1 SYNTHESIS OF 2-AMINOTHIAZOLIDIN-4-ONES FROM ( HEPTA-O-ACETYL-β-MALTOSYL ) THIOSEMICARBAZONES OF SUBSTITUTED ACETOPHENONES

Reaction of substituted acetophenone (hepta-O-acetyl-β-maltosyl)thiosemicarbazones with ethyl bromoacetate was investigated. It’s indicated that the nature of solvents and the catalysts affected the reaction yields, and that the microwave-assisted heating method gave higher yields of products than the conventional heating one. Based on the optimum conditions, ionic liquid [HOCH2CH2NH3]OAc, dried chloroform and microwave-assisted heating, the synthesis of some 2-iminothiazolidin-4-ones containg maltose moiety were synthesized. Their structure have been confirmed by spectral data (FTIR, 1H NMR, 13C NMR and MS).

2 and solvents, also obtained results were represented in Table 1.Acetophenone hepta-O-acetyl-βmatosylthiosemicarbazone 1g was used in this investigation.From Table 1, it's shown that the reaction of thiosemicarbazones 1g with ethyl bromoacetate did not occurred when tertiry amines, such as triethylamine and DABCO, were used in any solvent that was chosen, such as ethanol, toluene, dichloromethane, chloroform, even if reaction time was extended until 12-16 h.This reaction was only occurred with good yields when sodium acetate was used as catalyst.In these cases, reaction time and yield of 2iminothiazolidin-4-one 2g also were changed according to the nature of solvents.For example, when solvent was absolute ethanol, then reaction time was 12 h, but a apolar solvent, such as (anhydrous) toluene, was used, then reaction time shortened to 8 h.The use of aprotic polar solvents, such as (anhydrous) chloroform or dichloromethane, made reaction time to shorten remarkably, simultaneously, the yield of 2-iminothiazolidin-4-one 2g was significantly increased.We realized that the performance of this reaction in anhydrous chloroform gave the higher yield obtained (67%) in the shorter reaction time (6 h).   3 and 4 showed 1 H NMR and 13 C NMR spectral data for only isomer 2a-j, the ones for isomer 2'a-j will be discussed in our other paper.ESI-MS spectra of 2-iminothiazolidin-4-ones 2 had molecular peaks, often [M+H] + or [M+Na] + peaks, with high intensity, and in general were base peaks (Table 3).

Experimental
Melting points were determined by open capillary method on STUART SMP3 instrument (BIBBY STERILIN-UK) and are uncorrected.IR spectra (KBr disc) were recorded on a Impact 410 FT-IR Spectrometer (Nicolet, USA). 1 H and 13 C NMR spectra were recorded on Bruker Avance Spectrometer AV500 (Bruker, Germany) at 500.13 MHz and 125.77MHz, respectively, using DMSO-d6 as solvent and TMS as an internal standard.
The solvent was removed under reduced pressure, the residue was washed with n-hexane for removing ethyl bromoacetate, and with water (2-3 times) for removing sodium acetate.The obtained solid was recrystallized from 95% ethanol to afford the title compounds 2 or 2'.

Table 1 .
-OAc, with yield of 90% for 20 min.The change of reaction time and yield of 2g in case of the use of anhydrous sodium acetate as catalyst could be summaried as follows: Investigation of influences of solvents and catalysts to reaction between The use of microwave-assisted synthetic method in this case gave the highest yield of 2g (88%) in the shortest reaction time (40 min vs. 6 h), and of ionic liquid named 2-hydroxyethylammonium acetate, [HOCH2CH2NH3 + ]

Table 2 .
The formation of 2-iminothiazolidin-4-ones 2 could be preliminarily confirmed by using IR spectroscopic method.In spectra of 2-iminothiazolidin-4-ones 2, the disappearance of absorption band at 1602-1622 cm -1 , which is characteristic for imine bond C=N, and apprearance of absorption band at 1613-1627 cm -1 , which is characteristic for C=O bond of lactam.Other absorption bands which belong to acetate group and benzene ring, in general, were only shifted insignificantly.From 1 H NMR spectra, we found that reaction of thiosemicarbazones 1b, 1d, 1f, 1h, 1i and 1j with ethyl bromoacetate gave unique product 2