A4: CATALYTIC HYDROGENATION AT ATMOSPHERIC PRESSURE.

HYDROGEN: Accidental leakage of H2 gas may cause an explosion. Do not bring any ignition sources into the vicinity of the apparatus and always vent the gas burette outside the window. Ensure that a key is fitted to the cylinder regulator at all times to minimise escape of H2 gas in the event of a rupture of the regulator diaphragm. Turn the hydrogen off at the regulator whenever the apparatus is not in use. Ensure that the cylinder is properly clamped.

PLATINUM Platinum metals are very toxic and platinum compounds

METALS:themselves are known mutagens. Avoid ingestion, inhalation of the dust and skin contact. Wash hands thoroughly with soap and water if contamination occurs. Spillage of small quantities which are not recoverable should be washed to waste with copious quantities of water. AT NO STAGE SHOULD A 'USED' CATALYST BE ALLOWED TO DRY OUT. THE METAL WILL BE SATURATED WITH HYDROGEN AND CONTACT WITH AIR MAY CAUSE A FIRE OR EXPLOSION.

Detailed information: BDH Hazard Data Sheets, p. 828 (Pt) and p. 758 (Pd).

MERCURY:Mercury is a toxic metal. Some of the equipment contains liquid mercury. In the event of a spillage, inform the Technician or a Demonstrator who will supervise its removal.

Detailed information: BDH Hazard Data Sheets, p. 642.

QUINOLINE:Quinoline is toxic. Avoid ingestion, inhalation and skin contact. Wash thoroughly with water if contact occurs. O.EL. not given Detailed information: BDH Hazard Data Sheets, p. 895.

The direct addition of hydrogen to olefinic and acetylenic linkages, the reduction, with hydrogen, of some unsaturated functional groups (e.g. -NO2 -> -NH2; -CN -> -CH2NH2; -CH=NOH -> -CH2NH2) and the hydrogenolysis of others (e.g. -N=N- -> 2 -NH2; ROCH2Ph -> ROH + MePh) can be effected at ordinary temperature and pressure with the aid of either heterogeneous or homogeneous catalysts. For example, a solution of the compound in water, ethanol, methyl or ethyl acetate or acetic acid may be shaken with hydrogen gas either in the presence of platinum, palladium, rhodium or Raney nickel, as the heterogeneous catalyst. Adam's platinum catalyst, with acetic acid as solvent for the substrate, is a powerful combination with which even aromatic rings may be hydrogenated at ordinary temperature and pressure. Supported catalysts and partially poisoned catalysts (e.g. Lindlar's palladium catalyst) are more selective. They enable partial reduction (such as -C[[equivalence]]C- -> -CH=CH-), or hydrogenolysis without reduction of unsaturated groups to be accomplished.

More recently, organometallic complexes such as chloro(tristriphenylphosphine)rhodium(I) (Wilkinson's catalyst) have found wide application as homogeneous catalysts. Often these are more efficient than their heterogeneous counterparts.²

Catalysts

Prepare one of the following catalysts, as appropriate to your chosen hydrogenation reaction, following consultation with a Demonstrator:--

Adam's Catalyst³

In a fume cupboard, dissolve chloroplatinic acid (H2PtCl6.6H2O, 0.10 g) in water (ca. 0.5 ml) in a porcelain crucible (3-4 cm diameter). Add sodium nitrate (1 g) and evaporate the mixture to dryness, over a low flame, with continuous stirring. Turn the Bunsen burner full on and stir the contents of the crucible vigorously until the mass has melted completely and the initial decomposition has subsided. Keep the bottom of the crucible at a dull red heat for a further 30 min. (too strong a heat decomposes the oxide to the metal). Allow the crucible to cool and wash the contents into a 250 ml. beaker with hot water from a wash bottle. Filter off the brown platinum oxide with a small ('Hirsch') funnel (Whatman paper No. 541) and wash the oxide with hot water (about 200 ml) until the washings are free from nitrate ion. Dry the catalyst over calcium chloride in a vacuum desiccator.

Palladium Black⁴

Heat a mixture of palladium chloride (0.50 g) and water (100 ml) to 80deg.C and carefully neutralise the suspension, to wide-range indicator paper, with 20% sodium hydroxide solution (if the end point is overshot, palladium hydroxide precipitates). Add 2.6% formic acid (2.5 ml) and, after about 2 min. make the solution strongly alkaline with 20% sodium hydroxide solution (5 ml). Add more of the formic acid (5 ml) and make sure that the solution is still alkaline. Heat the mixture on a steam bath for 2 hours. Filter off the precipitate with a small ('Hirsch') funnel (Whatman filter paper No. 541), wash it free from alkali and dry it over calcium chloride in a vacuum desiccator.

5% Palladised Charcoal⁵

Heat decolourising charcoal (7.5 g) on a steam bath for 2-3 hours with conc. hydrochloric acid (5 ml) and water (150 ml). Wash the charcoal by decantation with hot water until free of acid, filter it off, and dry it in an oven at <100deg.C.

Warm palladium chloride (0.5 g) in conc. hydrochloric acid (0.75 ml) and water (5 ml) on the steam bath for ~ 20 min. Add the solution to AnalaR sodium acetate (17.5 g) in water (50 ml) contained in a hydrogenation flask. Introduce the purified charcoal (5.8 g) and hydrogenate the mixture until no more hydrogen is absorbed (~ 2 h). The hydrogenation procedure is described below. Collect the catalyst on a 7 cm Buchner filter (3 thicknesses of Whatman No. 1 filter paper), wash it with water (5 x 100 ml) and drain it on the filter with suction. Dry the catalyst over fresh silica gel in a vacuum desiccator and store it in a tight stoppered bottle.

Lindlar's Catalyst (5% Pd on CaCO3, poisoned with Pb)⁶

Stir calcium carbonate (precipitated, light; 1.1 g) in water (10 ml) in a flask which is fitted with a thermometer and mounted on a magnetic stirrer/hotplate. Whilst continuing the stirring, add palladium chloride (90 mg) to the suspension and after 5 min., raise the temperature to 80deg.C for a further 10 min. Cool the mixture and transfer it to a hydrogenation flask, using ~ 10 ml of water for rinsing. Hydrogenate the mixture until hydrogen absorption (10-20 ml) is complete (ca. 15 min); the hydrogenation procedure is described below. Collect the reduced catalyst on a small 'Hirsch' funnel (Whatman filter paper No. 1) and wash the catalyst with distilled water (20 ml). Add the damp catalyst to distilled water (10 ml) in a flask on the magnetic stirrer/hotplate. Switch on the stirrer, add a 5% (w/v) solution of AnalaR lead acetate in water (2 ml) and, after 10 min., raise the temperature to 90deg.C for 40 min. During this time, add distilled water, as necessary, to compensate for evaporation losses. Cool the mixture, collect the catalyst on Whatman No. 1 paper in a small 'Hirsch' funnel and wash the catalyst with distilled water (total, ~ 50 ml). Transfer the catalyst to a clean, tared, specimen tube and dry the catalyst in a pistol at 40deg.C to constant weight (~ 1-3 h). Crush the dry catalyst to a powder with a clean spatula or glass rod and stopper and label the tube (catalyst yield: 0.9-1 g).

Hydrogenation

Complete either 1, 2 or 3 after consultation with a Demonstrator.

1. Hydrogenation of an Olefinic Bond: Use of either Pd Black or Pd on Charcoal.

Discuss your choice of catalyst with a Demonstrator. The experiment will be carried out on the macro-scale atmospheric pressure hydrogenator.

HO2CCH=CHCO2H + H2 -> HO2CCH2CH2CO2H

Preliminaries.-- Examine the taps and ensure that they are well fitting, properly greased and that the bores are free of obstruction. Apply, as necessary, a thin smear of grease around the upper part of the cone k (do not attach the hydrogenation flask yet). See that there is sufficient water (containing a small amount of copper sulfate to suppress algal growth) in the reservoirs attached to the burettes f and i. Connect tap b to the water pump, or other source of vacuum, via a trap and a 3-way stopcock. Connect the hydrogen cylinder regulator outlet to the the inlet a with pressure tubing. There is a mercury safety bubbler at d which prevents overpressurisation of the apparatus.

Procedure.-- Dissolve maleic acid (3 g) in ethanol (40 ml) in a hydrogenation flask (250 ml) and add the catalyst palladium black (30 mg) or palladised charcoal (100 mg) and a magnetic stirrer bar. Calculate the expected uptake of hydrogen in order to determine whether the gas burettes will require refilling during the experiment.

Open tap j. Raise the reservoirs attached to the burettes and thus fill the burettes with water up to the taps e and h. Close taps e and h. Lower the reservoirs.

Attach the charged hydrogenation flask l at k and fit the safety spring across the joint and place a magnetic stirrer under the flask.

With the tap a open, and taps c, e and h closed, evacuate the apparatus with the water pump vacuum via tap b.

Close tap b and fill the apparatus with hydrogen, via tap c, to atmospheric pressure (indicated on manometer g). Close tap c.

Re-evacuate the apparatus through tap b and then close b.

Refill with hydrogen through tap c, then carefully open taps e and h so that the burettes will fill with hydrogen. Close tap c.

With taps b and c closed and e, h and j open, level the water in the reservoirs against that in the burettes (to bring the hydrogen to atmospheric pressure). Note the water levels in the burettes (total volume, R0). Close the tap h.

Switch on the stirrer and from time to time, adjust the level of the reservoir attached to the burette f so as to maintain the hydrogen at a pressure slightly greater than atmospheric. At intervals, level the water in the reservoir against that in the burette(s), stop the stirrer and note the reading(s) (total volume, Rt). Restart the stirrer.

Plot the hydrogen uptake Rt (in ml) against time (in min).

When the hydrogen is almost used up, level off the reservoir, take the burette reading, and close tap e. Open tap h and use the hydrogen in i.

When absorption of hydrogen ceases, adjust the level of the reservoir of i and read the burette. Close tap h and switch off the stirrer.

With taps e and h closed, evacuate the apparatus through tap b. Admit air through b and remove the flask l.

Filter off the catalyst through a thin layer of acid-washed Kieselguhr filter aid in a Hirsch funnel, wash it with a little ethanol and place the catalyst, together with the filter paper and filter aid in the catalyst residue bottle.

Evaporate the filtrate under reduced pressure, recrystallise the residue (water) and determine the yield, m.p., i.r. and n.m.r. of the pure product. Interpret these data.

From the hydrogenation curve, determine the activity of the catalyst, (expressed as the half-hydrogenation time, tH1/2, see Figure 2) and the total hydrogen uptake by the substrate and the catalyst as demonstrated in Figure 2. Submit the excess catalyst, labelled with its identity and activity (tH1/2), along with the product, for assessment.

2. Semi-hydrogenation of an Acetylenic Bond: Use of Lindlar's Catalyst.

Lindlar's catalyst, additionally poisoned with quinoline, is used to semi-hydrogenate 3-phenylpropyn-3-ol using the macro-scale atmospheric hydrogenator.

PhCH(OH)C[[equivalence]]CH + H2 -> PhCH(OH)CH=CH2

Preliminaries.-- See above

Procedure.-- Dissolve 3-phenylpropyn-3-ol (5 g) in toluene (50 ml) in a hydrogenation flask (250 ml) and add Lindlar's catalyst (150 mg) and quinoline (400 mg).

Calculate the theoretical uptake of hydrogen at room temperature and pressure in order to determine whether the gas burettes will require refilling during the experiment.

Hydrogenate the substrate as described in Experiment 1 above until ~1.05 equivalents of hydrogen have been absorbed.

Plot the uptake of hydrogen (in ml) against time (in min) and note the abrupt change of rate when semihydrogenation is complete.

Filter off the catalyst with a Hirsch funnel (Whatman No. 1 paper), wash it with toluene (~5 ml) and place the used catalyst in the correct residue bottle. Evaporate the filtrate under reduced pressure (Rotavapor) and distil the residue with a Büchi kugelrohr apparatus.

Record the b.p., yield and i.r. and n.m.r. spectra and interpret the latter.

3. Hydrogenation of Cholesterol: Use of Adam's Catalyst.

The sterol is hydrogenated with Adam's catalyst in the micro-hydrogenation apparatus.

Preliminaries:--Purify a sample (~ 500 mg) of cholesterol by recrystallisation from ethanol and drying it in a vacuum pistol overnight. Clean, as necessary, and lightly grease the joints J1 and J2 with Apiezon M grease.

Procedure:--Ensure that the tap T1 is closed and that the indicator liquid levels in the manometer M are near the middle of the scale. Place THF (10 ml), acetic acid (1 drop) and purified cholesterol (<=80 mg, weighed accurately) in flask F1 and a similar volume of THF/AcOH only in flask F2. Calculate the expected uptake of hydrogen from the weight of cholesterol taken. (Correction to STP has to be made in estimating the volume, the accuracy of the burette is 4%). This volume should be less than 5.5 ml, the capacity of the burette. Connect them to the apparatus using the springs provided.

