The reaction of thionyl chloride with β amino alcohols: A computational investigation to delineate the mechanisms of the well-established synthesis that forms the 1-chloro-(2-alkylamino)ethanes and the 1,2,3 alkyloxathiazolidine-2-oxide compounds

The substitution reaction mechanism of β-amino alcohols and thionyl chloride to form the 1-chloro-(2-alkylamino)ethane and the 1,2,3-alkyloxathiazolidine-2-oxide products was investigated using computational methods. The reactions that result in these compounds are very similar, they both use the N-(2-alkyl/arylamino)ethanols and thionyl chloride, however the synthesis of 1,2,3-alkyl/aryloxathiazolidine-2-oxide requires the use of an amine base, which quite commonly results in a purer product, not a different compound as is the case here. The mechanism of the formation of 1-chloro-(2-alkylamino)ethanes, involves the formation of a quaternary nitrogen species as one of the first steps. This step has a low relative energy barrier and occurs readily. It occurred in the reaction of all substituents tested except for the methyl and phenyl substituents. Based on this work it was demonstrated that the amine base is not actually needed to form the 1,2,3-alkyl/aryloxathiazolidine-2-oxide. Experimental reactions to produce the 1-chloro-(2-alkylamino)ethanes were performed and the products were characterized by 1H and 13C-NMR and GC-MS. The GC-MS experimental results supported the computational results, in that trace amounts of the 1,2,3-oxathiazolidine-2-oxides were found in the residue of this reaction. This demonstrated that the 1,2,3-oxathiazolidine -2-oxides can be formed in trace amounts without a base. The base would be required to make the 1,2,3-alkyloxathiazolidine-2-oxides in higher yields. The computational chemistry results demonstrate that the amine base suppresses the quaternization of the nitrogen by reacting preferentially with the acidic protons, which is the normal mode of action of the amine base in thionyl chloride reactions.