Hydrogenation

|date=1996|location=Washington, D.C.|pages=429|id=ISBN 0-8412-3344-6]

Because of the importance of hydrogen, many related reactions have been developed for its use. Most hydrogenations use gaseous hydrogen (H₂), but some involve the alternative sources of hydrogen, not H₂: these processes are called transfer hydrogenations. The reverse reaction, removal of hydrogen from a molecule, is called dehydrogenation. A reaction where bonds are broken while hydrogen is added is called hydrogenolysis, a reaction that may occur to carbon-carbon and carbon-heteroatom (O, N, X) bonds. Hydrogenation differs from protonation or hydride addition: in hydrogenation, the products have the same charge as the reactants.

An illustrative example of a hydrogenation reaction is the addition of hydrogen to maleic acid to succinic acid depicted on the right. ["Catalytic Hydrogenation of Maleic Acid at Moderate Pressures A Laboratory Demonstration" Kwesi Amoa 1948 Journal of Chemical Education • Vol. 84 No. 12 December 2007] Numerous important applications are found in the petrochemical, pharmaceutical and food industries. Hydrogenation of unsaturated fats produces saturated fats and, in some cases, trans fats.

Process

Hydrogenation has three components, the unsaturated substrate, the hydrogen (or hydrogen source) and, invariably, a catalyst. The reaction is carried out at different temperatures and pressures depending upon the substrate and the activity of the catalyst.

ubstrate

The addition of H₂ to an alk"e"ne affords an alk"a"ne in the protypical reaction::RCH=CH₂ + H₂ → RCH₂CH₃ (R = alkyl, aryl)Hydrogenation is sensitive to steric hindrance explaining the selectivity for reaction with the exocyclic double bond but not the internal double bond.

An important characteristic of alkene and alkyne hydrogenations, both the homogeneously and heterogeneously catalyzed versions, is that hydrogen addition occurs with "syn addition," with hydrogen entering from the least hindered side. ["Advanced Organic Chemistry" Jerry March 2nd Edition] Typical substrates are listed in the table

Catalysts

With rare exception, no reaction below 480 °C occurs between H₂ and organic compounds in the absence of metal catalysts. The catalyst binds "both" the H₂ and the unsaturated substrate and facilitates their union. Platinum group metals, particularly platinum, palladium, rhodium, and ruthenium, form highly active catalysts, which operate at lower temperatures and lower pressures of H₂. Non-precious metal catalysts, especially those based on nickel (such as Raney nickel and Urushibara nickel) have also been developed as economical alternatives, but they are often slower or require higher temperatures. The trade-off is activity (speed of reaction) vs. cost of the catalyst and cost of the apparatus required for use of high pressures. Notice that the Raney-nickel catalysed hydrogenations require high pressures: [OrgSynth | author = C. F. H. Allen and James VanAllan| title = m-Toylybenzylamine| collvol = 3| collvolpages = 827| year = 1955 | prep = CV3P0827] [OrgSynth | author = A. B. Mekler, S. Ramachandran, S. Swaminathan, and Melvin S. Newman| title = 2-Methyl-1,3-Cyclohexanedione| collvol = 5| collvolpages = 743| year = 1973 | prep = CV5P0567]

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Two broad families of catalysts are known - homogeneous catalysts and heterogeneous catalysts. Homogeneous catalysts dissolve in the solvent that contains the unsaturated substrate. Heterogeneous catalysts are solids that are suspended in the same solvent with the substrate or are treated with gaseous substrate.

Homogeneous catalysts

Illustrative homogeneous catalysts are include the rhodium-based compound known as Wilkinson's catalyst and the iridium-based Crabtree's catalyst: [OrgSynth | author = S. Robert E. Ireland and P. Bey| title = Homogeneous Catalytic Hydrogenation: Dihydrocarvone| collvol = 6| collvolpages = 459| year = 1988 | prep = CV6P0459]

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The activity and selectivity of homogeneous catalysts is adjusted by changing the ligands. For prochiral substrates, the selectivity of the catalyst can be adjusted such that one enantiomeric product is favored. Asymmetric hydrogenation is also possible via heterogeneous catalysis on a metal that is modified by a chiral ligand. [Mallet, T., et al, Chem. Rev, 2007, 107, 4863-4890]

