Imidazol 2, 3 Raney-Nickel

Butenolide 231 was obtained by a procedure that did not involve a pyrolytic step (237). Thus, the 5-trityl ether 223c was converted into the thioxocar-bonate 230 upon treatment with A,A -thiocarbonylbis(imidazole). Raney nickel effected the conversion of 230 into 231. 

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... 

Durch katalytische Hydrierung mit Raney-Nickel in Ethanol bei 100 bar/100o lassen sich 1,2-disubstituierte 4- oder 5-Chlor-imidazole497 zu 1,2-disubstituierten Imidazolen und mit Palladium auf Aktivkohle in Eisessig 4-Acetylamino-l-benzyl-2-brom-imidazol498 zu 4-Acetyl-amino- 1-benzyl-imidazol enthalogenieren. 

Mit Raney-Nickel wurden zahlreiche 2-Mercapto-imidazole entschwefelt4h5a, M 8 ... 

Zur Losung von 30 mg (0,011 mmol) 4-Brom-5-methoxycarbonyl-l-methyl-2-methylthio-imidazol in 5 ml Tetrahydrofuran gibt man bei 0° 10 mg feuchtes Raney-Nickel (W-2). Dann ruhrt man 30 min. bei 20°, filtriert das Nickelsulfid ab und dampft zur Trockcne ein Ausbeute 24 mg (93%) Schmp. 91 94°. 

Aus l-Amino-2-mercapto-4-phenyl-imidazol wird mit Raney-Nickel sowohl die Mercapto- als auch die 1-Amino-Gruppe abgespalten476, und man erhalt 4-Phenyl-imidazol zu 83% ... 

Reduction of l,2,4-triazin-3-ones (84) with Raney nickel, zinc and acetic acid, lithium aluminum hydride, sodium borohydride, titanium(III) chloride, p-toluenethiol, hydrogen and a palladium catalyst, or electrochemically, produces 4,5-dihydro-l,2,4-triazin-3-ones (268) (78HC(33)189, p. 246, 80JHC1237), which may be further reduced to 1,4,5,6-tetrahydro-l,2,4-triazin-3-ones (269). l,2,4-Triazin-3-ones (84) with hydriodic acid and phosphorus yielded imidazoles (05LA(339)243). 3-Alkoxy-l,2,4-triazines (126) and sodium borohydride gave the 2,5-dihydro derivatives (270) (80JOC4594). 

The N-hydroxy structure (26) was preferred123 to an iV-oxide representation on account of the amphoteric nature of the product and because the derived acetate formed a well-defined hydrochloride salt. Hydrogenation of these N-hydroxyimidazoles over Raney nickel gives imidazoles in 60-94% yields.122 The reaction has been adapted for the preparation of 4-mercaptoimidazoles, using an a-ketothionamide (27) with an aldimine.124... 

A new method of synthesis162 of the imidazole ring by the use of A-cyaniminodithiocarbonic esters (41) involves formation of the 4 5-bond. Reaction of (42) with KNCO in acetic acid yielded the corresponding amide (43) which was cyclized by sodium hydroxide to the substituted purine (44). Treatment of (42) with Raney nickel and hydrogen produced 4-amino-5-carbethoxy-l-methyl-4-imidazo-line (45), which could also be cyclized to a purine (46).162... 

Removal of an AT-oxide function utilizes the usual reagents such as zinc and acetic or hydrochloric acids, sodium borohydride, hydriodic acid, phosphoryl chloride, sodium dithionite, phosphorus trichloride or hydrogenation over Raney nickel. When l-hydroxy-2-methyl-5-phenylimidazole (262) reacts with butyllithium and hexachlofodisilane this also induces dehydroxylation (Scheme 152) (80AHC(27)24l). At times, as with other heterocyclic AT-oxides, deoxygenation with phosphorus halides can introduce a halogen atom at C-2 of imidazole (75JCS(P1)275). 

To the above mercaptoester (3.0 g, 19 mmol) in ethanol (20 ml) is added a wet suspension of freshly prepared Raney nickel [26] in ethanol ( 5 g). The mixture is heated under reflux and monitored by TLC on silica (ethyl acetate). The desulfurization is complete in about 1 h. The suspension is then treated with activated charcoal, filtered (Celite) and washed with a little ethanol, and then the filtrate is rotary evaporated. Recrystallization of the residue from aqueous ethanol gives methyl imidazole-4-carboxylate (1.27g, 53%), ra.p. 149°C. 

Such hydroxyimidazoles or oxides are capable of complete reduction to the unoxygenated imidazoles, while the 1-hydroxyimidazole 3-oxides can also be partically reduced with, for example, NaBUi [53], or completely deoxygenated with Raney nickel [52, 54], Although most cyclizations of a-ketooximes lead to A -oxygenated imidazoles, there are exceptions. When an o(-oximino-)6-dicarbonyl compound is refluxed with benzylamine in a suitable solvent (c.g. DMSO, acetonitrile, toluene), 4-acylimidazoles (11) are formed in moderate to good yields. The reaction is readily adapted to the synthesis of imidazole-4-carboxylates and -amides (Scheme 4.1.7)... 

Imidazole- and benzimidazole-2-thiols usually exist largely as the thione tautomers. The thiol (thione) group is susceptible to alkylation (especially in alkaline media), and can be oxidized to sulfide, disulfide and sulfonic acid. This oxidation can often be carried out quite selectively by careful choice of oxidizing agent. The sulfur function can be removed with nitric acid, iron(III) chloride, hydrogen peroxide or, most commonly, Raney nickel. Alkyl- and arylthio groups can be oxidized to sulfoxide or sulfone. 

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. ... 

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