Synthesis of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indole-2-thione and 1,5,6,10b-Tetrahydroimidazo[2,1-a]-isoquinoline-2(3H)-thione derivatives

Abstract

Thionation of heterocyclic compounds bearing lactam moieties is most commonly performed using phosphorus pentasulfide [1,2] or 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawessons's reagent) [3,4]. The latter reagent usually gives the expected thiolactams, while heating of the lactam moiety containing heterocycles, e.g., 2,3,4,5-tetrahydro-1,5-benzodiazepin-2-one derivative, with phosphorus pentasulfide in pyridine affords a mixture of tautomeric thiolactam and imino thiol [2].In the present work we investigated the replacement of carbonyl oxygen of five-membered lactam-type rings annelated to the a-edge of indole or isoquinoline nucleus by the use of Lawessons's reagent as a thionation agent.Starting imidazo[1,2-a]indol-2-one derivatives 1a,b were obtained from 2,3,3-trimethyl-and 2,3,3,5-tetramethyl-3H-indoles by the method described in [5]. Compound 1c was prepared from 4a-methyl-2,3,4,4a-tetrahydro-1H-carbazole by a similar way [6].Thionation reactions of compounds 1a-c with Lawesson's reagent were carried out in boiling toluene and furnished thiolactams 2a-c in fairly good yields (63-72%). No tautomerization of the thiolactam moiety or possible rearrangement of the annelated imidazolidine ring to the thiazolidine ring via ring opening-closure was observed. The structure of prepared compounds 2a-c was proved by IR, 1 H and 13 C NMR, and microanalyses. In the IR spectrum of 2a N-H stretching vibrations characteristic of secondary thioamides [7] were observed at 3135 cm -1 , and no absorption band characteristic of stretching vibrations of C=O group of 1a at 1700 cm -1 was found.A comparison of the chemical shifts of the 1 H and 13 C nucleus of imidazo[1,2-a]indol-2-one 1a and the corresponding thione 2a showed that substitution of carbonyl oxygen for sulfur at C-2 induces significant lowfield shifts of the imidazolidine ring atom nucleus. In the 1 H NMR spectrum (CDCl 3 ) of 2a, the diastereotopic __________________________________________________________________________________________