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Reduction using Catalytic hydrogenation

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Catalytic hydrogenation

1) Catalytic hydrogenation is one of the most convenient available for reduction of organic compounds. Reduction is carried out easily by stirring or shaking the substrate with the catalyst in a suitable solvent or without a solvent if the substance being reduced is a liquid in an atmosphere of hydrogen gas. Once the reaction is completed, the catalyst is filtered off and the product is recovered from the filtrate, often in a high state of purity.

2) In many cases reaction proceeds smoothly at room temperature and at atmospheric or slightly elevated pressure. However, in some cases, high temperatures (100–200°C) and pressures (100–300 atmospheres) are necessary, requiring special high-pressure equipment.

3) Catalytic hydrogenation may result simply in the addition of hydrogen to one or more unsaturated groups in the molecule, or it may be accompanied by fission of a bond between atoms. The latter process is known as hydrogenolysis.

4) Under appropriate conditions, catalytic hydrogenation can be used to reduce unsaturated groups such as alkenes, alkynes, carbonyl groups, nitriles, nitro groups and aromatic rings.

5) Certain groups, notably allylic and benzylic hydroxyl and amino groups and carbon–halogen single bonds readily undergo hydrogenolysis, resulting in cleavage of the bond between the carbon and the heteroatom.

H2,Pd/C

MeOH

100 %

6) An alternative procedure that is sometimes advantageous is ‘catalytic

transfer hydrogenation’, in which hydrogen is transferred to the substrate

from another organic compound. The reduction is carried out simply by

warming the substrate and hydrogen donor such as isopropanol or a salt of

formic acid) together in the presence of a catalyst, usually palladium.

7) Catalytic-transfer hydrogenation can show different selectivity towards

functional groups from that shown in catalytic reduction with molecular

hydrogen.

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Catalyst for hydrogenation 1) The most commonly used catalyst in the laboratory for catalytic

hydrogenations are the platinum palladium and nickel and sometimes rhodium, Iridium and ruthenium and are used either as the finely divided metal or more commonly, supported on a suitable carrier such as activated carbon, alumina or barium sulphate.

2) Platinum is often used in the form of its oxide PtO2 (Adams’ catalyst), which is reduced to metallic platinum by hydrogen in the reaction medium.

H2,PtO2

AcOH

72 %

3) Most platinum metal catalysts (with the exception of Adams’ catalyst) are

stable and can be kept for many years without appreciable loss of activity, but can be deactivated by many substances, particularly by compounds of divalent sulphur.

4) Catalytic activity is sometimes increased by addition of small amounts of platinum or palladium salts or mineral acid. The increase in the activity may simply be the result of neutralization of alkaline impurities in the catalyst.

Reduction Selectivity

1) Many hydrogenations proceed satisfactorily under a wide range of conditions, but where a selective reduction is wanted, conditions may be more critical.

2) The choice of catalyst for a hydrogenation depends on the activity and selectivity required. In general, the more active the catalyst the less discriminating it is in its action and for greatest selectivity reactions should be run with the least active catalyst and under the mildest possible conditions consistent with a reasonable rate of reaction.

3) The rate of a given hydrogenation may be increased by raising the temperature, by increasing the pressure or by an increase in the amount of catalyst used, but all these factors may result in a decrease in selectivity.

4) Hydrogenation of ethyl benzoate with copper chromite catalyst under the appropriate conditions leads to benzyl alcohol by reduction of the ester group, while Raney nickel gives ethyl cyclohexane carboxylate by selective attack on the benzene ring.

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H2,Raney Nickel

50°C, 100 atm

H2,CuCr2O4

160°C, 250 atm

5) Both the rate and, sometimes, the course of a hydrogenation may be

influenced by the solvent used. The most common solvents are methanol, ethanol and acetic acid, although other solvents can be used. Many hydrogenations over platinum metal catalysts are favoured by strong acids.

6) Example, reduction of nitro styrene in acetic acid–sulfuric acid is rapid and

gives 2-phenyl-ethylamine (90% yield), but in the absence of sulfuric acid reduction is slow and the yield of amine is poor. Not all functional groups are reduced with equal ease. Below table shows the approximate order of decreasing ease of catalytic hydrogenation of a number of common groups.

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Hydrogenation of alkenes

Hydrogenation of carbon–carbon double bonds takes place easily and, in most

cases, can be done under mild conditions. Only a few highly hindered alkenes

are resistant to hydrogenation and even these can generally be reduced under

more vigorous conditions. Palladium and platinum are the most-frequently used

catalysts. Both are very active and the preference is determined by the nature

of other functional groups in the molecule and by the degree of selectivity

required.

