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Synthesis and X-ray diffraction data of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate, C14H13ClN4O3S

Published online by Cambridge University Press:  06 November 2019

Fausto M. Güiza ,
Arnold R. Romero Bohórquez ,
J. A. Henao  and
H. A. Camargo Open the ORCID record for H. A. Camargo [Opens in a new window]
Fausto M. Güiza
Affiliation:
Grupo de Investigación en Compuestos Orgánicos de Interés Medicinal (CODEIM), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria, Bucaramanga, Colombia
Arnold R. Romero Bohórquez
Affiliation:
Grupo de Investigación en Compuestos Orgánicos de Interés Medicinal (CODEIM), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria, Bucaramanga, Colombia
J. A. Henao
Affiliation:
Grupo de Investigación en Química Estructural (GIQUE), Escuela de Química, Facultad de Ciencias, Universidad Industrial de Santander, A.A. 678, Carrera 27, Calle 9 Ciudadela Universitaria, Bucaramanga, Colombia
H. A. Camargo*
Affiliation:
Grupo de Investigación en Nuevos Materiales y Energías Alternativas (GINMEA), Universidad Santo Tomás, Facultad de Química Ambiental, Campus Universitario Floridablanca, Santander, Colombia
*
a)Author to whom correspondence should be addressed. Electronic mail: hernando.camargo@ustabuca.edu.co
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Abstract

The new compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate was synthesized by the 1,3-dipolar cycloaddition reaction between (4R)-methyl-3-propionyl-thiazolidin-4-carboxylate (1) and 4-chlorophenylazide using the click chemistry approach. Molecular characterization was carried out by infrared spectroscopy and mass spectrometry. The X-ray powder diffraction study determined that the title compound crystallized in an orthorhombic system with unit-cell parameters a = 20.876 (2) Å, b = 12.111 (1) Å, and c = 6.288 (9) Å. The volume of the unit cell is V = 1589.7 (2) Å3. All measured diffraction maxima were indexed and are consistent with the P2221 space group (No. 17). No detectable impurities were observed.

Keywords

thiazolidinesantineoplastic activityX-ray powder diffraction
Type
New Diffraction Data
Information
Powder Diffraction , Volume 35 , Issue 1 , March 2020 , pp. 41 - 44
Copyright
Copyright © International Centre for Diffraction Data 2019

I. INTRODUCTION

Thiazolidines are a family of heterocyclic compounds with meaningful biological activity shown in the different biological tests that have been carried out (Eftekhari-Sis and Zirak, Reference Eftekhari-Sis and Zirak2015). The antineoplastic activity of the thiazolidine compounds has been widely studied. The 2-arylthiazolidine-4-carboxylamide derivatives (ATCAAs) developed have presented the most striking IC50 values (Li et al., Reference Li, Lu, Wang, Dalton and Miller2007). These compounds contain within their structure the residual fragment of the aldehyde used in the synthesis, and according to the aldehyde used (Gududuru et al., Reference Gududuru, Hurh, Sullivan, Dalton and Miller2005), a chiral center within the thiazolidine ring can be generated or not. This chiral center generates conformational isomers that at the time of the biological tests must be separated, which in some cases cannot be carried out by traditional methods. The use of formaldehyde in the synthesis of thiazolidine generates the ring without this new chiral center, which leads to a single compound.

Another heterocycle of great interest in medicinal chemistry is 1,2,3-triazole. This five-member heterocyclic nucleus has three nitrogen atoms within an aromatic electronic cloud, which gives this ring special properties that lead to a wide range of biological activities. There are many drugs that contain the 1,2,3-triazole ring within its structure. Rufinamide (Bonacorso et al., Reference Bonacorso, Moraes, Wiethan, Luz, Meyer, Zanatta and Martins2013), cefatrizine (He et al., Reference He, Sun, Zhao, Hai and Wu2014), and vorozole (Wouters et al., Reference Wouters, Snoeck and De Coster1994) are some examples. The antitumor activity of vorozole led to the creation of many triazole derivatives, in which it was sought to enhance this activity. In this search, molecular hybridization (Esra Önen et al., Reference Esra Önen, Boum, Jacquement, Spanedda, Jaber, Scherman, Myllykallio and Herscovici2008) has turned out to be a very powerful tool for the synthesis of biologically active compounds.

In order to obtain new heterocycle compounds with promising antitumoral activity, we have focused our efforts on the synthesis and characterization of new hybrids thiazolidine/1,2,3-triazole compounds. In this sense, in the present work, the simple synthesis of the compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate (3) through the 1,3-dipolar cycloaddition reaction, based on the click chemistry approach, is shown. Furthermore, the results of molecular characterization (FTIR and GC-MS) and X-ray powder diffraction (XRPD) data are reported.