Heterogeneous catalysts

Heterogeneous catalysts for hydrogenation are more common industrially. As in homogeneous catalysts, the activity is adjusted through changes in the environment around the metal, i.e. the coordination sphere. Different faces of a crystalline heterogeneous catalyst display distinct activities, for example. Similarly, heterogeneous catalysts are affected by their supports, i.e. the material upon with the heterogeneous catalyst is bound. In many cases, highly empirical modifications involve selective "poisons." Thus, a carefully chosen catalyst can be used to hydrogenate some functional groups without affecting others, such as the hydrogenation of alkenes without touching aromatic rings, or the selective hydrogenation of alkynes to alkenes using Lindlar's catalyst. For example, when the catalyst palladium is placed on barium sulfate and then treated with quinoline, the resulting catalyst reduces alkynes only as far as alkenes. The Lindlar catalyst has been applied to the conversion of phenylacetylene to styrene. [OrgSynth | author = H. Lindlar and R. Dubuis| title = Palladium Catalyst for Partial Reduction of Acetylenes| collvol = 5| collvolpages = 880| year = 1973 | prep = CV5P0880] :Asymmetric hydrogenation is also possible via heterogeneous catalysis on a metal that is modified by a chiral ligand. [Mallet, T., et al, Chem. Rev, 2007, 107, 4863-4890]

Hydrogen sources

The obvious source of H₂ is the gas itself, often used at greater than one atmosphere of pressure. Hydrogen gas is either used from a hydrogen cylinder or can be generated by the electrolysis of water.

Hydrogen can also be transferred from "hydrogen-donors", such as hydrazine, dihydronaphthalene, dihydroanthracene, isopropanol, and formic acid. [van Es, T.; Staskun, B. "Org. Syn.", Coll. Vol. 6, p.631 (1988). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0631 Article] )]

The hydrogenation of ketones, aldehydes, and imines, proceed via a wider range of mechanisms than typical for alkenes. In addition to following the pathway for alkene hydrogenation, these polar substrates undergo reduction by transfer hydrogenation.Transfer hydrogenation can be metal catalysed.

Thermodynamics and mechanism

Hydrogenation is a strongly exothermic reaction. In the hydrogenation of vegetable oils and fatty acids, for example, the heat released is about 25 kcal per mole (105 kJ/mol), sufficient to raise the temperature of the oil by 1.6-1.7 °C per iodine number drop. The mechanism of metal-catalyzed hydrogenation of alkenes and alkynes has been the extensively studied. [Kubas, G. J., "Metal Dihydrogen and σ-Bond Complexes", Kluwer Academic/Plenum Publishers: New York, 2001] First of all isotope labeling using deuterium confirms the regiochemistry of the addition::RCH=CH₂ + D₂ → RCHDCH₂D

In many hydrogenation processes, the metal binds to both components to give an intermediate alkene-metal(H)₂ complex. The general sequence of reactions is:
*binding of the hydrogen to give a dihydride complex ("oxidative addition")::L_nM + H₂ → L_nMH₂
*binding of alkene::L_nM(η²H₂) + CH₂=CHR → L_n-1MH₂(CH₂=CHR) + L
*transfer of one hydrogen atom from the metal to carbon (migratory insertion):L_n-1MH₂(CH₂=CHR) → L_n-1M(H)(CH₂-CH₂R)
*transfer of the second hydrogen atom from the metal to the alkyl group with simultaneous dissociation of the alkane ("reductive elimination"):L_n-1M(H)(CH₂-CH₂R) → L_n-1M + CH₃-CH₂RPreceding the oxidative addition of H₂ is the formation of a dihydrogen complex.

Inorganic substrates

The hydrogenation of nitrogen to give ammonia is conducted on a vast scale by the Haber-Bosch process, consuming an estimated 1% of the world's energy supply.:Oxygen can be partially hydrogenated to give hydrogen peroxide, although this process has not been commercialized.

In the food industry

Hydrogenation is widely applied to the processing of vegetable oils and fats. Complete hydrogenation converts unsaturated fatty acids to saturated ones. In practice the process is not usually carried to completion. Since the original oils usually contain more than one double bond per molecule (that is, they are poly-unsaturated), the result is usually described as partially hydrogenated vegetable oil; that is some, but usually not all, of the double bonds in each molecule have been reduced. This is done by restricting the amount of hydrogen (or reducing agent) allowed to react with the fat.

