Small Molecules Effective for Conversion of Lignocellulosic Biomass to Furfural and Its Derivatives

Abstract

This review summarizes recent applications of small organic and inorganic molecules as catalysts or solvents (chemical hands and scissors) in the production of furfural (FA), 5-(hydroxymethyl)furfural (HMF), and 5-(chloromethyl)furfural (CMF). The possible transformation of lignocellulosic biomass into a one-pot configuration and two-step technique based on the preliminary separation of hemicellulose, lignin and cellulose with the subsequent hydrolysis of separated polysaccharides is compared and discussed. Interestingly, these rather simple and cheap molecules are catalytically active and enable a high rate of conversion of polysaccharides into furfural and its derivatives. Usually, elevated pressure and reaction temperatures above 150 °C are necessary for effective hydrolysis and dehydration of in situ formed monosaccharides; nevertheless, ionic liquids or deep eutectic solvents enable a significant decrease in the reaction temperature and performance of the discussed process at ambient pressure.

1. Introduction

Non-edible and abundant lignocellulosic biomass is considered among the most promising feedstocks for the production of chemicals, fuels, and materials in the near future [1]. A recent literature survey revealed that global biomass production has reached 170 billion metric tons per year [2]. However, over the years, it has been noticed that the agriculture sector has contributed more significantly to this huge production of biomass. As per a recent data analysis, around 80% of biomass usually comes from crop residues. The major crop residues involved are rice straw and husk, wheat straw, sugarcane bagasse, and corn stover, and there are many other minor residues. Through the literature investigation, it was found that rice, being the third most cultivated grain crop, contributed about 1037 million metric tons of straw annually as waste [3]. Similarly, the global annual production of sugarcane bagasse was estimated to be around 540 million tons, and for corn stover, it was around 909 million tons [4,5]. Moreover, wheat straw obtained after the harvesting of wheat grains has an annual global production of 481 million metric tons [6]. It is estimated that at least 30% of bulk chemicals will be produced from renewable biobased resources by 2050 [7]. Hence, proper disposal mechanisms and complete utilization is highly needed and desirable. Lignocellulosic biomass mainly consists of three polymers: 10–25% lignin, 40–60% cellulose, and 20–40% hemicellulose, along with minor minerals and extractives [8]. Therefore, the valorization of these three polymers into chemicals is critical for the efficient utilization of biomass and has recently received significant attention [9,10]. Cellulose and hemicellulose are polysaccharides that are biochemically synthetized from hexoses and pentoses. After hydrolysis of these polysaccharides, the produced sugars serve as the starting materials for the manufacturing of furan derivatives by acid-catalyzed dehydration.

The remaining lignin serves as a potential renewable source of aromatic compounds, accounting for 10–35% of the weight of the lignocellulosic biomass. The depolymerization of lignin into valuable aromates (phenols, aromatic ketones, benzaldehydes, benzoic acids, etc.) plays an important role in improving the economics of the overall biorefining of mentioned biomass [8,9,10]. Furan-2-aldehydes such as furfural (furan-2-carbaldehyde, FA), 5-(hydroxymethyl)furfural HMF, and its chlorinated analog 5-(chloromethyl)lfurfural CMF are recognized as the most promising sugar-based platform chemicals, which are considered to be general intermediates and feedstocks for the organic fine chemicals and monomers required for polymer applications (

Table 1. Physical properties of furfural and its derivatives.

Heterocycle (Abbreviation) Mr	Structure	M.p. (°C)	B.p. (°C)	Density (g/mL)	Aq. Solubility	Remarks
Furfural (FA) 96.1 g/mol		−37	162	1.16	8.3 g/100 mL	Sol. in EtOH Insol. in alkanes
5-hydroxymethyl-furfural (HMF) 126.1 g/mol		30–34	114–116/1 mm Hg	1.29	Soluble	Sol. in alcohols, acetone, esters
5-chloromethyl-furfural (CMF) 144.5 g/mol		37–39	137–138/5 mm Hg	1.24	Soluble	Sol. in alcohols, MIBKtoluene, 1,2-DCE, CH2Cl2 Ph-Xs, Ph-OMe, CPME

) [11,12]. Small molecules, acting as cheap and recyclable solvents, and catalytically active sustainable compounds should be used for the economically acceptable production of the aforementioned furan-based platform chemicals used as substitutes for crude oil-based chemicals. In order to reach the corresponding techno-economic benefits, sustainable production should avoid toxic and non-biodegradable chemicals and highly energy-demanding processes that enable the application of circular economy principles.

2. Utilization of Hemicellulose from Lignocellulosic Biomass for Furfural Production

Hemicellulose functions as the link between cellulose (bound through the hydrogen bonds) and lignin (bound through the covalent bonds).

Hemicellulose is the most simply separable component from the cell walls of lignocellulosic biomass and can be hydrolyzed to pentoses such as xylose and arabinose and/or xylo-oligosaccharides, which can be dehydrated to the simplest furan-2-carbaldehyde, furfural FA (see Figure 1). For both hydrolysis and subsequent dehydration, small molecules such as Broenstedt or Lewis acids have a crucial catalytic effect as “molecular scissors” [13].

Temporarily, furfural has been industrially produced from lignocellulosic feedstocks on a commercial scale since 1921, using mineral acids (typically using cheap hydrochloric acid HCl or sulfuric acid H₂SO₄) as catalysts in quantities around 200,000 tons/year [14].

Producers conventionally applied a catalyzed two-step percolation process using dilute sulfuric acid for furfural production. In the first step, xylans present in lignocellulosic biomass such as sugarcane (contain ca. 26.5% of hemicellulose) are hydrolyzed to xylose and the insoluble part containing lignin and cellulose is filtered. Xylose dissolved in filtrate is dehydrated in the subsequent reaction step, producing furfural. The furfural formed is recovered by steam distillation and fractionation. Recently, furfural is produced in a yield of ca. 40–50% of the theoretical maximum [15,16].

The production of furfural is performed in a continuous or batch mode. The suitable biomass-based sources for furfural production are feedstocks containing xylan, mainly sugarcane bagasse, crop straws or corncob [17].

2.1. One-Pot Processes for Furfural Production

The advantage of one-pot production of furfural from hemicellulose-rich lignocelluloses is the simple performance in one reactor equipped with a distillation column to remove produced furfural by steam distillation. Both acid-catalyzed hydrolysis of hemicellulose and dehydration occur side-by-side.

The disadvantages of the one-pot process are (a) the necessity to use harsh reaction conditions (at least 160 °C); and (b) the parallel hydrolysis of cellulose and partial dissolution of lignin that occur in lignocellulosic biomass.

Typical reaction temperatures for one-pot furfural production from lignocellulosic biomass vary between 190 and 210 °C when using diluted aqueous acid catalyst(s), including under elevated pressure.

Concentrated acid hydrolysis applies concentrated mineral acid solutions (typically sulfuric or hydrochloric acid), enabling hydrolysis of hemicellulose even at lower reaction temperatures (100–150 °C) and atmospheric pressure. Zhou et al. compared yields of soluble sugars in different processes based on hydrolyses of lignocellulosic biomass [18].

The advantage of concentrated hydrochloric acid is sufficient volatility for its simple recycling by distillation (Bergius-Rheinau process) [19].

However, the yield of sugars is significantly lower (probably due to the formation of chlorinated by-products) in the case of HCl compared with processes that apply sulfuric acid (Hokkaido process, Bellamy and Holub, Harmer and Sabesan) [20,21,22]. On the other hand, the application of concentrated sulfuric acid solutions for biomass hydrolysis is accompanied by the production of huge quantities of gypsum formed through the neutralization of H₂SO₄ with lime.

Phosphoric acid can efficiently disrupt recalcitrant lignocellulose structures at concentrations above 83% at 50 °C for one hour of action [23]. However, even H₃PO₄ is not distillable, causing problems with possible recycling.

Instead of the above-mentioned problems, strong mineral acid-catalyzed processes pose the following problems: corrosion of used equipment; difficult recovery from the reaction mixture; environmental pollution; and health risks.

Due to these reasons, simpler recyclable or at least biodegradable organic acids were tested as substituents of strong mineral acids (

Table 2. Small molecules (agents and solvents) effective in one-pot furfural production.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Aqueous solution of hydrochlorid acid	Aq. HCl	102 (4%HCl)–110 (21%HCl)	1.02 (4%HCl)–1.10 (20.4%HCl)	Miscible	Reagent and solvent	[18,19,24]
Aqueous solution of sulfuric acid	Aq. H2SO4	101 (4% H2SO4)–108 (30% H2SO4)	1.02 (4% H2SO4)–1.22 (30% H2SO4)	Miscible	Reagent and solvent	[18,19,20,21,22,25]
Concentrated phosporic acid	85% H3PO4	213 (decomp.)	1.69 (85% H3PO4)	Miscible	Reagent and solvent	[23]
Aqueous solution of sodium chloride	Aq. NaCl	101.6 (10%)–104.6 (25%)	1.07 (10% aq.NaCl)–1.2 (26% aq.NaCl)	Miscible	Reagent	[26]
Tetrahydrofuran		65–66 (64 azeotrope with 6% H2O)	0.89	Miscible (sparingly miscible in aq. NaCl)	Solvent and extractant	[26]
Formic acid	HCOOH	100.7	1.22	Miscible	Reagent	[26]
Sulfanilic acid (solid)		280 (decomp.)	1.49	1 g/100 mL (6.67 g/100 mL at 100 °C)	Reagent	[27]
Ferric chloride (solid)	FeCl3	315 (Hexahydrate decomp. 280)	2.9	Higly soluble (97 g/100 mL)	Lewis acid (reagent)	[17,28]
Acetic acid	CH3COOH	118.1	1.05	Miscible	Reagent	[17,28]
1-butyl-3-methylimidazolium chloride (IL)		Decomp. above 246 °C (Melting point: 41)	1.08	Soluble	Solvent	[29]

).

