Ionic liquids - Advanced reaction media for organic synthesis

Article abstract of DOI:10.1080/10426507.2010.538557

The advantages in the application of ionic liquids as reaction media in organic synthesis, i.e., in the preparation of chromane derivatives, substituted pyrazines, 4-aminofuran-2(5H)-ones, or in bromination of Levulinic acid or dehydration of alcohols, saccharides, and polysaccharides, have been demonstrated on several examples. Ionic liquids with Bronsted acidity have been shown to possess catalytic activity and provide access to convenient technologies for the preparation of various useful compounds. Copyright Merck KGaA.

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Phosphorus, Sulfur, and Silicon and the
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Ionic Liquids—Advanced Reaction Media
for Organic Synthesis
Nikolai V. Ignat'ev a , Michael Schulte a , Karsten Koppe b , Peter
Barthen b , Sergei G. Zlotin c , Nina N. Makhova c , Aleksei B.
Sheremetev c & Anabela A. Valente d
a Merck KGaA, PC-RL, Ionic Liquid Research Laboratory, Darmstadt,
Germany
b Institut für Anorganische Chemie und Strukturchemie II, Heinrich-
Heine Universität, Düsseldorf, Germany
c N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, Moscow, Russian Federation
d Department of Chemistry, CICECO, University of Aveiro, Campus de
Santiago, Aveiro, Portugal
Published online: 12 Jul 2011.
To cite this article: Nikolai V. Ignat'ev , Michael Schulte , Karsten Koppe , Peter Barthen , Sergei G.
Zlotin , Nina N. Makhova , Aleksei B. Sheremetev & Anabela A. Valente (2011) Ionic Liquids—Advanced
Reaction Media for Organic Synthesis, Phosphorus, Sulfur, and Silicon and the Related Elements,
186:5, 1205-1216, DOI: 10.1080/10426507.2010.538557
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Phosphorus, Sulfur, and Silicon, 186:1205–1216, 2011
Copyright ꢀC Merck KGaA
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.538557
IONIC LIQUIDS—ADVANCED REACTION MEDIA
FOR ORGANIC SYNTHESIS
Nikolai V. Ignat’ev,1 Michael Schulte,1 Karsten Koppe,2
Peter Barthen,2 Sergei G. Zlotin,3 Nina N. Makhova,3
Aleksei B. Sheremetev,3 and Anabela A. Valente4
1Merck KGaA, PC-RL, Ionic Liquid Research Laboratory, Darmstadt, Germany
2Institut fu¨r Anorganische Chemie und Strukturchemie II, Heinrich-Heine
Universita¨t, Du¨sseldorf, Germany
3N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
Moscow, Russian Federation
4Department of Chemistry, CICECO, University of Aveiro, Campus de Santiago,
Aveiro, Portugal
Abstract The advantages in the application of ionic liquids as reaction media in organic syn-
thesis, i.e., in the preparation of chromane derivatives, substituted pyrazines, 4-aminofuran-
2(5H)-ones, or in bromination of Levulinic acid or dehydration of alcohols, saccharides, and
polysaccharides, have been demonstrated on several examples. Ionic liquids with Brønsted
acidity have been shown to possess catalytic activity and provide access to convenient tech-
nologies for the preparation of various useful compounds.
Keywords Ionic liquids; organic synthesis; reaction media
INTRODUCTION
Ionic liquids (ILs) or liquid salts are chemical substances that consist of an organic
cation and organic or inorganic anion. They typically do not comprise neutral molecules and
usually have melting points below 373 K. Ionic liquids that are liquid at room temperature,
or room temperature ionic liquids (RTIL) are of major interest for their application in
organic synthesis.
Intensive research dealing with the synthesis of new ionic liquids and their appli-
cations in different fields, e.g., electrochemistry, energy storage and conversion, organic
chemistry, catalysis, chemical engineering, material science, etc., is currently in progress
in all industrially developing countries. The reasons for this are the unique properties of
this new class of chemical substances, e.g., negligible vapor pressure, liquid state over
large temperature scale, nonflammability, electrical conductivity, and high electrochemical
and thermal stability. Review articles on ionic liquids are, for example in Refs.1–7 Several
Received 13 October 2010; accepted 4 November 2010.
Address correspondence to Nikolai V. Ignat’ev, Merck KGaA, PC-RL, Ionic Liquid Research Laboratory,
Frankfurter Str. 250, 64293, Darmstadt, Germany. E-mail: nikolai.ignatiev@merck.de
1205

