Utilisation of Home Laundry Effluent (HLE) as a catalyst for expeditious one-pot aqueous phase synthesis of highly functionalised 4-thiazolidinones
© Singh et al.; licensee Springer. 2013
Received: 30 April 2013
Accepted: 9 September 2013
Published: 16 September 2013
The impact of global warming and associated climate changes have built up pressure to focus on the option of green chemistry over traditional one for long term sustainability of the environment. Considering the fact, for the first time, efficient HLE catalysed expeditious one-pot synthesis of highly functionalised 4-thiazolidinones has been developed.
These hybrid molecules were synthesized in good to excellent yields. The ease of work-up of the reactions less time required and mild conditions are notable features of this protocol. It was inferred that halogen containing derivatives were well suited to this condensation-cyclization reaction with varying rates to afford 4-thiazolidine derivatives. In general, the substitution on the aldehyde part was shown as a main determinant for reaction time and the product yield.
For the first time home laundry effluent (HLE) owing to the surfactant like property has been successfully utilised as catalyst for the synthesis of a series of novel 4-thiazolidinone derivatives through one pot, three component condensation-cyclization reaction. The uniqueness of the present protocol lies in the operational simplicity, ability to reduce the demand for organic solvents, reduce the energy and carbon footprint, and meet a wide range of economic needs.
The design, synthesis and development of novel heterocyclic scaffolds of pharmacological importance have fascinated both organic as well as medicinal chemists. Among from the established heterocyclic pharmacophores, 4-thiazolidinone derivatives are deemed to be of considerable importance due to their wide array of biological properties. These derivative posses various pharmacological actions, for instance, antibacterial (Zevzikoviene et al. 2012), anti-HIV (Rawal et al. 2005), antifungal (El Bialy et al. 2011), anticonvulsants (Siddiqui et al. 2010), follicle stimulating hormone (FSH) receptor agonist activity (Wrobel et al. 2006), anti-inflammatory activity (Eleftheriou et al. 2012), anticancer (Havrylyuk et al. 2011), etc. Besides, they are also utilised as chemical antecedents for many compounds, for example polymethine cyanine dyes (El-Aal 2003). More recently, these derivatives were used in the synthesis of pyrazolothiazole derivatives (Turgut et al. 2007) and monofluoro-β lactams (Fuchigami et al. 1992). Consequently, number of protocols have been developed and reported for the synthesis of 4-thiazolidinone including one-step, two-step or via one-pot multicomponent reactions (Kumar et al. 2013). The one-pot multicomponent reactions to synthesize these nuclei offer several advantages and are preferred over traditional synthesis because of their ability to synthesize small drug-like molecules in efficient manner by virtue of minimal workup, high atom economy and being highly modular with several degrees of structural diversity (Orru & de Greef 2003). The reaction involved in synthesis of thiazolidinone proceeds via formation of schiff base intermediate at the initial followed by an attack of a sulphur nucleophile, a mercapto-carboxylic acid, resulting in intermolecular cyclization and eviction of water to yield the desired product (Bolognese et al. 2004). However, removal of the water in the last step is presumably believed as a rate determining step and considered to be critical for obtaining the 4-thiazolidinediones in high yields. As a result, several strategies have been developed for removal of the in situ generated of water for efficient yield of the target molecules. Most commonly followed protocols for water removal involve azeotropic distillation using a Dean Stark trap with either benzene or toluene as solvent medium, molecular sieves and dehydrating agent like DCC (N,N'-Dicyclohexylcarbodiimide) (Tierney 1989; Surrey 1947).
However, the conventional protocols for the synthesis of 4-thiazolidinedione have been associated with numerous shortcomings including the use of perilous solvents, expensive catalysts, long work-up procedures, harsh reaction conditions, in-efficient atom economy, and generation of the by-products. More recently, commercially available surfactant p-dodecylbenzenesulfonic acid (DBSA) has been reported for synthesis of 2,3-di substituted 4-thiazolidinones derivatives (Prasad et al. 2012). Thus, there has been an urgent need to develop a benign, eco-friendly and inexpensive protocol for the synthesis of 4-thiazolidinone derivatives.
