| 86% |
Stage #1: 4-(2-naphthyl)-4-oxobutyric acid With hydrazine hydrate In diethylene glycol at 100℃; for 1h; Inert atmosphere;
Stage #2: With potassium hydroxide In diethylene glycol at 200℃; for 2h; Inert atmosphere; |
1 Synthesis of Compound 5:
Under the protection of nitrogen, Compound 4 (2.6g, 10.9mmol, 1.0eq.), diethylene glycol (60mL) and hydrazine hydrate (2mL, 38.5mmol, 3.5eq.) were added to a 100mL flask, heated to 100 °C for 1h, and then added potassium hydroxide solids (1.46g, 36.3mmol, 3.3eq.), and then heated up to 200 °C for 2h. After cooling to room temperature, adding water (30mL) and 6mol/L hydrochloric acid (30mL) had a white precipitate precipitate, filtered to give Compound 5 (white solid powder, 2.1g), yield 86% |
| 85% |
Stage #1: 4-(2-naphthyl)-4-oxobutyric acid With hydrazine hydrate In diethylene glycol at 100℃; for 1h; Inert atmosphere; Glovebox; Schlenk technique;
Stage #2: With potassium hydroxide In diethylene glycol at 260℃; for 2h; Inert atmosphere; Glovebox; Schlenk technique; |
|
| 76% |
With potassium hydroxide; hydrazine hydrate In diethylene glycol at 200℃; for 6h; |
|
| 73% |
With 10 wt% Pd(OH)2 on carbon; hydrogen In acetic acid at 20℃; for 48h; |
|
| 42% |
With hydrazine hydrate; potassium hydroxide In diethylene glycol at 100 - 230℃; for 1.66667h; Inert atmosphere; |
8 Example 8: Synthesis of Compound 14( 4-(naphthalen-2-yl)butanoic acid)
A two-necked flask was dried under vacuum, followed bybeing filled with nitrogen gas. The compound 13 (228 mg,1 mmol), hydrazine (0.05 mL, 1 mmol) and potassiumhydroxide (190 mg, 1.3 mmol) were dissolved in bis(2-hydroxy-ethyl) ether (1.7 mL), followed by heating to 100°C. for 100 minutes in an oil bath. Then, the flask wasremoved from the oil bath, followed by vacuum for 2-3hours. The flask was then filled with nitrogen gas and heatedto 230° C. for 5 hours. After the flask was cooled down, itwas then placed in an ice bath. The reaction mixture wasthen washed by hydrochloric acid (15 mL, 6N) for severaltimes to obtain a crude product. The crude product was then extracted by ether (100 mL) to collect the organic layer. Thecollected organic layer was dried by adding magnesiumsulfate, followed by condensation by a rotary evaporator.The resulting product was then recrystallized with cyclohexaneto obtain the compound 14 (90 mg, yield: 42%). The above reaction is represented by the chemical equation (2-1 ).Spectral data as follow: M.W.: 214.26; 1H NMR (400MHz, CDC13 ) o 7.79 (t, 1=8.5, 3H), 7.62 (s, lH), 7.45-7.41(m, 2H), 7.33 (d, 1=8.2, lH), 2.84 (t, 1=7.4, 2H), 2.41 (t,1=7.4, 2H), 2.06 (t, 1=7.4, 2H); 13C NMR (100 MHz CDC13 ) o 179.29, 138.69, 137.33, 133.63, 132.15, 128.82,128.07, 127.63, 127.47, 127.20, 126.94, 126.65, 126.23,125.99, 125.93, 125.54, 125.51, 125.28, 123.71, 35.16,33.57, 33.26, 32.21, 26.09, 25.51 |
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With hydrogenchloride; amalgamated zinc; acetic acid weiteres Reagens: Toluol; |
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With hydrogenchloride; amalgamated zinc |
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With hydrazine hydrate; diethylene glycol |
|
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With sodium hydroxide; hydrazine hydrate In diethylene glycol at 200 - 220℃; |
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With hydrogenchloride; mercury; zinc Yield given; |
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With potassium hydroxide; hydrazine hydrate In diethylene glycol |
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With potassium hydroxide; hydrazine hydrate In ethylene glycol for 1.5h; Heating; |
|
| 94.9% by weight |
With potassium hydroxide; hydrazine hydrate In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol |
1.ii Preparation of the compound having the formula STR3
(ii) To 300 ml of triethylene glycol contained in a 1-liter, 3-neck flask equipped with a magnetic stirrer, thermometer and take-off condenser was added 77.0 g (0.34 mole) of 4-(2-naphthyl)-4-oxobutyric acid, 61.2 g (1.09 moles) potassium hydroxide pellets and 45.44 ml of hydrazine monohydrate. The reaction mixture was heated up to 100°-110° C. with stirring and held there for 90 minutes. The temperature was gradually increased to 195° C. over 4 hours. Strong gas evolution commenced at about 130° C. with some distillate coming over above 140° C. The reaction mixture was allowed to cool and then stirred at room temperature overnight. Next morning the reaction mixture was diluted with ice water and while cooling in ice was acidified with conc. hydrochloric acid. The white solids were collected by filtration, washed with warm water and air-dried to yield 69.0 g (94.9% by weight yield) of γ-(2-naphthyl) butyric acid. M.P. 96°-99° C.; M/e 214; λmax 276 (5,580) ethanol. |
| 94.9% by weight |
With potassium hydroxide; hydrazine hydrate In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol |
2.ii Preparation of the compound having the formula STR4
(ii) To 300 ml of triethylene glycol contained in a 1-liter, 3-neck flask equipped with a magnetic stirrer, thermometer and take-off condenser was added 77.0 g (0.34 mole) of 4-(2-naphthyl)-4-oxobutyric acid, 61.2 g (1.09 moles) potassium hydroxide pellets and 45.44 ml of hydrazine monohydrate. The reaction mixture was heated up to 100°-110° C. with stirring and held there for 90 minutes. The temperature was gradually increased to 195° C. over 4 hours. Strong gas evolution commenced at about 130° C with some distillate coming over above 140° C. The reaction mixture was allowed to cool and then stirred at room temperature overnight. Next morning the reaction mixture was diluted with ice water and while cooling in ice was acidified with conc. hydrochloric acid. The white solids were collected by filtration, washed with warm water and air-dried to yield 69.0 g (94.9% by weight yield) of γ-(2-naphthyl) butyric acid. M.P. 96°- 99° C.; M/e 214; λmax 276 (5,580) ethanol. |
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