1206
N. V. IGNAT’EV ET AL.
books devoted to synthesis and practical applications of ionic liquids have been published
recently; see for instance Refs.8–10
The properties of ionic liquids, for example melting point, thermal and electrochem-
ical stability, and viscosity, are strongly influenced by the nature of the anion. The polarity
and the hydrophilicity or lipophilicity of ionic liquids can be varied by a suitable choice
of the cation/anion pair. The combination of available (known) anions and cations gives
the possibility of constructing thousands of different ionic liquids with various properties,
but it is still a challenge to synthesize ionic liquids having low viscosity and high thermal,
electrochemical, and hydrolytic stability at the same time. For example, the tetrafluorobo-
rate anion, [BF4]−, is one of the favored anions for the preparation of hydrophilic (water
miscible) ionic liquids. The major disadvantages of tetrafluoroborate ionic liquids are their
not perfect hydrolytic stability (in particular at raised temperature) and their relatively high
viscosity. Recently, we have improved the properties of such ionic liquids by introducting
the tetracyanoborate anion, [B(CN)4]−,11 instead of the [BF4]− anion. That greatly improves
the hydrolytic stability and reduces the viscosity of the ionic liquid.
The typical example of hydrophobic (water immiscible) ILs are ionic liquids that
bear, for example, the [PF6]− anion. These ionic liquids are even less hydrolytically stable
than ILs with the [BF4]− anion. In contact with water (or with moisture), these ionic liquids
can generate hydrogen fluoride (HF), which can not only influence the performed chemical
reaction but create additional inconveniences related to the toxicity of HF. Recently, we
have developed a new generation of hydrophobic ionic liquids with the [(C2F5)3PF3]−
anion (FAP anion) having superior hydrolytic stability, low viscosity, and high thermal and
electrochemical stability.12 More information about new ionic liquids that are now available
in commercial quantities from Merck KGaA, Darmstadt, Germany, can be found on the
following Web site: http://www.ionicliquids-merck.de
RESULTS AND DISCUSSION
Ionic liquids can be used as inert reaction media for organic synthesis to re-
place volatile organic solvents or additionally as reactive substances to catalyze chemical
reactions.
We have found that volatile Brønsted acids dissolved in ionic liquid with the same
counter anion stay in the mixture, even at temperatures well above the boiling point of
the pure Brønsted acid. For example, trifluoroacetic acid (bp 72◦C) dissolved in 1-butyl-3-
methylimidazoliumtrifluoroacetate[BMIM][TFA], (concentration20%)does notevaporate
from this mixture up to the temperature of about 120◦C (see Figure 1).
It is most likely that a high concentration of trifluoroacetate anions in the mixture of
[BMIM][ATF]/CF3COOH leads to a solvation of the proton by many trifluoroacetate anions
(cluster formation), which dramatically reduces the volatility of the dissolved trifluoroacetic
acid in the ionic liquid. This phenomenon is observed for various combinations of ionic
liquids and Brønsted acids, namely 1,3-dialkylimidazolium triflate + triflic acid; 1,1-
dialkylpyrrolidinium triflate + triflic acid, and 1,3-dialkylimidazolium hydrogensulfate
([HSO4]−) + sulfuric acid. The hydrogensulfate ionic liquids themselves possess certain
Brønsted acidity by means of proton activity in the hydrogensulfate anion, but the addition
of sulfuric acid to the ionic liquid allows for smooth tuning of the acidity of this catalytic
system. In many cases, the acidity of hydrogensulfate ionic liquids themselves is sufficient
enough to f.e. dehydrate secondary alcohols (Scheme 1).13

