Synthesis of bis-oxathiaaza[3.3.3]propellanes via nucleophilic addition of (1,ω-alkanediyl)bis( N' -organylthioureas) on dicyanomethylene-1,3-indanedione

A concise and efficient route for synthesis of bis-oxathiaaza[3.3.3]propellanes by reaction of N,N,-N ''-(1, ω -alkanediyl)bis-( N ''-organylthioureas) with (1,3-dioxo-2,3-dihydro-1 H -inden-2- ylidene)propanedinitrile is reported. The structures of the products have been confirmed by using NMR as well as single crystal X-ray analysis for one product. A plausible mechanism for formation of the products is presented.


Introduction
Propellane is considered as annulated tricyclic systems, 1 with skeletons occupying a privileged place in synthetic organic chemistry.3][4][5] The natural products including propellanes have been evaluated for their anticancer 6 and antifungal 7 activities.
The molecular structures of products 7a-e were elucidated from their mass spectrometric analyses, IR, 1 H NMR and 13 C NMR spectra, for example 7a.The mass spectrum of 7a displayed the molecular ion peaks at m/z 746 which is in agreement with the proposed structure and which clearly shows the addition of one molecule of 5a to one molecule of 6 without any elimination.The IR spectrum of 7a shows absorption bands at 3321 and 3208 cm -1 due to NH2, sharp band at 2186 cm -1 and four absorption bands 1734, 1624, 1589 and 1099 cm -1 relating to C≡N, C=O, C=N, Ar-C=C and C-O-C stretching frequencies clearly indicated on the most significant functional groups of 7a.
Compounds 5a-e may react at least with their Sulphur atom, and NH , s as nucleophilic sites.
Several alternative structures could be excluded on the basis of 13 C NMR spectrum and absence of C=S signal in 7a-e.Without reference compounds, it would not be easy to compare the 1 H NMR or 13 C NMR chemical shifts for possible sets of isomers 7 and it would not be easy to assess the correct structure just from spectroscopic data.The structure of 7a with crystallographic Ci-symmetry was unequivocally resolved by X-ray crystallography (Fig. 1) and Tables S1-S7 in the supplementary data (note that the crystallographic numbering does not correspond to systematic IUPAC numbering rules).The C4-C( 12  As a result, it was found that solvent, temperature and molar ratio of reactants may all play a critical role on the reaction efficiency.Different solvents were used and studied their effect on the reaction pathway, tetrahydrofuran (THF) was a superior solvent compared to ethyl acetate, DMF, CH3CN and ethyl alcohol.
Two molecules of 6 were necessary to obtain the products in high yield.Traces of the products were formed upon applying this reaction at room temperature for long time.Subjecting the reaction under reflux in THF for 14 hours, satisfied yield of the products were observed.
Based on these results, a plausible mechanism for the formation of products 7a-e has been proposed (Scheme 3).In order to rationalize the formation of propellanes 7a-e, the bithioureas with initially attack the C=C of 6 via nucleophilic sulfur atom to form the intermediate 8, followed by addition another molecule of 6 afforded the adduct 9. Attack of NH on C=O gave the intermediate 10.Attack of the formed OH on one of the cyano groups followed by tautomerism of the imine to enamine gave the more stable propellanes 7a-e.Scheme 3. A plausible mechanism for the formation of 7a-e.
Aromatic protons gave rise to characteristic signals in the aromatic region of the spectrum at 7.05-8.05ppm.