The highest yields of furfurals (FA 7.3 wt.%, HMF 10.6 wt.%, and 5-methylfurfural 17.8 wt.%) were obtained in the presence of formic acid in a water-tetrahydrofuran-NaCl biphasic system at 200 °C. Formic acid acted as the catalyst for hydrolysis and dehydration, while THF acted as the protector for the formed furfurals in the water-tetrahydrofuran-NaCl biphasic system. Furthermore, the increase in reaction temperature or the addition of NaCl promoted the conversion of saccharides into furfurals and the formation of levulinic acid [26].

Mirzae and Karimi used sulphanilic acid as a recyclable bifunctional organocatalyst in a biphasic solvent system and reported the production of HMF and FA in yields approaching 41% and 41–50%, respectively, from untreated straw and barley husk at 150 °C in 60 min [27].

Nevertheless, a yield of FA around 70–80% with selectivity above 70% is achieved under semi-batch process conditions using FeCl₃ in the co-action of aqueous AcOH vapours with lignocellulose/aq. FeCl₃ in a fixed bed at 190 °C [17,28].

Anhydrous conditions using convenient ionic liquid (IL), such as BMIMCl, in co-action with the Lewis acid CrCl₃ were also tested with the aim of increasing the overall yield of furan aldehydes from lignocellulosic biomass such as pine wood, rice straw and corn stalk. Both 5-hydroxymethylfurfural and furfural were obtained in yields of 45–52% (HMF) and 23–31% (FA), respectively, by applying microwave heating [29] (Table 2).

Corn stover heated with the ionic liquid mixture EMIMCl in co-action with a mixture of CrCl₃/HCl in N,N-dimethylacetamide was transformed into 48% HMF and 34% FA after 2 h of action at 140 °C. The addition of EMIMCl significantly increased the yield of furan2-aldehydes directly produced from crude biomass (corn stover) [30] (

Table 3. Small molecules (agents and solvents) effective in one-pot furfural production.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Chromium chloride	CrCl3	950 (subl.)	2.8	Sparingly soluble	Lewis acid (reagent)	[30]
Dimethyl acetamide	CH3CON(CH3)2	165	0.94	Miscible	Solvent	[30]
1-ethyl-3-methylimidazolium chloride (IL)		Decomp. above 246 °C (M.p.: 80)	1.12	Soluble	Solvent	[30]
Aluminium chloride	AlCl3 or AlCl3·6H2O	180 (M. p.: 100 hexahydrate)	2.44 (2.4 hexahydrate)	Soluble (45 g/100 mL)	Lewis acid	[31]
Tin(IV) chloride (liquid)	SnCl4	114 (M.p.: 56 pentahydrate)	2.22 (2.04 pentahydrate)	Anhydrous reacts with H2O; pentahydrate miscible	Lewis acid	[31]
Tellurium chloride (solid)	TeCl4	390 (M.p.: 224)	3.26	Anhydrous reacts with H2O		[31]
Choline chloride (solid)		Nondistillable (M.p.: 302 with decomp.)	1.2	Miscible	Component of DES	[32]
Oxalic acid (solid)	(COOH)2 or (COOH)2·2H2O	Decomp. (M.p.: 189.5) (M.p.: 101.5 dihydrate)	1.9 (1.65 dihydrate)	10 g/100 mL	Acid and/or component of DES	[32]

).

The performance of different Lewis acids such as FeCl₃, AlCl₃, SnCl₄, and TeCl₄ as catalysts was investigated in an aqueous choline chloride-oxalic acid (16.4 wt.% H₂O) deep eutectic solvent (DES) system for producing FA from oil palm fronds (OPFs). By action of 2.50 wt.% SnCl₄ in an aqueous DES reaction mixture (120 °C, 45 min), a furfural yield of 59.4% was obtained [31].

Deep eutectic solvents serve as cheap nonvolatile solvents comparable to ILs. They are applicable for the effective separation of lignin and hemicellulose from lignocellulosic biomass.

At 100 °C, the aqueous choline chloride-oxalic acid (1:1 M ratios) mixture containing 16.4 wt.% H₂O caused the highest FA yield of 26.34% and provided cellulose compositions up to 72.79% in the reacted oil palm fronds OPF (using 1 g OPF/110 mmol DES). The compositions of raw OPF (dry weight basis) used in this study were glucan (45.00 ± 0.45%), xylan (19.79 ± 0.63%), arabinan (0.77 ± 0.44%), lignin (19.53 ± 0.08%), ash (0.40 ± 0.21%), water extractives (11.33 ± 0.71%), and ethanol extractives (3.77 ± 0.49%) [32]. However, the recycling of non-distillable ionic liquid or DES is tremendous, generally. In addition, the application of soluble heavy metal salt such as CrCl₃ is questionable due to the environmental risks. Generally, one-pot production of furfural from lignocellulosic biomass is accompanied by the hydrolysis of cellulose and subsequent dehydration of produced hexoses to HMF. The formation of unstable HMF is accompanied by resinification and the production of humins by the side reactions. Humins are not utilizable in chemical industry. In addition, some by-products formed during mineral acid-catalyzed reactions are toxic for microorganisms, which prevents the utilization of residual organic matter in fermentation processes (Scheme 1).

Deep eutectic solvents serve as cheap nonvolatile solvents comparable to ILs. They are applicable for the effective separation of lignin and hemicellulose from lignocellulosic biomass (Table 3).

In summary, the utilization of pentoses from hemicellulose in one-pot processes is limited due to the side reactions of other parts of lignocellulosic biomass. Residues of treated lignocellulosic biomass obtained through the one-pot production of FA are not simply applicable to produce other organic platform chemicals. This factor significantly decreases the atom economy of the one-pot processes mentioned.

Due to these reasons, prior separation of hemicellulose from other parts of lignocellulosic biomass seems to be crucial for high-yield FA production and for the subsequent utilization of cellulose and lignin for organic chemical production according to the biorefinery concept.

2.2. Role of Small Molecules in Separation of Hemicellulose from Lignocellulosic Biomass

To ensure profitable production of FA, the harvesting of valuable co-products is vital. Integrated production of furfural, together with glucose and/or ethanol (produced from hydrolyzed cellulose), is often mentioned. For this purpose, the separation of hemicellulose before the subsequent hydrolysis and dehydration step is usually included [17,33,34]. Even though hemicellulose is the most simply separable component from the cell walls of lignocellulosic biomass, there are virtually no procedures that can extract hemicellulose completely without dissolving part of lignin and/or cellulose [35].

The hemicellulose in plant cell walls is separated by breaking the hydrogen bonds between cellulose and hemicellulose and the ester bonds between lignin and hemicellulose. Various methods and reagents have been used to isolate hemicellulose from lignocellulosic biomass (Table 4).

Typically, the widely used Kraft process (action of NaOH/Na₂S at 170 to 176 °C during approximately 2 h) in the modern pulp and paper industry separates insoluble cellulose and burns the extracted soluble mixture of hemicellulose together with Kraft lignin to produce steam. However, the calorific value of the hemicellulose is low (13.6 MJ/kg) and accounts for half of the lignin. This kind of hemicellulose is underutilized, which is a great waste of resources [36,37].

Hemicellulose is potentially separated from lignocellulosic biomass by dissolution, which is often accompanied by hydrolysis. In addition, hemicellulose in a hydrolysate mixture can be isolated and purified. The dissolution of hemicellulose from biomass is called separation and the isolation of hemicelluloses is called extraction.

Nevertheless, the hydrolysis accompanying the dissolution of hemicellulose is not problematic because of the subsequent dehydration of the obtained pentoses to furfural. Efficient separation is fundamental to the high-value utilization of hemicellulose for furfural production [36,37].

The simplest way for hemicellulose separation from lignocellulosic biomass is the process of hydrothermal extraction, which is based on the action of pressurized water at 170–180 °C. The cooling of the hot aqueous extract, accompanied by the addition of a precipitating agent (for example, ethanol), enables the isolation of the precipitated hemicellulose. The hydrolyzed sugars remain in filtrate [38].

Yao et al. extracted hemicellulose by the hydrothermal treatment and co-action of NaOH. To reduce the degradation of cellulose and obtain a high molecular weight of hemicellulose from the extracts, a pH pre-corrected hot water pretreatment (temperature 170 °C for 60 min) was developed by employing sodium hydroxide (3.9 mol/L), resulting in extracts with a pH of about 4. The yield of extracted hemicellulose was estimated to be ca. 43% under the optimum reaction conditions. In this case, the addition of NaOH buffered the produced uronic acids [39].

Aqueous magnesium chloride has also been investigated as a hemicellulose separating agent. The results showed that the pretreatment using 0.2 mol/L aqueous MgCl₂ had a strong degradation effect on hemicellulose, whose removal rate was nearly 100% at 210 °C for 20 min [40].

However, the above-mentioned hydrothermal methods are highly energy-demanding processes.

Generally, alkali treatment is an effective extraction method, especially at elevated temperatures [36,41].

On the contrary, when applying an alkali extraction at higher temperatures, the extracted hemicellulose contains more lignin, which is difficult to separate [42].