IONIC LIQUIDS AS ADVANCED REACTION MEDIA
1207
Scheme 1 Synthesis of 1-phenylcyclohex-1-en in ionic liquid.
The application of 1-ethyl-3-methyl-imidazolium hydrogensulfate, [EMIM][HSO4],
provides a convenient synthesis of 1-phenylcyclohex-1-ene in very high yield. The ionic
liquid can be reused several times without losing its activity in the dehydration of 1-phenyl-
1-cyclohexanol (see Table 1).
The 1-phenyl-cyclohexan-1-ol possesses a good solubility in ionic liquid. But, after
conducting the reaction (80–90◦C, 1 h) and cooling the reaction mixture to room temper-
ature, the product, 1-phenylcyclohex-1-ene, forms an upper phase and can be easily sepa-
rated by means of decantation. This procedure can be repeated several times (see Table 1)
without treatment of the recycled ionic liquid. It appears as though the water formed is
solubilized in the ionic liquid’s medium and does not influence the dehydration process to
disrupt it. Only after converting four or five recharges of reactant should the ionic liquid be
dried in vacuum to remove the formed water (see Table 1, note b).
Figure 1 Thermogravimetric analysis (TGA) of the mixture containing 20% of CF3COOH dissolved in 1-butyl-
3-methylimidazolium trifluoroacetate.

1208
N. V. IGNAT’EV ET AL.
Table 1 Dehydration of 1-phenyl-cyclohexanol in 1-ethyl-3-methyl-imidazolium hydrogensulfate,
[EMIM][HSO4]
Experiment no.
Loading of phenyl cyclohexanol [g]
Yield [g]
Yield [%]
1
2
3
4
10.27
6.17
8.86
6.92
7.85
5.89
8.30
6.35
85
106a
104a
102a
IL dryingb
5
6
7
8
6.55
4.29
7.56
7.25
5.20
4.65
3.95
6.16
5.85
4.73
79
102a
91
90
101a
9
IL dryingb
Total yield: 97%
aAdditional quantity of product comes from previous charges and is therefore above 100%.
bDrying the IL for 2 h in vacuum (10−3 mbar) at 150◦C.
The dehydration of primary alcohols required stronger acidic conditions. It can be
successfully carried out in the following mixture: ionic liquid + Brønsted acid; for example
in the system 1-ethyl-3-methylimidazolium hydrogensulfate, [EMIM][HSO4] + concen-
trated sulfuric acid (see Scheme 2).13
Scheme 2 Dehydration of 1-heptanol in the system ionic liquid + Brønsted acid.
This catalytic system can also be successfully applied for dehydration of secondary
alcohols, for example cyclohexanol, and tertiary alcohols, for instance tert-butanol (see
Scheme 3).13
Scheme 3 Dehydration of secondary and tertiary alcohols in the catalytic system ionic liquid + Brønsted acid.

