The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Abstract

Pyrazines are an underreported class of N‐heterocycles available from nitrogen‐rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin–West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α‐acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ‐amino‐levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal–organic frameworks.

Biobased Pyrazine-Containing Polyesters

“…Dimethyldipropionic acid pyrazine (DMDPP) and dipropionic acid pyrazine (DPP) were synthesized according to the literature . The dimethyl esters of these compounds were synthesized by Fischer esterification in methanol and used after workup (see Supporting Information (SI), pp 4–9).…”

“…Dimethyldipropionic acid pyrazine (DMDPP) and dipropionic acid pyrazine (DPP) were synthesized according to the literature. 2 The dimethyl esters of these compounds were synthesized by Fischer esterification in methanol and used after workup (see Supporting Information (SI), pp 4−9). 1,4-Butanediol, 1,6-hexanediol, 1,10-decanediol, neopentylglycol, and m-xylene were supplied by Sigma-Aldrich in >97% purity and used as received.…”

“…1 Our research group recently developed a scalable synthesis for biobased pyrazine building blocks starting from nitrogenrich biomass in the form of proteinogenic amino acids. 2 Pyrazines hold a special place within the heterocyclic aromatic systems as one of the most benzene-like structures known, possessing a degree of aromaticity 89% of that of benzene. As opposed to benzene, pyrazines also possess two electron lone pairs which might be exploited as handles for added functionality.…”

Post-Modification of Biobased Pyrazines and Their Polyesters

“…More specific, biobased pyrazine diacids are dimethyldipropionic and dipropionic acid pyrazine ( DMDPP and DPP , respectively) (see Figure ). Both are prepared using a straightforward process from simple amino acids (glutamic- and δ-amino-levulinic acid) and were employed to access our polyesters …”

“…Both are prepared using a straightforward process from simple amino acids (glutamic-and δ-amino-levulinic acid) and were employed to access our polyesters. 7 Both nitrogen atoms in the pyrazine core still have an electron lone pair available for post-modification reactions. This feature in combination with their specific aromatic character makes pyrazines interesting building block candidates for added functionality materials.…”