Jie Wei,Maoshuai Li*,Meiyan Wang,Shixiang Feng,Weikang Dai,Qi Yang,Yi Feng,Wanxin Yang,Cheng Yang,Xinbin Ma*

Key Laboratory for Green Chemical Technology of Ministry of Education,Collaborative Innovation Center of Chemical Science and Engineering,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China

Keywords:Formaldehyde Syngas Hydroformylation Glycolaldehyde Ethylene glycol Mechanism

ABSTRACT Hydroformylation of formaldehyde to glycolaldehyde (GA),as a vital reaction in both direct and indirect process of syngas to ethylene glycol(EG),shows great advantages in the aspects of the process complexity and clean production.The hydroformylation of formaldehyde to GA is thermodynamically unfavourable,requiring the development of highly efficient hydroformylation catalytic systems,appropriate reaction conditions and in-depth understanding of the reaction mechanisms.In this review,we have made a detailed summary on the reaction in terms of the reaction network,thermodynamics,metal complex catalysts (including central metals and ligands),reaction conditions (e.g.,temperature,pressure,formaldehyde source and solvent)and promoters.Furthermore,the reaction mechanisms,involving neutral and anionic complex in the catalytic cycle,have been summarized and followed by a discussion on the impact of the crucial intermediates on the reaction pathways and product distribution.A brief overview of product separation and catalyst recovery has been presented in the final part.This review gives new insights into the factors that impact on the formaldehyde hydroformylation and reaction mechanisms,which helps to design more efficient catalytic systems and reaction processes for EG production via the hydroformylation route.

1.Introduction

As a bulk chemical,ethylene glycol (EG) is widely used as raw material for the production of polyethylene terephthalate,antifreeze,and plasticizer [1].The global market demand for EG has been increasing rapidly to meet the expansion of the polyester industry.The EG consumption up to 16 million tons in China ranked first in the world,with 60% of the total EG imported in 2018.The limited production capacity of EG implies a vast market potential.The production of EG currently relies on the petroleum routeviahydration of ethylene [2].However,the shortage of oil resource requires relatively more sustainable production routes as an alternative.Production of EG from syngas is more attractive as syngas can be produced from a variety of renewable sources(e.g.,biomass,recycled plastics,biogas and carbon dioxide),in addition to fossil fuels (e.g.,petroleum,coal and natural gas).

At present,the syngas to EG route includes direct and indirect processes(Fig.1).In the direct process,EG is synthesised from syngas in one step by Rh or Co catalysis under extremely high temperature and pressure [3–6] (pathway 1).According to the previous research[7–10],the direct synthesis of EG involves three consecutive reaction steps,e.g.,syngas to formaldehyde,subsequent hydroformylation to glycolaldehyde and hydrogenation of glycolaldehyde to EG.Conversion of syngas straightforward to formaldehyde is thermodynamically unfavorable [11],which has been considered as the rate-limiting step for the overall reaction.Though,the direct synthesis of EG from syngas is an ‘‘a(chǎn)tom economic reaction”,the harsh reaction conditions make it difficult for practical application.

Fig.1.The process to ethylene glycol from syngas.

EG can be produced from syngasviathe indirect processes by carbonylation of formaldehyde [12–14] (pathway 2),CO coupling reactions [15,16] (pathway 3),hydroformylation of formaldehyde(pathway 4).The carbonylation of formaldehyde route includes methyl glycolate generation from formaldehyde and CO by carbonylation and esterification with final hydrogenation to EG.The catalytic system with acid causes severe corrosion of equipment and environmental pollution[17].The CO coupling pathway catalysed by Pd involves the conversion of methyl nitrite to dialkyl oxalate (e.g.,dimethyl oxalate) as an intermediate which is hydrogenated to EG,has a complicated process and many by-products.A large volume of published studies investigated the hydrogenation of dimethyl oxalate based on Cu catalyst [18–22].However,there are several hurdles(e.g.,the high partial pressure of H2,challenging to manipulate product selectivity and NO pollution)in the CO coupling pathway[23].The hydroformylation of formaldehyde using formaldehyde and syngas as feeding stock produces glycolaldehyde as an intermediate that can be further hydrogenated to produce EG.In contrast to the syngas direct to formaldehyde,the syngas to methanol has been commercially established with the methanol conversion to formaldehydeviaoxidation.Hydrogenation of glycolaldehyde(GA)to EG has been studied[24,25].Besides,hydroformylation can be carried out under mild conditions with a high glycolaldehyde yield.Thereby,it shows vast prospects for developing EG production from syngasviahydroformylation of formaldehyde.Roth and Orchin have started to study the formaldehyde hydroformylation in the 1970s [26].Since then,it has attracted extensive attention from both the academic and industrial communities,and a large number of articles and patents on the development of high-performance homogeneous catalytic systems and reaction mechanism were published during 1980 to 1995.However,a search through the existing literature found one review associated with the formaldehyde hydroformylation since 1989 [27],which focused on the effect of amide solvents and basic promoters.A few reviews on the direct synthesis of EG have involved description of hydroformylation of formaldehyde as one of the sections [4,28].Related books [29,30] about the formaldehyde hydroformylation did not cover ionic mechanism,the full reaction pathways of GA and catalyst recovery.

Recently the hydroformylation of formaldehyde as a promising process for the coal to EG production has gained renewed interest.In this article,we attempt to supplement the previous review and give a comprehensive summary of the reaction of formaldehyde hydroformylation.The reaction network and thermodynamic analysis will be introduced at the beginning.In the second section,we will focus on the review of metals,ligands,reaction conditions(temperature,pressure,H2/CO,formaldehyde source,solvents)and promoters on the catalytic activity,product distribution and stability.Then,a picture for the catalytic mechanism of hydroformylation of formaldehyde and its establishment process will be described in detail.The full reaction pathways of GA generation and factors that may affect the selectivity of GA are to be discussed from the perspective of the reaction mechanism.Finally,we will focus on product separation and catalyst recovery methods.

