1.4 Antecedentes del Estudio
1.4.1 Investigaciones Nacionales
The Rosenmund Reduction is the Pd catalyzed hydrogenation of an acyl chloride to the corresponding aldehyde
The classical catalyst for this reaction is Pd/BaSO4, but in most cases Pd/carbon powders can be substituted with advantage.
The operating conditions must be mild (temperatures of 5–50°C and pressures of 1–3 bar), otherwise over-hydrogenation to the primary alcohol will occur. In order to preserve the selectivity to the aldehyde, nitrogen or sulfur-containing compounds are often added to modify the catalyst.
Typical additives include thiourea or thioquinanthrene.
These well-defined compounds have largely eclipsed the use of the variable “quinoline/sulfur” reagent. The reaction must be carried out in the absence of water, otherwise hydrolysis of the feedstock to the corresponding carboxylic acid will occur. Dry powder Pd/C catalyst must therefore be used (as opposed to water-wet pastes) to maintain the anhydrous conditions.
As with other hydrodechlorinations, a basic chloride acceptor is often utilized. Examples include 1,2-butylene oxide, aliphatic amines, sodium carbonate, magnesium oxide, 2,6–dimethylpyridine etc. (again at least 2 equivalents per equivalent of halide).
Sometimes, due to the ease of acid chloride
hydrodechlorinations, it is possible to remove the liberated HCl with a nitrogen sparge or by operating at sub-atmospheric pressures so that the addition of specific chloride acceptors is not necessary.
COCl Pd
R R
CHO + HCl
4.1.12 Transfer Hydrogenations
1When hydrogen gas and/or hydrogenation plant is not readily available, then the hydrogenation may be achieved using a chemical hydrogen donor. In effect the catalyst dehydrogenates the donor molecule to generate hydrogen to carry out the hydrogenation. The donor molecule and catalyst should be selected with care so that the rate of hydrogen release is comparable to the rate of
hydrogenation of the feedstock. Typical donor molecules include cyclohexene, formates, phosphinates, propan–2–ol and indolene.
Pd and Pt are the heterogeneous catalysts of choice.
Transfer hydrogenations are often performed under reflux but it is possible to operate at lower temperatures when required. Different selectivities are sometimes achieved by transfer hydrogenation rather than H2gas.
Transfer hydrogenation can be accomplished using homogeneous catalysts. For example, tetralone has been hydrogenated with Rh-120 with an amine ligand in the presence of a hydrogen donor, propan-2-ol.
Examples of PGM precursors of homogeneous catalysts used for transfer hydrogenations in the literature are Iridium (Ir-93 [IrCl(COD)]2), Rhodium (Rh-93 [RhCl(COD)]2), (Rh-120 [RhCl2(CP*)]2) and Ruthenium (Ru-120 [RuCl2(pcymene)]2).
Please refer to section 4.13 for information on asymmetric hydrogenation.
Reaction Temperature Pressure Solvent Catalyst
(°C) (bar)
Hydrodehalogenation 5–100 1–10 Alcohols, ethyl Pd/C A402002-5, A405028-5
acetate or vapor Pd/c A503023-5, A503038-5, phase Pd/cA102023-5, A570129-5,
Pd/cA570201-5
Rosenmund Reduction 5–50 1–3 Toluene, xylene, Pd/C A302023-5, A302038-5,
(acyl chloride → aldehyde) acetone or Pd/cA701023-5
THF
Pd/BaSO4A308053-5, A201053-5, A201053-10
O OH
(CH
3)
2CHOH (CH
3)
2CO
+ +
1 R.A.W. Johnstone et al. Chem. Rev. (1985) 85 129–170
4.2 DEHYDROGENATION
Dehydrogenation is an endothermic process, and hence high operating temperatures (up to 250°C) and high catalyst loadings (3–10% with respect to feedstock) are often necessary. At such high temperatures, most PGM complexes decompose, so homogeneously catalyzed dehydrogenations in the liquid phase are usually not feasible.
Traditionally, nitrogen has been used to purge the liberated hydrogen from the reaction, but increasingly the use of hydrogen acceptors is finding favor.
