Formation of acetals under rhodium-catalyzed hydroformylation conditions in alcohols

Article abstract of DOI:10.1002/adsc.201100707

Hydroformylation of terminal alkenes in alcohol solvents leads to the selective formation of the corresponding acetals. The Xantphos ligand gave the best results as well as acetal selectivities higher than 99% and linear/branched ratios of up to 52 were obtained. The scope of the reaction was studied. Acetals were found to be unreactive under hydroaminomethylation conditions. Copyright

Full text of DOI:10.1002/adsc.201100707

FULL PAPERS
DOI: 10.1002/adsc.201100707
Formation of Acetals under Rhodium-Catalyzed
Hydroformylation Conditions in Alcohols
Olivier Diebolt,a Clꢀment Cruzeuil,a Christian Mꢁller,a and Dieter Vogta,*
a
Schuit Institute of Catalysis, Laboratory of Homogeneous Catalysis, Eindhoven University of Technology, P.O. Box 513,
5600 MB Eindhoven, The Netherlands
Fax : (+31)-40-245-5054; e-mail: d.vogt@tue.nl
Received: September 9, 2011; Revised: December 16, 2011; Published online: February 23, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100707.
Abstract: Hydroformylation of terminal alkenes in ied. Acetals were found to be unreactive under hy-
alcohol solvents leads to the selective formation of droaminomethylation conditions.
the corresponding acetals. The Xantphos ligand gave
the best results as well as acetal selectivities higher
than 99% and linear/branched ratios of up to 52 Keywords: acetals; alcohols; alkenes; hydroformyla-
were obtained. The scope of the reaction was stud- tion; phosphorus ligands; rhodium
Introduction
Results and Discussion
The last 40 years have seen considerable progress in Ligand and Parameter Screening
the field of rhodium-catalyzed hydroformylation.[1]
Many catalytic systems have been reported and nowa- We reported recently on the excellent activities and
days excellent selectivities and turnover frequencies selectivities obtained in hydroaminomethylation using
can be achieved under mild reaction conditions. Rep- a combination of a rhodium source and the DPX
resenting a potential atom efficient route to amines, ligand (Scheme 2).[4a] Ethanol and methanol were the
we are interested in the hydroaminomethylation most suitable solvents for this transformation. Hence,
(HAM),[2,3] a cascade reaction involving hydroformy- the hydroformylation of 1-octene using a DPX-modi-
lation and
a
reductive amination step (see fied rhodium catalyst was carried out in methanol. A
Scheme 1).[4] This reaction proceeds faster and with new product was formed in high selectivity which was
better selectivities using alcohols as co-solvent.[4a] In identified as the acetal 1,1-dimethoxynonane (see
order to understand the role of the alcohol in the cat- Scheme 2). The amount of aldehyde in the final mix-
alytic cycle, we decided to investigate in the first ture composition was only 0.2% (Table 2 entry 6).
place the hydroformylation reaction in alcohol sol-
vents.
Scheme 1. Hydroaminomethylation reaction.
Scheme 2. Acetal formation in methanol.
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Formation of Acetals under Rhodium-Catalyzed Hydroformylation Conditions in Alcohols
Table 1. Hydroformylation of 1-octene in methanol using monodentate ligands.[a]
Entry
L
Cone angle c[b]
Conversion[c] % Octane Acetal selectivity [%][d] l/b ratio acetal
1
2
3
4
5
6
7
8
none (CO)
–
145
–
–
–
49.7
97.9
15.2
1.1
0.1
31.6
10.4
2.9
0.8
12.1
0.2
0.4
44.4
95.6
96.3
95.5
91.9
60.3
95.6
0.0
91.1
81.8
0.7
1.5
4.4
2.1
1.4
2.0
4.3
n.d.
2.4
4.5
1.5
2.8
P
G
phosphabenzene[e]
24.0[h] 95.7
P(OAr)3[g]
G
175
175
128
128
141
145
132
170
30.0
30.0
29.2
29.2
28.0
12.8
4.2
99.2
100
PACHTUNGTRENNUNG
P
T
96.9
22.6
99.0
93.9
91.7
96.8
P
R
P(O-o-tolyl)3
PPh3
PBu3
9
10
11
PCy3
0.3
65.1
[a]
Reaction conditions: in a 10 mL autoclave were placed 1-octene (1 mmol), dodecane (0.2 mmol, internal standard for
GC), methanol (20 mmol), [Rh(cod)2]BF4 (10 mmol, S/Rh=100), ligand (30 mmol, L/Rh=3), CO/H2 (30 bar, 1:2 ratio),
1108C, 1 h. For full details on final mixture composition, see Supporting Information, Table S1.
