Sustainable Chemistry and Pharmacy 18 (2020) 100322

Available online 15 September 20202352-5541/© 2020 Elsevier B.V. All rights reserved.

Ethyl lactate and its aqueous solutions as sustainable media for organic synthesis

Anton V. Dolzhenko School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, 47500, Malaysia

A R T I C L E I N F O

Dedicated to 95th birthday of Professor Victor E. Kolla.

Keywords: Ethyl lactate Bio-based solvent Green solvent Organic synthesis Multicomponent reactions

A B S T R A C T

Ethyl lactate is an amphiphilic bio-based solvent with beneficial safety characteristics and ecotoxicity profile. The miscibility of ethyl lactate with water allows adjustments of the medium properties using aqueous solutions of various concentrations to achieve the desired reaction outcome. This review discuses current applications of ethyl lactate and its aqueous solutions as media for organic synthesis. The effectiveness of these media has been demonstrated in several coupling reactions, olefin metathesis, carbonyl group reactions, heterocyclizations, various multicomponent reactions and other chemical transformations. These reactions often benefit from the application of non-conventional energy sources (microwave, ultrasound, and visible light irradiation). The re-action yields are typically comparable or higher than that obtained in conventional solvents.

1. 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 char-acteristics 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 ([α]20D

= − 10.6◦ (Clary et al., 1998)) L-isomer (ethyl (S)-2-hydrox-ypropanoate), meets these requirements and represents bio-based sol-vents 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 fermenta-tions 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 Lacto-bacillus 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 concentra-tion 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 hy-drocarbons (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 po-tential 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

E-mail address: anton.dolzhenko@monash.edu.

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https://doi.org/10.1016/j.scp.2020.100322 Received 9 July 2020; Received in revised form 20 August 2020; Accepted 29 August 2020

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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 sepa-ration of polar compounds (Kamalanathan et al., 2018a, 2018b) and chromatographic methods utilizing ethyl lactate as a mobile phase component (Judge and Aab, 2013; Micale 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.

2. 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, re-actions of carbonyl compounds, synthesis of diverse heterocyclic com-pounds, multicomponent reactions and others.

2.1. Coupling reactions

Ethyl lactate was found to be a solvent suitable for the Glaser coupling (Wan et al., 2014). The conditions, optimized using the model reaction of phenylacetylene (Scheme 2), were applied to the homo- and cross-couplings of aromatic and aliphatic terminal alkynes. Even though yield of 1 under the optimized conditions was good, yields of other conjugated alkynes strongly depended on the substrate structure and varied from 26% to 80% (20 examples). It was proposed that in addition to its role as a medium, ethyl lactate also functions as a ligand of the copper catalyst (Fig. 1) facilitating the reaction.

The Suzuki-Miyaura reaction was successfully carried out in aqueous ethyl lactate in a ligand-free manner (Wan et al., 2012). In the model reaction of iodobenzene and phenylboronic acid (Scheme 3), aqueous ethyl lactate was more efficient for the preparation of 2 than pure ethyl lactate (93% vs 62% yields, respectively). The reaction under the opti-mized conditions was rather general tolerating various aryl halides and arylboronic acids with yields ranging from 43% to 96%. Aryl iodides (12 examples) were expectedly more reactive than aryl bromides (16 ex-amples), which required higher temperature (80 ◦C).

The palladium catalyst loading in the Suzuki-Miyaura coupling was reduced by one order applying melamine as a ligand (Edwards et al., 2014). The reaction of phenylboronic acid with 4-bromoacetophenone in ethyl lactate afforded 3 in good yield when this catalytic system was utilized (Scheme 4) (Edwards et al., 2014). However, an attempt to use 4-chloroacetophenone in this reaction resulted in a lower yield of 3 (57%) even at higher temperature (130 ◦C). Variations in the structure of aryl bromides and aryl boronic acids were used to prepare ten ana-logues of 3 in yields ranging from 64% to 99%.

The oxidative homocoupling of thiols in ethyl lactate was effectively performed in open air and did not require addition of any catalyst (Liu et al., 2013). Thiophenol in ethyl lactate at 60 ◦C in an open-air vessel produced disulfide 4 in 90% yield (Scheme 5). Under oxygen atmo-sphere, the same reaction required just 2 h affording 4 in 95% yield. The reaction conditions in open air were successfully applied to various ar-omatic and aliphatic thiols (14 examples, 57–97% yields). For most of the substrates, yields were good (74–97%), but substituents in

Table 1 Selected physical properties of ethyl lactate (Clary et al., 1998; Pereira et al., 2011; Lomba et al., 2013, 2014; Jessop et al., 2012; Salavagione et al., 2017).

Boiling point (◦C) 153

Melting point (◦C) − 23 Flash point (◦C) 61 Density, ρ (g/cm3) 1.0284 (at 25 ◦C) Absolute viscosity, η (mPa ⋅ s) 2.3753 (at 25 ◦C) Surface tension (mN⋅m− 1) 29.49 (at 25 ◦C) Vapor pressure, p (kPa) 0.436 (at 30 ◦C) Refractive index, n20

D 1.4107

Molar refraction, Rm (cm3⋅mol− 1) 28.506 Kamlet–Taft dipolarity/polarizabilty, π* 0.82 Reichardt’s solvatochromic parameter, EN

T 0.63

Hansen solubility parameters (MPa1/2): dispersion forces, δD, dipole forces, δP, hydrogen bonding interactions, δH

16.0 7.6 12.5

Hildebrand solubility parameter, δ (MPa1/2) 21.3 Solubility in water miscible LogP (octanol/water) 0.06 Critical aggregation concentration (mol ⋅ kg− 1) 1.107 (at 25 ◦C)

Fig. 1. Putative interaction of ethyl lactate with the copper catalyst.

scheme 2. Glaser coupling of phenylacetylene in ethyl lactate.

scheme 1. Synthesis of ethyl lactate. Fig. 2. Putative activation of N- and S-nucleophiles and aldehydes by ethyl lactate.

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ortho-position of thiophenols increased steric hindrance reducing yields to 57–67%.

The oxidative cross-coupling of β-enaminones and thiophenols under the potassium iodate catalysis was efficient using ethyl lactate as a medium (Wan et al., 2016a). The model reaction in ethyl lactate (Scheme 6) afforded 5 in higher yield than when it was performed in DMSO, DMF or other common organic solvents (18–70%). Under opti-mized conditions, the reaction was rather general tolerating a variety of β-enaminones and other electron-deficient enamines in their coupling

with thiophenols (24 examples, 75–85% yields).

