Solvent-free Organic Synthesis on Mineral Supports Using Microwave Irradiation

Saeed Balalaie^*, M. Golizeh

Department of Chemistry, K. N. Toosi University of Technology, P.O. Box 15875-4416 Tehran- Iran
Fax: +98-21-2853650 E-mail http://www.mdpi.net/ecsoc-5/e0025/[email protected]

Received: 15 August 2001 / Uploaded 22 August 2001

The coupling of microwave irradiation with the use of mineral supports under solvent-free condition provides clean chemical processes. Heterogenous organic reactions have proven useful to chemists in the laboratory as well as in the industrial context. These reactions are affected by the reagents immobilized on the porous solid supports and have advantages over the conventional solution phase reaction such as enhanced reaction rates, higher yields, greater selectivity and ease of manipulation. The main advantage of this method is elimination of pollutant organic solvents and the environmentally friendly character.¹

In our research laboratory, we carried out a wide range of reactions in solvent-free conditions via combination of supported reagents and microwave irradiation in domestic ovens. Some of these reactions are as follows:
 
 

1. Synthesis of Triazones and 4-Oxo-Oxadiazinane in Dry Media.

Triazones are applied in industry for improving of resins. Meanwhile, they are used as amino protecting groups for the synthesis of polyamines, polyfunctional amino acids and aminoalcohols. Many water-soluble triazones are used as fertilizers.

Condensation of dimethyl urea and paraformaldehyde supported on montmorillonite K–l0 in dry media using microwave irradiation gave 4-oxo-oxadizinane (3) and three component condensation of dimethyl urea, paraformaldehyde and primary amines supported on montmorillonite K-10 yielded triazones 5a-f.²

 

		R		Yield%
a b c d e f	Me Et Pr i-Pr n-Bu sec-Bu		71 76 79 83 84 74

In this work, montmorillonite has Lewis acid character and it seems that in the presence of montmorillonite K-10, paraformaldehyde is slowly decomposed to formaldehyde which reacts with dimethyl urea and amines.

Elimination of acidic condition, replacement of aqueous formaldehyde with paraformaldehyde, high yields, and low reaction times are the advantages of this method when compared with classical methods.

2. Synthesis of alkenes via Knoevenagel condensation

The Knoevenagel condensation is one of the most important methods for the preparation of alkenes. This reaction is catalyzed by primary and secondary amines or their corresponding ammonium salts in harmful solvents or with Lewis acids. We reported that ammonium acetate-basic alumina is a highly efficient catalyst for condensation of aldehydes and ketones with active methylene compounds under solvent-free condensation by MW irradiation. Aldehydes and ketones reacted with malononitrile, methylcyanoacetate and cyanoacetamide according to Scheme 2.

This methodology is fast, clean and applicable for the preparation of trisubstituted alkenes. It has simple set-up and work-up and is environmentally friendly and the condition of the reactions are comparable to other methods but we avoided the use of organic bases, Lewis acids and solvents.³

3. Synthesis of coumarins

Coumarins substituted at C-3 are an important class of organic compounds which are used in pharmaceutical chemistry. Coumarins have wide range of activities i.e. anthelmintic, hyprotic antimicrobial, anticancer properties and they are used as fluorescent brightner and fluorescent dyes.

We reported that ammonium acetate on basic-alumina or silica gel is a highly efficient catalyst for the synthesis of coumarins via knoevenagel condensation of salicylaldehyde derivatives and 2-hydroxy-1-naphthaldehyde with ethyl and methyl malonate in solvent- free condition under microwave irradiation.⁴

In the classical approach, cyclocondensation of salicylaldehyde and 2-hydroxy
1-naphtaldehyde with methylene active compounds requires many hours with heating in ethanol or other solvents at reflux in the presence of a base e.g. pyridine or piperidine. In contrast the same reaction required 2-15 minutes with high yield, when carried out under our reported condition, without any solvent or organic base. We developed a general, rapid, facile and solvent-free protocol for the synthesis of coumarins catalyzed by ammonium acetate.

