- Small molecule recognition of mephedrone using an anthracene molecular clip
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An anthracene molecular probe has been synthesised and shown to target mephedrone, a stimulant drug from the cathinone class of new psychoactive substances (NPS). A protocol has been developed to detect mephedrone via the probe using NMR spectroscopy in a
- Kellett, Kathryn,Broome, J. Hugh,Zloh, Mire,Kirton, Stewart B.,Fergus, Suzanne,Gerhard, Ute,Stair, Jacqueline L.,Wallace, Karl J.
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Read Online
- Preparation method of thiourea alkylation derivative
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The invention discloses a preparation method of a thiourea alkylation derivative, which comprises the following steps: stirring an aldehyde, N-arylthiourea, trichlorosilane and Lewis base in an organic solvent at a range of -10 DEG C to room temperature for reaction, and carrying out after-treatment to obtain the thiourea alkylation derivative, wherein the molar ratio of the aldehyde to the N-arylthiourea is 1:2 to 2:1, the molar ratio of the aldehyde to the Lewis base is 1:(0.01-0.20), the molar ratio of the aldehyde to trichlorosilane is 1:(1-2), R1 is a C1-C5 saturated alkyl group, or an unsubstituted or substituted aromatic ring, and R2 is H, an electron withdrawing substituent or an electron donating substituent. According to the method, trichlorosilane is catalyzed by the micromolecular Lewis base, reductive alkylation of thiourea is realized, synthesis can be realized by a one-pot method, and the method is simple to operate, short in reaction time, low in substrate toxicity, lowin cost, easy to obtain, mild in reaction condition and high in safety.
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Paragraph 0037-0044
(2021/03/31)
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- Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules
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A new series of quinolone-thiazolidinone hybrid molecules 8a-o were prepared. Quinoline compounds were synthesized by Meth-Cohn synthesis and were condensed with 2,3-disubstituted thiazolidinone. These molecules were screened for their anticancer activities against MDA-MB-231 and MCF-7 cell line using MTT assay. Potent compounds were tested for their cytotoxicity on normal HEK 293 cell lines and most potent compound was tested for its cell cycle analysis. Molecular docking and molecular dynamic studies were performed on human N-acetyl transferase (hNAT-1) protein using Schrodinger molecular docking toolkit. Compound 8n emerged as potent with IC50 8.16?μM against MDA-MB-231 cell line followed by 8e with IC50 17.68?μM. Compound 8n arrested cell cycle at G2/M phase and was non-toxic to human normal kidney cell line. The potent compound 8n binds well with human NAT-1 protein with remarkable hydrogen bonding and π–π interactions. Molecular dynamic studies of 8n further confirm the target for these molecules. Target quinolinone-thiazolidinones were found to be new class of compounds targeting hNAT-1 and can serve as new lead compounds in drug discovery.
- Krishnappagowda, Lokanath Neratur,Kumar, Vasantha,Pai, Vinitha R.,Poojary, Boja,Rai, Vaishali M.,Shivalingegowda, Naveen,Udupi, Vishwanatha
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- Hydrogen-Bond Catalysis of Imine Exchange in Dynamic Covalent Systems
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The reversibility of imine bonds has been exploited to great effect in the field of dynamic covalent chemistry, with applications such as preparation of functional systems, dynamic materials, molecular machines, and covalent organic frameworks. However, acid catalysis is commonly needed for efficient equilibration of imine mixtures. Herein, it is demonstrated that hydrogen bond donors such as thioureas and squaramides can catalyze the equilibration of dynamic imine systems under unprecedentedly mild conditions. Catalysis occurs in a range of solvents and in the presence of many sensitive additives, showing moderate to good rate accelerations for both imine metathesis and transimination with amines, hydrazines, and hydroxylamines. Furthermore, the catalyst proved simple to immobilize, introducing both reusability and extended control of the equilibration process.
- Schaufelberger, Fredrik,Seigel, Karolina,Ramstr?m, Olof
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p. 15581 - 15588
(2020/10/02)
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- Hydroamination of isocyanates and isothiocyanates by alkaline earth metal initiators supported by a bulky iminopyrrolyl ligand
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A series of new heteroleptic alkaline earth (Ae) metal complexes of general formula [{(Ph2CHN-CH)2C4H2N}AeI(THF)3] {Ae = Ca (2), Sr (3), and Ba (4)} were synthesizedviasalt metathesis by reacting potassium salt of ligand1-K[{(Ph2CHN-CH)2C4H2N}K(THF)2] with anhydrous alkaline earth metal diiodides (AeI2). The homoleptic calcium and barium complexes [{(Ph2CHN-CH)2C4H2N}2Ae] [Ae = Ca (5), Ba (6)] were prepared by treating metal bis-hexamethyldisilazide [Ae{N(SiMe3)2}2(THF)2] with the protic ligand1-H[(Ph2CH-N-CH)2C4H2NH] in a 1:2 molar ratio. Calcium complex5was used as an active pre-catalyst for the addition of N-H bond of arylamines across the heterocumulenes such as phenylisocyanate (PhNCO) and phenylisothiocyanate (PhNCS) under neat conditions, and up to 99% yields of the corresponding urea and thiourea derivatives were obtained.