2.2. Transamination

The transamination of N,N-dimethyl-substituted enaminones was successfully achieved using prolonged heating with amines in ethyl lactate (Gao et al., 2017a). The reaction of N,N-dimethylaminoacrylo-phenone with 4 molar equivalents of morpholine resulted in the for-mation of 6 in good yield (Scheme 7). The process was found to be

scheme 8. Synthesis of metathesis catalyst [Ru] in ethyl lactate.

scheme 6. Oxidative cross-coupling between N,N-dimethylaminoacrylophenone and p-thiocresol in ethyl lactate.

scheme 7. Transamination of N,N-dimethylaminoacrylophenone with morpholine.

scheme 4. Suzuki-Miyaura coupling between phenylboronic acid with 4-bromoacetophenone in ethyl lactate.

scheme 3. Suzuki-Miyaura coupling between iodobenzene and phenylboronic acid in aqueous ethyl lactate.

scheme 5. Oxidative homocoupling of thiophenols in ethyl lactate.

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reversible and N,N-dimethylaminoacrylophenone was prepared in 93% by the treatment of 6 with 40% aqueous solution of dimethylamine under standard conditions in ethyl lactate. A variety of secondary amines was effectively involved in the transamination of N,N-dime-thyl-substituted enaminones and electron-deficient enamines (20 ex-amples, 63–87% yields).

2.3. Olefin metathesis

Ethyl lactate was used as a medium for the synthesis of metathesis catalyst [Ru] (Scheme 8). Once prepared, this catalyst was also re-ported (Planer et al., 2019) to be effective in the ring-closing metathesis performed in ethyl lactate. In the synthesis of 7, 95–97% conversion was observed and the product was isolated in 85% yield when the reaction was carried out under argon (Scheme 9). Under the same conditions, the

reaction was efficient with a variety of dienes (7 examples, 64–93% yields). Yields of 7 in the reaction performed in ethyl lactate under argon and in open air were identical.

Ethyl lactate and [Ru] also demonstrated excellent results in the preparation of 8 via the enyne cycloisomerization (Scheme 10). The same medium was also successfully applied for several cross-metathesis reactions, e.g. synthesis of alkene 9 (Scheme 11), which was obtained as a mixture of E- and Z-isomers (8:1). The identical outcome was observed for the reactions performed under argon or in the open-air conditions.

2.4. Carbonyl group transformations

Ethyl lactate serves as a medium for the reactions of aldehydes and ketones with various nucleophiles. The chiral character of ethyl L

(-)-lactate was utilized for asymmetric induction in the reduction of acetophenone with sodium borohydride (Hüttenhain, 2006). The reduction of acetophenone to 1-phenylethanol at − 40 ◦C in ethyl lactate without other additives was complete, but suffered from low e.e. (15%) for the targeted R(+)-isomer 10. The application of a Lewis acid helped to improve the process enantioselectivity to 36% e.e., but with only 70% conversion (Scheme 12). Using borane as a reducing agent under the identical conditions allowed to obtain 10 with even higher enantiose-lectivity (46% e.e.). However, this increase in e.e. was achieved at the expense of the conversion, which dropped to 50%. Another issues

scheme 14. Synthesis of Schiff’s bases 12 in ethyl lactate.

scheme 11. Olefin cross-metathesis in ethyl lactate.

scheme 10. Enyne cycloisomerization in ethyl lactate.

scheme 13. Condensation of cinnamaldehyde with aniline in aqueous ethyl lactate.

scheme 12. Asymmetric reduction of acetophenone in L-ethyl lactate.

scheme 9. Ring-closing olefin metathesis in ethyl lactate. scheme 15. Condensation of acetophenone and hydroxylamine hydrochloride in ethyl lactate.

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associated with the application of ethyl L(-)-lactate for asymmetric in-duction in this reaction arises from its low selectivity due to the competitive attack by reducing agents to the ethyl lactate ester group.

The Schiff’s bases were conveniently prepared using reaction of benzaldehydes or cinnamaldehyde with anilines in ethyl lactate or its aqueous solutions (Bennett et al., 2009). Tuning properties of the me-dium by adding water as a co-solvent to ethyl lactate was used to achieve an optimal ratio of solvents for the best balance of the reaction rate and outcome. For example, reaction of cinnamaldehyde with aniline was performed in aqueous ethyl lactate affording aldimine 11 in excellent yield and purity by simple filtration of the precipitated product (Scheme 13). Pure products were obtained in good yields using this approach for reactions of benzaldehydes or cinnamaldehyde in their reactions with anilines (17 examples, 90–99% yields) (Bennett et al., 2009). Additional 70 examples of the preparation of aldimines in ethyl lactate or its aqueous solutions were included in the patent (Bennett, 2011). Depending on the substrates, the reaction time varied from a few sec-onds to an hour, but yields were generally good (82–99%), except for the product of reaction between 4-hydroxybenzaldehyde and 4-phenoxyani-line (54%).

For a crystallographic study, synthesis of the Schiff’s base from 2- amino-6-methylbenzothiazole and 2-methoxy-1-naphthaldehyde was performed in ethyl lactate and its aqueous solutions at ambient tem-perature (Demircioglu et al., 2020). The best results were obtained when ytterbium(III) triflate (4 mol%) was used as a catalyst in the ethyl lactate medium: the reaction was completed in 10 min and the product was isolated in 90% yield.

Ethyl lactate was also applied as a medium in the process of prepa-ration of highly conjugated Schiff’s bases 12 possessing semiconductor properties (Scheme 14) (Moussallem et al., 2012). However, due to lower reactivity of starting amines, the reaction required longer time and was performed in the presence of catalytic amounts of phosphorus pentoxide.

The synthesis of oxime 13 from acetophenone and hydroxylamine hydrochloride was reported (Liu and Wen, 2015) to proceed in ethyl lactate smoothly and without any catalyst (Scheme 15). Acetophenones and benzaldehydes were efficiently employed as substrates for this re-action (13 examples, 77–91% yields). Ethyl lactate was also used as a medium for the further transformation of oximes to amides 14 via the Beckmann rearrangement catalyzed by ferric chloride and cyanuric chloride (TCT) (Scheme 16) (Liu and Wen, 2015).

It was reported (Wan et al., 2016b) that reaction of 4-chlorobenzal-dehyde with ethanethiol in ethyl lactate at room temperature resulted in

the formation of dithioacetal 15 in 84% yield (Scheme 17). Only traces of 15 were detected when the same reaction was performed in aceto-nitrile or p-xylene; the reaction did not proceed in water. The evaluation of substrate scope demonstrated that the method was compatible with aromatic, heteroaromatic, and aliphatic aldehydes in their reactions with alkylthiols, cyclic dithiols, and thiophenols (19 examples, 59–84% yields).

Good reactivity of N- and S-nucleophiles with carbonyl compounds in ethyl lactate without addition of catalysts could be attributed to the activation of both the substrates by hydrogen bonding and keeping them close to each other for the effective nucleophilic attack (Fig. 2) (Wan et al., 2016b).

