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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.
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- 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
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