Open Chemistry 2021; 19: 511–517 Research Article Ayodele T. Odularu*, Peter A. Ajibade, Opeoluwa O. Oyedeji, Johannes Z. Mbese, Horst Puschmann Synthesis and crystal structure of N,N′-bis(4- chlorophenyl)thiourea N,N-dimethylformamide https://doi.org/10.1515/chem-2020-0061 Chemistry name is 2-thiourea, while the atomic formula received October 21, 2018; accepted April 2, 2020 for thiourea is CS(NH2)2 [1]. Thiourea has numerous [ ] Abstract: This study is about the synthesis of N,N′-bis(4- applications in agriculture, health and metallurgy 1 . Thiourea derivatives are useful anticancer agents [1,3]. chlorophenyl)thiourea N,N-dimethylformamide (C16H17Cl2N3OS) compound. Single crystals of the compound were obtained Several ways of synthesizing thiourea have been [ ] by slow evaporation of N,N′-bis(4-chlorophenyl)thiourea reported 1,2 . Methods reported to synthesize thiourea (C H Cl N S) in N,N-dimethylformamide (C H NO; DMF) involve intermediaries, such as carbon disulphide and 13 10 2 2 3 7 - through recrystallization under mild condition. Important ammonium thiocyanate isomerization, cyanamide, cya – – classical N–H⋯O links the two molecules together. Results namide hydrogen sulphide, lime nitrogen, urea calcium – [ – ] revealed that C H Cl N OS crystallized in the monoclinic cyanamide and urea cyanamide 4 6 . 16 17 2 3 – space group P2 /c with the respective cell parameters of The synthetic method to yield thiourea from urea 1 - a = 92,360 (4) Å, b = 7.2232 (3) Å, 25.2555 (11) Å, β = 91.376 cyanamide involves dehydrated urea under normal pres sure from the reaction of ammonia and carbon(IV) oxide (3), α = γ = 90°, V = 1684.40 (12) Å3, T = 119.94 (13) Kand to form cyanamide (H CN )[5]. The H CN reaction with Z = 4andZ′ = 1. 2 2 2 2 hydrogen sulphide forms thiourea. This method, which Keywords: thiourea, dimethylformamide, crystal struc- is of high production cost, usually gives a low yield ture, monoclinic of thiourea because of many side reactions which take place during the reaction process. Another demerit in this method is the difficulty encountered in the reaction because of carbon(IV) oxide inertness [5]. 1 Introduction In the case of method involving urea–calcium cyana- mide (Ca(OCN)2) as intermediary, calcium cyanamide Thiourea belongs to the class of organic compounds con- and calcium oxide are used as reactants to form the inter- taining sulphur [1]. It is a broad-spectrum compound mediate product, namely Ca(OCN)2. The Ca(OCN)2 reacts used in synthetic chemistry [2]. Thiourea belongs to the with H2S to form thiourea. This method is also flawed thioamide class of compounds. The structure is similar to with high production cost and low product yield. urea and has a general formula of (R1R2N)(R3R4N)C]S Additionally, the produced viscous Ca(OCN)2 as inter- [1]. Thiourea is also referred to as thiocarbamide and mediate during the reaction process cannot be removed sulphourea. The International Union of Pure and Applied from the subsequent reaction in the thiourea synthesis, due to the lack of supporting apparatus [5]. The by-pro- duct, calcium hydroxide (Ca(OH)2), produced along with H2S, has low solubility in water, which forms a thick * Corresponding author: Ayodele T. Odularu, Department of agglomerate in the reaction vessel, and as a result affects Chemistry, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa, e-mail: [email protected], reaction progress. [email protected] The method involving carbon(IV) sulphide (CS2) uses Peter A. Ajibade: Department of Chemistry, School of Chemistry and CS2 and ammonia (NH3) as reactants, as the same reac- Physics, University of KwaZulu-Natal, Pietermaritzburg Campus, tants apply to the synthesis of dithiocarbamate [5,7]. The Scottsville 3209, South Africa decomposition reaction between both reactants gives Opeoluwa O. Oyedeji, Johannes Z. Mbese: Department of Chemistry, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa ammonium thiocyanate, which is isomerized to form - [ ] Horst Puschmann: Chemistry Department, Durham University, thiourea, and H2Sasbyproduct 5 . This method also Dublin, United Kingdom gives a low yield because of ammonium thiocyanate Open Access. © 2021 Ayodele T. Odularu et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 International License. 