APPLICATION
TCI Practical Example: Condensation using 1,1'-Carbonyldiimidazole
Used Chemicals
N-Carbobenzoxyglycine [C0575]
1,1'-Carbonyldiimidazole [C0119]
Anhydrous tetrahydrofuran
L-Tyrosine ethyl ester [T0551]
Procedure
To a solution of N-carbobenzoxyglycine (2.10 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) was added 1,1'-carbonyldiimidazole (1.64 g, 10 mmol). The mixture was stirred at room temperature for 4 hours. L-tyrosine ethyl ester (2.10 g, 10 mmol) was added to the reaction mixture. The mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), treated with 1 mol/L HCl solution (50 mL), and stirred for 10 min. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (20 mL x 2). The combined organic layers were washed with saturated aqueous NaHCO3 solution (30 mL), washed with brine (30 mL), dried over Na2SO4 and filtered. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (eluent: dichloromethane/ethyl acetate, 90/10→75/25→50/50) to obtain 1 as a white solid (3.54 g, 88%).
Experimenter's Comments
The reaction mixture was monitored by TLC (hexane/ethyl acetate = 5/1, Rf = 0.17) and 1H NMR. After the reaction mixture was concentrated and quenched by 1 mol/L HCl solution, the recrystallization with ethanol was conducted. Sticky white solid was precipitated at low temperature but it can't be filtered.
Analytical Data（Compound 1）
1H NMR (400 MHz, CDCl3); δ 7.35 (m, 5H), 6.92 (d, J =8.24 Hz, 2H), 6.67(dd, 3J =8.24 Hz, 4J =1.83 Hz, 2H), 6.45(d, J =6.87 Hz, 1H), 5.69 (s, 1H), 5.40 (br s, 1H), 5.12 (s, 2H), 4.81(q, J =5.95 Hz, 1H), 4.18 (q, J =7.32 Hz, 2H), 3.84 (m, 2H), 3.03 (m, 2H), 1.27 (t, J=7.32 Hz, 4H)
13C NMR (101 MHz, CDCl3); δ 171.55, 168.74, 156.61, 155.24, 135.99, 130.50, 130.39, 128.57, 128.29, 128.14, 126.93, 115.52, 115.37, 67.30, 61.78, 61.50, 53.16, 44.31, 36.95, 14.17, 14.07.
Lead Reference
N,N'-Carbonyldiimidazole, a New Peptide Forming Reagent
R. Paul, G. W. Anderson, J. Am. Chem. Soc. 1960, 82, 4596.
Application
Condensation of Amino Acides Using 1,1’- Carbonyldiimidazole
Typical Procedure:
To a solution of N-Cbz-glycine (2.09 g, 0.010 mol) in dry THF (10 mL) is added 1,1’-carbonyldiimidazole (CDI) (1.62 g, 0.010 mol). After stirring for 1.5 hour, L-tyrosine ethyl ester (2.09 g, 0.010 mol) is added to the solution and the reaction mixture is stirred overnight. Then THF is removed by an evaporator and 1 N-HCl (50 mL) is added. Cooling of the solution gives a solid. This is washed with water and 5% NaHCO3. The solid is filtered and washed with water again. After drying, the product is recrystallized from 50% ethanol to give ethyl N-Cbz-glycine- L -tyrosine ethyl ester (3.79 g, yield 95%).
![1,1'-Carbonyldiimidazole [Coupling Agent for Peptides Synthesis], CAS RN: 530-62-1, Product Number: C0119](https://content.labscoop.com/products/0ff31cda-914c-44c2-98d5-0ab210f61f0e/xrPoNC0119.jpg)
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