74 %

H2,10 % Pd/C

EtOH

A few different conditions can be employed to minimize hydrogenolysis, such

as the addition of ethylenediamine (en) and THF as solvent

H2,5 % Pd/C

EtOHEthylene diamine

93 %

Rhodium and ruthenium catalysts may alternatively be used and sometimes

show useful selective properties. Rhodium allows hydrogenation of alkenes

without hydrogenolysis of an oxygen function.

H2,5 % Rh-Al2O3

EtOH

The ease of reduction of an alkene decreases with the degree of substitution of

the double bond and this sometimes allows selective reduction of one double

bond in a molecule which contains several other double bonds.

For example, limonene can be converted into p-menthene by reduction of

disubstituted terminal alkene in almost quantitative yield by hydrogenation

over platinum oxide. In contrast, the isomeric diene having two disubstituted

double bond gives only the completely reduced product without selectivity.

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H2, PtO2

EtOH

Limonene

H2, PtO2

EtOH

99 %

p-menthene No selectivity

Selective reduction of carbon–carbon double bonds in compounds containing other unsaturated groups can usually be accomplished, except in the presence of triple bonds, aromatic nitro groups and acyl halides.

Stereochemistry and mechanism

Hydrogenation of an unsaturated compound takes place by adsorption of the compound on to the surface of the catalyst, followed by transfer of hydrogen from the catalyst to the side of the molecule that is adsorbed on it. Adsorption onto the catalyst is largely controlled by steric factors, and it is found in general that hydrogenation takes place by cis addition of hydrogen atoms to the less-hindered side of the unsaturated centre. For example, hydrogenation of the E-alkene gives the racemic dihydro compound by cis addition of hydrogen, while the Z-alkene gives the meso isomer.

H2, Pd

EtOH

98 %

MesoZ-alkene

H2, Pd

EtOH

98 %

RacemicE-alkene

Hydrogenation of the ketone gave products formed by cis addition of hydrogen to the more accessible side of the double bonds.

H2,PtO2

AcOH

83 % 17 %

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The hydrogenation of substituted cyclic alkenes is irregular in many cases in that substantial amounts of trans-addition products are formed, particular with palladium catalysts. For example, the bicyclic alkene on hydrogenation over palladium in acetic acid gives mainly trans-decalin and the alkene 1,2-dimethylcyclohexene gives variable mixtures of cis- and trans-1,2- dimethyl cyclohexane depending on the conditions.

H2,Pd/C

AcOH

21 % 79 %

H2,Pd/C

AcOH16 % 46 %

H2,PtO2

AcOH82 % 18 %

The reason for the formation of the trans products is thought to be because of

migration of the double bond in a partially hydrogenated product on the

catalyst surface. Although catalytic hydrogenation of alkenes may be

accompanied by migration of the double bond, no evidence of migration

normally remains on completion of the reduction.

Hydrogenation of alkynes

Catalytic hydrogenation of alkynes takes place in a stepwise manner and both the alkene and the alkane can be isolated. Complete reduction of alkynes to the saturated compound is easily accomplished over platinum, palladium or Raney nickel. A complication which sometimes arises, particularly with platinum catalysts, is the hydrogenolysis of hydroxyl groups to the alkyne.

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H2, Pt

The partial hydrogenation of alkynes to Z-alkenes is achieved with palladium-calcium deactivated by addition of lead acetate (Lindlar’s catalyst) or quinoline. It is aided by the fact that the more electrophilic alkynes are absorbed on the electron-rich catalyst surface more strongly than the corresponding alkenes. An important feature of these reductions is their high stereoselectivity.

Lindlar catalyst

Hydrogenation of aromatic compounds

Reduction of aromatic rings by catalytic hydrogenation is more difficult than that of most other functional groups, and selective reduction is not easy. Hydrogenation of phenols, followed by oxidation of the resulting cyclohexanols is a convenient method for the preparation of substituted cyclohexanones.

i) 55 atm,H2,EtOH

5 %Rh-Al2O3,AcOH

ii) CrO3, H2SO4

Acetone, H2O

Reduction of benzene derivatives carrying oxygen or nitrogen functions in benzylic positions is complicated by the easy hydrogenolysis of such groups, particularly over palladium catalysts. Preferential reduction of the benzene ring in these compounds is best achieved with ruthenium or rhodium catalysts, which can be used under mild conditions.