2.Reaction Network

The hydroformylation of formaldehyde is a complicated reaction network,which involves many different types of secondary reactions and by-products.As illustrated in Fig.2,the hydroformylation of formaldehyde with syngas (CO and H2) gives rise to the target glycolaldehyde (GA,step 1).Although the formose reaction can also generate GA,evidence from material balance suggests that GA is exclusively generated by hydroformylation [31].GA monomer (Fig.3(a)) is not stable that can be transformed into dioxan dimer(b),hydrated GA(c)and(d)when the state and/or chemical environment changes.Monomer (a) is the exclusive form in the gaseous state with dioxan dimer (b),a cyclic dimer of (a),for the solid state [32].When it comes to the liquid phase,the solvent is critical in determining the existence of GA.It has been shown that 70%of GA is in the form of(c)for water solvent,100%monomer forn-heptane and CH2Cl2solvent,6%monomer in Me2SO-d6,while no dimer (100% dioxan) for dimethylacetamide (DMA) [31,33].

Ezhovaet al.[31],examining the effect of temperature on the formation of GA from the perspective of thermodynamics,indicated that high temperature (>84 °C) did not favour the hydroformylation of formaldehyde to GA (monomer),since the Gibbs free energy (ΔG) >0.In the majority of the reported studies,the reaction was conducted at higher temperature,for example,at 110 °C (ΔG1,110°C=6 kJ·mol-1),to enhance the reaction rate.A switch of GA monomer to dioxan dimer (generated from step 1+2) as the product,resulted in a lower value for ΔG1+2,110°C=-96 kJ·mol-1,suggesting dimer is a thermodynamically favourable product relative to monomer (a).GA produced from reaction (1)has an unexpected inhibitory effect on moving the reaction towards the product [34,35].It was demonstrated the yield of GA was decreased from 40% to 8% by addition of GA to the solvent.The author pointed out GA,which acted as a bidentate ligand,competed with formaldehyde for the coordination with the metal centre.

In the reaction network (Fig.2),GA monomer can be further hydrogenated to ethylene glycol(step 3)by metal catalysis.In parallel,as mentioned above,GA can be converted to dioxan dimerviadimerisation in the presence of acid (step 2),or to formose sugars(typically C3-C4 sugars)viathe Aldol reaction with HCHO and/or GA by base at high temperature (step 4) [36].The formation of heavy sugars with high-boiling points makes it difficult for product separation and analysis.It should be noted that GA dimer cannot make the hydrogenation or condensation happen.In addition,direct hydrogenation of formaldehyde generates methanol as the main by-product(step 5).Methanol and formic acid can be formedviathe disproportionation reaction of formaldehyde (Cannizzaro reaction,step 6),which is catalysed by base.As a consequence,the Cannizzaro reaction probably occurs prior to hydroformylation.It is probable that methyl formate is produced by the reaction of formaldehyde with CO and H2in the presence of metal hydridesviastep 7.The formation of formic acid and methyl formate byproducts is quite limited in the reaction pathways,which have little effect on changing the product selectivity.(Selectivity refers to the selectivity of GA unless otherwise stated.).

3.Catalytic Systems

3.1.Metals

Fig.2.Reaction network in the hydroformylation of formaldehyde.

Fig.3.Different forms of glycolaldehyde (a:monomer,b:dioxan dimer,c:hydrated GA,d:dioxolan dimer).

The classical catalysts for hydroformylation of formaldehyde are homogeneous catalysis with metal(e.g.,Co,Rh,Ru)complexes.Cobalt complex Co2(CO)8was the first formaldehyde hydroformylation catalyst investigated by Yukawaet al.[37] in 1975,where 25% yield of GA was achieved under the conditions of 120 °C and 20 MPa (Table 1,entry 1).The Co-catalysed system is commonly referred to high pressure for inhibiting the catalyst decomposition to cobalt.Due to the weak capacity of Co to form the C-C bond by CO insertion,the activity of the Co-based catalyst system is rather low,and higher temperature is also needed to get a satisfactory reaction rate [28].In 1977,Monsanto [34] published a patent that examined Rh as the hydroformylation catalyst and found that the formaldehyde conversion was much improved (Table 1,entry 2).The Rh complexes,especially for phosphine-coordinated catalysts,have a much higher catalytic activity for hydroformylation than Co and can catalyse hydroformylation under milder temperature and pressure.Therefore,the focus in terms of the metal centre has been mainly on Rh since 1977.The nature/number of ligands can modify the catalyst precursors that in turn exert distinctive effects on the reaction.For example,the Rh complex precursors with different types and numbers of ligands,Rh4(CO)12,HRh(CO)(PPh3)3and RhCl(CO)(PPh3)2,exhibited a distinctive variation in the yield of GA (Table 1,entry 3–5).Additionally,there is an optimal catalyst concentration,and the yield of GA will drop beyond the appropriate concentration[34].Ru was studied later in 1989 to expand the metal range in the form of Ru3(CO)12(Table 1,entry 6),[HRu3(-CO)11]-and [Ru(CO)3I3]-[38],but the catalytic performance was inferior to the Co system.Taking an overall view,the sequence of the frequency of metal usage in the hydroformylation of formaldehyde is as follows:Rh ?Co>Ru[39],which is consistent with the order of the catalytic activities.However,very little was found in the literature to reveal the difference in product selectivity between metals under the same conditions.

Table 1The catalytic performance in hydroformylation of formaldehyde with different catalyst systems①

Several studies have been reported on the development of mixed-metal catalysts.From 1986 to 1989,Marchionnaet al.[38,40,41] carried out investigations into the synergetic catalysis with different metals or Rh in different oxidation states.Rhodium carbonyl clusters were the most efficient catalysts for the direct conversion of syngas to EG.However,Rh4(CO)12alone was inactive for the hydroformylation reaction.Surprisingly,when Rh4(CO)12was mixed with CoCl2·H2O,55% conversion and 51% selectivity were reached (Table 1,entry 7).The study found that the Co salt did not play a decisive role.The function of CoCl2was to maintain an average oxidation state of Rh between -0.2 and +1,at which hydroformylation rather than hydrogenation can prevail.In a follow-up study,Marchionnaet al.examined the catalytic capacity of mixed[Rh(CO)2Cl2]-and[Rh5(CO)15-x(PPh3)x]-(different oxidation states of Rh) catalysts (Table 1,entry 8).It was shown that only when both were present in the solution,a higher yield of GA could be obtained.Subsequently,Pt,Ir,Ru and Fe were mixed with Rh respectively to investigate synergetic catalytic properties of different metals.No higher GA yield than homometallic Rh system was observed except for[Rh(CO)2Cl2]-/[HRu3(CO)11]-/Cl-pair(Table 1,entry 9).However,the latter rapidly lost selectivity with increasing temperature.

3.2.Ligands

A ligand that binds to a central metal atom to generate a coordination complex serves to modify the catalytic capacity in terms of reactivity,enantioselectivity and stability in homogeneous catalysis.A ligand usually exhibits two essential properties:electronic and steric effect.The early systematic study of ligand’s effects on catalyst properties and/or performance using quantitative chemical approaches was reported by Tolman [42],in which he proposed electronic (νCO) and steric (θ) parameter as ligand descriptors.The former parameter (νCO),derived from infrared(IR) spectroscopic measurements,is the highest A1 stretching frequency of the CO bonds in Ni(CO)3L complex.Ligands with high νCOvalues stand for strong π-acceptors,while low νCOvalues suggest strong σ-donor ability.The latter descriptor(θ),usually called Tolman cone angle,is one of the most widely used parameters that characterises the steric size of the monodentate phosphine ligands.High θ values imply large steric hindrance.A virtually unlimited alteration of the electronic and steric properties of carbonyl complex can be actualised using organic ligands.Other ligands(e.g.,H,CO,alkyl)coordinated to the metal centre can be stabilised or destabilised after the coordination of organic ligands.Also,catalytic reactions can be extraordinarily accelerated or totally blocked under the influence of electronic and steric effect.In hydroformylation,the most widely used ligands are trivalent phosphorus ligands (Fig.4),especially PPh3(L1).The formaldehyde hydroformylation reaction rate was accelerated with phosphine modified rhodium catalysts.Therefore,a higher GA yield under mild conditions can be obtained with phosphine modified rhodium catalyst than the original carbonyl complex.

The activated P-C bond resulting from phosphine coordination to metal is facile to be broken forming the ortho-metallated complex [30,39],which results in catalyst deactivation.Tanakaet al.[43] showed that PAr3was decomposed to various fragment species under the hydroformylation conditions (1).Garrouet al.[44]demonstrated the electron-withdrawing groups on the phenyl ring accelerated the scission of P-C bond.The activity of the central metal for P-C bond scission is in the order:Rh >Co >Ru.The P-C bond breakage is in line with the degree of coordinative unsaturation,where the higher degree of unsaturation generally results in a facile breakage.So,an excess of phosphine ligands is used to stabilise the catalysts [45].An excess of phosphine,however,suppress the catalytic activity,causing a decrease in GA yield,e.g.,24%yield of GA with P/Rh=2 while only 4%yield of GA with P/Rh=10 [35].The suppression of excess phosphine ligands on hydroformylation activity can be relieved with the addition of a small amount of NEt3,as to be described in Section 3.4.In addition,the phosphine ligands are sensitive to air,traces of oxygen and hydroperoxides,generally leading to the ligand decomposition.Thus,it is necessary to remove all the impurities from the catalytic solution.

In 1980,Spencer [35] investigated the effects of various phosphine ligands on the hydroformylation of formaldehyde using RhCl(CO)L2complexes (Table 2).The variation of GA yield with νCOand θ of the phosphine ligands was drawn for a more explicit comparison (Fig.5).As shown in Fig.5,high GA yields appear in the central area.There is no clear relationship between electronic or steric properties and GA yield,not to mention the activity and selectivity.In contrast to Spencer’s results,Chanet al.[46] found activity and selectivity remarkably increased with a stronger πacceptor ligand P(PhCF3)3than PPh3.This result was in agreement with Drent’s findings which showed that the conversion and selectivity were 98% and 89% with stronger π-acceptor ligand P(PhCl)3,whereas 80% conversion and 54% selectivity were achieved using PPh3[47].These results imply that π-acceptor ligands are more suitable for the hydroformylation of formaldehyde.This is also consistent with the observation that the hydroformylation activity(or selectivity) is increased with strong π-acceptor ligands in the hydroformylation of olefin [48–52].

Table 2Effects of phosphine ligand on the hydroformylation of formaldehyde catalysed by RhCl(CO)L2 complexes①

The use of solvents and promoters,including amide solvents,triethylamine and phosphine oxide favours the formation of GA but enhances the condensation reactions at the same time.To avoid the use of basic solvents and promoters to minimise the by-product formation,Jacobsonet al.[53] tried to graft the corresponding basic groups to the phosphine ligands.The reaction using phosphine-phosphine oxide ligand (L11) Figure 6 showed a very poor selectivity and GA yield.Phosphine-amine ligand (L12) was not effective in the improvement of GA yield,but the primary by-product was methanol rather than high-boiling sugars.The amine function was unavailable for catalysing condensation reactions due to proximity to the metal.The highest GA yield was obtained with phosphine-amide ligand (L13).Whereas L13 had a GA yield that was approximate to PPh3in DMA,and the yield with L13 far exceeded PPh3in common organic solvents.

Fig.4.Monodentate phosphine ligands used by Spencer [35].

Fig.5.Effects of steric(θ)and electronic(νCO)properties on the hydroformylation of formaldehyde.

Pucketteet al.[54–56] reported that fluorophosphite was an efficient ligand in the hydroformylation of olefin and applied it to the hydroformylation of formaldehyde.The results of these studies showed that basic promoters could be avoided using fluorophosphite ligands as an alternative.Hydroformylation of formaldehyde with Rh(CO)2acac as catalyst precursor reached 78% of conversion and 99% of selectivity using Ethanox 398TM(L14),PFA at 100 °C,13.8 MPa in DMA.Koprowskiet al.[57] suggested that the cone angle θ in the range of 157° to 171° of phosphine was necessary for high activity and selectivity using formalin as the formaldehyde source.Likewise,in aqueous formaldehyde system,Shell Oil Company [58] reported a super high GA yield of 90% using 2-PACH2CH2C(O)NMe2(L16) as the ligand.

3.3.Reaction conditions

3.3.1.Temperature and pressure

In the hydroformylation of formaldehyde,the catalytic activity and product distribution are dependent on the reaction conditions(e.g.,temperature,pressure and CO/H2ratio) employed.However,the relationship between temperature or pressure and conversion or selectivity depends on a specific catalytic system (Fig.7).A lower temperature(<84°C)favours the formation of GA thermodynamically,but kinetically decreases the reaction rate so largely that no conversion can be detectable in short reaction time.As a result,the reactions have been rarely conducted at temperatures below 84°C.Generally,the higher temperature would help the catalyst speed up the hydroformylation reaction delivering appreciably larger reaction rates and conversions.However,we can note an exception (Fig.7a) that the formaldehyde conversion was decreased (from 55% to 50%) with increasing the reaction temperature (125–145 °C) has been reported by Marchionnaet al.[40].Meanwhile,the reaction temperature significantly impacts on the product distribution and solvent stability.Increasing the reaction temperature has been known to enhance the hydrogenation and condensation of formaldehyde,generating various by-products including methanol,methyl formate and formose sugars.Moreover,decomposition of amide solvents occurred (120–140 °C),as shown by the presence of di-and tri-methylamine in the reaction solution,with reducing Rh to lower oxidation states [41].The loss of activity with increasing the temperature,as mentioned above,is a consequence of the decomposition of dimethylformamide(DMF),which simultaneously reduce Rh(I) to the inactive species [Rh(CO)4]-.To compromise the conversion rate and target selectivity,the reaction temperature cannot be too high.Mostly,the optimum temperature is within 100–120°C,where the reaction would exhibit decent conversion and target selectivity.

Fig.6.Novel ligands used in the hydroformylation of formaldehyde.

Fig.7.Effects of temperature (a) and pressure (b) on the conversion,reaction rate and GA selectivity in the hydroformylation of formaldehyde.

Pressure in the hydroformylation of formaldehyde generally ranges between 6 and 20 MPa.The operating pressure depends on the activity of metals and ligands.The Rh complex usually requires lower reaction pressure relative to the high-pressure Cobased catalytic system.The activity increases with increasing pressure regarding one specific catalyst system.Compared with activity,there is no consistent observation regarding the effect of pressure on the selectivity.As shown in Fig.7b,in the case of[PPN][Rh5(CO)15]/[Rh(CO)2Cl2]/PPh3,the effect of pressure on the product selectivity is negligible [41].By contrast,the selectivity increases at first and then decreases with the increase of pressure in the reaction for the Rh4(CO)12-CoCl2·6H2O system [40].

The ratio of the partial pressures of CO/H2also affects the result of the hydroformylation.The hydroformylation is favoured with equal partial pressures of CO and H2[59].An excess of CO promotes the formation of the hydroxyacetyl-metal complex (M-C(O)CH2OH),thus improving formaldehyde hydroformylation.On the other hand,an excess of H2favours the reductive elimination of hydroxymethyl-metal complex (M-CH2OH) to methanol,thus improving the formaldehyde hydrogenation [40].It does not indicate that higher CO/H2is beneficial,as the CO/H2ratio diverged from one leads to a lower hydroformylation activity.

3.3.2.Formaldehyde sources

Different forms of formaldehyde,including paraformaldehyde(PFA),formalin(aqueous formaldehyde),hemi-formals and methylal,have been used as formaldehyde sources in the hydroformylation of formaldehyde.A considerable number of works have been focused on paraformaldehyde due to higher GA yield.The concentration for formaldehyde has an influence on the conversion efficiency.As shown in the example of the RhCl(CO)(PPh3)2catalyst,the formaldehyde conversion increased from 27% to 50% with increasing the concentration of HCHO from 0.125 mol·L-1to 1 mol·L-1,and then decreased to 45% with 2 mol·L-1HCHO [35].However,PFA is expensive.Several attempts have been made to make use of cheaper raw materials,such as formalin and aqueous formaldehyde.In most cases,the hydroformylation activity and GA selectivity decrease while methanol selectivity increases with increasing the water composition in the solution.Marchionnaet al.[41] reported that a change of PFA to formalin caused a two-fold decrease of conversion from 80%to 44%,and of GA selectivity(from 88%to 39%),but an appreciable increase in the methanol selectivity from 9% to 61% for the reaction over [PPN][Rh5(CO)15]/[PPN][Rh(CO)2Cl2] at 110 °C,12.5 MPa in acetone.In some cases,water could also increase the hydroformylation activity [60].The reaction using 3 mol·L-1H2O/DMA solvent showed thirty times larger conversion rates than that for 0.1 mol·L-1H2O(RhCl3,110 °C and 13 MPa),as demonstrated by Ezhovaet al.[31].Nevertheless,the negative effect of water addition on GA selectivity limits the use of aqueous formaldehyde for the catalyst systems of formaldehyde.In order to achieve a high selectivity in the aqueous formaldehyde system,Koprowskiet al.[57] reported 94% GA selectivity for 50% aqueous formaldehyde using Rh and PCy3(L6)as ligand under the conditions of 100°C,24.8 MPa in tetraglyme.Up to 90% GA selectivity was achieved by Shell Oil Company in the hydroformylation of formalin with 2-PA-CH2CH2C(O)NMe2(L15)as ligands[58].With regard to hemi-formals,the insolubility in water makes a lesser loss of unreacted formaldehyde when extracting GA using water in product separation.In addition,the condensation reaction can be suppressed by hemi-formals to lower by-product formation.Auvilet al.[61] investigating the effect of hemi-formals (Cy-O-CH2OH) as formaldehyde source on the hydroformylation of formaldehyde,found that the GA yield was comparable to that recorded in the reaction using PFA.A study by Spencer[34]showed that no GA was produced using trioxane as the formaldehyde source (Rh(CO)Cl(PPh3)2,DMF,110 °C,8 MPa)because trioxane could not be decomposed to formaldehyde.

3.3.3.Solvents

As the place where the chemical reactions take place,the solvent characteristics such as polarity,solubility,acidity and basicity have an essential influence on the catalytic performance.Different from the fact that almost all the organic solvents are workable in the hydroformylation of olefin to aldehydes,the range of solvents effective for the hydroformylation of formaldehyde to GA is limited[62–65].The early studies on the solvent effect considered thatN,N-disubstituted amides (e.g.,DMA) were the sole solvent system that could promote GA generation.Spencer [34,35] investigated the HRh(CO)(PPh3)3-catalyzed hydroformylation of formaldehyde in a series of solvents using PFA at 110 °C,8 MPa.The results revealed that methanol was the predominant product with no GA formation in acetone,benzene,ethanol and acetic acid solvent.While 3%and 12.3%yield of GA was achieved in pyridine and DMA,respectively,suggesting the nature of solvent is critical in determining the reaction pathways.Further research on the molecule size of amide solvents(e.g.,(CH3)2NCHO,(n-C4H9)2NCHO)suggests that the lager substituted groups (relative to ethyl) on nitrogen or carbonyl-carbon atoms could reduce the GA yield.The remarkable difference in the GA yields (0vs.15%) for the reactions in CH3(C6-H5)NCHO and CH3(C6H11)NCHO indicates the electronic effects of amide solvents cannot be negligible.Therefore,it can be inferred that the amide solvent participates in the catalytic cycle and act through electronic and steric effects.Ohgomoriet al.[66],investigating the catalytic selectivity for the reaction over Rh4(CO)12using the cyclic amides,found that DMI promoted hydroxymethyl-metal complex (M-CH2OH) formation,which favoured GA production.While NMP facilitated the formation of the methoxy-metal complex (M-OCH3) that was selective to methanol production.Rh4(-CO)12was converted exclusively to [Rh(CO)4]-in NMP,which was active for the hydrogenation to methanol without any activity for hydroformylation.Additionally,we would like to note that the reaction can occur in common organic solvents in the presence of promoters,such as NEt3and phosphine oxide.This will be reviewed in Section 3.4.

Korneevaet al.[67]compared the electronic absorption spectra and IR spectra of RhCl(PPh3)3in CH2Cl2and DMA(or DMF)solvent and found that DMA(or DMF)appeared in the coordination sphere.This confirmed DMA(or DMF)served as not just a solvent that carried the reactant but also involved in the catalytic process.Whether the amide molecule coordinates to Rh only by nitrogen atom as a monodentate ligand or by nitrogen and oxygen atom together as a bidentate ligand,there must be the participation of nitrogen atom.Moreover,the coordination of amide is reversible.Amide can be replaced by the PPh3ligand.Formaldehyde was coordinated to Rh to form η2-HCHO which was unstable in a solution of RhCl(PPh3)3and CH2Cl2,and rapidly decomposed into CO and H2.N-coordinated amide was able to stabilise η2-HCHO in the coordination sphere.Unsubstituted amide H2NCHO and monosubstituted amide H(CH3CH2CH2)NCHO with strong hydrogen bonds tended to be associated and cannot coordinate to Rh to stabilise η2-HCHO or increase the GA yield.However,Chanet al.[60] proposed that the promoting effect of amide was not linked to the involvement in the coordination process,based on the observation that addition of alkaline NEt3enhanced the hydroformylation activity.The presence of amides served to enhance the formation of active anionic complexes.Okanoet al.[59] reported a super high GA yield of 94% with RhCl(CO)(PPh3)2using PFA in 4-methylpyridine under the conditions of 70 °C,9 MPa within 6 h.

3.4.Promoters

Promoters have a great impact on the catalytic activity and product distribution in the formaldehyde hydroformylation.Several basic and acidic compounds were examined as promoters.It was early recognised that amines were beneficial for the activity and selectivity of GA.A seminal article published in 1983 by Chanet al.[68]studied the impact of basic organic amines on the hydroformylation of formaldehyde.The addition of triethylamine (NEt3)showed somewhat higher conversions than that of secondary,tertiary amines and diamines.The formaldehyde hydroformylation catalysed by RhCl(CO)(PPh3)2inN,N-dibutylformamide using PFA as formaldehyde source at 110 °C and 28.5 MPa in the presence of a small amount of NEt3delivered up to 86% conversion and 91%selectivity of GA.Moreover,the addition of NEt3still generated high activity and stability,although the formaldehyde hydroformylation reaction rates were decreased by the excess of phosphine ligands.When NEt3was added to the Rh catalyst system containing excessive phosphine ligands,the reaction rates increased dramatically (Table 3,entry 1,2) [60].The discovery of the promoting effect of NEt3provided a strategy to formulate a stable and highly active formaldehyde hydroformylation catalytic system.

With the promoting effect of NEt3,the common organic solvents such as acetone,tetraglyme turn to be effective for the production of GA from the hydroformylation of formaldehyde,giving a comparable GA yield to that of the amide solvents (Table 3,entry 3).The inclusion of NEt3in the reaction system greatly expanded the range of suitable solvents.However,the amount of NEt3added to the reaction was found to have a remarkable effect on the product distribution.The condensation reaction would be enhanced using an excess of NEt3.The selectivity of by-products (e.g.,C3-C4 sugars) due to the condensation reaction dramatically went up from 9% to 27% with increasing the NEt3concentration from 0.84 mol·L-1to 1.8 mol·L-1[60].

A possible explanation for the promoting effect of amine might be that amine is a bifunctional promoter,which deprotonates the rhodium hydride species to form an active anionic catalyst (2)and serves as a proton source to form hydroxymethyl-rhodium complexes(3).Strong bases,like KOH and KOAc,cause more severe condensation,although make hydroformylation of formaldehyde occurs in the common organic solvents.In addition to theN-containing basic promoters,Goetzet al.[69] discovered that phosphine oxide,strong Lewis base,added in the reaction system promoted the hydroformylation to GA in the common organic solvents.It was demonstrated that GA yield was 51% and 5% within and without tributylphosphine oxide in the tetraglyme solvent(Table 3,entry 4).Ezhovaet al.[70]suggested that the role of phosphine oxide in the formaldehyde hydroformylation was similar to that of amide and amine,which helped to promote the deprotonation of rhodium hydride to anionic rhodium catalyst.

Detailed examination of acidic promoters,including strong and weak acids,organic and inorganic acids by Drent has been carried out from 1983 to 1990.The investigation of organic (e.g.,p-CH3C6H4SO3H)and inorganic(e.g.,HCl)acids suggested that acids served to improve the conversion and yield of GA.HCl was found to be the most effective among the acid promoters with 84% conversion and 95% selectivity achieved in the reaction (110 °C,6 MPa,DMF) using [RhCl(CO)2]2and PFA after 15 h (Table 3,entry 5)[71].A super high GA yield of 92%was reported in 1986 with acetic acid as the promoter[72].The degree of acidity of the acid promoters appears to have an impact on their efficiency.The weak acids have a more considerable improvement in the GA yield than the strong acids.29%yield of GA withp-CH3C6H4SO3H(TsOH)whereas 42%yield of GA with acetic acid under the identical conditions were reported (Table 3,entry 6,7) [47].This finding is consistent with that of Jacobsonet al.[53],who got a higher GA yield with the weak acid CF3COOH than that with the strong acid HCl.

