Crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) tethered to nano-Fe3O4 as a superior catalyst for the synthesis of 1,3-thiazoles

Crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) attached to nano-Fe3O4 as a superior catalyst has been used for the synthesis of 3-alkyl-4-phenyl-1,3-thiazole-2(3H)-thione derivatives through a three-component reactions of phenacyl bromide or 4-methoxyphenacyl bromide, carbon disulfide and primary amine under reflux condition in ethanol. A proper, atom-economical, straightforward one-pot multicomponent synthetic route for the synthesis of 1,3-thiazoles in good yields has been devised using crosslinked sulfonated polyacrylamide (Cross-PAA-SO3H) tethered to nano-Fe3O4. The catalyst has been characterized by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA) and vibrating-sample magnetometer (VSM).


Characterization of the nanocatalyst
In this study, we synthesized the crosslinked sulfonated polyacrylamide (Cross-PAA-SO 3 H) with simultaneous radical co-polymerization in presence of initiator and crosslinking agent. The FT-IR absorbance spectra of the dried crosslinked sulfonated polyacrylamide (poly AAMco-AAMPS), Fe 3 13:120 are shown in Fig. 1 (AAM is abbreviation acrylamide; AAMPS is abbreviation 2-acrylamido-2-methylpropanesulfonic acid). The peaks at 3100-3500 cm −1 are related to O-H (sulfonic acid group) and N-H (amide groups) in AAM and AAMPS. The strong band in the 1654 cm −1 can be ascribed to the stretching vibrations of carbonyl groups in both AAM and AAMPS. The sharp peak at 1040 cm −1 is related to sulfonic acid (-SO 3 H) group. The bands at 700-800 cm −1 and 1540 cm −1 are related to the bending vibration of the N-H bond (primary and secondary amide respectively). Table 1 gives the main characteristic peak assignment of the FT-IR spectra. Meanwhile, a schematic illustration of the reaction is presented in the Scheme 3. The results in Fig. 1c suggest the integration of Fe 3 O 4 NPs and Cross-PAA-SO 3 H. The carbon nuclear magnetic resonance ( 13 C NMR) of Cross-PAA-SO 3 H is displayed in Fig. 2 Fig. 2. The 13 C NMR spectrum of the Cross-PAA-SO 3 H in DMSO-d 6 displayed two peaks at 176.36 and 173.89 ppm due to amide groups.
The morphology of Cross-PAA-SO 3 H@nano-Fe 3 O 4 was determined by Scanning Electronic Microscopy (SEM). It is observed that the particles are strongly aggregated and glued with very large and continuous aggregates (Fig. 3). In order to investigate the size distribution of nanocatalysts [24,25], dynamic light scattering (DLS) measurements of the nanoparticles were showed in Fig. 4 Fig. 5. The patterns for Cross-PAA-SO 3 H indicate a peak at 2θ = 28° which is the most intense peak height (Fig. 5a). All the strong peaks appeared at 2θ = 30.08°, 35.40°, 43.17°, 53.59°, 57.20°, 62.86°, and 74.02° can be easily indexed to nano-Fe 3 O 4 (Fig. 5b). The pattern agrees well with the reported pattern for Fe 3 O 4 (JCPDS No. 75-1609). The particle size diameter (D) of the nanoparticles has been calculated by the Debye-Scherrer equation (D = Kλ/β cosθ), where β FWHM (full-width at halfmaximum or half-width) is in radian and θ is the position of the maximum of the diffraction peak. K is the so-called shape factor, which usually takes a value of about 0.9, and λ is the X-ray wavelength (1.5406 Å for CuKα). The crystallite size of Cross-PAA-SO 3 H@nano- An EDS (energy dispersive X-ray) spectrum of Cross-PAA-SO 3 H@nano-Fe 3 O 4 ( Fig. 6) exhibits that the elemental compositions are carbon, oxygen, sulfur, iron and nitrogen.
The magnetic attributes of nano-Fe 3 O 4 and Cross-PAA-SO 3 H@nano-Fe 3 O 4 were given with the help of a vibrating sample magnetometer (VSM) (Fig. 7). The amount of saturation-magnetization for nano-Fe 3 O 4 and Cross-PAA-SO 3 H@nano-Fe 3 O 4 is 47.2 emu/g and 26.8 emu/g. Thermogravimetric analysis (TGA) evaluates the thermal stability of the Cross-PAA-SO 3 H and Cross-PAA-SO 3 H@nano-Fe 3 O 4 . The curve displays a weight loss about 37.5% for Cross-PAA-SO 3 H@nano-Fe 3 O 4 from 240 to 550 °C, resulting from the destruction of organic spacer attaching to the nanoparticles. Hence; the nanocatalyst was stable up to 240 °C, confirming that it could be stably utilized in organic reactions at temperatures between the ranges of 80-160 °C (Fig. 8).

