Nitro-ketones, reduction with zinc

Deoxygenation of a nitrone. Some years ago Todd and co-workers noted that 1-pyrroline-1-oxides can be obtained by reductive cyclization of a y-nitro ketone. This reaction was used recently in a synthesis of chlonns related to vitamin B,. Thus the nitro ketone 1 on reduction with zinc and acetic acid gives the pyrroline N-oxide 2 in high yield. The N-oxide is stable to triphenylphosphiue or trimethyl phosphite, but is reduced to the imine 3 in high yield by TiCl,. 

The starting phenylenediamine (12) was prepared by reaction of a 2-fluoronitro benzene (9) with an aniline (10) in the presence of potassium fluoride and subsequent reduction of the nitro derivative (11). The resulting amine (12) was generally alkylated with an alkyl bromide in the presence of sodium iodide to obtain the intermediate (13). However, when bulky groups had to be introduced, the intermediate (13 ) was conveniently obtained by reductive amination of either aldehydes or ketones. Condensation of (13) with (phenylhydrazono)malonyl dichloride followed by reduction with zinc and acetic acid led to the 3-amino substituted benzodiazepines (15). 

Also in the hexos-3-ulose series the ketone (7) has been made easily from the D-galacto-alcohol by use of PCC on alumina under reflux in benzene, the D-ribo-compounds (8) were obtained by treatment of the corresponding 3-nitro-D-allo-2,3-epoxide with nucleophiles (epimerization occurring at C-2), and reduction with zinc borohydride of the enolone (9) gave the 3-ulose derivative (10),... 

The popularity of the Nef reaction is due in part to the ready availability of nitro compounds. Primary and secondary halides react with sodium nitrite in dimeAyl sulfoxide (DMSO) or dimethylform-amide (DMF) to give useful yields of nitro compounds. Primary amines can be oxidized to nitro compounds with potassium permanganate, m-chloroperbenzoic acitP or ozone. Chlorination of oximes with hypochlorous acid and reduction with magnesium, zinc or hydrogen/lpalladium gives secondary nitro compounds. Stabilized carbanions can be nitrated by treauitent with a nitrate ester, and enol acetates are nitrated by acetyl nitrate to give nitro ketones. ... 

The nitroparaffins are condensed with aldehydes to yield nitro alcohols (70-80%), which on acetylation and treatment with an aqueous methanolic solution of sodium bicarbonate are converted to nitroolefins (80-84%). These compounds are reduced to the corresponding ketoximes by zinc and acetic acid (50-60%). Reduction with iron and dilute hydrochloric acid gives good yields of either ketones or ketoximes, depending upon the amount of hydrochloric acid used. The ketoximes can be hydrolyzed to ketones by refluxing with dilute sulfuric acid in the presence of formalin, which acts as a hydroxylamine acceptor (80%). The over-all yields from the nitroolefins are 40-60%. In this manner, certain otherwise difficultly obtainable ketones are prepared. Semicarbazones have been converted to ketones by treatment with sodium nitrite in glacial acetic acid, with aqueous oxalic acid, or with phthalic anhydride. ... 

Two novel complex hydrides are likely to find applications in steroid chemistry lithium perhydro-9b-boraphen yl hydride affords unusually high proportions of axial alcohols in model compounds sodium bis(methoxyethoxy)aluminium dihydride, Na (MeOCH2CH20)JAlH2, a very safe and convenient substitute for lithium aluminium hydride, readily reduces not only ketones but also acids, nitro-compounds, oximes, amides, lactones, etc. An improved procedure for Clemmensen reduction of steroid ketones involves saturating an ethereal solution with hydrogen chloride while stirring with zinc. 5a-Cholestane was obtained from the 3-one in 89% yield. ... 

Michael addition of the (S nitroester 95 to the unsaturated ketone 96 gave a mixture of 97 and the (22S)-isomer (207, 208). Sodium borohydride reduction of 97 in an acidic medium afforded the nitrodiol 98 in excellent yield. Reduction of the nitro group and subsequent lactam formation (99) proceeded smoothly when the nitrodiol 96 was refluxed with zinc and acetic acid. Further reduction of the amide 99 with LAH yielded the piperidine 100, which was converted into its iV-chloro derivative. Treatment of this compound with sodium methoxide effected dehydrochlorination which was... 

We have briefly met one method of reducing a ketone to a hydrocarbon, the Clemmensen reduction, using zinc amalgam and concentrated HCI (Figure 13.36). We note that the reaction works for both aldehydes and ketones. However, the reaction conditions are strongly acidic, so it is not compatible with acid-sensitive functional groups. The reaction is incompatible with nitro groups, which are often also reduced under these conditions. 

This ketone can then be reduced to propylbenzene by several methods. One general method—called the Clemmensen reduction—consists of refluxing the ketone with hydrochloric acid containing amalgamated zinc. [Caution As we shall discnss later (Section 20.4B), zinc and hydrochloric acid will also rednce nitro groups to amino groups.]... 

A zinc-silver couple has been reported to be an improved reagent for the reductive addition of allylic bromides to nitriles. l-Trimethylsilyl-2-methyl-cyclopropane is a convenient regio- and stereospecific precursor of unsaturated ketones [equation (37)]. The reaction of allylsilanes with a-nitro-olefins has been found to proceed smoothly in the presence of aluminium trichloride [equation (38)]. The unstable nitronic acid product may be converted readily into the unsaturated ketone by the Nef reaction. 

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