Continuous Microflow Synthesis of Fuel Precursors from Platform Molecules Catalyzed by 1,5,7-Triazabicyclo[4.4.0]dec-5-ene

Article abstract of DOI:10.1021/acs.oprd.7b00141

The first continuous flow synthesis of C₈-C₁₆ alkane fuel precursors from biobased platform molecules is reported. TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) was found to be a recyclable and highly efficient organic base catalyst for the aldol condensation of furfural with carbonyl compounds, and the selectivity of mono- or difuryl product can be easily regulated by adjusting the molar ratio of substrates. By means of flow technique, a shorter reaction time, satisfactory output, and continuous preparation are achieved under the present procedure, representing a significant advance over the corresponding batch reaction conditions.

Full text of DOI:10.1021/acs.oprd.7b00141

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Communication
Continuous Micro-flow Synthesis of Fuel Precursors from Platform
Molecules Catalyzed by 1,5,7-Triazabicyclo[4.4.0]dec-5-ene
Tao Shen, Jingjing Tang, Chenglun Tang, Jinglan Wu, Linfeng Wang, Chenjie Zhu, and Hanjie Ying
Org. Process Res. Dev., Just Accepted Manuscript • Publication Date (Web): 16 May 2017
Downloaded from http://pubs.acs.org on May 21, 2017
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Continuous Micro-flow Synthesis of Fuel Precursors from Platform
Molecules Catalyzed by 1,5,7-Triazabicyclo[4.4.0]dec-5-ene
8
Tao Shena,b, Jingjing Tanga,b, Chenglun Tanga,b, Jinglan Wua,b, Linfeng Wangd, Chenjie
Zhua,b,c *, Hanjie Yinga,b,c
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a College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University,
Nanjing, China
b National Engineering Technique Research Center for Biotechnology, Nanjing, China
c Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM)
d
State Key Laboratory of Motor Vehicle Biofuel Technology，Nanyang 473000,
China
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ABSTRACT
The first continuous flow synthesis of C8-C16 alkane fuel precursors from bio-based
platform molecules is reported, TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) was found
to be a recyclable and highly efficient organic base catalyst for the aldol condensation
of furfural with carbonyl compounds, and the selectivity of mono- or difuryl product
can be easily regulated by adjusting the molar ratio of substrates. By means of flow
technique, a shorter reaction time, satisfactory output, and continuous preparation are
achieved under the present procedure, representing a significant advance over the
corresponding batch reaction condition.
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KEYWORDS: Renewable hydrocarbon fuels; Lignocellulose biomass; C8-C16 alkane;
Aldol condensation; Flow technique; Bio-based platform molecules.
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INTRODUCTION
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With the consumption of fossil resources and growing environmental problems,
the development pathways for the utilization of biomass feedstocks into renewable
fuels is attractive.1-3 In this context, lignocellulosic biomass can be substituted for
fossil resources as it is an abundant, renewable and carbon-neutral resource.4-7
Generally, lignocellulose biomass conversed into liquid hydrocarbon fuels has two
major strategies: one is to treatment of integral lignocellulose conversed to scalable
stocks such as syngas or bio-oil by fast pyrolysis,8,9 gasification and liquefaction10,11
followed by Fischer-Tropsch synthesis.12-14 Another refers to depolymerization of
lignocellulose to produce platform compounds such as furan-based compounds.
(furfural, 2-methyfuran or hydroxymethylfurfural, etc.) Catalytic transformation of
these platform compounds through hydrogenation and oxygen removal process along
with carbon chain elongation reactions is another important approach to convert
lignocellulosic biomass into liquid fuels.15,16 To meet the carbon number for the
corresponding fuel range, such as jet and diesel fuels, various reactant have been
applied as building blocks for the growth of carbon chain, for example, acetone,17-21
mesityl oxide,22 hydroxyacetone,23,24 methyl isobutyl ketone,25 and butanal26-28. This
route is meaningfully while these feedstock is originated from lignocellulose.
