RIETAL JURAL F CEMITRY An International pen Free Acce, Peer Reviewed Reearch Journal www.orientjchem.org I: 0970-020 X CDE: JCEG 207, Vol. 33, o. (): Pg. 2090-209 olvent Free and Catalyt Free ynthei of ctahydroquinazolinone via Grindtone Chemitry: A Total Green Approach Tanay Pramanik*, Kounar Majeed and Richa Gupta Department of Chemitry, Faculty of Technology and cience, Lovely Profeional Univerity, Phagwara, Punjab-, India. *Correponding author E-mail: tanay.pramanik@gmail.com http://dx.doi.org/0.3005/ojc/33059 (Received: June 02, 207; Accepted: June 30, 207) ABTRACT ctahydroquinazolinone i a heterocyclic compound of immene importance in the field of medicinal and pharmaceutical chemitry. Although a large number of method are reported in literature for ynthei of ctahydroquinazolinone via one pot multi component cyclo condenation reaction of dimedone, thio urea and aromatic aldehyde, grindtone ynthei of thi heterocyclic compound i not reported till date. ereby a green method i reported for the very firt time for grindtone ynthei of ctahydroquinazolinone in a completely olvent free and catalyt free condition. A erie of derivative of thi heterocyclic compound were yntheized uing variou derivative of aromatic aldehyde a reactant. After completion of reaction the crude product wa re-crytallized from hot ethanol to obtain pure compound which were further characterized by melting point, IR and MR pectrocopy. Keywork- ctahydroquinazolinone, green ynthei, grindtone chemitry. ITRDUCTI For lat few decade cta hydro quinazolinone which i an -containing heterocyclic compound ha attracted much attention from the reearcher. Thank to it divere therapeutic, antimicrobial 2, 3 analgeic and antiinflammatory 5 activitie. The mot convenient and eay method for ynthei of octahydroquinazolinone i one pot multi component cyclo condenation Biginelli reaction employing equimolar quantity of dimedone, thio urea and aromatic aldehyde a reactant. everal method which have been developed by the reearcher involve the uage of non eco friendly catalyt 6 and toxic olvent 7 for ynthei of thi heterocyclic molecule. A part of our ongoing proce for development of environmentally benign ynthetic protocol for biginelli reaction, variou eco friendly and novel methodology uch a olvent free and catalyt free Biginelli 8, Biginelli reaction in fruit juice medium 9-0, microwave and light 2 aited biginelli reaction ha already been developed and
209 Pramanik et al., rient. J. Chem., Vol. 33(), 2090-209 (207) reported by our reearch group but green ynthei of octahydroquinazolinone ha never been attempted by our reearch group till date. Multi component reaction via grindtone methodology i well known and well documented in literature. Grindtone technique i conidered to be environmentally benign method a thi method completely avoid the uage of any olvent. Literature reported 3, Biginelli reaction via grindtone chemitry have made ue of toxic chemical like p-ta a catalyt and our extenive literature earch ha revealed that ynthei of octahydroquinazolinone via grindtone methodology in completely olvent free and catalyt free condition i not reported in literature till date. o the need of developing a new and green methodology for grindtone ynthei of thi heterocycle in completely olvent and catalyt free condition i till there. Thu hereby we are repor ting a olvent and catalyt free green ynthei of octahydroquinazolinone via grindtone chemitry for the very firt time ever. EXPERIMETAL The tarting material were obtained from the upplier and were ued for our reaction without doing any more purification. General method for ynthei A indicated in cheme-, a mixture of 0.02 mole aldehyde, 0.02 mole of dimidone and 0.02 mole of thiourea wa grinded together thoroughly in an appropriate ize of mortar