The environmental imbalances have compelled us to adopt the concept of green chemistry in our modern day researches. The green chemistry is a philosophy of chemical research that encourages the design of products and processes that minimize the use and generation of hazardous substances. It aims to protect the environment by inventing new chemical processes that do not pollute, rather than by cleaning up (2012). Water is the most abundant and environmental friendly solvent available in nature and the organic reaction performed in it gained significant attention owing to its various advantages, viz. low cost, safety and environment friendly nature (Dunn 2010). Yet its application in organic synthesis is limited as most organic substrates have poor solubility in water (Shapiro & Vigalok 2008). A good number of strategies have been devised to solve this problem by creating the organic micro-environment in aqueous phase by using surfactants, organic co-solvents or hydrophobic auxiliaries (Lindstrom 2002). On another hand reaction catalysed by surfactants are considered environment benign and are preferred over others (Zhao et al. 2011). Albeit, owing to eco-friendly approach showed by surfactants, its high cost is a major limiting factor for the reactions to be carried out. Therefore, development of novel solvent system which has surfactant like properties at minimal cost is more viable option. Prompted from these ideas, we tried to utilise the surfactant like properties of home laundry effluent (HLE) to catalyse the reactions (Ariel, a laundry detergent (washing powder)). The HLE is categorised as a type of greywater generated from household on washing clothes and has been disposed off in the open environment causing environment pollution. It is entirely different from more heavily contaminated “black water” from toilets. Greywater can be of far higher quality than black water because of its low level of contamination and higher potential for reuse (Allen et al. 2010). Further, use of HLE as reaction media has ability to reduce the demand for organic solvents, reduce the energy and carbon footprint, and meet a wide range of economic needs. This surfactant rich effluent possibly catalyses the reactions through the same way as a surfactant did and provides a greener way of synthesis with economic viability in comparison to the expensive surfactants.
The hybridisation of different pharmacophores in single chemical entity is gaining attraction from the medicinal chemists owing to its synergistic or addition effects, enlarged spectrum of action, less prone to spontaneous mutation and resistance development and possibility of dual drug targeting at more than one site (Morphy & Rankovic 2005). 1,3,5-Triazine, an important heterocyclic scaffold has been found to possess variety of pharmacological activities, such as antibacterial (Gahtori & Ghosh 2012), anti-HIV (Lozano et al. 2011), antifungal (Singh et al. 2012a), antimalarial (Bhat et al. 2013), and anticancer (Bekircan et al. 2005). The hybridisation of this bioactive heterocyclic moiety with another pharmacophores is a matter of investigation of our research programme and till now we have reported numerous hybrid conjugates of 1,3,5-triazine with thiazole (Singh et al. 2011), piperazine (Ghosh et al. 2012), 1,3-thiazine (Singh et al. 2012b) and 1,3,4-thiadiazole (Dubey et al. 2012) as antimicrobial agents.
Results and discussion
Catalytic activity evaluation for reaction a
Type of surfactant
Effect of temperature on the reaction a
Synthesis of highly functionalised 4-thiazolidinones catalysed by HLE
It was inferred that halogen containing 1,3,5-traizine and aldehyde derivatives were well suited to this condensation-cyclization reaction with varying reaction time & yield to afford 4-thiazolidine-1,3,5-traizine hybrid conjugates. In general, the substitution on the aldehyde part was found as the main determinant for the reaction time and product yield. It was evident from Table 3 that the reaction proceeded well with aldehyde having the substitution far apart from the reaction centre, i.e., para positions (4a, 4c, 4e, 4g, 4i and 4l) and was not favoured with substitution near to reaction centre, i.e., ortho positions (4b, 4d, 4f, 4h, 4j, 4k, 4m and 4n). The generation of steric hindrance due to the presence of substituent in the close proximity of reaction centre of aldehyde might be the probable cause of this observation.
General procedure for synthesis of title hybrid analogues 4 (a-n)
To a solution of HLE (25 mol%), amine (1, 0.01 mol), aldehyde (2, 0.01 mol) and thioglycolic acid (3, 0.01 mol) were added successively at 45°C and the reaction mixture was stirred for time duration as reported in Table 3. After completion of the reaction, a saturated NaHCO3 solution was added followed by the addition of saturated brine solution. The product was extracted with ethyl acetate (3 times). The organic layers were combined, washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure to dryness. Purification of crude product was carried out by column chromatography using silica gel (60–120 mesh size) via 10–30% ethyl acetate in heptane as an eluent to furnish the desired product.
