for generating C-substituted imidazoles. In one microwave modification, the reactants are benzil, benzaldehyde and ammonia in glacial acetic acid, forming 2,4,5-triphenylimidazole ("lophine"). Imidazole can be synthesized by numerous methods besides the Debus method. Many of these syntheses can also be applied to different substituted imidazoles and imidazole derivatives by varying the functional groups on the reactants. These methods are commonly categorized by which and how many bonds form to make the imidazole rings. For example, the Debus method forms the (1,2), (3,4), and (1,5) bonds in imidazole, using each reactant as a fragment of the ring, and thus this method would be a three-bond-forming synthesis. A small sampling of these methods is presented below. Formation of one bond The (1,5) or (3,4) bond can be formed by the reaction of an imidate and an α-aminoaldehyde or α-aminoacetal. The example below applies to imidazole when R1 = R2 = hydrogen. Formation of two bonds The (1,2) and (2,3) bonds can be formed by treating a 1,2-diaminoalkane, at high temperatures, with an alcohol, aldehyde, or carboxylic acid. A dehydrogenating catalyst, such as platinum on alumina, is required. The (1,2) and (3,4) bonds can also be formed from N-substituted α-aminoketones and formamide with heat. The product will be a 1,4-disubstituted imidazole, but here since R1 = R2 = hydrogen, imidazole itself is the product. The yield of this reaction is moderate, but it seems to be the most effective method of making the 1,4 substitution. Formation of four bonds This is a general method that is able to give good yields for substituted imidazoles. In essence, it is an adaptation of the Debus method called the Debus-Radziszewski imidazole synthesis. The starting materials are substituted glyoxal, aldehyde, amine, and ammonia or an ammonium salt. Formation from other heterocycles Imidazole can be synthesized by the photolysis of 1-vinyltetrazole. This reaction will give substantial yields only if the 1-vinyltetrazole is made efficiently from an organotin compound, such as 2-tributylstannyltetrazole. The reaction, shown below, produces imidazole when R1 = R2 = R3 = hydrogen. Imidazole can also be formed in a vapor-phase reaction. The reaction occurs with formamide, ethylenediamine, and hydrogen over platinum on alumina, and it must take place between 340 and 480 °C. This forms a very pure imidazole product. Van Leusen reaction The Van Leusen reaction can also be employed to form imidazoles starting from TosMIC and an aldimine. The Van Leusen Imidazole Synthesis