Matilde V.
Solmi
a,
Jeroen T.
Vossen
ab,
Marc
Schmitz
a,
Andreas J.
Vorholt
b and
Walter
Leitner
*ab
aInstitute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany
bMax Planck Institute for Chemical Energy Conversion, Stiftstraße 34–36, 45470 Mülheim an der Ruhr, Germany. E-mail: walter.leitner@cec.mpg.de
First published on 17th May 2024
This work focuses on the development and investigation of a Rh/TPP catalytic system for the synthesis of saturated aliphatic carboxylic acids from readily available oxygenated substrates, H2 and non-toxic, renewable CO2. Optimization of the reaction conditions and reagents was carried out using 2-butanol and 1-butanol as typical secondary and primary alcohols. Afterwards, the reaction system was investigated in-depth with a separate investigation of the reverse water–gas-shift-reaction and the carbonylation reaction as key steps of the overall tandem transformation. Based on these results, a reaction network was established with two distinct main pathways. While the secondary alcohols are converted preferentially via acid catalysed dehydration to the corresponding olefins followed by hydroxycarbonylation, the primary alcohols react primarily via nucleophilic substitution to the iodide compound followed by a Monsanto-type carbonylation. Based on these results, a broad range of alcohols including bio-based substrates was converted to the corresponding C1 elongated carboxylic acids. Additionally, other oxygenated substrates such as aldehydes, ketones and industrially relevant substrate mixtures were applied successfully.
CO2 is a highly attractive renewable and non-toxic alternative to CO as a C1 building block. It can be used directly for carboxylations or in combination with “green” hydrogen as a reductant to provide in situ CO for carbonylations.35 Several substrate classes have been converted to carboxylic acids using CO2 as a C1 building block, such as boronic esters,36,37 organohalides,38–41 tosylates/mesylates,38,41 alkenes42,43 and dienes.44
Previously, our group reported a rhodium-based system, which produces carboxylic acids from simple alkenes with yields up to 91% using CO2 and H2 in a formal hydroxycarbonylation (Scheme 1). Mechanistic and labelling studies suggest the in situ formation of CO and H2O by a reverse Water–Gas Shift Reaction (rWGSR), which occurs in hydroxycarbonylation. Similar to the catalytic systems used in the Monsanto process for the carbonylation of methanol to acetic acid, the reaction requires acidic conditions and an iodide promoter and PPh3 as a ligand.45 The conversion of alcohols to carboxylic acids under these reaction conditions was also mentioned briefly in this preliminary study. Since then, Han et al. investigated the conversion of methanol to acetic acid with CO2/H2 using Rh/NHC catalytic systems with LiI as a promotor46,47 and Zhang et al. investigated the reaction with LiI as a promotor and iridium(III) acetate as a catalyst.48
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Scheme 1 Formal hydroxycarbonylation of oxygenated substrates (primary and secondary alcohols, ketones, aldehydes) with CO2, H2 and Rh catalyst.45 |
Herein, we report the use of a Rh-based homogeneous catalytic system for the synthesis of carboxylic acids from various oxygenated substrates such as alcohols, ketones, aldehydes and mixtures of substrates with CO2 and H2. The two reactions involved, rWGSR and hydroxycarbonylation, will be studied in detail to investigate the reaction pathway and potential intermediates in the process. Based on the findings for the different substrate classes, a reaction network will be established, and the broad applicability will be demonstrated.