- Bano, Kulsum,Anga, Srinivas,Jain, Archana,Nayek, Hari Pada,Panda, Tarun K.
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supporting information
p. 9419 - 9428
(2020/06/17)
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- Development of phenylthiourea derivatives as allosteric inhibitors of pyoverdine maturation enzyme PvdP tyrosinase
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Infections caused by Pseudomonas aeruginosa become increasingly difficult to treat because these bacteria have acquired various mechanisms for antibiotic resistance, which creates the need for mechanistically novel antibiotics. Such antibiotics might be developed by targeting enzymes involved in the iron uptake mechanism because iron is essential for bacterial survival. For P. aeruginosa, pyoverdine has been described as an important virulence factor that plays a key role in iron uptake. Therefore, inhibition of enzymes involved in the pyoverdine synthesis, such as PvdP tyrosinase, can open a new window for the treatment of P. aeruginosa infections. Previously, we reported phenylthiourea as the first allosteric inhibitor of PvdP tyrosinase with high micromolar potency. In this report, we explored structure-activity relationships (SAR) for PvdP tyrosinase inhibition by phenylthiourea derivatives. This enables identification of a phenylthiourea derivative (3c) with a potency in the submicromolar range (IC50 = 0.57 + 0.05 μM). Binding could be rationalized by molecular docking simulation and 3c was proved to inhibit the bacterial pyoverdine production and bacterial growth in P. aeruginosa PA01 cultures.
- Dekker, Frank J.,Quax, Wim J.,Voet, Julian M.,Wibowo, Joko P.,Xiao, Zhangping
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supporting information
(2020/07/21)
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- Facile synthesis of phthalidyl fused spiro thiohydantoins through silica sulfuric acid induced oxidative rearrangement of ninhydrin adducts of thioureas
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A one-pot three-component sequential synthetic protocol produces structurally and biologically important phthalidyl fused spiro N,N′-disubstituted thiohydantoins from readily available aromatic isothiocyanates, primary amines and ninhydrin. In this three-step synthesis while the initial two steps are catalyst-free, in the final step silica sulfuric acid (SSA) induces an oxidative rearrangement in [3.3.0]-bicyclic 1,2-diol adducts of ninhydrin and thioureas under solvent-free condition to generate the final products spiro-fused thiohydantoins. The adequate acidity of SSA in cooperation with moderate oxidizing property promotes a facile oxidative rearrangement in 1,2-diol intermediates to produce the spiro-fused thiohydantoins with diverse functionalities. Easy recyclability of SSA, good to excellent yield of the products, wider substrate scope, shorter reaction time, solvent-free two steps out of three and high atom economy make this method attractive and practicable.
- Mandal, Subhro,Pramanik, Animesh
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- Synthesis of metronidazole based thiazolidinone analogs as promising antiamoebic agents
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Metronidazole and its derivatives are widely used for the treatment of amoebiasis. However, metronidazole is considered as the standard drug but it has many side effects. The present study describes the synthesis of a series of metronidazole based thiazolidinone analogs via Knoevenagel condensation of 4-[2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethoxy]benzaldehyde 1 with various thiazolidinone derivatives 2–14 to get the new scaffold (15–27) having better activity and lesser toxicity. Six compounds have shown better efficacy and lesser cytotoxicity than the standard drug metronidazole towards HM1: IMSS strain of Entamoeba histolytica. These compounds may combat the problem of drug resistance and might be effective in identifying potential alternatives for future drug discovery against EhOASS.
- Ansari, Mohammad Fawad,Inam, Afreen,Ahmad, Kamal,Fatima, Shehnaz,Agarwal, Subhash M.,Azam, Amir
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supporting information
(2020/10/12)
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- One-step construction of unsymmetrical thioureas and oxazolidinethiones from amines and carbon disulfide: Via a cascade reaction sequence
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A concise and versatile method for the construction of unsymmetrical thioureas and oxazolidinethiones from amines and carbon disulfide has been achieved in DMSO without addition of extra reagents. The present protocol is compatible with various secondary amines and primary amines, and suitable for intermolecular and intramolecular reactions. Diverse unsymmetrical thioureas and oxazolidinethiones were efficiently obtained in good to excellent yields via a cascade reaction sequence.
