3-Ethyl-2-( ethylimino )-4-methyl-2 , 3-dihydro-1 , 3-thiaz ole-5-carboxylate Ethyl Ester

An efficient procedure to obtain the new compound 1a from ethyl acetoacetate (2a), NBS and N,N′-diethylthiourea (4a) was reported. In comparison with the traditional method to synthesize its analogues, this efficient, catalyst-free, and one-pot synthetic method is facile. The work-up procedure is easy and gives the pure target compound under milder reaction conditions in a relatively high yield of 75%.

The attempt in our research group to acquire the title compound-3-ethyl-2-ethylimino-4-methyl-2,3-dihydro-1,3-thiazole-5-carboxylate ethyl ester (1a)-using the reported DBTBE method led to the complete recovery of the starting materials.The conventional synthesis of 1a via Scheme 1 involved a tedious work-up with very low overall yield, which could not be used efficiently.
The attempt in our research group to acquire the title compound-3-ethyl-2-ethylimino-4-methyl-2,3-dihydro-1,3-thiazole-5-carboxylate ethyl ester (1a)-using the reported DBTBE method led to the Molbank 2016, 2016, M919; doi:10.3390/M919www.mdpi.com/journal/molbankcomplete recovery of the starting materials.The conventional synthesis of 1a via Scheme 1 involved a tedious work-up with very low overall yield, which could not be used efficiently.As part of our recent studies on the new biological heterocyclic compounds [12,13], we now report a successful simple procedure to synthesize 1a from ethyl acetoacetate (2a), NBS, and N,N -diethylthiourea (4a).While 1a shares a similar structure with the reported analogues [8], it was still reported for the first time by our research group in this paper.
Comparing with the traditional method of synthesizing its analogues, this efficient, catalyst-free, and one-pot synthetic method is facile; the work-up procedure is easy and gives the pure target compound under milder reaction conditions with a relatively high yield of 75%.This method offers an alternative way to provide 2,3-diethyl-2,3-dihydro-1,3-thiazole (1a) instead of the traditional two-step method from disubstituted thioureas and β-keto ester derivatives (Scheme 2).As part of our recent studies on the new biological heterocyclic compounds [12,13], we now report a successful simple procedure to synthesize 1a from ethyl acetoacetate (2a), NBS, and N,N′-diethylthiourea (4a).While 1a shares a similar structure with the reported analogues [8], it was still reported for the first time by our research group in this paper.
Comparing with the traditional method of synthesizing its analogues, this efficient, catalyst-free, and one-pot synthetic method is facile; the work-up procedure is easy and gives the pure target compound under milder reaction conditions with a relatively high yield of 75%.This method offers an alternative way to provide 2,3-diethyl-2,3-dihydro-1,3-thiazole (1a) instead of the traditional two-step method from disubstituted thioureas and β-keto ester derivatives (Scheme 2).

Scheme 2. The efficient one-pot synthesis of the title compound (1a).
The methods developed in this paper will enrich the limited arsenal for efficiently constructing various functionalized 2,3-dihydro-1,3-thiazoles, which would be a benefit for further exploration of their potent unknown biological activities.In addition, this method is expected to be useful for the expedient synthesis of a variety of heterocyclic compounds with a thiazole core in more complex structures other than the simple substituted 1a.

Experimental Section
Melting points were taken on an X-4 digital melting point apparatus (Shanghai Yice Apparatus & Equipments Co., Ltd, Shanghai, China) and are uncorrected.Elemental analyses were performed on a Carlo-Erba 1106 elemental analyzer (Thermo Scientific, Waltham, MA, USA).IR spectra were recorded on a Nicolet FT-IR 360 spectrophotometer (Thermo Scientific, Waltham, MA, USA). 1 H-NMR and 13 C-NMR spectra were determined on a Bruker AM-400 (400 MHz) spectrometer (Brucker Company, Fä llanden, Switzerland) with tetramethylsilane (TMS) as an internal standard.Chemical shifts are reported in δ.Mass spectra were measured on a HP5988A instrument (Hewlett-Packard, Palo Alto, CA, USA) by direct inlet at 70 eV.All materials were obtained from commercial suppliers and used as received.

Experimental Section
Melting points were taken on an X-4 digital melting point apparatus (Shanghai Yice Apparatus & Equipments Co., Ltd, Shanghai, China) and are uncorrected.Elemental analyses were performed on a Carlo-Erba 1106 elemental analyzer (Thermo Scientific, Waltham, MA, USA).IR spectra were recorded on a Nicolet FT-IR 360 spectrophotometer (Thermo Scientific, Waltham, MA, USA). 1 H-NMR and 13 C-NMR spectra were determined on a Bruker AM-400 (400 MHz) spectrometer (Brucker Company, Fällanden, Switzerland) with tetramethylsilane (TMS) as an internal standard.Chemical shifts are reported in δ.Mass spectra were measured on a HP5988A instrument (Hewlett-Packard, Palo Alto, CA, USA) by direct inlet at 70 eV.All materials were obtained from commercial suppliers and used as received.

Scheme 2 .
Scheme 2. The efficient one-pot synthesis of the title compound (1a).