Reduction of 1,4-dihydro compounds

TABLE 1-3 Further Reduction of 1,4-Dihydro Compounds under Birch Reduction Conditions30... 

Residual aromatic ether concentrations are determined from the absorbance at 278 mfi of the crude reduction products in methanol solution. Steroidal ether concentrations of 1 mg/ml are employed. The content of 1,4-dihydro compound is determined, when possible, by hydrolysis to the a, -unsaturated ketone followed by ultraviolet analysis. A solution of the crude reaction product (usually 0.01 mg/ml cone) in methanol containing about 1/15 its volume of water and concentrated hydrochloric acid respectively is kept at room temperature for 2 to 4 hr. The absorbance at ca. 240 mfi is measured and, from this, the content of 1,4-dihydro compound can be calculated. Longer hydrolysis times do not increase the absorbance at 240 mp.. 

The reduction in acid solution of di- and tetrahydropyridazines is often best understood when their resemblance to hydrazones is considered the reduction of such compounds has been briefly discussed in Section IV, B, and the primary step is a hydrogenolysis of the nitrogen-nitrogen bond. The reduction of 1,4-dihydro- l-methyl-5-i-butyl-3,6-diphenylpyridazine was also described above (Section IV, B),... 

The polarographic behavior of the 1-oxides and 1,4-dioxides of pyrazine, 2,5-dimethylpyrazine, and tetramethylpyrazine at various pH values has been investigated. It was assumed that at lower pH values, the A -oxide group was reduced in its protonated form. In acid media the 1-oxides exhibited double waves, the first of which is attributable to the reduction of jV-oxide groups and the second to that of the pyrazine nucleus (production of 1,4-dihydro compounds). Reduction of both A -oxide groups of pyrazine-1,4-dioxide proceeded simultaneously (588). Half-wave potentials of the voltammetric oxidation and reduction of pyrazine mono- and di-A -oxides have been measured in dimethylformamide, and in acetonitrile by the technique of a rotating platinum electrode (750). 

The A-ring of the 17-ol (25) derived from equilenin 3-methyl ether is reduced rapidly under Birch reduction conditions, since the 1,4-positions are unsubstituted. The B-ring is reduced at a much slower rate, as is characteristic of aromatic compounds in which 1,4-reduction can occur only if a proton enters an alkylated position. Treatment of (25) with sodium and t-butyl alcohol in ammonia reduces only the A-ring to afford the corresponding 1,4-dihydro compound in over 85% yield.On the other hand,... 

Bates and his associates have found that cyclohexadienyl carbanion itself protonates at the central carbon atom from three to eight times as rapidly as at a terminal one, but the conditions involved were different from those encountered in a Birch reduction. Since the Birch reduction of many 3-meth-oxyestra-l,3,5(10)-triene derivatives affords 1,4-dihydro compounds in yields approaching 90%, the cyclohexadienyl carbanions involved in these reductions must protonate about eighteen times faster at the central carbon atom than at a terminal one. 

Reduction of aryl esters.1 Alkyl benzoates are reduced to 1,4-dihydro compounds by sodium in THF NH3 if 1 2 equivalents of water is present before addition of the metal (equation I). The presence of water can be useful for reduction of other aromatic systems (equation II). 

The electrochemical reduction of aromatics to the corresponding 1,4-dihydro compounds can be performed by a procedure similar to the Birch reduction. It has been studied intensively in industry. Two different process modifications are to be distinguished ... 

Catalytic hydrogenation of 3-phenylpyrido[3,4-e]-l,2,4-triazine (45b) over a palladium catalyst gave the 1,4-dihydro compound (29) in a 90% yield this is an unusual result as the position of the pyridine nitrogen atom does not seem to affect the formation of 1,4-dihydro derivatives (see also Section 7.17.5.4). Electrochemical reduction of the pyrido-l,2,4-triazine (45b) in both protic and... 

Catalytic hydrogenation of compound (44) and LAH reduction of compound (45) both yielded the 1,2,3,4-tetrahydro-derivative whereas Zn/acetic acid or electrochemical reduction gave the air-sensitive 1,4-dihydro-compounds <87CJC1619>. Instead of the formation of the expected 5-methyl compound, MeLi attacked the highly hindered 2-position of compound (24 R = Bul) to yield compound (25 R = Me) <84LA133>. 

In aqueous alkaline solution a dimeric product is formed on reduction of quinoxaline besides the 1,4-dihydro compound on acidification it dissociates.173... 

The method of choice for the preparation of the 1,4-dihydro compound (99) therefore entails reduction of (95) with lithium in ammonia in the absence of alcohol, followed by quenching with ammonium chloride. Acid (99) is also susceptible to rearrangement under acidic conditions, however, and the isomer (100) is formed at pH 4-5 (conditions which might readily prevail during the isolation procedure). 3-Methoxybenzoic acid (95) undergoes reductive alkylation at C-1 without difficulty, and has been used extensively in synthesis. 

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