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. Plausible mechanism for pechmann condensation using eaa and phloroglucinol promoted. After such initiation, the exothermic reaction proceeds on its own to completionwithout additional energy input. 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. Based on density functional theory with the m062x functional, pornsatitworakul et al. The prepared catalysts showed high catalytic activities for the synthesis of 7hydroxy4methyl coumarin via the pechmann condensation reaction of resorcinol with ethyl acetoacetate. Coumarins are synthesized by pechmann pechmann and duisberg, 1884 2, perkin, witting et al. The applicability of cannizzaro reaction in organic synthesis is limited as the yield is not more than. With r1oh we have 4hydroxycoumarin, the starting material for the preparation of warfarin.
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. 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. 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. Synthesis of coumarins via pechmann condensation using. The route to the corresponding thiophenecontaining analogue of 1, i. 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. Initially, the experimental conditions such as the amount of catalyst and temperature reaction were optimized over amberlyst15. A theoretical study one of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the pechmann reaction.
Various coumarin derivatives have been efficiently synthesized via barium dichloridecatalyzed pechmann condensation reaction of various phenols and. Pechmann condensation, perkin reaction, knoevenagel condensation, wittig reaction etc. A simple and efficient condition for pechmann condensation for the synthesis of coumarins involving grinding of different phenols and. Two benzocoumarins and a benzochromone were synthesized starting from 2,7dihydroxynaphthalene and ethyl acetoacetate in the presence of amberlyst15 as condensing agent. The temperature of the reaction mixture started to rise. Identifiers organic chemistry portal the pechmann condensation is a synthesis of coumarins, starting from a phenol and a carboxylic acid or ester containing a.
A solid acidcatalyzed version of the pechmann reaction for the synthesis of coumarins is described. Gibbs free energy diagram for a mechanism upper panel, b. Sandhu department of chemistry, punjabi university, patiala 147 002, india email. Scheme 2 proposed mechanism of pechmann reaction of resorcinol with eaa at 40 c under solventfree conditions. Kinetics and mechanism of pechmann condensation reaction.
Amphoteric groups and the solvent have a crucial role in. High yield 94% with 100% selectivity of 7hydroxy4methyl coumarin was. One molecule of aldehyde is reduced to the corresponding alcohol, while a second one is oxidized to the carboxylic acid. Barium dichloride as a powerful and inexpensive catalyst. In modified form the pechmann reaction can be carried out in refluxing toluene catalyzed by zinc and iodine or wzro 2, or under solventfree conditions in the presence of ptsoh, titaniumiv chloride, bismuthiii chloride, wellsdawson heteropolyacid h 6 p 2 w 18 o. Studying of pechmann condensation products of ethyl.
To study the orientation of electrophilic substitution reaction. Department of chemistry, rbvrrwc 5 20172018 preparation of pbromo acetanilide aim. Synthesis, structure, absorption and fluorescence of. The reaction is conducted with a strong bronstedt acid such as methanesulfonic acid or a lewis acid such as alcl 3. Coumarin, which is an important material class of substrate in agricultural and pharmaceutical industries, can be obtained by the pechmann condensation reaction. The pechmann reaction catalyzed by barium dichloride. Modified pechmann condensation using grinding technique. Solventfree condensation of phenol derivatives and. Pechmann condensation coumarin synthesis request pdf. The reaction of phloroglucinol and ethyl acetoacetate under various conditions. The condensation is performed under acidic conditions. The gibbs freeenergy profiles of the possible routes suggest that three parallel channels featuring water elimination, transesterification, and electrophilic attack. H 2 so 4, lewis acids alcl 3, zncl 2, zncl 2 al 2 o 3, zrcl 4 etc.
Pdf pechmann reaction promoted by boron trifluoride. Moreover, some other harsh catalysts used in the pechmann reaction are incl 3, zrcl 4, ybotf 3, and ptsoh. The maximum yield of 3a achieved was 88%, in solventfree reaction. Cux 2 xcl, br are found to be efficient catalysts 10 mol% for the pechmann condensation reaction of phenols and. The pechmann condensation main reaction mechanism table of reagents and products resorcinol ethyl acetoacetate amberlyst 15 4 methylumbelliferone mw gmol 110. One pot synthesis of coumarin derivatives via pechmann. 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. Then, the reaction was quenched by the addition of. In this work, coumarin was synthesized from ethyl acetoacetate and resorcinol with sulfuric acid as the catalyst with 86% yield under a mild condition. Resultsanddiscussion a mixture of resorcinol and ethylacetoacetate was ground in the presence of ptoulenesulfonic acid ptsa in a mortar by a pestle scheme 1. 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%. The pechmann condensation allows the synthesis of coumarins by reaction of phenols with. Note synthesis of coumarin by yb0tf catalyzed pechmann.