AHCTUNGTRENNUNG
[b]
[c]
[d]
[e]
[f]
Tolman electronic parameter. c[PACHTUNGTRNEUNG
(t-Bu)3]=0 (see ref.[8]).
Conversion based on octenes consumption.
Selectivities calculated amongst C9 products.
2,4,6-Triphenylphosphabenzene.
Ar=2,4-(t-Bu)2C6H3.
[g]
[h]
P/Rh=10.
Based on the complex trans-[L2Rh(CO)Cl] (see ref.[9]).
Table 2. Hydroformylation of 1-octene in methanol with bidentate ligands.[a]
Entry
L
Bite angle bn (8) Conversion[b] % Octane Acetal selectivity [%][c] l/b ratio acetal
1
2
3
4
5
6
7
dppm
dppe
72
85
93
99
3.2
1.0
4.3
29.2
91.3
84.5
78.8
3
0.9
1
11.5
7
22.6
4
n.d.
n.d.
71.9
32.2
97.9
99.7
97.6
n.d.
n.d.
2.3
9.3
4.1
(R)-Binap
dppf
rac-bidentate phosphite 101
DPX
Xantphos
111
111
14.9
42.3
[a]
Reaction conditions: in a 10 mL autoclave were placed 1-octene (1 mmol), dodecane (0.2 mmol, internal standard for
GC), methanol (20 mmol), [Rh(cod)2]BF4 (10 mmol, S/Rh=100), ligand (30 mmol, L/Rh=3), CO/H2 (30 bar, 1:2 ratio),
AHCTUNGTRENNUNG
1108C, 1 h. For full details on final mixture composition, see Supporting Information.
Conversion based on octenes consumption.
Selectivities calculated amongst C9 products.
[b]
[c]
The formation of acetals from alkenes under hydro- was slow, 50% octene being left unreacted (entry 1).
formylation conditions has been already described in The very p-accepting 2,4,6-triphenylphosphabenzene[9]
the literature.[5] This reaction has been reported to be and P
ACTHNUGTRNEU(GN pyrrolyl)3 ligands gave excellent acetal selec-
[10]
catalyzed by various metal precursors including tivies, the latter leading to a better l/b ratio (entries 2
cobalt, palladium, platinum and rhodium in alcohol and 3). The more significant steric bulk of 2,4,6-tri-
media[6] or by using orthoformate derivatives.[7] We phenylphosphabenzene appeared deleterious for the
report here on a systematic study of the influence of regioselectivity. The same trend was observed with
different reaction parameters (ligand, alcohol, sub- phosphite ligands, the cone angle having a considera-
strate, etc.) on the acetal selectivity in the rhodium- ble impact on both yields and linearities (entries 4, 6
catalyzed reaction. To understand the formation of and 8). Increasing the ratio P/Rh had an important
acetals, the same reaction was conducted using mono- effect on the acetal formation (entries 5 and 7). In the
dentate ligands with different steric and electronic case of P
ACHTUNGRTENN(UNG OAr)3, known to lead selectively to mono-
properties (see Table 1).[8] coordinated rhodium species,[11] similar hydroformyla-
When performing the reaction without any phos- tion activities were observed. However, high P/Rh
phorus ligand, the acetal selectivity was high but the ratios reduced the acetalization activity (entry 5). In-
l/b ratio was expectedly poor. Moreover the reaction creasing the amount of PACTHNUTRGNEUNG(OPh)3, known to form di-
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Olivier Diebolt et al.
FULL PAPERS
and tri-coordinated complexes with rhodium, led to
a dramatic decrease of both hydroformylation and
acetalization activities (entry 7). This effect was al-
ready observed by El Ali et al.[6f] Surprisingly PPh3
gave mainly acetals, but with lower acetal selectivity
than with p-acceptor ligands (entry 9). The highly s-
donating PBu3 and PCy3 ligands gave lower acetal
yields (entries 10 and 11). Interestingly, PBu3 hardly
allowed the formation of acetal and a significant
amount of alcohols was formed instead (28.8% with
l/b ratio of 6.9).[12] It is important to note that no un-
Figure 2. rac-Bidentate phosphite used.
saturated ethers were detected in this case by gas (Figure 2) gave a very good selectivity to the acetal
chromatography.[6f] From this monodentate ligand but relatively low l/b ratio (Table 2, entry 5). The best
study it appears clear that the more p-accepting the results were obtained with the large bite-angle ligands
ligand, the better the acetal selectivity (Figure 1).
DPX[4a,16] and Xantphos[17] (Table 2, entries 6 and 7).
Although the DPX ligand gave 22.6% octane and
a low l/b ratio, it gave an excellent acetal selectivity.
Xantphos produced only a small amount of octane,
a good acetal selectivity and an excellent l/b ratio of
42. This is why Xantphos was chosen for further in-
vestigations. It is important to note that the l/b ratio
of the acetals was always higher than that of the re-
maining aldehyde, strongly suggesting that acetaliza-
tion of linear aldehydes is preferred (also see Sup-
porting Information).
Different parameters were then changed (see
Table 3). Increasing the S/Rh to 200 and 300 ratio did
not significantly affect the final mixture composition
(Table 3, entries 2 and 3). The following experiments
have been conducted with an S/Rh ratio of 200. Using
Figure 1. Electronic effect on selectivity.
Next, bidentate ligands of increasing bite-angle syngas with a ratio CO/H2 1:1, the reaction was slight-
[13]
bn
and p-accepting character were tested. Large ly faster but significantly less selective towards acetal
bite-angle ligands are known to give high regioselec- formation (85.5% instead of 92.1% with CO/H2 1:2).
tivties for the linear products.[14] The results are Moreover, the regioselectivity dropped, the l/b ratio
shown in Table 2. Small bite angle ligands (dppm, being 34.6 in this case (Table 3, entry 4). Decreasing
dppe and binap, entries 1 to 3) gave very low conver- the reaction temperature only led to lower activities
sions. The dppf ligand (bn =998) led to a more active and lower linearities (Table 3, entries 5 and 6). De-
catalytic system, but the conversion was only 29% creasing the reaction pressure to 20 bar did not signif-
after 1 h of reaction with low acetal selectivity icantly affect the product distribution, though the
(Table 2, entry 4). The bidentate phosphite[15] l/b ratio decreased to 46.3 (Table 3, entry 7).
Table 3. Hydroformylation of 1-octene using Xantphos as ligand.[a]
Entry
Reaction parameters
Conversion [%][b]
% Octane
Acetal selectivity [%][c]
l/b ratio acetal
1
2
3
4
5
6
7
S/Rh=100
S/Rh=200
S/Rh=300
CO/H2 30 bar 1:1
T=958C
78.8
86.3
84.2
96.6
78.8
65.9
82.2
4
97.6
92.1
91.9
85.5
94.2
95.9
94.1
42.3
52.4
51.1
34.6
26.0
13.6
46.3
2.4
2.0
2.6
2.5
4.5
2.1
T=808C
P=20 bar
[a]
Reaction conditions: in a 10 mL autoclave were placed 1-octene, dodecane (0.2 mmol, internal standard for GC), metha-
nol (20 mmol), [Rh(cod)2]BF4 (10 mmol), ligand (30 mmol, L/Rh=3), CO/H2 (P=30 bar, 1:2), 1108C, 90 min. For full de-
AHCTUNGTRENNUNG
tails on final mixture composition, see Supporting Information.
Conversion based on octenes consumption.
Acetal selectivities based on C9 products.
[b]
[c]
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Formation of Acetals under Rhodium-Catalyzed Hydroformylation Conditions in Alcohols
Reaction Profile
duced 120 moles of acetal per hour (at 20% acetal
yield).
As can be seen in Figure 4, during this reaction, the
The reaction was then set up using a substrate/rhodi-
um ratio of 400 in a 75-mL autoclave equipped with l/b ratio of both aldehyde and acetal decreased in
a capillary sampling system (Figure 3). Linear alde- time. But gratifyingly, the l/b ratio of the acetal is
hyde was the main intermediate product, reaching always higher than the one of the aldehyde, suggest-
53% of the product composition after 40 min of reac- ing again that the acetalization of the linear aldehyde
tion. The acetal formation from the aldehyde ap- is strongly preferred.
peared to be slower.
The TOF of the reaction at 50% conversion of 1-
octene (after 12 min) was estimated to 1000 hÀ1. The Scope of the Reaction
acetal formation was slower: one mole of catalyst pro-
Different alcohols were used as solvent (see Table 4).
The acetal selectivity decreases from primary alcohols
Figure 3. Reaction profile of the 1,1-dimethoxynonane for-
mation. 1-octene (10 mmol), [Rh
N
Figure 4. Evolution of l/b ratio in time. 1-octene (10 mmol),
[Rh(cod)2BF4] (S/Rh=400), Xantphos (L/Rh=3), MeOH
(200 mmol), CO/H2 (30 bar, 1:2), 1108C.
Xantphos (L/Rh=3), MeOH (200 mmol), CO/H2 (30 bar,
1:2), 1108C.
ACHTUNGTRENNUNG
Table 4. Scope of the reaction; different alcohols.[a]
Entry
Product
Conversion [%][b]
% Octane
2.4
Acetal selectivity [%][c]
l/b ratio acetal
1
2
3
86.3
87.7
88.2
92.1
85.2
68.7
52.4
53.9
89.2
12.1
2.2
83.6
8.4
5.6
6.9
<0.5
16.6
93.5[d]
n.d.[e]
4
5
70.1
92.1
9.6
3.7
99.3
93.6
25.6
9.1
6
[a]
Reaction conditions: in a 10 mL autoclave were placed 1-octene (2 mmol), alcohol or diol (20 mmol), [RhACTHNUTRGNEUNG(cod)2]BF4
(10 mmol), Xantphos (30 mmol), CO/H2 (30 bar, 1:2 ratio), 1108C, 90 min. For full details on final mixture composition,
see Supporting Information.
Conversion based on octenes consumption.
Acetal selectivities based on C9 products.
Reaction conducted at 1408C.
[b]
[c]
[d]
[e]
Not determined. Mainly aldehydes, aldol condensation products and alcohols were obtained.
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Olivier Diebolt et al.
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to tertiary alcohols (Table 4, entries 1 to 4). The terti- l/b ratio was 1.0 and a significant amount of ethylben-
ary 2-methylbutan-2-ol gave only 6.9% acetal selectiv- zene (hydrogenation product) was produced
ity (Table 4, entry 4). In this case, the major product (24.0%).[18] A screening of ligands showed that the
was the linear aldehyde. Increasing the temperature linear product is difficult to form and that the regiose-
led to a mixture of various C9 and C18 products and lectivity is very different than in toluene.[19] Triphenyl-
no acetal was detected. Diols are widely used as pro- phosphine proved to be the most selective towards
tecting agents for aldehydes. Thus our attention was the branched product, the l/b ratio being 0.31 in this
focussed on the use of ethylene glycol and propylene case. Norbornene (Table 5, entry 3) was also a suitable
glycol (Table 4, entries 5 and 6). Gratifyingly, the substrate for this transformation and 92.0% acetal se-
acetal selectivities were very high (up to 99.3% for lectivity was obtained (5% alcohol and 3% aldehyde
ethylene glycol). This reaction can thus find interest- were obtained as side products). Phenylacetylene was
ing application in synthesis since the produced alde- submitted to the same reaction conditions (Table 5,
hyde can be changed to a 2-alkyldioxolane or 2-alkyl- entry 4). In this specific case, the saturated acetals are
1,3-dioxane in the same pot. Interestingly, technical obtained, suggesting a cascade hydroformylation–ace-
grade diols could be used in this case, showing that talization–hydrogenation reaction. The reaction was
the presence of traces of water was not deleterious followed over time and saturated and unsaturated al-
for the reaction.
dehydes were detected. However, no trace of unsatu-
The scope was then further investigated by using rated acetal was observed, suggesting that the acetali-
different alkenes in ethylene glycol, producing 2-al- zation of the unsaturated aldehyde is not favored (see
kyldioxolanes (Table 5). With internal alkenes (cis-cy- Scheme 3).
clooctene here), the reaction was very slow (Table 5,
entry 1). Even after 63 h, the conversion was only
27%. However, a very good acetal selectivity was ob- Tolerance to Ketone Functionalities
tained and only little octane was formed (0.5%). As
only one product can be formed, the reaction was per- The reaction described above allows the direct forma-
formed using PACHTUNGTRENNUNG(OPh)3 as ligand. In this case, excellent tion of protected aldehydes from an alkene or alkyne
conversion and selectivities were obtained in a short source. It appeared interesting to check whether ke-
reaction time. We then moved to styrene (Table 5, tones were also protected under our reaction condi-
entry 2). The conversion was very high, and the selec- tions. We decided then to focus our attention on the
tivity towards acetal was 91.4%. However, the hydroacetalization of a ketoalkene. As a simple and
Table 5. Scope of the reaction; different alkenes.[a]
Entry
Substrate
Product
Conversion [%]
% Alkane
Acetal selectivity [%]
l/b ratio acetal
6.6
0.4
0.5
0.5
8.9
94.7
98.9
–
–
–
27.0[b]
97.8[c]
1
95.3
24.0
19.9
14.3
5.4
91.4
96.8
94.9
96.8
98.2
1.0
1.0
1.34
0.31
0.55
96.8[d]
94.8[e]
100[f]
100[g]
2
3
4.8
>99.5
<0.5
<0.5
92.0
8.6[h]
4
91.1
96.5
2.5
[a]
Reaction conditions: in a 10 mL autoclave were placed alkene (2 mmol), ethylene glycol (20 mmol), [Rh
(10 mmol), Xantphos (30 mmol), CO/H2 (30 bar, 1:2 ratio), 1108C, 90 min.
Reaction time was 63 h.
ACHTUNGTERN(NUNG cod)2]BF4
[b]
[c]
[d]
[e]
[f]
PACHTUNGTRENNUNG(OPh)3 (30 mmol) used as ligand.
No ligand was used.
Bidentate phosphite was used as ligand; P/Rh=6. See ref.[19]
Using PPh3 as ligand; P/Rh=3.
[g]
[h]
Using P
ACHTUNGTRENNUNG[O-2,4-ACHTUNGTRENNUNG(t-Bu)2C6H3]3 as ligand; P/Rh=3.
The endo/exo ratio, determined by GC.
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Formation of Acetals under Rhodium-Catalyzed Hydroformylation Conditions in Alcohols
Scheme 3. Reaction with phenylacetylene.
commercially available substrate, 5-hexen-2-one (all- gest that the rhodium precursor and molecular hydro-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
glycol, as expected, the acetal formation was fast, ity was already observed in the hydroaminomethyla-
leaving only traces of the intermediate ketoaldehyde tion reaction.[4b] Finally, nonanal was reacted using
(Table 6, entry 3). Both the ketoacetal[20] and diacetal only HFB4 as catalyst which showed good acetaliza-
were produced in a 2.1:1 ratio. The l/b ratios were sig- tion ability (Table 7 , entries 6 and 7) but did not out-
nificantly lower in that case.
perform [RhACTHNGUTERN(NUG cod)2BF4]. These experiments suggest
that the good acetal selectivities obtained above are
due to a cooperative effect between the rhodium spe-
cies and the in situ formed acid HBF4.
Understanding the Acetal Formation
In order to get more insight in the in situ acetal for-
mation, nonanal was submitted to our “standard reac- Acetal as Intermediate in HAM?
tion conditions”.[21] Expectedly, nonanal is converted
into 1,1-dimethoxynonane (in methanol) or into 2- As described above, alcohol co-solvents have ap-
nonyldioxolane (in ethylene glycol) in excellent yields peared necessary for good activity in rhodium-cata-
(see Table 7, entry 1). Without rhodium present, very lyzed hydroaminomethylation (HAM).[4] In the ab-
little acetal was formed (Table 7, entry 2). Interesting- sence of amine reactant (present catalytic system),
ly, running the reaction without H2 (reaction pressur- acetals are formed selectively.[3b] However, acetals
ized only with 10 bar of CO), the acetal formed in were never detected during HAM processes.[2,3,4] We
only 4.6% yield (Table 7, entry 3). These results sug- decided then to investigate whether acetals could be
Table 6. Tandem hydroformylation-acetalization of 5-hexen-2-one (allylacetone).[a]
Entry Solvent
Conversion [%] % Alkane B selectivity [%] % A (l/b ratio) % B (l/b ratio) % C (l/b ratio)
1
2
3
methanol
96.2
99.8
8.6
8.5
85.6
85.2
49.3
12.6 (9.8)
13.4 (10.3)
0.6 (n.d.[b])
74.8 (20.2)
77.2 (21.1)
35.2 (6.7)
<0.2 (n.d.[b])
<0.2 (n.d.[b])
16.5 (6.5)
methanol[c]
ethylene glycol[d] 83.7
19.2
[a]
Reaction conditions: in a 10 mL autoclave were placed alkene (2 mmol), alcohol (20 mmol), [Rh
Xantphos (30 mmol), CO/H2 (30 bar, 1:2 ratio), 1108C, 1 h.
Not determined.
ACHTUNGTREN(UNGN cod)2]BF4 (10 mmol),
[b]
[c]
[d]
Reaction time is 5 h.
19.1% of the substrate was acetalized at the ketone position without hydroformylating the alkene.
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Olivier Diebolt et al.
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Table 7. Acetalization of nonanal.
Entry
Deviation from “standard conditions”
Acetal yield [%]
1
2
3
4
5
6
7
none
no Rh
no H2
93
1.4
4.6
44.5
0
71.1
87.1
[Rh
ACHUTNGTRNE(NGU acac)(CO)2] instead of [RhACHTUNTGREN(NUGN cod)2BF4]
acacH[a,b]
no Rh, no Xantphos, HBF4 0.5 mol%
no Rh, no Xantphos, HBF4 10 mol%
[a]
acacH: acetylacetone, 0.5 mol%.
Aldol condensation product was formed (ca. 50%).
[b]
reaction intermediates in hydroaminomethylation re- mated at 120 hÀ1. Acetals do not undergo reductive
actions. When a mixture of nonanal/1,1-dimethoxyno- amination under typical HAM conditions. Hence they
nane (1:6) was subjected to the hydroaminomethyla- can be ruled out as, however short lived, intermedi-
tion conditions described by Beller[3b] using piperidine ates. Nevertheless, the exact role of alcohol co-sov-
as amine source, nonanal was quantitatively convert- lents in HAM reactions remains unclear. There is still
ed to 1-nonylpiperidine and 1,1-dimethoxynonane the possibility of hemiaminal participation as suggest-
was left unreacted. Moreover, the ratio 1-nonylpiperi- ed by Bçrner.[22]
dine/1,1-dimethoxynonane was still 1:6 showing that
Performing the reaction with 5-hexen-2-one showed
nonanal was not converted to 1,1-dimethoxynonane that the aldehyde group was selectively acetalized in
in the presence of an amine (see Scheme 4). This methanol. However the selectivity dropped when
result shows that acetals are not an intermediate in moving to ethylene glycol. Finally we could show that
HAM.
the good acetal selectivities are due to a cooperative
effect of the rhodium species and HBF4 formed in
situ from the catalyst precursor.
Conclusions
Hydroformylation of terminal and internal alkenes Experimental Section
with a rhodium/Xantphos system in alcohols as sol-
vent led to the highly selective formation of the corre- General Procedure
sponding acetals. Especially in methanol and ethylene
Reactions were performed in home-made 10 mL autoclaves.
glycol, good to excellent selectivites were obtained.
Small amounts of water were tolerated, so technical
grade alcohols could be used without the need of des-
sicating agents. An autoclave equipped with a capillary
sampling device permitted to draw the reaction pro-
file which showed the aldehyde formation to be fast
(TOF=ca. 1000 hÀ1) and the acetalization to be the
limiting step. The rate of acetal formation was esti-
The autoclave was charged with [RhACTHNUTRGEN(UNG cod)2]BF4 (10 mmol;
cod=1,5-cyclooctadiene), alkene (2 mmol) and ligand
(30 mmol) in 20 mmol of solvent (alcohol or diol) under an
argon atmosphere. The autoclave was purged three times
with H2 (P=10 bar) to remove the remaining argon from
the autoclave. Subsequently, the autoclave was pressurized
with CO and H2 to the desired pressure and heated to reac-
tion temperature using a preheated oil bath. After a certain
reaction time, the autoclave was cooled to room tempera-
ture and the mixture was removed from the autoclave, fil-
tered and analyzed by GC.
Reaction Profile
The reaction profile (Figure 3) was obtained using a home-
made 75-mL autoclave equipped with a high pressure sam-
pling system. A solution containing all the ingredients was
prepared in a Schlenk flask under argon and injected into
the autoclave which was purged three times with H2 (P=
Scheme 4. Acetal is not an intermediate in HAM.
676
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ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 670 – 677

Formation of Acetals under Rhodium-Catalyzed Hydroformylation Conditions in Alcohols
10 bar) to remove the remaining argon. Subsequently, the
autoclave was pressurized with CO and H2 to the desired
pressure and heated to the reaction temperature. Samples
were taken regularly and analyzed by GC.
A. Ruiz, C. Claver, S. Castillꢃn, Chem. Commun. 1998,
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Acknowledgements
This work was financially supported by ACTS-Aspect. We
are grateful to Ton Staring for technical assistance. C.M.
thanks The Netherlands Organization for Scientific Research
(NWO-CW) for financial support.
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