4. Synthesis of Imidazoles

Imidazole derivatives have many biological activities, e.g. herbicidal, fungicidal, antiinflammatory. We show that Zeolite HY and silica gel are new and efficient heterogenous catalysts for the synthesis of triaryl imidazoles via three component condensation of benzil, benzaldehyde derivatives and ammonium acetate under microwave irradiation.⁵

Imidazoles are versatile intermediates in the manufacture of pharmacologically active products but current methods of synthesis can lead to relatively large amounts of waste. In this work a number of green chemistry-related improvements to the synthesis of tetrasubstituted imidazoles are reported. The number of steps is reduced to one through a very efficient four-compound condensation, solvents are avoided and reusable solid catalysts are employed. We performed four component condensation of benzil, benzaldehyde derivatives, primary amines and ammonium acetate catalyzed by zeolite HY and silica gel under microwave irradiation as the efficient and facile one-pot method for the synthesis of tetrasubstituted imidazoles.⁶

5. Synthesis of Isoxazoles and pyrazoles

Reaction of 1,3-diketones (acetylacetone, dibenzylmethane, benzoylacetone) with hydroxylamine, hydrazine and phenylhydrazine on silica gel under microwave irradiation leads to the synthesis of isoxazole and pyrazole derivatives in high yields. In the classical method, reaction of 1,3-diketones with hydroxylamine hydrochloride or cyclization of oximes needs many hours in reflux condition, but in our method reactions were carried out within 2 min. without any solvent. ⁷

6. Clean oxidation of benzoins on "Zeolite A " under solvent-free condition and microwave irradiation.

Oxidation remains one of the great challenges for green chemistry. Industry still runs many oxidations with toxic metal reagents and even catalytic oxidations often present problems due to such factors as acidic solvents and use of promoters. In this work a remarkably simple oxidation procedure is described using only substrate and catalyst. This is a good example of one of the essential principles of green chemistry: to minimise the components. The less you use the less there is to waste!

Benzils have received a great deal of attention because of their practical applications, i.e. as photosensitive agents and as synthetic agents in organic and pharmaceutical chemistry. Oxidation of benzoin derivatives with an oxidizing agent is a common method for preparation of benzils. There are many reagents for this oxidation, but long reaction periods, and use of toxic metallic compounds and corrosive acids are some disadvantages of these methods. Due to environmental concerns, there is increasing need and interest in developing processes that minimize production of toxic wastes.

Oxidation of benzoins were efficiently performed with Zeolite A without any oxidizing agent under solvent-free condition and microwave irradiation. (Scheme 7) ⁸

This method is facile, clean and environmentally friendly. Reusability of catalyst and elimination of organic solvents and oxidizing agents are advantages of this method.

Additional works:

Meanwhile Quinazolines⁹, N-substituted 4-aryl-1,4-dihydropyridines¹⁰ were synthesized with heterogenous catalysts. Oxidation of alcohols, phenols, benzoins¹¹, deoximation of aldoximes and ketoximes¹² were carried out with zinc chlorochromate supported on Montmorillonite K-10 with high yields. Protection of carbonyl group gave acetals in the presence of acidic zeolite under MWI without Lewis acids¹³. Specific formylation of b-naphtol with HMTA-pTsOH (Hexamethylene tetraamine) on silica gel under MWI gave 2-hydroxy-l-naphthaldehyde.¹⁴

Conclusions

The above summary of recent research activities from our laboratory highlights the eco-friendly features of these solvent-free reactions that are activated by exposure to microwave irradiation. High yields, low reaction times, easy set-up and work-up are the common advantages of this environmentally friendly method. This method could be used for the preparation of high value chemicals that could be expanded to large scale production.

Acknowledgments:

I am grateful to the research council of K.N. Toosi University of Technology for financial support and M. S. students: N. Nemati, H. Salimi, A. Arabanian, M. Golizeh, B. Ahangarian and E. Kowsari.

References: