(+)-CSA Catalyzed Multicomponent Synthesis of 1-[(1,3-Thiazol-2-ylamino)methyl]-2-naphthols and Their Ring-Closure Reaction under Ultrasonic Irradiation

New 1-[(1,3-thiazol-2-ylamino)methyl]-2-naphthols were obtained by condensation of 2-aminothiazole, aromatic aldehydes, and 2-naphthol in the presence of (+)-camphor-10-sulfonic acid ((+)-CSA) as an effective catalyst under ultrasound-promoted solvent-free conditions.The 1-[(1,3-thiazol-2-ylamino)methyl]-2-naphthol derivatives were converted in ring-closure reaction with formaldehyde to the corresponding naphthoxazine derivatives.


Introduction
Multicomponent reactions have increasing importance in synthetic organic chemistry because they allow the building of several new bonds in a single step [1][2][3][4].Some of the significant advantages of multicomponent reactions over conventional reactions are a high degree of atomic economy, structural diversity, easier progress of reactions, decreased reaction times, low power consumption, and lack of waste products [5,6].
The development of efficient and environmentally friendly chemical processes has an increasing popularity in organic chemistry.In this context, ultrasound-assisted organic reactions have become an important research area in recent years [39][40][41][42][43]. Ultrasound irradiation is able to activate many organic reactions due to cavitational collapse [44,45].Compared with traditional methods, a broad range of organic syntheses can be successfully performed in higher yields and selectivity, shorter reaction times, and milder reaction conditions under ultrasonic irradiation [46][47][48].

Experimental
2.1.Materials and Methods.NMR spectra were determined on a Bruker Avance III-500 MHz NMR.Chemical shifts are given in ppm downfield from Me 4 Si in DMSO- 6 or CDCl 3 solution.Coupling constants are given in Hz.The FTIR spectra were recorded on a Perkin-Elmer FTIR spectrometer (ATR) and absorption frequencies are reported in cm −1 .MS spectra were recorded on a Thermo Elemental X Series ICP-MS.Elemental analyses were measured with Flash EA 1112 Series apparatus and were in good agreement (±0.2%) with the calculated values.Ultrasonication was performed in a Bandelin Sonorex Ultrasonic Bath (Super RK) with a frequency of 35 kHz and a power of 230 W. The internal dimensions of the ultrasonic cleaner tank were 240 × 140 × 100 mm with liquid holding capacity of 3 L.The reactor was a 100 mL Pyrex round-bottom flask.The reaction flasks were suspended in the center of the bath, and the addition or removal of water controlled the temperature of the water bath.Melting points were measured on a Gallenkamp melting-point apparatus.Silica gel 60 (Merck) was used for column separation.TLC was conducted on standard conversion aluminum sheets precoated with a 0.2 mm layer of silica gel.All reagents were commercially available.Anhydrous (+)-CSA was purchased from commercial suppliers.

General Procedure for the Synthesis of 1-[(1,3-Thiazol-2ylamino)methyl]-2-naphthols (1a-n) under Ultrasonic Irradiation.
A mixture of (+)-CSA (11.6 mg, 0.05 mmol), 2aminothiazole (1.00 mmol), aromatic aldehyde (1.00 mmol), and 2-naphthol (1.00 mmol) was irradiated with ultrasound of low power (with a frequency of 35 kHz and a nominal power of 230 W) at 50 ∘ C for the period of time indicated in Table 3 and Scheme 3. The reaction flask was located at the maximum energy area in the cleaner and the surface of the reactants was placed slightly lower than the level of the water.The addition or removal of water controlled the temperature of the water bath.After completion of the reaction, as indicated by TLC monitoring, the resultant solid was crystallized from acetone to give products 1a-n.(1,3- 1c, 1d, 1k, 1m, and 1n (1 mmol) were dissolved in THF (3 mL) and 35% aqueous formaldehyde (1.2 mmol) was added.The solution was irradiated with ultrasound of low power (with a frequency of 35 kHz and a nominal power of 230 W) at 50 ∘ C for 3 hours.The reaction flask was located at the maximum energy area in the cleaner and the surface of the reactants was placed slightly lower than the level of the water.The addition or removal of water controlled the temperature of the water bath.Solvent was removed and the residue was dried under reduced pressure.The crude oil was purified by column chromatography eluting with EtOAc/hexane.Page 10) [1,3]

Results and Discussion
Li and Mao reported that the reaction of 2-aminothiazole, 2naphthol, and benzaldehyde under solvent-free conditions at 120 ∘ C gave the desired product in 6 h (Lit.[23]).We decided to perform this reaction under ultrasonic irradiation to get a shorter reaction time, milder reaction conditions, and higher yield.
Next, in order to observe the effect of the amount of (+)-CSA on the reaction, we also performed the experiments  using different amounts of catalyst (Table 2 and Scheme 2).The best result was obtained by carrying out the reaction using 5 mol% of (+)-CSA at 50 ∘ C under solvent-free conditions (Table 2 and Scheme 2).With these optimal reaction conditions, we then examined a variety of aromatic and heteroaromatic aldehydes in ultrasound-promoted catalytic Mannich-type reactions.As shown in Table 3 and Scheme 3, the one-pot three-component reactions work well with a variety of aromatic and heteroaromatic aldehydes, and the desired compounds were obtained in good yields.However, the aryl aldehydes which contain electron-withdrawing groups gave the desired products in lower yields.On the other hand, reactions with pyridine-2-carbaldehyde and pyridine-4-carbaldehyde did not give the desired product.
The structures of the newly generated compounds have been confirmed by Fourier transform-infrared (FTIR), mass, and NMR techniques.The characteristic absorption bands of OH and NH bands were observed at 3326-3385 cm −1 in The mass spectra of all new compounds showed the expected molecular ion peak.1,3-Oxazine derivatives were prepared by the ring-closure reactions of 1-[(1,3-thiazol-2-ylamino)methyl]-2-naphthols 1a, 1c, 1d, 1k, 1m, and 1n with formaldehyde under ultrasound irradiation at 50 ∘ C (Table 4 and Scheme 4) in THF solvent.The ring-closure reaction of 1a (1.00 mmol) with formaldehyde (1.20 mmol) without a catalyst under conventional conditions at room temperature gave the desired product in 15 h with 40% yield.The best result was obtained by carrying out the reaction at 50 ∘ C under ultrasonic irradiation.
In the 1 H NMR spectra of 1,3-oxazine derivatives the CH 2 protons which are between N and O atoms appeared in the ranges 4.98-5.37 and 5.51-5.70ppm.The CH protons which are near the Ar group were observed at 6.75-7.02ppm.
a Isolated yield.
a Isolated yield. the
a Isolated yield.