Facile Synthesis of Functionalized Isoxazole and Pyrazole Precursors
2037
Preparation of the 3-(N,N-dimethylhydrazone) of 2,3,5-hexanetrione
(7). To a solution of 2.21 g (0.02 mol) of hex-3-yne-2,5-dione (2)[6] in
50 mL of carbon tetrachloride, which had been cooled to 210 8C, 1.53 mL
(0.02 mol) of 1,1-dimethyl hydrazine in 10 mL of carbon tetrachloride was
added over a 15-min period. After the addition, the solvent was removed
under vacuum. The tarry product was purified via a short-path filtration on
silica gel using diethyl ether as the eluent to yield 1.64 g of the hydrazone 7
1
in a 48% yield. The hydrazone 7 had H NMR (CCl4) d 2.12 (s, 3H), 2.22
(s, 3H), 3.00 (s, 6H), 3.53 (s, 2H); IR (film) 5.81 (s), 6.02 (s), 6.41 (s), 7.35
1
(m) mm. A H NMR spectrum taken immediately after the addition showed
the presence of the ene-hydrazine 6. The ene-hydrazine 6 had the following
1
properties: H NMR (CCl4) d 2.03 (s, 3H), 2.30 (s, 3H), 2.57 (s, 6H), 4.87
(s, 1H). The NH resonance was not observed.
Preparation of 3-(N,N,N-trimethylhydrazone)-2,3,5-hexanetrione tri-
fluorosulphonium salt (8). Under a nitrogen atmosphere, a solution of
1.61 g (9.46 mmol) of the hydrazone 7 in 30 mL of anhydrous diethyl ether
was cooled to –10 8C and 1.07 mL (9.46 mmol) of methyl triflate in 5 mL of
anhydrous ether was added. Cooling was removed and the reaction was
held for 1.5 h at room temperature. A filtration was followed by evaporation
of the solvent. Methylene chloride was added and the product was filtered
to yield 1.19 g (38% yield) of the triflate salt 8 as a white solid. An analytical
sample was prepared by recrystallization from a solvent mixture of 75%
benzene and 25% acetone. The triflate salt 8 had the following properties:
mp 166.5–1678C; anal. calcd. for C10H17F3N2O5S: C, 35.93; H, 5.13; N,
8.38; S, 9.59. Found: C, 35.64; H, 4.87; N, 8.19; S, 9.85. 1H NMR
(CD3CN) d 1.60 (s, 3H), 2.20 (s, 3H), 3.33 (s, 9H), 5.87 (s, 1H), 5.97
(s, 1H); 13C NMR (CD3CN) d 16.96, 25.09, 94.37, 111.39, 120.54 (q, CF3),
176.27, 184.51; IR (KBr) 2.99 (m), 6.02 (w), 6.33 (s), 7.25 (s), 9.43 (m) mm.
Base-catalyzed elimination of the triflate salt (8). To 0.33 g (1.00 mmol)
of the triflate salt 8 in 5 mL of acetonitrile, 157 mL (2.00 mmol) of freshly
distilled t-butyl amine was added. The solution was held for two days at
room temperature. Water and ether were added and the layers were
separated. The ether layer was washed with 5% hydrochloric acid, saturated
sodium bicarbonate solution, and saturated sodium chloride solution. The
ether layer was dried over magnesium sulfate and the solvent was removed
at atmospheric pressure to yield 0.0620 g (54%) of t-butyl acetamide (9).
The sodium bicarbonate layer was acidified, saturated with solid sodium
chloride, and extracted with ether. Drying over magnesium sulfate was
followed by evaporation of the solvent. A product residue (0.016 g) was
1
obtained that contained (by H NMR) a 50:50 mixture of t-butyl acetamide
(9) (5%) and 3-cyano-2,4-pentanedione (10) (6%).[2]