the exercise of metal / metal oxide nanoparticles as a frontier between the homogeneous catalysis and heterogeneous catalysis   in organic synthesis has invoked tremendous interests   in the recent times . the interesting features inherited with these small particle sizes are their large surface area along with more edges and corners and distinct electronic , optical , magnetic , thermal , and chemical properties [ 35 ]
. the crucial role of nanoparticles in organic transformations is their excellent catalytic activity , straightforward recoverability , better selectivity , criteria of evolution , and their versatile role in green chemistry [ 610 ] .
thus , the domain of metal nanoparticle catalysis [ 1113 ] should offer opportunities for mining new chemical reactions [ 1416 ] which include the synthesis of biologically important and synthetically challenging natural products . in the context of green chemistry , organic synthesis in solvent - free reaction condition [ 1821 ]
has occupied a significant position in the recent years since solvent - free reaction condition involves the best reaction medium with  no medium  .   
one of the key motifs present in the biopolymer rna [ 2326 ] is uracil , a nucleobase of the pyrimidine family which participates in various functions in our life processes .
uracil derivatives also have several potent medicinal properties such as bronchodilators and anticancer [ 28 , 29 ] , antiallergic [ 30 , 31 ] , antiviral [ 32 , 33 ] , antihypertensive , and adenosine receptor antagonists [ 34 , 35 ] .
recently , our research group reported a greener protocol for the synthesis of bisuracil derivatives .
some of the n - substituted bisuracil analogues have been screened for bioactivities against several diseases . to explore the possible applications of the metal / metal oxide nanoparticles in organic synthesis ,
we have been focusing on the advancement of a protocol termed  nose  ( nanoparticles - catalyzed organic synthesis enhancement ) [ 3941 ] chemistry in our laboratory . to the best of our knowledge
, there has been no report on nano - rod - shaped al2o3 catalyzed n , n - diformylation of bisuracil derivatives .
recently , we reported n - formylation of amines catalyzed by nano - al2o3 under solvent - free reaction condition .
this work inspired us to focus on nano - al2o3 catalysis for the n , n - diformylation of bisuracil analogous .
therefore , in this paper , we wish to account for the same ( scheme 1 ) .
nano - al2o3 draws our attention due to its crystalline size and shape , abrasive and insulating properties , less toxicity , large surface area , basic surface characteristics , high resistant towards bases and acids and excellent wear resistance [ 4044 ] .
rod - shaped nano - al2o3 ( the average particle diameter is 8.12  nm and average length 25.5  nm , sbet = 185.63  m  g ,  = 3.98  g  cm , and purity is 99.99% ) were purchased from sigma aldrich and used as received .
the chemicals and reagents were purchased from sigma - aldrich , merck , m / s s.d .
fine chemicals pvt . ltd . , and loba chemie , and used without further purification .
ir spectra were recorded as kbr pallets in a nicolet ( impact 410 ) ft - ir spectrophotometer .
h and c nmr spectra were recorded in a 400  mhz nmr spectrophotometer ( jeol , jnm ecs ) using tetramethylsilane ( tms ) as the internal standard , and coupling constants are expressed in hertz .
elemental analyses were carried out in a perkin - elmer chn analyser ( 2400 series ii ) .
mass spectra were recorded with a waters q - tof premier and an acquity uplc spectrometer .
reactions were monitored by thin - layer chromatography using aluminium sheets with silica gel 60 f254 ( merck ) . in a two - neck round bottom flask ( 50  ml ) , nanorod - shaped basic al2o3 ( 7.0  mol% , 7.12  mg ) were taken , and then 1 g ( 1.0  mmol , 414  mg ) and formic acid ( 98% , 6.0  mmol , 0.23  ml ) were added .
after that , it was allowed to stir on a pre heated oil bath at 40c for the required time ( the progress of the reaction was judged by tlc ) .
the reaction mixture was brought to room temperature after its completion , and ethyl acetate ( 3  10  ml ) was added and then centrifuged ( 3,000  r.p.m ) to recover the nanocatalyst . having done this , the reaction mixture was washed with water and brine , dried over anhydrous na2so4 , and concentrated in a rotary evaporator , and finally the crude product was purified by column chromatography ( 30% ethyl acetate : hexane as an eluent ) .
the recovered catalyst was washed with hot ethanol ( 3  10  ml ) to remove the organic impurities , decanted , dried in an oven at 80c for 6  h , and reused for evaluating the performance in the next run in the reaction as shown in scheme 2 .
