New N-bridgehead heterocyclic compounds . I . Carbamoyl-substituted indolizines and benzoindolizines

Quaternary salts obtained by the reaction of several pyridines and benzopyridines with chloroor bromoacetanilides were reacted with corresponding activated alkynes in the presence of an oxirane, yielding new carbamoyl-substituted indolizines and benzoindolizines derivatives. Other new 3-carbamoyl substituted indolizine and pyrrolo[2,1-a]isoquinoline derivatives were obtained by heating the intermediate N-metylcarbamoyl quaternary salts, in the presence of an acid acceptor, with alkenes and tetrapyridinecobalt(II)dichromate as a reaction promoter and dehydrogenating catalyst. The new compounds are fully characterised by elemental microanalysis and IR, H and C NMR spectra.


Introduction
The indolizines have been subject of considerable interest from physical, chemical and biological points of view. 1,2The presence of a carbamoyl group on the pyrrole ring of the indolizines should have interesting effects on their chemical and biological properties.4][5] The N-heterocyclic ylides could be obtained by the dehydrohalogenation of the corresponding quaternary salts of N-heterocyclic compounds. 4,5erein we report new carbamoyl-substituted N-bridgehead heterocyclic compounds obtained by the reactions of N-heterocyclic compounds with chloroacetanilides or bromoacetanilides

Carbamoyl-substituted indolizines and benzoindolizines
By the direct reaction of the intermediate N-methylcarbamoyl pyridinium salts 1 with activated alkynes in an epoxide, as acid acceptor and reaction solvent, new indolizines bearing a carbamoyl group on the pyrrolo ring 5-12 were obtained (Scheme 2, Table 2).
In conclusion, the otherwise not easily accessible indolizines and benzoindolizines bearing carbamoyl groups on the pyrrolo ring are readily prepared by the simple one-pot synthesis described herein.

Carbamoyl-substituted indolizines and benzoindolizines. General procedure
A mixture of N-methylcarbamoyl quaternary salt (10 mmol) and acetylenic compound (15 mmol) in propenoxid (50 mL) was stirred at room temperature for 10-12 days and then was concentrated under reduced pressure.The residue was treated with methanol (10 mL) and kept refrigerated overnight.The solid was filtered and washed with cold methanol and then with diethyl ether.All crude products were recrystallised from chloroform/methanol.General procedure for carbamoyl substituted indolizine 30 and pyrrolo[2,1-a]isoquinolines 31-32 (a) A solution of N-methylcarbamoyl quaternary salt (10 mmol), olefine (acrylonitrile or crotononitrile, 40 mmol), TPCD (4.0 g, 6.5 mmol) and pyridine (2.0 mL) in DMF (40 mL) was stirred at 90 o C for 2 h.The mixture was then cooled to room temperature and poured into 5% aq.HCl (100 mL).The solution was extracted with chloroform (4 x 50 mL) and the combined extracts were washed with water (2 x 50 mL), dried (Na 2 SO 4 ) and evaporated to give a solid compound.This was purified by recrystallisation.(b) The olefinic compound (40 mmol) was added at room temperature to a stirred mixture of N-methylcarbamoyl quaternary salt (10 mmol) and TPCD (4.0 g, 6.5 mmol) in 1,2-epoxybutane (50 mL).The reaction mixture was heated to reflux for 5-8 h, then it was concentrated under reduced pressure.The residue was cooled to room temperature and then was treated with 5% aq.HCl (100 mL) and was worked up as described above.
The yields and m. p. for compounds 30-32 are shown in Table 4; the spectral data are given below.