Inorganic chemistry,hydroformylation, also known asoxo synthesis oroxo process, is an industrial process for the production ofaldehydes (R−CH=O) fromalkenes (R₂C=CR₂).^[1][2] This chemical reaction entails the net addition of aformyl group (−CHO) and ahydrogen atom to a carbon-carbondouble bond. This process has undergone continuous growth since its invention: production capacity reached 6.6×10⁶ tons in 1995. It is important because aldehydes are easily converted into many secondary products. For example, the resultant aldehydes are hydrogenated toalcohols that are converted todetergents. Hydroformylation is also used inspeciality chemicals, relevant to theorganic synthesis offragrances andpharmaceuticals. The development of hydroformylation is one of the premier achievements of 20th-centuryindustrial chemistry.

The process entails treatment of an alkene typically with high pressures (between 10 and 100atmospheres) ofcarbon monoxide and hydrogen at temperatures between 40 and 200 °C.^[3] In one variation,formaldehyde is used in place of synthesis gas.^[4]Transition metalcatalysts are required. Invariably, the catalyst dissolves in the reaction medium, i.e. hydroformylation is an example ofhomogeneous catalysis.

The process was discovered by the German chemistOtto Roelen in 1938 in the course of investigations of theFischer–Tropsch process. Aldehydes and diethylketone were obtained when ethylene was added to an F-T reactor. Through these studies, Roelen discovered the utility of cobalt catalysts.HCo(CO)₄, which had been isolated only a few years prior to Roelen's work, was shown to be an excellent catalyst.^[5][6] The term oxo synthesis was coined by the Ruhrchemie patent department, who expected the process to be applicable to the preparation of both aldehydes and ketones. Subsequent work demonstrated that the ligandtributylphosphine (PBu₃) improved the selectivity of the cobalt-catalysed process. The mechanism of Co-catalyzed hydroformylation was elucidated byRichard F. Heck andDavid Breslow in the 1960s.^[7]

In 1968, highly active rhodium-based catalysts were reported.^[8] Since the 1970s, most hydroformylation relies on catalysts based onrhodium.^[9] Water-soluble catalysts have been developed. They facilitate the separation of the products from the catalyst.^[10]

A key consideration of hydroformylation is the "normal" vs. "iso"selectivity. For example, the hydroformylation ofpropylene can afford twoisomeric products,butyraldehyde orisobutyraldehyde:

These isomers reflect the regiochemistry of the insertion of the alkene into the M–H bond. Since both products are not equally desirable (normal is more stable than iso), much research was dedicated to the quest for catalyst that favored the normal isomer.

Markovnikov's rule addition of the cobalt hydride to primary alkenes is disfavored by steric hindrance between the cobalt centre and the secondary alkyl ligand. Bulky ligands exacerbate this steric hindrance. Hence, the mixed carbonyl/phosphine complexes offer a greater selectivity for anti-Markovnikov addition, thus favoring straight chain products (n-) aldehydes. Modern catalysts rely increasingly on chelating ligands, especially diphosphites.^[12]

Additionally, electron-rich the hydride complex are less proton-like. Thus, as a result, theelectronic effects that normally favour the Markovnikov addition to an alkene are less applicable. Thus, electron-rich hydrides are more selective.

To suppress competing isomerization of the alkene, the rate of migratory insertion of thecarbonyl into thecarbon-metal bond of the alkyl must be relatively fast. The rate of insertion of the carbonyl carbon into the C-M bond is likely to be greater than the rate of beta-hydride elimination.^[13]

Hydroformylation ofprochiral alkenes creates newstereocenters. Usingchiral phosphineligands, the hydroformylation can be tailored to favor oneenantiomer.^[14][15] Thus, for example,dexibuprofen, the (+)−(S)-enantiomer ofibuprofen, can be produced by enantioselective hydroformylation followed by oxidation.

The industrial processes vary depending on the chain length of the olefin to be hydroformylated, the catalyst metal and ligands, and the recovery of the catalyst. The original Ruhrchemie process produced propanal from ethene andsyngas usingcobalt tetracarbonyl hydride. Today, industrial processes based on cobalt catalysts are mainly used for the production of medium- to long-chain olefins, whereas the rhodium-based catalysts are usually used for the hydroformylation ofpropene. The rhodium catalysts are significantly more expensive than cobalt catalysts. In the hydroformylation of higher molecular weight olefins the separation of the catalyst from the produced aldehydes is difficult.