Recently, we reported acetoin was used as a C4 bio-based synthons for the synthesis
of jet fuel range hydrocarbon fuels.29 However, for the production of fuels, compared
to the other bulk feedstock, the production output of acetoin is relatively small, such
as furfural, which has been fabricated on an industrial scale (280,000 t/a) by
hydrolysis of hemicellulose part in lignocellulose.30
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Inspired by the pioneering research of Huber and Dumesic group,17-20 furfural is
known to undergo base-catalyzed aldol condensation reactions with carbonyl
compounds to fuel precursors mono- or difuryl components. Mineral base and solid
base were the traditional catalysts for this reaction. However, compared with the
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reaction with acetone, these catalysts showed poor catalytic performance for the
reaction with long chain aliphatic carbonyl compounds. Recently, we reported using
DBU as a catalyst for the aldol reaction of furan aldehyde with long chain carbonyl
compounds.31 However, this method still has some shortcomings: (i) high dosage of
catalyst (> 30 mol%) had to be used to obtain double condensation difuryl
components; (ii) long reaction time is required to achieve a reasonable condensation
yield; (iii) difficult to separate this homogeneous catalyst from the reaction mixture.
Thus, the development of a high reactivity and readily recyclable catalyst is highly
desirable.
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On the other hand, the production of fuels through platform molecules route was
traditionally conducted in a batch reactor in lab scale experiments. However, for
industrial application on large scales, the continuous reaction mode is required to
ensure high production intensity in the chemical engineering operation. Recently,
process intensification based on flow techniques and microreactors have drawn
considerable attention in the fields of chemical synthesis.32 With the advantage of
their high mixing and heat transfer rates, safe operation, and easy modulation, the
technologies of microfluidic are rapidly emerging as complements to traditional batch
synthesis. Moreover, the potential to run an uninterrupted microreactor sequence,
multistage continuous reactions, and easy to enlarge production using continuous flow
technology is also beneficial in terms of industrial scale.33-34 These significant
advances in the microreactor technology prompted us to exploit new process to
improve the renewable fuels production efficiency.
In a continuation of our efforts for the biomass catalytic conversion,29,31,35,36 we
report herein a continuous flow system for the production of C8-C16 alkane fuel
precursors from platform molecules using TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene)
as a highly efficient and recyclable organic base catalyst for the aldol condensation
(Figure 1).
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Figure 1. Process diagram for continuous micro-flow synthesis of fuel precursors.
EXPERIMENTAL SECTION
Aldol condensation of 3-pentanone with furfural in batch reactor
Aldol condensation of 3-pentanone with furfural was performed in a 25 mL flask
reactor in the presence of amine-based organic catalysts (1-3 mmol). In a typical
experiment, furfural (10-25 mmol) and 3-pentanone (10 mmol) were loaded into the
reactor and stirred at given temperature under solvent-free conditions for several
hours while checking the course of reaction by GC-MS. After reaction, the liquid oil
product was diluted and extracted with EtOAc and water, the analytically pure
product was obtained after concentrated the organic layer and purified by column
chromatography.
Aldol condensation of furfural with ketones under batch condition in Table 3
Aldol condensation of furfural with carbon compounds was performed in a 50
mL flask reactor in the presence of TBD (1 mmol). In a typical experiment, furfural
(10-25 mmol) and carbon compounds (10 mmol), solvent (8 mL MeOH/H2O (1:1) for
3-pentanone, acetone, 2-pentanone, and 2-hexanone, and 16 mL CH2Cl2 for
cyclopentanone and cyclohexanone) were loaded into the reactor and stirred at given
temperature under solvent-free conditions for several hours while checking the course
of reaction by GC-MS. After reaction, the reaction solutions was diluted and extracted
with EtOAc or water, the aqueous phase was collected and evaporated to recover the
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catalyst TBD, and the analytically pure product was obtained after concentrated the
organic layer and purified by column chromatography.
