Proton transfers in the Strecker reaction revealed by DFT calculations

Abstract

SummaryThe Strecker reaction of acetaldehyde, NH3, and HCN to afford alanine was studied by DFT calculations for the first time, which involves two reaction stages. In the first reaction stage, the aminonitrile was formed. The rate-determining step is the deprotonation of the NH3 + group in MeCH(OH)-NH3 + to form 1-aminoethanol, which occurs with an activation energy barrier (ΔE ≠) of 9.6 kcal/mol. The stereochemistry (R or S) of the aminonitrile product is determined at the NH3 addition step to the carbonyl carbon of the aldehyde. While the addition of CN− to the carbon atom of the protonated imine 7 appears to scramble the stereochemistry, the water cluster above the imine plane reinforces the CN− to attack the imine group below the plane. The enforcement hinders the scrambling. In the second stage, the aminonitrile transforms to alanine, where an amide Me-CH(NH2)-C(=O)-NH2 is the key intermediate. The rate-determining step is the hydrolysis of the cyano group of N(amino)-protonated aminonitrile which occurs with an ΔE ≠ value of 34.7 kcal/mol. In the Strecker reaction, the proton transfer along the hydrogen bonds plays a crucial role.

Isotope effects at the origin of life: Fingerprints of the Strecker synthesis

“…during H1, the C-1 site changes hybridization from sp to sp 2 , and during H2, the C-1 site changes from sp 2 to sp 3 then back to sp 2 . Theoretical and experimental work also suggests indirect involvement of the amine N during the two hydrolysis steps, by stabilizing the water lattice via hydrogen bonding but no involvement of the C-2 or C-3 sites (Yamabe et al, 2014). Given that the hydrolysis steps are irreversible and involve the formation of new bonds only at the C-1 site, we expect a primary normal KIE on the C-1 site for each hydrolysis step and no isotope effects at the C-2 and C-3 sites.…”

“…Past experimental and theoretical studies of Strecker synthesis have detailed the effects of physiochemical conditions on its reaction mechanism and kinetics (Ogata and Kawasaki, 1971;Van Trump, 1975;Miller and Van Trump, 1981;Moutou et al, 1995;Atherton et al, 2004;Yamabe et al, 2014;Magrino et al, 2021). These studies show that Strecker synthesis occurs in the aqueous phase, at basic or acidic pH, and has a water-dependent hydrolysis step (Van Trump, 1975;Moutou et al, 1995).…”

Miller–Urey Spark‐Discharge Experiments in the Deuterium World

“…With the exception of a few subtle changes, the product distribution of primary amines appears to be very similar in both the deuterated and the non‐deuterated experiment (see Figures 2 a and c). Amino acid formation in the Miller–Urey system is known to take place via the Strecker mechanism, the rate‐determining step of that reaction being a deprotonation and subsequent hydrolysis . This might lead to the expectation of a notable difference in product distribution of amino acids between the deuterated and non‐deuterated experiments.…”

Miller–Urey Spark‐Discharge Experiments in the Deuterium World

“…Amino acid formation in the Miller-Urey system is known to take place via the Strecker mechanism, the rate-determining step of that reaction being ad eprotonation and subsequent hydrolysis. [11,12] This might lead to the expectation of anotable difference in product distribution of amino acids between the deuterated and non-deuterated experiments.H owever,t he observed near-invariance in the amine product distribution suggests that any differences that might be seen in the kinetics are not great, though following the changes in product distribution during the experiment would be an interesting candidate for afuture on-line analysis.…”