Raney Ni-catalyzed hydrogenation

This compound was prepared from 4-cyanobenzoic acid (14 g, 0.09 mol) using a Raney Ni catalyzed hydrogenation after crystallization (H20), a pink-colored product was obtained yield 11.5 g (80%) mp 347-350 C. 

The Wittig reaction of dialdehyde 175, prepared by chromic anhydride-pyridine oxidation of diol 94 (53), with 176 in dilute methylene chloride solution produced cyclophane 177 in 86% yield. Epoxidation of 177 with m-chloroperbenzoic acid followed by hydrogenolysis over Pd/C, acetylation, and PtOz-Raney Ni-catalyzed hydrogenation afforded the cis-substituted piperidine derivative (178). 

In the Raney Ni catalyzed hydrogenation of 3-methoxy-2-hydroxypropionitrile (methoxyacetaldehyde cyanohydrin), the hydroxyl group had been protected by the reaction with ethylal and a trace of acid to form 2-(ethoxymethoxy)-3-methoxypropionitrile (eq. 7.53), because direct hydrogenation of the cyanohydrin was not successful because of decomposition.103... 

Alkaline substances have been used as promoters in the Raney Ni-catalyzed hydrogenation of phenol and alkylphenols.72,73 The hydrogenations were most effectively promoted by small amounts of anhydrous salts of phenols in the absence of solvents. For example, hydrogenation of 0.53 mol of phenol over 3 g Raney Ni at 100°C and 13-15 MPa H2 was completed in 0.6 h in the presence of 0.4 mol% of sodium phe-noxide (eq. 11.13), compared to 1 h with addition of 1 ml of 40% aqueous sodium hydroxide, while 3 h or longer was required without an alkaline additive. 

The presence of acetic acid increases the selectivity to ar-2-TL.239 According to one patent, ar-2-TL was obtained in 80-86% yield and the formation of ac-2-TL was depressed to 0-14% in the hydrogenation over Pd-C in methanol-acetic acid (eq. 11.72).245 A similar effect of acid was also observed in the Raney Ni catalyzed hydrogenation of 2-methoxynaphthalene where 6-methoxyteralin was obtained in 91% yield with addition of acetic acid to ethanol (eq. 11.73).239... 

Freifelder and Stone have shown that over ruthenium dioxide, pyridine and its derivatives are readily converted to piperidines under much milder conditions (90-100°C and 7-10 MPa H2) than required for Raney Ni catalyzed hydrogenations.27 Thus, pyridine was hydrogenated to piperidine quantitatively at 95°C and 7-10 MPa H2 in less than 0.5 h over 2 wt% of the ruthenium catalyst (eq. 12.17). At200°C as little as 0.1% of the catalyst was sufficient to carry the hydrogenation to completion in little more than 1 hr. 

Generally, the N-N bond may be stabilized toward hydrogenolysis by acetylation or hydrogenation in acetic anhydride, as in eq. 12.72 in the Raney Ni-catalyzed hydrogenation of a pyrazoline derivative at a high temperature and pressure.133 In contrast, 5-methylpyrazoline was hydrogenolyzed to give butane-1,3-diamine in 67% yield under even milder conditions (eq. 12.73).134... 

A chirally modified Raney Ni catalyzes the hydrogenation of 1,3-diketones selectively to give the anti 1,3-diols in about 90% ee (Fig. 32.19) [67]. Natural compounds such as africanol and ngaione are synthesized via this method [68]. 

Despite the fact that Nature uses nickel for the activation of dihydrogen, and that Raney-Ni is one of the oldest and the most important heterogeneous hydrogenation catalysts, very few nickel complexes are known to catalyze the homoge-... 

Raney Ni-U = ultrasonic irradiated Raney Ni Fig. 32.14 Hydrogenation of ft- keto esters catalyzed by modified Raney Ni. 

Enantioselective hydrogenation of />-kelo esters catalyzed by the modified Raney Ni is useful for the synthesis of biologically active compounds, as shown in Figure 32.15 [56-58]. A large-scale synthesis of (-)-tetrahydroHpstatin (orlistat), a pancreatic lipase inhibitor (F. Hoffmann-La Roche AG), is carried out using this method [58]. 

Hydrogenolysis of tert-alcohols.1 2 3 This deoxygenation can be effected with Raney Ni slurry (Aldrich 50% slurry in water) that has been washed eight times with distilled water and twice with 1-propanol. Thus reaction of a tertiary alcohol with washed Raney Ni for a short time yields a mixture of alkenes that furnish a single alkane on hydrogenation catalyzed by Pd/C. 

Figure 1.13. Examples of biologically active compounds obtainable via hydrogenation of a- or (5-keto esters catalyzed by chirally modified Raney Ni or Pt/Al203.

Unhindered simple olefins are usually rapidly hydrogenated under very mild conditions over platinum metal catalysts such as platinum, palladium, and rhodium as well as over active nickel catalysts such as Raney Ni, nickel boride, and Urushibara Ni. For example, 0.1 mol of cyclohexene is hydrogenated in 7 min over 0.05 g of Adams platinum oxide in ethanol at 25°C and 0.2-0.3 MPa H2 (eq. 3.1).5 1-Octene and cyclopentene (eq. 3.2) are hydrogenated in rates of 11.5 and 8.6 mmol (258 and 193 ml H2 at STP) g Ni 1-min 1, respectively, over P-1 Ni in ethanol at 25°C and 1 atm H2.18 Hydrogenation of cyclohexene over active Raney Ni proceeds at rates of 96-100 ml H2 at STP (4.3-4.5 mmol) g Ni min-1 in methanol at 25°C and 1 atm H2 49,50 and can be completed within a short time, although usually larger catalyst substrate ratios than required for platinum catalyzed hydrogenations are employed (eq. 3.3).50... 

Rhenium compounds such as Re2Sc7 are more reactive hydrogenation catalysts for the reduction of carbonyls than for olefins, except in conjugated systems . Unsaturated carbonyls have been selectively hydrogenated to unsaturated alcohols, catalyzed by a chromium-promoted finely divided Ni (Raney Ni) catalyst" ... 

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