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Aldol condensation of furfural with ketones under MFS condition in Table 3
Generally, in the flow system, stream 1 was composed of furfural (100-200
mmol) and ketones (100 mmol) were diluted with solvent to 40 mL. Stream 2 was
composed of TBD (10 mmol) was diluted with solvent to 40 mL. Two streams was
purged in a given speed into slit plate mixer and at the given temperature passed
tubing reactor while checking the reaction progress by using GC-MS. Finally, the
product was extracted using EtOAc, the analytically pure product was obtained after
concentrated the organic layer and purified by column chromatography, and the
aqueous phase was collected and reused. For reaction details see the support
information.
RESULTS AND DISCUSSION
Aldol condensation of 3-pentanone with furfural in batch reactor
Initial “in-flask” experiments was first carried out using furfural and 3-pentanone
as the model reaction, in our previous work, mineral base and solid base catalysts
showed poor activity for this reaction, and double condensation product C15 precursor
Figure 2. The structures of the catalysts used in this study.
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1,5-di(furan-2-yl)-2,4-dimethylpenta-1,4-dien-3-one 1b cannot be obtained. In order
to search for a high activity catalyst, a series of amine-based organic catalysts were
tested for this reaction, for example, 1,4-diazabicyclo[2.2.2]octane (DABCO),
iPr2NEt, tryptophan and L-proline (see Figure 2). However, all of them were failed
to catalyze this reaction. To our delight, from the results of entry 6 in Table 1, we find
that under the situation of using 10 mol% TBD as the aldol condensation catalyst, the
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desired double
condensation
product
1b has 93% yield in 2 h.
Table 1. Results of different catalysts catalyzed the aldol condensation between of
furfural and 3-pentanone under solvent-free condition.
Furfural/
3-pentanone
(molar ratio)
Catalyst
loading
(mol %)a
10
Yield (%)a
1a 1b
T
(K)
Time
(h)
Entry
Catalyst
1
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9
DABCO
L-proline
Tryptophan
iPr2NEt
DBU
1.0
1.0
1.0
1.0
2.5
2.5
2.5
1.0
1.0
1.0
298
298
298
298
353
353
298
298
353
298
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12
12
12
10
2
10
4
1
0
0
0
0
0
0
0
10
10
10
30
10
10
10
10
0
8
5
7
94
87
92
88
93
90
3
TBD
TBD
TBD
TBD
8
4
10
MTBD
10
20
a 3-pentanone is relative to the limiting reactant.
In our previous work, 30% DBU had to be used to afford 88% yield of 2b in 10 h
(Table 1, entry 5). Furthermore, this reaction can even performed at room temperature,
although required a longer reaction time (Table 1, entry 7), which clearly
demonstrates its superior catalytic activity. It is noteworthy that the selectivity of
mono- or difuryl product could be easily regulated by adjusting the molar ratio of
substrates, From the result of entry 8 in Table 1, while the molar ratio of
3-pentanone/furfural is 1, the yield of single condensation product 1a increases up to
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94%, which pointed out the selectivity of double condensation is kinetic control
instead of thermodynamic control (Table 1, entry 9). This finding is very helpful
because it provides an available tool to change the ultimate desired ingredient of
mono- or difuryl product.
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Figure 3. Results of the aldol condensation between of furfural with 3-pentanone
catalyzed by TBD. Reaction conditions: furfural (25 mmol) and 3-pentanone (10 mmol)
catalyzed by TBD (1 mmol) without solvent at 600 stirring speed under air conditions
at room temperature.
To understand the reaction pathway of the 1b formation, the kinetic curves of the
reaction are presented in Figure 3. Following the reaction with time, two main
compounds, single condensation product 1a and double condensation product 1b were
detected during the reaction. As shown in Figure 3, at the initial stage of the reaction,
the concentration of 1a increases up to nearly 100 mol% yield, and then decreases
after the first hour of reaction while the yield of 1b increases, 1b was practically not
formed before all 3-pentanone was converted into 1a, indicating the pathway of 1b
formation was not through “one-step process” (Scheme 1, path a: one molecule
3-pentanone reacted with two molecule furfural at the same time), a stepwise process
(path b) was proposed in this reaction, which comprises four steps: (i) the aldol
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addition of one molecule 3-pentanone with one molecule furfural to afford 1a’; (ii)
the single aldol condensation product 1a was produced through dehydration of 1a’;
(iii) the aldol condensation of 1a with one molecule furfural to afford 1b’; (iv)
dehydration of 1b’ to obtain the desired difuryl product 1b. As also can be inferred
from Figure 3, the generation rate of 1b was much slower than 1a, and the
dehydration precursors 1a’ and 1b’ was never detected during the reaction, indicating
that the step 3 can be considered as the rate-determining step of this reaction.