petle for pecific time period. All the three reactant were initially olid but after grinding for ome time the texture of the reaction mixture change to emi olid. The progre of the reaction wa monitored by checking TLC after every 0 minute of grinding proce. After completing of the reaction a indicated by TLC, the crude product obtained wa re crytallized from hot ethanol to obtain pure product a white olid powder. After re crytallization, the pure product were characterized by uing MR, IR, and melting point. The oberved data were identical to thoe of reported one. Characterization (-chlorophenyl)-7,7-dimethyl-2-thioxo-,2,3,,7,8-hexahydroquinazolin-5(6)-one [Compound C] Melting point- 78 0 C 2960, 585.5, 093, 587, 58, 669.32 cm - -MR (00 Mz, DM d 6 ) d.00 (t, 6), 2.8(d, 2),.2(, ), 7.5(d, 2), 7.23 () 7.25 (d,2). -(-bromophenyl)-7,7-dimethyl-2-thioxo-,2,3,,7,8-hexahydroquinazolin-5(6)-one [Compound B] Cl Br + + C 2 2 2 3 Grindtone cheme : Grindtone ynthei of ctahydroquinazolinone
Pramanik et al., rient. J. Chem., Vol. 33(), 2090-209 (207) 2092 Melting point- 86 0 C 585, 59, 508, 589, 2953 cm - -MR (00 Mz, DM d 6 ).00(t, 6), 2.2(d, 2), 2.8(d, 2),.2 (, ), 6.99(d, ), 7.35(d, ), 7.38(). 7,7-dimethyl--(-nitrophenyl)-2-thioxo-,2,3,,7,8-hexahydroquinazolin-5(6)-one [Compound ] Melting point- 23 0 C 2, 77, 590, 2875, 2960 cm - -MR (00 Mz, DM d 6 ).00 (t, 6), 2.3(d, 2), 2.8(d, 2),.3 (, ), 7.3() 7.33(d, 2), 8.07(d, 2) -(2-itrophenyl)-2thioxo-,2,3,,7,8 hexahydroquinazolin-5(6)-one[compound 2] REULT AD DICUI different derivate of benzaldehyde were ued a reactant along with thio urea and dimedone, for ynthei of different derivative of quinazolinone via grindtone methodology. It wa oberved that the nature and type of the benzaldehyde ued a reactant, ha a great influence on the rate of the reaction. At firt the grindtone ynthei uing chloro benzaldehyde a reactant, wa performed in preence a well a in abence of catalyt. Thi i an acid catalyt reaction and clove i acidic in nature o catalytic amount of clove wa ued a catalyt for performing our grindtone Biginelli reaction where the clove were grinded along with equimolar mixture of the three reactant inide the mortar. From the literature reported 8 mechanim [cheme-2] of the Biginelli reaction it i clearly evident that the preence of acid can make thi reaction feaible. Conidering the fact that our concerned reaction of thi report follow the ame mechanim a that of cheme-2, thi reaction i performed in preence of mild acidic ubtance. Clove ha already been ued in literature 5 a catalyt for Biginelli reaction in water medium but clove ha never been ued a catalyt for any olvent free grindtone Biginelli reaction. o thi i the firt of it kind tudy where clove i being ued a catalyt for a completely olvent free grindtone Biginelli reaction. Melting point- 92 0 C 2 After completion of reaction (a indicated by TLC), the crude product were re crytallized from hot ethanol to obtain pure product. The ame reaction wa then repeated without uing any clove or any other catalyt. The reult oberved in preence and abence of catalyt are ummarized in Table- 3255, 35, 295, 720, 523, 67,.79 cm - -MR (00 Mz, DM d 6 ) 0.89(t, 6), 2.0(d, 2), 2.35(d, 2),.52(, ), 7.3(d, 2), 7.76(d, 2), 7.9 (). A oberved from table-, the reaction take almot ame time (.5 hour) to go for completion in preence a well a in abence of catalyt. o the preence of clove a catalyt doe not make any ignificant difference on the rate of reaction. A the catalyt i making no ignificant difference on the reaction rate, the ret of the erie