Entry | Volume of acetic acid (ml) | p-TsOH·H2O (mol molRh−1) | Temperature (°C) | H2-pressure (bar) | Carboxylic acid yield (%) |
---|---|---|---|---|---|
If not specified, conversion is over 99%, the VA/2-MBA ratio is about 2/1 and the mass balance is around or above 80%. Reaction conditions: 1.88 mmol 2-BuOH, 46 μmol [RhCl(CO)2]2, acetic acid as solvent, 2.5 mol molRh−1 CHI3, 5 mol molRh−1 PPh3, and 20 bar CO2. | |||||
1 | 1 | 3.5 | 140 | 10 | 45 |
2 | 2 | 3.5 | 140 | 10 | 67 |
3 | 3 | 3.5 | 140 | 10 | 8 |
4 | 2 | — | 140 | 10 | 2 |
5 | 2 | 3.5 | 160 | 10 | 77 |
6 | 2 | 3.5 | 180 | 10 | 66 |
7 | 2 | 3.5 | 160 | 5 | 26 |
8 | 2 | 3.5 | 160 | 20 | 26 |
Firstly, the influence of solvents and their volume on the reaction was studied. Neat conditions mainly lead to the formation of ethers in the presence of p-TsOH.49 After a solvent screening (ESI, Table S1†), acetic acid turned out to be the best of the tested solvents with a total yield of 67%. The amount of solvent also influenced the reaction with 2 ml of acetic acid showing better results than 1 or 3 mL (Table 1, entries 1–3). The influence of p-TsOH·H2O on the yield of carboxylic acids is related to the amount of solvent. In 1 ml of acetic acid, the presence of p-TsOH·H2O does not have any influence on the carboxylic acid yield (ESI, Table S1†). The best result was obtained using 2 mL of acetic acid in the presence of p-TsOH·H2O (Table 1, entry 2), while the absence of the additive only led to traces of the desired product (Table 1, entry 4). This demonstrates that sufficient Brønsted acidity of the reaction medium is vital for the conversion. The influence of temperature in the range between 140 °C and 180 °C was tested afterwards, with the best result obtained at a temperature of 160 °C (Table 1, entries 2, 5 and 6). The yield of VA and 2-MBA rises to 77%, due to a reduced production of side products. A further increase to 180 °C results in a drop in carboxylic acid yield, probably due to a deactivation of the catalyst via ligand dissociation from the metal centre.
Reducing the H2-pressure to 5 bar (Table 1, entry 7) or increasing it to 20 bar (Table 1, entry 8) caused a drastic reduction of the carboxylic acid yield. With the H2 pressure set at 10 bar, a screening of the CO2 pressure was carried out (10–30 bar, ESI, Table S1†). 20 bar of CO2 was chosen for further studies, because no significant improvement could be reported for any other pressure. With these reaction parameters further experiments on the CHI3 and PPh3 amounts and Rh precursor were performed which can be found in the ESI, Table S2.†50 Under the optimized reaction conditions, a yield of 77% of carboxylic acids with a 2
:
1 ratio of VA
:
2-MBA was obtained.
The corresponding primary alcohol 1-BuOH was also investigated to determine the influence of the electronic structure of the alcohol group (Table 2). Tables with solvent, precursor and parameter screening can be found in the ESI (Tables S3 and S4†). The solvent screening shows similar trends to that for 2-BuOH with the best yield obtained in acetic acid. In contrast to the secondary alcohol, however, higher carboxylic acid yields were obtained for the primary alcohols without p-TsOH·H2O (Table 2, entry 4). This became even more apparent when increasing the temperature from 140 °C to 160 °C: the yield of carboxylic acids decreased from 35% to 26% if p-TsOH·H2O was present, while it increased to 59% if p-TsOH·H2O was omitted (Table 2, entry 6–8). This may be due to an increased formation of side products, in particular n-butyl ester, at a higher temperature in the presence of p-TsOH·H2O.49 The pressure also showed a significant influence as a hydrogen pressure of 20 bar increased the yield, whereas it reduced the yield for 2-BuOH (Table 2, entry 9–11). The highest yield of 64% (VA:
2-MBA = 2
:
1) was obtained with 1 mL acetic acid, 20 bar H2, without p-TsOH·H2O at 160 °C (Table 2, entry 10).
Entry | Volume of acetic acid (ml) | p-TsOH·H2O (mol molRh−1) | Temperature (°C) | H2-pressure (bar) | Carboxylic acid yield (%) |
---|---|---|---|---|---|
If not specified, conversion is over 99%, the VA![]() ![]() ![]() ![]() |
|||||
1 | 1 | 3.5 | 140 | 10 | 30 |
2 | 2 | 3.5 | 140 | 10 | 35 |
3 | 3 | 3.5 | 140 | 10 | 3 |
4 | 1 | — | 140 | 10 | 44 |
5 | 2 | — | 140 | 10 | 2 |
6 | 2 | 3.5 | 160 | 10 | 26 |
7 | 1 | — | 160 | 10 | 59 |
8 | 1 | — | 180 | 10 | 47 |
9 | 1 | — | 160 | 5 | 44 |
10 | 1 | — | 160 | 20 | 64 |
11 | 1 | — | 160 | 30 | 56 |
The rWGSR was tested by using the optimized conditions for either primary or secondary alcohols. The resulting gas phase was collected in a gas bag and analysed by GC. A CO yield of 2.6% was obtained for secondary alcohols and 3.1% for primary alcohols. The relatively high yield given the comparatively low reaction temperature for the rWGSR (Fig. 1) is largely due to the operation in the condensed phase. The same experiments were carried out in the absence of the precursor, demonstrating the catalytic role of the rhodium metal component (ESI, Table S9†).
