Methylene Amino acetonitrile

Amino-2-methylpropane, Methylene chloride, 1,3,5-Trifluoro-2,4,6-trinitrobenzene, Potassium hydrogen carbonate, Trifluoroacetic acid, Cyanotrimethylsilane, Nitromethane, Acetonitrile, Sulfuric acid... 

Assuming we have selected the proper mode of chromatography, will the mixture dissolve in the mobile phase Ion-exchange columns must be run in polar-charged solvents. Size separation columns are not, in theory, affected by solvent polarity, and size columns for use in both polar and nonpolar solvents are available. In partition chromatography, we have nonpolar columns that can be run in polar or aqueous solvents, and polar columns that are only run in anhydrous, nonpolar solvents. Intermediate columns such as cyanopropyl or diol can be run in either polar or nonpolar solvents, although often with differing specificity. An amino column (actually a propylamino) acts in methylene chloride/hexane like a less polar silica column but in acetonitrile/water... 

When I make a diagram of column polarities versus solvent polarities, I tend to think of the columns as being a continuous series of increasing polarity from Cis to silica C18, phenyl, C8, cyano, C3, diol, amino, and silica (Fig. 5.5). Under that, I have their solvents in opposite order of polarity from hexane under Ci8 to water under silica hexane, benzene, methylene chloride, chloroform, THF, acetonitrile, i-PrOH, MeOH, and water. The cyano column and THF are about equivalent polarity. In setting up a separation system, we cross over nonpolar columns require polar mobile phase and vice versa to achieve a polarity difference. 

The de novo discovery synthesis of capecitabine (1) was reported by the Nippon Roche Research Center scientists9,19 and was followed up with a preparation invented by a team at the Hoffinann-La Roche laboratories in New Jersey for the conversion to 1 from 5 -DFCR (10).2° In the first route, 5-fluorocytosine (15) was mono-silated using one equivalent of hexamethyldisilazane in toluene at 100 °C followed by stannic chloride-catalyzed glycosidation with known 5-deoxy-l,2,3-tri-0-acetyl-p-D-ribofuranoside (17) in ice-cooled methylene chloride. While this procedure provided the 2, 3 -di-0-acetyl 5-fluorocytidine 18 in 76% yield on a 25-g scale, an alternative method was also devised using in situ-generated trimethylsilyl iodide in acetonitrile at 0°C to provide a 49% yield of 18 on smaller scale. Acylation of the N -amino group of the bis-protected 5 -DFCR derivative was accomplished by the slow addition of two equivalents of -pentyl chloroformate to a solution of 18 in a mixture of pyridine and methylene chloride at -20 °C, followed by a quench with methanol at room temperature to provide the penultimate intermediate 19 on 800-g scale. The yield of intermediate 19 was assumed to be quantitative and was subjected to the final deprotection step, with only a trituration to... 

The silylation of amino acids with BSTFA was studied in detail by Gehrke and coworkers [254—256]. BSTFA—acetonitrile (1 1) was applied first and fourteen amino acids were silylated at 135°C for 15 min. Glu, Arg, Lys, Trp, His and Cys, however, require up to 4 h, in order for measurable peaks to be obtained in the chromatogram. Despite such a long reaction, Gly and Glu gave two peaks and also it was difficult to separate the tris-TMS derivative of Gly from the derivatives of lie and Pro. The influence of polar and non-polar solvents was demonstrated later and was decisive mainly with respect to uniformity of the products. Only the bis-TMS derivative was produced in hexane, methylene chloride, chloroform and 1,2-dichloroethane bis- and tris-derivatives were produced in six more polar solvents. On the other hand, Arg did not provide any peak in the less polar solvents that were used and only one peak in the six more polar solvents. The best and most reproducible results were obtained when silylating seventeen amino acids with BSTFA—acetonitrile (1 1) at 150°C for 15 min 2.5 h at 150°C were necessary for the reproducible derivatization of Gly, Arg, and Glu. These reaction conditions were recommended for the analysis of all twenty amino acids. The TMS derivatives of amino acids were found to be stable on storing them in a sealed vial at room temperature for 8 days, with no decomposition. 

