Benzyl Alcohol → Ethylacetamide

関与物質

反応手順

The applicants have previously reported the dehydrogenative coupling of alcohols with amines to form amides, catalyzed by complex 1, with liberation of hydrogen gas (Gunanathan 2007). To explore whether it might be possible to reverse this reaction by the application of hydrogen pressure, complexes 1-4 were tested as catalysts for the hydrogenation of amides. Thus, upon treatment of N-benzyl-2-methoxyacetamide with dihydrogen (10 atm) at 110° C. (bath temperature) in dry THF for 48 h with a catalytic amount of 1 (1 mol %), 62.7% of 2-methoxyethanol and 62.0% of benzyl amine were obtained. Performing the reaction at 140° C. using 1,4-dioxane as solvent did not significantly improve the yield (alcohol yield 66.3%). It was significant that the reaction was selective and the corresponding secondary amine was not observed. Under the same conditions complex 2 was inactive. Remarkably, employing complex 3 (1 mol %) as catalyst, hydrogenation of N-benzyl-2-methoxyacetamide under identical conditions (THF, 110° C.) resulted in the selective formation of 89.2% 2-methoxyethanol and 89.6% benzyl amine (Table 1B, entry 1). Thus, the normally observed C—O hydrogenolysis did not take place at all. Of practical significance, the air-stable complex 4 (which is stable in air for at least two days in solution) in the presence of one equivalent (relative to Ru) of base also efficiently catalyzes the hydrogenation of amides to alcohols and amines, by generation of the catalyst 3 in situ. Thus, upon heating a THF solution of 4 (1 mol %) with KOtBu (1 mol %) and N-benzyl-2-methoxyacetamide (1 mmol) at 110° C. under H2 (10 atm) for 48 h, 80.2% of alcohol and 81.8% of amine were formed. No reaction took place in the absence of base. Hydrogenation of N-hexyl-2-methoxyacetamide catalyzed by 3 yielded 2-methoxy ethanol and hexyl amine in 90.7% and 90.3% yields, respectively (Table 1B, entry 2). N-hexyl-3-methyloxetane-3-carboxamide undergoes hydrogenation to the alcohol and amine without hydrogenolysis of the strained oxetane ring (Table 1B, entry 3). The heterocyclic amide, N-hexylfuran-2-carboxamide was hydrogenated to yield 68.8% of furfuryl alcohol and 68.1% of hexylamine (Table 1B, entry 4). The aromatic non-activated amide, N-benzylbenzamide is also hydrogenated to benzyl alcohol and benzyl amine (Table 1B, entry 5), but the yield is lower, probably because of steric reasons. Significantly, the aliphatic non-activated amides, N-ethylacetamide and N-methylpropionamide also underwent hydrogenation to yield the corresponding alcohols and amines (71% of ethanol and ethylamine for entry 6 and 68.4% of n-propanol and methylamine for entry 7). The product gaseous amines were analyzed by GC-MS spectrometry of the gas phase and not quantified. As expected, the activated amides, anilide derivatives, were converted into their corresponding alcohols and aniline in excellent yields (91-95%; Table 1B, entries 9-12) along with trace amounts of the secondary amines (detected by GC-MS) under similar conditions. The reaction is also effective for bis-amides. Thus, N,N′-(ethane-1,2-diyl)bis(2-methoxyacetamide) (0.5 mmol) was also hydrogenated using catalyst 3 under mild conditions (Table 1B, entry 13). Noteworthy, tent-amides also underwent hydrogenation almost quantitatively to yield alcohols and secondary amines in equivalent amounts (Table 1B, entries 14-16). Gratifyingly, heating a solution of N-formymorpholine (1 mmol) and complex 3 in THF at 110° C. yielded after 32 h 97.1% of methanol and 98.3% of morpholine; no decarbonylation of the formyl group took place (Table 1B, entry 17). These results highlight the substantial scope of the unprecedented, selective hydrogenation of amides catalyzed by 3, or by the air-stable 4 with an equivalent of base (which generates 3 in situ).

情報源と証拠