- Ding, Chaochao,Wang, Shaoli,Sheng, Yaoguang,Dai, Qian,Zhao, Yunjie,Liang, Guang,Song, Zengqiang
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p. 26768 - 26772
(2019/09/06)
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- Preparation method of asymmetric thiourea compound
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The invention discloses a preparation method of asymmetric thiourea compounds, and the method comprises the following steps: synthesizing the asymmetric thiourea compounds by taking amine compounds and carbon disulfide as substrates in a DMSO or DMF solvent. The method synthesizes the asymmetric thiourea compounds in one step through series reaction of three components. The reaction raw materialsare cheap and easily available, and the preparation method is simple. The reaction requires only the solvent, does not need other additives, has high yield and simple operation, and is suitable for the synthesis of different types of asymmetric thiourea compounds. The method can be used for synthesizing a series of asymmetric thiourea compounds, and the synthesized products can not only be used asintermediate compounds, but also be used for further constructing complex active compounds; at the same time, the compounds have great potential for drug activity.
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Paragraph 0142-0146
(2019/10/23)
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- Synthesis Of di- and tri-substituted thiourea derivatives in water using choline chloride–urea catalyst
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In this work, di- and tri-substituted thiourea derivatives have been synthesized via a one-pot, three-component reaction from carbon disulfide and aliphatic or aromatic amines using choline chloride-urea deep eutectic solvent as a catalyst in water. Both cyclic and acyclic thiourea derivatives with two or three substituents were synthesized successfully. The reactions were done at 25–100°C, using 5–20 mol% catalyst, in 3–5 h and the GC-Mass yields were between 60% and 95%. All products were characterized using FT-IR, 1H-NMR, 13C-NMR, GC-MS and melting point analyses. The results showed that both water and the DES have important effects on the yield and the rate of this reaction and both of them are necessary to obtain higher yields in less time. The extra experiment, which was designed to study the mechanism of the reaction, showed that an isothiocyanate intermediate was formed in the reaction. Finally, the results showed that by the increase of the amine's nucleophilicity, the reaction occurs faster and gives higher yield.
- Tavakol, Hossein,Mahmoudi, Amir,Ranjbari, Mohammad-Amin
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p. 113 - 123
(2018/10/24)
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- Micelle-Enabled One-Pot Guanidine Synthesis in Water Directly from Isothiocyanate using Hypervalent Iodine(III) Reagents under Mild Conditions
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In this work, we developed a one-pot synthesis of guanidine directly from isothiocyanate using DIB (diacetoxyiodobenzene) as a desulfurizing agent under micellar conditions in water. Our optimization study revealed that the use of 1 % TPGS-750-M as a surfactant with NaOH as an additive base at room temperature can convert a variety of isothiocyanates and amines into corresponding guanidines in excellent yields (69–95 %). This synthetic process in water can be applied to prepare guanidine at gram-scale quantity. Our aqueous micellar medium also demonstrated high reusability as the reaction can be performed for several cycles without losing its efficiency. The reaction is metal-free, utilizes water as solvent and practical (room temperature and open flask).
- Srisa, Jakkrit,Tankam, Theeranon,Sukwattanasinitt, Mongkol,Wacharasindhu, Sumrit
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p. 3335 - 3343
(2019/09/12)
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- Synthesis of thioureido peptidomimetics employing alkyl azides and dithiocarbamates
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An unprecedented approach for the assembly of thioureido peptidomimetics is developed employing alkyl azides and dithiocarbamates. Dithiocarbamates react with alkyl azides with the liberation of N2 and elemental sulfur thereby leading to thiourea in a traceless manner. Thioureido peptidomimetics are thus furnished in good yields with no epimerization. This process is mild, free from the use of a base, scalable and step economic. The practicability of this methodology has been highlighted by the synthesis of N,N′-orthogonally protected thioureido peptidomimetics.
- Roopesh Kumar,Panduranga, Veladi,Vishwanatha,Shekharappa,Sureshbabu, Vommina V.
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p. 2258 - 2263
(2018/04/05)
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- Investigations into the carbonic anhydrase inhibition of COS-releasing donor core motifs
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Carbonyl sulfide (COS) releasing scaffolds are gaining popularity as hydrogen sulfide (H2S) donors through exploitation of the carbonic anhydrase (CA)-mediated hydrolysis of COS to H2S. The majority of compounds in this emerging class of donors undergo triggerable decomposition (often referred to as self-immolation) to release COS, and a handful of different COS-releasing structures have been reported. One benefit of this donation strategy is that numerous caged COS-containing core motifs are possible and are poised for development into self-immolative COS/H2S donors. Because the intermediate release of COS en route to H2S donation requires CA, it is important that the COS donor motifs do not inhibit CA directly. In this work, we investigate the cytotoxicity and CA inhibition properties of different caged COS donor cores, as well as caged CO2 and CS2 motifs and non-self-immolative control compounds. None of the compounds investigated exhibited significant cytotoxicity or enhanced cell proliferation at concentrations up to 100 μM in A549 cells, but we identified four core structures that function as CA inhibitors, thus providing a roadmap for the future development of self-immolative COS/H2S donor motifs.
