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
Bibliographic record
Abstract
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 gas chromatography mass spectrometry (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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".