2-methylbutan-2-ol

ChEBI · EMBL-EBI ↗ · Källdatum saknas · Källans villkor

A tertiary alcohol that is propan-1-ol in which both of the hydrogens at position 1 have been replaced by methyl groups.

Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM from Thermomyces lanuginosus† ↗ · 16 dec. 2024 · Källans villkor

The use of enzymes in organic solvents for chemical biosynthesis offers a number of potential advantages, as the nature of the solvent can have a profound effect on the substrate specificity, regioselectivity and enantioselectivity of the enzyme. In general, solvents are selected based on their hydrophobicity (log P) value, which ranges from 0.6 to 3.5, as the activity and stability of enzyme can be maximum in this range.50 The ammonolysis reaction of pyrazine-2-carboxylate and benzylamine was carried out using Lipozyme® TL IM from Thermomyces lanuginosus in the continuous flow reactors. We performed a blank control experiment without any enzyme and found that only trace amounts of product were generated. The effect of various organic solvents on the synthetic reaction was studied and the solvents used were methanol, ethanol, isopropanol, isobutanol, tert-amyl alcohol, acetonitrile, dichloromethane, DMSO, THF and 2-MeTHF. The log P values of the solvents used in the experiment and yields of product are shown in the Table 1. As shown in Table 1, the product yield was higher when tert-amyl alcohol was used as the solvent, while by-products such as pyrazine esters were produced in ethanol, isopropanol, and isobutanol. The yield was lower in methanol, acetonitrile, dichloromethane, DMSO, THF and 2-MeTHF. Therefore, tert-amyl alcohol was selected as the reaction solvent for further research on the enzymatic synthesis of pyrazinamide derivatives in continuous-flow microreactors. As shown in Table 2, we conducted an experiment on the direct aminolysis of 2-pyrazinecarboxylic acid and benzylamine to synthesize pyrazinamide (3j) catalysed by CAL-B, and the yield of pyrazinamide (3j) was 73.2%. Therefore, we chose Lipozyme® TL IM as the catalyst.

Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM from Thermomyces lanuginosus† ↗ · 16 dec. 2024 · Källans villkor

Then, the scope and limitations of biocatalytic aminolysis of pyrazinamide derivatives are explored, and the experiments are processed in the continuous flow microreactor and shaker reactors under optimal reaction conditions. As shown in Table 4, the yield of ammonolysis reaction with aliphatic amine (e.g., entry 1, 86.4%) was higher than which with benzylamine (e.g., entry 10, 80.3%). Meanwhile, benzylamine with an electron-donating group (e.g., entry13, 83.5%) were more favourable for the reaction than benzylamine with an electron-withdrawing group (e.g., entry 16, 67.7%).

Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM from Thermomyces lanuginosus† ↗ · 16 dec. 2024 · Källans villkor

As shown in Table 5, the steric hindrance of pyrazine esters also has an effect on the aminolysis reactions, and a large steric hindrance is not conducive to the reaction.

Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM from Thermomyces lanuginosus† ↗ · 16 dec. 2024 · Källans villkor

Due to steric hindrance, N-aminomorpholine is difficult to carry out the ammonolysis reaction with pyrazine esters (e.g., entry 8, trace).