- Steiger, Andrea K.,Zhao, Yu,Choi, Won Jin,Crammond, Alder,Tillotson, McKinna R.,Pluth, Michael D.
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p. 124 - 130
(2017/12/04)
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- Nickle Catalysis Enables Access to Thiazolidines from Thioureas via Oxidative Double Isocyanide Insertion Reactions
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An efficient synthesis of thiazolidine-2,4,5-triimine derivatives was developed via Ni-catalyzed oxidative double isocyanide insertion to thioureas under air conditions, in which thioureas play three roles as a substrate, a ligand, and overcoming isocyanide polymerization. The reaction is featured by employing a low-cost and low loading Ni(acac)2 catalyst, without any additives, and high atom economy. This is the first example to directly apply a Ni(II) catalyst in oxidative double isocyanide insertion reactions.
- Yuan, Wen-Kui,Liu, Yan Fang,Lan, Zhenggang,Wen, Li-Rong,Li, Ming
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supporting information
p. 7158 - 7162
(2018/11/25)
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- An isocyanide based multi-component reaction under catalyst- and solvent-free conditions for the synthesis of unsymmetrical thioureas
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A new and efficient method for the synthesis of thiourea derivatives by a sequential one-pot, three-component reaction between aromatic isocyanides, amines, and 1,2-di-tert-butyldisulfane (DTBS) was developed and 27 different examples were synthesized in good to excellent yields. DTBS was identified as an effective sulfur surrogate without the use of both catalysts and solvents. This protocol does not employ any transition metal catalyst or special experimental setup.
- Singh, Karandeep,Sharma, Siddharth
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p. 197 - 201
(2016/12/28)
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- Antileishmanial thioureas: Synthesis, biological activity and in Silico evaluations of new promising derivatives
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Leishmaniasis is a neglected tropical disease caused by protozoan parasites belonging to the genus Leishmania. Currently, the drugs available for treatment of this disease present high toxicity, along with development of parasite resistance. In order to overcome these problems, efforts have been made to search for new and more effective leishmanicidal drugs. The aim of this study was to synthesize and investigate the leishmanicidal effect of N,N′-disubstituted thioureas against Leishmania amazonensis, with evaluation of their in silico pharmacokinetics and toxicity profiles. Our results showed that different thioureas could be obtained in high to moderate yields using simple reaction conditions. Nine thiourea derivatives (3e, 3i, 3k, 3l, 3p, 3q, 3v, 3x and 3z) were active against parasite promastigotes (IC50 21.48–189.10μM), with low cytotoxicity on mice peritoneal macrophages (CC50>200μM), except for thiourea 3e (CC50=49.22μM). After that, the most promising thioureas (3k, 3l, 3p, 3q and 3v) showed IC50 ranging from 70 to 150μM against L. amazonensis amastigotes in infected macrophages. Except for thiourea 3p, the leishmanicidal activity of the derivatives were independent of nitric oxide (NO) production. Thioureas 3q and 3v affected promastigotes cell cycle without disturbing the mitochondrial membrane potential. Furthermore, our derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. These data indicate that thiourea derivatives are good candidates as leading compounds for the development of new leishmanicidal drugs.
- Viana, Gil Mendes,Do Amaral, Lilian Henriques,Meireles, Paloma Wetler,Nunes, Raquel Pinto,Da Silva, Luiz Cláudio Rodrigues Pereira,De Sousa, Valeria Pereira,Sathler, Plínio Cunha,Cabral, Lucio Mendes,Soares, Deivid Costa,Saraiva, Elvira Maria,Santana, Marcos Vinicius,Castro, Helena Carla,De Sequeira Aguiar, Lúcia Cruz,Rodrigues, Carlos Rangel,Abreu, Paula Alvarez
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p. 911 - 919
(2018/10/31)
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- Ph3P/I2-mediated synthesis of N,N′,N″-substituted guanidines and 2-iminoimidazolin-4-ones from aryl isothiocyanates
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A convenient one-pot procedure for the synthesis of acyclic and cyclic guanidines mediated by the Ph3P/I2 system is described. Sequential condensation of aryl isothiocyanates with amines followed by dehydrosulfurization and guanylation could lead to both symmetric and unsymmetric N,N′,N″-substituted derivatives. Through a tandem guanylation-cyclization, a series of 2-iminoimidazolin-4-ones could also be prepared in good yields from the reaction of aryl isothiocyanates with amino acid methyl esters.