512 Ayodele T. Odularu et al. isomerization as well as properties of both ammonium Merck (Germany). All chemicals and reagents were used thiocyanate and thiourea. Additionally, no efficient separa- as received without further purification. tion method was used in the synthesis due to the reaction vessel’s neck. The method involving ammonium thiocya- nate isomerization uses ammonium thiocyanate as the reac- tant to obtain thiourea. The reaction’sdemeritsarehigh 2.2 Synthesis of C13H10Cl2N3S production cost and low yield. The method involving lime nitrogen uses calcium oxide and water as reactants to pro- The methods used were in line with Azizi et al. and duce lime milk, which absorbs hydrogen sulphide to obtain Maddani and Prabhu methods, though with some modifi- calcium hydrosulphide with a better yield [5]. cations [10,11]. To a methanolic solution containing Synthesis of thiourea through cyanamide–hydrogen para-chloroaniline (1 mmol) and cold carbon(IV) sulphide sulphide uses cyanamide and a catalyst (as an improved (6.00 mL, 1 mmol),ammoniasolution(4.00 mL) was added atmospheric molecular sieve) in the urea atmospheric dropwise. Reaction temperature was less than 4°C with con- pressure dehydration stage, which is accomplished in an tinuous stirring for 3 h at room temperature (298 K),which ammonia atmosphere to form cyanamide. The thiourea is gave a product of white precipitates. The product was fil- then synthesized in a concentrated cyanamide solution tered, washed several times with diethyl ether solvent to and hydrogen sulphide gas. It gives a low reaction product remove unreacted reactants [7] and dried in vacuo over of thiourea [5,7]. Among the aforementioned methods, the silica gel. Yield was high to give 84% of the product. The CS2 method was applicable to this study because of the chemical reaction is shown in Scheme 1. availabilities and accessibilities of the reactants [7]. However, in an attempt to synthesize chloroaniline dithiocarbamate (C7H6ClN2S2NH4), a new crystalline com- pound of thiourea (C13H10Cl2N2S) was formed. The thiourea 2.3 Formation of C16H17Cl2N3OS crystals was formed from a mixture of chloroaniline, carbon(IV) sulphide and ammonia solution in methanol at a tempera- The C13H10Cl2N2S (50 mg, 0.11 mmol) was placed in a 100- ture of less than 4°C [5]. In order to confirm the structure, mL conical flask. Methanol (7mL) and DMF (5mL) were crystal growth by slow evaporation at room temperature added to C13H10Cl2N2S in the 100 mL conical flask. This was carried out on a quantity of the product (solid white was stirred on a magnetic stirrer until all the solute dis- precipitate) in N,N-dimethylformamide (DMF). The struc- solved in the solvent mixture to give a clear solution. The tural determination was carried out with single crystal flask was covered with punched aluminium foil and kept X-ray diffraction characterization technique. In this article, in a fume cupboard. The reaction vessel was allowed to we present the crystal structure of C16H17Cl2N3OS. Specific evaporate slowly at room temperature. Filtration method intermolecular interactions are halogen bonds, orthogonal was used to collect single, large and white polygon crys- multipolar interactions, halogen and aromatic rings, hydro- tals, which were dried over silica gel in a desiccator. The phobic interaction and hydrogen bonds (Scheiner 2016). percentage yield obtained was 84%. Existence of specific interaction, such as NH–O between two partner molecules, has made molecular recognition to rely on it for stability and strength [8,9]. 2.4 Study of C16H17Cl2N3OS A suitable crystal 0.17 mm3 × 0.12 mm3 × 0.10 mm3 was 2 Experimental selected and mounted on a tip of a glass fibre with a small quantity of silicon grease and later placed on a goniometer head [12]. Data were collected on a Xcalibur, AtlasS2, 2.1 Materials Gemini ultra diffractometer (Agilent Technologies XRD P-Chloroaniline and ammonia solution were purchased from BDH Laboratory Reagents (England),whilecarbon(IV) 2C6H4ClNH2(aq) + CS2(l) + 2NH3(l) C13H10Cl2N2S(s) + 3H2(g) +H2S(g) +N2(g) sulphide was supplied by Associated Chemical Enterprises (Pty) Ltd (South Africa). N,N-DMF was purchased from Scheme 1: Synthesis of N,N′-bis(4-chlorophenyl)thiourea. Synthesis and crystal structure of C16H17Cl2N3OS 513 Products, Oxfordshire, United Kingdom) with graphite-mono- Table 1: Single-crystal X-ray diffraction analysis of C16H17Cl2N3OS chromatized Mo-Kα radiation at 150 K. The crystal was kept and its structural refinement parameters at T = 119.94 (13) K during data collection. CrysAlisPro soft- ware package was used to refine, reduce and integrate Crystal data - the data for Lorentz polarization. Corrections for the absorp Empirical formula C16H17Cl2N3OS tion (multi-scan) were also performed using CrysAlisPro Formula weight (Mr) 370.30 1.171.39.12b [13]. Empirical absorption correction using Crystal colour White ( ) × × spherical harmonics was implemented in SCALE3 ABSPACK Crystal size mm 0.17 0.12 0.10 Crystal system Monoclinic scaling algorithm. Coordinates of bulk non-hydrogen atoms Space group P21/c were established by direct methods using CrysAlisPro [13]. Shape Polygon Locations of the outstanding non-hydrogen bonding were a/Å 9.2360 (4) positioned with a combination of least-square refinement b/Å 7.2232 (3) c ( ) in CrysAlisPro program. Other hydrogen atoms were posi- /Å 25.2555 11 α/° 90 tioned in geometrically calculated locations. The model β/° 91.376 (3) fi fi [ ] was re ned with version 2017/1 of olex2.re ne 14 using γ/° 90 Gauss–Newton minimization. Crystal data and refinement V/Å3 1684.40 (12) parameters are shown in Table 1.