The effect of the amount of CHI3 and PPh3 on the rWGSR was investigated (Fig. 1). CHI3 is required for the CO2 conversion to occur, as also reflected in the overall reaction system which barely shows any conversion without CHI3 (ESI, Fig. S4–S7†). However, large amounts reduce the CO yield, which may be due to the formation of inactive catalyst species at high I− concentrations. The phosphine ligand PPh3 has little influence on the rWGSR and presumably acts mainly as a stabilizing ligand for Rh species at low CO pressures.
Varying the amount of iodide additive in the carbonylation step shows the same results already observed for the rWGSR with the best yield at small amounts (Fig. 1 and ESI, Fig. S2†). Similar experiments were performed by varying the amount of PPh3 (Fig. 1 and ESI, Fig. S3†). In a reaction using CO and H2O directly, the stabilizing ligand is not required to obtain the desired product as the CO stabilizes the complex, being readily available from the beginning of the reaction, unlike with CO2 and H2 where it has the stabilizing effect for the complex at low CO pressures. The maximum activity observed is obtained with 10 eq. of PPh3. Increasing the amount of phosphine to 20 eq. results in a decrease of activity.
Blank tests without the catalyst were performed to see which reactions take place in the absence of the catalyst (Fig. 3). The corresponding iodide, acetate, alkane and olefin are formed in the absence of the transition metal catalyst. The olefin is formed preferentially over the iodide for 2-BuOH in comparison with that for 1-BuOH, reflecting that the dehydration of secondary alcohols is faster. 1-BuOH in turn forms more alkyl iodide, as the SN2 reaction is faster for primary alcohols in comparison with secondary alcohols.
![]() | ||
Fig. 3 Comparison between the blank test and the results obtained with the pre-catalyst for the preliminary reaction conditions and the optimized conditions for 2-BuOH (left) and 1-BuOH (right). |
Based on these investigations and results from the previous sections, an overall reaction network is proposed in Scheme 2. The alcohol can react via a first path in an SN2 reaction to form the iodide compound with an iodide source such as CHI3 or HI. The iodide can then react similarly to the Monsanto process by carbonylation forming iodic acid initially which cannot be detected as it is hydrolysed to the acid in the presence of water right away forming the carboxylic acid and HI. This path is more likely for primary alcohols as the SN2 reaction is faster in comparison with that for secondary alcohols. The alternative path occurs via the olefin through an acid catalysed dehydration of the alcohol, with the acetic acid solvent, p-TsOH·H2O and/or HI generating the required Brønsted acid. This step is more likely for secondary alcohols as they are dehydrated more easily than primary alcohols. The olefin can react in the carbonylation to form each of the acid product isomers, and it can also isomerize in the presence of the rhodium catalyst. The internal olefin can only form iso-products. In the presence of hydrogen, the rhodium complex can also hydrogenate the olefin to the corresponding alkane.
As observed in the screening experiments, without the iodide additive and without the acid additive p-TsOH·H2O or the acidic solvent acetic acid, the hydroxycarbonylation does not occur. This indicated that a direct reaction from the alcohols to the acids via a CO insertion is not possible and the reaction has to follow one of the two routes with iodoalkanes or olefins as intermediates. The acid-catalysed esterification to form acetates is considered as off-loop equilibrium as the direct conversion of acetates without hydrolysis to the alcohol has not been observed and, to the best of our knowledge, it is not known in the literature.