Catalytic behaviors of Cross-PAA-SO 3 H@nano-Fe 3 O 4 for the synthesis of 1,3-thiazoles
Initially, we had optimized conditions for the synthesis of 3-alkyl-4-phenyl-1,3-thiazole-2(3H)-thione derivatives by the reaction of phenacyl bromide, carbon disulfide and benzyl amine as a model reaction. The model reactions were performed by CAN, NaHSO 4 , InCl 3 , ZrO 2 , p-TSA, nano-Fe 3 O 4 , Cross-PAA-SO 3 H and Cross-PAA-SO 3 H@ nano-Fe 3 O 4 . The reactions were tested using diverse solvents including ethanol, acetonitrile, water or dimethylformamide. The best results were gained in EtOH and we found that the reaction gave convincing results in the presence of cross-PAA-SO 3 H@nano-Fe 3 O 4 (7 mg) under reflux conditions (Tables 2). However, the activity of catalysts is determined by the acid-base properties, surface area, the distribution of sites and the polarity of the surface sites [26,27]. We studied the feasibility of the reaction by selecting some representative substrates (Table 3). To investigate the extent this catalytic process, phenacyl bromide or 4-methoxyphenacyl bromide, carbon disulfide and primary amine were elected as substrates. Seeking of the reaction scope demonstrated that various primary amines can be utilized in this method (Table 3).  The reusability of Cross-PAA-SO 3 H@nano-Fe 3 O 4 was studied for the reaction of phenacyl bromide, carbon disulfide and benzyl amine and it was found that product yields reduced to a small extent on each reuse (run 1, 94%; run 2, 94%; run 3, 93%; run 4, 93%; run 5, 92%; run 6, 92%;). After completion of the reaction, the To study the applicability of this method in larger scale synthesis, we performed selected reactions at 10 mmol scale. As can be seen, the reactions at large scale gave the product with a gradual decreasing of reaction yield (Table 4).
To compare the efficiency of Nano Fe 3 O 4 @ PAA-SO 3 H with the reported catalysts for the synthesis of 1,3-thiazoles, we have tabulated the results in Table 5. As Table 5 indicates, nano Fe 3 O 4 @ PAA-SO 3 H is superior with respect to the reported catalysts in terms of reaction time, yield and conditions. As expected, the increased surface area due to small particle size increased reactivity of catalyst. This factor is responsible for the accessibility of the substrate molecules on the catalyst surface.

Conclusions
In conclusion, we have reported an efficient way for the synthesis of 3-alkyl-4-phenyl-1,3-thiazole-2(3H)-thione derivatives using cross-PAA-SO 3 H@nano-Fe 3 O 4 under reflux condition in ethanol. The method offers several advantages including easy availability, high yields, shorter reaction times, reusability of the catalyst and low catalyst loading. The present catalytic procedure is extensible to a wide diversity of substrates for the synthesis of a varietyoriented library of thiazoles.

Chemicals and apparatus
NMR spectra were obtained on a Bruker spectrometer with CDCl 3 as solvent and TMS as an internal standard. Chemical shifts (δ) are given in ppm and coupling constants (J) are given in Hz. FT-IR spectra were recorded with KBr pellets by a Magna-IR, spectrometer 550 Nicolet. CHN compositions were measured by Carlo ERBA Model EA 1108 analyzer. Powder X-ray diffraction (XRD) was carried out on a Philips diffractometer of X'pert Company with monochromatized Cu Kα radiation (λ = 1.5406 Å). Microscopic morphology of products was visualized by SEM (MIRA3). The thermogravimetric analysis (TGA) curves are recorded using a V5.1A DUPONT 2000. The mass spectra were recorded on a Joel D-30 instrument at an ionization potential of

Preparation of crosslinked sulfonated polyacrylamide (Cross-PAA-SO 3 H)
In a round-bottom flask (200 mL) equipped with magnetic stirrer and condenser, 5 g of acrylamide (AAM) (70 mmol) and 5.17 g of 2-acrylamido-2-methylpropanesulfonic acid (25 mmol) (AAMPS), [approximately AAM/AAMMPS (3/1)] and 0.77 g of N,N-methylenebis-acrylamide (NNMBA) (5 mmol) as crosslinking agent and benzoyl peroxide as initiator were added to 80 mL EtOH under reflux condition for 5 h. After completion of reaction, the white precipitate was formed, filtered, washed and dried in vacuum oven in 70 °C for 12 h. The weight of polymer was 10.1 gr with the yield of 91.8%. Cross-PAA-SO 3 H was characterized with infrared spectroscopy and back titration acid-base to confirm sulfonation and determine accurate sulfonation levels. Acidic capacity of this catalyst was estimated 1.1 mmol/g.

General procedure for the synthesis of 1,3-thiazoles
A mixture of primary amine (1.0 mmol) and carbon disulfide (1.0 mmol) in ethanol (8 mL) was stirred for 5 min and then phenacyl bromide or 4-methoxyphenacyl bromide (1.0 mmol) and Cross-PAA-SO 3 H attached to nano-Fe 3 O 4 (7 mg) were added, and the mixture was stirred for the appropriate times. The reaction was monitored by TLC (n-hexane/ethyl acetate 8:2). After completion of the reaction, the nanocatalyst was easily separated using an external magnet. The solvent was evaporated and the solid obtained washed with EtOH to get pure product. The characterization data of the compounds are given below and in Additional file 1.