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Scheme 1. The reaction pathway of the formation of 1b
.
A plausible catalytic mechanism of TBD is depicted in Scheme 2. N1 in TBD
first induced the deprotonation of α-H from 3-pentanone to form enol. This
intermediate state acted as a carbonyl donor to attack furfural to produce 1a’, which
then dehydration via E2 elimination to generate the single condensation 1a. If the
dehydration is E1 elimination, the corresponding carbocation 1e’ would serve as
nucleophilic receptor to react with enol to afford product 1e. However, 1e was not
detected during the reaction according to the GC-MS. The regenerated TBD then
reacts with 1a to provide another enol intermediate, which undergoes similar reaction
process to produce the difuryl product 1b. Furthermore, TBD could also activate the
furfural to promote the above process due to the H-N7 in TBD increases the positive
charge of the homologous carbon atom through hydrogen-bonding synergism. Thus,
TBD served as a bi-functional catalyst during the reaction, which not only promotes
the deprotonation process (the role of N1 in TBD), but also motivates the furfural by
generating hydrogen-bonding synergism (the role of H-N7 in TBD), that can be used
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to explain why TBD has better catalytic activity than DBU. To confirm this point, the
control experiment was conducted under the same reaction conditions using
7-methyl-1,5,7-triazabicyclo [4.4.0] dec-5-ene (MTBD) as a catalyst. The basicity of
MTBD (pKa = 24.97) is similar to TBD (pKa = 24.70),37 however, the hydrogen atom
in N7 position of MTBD is replaced by methyl group, which means it cannot form the
hydrogen-bonding network with furfural. As can be seen from Table 1, entries 8 and
10, a sharply decreased catalytic activity of MTBD was observed compared to the
TBD. Thus, the reaction pathway catalyzed by TBD was not merely base-catalyzed
condensation, a synergistic catalysis effect was believed to occur during the reaction.
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Scheme 2. Tentative mechanism for the aldol condensation of furfural with 3-pentanone
catalyzed by TBD.
Aldol condensation of 3-pentanone with furfural in flow system
Based on the results of “in-flask” experiments, “in flow system” experiments
were then carried out also using furfural and 3-pentanone for comparison. One of the
chief concerns in the fluidic experiment is the formation of solids in the reactor, which
could block the slit plate mixer and tubing reactor. Thus, a significant challenge of
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converting batch conditions into a flow process is the poor solubility of double aldol
condensation products in common organic solvents. Hence, we first examined the
effects of solvents under the present flow system. As can be seen from Table 2, the
property of the solvent plays a significant role in this system, for example, using THF,
EtOAc or CH2Cl2 as the solvent was not successful for this reaction, which is due to
the poor solubility of TBD in EtOAc, and poor solubility of double aldol condensation
product in CH2Cl2 or THF, respectively. Hence, the solvent used in this reaction
should dissolve all of the components of the reaction: substrate, single aldol
condensation product, double aldol condensation product, and the catalyst TBD.