It is known that diluted alkali metal hydroxide causes the swelling of cellulose, hydrolysis of ester linkages, and disruption of intermolecular hydrogen bonds between cellulose and hemicelluloses, dissolving a portion of the hemicellulose [43].

The more concentrated solution of alkali metal hydroxide results in higher yields of extraction when performed at room temperature, indicating a disruption of stronger linkages, such as ferulic acid bridges between hemicelluloses and lignin [44].

The optimum alkaline treatment was achieved using 2 M NaOH at 80 °C for the extraction of hemicellulose from three different wood pulps [45].

In this case, the lower energy consumption is compensated for by the action of quantities of hard alkali metal hydroxide base. Nevertheless, the subsequent dehydration of the separated mixture of hemicellulose, xylose, and xylo-oligosaccharides requires acid catalyst(s), which disfavors the application of alkali metal hydroxides for the isolation of hemicelluloses from biomass. It is well known that hemicellulose is separated and degraded to monosaccharides by inorganic acid treatment, especially at temperatures ranging from 150 to 180 °C and when using cheap 0.3–5% sulfuric acid [25]. This is actually an efficient separation of hemicellulose and not an extraction method; instead, it serves as an isolation method for oligo- and/or monosaccharides.

The addition of suitable ether to a strong aqueous Broenstedt acid, like hydrochloric acid, suppresses the hemicellulose hydrolysis. Using a 2M aqueous HCl/dioxane mixture (1:9, v/v) seems to be one of most effective and efficient techniques for hemicellulose isolation at lower temperatures (40–85 °C) after a few hours of action using a solvent/dried biomass ratio of 25 mL per gram [24].

Using the more environmentally benign method, hemicellulose was efficiently separated by organic acid treatment. Li et al. used acetic acid (AcOH) in a pressurized H₂O/CO₂ mixture to extract hemicellulose. The carbonic acid (formed in situ) and acetic acid catalyzed the selective hydrolysis of hemicellulose. However, this method suffers from high energy consumption due to the necessity of using a high temperature (180 °C) (Table 4) [46,47].

Glycolic acid (in an optimal 5.40% aq. solution) was the other carboxylic acid described in the literature as an effective agent in aqueous solutions for the isolation of hemicellulose at a lower temperature (140 °C/3 h). This acid is recyclable by distillation and the recovery rate of glycolic acid is 91%. The depolymerization and repolymerization of lignin are inhibited and the integrity of the cellulose structure is preserved. Compared to formic acid, the yield of xylose increased to 10.33% while that of lignin decreased to 11.08%. It shows high selectivity for hemicellulose separation, yielding 65.48% hemicellulose with 72.08% purity [48].

The effective action of tropic (3-hydroxy-2-phenylpropanoic) acid was demonstrated under optimized conditions (5% aq. tropic acid, 160 °C, 80 min). Hemicellulose was separated and hydrolyzed to xylose and oligo-xylosaccharides in the tropic acid-catalyzed hydrothermal pretreatment of eucalyptus. The maximum yield of hemicellulose-derived sugars was 85.78% with ca. 71% xylose selectivity (based on the total xylose in raw material) using the mentioned conditions [49].

Oxalic acid was evaluated as an alternative reagent to commonly used mineral inorganic acids in the pretreatment of corncob to achieve a high xylose yield in addition to a highly digestible solid residue. The xylose yield reached above 94% under the pretreatment condition of 140 °C for 40 min with 0.5 wt.% oxalic acid at a solid loading of 7.5% [50].

Maleic acid has been discovered to be a good catalyst for hydrolyzing hemicellulose to yield xylose at high yields, due to the low degradation of the xylose. Using 20 mL of aqueous maleic acid (0.25 M (pH 1.26) per 1.2 g of dry biomass), the suspension was processed at 160 °C for 19 min [51].

Hemicellulose together with a part of lignin is soluble by the action of a mix of acetic acid and formic acid (65/35 mass ratio, 85% in water) used in a total volume of 3.0 L per 289 g of dry wheat straw after treatment at 105 °C for 3 h [52].

A formic acid/water binary solvent extraction was used to extract hemicellulose-derived saccharides from poplar wood. To reduce cellulose hydrolysis and facilitate downstream xylose crystallization, mild conditions at 90 °C and 4 h were recognized as the optimal choice, which led to a xylose yield above 73%. The concentration of HCOOH in the aqueous mixture used was 72%, lower than azeotrope level of 77.5%. This means that the formic acid/water solvent used could be recycled after being concentrated to a working level though fractional distillation. This extraction process has high feasibility for industrial application since the low boiling point of the HCOOH/water azeotrope (below 100 °C allows simple for the recovery and concentration of used solvent. In addition, its high extraction selectivity enables further utilization of the remaining cellulose [53] (Table 4).

Table 4. Small molecules (agents and solvents) effective in hemicellulose separation processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Aq. solution of sodium hydroxide	Aq. NaOH	106 (10%NaOH)–119 (40%NaOH)	1.11 (10%NaOH)–1.43 (10%NaOH)	Miscible	Reagent	[36,37,39,41,42,43,44,45]
Aqueous solution of sodium sulfide	Aq. Na2S	100	1.58 (pentahydrate)	18.6 g/100 mL	Reagent and solvent	[36,37]
Magnesium chloride hexahydrate	MgCl2·6H2O	102.2 (10% MgCl2) 106.5 (25% MgCl2) 120.4 (50% MgCl2)	1.57 (hexahydrate)	54.3g MgCl2/100 mL	Reagent	[40]
dioxane		101.3	1.03	Miscible	Solvent	[24]
Glycolic acid (solid)	HOCH2COOH	100 (with decomp.) M.p.:79–80	1.49	70% solution	Acid catal. reagent	[48]
Tropic acid (solid)		322.5 (M.p.: 116)	1.26	5% solution	Acid catal. reagent	[49]
Oxalic acid (solid)	(COOH)2 or (COOH)2·2H2O	Decomp. (M.p.: 189.5) (M.p.: 101.5 dihydrate)	1.9 (1.65 dihydrate)	10 g/100 mL	Acid catal. and/or component of DES	[50]
Maleic acid (solid)		Decomp. (M.p.: 130.5)	1.59	47.8 g/100 mL	Acid catal. reagent	[51]
Formic acid	HCOOH	100.7	1.22	Miscible	Acid catal. reagent	[47,52,53]
Acetic acid	CH3COOH	118.1	1.05	Miscible	Acid catal. reagent	[52]

Table 4. Small molecules (agents and solvents) effective in hemicellulose separation processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Aq. solution of sodium hydroxide	Aq. NaOH	106 (10%NaOH)–119 (40%NaOH)	1.11 (10%NaOH)–1.43 (10%NaOH)	Miscible	Reagent	[36,37,39,41,42,43,44,45]
Aqueous solution of sodium sulfide	Aq. Na2S	100	1.58 (pentahydrate)	18.6 g/100 mL	Reagent and solvent	[36,37]
Magnesium chloride hexahydrate	MgCl2·6H2O	102.2 (10% MgCl2) 106.5 (25% MgCl2) 120.4 (50% MgCl2)	1.57 (hexahydrate)	54.3g MgCl2/100 mL	Reagent	[40]
dioxane		101.3	1.03	Miscible	Solvent	[24]
Glycolic acid (solid)	HOCH2COOH	100 (with decomp.) M.p.:79–80	1.49	70% solution	Acid catal. reagent	[48]
Tropic acid (solid)		322.5 (M.p.: 116)	1.26	5% solution	Acid catal. reagent	[49]
Oxalic acid (solid)	(COOH)2 or (COOH)2·2H2O	Decomp. (M.p.: 189.5) (M.p.: 101.5 dihydrate)	1.9 (1.65 dihydrate)	10 g/100 mL	Acid catal. and/or component of DES	[50]
Maleic acid (solid)		Decomp. (M.p.: 130.5)	1.59	47.8 g/100 mL	Acid catal. reagent	[51]
Formic acid	HCOOH	100.7	1.22	Miscible	Acid catal. reagent	[47,52,53]
Acetic acid	CH3COOH	118.1	1.05	Miscible	Acid catal. reagent	[52]

Methanesulfonic acid (MSA) used in a 0.1 M aq. solution at 180 °C for 20 min proved to be very effective for the hydrolysis and dehydration of hemicellulose and also in producing furfural. The higher MSA concentration (0.3 M solution) is more effective for the rapid hydrolysis of cellulose at 180 °C for 40 min of action and results in levulinic and formic acid formation [54].

Different arenesulfonic acids, including benzenesulfonic acid, phenolsulfonic acid, 4-chlorobenzenesulfonic acid, p-toluenesulfonic acid (PTSA), and 5-sulfosalicylic acid [55] were compared to consider effectivity of hemicellulose extraction. Concentrated aq. benzenesulfonic acid and p-toluenesulfonic acid (conc. 60–80 wt.%) were compared for extraction of hemicellulose and lignin from eucalyptus-based wood. After treatment at 80 °C for 20 min, 70% benzenesulfonic acid was recognized as the most effective for hemicellulose dissolution and delignification of this type of biomass [56].

Bagasse hemicellulose was efficiently separated and extracted by using a 3% aq. PTSA treatment at 80 °C for 120 min, using bagasse and the 3% aq. PTSA treatment at a ratio of 1:20 (w/v). The hydrolysis of polysaccharides was inhibited during the treatment [57].

Mixtures of organic solvents with diluted aqueous acid solutions work effectively in the dissolution of lignocellulosic biomass above 120 °C. However, the selectivity for hemicellulose is not high.

