Inhibitors and Poisons

Various types of substances have been known to retard hydrogenation or prevent it from going to completion. These substances are referred to as inhibitors or poisons, although there appears to be no distinct difference between them. Customarily poisons may be regarded as those substances that exert a marked inhibitory effect when present in small amounts, irrespective of the nature of catalyst and substrate, and cannot be removed easily. Inhibitors usually cause different degrees of deactivation depending on catalyst and substrate, and retard hydrogenation seriously only when present in ap-preciable concentration. They may be removed often by mere washing.

Maxted classified from a large body of experiments the poisons for metallic cata-lysts into three classes of substance: (1) the compounds of groups VA and VIA (or groups 15 and 16) elements with at least one unshielded electron pair; (2) heavy metal and metal ions possessing the outer d shells, each of which is occupied entirely by at

2.2 REACTION CONDITIONS 53

least one electron; and (3) certain compounds or ions with multiply unsaturated bonds.² Typical examples of toxic structures of groups VA and VIA elements are shown in Table 2.1 in comparison with the corresponding nontoxic counterparts.

Phosphite and hypophosphite ions show inhibitory effects in spite of their shielded structure. Table 2.2 shows the relationship of poisonous metal ions and the occupied states of their outer d-shell electrons. It is noted that Cr³⁺ and Cr²⁺ with two and one unoccupied d shells, respectively, are nontoxic, while Mn²⁺ with the d shells filled by each one electron is toxic. Typical examples of catalyst poisons belonging to class 3 (listed earlier in this paragraph) are carbon monoxide and cyanide ion.

Besides the poisons of the three classes mentioned above, halide ions or hydrogen halides have often been observed to inhibit hydrogenation, although the degree of in-hibition by the halides greatly depends on the catalyst employed, the substrate to be hydrogenated, and particularly on the nature of the halides. Among the halides, io-dides have been known to be more poisonous than the other halides. The hydrogena-tion of p-nitrotoluene over 5% Pd–C in 2-propanol–water (4:1) at room temperature and 0.4 MPa H₂ was completely inhibited by 5 mol% of sodium iodide based on p-nitrotoluene, similarly as by sodium sulfite, cyanide, sulfide, and bisulfite, while no inhibition was shown by sodium fluoride, chloride, and bromide as well as by sodium nitrate, acetate, carbonate, phosphate, and hydroxide.³ Sodium iodide was definitely more poisonous than sodium chloride and sodium bromide in the hydrogenation of cinnamic acid over Pd–C in methanol.⁴ The hydrogenation of 1-octene and dipropyl ketone over Raney Ni in butanol was depressed by alkali halides in the order KI ≈ NaI

> KBr > KCl.⁵ The inhibitory effect of iodides on the hydrogenation of the carbonyl group in mesityl oxide in ethanol over Raney Ni or Ni–kieselguhr was in the order CdI₂ > BaI₂ > KI.⁶ The poisonous effect of iodides has been applied for depressing overhydrogenation to alcohols in the hydrogenation of benzalacetone, mesityl oxide, and isophorone over Raney Ni.⁷

Ruthenium and rhodium are more susceptible to inhibition by hydrogen halides than are platinum and palladium. Under mild conditions ruthenium is inhibited even by acetic acid, which is generally a good solvent for hydrogenations over rhodium, palladium, and platinum. Hydrogen chloride may become an inhibitor for rhodium-catalyzed hydrogenations. Freifelder has shown that hydrochloric acid is a strong

in-TABLE 2.1 Toxic and Nontoxic Structures of Group VA and VIA Elements

Group Element Toxic Compounds Nontoxic Compounds

VA N NH₃, RNH₂, Py, quinoline NH₄⁺, RNH₃⁺, PyH⁺, quinolinium⁺ P PH₃, R₃P, Ph₃P, HPO₃²⁻, H₂PO^– R₃PO, Ph₃PO, PO₄³⁻

As AsH3 AsO43−

VIA O O₂, (OH^–)^a, (RO^–)^a ROH

S H₂S, RSH, R₂S, RSSR, R–SO–R, SO₃²⁻

R–SO₂–R, RSO₃⁻, SO₄²⁻

Se H₂Se, R₂Se, SeO₃²⁻ SeO₄²⁻

aWeakly toxic or nontoxic depending on the nature of catalyst and substrate.

