Hydrogenation With Raney nickel

Reduction. Just as aromatic amine oxides are resistant to the foregoing decomposition reactions, they are more resistant than ahphatic amine oxides to reduction. Ahphatic amine oxides are readily reduced to tertiary amines by sulfurous acid at room temperature in contrast, few aromatic amine oxides can be reduced under these conditions. The ahphatic amine oxides can also be reduced by catalytic hydrogenation (27), with 2inc in acid, or with staimous chloride (28). For the aromatic amine oxides, catalytic hydrogenation with Raney nickel is a fairly general means of deoxygenation (29). Iron in acetic acid (30), phosphoms trichloride (31), and titanium trichloride (32) are also widely used systems for deoxygenation of aromatic amine oxides. 

Alkylthio groups are oxidized to sulfoxides by H2O2 and readily by various oxidizing reagents to sulfones, e.g. in the imidazole series. The SR group is replaced by hydrogen with Raney nickel, and dealkylation is possible, e.g. of 3-alkylthio-l,2-dithiolyliums to give... 

Nickel(II) chlorophyll derivatives undergo catalytic hydrogenation with Raney nickel as catalyst to yield stereoisomeric isobacteriochlorins in which ring A of the chlorophyll derivatives is reduced.16... 

These are converted into chiral a-amino acids (5) on hydrogenation with Raney nickel. 

Buspirone Buspirone, 8-[4-[4-(2-pyrimidyl)-l-piperazinyl]butyl]-8-azaspiro [4,5] decan-7,9-dione (5.2.6), is synthesized by the reaction of l-(2-pyrimidyl)-4-(4-aminobutyl)piperazine (5.2.4) with 8-oxaspiro[4,5]decan-7,9-dione (5.2.5). In turn, 1-(2-pyrimidyl)-4-(4-aminobutyl)piperazine (5.2.4) is synthesized by the reaction of l-(2-pyrimidyl)piperazine with 4-chlorobutyronitrile, giving 4-(2-pyrimidyl)-l-(3-cyanopropyl)piperazine (5.2.3), which is hydrogenated with Raney nickel into buspirone (5.2.4) [51-55]. 

The first manufacturing route of the GEM side-chain relied on a-cyanoketone 125 however, the number of chemical steps from 125 to the final side-chain was reduced by one step (Noh et ah, 2004a). The sequence began with a selective hydrogenation with Raney nickel followed by double bond migration to enamine 131 (Scheme 4.25). The amino functionality of 131 was then monoprotected, and the double bond was reduced under hydrogenation conditions to afford pyrrolidine-3-one 133. Treatment of 133 with methoxylamine yielded methoxyoxime 129. Deprotection of the carbamate functionality was achieved with methanesulfonic acid to afford the C7-side-chain as the bis-methansulfonate salt. 

Nakazaki s synthetic approach is conspicuous by its remarkable straightforwardness it has been proved to be so far the simplest synthetic route to the target compounds. In their first synthesis of 61a54a), Nakazaki and coworkers started from cyclododecyne (62a), whose oligomerization with two molecules of butadiene afforded the bicyclic 63a. The cis[10.8] precursor 64a, obtained by partial catalytic hydrogenation with Raney nickel catalyst, was dissolved in cyclohexane, which contained xylene as photosensitizer, and the solution was irradiated with a medium pressure Hg lamp for 12 h. Examination of the reaction mixture by means of GLC indicated that the product was a 2.4 1 mixture of (Z) 64a and (E) 61 a, and the further study54b) showed that this ratio could be raised to 1 2 by irradiation of a hexene solution with a low pressure Hg lamp. 

On the other hand, hydrogenation with Raney nickel causes reduction mainly in the substituted aromatic ring [Eq. (11.16)]. Differences in product composition brought about by the different metals are explained in terms of steric hindrance of the substituted ring (Pt, Pd) versus the anchor effect of the methyl substituent (Ni).106... 

The reduction of 1,10-phenanthroline (4) occurs preferentially in the pyridine rings. Chemical reduction affords a low yield of 1,2,3,4-tetrahydro- 1,10-phenanthroline,243 but hydrogenation with Raney nickel as catalyst gives good yields of the 1,2,3,4-tetrahydro (45) and/or the 1,2,3,4,7,8,9,10-octahydro (46) derivative depending on reaction conditions.244 Hydrogenation of certain substituted 1,10-... 

An equimolar mixture of 3,4,5-trimethoxy phenyl iodide 157, lithium propargyl alkoxide 158, and diethyl ethoxymethylene malonate 159 was stirred at room temperature in the presence of a palladium catalyst. Then, to the resulting intermediate 161 potassium t-butoxide was added, and the ensuing base-promoted decarboxylative aromatization afforded tetrahydrofuran MCR adduct 162 in good yield. The ester was first reduced and the furan ring was hydrogenated with Raney nickel to furnish a diastereomeric mixture of products 163 in high yield. Further synthetic manipulations then provided a known precursor to the natural product. 

Amidone (6-dimethylamino-4,4-diphenyl-3-heptanone), while resistant to hydrogenation with Raney nickel, could be hydrogenated to the alcohol with platinum oxide as catalyst.140 However, isoamidone (6-dimethylamino-4,4-diphenyl-5-methyl-3-hexanone)(15, R = Me) did not absorb hydrogen in the presence of platinum oxide and the reduction to the corresponding alcohol was achieved by reduction with lithium aluminum hydride.141... 

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