Optimization of Amidation Reactions Using Predictive Tools for the Replacement of Regulated Solvents with Safer Biobased Alternatives

TY - JOUR

T1 - Optimization of Amidation Reactions Using Predictive Tools for the Replacement of Regulated Solvents with Safer Biobased Alternatives

AU - Petchey, Tabitha Holly Marguerite

AU - Comerford, James William

AU - Farmer, Thomas James

AU - MacQuarrie, Duncan James

AU - Sherwood, James Richard

AU - Clark, James Hanley

N1 - © 2018 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2018/2

Y1 - 2018/2

N2 - Catalytic methods for the synthesis of amides are much sought after. Silica catalysts have shown promise, but yields are generally moderate and the use of toluene, a toxic and regulated solvent, is required. Here, the Hansen Solubility Parameters in Practice (HSPiP) software package has been used along with the Yalkowsky approximation to make predictions about the solubility of a series of aliphatic and aromatic amides in less hazardous solvents. The conventional solvent toluene has been modeled, alongside potential bioderived alternatives, to find a safer and more productive reaction medium for amidation chemistry. The best candidate, 4-methylisopropylbenzene (p-cymene) was then examined experimentally against toluene in a range of silica-catalyzed reactions between carboxylic acids and amines, including both aromatic and aliphatic reactants. The increased temperatures achievable in the higher boiling p-cymene are shown to provide a significant improvement to yields compared to toluene. The low solubility of many of the amides in cold p-cymene proves an aid to separation. In general, higher polarity amides exhibit more favorable yields. In addition, tests run in a continuous flow system demonstrate the potential for further efficiency improvements by the recirculation of reactants.

AB - Catalytic methods for the synthesis of amides are much sought after. Silica catalysts have shown promise, but yields are generally moderate and the use of toluene, a toxic and regulated solvent, is required. Here, the Hansen Solubility Parameters in Practice (HSPiP) software package has been used along with the Yalkowsky approximation to make predictions about the solubility of a series of aliphatic and aromatic amides in less hazardous solvents. The conventional solvent toluene has been modeled, alongside potential bioderived alternatives, to find a safer and more productive reaction medium for amidation chemistry. The best candidate, 4-methylisopropylbenzene (p-cymene) was then examined experimentally against toluene in a range of silica-catalyzed reactions between carboxylic acids and amines, including both aromatic and aliphatic reactants. The increased temperatures achievable in the higher boiling p-cymene are shown to provide a significant improvement to yields compared to toluene. The low solubility of many of the amides in cold p-cymene proves an aid to separation. In general, higher polarity amides exhibit more favorable yields. In addition, tests run in a continuous flow system demonstrate the potential for further efficiency improvements by the recirculation of reactants.

KW - Heterogeneous Catalysis

KW - amide

KW - Solvent substitution

KW - Flow chemistry

KW - Hanson solubility parameters

KW - Yalkowsky approximation

KW - para-cymene

U2 - 10.1021/acssuschemeng.7b04257

DO - 10.1021/acssuschemeng.7b04257

M3 - Article

SN - 2168-0485

VL - 6

SP - 1550

EP - 1554

JO - ACS Sustainable Chemistry & Engineering

JF - ACS Sustainable Chemistry & Engineering

IS - 2

ER -