Ziegler-Thorpe cyclization

Thiurets — see 1,2,4-Dithiazolidines, diimino-Thonzylamine antihistamine, 3, 153 Thorpe reaction benzothiophenes from, 4, 876 Thorpe-Ziegler cyclization, 2, 74 Three-membered heterocyclic compounds basicity, 7, 23... 

Synthesis of amino derivatives of five-membered heterocycles by Thorpe-Ziegler cyclization 99AHC(72)79. 

The use of classical condensation reactions is important. Thus, the Dieckmann reaction (equation 38) and the Thorpe-Ziegler cyclization (equation 39) have been used for almost a century for the preparation of a wide range of monocyclic and benzo-fused heterocycles. The aldol condensation and related reactions have also been fairly widely exploited, especially for the synthesis of 4-quinolones (the Camps reaction, e.g. equation 40), and various extensions of this general approach are described in the monograph chapters. 

Highly substituted [l,6]naphthyridines have been prepared by the Michael addition and subsequent Thorpe-Ziegler cyclization of a series of chalcones with malononitrile in the presence of pyrrolidine, over extended periods of heating <1999SC3881>. Attempts to reduce the reaction times using microwave irradiation gave mixtures of products... 

Synthesis of Amino Derivatives of Five-Membered Heterocycles by Thorpe-Ziegler Cyclization... 

The present review covers the Thorpe-Ziegler syntheses of 3-aminofurans, 3-aminopyrroles, 3-aminothiophenes, 3-aminoselenophenes, and diverse aminoazoles as well as the corresponding annulated systems that appeared from 1983 to 1996 but excludes examples considered in the 3-cyanopyridine review (92MI1). Moreover, examples are included that do not report a separate Thorpe-Ziegler cyclization but are likely to involve this type of reaction (e.g., cases in which precursors 1 were not isolated and identified but directly formed in the reaction mixture). Special attention is paid to synthetic aspects, although some reaction mechanisms are discussed too. 

Lithium diisopropyl amide (LDA) assisted Thorpe-Ziegler cyclization of cyanoenolethers (11) was used to synthesize the ribose-C-glycoside 12, which was further transformed into a furo[3,2-d] pyrimidine (86TL815 90MI1). Other bases such as NaOEt, l,5-diazabicyclo[4,3,0] non-5-ene (DBN), r-BuOK or n-BuLi that were successfully used in pyrrole syntheses (see Section III. A) were not suitable for this furan formation (Scheme 3). 

Aminofuran-2-ones (15) (R = COAr, COMe) could be synthesized by Thorpe-Ziegler cyclization of acylmethyl esters 13 and 14 in the presence of NEt3 and NaOEt, respectively. However, the less acidic ethoxycarbonyl-methyl componds 13 and 14 (R = COOEt) or cyanomethyl esters (R = CN) failed to ring close (84LA1702) (Scheme 4). The starting esters could... 

Thorpe-Ziegler cyclization was further employed for the synthesis of aminofuro[2,3-c]pyridazine carboxylates (50) (90JPR104) and amino-furodibenz[b,/]azocines (52) (91KGS109) (Scheme 12). 

Thorpe-Ziegler cyclization of CH-acidic 3-aminocrotonitriles (54) was frequently used in the synthesis of 3-aminopyrroles (55) (Scheme 13). Usually this pyrrole formation proceeds more easily than the synthe-... 

Finally, cyanoalkynes (172) also were used as precursors for 3-aminothiophenes (86JHC1757). Presumably, this synthesis starts with the addition of cyanomethylthiolate, affording intermediate /3-cyanomethylthioacryloni-triles similar to 166 that finally undergo Thorpe-Ziegler cyclization to 173 (Scheme 43). 

Alternatively, the acidic methylthio group was introduced by substitution of a suitable leaving group (OAlkyl, SMe, Halo, N02) in a cyanoheterocycle or cyanocarbocycle to obtain precursors for Thorpe-Ziegler cyclizations. In this way pyrrolo[4,3-b]thiophenes (195) (via 193,194) (Scheme 49) (88S449),... 

The Thorpe-Ziegler cyclization was also used in a new synthesis of hydroindoles according to Scheme 1 (93MC160). The utilization of a-cyanoenamines has proven to be very advantageous. Thus, for example,... 

The second chapter, by Drs. V. G. Granik and A. V. Kadushkin (Moscow, Russia) and Professor J. Liebscher (Berlin, Germany), covers the synthesis of amino derivatives of heterocycles by the Thorpe-Ziegler cyclization of cyanides. The chapter concentrates on work that appeared from 1983 to 1996 and extends earlier reviews. 

Granik, V. G., Kadushkin, A. V., Liebscher, J., Synthesis of Amino Derivatives of Five-Membered Heterocycles by Thorpe-Ziegler Cyclization, 72, 79. 

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