It was found that reaction of benzaldehyde with two indole mole-cules in 60% aqueous ethyl lactate under ultrasound irradiation (Scheme 18) was more efficient than in common organic solvents (Gao et al., 2017b). The reaction yield in pure ethyl lactate was also lower (36%) than in its aqueous solution (95%). The yield of 16 in aqueous ethyl lactate after the scale increase from 1 mmol to 100 mmol remained nearly the same (93%). The reaction scope was also wide and a repre-sentative library (28 examples, 80–95% yields) was prepared under the same conditions using the reaction time from 15 min to 45 min. The reaction tolerated various substituents in the indole ring and was effi-cient with a range of aliphatic, aromatic, and heterocyclic aldehydes.

The same medium was found to be effective in the reaction of two indole molecules with isatin affording 17 in 95% yield (Scheme 19) (Gao et al., 2017b). Substituents in the benzene ring of indole and isatin did not significantly alter efficiency of the process (15 examples, 89–95% yields).

Ethyl lactate was used as a medium in the synthesis of squaraine dye 18 (Scheme 20) (Minkovska et al., 2018). The reaction was effectively performed under microwave irradiation affording desired product 18 in good yield after heating at 140 ◦C for 4 min only.

2.5. Dehydration of sugars

The selective dehydration of sugars to 5-hydroxymethylfurfural (19) was carried out in ethyl lactate under microwave irradiation in the presence of graphene oxide (Mondal et al., 2014). Choline chloride, applied as an additive, was found to improve effectiveness of the pro-cess. From the tested substrates, D-fructose was the most effective affording 19 in 76% yield (Scheme 21). Other monosaccharides

scheme 16. Synthesis of N-arylacetamides 13 via Beckmann rearrangement of oximes in ethyl lactate.

scheme 19. Reaction of isatin with two indole molecules in aqueous ethyl lactate.

scheme 18. Reaction of benzaldehyde with two indole molecules in aqueous ethyl lactate.

scheme 17. Dithiolation of 4-chlorobenzaldehyde with ethanethiol in ethyl lactate.

Fig. 3. Putative activation of phenylhydrazine by ethyl lactate.

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(D-glucose, D-galactose, and D-mannose) and D-sucrose were also con-verted to 19 by this method, but yields were below 60%.

2.6. Heterocyclizations

Several monocyclic and fused five- and six-membered heterocycles

have been prepared using ethyl lactate or its aqueous solutions as re-action media. Many heterocyclic compounds were prepared in these solvents using multicomponent reactions and they are discussed in the proceeding section of this review.

Aqueous ethyl lactate was found to be a suitable solvent for the pyrazoline ring closure in the reaction of substituted chalcones with phenylhydrazine under the cerium(III) chloride catalysis (Bhat et al., 2017). Using this method, pyrazoline 20 was obtained and isolated by simple filtration in 87% yield (Scheme 22). The subsequent runs of this reaction reusing the filtrate afforded 86%, 83%, and 78% of 20, thus demonstrating that solvent and catalyst can be reused without sub-stantial loss of activity. It should be noted that attempts to prepare similar compounds using different chalcones were often unsuccessful and yields in the prepared library of fourteen pyrazolines varied significantly (38–87%). It was suggested (Bhat et al., 2017) that ethyl lactate activates phenylhydrazine in the reaction by increasing its nucleophilicity via hydrogen bonding (Fig. 3).

The thiazolidinone ring closure in the reaction of N,N′-disubstituted thioureas and acetylenedicarboxylates was reported to proceed smoothly in aqueous ethyl lactate under mild conditions (Choudhary and Peddinti, 2014). For example, N,N′-diphenylthiourea reacted with dimethyl acetylenedicarboxylate to afford thiazolidinone 21 in 95% yield (Scheme 23). The reaction required no catalyst and was completed in just 6 min. Under similar conditions, adjusting concentration of aqueous ethyl lactate within 40–80% range, eighteen thiazolidinones

scheme 20. Microwave-assisted synthesis of squaraine dye 18 in ethyl lactate.

scheme 22. Synthesis of pyrazoline 20 in aqueous ethyl lactate.

scheme 23. Reaction of N,N′-diphenylthiourea with dimethyl acetylenedi-carboxylate in aqueous ethyl lactate.

scheme 24. Reaction between o-aminothiophenol and benzaldehyde in ethyl lactate.

scheme 21. Dehydration of D-fructose in ethyl lactate.

scheme 25. Synthesis of chromone 23 in ethyl lactate.

scheme 26. Synthesis of 3-phenylselenylated chromones 24 in ethyl lactate. scheme 27. Synthesis 3-iodochromone in ethyl lactate.

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were prepared in excellent yields (91–98%). A mild heating (50 ◦C) was required for one substrate (N,N′-dibenzylthiourea), while others quickly (3–6 min) reacted at room temperature.

The synthesis of benzothiazoles via the reaction of o-amino-thiophenol and aldehydes in ethyl lactate was effectively catalyzed by the proline-based ionic liquid (Yu et al., 2016). Using ethyl lactate as a medium, 2-phenylbenzothiazole (22) was prepared from o-amino-thiophenol and benzaldehyde in 90% yield (Scheme 24), while typical organic solvents were less effective under these conditions. Expanding scope of this method to other aldehydes, it was found that benzalde-hydes and thiophen-2-carboxaldehyde afforded products in similar

yields (9 examples, 82–92% yields), but yield dropped to 55% when valeraldehyde was allowed to react with o-aminothiophenol.

The domino reaction, involving coupling of thiols and enaminones under the potassium iodate catalysis (cf. Scheme 6) and the chromone ring closure, was successfully carried out in ethyl lactate (Zhong et al., 2017). The model reaction in ethyl lactate produced chromone 23 (Scheme 25) in the yield higher than those obtained when conventional organic solvents were used for the reaction. In the absence of a thiol, the

chromone ring was not formed under the standard conditions and an attempt to perform coupling of chromone with thiol was also unsuc-cessful. The addition of a radical scavenger, 2,2,6,6-tetramethyl-1-piper-idinyloxyl (TEMPO), to the reaction did not change its outcome suggesting that mechanism of this domino reaction is not radical. The reaction tolerated different substituents in the aromatic ring of starting enaminones and various aromatic thiols affording 3-sulfenylated chro-mones in consistently good yields (26 examples, 76–88% yields). Furthermore, the same solvent and conditions were suitable for the synthesis of 3-phenylselenylated chromones 24 (Scheme 26) (Zhong et al., 2017).

scheme 28. Reaction between anthranilamide and acetylacetone in aqueous ethyl lactate.

scheme 29. Reaction between anthranilamide and cyclohexane-1,3-dione in aqueous ethyl lactate.

scheme 30. Photocatalytic synthesis of benzyl in ethyl lactate.

scheme 31. One-pot photocatalytic synthesis of 2,3-diphenylquinoxaline in ethyl lactate.

scheme 32. Reaction between o-aminothiophenol and N,N-dimethylaminoa-crylophenone in ethyl lactate.

scheme 33. Reaction between furfural and morpholine.

scheme 34. Ultrasound-promoted three-component reaction between aniline, benzaldehyde, and triethyl phosphate in aqueous ethyl lactate.

scheme 35. Microwave-assisted three-component reaction between phthalhy-drazide, benzaldehyde, and dimedone in ethyl lactate.

