Cyanoethylation of Alpha Amino Acids. I. Monocyanoethyl Derivatives²

Study of the Chemoselectivity of Grignard Reagent Addition to Substrates Containing Both Nitrile and Weinreb Amide Functionalities

“…to a stirred solution of N-(2-cyanoethyl)glycine [13] (1 g, 7.81 mmol) in dioxane/water (2:1, 25 mL) maintaining the pH at 9-10 at 0°C. The mixture was heated to 45°C and stirred for 2 h. The reaction mixture was cooled to 0°C, N,O-dimethylhydroxylamine hydrochloride (1.10 mmol) and triethylamine (2.50 mmol) were added and the reaction mixture was allowed to warm to room temperature and stirred for 2 h. It was then diluted with DCM (10 mL) and washed with saturated aq.…”

“…The organic material was extracted with EtOAc (2 ϫ 15 mL) and the combined organic layers were washed with water (5 ϫ 15 mL) to remove DMF, dried with Na 2 SO 4 13 The reaction mixture was allowed to warm to room temperature and stirred for 2 h. Upon completion of the starting material, as revealed by TLC, the organic materials were extracted with DCM (2 ϫ 20 mL). The reaction mixture was stirred for 0.5 h at room temperature and then quenched with a saturated ammonium chloride solution.…”

“…13 N-(Cyanomethyl)-N-[2-oxo-2-(thiophen-2-yl) 13 The reaction mixture was stirred for 0.5 h at 0°C and then allowed to warm to room temperature.…”

Effects of Alkyl Nitriles on the Gastrointestinal Tract

“…[62] with 1-I4C-and 2,3-l4C-acrylonitrile suggest that the highest level of radioactivity after the admin istration of either of these compounds is re covered from the GI tract [62,63], A good part of this radioactivity, especially after 2,3-l4C-acrylonitrile is irreversible, covalentlybound to tissue macromolecules [62][63][64], We suggested earlier, after detecting a dose-and time-dependent depletion of GSH in several organs after injection of acrylonitrile, that the acute toxicity of this chemical might be at tributed to its irreversible binding with cellu lar nucleophiles such as sulfhydryls [51]. Acrylonitrile-initiated cyanoethylation of amino acids has been detected in vitro [65], and irreversible binding to several proteins in in vivo experiments has been recently de scribed [66,67]. Data from several laborato ries indicate that probably a metabolically modified form of acrylonitrile, most likely the vinyl moiety, similar to the vinyl chloride molecule, would participate in the covalent bond [67.…”

Studies on pyrrolidinones. Michael reaction of glutamic acid and diethylglutamate

“…In 1950, McKinney et a1 described the addition of eleven aminoacids to acrylonitrile, and the hydrolysis of seven of the obtained cyanoethylaminoacids 6 to the diacids 7; in this sequence, glutamic acid (2) yielded N-(cya-noethy1)pyroglutamic acid (8). But curiously, McKinney does not describe the diacid 9 [4,5] (Scheme 2).…”