- Wangngae, Sirilak,Pattarawarapan, Mookda,Phakhodee, Wong
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p. 10331 - 10340
(2018/05/31)
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- Convenient synthesis of unsymmetrical N,N′-disubstituted thioureas in water
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A simple and convenient two-step method has been developed and used to synthesise 25 (4 of which are novel) unsymmetrical N,N′-disubstituted thioureas in water. Alkylamines or variously substituted arylamines reacted smoothly with phenyl chlorothionoformate at room temperature to form thiocarbamates, which were then reacted with another alkyl- or arylamine in water at reflux to afford the unsymmetrical N,N′-disubstituted thioureas in good to excellent yields. Mild conditions, simple work-up, high yields as well as using water as solvent are the major advantages of the method.
- Li, Zhengyi,Chen, Yuan,Yin, Yue,Wang, Zhiming,Sun, Xiaoqiang
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p. 670 - 673
(2016/11/18)
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- Cerium ammonium nitrate-catalyzed aerobic oxidative coupling of dithiocarbamates: Facile synthesis of thioureas and bis(aminothiocarbonyl)disulfides
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Diverse disubstituted and trisubstituted thioureas were synthesized by the condensation of dithiocarbamate TEA (or DABCO) salts and amines using cerium ammonium nitrate (CAN) as a catalyst in high yields at room temperature. It is a one-pot method and it is unnecessary to isolate isothiocyanates. This reaction probably took place through nucleophilic addition of amines to isothiocyanates, which were generated by oxidative coupling of dithiocarbamates and the following decomposition of bis(aminothiocarbonyl)disulfides. When secondary amines and CS2served as the reactants, bis(aminothiocarbonyl)disulfides were obtained via tandem nucleophilic addition/oxidative coupling reactions in moderate to excellent yields. In all the coupling reactions, the oxidant was air and CAN possibly acted as an SET catalyst.
- Li, Tian-Tian,Song, Xiang-Hai,Wang, Mei-Shuang,Ma, Ning
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p. 40054 - 40060
(2014/12/10)
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- Synthesis and characterisation of [(en)2Co]3+ complexes coordinated by substituted thiourea ligands
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Substituted thiourea ligands bind in a bidentate manner forming a four-membered ring through the sulfur atom and a deprotonated thiourea nitrogen atom when reacted with [(en)2Co(OSO2CF3)2]+ in tetramethylene sulfone. Reaction of unsymmetrical ligands results in the formation of coordination isomers, some of which can be separated by column chromatography using Sephadex SPC-25. Coordination isomers are easily distinguishable based on visible and 1H NMR spectroscopy . Twelve para-substituted and one meta-substituted ligands were studied: N,N′-dibenzylthiourea (1a); N-(R)phenyl-N′-benzylthiourea R≤H (2a), NO2 (2b), CH3 (2c); N-(R)phenyl-N′-(R′)phenylthiourea R, R′: H, H (3a), H, CH3 (3b), OCH3, NO2 (3c), CH3, NO2 (3d); N-methyl-N′-(R)phenylthiourea R≤H (4a), CH3 (4b), OCH3 (4c), NO2 (4d), 3-CH3 (4e). The solid state structure (X-ray) of one isomer of Co-4a as its perchlorate salt confirms the coordination mode suggested by 1H NMR spectroscopy and shows that the Co-N bond trans to the coordinated thiourea sulfur induces a structural trans effect of 0.019A.
- Roecker, Lee,Aiyegbo, Mohammed,Al-Haddad, Aladdin,Fletcher, Emily,Kc, Ravi,Hurst, Jason,Lane, Timothy,Larsen, Ryan,Noinaj, Nicholas,Teh, Say Lee,Wade, Samuel K.,Parkin, Sean
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p. 944 - 951
(2013/09/12)
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- Synthesis of thioureas in ionic liquid medium
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A highly efficient procedure for the synthesis of symmetrical thioureas by means of simple condensation of primary amines and carbon disulfide in 1-butyl-3-methylimidazolium chloride [BMIM][Cl] as a cheap and commercially available ionic liquid is presented. This procedure works for aromatic and aliphatic primary amines and give high to excellent yields of symmetrical thioureas without need for any catalyst or tedious work-up.
- Halimehjani, Azim Ziyaei,Farahbakhsh, Fataneh
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p. 284 - 288
(2013/08/26)
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- Water promoted one pot three-component synthesis of tetrazoles
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A one pot, three component synthesis of tetrazoles via thiourea has been accomplished in water. Water enhances the solubility of a higher number of components in the three component protocol thus promoting the reaction. The synthesis involves a chemoselective exocyclic reaction, regioselective electrocyclisation and a preferred conformational orientation of the tetrazole side chain which are rationalised based on the relative magnitude of Garbisch angle strain/allylic strains anticipated during the course of the reaction.
