Wolff-Kischner reduction

Methylation of carbazole phenolic oxygen has been achieved using dimethyl sulfate without reaction at nitrogen. Demethylation of carbazole methyl ethers has been achieved with hydrobromic acid-acetic acid, boron trichloride,and pyridine hydrochloride. Selective demethylation of methoxyl ortho to an aldehydo function has been achieved using boron trifluoride. ° ° Partial demethylation of 1-methoxy-3-formylcarbazole occurred during Wolff-Kischner reduction." ... 

The Wolff-Kischner reduction of 110 gave the product 61 with a five-membered ring in 65 % yield. 

Step 3 Wolff-Kischner reduction (Huang-Minlong modification). Step 4 Acetal hydrolysis. 

The sodium salt of the JV-methoxycarbonyl hydrazone rearranges faster than the hydrazone itself or the parent ketone. This method has been used for the construction of vicinal quaternary centers, since the accelerating functionality can simply be removed by Wolff Kischner reduction. For charge-accelerated Claisen rearrangements of related systems see refs 85 and 113— 118. 

Another route by which rubijervine is convertible into known solanidine derivatives is by way of the saturated diol V, which was first oxidized with chromic acid in acetic acid to the diketone (XIV), the bis(semi-carbazone) of which on Wolff-Kischner reduction afforded a mixture of 3/3-solanidanol (IX, p. 256) and solanidane (V, p. 256) (57). Dehydrogenation of rubijervine with selenium gave the typical dehydrogenation... 

The stability of dialkyl-acetals and -ketals to neutral and alkaline reaction conditions generally parallels that of dioxo-lans. Unlike the latter, however, they may decompose to enol ethers at higher temperatures, e.g., during Wolff-Kischner reduction [31]. 

The main interest in dithio-ketals and -acetals has been in connection with their hydrogenolysis by Raney nickel to give the corresponding hydrocarbons, as an alternative to the Clemmensen or Wolff-Kischner reduction on the parent carbonyl compound. This subject has been thoroughly reviewed [90]. Hydrogenolysis of thioketals has also been effected by hydrazine [91, 92, 93] and by alkali metals in liquid ammonia [94]. 

An indolone comprises a prominent moiety in the dopamine D2 selective antipsychotic agent ziprasidone (32-8). Reduction of the ketonoid carbonyl group on the indoxyl (32-1) under Wolff-Kischner conditions affords the indolone (32-2). Acylation of the product with chloroacetyl chloride in the presence of aluminum chloride then affords the reactive chloroacetyl derivative (32-3). In a convergent sequence, reaction of isothiazolone (32-4) with phosphorus oxychloride leads to... 

Answer The Friedcl-Crafts alkylation reaction is useless in the naphthalene scries because of the polyalkylation that frequently occurs. The best method.of placing an alkyl group on a naphthalene nucleus involves the reduction of a ketone using the Wolff-Kischner or Clemmensen reductions as shown in procedure XVI-7. Thus wc need A. 

There are two main synthetic routes to naphthalene the Haworth synthesis and a Diels-Alder approach. In the Haworth synthesis (Scheme 12.1), benzene is reacted under Friedel-Crafts conditions with succinic anhydride (butanedioic anhydride) to produce 4-oxo-4-phenylbutanoic acid, which is reduced with either amalgamated zinc and HCl (the Clemmensen reduction) or hydrazine, ethane-1,2-diol and potassium hydroxide (the Wolff-Kischner reaction) to 4-phenylbutanoic acid. Ring closure is achieved by heating in polyphosphoric acid (PPA). The product is 1-tetraione and reduction of the carbonyl group then gives 1,2,3,4-tetrahydronaphthalene (tetralin). Aromatization is achieved by dehydrogenation over a palladium catalyst. 

Most usual oxidizing agents act normally with imidazole aldehydes and ketones but l-benzylimidazole-2-carbaldehyde is reportedly somewhat resistant to selenium dioxide oxidation. Reduction of ketone functions under Clemmensen and Wolff-Kischner conditions is usually successful. Zinc dust and acetic acid reduce acetyl groups to a mixture of secondary alcohol and ethyl borohydride gives the alcohol exclusively (B-76M140701). 

Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkyl-thiophenes, hypochlorite oxidation of acetyl-thiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylamino-thiophenes and hence amino-thiophenes, and esters and acids are interconvertible without complications. 

Conversion of isatins into oxindoles can be achieved by catalytic reduction in acid, or by the Wolff-Kischner process.3-Substituted indoles result from Grignard addition at the ketone carbonyl, followed by lithium aluminium hydride reduction of the residual amide, then dehydration. The reaction of isatin with triphenylphosphine provides an easy synthesis of 3-(triphenylphosphorylidene)oxindole, a Wittig reagent. ... 

Here, the parallels with benzenoid counterparts continue, for these compounds have no special properties - their reactivities are those typical of benzenoid aldehydes, ketones, acids, and esters. For example, in contrast to the easy decarboxylation of a-acids observed for pyrrole and furan, thiophene-2-acids do not easily decarboxylate. Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkylthiophenes, hypochlorite oxidation of acetylthiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylaminoth-iophenes and hence aminothiophenes, and esters and acids are interconvertible with no complications. 

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