Reductions hydrazones, lithium aluminum hydride

Finally, when ketones and aldehydes are treated with p-toluene suRonyl hydrazine (P-CH3C6H4SO2NHNH2, Chapter 10) in the presence of an acid catalyst, addition to the carbon of the carbonyl occurs (vide infra) with the formation of the corresponding p-toluene sulfonyl hydrazone by a process formally identical with that of the addition of hydrazine (H2NNH2) itself (Scheme 9.12). Reduction of the hydrazone with lithium aluminum hydride (LiAlH4) produces the corresponding hydrocarbon (Scheme 9.14). 

In certain cases this reduction (with lithium aluminum hydride) takes a different course, and olefins are formed. The effect is dependent on both the reagent concentration and the steric environment of the hydrazone. Dilute reagent and hindered hydrazone favor olefins borohydride gives the saturated hydrocarbon. The hydrogen picked up in olefin formation comes from solvent, and in full reduction one comes from hydride and the other from solvent. This was shown by deuteriation experiments with the hydrazone (150) ... 

Lead tetraacetate, oxidation of a hydrazone to a diazo compound, 50, 7 Lithio ethyl acetate, 53, 67 Lithium, reductions in amine solvents, 50, 89 Lithium aluminum hydride, reduction of exo-3,4-dichloro-bicyclo-[3.2.l]oct-2-ene to 3-chlorobicyclo[3.2.l]oct-2-ene, 51, 61... 

Like any aldehydes aromatic aldehydes undergo Clemmensen reduction [758, 778] and Wolff-Kizhner reduction [759, 774] and give the corresponding methyl compounds, generally in good yields. The same effect is accomplished by conversion of the aldehydes to p-toluenesulfonyl hydrazones followed by reduction with lithium aluminum hydride (p. 106). 

Aldoximes yielded primary amines by catalytic hydrogenation benzaldehyde gave benzylamine in 77% yield over nickel at 100° and 100 atm [803, with lithium aluminum hydride (yields 47-79%) [809, with sodium in refluxing ethanol (yields 60-73%) [810] and with other reagents. Hydrazones of aldehydes are intermediates in the Wolff-Kizhner reduction of the aldehyde group to a methyl group (p. 97) but are hardly ever reduced to amines. 

Hydrazones treated with alkalis decompose to nitrogen and hydrocarbons [845, 923] Woljf-Kizhner reduction) (p. 34), and p-toluenesulfonylhydra-zones are reduced to hydrocarbons by lithium aluminum hydride [812], sodium borohydride [785] or sodium cyanoborohydride [813]. Titanium trichloride hy-drogenolyzes the nitrogen-nitrogen bond in phenylhydrazones and forms amines and ketimines which are hydrolyzed to the parent ketones. Thus 2,4-dinitrophenylhydrazone of cycloheptanone afforded cycloheptanone in 90% yield [202]. 

The methyl group was introduced by a two-step procedure. Thus, the hydrazone Michael adducts 52 were converted into the enol pivaloates 53 in excellent yields and diastereomeric excesses de > 96%) by treatment with pivaloyl chloride and triethylamine. After treatment with lithium dimethylcuprate the chiral auxiliary was removed by addition of 6n HCl in order to obtain the 5-substituted 2-methylcyclopentene carboxylate 54 in good yields and with excellent stereoselectivity (de, ee > 96%). Finally, the asymmetric synthesis of dehydroiridodiol (55, R = Me, = H) and its analogues was accomplished by reduction of 54 with lithium aluminum hydride or L-selectride leading to the desired products in excellent yields, diastereo- and enantiomeric excesses (de, ee > 96%). 

Amide reduction with lithium aluminum hydride, 39, 19 Amine oxide formation, 39, 40 Amine oxide pyrolysis, 39, 41, 42 -Aminoacetanilide, 39, 1 Amino adds, synthesis of, 30, 7 2-Amino-4-anilino-6-(chloro-METHYl) -S-TRIAZINE, 38, 1 -Aminobenzaldehyde, 31, 6 hydrazone, 31, 7 oxime, 31, 7 phenylhydrazone, 31, 7 > -Aminobenzoic add, 36, 95 2-Aminobenzophenone, 32, 8 c-Aminocaproic acid, 32, 13 6-Aminocaproic acid hydrochloride,... 

The N-N bond of polystyrene-bound hydrazines, which are prepared by reaction of organolithium compounds with resin-bound hydrazones [457], can be cleaved by treatment with borane to yield a-branched, primary amines (Entry 9, Table 3.23). An additional example of reductive cleavage to yield amines is shown in Entry 10 (Table 3.23), in which a resin-bound a,a-disubstituted nitroacetic ester undergoes decarboxylation and reduction to the primary amine upon treatment with lithium aluminum hydride. 

The only reference to this ring system names the perhydro heterocycle as piperazino[l,2-a]piperazine. Reduction of the 2,4-dinitrophenyl-hydrazone 1 with Raney nickel gave the dioxo derivative 2 in 26% yield. This compound was reduced with lithium aluminum hydride to give the product 3. 

Reductions of Imines and Derivatives. Preformed imines (eq 7), iminium ions (eq 8), oximes (eq 9), oxime derivatives (eqs 10 and 11), hydrazones (eq 12), and other iV-heterosubstituted imines (eqs 13 and 14) are reduced to the corresponding amine derivatives by NaBHsCN, usually in acidic media (see also Lithium Aluminum Hydride and Sodium Boro-hydride). 

The process of imine formation and reduction can be accomplished as a one-pot process, described as reductive amination (Figure 22.15). Oximes and hydrazones can also be reduced with lithium aluminum hydride, but these reactions only occasionally have any synthetic advantage over imine reduction. 

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