Temperature dependent green chemical synthesis of 3-carboxycoumarins and 3,4-unsubstituted coumarins

Jack van Schijndel (Corresponding author), Dennis Molendijk, Luiz Alberto Canalle, Erik T. Rump, Jan Meuldijk

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts like pyridine and piperidine but only use ammonium bicarbonate as the catalyst. Materials and Methods: To investigate the scope of the Green Knoevenagel condensation for the synthesis of 3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in the optimized two-step procedure developed for 2-hydroxybenzaldehyde. Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially kept at 90°C for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is increased to 140°C for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95%. Conclusion: A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of Green Chemistry. It was shown that by initially capping the temperature at 90°C, premature decarboxylation can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased to 140°C finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green Knoevenagel condensation and the decarboxylation step.

Original languageEnglish
Pages (from-to)130-135
Number of pages6
JournalCurrent Organic Synthesis
Volume16
Issue number1
Early online dateOct 2018
DOIs
Publication statusPublished - 2019

Fingerprint

Coumarins
Decarboxylation
Condensation
Temperature
Derivatives
Poisons
Cyclization
Esterification
Purification
Catalysts
ammonium bicarbonate
salicylaldehyde
coumarin

Keywords

  • 3,4-unsubstituted coumarins
  • Ammonium bicarbonate
  • Catalysis
  • Coumarin-3-carboxylic acids
  • Green chemistry
  • Green knoevenagel

Cite this

van Schijndel, Jack ; Molendijk, Dennis ; Canalle, Luiz Alberto ; Rump, Erik T. ; Meuldijk, Jan. / Temperature dependent green chemical synthesis of 3-carboxycoumarins and 3,4-unsubstituted coumarins. In: Current Organic Synthesis. 2019 ; Vol. 16, No. 1. pp. 130-135.
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abstract = "Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts like pyridine and piperidine but only use ammonium bicarbonate as the catalyst. Materials and Methods: To investigate the scope of the Green Knoevenagel condensation for the synthesis of 3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in the optimized two-step procedure developed for 2-hydroxybenzaldehyde. Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially kept at 90°C for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is increased to 140°C for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95{\%}. Conclusion: A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of Green Chemistry. It was shown that by initially capping the temperature at 90°C, premature decarboxylation can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased to 140°C finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green Knoevenagel condensation and the decarboxylation step.",
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Temperature dependent green chemical synthesis of 3-carboxycoumarins and 3,4-unsubstituted coumarins. / van Schijndel, Jack (Corresponding author); Molendijk, Dennis; Canalle, Luiz Alberto; Rump, Erik T.; Meuldijk, Jan.

In: Current Organic Synthesis, Vol. 16, No. 1, 2019, p. 130-135.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Temperature dependent green chemical synthesis of 3-carboxycoumarins and 3,4-unsubstituted coumarins

AU - van Schijndel, Jack

AU - Molendijk, Dennis

AU - Canalle, Luiz Alberto

AU - Rump, Erik T.

AU - Meuldijk, Jan

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AB - Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts like pyridine and piperidine but only use ammonium bicarbonate as the catalyst. Materials and Methods: To investigate the scope of the Green Knoevenagel condensation for the synthesis of 3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in the optimized two-step procedure developed for 2-hydroxybenzaldehyde. Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially kept at 90°C for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is increased to 140°C for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95%. Conclusion: A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of Green Chemistry. It was shown that by initially capping the temperature at 90°C, premature decarboxylation can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased to 140°C finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green Knoevenagel condensation and the decarboxylation step.

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KW - Coumarin-3-carboxylic acids

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