ChemInform Abstract: Zinc Chloride Promoted Efficient and Facile BOC Protection of Amines.

Abstract

Zinc Chloride Promoted Efficient and Facile BOC Protection of Amines. -The protection protocol appears to be competitive and in some cases even superior to previously reported procedures that require basic conditions. -(ARIFUDDIN*, M.; LAKSHMIKANT, N.; RAJASEKAR, N.; SHINDE, D. B.; Indian J.

Concept-Driven Chemoselective O/N-Derivatization of Prolinol: A Bee-Line Approach to Access Organocatalysts

“…Other solvents and reagents were used as obtained from the supplier unless otherwise noted. The 1 H NMR and 1 H decoupled 13 C NMR spectra were recorded in CDCl 3 on a Bruker, Avance III ( 1 H 400.13 MHz; 13 C 101.15 MHz) spectrometer. The 1D and 2D NMR spectra were analyzed using MestReNova software (version-14.1.2-25024), and the chemical shifts are reported in ppm relative to the residual solvent peaks in CDCl 3 (δ 7.26 ppm) and (CD 3 ) 2 SO (δ 2.50 ppm) for 1 H NMR.…”

“…The organic layer was dried using anhydrous Na 2 SO 4 and concentrated to provide the pure product as a colorless viscous liquid (2.5 g, 82%), which was used without any further purification. 23,24 R f (EtOAc/ petroleum ether 3:7) = 0.25; [α] D = +6.4 (c 0.9 in CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 4.14 (dd, J = 11.3, 3.1 Hz, 1H), 3.67 (dd, J = 11.3, 3.1 Hz, 1H), 3.41−3.28 (m, 1H), 3.07 (m, 1H), 2.89 (m, 1H), 2.06−1.77 (m, 4H); 13 General Procedure for Synthesis of 3. To a stirred solution of (S)-prolinol (1) in dry THF at 0 °C, NaH (60% suspension in mineral oil) was added under an inert (nitrogen) atmosphere.…”

“…The crude reaction mixture was purified over neutral alumina using a gradient mixture of EtOAc/petroleum ether (10−20%) to yield the pure compound 3a as a faint straw yellow viscous liquid (256 mg, 85% yield), which solidifies in the refrigerator (2−5 °C). R f (EtOAc/ petroleum ether 3:7) = 0.67; [α] D = −21.9 (c 1.0 in CHCl 3 ); IR (film, cm −1 ): 3230, 2358, 1720, 1257, 1159, 690; 1 H NMR (400 MHz, CDCl 3 ): δ 4.49 (dd, J = 12.0, 2.88 Hz, 1H), 4.20 (dd, J = 12.0, 3.53 Hz, 1H), 3.37−3.34 (m, 1H), 3.32−3.22 (m, 1H), 2.89−2.94 (m, 1H), 2.10−1.99 (m, 2H), 1.86−1.81 (m, 2H), 1.49 (s, 9H); 13 (S)-Pyrrolidin-2-ylmethyl Acetate (3b). The crude reaction mixture was purified over silica gel using a gradient mixture of EtOAc/petroleum ether (7−30%) to yield the pure compound 3b as a colorless liquid (39 mg, 55% yield).…”

“…Boc-anhydride has been a conventional protecting agent for the NH group because of its easy protection and deprotection protocols. Previous literature has reported the exclusive reactivity of the NH group in either basic, − Lewis-acidic, or neat conditions to form the N -Boc derivative of prolinol ( 2a ). Base-solvent combinations such as NaOH–THF, NaOH–THF:H 2 O, NaOH–dioxane:H 2 O, aq NaOH−DCM, KOH−THF, Na 2 CO 3 –NaOH–dioxane, NaHCO 3 –THF:H 2 O, Et 3 N–MeOH, and Et 3 N–DCM , have been used for the selective N -Boc protection of prolinol.…”

“…Base-solvent combinations such as NaOH–THF, NaOH–THF:H 2 O, NaOH–dioxane:H 2 O, aq NaOH−DCM, KOH−THF, Na 2 CO 3 –NaOH–dioxane, NaHCO 3 –THF:H 2 O, Et 3 N–MeOH, and Et 3 N–DCM , have been used for the selective N -Boc protection of prolinol. Selectivity toward N -Boc protection of 2-aminophenol has also been reported using ZnCl 2 as Lewis acid in CH 3 CN:H 2 O media . Similar selectivity has been reported in the absence of any additives by using Boc 2 O in DCM as a solvent .…”