High methanol selectivity for the aqueous system limits the use of formalin as cheaper feeding stock.Drent [73] invented a new method to suppress the hydrogenation of formaldehyde to produce methanol in the aqueous system by exposing the reaction solution to a CO/SO2gas mixture for seconds(e.g.,30 s) before the reaction(Table 3,entry 8).This brought about an appreciable increase of GA selectivity to 77%(from 38%).A strong linear relationship between the reaction rates and pH has been reported by Ezhovaet al.[70].It has been demonstrated that the reaction rates increased with decreasing pH.

Table 3Hydroformylation of formaldehyde in the presence of promoters①

There are two different explanations for the role of acid promoters.Giuseppe Braca [74] suggested that protonic acid involved in the activation of HCHO (4).Drent [47] argued that the promoting effect stems from anions.High electron affinity anions (e.g.,tosylate anions) reduce the electron density on the Rh centre,thus leading to a more acidic rhodium hydride which favour the formation of GA.

It is probable that the proton (H+) is not the only factor that plays a promoting role in the formaldehyde hydroformylation with HCl as the promoter.Spencer[35]carried out an investigation into the effect of anionic ligand via RhX(CO)(PPh3)3(X=F,Cl,Br,I)complexes and found chloride complex was superior to other halogens.This also accords with Marchionna’s [38,75] observation in the experimental study of the effect of halides on the catalytic activity and GA selectivity that the order of halogens was Cl>I>Br>F.It is noted that Rh4(CO)12decompose to[Rh(CO)2X2]-and[Rh5(CO)15]-in the presence of Cl-and thus hydroformylation can occur in acetone(Table 3,entry 9).These results suggest that Cl-is a promoter for the reaction.The function of Cl-is probably to convert Rh to the more active anion Rh complexes.Use of Bis(triphenylphosphine)i minium cation (PPN+) as the Cl-counterion provides the highest activity and selectivity.Whereas alkali chlorides,e.g.,Na+,Cs+,are ineffective for formaldehyde hydroformylation in acetone.Instead,alkali chlorides turn to be equally effective as that of PPN+in terms of the GA yield upon the addition of water or use of aqueous formaldehyde as feeding stock.Hence,the solubility of chlorides cannot be ignored when using chlorides as the promoters.

4.Mechanism of Hydroformylation of Formaldehyde

As described above,the nature of the metal,ligand,promoters and the reaction conditions strongly influence the catalytic activity and product selectivity in the hydroformylation of formaldehyde.The results clearly demonstrate that Rh complex with phosphine ligand shows higher hydroformylation activity and GA selectivity.Use of amide solvent and amine promoters serve to further enhance the catalytic performance.Indeed,this is a general trend in the hydroformylation of formaldehyde and constitutes a fundamental point for a rationalisation of the impact of these factors on the reaction pathways.In this context,we are going to examine the above results in the light of the generally accepted mechanism for the formaldehyde hydroformylation.

4.1.Neutral mechanism

There are two types of reaction mechanisms proposed in the existing literature for the formaldehyde hydroformylation.Some early studies believe that it occurs similarly to the olefin hydroformylation where neutral metal complex acts as catalytic sites.Chanet al.[60] initially proposed a dissociative mechanism that involved neutral rhodium complex (HRh(CO)2(PPh3)) as catalytic active species based on the observation that the dissociation of phosphine to provide an unsaturated complex was suppressed by an excess of phosphine.The catalytic cycle (Fig.8) consists of five main steps:1) phosphine ligand dissociation and exchange with CO to form a vacant site on rhodium.2)formaldehyde coordination to the metal centre.3) formation of the hydroxymethyl rhodium species by insertion of formaldehyde into the Rh-H bond.4) generation of hydroxyacetyl rhodium speciesviaCO insertion.5)hydrogenolysis of hydroxyacetyl rhodium intermediate to give GA at the end of the circle and regeneration the active neutral rhodium complex.However,the suggested dissociative mechanism has not been verified by spectroscopic characterisation.

In 1982,Suzuki [76] investigated the reaction kinetics using RhCl(CO)(PPh3)2as the catalyst in DMF based on the neutral mechanism.The equilibrium constants and rate constants for each elementary reaction (5)–(9) have been calculated at 100 °C asK1=1 × 10-4mol·L-1,K2=3 × 10-3kg-1·cm2,K3=4 mol·L-1,K4=1× 10-2kg-1·cm-1andK5=0.5 s-1.The hydrogenolysis reaction(9) was determined as the rate-determining step.The apparent activation energy was 76.6 kJ·mol-1.A complex reaction rate equation (10) was proposed,where the reaction order was -1 for the reactants (H2,CO and HCHO) and 0.5 with respect to the Rh concentration.

4.2.Anionic mechanism

Fig.8.Mechanism of hydroformylation of formaldehyde catalysed by neutral complexes.

In addition to the reaction mechanism based on the neutral metal complex,there is some evidence suggesting that the hydroformylation of formaldehyde involves anionic metal complex.For rhodium complex with an excess of phosphine ligand,a common starting complex is HRh(CO)2(PPh3)2(A) under the hydroformylation conditions.A can be converted into [Rh(CO)4]-(a) and [Rh(CO)3(PPh3)]-(b) after addition of a small amount of NEt3in the reaction solution(11),which consequently results in a remarkable increase in the activity [60].A possible explanation for this might be that complex a and b in some way participate in the catalytic cycle.The hypothesis for the transformation of the metal complex precursors was experimentally confirmed by Marchionnaet al.[40]who demonstrated that [Rh5(CO)15]-(c) was the actual form of rhodium in the reaction solution of Rh4(CO)12(B)-CoCl2.A following-up study for the effect of onium chloride promoters provided strong evidence for the formation of anionic rhodium complex.As demonstrated in the literature [75],B was decomposed to c and[Rh(CO)2Cl2]-(d)in the presence of Cl-(12).A solid mixture of c,d,and chloride salts was obtained from the solution after evaporation in vacuo.Addition of acetone and formaldehyde to the solid mixture catalysed the reaction at the working conditions leading to a comparable activity and selectivity.Further elaboration on the catalytic function of the anionic complexes c and d in the reaction was affordedviaa series of mixed catalysts [41].c with PPh3was rapidly converted to [Rh5(CO)15-x(PPh3)x]-(e)(13) that could represent c in the experiments.Rh(PPh3)2(CO)Cl(C) was taken as the reference due to low activity and selectivity.When C mixed with d,GA selectivity increased.Instead,a mixture of C and e resulted in increased activity.A significant increase in both activity and selectivity was observed with a combination of complex d with e.Marchionnaet al.suggested that complex e is critical in determining the activity,which serves to activate formaldehyde to give hydroxymethyl intermediate;while complex d is responsible for the catalytic transformation of the generated hydroxymethyl intermediate to hydroxyacetyl intermediate,a crucial active species in determining the selectivity.