The best selectivity for hemicellulose (ca. 60%) and lignin (ca. 40%) extraction was observed in the case of 80% DMSO in 2% aq. H₂SO₄ at 120 °C after 30 min of action together with 0.5–1% cellulose.

The 2% aq. H₂SO₄ solution alone dissolved only ca. 20% hemicellulose, ca. 30% lignin and 0.5–1% cellulose under identical treatment conditions.

The mixture of 80% 1-pentanol in 2% aq. H₂SO₄ provided even better extraction efficiencies; however, the selectivity for hemicellulose was low. The compound 1-Pentanol is available from renewable resources as undesirable byproduct of alcohol fermentation.

Other solvents (glycerol, toluene, pentane) in the same ratios (4 vol. parts of solvent together with 1 vol. part of 2% aq. H₂SO₄) were tested, with significantly worse results.

The ratio of aqueous treatment solution to lignocellulosic biomass (bamboo particles) for all the above-mentioned organosolvent pretreatments was 6:1 (mL: g) [58].

An aqueous mixture of green polar aprotic solvent γ-valerolactone (GVL) at 160 °C separates insoluble cellulose and soluble xylans and lignin. Water present in the mixture promoted the cleavage of chemical bonds linking hemicellulose, lignin, and cellulose in lignocellulosic biomass. The γ-Valerolactone helped the co-dissolution of hemicellulose (93.6 wt.%) and lignin derivatives (80.2 wt.%), leaving a high-purity insoluble cellulose (83.3 wt.%) [59].

Higher selectivity for hemicellulose extraction was obtained even when using nonaqueous reaction systems.

Switchable ionic liquids (SILs) prepared from hexanol or butanol mixed with an amidine (1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU)) and saturated with CO₂ were investigated as dissolution/fractionation solvents for spruce wood Scheme 2 [60].

After 120 h of treatment at 55 °C, the undissolved fraction contained 38 wt.% less hemicelluloses compared to native spruce. Only about 2% of the lignin was removed from the native wood [60].

Imidazole was found to be effective for the common extraction of hemicellulose (ca. 77%) and cellulose (87%) from cotton spinning residues using a constant imidazole/biomass mass ratio of 9:1 (dry basis) at 120 °C for 1 h. The yield of extracted lignin under these conditions is only ca. 12% [61].

The effective extraction of xylans from Eucalyptus globulus wood using aqueous solutions of choline chloride/urea-derived DES was demonstrated, including the recycling of used DES and the separation of dissolved hemicellulose [62]. The other effective DES described in the literature is the eutecticum of 90% lactic acid/choline chloride/water [63].

DESs containing choline chloride (ChCl)- and CaCl₂·6H₂O or MgCl₂·6H₂O were effectively used for the pretreatment of oil palm fronds (OPF). Under atmospheric conditions, pretreatment with ChCl:CaCl₂·6H₂O = 1:2 (125 °C and 4.5 h) resulted in dual biomass valorization effects with a delignification of 46.51%, followed by xylose recovery and xylan removal at 54.12% and 78.67%, respectively (Table 5) [64].

A three-component deep eutectic solvent containing choline chloride-oxalic acid (molar ratio 1:1) + 2 wt.% ethylene glycol can remove 91% of xylan under a solid to liquid ratio of 1:10 (w/v) at 130 °C/6 h from bamboo residues [65].

One interesting example of hemicellulose mining is based on the extraction of Kraft cellulose (paper-grade Kraft cellulose contains additional hemicellulose (26 wt.%)) and lignin (6 wt.%) with DESs based on equimolar mixtures of choline acetate with imidazol or levulinic acid. The authors prove the highly efficient dissolution of residual hemicellulose and lignin from Kraft cellulose at 80 °C/24 h. The saturated DES phase is treated with ethanol for selective precipitation of hemicellulose. The filtrate obtained after the removal of ethanol is diluted with water for the precipitation of lignin. From the diluted aqueous DES filtrate, the DES phase was recycled by evaporating the water (

Table 6. Small molecules (agents and solvents) effective in hemicellulose separation processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Choline chloride/ Oxalic acid = 1:1 (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	DES	[66]
Choline acetate/ imidazol = 1:1 (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	DES	[66]
Choline acetate/ Levulinic acid = 1:1 (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	DES	[66]
Ethanol	CH3CH2OH	78.3	0.789	Miscible	Biobased precipita-tion agent	[66]

) [66].

Table 5. Small molecules (agents and solvents) effective in hemicellulose separation processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Methanesulfonic acid (liquid)	CH3SO3H	167 (M.p.: 17–19)	1.48	Miscible	Acidic catal.	[54,67]
Benzenesulfonic acid (solid)		190 (M.p.: 51)	1.32	Soluble (45 g/100 mL)	Acidic catal.	[55,56]
Toluenesulfonic acid monohydrate (solid)		Decomp. (M.p.: 105–107)	1.24	67 g/100 mL	Acidic catal.	[55,56,57]
Dimethyl sulfoxide		189	1.1	Miscible	Biobased solvent	[58]
1-pentanol	CH3CH2CH2CH2CH2OH	138	0.81	2.2 g/100 mL	Biobased solvent	[58]
γ-valerolactone		205	1.05	1 g/100 mL	Biobased aprotic solvent	[59,68]
DBU (diazabicyclo(5,4,0)-undec-7-ene)		261 (M.p.: −70)	1.02	Insoluble	Base reagent Component of protic IL	[60]
Imidazole		257 (M.p.: 89)	1.23	63.3 g/100 mL	Base reagent	[61]
Choline chloride/urea = 1:2 (solid)		Decomp. (M.p.: 12)	0.95	Miscible	DES	[62]
Choline chloride/ CaCl2·6H2O = 1:2 (solid)		Decomp. (M.p.: 2.7)	1.37	Miscible	DES	[64]

Table 5. Small molecules (agents and solvents) effective in hemicellulose separation processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Methanesulfonic acid (liquid)	CH3SO3H	167 (M.p.: 17–19)	1.48	Miscible	Acidic catal.	[54,67]
Benzenesulfonic acid (solid)		190 (M.p.: 51)	1.32	Soluble (45 g/100 mL)	Acidic catal.	[55,56]
Toluenesulfonic acid monohydrate (solid)		Decomp. (M.p.: 105–107)	1.24	67 g/100 mL	Acidic catal.	[55,56,57]
Dimethyl sulfoxide		189	1.1	Miscible	Biobased solvent	[58]
1-pentanol	CH3CH2CH2CH2CH2OH	138	0.81	2.2 g/100 mL	Biobased solvent	[58]
γ-valerolactone		205	1.05	1 g/100 mL	Biobased aprotic solvent	[59,68]
DBU (diazabicyclo(5,4,0)-undec-7-ene)		261 (M.p.: −70)	1.02	Insoluble	Base reagent Component of protic IL	[60]
Imidazole		257 (M.p.: 89)	1.23	63.3 g/100 mL	Base reagent	[61]
Choline chloride/urea = 1:2 (solid)		Decomp. (M.p.: 12)	0.95	Miscible	DES	[62]
Choline chloride/ CaCl2·6H2O = 1:2 (solid)		Decomp. (M.p.: 2.7)	1.37	Miscible	DES	[64]

In summary, the above-described separation and/or isolation processes enable the removal of most labile hemicellulose, usually together with part of the lignin, by dissolution. This produces adequately pure insoluble cellulose for further processing.

2.3. Role of Small Molecules in Hydrolysis and Dehydration of Extracted Hemicellulose

Further conversion of isolated hemicellulose fractions to FA usually requires quite harsh reaction conditions using different small molecule-based catalysts or solvents (

Table 7. Small molecules (agents and solvents) effective in hemicellulose hydrolysis and xylose dehydration processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility (at R.T.)	Role	Ref.
Methanesulfonic acid (liquid)	CH3SO3H	167 (M.p.: 17–19)	1.48	Miscible	Acidic catal.	[67]
γ-valerolactone		205	1.05	1 g/100 mL	Biobased aprotic solvent	[68,69]
Toluene		110.6	0.87	Immiscible	Aromatic extractant	[68]
1-butyl-3-methylimidazolium hydrogensulfate		Decomp. (M.p.: n.d.)	n.d.	Miscible	Acidic IL Reagent and solvent	[70]
Methyl-isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Extractant	[70]
1-ethyl-3-methylimidazolium bromide SnCl4		Decomp. (M.p.: n.d.)	n.d.	Miscible	Acidic IL Reagent and solvent	[71]
Triethylammonium hydrogensulfate		Decomp. (M.p.: n.d.)	n.d.	Miscible	Acidic IL Reagent and solvent	[72]
Choline chloride/ Oxalic acid = 1:1 (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	DES	[69]
Choline chloride/ PTSA = 1:1 (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	DES	[69,73]
1-chlorobutane	CH3CH2CH2CH2Cl	78	0.89	Immiscible (0.5 g/L)	Extractant	[74]
2-methyl-tetrahydrofuran		80.2	0.854	14 wt.%	Extractant solvent	[75]
Choline glycinate (solid)		Decomp. (M.p.: n.d.)	n.d.	Miscible	IL	[76]

).

Methanesulfonic acid MSA used in a 0.1 M aq. solution at 180 °C and 20 min was proved to be very effective for the hydrolysis and dehydration of hemicellulose and also in producing furfural. A higher MSA concentration (0.3 M solution) is more effective for the rapid hydrolysis of cellulose at 180 °C for 40 min of action and results in levulinic and formic acid formation [54].

Luo et al. tested an aqueous solution of γ-valerolactone GVL for the smooth separation of soluble xylans and lignin from insoluble cellulose at 160 °C [59].