Among the tested solvents, MeOH meets the above conditions, however, methanol
could reacted with furfural catalyzed by TBD to afford the corresponding
etherification by-product (Figure S2). After further screening, to our delight, we found
a mixed solvent of methanol and water could inhibit this side reaction effectively. In
the case of using MeOH-H2O (v/v = 1/1) as the solvent, the desired double
condensation product 1b was obtained in 87% yield (Table 2, entry 6, Figure S6). It is
worth mentioning that the reaction time in flow system was reduced dramatically,
which only need 20 min to complete the reaction, and that is diminished about 6-fold
compared to the batch system (Table 1, entry 6). Furthermore, under batch synthesis
conditions, side reactions such as resinification of furfural, Cannizaro reaction, and
Michael addition to the formed enol intermediate may happen during the reaction.38,39
In order to obtain the double condensation product 1b, over-dose of furfural (at least
2.5 equiv. to 3-pentanone) has to be used in the reaction. However, these side
reactions were effective suppressed under the present flow system, and the dosage of
furfural could be decreased to its theoretical ratio (2 equiv.) without loss of yield of 1b
(Table 2, entry 6), which clearly demonstrated the advancement of the present system.
Furthermore, similar to the batch reaction, the selectivity of this reaction could be also
easily regulated by adjusting the molar ratio of substrates, when the reaction was
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conducted at the molar ratio of 3-pentanone/furfural is 1, the yield of single
condensation product 1a increases up to 91% (Table 2, entry 7, Figure S6), which
means the present flow system did not change the intrinsic kinetics of the reaction.
For product separation and recovery of TBD catalyst, the method is very simple and
easy. TBD is completely soluble in water, but has poor solubility in EtOAc (Figure
S3), which could be beneficial since it provides a convenient method to separate the
catalyst and the products. After the reaction, using EtOAc to extract the mixture
resulted in the separation between the condensation products and the catalyst TBD.
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Table 2. Optimization of double aldol condensation of 3-pentanone with furfural catalyzed by
TBD under flow system.a
Ratio
(Furfural:
Flow rate
(mL/min)
(Stream 1:2)
0.2:0.2
Yield (%)
Time
(min)
Entry
Solvent
1a
1b
3-pentanone:TBD)
6.25M:2.5M:0.25M
6.25M:2.5M:0.25M
6.25M:2.5M:0.25M
6.25M:2.5M:0.25M
6.25M:2.5M:0.25M
5M:2.5M:0.25M
2.5M:2.5M:0.25M
1
2
3
4
5
6
THF
CH2Cl2
EtOAc
MeOH
20
20
20
20
20
20
20
51
31
14
13
7
34
23
7
78
89
87
2
0.2:0.2
0.2:0.2
0.2:0.2
0.2:0.2
0.2:0.2
0.2:0.2
MeOH-H2O
MeOH-H2O
MeOH-H2O
5
91
7
a
Reaction conditions: flow reaction were run in 1.0 mm i.d. PFA (perfluoroalkoxy)
tubing reactor, residence time was controlled by adjusting the flow rate at 353K unless
specified otherwise.
These interesting results encouraged us to find the best reaction conditions for
this system, various parameters of this reaction was then screened, such as material
concentration, flow rate and reaction temperature (for more reaction details see Table
S1). By retaining the whole of key parameters of this the present flow system, this
procedure was applied for the synthesis of various fuel precursors using micro-flow
system (MFS in Table 3). The batch synthesis system under similar reaction
conditions was also applied for the comparative purposes (Batch in Table 3). As
shown in Table 3, compared to the batch condition, the reaction time under the present
flow system are declined significantly, which probably due to the high heat and mass
transfer efficiency of MFS (Figure S23). Most substrates underwent smooth
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Table 3 Synthesis of fuel precursors catalyzed by TBD under Batch or MFS System.
5
6
7
8
T
Time
Yield
(%)
91
Entry Substrate
Product
Methoda
MFS
(K) (min)
353
353
20
9
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(furan-2-yl)-2-methylpent-1-en-3
Batch
240
92
-one (1a
)
MFS
Batch
MFSb
353
353
R.T.
20
87
89
3-pentanone
2
600
1,5-di(furan-2-yl)-2,4-dimethyl
-penta-1,4-dien-3-one (1b
)
10
120
20
86
81
92
3
Batchb R.T.
1-(furan-2-yl)pent-1-en-3-one (2a
)
MFS
R.T.
R.T.
