0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via Variation 1: The Huang-Minlon Modification

DOI: 10.1055/sos-SD-048-00026

Wicha, J.Science of Synthesis, (200948114.

The carbonyl group oxygen atom in aldehydes and ketones is replaced by two hydrogen atoms, via the hydrazone, under various conditions presently associated with the Huang-Minlon modification of the WolffKishner reduction,[‌121‌,‌122‌] which was at first developed for the reduction of 4-oxo-4-(4-phenoxyphenyl)butanoic acid (Table 3, entry 1).[‌108‌] The reagents used are 85% hydrazine hydrate and potassium hydroxide in triethylene glycol, with the temperature increased from reflux to 195°C (with any accumulated water being removed from inside the condenser before the temperature increase). The yield of 4-(4-phenoxyphenyl)butanoic acid is significantly higher than that attainable in the earlier modifications of the WolffKishner reduction or by the Clemmensen reduction (see Section A detailed procedure for the reduction of the oxo group in an oxo diacid is available (entry 2).[‌123‌] 3,4,5-Trimethoxybenzaldehyde is transformed into the corresponding toluene derivative under relatively mild conditions (70°C, then 120°C); the mild conditions presumably result from electronic effects (entry 3).[‌124‌] A specific procedure for the reduction of 2,2,6,6-tetramethylpiperidin-4-one into 2,2,6,6-tetramethylpiperidine using hydrazine hydrate, with a small amount of diethylene glycol mixed with paraffin oil as the solvent, has been developed (entry 4);[‌125‌] the product (and released water) is continuously removed by distillation. WolffKishner reduction of a highly strained cyclopropyl ketone proceeds without cyclopropane ring opening to give the corresponding hydrocarbon in 67% yield (entry 5). It is noteworthy that attempted deoxgenation of this ketone via borane reduction of its tosylhydrazone (see Section affords a product of skeletal rearrangement.[‌126‌,‌127‌] An intermediate in a pheromone synthesis is efficiently deoxygenated using hydrazine hydrate and potassium hydroxide in triethanolamine at 190200°C (entry 6).[‌128‌] A sterically hindered carbaldehyde group can be converted into a methyl group using a large excess of hydrazine hydrate and potassium hydroxide in ethylene glycol (entry 7).[‌129‌] In another example, an amide is transformed into the respective amine (entry 8).[‌130‌] Although heteroaromatic ketones are smoothly reduced under the standard Huang-Minlon conditions,[‌131‌] in certain cases the use of the semicarbazone instead of the hydrazone is advantageous.[‌113‌,‌132‌] For example, reaction of 2-benzoyl-4-phenylquinoline with hydrazine hydrate gives poor results, while the procedure involving isolated semicarbazone 24 provides 2-benzyl-4-phenylquinoline (25) in 64% overall yield (Scheme 29).[‌132‌]

Meeeeeee eeeeeeee eee eeeeeeeeeeee eeeeeee ee eee MeeeeMeeeeee eeeeeeeee.[‌888‌] Meeeeeeee eeeeeeeeeee eeeee eee Meeee-Meeeee eeeeeeeeee ee eeee eeeeeeee.[‌888‌]

Meeee 8 Meeeeeee Meeeeeee ee Mee Meeee-Meeeee Meeeeeeee ee Meeeeeeee eee Meeeeee[‌888‌,‌888‌‌888‌,‌888‌‌888‌]

Meeee M8 M8 Meeeeeeeee Meeee (%) Mee
8 8-MeMM8M8 (MM8)8MM8M 88% M8MMM8M8M (ee. 8 eeeee), MMM (8.8 eeeee), eeeeeeeeeee eeeeee, 888888°M 88 [‌888‌]
8 (MM8)8MM8M (MM8)8MM8M 88% M8MMM8M8M (8.8 eeeee), MMM (8 eeeee), eeeeeeeeee eeeeee, 888888°M (eeeeeeeee eeeeeeeee eee), eeee 888888°M, 8e 8888 [‌888‌]
8 M 8,8,8-(MeM)8M8M8 88% M8MMM8M8M (8 eeeee), MMM (8.8 eeeee), eeeeeeee eeeeee, 88°M, 8e, eeee 888°M, 8e 88 [‌888‌]
8 8. M8MMM8M8M (8.8 eeeee)
8. MMM (8.88 eeeee), eeeeeeeeee eeeeee, eeeeeeee eee, eeeeeeeeeeee
88 [‌888‌]
8 88888% M8MMM8M8M (8.8 eeeee), MMM (8.8 eeeee), eeeeeeeeee eeeeee, 888°M, 8e, eeee 888°M, 8e 88 [‌888‌]
8 M8MMM8M8M (8.8 eeeee), MMM (8.8 eeeee), eeeeeeeeeeeeeee, 888888°M 88 [‌888‌]
8 M 88% M8MMM8M8M (888 eeeee), MMM (88 eeeee), eeeeeeee eeeeee, 888°M, 8e, eeee 888°M, 8e 88 [‌888‌]
8e 8. M8MMM8M8M (8.8 eeeee), eeeeeeee eeeeee, 88°M, 88e
8. MMM (8.8 eeeee), 888°M, 88e
88 [‌888‌]

e Mee eeeeeeee eeeee ee eeeeee ee eeeeeeeeeeeeee eeeeeeeeeee ee ee eeeee eeeee eeeeeeeee. Meeee ee eeeee ee eeee eeeeeeeee.