Horvath et al. mentioned GVL as a both suitable and sustainable solvent applicable for one-pot production of additional GVL through the acid-catalyzed dehydration of hemicellulose and the subsequent transfer hydrogenation of FA caused by formic acid [67].

Mixtures of aqueous GVL with aromatic hydrocarbons Ar-Hs were recognized as effective extractants for hemicellulose and lignin at 160 °C, with advantageous partitioning of the low polar aromatic hydrocarbon phase containing FA and the aqueous GVL phase saturated with dissolved carbohydrates (including xylose) at room temperature (ratio GVL:water:Ar-H = 60:20:20 by weight). Repeated extraction of the obtained aqueous phase enables the simple recycling of used GVL and easier potential biological utilization of the aqueous solution of carbohydrates obtained for ethanol production, etc. [68].

Aqueous solutions of acidic ionic liquids, such as 1-butyl-3-methylimidazolium hydrogen sulfate (0.847 mol [BMIM]HSO₄/L aqueous phase) or 1-(3-sulfopropyl)-3-methylimidazolium hydrogen sulfate (0.49 mol C₃SO₃HMIM]HSO₄/L aqueous phase) mixed with MIBK, were evaluated for effective hydrolysis and dehydration of a mixture of xylan and xylose (the liquid phase from hydrothermal treatment containing 4–10 g/L of xylose) at 180 °C for 30 min [70].

A furfural yield in the range of 68–71% was obtained at a high xylose loading (20 wt.%) from the single-phasic reaction system whereby SnCl₄ (10 mol%) or a mixture of 5 mol% SnCl₄ and 5 mol% MgCl₂ were used as the Lewis acid catalyst and ionic liquid 1-ethyl-3-methylimidazolium bromide (EMIMBr) was used as the reaction medium.

The EMIMBr/SnCl₄ system with appropriate water was also tested as efficient to convert xylan or even corn stalk into furfural in 54–57% yields [71].

The remarkably low-cost IL triethylammonium hydrogen sulfate Et₃N·H₂SO₄ was satisfactorily evaluated for the fractionation of the grass Miscanthus x giganteus into a cellulose rich pulp and solution of hemicellulose (100%) and lignin (85%) at 120 °C with a 1:10 solids loading (80% aq. Et₃N·H₂SO₄). The hemicellulose was dissolved mainly in monomeric form, and the pentoses were partially converted into furfural under these conditions [72].

Using different DESs, the best results for hemicellulose transformation with a higher yield of furfural were obtained using 50 mmol DES (ChCl/PTSA (1:1) or ChCl/oxalic acid (1:1.2)) per gram of xylan at pH 1.0 for 1.5 h at 120 °C with GVL used as the optimal reaction solvent [69].

2.4. Examples of Two-Step Furfural Production Processes

Bao et al. described several profitable integrated lignocellulosic biomass treatment processes to produce furfural and other commercially utilizable products such as lignin, glucose, and/or ethanol [17].

Poveda-Giraldo et al. published a biorefinery process for the production of furfural and levulinic acid from hemicellulose, cellulose, and phenolic compounds such as vanillin and syringaldehyde from lignin. Rice husks were used in this process as the raw material [33].

The dilute acid-wet air oxidation (DA-WAO) sequence was proved for biorefinery design as it is possible to solubilize up to 80% of hemicellulose during the first stage and subsequently fractionate almost 90% of lignin after the second stage. The insoluble part of DA-WAO treated solid includes a high cellulose content. The isolated lignocellulosic fractions were used as platform products to obtain furfural, levulinic acid, and phenolic compounds. As a main result, yields and conversions were improved when valorizing the cellulose platform based on sequential pretreatment. In contrast, valorizing the black liquor after a combination scheme decreased aldehyde yields such as vanillin and syringaldehyde by 4.8–11.9% [33].

A techno-economic analysis of furfural production from palm oil empty fruit bunches was published by Mohammed et al. [74].

The production capacity of 10 kilotons per year (ktpy) of glucose and 4.96 ktpy of furfural with a purity of 98.21 and 99.54%, respectively, was achieved from 35.13 ktpy of the aforementioned palm oil empty fruit bunches [74].

Choline chloride (ChCl) seems to be crucial for the achievement of high yields of furfural in the proposed biorefineries due to the facilitating isomerization of xylose to xylulose, which is more easily dehydrated to furfural compared with xylose.

Zang et al. elaborated a techno-economic analysis of biorefinery focused on one-pot lignocellulosic biomass separation with furfural production, introducing choline chloride as a fairly expensive agent (1200 USD/t) to joint furfural and ethanol production from switchgrass. In the proposed technology, aqueous 70 wt.% ChCl in co-action with 0.6 wt.% H₂SO₄ is the reaction medium for simultaneous pretreatment and hemicellulose conversion at 170 °C/60 min, while MIBK is the organic phase for in situ furfural extraction. The insoluble part, mainly containing cellulose, was treated by enzymatic hydrolysis and subsequent fermentation to produce ethanol [77].

It was calculated that 49% of the total carbon from the switchgrass was converted to the target products (17.9% to furfural, 16.0% to lignin, and 15.1% to ethanol) [77].

DES prepared by melting an equimolar mixture of choline chloride with p-toluenesulfonic acid (PTSA) dissolved in an aqueous solution (1.8% aq. DES) was used for the separation and hydrolysis of corncob hemicellulose (1 g corncob per 6 g of 1.8% aq. DES) at 140 °C/20 min. The obtained DES extract of hemicellulose and its hydrolysis product xylose were recycled four times. The obtained aqueous DES extract of corncob contains about 11% of xylose (beside low concentrations (thousands of ppm) of glucose, acetic acid and furfural) after four separation steps, with a xylose yield 76–78%.

The dehydration reaction was subsequently conducted at 168 °C for a period of 75 min with 11% xylose extract in the mentioned aq. DES filtrate to achieve a furfural yield of ca. 69% by stripping with nitrogen.

The originating furfural was sequentially (a) extracted from an aqueous condensate into either the methyl isobutyl ketone (MIBK) or into the hydrophobic eutectic solvents mixture, such as tetradecane-1-ol:thymol 1:2, and (b) isolated by distillation.

In total, 93% of corncob cellulose was recovered after this process for further work-up. The yield of cellulose is much higher using the described DES compared with furfural production based on aqueous H₂SO₄ treatment [73].

The effect of ChCl in co-action with hydrochloric acid was studied in full detail. The first step consisted of pretreating the corn stover with a 10% aq. HCl at 170 °C for 60 min. From this hydrolysis step, the solid residue containing 38% cellulose and 17% lignin and the liquid hydrolysate containing 19% xylose were obtained.

The xylose concentrate was dehydrated after the addition of ChCl, producing a 14% furfural yield (14 g furfural from 100 g of corn straw) by extraction in immiscible 2-methyltetrahydrofuran. Excluding furfural, the lignin fraction (14 wt.% of starting corn straw) and the 33 wt.% cellulose were isolated separately. After enzymatic saccharification, the 31 wt.% glucose was obtained from aforementioned cellulose [75].

Halder and Shah published a techno-economic analysis dealing with the biorefinery of sugar cane straw with a focus on furfural and levoglucosenone production. The authors calculated that from 1800 kg/h of dry sugarcane straw, the biorefinery plant could produce about 260 kg/h of furfural and 65 kg/h of levoglucosenone (LGO), together with lignin, biochar, bio-oil, and py-gas. The sugar cane-based lignocellulosic biomass was treated using choline glycinate IL (8 g per gram of dried biomass) at 100 °C/60 min and the obtained solid cellulose reach residue was pyrolyzed at 380–400 °C. Furfural and levoglucosenone were separated from bio-oil by extraction using MIBK (4 kg per kilogram of bio-oil) and water used in a 1:1 ratio with bio-oil. Furfural was isolated from the MIBK phase by distillation, while levoglucosenone was extracted from the aq. phase with chloroform and then isolated by distillation [76].

2.5. Conversion of Pentoses to Furfural

Concentrated aqueous formic acid enables the transformation of xylose to furfural at 150 °C and an elevated pressure with a 50% yield. A high temperature (min. 150 °C) is necessary for the effective dehydration of pentoses to furfural in the case of soft formic acid, which could be a limiting factor for its use (the boiling point of HCOOH is 100 °C) [78].

The kinetics of both formic acid-catalyzed xylose dehydration into furfural and furfural decomposition were investigated by Lamminpää et al. using batch experiments within a temperature range of 130–200 °C. Initial xylose and furfural concentrations of up to 0.2 and 0.08 mol/L, respectively, were used [79].

Attempts to convert xylose to furfural in a biphasic mixture of aqueous organic solvents, such as dimethyl sulfoxide, methyl isobutyl ketone, and 2-butanol, were performed at 170 °C using a catalytic amount of HCl. High yields of furfural were obtained during the extraction of methyl isobutyl ketone/2-butanol organic phases using this extraction-assisted synthesis [80].

Advantages of extraction-assisted synthesis were reported by Gürbüz et al., who used an aqueous HCl/2-sec-butylphenol solvent system at 170 °C (1.5 wt.% xylose in 0.1M HCl saturated with NaCl), which resulted in a far higher conversion of xylose and yield of furfural ca. 78%. The authors reported a high solubility of the furfural produced in used 2-sec-butylphenol compared with other earlier published extractants (MIBK, etc.) [81].

The main disadvantages of the above-mentioned methods are the harsh and highly energy-demanding reaction conditions, including reaction temperatures of 170 °C or higher, elevated pressure, and the use of highly corrosive mineral acids.

