[reaction: see text] 1,3-Diketones were synthesized directly from ketones and acid chlorides and were then converted in situ into pyrazoles by the addition of hydrazine. This method is extremely fast, general, and chemoselective, allowing for the synthesis of previously inaccessible pyrazoles and synthetically demanding pyrazole-containing fused rings.

Since at least the 1960s, organic chemistry textbooks have featured pK a tables for organic acids that include values for H2O and H3O+ (15.74 and −1.74, respectively) that are thermodynamically and chemically indefensible. Here we trace this error back to Brønsted’s early contributions in the 1920s to the Brønsted–Lowry Theory of acids and bases. Organic chemists generally defend the use of these values by citing measurements of the equilibrium constant for the water + methoxide acid–base reaction that suggested that methanol (pK a = 15.54) is a stronger acid than water; from this, organic chemists have concluded that pK a of water must be 15.74 rather than 14.00. Here we discuss the problems that invalidate this conclusion, the most important being that it is based on the use of the pure liquid standard state (mole fraction = 1) that is quite different from the standard state for acidities determined in dilute solution (molality = 1). Using the latter standard state, the equilibrium constant for the water/methoxide reaction ranges from 4 to 70, showing water to be a stronger acid than methanol, and justifying the use of the thermodynamically correct value, pK a(H2O) = 14.00.

No abstract

Imidazole carbamates and ureas were found to be chemoselective esterification and amidation reagents. A wide variety of carboxylic acids were converted to their ester or amide analogues by a simple synthetic procedure in high yields.

Carbonylimidazole derivatives have been found to be highly active acylation reagents for esterification and amidation in the presence of pyridinium salts. These reactions are thought to involve both Brønsted acid and nucleophilic catalysis. This mode of activation has been applied to the synthesis of difficult to access oxazolidinones, as well as esters and amides. Finally, the use of pyridinium salts has been shown to accelerate the esterification of carboxylic acids with imidazole carbamates.

A one-pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole-bearing carbonyl linchpin reagent (carbonyl linchpin N,O-dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.

Research experiences are widely understood to be valuable for the intellectual and professional development of undergraduate science students. Course-based undergraduate research experiences (CUREs) have become popular as a means of engaging large numbers of students in research by leveraging institutional supports for laboratory courses. At Willamette University, we have adapted a guided-inquiry experiment that gave unexpected results into a CURE in the lower-division organic chemistry curriculum. This experience has engaged several cohorts of students in a 7 week investigation focused on identifying the mechanistic origin of a nonstereospecific hydroxybromination of Z-stilbene, an observation that contradicts how this addition reaction is presented in standard organic chemistry curricula. Each year, the cohort experimentally “discovers” the anomalous stereochemical outcome of the addition reaction. Students then participate in a workshop focused on developing mechanistic hypotheses that can account for the result and on designing experiments that will address their hypotheses. Over the next three lab sessions, students execute their experiments, reconsidering and revising their hypotheses as their data dictate. The experience culminates in formal oral and written presentations of results. Student perceptions of the pedagogical value of the CURE, the effect of the lab on their self-efficacy, and the novelty of research being conducted were assessed in multiple class cohorts, while faculty perceptions of changes in student behavior and skill were also documented.

No abstract