Desulfurization, with Raney nickel

Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2.3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from Ai-chloroanilines and ot-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[l]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclizalion occurs on treatment of the anilinosulfonium salts with EtjN. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurized with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituled indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fiuoroacetic acid/thiosalieylie acid is a possible alternative to Raney nickel for desulfurization[3]. 

The Gassman synthesis has been a particularly useful method for the synthesis of oxindolcs[lb,8]. Use of methylthioacetate esters in the reactions leads to 3-(methylthio)oxindoles which can be desulfurized with Raney nickel. Desulfurization can also be done by reduction with zinc or tin[10,ll]. 

The thiones are readily desulfurized with Raney nickel to give the corresponding unsubstituted compounds in bicyclic systems in the 2-, 4- and 7-positions, and in tricyclic systems such as (95). The 2-methylthio derivatives may be similarly desulfurized. Thione groups in the 4-position, but not the 2-position, in pyrido-[2,3- f ]- and -[3,2- f]-pyrimidines may be replaced directly with ammonia or amines. 

Thiol groups in the 2-, 3- and 6-positions have been desulfurized with Raney nickel under the usual conditions to give the corresponding unsubstituted compounds. 

An older method,which also retains the double bond in its original location, utilizes the fact that thioketal formation from A" -3-ketones does not induce bond migration. Subsequent desulfurization with Raney nickel gives the A" -olefin (see section XI-D). 

In the course of synthesis of B-homo-progesterone (66) Himizu and Schichita utilized the Ringold procedure to convert 3j5,20 -dihydroxy-5a-pregnan-7-one diacetate (63) to 3/3,20yS-dihydroxy-B-homo-5a-pregnan-7-one diacetate (64). The latter is desulfurized with Raney nickel after prior... 

Since these adducts undergo reductive desulfuration with Raney nickel, optically active aryl methyl sulfoxides are versatile reagents for the conversion of imines to optically active amines. 

The addition of the lithium enolates of various acetic add esters to (S)-3-(4-methylphcnyl-sulfmyl)-2(5//)-liiranone and (,S)-5,6-dihydro-3-(4-methylphenylsulfinyl)-2//-pyran-2-one gives, after desulfurization with Raney nickel, 4-substituted dihydro-2(3//)-furanoncs and 4-substituted tetrahydro-2//-pyran-2-ones, respectively, in good to quantitative enantiomeric excess. Addition of the enolate occurs via the nonchelate mode. The enolate of methyl (phenylthio)acetatc is best overall in regards to chemical yields and enantiomeric purity of the final lactone product13. 

Docosanedioic acid has been prepared by Wolff-Kishner reduction of 6,17-diketodocosanedioic acid, formed by reaction of the half-ester acid chloride of adipic acid with the a,co-cadmium derivative of decane (%26 overall yield).3 Reduction of Wolff-Kishner method, followed by simultaneous reduction and desulfurization with Raney nickel of the 2,5-bis(co-carboxyoctyl)thiophene pro-... 

Chrzanowska and Rozwadowska (60) performed a total synthesis of ( )-43, using amine 49 and the thioacetal of methoxycarbonylpiperonal (26) as substrates (Scheme 13). These two synthons were joined together under the influence of LDA, and the resulting addition product 50 was subjected to reductive desulfurization with Raney nickel to give racemic peshawarine (43). 

Reductive desulfurization with Raney nickel is a reaction which requires but the simplest of techniques, is carried out under rather mild conditions and affords relatively good yields it is now. a standard and well-recognized reaction, having found use in practically all the various... 

Reductive desulfurizations with Raney nickel have been conducted in absolute alcohol, aqueous alcohol, dioxane, and ether, the first two solvents being most frequently used. Presumably any neutral solvent, containing neither halogen nor sulfur and not readily reduced, could be employed. 

Reductive desulfurization with Raney nickel of the mercaptolysis products of streptomycin has supplied one of the keys to the elucidation of the structure and configuration of that antibiotic. Since the chemistry of streptomycin has recently been reviewed37 the reactions discussed here will be considered solely as examples of hydrogenolysis and their bearing upon the problem of the structure and configuration of streptomycin will be ignored. 