Nevertheless, ionic liquids allow for a significantly decreased effective dehydration temperature. This is probably caused a decrease in thermodynamic and kinetic barriers, along with the dehydration of saccharides in commonly used acidic aqueous solutions or non-ionic organic solvents [82].

As was published by Lima et al., pentose (xylose) is transformed to furfural in acidicionic liquid solutions, such as EMIMHSO_4, with high resulting yields at significantly lower temperatures of 100–120 °C compared with traditional reaction systems (

Table 8. Small molecules (agents and solvents) effective in hemicellulose hydrolysis and xylose dehydration processes.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility (at R.T.)	Role	Ref.
Formic acid	HCOOH	100.7	1.22	Miscible	Acid catal. reagent	[78,79]
Dimethyl sulfoxide		189	1.1	Miscible	Biobased solvent	[80]
Methyl-isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Biobased extractant	[80,81,82]
2-butanol		98–100	0.81	29 g/100 mL	Extractant	[80]
2-sec-butylphenol		226–228	0.98	1.4 g/L	Extractant	[81]

) [82].

3. Role of Small Molecules in Hydrolysis of Separated Cellulose and Dehydration of Produced Hexoses

Cellulose, as the least soluble part of lignocellulosic matter, is mostly obtained as the insoluble residue using the above-mentioned hemicellulose separation processes.

Insoluble cellulose is often enzymatically transformed to oligo- or monosaccharides, which serve as a cheap source of ethanol obtained by fermentation. However, at least one-third of organically bound carbon in hexose is lost due to the formation of undesirable CO₂.

In contrast, chemical acid-catalyzed dehydration of hexoses produces HMF and three molecules of water without the loss of organically bound carbon (Scheme 3).

Taking into account the important role of biomass as a replacement of nonrenewable sources (crude oil, coal, or natural gas) in the production of platform chemicals, the effective transformation of cellulose and hexoses to HMF and its derivatives (CMF, etc.), together with levoglucosan and levoglucosenone, creates an unsubstitutable source of bulk chemicals through the quantitative utilization of organically bound carbon.

HMF is the starting chemical for harvesting levulinic acid, 2,5-dimethylfuran, and key mass-produced chemicals such as adipic acid, caprolactone, polyamide 6, alternative monomers for sustainable polyesters such as 2,5-bis(hydroxymethyl)-furan, furan-2,5-dicarboxylic acid, and others [83].

Nevertheless, an industrial-scale production of HMF has still not been implemented, mainly due to the combination of high cost of hexoses and low yield of dehydration processes. These disadvantages are accompanied by the side-reactions that produce levulinic, formic acid, and/or humins, along with the associated complicated isolation of hydrophilic HMF from reaction mixtures. Only a few producers (for example AVA Biochem, Muttenz, Switzerland) tend to approach the industrial-scale production of HMF [84,85].

One of the mentioned processes of converting cellulose into HMF, in which it is catalyzed by amido sulfonic acid (NH₂SO₃H) in an aqueous γ-valerolactone, produces only ca. 30% HMF at 180 °C/3 h (Table 9) [86].

Direct high-temperature acid hydrolysis of corn stover or wooden waste produces a varied mixture of products, with the highest HMF content being below 64 g HMF per liter of reaction mixture [87,88].

The application of molten metal chloride hydrates instead of Broenstedt acid catalysts seems to be more effective. Wei et al. achieved an almost 49% yield of HMF from cellulose with mixed hydrates ZnBr₂·3H₂O/LiCl·3H₂O at 180 °C for 3 h, using MIBK for continual extraction of the product. In this case, molten salts probably act as ionic liquids [89].

The continuous transfer of HMF into the immiscible organic phase (MIBK, etc.) significantly improves the yield of HMF.

The HCl catalyst converts bamboo powder (lignocellulose) into HMF with a 35% yield after 120 min of action in the MIBK/H₂O mixture at 177 °C under microwave heating [90].

A mixture of γ-valerolactone with aqueous NaCl and Al₂(SO₄)₃ catalysts was reported by Shen et al. to produce 30–35% of HMF from rice straw or corn straw at 165 °C/50 min [91].

It was reported by Shi et al. that the HMF yield is positively influenced by the extraction system providing a low solubility of acid catalysts. They demonstrated that the addition of cyclohexane to THF in the aq. Al₂(SO₄)₃ solution decreases the solubility of aluminium sulfate in the organic phase, thereby increasing HMF stability in biphasic system. The reported HMF yield from the cellulose was ca. 25% higher (71% HMF) compared with the THF/aq. Al₂(SO₄)₃ mixture without added cyclohexane at 180 °C/60 min. Nevertheless, the reported organic/aqueous phase ratio was higher than 50:1 [92].

Hexoses, as products of complete cellulose hydrolysis, are much more suitable for dehydration to HMF. Fructose is the ideal feedstock for high-yield HMF production. It has been proven that the dehydration of fructose is generally non-selective in pure water containing a catalytic quantity of strong acid, leading to many side products. By using inorganic chlorides in high concentrations (dehydration in acidified brine instead of water), the selectivity significantly increases.

Chen et al. reported the application of methanesulfonic acid in brine with addition of sparingly miscible dioxane or acetonitrile as a suitable reaction medium for high-yield (76–79%) HMF production process using fructose at 110 °C/20 min [93].

The highest yield of HMF by dehydration of fructose using small molecules was reported by Cao et al. Using ethylenediaminetetraacetic acid (EDTA) in an aqueous MIBK/2-butanol/polyvinylpyrrolidone mixture, HMF was obtained in ca. 89% of the total yield using 160 °C for 2 h at ambient pressure. The reported high yield is explained by the impossibility of subsequent rehydration of HMF to levulinic acid (Scheme 4) [94].

Conversion of HMF to levulinic acid requires highly acidic conditions. Besides this, simple recycling of EDTA was reported (Table 10) [94].

The effectivity of different extractants (MIBK, 1-hexanol, 1- and 2-butanol and 2-butanol with toluene) in extraction-assisted synthesis of HMF was compared by Leshkov et al. The experiments were conducted at 180 °C using 30 wt.% fructose in a 35% aq. NaCl solution containing 0.25 M HCl. For the extraction of the produced HMF, the above-mentioned organic extractants (V_org/V_aq. = 3.2:1) were used. The conducted experiments demonstrate that the optimal extractants are 1-butanol or 2-butanol; however, only a selectivity below 90% and a current conversion of fructose below 80% were reached, even under optimal reaction conditions [95].

Table 9. Small molecules (agents and solvents) effective in hemicellulose hydrolysis and xylose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility (at R.T.)	Role	Ref.
Amidosulfonic acid	NH2SO3H	Decomp. M.p.: 205 (decomp.)	2.15	Moderate with slow hydrolysis	Acid catal.	[86]
Zinc bromide hydrate	ZnBr2·nH2O	Decomp. M.p.: below 100	n.d.	388 g ZnBr2/100 mL	Lewis acid catal.	[89]
Lithium chloride trihydrate	LiCl·3H2O	Decomp. M.p.: below 100	n.d.	83 g/100 mL	Co-catalyst	[82,89]
Aluminium sulfate octadecahydrate	Al2(SO4)3·18H2O	Decomp. M.p.: 86.5	1.6	3.6 g/100 mL (anhydrous)	Lewis acid	[91,92]
Sodium chloride	NaCl	1465	2.2	36 g/100 mL	Catalyst	[91,93,95]
γ-valerolactone		205	1.05	1 g/100 mL	Biobased aprotic solvent	[91]
Cyclohexane		81.4 (69 azeotrope cont. 8.4% H2O)	0.78	Immiscible	Solvent	[92]
Tetrahydrofuran		65–66 (64 azeotrope with 6% H2O)	0.89	Miscible (sparingly miscible in aq. NaCl)	Solvent and extractant	[92]

Table 9. Small molecules (agents and solvents) effective in hemicellulose hydrolysis and xylose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility (at R.T.)	Role	Ref.
Amidosulfonic acid	NH2SO3H	Decomp. M.p.: 205 (decomp.)	2.15	Moderate with slow hydrolysis	Acid catal.	[86]
Zinc bromide hydrate	ZnBr2·nH2O	Decomp. M.p.: below 100	n.d.	388 g ZnBr2/100 mL	Lewis acid catal.	[89]
Lithium chloride trihydrate	LiCl·3H2O	Decomp. M.p.: below 100	n.d.	83 g/100 mL	Co-catalyst	[82,89]
Aluminium sulfate octadecahydrate	Al2(SO4)3·18H2O	Decomp. M.p.: 86.5	1.6	3.6 g/100 mL (anhydrous)	Lewis acid	[91,92]
Sodium chloride	NaCl	1465	2.2	36 g/100 mL	Catalyst	[91,93,95]
γ-valerolactone		205	1.05	1 g/100 mL	Biobased aprotic solvent	[91]
Cyclohexane		81.4 (69 azeotrope cont. 8.4% H2O)	0.78	Immiscible	Solvent	[92]
Tetrahydrofuran		65–66 (64 azeotrope with 6% H2O)	0.89	Miscible (sparingly miscible in aq. NaCl)	Solvent and extractant	[92]

The combination of the Lewis and Broenstedt acids CrCl₃/EMIMHSO₄ with an immiscible solvent (toluene, isobutyl methyl ketone) should significantly improve the yield of HMF at 100–120 °C (

Table 11. Small molecules (agents and solvents) effective in fructose or glucose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Dimethyl acetamide	CH3CON(CH3)2	165	0.94	Miscible	Solvent	[82]
Chromium chloride	CrCl3	950 (subl.)	2.8	Sparingly soluble	Lewis acid	[82]
Sodium bromide	NaBr	1390 M.p.: 747	3.2	94.3 g/100 mL	Co-catalyst	[82]
Methyl-isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Extractant	[96]
Choline chloride (solid)		Nondistillable (M.p.: 302 with decomp.)	1.2	Miscible	Component of DES	[96]
Tin(IV) chloride (liquid)	SnCl4 or SnCl4·5H2O	114 (M.p.: 56 pentahydrate)	2.22 (2.04 pentahydrate)	Anhydrous reacts with H2O; pentahydrate miscible	Lewis acid	[96]
Aq. solution of hydrochlorid acid	Aq. HCl	102 (4%HCl)–110 (21%HCl)	1.02 (4%HCl)–1.10 (20.4%HCl)	Miscible	Reagent and solvent	[82]
Sodium chloride	NaCl	1465	2.2	36 g/100 mL	Catalyst	[97]
Aluminium chloride	AlCl3 or AlCl3·6H2O	180 (M.p.: 100 hexahydrate)	2.44 (2.4 hexahydrate)	Soluble (45 g AlCl3/100 mL)	Lewis acid	[97]
2-sec-butylphenol		226–228	0.98	1.4 g/L	Extractant	[97]

) [82].

