Reduction with hydrogen/Raney

A-Methylcodonocarpine (105) was transformed to derivative 107 by reduction with H2-Raney nickel, followed by O-ethylation with diazoethane (see Scheme 16). Compound 107 did not give the expected Hofmann degradation product, but rather the ring-closed pyrrolidine derivative 108 after transformation to the quaternary hydroxide followed by pyrolysis. After repeating the methylation and pyrolysis of the quaternary hydroxide followed by catalytic hydrogenation, compound 109 was obtained (95). The degradation product 109 has been synthesized according to Scheme 17 (96). 

Many hydroxypyrazine A oxides have been A(-deoxygenated to pyrazines with a variety of reducing agents which include heating with hydrazine hydrate in alcohols hydriodic acid and red phosphorus in acetic or phosphoric acid iodine and red phosphorus in refluxing acetic acid phosphorus tribromide in ethyl acetate sodium dithionite catalytic reduction with hydrogen over Raney nickel dry distillation with copper-chromite catalyst and titanium trichloride in tetrahydrofuran at room temperature. 

The oxide function can be removed using phosphorus trichloride, or phosphorus oxychloride, by reduction with hydrogen and Raney nickel" with sodium borohydride, and with hexachlorodisilane in chloroform. The reduction of 4H-imidazole N-oxides with borohydride leads to the 1-hydroxyimidazoline or imidazolidine derivatives under the same conditions 4if-imidazole JV,N -dioxides give 1,3-dihydroxy-imidazolidines. ... 

Tetrahydroindoxazene-3-carboxylic acids (89) are transformed into 3-amino-2-phenyl-4,5,6,7-tetrahydroindazoles by boiling phenylhydra-zine.98 On reduction with hydrogen and Raney nickel in ethanol, the acid hydrazides of 89 undergo ring opening to the imines 90 followed by cyclization to 4-amino-5,6,7,8-tetrahydrocinnolin-3-ones." The phenylhydrazone of 3-benzoyl-4,5,6,7-tetrahydroindoxazene behaves similarly.100... 

Although 1,5-dihydro-l-oxo derivatives of this ring system are quite stable to reduction, reductive cyclization of quinoxalinylpropionic acids yields hexahydro-l-oxo compounds. Thus reduction with hydrogen and Raney nickel of the acids 53 yields the hexahydro compounds 54. The earliest preparation of the ring system involved hydrogenation of the keto ester 55 at high temperature and pressure over copper chromite. The perhydro compound 56 was obtained by this approach. The use of hydrogen and Raney nickel resulted in the synthesis of compound 57. ... 

Examples of the Wolff-Kishner reduction are given in Figure 14.46. In the first example, notice that the ester group is not reduced—esters don t form hydrazones. In the second example, the acetal group survives the conditions of the Wolff Kishner a Clemmensen reduction would not have succeeded here because of the sensitivity of the acetal to acid conditions. Neither the Clemmensen nor the Wolff-Kishner reductions are generally successful for enones. One final method that may be employed involves the formation of a dithioacetal, followed by treatment with hydrogen/Raney nickel (Figure 14.47). We will explore the affinity for this specially prepared type of nickel for sulfur in Chapter 23. 

The chemical production of aminophenols via the reduction of nitrobenzene occurs in two stages. Nitrobenzene [98-95-3] is first selectively reduced with hydrogen in the presence of Raney copper to phenylhydroxylamine in an organic solvent such as 2-propanol (37). With the addition of dilute sulfuric acid, nucleophilic attack by water on the aromatic ring of /V-phenylhydroxylamine [100-65-2] takes place to form 2- and 4-aminophenol. The by-product, 4,4 -diaminodiphenyl ether [13174-32-8] presumably arises in a similar manner from attack on the ring by a molecule of 4-aminophenol (38,39). Aniline [62-53-3] is produced via further reduction (40,41). 

This group is prepared by the reaction of the anion of 9-hydroxyanthracene and the tosylate of an alcohol. Since the formation of this group requires an S 2 displacement on the alcohol to be protected, it is best suited for primaiy alcohols. It is cleaved by a novel singlet oxygen reaction followed by reduction of the endo-peroxide with hydrogen and Raney nickel. 

From 13.1 g of N-preduction with Raney-nickel and hydrogen, in which reaction the substance may be suspended in methanol or dissolved in methanol-ethyl acetate at normal pressure and at about 40°C with combination of the theoretical quantity of hydrogen, 12.2 g are obtained of o-emino-N-pfrom aqueous methanol hasaMPof90°C. 

Complete reduction of the azepine ring to hexahydroazepine has been effected with hydrogen and palladium,40 or platinum,135 239 catalysts. For example, ethyl 1 f/-azepine-l-carboxylate is reduced quantitatively at room temperature to ethyl hexahydroazepine-l-carboxylate (92% bp 118 —120 3C).134 136 TV-Phenyl-S/Z-azepin -amine (1), however, with platinum(IV) oxide and hydrogen in methanol yields the hexahydroazepine 2 in which the amidine unit is preserved in the final product.34 The same result is obtained using 5% palladium/barium carbonate, or 2 % palladium/Raney nickel, as catalyst. 

Dimethylpyrrolidine has been prepared by the hydrogenation of 5-amino-2,2-dimethylpyrroline-N-oxide or 5-imino-2,2-dimethylpyrrolidine in the presence of Raney nickel8 or by reduction with sodium and alcohol.8 This method is from unpublished work of the submitter. 

Similar addition reactions of alkyl 3-lithiopropiolates to nitrones with subsequent Raney Ni hydrogen reduction and amino group protection, led to the synthesis of (S) and (R)-vigabatrin (659). 

Finally, the amino metabolites of the NMs have been synthesized by researchers and used as standards. These synthesis methods include reduction of NMs with hydrogen in the presence of Pd/charcoal to form the amino metabolites [ 15,16,23] or reaction of NMs with hydrazine hydrate and Raney nickel [ 14,23]. A metabolite of HHCB, HHCB-lactone, has also been synthesized and used as a standard [17]. 

The 3,6-anhydro-D-glucose (XIX) of Fischer and Zach13 on reduction with sodium amalgam or with hydrogen in the presence of Raney nickel14 gives 3,6-anhydro-D-sorbitol (XX), a method of synthesis which establishes the ring structure of the substance since that of 3,6-anhydro-D-... 

Cyclododecene may be prepared from 1,5,9-cyclododecatriene by the catalytic reduction with Raney nickel and hydrogen diluted with nitrogen, with nickel sulfide on alumina, with cobalt, iron, or nickel in the presence of thiophene, with palladium on charcoal, with palladimn chloride in the presence of water, with palladium on barium sulfate, with cobalt acetate in the presence of cobalt carbonyl, and with cobalt carbonyl and tri- -butyl phosphine. It may also be obtained from the triene by reduction with lithium and ethylamine, by disproportionation, - by epoxidation followed by isomerization to a ketone and WoliT-Kishner reduction, and from cyclododecanone by the reaction of its hydrazone with sodium hydride. ... 

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