Hydrogenation results in the conversion of liquid vegetable oils to solid or semi-solid fats, such as those present in margarine. Changing the degree of saturation of the fat changes some important physical properties such as the melting point, which is why liquid oils become semi-solid. Semi-solid fats are preferred for baking because the way the fat mixes with flour produces a more desirable texture in the baked product. Since partially hydrogenated vegetable oils are cheaper than animal source fats, are available in a wide range of consistencies, and have other desirable characteristics (e.g., increased oxidative stability (longer shelf life)), they are the predominant fats used in most commercial baked goods. Fat blends formulated for this purpose are called shortenings.

Health implications

A side effect of incomplete hydrogenation having implications for human health is the isomerization of the remaining unsaturated carbon bonds. The cis configuration of these double bonds predominates in the unprocessed fats in most edible fat sources, but incomplete hydrogenation partially converts these molecules to trans isomers, which have been implicated in circulatory diseases including heart disease (see trans fats). The catalytic hydrogenation process favors the conversion from cis to trans bonds because the trans configuration has lower energy than the natural cis one. At equilibrium, the trans/cis isomer ratio is about 2:1. Food legislation in the US and codes of practice in EU has long required labels declaring the fat content of foods in retail trade, and more recently, have also required declaration of the trans fat content. Further, trans fats are banned in Denmark, Switzerland, and New York City. [cite news |url=http://www.independent.co.uk/life-style/health-and-wellbeing/healthy-living/deadly-fats-why-are-we-still-eating-them-843400.html |title=Deadly fats: why are we still eating them? |date=2008-06-10 |publisher=The Independent |accessdate=2008-06-16]

Hydrogenation of coal

:"Main article: Bergius process"

History

The earliest hydrogenation is that of platinum catalyzed addition of hydrogen to oxygen in the Döbereiner's lamp, a device commercialized as early as 1823. The French chemist Paul Sabatier is considered the father of the hydrogenation process. In 1897 he discovered that the introduction of a trace of nickel as a catalyst facilitated the addition of hydrogen to molecules of gaseous hydrocarbons in what is now known as the Sabatier process. For this work Sabatier shared the 1912 Nobel Prize in Chemistry. Wilhelm Normann was awarded a patent in Germany in 1902 and in Britain in 1903 for the hydrogenation of liquid oils, which was the beginning of what is now a world wide industry. The commercially important Haber-Bosch process, first described in 1905, involves hydrogenation of nitrogen. In the Fischer-Tropsch process, reported in 1922 carbon monoxide, which is easily derived from coal, was hydrogenated to liquid fuels. Also in 1922, [http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1922/44/i06/f-pdf/f_ja01427a021.pdf Voorhees and Adams] described an apparatus for performing hydrogenation under elevated pressures. The Parr shaker, the first product to allow hydrogenation using elevated pressures and temperatures, was commercialised in 1926 based on Voorhees and Adams’ research and remains in widespread use. In 1938, Otto Roelen described the oxo process which involves the addition of both hydrogen and carbon monoxide to alkenes, giving aldehydes. Since this process entails C-C coupling, it and its many variations (see carbonylation) remains highly topical into the new decade. [Perspective: Hydrogen-Mediated C-C Bond Formation: A Broad New Concept in Catalytic C-C Coupling Ming-Yu Ngai, Jong-Rock Kong, and Michael J. Krische J. Org. Chem.; 2007, 72, pp. 1063–1072. DOI|10.1021/jo061895m] The 1960's witnessed the development of homogeneous catalysts, e.g., Wilkinson's catalyst. In the 1980's, the Noyori asymmetric hydrogenation represented one of the first applications of hydrogenation in asymmetric synthesis, a growing application in the production of fine chemicals. In 2004, the H-Cube flow hydrogenation system was developed.

Metal-free hydrogenation

For all practical purposes, hydrogenation requires a metal catalyst. Hydrogenation can however proceed from some hydrogen donors without catalysts, examples being diimide and aluminium isopropoxide. Although, some metal-free catalytic systems have been investigated in academic research. One such system for reduction of ketones consists of "tert"-butanol and potassium tert-butoxide and very high temperatures. ["Homogeneous Hydrogenation in the Absence of Transition-Metal Catalysts" Cheves Walling, Laszlo Bollyky J. Am. Chem. Soc.; 1964; 86(18); 3750–3752. DOI|10.1021/ja01072a028] The reaction depicted below describes the hydrogenation of benzophenone:

:A chemical kinetics study ["Hydrogenation without a Transition-Metal Catalyst: On the Mechanism of the Base-Catalyzed Hydrogenation of Ketones" Albrecht Berkessel, Thomas J. S. Schubert, and Thomas N. Muller J. Am. Chem. Soc. 2002, 124, 8693–8698 DOI|10.1021/ja016152r] found this reaction is first order in all three reactants suggesting a cyclic 6-membered transition state.