Table 10. Small molecules (agents and solvents) effective in fructose or glucose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Methyl isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Extractant	[82,94]
Dimethyl acetamide	CH3CON(CH3)2	165	0.94	Miscible	Solvent	[82]
Chromium chloride	CrCl3	950 (subl.)	2.8	Sparingly soluble	Lewis acid	[82]
Aq. solution of hydrochlorid acid	Aq. HCl	102 (4%HCl)–110 (21%HCl)	1.02 (4%HCl)–1.10 (20.4%HCl)	Miscible	Reagent and solvent	[82]
1-ethyl-3-methylimidazolium chloride (EMIMCl)		Decomp. M.p.: 77–79	1.44	Miscible	Reagent and solvent	[82]
Methanesulfonic acid (liquid)	CH3SO3H	167 (M.p.: 17–19)	1.48	Miscible	Acidic catal.	[93]
Acetonitrile	CH3CN	81	0.79	Miscible	Extractant	[93]
Dioxane		101.3	1.03	Miscible	Solvent	[93]
Ethylenediamine-tetraacetic acid		Decomp.	0.86	Sparingly soluble	Acidic catal.	[94]
1-butanol	CH3CH2CH2CH2OH	78	0.89	Immiscible (0.5 g/L)	Extractant	[95]
2-butanol		98–100	0.81	29 g/100 mL	Extractant	[94,95]

Table 10. Small molecules (agents and solvents) effective in fructose or glucose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Methyl isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Extractant	[82,94]
Dimethyl acetamide	CH3CON(CH3)2	165	0.94	Miscible	Solvent	[82]
Chromium chloride	CrCl3	950 (subl.)	2.8	Sparingly soluble	Lewis acid	[82]
Aq. solution of hydrochlorid acid	Aq. HCl	102 (4%HCl)–110 (21%HCl)	1.02 (4%HCl)–1.10 (20.4%HCl)	Miscible	Reagent and solvent	[82]
1-ethyl-3-methylimidazolium chloride (EMIMCl)		Decomp. M.p.: 77–79	1.44	Miscible	Reagent and solvent	[82]
Methanesulfonic acid (liquid)	CH3SO3H	167 (M.p.: 17–19)	1.48	Miscible	Acidic catal.	[93]
Acetonitrile	CH3CN	81	0.79	Miscible	Extractant	[93]
Dioxane		101.3	1.03	Miscible	Solvent	[93]
Ethylenediamine-tetraacetic acid		Decomp.	0.86	Sparingly soluble	Acidic catal.	[94]
1-butanol	CH3CH2CH2CH2OH	78	0.89	Immiscible (0.5 g/L)	Extractant	[95]
2-butanol		98–100	0.81	29 g/100 mL	Extractant	[94,95]

Deep eutectic solvents (DES) based on choline chloride mixed with MIBK and a co-action of SnCl₄ seem to be very effective reaction media for high-yield formations of HMF (ca. 82%) under mild reaction conditions of 100 °C/4 h [96].

Glucose, the hydrolysis product of cellulose, is cheaper. Nevertheless, difficulties accompanied by the isomerization into fructose lead to a 10–30% drop in the overall yield of HMF compared with fructose. In addition, problems still remain regarding the side reactions of quite reactive HMF and the complicated isolation of hydrophilic HMF from aqueous reaction mixtures. Co-action with both Broensted and Lewis acids (AlCl₃ and HCl) is essential for a selectivity and yield of HMF comparable with those resulting from glucose in a two-phase reaction system of brine/2-sec-butylphenol. The added Lewis acid, together with HCl, facilitates the isomerization of glucose into fructose. Fructose produced in situ is dehydrated to HMF with a 62% yield and 68% selectivity, reaching a glucose conversion of 91% [97].

The isolation of simple products from organic extractants is crucial for the potential production of HMF. Nevertheless, in the case of 2-sec-butylphenol, the recovery of HMF is very complicated due to the similar boiling points of both these chemicals. Due to this reason, the extracted HMF is converted to γ-valerolacton directly dissolved in 2-sec-butylphenol [85].

The addition of DMSO to aq. solutions of both glucose or fructose improves the selectivity and dehydration rates of both these hexoses. DMSO facilitates fructose dehydration through solvation. Fu et al. describe that DMSO is much more effective for HMF production compared with γ-valerolactone or N-methylpyrrolidone. The reason is the favored formation of β-fructofuranose in DMSO and its straightforward dehydration into HMF. The other mentioned aprotic polar solvents transform fructose through α-fructopyranose, which is simply convertible to levulinic acid [98].

Diphenyl sulfoxide was described as a reaction medium for the efficient dehydration of fructose into HMF with a ca. 68% yield at 140 °C after 11 h of action. Easy HMF separation was performed by water extraction due to the high partition coefficient of HMF in the water/diphenyl sulfoxide biphasic media, where HMF is soluble in water while diphenyl sulfoxide is only slightly soluble in water, with a measured solubility of 1.2 g L⁻¹. HMF is simply extracted into the aqueous phase after dilution of the obtained reaction mixture, with water and humins remaining in the diphenyl sulfoxide phase (

Table 12. Small molecules (agents and solvents) effective in fructose or glucose dehydration.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Dimethyl sulfoxide		189	1.1	Miscible	Biobased solvent	[98]
Diphenyl sulfoxide (solid)		n.d. M.p.: 69–71	>1	1.2 g/L	Reaction solvent	[99]
1-butyl-3-methylimidazolium chloride (IL)		Decomp. above 246 °C (Melting point: 41)	1.08	Soluble	Solvent	[100]
1-butyl-3-methyl-imidazolium hydrogensulfate		Decomp. (M.p.: n.d.)	n.d.	Miscible	Acidic IL Reagent and solvent	[101]
1-methyl-imidazolium chlorid HMIMCl		Decomp. (M.p.: n.d.)	n.d.	Miscible	Acidic IL Reagent and solvent	[102,103,104]

) [99].

The addition of a water-immiscible MIBK/2-butanol mixture increases the yield of HMF due to the extraction of the produced HMF into the organic phase, which suppresses subsequent hydration of HMF into levulinic acid [80].

As was mentioned earlier, the application of ionic liquid instead of traditional reaction media enables a significant decrease in the effective dehydration temperature [82].

Li et al. reported a high-yield Y_HMF for [BMIM]HSO₄ (80% Y_HMF at 80 °C/30 min), which was used in catalytic amounts (5.9 and 7.7 mol%, respectively) with BMIMCl as the solvent (10 wt.% fructose) [100].

The application of ionic liquids such as BMIMCl diluted with glycerol and acidified by HCl enables a decrease in the reaction temperature for effective dehydration of fructose (1 g fructose dissolved in 2.5 g of solvent mixture (BMIMCl:glycerol = 65:35) at 110 °C/10 min). Using extraction-assisted synthesis with a quantity of MIBK 4 times greater than that of the BMIM/glycerol mixture, the reported HMF yield reached 70%. The separation of HMF was based on the simple evaporation of MIBK from the separated immiscible MIBK phase. In addition, the replacement of glycerol-by-glycerol carbonate enabled a decrease in the quantity of BMIMCl used [101].

Under quite moderate reaction conditions, 70–92% HMF was obtained in the dehydration of fructose (10–35 wt.%) at 80–90 °C, in about 30 min to 1 h reaction time, using the ILs N-methylimidazolium hydrochloride (HMIMCl) and without adding any other solvent [102,103].

For the same initial concentration of fructose, but with a slightly higher reaction temperature (90 °C) and shorter reaction time (45 min), Moreau et al. reported that HMIMCl (IL purity 98%) gave 92% Y_HMF (92% C); after removing the water from the IL, the latter could be used in five consecutive runs without a decrease in the Y_HMF [104].

The transformation process of cellulose into HMF includes a series of tandem catalytic reactions, involving the complete hydrolysis of cellulose, glucose isomerization, and fructose dehydration [11]. Generally, the formation of HMF is accompanied by side reactions, including the production of insoluble humins and soluble polymerized HMF, as well as rehydration reactions to levulinic acid.

