Hydration of nitriles: an examination in terms of No Barrier Theory
Bibliographic record
Abstract
Nitriles pose an interesting problem to the explanatory powers of organic chemistry because, despite the favorable overall thermodynamics of hydrolysis to the corresponding amides, the reactions are inherently slow. The rate determining step is hydration of the nitrile to give the imidic acid, which quickly tautomerizes to the amide. In terms of Marcus Theory, the intrinsic barriers for acid and base‐catalyzed hydration are higher for nitriles than for amides, which are themselves slow reactions. It is remarkable that hydration of a nitrile, for which the free energy change is close to zero except for polyhaloacetonitriles, is much slower than hydration of an amide, which is energetically unfavorable. This can be explained by No Barrier Theory in terms of the high energetic cost of the geometrical distortions in “one thing at a time” corner species. There are no experimental equilibrium constants for this initial hydration step, so we have determined them computationally. The free energy change for the initial hydration is small; it is the fast and energetically downhill second step, tautomerization to the amide, which makes the overall hydrolysis of nitrile to amide thermodynamically favorable. Very few of the pKa values needed in the acid and base‐catalyzed mechanisms are known, so we used linear free energy relations and treat the parent pKa values as adjustable parameters. This procedure leads to pKa values in accord with expectation based on such data as are available and permits calculation of rate constants in satisfactory agreement with experiment. Copyright © 2013 John Wiley & Sons, Ltd.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.004 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".