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A similar synthesis of 3-iodo- and 3-bromo-substituted chromones in ethyl lactate utilized the ring closure and in situ oxidation of the cor-responding halides with hypervalent iodine(III) (Lin et al., 2020). In the model reaction, 3-iodochromone (25) was formed in 78% yield at ambient temperature under the oxidation by phenyliododiacetate (Scheme 27). Under the standard reaction conditions, addition of radical scavengers TEMPO or butylated hydroxytoluene (BHT) to the reaction mixture did not inhibit formation of 25 thus supporting non-radical mechanism of transformations in the synthesis of 25. The formation of 25 in 69% yield was observed when potassium iodide and phenyl-iododiacetate were replaced in the reaction by molecular iodine. The iodination was suggested to take place prior to the chromone ring closure, since attempts to perform iodination of chromone under stan-dard conditions did not afford 25. The method for the synthesis of 3-hal-ochromones was equally effective with potassium iodide and potassium bromide and tolerated various substituents in the fused benzene ring (21 examples, 31–91%).

The synthesis of quinazolones was effectively performed in aqueous ethyl lactate using the reaction of anthranilamides and 1,3-diketones catalyzed by camphoresulfonic acid (Shen et al., 2015). In the model reaction, anthranilamide reacted with acetylacetone resulting in the C–C bond cleavage of the ketone and the quinazolone ring closure to afford 26 in excellent yield (Scheme 28). The same product 26 was obtained in reactions of anthranilamide with non-symmetrical 1,3-diketones pos-sessing terminal methyl group at one of the carbonyl groups. The scope of this reaction was explored using substituted anthranilamide and various 1,3-diketones to complete a library of sixteen quinazolones

prepared in 56–98% yields. The method was further extended to cyclic 1,3-diketones. It was

found that in aqueous ethyl lactate and under the same catalysis, the carbocylic ring of cyclohexane-1,3-dione opened in the reaction with anthranilamide resulting in the formation of 27 (Scheme 29) (Shen et al., 2015). The reaction scope was successfully expanded to the syn-thesis of additional ten substituted quinazolones from various anthra-nilamides and cyclohexane-1,3-diones (55–98% yields). The reaction was found to tolerate substituted anthranilamides and cyclohexane-1, 3-diones with one or more methyl groups in the ring, but failed to give products in attempts to employ cyclopentane-1,3-diones as substrates.

The synthesis of 2,3-diarylquinoxalines was performed starting from N,N-dimethyl-substituted 1,2-diarylenaminones in a two-step one-pot manner under photocatalytic conditions using ethyl lactate as a medium (Cao et al., 2015). The optimization of reaction conditions for the first step identified that yield of benzyl (28), formed in ethyl lactate (Scheme 30), was higher compared to that obtained in common organic solvents. The subsequent treatment of benzyl under the same conditions with o-phenylenediamine resulted in the formation of 2,3-diphenylquinoxa-line (29) (Scheme 31). Analogously, a series of eighteen 2,3-diarylqui-noxalines with substituents in the aromatic rings was prepared using this protocol in yields ranging from 47% to 90%.

Ethyl lactate was used as a medium for the synthesis of 2-aroyl-1,4- benzothiazines from o-aminothiophenols under the catalysis by iodine (Wan et al., 2018). The reaction of o-aminothiophenol with N,N-dime-thylaminoacrylophenone in ethyl lactate afforded 2-benzoyl-1,4-benzo-thiazine (30) in 82% yield (Scheme 32). Under the same conditions, the reaction was found to tolerate various substituents in the aromatic rings of both substates (17 examples, 62–92% yields), except a hydroxy group in ortho-position of the enaminone.

2.7. Multicomponent reactions

Ethyl lactate and its aqueous solutions were effectively used as a medium for various types of multicomponent reactions. Under the erbium(III) chloride catalysis in ethyl lactate, furfural reacted with two molecules of morpholine and after the furan ring rearrangement affor-ded trans-4,5-dimorpholinocyclopent-2-enone (30) in quantitative yield (Scheme 33) (Procopio et al., 2013). Eight analogues of 31 were pre-pared in quantitative yields using reaction of furfural with various sec-ondary aliphatic and aromatic amines. However, yield was lower (88%) when bulky diisobutylamine was used as a substrate in this reaction. Attempts to involve primary amines in this rearrangement were less successful. Benzylamine reacted with furfural producing the corre-sponding Schiff base as a sole product. The reaction of furfural with aniline required twice longer time and the resulted trans-4,5-bis(phe-nylamino)cyclopent-2-enone was obtained in lower purity and in 25%

scheme 37. Light-induced synthesis of Hantzsch 1,4-dihydropyridine 35 in aqueous ethyl lactate.

scheme 36. Three-component reaction between anisaldehyde, hydroxylamine hydrochloride, and ethyl acetoacetate in aqueous ethyl lactate.

scheme 38. Light-induced synthesis of unsymmetrical 1,4-dihydropyridines 36 in aqueous ethyl lactate.

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yield only. Ethyl lactate outperformed typical organic solvents in the synthesis

of α-aminophosphonate 32 (75% yield) using a three-component reac-tion of aniline, benzaldehyde, and triethyl phosphate under ultrasound irradiation (Gao et al., 2019). The yield was further improved by tuning proprieties of the medium by the addition of water. The optimal con-centration of the ethyl lactate aqueous solution was found to be 60%, which allowed preparation of 32 in 95% yield (Scheme 34). The reaction scope was explored using substituted anilines and various aldehydes. Good yields were obtained for the reactions of benzaldehydes or furfural

(23 examples, 89–95% yields). However, a decrease in yield to 79% was observed when cyclohexanecarboxaldehyde was used in this reaction.

The three-component synthesis of fused phthalazines was effectively performed in ethyl lactate under controlled microwave irradiation using a Discover (CEM) reactor (Rego et al., 2019). In the model reaction, p-sulfonic acid calix[4]arene (PSAC[4]A) was found to be a suitable catalyst for the preparation of 33 from phthalhydrazide, benzaldehyde, and dimedone (Scheme 35). The scope of the reaction was explored using various aldehydes (14 examples). While aromatic aldehydes, particularly those possessing electron-withdrawing groups, afforded products in higher yields (up to 94%), aliphatic aldehydes were less reactive (30–35% yields) and only 11% of the targeted product was obtained under these conditions using formaldehyde. Some of the ob-tained products demonstrated antiproliferative activity against cancer cells.

