Cyano column Chromatography

High performance liquid chromatography-mass spectrometric methods Nitin et al. [75] developed and validated a sensitive and selective liquid chromatography-tandem mass spectrometric method (LC MS MS) for the simultaneous estimation of bulaquine and its metabolites primaquine in monkey plasma. The mobile phase consisted of acetonitrile ammonium acetate buffer (20 mM, pH 6) (50 50, v/v) at a flow rate of 1 mL/min. The chromatographic separations were achieved on two Spheri cyano columns (5 pm, 30 cm x 4.6 mm), connected in... 

Purification by flash column chromatography (heptane/EtOAc 4 1) provided 2-cyano-2-methylnonamide (24 mg, 85 %, 98 % ee) as a white solid. 

The mixture of products was separated by column chromatography on a silica gel column with hexane/ethyl acetate (7 3) as the eluent. (5)-4-Chloro-3-hydroxybutanoate eluted first from the column followed by (5)-4-cyano-3-hydroxybutanoate. 

A mixture of rhodium II) acetate (228 mg, 0.516 mmol), the imidazolidinone (1.70 g, 6.15 mmol), and dry chlorobenzene (20 mL) is heated under reflux for 18 h in a flask fitted with a Soxhlet extraction apparatus into which a thimble is placed containing an oven-dried mixture of sodium carbonate and sand (2 1, 5 g). The progress of the ligand-exchange reaction can be monitored by HPLC (p-Bondapak-CN column, methanol). The resulting blue solution is concentrated under reduced pressure, and the residue is purified by column chromatography (reversed phase silica, Bakerbond Cyano 40 mm prep. LC packing, methanol). 

A mixmre consisting of the Step 7 product (34.5 mmol), 3-cyano-4,5,5-trimethyl-2-(2,2-dicyanovinylidene)-2,5-hydrofuran (41.5 mmol), piperidene (catalytic amount), and 15 ml of CHCI3 were refluxed for 5 hours. The mixture was then purified by flash column chromatography with hexane/EtOAc/CH2Cl2, 4 1.2 4, respectively, and the product was isolated in 45% yield. 

Ethyl 9-bromo-5,6-dihydropyrrolo[l,2-c]quinazoline-2-carboxylate (68) reacted with copper cyanide in dimethylformamide to yield the 9-cyano-5,6-dihydro derivative 69 together with 9-cyanopyrroloquinazoline-2-car-boxylate (70) and the 9-bromo-5,6-dehydro derivative 71, isolated by column chromatography. 

Termite soldiers produce a large number of different chemical defense agents. Several of these molecules are unusual bioactive terpenoids such as the secotrinervitanes that have been isolated and their structure elucidated. In the laboratory of T. Kato, the total synthesis of (+)-3a-acetoxy-7,16-secotrinervita-7,11-dien-15P-ol was accomplished. The Nagata hydrocyanation was used to introduce a carbon at the P-position of a macrocyclic enone intermediate. The substrate was treated with excess diethylaluminum cyanide in dry toluene and the addition resulted in the formation of a 1 1 mixture of diastereomers, which could be readily separated by column chromatography. The cyano group was later converted to the corresponding methyl ester. 

A mixture of 3-cyano-3-methylcyclopropene (0.04 mol) and the amine (0.10 mol) was kept for 7 d at rt in a sealed ampule. For 3-methyl-3-phenyl- and 3-methyl-3-vinylcyclopropenes the reactions were carried out at 60 C and 80 C, respectively, in the presence of NaOMe (0.004 mol). The excess of amine was removed under vacuum and the products were isolated by column chromatography (silica gel). 

Most applications of liquid column chromatography are now made on silica which has been chemically modified (bonded phase chromatography). The modification is made by chemical reaction between the silanol groups and a chlorosilane compound. The carbon radicals of the chlorosilane compound determines the nature of the final column material. Using silanes containing alkyl carbon chains with 8-22 carbon atoms gives the particles hydrophobic surfaces, but more polar surfaces may be obtained by incorporation of alcohol, amino, cyano or other groups in the alkyl chain. 

