Pyrrole-2-carbonitrile

clear yellow to orange liquid

General procedure: Synthesis of 5-(thiophen-3-yl)-1H-tetrazole (2a). 3-Thiophenecarbonitrile 1a (218 mg, 2 mmol), NaN3 (260 mg, 4 mmol), CeCl3·7H2O (75 mg, 0.2 mmol), and 8 mL of a 3:1isopropanol/water mixture were added to a 30-mL Pyrexmicrowave vessel and capped. The microwave vessel wasthen placed in a multi-mode microwave reactor. The reactionwas magnetically stirred and heated for 1 hour at 160 C.The pressure in the vessel was not determined. The reactionwas monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reactionmixture was diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (2 x 15 mL).The aqueous sodium bicarbonate layer was cooled with iceand acidified to a pH of 2 or less with concentrated hydrochloricacid, which was added drop-wise. The precipitateformed was extracted with ethyl acetate (3 x 15 mL). Thecombined organic layers were dried over anhydrous sodiumsulfate and decanted into a tared round bottom flask. Theorganic layer was concentrated under reduced pressure. Thetetrazole product was recrystallized from ethyl acetate andhexane. All reagents mentioned above were used unpurified.lH-Pyrrole-2-carbonitrile (3.36 g, 36.5 mmole) was dissolved in 100 ml dimethyl- formamide to which potassium carbonate (7.51 g, 54.75 mmole) was added followed EPO Step 11) 1 -amino- lH- (26.71 g, 0.29 mol) was dissolved in anhydrous tetrahydrofuran (600 mL) and the solution was then placed at 0 C to which NaH (60% [w / w] suspended in mineral oil, 13.91 g, 0.35 mol) and stirred at ambient temperature for 1 hour. Next, the mixed solution was again cooled to 0 C, and then O-(2, 4-dinitrophenyl)hydroxylamine (80.61 g, 0.40 mol) was added thereto in portions to obtain a reaction system. The resulting reaction was stirred at ambient temperature overnight. After the reaction was completed, the reaction was quenched with water (300 mL) and extracted with ethyl acetate (300 mL x 6). The organic phases were combined. The combined organic phases were successively dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (EtOAc / PE (v / v) = 1/5) to give the title compound as a yellow oil (19.50 g, 63%).In a 25mL reaction vial, NaH (1370mg, 60%) was slowly added to a solution of At room temperature, 2-cyanopyrrole (10) (1.8 g, 19 mmol) was dissolved in DMF (10 ml)NaH (60%, 1.37 g) was added in portions for 1 hour.A solution of ammonium chloride (homemade, 195 ml) was added dropwise to the reaction solution overnight.After stopping the reaction, The reaction solution was filtered, The filtrate was concentrated to remove most of the ether, Add ice water, Ethyl acetate extraction (30 ml * 4)Dried over anhydrous sodium sulfate, The product was purified by column chromatography (petroleum ether: ethyl acetate 8: 1) to give the product (1.122 g, 53.7%).00229] Step A. Synthesis of 1 -amino- lH-pyrrole-2-carboxamide: To a solution of lH-General procedure: A mixture of aldoximes (1 mmol) and imidazole (3 mmol) in anhydrous DCM (10-15 mL) was charged into an oven-dried round-bottom flask under nitrogen and the reaction mixture was stirred at r.t. for 20 min, after which triflic anhydride (0.4-1.0 mmol) was added dropwise via syringe under nitrogen, and the reaction mixture was allowed to stir at r.t. for a specific time (Table 1). Progress of the reaction was monitored by TLC and/or by GC-MS. Upon completion, the reaction mixture was quenched with dilute NaHCO3 solution and the product mass was extracted in DCM. The solvent was removed under reduced pressure to yield the crude product which was purified by prep TLC (ethyl acetate-hexane mixture) (80:20), to give the corresponding nitrile (61-88% yield). The structure of the products was confirmed by comparison of their mp or bp, TLC, IR, GC-MS, 1H NMR and 13C NMR data with authentic samples obtained commercially or prepared by literature methods.General procedure: at room temperature, n-C4F9SO2F (20.0mmol, 2.0equiv.) was slowly dropped via syringe into a solution of substrate 1a (10.0mmol) and 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU, 50.0mmol, 5.0equiv.) in CH2Cl2 (20mL). The resulting solution was stirred at this temperature for 10min. Evaporation under vacuum to remove volatile components offered residue which was purified through silica gel column chromatography (eluted with a mixture of petroleum ether and ethyl acetate), generating nitrile 2a in 95% yield.

Molecular Weight:92.10
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:92.037448136
Monoisotopic Mass:92.037448136
Topological Polar Surface Area:39.6
Heavy Atom Count:7
Complexity:99.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes