Synthesis of Adipic Acid, 1,6-Hexanediamine, and 1,6-Hexanediol via Double-n-Selective Hydroformylation of 1,3-Butadiene

Article abstract of DOI:10.1021/acscatal.6b00189

A method for the synthesis of the industrially relevant monomers adipic acid, 1,6-hexanediol (HDO), and 1,6-hexanediamine (HMD) via isomerizing hydroformylation of 1,3-butadiene is described. The aldehyde intermediates are protected in situ as acetals to avoid hydrogenation to pentanal. Adipic aldehyde diacetal is obtained in good yields, and the first examples for the conversion toward adipic acid, 1,6-hexanediol, and 1,6-hexanediamine are shown.

Full text of DOI:10.1021/acscatal.6b00189

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Article
Synthesis of Adipic Acid, 1,6-Hexanediamine and 1,6-Hexanediol
via Double n-Selective Hydroformylation of 1,3-Butadiene
Jaroslaw Mormul, Jan Breitenfeld, Oliver Trapp, Rocco Paciello, Thomas Schaub, and Peter Hofmann
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b00189 • Publication Date (Web): 15 Mar 2016
Downloaded from http://pubs.acs.org on March 22, 2016
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Synthesis of Adipic Acid, 1,6-Hexanediamine and
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1
,6-Hexanediol via Double n-Selective
Hydroformylation of 1,3-Butadiene
a
Jaroslaw Mormul , Jan Breitenfeld , Oliver Trapp , Rocco Paciello , Thomas Schaub and
a
a,b
c
a,c*
b#
Peter Hofmann
a
Catalysis Research Laboratory (CaRLa), University of Heidelberg, Im Neuenheimer Feld 584,
D-69120 Heidelberg, Germany
b
Organisch-Chemisches Institut, University of Heidelberg, Im Neuenheimer Feld 270, D-69120
Heidelberg, Germany
c
BASF SE, Carl-Bosch-Strasse 38, D-67056 Ludwigshafen, Germany
#
†
15. August 2015
Abstract A method for the synthesis of the industrially relevant monomers adipic acid,
1,6-hexanediol (HDO) and 1,6-hexanediamine (HMD) via isomerizing hydroformylation of 1,3-
butadiene is described. The aldehyde intermediates are protected in situ as acetals to avoid
hydrogenation to pentanal. Adipic aldehyde diacetal is obtained in good yields and first examples
for the conversion towards adipic acid, 1,6-hexanediol and 1,6-hexanediamine are shown.
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Keywords
Hydroformylation, 1,3-Butadiene, Adipic Aldehyde, Acetal, Adipic Acid, 1,6-Hexanediol,
Hexamethylenediamine, Rhodium
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Introduction
Adipic acid, 1,6-hexanediamine (HMD) and 1,6-hexanediol (HDO) are important industrial
monomers for the synthesis of polyesters, polyamides and polyurethanes and therefore produced
1
on a large scale of several million tons per year. The main synthetic pathway for adipic acid is
,2
a multi-step oxidation of cyclohexane. The drawbacks of this process are overoxidation of
cyclohexane in the first step and large amounts of N O waste resulting from the use of nitric acid
2
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as the oxidant for the second step. Hydrogenation of adipic acid or its esters gives HDO.
,4
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HMD can be synthesized by amination of the diol but is predominantly produced by Ni-
catalyzed hydrocyanation of 1,3-butadiene to adiponitrile and subsequent hydrogenation to the
6
diamine. The hydrocyanation is a rather complicated multi-step process and requires the use of
the relatively expensive HCN gas. A possible replacement for the synthesis of 1,6-
difunctionalized hexane derivatives would be the utilization of adipic aldehyde, which can be
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obtained by double n-selective hydroformylation of 1,3-butadiene (Scheme 1).
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Scheme 1. Double n-selective hydroformylation of 1,3-butadiene towards adipic aldehyde and
possible subsequent conversion to adipic acid, HDO and HMD.
The selective hydroformylation of 1,3-butadiene is, therefore, of great interest and has been
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investigated in academic and industrial laboratories for more than 60 years.
The slower
reaction rate as well as difficulties in controlling the regioselectivity, however, makes it an
extremely challenging substrate with up to 14 different isomers and side products that may be
formed. The highest selectivity towards the desired linear dialdehyde previously was about 50 %,
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which is still insufficient for industrial applications. Another problem for commercialization is
the sensitivity of adipic aldehyde towards the intramolecular aldol reaction. Therefore, this
aldehyde is not compatible with typical industrial workup methods, e.g. distillation in the
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presence of a catalyst.
Most likely, the reason for the low selectivity in the rhodium catalyzed system is the
thermodynamically favored allyl-type intermediate I which is formed after iso-insertion of the
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first double-bond and results in the formation of 3-pentenal (Scheme 2).
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Scheme 2. Simplified section of the reaction mechanism showing n- and iso-insertion of the first
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double-bond giving 4- and 3-pentenal as the main products.
Recently, we have shown that the product after n-insertion (4-pentenal) can be converted
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selectively to adipic aldehyde under typical hydroformylation conditions. Since 3- and 4-
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pentenal are just double bond isomers, we saw a chance to solve this challenge by using the
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concept of isomerizing hydroformylation. However, the problem in this special case is the
formation of the thermodynamically most favored α,β-unsaturated isomer 2-pentenal, which is
known to be easily hydrogenated under typical hydroformylation conditions (Scheme 3,
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,17,23–25
Top).
Therefore, our challenge was to find a simple approach to avoid hydrogenation of
the unsaturated monoaldehyde-derivatives.
Scheme 3. Top: Isomerization of 3-pentenal giving 2-pentenal as the main product which is
hydrogenated under typical hydroformylation conditions. Bottom: Approach to avoid the
conjugated system by protection as an acetal (e. g. as its 1,3-dioxolane derivative).
One possibility to avoid the conjugated system is to protect the aldehyde as an acetal, which
might hamper the irreversible hydrogenation (Scheme 3, Bottom). Additionally, the acetal
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protection should also prevent the final product from decomposition by aldol reaction. So the
idea was to realize a tandem isomerizing hydroformylation with in situ acetalization. In 1994,
this concept was reported in a patent by Union Carbide with the highest selectivity for adipic
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aldehyde diacetal of 57 %. To improve the selectivity, we wanted to investigate this tandem
reaction in more detail. As mentioned before, the biggest problem is the hydrogenation of 2-
pentenal. To test our concept, we started our investigation with the isomerizing hydroformylation
of two different 2-pentenal acetals with and without additional diol and then used our insights to
move on to the crucial step, the isomerizing hydroformylation/acetalization of 1,3-butadiene.
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Results and Discussion
In a first set of reactions a “Chemspeed” robot system was used to investigate the isomerizing
hydroformylation without in situ acetalization. We tested both a 5- and 6-membered ring acetal
derivative of 2-pentenal and three bisphosphite ligands at 5 and 10 bar syngas pressure (Figure
1).
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Figure 1. Tested 5- and 6-membered ring acetals A and B and ligands L1-L3.
L1 represents a ligand from our triptycene-based bisphosphite family which showed the best
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selectivity in the double n-selective hydroformylation of 1,3-butadiene.
The biphenol-based
ligands L2 and L3 were chosen because of their remarkable selectivity in the isomerizing
22,27–29
hydroformylation of various internal olefins.
Five products were expected after the reaction, the hydrogenated pentanal acetal (1, Scheme 4)
and four hydroformylated isomers (2 - 5).
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Scheme 4. Isomerizing hydroformylation of substrates A (5-membered ring acetal) and B
(6-membered ring acetal) and expected products 1-5. Shown values represent the best obtained
results (both at 5 bar syngas pressure and with L2 as ligand).
The best results for both substrates were obtained by using ligand L2 and a syngas pressure of
5
bar. The use of the other ligands led to lower selectivities towards the desired linear aldehyde,
but with a different product distribution. L1 gave more of the branched hydroformylation
products 3 and 4, whereas a remarkable amount of the sterically crowded 2 was obtained by
using L3. For all ligand/substrate combinations, a lower syngas pressure was beneficial for the
selectivity. But most importantly, only small amounts of the hydrogenation product 1 were
obtained, which was a first proof for our concept (depending on the system a varying amount of
starting material and unknown side products were observed after the reaction, for a detailed
analysis see Supporting Info).
In the next set of reactions, we investigated the isomerizing hydroformylation using ligand L3
in the presence of the corresponding diol (Scheme 5). The main products were the hydrogenated
A/B
pentanal-acetal (1 ), linear and branched dialdehydes with one protecting acetal group
(“monoacetals”) and dialdehydes with both groups protected (“diacetals”).
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Scheme 5. Isomerizing hydroformylation of 2-pentenal acetals A and B in the presence of the
corresponding diol (ethylene glycol for substrate A and neopentyl glycol for substrate B).
Compared to the results without in situ acetalization, the linear to branched ratio was almost
not affected by the addition of a diol. Hydroformylation of substrate A with 4 equivalents of
A
ethylene glycol (MEG) gave 24 % of the hydrogenation product 1 and 72 % of the desired
diprotected compounds. Hardly any hydrogenation (3 %) was observed by using neopentyl
glycol (NPG) and the six-membered ring acetal B. However, after 20 hours reaction time, the
monoacetal derivatives represented the major part of the product mixture, indicating that the
acetalization is slower with NPG than with MEG. Despite the reduced hydrogenation, this is an
important drawback for an application since the final process starting from 1,3-butadiene
requires a rapid acetal formation.
The stability of the two different 2-pentenal acetal derivatives A and B against hydrolysis was
examined by adding an aqueous HCl solution to a toluene-d solution thereof. Under these
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conditions, the 5-membered ring acetal A was converted within a few hours to 2-pentenal,
whereas the 6-membered ring derivative was much more stable with only 20 % of the free
aldehyde after 2 days at room temperature. Even after 3 days heating to 60 °C about 50 % of the
starting material was still present. (See SI for details)
Since water is formed during the acetalization, this would explain the larger amount of
hydrogenation using substrate A in contrast to substrate B. In fact, hydroformylation of A in the
A
presence of 4 equivalents of water gave more than 70 % of the hydrogenation product 1
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(
Scheme 6). Four equivalents of water just increase the intermediate concentration of
unprotected 2-pentenal (which is rapidly hydrogenated) but are not enough to shift the
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equilibrium towards pentanal and 1 is still obtained as the main product.
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Scheme 6. Hydroformylation of A in the presence of 4 equivalents of water.
With this information in hand, we turned our attention to the hydroformylation of
1
,3-butadiene. This process consists of two consecutive steps; first: hydroformylation of
A
butadiene to a mixture of 3-pentenal acetal 6 and 4-pentenal acetal (which reacts rapidly to
2
adipic aldehyde diacetal and is, therefore, only observed in trace amounts) , second: isomerizing
1
A
hydroformylation of 3-pentenal acetal 6 to a mixture of linear and branched diacetals and
A
hydrogenation to pentanal acetal 1 as a side product (Scheme 7).
Scheme 7. Two consecutive steps in the isomerizing hydroformylation of 1,3-butadiene with in
situ acetal formation.
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Although the biphenol-based ligand L2 gave the highest selectivity in the isomerizing
hydroformylation experiments, we also tested the triptycene-based ligand L1 because of its
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superior selectivity in the hydroformylation of 1,3-butadiene toward adipic aldehyde.
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Preliminary tests with neopentyl glycol (NPG) led to major formation of the hydrogenated
B
product 1 . This is, in accordance with the in situ acetalization experiments, probably a result of
the slow acetalization and confirms that NPG is not a suitable diol for the final process. The
results for the tandem isomerizing hydroformylation/acetalization of 1,3-butadiene with MEG
are given in Table 1.
Table 1. Isomerizing hydroformylation of 1,3-butadiene with in situ acetal formation.
a
A
A
Entry Ligand Syngas
pressure [°C]
bar]
Temperature Acid
1
[%] [%] linear/branched
6
“diacetals”
b
[
[%] (n/iso)
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1
L1
L1
L2
L2
L1
L1
L2
L2
L1
L1
L1
30
30
30
30
10
30
10
30
80
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
2
61
0
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6
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39/6 (6.5)
63/19 (3.3)
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44/7 (6.3)
63/16 (3.9)
30/4 (7.5)
65/9 (7.2)
73/12 (6.1)
65/12 (5.4)
65/12 (5.4)
120
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120
80 → 120
80 → 120
80 → 120
80 → 120
30 → 10 80 → 120
30 → 10 80 → 120
30 → 10 80 → 120
0
1
Acetic acid 18
None 21
Reaction conditions: 2.25 mmol of 1,3-butadiene as stock solution in toluene (2.25 M, 1 ml),
ml ethylene glycol (18 mmol), Rh: 1 mol%, L/Rh=3, n-nonane as internal standard, 5 ml
1
toluene, overall reaction time: 20 h, determined by gas chromatography, TFA = trifluoroacetic
a
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acid (0.3 mol%), “linear diacetal” = diacetal of adipic aldehyde ; “branched diacetals” =
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diacetal derivatives of 2 , 3 and 4 (Scheme 4).
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To compensate inaccuracies during the addition of the volatile 1,3-butadiene to the preformed
catalyst mixture, we also determined n/iso ratios of the diacetal products (which is independent
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from the exact amount of added butadiene). Entries 1-4 show the effect of different temperatures.
A
At 80 °C L1 gives mainly a mixture of 3-pentenal acetal 6 and adipic aldehyde diacetal (Entry
1). This indicates that the isomerization is very slow under these conditions and that the reaction
virtually stops after the first step in Scheme 7.
Increasing the temperature to 120 °C enabled the isomerization and gave 19 % hydrogenation
A
towards 1 and 63 % of adipic aldehyde diacetal with a low n/iso ratio of 3.3 (Entry 2). Under
A
the same conditions, L2 showed a higher isomerization rate with almost full conversion of 6
A
even at 80 °C, but also much more of the hydrogenation product 1 (Entries 3 and 4). Since we
knew that the n-selective hydroformylation of 1,3-butadiene needs different conditions than the
A
isomerizing hydroformylation of 6 , we investigated the effect of changing the conditions after
two hours reaction time. Entries 5-8 are showing the consequence of changing the temperature.
Performing the reaction at 10 bar and change of the temperature from 80 °C to 120 °C led to high
A
n/iso ratios with both ligands (6.3 for L1; 7.5 for L2), but also to a huge amount of 1 (Entries 5
and 7). The hydrogenation was suppressed by conducting the procedure at 30 bar syngas
pressure. Again, L2 showed a superior isomerizing hydroformylation with a slightly worse n/iso
ratio of 7.2, but still more than 30 % hydrogenation (Entry 6). Using L1 at 30 bar gave just 14 %
hydrogenation, but with a decreased n/iso ratio of 3.9. Since there was room for improvement
using L1, we also tested the effect of changing both temperature and pressure after two hours
reaction time. The n/iso ratio could be increased to 6.1 with an overall selectivity of 73 % for the
desired adipic aldehyde diacetal by reducing the pressure to 10 bar after 2 hours (Entry 9).
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Entries 10 and 11 show that the use of a strong acid is necessary to reach high selectivities, due
to fast acetalization.
As already mentioned in the introduction, adipic aldehyde diacetal would only serve as an
intermediate for industrially relevant compounds like adipic acid, HDO and HMD, with recovery
of the used diol. To prove our concept, it was important to show that these transformations can
be done in a simple manner. Due to the limited size of our autoclaves, a reasonable amount of
adipic aldehyde diacetal was independently synthesized by oxidation of 1,2-cyclohexanediol and
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subsequent acetalization.
Even though the oxidation of acetal groups to acids or esters is known in the literature, it was,
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to the best of our knowledge, never shown for the synthesis of dicarboxylic acids.
To obtain
adipic acid, we used Oxone® (KHSO · 0.5 KHSO · 0.5 K SO ) and oxygen gas (Scheme 8).
5
4
2
4
About 70 % of the desired compound was obtained with both oxidants, together with small
amounts of starting material, adipic aldehyde, the corresponding glycol ester and ethylene glycol.
Glycolic acid (a possible oxidation product of ethylene glycol) was not observed in the NMR
spectra, but its formation cannot be excluded at this stage.
Scheme 8. Oxidation of adipic aldehyde diacetal (independently synthesized from 1,2-cyclo-
hexanediol) to adipic acid using Oxone® and oxygen gas as oxidants.
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The oxidation was also successful with a product mixture from the hydroformylation of
1
,3-butadiene giving 52 % adipic acid (Scheme 9). This value is in good agreement with the GC
selectivity of the hydroformylation shown in Table 1.
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Scheme 9. Oxidation of adipic aldehyde diacetal obtained by the hydroformylation of
1
,3-butadiene.
Reports about the reduction of acetals are scarce in the literature, and in most cases the
38–41
corresponding ethers are formed instead of alcohols.
We were able to obtain HDO in good
yield by simply using an aqueous suspension of Raney-Nickel as catalyst (Scheme 10). Again,
the reaction was successfully repeated with a product mixture from the hydroformylation of 1,3-
butadiene with a yield of 74 % for the hydrogenation step. A remaining challenge is the complete
separation of ethylene glycol from HDO, which should be possible by distillation on a bigger
scale.
Scheme 10. Reduction of adipic aldehyde diacetal (independently synthesized from 1,2-cyclo-
hexanediol) to 1,6-hexanediol and subsequent amination to 1,6-hexanediamine.
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To the best of our knowledge, there are only two publications about the direct reductive
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amination of an acetal group and both need aromatic amines and expensive reductants.
The
reason for the lack of a direct method is the incompatibility of the acetal cleavage (aqueous and
acidic conditions) with an effective reductive amination (water free and excess of ammonia). We
were able to circumvent this challenge by using just a small amount of water, harsh conditions
and ammonium salts as nitrogen source, but the only detected product under these conditions
was the 7-membered ring azepane. Although this shows that the direct reductive amination of an
acetal group is in principle possible, the huge excess of an ammonium salt which would be
needed to obtain the linear diamine would definitely not be applicable for an industrial process.
Finally, HMD was obtained by amination of HDO using an acridine-based ruthenium pincer
complex with a very good yield giving water as the only byproduct (Scheme 10). It should be
noticed that these reactions are only intended to show the applicability of adipic aldehyde
diacetal as a platform for industrially relevant compounds and do not represent optimized
reaction conditions or purification procedures. Further work is needed to establish a technical
process.
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In summary, we have shown significant advances in the double n-selective hydroformylation
of 1,3-butadiene with in situ acetalization to adipic aldehyde diacetal. To obtain further insight
into this reaction, we investigated the isomerizing hydroformylation of different 2-pentenal
acetals with and without in situ acetalization. The findings were used to establish a one-pot
procedure where we show the importance of changing the reaction conditions after a certain
reaction time to switch on the isomerization giving the desired compound in 73 % selectivity.
Additionally, preliminary experiments concerning possible applications of adipic aldehyde
diacetal were carried out. Oxidation to adipic acid was conducted with Oxone® and oxygen gas
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as oxidant. Hydrogenation to 1,6-hexanediol was achieved using hydrogen gas and Raney-Ni and
trifluoroacetic acid as catalysts. Remaining challenges for an industrial application are to assure
that oxidation of ethylene glycol doesn’t take place and to elaborate a distillation procedure for
HDO. 1,6-Hexanediamine was obtained by simple amination of the diol giving water as the only
byproduct. To the best of our knowledge, this is the first time that the synthesis of all these three
industrially relevant compounds was shown starting with the shared hydroformylation of 1,3-
butadiene. In particular, our process for the synthesis of 1,6-hexanediamine could show a
significant cost advantage by replacing hydrogen cyanide by synthesis gas.
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Experimental Section
General Experimental Details
Unless otherwise noted, all reactions and manipulations were carried out under an Ar
atmosphere using standard Schlenk and high-vacuum-line techniques or in a Braun inert-
atmosphere glovebox (Ar) at ambient temperature. All NMR chemical shifts are reported as δ in
1
parts per million (ppm). H NMR spectra were referenced to residual protiated solvent and
1
3
1
chemical shifts are reported in parts per million downfield from tetramethylsilane. C{ H} NMR
spectra were referenced to the solvent. Gas chromatographic analysis was performed on an
Agilent Technologies 6890N Network GC System equipped with a 30 m HP-5 column ((5%-
Phenyl)-methylpolysiloxane). The He flow rate was kept at 2.0 mL/min. The column
temperature was initially held at 40 °C for 1 min, then ramped at 4 °C/min to 90 °C, followed by
an immediate temperature ramp of 30 °C/min to 200 °C, held at this temperature for 5 min,
followed by a temperature ramp of 20 °C min to 250 °C and held at this temperature for 5
minutes. Typical retention times (min) are as follows: 2.0 (1,3-butadiene), 8.1 (nonane); acetals
with ethylene glycol: 9.2 (4-pentenal ethylene acetal), 9.6 (pentanal ethylene acetal), 9.8/10.1 (3-
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pentenal ethylene acetal trans/cis), 10.3/10.8 (2-pentenal propylene acetal cis/trans), 12.7
A
A
A
A
A
A
(
1-pentenal ethylene acetal), 15.6 (2 ), 15.7 (3 or 4 ), 15.8 (3 or 4 ), 16.2 (5 ), 17.9 (adipic
aldehyde diacetal); acetals with neopentyl glycol: 14.5 (4-pentenal propylene acetal), 14.7
pentanal propylene acetal), 14.8/14.1 (3-pentenal propylene acetal trans/cis), 14.9/15.3 (2-
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(
B
B
B
B
B
pentenal propylene acetal cis/trans), 16.9 (2 ), 17.0 (3 or 4 ), 17.0 (3 or 4 ), 17.3 (5 ), 20.6
B
(
adipic aldehyde diacetal). GC calibration curves were constructed for 1,3-butadiene, 2- and 4-
pentenal ethylene acetal and adipic aldehyde di(ethylene acetal). The amounts reported for
3-pentenal ethylene acetal are estimates made using the effective carbon number concept by
44
comparison with 2- and 4-pentenal ethylene acetal, as described in the literature.
Since the use of syngas is a potential hazard following measures were taken: The syngas bottle
was stored outside the lab and permanently connected to a gas distribution system equipped with
magnetic safety valves. The valves were connected to CO sensors inside the laboratory.
Additionally, personal CO sensors were used while working with syngas.
Three types of autoclaves were used for the experiments: Glass autoclave (volume: 20 ml,
overhead stirrer: 900 rpm, material: glass), Premex autoclave (volume: 60 ml, overhead stirrer:
800 – 900 rpm, material: stainless steel (1.4571)), selfmade Swagelok autoclave (volume: 20 ml,
internal stirring bar: 500 rpm, material: stainless steel 316). Pictures of the autoclaves are shown
in the Supporting Info.
Materials
Unless otherwise noted, reagents were purchased from commercial suppliers and used without
further purification. Toluene for the catalytic reactions was additionally degassed by either three
freeze-pump-thaw cycles or by sparging with Ar for a minimum of 15 min. The 1,3-butadiene
solution was purchased from Sigma-Aldrich and the concentration was checked over time with
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GC and NMR methods. The ligand L2 (BIPHEPHOS) was purchased from commercial suppliers
and used without further purification. The ligands L1 and L3 were synthesized by using or
9
,20,29
modifying literature known procedures.
Chlorocarbonylhydrido[4,5-bis-(di-cyclohexyl-
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phosphinomethyl)acridine]ruthenium(II) was a donation from BASF. Acetal derivatives, which
were used for comparison and GC-calibration were synthesized from the corresponding aldehyde
3
using a literature known procedure. The diacetal of adipic aldehyde was independently
1
synthesized by literature known procedures and used for calibration and subsequent
3
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reactions.
1
NMR spectra of 1,4-di(1,3-dioxolan-2-yl)butane (adipic aldehyde diacetal) for comparison: H
3
NMR (200.15 MHz, DMSO-d6) δ (ppm): 4.73 (t, JHH = 4.6 Hz, 2H, CH(OR) ), 3.64 – 3.92 (m,
2
1
8H, OCH CH O), 1.44 – 1.61 (m, 4H, CHCH ), 1.25 – 1.44 (m, 4H, CHCH CH ). C{ H}
3
1
2
2
2
2
2
NMR (50.33 MHz, DMSO-d6) δ (ppm): 103.6 (CH(OR) ), 64.2 (OCH CH O), 33.4 (CHCH ),
2
2
2
2
23.7 (CHCH CH ).
2 2
Isomerizing hydroformylation of 2-pentenal acetals
The isomerizing hydroformylation of 2-(but-1-en-1-yl)-1,3-dioxolane (A) and 2-(but-1-en-1-
yl)-5,5-dimethyl-1,3-dioxane (B) was conducted using a ChemSpeed Accelerator SLT 106 high-
throughput robot system. Two substrates, three ligands and two syngas pressures (5 and 10 bar)
were tested. All manipulations were conducted under a nitrogen atmosphere.
Reaction conditions: 1 mmol substrate, 100 °C, 5 or 10 bar H :CO (1:1), 6 h, 6 ml toluene,
2
[
Rh]: 2 mol %, L/Rh=1.5
For the reaction stock solutions were prepared for [Rh(acac)(CO) ] (3.3 mM in toluene) and
2
for each substrate (167 mM in toluene). The ligands were used as solids and filled directly into
suitable test tubes (L1: 23.1 mg per test tube; L2: 26.7 mg per test tube; L3: 23.3 mg per test
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tube). For reproducibility each ligand was tested twice. The test tubes were transferred into two
steel blocks with 16 autoclaves each (4 of them each containing empty test tubes for blank
reactions). 4 ml of the rhodium stock solution were added, the system pressurized with 10 bar
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syngas (H :CO 1:1) and stirred (vortex, 800 rpm) for one hour at 100 °C (catalyst preforming).
2
After cooling down to 10 °C, 2 ml of the respective substrate stock solution were added to each
reactor. One block was pressurized with 5 bar, the other one with 10 bar syngas and stirred for 4
h at 100 °C. After cooling down to 10 °C samples were taken and analyzed by gas
chromatography without using correction factors.
Isomerizing hydroformylation of A at 70 °C in a pressure glass reactor
In a pressure glass reactor (max. pressure 15 bar, overhead stirrer) a mixture of 10 mg
[Rh(acac)(CO) ] and 45 mg L3 was dissolved in 10 ml toluene, pressurized with 10 bar syngas
2
(H :CO 1:1) and stirred (900 rpm) at 100 °C for 80 minutes (including the heating and cooling
2
time). After cooling to about 30 °C 0.5 g of A were added. The reactor was pressurized with
0 bar syngas, closed and stirred (900 rpm) at 70 °C for 20 hours. After cooling to room
1
temperature samples were taken and analyzed by gas chromatography without using correction
factors.
Isomerizing hydroformylation of 2-pentenal acetals with in situ acetalization
The procedure is shown for Entry 1 in Table 1 in the Supporting Info:
In a pressure glass reactor (max. pressure 15 bar, overhead stirrer) a mixture of 10 mg
[
(
Rh(acac)(CO) ] and 91 mg L3 was dissolved in 5 ml toluene, pressurized with 10 bar syngas
2
H :CO 1:1) and stirred (900 rpm) at 100 °C for 80 minutes (including the heating and cooling
2
time). After cooling to about 30 °C 0.5 g A and 0.5 ml of monoethylene glycol were added. The
reactor was pressurized with 10 bar syngas, closed and stirred (900 rpm) at 100 °C for 20 hours.
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The pressure decreased during the reaction time to about 6.5 bar. For reproducibility, every
reaction was done twice. Samples were analyzed by gas chromatography without using
correction factors. The reaction with cyclohexane as solvent was done in the same manner.
Stability of 2-pentenal acetals against hydrolysis
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Small portions of substrates A and B were added to screw cap NMR tubes and dissolved in
toluene-d (every substrate twice -> 4 NMR tubes). To each mixture 2 equivalents of a diluted
8
aqueous HCl solution (~ 0.1 M) were added, thoroughly shaken and analyzed over several days
by proton NMR. Results see Supporting Info.
Hydroformylation of A in the presence of 4 equivalents of water
The reaction was carried out in the glass reactor in the same manner like the in situ
acetalization experiments. Instead of the diol, four equivalents of water were added together with
the substrate. The product mixture was analyzed by gas chromatography without using
correction factors.
Isomerizing hydroformylation of 1,3-butadiene with in situ acetalization
A solution of 45 mg L1 or 45 mg L2, respectively, 5 mg [Rh(acac)(CO) ] and 25 ul n-nonane
2
(internal standard) in 5 ml toluene was added to a Swagelok steel autoclave (volume ~ 20 ml).
The autoclave was flushed several times with syngas and finally pressurized to 15 bar syngas.
After heating to 100 °C the mixture was stirred (stirring bar, 500 rpm) for 1 hour. After the
catalyst preforming was complete, the autoclave was cooled down to 0 °C and 1 ml of a 1,3-
butadiene stock solution (2.25 M in toluene), 1 ml ethylene glycol and 50 ul of a trifluoroacetic
acid solution (0.14 M in toluene) were added very carefully using a very weak syngas
counterflow. The autoclave was closed and subjected to the conditions shown in Table 1. For
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reactions 5-8 the temperature was changed after two hours reaction time. For reactions 9-11 the
autoclave was cooled to 0 °C after two hours reaction time, the pressure adjusted to 10 bar and
stirred at the indicated temperature for another 18 hours. The analysis of the product mixture was
done with gas chromatography without further purification. To compensate inaccuracies during
the addition of 1,3-butadiene to the preformed catalyst mixture the n/iso ratio of the diacetal
products was also determined.
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Oxidation of adipic aldehyde diacetal to adipic acid with Oxone®
580 mg (2.9 mmol) of 1,4-di(1,3-dioxolan-2-yl)butane (adipic aldehyde diacetal) were mixed
with 4 ml water and 0.15 ml sulfuric acid. After stirring for 15 minutes 1 g Oxone® (KHSO5 ·
0.5 KHSO · 0.5 K SO ) (3.3 mmol) was added. After stirring for 3 hours another 0.5 g Oxone®
4 2 4
were added and stirred for 16 hours. The mixture was extracted with EtOAc (5 x 10 ml) and the
solvent removed under reduced pressure to obtain 530 mg of an oily solid. An NMR sample with
naphthalene as internal standard showed a 75 % yield of adipic acid.
Oxidation of adipic aldehyde diacetal to adipic acid with oxygen gas
130 mg (0.64 mmol) of 1,4-di(1,3-dioxolan-2-yl)butane (adipic aldehyde diacetal) were mixed
with 5 ml water and 0.2 ml sulfuric acid. 45 mg (0.16 mmol) FeSO x 7 H O were added and the
4
2
colorless solution transferred to a Swagelok steel autoclave. Under vigorous stirring the system
was pressurized and depressurized several times with oxygen gas (2.5 bar) to remove nitrogen
and other inert gases. After finally pressurizing with oxygen (2.5 bar) the autoclave was closed
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and stirred for 4 days at room temperature. The product mixture was extracted with EtOAc (4 x
10 ml) and the solvent removed under reduced pressure to obtain 90 mg of an oily solid. An
NMR sample with naphthalene as internal standard showed a 70 % yield of adipic acid.
Hydroformylation of 1,3-butadiene and subsequent oxidation to adipic acid
2 ml of a 1,3-butadiene solution in toluene (containing 3.9 mmol 1,3-butadiene) were
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hydroformylated according to the standard procedure (Entry 9 in Table 1). After adding Na CO3
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to the product mixture to ensure basic conditions, the mixture was filtered over a short plug of
silica to obtain the organic phase with the desired product. The solvent and the volatiles, e.g.
nonane, pentanal acetal, were removed under reduced pressure. 4 ml of water were added
together with about 0.15 ml of sulfuric acid (conc.). The emulsion was stirred for 15 minutes and
then 1 g of Oxone® (KHSO ·0.5 KHSO ·0.5K SO ) (3.3 mmol) was added. After stirring for 3
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hours another 0.5 g Oxone® were added and stirred for 16 hours. The mixture was extracted
with EtOAc (5 x 10 ml) and the solvent removed under reduced pressure to obtain 490 mg of an
oily solid. Two samples were taken for NMR analysis with naphthalene as an internal standard.
The overall yield of adipic acid was 52 % based on 1,3-butadiene (51.3 % in sample 1, 52.8 % in
sample 2). For purification the rest of the product was washed with 3 ml of a CH Cl /petroleum
2
2
ether mixture (2:1) giving a yield of 240 mg (45 %, not optimized).
