Radziszewski reactions

Pyrimidine-5-carbonitrile, 4-amino-Radziszewski reaction, 3, 83 reactions... 

The imidazole ring is often found in biologically active molecules and is as such important in medicinal chemistry [16]. An interesting route for the production of substituted imidazoles is the Debus-Radziszewski reaction. This is a three-component reaction of a diketone, an amine and an aldehyde to form trisubstituted imidazoles (Scheme 3). 

Scheme 5 Modified Radziszewski reaction performed under microreactor conditions [17]...

This reaction has been extended by Weidenhagen through the condensation of Qf-acetoacetone, cupric acetate, and aqueous ammonia to afford imidazoles in yields up to 60%. " This method is thus known as the Weidenhagen modification or Weidenhagen Synthesis. In addition, the Radziszewski reaction has been further modified to proceed in acetic acid by the use of ammonium acetate or ammonium carbonate as the source of ammonia to give imidazoles of markedly improved yields,and this protocol has been recently carried out under microwave irradiation. Furthermore, it has been reported that the reaction of an amidine with an of-halo ketone also readily yields imidazoles. 

Other references related to the Radziszewski reaction are cited in the literature. ... 

Radziszewski reaction 24, 204s31 Raney catalysts s. Nidcel Rays s. Irradiation Reaction gas chromatography 24, 501S31... 

In general, Radziszewski reaction is the synthesis of an imidazole derivative 4 by the condensation of an a-dicarbonyl compound 1 (e.g., glyoxal, pyruvaldehyde, porphyrin-2,3-diones, and benzil), an aldehyde 2, and two equivalents of dry ammonia in alcohol. Interestingly, the replacement of one equivalent of ammonia with a primary amine 3 results in the formation of 1-substituted imidazoles 4 (Scheme 12.1). 

Modifled Radziszewski Reactions Efficient Tool for the Synthesis of Substituted Imidazoles... 

Among other reported methods, Radziszewski reaction has demonstrated to be an efficient tool for the synthesis of substituted imidazoles. Regioselectivity in this kind of reaction is a very difficult task however, playing with the... 

SCHEME 12.2 General mechanistic hypothesis for Radziszewski reaction. 

SCHEME 12.3 An example of application of Radziszewski reaction in the preparation of a pyrimidine-imidazole-based library. 

A considerable number of methods base on the Radziszewski reaction employing heterogeneous catalytic systems have come out, allowing the synthesis of 2,4,5-tri-substituted imidazoles in a very efficient way, in terms of yields and time reactions. The authors proclaimed simplicity of the operations and environmental friendliness as additional advantages of the methods. In many cases, the reactions are carried out under solvent-free conditions, and in some cases, it is possible to perform them at room temperature. Some selected examples are those using as catalysts... 

Microreactor Technology In the last years, some examples of Radziszewski reaction have been reported using microreactor technology, which allows the development of more sustainable methods thanks to the miniaturization and increased safety and efficiency [60, 61]. In particular, the Stevens and the Orru groups developed in cooperation a procedure for the continuous production of highly substituted imidazoles [62, 63]. They were motivated by the possibility of making the method previously reported by Orra [64] more interesting for industrial applications. The latest procedure... 

Weidenhagen Synthesis The Weidenhagen synthesis of imidazoles is a modification of the Radziszewski reaction [65] and was first pubhshed in 1935 [66]. In this... 

There are numerous examples in the literature where tri- and tetrasubstituted imidazoles are achieved efficiently by means of suitable catalyst for the Radziszewski reaction. In order to increase the efficiency and greenness, different methods have been applied, such as MW irradiation, sonication, microreactor technology, etc. Some of these methods, as well as a great number of different catalysts, have been used in the other protocol which leads to a heterocycle (2-aminothiophenes) the Gewald reaction. With respect to the other methodologies covered in this chapter, many works have come out since... 

Z. Wang, 518. Radziszewski, in Comprehensive organic name reactions and reagents. John Wiley Sons, Inc., Hoboken, NJ, 2009, Vol. 3, pp. 2295-2291. Radziszewski reaction. 

For an example of the application of Radziszewski reaction for intra- and intermolecular polymer coupling, see K.-S. Krannig, D. Esposito, M. Antonietti, Macromolecules 2014, 47, 2350-2353. Highly efficient transfer of amino groups to imidazolium entities for polymer coupling and cross-linking. 

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