Weigh out ~5 mg of Adam's catalyst in one of the small tubes provided. Ensure that the flask F1 is so rotated with respect to the joint J1 that the side arm A is closed off from the flask and then carefully place the tube containing the sample in the side arm. Replace the side arm stopper.

With the taps T2, T3, T4, T5, T6 and T7 open and T9 closed, and with the mercury kept at the bottom of the reservoir B by means of the closed screw clip on the connecting rubber tubing, slowly evacuate the apparatus through tap T8, which is connected to a vacuum (water) pump. Agitate the liquid in flasks F1 and F2 by tapping them occasionally whilst they are being evacuated, in order to remove dissolved or occluded air, but avoid evaporating too much solvent. Close the tap T8.

Carefully turn on the stream of hydrogen until it bubbles through the mercury in the safety bubbler (not illustrated); a fast but steady stream of gas is required. After a minute or two, slowly open the tap T9 so that the hydrogen enters the system until the whole apparatus, including the burette, is filled with gas to atmospheric pressure (indicated by the manometer).This operation must be performed carefully in order to avoid suck-back of the mercury in the bubbler. Close the tap T9 to the hydrogen supply.

The sequence of evacuation and hydrogen admittance must be repeated at least 2 more times in order to effect complete deoxygenation of the gas in the apparatus. However, in the subsequent purging operations, prolonged evacuation of the system is not necessary.

Release the screw clip om the burette rubber tubing and adjust the level of the mercury reservoir R until the mercury just comes to the calibrated part of the burette B. Close taps T3 and T5 and turn off the hydrogen supply at the cylinder head. Commence shaking the flask and after 2-3 min. check that the burette reading remains constant (no leaks/uncatalysed uptake by substrate).

Stop the shaker, adjust, as necessary, the reservoir R height until the level of the liquid in the 2 arms of manometer M is equal and note the burette reading (R0). Rotate the flask F1 on its joint until the tube containing the catalyst drops into the flask. Carry out this operation as smoothly and quickly as possible and avoid holding the flask or glass spiral more than absolutely necessary to minimise heating by the hand. A slight drop in the level of the right hand limb of the manometer M can be ignored.

Recommence the shaking of the flask. As reduction proceeds, the level in the left hand limb of manometer M rises. At regular time intervals, (initially 2 min, later 5 or 10 min) readjust the mercury level in R to rebalance M and take a burette reading. Record the time and the burette reading (Rt) and plot a hydrogenation curve (see 1 above). Continue until hydrogen uptake (by catalyst + substrate) ceases.

Quickly lower the mercury reservoir R and reclose the screw clip. Open T3 and T5 and evacuate the apparatus via tap T8 before releasing air into the system. Remove the flasks F1 and F2.

N.B. During reduction and when the system is not being handled, ensure that the cupboard doors are closed. This protects the apparatus from draughts and therefore from misleading fluctuations in the internal pressure.

Filter the solution from the flask F1 through a plug of neutral alumina and wash the product through with diethyl ether. Evaporate the combined filtrates on a Rotavapor at <=50deg.C and recrystallise the product from aqueous ethanol. Dry in a drying pistol overnight at ~50deg.C.

Record the m.p., specific rotation (as [[[alpha]]]D = 100[[alpha]]/cl; c in g/100ml; l= pathlength in decimeters), and nmr and i.r. spectra of the product and compare with those of the starting substrate.

From the hydrogen uptake/time plot deduce the volume absorbed by the catalyst and the half-hydrogenation time (see Figure 2).

References

1. There are many excellent reviews on catalytic hydrogenation. For a recent example, see Jerry March, 'Advanced Organic Chemistry', 4th edn, John Wiley and Sons, 1992, p 771 and references cited there.

2. For a comprehensive and well referenced review, see P.A. Chaloner, 'Handbook of Coordination Catalysis in Organic Chemistry', Butterworths, London, 1986, pp 9 - 217.

3. R. Adams, V. Voorhees and R.L. Shriner, Org. Synth., 1941, 1, 463.

4. H. Wieland, Chem. Ber., 1912, 45, 484.

5. B.S. Furniss, A.J. Hannaford, P.W.G. Smith and A.R. Tatchell in 'Vogel's Textbook of Practical Organic Chemistry', 5th edn, Longman, London, 1989, p. 452.

6. A. Lindlar, Helv. Chim. Acta, 1952, 35, 446; see also R.L. Augustine in 'Catalytic Hydrogenation: Techniques and Applications in Organic Synthesis'