Facile Synthesis of Cyclic Vinamidinium p-Toluenesulfonates

Abstract

Recently we have reported on the α-iodination reaction of some cyclic enaminones. The required cyclic enaminones have been synthesized by the reaction of cyclohexane-1,3dione and amines such as aniline in the presence of ptoluenesulfonic acid as the catalyst. During the reaction small amounts of cyclic vinamidinium salt was isolated. From the reaction mixture we could not find and isolate any salt-free vinamidine itself. Elimination of p-toluenesulfonic acid from the salt could be carried out by treatment with triethylamine to afford the cyclic vinamidine (vide infra). The synthesis of vinamidine in a direct method in high yield could not be achieved with excess use of aniline (up to 5 equiv.). The failure might be arised from the basic nature of vinamidine, which trap the acid catalyst and presented as its salt, namely vinamidinium salt. Electronic interactions between p-donor atoms (saturated nitrogen atom in this case) and π-acceptor groups (imino group in this case) through an intervening carbon-carbon double bond make vinamidine as a strong base. Vinamidinium salts have been used as versatile threecarbon building blocks in the synthesis of benzenoid, nonbenzenoid, and hetereocyclic aromatic rings. Certain vinamidinium salts can be used as a UV absorber. Thus, we intended to develop a facile preparation method of cyclic vinamidinium salt and wish to report herein the results. As mentioned above the synthesis of vinamidine in a direct method in high yield could not be carried out with excess use of aniline. We envisioned that the problem could be solved by the use of excess amounts of acid catalyst. The acid catalyst might improve the electrophilicity of the carbonyl carbon of enaminone intermediate 3 and also act as a template for the approach of aniline toward the protonated enaminone (Scheme 1). Thus, we examined the reaction of cyclohexane-1,3-dione (1a) and aniline (2a, 2.0 equiv.) in the presence of p-TsOH (1.0 equiv.). As expected the corresponding vinamidinium salt 4a was isolated in high yield (94%, entry 2). The same experiment with 0.1 equiv. of p-TsOH gave trace amounts of 4a (6%) together with the enaminone 3a (66%) as the major product. As shown in Table 1, the reaction of 1a and 4chloroaniline (2b) or 4-methoxyaniline (2c) showed similar pattern of reaction (entries 2 and 3). The use of dimedone (1b) showed same tendency as those of the cyclohexane-1,3dione cases (entries 5 and 6). It is interesting to note that the use of picric acid instead of p-TsOH also produced the corresponding vinamidinium salt 4d in moderate yield (entry 4). As mentioned before synthesis of salt free vinamidine itself (5a and 5b) could be carried out by the use of Et3N or