A critical study of the preparation of the two anomeric 6-desoxy-D-glucose tetraacetates (LXXXIV) from D-glucose has been made by Hardegger and Montavon.70 The final step, namely, the reduction of the two 6-iodo-6-desoxy-D-glucose tetraacetates (LXXXII) in high yield, proved to be particularly difficult and a variety of methods were studied. Highest yields were obtained when LXXXII was allowed to react with thiourea to form the S-substituted isothiuronium iodide (LXXXIII) which was then desulfurized with Raney nickel. In actual practice the 6-iodo derivative was refluxed briefly in amyl alcohol with thiourea and... 

Reaction of 299 with benzaldehyde was found to give an equimolar mixture of diastereomeric j3-hydroxysulfoxides (314). Addition of 299 to a-tetralone 300 was more satisfactory, since the corresponding diastereomeric/3-hydroxysulfoxides 301 were formed in a 1.8 1 ratio. Their subsequent desulfuration with Raney nickel yielded levorota-tory 1-hydroxy-1-methyl-1,2,3,4-tetrahydronaphthalene 302 of unknown absolute configuration and optical purity. Similarly, addition of 299 to cyclohexene oxide leads to the formation of diastereomeric /3-hydroxysulfoxides 303 in a 2 1 ratio which, after separation, may be desulfurized to give (R,R)- and (S,S)- trans-2-methylcyclo-hexanols 304, respectively. Analysis of NMR spectra of the... 

Aliphatic and aromatic sulfides undergo desulfurization with Raney nickel [673], with nickel boride [673], with lithium aluminum hydride in the presence of cupric chloride [675], with titanium dichloride [676], and with triethyl phosphite [677]. In saccharides benzylthioethers were not desulfurized but reduced to toluene and mercaptodeoxysugars using sodium in liquid ammonia [678]. This reduction has general application and replaces catalytic hydrogenolysis, which cannot be used [637]. 

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

DESULFURIZATION WITH RANEY NICKEL Preparation of Aldehydes from Thiol Esters [1101]... 

Novitskii, Khachaturova and Yur ev obtained 4i/,6/f-thieno[3,4-c]-furan (128) from 3,4-bischloromethylfuran (127) and sodium sulfide. The thienofuran (128) was converted into an adduct (129) with maleic anhydride and into 3,4-dimethylfuran (130) by desulfurization with Raney nickel [Eq. (40)]. 

Similarly, acetylation of thieno[3,2-6]thiophene (2) afforded 2-acetyl-thieno[3,2-6]thiophene, which was converted into methyl n-hexyl ketone by desulfurization with Raney nickel. Oxidation of 2-acetylthieno-[3,2-i]thiophene followed by nitration gave 5-nitrothieno[3,2-6]-thiophene-2-carboxylic acid. Decarboxylation of the latter furnished 2-nitrothieno[3,2-ft]thiophene identical with the compound obtained by direct nitration of thienothiophene 2 [Eq. (60)]. 

Wynberg and Feijen studied thieno[3,4-6]thiophene (3) formylation and found that both positions 4 and 6 are attacked. This is in accordance with theoretical predictions. The reaction produces a mixture (7 3) of 4-formyl- (194) and 6-formylthieno[3,4-6]thiophene (195) in 56% total yield after separation and purification. The formyl derivatives obtained were oxidized to the corresponding carboxylic acids 196 and 197, which were converted into 3-ethylpentanoic 198 and 4-methylhexanoic (199) acids by desulfurization with Raney nickel [Scheme 15]. 

Thienothiophenes, like thiophenes and benzo[h]thiophenes, easily undergo reductive desulfurization with Raney nickel. The method was fvst applied in this series by Challenger et to determine the structures of 2-acetylthieno[3,2-h]thiophene and 2-acetylthieno[2,3-hl-thiophene the former gave 2-octanone (229), and the latter 5-methyl-heptan-2-ol (230) [Eqs. (75) and (76)]. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

Another useful application of this reaction stems from the fact that dithianes can be desulfurated with Raney nickel (4-36). Aldehydes can therefore be converted to chain-extended hydrocarbons 1510... 

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