IONIC LIQUIDS AS ADVANCED REACTION MEDIA
1209
The dehydration of tert-butanol to isobutylene proceeds very efficiently in acidic
ionic liquids. This process does not require high temperatures and can be easily performed
continuously because of the low boiling point of isobutylene (−7◦C), which can constantly
be removed from the reaction mixture.
The technology described can also be applied for the preparation of basic chemicals
out of natural products. For example, acidic ionic liquids are suitable reaction media for
the conversion of mono-, di-, and poly-saccharides into furan derivatives (see Schemes 4,
5, and 6)13,14—important building blocks for fine chemistry.
Scheme 4 Conversion of xylose (pentose) to furfural in [EMIM][HSO4].
The xylose is converted very efficiently to furfural (see Scheme 4). The yield of fur-
fural has been improved up to 84% by use of a two-phase system of [EMIM][HSO4]/toluene
and longer reaction time (6 h). The ionic liquid, [EMIM][HSO4], can be effectively recycled
and used several times in the conversion of xylose to furfural.
Hexoses, for instance fructose, can be converted to 5-(hydroxymethyl)-2-furaldehyde
(HMF) by use of the two phase system of [EMIM][HSO4]/methyl isobutyl ketone (Scheme
5).14
Scheme 5 Conversion of fructose (hexose) to 5-(hydroxymethyl)-2-furaldehyde (HMF) in [EMIM][HSO4].
Dehydration of glucose in the biphasic system [EMIM][HSO4]/toluene gives 95%
conversion but only 9% HMF yield at 100◦C within 4 h.14 The rather low HMF yield may be
dueto thelack of selectivityin thedehydrationof glucose units inthis system. Toimprovethe
yield of HMF from glucose, the isomerization of glucose into fructose is required to increase
the selectivity of this process. It can be achieved with the application of Lewis acid catalysts,
for example in the system CrCl2/[BMIM][Cl] reported by Zhang and co-workers.15 More
stable and readily available CrCl3 can be effectively used instead of CrCl2. The HMF can be
obtained in 81% yield from glucose in the system [BMIM][Cl]/CrCl3 (i.e., no co-solvent)
within 4 h at 100◦C.14 Application of the biphasic system [BMIM][Cl]/CrCl3/toluene further
improves the yield of HMF to 91%.14
Not only mono- or disaccharides can be converted into 5-(hydroxymethyl)-2-
furaldehyde and also some polysaccharides, for instance inulin, which undergoes conversion
to HMF in acidic ionic liquids (see Scheme 6).14

1210
N. V. IGNAT’EV ET AL.
Scheme 6 Conversion of the polysaccharide inulin to 5-(hydroxymethyl)-2-furaldehyde (HMF) in
[EMIM][HSO4].
HMF is a useful substance for multipurpose applications.16 It can be used for example
as starting material for production of bio-fuel or fuel additives.
The catalytic system of ionic liquid and Brønsted acid can not only be used for
dehydration processes, but it also allows for combination of the alkylation and ring closure
reaction by means of water abstraction, for example in the synthesis of chromane derivatives
(see Scheme 7).17
Scheme 7 Synthesis of the 6-bromo-2,2,5,7-tetramethylchromane in two-phase system ionic liquid with Brønsted
acid and hexane.
Reaction of 4-brom-3,5-dimethyl-phenol and buten-2-ol proceeds in a two-phase
system at relatively low temperature (55–60◦C) and results in the formation of the desired
product in a very short time (15 min) in good yield (89%).
The same system can be applied for the synthesis of vitamin E (D,L-α-
tocopherole)—an industrial product with multi-ton production per year. Typical
technology is based on the application of special catalyst (strong Brønsted acid) to
induce the condensation of 2,3,5-trimethyl hydroquinone with isophytol. Application of
acidic ionic liquids as reaction media and catalyst simplifies the process and provides
the possibility to reduce the costs (see Scheme 8). The synthesis was optimized by use
of a two-phase system: ionic liquid/hexane. The ionic liquid can be recycled several
times.17

