Background

Transformation of carbonyl compounds into oximes is one of the most important synthetic reactions in organic chemistry. Oximes are not only useful for protection, purification, and characterization of carbonyl compounds [1] but also they can serve as intermediates for conversion into nitro compounds [2], amides [3], nitriles [4], and amines [5]. In addition, all compounds that contain the oxime fragment, which represents a pharmacophore group, exhibit diverse biological activities. These derivatives are also recommended as insecticides, fungicides, pesticides, herbicides, protozoacides, and plant growth regulators [6]. A wide spectrum of biological activity was revealed for oximes of pyridine, indole, isatin, and pyrroleandquinoline series [7]. Oximes of α, β-unsaturated ketones are known as insecticides, vasorelaxants, and antimicrobial agents [6].

The literature review shows that many improvements have been carried out for the preparation of oximes. NH2OH·HCl/K2CO3[8], DOWEX(R)50WX4 [9], ethylenediamine/oxone [10], ultrasound/Na2SO4[11], Bi2O3[12], heterogeneous polyoxometalates [13], phase transfer catalysis [14], and TiO(acac)2[15] are some of the reagents or protocols which have been reported for transformation of carbonyl compounds to oximes. Generally low yields, long reaction times, and limitation to use acid- or base-sensitive functionality in carbonyl compounds are the major limitations of these methods.

On the other hand, nanoparticles exhibit high catalytic activity and chemical selectivity under mild conditions [16]. The extremely small-size particles maximize the surface area which, when exposed to the reactant, allow more reactions to occur at the same time and thus speed up the process [17]. Thus, in the line of the outlined strategies, herein, we wish to report a green and practical method for solvent-free conversion of various carbonyl compounds to the corresponding oximes by NH2OH·HCl catalyzed by magnetically nano Fe3O4 (Scheme 1).

Scheme 1
scheme 1

A green and practical method for solvent-free conversion of various carbonyl compounds.

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Results and discussion

Magnetically nano Fe3O4 due to highly active and specific centers of ultra-size coupled with high magnetic specification has been found some useful applications in organic synthesis [18]. Continuation of our research program directed to the oximes reactions under mild and green reaction conditions [3] and lack of information to use magnetically nano Fe3O4 in preparation of oximes from carbonyl compounds by NH2OH·HCl encouraged us to investigate the titled transformation.

The promotion effect of nano Fe3O4 in the formation of oximes was studied by the reaction of benzaldehyde with NH2OH·HCl under different reaction conditions. The effects of molar ratio of the reaction components and solvent were investigated in the typical experiment (Table 1). As it is seen, the combination system of hydroxylamine hydrochloride with nano Fe3O4 in a molar ratio of 2:1.5, respectively, in oil bath (70°C to 80°C) at solvent-free conditions showed a perfect efficiency for complete conversion of 1 mmol benzaldehyde to benzaldehydeoxime within 20 min(entry 6). This success encouraged us to further explore the capability of NH2OH·HCl/nano Fe3O4 system for oximation of different carbonyl compounds at the optimized reaction conditions. The summarized results in Tables 2 and 3 show that all reactions were carried out successfully in oil bath (70°C to 80°C) at solvent-free conditions, and the corresponding aldoximes or ketoximes were obtained in high to excellent yields within 15 min to 3 h. In addition, due to inherent less reactivity of ketones versus aldehydes, the oximation reactions took excess amounts of NH2OH·HCl and nano Fe3O4 in longer reaction times (Table 3). α,β-Unsaturated aldehydes and ketones were successfully converted to the corresponding conjugated oximes with NH2OH·HCl/nano Fe3O4 system in high yields and without any side reaction (Table 2: entry 8 and Table 3: entry 9). We also observed that oximation of carbonyl compounds with two carbonyl moieties was carried out selectively. By using the controlled amounts of NH2OH·HCl in an appropriate time, oximation of one or both of the carbonyl group took place efficiently (Table 3: entries 7 and 8).

Table 1 Optimization experiment for oximation of benzaldehyde with NH 2 OH·HCl/nano Fe 3 O 4 system under different reaction conditions (all reactions were carried out with 1 mmol of benzaldehyde)
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Table 2 Oximation of aldehydes with NH 2 OH·HCl/nano Fe 3 O 4 system (all reactions were carried out in oil bath (70°C to 80°C) under solvent-free conditions)
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Table 3 Oximation of ketones with NH 2 OH·HCl/nano Fe 3 O 4 system (all reactions were carried out oil bath (70°C to 80°C) under solvent-free conditions)
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A plausible mechanism for the nanoFe3O4 catalyzed was illustrated in Scheme 2. The nano Fe3O4 facilitates the oximation process through coordination of its Fe3+ with O of carbonyl.

Scheme 2
scheme 2

A plausible mechanism for the nano Fe 3 O 4 catalyzed.

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In the next attempt, we turned our attention to recyclable of catalyst; the catalyst was easily separated from the reaction system and reused (after washing with distilled water/acetone and dried under vacuum) for three consecutive runs, and no obvious diminishing activity was observed (the conversions and selectivities were 100% and 100% for first run; 99% and 100% for second run; 91% and 95% for third run; 91% and 90% for fourth run).

Conclusions

In this paper, we have shown that magnetically nano Fe3O4 promoted oximation of various carbonyl compounds byhydroxylamine hydrochloride in oil bath (70°C to 80°C) under solvent-free conditions. Aldoximes and ketoximes were obtained in high yields within 15 min to 3 h. This method offers some advantages in term of clean reaction conditions, easy work-up procedure, short reaction times, and suppression of any side product. So we think that NH2OH·HCl/nano Fe3O4 system could be considered a new and useful addition to the present methodologies in this area.

Methods

General

All solvents and reagents were purchased from commercial sources with the best quality and they were used without further purification. Nano Fe3O4 are prepared in high purity according to the reported procedures in literature [19] (Figures 1, 2, and 3). 1H, 13C NMR, and IR spectra were recorded on 300 MHz Bruker Avance and Thermo Nicolet Nexus 670 FT-IR spectrometers (Bruker AXS, Inc., Madison, WI, USA). All products are known and were characterized by their spectral data. Yields refer to isolated pure products. Thin layer chromatography (TLC) was applied for monitoring of the reactions over silica gel 60 F254 aluminum sheet.

Figure 1
figure 1

XRD pattern of obtained samples and XRD pattern of[19].

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Figure 2
figure 2

Infrared spectra of the samples (a) and (b)[19].

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Figure 3
figure 3

Process synthesis nano Fe 3 O 4 [19].

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A typical procedure for solvent-free oximation of acetophenone to acetophenone-oxime with NH2OH·HCl/nano Fe3O4 system

A mixture of Acetophenone (0.120 g, 1 mmol) and nano Fe3O4 (0.462 g, 2 mmol) was ground in a mortar. NH2OH·HCl (0.2085 g, 3 mmol) was then added to the mortar, and the grinding of the reaction mixture was continued for a moment. The mixture was stirred magnetically in oil bath (70°C to 80°C) under solvent-free conditions for 60 min. TLC monitored the progress of the reaction (eluent; n-hexane/EtOAc: 5/3). After completion of the reaction, the mixture was washed with EtOAc (3 × 5 ml). Evaporation of the solvent affords the white solid Acetophenone Oxime in 90% yield (1215 g, Table 2: entry 1).white solid, m.p. 58°C to 60°C. IR (KBr, νmax): 3,235, 3,084, 2,924, 1,496, 1,444, 1,370, 1,300, 1,079, 1,005, 924, 847, 773, 756, 688, and 651 cm−1. 1H NMR (300 MHz, CDCl3, δ ppm): 8.86 (br s, 1H), 7.69 to 7.58 (m, 2H), 7.43-7.36 (m, 3H), 2.32 (s, 3H),13C NMR (75 MHz, CDCl3, δ ppm): 156.1, 136.6, 129.3, 128.6, 126.1, 12.3; MS (EI) m/z (% rel. intensity) 135 (M+, 86), 118 (14), 106 (22), 103 (26), 94 (32), 77 (100), 66 (16), and 51 (33).