Aqueous ethyl lactate was used a medium for the three-component reaction of aldehydes, hydroxylamine, and ethyl acetoacetate (Vaidya et al., 2016). The model reaction of anisaldehyde, hydroxylamine hy-drochloride, and ethyl acetoacetate catalyzed by cerium(III) chloride afforded isoxazolone 34 (Scheme 36). Using various aldehydes, a series

scheme 39. Light-induced synthesis of tetrahydroquinolones 37 in aqueous ethyl lactate.

scheme 40. Three-component reaction between p-toluidine and benzaldehyde, and ethyl lactate.

scheme 41. Photocatalytic three-component reactions of isatin and malononitrile with ethyl acetoacetate or acetylacetone in aqueous ethyl lactate.

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of isoxazolones was prepared using this method (14 examples, 44–85% yields).

Ethyl lactate was a more efficient medium than common organic solvents in the synthesis of Hantzsch 1,4-dihydropyridines under the visible light irradiation (tungsten, 150 W) (Ghosh et al., 2013). In the model reaction of p-nitrobenzaldehyde, ethyl acetoacetate, and ammo-nium formate in ethyl lactate, 1,4-dihydropyridine 35 was formed in 75% yield. The further screening of aqueous solutions of ethyl lactate identified that 50% concentration of ethyl lactate was optimal improving yield of 35 up to 92% (Scheme 37). Varying aldehyde structure (aromatic, aliphatic, and heterocyclic) and using acetylacetone as an acetoacetate equivalent in this reaction allowed preparation of a

library of twenty symmetrical 1,4-dihydropyridines in 80–92% yields. Using simultaneously in the same reaction ethyl acetoacetate and ace-tylacetone, unsymmetrical 1,4-dihydropyridines 36 were also prepared (Scheme 38). This light-induced reaction in aqueous ethyl lactate was also suitable for the synthesis of tetrahydroquinolones 37 using dime-done in combination with ethyl acetoacetate or acetylacetone (Scheme 39).

Ethyl lactate played both medium and building block roles in the three-component synthesis of ethyl 2-arylquinoline-4-carboxylates (Yang and Wan, 2020). In the model reaction of p-toluidine and benz-aldehyde in ethyl lactate, ferric chloride was identified as a suitable catalyst affording 38 in good yield (Scheme 40). The reaction was found

scheme 42. Photochemical three-component reaction of isatin and malononitrile with dimedone, 4-hydroxycoumarin or 2-hydroxy-1,4-naphthoquinone in aqueous ethyl lacatate.

scheme 43. Three-component reaction of 4-aminocoumarin and benzaldehyde with dimedone or 1,3-indandione in ethyl lactate.

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to tolerate a variety of substrates and 23 examples were prepared in 53–79% yields using different combinations of anilines and benzalde-hydes. The experiments, attempting to elucidate possible mechanism of the reaction, suggested conversion of ethyl lactate to reactive ethyl py-ruvate in the course of the reaction.

The three-component reaction of isatin, malononitrile, and ethyl acetoacetate under photocatalytic conditions was more efficient in ethyl lactate than in conventional organic solvents (Chen et al., 2020). Even better results were obtained in aqueous solutions of ethyl lactate with the 60% solution being the most efficient for the synthesis of spiro-fused indole 40 (Scheme 41). Slightly higher yield was obtained under green vs. white light. The yield of the reaction scaled-up from 1 mmol to 10 mmol remained nearly identical.

The same product (40) was also prepared via the two-step process under identical reaction conditions. The Knoevenagel condensation of isatin and malononitrile afforded 39, which underwent spirocyclization with ethyl acetoacetate producing 40.

It was suggested that the reaction involved a radical mechanism initiated by light since the three-component reaction did not proceed in dark and was also inhibited in the presence of TEMPO. The photo-catalytic reaction in aqueous ethyl lactate was rather general affording the desired products (34 examples, 85–94% yields) using various β-keto esters and substituted isatines as substrates. The replacement of β-keto

esters in the three-component reaction with acetylacetone resulted in the formation of a similar spiro-fused indole 41. The scope of this re-action was also explored using substituted isatins (10 examples, 85–93% yields).

The light-induced multicomponent reaction using aqueous ethyl lactate as a medium was efficiently performed using isatin, malononi-trile, and dimedone at ambient temperature and without any catalyst affording spiro-compound 42 in 95% yield (Scheme 42) (Zhang et al., 2017). Equally effective this multicomponent reaction proceeded using 4-hydroxycoumarin or 2-hydroxy-1,4-naphthoquinone instead of dimedone (Scheme 42). Under the same conditions, these substrates led to the formation of spiro-fused isatins 43 and 44, which were isolated in 95% yield. The scope of the reaction was also explored using substituted isatins in the synthesis of analogues of 42, 43, and 44 resulting in the corresponding sixteen-membered libraries for each of the three types of compounds, which were obtained in good yields (82–96%). The pre-parative utility of the developed method was demonstrated by the suc-cessful scale-up of the synthesis of 44 from 1 mmol to 10 mmol (96% yield). Attempts to use other solvents (including pure ethyl lactate) for the synthesis of 44 under otherwise identical conditions resulted in significantly lower yields.

scheme 45. Photochemical multicomponent reaction between 2-hydroxy-4-methoxybenzaldehyde and multiple equivalents of malononitrile in aqueous ethyl lactate.

scheme 44. Photochemical multicomponent reaction between salicylaldehyde, indole, and malononitrile in aqueous ethyl lactate.

scheme 46. Decarboxylative condensation of proline, naphthoquinone, and isatine in aqueous ethyl lactate.

scheme 47. Biginelli reaction between ethyl acetoacetate, benzaldehyde, and thiourea in ethyl lactate.

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Ethyl lactate was a preferred medium for the three-component re-action of 4-aminocoumarin and aromatic aldehydes with dimedone or 1,3-indandione under the lactic acid catalysis (Paul and Das, 2012). Heating 4-aminocoumarin, benzaldehyde, and dimedone in ethyl lactate in the presence of lactic acid resulted in the formation of 45 in 87% yield (Scheme 43). The structure of this product (45) was confirmed by the X-ray crystallography. The same compound (45) was also obtained stepwise via the initial Knoevenagel condensation, followed by the re-action of the intermediate product with 4-aminocoumarin. The three-component reaction of 4-aminocoumarin, benzaldehyde, and 1, 3-indandione proceeded similarly affording 46 in 77% yield (Scheme 43). The Knoevenagel condensation of benzaldehyde with 1,3-indan-dione and the subsequent reaction of the product with 4-aminocoumarin under the same conditions resulted in the formation of 46 in comparable yield (80%). The scope of the three-component reaction was expanded using various aromatic aldehydes to produce seven analogues of 45 (78–91% yields) and seven analogues of 46 (73–85% yields). The loading of catalyst required for the reactions was rather high but the solvent-catalyst system was reused four times without significant loss in activity.