II. EXPERIMENTAL

A. Synthesis

The synthetic scheme to synthetize the title compound (3) is as follows (Figure 1): first, 0.192 g (0.955 mmol) of thiazolidine (1) was dissolved in a methanol/water mixture, then 0.269 g (0.764 mmol) of sodium ascorbate and 0.011 g (0.047 mmol) of copper sulfate (CuSO4·5H2O) were added. Once homogenized and under vigorous stirring, 0.220 g (1432 mmol) of 4-chlorophenylazide (2) performed was added. Finally, the reaction mixture was left at room temperature for 11 h. After the reaction, the mixture was diluted in water (30 ml) and extracted with ethyl acetate (3 × 40 ml). The organic phase was separated and dried over anhydrous Na2SO4, concentrated in vacuo, and the resulting product was purified by column chromatography using silica gel and a petroleum ether:ethyl acetate mixture to obtain the compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate (3) as a white powder in a yield of 80%. The melting temperature (uncorrected) was between 145 and 147°C and the density was 1.507 g cm−3, which was taken by the flotation method in an aqueous solution of potassium iodine. The measured density is in accordance with the calculated density (1.550 g cm−3).

Figure 1. Synthesis of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

The structural characterization was carried out using Fourier transform-infrared spectroscopy (FTIR) and mass spectrometry with electron impact (MS-EI). Analysis of FTIR revealed the following characteristic absorption bands (υ, cm−1) 2968 (C–H); 1591 (C=C); 1541 (C=C), and 1375 (C–H), while that MS-EI analysis showed the characteristic molecular peak m/z = 326 (M +·), which agrees with the molecular weight calculated with the formula of the title compound.

B. Powder data collection

A small portion of the title compound C14H13ClN4O3S was gently ground in an agate mortar and sieved to a grain size less than 38 µm. The specimen was mounted on a polymethyl methacrylate (PMMA) holder. The XRPD pattern was recorded with a D8 ADVANCE BRUKER diffractometer operating in DaVinci geometry equipped with an X-ray tube (CuKα radiation: λ = 1.5418 Å, 40 kV, and 30 mA) using a nickel filter and a one-dimensional LynxEye detector. A receiving slit (RS) of 0.6 mm and the primary and secondary soller slits (SS) of 2.5° were used. The scan range was 2°–70° in 2θ with a step size of 0.01526° and a counting time of 2 s step−1. XRPD data were collected at room temperature (298 K).

PowderX program (Dong, Reference Dong1999) was used to remove the background (Sonneveld and Visser, Reference Sonneveld and Visser1975) and smoothing (Saviztky and Golay, Reference Saviztky and Golay1964) as well as to eliminate the Kα 2 component (Rachinger, Reference Rachinger1948), and the second derivative method was used to determine the position and intensities of the diffraction peaks.

III. RESULTS AND DISCUSSION

The XRPD data for the compound (3) are given in Table I. All reflections were indexed successfully using the DICVOL14 program (Boultif and Loüer, Reference Boultif and Loüer2004) on an orthorhombic system unit cell. A maximum absolute error of 0.03° 2θ was the Δ2θ limit for indexing a given observed diffraction line. The CHEKCELL program (Laugier and Bochu, Reference Laugier and Bochu2002) suggests P2221 (No. 17) as the possible space group, which is consistent with the systematic absences and with the crystal density. The unit-cell parameters of compound (3) were refined with the program NBS*AIDS83 (Mighell et al., Reference Mighell, Hubbard and Stalick1981). The crystal data, density, and figures of merit M 20 (de Wolff, Reference de Wolff1968) and F 20 (Smith and Snyder, Reference Smith and Snyder1979) are compiled in Table II. The XRPD pattern of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate (3) is shown in Figure 2.

Figure 2. XRPD of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

TABLE I. XRPD data of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

TABLE II. Parameters obtained by XRPD for the compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

DEPOSITED DATA

CIF and/or RAW data files were deposited with ICDD. You may request this data from ICDD at .

ACKNOWLEDGEMENTS

The authors thank Unidad de Investigaciones of Universidad Santo Tomás (Bucaramanga, Colombia) for its support with the project approved in the X internal call of research projects. The authors specially thank the Laboratorio de Rayos-X PTG of Universidad Industrial de Santander (Bucaramanga, Colombia) for data collection.

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Figure 0

Figure 1. Synthesis of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

Figure 1

Figure 2. XRPD of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

Figure 2

TABLE I. XRPD data of (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.

Figure 3

TABLE II. Parameters obtained by XRPD for the compound (4R)-methyl-3-(1-(4-chlorophenyl)-1H-1,2,3-triazole-4-carbonyl)thiazolidin-4-carboxylate.