- Sathishkumar, Murugan,Shanmugavelan, Poovan,Nagarajan, Sangaraiah,Dinesh, Murugan,Ponnuswamy, Alagusundaram
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supporting information
p. 488 - 493
(2013/03/13)
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- Powerful approach to heterocyclic skeletal diversity by sequential three-component reaction of amines, isothiocyanates, and 1,2-diaza-1,3-dienes
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By highly efficient, one-pot, three-component reactions, combining one set of 1,2-diaza-1,3-dienes (DDs), primary amines, and isothiocyanates in a different sequential order of addition, heterocyclic skeletal diversity can be achieved. The key feature dis
- Attanasi, Orazio A.,Bartoccini, Silvia,Favi, Gianfranco,Giorgi, Gianluca,Perrulli, Francesca Romana,Santeusanio, Stefania
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experimental part
p. 1161 - 1167
(2012/03/12)
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- A versatile thiouronium-based solid-phase synthesis of 1,3,5-triazines
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A thiouronium-based solidphase synthesis of a 1,3,5-triazine scaffold has been developed. The key feature of the synthesis is the use of a readily accessible solid-supported thiouronium salt as a primary precursor for the stepwise assembly of the 1,3,5-tri-azine substrate. The sulfur linker employed in the synthesis is stable under both acidic and basic conditions and is versatile enough to provide access to monocyclic, bicyclic, and spirocyclic compounds with the 1,3,5-triazine scaffold. By using this synthetic strategy, a representative set of 79 compounds containing the 1,3,5-triazine scaffold were prepared.
- Kong, Kah Hoe,Tan, Chong Kiat,Lin, Xijie,Lam, Yulin
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experimental part
p. 1476 - 1486
(2012/03/26)
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- A model for a solvent-free synthetic organic research laboratory: Click-mechanosynthesis and structural characterization of thioureas without bulk solvents
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The mechanochemical click coupling of isothiocyanates and amines has been used as a model reaction to demonstrate that the concept of a solvent-free research laboratory, which eliminates the use of bulk solvents for either chemical synthesis or structural characterization, is applicable to the synthesis of small organic molecules. Whereas the click coupling is achieved in high yields by simple manual grinding of reactants, the use of an electrical, digitally controllable laboratory mill provides a rapid, quantitative and general route to symmetrical and non-symmetrical aromatic or aromatic-aliphatic thioureas. The enhanced efficiency of electrical ball milling techniques, neat grinding or liquid-assisted grinding, over manual mortar-and-pestle synthesis is demonstrated in the synthesis of 49 different thiourea derivatives. Comparison of powder X-ray diffraction data of mechanochemical products with structural information found in the Cambridge Structural Database (CSD), or obtained herein through single crystal X-ray diffraction, indicates that the mechanochemically obtained thiourea derivatives are pure in a chemical sense, but can also demonstrate purity in a supramolecular sense, i.e. in all structurally explored cases the product consisted of a single polymorph. As an extension of our previous work on solvent-free synthesis of coordination polymers, it is now demonstrated that such polymorphic and chemical purity of selected thiourea derivatives, the latter being evidenced through quantitative reaction yields, can enable the direct solvent-free structural characterization of mechanochemical products through powder X-ray diffraction aided by solid-state NMR spectroscopy.
- Strukil, Vjekoslav,Igrc, Marina D.,Fabian, Laszlo,Eckert-Maksic, Mirjana,Childs, Scott L.,Reid, David G.,Duer, Melinda J.,Halasz, Ivan,Mottillo, Cristina,Friscic, Tomislav
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supporting information
p. 2462 - 2473
(2013/02/21)
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- A simple and green procedure for the synthesis of N-benzylthioureas
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A simple and efficient reaction protocol for the synthesis of N-benzylthioureas is described from benzylisothiocyanate (BITC: 94% pure/GC-MS), isolated from crushed papaya seeds.
- De Sequeira Aguiar, Lucia C.,Viana, Gil M.,Dos Santos Romualdo, Marcus V.,Costa, Marcio V.,Bonato, Bruno S.
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experimental part
p. 540 - 544
(2012/06/01)
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- Diphenylthiourea, a common rubber chemical, is bioactivated to potent skin sensitizers
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Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical-and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU works as a contact allergen has not been described; thus, the aim of the present study was to investigate if DPTU is a prohapten that can be activated by skin metabolism. The metabolic activation and covalent binding of 14C-labeled DPTU to proteins were tested using a skinlike cytochrome P450 (P450) cocktail containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6, 2E1, and 3A5) and human liver microsomes. The incubations were carried out in the presence or absence of the metabolite trapping agents glutathione, methoxylamine, and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography, LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU. The sensitizing capacity of the substrate (DPTU) and three metabolites was tested in the murine local lymph node assay. Two out of three metabolites tested were strong skin sensitizers, whereas DPTU itself, as previously known, was negative using this mouse model. In conclusion, DPTU forms highly reactive metabolites upon bioactivation by enzymes present in the skin. These metabolites are able to induce skin sensitization and are probable causes for DPTU allergy. To increase the possibilities of diagnosing contact allergy to DPTU-containing items, we suggest that suitable metabolites of DPTU should be used for screening testing.