IONIC LIQUIDS AS ADVANCED REACTION MEDIA
1211
Scheme 8 Synthesis of vitamin E in the two phase system ionic liquid and Brønsted acid.
The last two examples clearly demonstrate that ionic liquids are advanced media
for multistep reactions (cascade reactions), which can be combined in one-pot synthesis.
It is not always necessarily to apply an acidic medium to such kind reactions. For ex-
ample, aza-Michael addition of NH-acids to functionalized alkynes proceeded very effec-
tively in “neutral” ionic liquids, such as in 1-butyl-3-methylimidazolium tetrafluoroborate,
[BMIM][BF4] (see Scheme 9).18,19
Scheme 9 Synthesis of 4-aminofuran-2(5H)-ones (3) from 3-(hydroxyalkyl) propargylic ester (1) and amines in
[BMIM][BF4].
The one-pot synthesis of 4-aminofuran-2(5H)-ones (3) from 3-(hydroxyalkyl)
propargylic ester (1) and amines is significantly accelerated in ionic liquids when
compared to traditional organic solvents (see Table 2). Ionic liquids can be reused many
times without decrease in the reaction rate and yield.
Table 2 Aza-Michael addition of NH-acids to functionalized alkynes in organic solvents and ionic liquid
[BMIM][BF4]
Reaction time, h
(solvent, temp◦C)
Reaction time, h
(IL, 20◦C)
Yield in organic
solvent (%)
Yield in
IL (%)
Entry
Amine
Piperidine
1
2
3
4
5
140 (Et2O, 20)
140 (Et2O, 20)
250 (Et2O, 20)
250 (Et2O, 20)
20 (MeOH, reflux)
1
1
2
4
6
67 (Et2O)
72 (Et2O)
82 (Et2O)
78 (Et2O)
62 (MeOH)
85
85
87
82
99
Morpholine
2-Methylpiperidine
Dibenzylamine
Anabazine

1212
N. V. IGNAT’EV ET AL.
It seems tobeageneral tendencythat ionicliquids accelerate the ring-closingreactions
based on the water or alcohol splitting in the intermediate state. This phenomenon can relate
to the ability of ionic liquids to solubilize these small polar molecules, resulting in a decrease
of their activity in side or back reactions.
Another example of such type of reaction is the formation of pyrazine ring by the
interaction of α-diketones with diamines (see Scheme 10).20
Scheme 10 Synthesis of pyrazines in ionic liquids.
The typical synthesis of pyrazine derivatives is based on the condensation of 1,2-
diamines (mostly aryl-1,2-diamines) with 1,2-dicarbonyl compounds in alcohol or in acetic
acid medium under reflux. The reaction proceeds very slowly and requires heating of the
reaction mixture for many hours.21–23
Surprisingly, the same reaction proceeds in ionic liquids much faster, even at room
temperature and gives the products in a good yield (see Table 3).
The product isolation procedure is very simple. The reaction mixture can be diluted
with water (in the case of ionic liquids A, B, C, D, E), and the product is filtered off or the
product can be extracted from ionic liquid (in the case F and G) with hexane. In both cases,
the ionic liquid can be regenerated and reused several times.20
Ionic liquid as reaction medium can influence not only the kinetic of chemical
reactions but also the regioselectivity in the synthesis of chemical substances, for example
in the bromination of levulinic acid (Scheme 11).24
Scheme 11 Bromination of levulinic acid in ionic liquids.24
If the bromination of levulinic acid (4) proceeds in methanol, the major product in the
reaction mixture is the mono-bromo compound (5). Replacement of methanol as reaction
medium with an ionic liquid not only accelerates the bromination process but also results
in the inversion in the regioselectivity. The major product that is formed in ionic liquid
medium is the mono-bromo compound (6) (see Table 4), which is of interest for further
derivatization. After separation of the brominated adducts, the ionic liquid can easily be
recovered and reused for the next charge.24

IONIC LIQUIDS AS ADVANCED REACTION MEDIA
1213
Table 3 Synthesis of diazines in ionic liquids20
Ionic Temp. Time
Yield
%
Diamin
1,2-Dicarbonyl
liquid∗
◦C
h
Product
Mp, ◦C
1
A
70
8,5
72 200–201
2
3
4
5
A
B
C
D
30
30
30
70
1
1
1
1
85 123–125
92 123–125
93 123–125
55 200–201
6
7
8
9
B
E
E
E
70
20
80
20
10,5
70 200–201
60 106–107
65 169–170
60 302–303
1
9
5
10
11
1
E
B
F
30
80
30
30
2
0,25
1
84 135–137
100
99–100
75 125–126
77 125–126
2
G
1
∗Ionic liquid: A 1-Ethyl-3-methylimidazolium (EMIM) tetrafluoroborat.
B N-Butyl-N-methylpyrrolidinium (BMPL) triflat.
C 1-Butyl-3-methylimidazolium (BMIM) methylsulfonat.
D 1-Ethyl-3-methylimidazolium (EMIM) hydrogensulfat.
E 1-Ethyl-3-methylimidazolium (EMIM) triflat.
F N-Butyl-N-methylpyrrolidinium (BMPL) bis(trifluoromethylsulfonyl)imide.
G Trihexyl(tetradecyl)phosphonium tris(pentafluoroethyl)trifluorophosphat.