Optical resolutions of the cyano, nitro and ammine complexes were carried out by column chromatography of SP-Sephadex C-25 in the Na" form. The two enantiomers were separated with 0.05 mol/dm Na2[Sb2(L-tart)2] 2 H2O as eluent. The iso-... 

To a solution of 0.015 mmol aluminum catalyst with (/ )-6,6 -dibromo-3,3 -bis (diphenylphosphinoylmethyl)-2,2 -dihydroxy-l,l -binaphthyl as ligand in CH2CI2 was added 0.6 mmol l-methyl-isoquinoUne in 2.25 mL CH2CI2, followed by 160 ixL TMSCN (1.2 mmol) and 91.8 fiL vinyl chloroformate (1.08 mmol) at —60°C. After 48 h, the reaction was quenched by 5% NH3 aqueous solution, and extracted with EtOAc. Upon removal of solvent under reduced pressure, the reside was purified by column chromatography using hexane/EtOAc as the eluent to afford 91% (+)-l-cyano-l-methyl-l,2-dihydroisoquinoline-2-carboxylic acid vinyl ester as a colorless oil, with 84% e.e. as determined by chiral HPLC analysis. 

At room temperature, 120 mg CuCN (1.3 mmol) was added to a stirred solution of 150 mg (3/ )-6-bromo-7-naphthalen-l-ylmethyl-5-oxo-8-phenyl-2,3-dihydro-57/-thiazolo[3,2-Q ]pyridine-3-carboxylic acid methyl ester (0.30 mmol) in 1.0 mL NMR The mixture was heated at 220°C for 20 min under microwave irradiation, and the solvent was then removed by lyophilization from deionized water. The residue was thoroughly extracted with CH2CI2, dried, and concentrated. Silica gel column chromatography using heptane/EtOAc (1 1) as the eluent afforded 110 mg (3R)-6-cyano-7-naphthalen-l-ylmethyl-5-oxo-8-phenyl-2,3-dihydro-5i/-thiazolo[3,2-o ]pyridine-3-carboxylic acid methyl ester as a white foam, in a yield of 82%. 

Recently, David Tupper [20] has reported the synthesis of 4-cyano p3crazole derivatives by starting with compounds similar to la. These workers have prepared 4-cyano pyrazole derivatives along with 5-amino pyrazole derivative by refluxing 3-dimethylamino-2-benzoyl-propenenitrile la with phenyl hydrazine or hydrazine in ethanol. However, the product was always a mixture of 4-cyano and 5-aminopyrazole derivatives. These workers have separated the mixture of p)rrazoles by column chromatography and observed that the reaction of hydrazine or phenyl hydrazine took place with 3-dimethylamino-2-aroyl-propenenitrile to furnished pyrazole carbonitrile as major and aminop3rrazoles as minor products. 

Typical procedure. Benzyl 7a.-[( R)-l-tert-butyldimethylsilyloxyethyl]-3-cyano-l-oxa-3-ce-phem-4-carboxylate 1463 [1109] To a solution of the oxime 1462 (290 mg) in di-chloromethane (3 mL) were added pyridine (373 mg) and thionyl chloride (187 mg), and the resulting mixture was stirred for 2 h at room temperature. It was then poured into cold 1 n aqueous HCl solution, and extracted with dichloro-methane. The combined organic layers were washed with cold 5% aqueous NaHCOj solution and brine, dried, and concentrated. The residue was purified by column chromatography on silica gel to give nitrile 1463 (290 mg, 100%) IR vmax = 2205, 1792, 1722 cm-i. 

A Hewlett Packard Model 1090 fitted with an automatic injector and an HP 3385A integrator were used with a Shimadzu RF-530 fluorimeter as detector. The excitation and emission wavelengths were 274 and 300 nm, respectively. Separation was effected by reverse-phase chromatography, on a Brownlee 5 p Cyano column (100 x 4.6 mm) fitted with the appropriate guard column (30 x 4.6 mm) using isocratic elution with acetonitrile/ 0.6% phosphoric acid (40 60) at a flow rate of 1.5 mL/min and a temperature of 40 C. Under these conditions the retention time for betaxolol and metoprolol, the internal standard, were 6.3 and 7.1 minutes, respectively. 

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