Ethyl lactate and its aqueous solutions as sustainable media for organic synthesis
Introduction
Solvents used as media for the organic reactions make a significant contribution to the sustainability of synthetic methods. Together with recyclability and good biodegradability, a sustainable solvent should also originate from renewable resources. Such solvents are often referred as bio-based solvents (Calvo-Flores et al., 2018). These characteristics of bio-based solvent, ideally complemented by safety related parameters, such as non-toxicity, high boiling point, and low vapor pressure, allow to classify them as “green” solvents.
Ethyl lactate, naturally occurring mainly as an optically active ( = −10.6° (Clary et al., 1998)) l-isomer (ethyl (S)-2-hydroxypropanoate), meets these requirements and represents bio-based solvents derived from biomass. The industrial production of ethyl lactate involves esterification of lactic acid with ethanol (Scheme 1) (Pereira et al., 2011).
Both lactic acid and ethanol are produced by microbial fermentations of carbohydrates, including starchy and cellulosic agricultural wastes. Microorganisms producing lactic acid in significant quantities are very diverse and include bacteria, fungi, and microalgae (Abdel-Rahman et al., 2013). Industrially, high tolerance of yeast and Lactobacillus strains to low pH made them more suitable for the production of lactic acid by the fermentation of carbohydrate sources. The microbial production of ethanol by the fermentation of carbohydrates is known for many bacteria and yeasts (Lin and Tanaka, 2006). However, the yeast Saccharomyces cerevisiae, which can tolerate relatively high concentration of ethanol and low pH, is typically used for the industrial production of ethanol.
Some physical properties of ethyl lactate are presented in Table 1. Ethyl lactate has boiling point and viscosity higher than those of many conventional organic solvents and density similar to that of water. As a protic polar amphiphilic solvent, ethyl lactate is well miscible with water (García et al., 2014; Aparicio and Alcalde, 2009) and with hydrocarbons (Zakrzewska et al., 2012). Aqueous solutions of ethyl lactate at different concentrations can be used to modulate properties of media adjusting them for particular applications.
The low volatility and high flash point of ethyl lactate reduce potential occupational exposure to the solvent and make it more suitable for industrial applications. Ethyl lactate demonstrates no corrosive, mutagenic, carcinogenic, or teratogenic properties. The LD50 values of ethyl lactate exceed 2000 mg/kg (rats, oral or dermal administration) (Clary et al., 1998). The LC50 value of ethyl lactate inhaled by rats for 4 h is greater than 5400 mg/m3 (Clary et al., 1998). In humans, esterases readily hydrolyze ethyl lactate to relatively harmless lactic acid and ethanol. The non-toxic nature of ethyl lactate is reflected by its food grade labelling.
The impact of ethyl lactate on the environment is lower than that of many conventional organic solvents. The biodegradation of ethyl lactate occurs readily (75% in 28 days) producing water and carbon dioxide (Bowmer et al., 1998). Relatively high critical aggregation concentration indicates that the bioavailability of ethyl lactate is low and ecotoxicological studies (Bowmer et al., 1998; Zuriaga et al., 2018) on different aquatic organisms classify ethyl lactate as practically non-toxic or relatively non-toxic to fish, crustacean, algae, and bacteria. Ethyl lactate demonstrates no volatile organic compound character and its vapors have no depleting effect on the ozone layer.
The sustainable nature, beneficial safety and ecotoxicological profile combined with high solvency power (Manic et al., 2012) of ethyl lactate and its aqueous solutions make these solvents suitable for numerous applications in different areas. Ethyl lactate was found to be useful for the soil remediation against contaminations by polycyclic aromatic hydrocarbons (Yap et al., 2012; Jalilian Ahmadkalaei et al., 2016; Sun et al., 2009) or heavy metals (Sun et al., 2009; Guo et al., 2010). Many effective protocols have been proposed for the extraction of polar and non-polar phytoconstituents from plants using ethyl lactate (Kua et al., 2016, 2018; Villanueva-Bermejo et al., 2017). The miscibility with water and tunable properties of aqueous solutions of ethyl lactate resulted in the development of biphasic aqueous systems for the separation of polar compounds (Kamalanathan et al., 2018a, 2018b) and chromatographic methods utilizing ethyl lactate as a mobile phase component (Judge and Aab, 2013; Micăle et al., 2015). Ethyl lactate was proposed as a safer and more efficient precipitating liquid embolic agent than DMSO (Dudeck et al., 2006) and as a non-toxic solvent replacing N-methylpyrrolidone in the polyetherimide membrane preparation (Alqaheem et al., 2018). A significant progress has been achieved in the application of ethyl lactate and its aqueous solutions as media for organic synthesis.
Section snippets
Organic synthesis in ethyl lactate and its aqueous solutions
Various effective organic synthesis methods have been developed over the last decade utilizing ethyl lactate and its aqueous solutions as reaction media. These transformations include coupling reactions, reactions of carbonyl compounds, synthesis of diverse heterocyclic compounds, multicomponent reactions and others.