The BASF-oxo process starts mostly with higher olefins and relies on cobalt carbonyl-based catalyst.^[16] By conducting the reaction at low temperatures, one observes increased selectivity favoring the linear product. The process is carried out at a pressure of about 30 MPa and in a temperature range of 150 to 170 °C. The cobalt is recovered from the liquid product by oxidation to water-soluble Co^{2 +}, followed by the addition of aqueousformic oracetic acids. This process gives an aqueous phase of cobalt, which can then be recycled. Losses are compensated by the addition of cobalt salts.^[17]

The Exxon process, also Kuhlmann- or PCUK – oxo process, is used for the hydroformylation of C6–C12 olefins. The process relies on cobalt catalysts. In order to recover the catalyst, an aqueous sodium hydroxide solution or sodium carbonate is added to the organic phase. By extraction with olefin and neutralization by addition ofsulfuric acid solution under carbon monoxide pressure themetal carbonyl hydride can recovered. This is stripped out with syngas, absorbed by the olefin, and returned to the reactor. Similar to the BASF process, the Exxon process is carried out at a pressure of about 30 MPa and at a temperature of about 160 to 180 °C.^[17]

The Shell process uses cobalt complexes modified withphosphine ligands for the hydroformylation of C7–C14 olefins. The resulting aldehydes are directly hydrogenated to thefatty alcohols, which are separated bydistillation, which allows the catalyst to be recycled. The process has good selectivity to linear products, which find use as feedstock fordetergents. The process is carried out at a pressure of about 4 to 8 MPa and at a temperature range of about 150–190 °C.^[17]

The Union Carbide (UCC) process, also known as low-pressure oxo process (LPO), relies on a rhodium catalyst dissolved in high-boiling thick oil, a higher molecular weight condensation product of the primary aldehydes, for the hydroformylation of propene. The reaction mixture is separated in a falling film evaporator from volatile components. The liquid phase is distilled and butyraldehyde is removed as head product while the catalyst containing bottom product is recycled to the process. The process is carried out at about 1.8 MPa and 95–100 °C.^[17]

The Ruhrchemie/Rhone–Poulenc process (RCRPP) relies on a rhodium catalyst with water-solubleTPPTS as ligand (Kuntz Cornils catalyst) for the hydroformylation of propene.^[20] The tri-sulfonation of triphenylphosphane ligand provides hydrophilic properties to the organometallic complex. The catalyst complex carries nine sulfonate-groups and is highly soluble in water (about 1 kg L⁻¹), but not in the emerging product phase.^[21] The water-soluble TPPTS is used in about 50-fold excess, whereby the leaching of the catalyst is effectively suppressed. Reactants are propene and syngas consisting of hydrogen and carbon monoxide in a ratio of 1.1:1. A mixture of butyraldehyde and isobutyraldehyde in the ratio 96:4 is generated with few by-products such as alcohols, esters and higher boiling fractions.^[21] The Ruhrchemie/Rhone-Poulenc-process is the first commercially available two-phase system in which the catalyst is present in the aqueous phase. In the progress of the reaction an organic product phase is formed which is separated continuously by means of phase separation, wherein the aqueous catalyst phase remains in the reactor.^[21]

The process is carried out in a stirred tank reactor where the olefin and the syngas are entrained from the bottom of the reactor through the catalyst phase under intensive stirring. The resulting crude aldehyde phase is separated at the top from the aqueous phase. The aqueous catalyst-containing solution is re-heated via a heat exchanger and pumped back into the reactor.^[21] The excess olefin and syngas is separated from the aldehyde phase in a stripper and fed back to the reactor. The generated heat is used for the generation of process steam, which is used for subsequent distillation of the organic phase to separate into butyraldehyde and isobutyraldehyde.^[21] Potential catalyst poisons coming from the synthesis gas migrate into the organic phase and removed from the reaction with the aldehyde. Thus, poisons do not accumulate, and the elaborate fine purification of the syngas can be omitted.^[21]

A plant was built inOberhausen in 1984, which was debottlenecked in 1988 and again in 1998 up to a production capacity of 500,000 t/a butanal. The conversion rate of propene is 98% and the selectivity to n-butanal is high. During the life time of a catalyst batch in the process less than 1 ppb rhodium is lost.^[22]

