Does Steric Hindrance Actually Govern the Competition between Bimolecular Substitution and Elimination Reactions?

Abstract

Bimolecular nucleophilic substitution (S N 2) and elimination (E2) reactions are prototypical examples of competing reaction mechanisms, with fundamental implications in modern chemical synthesis. Steric hindrance (SH) is often considered to be one of the dominant factors determining the most favorable reaction out of the S N 2 and E2 pathways. However, the picture provided by classical chemical intuition is inevitably grounded on poorly defined bases. In this work, we try to shed light on the aforementioned problem through the analysis and comparison of the evolution of the steric energy ( E ST ), settled within the IQA scheme and experienced along both reaction mechanisms. For such a purpose, the substitution and elimination reactions of a collection of alkyl bromides (R-Br) with the hydroxide anion (OH – ) were studied in the gas phase at the M06-2X/aug-cc-pVDZ level of theory. The results show that, generally, E ST recovers the appealing trends already anticipated by chemical intuition and organic chemistry, supporting the role that SH is classically claimed to play in the competition between S N 2 and E2 reactions.

Thiol Reactome: A Nontargeted Strategy to Precisely Identify Thiol Reactive Drinking Water Disinfection Byproducts

“…The pseudo first-order reaction rate constants for iodoacetamide (IAM) and iodoacetic acid (IAA) with 1 mM of GSH were 1.00 × 10 –2 and 6.58 × 10 –3 min –1 , respectively, while the rate constants for bromoacetamide (BrAM) and bromoacetic acid (BrAA) with GSH were 8.84 × 10 –3 and 6.09 × 10 –3 min –1 , respectively, both about 1–2 orders of magnitude higher than those of their chlorinated analogues (Figure a and Figure S7). The weak thiol reactivity of chlorinated analogues of DBPs was consistent with previous studies. , No significant GSH reactivity was detected for haloacetamides or haloacetic acids with more than one halogen, which was attributed to S N 2 sensitivity to steric hindrance . Consistent with detection of the adducts, trichloroacetonitrile exerted strong GSH reactivity and the reaction was completed within the first hour as evidenced by the steady abundances of adducts after 1 h (Figure b), faster than haloacetamides.…”

“…22,25 No significant GSH reactivity was detected for haloacetamides or haloacetic acids with more than one halogen, which was attributed to S N 2 sensitivity to steric hindrance. 41 Consistent with detection of the adducts, trichloroacetonitrile exerted strong GSH reactivity and the reaction was completed within the first hour as evidenced by the steady abundances of adducts after 1 h (Figure 3b), faster than haloacetamides. The formation of adducts for dichloroacetonitrile was also observed albeit with ∼50 times lower abundances.…”

Atoms in molecules in real space: a fertile field for chemical bonding

“…, ) supports the kinetic role of SH that is traditionally claimed to play in the competition between S N 2 and E2 reactions. 156 On the other hand, the geometric and electronic deformation of a diene/dienophile helps to understand the origin of the endo–exo preference in prototypical Diels–Alder reactions 157 while the atomic IQA decomposition of the IRC profiles explains the synchronous or asynchronous character of the polar Diels–Alder reactions. 126 Focusing also on the proper fragment quantities, the IQA study of the bifunctional catalysis played by water clusters 158 shows how water monomers encompassing the reaction between SO 3 and H 2 O to yield H 2 SO 4 mitigate the changes in chemical bonding across the rate-limiting step of the process, thereby reducing the activation energy as more water molecules are included in the system.…”

π‐hole driven N⋅⋅⋅O/N⋅⋅⋅π Pnicogen and C⋅⋅⋅O Tetrel Bonding inNitromethane‐Carbonyl Dimers: Comprehensive Study using Matrix Isolation Infrared Spectroscopy and Quantum Chemical Computations

“…The number of reports on the influence of steric effect in altering the conformers and the geometry of the aggregates is sparse. [71] Electrostatic potential over the molecules change adequately on substitution, mainly due to field effects exerted by them. [72] The present work involving heterodimers of nitromethane (NM) with three carbonyl systems: formaldehyde (FMD; NMFMD), acetaldehyde (ACD; NMACD) and acetone (ACN; NMACN) focuses at the following, (i) Evidencing the formation of NMFMD, NMACD and NMACN dimers at low temperatures using matrix isolation infrared spectroscopy.…”

“…Steric hindrance plays a vital role in determining the geometry, orientation or chemical reactivity of a particular molecule. The number of reports on the influence of steric effect in altering the conformers and the geometry of the aggregates is sparse [71] . Electrostatic potential over the molecules change adequately on substitution, mainly due to field effects exerted by them [72] …”