Chanet al.[77,78] proposed an anionic mechanism for the hydroformylation of formaldehyde in 1993 (Fig.9).Hydroxymethyl rhodium intermediate HOCH2-Rh(CO)2(PPh3)2(I) and hydroxyacetyl rhodium intermediate HOCH2(CO)-Rh(CO)2(PPh3)2(II) were undetectable because the reaction of formaldehyde with[Rh(CO)2(PPh3)2]-was the rate-limiting step,and I and II were consumed immediately after formation.The authors tried to synthesise and characterise the two key intermediates I and II to verify the reaction mechanism.However,the intermediate I was unstable and easily converted into A owing to a facile β-hydride elimination.I and II had to be replaced by similar species,CH3OCH2-Rh(CO)2(PPh3)2(III) and CH3OCH2(CO)-Rh(CO)2(PPh3)2(IV),respectively.However,III cannot be obtained either as a result of a rapid CO insertion into the rhodium-alkyl bond.The chemistry of the iridium complex is similar to the corresponding rhodium complex but more stable.The successful synthesis of iridium intermediate CH3OCH2-Ir(CO)2(PPh3)2(V) and CH3OCH2(CO)-Ir(CO)2(PPh3)2(VI),as substitutes of I and II,enabled to complete the following reaction steps in the catalytic cycle,indirectly identifying the intermediates of I and II.The work by Chanet al.confirmed the anionic mechanism [79].The main difference between the neutral and anionic mechanism is the way how the metal complex attacked by formaldehyde.The neutral metal complex follows the former reaction mechanism while the anionic complex for the latter.Negative valence rhodium,as electron-rich metal,is more easily attacked by positively charged formaldehyde carbon atom and leads to high activity.

In 1995,Ezhovaet al.[80]detected the evolution of the Wilkinson’s complex precursor,RhCl(PPh3)3,to the formation of the anionic complex [Rh(CO)2(PPh3)x(DMA)y]-(x=1,2;y=1,0) under pressurised syngas (6 MPa,100 °C) in DMA solvent byin situIR spectroscopy(Fig.10).This work indirectly explains the promoting effect of basic solvents/promoters on the transformation of neutral metal complex to the anionic complex.The transformation process is independent of the catalyst precursors.When the precursor is changed to HRh(CO)(PPh3)3and RhCl(CO)(PBu3)2,detectable quantities of anionic complexes[Rh(CO)2Lx(DMA)y]-(L=PPh3,PBu3;x=1,2;y=1,0;)(f)were observed in the reaction solution.The initial reaction rate was proportional to the initial concentration of the anionic complex f [70].

Fig.9.Mechanism of hydroformylation of formaldehyde catalysed by anionic complexes.

Fig.10.Anionic complexes generated from RhCl(PPh3)3 in DMA under syngas.

5.Crucial Intermediates and Reaction Pathways

5.1.Formation of hydroxymethyl intermediate

The selectivity of GA in the hydroformylation of formaldehyde mainly depends on the formation of hydroxymethyl intermediate and the competition of CO insertion with reductive elimination for hydroxymethyl intermediate.

In general,the aldehyde is coordinated to metal onlyviathe oxygen atom[81],e.g.,in the case of the hydrogenation of aldehyde to alcohol.With an exception,formaldehyde can generate π-type coordination (η2-HCHO) complex with weak C=O bond [27].Fig.11 provides the common reactions of the coordinated formaldehyde.In the pathway 1,formaldehyde migratory insertion is involved in the hydroformylation.When L=H,two intermediates:hydroxymethyl-metal complex (M-CH2OH) and methoxymetal complex (M-OCH3) can be produced from the reaction.In the reported work,a limited number of studies are available on methoxy-metal complex derived from formaldehyde.But we can note that the reaction of [CpRe(NO)(PPh3)(η2-CH2O)]+with CpRe(NO)(PPh3)(CHO) yielded CpRe(NO)(PPh3)(OCH3) [82].In contrast,there are numerous examples of the insertion of formaldehyde in the M-H bond with different metals to give hydroxymethylmetal complexes [83].

Fig.11.General reactions for η2-HCHO in the transition metal complex.1)Insertion of HCHO in M-L bond.2) Formation of a formyl derivative by oxidative addition.3) Attach on the oxygen atom by an electrophile.4) Replaced by another ligand.

Roth and Orchin [26] investigated the stoichiometric hydroformylation of formaldehyde with HCo(CO)4at 0 °C (14).GA was the sole product with no methanol or methyl formate formation under the reaction conditions,implying the methoxy-metal complex was hardly generated.The Ir-O bond is weaker than the Ir-C bond in iridium complexes[84].Costa[85]also suggested that the hydroxymethyl-metal rather than methoxy-metal was the coordinated formaldehyde intermediate.Methyl formate,observed in some cases,obviously cannot be derived from the hydroxymethyl-metal intermediate.The author proposed a mechanism(Fig.12)that methyl formate was formed by the reaction of formaldehyde with metal-formyl complex,the production of CO insertion into a metal hydride bond,and subsequent intermolecular proton transfer to the coordinated ester intermediate from a metal hydride.

The formation of the hydroxymethyl has been linked to the acidity of the hydride ligand.A highly acidic hydrogen atom may be more selectively transferred to the formaldehyde oxygen atom,producing the hydroxymethyl ligand.This appears to work in the case of cobalt catalysts (e.g.,HCo(CO)4),which can catalyse the hydroformylation of formaldehyde exclusively to GA,as indicated in the work of Roth and Orchin.The hydride transfer involves two possible mechanisms of intermolecular and intramolecular hydrogen migration.In addition to the metal hydride,other proton sources,e.g.,[Et3NH]+,serve as intramolecular hydrogen and probably play a decisive role in the anionic mechanism for the generation of hydroxymethyl species.

From the above,a conclusion can be drawn that both methanol and GA are derived from the hydroxymethyl species,although the elimination of methoxy to methanol is more prone to take place than hydroxymethyl in other catalytic systems [86].