2093 Pramanik et al., rient. J. Chem., Vol. 33(), 2090-209 (207) Table : Grindtone ynthei in preence and abence of clove catalyt Aldehyde Catalyt Time % yield Melting point Chloro Clove and half hour 85% 7-76 c benzyldehyde Chloro and half hour 83% 7-76 c benzyldehyde R Table 2: Grindtone ynthei with different benzaldehyde in abence of catalyt and olvent R group Time % yield Melting point R - 2 2 2 R + + 5 -chloro phenyl.5 hour 80 % 77 -bromo phenyl 70 min 85 % 85 -nitro phenyl 60 min 79 % 23 2-nitro phenyl 50 min 83 % 90 itro group how meomeric effect which i much tronger than inductive effect hown by halogen. Thu it the meomeric (-M) effect of nitro group which make the reaction of nitro benzaldehyde fater than the reaction of halo benzaldehyde. In fact with increae in electron withdrawing trength of the ubtituent the electrophilicity of the carbonyl centre increae that in turn increae the rate of reaction. R cheme 2: General mechanim of Biginelli reaction 8 of grindtone reaction with different aromatic aldehyde were performed without uing any catalyt. The reult obtained for the grindtone reaction (in abence of catalyt) with four different benzaldehyde are ummarized in Table-2. A een from table-2, the rate of reaction i greatly influenced by the electronic nature of the benzaldehyde. Reaction with 2-nitro benzaldehyde take 50 min time to go for completion under grindtone condition wherea the ame reaction with -chloro benzaldehyde take.5 hour time to go for completion under identical reaction condition. Although no external ource of heat energy wa upplied to thi reaction mixture, the heat energy generated while doing the grinding of reactant uing mortar and petle upplie the neceary energy of activation for thi reaction. CCLUI erein a imple, eco friendly, cot effective, efficient and green methodology i developed for the very firt time by our group for the ynthei of octahydroquinazolinone via olvent free and catalyt free grindtone method. Till date thi i the firt of it kind tudy where a grindtone multi component condenation reaction i being performed in a completely olvent free and catalyt free condition. Although the uage of clove a catalyt for Biginelli reaction i well documented in literature 5, our preent tudy ha uccefully proved that the
Pramanik et al., rient. J. Chem., Vol. 33(), 2090-209 (207) 209 reaction in abence of catalyt i a good a that of in preence of catalyt. ur current work ha opened a new door of opportunity for the reearcher to carry out many uch multi component reaction in near future via grindtone method by completely avoiding olvent and catalyt. o hopefully thoe day are not far away when we will be able to ave our environment by completely avoiding the toxic effect of olvent and catalyt while doing organic reaction. ACKWLEDGEMET Immene financial and technical upport from Department of Chemitry, Lovely Profeional Univerity i gratefully acknowledged. REFRECE. Yakhontov, L..; Liberman,..; Zhikhareva, G.P.; Kuz mina, K.K. Khim.-Farm. Zh., 977,,. 2. Kung, P.P.; Caper, M.D.; Cook, K.L.; Lingardo, L.W.; Rien, L.M.; Vicker, T.A. J. Med. Chem., 999, 2, 705. 3. Alagaramy, V.G.; Muruganathan, R.V. Biol. Pharm. Bull. 2003, 26, 7.. igam, R.; warup,.; axena, V.K. Indian Drug, 990, 27, 38. 5. Marakun, M. Y. Japan Kokai, 97, 77, 5. 6. Dallinger, D.; Kappe.. ature Protocol, 2007, 2, 37. 7. aani, Z.; Ilami, M. R.; Kalantari, M. Bioorganic & Medicinal Chemitry Letter, 2006, 6, 79. 8. Pramanik, T.; Wani, T. A.; ingh, A. rient J Chem., 203, 29, 209 9. Pramanik, T.; Pathan, A.. Re J Pharm Biol Chem ci., 20, 5, 0. Pramanik, T.; Maji, P. Int J Pharm Pharm ci., 205, 7, 376.. Pramanik, T.; Padan,. K. Int J Pharm Pharm ci., 206, 8, 396. 2. Pramanik, T.; Padan,.K.; Gupta, R. Der Pharmacia Lettre, 206, 8, 7. 3. Khakel, A.; Gogoi, P.; Barman, P.; Bandyopadhyay, B. RC Advance, 20, 6, 35559.. Boe, A. K.; Pednekar,.; Ganguly,..; Manha, M.. Tetrahedron Letter, 200, 5, 835. 5. Elnabi, A..; ameed, A. M. A.; Awed, R. R. adek, K. U. Green and utainable Chemitry, 203, 3,.