Reagents for new heteroannelation reactions. Part VI: 2-(methylsulfanyl)-1,4,5,6-tetrahydropyrimidine

2002 ARKIVOC  
The reaction of heteroaromatic 2-aminoesters and 2-aminonitriles with 2-(methylthio)-1,4,5,6-tetrahydropyrimidine results in annelation of a pyrimido[1,2-a]pyrimidine moiety in a one-pot process, providing access to a number of predominantly novel triand tetracyclic hetero-systems. Scheme 1 In addition, 2-aminonitriles were employed as starting materials and afforded the corresponding imino derivatives (Scheme 2). Scheme 2 In continuation of the above-mentioned work with cyclic reagents this
more » ... ic reagents this paper describes the utilization of 2-(methylsulfanyl)-1,4,5,6-tetrahydropyrimidine (1) within the BMMA strategy, thus expanding the scope of this reactions towards the annelation of a pyrimido[1,2-a]pyrimidine unit. Results and Discussion The reaction of a variety of heteroaromatic aminoesters and aminonitriles with 1 furnished the desired tri-and tetracyclic fusion products 2, 3 and 4, 5, respectively (Scheme 3). In a series of experiments, solvent and temperature conditions were optimized. Heating the starting materials in HMPA to 150 °C or without solvent to 170 °C for several hours gave best results. Scheme 3 The reaction of 1 with a number of monocyclic heterocycles with vicinal amino and ester functionalities gave the tricyclic oxo compounds 2, and from the reaction of 1 with accordingly substituted heterocyclic amino nitriles the imino derivatives 3 were obtained. Cycloalkane-and heterocycle-fused thiophenes with 2-amino and 3-ester or 3-nitrile functionalities as well as 2-amino-4,5,6,7-tetrahydrobenzofuran-3-carbonitrile were the suitable starting materials (easily accessible from suitable cyclic ketones via the Gewald reaction; references are provided in the Experimental part) for the preparation of the corresponding tetracyclic oxo and imino compounds 4 and 5, respectively. Compound 4b has already been prepared by a similar reaction 5 in very poor yield, and was identified only by its molecular ion peak in a mass spectroscopic analysis. In contrast, the method described here provides easy, one-step access to polynuclear heterocyclic compounds in fair to good yields starting from relatively simple substrates. Experimental Section General Procedures. Melting points (mp) were determined on a Kofler hot stage apparatus. 1 H and 13 C NMR spectra were recorded on a Bruker AC 200 spectrometer (200 MHz for 1 H; TMS as internal standard, DMSO-d 6 as solvent, δ values in ppm). Elementary analyses were performed at the Microanalytical Laboratory, Institute of Physical Chemistry, University of Vienna (Mag. J. Theiner). 2-(Methylsulfanyl)-1,4,5,6-tetrahydropyrimidine (1) was prepared via a two-step procedure from 1,3-propanediamine and CS 2 followed by methylation with methyl iodide (applying procedures originally published for 2-(methylsulfanyl)-2imidazoline 6,7 ). Aminoesters and aminonitriles as starting materials were prepared according to known procedures (references given at the respective experiments). General procedure for the cyclization reaction 2-(Methylsulfanyl)-1,4,5,6-tetrahydro-pyrimidine (1.56 g, 12 mmol) and the appropriate aminoester or aminonitrile (10 mmol) were heated under a nitrogen atmosphere either in HMPA (10 mL) to 150 °C or without solvent to 170 °C for a given period of time. After
doi:10.3998/ark.5550190.0002.218 fatcat:42mcc2gf2zfalisi4ycpzq7f7i