The photochemical multicomponent reaction of salicylaldehyde with indole and two equivalents of malononitrile in aqueous ethyl lactate was reported (Zhang et al., 2019) to proceed better in green light affording 48 in 92% yield (Scheme 44). The same synthesis performed under white or blue light gave slightly lower yields of 48 (90%). The yield obtained under UV light further dropped to 87%, while only traces of 48 were detected even after prolonged stirring of the reaction mixture in the dark. The reaction was found to proceed as a pseudo four-component process via formation of 47 as an intermediate. This compound (47) was isolated in 85% yield (together with 6% of 48) when only one equivalent of malononitrile was used in the reaction under identical conditions for 4 h. Moreover, upon the treatment with malononitrile for 2 h, 47 was effectively converted into 48 in 88% yield. The multicomponent syn-thesis of 48 was suggested to involve radical formation and this assumption was confirmed by the inhibition of the reaction by the addition of radical trapping reagents (TEMPO and BHT).

The preparative utility of the developed multicomponent reaction was demonstrated by the successful scale-up of the synthesis of 48 from 1 mmol to 10 mmol (93% yield) and by expanding the reaction scope to other twenty examples via variations of substituents at salicylaldehyde or/and indole (70–93% yields).

In the absence of indole, the multicomponent reaction of 2-hydroxy- 4-methoxybenzaldehyde with malononitrile depended on quantities of the latter. The subsequent formation of the chromene and pyridine rings took place affording 50 when three equivalents of malononitrile were used (Scheme 45). However, it was demonstrated that intermediate chromene 49 could be isolated in 95% yield under identical conditions with two equivalents of malononitrile.

As a medium for the decarboxylative condensation of proline, naphthoquinone, and isatine, ethyl lactate was significantly more effi-cient than common organic solvents (Dandia et al., 2013). Under mild conditions and without any catalyst, compound 51 was formed in 82% yield. By tuning properties of the medium with water, it was identified that in the optimal 80% concentration of aqueous ethyl lactate, yield of

51 was improved to 93% (Scheme 46). The assigned structure of 51 was supported by the X-ray crystallography data. The reaction remained effective utilizing substituted isatins as substrates (8 examples, 88–93% yields).

In the presence of trimethylsilyl chloride (TMSCl), ethyl lactate was found to be a suitable medium for the Biginelli reaction (Xu et al., 2014). In the model reaction of ethyl acetoacetate, benzaldehyde, and thiourea, pyrimidine-2-thione 52 was isolated in 75% yield (Scheme 47). The reaction was also successful with substituted benzaldehydes and when N-methylthiourea was used instead of thiourea (10 examples, 66–89% yields). Attempts to involve urea in this reaction failed. However, another group of researchers successfully performed the Biginelli reac-tion in ethyl lactate using urea as a substrate (Dias Beninca et al., 2020). The reaction required no catalysts and was carried out in a two-step manner: initial heating of ethyl acetoacetate with urea in ethyl lactate was followed by the one-pot reaction with (-)-(1R)-myrtenal to afford 53, which was isolated in 35% yield as a single strereoisomer (Scheme 48). The stereochemistry of 53 was assigned on the basis of the X-ray crystallographic analysis data.

3. 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, ultra-sound, and visible light irradiation). Significant advancements have been achieved when ethyl lactate or its aqueous solutions were used as media for coupling reactions, synthesis of heterocycles, and particularly multicomponent reactions. No doubts, ethyl lactate and its aqueous solution are safer and more sustainable alternatives for conventional solvents in a wide range of organic reactions, which scope will continue to expand.

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

Abdel-Rahman, M.A., Tashiro, Y., Sonomoto, K., 2013. Recent advances in lactic acid production by microbial fermentation processes. Biotechnol. Adv. 31, 877–902.

Alqaheem, Y., Alomair, A., Alhendi, A., Alkandari, S., Tanoli, N., Alnajdi, N., Quesada- Perez, A., 2018. Preparation of polyetherimide membrane from non-toxic solvents for the separation of hydrogen from methane. Chem. Cent. J. 12, 80.

scheme 48. Stereospecific Biginelli reaction between ethyl acetoacetate, urea and (-)-(1R)-myrtenal in ethyl lactate.

A.V. Dolzhenko

Sustainable Chemistry and Pharmacy 18 (2020) 100322

13

Aparicio, S., Alcalde, R., 2009. Insights into the ethyl lactate + water mixed solvent. J. Phys. Chem. B 113, 14257–14269.

Bennett, J.S., 2011. Green synthesis of aryl aldimines using ethyl lactate. US Patent, 20110196174.

Bennett, J.S., Charles, K.L., Miner, M.R., Heuberger, C.F., Spina, E.J., Bartels, M.F., Foreman, T., 2009. Ethyl lactate as a tunable solvent for the synthesis of aryl aldimines. Green Chem. 11, 166–168.

Bhat, P., Shridhar, G., Ladage, S., Ravishankar, L., 2017. An eco-friendly synthesis of 2- pyrazoline derivatives catalysed by CeCl3⋅7H2O. J. Chem. Sci. 129, 1441–1448.

Bowmer, C.T., Hooftman, R.N., Hanstveit, A.O., Venderbosch, P.W.M., van der Hoeven, N., 1998. The ecotoxicity and the biodegradability of lactic acid, alkyl lactate esters and lactate salts. Chemosphere 37, 1317–1333.

Calvo-Flores, F.G., Monteagudo-Arrebola, M.J., Dobado, J.A., Isac-García, J., 2018. Green and bio-based solvents. Top. Curr. Chem. 376, 18.

Cao, S., Zhong, S., Xin, L., Wan, J.-P., Wen, C., 2015. Visible-light-induced C=C bond cleavage of enaminones for the synthesis of 1,2-diketones and quinoxalines in sustainable medium. ChemCatChem 7, 1478–1482.

Chen, M.-N., Di, J.-Q., Li, J.-M., Mo, L.-P., Zhang, Z.-H., 2020. Eosin Y-catalyzed one-pot synthesis of spiro[4H-pyran-oxindole] under visible light irradiation. Tetrahedron 76, 131059.

Choudhary, G., Peddinti, R.K., 2014. 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. 55, 5597–5600.

Clary, J.J., Feron, V.J., van Velthuijsen, J.A., 1998. Safety assessment of lactate esters. Regul. Toxicol. Pharmacol. 27, 88–97.

Dandia, A., Jain, A.K., Laxkar, A.K., 2013. Ethyl lactate as a promising bio based green solvent for the synthesis of spiro-oxindole derivatives via 1,3-dipolar cycloaddition reaction. Tetrahedron Lett. 54, 3929–3932.

