis, a high aldehyde product isomer ratio via cobalt-catalyzed hydroformylation requires high CO partial pressures, eg, 9 MPa (1305 psi) and 110°C. Under such conditions alkyl isomerization is almost completely suppressed, and the 4.4 1 isomer ratio reflects the precursor mixture which contains principally the kinetically favored -butyryl to isobutyryl cobalt tetracarbonyl. At lower CO partial pressures, eg, 0.25 MPa (36.25 psi) and 110°C, the rate of isomerization of the -butyryl cobalt intermediate is competitive with butyryl reductive elimination to aldehyde. The product n/iso ratio of 1.6 1 obtained under these conditions reflects the equihbrium isomer ratio of the precursor butyryl cobalt tetracarbonyls (11). 

Conceptually at least, these compounds can be obtained via initial enantioselective hydroformylation of the appropriate vinyl aromatic to branched chiral aldehyde and subsequent oxidation. 

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