Silica-gel column chromatography

MICROWAVE-ASSISTED SOLVENT EXTRACTION AND A NEW METHOD FOR ISOLATION OF TOTAL PETROLEUM HYDROCARBONS (TPH) FROM PLANTS WITH COLUMN CHROMATOGRAPHY (SILICA GEL AND ALUMINA) AND DETERMINATION WITH SPECTROFLUOROPHOTOMETRY... 

Olmethyl-3-methoxy-3-phenyl-l-(2,6-dimethyiphenyi)-lH>lmldazo(l,2 b) pyrrazol-2(3H)-one (3) Phosphorane 2 (t 48 g 3 mmol) and 2 6 dimethylphenylisocya-nate 3 (0 59 g 4 mmol) in PhMe (30 mL) was heated under reflux with stimng for 16 h (TLC EtOAc hexane I 6) Evaporation and column chromatography (silica gel EtOAc/hexane 1 6) afforded crude 4 Recrysiallization from EtaO petroleum ether gave 0 930 g (66%) mp 126 5 130"C... 

The next step yields 1-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester. L-proline tert-butyl ester (5.1 g) is dissolved in dichloromethane (40 ml) and the solution stirred and chilled in an ice bath. Dicyclohexylcarbodiimide (15 ml) is added followed immediately by a solution of 3-acetylthio-2-methylpropanoic acid (4.9 g) in dichloromethane (5 ml). After 15 minutes stirring in the ice bath and 16 hours at room temperature, the precipitate is filtered off and the filtrate is concentrated to dryness in vacuo. The residue is dissolved in ethyl acetate and washed neutral. The organic phase is dried over magnesium suifateand concentrated to dryness in vacuo. The residue 1-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester is purified by column chromatography (silica gel-chloroform), yield 7.9 g. 

Ben2yloxyindolyl-3)-Q -acetvlamino-Q -methylthiopropionic acid methanethiol ester (449 mg) was added to 10 ml of ethanol and further 1 ml of triethylamine was added to the mixture. Then, the reaction mixture was refluxed for 17 hours, after condensation under reduced pressure and subsequent separation of the residue by column chromatography (silica gel, ethyl acetate), 353 mg of methyl -(5-benzyloxyindolyl-3)-Q -acetylamino-Q -methylthio-propionate was obtained as colorless glasslike substance in the yield of 81.5%. Recrystallization of the substance from methanol water afforded 287 mg of crystals. 

Raney nickel (3.5 cc) was suspended in 10 ml of ethanol and 356 mg of methyl -(5-ben2yl-oxyindolyl-3)-a -aminoacetyl-a -methylthiopropionate was added to the mixture together with 20 ml of ethanol. Then, the reaction mixture was stirred for 1 hour at room temperature and thereafter filtered to remove insoluble substances. The residue was washed with 100 ml of ethanol and 50 ml of acetone and both the filtrate and the wash liquid were combined and concentrated under reduced pressure. By column chromatography (silica gel and acetone), 210 mg of methyl -(5-hydroxyindolyl-3)-0 -acetylaminopropionate as colorless glasslike substance in the yield of 90%. 

A solution of dimethyl 3-acetyl-3-azatetracyclo[3.2.0.02-7.04 6]heptane-l,5-dicarboxylate (2, R1 = Ac R = H), formed by the photolysis (14 h 125-W Hg lamp under N2) of dimethyl 7-acetyl-7-azabicyclo-[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (1 R1 = Ac, R2 = H 1 g, 4mmol) in Et20 (400 mL) at — 40 C, was evaporated to dryness under reduced pressure. The residue (0.7 g, 2.8 mmol) was dissolved in CHC1, and the solution heated under reflux for 1 h. Evaporation of the solvent yielded the crude product which was purified by column chromatography (silica gel, C,H2C12). The yellow fractions were collected and, after removal of the solvent, the residual oil was distilled in a sublimation apparatus to give 3 (R1 = Ac R2 = H) as a yellow oil yield 0.8 g (80%) bp 50 60 C/5 x 10 4 Torr. 

Hematoporphyrin dimethyl ester (15, 1.52 g, 2.43 mmol) (diastereomeric mixture) and Af.At-dimethyl-acetamide dimethyl acetal (8 mL) were suspended in o-xylcnc (100 mL), degassed and then heated with exclusion of light in a flask equipped with a reflux condenser and a Soxhlet apparatus containing 3 A molecular sieves. The temperature was raised during 15 min from rt to 115 C and kept at this temperature for 30 min. Then the temperature was raised to 155 C and the mixture kept at this temperature for 3 h. The mixture was evaporated in a bulb tube and the residue subjected to column chromatography [silica gel (ICN), CH2Cl2/MeOAc/MeOH 10 5 0.5] with exclusion of light yield of pure 16A 305 mg (17 %) yield of pure 16B, 375 mg (20%) and 187 mg (10%) of a mixture of 16 A and B. 

A solution of racemic 3-(2-ethylhexyIoxy)phthaIonitriIe (5 2 g, 7.8 mmol) in 2-(dimcthylainino)cthanol was heated with NiCl2 (0.26 g, 2 mmol) for 24 h at 140 C. The solvent was distilled off under vacuum and the product was purified several times by column chromatography (silica gel, toluene/hexane 7 3). A dark-blue solid was obtained yield 0.22 g (10%). 