Reactant Product Donor Solvent Temperature Catalyst
(˚C)
Nitro Amine Formic acid, Methanol, 50–80 Pd/C A503023-5, A503038-5,
phosphinic acid, ethanol or Pd/cA102023-5, A102038-5,
sodium formate, THF Pd/cA570129-5
sodium phosphinate, tetraethyl ammonium formate
Halonitro Haloamine Formic acid, Methanol, 60–80 Pt/C B101032-3, B103032-3,
phosphinic acid, ethanol or Pt/cB170147-3, B102032-1,
sodium phosphite water Pt/cB101038-1, B105047-1,
Pt/cB170147-1
Imine Amine Formic acid & None or 0–60 Ir–93
Et3N, propan–2–ol acetonitrile Rh–93, Rh–120
Alkene Alkane Cyclohexene, None Reflux Pd/C A503023-5, A503038-5,
indolene, Pd/cA102023-5, A102038-5,
triethyl ammonium Pd/cA570129-5
formate
Carbonyl Alcohol Cyclohexene, Ethanol or Reflux Pd/C A503023-5, A503038-5,
phosphinic acid, THF Pd/cA102023-5, A102038-5,
sodium phosphinate Pd/cA570129-5
Ketone Alcohol Formic acid & Et3N, None or 0–60 Ir–93
propan–2–ol acetonitrile Rh–93, Rh–120
Debenzylation Formic acid, Ethanol, 50–80 Pd/C A503023-5, A503032-5,
sodium formate methanol or Pd/cA470129-5, A402028-10,
THF Pd/cA501023-10, A501032-10,
Pd/cA470129-10
Hydrogen Acceptor Product
Nitrotoluene Toluidine (+ water) Nitrobenzene Aniline (+ water) Maleic acid Succinic acid Dimethylmaleate Dimethylsuccinate
α–methylstyrene Cumene
trans–stilbene Dibenzyl
Tetralin Decalin
Indene Indane
Hydrogen acceptors should be used in 0.5–2.0 molar quantities with respect to the liberated hydrogen. Where the products include water, care should be taken, because the steam which is liberated can cause bumping of the reactor contents in liquid phase reactions.
For the same reason it is desirable to use dry powder catalysts for liquid phase reactions and dry pelleted catalysts for gas phase reactions.
It is highly desirable to use a hydrogen acceptor if at all possible, thus permitting lower temperature operation than would be possible without a hydrogen acceptor.
The operating temperature should be as low as possible, consistent with acceptable product yields in order to
minimize:-•metal crystallite sintering – see section 2.1.7
•product decomposition and/or by–product formation Typical high boiling point solvents used include biphenyl and polyglycol ethers. It is possible sometimes to use the hydrogen acceptor as the solvent.
The ease of dehydrogenation is dependent on the substrate and operating conditions. However, the following general comments can be
made:-•easier if at least one double bond is close to the dehydrogenation site
•easier if the end product is a fully aromatic compound
•6 and 7-membered or larger ring systems are easier to dehydrogenate than 5-membered rings1.
The catalysts of choice for liquid phase dehydrogenations are
Pd > Pt > Rh
Catalyst performance can be enhanced by the addition of inorganic bases such as Na2CO3, MgO (up to about 5% by weight with respect to the catalyst). Addition of base neutralizes any acidic sites on the catalyst, which if left untreated, could cause by–product formation.
Very small additions (2–10 ppm with respect to the feedstock) of organic sulfur compounds such as diphenyl sulfide can promote some dehydrogenation reactions.
Such additions have to be very carefully optimized.
A particular dehydrogenation of industrial importance is the formation of iminostilbene from iminodibenzyl
The product is an intermediate in the preparation of Carbamazepine – a treatment for epilepsy.
For the dehydrogenation of cyclohexanols and cyclohexanones, the favored hydrogen acceptors are olefins e.g. α−methylstyrene.
A common problem with operating catalysts at high temperatures in the vapor phase for extended periods is that coking may occur (see section 2.1.7). This has the effect of masking individual metal crystallites. One way of reducing this effect on the Pd or Pt pelleted catalysts is to introduce a small quantity of hydrogen into the feedstock.