As a concluding remark, for the first time home laundry effluent (HLE) owing to the surfactant like property has been successfully utilised as catalyst for the synthesis of a series of novel 4-thiazolidinone derivatives through one pot, three component condensation-cyclization reaction. The uniqueness of the present protocol lies in the operational simplicity, ability to reduce the demand for organic solvents, reduce the energy and carbon footprint, and meeting a wide range of economic needs. However, the investigations of the characterisation of HLE as catalyst and medicinal properties of these novel compounds are still underway and will be reported in due course of time.
Authors are thankful to SAIF, Punjab University, India and SHIATS, India for providing spectroscopic data of compounds synthesized herein necessary infrastructural facilities, respectively.
- 2012.http://www.epa.gov/greenchemistry/ , Accessed on Dec 28
- Ariel, a laundry detergent (washing powder) used as surfactant source, product made in India by Procter and Gamble home products Ltd. Mumbai 400099, the common Laundry detergent contains alkylbenzenesulfonates. For this reaction, washed over effulent from the home washing machine of daily use clothes like shirts, pants, scarf’s and etc. in mild dirty condition was selected, this liquid was further filtered to remove any solid particles before using as reaction media.Google Scholar
- Allen L, Christian-Smith J, Palaniappan M: Overview of greywater reuse: the potential of greywater systems to aid sustainable water management. California USA: Pacific Institute; 2010.Google Scholar
- Bekircan O, Küxük M, Kahveci B, Kolayli S: Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents. Archiv der Pharmazie 2005, 338: 365-372. doi:10.1002/ardp.200400964 10.1002/ardp.200400964View ArticleGoogle Scholar
- Bhat HR, Singh UP, Gahtori P, Ghosh SK, Gogoi K, Prakash A, Singh RK: Antimalarial activity and docking studies of novel bi-functional hybrids derived from 4-aminoquinoline and 1,3,5-triazine against wild and mutant malaria parasites as pf -DHFR inhibitor. RSC Adv. 2013, 3: 2942-2952. doi:10.1039/C2RA21915H 10.1039/c2ra21915hView ArticleGoogle Scholar
- Bolognese A, Correale G, Manfra M, Lavecchia A, Novellino E, Barone V: Thiazolidin-4-one formation. Mechanistic and synthetic aspects of the reaction of imines and mercaptoacetic acid under microwave and conventional heating. Org Biomol Chem 2004, 2: 2809-2813. doi:10.1039/B405400H 10.1039/b405400hView ArticleGoogle Scholar
- Dubey V, Bhat HR, Singh UP: Design, facile synthesis, and antibacterial activity of hybrid 1,3,4-thiadiazole-1,3,5-triazine derivatives tethered via -S- bridge. Chem Biol Drug Des 2012, 80: 598-604. doi:10.1111/j.1747-0285.2012.01433.x 10.1111/j.1747-0285.2012.01433.xView ArticleGoogle Scholar
- Dunn P: Water as a Green Solvent for Pharmaceutical Applications. Handbook of Green Chemistry 2010, 5: 363. doi:10.1002/9783527628698.hgc058Google Scholar
- El Bialy SA, Nagy MM, Abdel-Rahman HM: Efficient regioselective three-component domino synthesis of 3-(1,2,4-Triazol-5-yl)-1,3-thiazolidin-4-ones as potent antifungal and antituberculosis agents. Archiv der Pharmazie 2011, 344: 821-829. doi:10.1002/ardp.201100001 10.1002/ardp.201100001View ArticleGoogle Scholar
