The Zwitterionic Imidazolium Salt : First Used for Synthesis of 4-Arylidene-2-phenyl-5 ( 4 H )-oxazolones under Solvent-Free Conditions

e zwitterionic imidazolium salt was prepared and characterized by H N�R. It was �rst used for synthesis of azlactones via Erlenmeyer synthesis from aromatic aldehydes and hippuric acid under solvent-free conditions. It was found that aldehyde substituents play an important role in these reactions. Better conversions and therefore higher isolated yields were observed when electron-withdrawing groups (EWG-) were present in the aromatic aldehyde. Opposite results were shownwhen electron-donating groups (EDG-) were present in the aromatic aldehyde. However, azlactones were obtained in moderate to high yields.


Introduction
4-Arylidene-2-phenyl-5(4H)-oxazolones are very important intermediates for the synthesis of a variety of bioactive molecules, �ne chemicals, and precursors of several biologically active molecules such as amino acids and peptides [1].ese compounds are especially active as anticancer [2], antitumor [3], and inhibitors of central nervous system.Besides, these compounds are unique precursors for the synthesis of amino acids, peptides [4], heterocyclic compounds [5], and biosensor [6,7].In fact, these precursors could be synthesized by Horner-Emmons, Heck, or Erlenmeyer-PlÖchl [8] reactions followed by a complementary asymmetric hydrogenation reaction.e most common route to oxazolones involves the condensation of aromatic aldehydes and hippuric acid with a stoichiometric amount of fused sodium acetate in the presence of acetic anhydride as the dehydrating agent [9], such methodology is known as the Erlenmeyer-Plöchl reaction [1].

Results and Discussion
e imidazolium salt (1) was synthetized [27] and characterized by 1 H NMR. In order to evaluate the catalytic activity of sulfonate, several sulfonates such as imidazolium salt (1), methanesulfonic acid, and sulfamic acid were tested in the Erlenmeyer reaction.e results are reported in Table 1.It was found that imidazolium salt (1) (Table 1, entry 1) provided azlactone 4e in the highest isolated yield in very simple procedure and was therefore selected for further study.e overall process de�ned as the Erlenmeyer reaction was initially studied using benzaldehyde 3e as the substrate (Table 2).As shown in Table 2, different conditions have been conducted such as the amount catalyst, temperature, and reaction time.e amounts of textbf1 were tested, and it was found that 5 mmol% of 1 was enough to accomplish the reaction (Table 2, entries 2-5) when 10 mmol% of stoichiometric amount were required as previously reported.Increasing the amount of catalyst did not obviously improve the yield.Besides, 2-phenyloxazol-5-one was found as byproduct when used without catalyst in the reaction which was in accordance with [23].2-phenyloxazol-5-one was proved as important intermediate in the Erlenmeyer reaction.Similarly, reaction temperature and time were also investigated.e isolated yield was low (15%, Table 2, entry 6) as the condensation of hippuric acid to 2-phenyloxazol-5-one needs high temperature.However, some unknown by-products were formed when reaction temperature heated up to re�ux temperature and caused lower yield than the yield in 60 ∘ C. In the re�ux temperature, heavy slurry was found causing initial reactor agitation problems and an extended process reaction time [24].It was found that four hours seem to be the optimum reaction time as shown in    b Not isolated yield, some by-products were found.
To explore the scope of our catalyst, a wide variety of aldehydes were investigated in this system including aromatic and aliphatic aldehdyes (Table 3, entries 1-12).Unfortunately, aliphatic aldehyde cannot be activated in this system (Table 3, entries [11][12].Interestingly, aromatic aldehyes with the electron-withdrawing groups (EWG) were present more active than that of opposite aldehydes (Table 3, entries 1-9).EDG aldehydes resulted in lower conversion and longer reaction time.Similar phenomenon was only mentioned by omas's research group [1,24,25].Compared to the previous report [26], it was thought that the existence of [bmin] made high catalyst activity of [bmim] 3 PW 12 O 40 and [bmim] 4 W 10 O 32 .According to this theory and our research, it can be deduced that the existence of sulfonate may cause the different electronic effect, and a supposed reaction mechanism was given [28,29] in Scheme 2. 2phenyloxazol-5-one (2 ′ ) was �rst generated in condensation reaction which happened in the presence of acetic anhydride as the dehydrating agent.e imidazolium salt could activate both aldehydic carbonyl oxygen and acidic hydrogen of 2phenyloxazol-5-one (2 ′ ).e zwitterionic imidazolium salt (1) may act as a bifunctional organocatalyst in this reaction.e electrophilic activation of the aldehyde carbonyl is expected to take place through hydrogen bond formation with C-2 hydrogen atom of the imidazolium moiety.Similar mechanisms were indicated in the aza-Henry reaction [28] and aza-Michael addition [29].

Conclusions
In summary, imidazole-based zwitterionic-type molten salts are a new class of catalyst for the synthesis of 4-arylidene-2phenyl-5(4H)-oxazolones through the Erlenmeyer reaction under solvent-free conditions.is present procedure is equally effective in aryl aldehydes with electron-withdrawing groups.e nonhazardous experimental conditions, ease of reaction, short reaction times, high yields, and metal-free catalyst are the notable advantages of this procedure.To the best of our knowledge, this is the �rst report of the Erlenmeyer reaction, promoted by a zwitterionic imidazolium salt under solvent-free conditions.e investigation of the mechanism of this reaction and the use of chiral zwitterions are underway and will be reported in due course.us, it provides a better and more practical alternative to the existing methodologies.

S 2 :
A plausible reaction mechanism.T 2: Reaction conditions in the Erlenmeyer reaction.

T 1 :
Evaluation of several sulfonates in the Erlenmeyer reaction.