5.2.Competition of reductive elimination and CO insertion

Followed by the formation of hydroxymethyl-metal species,there are two reactions,CO insertion and reductive elimination(or hydrogenolysis),in the catalytic cycle (Fig.13).The ‘‘CO insertion”with subsequent reductive elimination gives rise to GA;while methanol results from direct reductive elimination of the hydroxymethyl intermediate.The competition of CO insertion and hydrogenolysis affects the selectivity of GA and methanol.

Very little information was found in the literature on the hydrogenolysis mechanism.Experimental [87] evidence reveals a dinuclear elimination rather than intramolecular hydrogenolysis(taking GA as an example,Eqs.(15) and (16)).

Fig.12.Methyl formate derived from the metal-formyl complex.

Fig.13.The competition of reductive elimination and CO insertion for the hydroxymethyl-metal complex.

The insertion of CO into a transition metal–carbon bond is a common reaction in organometallic chemistry and expected to be reversible (Fig.13).The reaction rate is affected by the nature of metal,migrating group and solvent.Cawse and Pruettet al.[88] noted that the CO insertion rate increased with electrondonating substituents on the migrating group.The central metal,e.g.,Rh,Co,Ru,and migrating group (-CH2OH) are not adjustable regarding a given system.Migration of the migrating group from the metal to CO leads to an unsaturated complex.An external ligand coordinated to the metal in the second step can suppress the abscission of the migrating group and decarbonylation,facilitating the CO insertion reaction indirectly.Wax and Bergman[89] confirmed that donor solvent could coordinate to the metal after alkyl migration to CO and increase the reaction rate.Thus,all the factors that promote CO insertion can improve GA selectivity.This accounts for high GA yield in the amide solvents as amide can accelerate the CO insertion.

6.Product Separation and Catalyst Recovery

The production of EG requires further hydrogenation of GA.However,the rhodium complex,as the most active hydroformylation catalyst,is not a satisfactory catalyst for hydrogenation of aldehyde,making it challenging to generate EG in one pot.Therefore,a separation of GA from the reaction solution posthydroformylation,with subsequent hydrogenation using a second catalyst system,e.g.,Co,Ru,is a better choice.Catalyst recovery is also crucial in the industrialisation of the homogeneous reaction process.In particular,the high cost and low abundance of noble metals (e.g.,Rh,Ru) requires low-loss catalyst recycling technologies to reduce the production cost.Separation of the catalyst from the products is an important consideration for the industrialisation of the formaldehyde hydroformylation.

Yukawaet al.[37] adopted a continuous distillation process at 120 °C to separate GA for the reaction conducted in a mixed solvent of DMA and dioxane with a cobalt catalyst.However,the instability of GA at high temperature makes the product separation unfeasible.Jacobsonet al.[53,90–92] proposed an improved twostep distillation process (Fig.14) for the reaction conducted in low-boiling acetonitrile solvent using rhodium and phosphineamide ligand PPh2(CH2)2C(O)N(CH3)(C18H37) (L14).A mixed solvent of acetonitrile-xylene-diethyl ether was used to avoid azeotrope of xylene and diethyl ether and separate the components.The lower-boiling components (acetonitrile,methanol and diethyl ether)were distilled first at 70°C under a CO sparge,which served to suppress the decomposition of the catalyst.The unreacted formaldehyde and GA were separated out from them-xylene solution while the rhodium-phosphine-amide catalyst was retained in them-xylene solution during distillation.The mixed formaldehyde and GA was washed with diethyl ether after filtration,and a lower concentration of catalyst(than 50 mg·L-1)remained in the precipitate.GA was purified by the second distillation,then dissolved in ethylene glycol and hydrogenated with ruthenium catalyst at 160 °C,3 MPa in a trickle-bed reactor.

Extraction was employed by Okanoet al.[59] to separate GA using 4-pentylpyridine as the solvent,which is immiscible with water.The authors claimed 99% of GA was achieved after extraction four times with 5 ml water,and the rhodium content in the aqueous extract was less than 2 mg·L-1.Pucketteet al.[93]discovered that use of bulky amide as the reaction solvent,although with low activity,showed less metal loss during the exaction using water as extractant due to the limited miscibility with water.The rhodium catalyst loss was less than 0.1 mg·L-1after extraction withN,N-di-n-hexyl-n-butyramide as the solvent.The separated organic phase can be re-added with formaldehyde to continue the reaction under the working conditions.

Fig.14.The simplified process of the two-step EG production and GA separation.

A heterogeneous catalyst Rh-TPPPTS/C was applied to overcome the problem of rhodium loss in catalyst recovery by Diwakar [94]in 2019.The catalyst could be separated from reaction mixtures by simple filtration with a lower risk of catalyst loss and decomposition.However,the conversion was only 18%at 110°C,5 MPa.The heterogeneous system presents significant advantages in the product/catalyst separation and recovery,but the catalytic performance requires dramatic improvement relative to the homogeneous reaction.

7.Conclusions and Outlook

The previous research on hydroformylation of formaldehyde has mainly focused on homogeneous reactions using the highly active rhodium centre and phosphorus ligands.Amide is an efficient solvent that can promote GA generation.The solvent range has been expanded to the common organic solvents with the aid of amine promoters,e.g.,NEt3.Neutral and anionic metal complex mechanism have been proposed to understand the catalytically active species and elemental reaction steps.Nevertheless,studies on reaction kinetics are limited.The full generation pathway and selectivity of GA were discussed from the perspective of the mechanism.Research on distillation and extraction for product separation and catalyst recovery was summarised.

The future study on the hydroformylation of formaldehyde has many directions that can be expanded.It has not yet been established the unambiguous relationship between the catalytic activity(or selectivity)and catalyst structure,e.g.,ligand.Since a number of useful ligands have been developed in the past decades,further investigation into ligand is strongly recommended to obtain high GA yield under milder conditions.Ligand effects (e.g.,electronic and steric) on the reaction is still not clearly understood,which requires an exploration using advancedin situcharacterisation techniques.Theoretical calculation studies are also needed to gain a better understanding of the origin of activity and selectivity of GA on the level of the reaction mechanism.Moreover,heterogeneous catalytic systems for the continuous and/or batch process are worthy of being developed considering the ease of product-catalyst separation.

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.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFA0704501).