The pechmann reaction is a multipletransformation process which is not a part of the normal. Solid acid catalysts for coumarin synthesis by the. Modified pechmann condensation using grinding technique under solventfree condition at room temperature. 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. The pechmann condensation of phenol and ethyl acetoacetate to afford 4methylcoumarin on microwaveassisted solvent free conditions was studied using different acid heterogeneous catalysts. The structures of the products have been elucidated by h nmr, c nmr, ftir spectral methods. Pechmann reaction of resorcinol and ethyl acetoacetate produced 7hydroxy4methylcoumarin over regenerable h. It has been widely employed for the synthesis of coumarins because of its preparative simplicity and inexpensive starting material. The pechmann reaction has been intensely studied over different catalysts. Synthesis of coumarins via pechmann reaction catalyzed by 3. Pechmann reaction in the synthesis of coumarin derivatives. Bariumdichlorideasapowerfulandinexpensivecatalystfor. The progress of the reaction was checked by thin layer. Cannizzaro reaction mechanism examples adichemistry.
In organic synthesis, it is not uncommon to produce a fairly complex structure via multiple reactions in a single step. Zirconiabased catalyst for the onepot synthesis of. Aniline undergoes electrophilic substitution with bromine at 2, 4, 6 positions to form tribromo aniline. 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. One of the most widespread synthetic routes to coumarins is the condensation of esters and phenols via the pechmann reaction. Activation enthalpy, entropy and free energy can be determined from the eyringpolanyi equation, which depends on transition state theory, as shown in eq. The disproportionation reaction of aldehydes without. Modified pechmann condensation using grinding technique under. The main method for the synthesis of coumarins is the pechmann reaction of substituted phenols of type 1 with methyl, 2, or ethyl acetoacetate in the presence of protonic acid conc. Kinetics and mechanism of pechmann condensation reaction over.
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 reaction of substituted phenols 1ae with methyl acetoacetate 2 can be activated by boron trifluoride dihydrate 3 to give the corresponding 4methyl. A mixture of phenol, ethylacetoacetate and ionic liquid 60 mol% in nb, in a molar ration of 50. Nanalogue 1 of pechmann dye scheme 2, table 1 was obtained by oxidative dimerization of 5phenylpyrrolinone ester under considerably milder reaction conditions. This methodology is very simple, costeffective, ecofriendly and the. A faster reaction and higher yields compared to the conventional methods are the advantages of present protocol.
An efficient solvent free synthesis of coumarins via solid. 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. Synthesis of 7substituted 4methyl coumarins by pechmann. Plausible mechanism for pechmann condensation using eaa and. Pdf the synthesis of coumarins via pechmann and knoevenagel condensation reactions under solvent free conditions is reported, in which waste. Pechmann reaction promoted by boron trifluoride dihydrate. For instance, the antibiotic novobiocin, coumermycin a 1, and chlorobiocin were isolated from microorganisms 1, 2. Coumarins play an important role in drug development with diverse biological applications. Request pdf pechmann reaction in the synthesis of coumarin derivatives the.
Despite the industrial and technological importance of the reaction, its mechanism is still poorly understood. Solvent free synthesis of coumarin by pechmann reaction. Zro2tio2, zro2zno, and zro2cellulose were identified through spectroscopic. Pdf pechmann reaction in the synthesis of coumarin.
Preparation, characterization of highly active recyclable. Pechmann condensation reaction was first reported by pechmann and duisberg in 1883. 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. The pechmann condensation of phenol and ethyl acetoacetate to afford 4methylcoumarin on microwaveassisted solventfree conditions was studied using different acid heterogeneous catalysts. 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. 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. The acid catalyses transesterification as well as ketoenol tautomerisation. A useful complement to the pechmann reaction, ultrasonics sonochemistry, 21, 3, 937, 2014. Among these, the pechmann reaction has been the most widely used method. Synthesis and application of nanocrystallinecellulose. This methodology offers significant improvements for the synthesis of coumarins with regards to yield of product, simplicity in operation, and avoiding toxic catalysts and. Heropoulos and theodora calogeropoulou, fecl3catalysed ultrasonicassisted, solventfree synthesis of 4substituted coumarins.