Acetone
4
1, 5-di(furan-2-yl)
Batch
480
90
-penta-1,4-dien-3-one (2b
)
MFS
Batch
MFS
333
333
353
20
240
40
90
90
82
5
1-(furan-2-yl)hex-1-en-3-one (3a
)
2-pentanone
6
Batch
353
1400
86
1-(furan-2-yl)-4-(furan-2-yl-
methylene)hex-1-en-3-one (3b
)
MFS
Batch
MFS
353
353
353
20
240
40
90
94
72
7
1-(furan-2-yl)hept-1-en-3-one (4a
)
2-hexanone
8
Batch
353
1400
80
1-(furan-2-yl)-4-(furan-2-yl-
methylene)hept-1-en-3-one (4b
)
MFS
Batch
MFS
R.T.
R.T.
R.T.
R.T.
5
91
92
90
93
9c
2,5-bis(furan-2-ylmethylene)
240
5
Cyclopentanone
cyclopentan-1-one (5b
)
10 c
2,6-bis(furan-2-ylmethylene)
Batch
240
Cyclohexanone
cyclohexan-1-one (6b)
For the detailed reaction conditions see support information. b Acetone was used as the
a
solvent for both MFS and Batch conditions. c CH2Cl2 was used as the solvent for this reaction
due to the poor solubility of products in MeOH-H2O system.
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transformation to afford the corresponding mono- or difuryl products in moderate to
excellent yields. For aliphatic straight-chain compounds, the reaction reactivity
decreased with the increase of carbon chain length, and the reaction of symmetric
carbonyl compound is relatively easy to those asymmetric compounds, and the
following order of substrate reactivity was observed: acetone > 3-pentanone >
2-pentanone > 2-hexanone (Figure S24). This phenomen on can be explained by the
steric effect, the longer alkyl side chain may prevent the carbonyl donor to attack enol,
and hence reduced the reaction efficiency.
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11
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Together with the satisfying results with aliphatic straight-chain compounds, the
yields of double condensation product produced from the reaction of naphthenone are
also quite high (Table 3, entries 9-10). It is well known that cyclic alkanes is another
important constituent which are used with the mass percentage of 20-50 wt% in the
military and commercial jet fuels.40,41 Cyclic alkanes usually have higher volumetric
heating values and energy density compared with straight alkanes due to their strong
ring strain.42-44 But it also should notice that single condensation products are hard to
get under the present flow system even under the condition of using excess
naphthenone. Double aldol condensation of naphthenone was the main reaction under
such conditions, which probably due to the high reactivity of naphthenone. Similar
situation was also occurred under the batch conditions, and that is in accord with
previous report.43
CONCLUSION
In conclusion, TBD was found to be a highly efficient and recyclable organic base
catalyst for the aldol reaction of furfural with carbonyl compounds. With the aid of
flow technology, a rapid, efficient and promising route for the continuous synthesis of
various alkane fuel precursors is presented. This study provides a new general
strategy for the production of fuel precursors using liquid biomass platform
compounds. Further studies on the continuous production of renewable fuels by
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nonseptate combination between flow equipment (for C-C coupling) with fixed bed
(for hydrodeoxygenation) are currently underway in our laboratory.
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9
ASSOCIATED CONTENT
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Supporting Information
Experimental details including reaction procedures and full spectral characterization
of all compounds (1H NMR, C NMR, GC-MS). This material is available free of
13
charge via the Internet at ACS Publications website.
AUTHOR INFORMATION
Corresponding Author
* Address: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech
University, Nanjing, China. E-mail: zhucj@njtech.edu.cn Phone/Fax: +86 25
58139389
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the Program for the National Natural Science
Foundation of China (Grant No.: 21406110) and the State Key Laboratory of Motor
Vehicle Biofuel Technology (Grant No.: KFKT2013001); Changjiang Scholars and
Innovative Research Team in University (Grant No.: IRT_14R28); Jiangsu Province
Natural Science Foundation for Youths (Grant No.: BK20140938); The Major
Research Plan of the National Natural Science Foundation of China (Grant
No.:21390204); And Jiangsu National Synergetic Innovation Center for Advanced
Materials (SICAM).
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