hibitor for the hydrogenation of toluene and benzoic acid in methanol over 5% Rh–C or Rh–Al₂O₃, although in rather large quantities (0.1 mol for 0.1 mol of the substrate).⁸ Dry hydrogen chloride may become an inhibitor even for platinum and palladium, as observed by Freifelder in the hydrogenation of cyclohexene in absolute ethanol.⁹ It is probable that the same degrees of inhibition by hydrogen chloride as observed in the examples given above would be effectuated in much lesser amounts in nonhydroxylic solvents. The amounts of hydrochloric acid required for the stereoselective hydro-genation of unhindered cyclohexanones to the axial alcohols over rhodium black were found to be much smaller in tetrahydrofuran than in isopropyl alcohol (see Table 5.8).¹⁰ The hydrogenation over rhodium was inhibited seriously by the addition of hy-drobromic acid. The stereoselectivity of the hydrogenation of 3-oxo-4-ene steroids to 3-oxo-5β steroids over palladium catalyst is increased by addition of hydrochloric acid or, better, by hydrobromic acid.¹¹ Hydrobromic acid in tetrehydrofuran functions much more effectively than in an alcohol, and it is as effective as or even more effec-tive than the hydrobromic acid in acetic acid.¹² Probably, the amounts of hydrobromic acid required for obtaining an optimal selectivity would be smaller in tetrahydrofuran than in acetic acid. The hydrogenation is slower in the presence of hydrobromic acid than in the presence of hydrochloric acid, and is completely inhibited by the addition of hydroiodic acid. The hydrogenation of 2- or 4-stilbazole methiodides (1) to the cor-responding phenethylpyperidines (eq. 2.1) proceeded smoothly over platinum oxide TABLE 2.2 Relationship between the Toxicity of Metal Ions and Outer d-Shell Electrons^a

Periodic

Number Metal Ion Outer d-Shell Electrons s-Shell Electrons Toxicity

4 K⁺, Ca²⁺ C C C C C C Nontoxic

5 Rb⁺, Sr²⁺, Zr⁴⁺ C C C C C C Nontoxic

6 Cs⁺, Ba²⁺, La³⁺ C C C C C C Nontoxic

6 Ce³⁺ C C C C C C Nontoxic

7 Th⁴⁺ C C C C C C Nontoxic

4 Cr³⁺ D D D C C C Nontoxic

4 Cr²⁺ D D D D C C Nontoxic

4 Mn²⁺ D D D D D C Toxic

4 Fe²⁺ E D D D D C Toxic

4 Co²⁺ E E D D D C Toxic

4 Ni²⁺ E E E D D C Toxic

4 Cu²⁺ E E E E D C Toxic

4 Cu⁺, Zn²⁺ E E E E E C Toxic

5 Ag⁺, Cd²⁺, In³⁺ E E E E E C Toxic

6 Au⁺, Hg²⁺ E E E E E C Toxic

6 Hg⁺ E E E E E D Toxic

5 Sn²⁺ E E E E E E Toxic

6 Tl⁺, Pb²⁺, Bi³⁺ E E E E E E Toxic

a Maxted, E. B. Adv. Catal. 1951, 3, 129. Reprinted with permission from Academic Press Inc.

2.2 REACTION CONDITIONS 55

in methanol.¹³ In contrast, Pd–C was completely and irreversibly poisoned by small amounts of iodide ion. From the results described above, it may be concluded that the degree of inhibition by hydrogen halides (or halide ions) increases in the order HCl <

HBr < < HI and the susceptibility of platinum metals to the inhibition decreases in the order Ru > Rh > Pd > Pt.

The inhibitory effect of nitrogen bases greatly depends on the structure of the bases and the substrate as well as the solvent employed in hydrogenation. Ammonia was a far more strong poison than cyclohexylamine or dicyclohexylamine in the hydrogena-tion of aniline over ruthenium and rhodium catalysts in isopropyl alcohol, although ruthenium was more resistant to poisoning by ammonia than rhodium.¹⁴ The toxicity of various amines as judged from the results on the hydrogenation of N-ethylaniline and pyridine over a rhodium black in isopropyl alcohol (80°C for N-ethylaniline and 60°C for pyridine at 7.8 MPa H₂) decreased in the order: NH₃ > > MeNH₂ > EtNH₂ >

Me₂NH > BuNH₂ > t-BuNH₂ > Et₂NH > EtNHC₆H₁₁ > Et₃N. The compounds BuNH₂, t-BuNH₂, Et₂NH, Me₃N, and Et₃N had little effect on the hydrogenation of pyridine. According to Maxted, the relative toxicity (the figures in parentheses) of ni-trogen bases (CN^– = unity) decreases in the order NH₃ (0.38) > BuNH₂ (0.23) >