Entry | Substrate | Products | Yield (%) | Ratio 1![]() ![]() ![]() ![]() |
---|---|---|---|---|
Reaction conditions: 1.88 mmol substrate, 46 μmol [RhCl(CO)2]2, 1 ml acetic acid (primary alcohols) or 2 ml acetic acid (secondary alcohols), 3.5 mol molRh−1p-TsOH·H2O (secondary alcohols), 2.5 mol molRh−1 CHI3, 5 mol molRh−1 PPh3, 20 bar CO2, 20 bar H2 (primary alcohols) or 10 bar H2 (secondary alcohols), and 160 °C. For all substrates a conversion of 99% or higher was obtained.a 1 mL propionic acid.b Conditions for secondary alcohols applied. | ||||
1a | H3C-OH |
![]() |
19 | 19 |
2 |
![]() |
![]() |
80 | 80 |
3 |
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45 | 33![]() ![]() |
4 |
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![]() |
65 | 44![]() ![]() |
5 |
![]() |
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64 | 42![]() ![]() ![]() ![]() |
6 |
![]() |
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30 | 21![]() ![]() |
7 |
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77 | 50![]() ![]() |
8 |
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66 | 43![]() ![]() ![]() ![]() |
9 |
![]() |
![]() |
72 | 72 |
10b |
![]() |
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44 | 44 |
11 |
![]() |
![]() |
80 | 80 |
The reaction was investigated starting with cyclohexanone (CHN) due to its simplicity, since just one acid-product can be formed (cyclohexanecarboxylic acid, CA). The best conditions for 2-BuOH were used for the optimization of ketones because of the parallels between the two classes of substrates. Under these initial conditions, 68% of CA is formed at a conversion >99% (Table 4, entry 1). The most influential parameters (H2 pressure, volume of acetic acid and the reaction temperature) were studied as for the secondary alcohols to obtain high yields. An increase of H2 pressure from 10 to 20 bar increases the yield of carboxylic acid to 83% (Table 4, entries 1–3). A further increase up to 30 bar does not lead to any improvement, since the hydrogenolysis reaction towards cyclohexane becomes favoured. This finding agrees with the stoichiometry of the reaction as higher amounts of H2 are needed to convert the ketone into secondary alcohols before reacting to form carboxylic acids. In particular, it is reported that Rh/phosphine systems are active in the reduction of ketones to alcohols in the presence of H2O, which acts as a promoter.53–58
Entry | Volume of acetic acid (ml) | Temperature (°C) | H2-pressure (bar) | Yield (%) |
---|---|---|---|---|
If not specified, conversion is over 99% and the mass balance is around or above 80%. Reaction conditions: 1.88 mmol CHN, acetic acid as solvent, 46 μmol [RhCl(CO)2]2, 2.5 eq. CHI3, 5 eq. PPh3, and 20 bar CO2. | ||||
1 | 2 | 160 | 10 | 68 |
2 | 2 | 160 | 20 | 83 |
3 | 2 | 160 | 30 | 82 |
4 | 1 | 140 | 20 | 54 |
5 | 3 | 180 | 20 | 53 |
6 | 2 | 140 | 20 | 66 |
7 | 2 | 180 | 20 | 76 |
Afterwards, the effects of different amounts of solvents and the temperature were investigated. The best temperature and solvent for ketones were found to be the same as for the secondary alcohols with 160 °C and 2 mL of acetic acid (Table 4, entries 2, 4–7). Under optimised conditions, a yield of 83% of cyclohexane carboxylic acid was achieved starting from cyclohexanone (details in the ESI, Table S5†). To the best of our knowledge, this yield is the highest obtained from ketones with CO2 and H2.59
The sequential hydrogenation/carbonylation process is also reflected by the pressure drop as for example in the conversion of 2-butanone or 2-butanol to the C5 carboxylic acids (ESI, Fig. S10†). While the pressure-drop measured for 2-butanol is 7 bar, the pressure-drop for 2-butanone is 15 bar, in line with the theoretical pressure drop calculated for the ketone (details are reported in the ESI, Scheme S1†). Analysis of the reaction solution at different reaction times also clearly shows 2-butanol as an intermediate in the reaction sequence (ESI, Fig. S1†).
Various ketones could be converted to the C1 elongated carboxylic acids. Conversions of the ketones were always complete and the range of by-products was independent of the substrate used (corresponding acetate, iodide, olefin and alkane) with the alkane being the main side product in all reactions. On increasing the chain length from C3 to C6 ketones, the yield increases from 35% to 75%. Interestingly, the α,β-unsaturated ketone 2-cyclohexen-1-one led to the monocarboxylic acid also in high yield (Table 5, entry 5, 79%).