A mixture of4-(dodecylsulfanyl)phthalonitrile(9, R = SC,2H25 0.25 g, 0.76 mmol), anhyd NiCI2 (0.028 g, 0.22 mmol) and quinoline (0.4 mL) was heated and stirred at 200 C for 5h under argon. After cooling to rt, the mixture was treated with EtOH (5 mL), filtered, and washed successively with the same solvent. Isolation of the metal phthalocyanine was carried out using column chromatography (silica gel, hexane/ CH2C12 5 3) yield 0.067 g (26%). 

A mixture of 3,6-diheptylphthalonitrile (324 mg, 1 mmol), Ni(OAc)2 4H20 (75 mg. 0.3 mmol) and DBU (152 mg, 1 mmol) was refluxed under N2 in pentan-1-ol (15 mL) for 48 h. The cooled solution was poured into MeOH (50 mL) and the precipitate was centrifuged, washed wilh F.tOAc and F.tOH, and dried. Further purification was carried out using column chromatography (silica gel. toluene) and rccrystallization from EtOAc yield 68 mg (20%). 

A mixture of 3,4,5,6-tetra(2,2,2-trifluoroelhoxy)phthalonitrile (0.52 g, 1.0 mmol) and NiCl2 (43 mg, 0.33 mmol) in freshly distilled Me2N(CH2)2OH (10 mL) was refluxed for 48 h under dry N2. The product was precipitated by adding dil aq NaCl, and then was washed with H20, collected and purified by column chromatography (silica gel, hexane/CII2Cl2 1 1). After evaporation of the solvent, the product was dried for 6 h at 50 C in vacuo yield 64 mg (12%). 

A mixture of l,4-di(hexyloxy)naphthalene-2,3-dicarbonitrile (756 mg, 2 mmol), Ni(OAc)2 (175 mg, 0.7 mmol), and DBU (1.5 mL) in hexan-l-ol (25 mL) was heated under N2 for 24 h under reflux. The cooled green-brown solution was poured into MeOH/H20 (1 1,150 mL) and the precipitate formed was filtered, washed with MeOH, and dried in vacuo. Further purification was achieved by column chromatography (silica gel, CHC13) in the dark to yield the title compound as a light-brown powder yield 480 mg (61 %). 

A mixture of benzo[/]isoindolinediimine (1.5g, 7.7 mmol), RuClj 3H20 (500mg, 1.9 mmol), DBU (1.02 g, 1 mL, 6.5 mmol), and 2-ethoxyethanol (30 mL) was refluxed for 24 h. After cooling, the mixture was poured into McOH and the precipitate was filtered, dried, and washed with hexane. The residue was stirred in pyridine for 1 h at 100 C. Excess solvent was removed at reduced pressure and the crude product was purified by column chromatography (silica gel. CHCI,) and dried at 100 C/0.01 Torr yield 610 mg (67%). 

A suspension of Li metal (0.02 g, 2.9 mmol) in octan-l-ol (3.0 mL) was heated to 170 C and stirred until a homogeneous solution was obtained. The solution was cooled to 20 C and 3-neopentyloxyphthalonitrile (150 mg, 0.7 mmol) in THF (1 mL) was added. The mixture was stirred for 7 10 d, after which excess Zn(OAc)2 was added and the mixture stirred for another 2 3 d. The reaction was quenched with McOH/ H20 (1 1) and washed with MeOH. The crude products were purified by column chromatography (silica gel) and the title compound was obtained as a blue solid yield 28 mg (18%). 

A suspension of hydroxyboron 2,9,16-triiodosubphthalocyaninc (208mg. 0.26 mmol) and Et3SiOH (1.7 mL) in PhCl (13 mL) was heated at reflux for 2.5 h. The precipitate obtained was filtered and purified by column chromatography (silica gel, EtOAc/hexane 10 1) yield 119 mg (50%). 

A mixture of 1.4 g (10 mmol) of 4-chlorobenzaldehyde and 0.71 g (5 mol %) of the chiral polymer E is stirred in 10 mL of dry toluene for 15 h, under a dry nitrogen atmosphere, to form the Schiff base. After cooling to 0lC, 15 mL (15 mmol) of 1 M diethyl/inc in hexane is added and the mixture is stirred for a further 24 h at O C. 1 N HC1 is then added dropwise at O C, and the chiral polymer is removed by filtration. The polymer is washed several times with 11,0 and Et,0. The aqueous layer is separated and extracted with Et20. The combined organic layer is dried over MgS04 and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel, CHC1,) yield 1.61 g (95 %) 99 % ee [a]2,0 —23.9 (r = 4.93, benzene). 

A mixture of 1 g (5.6 mmol) of (1 R,2S)-A -aminoephedrine and 0.67 g (5.6 mmol) of 4-mcthylbenzaldehyde in 100 mL of benzene is refluxed for 3 h using a Dean Stark trap. After removal of the solvent the residue is purified by column chromatography (silica gel, CH2C12) to provide the product yield 1.43 g (91%). (R)-a-Phcnylcthylamine Typical Procedure18 ... 

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