Demircioglu, Y.S., Sakarya, H.C., Süzen, Y., 2020. Synthesis, X-ray crystal structure and spectroscopic studies of benzothiazole Schiff base. Bulg. Chem. Commun. 52, 9–13.

Dias Beninca, L.A., Ligiero, C.B.P., da Silva Santos, J., Junior, J.J., da Silva, F.M., 2020. Eco-friendly and enantiospecific Biginelli synthesis using (+)-myrtenal as the substrate - an impeccable and unequivocal analysis of the product. Curr. Org. Synth. 17, 389–395.

Dudeck, O., Jordan, O., Hoffmann, K.T., Okuducu, A.F., Tesmer, K., Kreuzer-Nagy, T., Rüfenacht, D.A., Doelker, E., Felix, R., 2006. Organic solvents as vehicles for precipitating liquid embolics: a comparative angiotoxicity study with superselective injections of swine rete mirabile. Am. J. Neuroradiol. 27, 1900–1906.

Edwards, G.A., Trafford, M.A., Hamilton, A.E., Buxton, A.M., Bardeaux, M.C., Chalker, J. M., 2014. Melamine and melamine-formaldehyde polymers as ligands for palladium and application to Suzuki-Miyaura cross-coupling reactions in sustainable solvents. J. Org. Chem. 79, 2094–2104.

Gao, Y., Liu, Y., Wei, L., Wan, J., 2017a. Synthesis of enaminones containing diverse N,N- disubstitution via simple transamination: a study with sustainable catalyst-free operation. Res. Chem. Intermed. 43, 5547–5555.

Gao, G., Han, Y., Zhang, Z.-H., 2017b. Catalyst free synthesis of bis(indolyl)methanes and 3,3-bis(indolyl)oxindoles in aqueous ethyl lactate. Chemistry 2, 11561–11564.

Gao, G., Chen, M.-N., Mo, L.-P., Zhang, Z.-H., 2019. Catalyst free one-pot synthesis of α-aminophosphonates in aqueous ethyl lactate. Phosphorus Sulfur Silicon Relat. Elements 194, 528–532.

García, G., Atilhan, M., Aparicio, S., 2014. Insights into alkyl lactate + water mixed fluids. J. Mol. Liq. 199, 215–223.

Ghosh, P.P., Paul, S., Das, A.R., 2013. Light induced synthesis of symmetrical and unsymmetrical dihydropyridines in ethyl lactate-water under tunable conditions. Tetrahedron Lett. 54, 138–142.

Guo, H., Wang, W., Sun, Y., Li, H., Ai, F., Xie, L., Wang, X., 2010. Ethyl lactate enhances ethylenediaminedisuccinic acid solution removal of copper from contaminated soils. J. Hazard Mater. 174, 59–63.

Hüttenhain, S.H., 2006. Asymmetric induction from ethyl lactate in the reduction of acetophenone to phenylethanol. Synth. Commun. 36, 175–180.

Jalilian Ahmadkalaei, S.P., Gan, S., Ng, H.K., Abdul Talib, S., 2016. Investigation of ethyl lactate as a green solvent for desorption of total petroleum hydrocarbons (TPH) from contaminated soil. Environ. Sci. Pollut. Res. 23, 22008–22018.

Jessop, P.G., Jessop, D.A., Fu, D., Phan, L., 2012. Solvatochromic parameters for solvents of interest in green chemistry. Green Chem. 14, 1245–1259.

Judge, M.D., Aab, C., 2013. Ethyl lactate as an environmentally friendly HPLC mobile- phase modifier in the analysis of acetaminophen, caffeine, and ASA. Can. J. Chem. 91, 352–356.

Kamalanathan, I., Canal, L., Hegarty, J., Najdanovic-Visak, V., 2018a. Partitioning of amino acids in the novel biphasic systems based on environmentally friendly ethyl lactate. Fluid Phase Equil. 462, 6–13.

Kamalanathan, I., Petrovski, Z., Branco, L.C., Najdanovic-Visak, V., 2018b. Novel aqueous biphasic system based on ethyl lactate for sustainable separations: phase splitting mechanism. J. Mol. Liq. 262, 37–45.

Kua, Y.L., Gan, S., Morris, A., Ng, H.K., 2016. 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. 4, 21–31.

Kua, Y.L., Gan, S., Morris, A., Ng, H.K., 2018. Optimization of simultaneous carotenes and vitamin E (tocols) extraction from crude palm olein using response surface methodology. Chem. Eng. Commun. 205, 596–609.

Lin, Y., Tanaka, S., 2006. Ethanol fermentation from biomass resources: current state and prospects. Appl. Microbiol. Biotechnol. 69, 627–642.

Lin, Y., Wan, J.-P., Liu, Y., 2020. Synthesis of 3-halochromones with simple KX halogen sources enabled by in situ halide oxidation. New J. Chem. 44, 8120–8124.

Liu, Y., Wen, W., 2015. A clean and practical catalyst free synthesis of keto and aldoximes as well as the Beckmann rearrangement by using ethyl lactate as an environmentally benign medium. Curr. Green Chem. 2, 399–402.

Liu, Y., Wang, H., Wang, C., Wan, J.-P., Wen, C., 2013. Bio-based green solvent mediated disulfide synthesis via thiol couplings free of catalyst and additive. RSC Adv. 3, 21369–21372.

Lomba, L., Giner, B., Zuriaga, E., Moya, J., Lafuente, C., 2013. Self-aggregation of liquids from biomass in aqueous solution. J. Chem. Thermodyn. 66, 131–136.

Lomba, L., Giner, B., Zuriaga, E., Gascon, I., Lafuente, C., 2014. Thermophysical properties of lactates. Thermochim. Acta 575, 305–312.

Manic, M.S., Villanueva, D., Fornari, T., Queimada, A.J., Macedo, E.A., Najdanovic–Visak, V., 2012. Solubility of high-value compounds in ethyl lactate: measurements and modeling. J. Chem. Thermodyn. 48, 93–100.

Micale, F., Albu, F., Iorgulescu, E.-E., Medvedovici, A., Tache, F., 2015. Ethyl lactate as a greener alternative to acetonitrile in RPLC: a realistic appraisal. J. Chromatogr. Sci. 53, 1701–1707.

Minkovska, S., Burdzhiev, N., Alexiev, A., Deligeorgiev, T., 2018. A novel fast green method for the preparation of the squaraine dye 3-oxo-4[(1,3,3-trimethyl-3H-indol- 1-ium-2-yl)methylene]-2-[(1,3,3-trimethylindolin-2-ylidene)methyl]cyclobut-1- enolate, inner salt. Chem. Pap. 72, 1549–1552.

Mondal, D., Chaudhary, J.P., Sharma, M., Prasad, K., 2014. Simultaneous dehydration of biomass-derived sugars to 5-hydroxymethyl furfural (HMF) and reduction of graphene oxide in ethyl lactate: one pot dual chemistry. RSC Adv. 4, 29834–29839.