- Samuelsson, Kristin,Bergstroem, Moa Andresen,Jonsson, Charlotte A,Westman, Gunnar,Karlberg, Ann-Therese
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experimental part
p. 35 - 44
(2012/01/13)
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- Structural requirement of phenylthiourea analogs for their inhibitory activity of melanogenesis and tyrosinase
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Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3- alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N′-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor.
- Thanigaimalai, Pillaiyar,Lee, Ki-Cheul,Sharma, Vinay K.,Joo, Cheonik,Cho, Won-Jea,Roh, Eunmiri,Kim, Youngsoo,Jung, Sang-Hun
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experimental part
p. 6824 - 6828
(2011/12/22)
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- Use of molecular oxygen as a reoxidant in the synthesis of 2-substituted benzothiazoles via palladium-catalyzed C-H functionalization/intramolecular C-S bond formation
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Molecular oxygen (O2) was successfully employed as a reoxidant in cyclizations of thiobenzanilides 1a-s through a palladium-catalyzed C-H functionalization/intramolecular C-S bond formation process, leading to an efficient, green method for the synthesis of 2-arylbenzothiazoles 2a-s. Addition of cesium fluoride (CsF) greatly enhanced the reactions, which produced variously substituted 2-arylbenzothiazoles with good functional group tolerance. Thioureas 4a-j were also found to be suitable substrates for the cyclization process using a palladium/O2 catalyst system, thus generating 2-aminobenzothiazoles 5a-j. One-pot syntheses of 2-aminobenzothiazoles 5a-j from aryl isothiocyanates 6 and amines 7 were also successful.
- Inamoto, Kiyofumi,Hasegawa, Chisa,Kawasaki, Junpei,Hiroya, Kou,Doi, Takayuki
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experimental part
p. 2643 - 2655
(2010/12/25)
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- A convenient one-pot three component approach to synthesis of highly substituted iminothiazolines
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An efficient one-pot three component method was developed for the synthesis of highly substituted 2-iminothizolines by the reaction of isothiocyanates, primary amines and α-bromoketones in ambient temperature. The reaction produced the desired products in a completely regioselective manner in excellent yields (78-94%). The Japan Institute of Heterocyclic Chemistry.
- Samimi, Heshmat Allah,Mamaghani, Manouchehr,Tabatabaeian, Khalil
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experimental part
p. 2825 - 2833
(2011/04/17)
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- Palladium-catalyzed synthesis of 2-substituted benzothiazoles via a C-H functionalization/intramolecular C-S bond formation process
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(Chemical Equation Presented) Catalytic synthesis of 2-substituted benzothiazoles from thiobenzanilides was achieved in the presence of a palladium catalyst through C-H functionalization/C-S bond formation. This method features the use of a novel catalytic system consisting of 10 mol % of Pd(II), 50 mol % of Cu(I), and 2 equiv of Bu4NBr that produced variously substituted benzothiazoles in high yields with good functional group tolerance.
- Inamoto, Kiyofumi,Hasegawa, Chisa,Hiroya, Kou,Doi, Takayuki
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supporting information; experimental part
p. 5147 - 5150
(2009/05/30)
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- Ultrasound-promoted scavenging: A rapid parallel purification for solution phase combinatorial synthesis
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Ultrasound irradiation enhances the mass transfer and reaction rate in scavenging, avoiding the trouble of time-consuming purification procedure in solution-phase parallel synthesis. An application of this technique is demonstrated in the scavenging of excess isothiocyanates from reaction mixtures.
- Peng, Yanqing,Song, Gonghua,Xu, Xiaoyong
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p. 261 - 263
(2007/10/03)
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- 1-(Methyldithiocarbonyl)imidazole: A useful thiocarbonyl transfer reagent for synthesis of substituted thioureas
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1-(Methyldithiocarbonyl)imidazole 1 and its N-methyl quaternary salt 2 have been shown to be efficient methyldithiocarbonyl and thiocarbonyl transfer reagents for the synthesis of dithiocarbamates, symmetrical and unsymmetrical mono-, di- and tri-substituted thioureas in high yields under mild and simple non-hazardous reaction conditions. (C) 2000 Elsevier Science Ltd.
- Mohanta, Pramod K.,Dhar, Sanchita,Samal,Ila,Junjappa
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p. 629 - 637
(2007/10/03)
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- A convenient route to cyanoguanidines
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A facile and versatile method for the preparation of cyanoguanidines 7 from amines 3 and isothiocyanates 4 via a methylation, cyanamide-treatment sequence is described.