Conclusion
Ethyl lactate has attracted significant attention as a bio-derived solvent for organic synthesis. Miscibility of ethyl lactate with water opens an opportunity to adjust properties of the solvent to the required optimum producing a medium more efficient than the pure solvent. Current applications of ethyl lactate and its aqueous solutions as media for various chemical transformations often benefit from the non-conventional energy sources for the activation (microwave, ultrasound, and visible
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
This research was supported by Ministry of Higher Education, Malaysia (FRGS/1/2018/STG01/MUSM/02/2).
References (66)
- et al.
Recent advances in lactic acid production by microbial fermentation processes
Biotechnol. Adv.
(2013) - et al.
The ecotoxicity and the biodegradability of lactic acid, alkyl lactate esters and lactate salts
Chemosphere
(1998) - et al.
Eosin Y-catalyzed one-pot synthesis of spiro[4H-pyran-oxindole] under visible light irradiation
Tetrahedron
(2020) - et al.
An efficient solvent-tuning approach for the rapid synthesis of thiazolidinone derivatives and the selective synthesis of 2-amino-4H-1,3-thiazin-4-one and dimethyl 3,3'-thiodiacrylates
Tetrahedron Lett.
(2014) - et al.
Safety assessment of lactate esters
Regul. Toxicol. Pharmacol.
(1998) - et al.
Ethyl lactate as a promising bio based green solvent for the synthesis of spiro-oxindole derivatives via 1,3-dipolar cycloaddition reaction
Tetrahedron Lett.
(2013) - et al.
Catalyst free one-pot synthesis of α-aminophosphonates in aqueous ethyl lactate. Phosphorus Sulfur Silicon Relat
Elements
(2019) - et al.
Insights into alkyl lactate + water mixed fluids
J. Mol. Liq.
(2014) - et al.
Light induced synthesis of symmetrical and unsymmetrical dihydropyridines in ethyl lactate-water under tunable conditions
Tetrahedron Lett.
(2013) - et al.
Ethyl lactate enhances ethylenediaminedisuccinic acid solution removal of copper from contaminated soils
J. Hazard Mater.
(2010)
Partitioning of amino acids in the novel biphasic systems based on environmentally friendly ethyl lactate
Fluid Phase Equil.
Novel aqueous biphasic system based on ethyl lactate for sustainable separations: phase splitting mechanism
J. Mol. Liq.
Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products
Sustain. Chem. Pharm.
Self-aggregation of liquids from biomass in aqueous solution
J. Chem. Thermodyn.
Thermophysical properties of lactates
Thermochim. Acta
Solubility of high-value compounds in ethyl lactate: measurements and modeling
J. Chem. Thermodyn.
Extended benzodifuran-furan derivatives as example of π-conjugated materials obtained from sustainable approach
Tetrahedron
An efficient green protocol for the synthesis of coumarin fused highly decorated indenodihydropyridyl and dihydropyridyl derivatives
Tetrahedron Lett.
Phthalazine-triones: calix[4]arene-assisted synthesis using green solvents and their anticancer activities against human cancer cells
Arab. J. Chem.
Recent advances in the processing of green tea biomolecules using ethyl lactate. A review
Trends Food Sci. Technol.
KIO3-Catalyzed aerobic cross-coupling reactions of enaminones and thiophenols: synthesis of polyfunctionalized alkenes by metal-free C-H sulfenylation
Org. Lett.
Ethyl lactate mediated thioacetalization of aldehydes at ambient temperature. Phosphorus Sulfur Silicon Relat
Elements
Iodine-catalyzed, ethyl-lactate-mediated synthesis of 1,4-benzothiazines via metal-free cascade enaminone transamination and C-H sulfenylation
Asian J. Org. Chem.
Evaluation of solubility of polycyclic aromatic hydrocarbons in ethyl lactate/water versus ethanol/water mixtures for contaminated soil remediation applications
J. Environ. Sci.
Liquid–liquid equilibria of mixtures with ethyl lactate and various hydrocarbons
Fluid Phase Equil.
Visible light-initiated catalyst-free one-pot, multicomponent construction of 5-substituted indole chromeno[2,3-b]pyridines
Adv. Synth. Catal.
Preparation of polyetherimide membrane from non-toxic solvents for the separation of hydrogen from methane
Chem. Cent. J.
Insights into the ethyl lactate + water mixed solvent
J. Phys. Chem. B
Green synthesis of aryl aldimines using ethyl lactate
US Patent
Ethyl lactate as a tunable solvent for the synthesis of aryl aldimines
Green Chem.
An eco-friendly synthesis of 2-pyrazoline derivatives catalysed by CeCl3·7H2O
J. Chem. Sci.
Green and bio-based solvents
Top. Curr. Chem.
Visible-light-induced C=C bond cleavage of enaminones for the synthesis of 1,2-diketones and quinoxalines in sustainable medium
ChemCatChem
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