Fischer indole ring closure

Fischer indole ring closure with - 24,948s31... 

A synthetic approach to the same tetracyclic y-carboline nucleus (235) is the consecutive Fischer indole and Bischler-Napieralski ring closure of o-acetamidoacetophenone methylphenyUiydrazone (234). The Bischler-Napieralski reaction has also been used in the synthesis of 3,4-benz-j8-carbolines (236) and 3,4-benz-3-carbolines, e.g. 237... 

On the other hand, the nonbiogenetic approach usually adopts a convergent process such as shown in Scheme 15. When 18 is cleaved through C-6—C-7 (as 18 - 60), phenylhydrazine and a tricyclic moiety (61) which contains six chiral centers result. The synthetic problem then becomes synthesis of 61 followed by a Fischer indole synthesis and a final ring closure between C-6 and C-7 (61 -> 60 - 18). 

The most useful route to indoles is the Fischer indole synthesis, in which an aromatic phenylhydrazone is heated in acid. The phenylhydrazone is the condensation product from a phenylhydrazine and an aldehyde or ketone. Ring closure involves a cyclic rearrangement process. 

Most indoles are synthesized by the Fischer indolization reaction. Here a phenylhydrazine is first reacted with an aldehyde, or ketone, carrying an a-methylene group (not acetaldehyde). The corresponding hydrazone is then treated with an acid, often hydrochloric acid. Ring closure occurs, through a [3,3]-sigmatropic change, and ammonia (as the ammonium cation) is lost (Scheme 7.14). 

Comparatively few examples exist of ring closure on to a phenyl ring, but where this is available normal Fischer indolization conditions can be used. Of particular interest are the synthesis of /3-carboline (5 Scheme 59) (72JCS(Pl)53l) and the pyrrolothiapyran (190 ... 

Thieno[2,3-Z>]pyrroles have been prepared from 2-thienylhydrazines and carbonyl compounds under the conditions of Fischer indolization (77S487). The Bu OCO group is eliminated, and the intermediate hydrazone can undergo ring closure (equation 15). Thieno[3,2-Z>]pyrroles were prepared similarly from acylated 3-hydrazinothiophenes (75CHE1133). 

The synthesis of azaindoles by the Fischer indole synthesis has been tried more often than by any other method. It has given varied results, with over thirty successful ring closures of pyridyl- or quinolyl-hydrazones reported. Most of these have led to carboline deriva-... 

Sulfuric acid Indolenines and indoles by Fischer ring closure... 

Fischer-Hepp rearrangement org chem The rearrangement of a nitroso derivative of a secondary aromatic amine to a p-nitrosoarylamine the reaction is brought about by an alcoholic solution of hydrogen chloride. fish ar hep re a rani mant) Fischer indole synthesis orgchem A reaction to form indole derivatives by means of a ring closure of aromatic hydrazones.. fish ar in.dol. sin tha sas )... 

Compounds in which other heterocyclic rings (pyrazoles, isoxazoles, imidazoles ) are fused to thiopyrans have been described. The interesting thiazolium salts (56) were prepared by allowing the betaines (55) to react with 4-thioxothiazolidin-2-ones. Application of the Fischer indole synthesis and the Friedlander reaction to tetrahydrothiopyran-3-one led to the exported indolo-and quinolino-derivatives. Ring closure of (57) under acidic conditions afforded the rearranged product (58). Syntheses of benzothiopyrano[4,3,2-flfe]-quinazolines (59) from 1-amino-thioxanthones and of their S- and 7V-oxides have been described. ... 

---