Calixarene aza-crown ether derivative, its preparation and use as metal ion fluorescent identification agent

[0026] Example 1

[0027] Preparation of 25,27-bis(3-bromopropoxy)-26,28-dihydroxy-5,11,17,23-tetra-tert-butylcalix[4]arene

[0028] Into a vessel equipped with a reflux condenser, acetonitrile (250 ml) dried with anhydrous magnesium sulfate for 24 hours was poured, and then p-tert-butyl calix[4]arene (6.46 g, 10 mmol), 1,3- Dibromopropane (10.2 mL, 100 mmol) and anhydrous potassium carbonate (3.45 g, 25 mmol). Heat and stir to reflux for 48 hours, cool, and rotate to evaporate the solvent acetonitrile under reduced pressure. Trichloromethane (200 ml) was added to the obtained solid, and washed with 5% hydrochloric acid, saturated sodium bicarbonate aqueous solution, and distilled water respectively, and washed three times for each sample, using 100 ml each time. Add 10 grams of anhydrous sodium sulfate to chloroform and dry for 24 hours. The desiccant magnesium sulfate was filtered off, and the solvent chloroform was rotary evaporated under reduced pressure to obtain a white solid (slightly yellow) crude product. According to the ratio of 1 gram of white solid to 27.7 ml of absolute ethanol, add absolute ethanol to the crude white solid product, and stir at reflux for 1 hour. After cooling and suction filtration under reduced pressure, 6.5 g of white solid product was obtained with a yield of 73%. Melting point: 289.4~290.2℃, literature value 288~290℃, same as literature. 1 HNMR(CDCl 3 , 500HZ, δ, ppm): 7.70 (s, 2H, OH), 7.15, 6.88 (s, 4H, ArH each), 4.27 (d, J=13.0Hz, 4H, ArCH 2 Ar), 4.12(t, J=7.8Hz, 4H, OCH 2 CH 2 CH 2 ), 4.01(t, J=8.0Hz, 4H, BrCH 2 CH 2 CH 2 ), 3.35(d, J=13.0Hz, 4H, ArCH 2 Ar), 2.53(m, 4H, BrCH 2 CH 2 CH 2 ), 1.27(s, 18H, CH 3 ), 1.02(s, 18H, CH 3 ). MS(FAB), m/z: 890(M + ).

[0029] Example 2

[0030] Preparation of Ethyl Serine Hydrochloride

[0031]Add re-distilled absolute ethanol (100 ml) to a three-necked flask equipped with a condenser, exhaust gas absorption device and air inlet device. Dry hydrogen chloride was passed through for 1 hour to make the absolute ethanol saturated with hydrogen chloride. Then it was cooled with an ice bath, 3.5 g of serine was added, and hydrogen chloride was continued to stir under the ice bath for 1 hour. Remove the ice bath and heat to reflux for half an hour. Cool, add 10 g of anhydrous magnesium sulfate and dry for 24 hours. Filter off the desiccant, evaporate half of the solvent, and let it stand overnight in the refrigerator to precipitate colorless crystals, filter and vacuum dry, and finally obtain a colorless crystalline product. Melting point: 160~160.8℃, literature value 159~162℃. IR(KBr, ν, cm -1 ): 3384.3, 2975.0, 1978.6, 1746.6, 1583.1. These values ​​are consistent with those reported in the literature.

[0032] Example 3

[0033] Preparation of the compounds of the invention

[0034] Into a container equipped with reflux condenser, pour acetonitrile (200 ml) dried with anhydrous magnesium sulfate for 24 hours, and then add 25,27-bis(3-bromopropoxy)-26,28-dihydroxy-5 , 11,17,23-tetra-tert-butylcalix[4]arene (Example 1, 2 g, 2.24 mmol), anhydrous potassium carbonate (4.03 g, 29.2 mmol). Serine ethyl ester hydrochloride 3.82 g (22.4 mmol), first add 1/3 of the amount, heat to reflux, and then add 1/3 of the amount every 8 hours, and add serine ethyl ester hydrochloride three times in total. After adding the last batch of serine ethyl ester hydrochloride, heating and stirring are refluxed for two days. After cooling, the solvent acetonitrile was evaporated by rotating under reduced pressure. Trichloromethane (100 ml) was added to the obtained solid, and washed with dilute hydrochloric acid, saturated sodium bicarbonate aqueous solution, and distilled water three times respectively. Add 10 grams of anhydrous sodium sulfate to chloroform and dry for 24 hours. The desiccant magnesium sulfate was filtered off, and the solvent chloroform was evaporated under reduced pressure to obtain a white solid. The white solid is purified by silica gel column chromatography, the eluent is selected (volume ratio, petroleum ether: ethyl acetate = 3:1), the second fluorescent point substance is collected, and the solvent is evaporated to dryness to obtain 1 g of crystalline solid product. The rate is 51.8%. Melting point: 268.5~269.2℃; IR(KBr, ν, cm -1 ): 3277.4, 2954.2, 2868.1, 1738.8, 1721.1, 1595.5, 1486.3; HNMR (CDCl 3 , 500HZ, δ, ppm): 1.25(s, 36H, Bu t ), 1.30(t, 3H, N-(CO)-O-C-CH 3 ), 2.23(m, 2H, Ar-O-C-CH 2 -C-N), 2.55(m, 2H, Ar-O-C-CH 2 -C-N), 3.37(d, 2H, Ar-CH 2 -Ar), 3.39(t, 2H, Ar-O-C-C-CH 2 -N), 3.44(d, 2H, Ar-CH 2 -Ar), 3.85(d, 2H, N-C-CH 2 -OH), 3.88(brs, 1H, -N-CH), 3.93(t, 2H, Ar-O-C-C-CH 2 -N), 4.04(t, 2H, Ar-O-CH 2 ), 4.08(t, 2H, Ar-O-CH 2 ), 4.19(d, 2H, Ar-CH 2 -Ar), 4.25(q, 2H, N-(CO)-O-CH 2 ), 4.36(d, 2H, Ar-CH 2 -Ar), 7.01 to 7.12 (m, 8H, Ar-H).