Silica-gel 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... 

R,5S,6R)-4-(t-Butoxycarbonyl)-5,6-dlphenyl-3>[(sthoxycarbonyt)methyl]-2,3,5,6-tetrahydro-4H-oxazln-2-one (6) To a stirred solution of erode 4 (226 mg 0 48 mmoQ m CH2CI2 (11 mL) was added ketene acetal 5 (450 mg, 2 42 mmol) followed by addition of 2nCl2 (575 mL, 0 44 mmol, 0 76M m THF) Alter 4 min ( was quenched with water Radial chromatography (silica gel EtOAc hexane 1 4) afforded 179 mg of 6 (78%)... 

Chromoionophore I [ETH 5294] [9-diethylamino-5-octadecanoyl-imino-5-//-benzo[a]-phenoxazine] [125829-24-5] M 583.9. Purified by flash chromatography (Silica Gel) and eluted with EtOAc. The coloured fractions are pooled, evaporated and recrystd from EtOAc. It is a lipophilic chromoionophore and is a selectophore for K and Ca ions. [Anal Chem 62 738 7990.]... 

To a solution of m-ethyl cinnamate (44, 352 mg, 85% pure, 1.70 mmol) and 4-phenylpyridine-A-oxide (85.5 mg, 29 mol%) in 1,2-dichloromethane (4.0 mL) was added catalyst 12 (38.0 mg, 3.5 mol%). The resulting brown solution was cooled to 4°C and then combined with 4.0 mL (8.9 mmol) of pre-cooled bleach solution. The two-phase mixture was stirred for 12 h at 4°C. The reaction mixture was diluted with methyl-t-butyl ether (40 mL) and the organic phase separated, washed with water (2 x 40 mL), brine (40 mL), and then dried over Na2S04. The drying agent was removed by filtration the mother liquors concentrated under reduce pressure. The resulting residue was purified by flash chromatography (silica gel, pet ether/ether = 87 13 v/v) to afford a fraction enriched in cis-epoxide (45, cis/trans . 96 4, 215 mg) and a fraction enriched in trans-epoxide cis/trans 13 87, 54 mg). The combined yield of pure epoxides was 83%. ee of the cis-epoxide was determined to be 92% and the trans-epoxide to be 65%. 

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. 

A solution of 2 -(bromomethyl)biphenyl-2-carbaldehyde (45 1 g 3.6 mmol) and 25 % aq NH3 (20 mL) in EtOH (100 mL) was heated under reflux for 5 h. The mixture was cooled and stirred for 15 min with 10% aq NaOH (20 mL). The basic solution was extracted with CH2C12, the extract dried, and the solvent evaporated to give the product as an oil which was purified by flash chromatography (silica gel, Et20/ hexane) yield 0.667 g (95%) mp 84-85 C... 

A stirred solution of the benzothiazepinone 2 (6.0 g, 33.9 mmol) in CH2C12 (200 mL) was treated with trimethyloxonium tetrafluoroborate (5.4 g, 36.5 mmol) and the mixture was stirred for 22 h. An excess of coned aq K2C03 was added, the mixture was filtered and the organic layer was separated and dried. Evaporation, followed by chromatography (silica gel, CH2C12) gave 6 as a yellow oil yield 5.8 g (89%). 

The sodium salt of the tosylhydrazone of 2-(diphcnylmethylene)cyclopentanone (4.99 g, 11 mmol) was boiled under reflux with cyclohexane (150mL) for 25 h and the precipitated sodium p-toluenesulfinate was filtered off. The filtrate was evaporated under reduced pressure and the residue was crystallized (EtOH) to give the product (2.38 g). An additional 0.13 g (total yield 80%) was obtained from the filtrate by chromatography (silica gel) yellow crystals mp 159-160 °C. 

A solution of a benzene-1,2-diaminc (15mmol) and an cnol ether 4 (15mmol) in o-xylene (lOmL) was heated in a domestic microwave oven for a specified time. The reaction mixture was cooled and evaporated under reduced pressure, and the residue was purified by chromatography (silica gel. hexane/ CHCl3 1 4). 

Tris(/m-butylsulfanyl)cyclopropeny]ium perchlorate (17 0.403 g, 1 mmol) in DMF (lOmL) was added dropwisc to a solution of benzene-1.2-diamine (0.216 g. 2 mmol) in DMF (20 mL). The mixture was stirred for 2 h and then poured into H20 (200 mL) containing NaCl. Extraction with Et20/hexane (1 1), followed by drying, evaporation in vacuo, chromatography (silica gel, Et20/hexane 1 2) and reerystallization (MeOH) gave the product yield 0.200 g (63%) pale-yellow crystals mp 136 C. 

Method A MsOH (0.96 g, 10 mmol) was added to a suspension of salicylohydrazide (1 1.52 g, 10 mmol) in toluene (50 mL) and the mixture was stirred for 10 min. An acid chloride or anhydride (10 mmol) was added and the mixture was heated under reflux for a specified time. The mixture was cooled, neutralized with sat. aq NaHCO, and the layers were separated. The aqueous layer was extracted with CH2C12 (2 x 20 mL) and the combined organic phases were dried (MgS04) and evaporated in vacuo. Chromatography (silica gel, CH2C12) gave the product, which separated from EtOH as colorless crystals. 

Method B A suspension of the hydrazide 1 (1.52 g, 10 mmol) in EtOH (lOmL) was treated with triethyl orthoformate or orthoacetate (lOmmol) and the mixture was refluxed for 17 h. Evaporation, followed by chromatography (silica gel, CH2C1,) gave the product. 

A refluxing solution of 3-phenyl-2//-azirine (0.468 g, 4 mmol) in toluene (10 mL) was treated with 3,6-diphcnyl-l,2.4.5-tetrazine (0.702 g, 3 mmol) in toluene (10 mL) and the solution was boiled under reflux for 22 h. On cooling, the mixture deposited an orange precipitate, which was filtered off and washed with pentane. Further product was obtained from the mother liquor by chromatography (silica gel). The combined solids were recrystallized (benzene/pentane) to give the product yield 0.664 g (68%) orange plates mp 210 C. 

Method A i01 Equivalent amounts of a 1,2,3-benzothiadiazole. sulfur (as S8) and DABCO were added to Decalin (10 mL per gram of benzothiadiazole) and N2 was passed through the mixture. The mixture was heated at 160-190 C until N2 evolution ceased (20-90 min). It was cooled and the Decalin was removed by Kugelrohr distillation at 50 C/0.5 Torr. The residue was twice triturated with CH2C12 and the extracts were combined and filtered from sulfur. Chromatography (silica gel, 1 % EtzO/hcxanc) gave the product. The preparations were carried out on a scale of 0.25-10.0 g benzothiadiazole. 

A solution of 1-phenyl-1//-pyrazolo[3,4-rf]pyridazinc-7-carbonitrilc (150 mg. 0.68 mmol) and A,A-diethyl-prop-l-ynamine(151 mg, 1.36 mmol) in l,4-dioxane(2 mL) was refluxed for 5 h. After cooling, the reaction mixture was poured onto excess ice, and extracted with CHC13. The extract was washed with H20, dried (Na2S04) and concentrated under reduced pressure. Purification by chromatography (silica gel, benzene then bcnzene/EtOAc 20 1) gave, from the benzene eluate, 6-diethylamino-1 -phenyl-1 //-indazole-7-carbo-nitrile [yield 81 mg (39 %) mp 104-105 C (benzene/petroleum ether)] as slightly yellow prisms and, from the second eluate, the diazocine 5 as yellow needles yield 90 mg (40 %) mp 121-122 C (benzene/ petroleum ether). 

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