with the previously reported catalyst characterizations in hand , to begin with , reaction of 6,6-diamino-1,1,3,3-tetramethyl-5,5-(benzylidene)bis[pyrimidine-2,4 ( 1h , 3h)-dione ]   ( 1a , 1  mmol ) with formic acid ( 6  mmol ) was chosen as the model reaction ( scheme 2 ) .
initially , the reaction was carried out without using catalyst under solvent - free reaction condition at 40c and 80c which did not yield any product ( table 1 , entries 1 and 2 ) .
various solvents were also tested under the mentioned condition , but they all failed ( table 1 , entries 311 ) to provide any product .
these negative results suggested that we look for an effective catalyst in the present study .
next , various lewis acid - base catalysts ( table 1 , entries 1214 ) along with the nanocatalysts ( table 1 , entries 1518 ) were surveyed to observe the influence on rate and yield of n , n - diformylation of 1a which were not fruitful .
interestingly , nanorod - shaped basic al2o3 stood out as a choice of catalyst at 7  mol% loading ( table 1 , entry 15 ) under solvent - free reaction condition at 40c . during the course of our experiment
, we observed that at higher temperature ( table 1 , entry 19 ) and at lower / higher catalyst loading the yield of the products was poor ( table 1 , entries 2022 ) .
thus , the yield of n , n - diformylation product of bisuracil derivatives is highly dependent upon the temperature and catalyst loading .   with this supportive optimized reaction condition in hand ,
a series of bisuracil derivatives ( entries 111 ) bearing different aliphatic , aromatic , and heterocyclic moieties were examined to explore the scope and limitations of this reaction and the outcomes are presented in table 2 .
it is clear from table 2 that bisuracil derivatives carrying both electron donating and electron withdrawing groups in benzene ring underwent n , n - diformylation reaction smoothly producing good yields ( table 2 , entries 18 ) .
however , longer reaction time was required for bisuracil derivatives substituted with furan and alkyl groups ( table 2 , entries 911 ) .
it is worth mentioning that 6-amino-1,3-dimethyluracil when treated with formic acid under the current condition gave n , n - diformylation product in lower yield ( 26% , 9  h ) .
the reactions were found to be clean , and no side products were formed .   to test the recyclability ( vide scheme 2 ) of nano - al2o3 ,
it was separated from the reaction mixture by adding ethyl acetate ( 10  ml ) , centrifuged at 3,000  rpm , to pellet out the catalyst .
the separated particles were washed with hot ethanol ( 3  10  ml ) to remove the organic impurities , decanted , dried in an oven at 80c for 6  h , and reused for further reactions .
the efficiency of the catalyst was found to be unaffected up to 4th run , and after that , its action started to decrease as shown in table 3 .
the tons were also retained from fresh up to the 5th cycle , and after that it decreased considerably .  
the recovered catalyst was also investigated through powder xrd and it was compared with the fresh nano - al2o3 ( figure 1 ) . in the powder xrd of the recovered catalyst after 6th run ( figure 1 ) , the intensity of the peaks ( 4 0 0 ) and ( 1 0 0 ) weakened and became broad .
it might be due to the blockage of the pores of the catalyst which caused a decrease in effective active sites and also due to the dislocation of the crystal planes after each run which in turn decreased the yield .
the sem micrograph of the fresh nano - al2o3 previously reported by us   was also compared with the recycled one ( figure 2 ) under the present study . as indicated in figure 2
, the recycled nano - al2o3 revealed the aggregation of the particles responsible for reducing its surface area and hence deactivated the catalyst after 4th run which caused the lower yield of product .
in conclusion , we have demonstrated a novel method for synthesis the n , n - diformylation of bisuracil derivatives in good yield under solvent - free reaction condition at 40c catalyzed by recyclable nano - al2o3 rods . nano - al2o3 catalyzed organic transformations
we believe that this work would find wide applications for new chemical transformations , including those which enable the synthesis of complex natural products and derivatives .
 a feasible  nose  ( nanoparticles - catalyzed organic synthesis enhancement ) protocol has been developed for n , n - diformylation of bisuracil derivatives using nano - al2o3 rods as an efficient , inexpensive , and recyclable catalyst under solvent - free reaction condition at 40c . 
 the catalyst was reused up to the 4th cycle without affecting the rate and yield of the n , n - diformylation products appreciably . 
1. Introduction
2. Materials and Methods
3. Results and Discussion
4. Conclusions