Thorpe-Ziegler reactions

The intramolecular version of the Thorpe reaetion, which is base-catalyzed selfcondensation of nitriles to yield imines that tautomerize to enamine. 

Rodriguez-Hahn, L. Parra M., M. Martinez, M. Synth. Commun. 1984,14, 967. 

Palladium-catalyzed allylation using nucleophiles with allylic halides, acetates, carbonates, etc. via intermediate allylpalladium complexes, and typically with overall retention of stereochemistry. 

Godleski, S. A. In Comprehensive Organic Synthesis Trost, B. M. Fleming, L, eds. Vol. 4. Chapter 3.3. Pergamon Oxford, 1991. (Review). 

Moreno-Manas, M. Pleixats, R. In Advances in Heterocyclic Chemistry Katritzky, A. R., ed. Academic Press San Diego, 1996, 66, 73. (Review). 

Example 1, A radical-mediated Thorpe-Ziegler reaction  

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 274, Springer International Publishing Switzerland 2014 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 255, Springer-Verlag Berlin Heidelberg 2009 

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Most probably, the last stage in the synthesis of 2-amino-4H-pyrans involves base-catalyzed nucleophilic addition of the enolic oxygen to a C=N group, which can be regarded as a hetero-Thorpe-Ziegler reaction (Scheme 21). 

The Thorpe-Ziegler reaction has been employed in the synthesis of thieno[3,4-t4pyritnidines by providing the thiophene 421. Heating this compound under reflux in formic acid leads to a series of thienopyrimidines 422 (Equation 157) <2002IZK854>. 

Thorpe Reaction (If intermodular, known as the Thorpe-Ziegler Reaction.)... 

There are numerous applications of the Thorpe-Ziegler reaction for the synthesis of thiophenes and annulated thiophenes. Only selected examples can be covered here. For more examples see reviews (85MI1 86MI1 92MI1). 

The formation of tetracyclic thiophene (232) (via 231) by the Thorpe-Ziegler reaction in the presence of N-bromsuccinimide (NBS) represents a special case, because the pyrimidine-2-thione 229 also served as precursor for the CH-acidic alkylation agent 230 (95H2195) (Scheme 59). 

The few thiophene syntheses reported in which the formation of the heterocycle is realized on an insoluble support (Entries 1-3, Table 15.10) are based on the intramolecular addition of C,H-acidic compounds to nitriles (Thorpe-Ziegler reaction), or on the Gewald thiophene synthesis. The mechanism of these cyclizations is outlined in Figure 15.6. In thiophene preparations performed on solid phase, the required a-(cya-... 

Catalytic Thorpe-Ziegler reaction (Addition of Nitriles to Nitriles)... 

Scheme 7. Iridium-catalyzed Thorpe-Ziegler reaction.

Compounds 2 and 3 react with sodium hydride in THF to give the products of a Thorpe-Ziegler reaction. The procedure under more conventional conditions (KOH/DMF) results in a mixture of closo- and tV/o8-carboranyl-thieno-pyridines and -pyrimidines (Scheme 3) ... 

Thorpe reaction The addition of the anion that results from the deprotonation of a nitrile compound, to another nitrile group. The resulting imine may be hydrolysed to yield a (3-cyanoketone. If the reaction is performed internally it is known as the Thorpe-Ziegler reaction. 

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