A rapid, convenient, solventless green approach for the synthesis of oximes using grindstone chemistry
© Saikia et al; licensee Springer. 2011
Received: 31 March 2011
Accepted: 4 October 2011
Published: 4 October 2011
Synthesis of oximes is an important reaction in organic chemistry, because these versatile oximes are used for protection, purification, and characterization of carbonyl compounds. Nitriles, amides via Beckmann rearrangement, nitro compounds, nitrones, amines, and azaheterocycles can be synthesised from oximes. They also find applications for selective α-activation. In inorganic chemistry, oximes act as a versatile ligand.
Several procedures for the preparation of oximes exist, but, most of them have not addressed the green chemistry issue. They are associated with generation of pollutants, requirement of high reaction temperature, low yields, lack of a generalized procedure, etc. Hence, 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, bismuth compounds are very useful as they are cheap in general, commercially available, air stable crystalline solids, safe, and non-toxic, hence easy to handle.
Carbonyl compounds (aliphatic, heterocyclic, and aromatic) were converted into the corresponding oximes in excellent yields by simply grinding the reactants at room temperature without using any solvent in the presence of Bi2O3. Most importantly, this method minimizes waste disposal problems, provides a simple yet efficient example of unconventional methodology and requires short time.
We have developed a novel, quick, environmentally safe, and clean synthesis of aldoximes and ketoximes under solvent-free grinding condition.
Keywordsoximes carbonyl compounds Bi2O3 grindstone chemistry solventless eco-friendly
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 , nitro compounds [4, 5], nitrones , amines , and synthesis of azaheterocycles  are some of the synthetic applications of oximes. They are also useful for selective α-activation  and are extensively used as intermediates for the preparation of amides by the Beckmann rearrangement [10, 11] and fungicides and herbicides . In inorganic chemistry, oximes act as a versatile ligand.
Classically, oximes are prepared  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 , CaO , and TiO2/(SO4 2-)  coupled with microwave irradiation under solvent-free condition have been claimed to be efficient methods for the preparation of oximes. Hashem Sharghi and Hosseini  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 .
2. Results and discussion
Preparation of aldoximes and ketoximes 2a
Isolated yield (%)
Optimization of catalyst loading in preparation of 2b
Catalyst loading (mol%)
Reusability of Bi2O3 in the preparation of 2b using 60 mol% of the catalyst
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.
5.1. Typical procedure for the formation of oxime 2
A mixture of aldehyde/ketone 1 (1 mmol), hydroxylamine hydrochloride (1.2 mmol), and Bi2O3 (0.6 mmol) was grounded in a mortar with a pestle for the required period of time. On completion of the reaction as monitored by TLC, ethyl acetate (2 × 10 mL) was added to the reaction mixture and filtered to separate the Bi2O3. The filtrate was concentrated down to approx. 6 mL, then added water to it when product precipitated out from the solution. The precipitate was filtered out and dried in high vacuum to furnish the pure oxime 2 in 60-98% yield.
- LD50 :
lethal dose that kills half (50%) of the animals tested
nuclear magnetic resonance.
The authors are very grateful to the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for financial support to the project CSIR (01(2147)/07/EMR-II).
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