Chlorohydrins synthesis

The chlorohydrin process (24) has been used for the preparation of acetyl-P-alkylcholine chloride (25). The preparation of salts may be carried out mote economically by the neutralization of choline produced by the chlorohydrin synthesis. A modification produces choline carbonate as an intermediate that is converted to the desired salt (26). The most practical production procedure is that in which 300 parts of a 20% solution of trimethyl amine is neutralized with 100 parts of concentrated hydrochloric acid, and the solution is treated for 3 h with 50 parts of ethylene oxide under pressure at 60°C (27). 

Heinecke JW, Li W, Mueller DM, Bohrer A, Turk J (1994) Cholesterol Chlorohydrin Synthesis by the Myeloperoxidase-Hydrogen Peroxide-Chloride System Potential Markers for Lipoproteins Oxidatively Damaged by Phagocytes. Biochemistry 33 10127... 

El-Qisairi, A. K., Qaseer, H. A., Henry, P. M. Oxidation of olefins by palladium(ll). 18. Effect of reaction conditions, substrate structure and chiral ligand on the bimetallic palladium(ll) catalyzed asymmetric chlorohydrin synthesis. J. Organomet. Chem. 2002, 656,168-176. 

Heinecke, J. W., W. Li, D. M. Mueller, A. Bohrer, and J. Turk. 1994. Cholesterol chlorohydrin synthesis by the myeloperoxidase-hydrogen peroxide-chloride system Potential markers for lipoproteins oxidatively damaged by phagocytes. 33(33) 10127-36. 

If high chloride concentrations are present in these reactions, the selectivity of the second step is strongly increased for the formation of C-Cl bonds, and P-hydride elimination is inhibited. This effect seems to originate from the saturation of the Pd coordination sites by the Cl and consequent inhibition of hydrogen coordination and thus prevention of the ehmination reactions [108]. The observation that the use of Pd pyridine complexes favored chlorination even at lower chloride concentrations gave rise to an asymmetric chlorohydrin synthesis from allyl ether 154 with the use of chiral bimetallic Pd complex 156 (Scheme 16.42). 

The studies described in the last section provided the background for the development of a new asymmetric chlorohydrin synthesis. If the neutral ligand that encourages chlorohy-drin formation is made chiral, there is the possibility of forming chiral chlorohydrins. First, pyridine was replaced with chiral monodentate ligands such as (5)-(-)-Af, Af-dimethyl-l-phenethylamine.f f Scheme 23 shows the general reaction sequence. As might be expected the enantioselectivities were low 10-15% for propene. The Wacker oxidation product, acetone, was a side product in the reaction. 

These observations resulted in the development of a new asymmetric chlorohydrin synthesis. Mono- and bimetallic Pd(ll) catalysts containing bidentate chiral ligands gave good to excellent enantioselectivities. 

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