T-butylmethyl ether

Chiral enantiopure 2,2 -dihydroxybiaryls are important as chiral ligands and are also structural motifs occurring in some natural products. Hydrolase-catalyzed resolution by acylation in organic solvents of some dihydroxybiaryls has been successfully achieved. Thus, the racemic binaphthols 111-113 have been resolved by mono acylation with vinyl acetate in t-butylmethyl ether ( ME) at 45 °C catalyzed by Pseudomonas sp. lipase (Scheme 4.35) [106]. In a similar way the 2,2 -dihydroxybiphenyl 114 can be acylated with vinyl acetate catalyzed by PSL immobilized on celite in TBME at 45 °C (Scheme 4.35) [107]. Butanolysis of the racemic monobutyrate of binaphthol rac-115 catalyzed by CALB in toluene at 80 °C for 72 h gives (R)-binaphthol (93% ) at ca. 50% conversion [108]. 

For the P-aminocarboxamides 134-137, CALA gave very low enantioselectivity. Because no ester function was present in the substrate, N-acylation proceeded satisfactory with CALB as the catalyst and trifluoroethyl butyrate as the acyl donor in t-butylmethyl ether/t-amylalcohol (TBME)/(TAME) mixtures at 45 °C (Scheme 4.40) [131]. 

A solution of 4-(2-chloroethylsulfonyl)phenol (24.4 mmol) dissolved in 50 ml CH2CI2 was treated at 37°C with triethylamine (26.4 mmol), stirred for 3.25 hour, and the product from Step 5 (22.0 mmol) dissolved in 40 ml CH2CI2 added. The mixture was stirred at 37 °C 3 hours, cooled to room temperature, and treated with 80 ml water and solid NaCl. The mixture was extracted 3 times with 70 ml CH2CI2, dried, concentrated to 70 ml, treated with 75 ml toluene, and concentrated to 100 ml. After 3 days at 0°C the suspension was concentrated to 50 ml, filtered, and crude product isolated as white crystals. They were purified by chromatography on silica gel using CH2Cl2/t- butylmethyl ether, 19 1, and the product isolated in 87.1% yield, mp = 155.5-156.2°C. MS Data supplied. 

Heat 17 ml of the tampon solution pH 6, which contains 0.06 mol 1 citrate and sodium hydroxide in a flask with stopper to 70 °C. Place 1.00 g of the testing material into the tampon solution in the flask, which is shaken well for 30 min. Add 3 ml of the sodium dithionite aqueous solution into the flask and keep reaction at 70 °C for 30 min. Then, cool the solution to 20-25 °C within 2 min. The solution is extracted by 40 ml of t-butylmethyl ether. After extraction, condense the solution of t-butylmethyl ether to around 1 ml and use for the chromatographic analysis. 

Figure 9.4 Elution strength of binary mixtures as used for adsorption chromatography on silica [reproduced with permission from M.D. Palamareva and V.R. Meyer, J. Chromatogr., 641, 391 (1993)]. The graph covers the 12 possible mixtures of hexane, dichloromethane, te/T-butylmethyl ether, tetrahydrofuran, ethyl acetate and isopropanol.

Fig. 9.3 Separation of a test mixture on silica with eluents of different strength. Top fe/t-butylmethyl ether, ° = 0.48 middle hexane-ferf-butylmethyl ether (9 1), ° = 0.29 bottom hexane, s = 0. The attenuation of the hexane chromatogram is only half as much as of the other two. Conditions column, 25cmx3.2mm i.d. stationary phase, LiChrosorb SI 60 5 irc flow-rate, 1mlmin - UV detector, 254nm. Peaks 1=p-xylene 2 = nitrobenzene 3 = acetophenone 4 = 2,6-dinitrotoluene.

Compound 11. Phenyl ester 9 was added as a THF (200 mL) solution to a sodium hydride (25.7 g, 1.07 mmol)/THF (1.6 L) suspension cooled to 0°C. A THF (200 mL) solution of 4 was then added to the reaction mixture at 0 C. After addition of 4, the resulting reaction mixture was slowly heated to reflux for 2.5 h, cooled to room temperature and quenched with chilled water (1.5 L). The pH was adjusted to 1.0 with HCl (3N, 1.0 L) and the mixture washed with t-butylmethyl ether (MTBE, 1.5 L). The resulting aqueous portion was adjusted to a pH of 8 with sodium hydroxide (5 N) and extracted with MTBE (2X1.1 L). After a brine wash (1.0 L), sodium sulfate was used to dry the combined extracts before concentrating to a residue (85.7 g, 86%). 

---