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H2,Rh-Al2O3

H2,Pd/C

Hydrogenation of aldehydes and ketones Hydrogenation of the carbonyl group of aldehydes and ketones is easier than that of aromatic rings, but not as easy as that of most carbon–carbon double bonds. For aliphatic aldehydes and ketones, reduction to the alcohol can be carried out under mild conditions over platinum or Raney nickel. Ruthenium is also an excellent catalyst for reduction of aliphatic aldehydes and can be used to advantage with aqueous solutions. Palladium is not very active for hydrogenation of aliphatic carbonyl compounds, but is effective for the reduction of aromatic aldehydes and ketones Prolonged reaction time particularly at elevated temperatures or in the presence of acid leads to hydrogenolysis and can therefore be used as a method for the reduction of aromatic ketones to methylene compounds.

Hydrogenation of nitriles, oximes and nitro compounds

Functional groups like nitriles, oximes, azides are readily reduced by catalytic hydrogenation into primary amines. Reduction of nitro compounds takes place easily and is generally faster than reduction of alkenes or carbonyl groups. Raney nickel or any of the platinum metals can be used as the catalyst, and the choice is governed by the nature of other functional groups in the molecule.

H2,5 % Pd/C

EtOH,H2SO4

Nitriles are reduced with hydrogen and platinum or palladium at room temperature, or with Raney nickel under pressure.

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However, large amounts of secondary amines may also be formed as an impurity due to the side reaction of the amine with the intermediate imine.

H2

Catalyst

H2

Catalyst

H2

Catalyst

-NH3

With the platinum-metal catalysts, the above reaction can be suppressed by conducting the hydrogenation in acid solution or in acetic anhydride, which removes the amine from the equilibrium as its salt or as its acetate. For reactions with Raney nickel, where acid cannot be used, secondary amine formation is prevented by addition of ammonia. Reduction of oximes to primary amines takes place under conditions similar to those used for nitriles, with palladium or platinum in acid solution, or with Raney nickel under pressure.

Homogeneous hydrogenation

1) The stereochemistry of reduction may not be easy to predict, since it depends on chemisorption and not on reactions between molecules. Some of these difficulties have been overcome by the introduction of soluble catalysts, which allow hydrogenation in homogeneous solution.

2) A number of soluble-catalyst systems have been used, but the most common are based on rhodium and ruthenium complexes, such as [(Ph3P)3RhCl] (Wilkinson’s catalyst) and [(Ph3P)3RuClH].

3) Wilkinson’s catalyst is an extremely efficient catalyst for the homogeneous hydrogenation of non-conjugated alkenes and alkynes at ordinary temperature and pressure. Functional groups such as carbonyl, cyano, nitro and chloro are not reduced under these conditions. Mono- and disubstituted double bonds are reduced much more rapidly than tri- or tetrasubstituted ones, permitting the partial hydrogenation of compounds containing different kinds of double bonds.

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H2, [(Ph3P)3RhCl]

benzene

80 %

H2, [(Ph3P)3RhCl]

benzene

4) An important practical advantage of this catalyst is that it does not bring

about hydrogenolysis, thus allowing the selective hydrogenation of carbon–carbon double bonds without hydrogenolysis of other susceptible groups in the molecule.

H2, [(Ph3P)3RhCl]

benzene

93 %

5) Wilkinson’s catalyst has a strong affinity for carbon monoxide and decarbonylates aldehydes, therefore alkene compounds containing aldehyde groups cannot normally be hydrogenated with this catalyst under the usual conditions. For example, cinnamaldehyde is converted into styrene in 65% yield, and benzoyl chloride gives chlorobenzene in 90% yield.

6) Addition of hydrogen to Wilkinson’s catalyst promotes oxidative addition of hydrogen. Dissociation of a bulky phosphine ligand and co-ordination of the alkene is followed by stepwise stereospecific cis transfer of the two hydrogen atoms from the metal to the alkene by way of an intermediate with a carbon–metal bond.

7) Diffusion of the saturated substrate away from the transfer site allows the released complex to combine with dissolved hydrogen and repeat the catalytic reduction cycle.

8) Another useful catalyst is the iridium complex [Ir(COD)py(PCy3)]PF4 (COD =

1,5-cyclooctadiene; py = pyridine; Cy = cyclohexyl). It reduces tri- and

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tetrasubstituted double bonds as well as mono- and disubstituted ones, although not so rapidly, and it appears to be unaffected by sulphur in the molecule. A valuable feature of this catalyst is the high degree of stereo control that can be achieved in the hydrogenation of cyclic allylic and homoallylic alcohols. (Hydrogens add from the same side as that of hydroxyl group).

H2, [Ir(COD)py(Pcy3)]PF4

H2, [Ir(COD)py(Pcy3)]PF4

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