- El-Aal RMA: Spiro-Azoles Thiazolidinone in the Synthesis of Polymethine Cyanine Dyes. Phosphorus, Sulfur Silicon Relat Elem 2003, 178: 681-692. doi:10.1080/10426500307791 10.1080/10426500307791View ArticleGoogle Scholar
- Eleftheriou P, Geronikaki A, Hadjipavlou-Litina D, Vicini P, Filz O, Filimonov D, Poroikov V, Chaudhaery SS, Roy KK, Saxena AK: Fragment-based design, docking, synthesis, biological evaluation and structure-activity relationships of 2-benzo/benzisothiazolimino-5-aryliden-4-thiazolidinones as cycloxygenase/lipoxygenase inhibitors. Eur J Med Chem 2012, 47: 111-124. doi:10.1016/j.ejmech.2011.10.029View ArticleGoogle Scholar
- Fuchigami T, Narizuka S, Konno A: Electrolytic partial fluorination of organic compounds. 4. Regioselective anodic monofluorination of 4-thiazolidinones and its application to the synthesis of monofluoro.beta.-lactams. J Org Chem 1992, 57: 3755-3757. doi:10.1021/jo00040a003 10.1021/jo00040a003View ArticleGoogle Scholar
- Gahtori P, Ghosh SK: Design, synthesis and SAR exploration of hybrid 4-chlorophenylthiazolyl-s-triazine as potential antimicrobial agents. J Enzyme Inhib Med Chem 2012, 27: 281-293. doi:10.3109/14756366.2011.587418 10.3109/14756366.2011.587418View ArticleGoogle Scholar
- Ghosh SK, Saha A, Hazarika B, Singh UP, Bhat HR, Gahtori P: Design, facile synthesis, antibacterial activity and structure-activity relationship of novel diand tri-substituted 1,3,5-triazines. Lett Drug Des Dis 2012, 9: 329-335. doi.org/10.2174/157018012799129846 10.2174/157018012799129846View ArticleGoogle Scholar
- Havrylyuk D, Kovach N, Zimenkovsky B, Vasylenko O, Lesyk R: Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates. Archiv der Pharmazie 2011, 344: 514-522. doi:10.1002/ardp.201100055 10.1002/ardp.201100055View ArticleGoogle Scholar
- Jain AK, Vaidya A, Ravichandran V, Kashaw SK, Agrawal RK: Recent developments and biological activities of thiazolidinone derivatives: A review. Bioorg Med Chem 2012, 20(11):3378-3395. doi:10.1016/j.bmc.2012.03.069 10.1016/j.bmc.2012.03.069View ArticleGoogle Scholar
- Kumar S, Bhat HR, Kumawat MK, Singh UP: Design and one-pot synthesis of hybrid thiazolidin-4-one-1,3,5-triazines as potent antibacterial agents against human disease-causing pathogens. New J Chem 2013, 37: 581-584. doi:10.1039/C2NJ41028A (a) Verma A, Saraf SK (2008) 4-thiazolidinone--a biologically active scaffold. Eur J Med Chem 43: 897-905. doi.org/10.1016/j.ejmech.2007.07.017 10.1039/c2nj41028aView ArticleGoogle Scholar
- Lindstrom UM: Stereoselective organic reactions in water. Chem Rev 2002, 102: 2751-2772. doi:10.1021/cr010122p 10.1021/cr010122pView ArticleGoogle Scholar
- Lozano V, Aguado L, Hoorelbeke B, Renders M, Camarasa MJ, Schols D, Balzarini J, San-Félix A, Pérez-Pérez MJ: Targeting HIV entry through interaction with envelope glycoprotein 120 (gp120): synthesis and antiviral evaluation of 1,3,5-triazines with aromatic amino acids. J Med Chem 2011, 54: 5335-5348. doi:10.1021/jm200560r 10.1021/jm200560rView ArticleGoogle Scholar
- Morphy R, Rankovic Z: Designed multiple ligands.An emerging drug discovery paradigm. J Med Chem 2005, 48: 6523-6543. doi:10.1021/jm058225d 10.1021/jm058225dView ArticleGoogle Scholar
- Orru RVA, de Greef M: Recent Advances in Solution-Phase Multicomponent Methodology for the Synthesis of Heterocyclic Compounds. Synthesis 2003, 10: 1471-1499. doi:10.1055/s-2003-40507View ArticleGoogle Scholar
