Discovery-Oriented Approach To Organic Synthesis: Tandem Aldol Condensation-Michael Addition Reactions. Identifying Diastereotopic Hydrogens in an Achiral Molecule by NMR Spectroscopy

Abstract

We have found a beautiful example of anisochrony of diastereotopic acyclic methylene hydrogens in a symmetric diketone, synthesized by techniques traditionally performed in an introductory organic laboratory course. Synthesis of the diketone is high-yielding and easy to carry out, and the products can be directly isolated with a good degree of purity with no need of further manipulation. The reaction can be accomplished in a single laboratory session.

A rubric to characterize inquiry in the undergraduate chemistry laboratory

“…Two of these inquiry laboratory curricula were purposefully structured by their authors so as to include some experiments with lesser degrees of inquiry (e.g., guided inquiry) and other experiments offering greater degrees of inquiry (e.g., open inquiry). Organic chemistry experiments (Senkbeil, 1999;Krishnamurty et al, 2000;Ciacco et al, 2001;Wachter-Jurcsak and Reddin, 2001;Amburgey-Peters and Haynes, 2005;Baru and Mohan, 2005;Cough and Goldman, 2005;Kjonaas and Mattingly, 2005;Nicaise et al, 2005;White and Kittredge, 2005) were selected from the Journal of Chemical Education, by searching on the keywords of inquiry and discovery-based learning.…”

A Braided Hetero[2](3)rotaxane

“…Moreover, the other aromatic hydrogen atoms H a , H e , H f , and H g were shifted upfield compared with noninterlocked host compound 1 because of the effects of the hydrogen-bonding interactions between crown ether and binding sites on the axle component. Remarkably, the signals of the methylene proton H d in the linker part of the two rings in compound 4 split into two double peaks (δ = 5.26 and 5.17 ppm) from a single peak, indicating proton H d existed as diastereotopic methylene hydrogens . This is the characteristic change of rotaxane 4 , which is different from other possible self-assemblies.…”

DFT investigations of the unusual reactivity of 2‐pyridinecarboxaldehyde in base‐catalyzed aldol reactions with acetophenone

“…In the mixed‐aldol reaction of acetophenone with 2‐pyridinecarboxaldehyde, the condensation product is not recovered, and only the Michael adduct is isolated if two equivalents of acetophenone are employed . As depicted in Scheme , initial nucleophilic acyl addition of the enolate to the aldehyde carbonyl generates β‐keto alkoxide intermediate 6 .…”

“…[22] 3 | RESULTS AND DISCUSSION In the mixed-aldol reaction of acetophenone with 2-pyridinecarboxaldehyde, the condensation product is not recovered, and only the Michael adduct is isolated if S C H E M E 1 Formation of chalcone (4) from the reaction of acetophenone (1) with benzaldehyde (2a), and formation of 1,5-diphenyl-3-(2-pyridinyl)-1,5-pentandione (5) from the reaction of 2-pyridinecarboxaldehyde (2b) with two equivalents of the enolate of acetophenone S C H E M E 2 Newman projections of the anti and gauche conformational isomers of intermediate 3 in the aldol condensation reaction resulting in trans or cis isomers, respectively, of the condensation product 4 two equivalents of acetophenone are employed. [23,24] As depicted in Scheme 3, initial nucleophilic acyl addition of the enolate to the aldehyde carbonyl generates β-keto alkoxide intermediate 6. Proton equilibration leads to ketol 3 that undergoes base-catalyzed elimination of water to form a conjugated product (4) via an E1cB pathway.…”