C₆H₁₁NH₂ (0.17) > (C₆H₁₁)₂NH (0.0028), as compared in the hydrogenation of cyclo-hexene over a platinum black in cyclohexane (aqueous alcohol for CN^–). Thus the relative toxicity of the nitrogen bases is a function of the molecular size and the steric requirement around the nitrogen atom, rather than their basicity. It is noted that the in-hibitory effects of these nitrogen bases can be depressed by the addition of either acid or alkali. Acetic acid appears to be one of preferred solvents for the hydrogenation of aromatic amines with rhodium,¹⁵ palladium,¹⁶ and platinum.^17,18 This is attributed to the fact that acetic acid forms their salts with the product cyclohexylamines that are much more stable than those with the aromatic amines, since cyclohexylamines are definitely more basic (pK_a = 10.5–11) than the parent aromatic amines [pK_a (aniline)

= 4.65], and thus depresses the inhibition by the products effectively without much af-fecting the adsorption of the starting aromatic amines. On the other hand, the inhibi-tory action of nitrogen bases can also be depressed almost completely by the addition of small amounts of an appropriate alkali (see Section 11.5). The addition of lithium hydroxide has been found to be more effective than any of other alkalies, including sodium hydroxide, potassium hydroxide, and sodium carbonate for the ruthenium-catalyzed hydrogenation of aromatic amines (see eqs. 11.59–11.63).¹⁹

Excellent examples of the use of nitrogen bases as catalyst poisons are seen in the selective hydrogenation of alkynes to alkenes (see Chapter 4). Quinoline is probably the base that has been most often employed for this purpose. In this selective hydro-genation, the nitrogen base effectively inhibits the hydrogenation of alkenes to alkanes

1

RT, 0.2–0.3 MPa H₂ MeOH Pt oxide/4 H₂

+ HI I^– N Me

CH CH

N

CH₂CH₂

Me (2.1)

without lowering seriously the rate of hydrogenation of alkynes. The Lindlar catalyst, one of the most effective catalyst system for this selective hydrogenation, uses a com-bination of two catalyst poisons: lead acetate and quinoline (see Sections 1.5.2 and 4.1). It is noted that the Lindlar catalyst should be used in aprotic solvents since its ef-fectiveness may be reduced in hydroxylic solvents.²⁰

Sulfur compounds with unshielded electron pairs are all strong poisons for metallic catalysts in hydrogenation of almost all types of substrate. Horner et al. studied the ef-fects of various poisonous compounds in the hydrogenation of cyclohexene over nickel catalyst in methanol.²¹ Thiols, sulfides, thiocyanates, thioureas, thioacids, thio-phenols, thiophene, and thiolane and similar cyclic thioethers were all shown to be highly poisonous. It is of interest that thiophene was less poisonous than thiolane. Un-expectedly, dodecyl methyl sulfoxide, with an unshielded electrons pair, did not show a marked inhibitory effect, although dibenzyl sulfoxide was a mild inhibitor. It has been suggested that the inhibitory effect of dibenzyl sulfoxide might be due to the thioether formed from the sulfoxide by slow hydrogenation. Sodium benzenesulfinate was an inhibitor. Sodium sulfide was a weaker poison than sodium polysulfide. Nei-ther diphenyl sulfone nor phenyl p-toluenesulfonate were inhibitors, as expected form the shielded structure or oxidized state of their sulfur atoms. Greenfield demonstrated that sodium sulfite inhibited completely the hydrogenation of p-nitrophenol over Pd–

C after slow uptake of one-third of the amount of hydrogen required for completion.³ According to Maxted, the toxicity of sulfite ion relative to hydrogen sulfide is 0.63.² The poisoning by sulfur compounds has been utilized in the Rosenmund reduction of acid chlorides to aldehydes. Overhydrogenation of the aldehydes produced from acid chlorides has been effectively depressed by poisoning the catalyst, usually Pd–BaSO₄, with a sulfur-containing material such as quinoline-S, thioquinanthrene, phenyliso-thiocyanate, or thiourea (Section 13.4.6). Addition of bis(2-hydroxyethyl)sulfide to platinum catalyst has been shown to be as effective as sulfided platinum catalysts for the hydrogenation of halonitrobenzenes to haloanilines without dehalogenation (Sec-tion 9.3.2).

