In organic synthesis, it is not uncommon to produce a fairly complex structure via multiple reactions in a single step. This novel and inexpensive method has advantages such as short reaction times, excellent product yields, and avoidance of organic solvents in agreement with green chemistry principles. Pdf the synthesis of coumarins via pechmann and knoevenagel condensation reactions under solvent free conditions is reported, in which waste. Zro2tio2, zro2zno, and zro2cellulose were identified through spectroscopic. Pechmann reaction in the synthesis of coumarin derivatives. Moreover, some other harsh catalysts used in the pechmann reaction are incl 3, zrcl 4, ybotf 3, and ptsoh. Amphoteric groups and the solvent have a crucial role in. Plausible mechanism for pechmann condensation using eaa and. Heterogeneously catalyzed pechmann condensation employing. The product was confirmed by ir, 1h nmr, and c nmr. Molybdate sulfuric acid msa has been found, prepared and used as a new and efficient catalyst for onepot synthesis of 4substituted coumarins via pechmann reaction. Synthesis and application of nanocrystallinecellulose.
Coumarins are synthesized by pechmann pechmann and duisberg, 1884 2, perkin, witting et al. One of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the pechmann reaction. The pechmann reaction procedure used in this paper was adapted from the literature. Synthesis of 7substituted 4methyl coumarins by pechmann. The prepared catalysts showed high catalytic activities for the synthesis of 7hydroxy4methyl coumarin via the pechmann condensation reaction of resorcinol with ethyl acetoacetate. Solid acid catalysts for coumarin synthesis by the. The pechmann reaction is one of the most valuable methods for synthesis of coumarin which starts by phenols and acidic catalysts like concentrated sulfuric acid and bronsted acidic ionic liquid. Activation enthalpy, entropy and free energy can be determined from the eyringpolanyi equation, which depends on transition state theory, as shown in eq. The coumarin products can be simply separated and the ionic liquid catalyst can be recycled and reused for at least six runs without noticeable decrease in the catalytic activity. Since it proceeds from very simple starting materials and gives good yield of variously substituted coumarins. Resultsanddiscussion a mixture of resorcinol and ethylacetoacetate was ground in the presence of ptoulenesulfonic acid ptsa in a mortar by a pestle scheme 1.
To study the orientation of electrophilic substitution reaction. The pechmann condensation main reaction mechanism table of reagents and products resorcinol ethyl acetoacetate amberlyst 15 4 methylumbelliferone mw gmol 110. Synthesis of coumarins via pechmann reaction catalyzed by. The pechmann reaction introduces one of the most significant and simple methods for the synthesis of a variety of heterocyclic compounds, particularly coumarin derivatives. Two benzocoumarins and a benzochromone were synthesized starting from 2,7dihydroxynaphthalene and ethyl acetoacetate in the presence of amberlyst15 as condensing agent. Solvent free synthesis of coumarin by pechmann reaction.
Initially, the experimental conditions such as the amount of catalyst and temperature reaction were optimized over amberlyst15. The temperature of the reaction mixture started to rise. A useful complement to the pechmann reaction, ultrasonics sonochemistry, 21, 3, 937, 2014. Modified pechmann condensation using grinding technique under solventfree condition at room temperature. Hymecromone, an important insecticide intermediate, were synthesized under solventfree conditions by pechmann reaction upon ultrasound irradiation in the presence of acid zeolites possessing different structural features. Herein, we present the synthesis of coumarin through pechmann reaction by using zirconiabased heterogeneous catalysts zro2tio2, zro2zno, and zro2cellulose in a solventfree condition at room temperature. A solid acidcatalyzed version of the pechmann reaction for the synthesis of coumarins is described. Synthesis of coumarins via pechmann reaction catalyzed by 3. A mixture of phenol, ethylacetoacetate and ionic liquid 60 mol% in nb, in a molar ration of 50. Aniline undergoes electrophilic substitution with bromine at 2, 4, 6 positions to form tribromo aniline. The structures of the products have been elucidated by h nmr, c nmr, ftir spectral methods. Sandhu department of chemistry, punjabi university, patiala 147 002, india email. Coumarin belongs to a class of flavonoids and a type of benzo2pyrone, which is a plant secondary metabolite isolated from natural plants and some microorganisms.
The yields of coumarin derivatives obtained via this new protocol, were equal or higher than those using the conventional method and the reaction time was reduced to a few minutes. Based on density functional theory with the m062x functional, pornsatitworakul et al. Among these, the pechmann reaction has been the most widely used method. The maximum yield of 3a achieved was 88%, in solventfree reaction. Modified pechmann condensation using grinding technique. H 2 so 4, lewis acids alcl 3, zncl 2, zncl 2 al 2 o 3, zrcl 4 etc. Preparation, characterization of highly active recyclable. The disproportionation reaction of aldehydes without. Heropoulos and theodora calogeropoulou, fecl3catalysed ultrasonicassisted, solventfree synthesis of 4substituted coumarins. In continuation of our interest, the current work represents the comparative study of synthesis of 7hydroxy4 methyl coumarin by pechmann condensation using different procedures and its influence with various aspects like yield, reaction time and conditions.
Various coumarin derivatives have been efficiently synthesized via barium dichloridecatalyzed pechmann condensation reaction of various phenols and. The route to the corresponding thiophenecontaining analogue of 1, i. Cholinium ionic liquids as cheap and reusable catalysts. One molecule of aldehyde is reduced to the corresponding alcohol, while a second one is oxidized to the carboxylic acid. Synthesis of coumarins via pechmann condensation using. The progress of the reaction was checked by thin layer. Zirconiabased catalyst for the onepot synthesis of. An efficient solvent free synthesis of coumarins via solid. Synthesis, structure, absorption and fluorescence of. A simple and efficient condition for pechmann condensation for the synthesis of coumarins involving grinding of different phenols and. Pechmann reaction of resorcinol and ethyl acetoacetate produced 7hydroxy4methylcoumarin over regenerable h. Pdf pechmann reaction in the synthesis of coumarin.