Entry | Substrate | Products | Yield (%) | Ratio 1![]() ![]() ![]() ![]() |
---|---|---|---|---|
Reaction conditions: 1.88 mmol substrate, 46 μmol [RhCl(CO)2]2, 1 ml acetic acid (primary alcohols) or 2 ml of acetic acid (secondary alcohols), 3.5 mol molRh−1p-TsOH·H2O (secondary alcohols), 2.5 mol molRh−1 CHI3, 5 mol molRh−1 PPh3, 20 bar CO2, 20 bar H2 (primary alcohols) or 10 bar H2 (secondary alcohols), and 160 °C. For all substrates a conversion of 99% or higher was obtained.a Determined by NMR. | ||||
1 |
![]() |
![]() |
35 | 24![]() ![]() |
2 |
![]() |
![]() |
54 | 37![]() ![]() |
3 |
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75 | 43![]() ![]() ![]() ![]() |
4 |
![]() |
![]() |
83 | 83 |
5 |
![]() |
![]() |
79 | 79 |
6 |
![]() |
![]() |
48 | 48 |
7 |
![]() |
![]() |
38 | endo: 1 |
exo: 37a |
For aldehydes the conditions optimized for primary alcohols were used as the starting point. A moderate yield of 37% of the C5 carboxylic acids was obtained starting from butanal (n:
iso = 2.3). Increasing the H2 pressure to 30 bar increased the yield up to 45%, reflecting the additional need for hydrogen during the reduction. While full optimization was not carried out in this case, the system clearly shows potential for the direct conversion of aldehydes to C1 elongated carboxylic acids as well.
Entry | Substrate | Products | Yield (%) | Ratio |
---|---|---|---|---|
Conversions: >99%.a Cyclohexanone![]() ![]() ![]() ![]() |
||||
1a | KA oil (ketone alcohol oil) |
![]() |
79 | 79 |
2b | ABE mixture (acetone–butanol–ethanol) 3![]() ![]() ![]() ![]() |
![]() |
C4: 28 | 20![]() ![]() |
C5: 43 | 30![]() ![]() |
|||
C3: 99 | 99 |
Bio-based feedstocks are also often complex mixtures, as for example acetone, butanol, and ethanol from the fermentation of carbohydrates (ABE process). Notably, the mixture obtained from ABE fermentation is transformed successfully to C3 (99%), C4 (28%), and C5 (43% yield) carboxylic acids using the optimized conditions for primary alcohols (Table 6, entry 1). This single step transformation from renewable alcohols is particularly interesting for the platform chemical valeric acid, which is currently produced in a two-step process via hydroformylation and oxidation from butene obtained from fossil resources (Scheme 4).1
![]() | ||
Scheme 4 Production of valeric acid via the current industrial two-step approach based on fossil resources vs. the single step renewable approach presented in this work. |
After the optimization, the reaction network was investigated in depth. The role of the individual components of the catalytic system was elucidated in detail. It was shown that the overall transformation is a tandem process comprising the reverse water–gas-shift-reaction of CO2 and H2 to CO and H2O, integrated with a subsequent carbonylation step. Both steps are catalysed by organometallic rhodium complexes formed from a single precursor under the reaction conditions. The carbonylation of the alcohols occurs either via the olefin formed by acid-catalysed dehydration or via the iodoalkane formed by nucleophilic substitution. Primary alcohols follow preferentially the substitution pathway, while secondary alcohols react mainly through the olefin path.
The scope of substrates of this reaction was extended from butanols used for the mechanistic investigation to a range of primary and secondary alcohols. Furthermore, it was shown that ketones and aldehydes can be hydrogenated in situ to alcohols before they undergo the hydroxycarbonylation reaction. Mixtures of substrates as applied in industry were successfully used in the reaction. In particular, the ABE fermentation mixture of acetone, butanol and ethanol is very promising, as it allows the conversion of biomass-derived C2 to C4 oxygenates to value-added products in a single reaction step.
In summary, the current study substantiates the potential of CO2/H2 as C1 building blocks for the general synthesis of carboxylic acids starting from alcohols, ketones, and aldehydes, and even mixtures thereof. This opens novel synthetic pathways to carboxylic acids based on renewable feedstocks as “short cuts” compared to the conventional sequence of hydroformylation and oxidation starting from fossil-based olefins.
Liquid substances were analysed using (±)-1-phenylethanol and/or n-dodecane as the standard. Acetone was used as a solvent for the work-up procedure (for cyclohexanol reactions acetone was substituted by dichloromethane). The correction factors were calculated preparing solutions with known amounts of substances and standard. The gaseous substances were quantified using ethane as a standard. As for the liquid samples, the correction values were obtained from self-made gas solutions with known amounts of gases.
Catalytic tests were repeated two or more times. The corresponding error bars are shown in the graphs or tables or indicated in the text. Errors for side products are not indicated for simplicity reasons, but they are usually around ±2%.
Footnote |
† Electronic supplementary information (ESI) available: Additional graphics, detailed experimental procedures and analytical data. See DOI: https://doi.org/10.1039/d4gc01732c |
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