Synthesis of New Imidazolidine and Tetrahydropyrimidine Derivatives

Synthesis of new imidazolidine and tetrahydropyrimidine derivatives 3a, b and 4a–c as cyclic 1,3-diamines under two reaction conditions (A andB) is described.Under reaction conditions-A, a suspension of (E)-2-cyano-2-(oxazolidin-2-ylidene)ethanethioamide 1 (1 eq.) and diaminoalkanes 2a–e (2 eq.) in absolute ethanol is heated under reflux for 16–22 h to afford 3a, b and 4a–c. Alternatively, under reaction conditions-B, a solution of thioamide 1 (1 eq.) in diaminoalkanes 2a–e (3 eq.) is stirred under solvent-free conditions at room temperature for 3 days to give desired products. Reaction conditions-A for having higher yields, shorter reaction times, and required less diamines is more effective than reaction conditions-B. Oxazolidine ring opening is observed by reacting compound 1 with all of the diamines 2a–e, but the thioamide group only reacts with nonbulky diamines 2a, b. The chemical structures of novel compounds were confirmed by H NMR, C NMR, elemental analysis, and FT-IR spectrometry.

The pyrimidine fragment is present in various biologically active compounds, many of which have been found to be used in medical practice [12,13].Recently, much attention has been paid to derivatives of pyrimidine, including their hydrogenation products.This class of compounds displays wide ranges of biological and pharmacological properties such as anti-inflammatory [14], analgesic [15], antitumor [16], antidepressant [17], antibacterial, antifungal, and antitubercular effects [18][19][20].
The application of these compounds in pharmaceutical field prompted us to synthesize some new imidazolidines and tetrahydropyrimidines under two reaction conditions.These synthesized compounds are characterized by NMR, IR spectral data, and elemental analysis.
A comparison between the results obtained from both reaction conditions leads us to the conclusion that reaction conditions-A is from 65% to 77% as efficient as reaction conditions-B, also the former has shorter reaction times and required less diamines but requires a supply of heat.It is worth noting that oxazolidine ring opening is observed by reacting compound 1 with all of the diamines 2a-e, but the thioamide group only reacts with nonbulky diamines 2a, b.This is probably due to the rigid structure of compound 1 that prevents the effective interaction with bulky diamines 2c-e.
A plausible mechanism is depicted for the formation of these compounds (Scheme 2).As depicted in Scheme 2, intermediates 3  a, b and 4a-c probably were produced from two successive Michael substitution reaction thioamide 1 and diaminoalkanes 2a-e.It predicts that during adding amine to oxazolidine ring, the C-O bond breaks faster than the C-N bond because alkoxy is a better leaving group than amine.Note that in this multistep synthesis, the likely key intermediates 3  a, b were not isolated except for intermediates 4a-c which were isolated and their structures identified by spectral analysis.When intermediates 3  a, b were treated with diaminoalkanes 2a, b, amidines 4  a, b that are produced as intermediates followed by a ring closure to 3a, b.
The structural assignments of compounds 3a, b and 4a-c were based on their analytical and spectral data.bonds.All this evidence plus microanalytical data strongly supports the formation of all products.

Conclusion
In summary, several new imidazolidines and tetrahydropyrimidines have been synthesized from the reaction of a single thioamide with several various diaminoalkanes.On the basis of our previously reported work [21], the thioamide itself was synthesized in a regioselective manner from functionalized oxazolidine with phosphorus pentasulfide.

Table 1 :
Comparing yields of compounds 3a, b and 4a-c obtained under two reaction conditions A and B.
a Only for reaction conditions-A.