To circumvent the instability of HMF in reaction mixtures and problems when dealing with HMF isolation, 5-(chloromethyl)furfural (CMF) was suggested as a target platform chemical instead of HMF. CMF is less hydrophilic and quite stable in acidic conditions used for hexoses dehydration (Scheme 5). These properties predestinate CMF to be a promising candidate for the main 5-substituted furfural-based biorefinery product [12].

With the aim of profitable production of CMF from cellulose, highly selective dehydration of hexoses to HMF and high-yield nucleophilic substitution of hydroxyl groups of HMF should be both achieved. Extraction-assisted synthesis is the best choice to fulfill each of above-mentioned requirements. Optimal reaction mixtures containing high concentrations of chloride ions and high acidity are necessary for nucleophilic substitution of hydroxyl groups bound in HMF. These demands optimally satisfy concentrated HCl combined with some immiscible and sufficiently stable organic solvents used for CMF extraction. A very effective solvent verified for high-yield synthesis of CMF, even from corn stover, is 1,2-dichloroethane. While 1,2-dichloroethane is not soluble in aq. HCl, it is a cheap platform chemical that can be simply accessed through the chlorination of ethylene [105]. Nevertheless, 1,2-dichloroethane is ambiguously “green”, being a toxic and hardly biodegradable compound. Due to this reason, research focused on finding an optimal green solvent has been performed. Fluorobenzene shows the highest CMF yield under comparable reaction conditions using the volume ratio solvent:aq. HCl = 3:1. Toluene has been recognized as the sole nonhalogenated solvent that is almost comparable with tested halogenated solvents; however, its CMF yield is about 15% worse compared with chloro- or fluorobenzene.

Gruter et al. described the industrial production of CMF in addition to other profitable chemicals from lignocellulosic biomass [106,107,108,109]. The mentioned process is applicable even for raw biomass, which gave CMF yields comparable to that of carbohydrates, based on the hexose content. It was found that catalysis based on mixed Lewis acids consisting of CrCl₃ and ZnCl₂ played an effective role in the transformation of carbohydrates to CMF [110] (

Table 13. Small molecules (agents and solvents) effective for cellulose transformation into CMF.

Active Agent	Structure or Formula	B.p. (°C)	Density	Aq. Solubility	Role	Ref.
Concentrated hydrochlorid acid	36% HCl	82	1.18	Miscible	Reagent and solvent	[105,106,107,108,109]
Chromium chloride	CrCl3	950 (subl.)	2.8	Sparingly soluble	Lewis acid	[108]
Zinc chloride	ZnCl2	732 (M.p.: 290)	2.9	432 g/100 mL	Lewis acid	[108,110]
Choline chloride (solid)		nondistillable (M.p.: 302 with decomp.)	1.2	Miscible	Component of DES	[107,108]
Oxalic acid (solid)	(COOH)2 or (COOH)2·2H2O	Decomp. (M.p.: 189.5) (M.p.: 101.5 dihydrate)	1.9 (1.65 dihydrate)	10 g/100 mL	Acid and/or component of DES	[108]
Aluminium chloride	AlCl3 or AlCl3·6H2O	180 (M.p.: 100 hexahydrate)	2.44 (2.4 hexahydrate)	Soluble (45 g/100 mL)	Lewis acid	[107]
1,2-dichloroethane	ClCH2CH2Cl	84	1.25	0.87 g/100 mL	Extractant	[105,106,107,108,109]
Chlorobenzene		131.7	1.1	0.5 g/100 mL	Extractant	[107]
Toluene		110.6	0.87	Immiscible	Extractant	[107]
Cyclopentyl methyl ether		106	0.86	Immiscible	Sustainable extractant	[108]
Fluorobenzene		84–85	1.0	Immiscible	Extractant	[107]
Anisole		154	1.0	Immiscible	Extractant	[111]
Methyl-isobutyl ketone (MIBK)		117–118	0.8	1.9 g/100 mL	Extractant	[107,112]

).

4. Conclusions

This review aims to denote the possible utilization of readily available industrial small molecules for effective furfural and/or furfural derivatives production. The direct high-yield catalytic transformation of biomass into furfural and its derivatives is questionable due to the series of consecutive hydrolysis, dehydration, and side reactions involved.

The separation of the most readily available hemicellulose, with subsequent utilization of insoluble cellulose, could yield optimal results by enabling separate hydrolysis and conversion of pentoses to furfural and hexoses obtained from cellulose to 5-hydroxymethylfurfural or even simpler, isolable 5-chloromethylfurfural.

Separated hemicellulose hydrolyzed into oligo- or monosaccharides and their dehydration enable the selective conversion of pentoses into furfural as the sole extractable or steam-distillable product.

The published alkaline and/or oxidative treatment of biomass for simple hemicellulose and/or lignin separation is effective; however, the consumption of used bases and/or oxidants is equimolar. This fact discourages the use of oxidation or hydroxide-based methods for sustainable treatment.

On the other hand, acid-based treatments are catalytical and potentially enable the recycling of used acid-based reagents. In addition, discounts based on industrial side streams, such as diluted sulfuric or hydrochloric acid, CaCl₂ aqueous solution (Solvay), or mixed metal chlorides (TiO₂ prod.), could serve these purposes.

Diluted sulfuric acid, which is broadly applicable for hemicellulose and cellulose separations and/or hydrolysis, is the usual waste stream from sulfonation and esterification procedures. Similarly applied diluted hydrochloric acid is produced as a common by-product during phosgenation or the production of organic acid chlorides. Aqueous calcium chloride solution, utilizable for effective hemicellulose separation, is produced in huge quantities during the Solvay process used for soda manufacturing.

Lewis acidic metal chlorides are by-products of the so-called chloride process in TiO₂ pigment production.

Besides acidic catalysts, appropriate organic solvents seem to be essential for the high-yield transformation of lignocellulosic biomass into furfural, and its derivatives, HMF and/or CMF. The application of recyclable solvents available from renewable sources is necessary for the sustainable production of FA, HMF and/or CMF as platform chemicals from waste biomass. This requirement fulfills 1-butanol, DMSO, glycerol, GVL, MIBK, 1-pentanol, 2-MeTHF or THF. However, several of these solvents (GVL, THF, 2-MeTHF), broadly used in basic research focused on biomass treatment, are generally unstable in acidic environments due to long-term treatment at elevated temperatures [113]. Due to these reasons, aromatic hydrocarbons seem to play an important role as cheap, easily recyclable, and stable extractants.

The development of an effective and, moreover, sustainable solvent system for high-yield transformation of lignocellulosic biomass into furfural and its derivatives remains a challenge. The acceptable conversion of sugars into furfural and its derivatives was reached in mixtures of water with polar aprotic solvents.

Notably, DMSO seems to be highlighted and cited in the literature on lignocellulosic biomass separation and conversion for its role as used catalyst(s) and as a solvent. DMSO is a non-toxic, cheap, biodegradable, and bio-based chemical, and an excellent and quite stable solvent, which can be recycled by vacuum distillation. The spent or not easily recyclable DMSO can be oxidized to dimethyl sulfone, a low-melting solid that also serves as an environmentally benign solvent.

As was documented by Horváth et al., the above-mentioned GVL serves as the general solvent candidate for lignocellulosic biomass conversion [67,113,114]. GVL is readily available from HMF by hydrolysis and subsequent transfer hydrogenation. Although GVL hydrolyzes to 4-hydroxyvaleric acid (4-HVA) in aqueous acid at elevated temperatures, 4-HVA readily undergoes reverse ring closure via acid-catalyzed dehydration to form GVL. Horváth et al. expect that the use of GVL for lignocellulose biomass treatment will eliminate the application of all other mentioned solvents, such as DMF, dimethylacetamide, or ionic liquids [67,113,114].

Nevertheless, ionic liquids (ILs) offer a reaction medium that can activate at significantly lower reaction temperatures compared with molecular solvents or aqueous acids. ILs offer unique solubilizing properties for polysaccharides that are necessary for their conversion to furfural and/or its derivatives. ILs can improve the accessibility of catalysts in the active site, which have unique advantages in stabilizing target furfurals and maintaining the yield during the biomass conversion process. ILs have several distinct advantages such as low vapor tension and excellent thermochemical stability. On the other hand, the recyclability or treatment of spent ILs is challenging. Moreover, the price and unpredictable environmental effects of high ILs further limit their commercial application.

Deep eutectic solvents (DES) were recognized as green nonvolatile solvents and as substitutes for traditional ILs. DES have been applied in lignocellulosic biomass treatment for their low cost, non-toxicity, and high biodegradability (in the case of choline chloride). Similarly to ILs, DES are applicable at lower temperatures and/or ambient pressures. Their recycling is possible even in several recycle runs. However, the treatment of spent DES seems to be extremely demanding compared to that of ILs.

In our opinion, while protic ILS (PILS), which are salts of amines with inorganic acids, seem to be more applicable compared with DES or ILs, they still remain undervalued. Our review mentioned that cheap triethylammonium hydrogensulfate [72] or N-methylimidazolium hydrochloride [102,103,104] were reported as repeatedly applicable without refining in ca. five recycle runs. In addition, after simple alkalifying with an alkali metal hydroxide solution, the released amines are readily distillable and prepared for subsequent protic IL performance through simple acidification with an appropriate inorganic acid.

The extensive utilization of produced furfural and its derivatives comprises the production of 2-methyltetrahydrofuran, which is widely used as a sustainable solvent, often replacing harmful dichloromethane and bis(hydroxymethyl)-furan in the manufacturing of polyurethane foams, and furan-2,5-dicarboxylic acid (applicable for polyesters production), and 2,5-bis(aminomethyl)furan (applicable for polyurethanes) [115].