1214
N. V. IGNAT’EV ET AL.
Table 4 Bromination of levulinic acid
Ratio 5–7
R
Solvent
Temp. (◦С)
Reaction time (h)
5
6
7
b
CH3OH
20
65
20
50
20
20
20
20
21
3.5
3.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
3.4
5.0
6.0
6.0
4.5
4.2
Nd
Nd
0.6
0.4
2.0
2.6
0.7
1.8
A
A
A
A
A
C
C
CH3OH(d)
[BMIM]Br
[OMIM]Br
[EMIM][HSO4]
[BMPL][N(CF3SO2)2]
[BMIM]Br
0.33
0.25
0.42
0.75
0.33
0.05
[EMIM][HSO4]
The products 5–7 have been isolated as methyl esters, which are formed with the participation of the solvent
(methanol).
Presumably, ionic liquids support the enolization of γ -diketones [for example le-
vulinic acid (4)] resulting in the formation of internal enol (4a), which undergoes fast
bromination into position 3 (Scheme 12).24
Scheme 12 Influence of ionic liquids on the bromination of levulinic acid.
CONCLUSION
Ionic liquids are new advanced media for organic synthesis. They are commercially
available from several companies around the world, including Merck KGaA, Darmstadt,
Germany.
Hydrogensulfate ionic liquids possess catalytic activity and provide access to conve-
nient technologies for the preparation of various useful compounds.
EXPERIMENTAL
Chemicals
Ionic liquids were prepared as described in the citations related to the patents or
patents applications or publications referred below. Other chemicals were purchased from
the companies or suppliers of chemical reagents and used without further purification unless
stated otherwise.

