Wolff-Kishner reduction modified procedures

Common catalyst compositions contain oxides or ionic forms of platinum, nickel, copper, cobalt, or palladium which are often present as mixtures of more than one metal. Metal hydrides, such as lithium aluminum hydride [16853-85-3] or sodium borohydride [16940-66-2] can also be used to reduce aldehydes. Depending on additional functionahties that may be present in the aldehyde molecule, specialized reducing reagents such as trimethoxyalurninum hydride or alkylboranes (less reactive and more selective) may be used. Other less industrially significant reduction procedures such as the Clemmensen reduction or the modified Wolff-Kishner reduction exist as well. 

The classical procedure for the Wolff-Kishner reduction—i.e. the decomposition of the hydrazone in an autoclave at 200 °C—has been replaced almost completely by the modified procedure after Huang-Minlon The isolation of the intermediate is not necessary with this variant instead the aldehyde or ketone is heated with excess hydrazine hydrate in diethyleneglycol as solvent and in the presence of alkali hydroxide for several hours under reflux. A further improvement of the reaction conditions is the use of potassium tcrt-butoxide as base and dimethyl sulfoxide (DMSO) as solvent the reaction can then proceed already at room temperature. ... 

Ethylthiophene may be obtained in 91% yield by a modified Wolff-Kishner reduction of 2-acetylthiophene. Other thiophene ketones, also aldehydes, have been converted in the same way in 70% to 90% yields. Reduction by the Clemmensen procedure gives 38% to 55% yields. °°... 

Since its introduction early in this century, the deoxygenation of aldehydes and ketones to methyl or methylene derivatives, respectively, via base treatment of hydrazone intermediates (equation 1) has proven to be one of the most convenient and synthetically useful processes available for this important type of transformation. The reaction is termed the Wolff-Kishner reduction in recognition of the two original independent discoverers.However, the initial recipes introduced proved tedious and unreliable with many structural, especially hindered, examples. This led to substantial efforts devoted over the years to developing more convenient and successful experimental procedures, resulting in a number of improved and more reliable modifications which are most often utilized at present. More recently, modified procedures have been provided which utilize hydride reductions of p-toluenesulfonylhydrazone (to-sylhydrazone) derivatives and subsequent decomposition to release the hydrocarbon products under much milder and less basic conditions than those normally required for Wolff-Kishner reductions (equation 2). 

Furrow, M. E., Myers, A. G. Practical Procedures for the Preparation of N-tert-ButyIdimethylsilylhydrazones and Their Use in Modified Wolff-Kishner Reductions and in the Synthesis of Vinyl Halides and gem-Dihalides. J. Am. Chem. Soc. 2004,126, 5436-5445. 

Barton, D.H.R., Bashiardes, G. and Fourrey, J.-L. (1983) An improved preparation of vinyl iodides. Tetra/iedronLeffew, 24, 1605-1608 Barton, D.H.R., Chen, M., Jaszberenyi, J.C. and Taylor, D.K. (1997) Preparation and reaction of 2-tert-butyl-l,L3,3-tetramethylguanidine 2,2,6-trimethylcyclohexen-l-yl iodide. Organic Syntheses, 74, 101-105 Furrow, M.E. and Myers, A.G. (2004) Practical procedures for the preparation of A-tert-butyldimethylsilylhy-drazones and their use in modified Wolff-Kishner reductions and in the synthesis of vinyl halides and gem-dihalides. Journal of the American Chemical Society, 126, 5436-5445. 

The preparation of butyric-4-C acid (50% yield) involves a two-step synthesis starting viuth glutamic-l,2-C acid (Mosbach et at., 195i). The procedure requires a deamination to succinaldehydic acid which is followed by a modified Wolff-Kishner reduction. In the first step the doubly labeled glutamic acid loses one labeled C moiety to become a singly labeled aldehyde. The unstable intermediary succinaldehydic acid is prepared as needed. Coon and Abrahamsen (1952) and Zabin and Bloch (1951) prepared butyric-3-C add from ethyl-l-G iodide in yields of 41 and 51%, respectively. 

Acylation. One of the most useful and important methods for preparations of alkylthiophenes is acylation. This is the reaction of carboxylic acids and carboxylic acid chlorides with thiophenes in the presence of a suitable catalyst and leads to 2-acylthiophenes in good yields (typically ca. 60-80% e.g. 23). Reduction of the ketone functionality by either a modified Wolff-Kishner procedure (8, 24) or with a mixed hydride, formed from aluminium trichloride and lithium aluminium hydride (25), yields the alkylthiophene (Figure 6). Alternatively, the ketone group can be alkylated, thereby giving access to 2-(r-alkyl)alkylthiophenes. 

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