Meeeee 88 Meeeeeeeeeeee ee e Meeeee eee e Meeeeeeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeeeeeeee)eeeeeeee Meee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee 8-eee-8-(8-eeeeeeeeeeeee)eeeeeeee eeee (888e, 8.88eee), MMM (888e, 8.88eee), 88% M8MMM8M8M (888eM, 8.88eee), eee eeeeeeeeeee eeeeee (8.8M) eee eeeeeeee eee 8.8e. M8M eee eeee eeeeeee eeee eee eeeeeeeee, eee eeeeeeeeeee eee eeeeeee ee eeee ee 888°M (eeeeee), eee eeeeeee eee eeeeeeeee eee 8e. Mee eeeeee eeee eee eeeeeee eeee M8M (8.8M) eee eeeeee eeeeee eeee 8M ee MMe (8.8M). Mee eeeee-eeeeeee eeeee eee eeeeeeeee eee eeeee; eeeee: 888e (88%).

8,8,8,8-Meeeeeeeeeeeeeeeeeeee (Meeee 8, Meeee 8):[‌888‌]

M8MMM8M8M (8.8M, 88eee) eee eeeee eeee 88eee ee eee 8,8,8,8-eeeeeeeeeeeeeeeeeeee-8-eee (ee 8888°M; 8.8ee, 88eee). Mee ee ee eeeeeeeeee eeeeeeee, eee eeeeeeeeeee eeee ee 88°M. Mee eeeeeee, eeeeeeeeeee, eeeee eeeeeee eee eeeeeeeeeeee ee e eeee (88°M) eee eeeeeeeeeee eeeeeeee ee eeeee ee e eeee (8.8e·eee8) eeee e eeee ee MMM (88e, 8.88eee) ee eeeeeeeeee eeeeee (8.88M) eee eeeeeeee eee (88eM) eeeeee ee 888°M. Mee eeeeeee eeeeeee eee M8M eeeeee eeee eeeeeeeeeeee eeeeeee ee eeeeeeeeeeee eeeeeee e 88-ee Meeeeee eeeeee. Mee eeeeeee eeeee eee eeeeeeeee eee eeeeeeeeeee; eeeee: 8.88ee (88%).

Meeeeeeeee[,8.88,8]eeeeee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee eeeeeeeeee ee eeeeeeeeee[,8.88,8]eeeee-8-eee (888ee, 8.8eeee), 88888% M8MMM8M8M (8.8eM, 8eeee), MMM (888ee, 8.8eeee), eee eeeeeeeeee eeeeee (88eM) eee eeeeee ee 888°M eee 8e eee eeee ee 888°M eee 8e. Meeeee eeee eeee, eee eeeeeee eeeeeeee. Mee eeeeeeeee eee eeeeeeeee eeee eeeeeee (88eM) eee eeeee (MeMM8). Mee eeeeeee eee eeeeeeeeee ee eeeeee e eeeee eeeee; eeeee: 888ee (88%).

8-Meeeee-8-eeeeeeeeeeeeeee (88); Meeeeee Meeeeeeee:[‌888‌]

MeMM (888eM) eee eeeee ee e eeee ee eeeeeeeeeeeee eeeeeeeeeeeee (8.8e, 88.8eeee) eee MeMMe8M8M (8.88e, 88.8eeee) ee M8M (88eM). Mee eeee eee eeeeeee eeeeee eee eeee eeeeeeee. 8-Meeeeee-8-eeeeeeeeeeeeeee (8.8e, 88.8eeee) eee eeeee ee eee eee eeeeeeee, eee eee eeeeeee eee eeeeee eeeee eeeeee eee 8e eee eeeeeeeeeeee ee eee eeeeeeee eeeeee ee ee. 88eM. Meeee eeeeeee, eee eeeeeeeeeee eee eeeeeeeee ee eeeeeeeeee eee eeeeee eeee MeMM (88eM) ee eeee eee eeeeeeeeeeeee 88 ee e eeee eeeeee eeeeee; eeeee: 8.88e (88%). Mee eeeeeeeeeeeee 88 (8e, 8.8eeee) eee eeeee ee eeeee eeeeeeee ee e eeee ee MMM (8.8e, 8.8eeee) ee eeeeeeeeee eeeeee (8eM), eeeeeee eeeee eeeee ee 888°M. Mee eeeeeee eee eeeeee ee 888°M eee 8.8e eee eeee ee 888888°M eee 8e, eeeeee, eee eeeeeee eeee M8M (88eM). Mee eeeeeee eee eeeeeeeee eeee eeeeeeeeeee (8×88eM). Mee eeeeeeee eeeeeee eee eeeeee eeee M8M (88eM) eee eeeee (MeMM8). Mee eeeeeee eee eeeeeeeeee ee eeee eeeeee eeeeeeee; eeeee: 8.88e (88%).