A rapid, convenient, solventless green approach for the synthesis of oximes using grindstone chemistry

Conversion of carbonyl functionalities into oximes is an important reaction in organic chemistry. Oximes are highly crystalline compounds that find applications not only for protection, but also for purification and characterization of carbonyl compounds [1, 2].Conversions into nitriles [3], nitro compounds [4, 5], nitrones [6], amines [7], and synthesis of azaheterocycles [8] are some of the synthetic applications of oximes. They are also useful for selective α-activation [9] and are extensively used as intermediates for the preparation of amides by the Beckmann rearrangement [10, 11] and fungicides and herbicides [12]. In inorganic chemistry, oximes act as a versatile ligand.

Classically, oximes are prepared [2] by refluxing an alcoholic solution of a carbonyl compound with hydroxylamine hydrochloride and pyridine. The method has multiple drawbacks such as low yields, long reaction time, toxicity of pyridine, and effluent pollution caused by the use of organic solvent. In recent times, solvent-free reactions have drawn considerable attention and popularity [13, 14], not only from an environmental point of view, but also for synthetic advantages in terms of yield, selectivity, and simplicity of the reaction procedure. Since chemical industry deals with larger quantity of materials, these factors are particularly very important therein. Over the years, many reagents and catalysts have been developed for the synthesis of oximes. Basic aluminia [15], CaO [16], and TiO₂/(SO₄ ^2-) [17] coupled with microwave irradiation under solvent-free condition have been claimed to be efficient methods for the preparation of oximes. Hashem Sharghi and Hosseini [18] described a solventless reaction protocol for synthesizing aldoximes from corresponding aldehydes using ZnO as catalyst at 80°C. Interestingly, they obtained Beckmann rearrangement product at higher temperatures (140-170°C). More recently, conversion of carbonyl compounds to oximes in aqueous biphasic medium and ionic liquid/water biphasic system [19, 20] has been reported. However, problems of generation of polluting HCl, high reaction temperature, occasionally low yields, and lack of a generalized procedure covering all types of aldehydes and ketones still present. Consequently, there is a demand for developing an efficient, convenient, and non-polluting or less polluting alternative method for the preparation of oximes. In this context, because of the rich chemistry of bismuth compounds [21–25], we became interested therein. Bismuth compounds are generally cheap, commercially available, air stable crystalline solids, safe, and non-toxic, hence easy to handle. Their Lewis acidity is also well known [26, 27]. Most bismuth(III) compounds have an LD₅₀ value which is comparable to or even less than that of NaCl [28].

In continuation to our interest in protection and deprotection chemistry [29, 30], we have developed a novel, quick, environmentally safe, and clean synthesis of aldoximes and ketoximes under grinding condition (Scheme 1) utilizing pestle and mortar under solvent-free condition. The method makes use of local heat generated by simply grinding the reactants and catalyzed by cheap and commercially available Bi₂O₃ for driving the chemical reaction at room temperature. The work up is easy and furnished the oximes in excellent yields. Most importantly, this method minimizes waste disposal problems and provides a simple yet efficient example of unconventional methodology, which is equally effective for all types of aldehydes and ketones. Earlier reports [15, 31] of similar type restricted their utility in carbonyl compounds (alicyclic and aliphatic) and aromatic aldehydes only and aromatic ketoximes were not obtained. In those reports, for ketoxime synthesis, microwave irradiation or addition of some other additives was necessary. In this regard, our method is superior, quite general, and versatile.

To the best of our knowledge, Bi₂O₃ has never been used in the synthesis of oximes earlier. In conclusion, the reported procedure is an interesting, extremely simple, suitable, fast, efficient, and novel method for the preparation of oximes. The methodology also offers chemical, economical, and environmental advantages. On the other hand, Bi₂O₃ is remarkably easier to use, non-hazardous, inexpensive and work under mild neutral conditions [32, 33].

Melting points were determined on a Büchi 504 apparatus and were uncorrected. IR spectra were recorded in KBr pallets on a Nicolet (Impact 410) FT-IR spectrophotometer.¹H NMR and¹³C NMR spectra were recorded on a JNM ECS 400 MHz FT-NMR (JEOL) spectrophotometer with TMS as the internal standard. Mass spectra were recorded on a Waters Q-TOF Premier & Aquity UPLC spectrometer. Surface area of the catalyst before and after use in the reaction was measured using surface area & pore size analyzer (NOVA 1000e, Quanta chrome Instruments). All the chemicals were used as-received.