TMS derivatives of amino acids were also combined with other procedures and some difficulties were thus avoided. N-TMS-methyl and -ethyl esters of most protein amino acids were prepared by the action of TMSDEA on alkyl esters of amino acids and were chromatographed on methylsilicone stationary phases [246], Their retention times were found to be 15—20% lower than those of the corresponding TMS derivatives. Despite having an additional step in comparison with direct silylation, the procedure was applied by Hardy and Kerrin [259] to the GC analysis of twenty protein amino acids, including Hypro and CysH. Amino acids were esterified with a 3 N HC1 solution in n-butanol at 150°C for 15 min with subsequent silylation with BSTFA for 90 min at the same temperature. Acetonitrile and methylene chloride were used as solvents for the silylation. In the former solvent double derivatives of Gly and Lys (bis- and tris-) were produced, whereas in the latter the less silylated form only was produced. As Arg, in contrast to direct silylation, also leads to one peak in this instance, methylene chloride is recommended as the silylation solvent. The separation of all twenty amino acids was achieved on a simple column with 2% of OV-7 on GLC-110 textured glass beads (100—120 mesh). 

The special effects of a mesoionic system as a substituent have been noted in the reactions with nucleophiles of 3-7V (4-chloro-3-nitrophenyl)sydnone. A synthesis, using two amino-debromination reactions, has been used to prepare phenothiazines analogous to methylene blue (23). An imusual susceptibihty to the nature of the counteranion has been observed in the kinetics of the reaction of iV-(2,4-dinitrophenyl)-4-dimethylaminopyridinium salts (24) with piperidine in acetonitrile, and may indicate participation of the anion in stabilising the intermediate. An ANRORC mechanism is imphcated in the reaction of A-(2,4-dinitrophenyl)-4-(4-pyridyl)pyridinium cations with arylamines. Ring-opening and ring-closure reactions... 

Die Synthese des 1,3-Thiazol-Geriisles aus N-C und C-S—C-Bausteinen bleibt bisher auf wenige spezielle Falle beschrankt. Nach diesem Aufbauprinzip lassen sich 2-Amino-3-tri-chlormethyl-1,3-thiazole aus m-Thiocyanat-acetophenonen und Trichlor-acetonitril gewin-nen1017. Dabei wird eine primare Addition des CH-aciden Methylen-C-Atoms an die Cyan-Gruppe von Trichlor-acetonitril angenommen z. B. ... 

The synthesis of Trp-P-2[2] started with an intermediate, indole-2-acetonitrile[9](24), prepared from commercially available indole-2-carboxylic acid[87. Vilsmeier reaction(25) of [9], with dimethylacetamideand phosphoryl chloride, gave 3-acetylindole-2-acetonitrile[10]. Cyclization of [10] on treatment with methanolic ammonia and aromatization involving a hydrogen transfer of the a-methylene group yielded the desired 3-amino-l-methyl-5H-pyrido (4,3b)indole[2] m/e 197(M+) vmax(KBr) 1635,1605 cm l 6 (CD3OD) 2.3(3H,s), 5.92(lH,s), 6.53-7.00(3H,m), 7.35(lH,d). 

Gentamicin, a polyfiinctional amino compound, was determined by using RP-HPLC after labelling with ben-zenesulphonyl chloride [20]. The derivatization reaction was complete in 10 min at 75 °C. The HPLC separation was carried out on a Cjg column with acetonitrile/ methylene dichloride/water/methanol as the mobile phase. Separation of gentamidn isomers was not achieved. 

The diester 23 was hydrolyzed to diacid 24, and then dehydrated to give anhydride 25. Subsequent reaction of this anhydride with amino amide 26 in acetonitrile gave two regioisomeric acid diamides 27 and 28 in the approximate ratio of 10 to 1. Pure 27 was isolated in 85% yield by heating the mixture in methylene chloride followed by extraction with 5% aqueous NaOH at room temperature. Treatment of 27 with 5% aqueous NaOH at 80 C then led to cyclization forming the desired imidazolinone 5. Its structure was confirmed by spectroscopic data and elemental analysis. 

In 1991, Wright et al. reported a procedure for the preparation of substituted 1-benzyl-1//-1,2,3-triazoles 21 and 23 from benzyl azides 20 under very mild conditions (Scheme 4.7) [9]. Benzyl azides 20 reacted with active methylene compounds in DMSO induced by potassium carbonate at 35-40 C to give 1-benzyl-1//-1,2,3-triazoles 21 and 23 usually in good yield. Acetonitrile derivatives 10 gave 5-amino-l-benzyl-l//-l,2,3-triazoles 21, whereas diethyl malonate gave 5-hydroxy-l-benzyl-l//-l,2,3-triazoles. l//-l,2,3-Triazole-4-carboxylate esters and l//-l,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and P-diketones, respectively. Benzyl methyl ketone reacted to give a 5-methyl-4-phenyl-l//-l,2,3-triazole, but acetone and acetophenone failed to react. Other active methylene compounds that did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate, and ethyl nitroacetate. 

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