Reduction of adipic aldehyde diacetal to 1,6-hexanediol
1.64 g (8.1 mmol) of 1,4-di(1,3-dioxolan-2-yl)butane (adipic aldehyde diacetal) were mixed
with 30 ml water and 0.3 ml trifluoroacetic acid and stirred for 15 minutes. 1.2 g of wet Raney
Nickel (washed several times with water to remove the base) were suspended in 5 ml water and
added to a Premex steel autoclave together with the mixture of the diacetal. The autoclave was
closed, pressurized with 50 bar hydrogen and stirred at 130 °C for 16 hours. After cooling down
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the suspension was filtered over celite and the solvent removed under reduced pressure giving
-
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.75 g of green oil which was purified by Kugelrohr distillation (3 flasks, 140 °C, 1 x 10 mbar).
The flask with the lowest temperature (ice bath) contained mainly ethylene glycol with traces of
the desired dialcohol. The middle flask contained a mixture of 75 wt% 1,6-hexanediol and 25
wt% ethylene glycol (determined with naphthalene as internal standard). The green residue was
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dissolved in 15 ml EtOAc and 0.5 g Na EDTA and 2 ml water were added. After vigorous
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stirring for 15 min the organic phase was removed and the blue residue extracted with another 10
ml EtOAc. The organic solvent was removed in vacuo giving 280 mg of an oil with an 1,6-
hexanediol content of 50 wt%. The sum of 1,6-hexanediol was 68 % based on the used
dialdehyde.
Amination of adipic aldehyde diacetal to 1,6-hexanediamine
810 mg (6.9 mmol) 1,6-hexanediol were mixed in a Premex steel autoclave with 31 mg
Chlorocarbonylhydrido[4,5-bis-(di-cyclohexyl-phosphinomethyl)acridine]ruthenium(II) and 20
ml of toluene. The autoclave was closed, cooled down to 0 °C and pressurized for 1 hour with
ammonia gas (~ 5 bar). The autoclave was heated to 155 °C and stirred for 16 h. After cooling
down the solvent was removed in vacuo and the product mixture analyzed by NMR spectroscopy
with naphthalene as internal standard. The amount of 1,6-hexanediamine in the crude mixture
was 88 % based on used 1,6-hexanediol. After Kugelrohr distillation 660 mg of the product were
obtained as colorless crystals (81 %).
Synthesis of 1,6-hexanediol and 1,6-hexanediamine starting from 1,3-butadiene
1
ml of a 1,3-butadiene solution in toluene (containing 1.9 mmol 1,3-butadiene) was
hydroformylated according to Entry 8 in Table 1. To obtain enough material for the subsequent
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transformations, this reaction was done 8 times and the product mixtures were collected. After
adding Na CO to the product mixture to ensure basic conditions, the mixture was extracted with
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brown solution (mainly consisting of toluene). After distillation (8 · 10 mbar, 130 °C) 2.3 g of a
colorless oil were obtained containing adipic aldehyde diacetal in 68 wt%. Yield: 51 %.
According to GC and GC/MS the side products were the branched diacetals and pentanal acetal.
2.15 g of the product mixture (corresponding to 1.46 g (7.2 mmol) of adipic aldehyde diacetal)
were mixed with 30 ml water and 0.3 ml trifluoroacetic acid and stirred for 15 minutes. 1.9 g of
wet Raney Nickel (washed several times with water to remove the base) were suspended in 5 ml
water and added to a Premex steel autoclave together with the mixture of the diacetal. The
autoclave was closed, pressurized with 50 bar hydrogen and stirred at 130 °C for 16 hours. After
cooling down the suspension was filtered over celite and the solvent removed under reduced
pressure giving a green oil. The product mixture was dissolved in 20 ml EtOAc and 0.21 g
Na EDTA and 2 ml water were added to remove most of the Ni impurity. After vigorous stirring
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for 15 min the organic phase was separated and the blue residue extracted 3 times with 10 ml
EtOAc. The organic solvent was removed in vacuo giving 1.83 g of a slightly green oil which
-1
was purified by Kugelrohr distillation (3 flasks, 140 °C, 3.5 · 10 mbar). The flask with the
lowest temperature (ice bath) contained mainly ethylene glycol and about 22 % (based on the
diacetal) of the desired dialcohol. The middle flask contained mainly 1,6-hexanediol with a yield
of 52 % (determined with naphthalene as internal standard). The combined yield was 74 %.
ASSOCIATED CONTENT
Supporting Information. Text and tables giving details about the isomerizing hydroformylation
(with and without acetalization) of the two 2-pentenal acetals, details about the stability of 5- and
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-membered ring acetals against hydrolysis, H NMR spectra for all subsequent reactions
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oxidation, reduction, amination) and pictures of the used autoclaves. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Author
* thomas.schaub@basf.com
Notes
The authors declare no competing financial interest.
Dedication
We dedicate this paper to the memory of Prof. Dr. Peter Hofmann.
ACKNOWLEDGMENT
CaRLa (Catalysis Research Laboratory) is being co-financed by the Ruprecht Karls University
of Heidelberg and BASF SE, Ludwigshafen, Germany.
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