3-METHYL-1-(TOLUENE-4-SULFONYL)-PIPERAZINE synthesis

Yield:178624-90-3 97%

Reaction Conditions:

Stage #1: (S)-2-methylpiperazinewith triethylamine in dichloromethane at 0; for 0.0833333 h;
Stage #2: p-toluenesulfonyl chloride in dichloromethane at 0 - 20; for 5 h;

Steps:

4.2.6 (2S)-1,2-Dimethyl-4-(para-toluenesulfonyl)piperazine 11

Triethylamine (190μl, 1.37mmol) was added to a solution of commercially available (S)-(+)-2-methylpiperazine (125mg, 1.25mmol) in CH₂Cl₂ (7mL) at 0°C and stirred for 5min. p-Toluenesulfonyl chloride (238mg, 1.25mmol) was then added and the mixture was stirred for 1h at 0°C before being allowed to warm to room temperature and stirred for a further 4h. Water was then added and the aqueous layer was separated and extracted with CH₂Cl₂, before being washed sequentially with 1M HCl (50mL), water (50mL), saturated aqueous NaHCO₃ solution (50mL) and saturated aqueous sodium chloride solution (50mL). The organic layer was separated, dried (Na₂SO₄), filtered and concentrated in vacuo to afford tosyl piperazine, (3S)-3-methyl-1-[(4-methylbenzene)sulfonyl]piperazine (310mg, 97%) as a white solid. The product could be used without further purification; mp 138.5-141°C (acetone); [α]23D=+38.9[α]D23=+38.9 (c 0.93, CHCl₃); ν_max (ATR)/cm^-1 3352, 2971, 2922, 2863, 2821, 1605, 1452, 1325, 1165, 1133, 1121, 997, 914, 861, 811, 754s, 655; δ_H (500MHz, DMSO-d₆) 7.61-7.59 (2H, m, 2×ArH), 7.47-7.44 (2H, m, 2×ArH), 3.41-3.37 (2H, m, CH₂NTs), 2.85 (1H, dt, J 12.1 and 2.8, CH₂NTs), 2.68-2.60 (2H, m, 3-H and CHHN(H)), 2.41 (3H, s, ArCH₃), 2.06 (1H, td, J 11.3 and 3.1, CHHN(H)), 1.70 (1H, t, J 10.8, CHHN(H)), 0.90 (3H, d, J 6.4, 3-(CH₃)); δ_C (126MHz, DMSO-d₆) 143.4, 131.9, 129.7, 127.5, 52.3, 49.5, 45.9, 44.3, 20.9, 18.8; m/z (CI⁺) 255 (MH⁺, 100%), 99 (M⁺ -Ts, 10); HRMS (CI⁺) MH⁺ calculated for C₁₂H₁₉N₂O₂S 255.1167, observed 255.1164.

References:

Armstrong, Alan;Pullin, Robert D. C.;Jenner, Chloe R.;Foo, Klement;White, Andrew J. P.;Scutt, James N. [Tetrahedron Asymmetry,2014,vol. 25,# 1,p. 74 - 86]