Caffeine Catalyzed Synthesis of Tetrahydrobenzo[b]pyran Derivatives: Synthesis and Insight into Kinetics and Mechanism

Author(s): Sayyed Mostafa Habibi-Khorassani, Mehdi Shahraki, Ebrahim Mollashahi, Sayyedeh Shadfar Pourpanah, Shabnam Keshavarz Majdabadi.

Journal Name: Combinatorial Chemistry & High Throughput Screening

Volume 19 , Issue 10 , 2016

Submit Manuscript
Submit Proposal


Aim and objective: Tetrahydrobenzo[b]pyran derivatives are considered as a special class in drug research because of their various biological and pharmacological benefiting usages. In the current work, we developed new synthetic methods for the preperation of tetrahydrobenzo[b]pyran derivatives using arylaldehydes 1, malononitrile 2 and dimedonein 3 in the presence of caffeine as catalyst as a cheap, easily accessible, biodegradable and green catalyst. Moreover, for the first time, we have described kinetic results together along with detailed mechanistic studies of the synthetic reaction of a derivative of 4Htetrahydrobenzo[ b]pyran based on a global kinetic analysis methodology using UVvis spectrophotometry apparatus.

Material and method: Products were characterized by comparison of physical data with authentic samples and spectroscopic data (IR and NMR). Infrared (IR) spectra were recorded on a JASCO FT IR460 plus spectrometer. 1H nuclear magnetic resonance (NMR) spectra were obtained with a Bruker DRX400 Advance spectrometer and using deuterated dimethylsulfoxide (DMSO) and acetone as solvents. Thinlayer chromatography (TLC) was performed on Silica–gel polygram SILG/UV 254 plates. Rate constants are presented as an average of several kinetic runs (at least 6-10) and are reproducible within ± 3%. The overall rate of reaction is followed by monitoring the absorbance changes of the products versus time on a Varian (Model Cary Bio-300) UV-vis spectrophotometer with a 10 mm light-path cell.

Results: For optimization, the reaction of benzaldehyde (1 mmol), malonitrile (1 mmol) and dimedone (1 mmol) was investigated. The desired results were obtained at 70 °C in the presence of (20 mol %) caffeine in H2O: EtOH (2:1). Moreover, the overall order of reaction for the formation of a 4Htetrahydrobenzo[ b]pyran derivative in the presence of caffeine followed second-order kinetics and the partial orders with regard to 4-nitrobenzaldehyde 1, malononitrile 2 and dimedone 3 were one, one and zero, respectively.

Conclusion: It was observed that the yield was a function of temperature, as the yield increased, the reaction temperature rose. At 70 ºC, the product was obtained with an excellent yield and higher temperatures did not increase the reaction yield any more. Also, 20 mol% was elected as a suitable amount of catalyst for this reaction. It is understood from the result that the rate of reaction speeds up in a solvent with a high dielectric constant (H2O/EtOH, 2:1) compared to those with a low dielectric constant (Ethanol and methanol) at all temperatures. In the studied temperature range, the second-order rate constant of the reaction was inversely proportional to the temperature, which was in agreement with the Arrhenius and Eyring equations. It was obvious that the high positive values of the activation parameters leads to a stiff reaction progress. The first step of the proposed mechanism was identified as a rate-determining step (k1) and this was confirmed based on the steady-state approximation.

Keywords: Caffeine, catalyst, kinetics, mechanism, Tetrahydrobenzo[b]pyran derivative.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2016
Page: [865 - 874]
Pages: 10
DOI: 10.2174/1386207319666161006103042
Price: $58

Article Metrics

PDF: 16
PRC: 1