- Prasad D, Preetam A, Nath M: DBSA catalyzed, one-pot three-component “on water” green protocol for the synthesis of 2,3-disubstituted 4-thiazolidinones. RSC Adv 2012, 2: 3133-3140. 10.1039/c2ra20171bView ArticleGoogle Scholar
- Rawal RK, Prabhakar YS, Katti SB, De Clercq E: 2-(Aryl)-3-furan-2-ylmethyl-thiazolidin-4-ones as selective HIV-RT inhibitors. Bioorg Med Chem 2005, 13: 6771-6776. doi.org/10.1016/j.bmc.2005.07.063 10.1016/j.bmc.2005.07.063View ArticleGoogle Scholar
- Romsted LS: “Micellization Solubilsation and Microemulsions”, vol II. New York: K.L.Mittal Plenum Press; 1977:509.View ArticleGoogle Scholar
- Shapiro N, Vigalok A: Highly Efficient Organic Reactions “on Water”, “in Water”, and Both. Angewandte Chemie 2008, 120: 2891-2894. doi:10.1002/ange.200705347 10.1002/ange.200705347View ArticleGoogle Scholar
- Siddiqui N, Arshad MF, Khan SA, Ahsan W: Sulfonamide derivatives of thiazolidin-4-ones with anticonvulsant activity against two seizure models: synthesis and pharmacological evaluation. J Enzyme Inhib Med Chem 2010, 25: 485-491. doi:10.3109/14756360903282833 10.3109/14756360903282833View ArticleGoogle Scholar
- Singh UP, Singh RK, Bhat HR, Subhaschandra YP, Kumar V, Kumawat MK, Gahtori P: Synthesis and antibacterial evaluation of series of novel tri-substituted- s -triazine derivatives. Med Chem Res 2011, 20: 1603-1610. doi:10.1007/s00044-010-9446-7 10.1007/s00044-010-9446-7View ArticleGoogle Scholar
- Singh UP, Bhat HR, Gahtori P: Antifungal activity, SAR and physicochemical correlation of some thiazole-1,3,5-triazine derivatives. J Mycol Méd 2012a, 22: 134-141. DOI: 10.1016/j.mycmed.2011.12.073View ArticleGoogle Scholar
- Singh UP, Pathak M, Dubey V, Bhat HR, Gahtori P, Singh RK: Design, synthesis, antibacterial activity, and molecular docking studies of novel hybrid 1,3-thiazine-1,3,5-triazine derivatives as potential bacterial translation inhibitor. Chem Biol Drug Des 2012b, 80: 572-583. doi:10.1111/j.1747-0285.2012.01430.x 10.1111/j.1747-0285.2012.01430.xView ArticleGoogle Scholar
- Surrey AR: The preparation of 4-thiazolidones by the reaction of thioglycolic acid with Schiff bases. J Am Chem Soc 1947, 49: 3105-3107. doi:10.1021/ja01177a048Google Scholar
- Tierney J: The formation of 2,3-disubstituted thiazolidin-4-ones from s-α'-aminomercaptoacetic acid derivatives. J Heterocyclic Chem 1989, 26: 997-1001. doi:10.1002/jhet.5570260419 10.1002/jhet.5570260419View ArticleGoogle Scholar
- Turgut Z, Yolacan C, Aydogan F, Bagdatli E, Ocal N: Synthesis of New Pyrazolothiazole Derivatives from 4-Thiazolidinones. Molecules 2007, 12: 2151-2159. doi:10.3390/12092151 10.3390/12092151View ArticleGoogle Scholar
- Wrobel J, Jetter J, Kao W, Rogers J, Di L, Chi J, Peréz MC, Chen GC, Shen ES: 5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists. Bioorg Med Chem 2006, 14: 5729-5741. doi.org/10.1016/j.bmc.2006.04.012 10.1016/j.bmc.2006.04.012View ArticleGoogle Scholar
- Zevzikoviene A, Zevzikovas A, Tarasevicius E, Pavlonis A, Dirse V: Synthesis and in vitro antimicrobial study of 4-thiazolidinone containing sulfanilamide. Acta Poloniae Pharmaceutica 2012, 69: 911-915.Google Scholar
- Zhao S, Cheng M, Li J, Tian J, Wang X: One pot production of 5-hydroxymethylfurfural with high yield from cellulose by a Brønsted-Lewis-surfactant-combined heteropolyacid catalyst. Chem Commun (Camb) 2011, 47: 2176-2178. doi:10.1039/c0cc04444j 10.1039/c0cc04444jView ArticleGoogle Scholar
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