IONIC LIQUIDS AS ADVANCED REACTION MEDIA
1215
Analytical Procedures
NMR samples were measured in a 5-mm precision glass NMR tube (Wilmad 507
or 528 PPT) at 24◦C. Ambient and low-temperature NMR spectra were recorded in the
deuterium-locked mode on a Bruker Avance II (300 MHz) or Avance III (400 MHz)
spectrometer.
The 1H NMR chemical shifts were referenced with respect to tetramethylsilane (TMS)
using the chemical shifts for the solvents CH2Cl2 (5.32 ppm) and CH3CN (1.95 ppm). The
13C NMR chemical shifts were referenced with respect to TMS using the chemical shifts
for the solvents CH2Cl2 (53.5 ppm) and CH3CN (118.7 ppm). The 19F NMR spectra were
referenced with respect to CFCl3 using either the internal standards C6F6 (−162.9 ppm) or
C6H5CF3 (−63.9 ppm), or externally to a neat CFCl3 reference sample at 25◦C. The 31P
NMR chemical shifts were referenced with respect to 85% H3PO4 in D2O.
The purity (quality) of ionic liquids was controlled by measuring the residual water
(Karl-Fischer titration; 831 KF-Coulometer, Metrohm) and halides (ion-chromotography,
Metrohm Advanced IC System; stationary phase: Metrosep A SUPP4 – 150).
The Synthesis Procedure
The syntheses of the compounds described here are given in the patents/patents
application or publications and literature cited therein.
REFERENCES
1. Earle, M. J.; Seddon, K. R. Pure Appl. Chem. 2000, 72, 1391–1398.
2. Chiappe, C.; Malvaldi, M.; Pomelli, C. S. Pure Appl. Chem. 2009, 81, 767–776.
3. Joglekar, H. G.; Rahman, I.; Kulkarni, B. D. Chem. Eng. Technol. 2007, 30, 819–828.
4. Murugesan, S.; Linhardt, R. J. Curr. Org. Synth. 2005, 2, 437–451.
5. Holbrey, J. D. Chem. Today 2004, 22, 35–37.
6. Welton, T. Chem. Rev. 1999, 92, 2071–2083.
7. Hagiwara, R.; Ito, Ya. J. Fluorine Chem. 2000, 105, 221–227.
8. Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis, 2nd ed.; Wiley-VCH: Weinheim,
Germany, 2008.
9. Ohno, H. Electrochemical Aspects of Ionic Liquids; Wiley: Hoboken, NJ, 2005.
10. Dyson, P. J.; Geldbach, T. J. Metal Catalysed Reactions in Ionic Liquids; Springer: Dordrecht,
Netherlands, 2005.
11. Welz-Biermann, U.; Ignatyev, N.; Bernhardt, E.; Finze, M.; Willner, H. WO 2004/072089, Merck
Patent GmbH, Darmstadt, Germany.
12. Ignat’ev, N. V.; Welz-Biermann, U.; Kucheryna, A.; Bissky, G.; Willner, H. J. Fluorine Chem.
2005, 126, 1150–1159.
13. Ignatyev, N.; Welz-Biermann, U.; Heckmeier, M.; Oldenburg, N.; Koppe, K.; Barthen, P.; Frohn,
H.-J. WO 2007/014613, Merck Patent GmbH, Darmstadt, Germany.
14. Lima, S.; Neves, P.; Antunes, M. M.; Ignatyev, N.; Valente, A. A. Appl. Catal., A 2009, 363,
93–99.
15. Zhao, H.; Holladay, J. E.; Brown, H.; Zhang, Z. C. Science 2007, 316, 1597–1600.
16. Kamm, B.; Gruber, P. R.; Kamm, M. Biorefineries—Industrial Process and Products: Status
Quo and Future Directions, Vol. 2; Wiley-VCH: Weinheim, Germany, 2006, pp. 133–138.
17. Ignatyev, N.; Koppe, K.; Barthen, P.; Frohn, H.-J. WO 2008/086847, Merck Patent GmbH,
Darmstadt, Germany.

1216
N. V. IGNAT’EV ET AL.
18. Zlotin, S. G.; Simirskaya, N. I.; Ignatyev, N. Patent Application, 2009, Merck Patent GmbH,
Darmstadt, Germany.
19. Simirskaya, N. I.; Ignat’ev, N. V.; Schulte, M.; Zlotin, S. G. Mendeleev Commun. 2011, 21,
94–96.
20. Sheremetev, A. B.; Alexandrova, N. S.; Ignatyev, N. Patent Application, 2009, Merck Patent
GmbH, Darmstadt.
21. Porter, A. E. A. Pyrazines and Their Benzo Derivatives: Comprehensive Heterocyclic Chemistry,
Vol. 3; A. R. Katritzky and C. W. Rees, Eds.; Pergamon Press: New York, 1984, pp. 157–197.
22. Vogel, A. I.; Tatchell, A. R.; Furnis, B. S.; Hannaford, A. J.; Smith, P. W. G. Vogel’s Textbook
of Practical Organic Chemistry, 5th ed.; Addison-Wesley Longman Ltd.: Harlow, Essex, UK,
1989, p. 1190.
23. Brown, D. J. Quinoxalines: Supplements II. In The Chemistry of Heterocyclic Compounds; E. C.
Teylor and P. Wipf, Eds. John Wiley and Sons: New York, 2004.
24. Zavozin, A. V.; Kravchenko, N. E.; Ignat’ev, N. V.; Zlotin, S. G. Tetrahedron Lett. 2010, 51,
545–547.