Moussallem, C., Gohier, F., Mallet, C., Allain, M., Frere, P., 2012. Extended benzodifuran- furan derivatives as example of π-conjugated materials obtained from sustainable approach. Tetrahedron 68, 8617–8621.

Paul, S., Das, A.R., 2012. An efficient green protocol for the synthesis of coumarin fused highly decorated indenodihydropyridyl and dihydropyridyl derivatives. Tetrahedron Lett. 53, 2206–2210.

Pereira, C.S.M., Silva, V.M.T.M., Rodrigues, A.E., 2011. Ethyl lactate as a solvent: properties, applications and production processes – a review. Green Chem. 13, 2658–2671.

Planer, S., Jana, A., Grela, K., 2019. Ethyl lactate: a green solvent for olefin metathesis. ChemSusChem 12, 4655–4661.

Procopio, A., Costanzo, P., Curini, M., Nardi, M., Oliverio, M., Sindona, G., 2013. Erbium (III) chloride in ethyl lactate as a smart ecofriendly system for efficient and rapid stereoselective synthesis of trans-4,5-diaminocyclopent-2-enones. ACS Sustain. Chem. Eng. 1, 541–544.

Rego, Y.F., da Silva, C.M., da Silva, D.L., da Silva, J.G., Ruiz, A.L.T.G., de Carvalho, J.E., Fernandes, S.A., de Fatima, A., 2019. Phthalazine-triones: calix[4]arene-assisted synthesis using green solvents and their anticancer activities against human cancer cells. Arab. J. Chem. 12, 4065–4073.

Salavagione, H.J., Sherwood, J., De bruyn, M., Budarin, V.L., Ellis, G.J., Clark, J.H., Shuttleworth, P.S., 2017. Identification of high performance solvents for the sustainable processing of graphene. Green Chem. 19, 2550–2560.

Shen, G., Zhou, H., Du, P., Liu, S., Zou, K., Uozumi, Y., 2015. Bronsted acid-catalyzed selective C-C bond cleavage of 1,3-diketones: a facile synthesis of 4(3H)- quinazolinones in aqueous ethyl lactate. RSC Adv. 5, 85646–85651.

Sun, Y., Ji, L., Wang, W., Wang, X., Wu, J., Li, H., Guo, H., 2009. Simultaneous removal of polycyclic aromatic hydrocarbons and copper from soils using ethyl lactate- amended EDDS solution. J. Environ. Qual. 38, 1591–1597.

Vaidya, S.P., Shridhar, G., Ladage, S., Ravishankar, L., 2016. A facile synthesis of isoxazolone derivatives catalyzed by cerium chloride heptahydrate in ethyl lactate as a solvent: a green methodology. Curr. Green Chem. 3, 160–167.

Villanueva-Bermejo, D., Reglero, G., Fornari, T., 2017. Recent advances in the processing of green tea biomolecules using ethyl lactate. A review. Trends Food Sci. Technol. 62, 1–12.

Wan, J.-P., Wang, C., Zhou, R., Liu, Y., 2012. Sustainable H2O/ethyl lactate system for ligand-free Suzuki-Miyaura reaction. RSC Adv. 2, 8789–8792.

Wan, J.-P., Cao, S., Jing, Y., 2014. Copper-catalyzed homo- and cross-coupling reactions of terminal alkynes in ethyl lactate. Appl. Organomet. Chem. 28, 631–634.

Wan, J.-P., Zhong, S., Xie, L., Cao, X., Liu, Y., Wei, L., 2016a. KIO3-Catalyzed aerobic cross-coupling reactions of enaminones and thiophenols: synthesis of polyfunctionalized alkenes by metal-free C-H sulfenylation. Org. Lett. 18, 584–587.

Wan, J.-P., Jing, Y., Liu, Y., 2016b. Ethyl lactate mediated thioacetalization of aldehydes at ambient temperature. Phosphorus Sulfur Silicon Relat. Elements 191, 1302–1305.

Wan, J.-P., Cao, S., Hu, C., Wen, C., 2018. Iodine-catalyzed, ethyl-lactate-mediated synthesis of 1,4-benzothiazines via metal-free cascade enaminone transamination and C-H sulfenylation. Asian J. Org. Chem. 7, 328–331.

Xu, Z., Jiang, Y., Zou, S., Liu, Y., 2014. Bio-based solvent mediated synthesis of dihydropyrimidinthiones via Biginelli reaction. Phosphorus Sulfur Silicon Relat. Elements 189, 791–795.

Yang, L., Wan, J.-P., 2020. Ethyl lactate-involved three-component dehydrogenative reactions: biomass feedstock in diversity-oriented quinoline synthesis. Green Chem. 22, 3074–3078.

Yap, C.L., Gan, S., Ng, H.K., 2012. Evaluation of solubility of polycyclic aromatic hydrocarbons in ethyl lactate/water versus ethanol/water mixtures for contaminated soil remediation applications. J. Environ. Sci. 24, 1064–1075.

Yu, Z.-Y., Fang, Q.-S., Zhou, J., Song, Z.-B., 2016. Reusable proline-based ionic liquid catalyst for the simple synthesis of 2-arylbenzothiazoles in a biomass medium. Res. Chem. Intermed. 42, 2035–2045.

Zakrzewska, M.E., Manic, M.S., Macedo, E.A., Najdanovic-Visak, V., 2012. Liquid–liquid equilibria of mixtures with ethyl lactate and various hydrocarbons. Fluid Phase Equil. 320, 38–42.

A.V. Dolzhenko

Sustainable Chemistry and Pharmacy 18 (2020) 100322

14

Zhang, M., Fu, Q.-Y., Gao, G., He, H.-Y., Zhang, Y., Wu, Y.-S., Zhang, Z.-H., 2017. Catalyst-free, visible-light promoted one-pot synthesis of spirooxindole-pyran derivatives in aqueous ethyl lactate. ACS Sustain. Chem. Eng. 5, 6175–6182.

Zhang, M., Chen, M.-N., Zhang, Z.-H., 2019. Visible light-initiated catalyst-free one-pot, multicomponent construction of 5-substituted indole chromeno[2,3-b]pyridines. Adv. Synth. Catal. 361, 5182–5190.

Zhong, S., Liu, Y., Cao, X., Wan, J.-P., 2017. KIO3-Catalyzed domino C(sp2)-H bond sulfenylation and C-N bond oxygenation of enaminones toward the synthesis of 3- sulfenylated chromones. ChemCatChem 9, 465–468.

Zuriaga, E., Giner, B., Ribate, M.P., García, C.B., Lomba, L., 2018. Exploring the usefulness of key green physicochemical properties: quantitative structure–activity relationship for solvents from biomass. Environ. Toxicol. Chem. 37, 1014–1023.

A.V. Dolzhenko