- Novak, Lajos,Hanania, Michel,Kovacs, Peter,Kovacs, Csilla Erika,Kolonits, Pal,Szantay, Csaba
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p. 1757 - 1766
(2007/10/03)
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- A new scavenger resin for amines
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Isatoic anhydride (1) can be attached to Merrifield resin by alkylation on its nitrogen. A maximum loading of 3.2 mmol of anhydride/g of 5 was achieved. This resin, due to the highly reactive anhydride moiety, completely removes primary and secondary aliphatic amines from reactions where they are used in excess.
- Coppola, Gary M.
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p. 8233 - 8236
(2007/10/03)
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- A facile conversion of symmetrical to unsymmetrical thioureas
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A convenient route for quantitative conversion of symmetrical thioureas into unsymmetrical thioureas is described. The method circumvents the use of toxic isothiocyanates and a case study is reported using 1,3-diphenylthiourea.
- Ramadas,Srinivasan,Janarthanan
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p. 6447 - 6450
(2007/10/02)
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- Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents
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A series of substituted 2-aminobenzothiazoles and derivatives useful for treating cerebrovascular disorders are disclosed. Also disclosed is a new method for treating such disorders.
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- Desulfurization of N,N'-Diarylthioureas by Lead Tetraacetate Oxidation
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Lead tetraacetae oxidation of N,N'-diarylthioureas in refluxing dichloromethane and pyridine gave the corresponding N,N'-diarylureas.Sulfur was isolated during each oxidation reaction.
- Debroy, Abhijit,Nandy Mazumdar, Sujit,Barua, Parag D.,Mahajan, Mahinder P.
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p. 315 - 316
(2007/10/02)
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- Studies on the Development of the Tritylsulfenyl Group as a Nitrogen Protecting Group and Application in a Synthesis of δ-Coniceine
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The (triphenylmethyl)sulfenyl (tritylsulfenyl, TRS) group was found to posses properties which should make it useful as a nitrogen protecting group.The almost instantaneous reaction of TrSCl (6) with amines produced the corresponding triphenylmethanesulfenamides.The TRS group was found to render the nitrogen atom nonbasic and relatively nonnucleophilic, was stable to aqueous acid, aqueous base, and various reducing agents, and was moderately stable to Moffat oxidation conditions.The TRS group could be cleaved under mild conditions, generating the amine with either CuCl2/EtOH-THF, HI/THF-H2O, or trimethylsilyl iodide (Me3SiI)/CH2Cl2.A synthesis of δ-coniceine (16) illustrates carbon-carbon bond formation with tritylsulfenimine methodology and the utility of the tritylsulfenyl group as a nitrogen protecting group.
- Branchaud, Bruce P.
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p. 3538 - 3544
(2007/10/02)
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- Synthesis of 3(S)-acylamino-1-[(phenyl)-(1H-tetrazol-5-yL)amino]-2-azetidinones
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1-Phenyl-1-(1-benzyl-1H-tetrazol-5-yl)hydrazine has been synthesized from N1-benzyloxycarbonyl-N2-phenylhydrazide and benzyl isothiocyanate. Coupling with N-(benzyloxycarbonyl)-L-serine 3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl ester
- Atherton,Lambert
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p. 2599 - 2608
(2007/10/02)
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- Heterocyclic Compounds: Sulphur as a Potential Oxidant: Preparation of 5-Alkyl/arylimino-2,4-dialkyl/aryl-3-thio/oxo-1,2,4-thiadiazolidines
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Some interesting observations involving reaction of excess of benzylamine and isoperthiocyanic acid (Ia), the so-called isothiocyanate sulphides (Ib-If) and isothiocyanate oxides (II) have been reported.In these reactions 5-alkyl/arylimino-2,4-dialkyl/aryl-3-thio-1,2,4-thiadiazolidines (III) and 5-arylimino-2,4-dialkyl/aryl-3-oxo-1,2,4-thiadiazolidines (VI) have been isolated.In all these reactions, elemental sulphur initially formed acts as a potential oxidant in the oxidative cyclisation of intermediates, viz., 2,4-dithiobiurets (IV) and 2-thiobiurets (VII).
- Jadhav, R. T.,Paranjpe, M. G.
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- Oxidation of Mixtures of Thioureas: Part VIII - Formation of 3-Amino-4-aryl-5-benzylimino-4,5-dihydro-1,2,4-thiadiazoles
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Oxidation of binary mixtures of 1-aryl-3-benzylthioureas and thiourea in acidic ethanol affords 3-amino-4-aryl-5-benzylimino-4,5-dihydro-1,2,4-thiadiazoles (3). 1-Aryl-3-benzylthioureas used are: 1-phenyl-3-benzyl-, 1-p-tolyl-3-benzyl-, 1-benzyl-3-p-chlorophenyl-, 1-p-anisyl-3-benzyl- and 1-benzyl-3-p-nitrophenyl-thioureas.
- Indukumari, P. V.,Joshua, C. P.
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p. 672 - 675
(2007/10/02)
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