Uses
2-tert-Butyl-1,1,3,3-tetramethylguanidine (Barton′s base) is an excellent alternative to traditional inorganic bases for promoting the coupling reaction.
Preparation
To an ovendried, 500-mL, three-necked, round-bottomed flask, equipped with a nitrogen inlet with gas bubbler, magnetic stirring bar, thermometer, condenser, and a 250-mL dropping funnel, were added triphosgene (14.8 g, 0.05 mol) and anhydrous toluene (120 mL). The mixture was kept under argon and cooled to ca. 10 C° with the aid of an external ice bath. A solution of N,N,N,N-tetramethylurea (18.0 mL, 0.15 mol) in dry toluene (50 mL) was then slowly added over a period of 30 min. After completion of the addition, the mixture was allowed to warm to ambient temperature, and stirring was continued for a further 1 h. During this time, a white precipitate formed, consisting of the Vilsmeier salt. Then, tert-butylamine (47.3 mL, 0.45 mol) was slowly added to the mixture over a period of 30 min. After completion of the addition, the mixture was heated under reflux for 5 h and then cooled to room temperature. Anhydrous diethyl ether (200 mL) was added and the white precipitate was quickly removed by filtration. This precipitate had to be collected as quickly as possible to avoid hydrolysis to the starting urea. The precipitate turns pale-yellow if hydrolysis is occurring. In some instances, additional diethyl ether (300 mL) was needed to ensure complete transfer of the solids to the filtration apparatus. The precipitate was washed with a further quantity of anhydrous diethyl ether (300 mL) (the filtrate must be colorless, indicating that all impurities have been removed) and immediately dissolved in aqueous 25% sodium hydroxide solution (100 mL). The mixture was then extracted with diethyl ether (3 × 300 mL). The combined organic layers were dried (potassium carbonate), filtered, and the solvent was removed under reduced pressure. The resulting colorless liquid was purified by distillation (bp 88–89 C°/36 mmHg) to afford 18.7 g (73%) of 2-tertbutyl- 1,1,3,3-tetramethylguanidine 1779.
General Description
2-
tert-Butyl-1,1,3,3-tetramethylguanidine (Barton′s base) is an excellent alternative to traditional inorganic bases for promoting the coupling reaction.
Synthesis
Oxalyl chloride (550 mmol) was added dropwise to a solution of 1,1,3,3-tetramethylurea (500 mmol) in toluene (80 mL) at room temperature and under argon protection. The reaction mixture was heated and stirred at 60 °C for 5 h, during which a white precipitate was generated. Upon completion of the reaction, the precipitate was collected by filtration through a Brinell funnel and washed with ether. The resulting white solid was suspended in acetonitrile (240 mL) and slowly added to a solution of tert-butylamine (550 mmol) and triethylamine (1 mol) in acetonitrile (300 mL) at room temperature and under argon protection. The mixture was heated to reflux for 3 hours. At the end of the reaction, the acetonitrile was evaporated under reduced pressure and the residual solid was washed with anhydrous ether with agitation to remove organic by-products, rapidly filtered and washed with anhydrous ether. The solid from filtration was dissolved in a mixture of ether and 20% aqueous NaOH (400 mL). After partitioning, the aqueous phase was extracted twice with ether. The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Finally, the target product 2-tert-butyl-1,1,3,3-tetramethylguanidine was obtained by distillation purification in 82% yield.
References
[1] Synlett, 2018, vol. 29, # 13, p. 1759 - 1764
[2] Organic Syntheses, 1997, vol. 74, p. 101 - 101
[3] Tetrahedron, 1970, vol. 26, p. 1805 - 1820
[4] Journal of the Chemical Society, Chemical Communications, 1981, # 21, p. 1136 - 1137
[5] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1982, # 9, p. 2085 - 2090