Despite the industrial and technological importance of the reaction, its mechanism is still poorly understood. Studying of pechmann condensation products of ethyl. Pechmann condensation coumarin synthesis request pdf. High yield 94% with 100% selectivity of 7hydroxy4methyl coumarin was. One pot synthesis of coumarin derivatives via pechmann. A theoretical study one of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the pechmann reaction. Barium dichloride as a powerful and inexpensive catalyst. In conclusion it can be stated that this is an efficient and low energy path for pechmann reaction where reaction under solvent free conditions producedcoumarin in good yield.
For instance, the antibiotic novobiocin, coumermycin a 1, and chlorobiocin were isolated from microorganisms 1, 2. The gibbs freeenergy profiles of the possible routes suggest that three parallel channels featuring water elimination, transesterification, and electrophilic attack. In this work, coumarin was synthesized from ethyl acetoacetate and resorcinol with sulfuric acid as the catalyst with 86% yield under a mild condition. Department of chemistry, rbvrrwc 5 20172018 preparation of pbromo acetanilide aim. The pechmann condensation allows the synthesis of coumarins by reaction of phenols with. Solventfree condensation of phenol derivatives and. It can easily be seen that the pechmann condensation proceeded smoothly under solventfree conditions and gave good to high yields ranging from 75% to 98%. Bariumdichlorideasapowerfulandinexpensivecatalystfor. After such initiation, the exothermic reaction proceeds on its own to completionwithout additional energy input. Kinetics and mechanism of pechmann condensation reaction over. The pechmann reaction of substituted phenols 1ae with methyl acetoacetate 2 can be activated by boron trifluoride dihydrate 3 to give the corresponding 4methyl. Note synthesis of coumarin by yb0tf catalyzed pechmann.
The reaction of phloroglucinol and ethyl acetoacetate under various conditions. The reaction is conducted with a strong bronstedt acid such as methanesulfonic acid or a lewis acid such as alcl 3. It has been widely employed for the synthesis of coumarins because of its preparative simplicity and inexpensive starting material. With r1oh we have 4hydroxycoumarin, the starting material for the preparation of warfarin. The pechmann reaction catalyzed by barium dichloride. The pechmann reaction has been intensely studied over different catalysts. The condensation is performed under acidic conditions. Cux 2 xcl, br are found to be efficient catalysts 10 mol% for the pechmann condensation reaction of phenols and. The acid catalyses transesterification as well as ketoenol tautomerisation.
Nanalogue 1 of pechmann dye scheme 2, table 1 was obtained by oxidative dimerization of 5phenylpyrrolinone ester under considerably milder reaction conditions. It is a modification of the aldol condensation a knoevenagel condensation is a nucleophilic addition of an active hydrogen compound to a carbonyl group followed by a dehydration reaction in which a molecule of water is eliminated hence condensation. Request pdf pechmann reaction in the synthesis of coumarin derivatives the. The applicability of cannizzaro reaction in organic synthesis is limited as the yield is not more than. A suitable methodology of synthesis of coumarin derivatives by pechmann reaction over heterogeneous solid acid catalysts in a free solvent media under microwave irradiation is described. Modified pechmann condensation using grinding technique under. Tetrakisacetonitrilecopperi hexafluorophosphate cuch 3 cn 4 pf 6 is used as an efficient catalyst in the pechmann condensation reaction of phenols with ethyl acetoacetate leading to the formation of coumarin derivatives in excellent yields under solvent free conditions at ambient temperature. The pechmann condensation reaction of other phenols and ethyl acetoacetate in the presence of msimhso 4 was accomplished under the optimized reaction conditions described above and the results are presented in table 2. The pechmann condensation of phenol and ethyl acetoacetate to afford 4methylcoumarin on microwaveassisted solventfree conditions was studied using different acid heterogeneous catalysts. A faster reaction and higher yields compared to the conventional methods are the advantages of present protocol. Gibbs free energy diagram for a mechanism upper panel, b. Then, the reaction was quenched by the addition of.
Identifiers organic chemistry portal the pechmann condensation is a synthesis of coumarins, starting from a phenol and a carboxylic acid or ester containing a. Pdf pechmann reaction promoted by boron trifluoride. This methodology is very simple, costeffective, ecofriendly and the. Coumarins play an important role in drug development with diverse biological applications. The pechmann reaction is a multipletransformation process which is not a part of the normal. The pechmann condensation of phenol and ethyl acetoacetate to afford 4methylcoumarin on microwaveassisted solvent free conditions was studied using different acid heterogeneous catalysts. Pechmann condensation, perkin reaction, knoevenagel condensation, wittig reaction etc. This methodology offers significant improvements for the synthesis of coumarins with regards to yield of product, simplicity in operation, and avoiding toxic catalysts and. Pechmann reaction promoted by boron trifluoride dihydrate. Scheme 2 proposed mechanism of pechmann reaction of resorcinol with eaa at 40 c under solventfree conditions. Cannizzaro reaction mechanism examples adichemistry. Coumarin, which is an important material class of substrate in agricultural and pharmaceutical industries, can be obtained by the pechmann condensation reaction. Plausible mechanism for pechmann condensation using eaa and phloroglucinol promoted.