Recipes have been developed for the hydroformylation on a laboratory scale, e.g. ofcyclohexene.^[3][15]

Cobalt carbonyl and rhodium complexes catalyse the hydroformylation offormaldehyde andethylene oxide to givehydroxyacetaldehyde and3-hydroxypropanal, which can then be hydrogenated toethylene glycol andpropane-1,3-diol, respectively. The reactions work best when the solvent is basic (such aspyridine).^[23][24]

In the case ofdicobalt octacarbonyl or Co₂(CO)₈ as a catalyst, pentan-3-one can arise from ethene and CO, in the absence of hydrogen. A proposed intermediate is the ethylene-propionyl species [CH₃C(O)Co(CO)₃(ethene)] which undergoes amigratory insertion to form [CH₃COCH₂CH₂Co(CO)₃]. The required hydrogen arises from thewater shift reaction. For details, see^[25]

If the water shift reaction is not operative, the reaction affords a polymer containing alternating carbon monoxide and ethylene units. Such aliphaticpolyketones are more conventionally prepared usingpalladium catalysts.^[26]

Functionalized olefins such asallyl alcohol can be hydroformylated. The target product1,4-butanediol and its isomer is obtained with isomerization free catalysts such as rhodium-triphenylphosphine complexes. The use of the cobalt complex leads by isomerization of the double bond to n-propanal.^[27] The hydroformylation of alkenyl ethers and alkenyl esters occurs usually in the α-position to the ether or ester function.

The hydroformylation ofacrylic acid andmethacrylic acid in the rhodium-catalyzed process leads to theMarkovnikov product in the first step.^[28] By variation of the reaction conditions the reaction can be directed to different products. A high reaction temperature and low carbon monoxide pressure favors the isomerization of the Markovnikov product to the thermodynamically more stable β-isomer, which leads to the n-aldehyde. Low temperatures and high carbon monoxide pressure and an excess of phosphine, which blocks free coordination sites, can lead to faster hydroformylation in the α-position to the ester group and suppress the isomerization.^[28]

Side reactions of the alkenes are the isomerization and hydrogenation of the double bond. While the alkanes resulting from hydrogenation of the double bond do not participate further in the reaction, the isomerization of the double bond with subsequent formation of the n-alkyl complexes is a desired reaction. The hydrogenation is usually of minor importance; However, cobalt-phosphine-modified catalysts can have an increased hydrogenation activity, where up to 15% of the alkene is hydrogenated.

Usingtandem catalysis, systems have been developed for the one-pot conversion of akenes to alcohols. The first step is hydroformylation.^[29]

Conditions for hydroformylation catalysis can induce degradation of supporting organophosphorus ligands.Triphenylphosphine is subject tohydrogenolysis, releasing benzene and diphenylphosphine. The insertion of carbon monoxide in an intermediate metal-phenyl bond can lead to the formation ofbenzaldehyde or by subsequent hydrogenation tobenzyl alcohol.^[30] One of the ligands phenyl-groups can be replaced by propene, and the resulting diphenylpropylphosphine ligand can inhibit the hydroformylation reaction due to its increased basicity.^[30]

Although the original hydroformylation catalysts were based on cobalt, most modern processes rely on rhodium, which is expensive. There has therefore been interest in finding alternative metal catalysts. Examples of alternative metals include iron and ruthenium.^[31][32]

• Koch reaction - related reaction of alkenes and CO to form carboxylic acids

• "Applied Homogeneous Catalysis with Organometallic Compounds: A Comprehensive Handbook in Two Volumes (Paperback) by Boy Cornils (Editor), W. A. Herrmann (Editor).ISBN 3-527-29594-1
• "Rhodium Catalyzed Hydroformylation" P. W. N. M. van Leeuwen, C. Claver Eds.; Springer; (2002).ISBN 1-4020-0421-4
• "Homogeneous Catalysis: Understanding the Art" by Piet W. N. M. van Leeuwen Springer; 2005.ISBN 1-4020-3176-9
• Imyanitov N.S./ Hydroformylation of Olefins with Rhodium Complexes // Rhodium Express. 1995. No 10–11 (May). pp. 3–62 (Eng)ISSN 0869-7876

• Addition reactions
• Organometallic chemistry
• Homogeneous catalysis
• Formylation reactions
• Carbon monoxide

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