Another system for metal-free hydrogenation is based on the phosphine-borane, compound 1, which has been called a "frustrated Lewis pair". It reversibly accepts dihydrogen at relatively low temperatures to form the phosphonium borate 2 which can reduce simple hindered imines. ["Metal-Free Catalytic Hydrogenation" Preston A. Chase, Gregory C. Welch, Titel Jurca, and Douglas W. Stephan Angew. Chem. Int. Ed. 2007, 46, 8050–8053 DOI|10.1002/anie.200702908]

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Equipment used for hydrogenation

Today’s bench chemist has three main choices of hydrogenation equipment:
*Batch hydrogenation under atmospheric conditions
*Batch hydrogenation at elevated temperature and/or pressure
*Flow hydrogenation

Batch hydrogenation under atmospheric conditions

The original and still the most commonly practised form of hydrogenation, this process is usually effected by adding solid catalyst to a round bottom flask of dissolved reactant which has been evacuated using nitrogen or argon gas and sealing the mixture with a penetrable rubber seal. Hydrogen gas is then applied by fixing a balloon filled from a cylinder to a syringe and needle using laboratory tape and inserting the needle through the rubber seal, with the resulting three phase mixture being mechanically stirred until the reaction has gone to completion.

Some scientists prefer to measure hydrogen uptake to monitor the process of their reaction. This is achieved by either using a graduated tube containing a coloured liquid, usually aqueous copper sulfate, or investing in a hydrogenation laboratory equipped with gauges for each reaction vessel.

Batch hydrogenation at elevated temperature and/or pressure

Many key hydrogenation reactions such as hydrogenolysis of protecting groups and the reduction of aromatic systems proceed extremely sluggishly (if at all) at atmospheric temperature and pressure, leading to the popularity of pressurised systems. In these cases, catalyst is added to a solution of reactant under an inert atmosphere in a pressure vessel. Hydrogen is added directly from a cylinder or built in laboratory hydrogen source and the system is mechanically rocked to provide agitation. Heat may also be used, as the pressure compensates for the associated reduction in gas solubility. This vastly increases the rate of reaction as described by the Arrhenius equation.

Flow Hydrogenation

In recent times, flow hydrogenation has become a very popular technique at the bench and increasingly the process scale. This technique involves continuously flowing a dilute stream of dissolved reactant over a fixed bed catalyst in the presence of hydrogen. Using established HPLC technology, this technique allows the application of pressures from atmospheric to 1,450 PSI. Elevated temperatures may also be used. At the bench scale, systems use a range of pre-packed catalysts which eliminates the need for weighing and filtering pyrophoric catalysts.

See also

* Dehydrogenation
* Transfer hydrogenation
* Hydrogenolysis
* Hydrodesulfurization, Hydrotreater and Oil desulfurization
* Timeline of hydrogen technologies

References

Further reading

*
*examples of hydrogenation from Organic Syntheses:Organic Syntheses, Coll. Vol. 7, p.226 (1990).http://orgsynth.org/orgsyn/pdfs/CV7P0226.pdf.Organic Syntheses, Coll. Vol. 8, p.609 (1993). http://orgsynth.org/orgsyn/pdfs/CV8P0609.pdf. Organic Syntheses, Coll. Vol. 5, p.552 (1973). http://orgsynth.org/orgsyn/pdfs/CV5P0552.pdfOrganic Syntheses, Coll. Vol. 3, p.720 (1955). http://orgsynth.org/orgsyn/pdfs/CV4P0603.pdfOrganic Syntheses, Coll. Vol. 6, p.371 (1988). http://orgsynth.org/orgsyn/pdfs/CV6P0371.pdfearly work on transfer hydrogenation: Davies, R. R.; Hodgson, H. H. "J. Chem. Soc." 1943, 281. Leggether, B. E.; Brown, R. K. "Can. J. Chem." 1960, "38", 2363. Kuhn, L. P. "J. Am. Chem. Soc." 1951, "73", 1510.

*cite book |author=Fred A. Kummerow|title=Cholesterol Won't Kill You, But Trans Fat Could|publisher=Trafford |year=2008 |isbn=142513808