N
H N
H Pd/C
nitrotoluene
OH
R
OH
R Pd/C
α-methyl styrene
1 M. Bartok Stereochemistry of Heterogeneous Metal Catalysis 1 Wiley Interscience (1985) 35–37
4.3 HYDROFORMYLATION
Hydroformylation is the largest and oldest homogeneously catalyzed industrial process, in which the simultaneous addition of one mole of CO and H2is made across a carbon–carbon double bond to produce an aldehyde.
Industrially, the most important alkene feedstock is propene.
The original cobalt-catalyzed high pressure process was discovered in Germany over 60 years ago. The replacement of Co by Rh in the mid 1960’s provided a major
breakthrough in the history of homogeneous catalysts. The main advantages
are:-•higher straight chain: branched chain product ratios (the straight chain product usually being the more commercially desirable)
•lower operating pressures, hence lower plant capital costs
•lower operating temperatures, hence less formation of oligomeric by-products
•lower feedstock consumption per tonne of product, hence increased yield
These more than compensate for the higher cost of Rh.
A consortium of three companies (Davy McKee/Johnson
The butyraldehyde is either reduced directly to n-butanol, or aldolized and dehydrated to 2-ethylhexenal and then reduced to 2-ethylhexanol – a well known plasticizer alcohol.
For terminal alkene hydroformylation, the Rh homogeneous catalyst is used together with a large excess (50-100 x molar with respect to the catalyst) of a tertiary phosphine such as triphenylphosphine. Many different Rh catalysts (or precursors) can be used. Typical Rh compounds include Rh-40 Rh(PPh3)2(CO)Cl, Rh-42 RhH(CO)(PPh3)3, Rh-43 Rh(acac)(CO)(PPh3) and Rh-50 Rh(acac)(CO)2.
Provided the Rh compound selected can enter into the catalytic cycle, the precise form of the precursor is of little importance. The factors affecting the choice of a particular precursor usually involves such “practical” properties
as:-•absence of halogen (important for long term stability in steel reactors – but not in glass equipment)
•ease of storage/handling in air
•minimal health hazards
•solubility in the reaction medium
•cost of conversion of the Rh metal to the particular complex
The propene hydroformylation process operated by Hoechst (Ruhrchemie) is interesting in that the reaction medium is a two phase aqueous/organic system in which the Rh catalyst is solubilized in the aqueous phase using a sodium sulfonate substituted triphenylphosphine as the ligand. Since the Rh is confined to the aqueous phase,
Reaction Temperature Solvent H2Acceptor Catalyst
(°C)
Cyclohexanones/anols 180–275 biphenyl Olefinic Pd/C A503023-5, A503038-5,
to Phenols (e.g. α−methylstyrene, Pd/cA102023-5, A102038-5,
tetralin) Pd/cA570129-5, A501023-10, Pd/cA501038-10, A101023-10, Pd/cA101038-10
Alkane to Alkene 180–250 Glycol, Nitrotoluene, Pd/C A503023-5, A503038-5,
PEG nitrobenzene Pd/cA102023-5, A102038-5,
Pd/cA570129-5, A501023-10, Pd/cA501038-10, A101023-10, Pd/cA101038-10
Alcohol to Carbonyl >200 None None Pt/C B103032-5, B103018-5,
(vapor phase) Pt/cB501032-5
Ni/Mo A-7000 Ni/MoA-7200
CO H2 CHO
CH3
+ CHO
+ +
straight chain branched chain
There have been many studies of the mechanism of hydroformylation. Suitable choice of operating conditions and ligand can drive the reaction to form the straight chain aldehyde, or the branched chain product. Thus the tailor-making of ligands to favor the formation of a particular product has become a practical proposition.
For example, Union Carbide has developed a phosphite ligand to give very high straight chain to branched chain ratios.
Other industrial processes incorporating a Rh catalyzed hydroformylation step
include:-•production of vitamin A
The BASF process involves the hydroformylation of a terminal alkene, whereas the Hoffmann–La Roche process hydroformylates an internal alkene
•production of 1,4-butanediol
The Kuraray process (operated by Lyondell) involves the hydroformylation of allyl alcohol
The vast majority of (and certainly all of the industrially important) processes use Rh as the catalytic metal of choice. The literature indicates that Pt has some activity as a hydroformylation catalyst, often used together with a SnCl2promoter.