Cu ( OH ) x : Clay Catalyst Promoted Synthesis of 4 , 5-dihydro-1 , 2 , 4-oxadiazole at Room Temperature

An easy and efficient scheme is described designed for the preparation of 4,5-dihydro-1,2,4oxadiazole using recyclable Cu(OH)x-Clay heterogeneous catalyst at room temperature. The cyclo-addition reaction is carried out between imine and oxime using an easy protocol where nitrile oxides are produced insitu from aldoximes and reacted with imines to construct 1,2,4-oxadiazolines in good yield and tremendous purity. Cu(OH)x-Clay catalyst shows excellent catalytic activity for the formation of 1,2,4-oxadiazole. The technique is practically uncomplicated, inexpensive, and excellent with wide range of functional group tolerance to generate structurally different 1,2,4-oxadiazoles. The prepared catalyst was investigated by XRD and SEM techniques. The final products of synthesized compound were characterized by FTIR, NMR spectroscopy and mass spectrometry.

Using heterogeneous catalysts for organic chemical transformations is a burning topic of research nowadays and has emerged as knowledgeable approach to deal with the challenges of green synthesis.Cu(OH)x-Clay has developed into trendy heterogeneous catalyst in our group owing to its distinguishing features such as high selectivity, better reactivity, and a simple work-up procedure [19,20].
Supplemental data (full experimental detail, IR, 1 H-NMR, 13 C-NMR and mass spectra) can be accessed on the publisher's website.

Cu(OH)x-Clay
(preparation given in experimental section) demonstrates excellent catalytic activity without formation of any side product.With this catalyst, the model reaction provided 92 % of the preferred product within 5 h in DCM as solvent at the expense of catalytic amount of Cu(OH)x-Clay.
The optimum amount of the catalyst in this one-pot, three component reaction, was found to be 10 mg (Table 1, entry 14).By lowering the catalyst amount to 3 mg, the preferred product was produced in lower yield (Table 1, entry 16), while increasing catalyst amount has no obvious conclusion on reaction kinetics as well as yield of the product (Table 1, entries 1-12).
With the optimized reaction conditions in hand, we proceeded to study the scope of this method, particularly in the construction of compound library.Different 4,5-dihydro-1,2,4-oxadiazoles were synthesized from various starting materials to evaluate this methodology.Cu(OH)x-Clay proved as excellent catalyst for one pot synthesis of 4, 5dihydro-1,2,4-oxadiazoles and the preferred products were obtained in good yields (Table 1SI -See Supplementary Material).The methodology was investigated for several substituted benzaldehydes (of imines) under the optimized conditions.To our delight an excellent functional group tolerance reaction was found with a variety of functional groups like F, Cl, Br, Me, OMe (electron donating groups) and NO 2 (an electron withdrawing group).The reactions progressed smoothly, to produce the desired 4,5-dihydro-1,2,4-oxadiazoles with no significant variation in yields.In the substrates possessing an aryl-OMe group, methyl ether groups were found to tolerate the nucleophilic cleavage.

Recyclability of the catalyst
For the investigation of recyclability of Cu(OH)x-Clay on the test reaction, separation of the catalyst was done through centrifugation of the reaction mixture diluted with DCM.The catalyst exhibits recyclability and reusability a number of times exclusive of any significant loss in catalytic activity.In each cycle the products were generated with excellent purities.The catalyst reusability for 5 cycles is shown in Figure 3.

Figure 3. Recyclability of Cu(OH)x clay catalyst
In conclusion, an efficient, chemo-selective and simple protocol for the one-pot synthesis of 4,5dihydro-1,2,4-oxadiazoles is presented.Catalytic amount of Cu(OH)x clay, simple experimental procedures and absence of competitive side reactions add to the important features of this technique.The catalyst is competent, economical, shelf stable, heterogeneous and can be recovered from the reaction mixture by simply centrifugation and reused several times.The method is rapid, and the desired products are produced in excellent yield with easy separation and purification.This simple procedure allows a synthesis of a series of 4,5-dihydro-1,2,4-oxadiazoles from low-cost and easily available starting materials.
3 o and 61 o are attributed to the presence of silica [SiO 2 ] and at 12.4 o , 19.8 o and 27.8 o owing to palygorskite.montmorillonite shows diffraction peak at 2θ = 8.9 ° (d 001 reflection), 19.7 o , 32.1 o , and 62 o .Presence of small peaks at 38.8 o , and 42.5 o is implied to kaolinite.No characteristic peak of CuO, Cu 2 O and metallic Cu loaded on montmorillonite-KSF are present but peaks matching to Cu(OH) 2 and (Cu 2 Cl(OH) 3 ) with very low intensity are observed at 2θ = 16.1, 18 o , 25.1 o , 32.3 o and 50.3 o .From XRD analysis it is obvious that copper hydroxide species are deposited with very low crystalline character.The Scanning Electron Microscope (SEM) image of the Cu(OH) x -Clay catalyst shown in Fig.2which exhibits that surface of the catalyst is not smooth but very rough so has increased surface area.The increased surface area of Cu(OH) x -Clay catalyst elevates its capability to adsorb the reactant to a large extent.