the widespread interest in 3,4-dihydropyrimidin-2(1h)-ones , biginelli compounds , has resulted in enormous efforts towards the synthesis of this biologically important moiety . several methods have been developed for the synthesis of these compounds , but most of these protocols involve expensive reagents , strong acid catalysts , solvents , of prolonged reaction time and even then provide the products in unsatisfactory yields . with the current global awareness of developing environmentally friendly technologies , it is a need to perform a reaction in neat and nonhazardous conditions for providing a green approach towards organic synthesis . therefore , it was decided to develop an efficient method for the synthesis of biginelli compounds . in this communication , we report a straightforward and simple procedures for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones using a mixture of phosphorus pentoxide - methanesulfonic acid ( eaton 's reagent ) . eaton 's reagent ( 1  :  10 phosphorus pentoxide in methanesulfonic acid ) is an inexpensive and commercially available substance synthesized by eaton in 1973 and found to be a good alternative to polyphosphoric acid which enables the drawbacks of many traditional catalysts to be overcome , because it has a much lower viscosity , it is easier to handle , and no complex separation procedures need to be employed . many processes that employ a mixture of p2o5/meso3h are not only more economical , but also they are more environmentally friendly and offer a number of distinct advantages such as safe in industrial scale , no additional solvent required , chlorine - free , rapid reactions , and high - purity products with excellent yields . the distinctive physical and chemical properties of eaton 's reagent make it a very useful substance in many different reactions with different applications . mcgarry and detty successfully used this reagent in cycloacylation reactions for producing chromones and flavones ; recently , zewge and coworkers used eaton 's reagent to promote the cyclization of aniline derivatives to produce 4-quinolones . p2o5/meso3h offers a simple means of producing poly(benzimidazoles ) from o - phenylenediamines and aromatic carboxylic acids . kaboudin and abedi employed this system for synthesis of aryl mesylates . in continuation of our efforts on developing environmentally benign , green methodologies for biologically active organic compounds [ 79 ] , herein we report a rapid , ambient temperature , and solvent - free method for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones using eaton 's reagent . 3,4-dihydropyrimidin-2(1h)-ones , biginelli compounds , have been synthesized by condensing aldehyde , ethylacetoacetate and urea or thiourea under acidic conditions . methanesulfonic acid   and phosphorus pentoxide   have been used as catalysts in the past decade . both of these transformations require conventional heating and use of organic solvents . in case of methanesulfonic acid , the reaction mixture is refluxed for 6 - 7  h using ethanol as solvent , and in phosphorus pentoxide , it is refluxed for 3 - 4  h. in view of these results , it was decided to use eaton 's reagent ( p2o5 and ch3so3h ) under solvent - free conditions at room temperature for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones . the synthesis of functionalized 3,4-dihydropyrimidin-2(1h)-one derivatives is the area of interest because a large number of biologically active molecules contain this moiety . many dihydropyrimidinones and their derivatives are pharmacologically important as they possess antitumor , antibacterial , and antiviral properties ; they have also emerged as integral backbones of several calcium - channel blockers , vasorelaxants , antihypertensive , and antimitotic agents [ 1317 ] . the literature survey reveals that numerous methods have been developed for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones by three - component cyclocondensation of aldehyde , urea , and ethylacetoacetate , which comprises the use of ionic liquids , microwave irradiation , ultrasound irradiation , bf3oet2 , nicl26h2o and fecl36h2o , cocl26h2o , bicl3 , incl3 , and inbr3 . zn(otf)2 , cu(otf)2 , bi(otf)3 , p - tsa , silica sulphuric acid , potassium hydrogen sulphate , formic acid , chloroacetic acid , chlorosulfonic acid , p2o5/sio2 , tfa , cf3coonh4 , p - tsa in biphasic media , zncl2 , and i2 . in our recent study about the synthesis of bis(indolyl)methanes under mild conditions , we found that reagent works extremely well for the coupling reaction . in this paper , herein we employed the reagent in a multicomponent , one - pot reaction for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones at room temperature . eaton 's reagent is a colorless , odorless liquid mixture of nonoxidizing methanesulfonic acid and a powerful dehydrating agent phosphorus pentoxide . the addition of phosphorus pentoxide increases the solubility of organic compounds in methanesulfonic acid ; this was introduced by eaton and has been used enormously in organic synthesis .   in order to standardize the reaction conditions for the condensation reaction , it was decided to synthesize 3,4-dihydropyrimidin-2(1h)-one ( 4a ) from benzaldehyde ( 1a ) , urea , and ethylacetoacetate using a mixture of p2o5/meso3h , and we found that the reaction is fast when compared to other reported methods . the results are compared with the reported methods , and it is clear from table 1 that the present method is more efficient .   to optimize the reaction condition , the condensation reaction was performed under different conditions ( table 2 ) . in the presence of eaton 's reagent ( 2  mmol for each operation ) , initially 4-chlorobenzaldehyde ( 1k ) was used as model for the reaction with ethylacetoacetate and urea . the reaction carried out at room temperature using ethanol as solvent required 2.3  h for completion , and the product ( 4k ) was obtained in 60% yield ( entry 1 ) . when the reaction was performed by using ethanol under refluxing conditions , it required 2  h and provided the product in 65% yield ( entry 2 ) . when the reaction was performed without any solvent at room temperature using 2  mmol of eaton 's reagent , the reaction was completed in 5  min , and the product ( 4k ) was obtained in 85% yield ( entry 3 ) . to explore the scope and limitations of this reaction , we extended the procedure to various aromatic aldehydes carrying either electron - releasing or electron - withdrawing substituents in the ortho- , meta- , and para - positions . we have also synthesized the compounds with thiourea and methylacetoacetate , and we found that the reaction proceeds very efficiently with all the cases , and the products are obtained in high yields ( table 3 ) . eaton 's reagent ( 7.7/92.3% by weight of p2o5/meso3h ) was purchased from sigma - aldrich . the purity of the compounds was checked by tlc on silica gel g ( merck ) . h nmr spectra were recorded on varian 300  mhz instrument , in dmso - d6 using tms as the internal standard . ir spectra were obtained using a nujol for solids on a perkin - elmer-1710 spectrophotometer . mass spectra were recorded on thermo finnigan ( model - lcq advantage max ) mass spectrometer . a mixture of aromatic aldehyde 1 ( 1  mmol ) , ethylacetoacetate 2 ( 1  mmol ) , and urea 3 ( 1.5  mmol ) was stirred with eaton 's reagent ( 2  mmol ) at room temperature for appropriate time ( mentioned in table 3 ) . after completion of the reaction ( monitored by tlc ) , the reaction mass was transferred to an excess saturated sodium carbonate solution . the solid products separated out , were filtered , and washed with sufficient water and dried . the crude products on recrystallization from ethanol provided 3,4-dihydropyrimidin-2(1h)-ones ( 4a4u ) in 7596% yield . mp 202204c ; ir(nujol ) cm : 3244 ( nh ) , 3108 ( nh ) , 1729 ( c = o ) , 1645 ( c = c ) , 1460 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.18 ( br s , 1h , nh ) , 7.73 ( br s , 1h , nh ) , 7.217.34 ( m , 5h , arh ) , 5.13 ( d , 1h , j = 3.3  hz , ch ) , 3.97 ( q , 2h , j = 7.15  hz , och2 ) , 2.24 ( s , 3h , ch3 ) , 1.08 ( t , 3h , j = 7.15  hz , ch3 ) ; ms ( m / z ) : 260 ( m ) . mp 248250c ; ir(nujol ) cm : 3357 ( nh ) , 3108 ( nh ) , 1696 ( c = o ) , 1646 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.32 ( br s , 1h , nh ) , 7.78 ( br s , 1h , nh ) , 7.277.56 ( m , 3h , arh ) , 5.67 ( d , 1h , j = 2.4  hz , ch ) , 3.88 ( q , 2h , j = 6.9  hz , och2 ) , 2.29 ( s , 3h , ch3 ) , 0.96 ( t , 3h , j = 7.15  hz , ch3 ) ; ms ( m / z ) : 329 ( m ) . mp 252254c ; ir(nujol ) cm : 3359 ( nh ) , 3108 ( nh ) , 1716 ( c = o ) , 1640 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.31 ( br s , 1h , nh ) , 7.76 ( br s , 1h , nh ) , 7.297.56 ( m , 3h , arh ) , 5.58 ( s , 1h , ch ) , 3.88 ( q , 2h , j = 7.15hz , och2 ) , 2.28 ( s , 3h , ch3 ) , 0.99 ( t , 3h , j = 6.9hz , ch3 ) ; ms ( m / z ) : 329 ( m ) . mp 216218c ; ir(nujol ) cm : 3345 ( nh ) , 3110 ( nh ) , 1704 ( c = o ) , 1645 ( c = c ) , 1462 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.20 ( br s , 1h , nh ) , 7.73 ( br s , 1h , nh ) , 7.48 ( d , 2h , j = 8.1  hz , arh ) , 7.14 ( d , 2h , j = 8.1  hz , arh ) , 5.07 ( d , 1h , j = 2.8  hz , ch ) , 3.93 ( q , 2h , j = 6.9  hz , och2 ) , 2.20 ( s , 3h , ch3 ) , 1.04 ( t , 3h , j = 7.15  hz , ch3 ) ; ms ( m / z ) : 339 ( m ) . mp 226228c ; ir(nujol ) cm : 3507 ( nh ) , 3108 ( nh ) , 1682 ( c = o ) , 1645 ( c = c ) , 1460 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.06 ( br s , 1h , nh ) , 7.57 ( br s , 1h , nh ) , 7.02 ( d , 2h , arh ) , 6.67 ( d , 2h , arh ) , 5.03 ( d , 1h , j = 2.9  hz , ch ) , 3.97 ( q , 2h , j = 7.15  hz , och2 ) , 2.22 ( s , 3h , ch3 ) , 1.09 ( t , 3h , j = 7.15  hz , ch3 ) ; ms ( m / z ) : 277 ( m+h ) . mp 208210c ; ir(nujol ) cm : 3326(nh ) , 3204 ( nh ) , 1695 ( c = o ) , 1666 ( c = c ) , 1460 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.24 ( br s , 1h , nh ) , 7.76 ( br s , 1h , nh ) , 7.117.27 ( m , 4h , arh ) , 5.13 ( d , 1h , j = 2.9  hz , ch ) , 3.51 ( s , 3h , ch3o ) , 2.24 ( s , 3h , ch3 ) ; ms ( m / z ) : 265 ( m+h ) . mp 212214c ; ir(nujol ) cm : 3334 ( nh ) , 3108 ( nh ) , 1704 ( c = o ) , 1650 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 9.21 ( br s , 1h , nh ) , 7.75 ( br s , 1h , nh ) , 7.217.31 ( m , 5h , arh ) , 5.13 ( s , 1h , ch ) , 3.51 ( s , 3h , ch3o ) , 2.23 ( s , 3h , ch3 ) ; ms ( m / z ) : 247 ( m+h ) . mp 194198c ; ir(nujol ) cm : 3323 ( nh ) , 3165 ( nh ) , 1670 ( c = o ) , 1575 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 10.28 ( br s , 1h , nh ) , 9.60 ( br s , 1h , nh ) , 7.12 ( d , 2h , j = 8.1  hz , arh ) , 7.06 ( d , 2h , j = 8.1  hz , arh ) , 5.10 ( d , 1h , j = 2.8  hz , ch ) , 3.97 ( q , 2h , j = 6.95  hz , och2 ) , 2.25 ( s , 3h , ch3 ) , 2.24 ( s , 3h , arch3 ) , 1.08 ( t , 3h , j = 7.15  hz , mp 196198c ; ir(nujol ) cm : 3357 ( nh ) , 3108 ( nh ) , 1670 ( c = o ) , 1644 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 10.24(br s , 1h , oh ) 9.55 ( br s , 1h , nh ) , 9.43 ( br s , 1h , nh ) , 6.99 ( d , 2h , j = 8.1  hz , arh ) , 6.69 ( d , 2h , j = 8.1  hz , arh ) , 5.04 ( d , 1h , j = 2.8  hz , ch ) , 3.98 ( q , 2h , j = 6.9  hz , och2 ) , 2.26(s , 3h , ch3 ) , 1.09 ( t , 3h , j = 6.9  hz , ch3 ) ; ms ( m / z ) : 293 ( m+h ) . mp 140142c ; ir(nujol ) cm : 3311 ( nh ) , 3165 ( nh ) , 1664 ( c = o ) , 1574 ( c = c ) , 1459 ( ch ) ; h nmr ( 300  mhz , dmso - d6 ) : h 10.28 ( br s , 1h , nh ) , 9.59 ( br s , 1h , nh ) , 7.12 ( d , 2h , j = 8.6  hz , arh ) , 6.89 ( d , 2h , j = 8.6  hz , arh ) , 5.10 ( d , 1h , j = 3.9  hz , ch ) , 3.99 ( q , 2h , j = 7.15  hz , och2 ) , 3.71 ( s , 3h , ch3o ) , 2.27 ( s , 3h , ch3 ) , 1.10 ( t , 3h , j = 7.15  hz , ch3 ) ; ms ( m / z ) : 307 ( m+h ) . in summary , we have developed an efficient , ecofriendly and solvent - free method for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones ( 4a4u ) . the present method which makes use of commercially available eaton 's reagent offers a very attractive features such as shorter reaction times , simple operations with extremely milder conditions , green aspects avoiding hazardous organic solvents , toxic catalyst , and provides good to excellent yields .
an expeditious , one - pot method for the synthesis of 3,4-dihydropyrimidin-2(1h)-ones using a mixture of phosphorus pentoxide - methanesulfonic acid ( eaton 's reagent ) at room temperature under solvent - free conditions is described . 
 the salient features of this method include short reaction time , green aspects , high yields , and simple procedure .