The sulfur compounds contained as impurities in a substrate or solvent may have a profound effect on hydrogenation, particularly over platinum metals where the amounts of catalyst used are usually much smaller than in the case of base metals. An excellent way to remove such impurities is to treat the sample with Raney Ni at slightly elevated temperatures²² (usually 50–80°C). The impurities in benzene or cy-clohexane can thus be removed simply by refluxing with Raney Ni for ~0.5 h (see Sec-tion 13.3). Granatelli applied this desulfurizaSec-tion with Raney Ni to determine quantitatively as little as 0.1 ppm of sulfur contained in 50 g of nonolefinic hydrocar-bons.²³

The transition metal sulfide catalysts are known to be resistant to poisoning by sul-fur-containing compounds. Rhenium heptasulfide (Re₂S₇)²⁴ and heptaselenide (Re₂Se₇)²⁵ have a lower tendency to cause hydrogenolysis of carbon–sulfur bonds than do the base metal sulfides. Thus, allyl phenyl sulfide was hydrogenated quanti-tatively to phenyl propyl sulfide over Re₂S₇ in ethanol at 150–160°C and 13 MPa H₂ and over Re₂Se₇ at 195°C and 29.2 MPa H₂. Thiophene was hydrogenated to give

thio-2.2 REACTION CONDITIONS 57

lane without ring opening over Re₂S₇ at 245°C and 13.6 MPa H₂ and over Re₂Se₇ at 250°C and 32.2 MPa H₂ (see eq. 13.98). Hydrogenation of sulfur-containing unsaturated compounds has also been achieved over palladium catalysts. Thiophene and substituted thiophenes,²⁶ dihydrothiophenes,²⁷ and 5,6-dihydro-2H- and -4H-thiopyrans²⁷ were con-verted to the corresponding saturated compounds over Pd–C under mild conditions, al-though large amounts of catalysts have usually been employed. Successful hydrogenolysis of dihydrobenzothiopyranones to the corresponding dihydrothiopyrans was achieved over molybdenum(VI) sulfide (MoS₃) as catalyst at 240°C and 10 MPa H₂ (eq. 2.2).²⁸ The hydrogenation of 2,3-dihydro-1H-naphtho[2,1-b]thiopyran-1-one (2, R¹, R² = benz; R³ = R⁴ = R⁵ = R⁶ = H) over MoS₃ under the same conditions gave a 96% yield of the corresponding dihydrothiopyran while over 5% Pd–C and 5%

PdS–C the yields were only 18 and 51%, respectively.

The poisoning by oxygen functions is not always observed and depends largely on the nature of catalysts as well as on the structure of the oxygen compounds. Oxidized products contained in olefins and ethers may have inhibitory effects on platinum metal catalysts, particularly on hydrogenations over rhodium, palladium, and platinum. To obtain reproducible results, careful purification of olefins by distillation and/or pas-sage through a column of alumina or silica has been recommended.²⁹ Hydrogenation of unpurified methyl linolenate over palladium catalysts is often selectively hydrogenated to methyl octadecenoates, with practically no further hydrogenation to methyl stearate.³⁰ Ethers usually contain inhibitors resulting from oxidized products and must be purified be-fore used as a solvent for hydrogenations over the platinum metals except ruthenium.

Tetrahydrofuran can be purified conveniently by drying and then distilling from lithium aluminum hydride, or by treating with a ruthenium catalyst and hydrogen until no more hydrogen has been absorbed, followed by distillation over sodium.¹⁰

Direct addition of methanol or ethanol to the platinum metal catalysts that have been stored in air may result in fire or partial loss of their catalytic activity due to for-mation of inhibitors (see, e.g., Tables 5.5 and 13.6). Freshly prepared Raney Ni, when stored under ethanol, not only loses gradually its high activity, but also its nature may be modified probably by the carbon monoxide abstracted from the ethanol (see Sec-tion 3.7.2). Acetic acid and other organic acids may contain substances that have in-hibitory effects on hydrogenations over platinum metals. Purification of acetic acid by boiling with potassium permanganate, as usually recommended, and a simple distil-lation³¹ has been found to be insufficient for use as the solvent in the hydrogenation of aromatic compounds over platinum and rhodium catalysts. Reproducible results

(5 mmol)

2 95%

(R¹ = R² = R³= R⁴ = R⁵= R⁶ = H ) 10 ml octane

240°C, 10 MPa H₂, 1.5 h MoS₃ (10 mmol) S

O R²

R¹

R³ S

R² R¹ R⁶

R⁵ R³

R⁶

R⁵

R⁴ R⁴

(2.2)

were obtained only by using acetic acid that had been purified by a careful and effi-cient fractional distillation.³² The benzoic acid prepared by air oxidation of toluene contains small amounts of various compounds harmful to the catalytic activity of platinum metal catalysts, and may be purified best by sublimation, or by treatment with Pd–C at 100–200°C under a high hydrogen pressure in a solvent for hydrogena-tion or with 0.2–10% (for benzoic acid) of concentrated sulfuric acid, followed by neutralization and distillation (see Section 11.4).