Angewandte
Chemie
Table 1: Dehydration of fructose with formic acid.[a]
Entry Solvent Additive
T [oC] t [h]
The utility of FA as both a hydrogen source and a
deoxygenating agent encouraged efforts to combine several
of the aforementioned steps. Gratifyingly, heating a solution
of HMF in refluxing THF with formic acid, H2SO4, and Pd/C
gave DMF. The reaction proceeded in excellent yield (> 95%,
15 h). NMR analysis of the reaction revealed signals that were
assigned to 2-hydroxymethyl-5-methylfuran (HMMF) as an
intermediate, thus implicating step-wise hydrogenolysis of
BHMF (Scheme 2).
Selectivity [%][c]
HMFþFMFþLA ꢁ 100
56
65
HMFþFMF
1
2
FA
FA
none
1 mol% H2SO4
120
120
10
1
3
FA
FA
DMSO
10 mol% H2SO4 120
none 150
10 mol% H2SO4 100
0.5 52
2
5
4
73
93
5[b]
[a] Typical reaction conditions: fructose (3.6 g), FA (20 mL), additive.
[b] 10 mL DMSO used. [c] Selectivity determined by H NMR analysis.
1
DMSO=dimethylsulfoxide.
Scheme 2. Pathway for dimethylfuran from HMF. See the Supporting
Information for details.
Deoxygenation of benzylic-like alcohols by in situ gen-
eration of formate esters was verified in control experiments.
Neither furfuryl alcohol nor benzyl alcohol undergoes hydro-
genolysis in the presence of formic acid and Pd/C in THF.
However, addition of
a catalytic amount of H2SO4
(0.065 equiv/ROH) to such solutions resulted in clean con-
versions into 2-methylfuran and toluene.
Scheme 3. One-pot process to generate DMF from fructose. The
conversions were carried out at about 1508C (left box) and 708C (right
box).
In view of the conversion of HMF into DMF, we
investigated the use of formic acid for conversions of fructose.
Therefore, by using 2.8 mL of formic acid per gram of
fructose, we obtained HMF and its formate ester (FMF), as
well as LA. HMFand FMFare equivalent precursors to DMF.
LA, which is also a promising precursor for biofuels
(Scheme 1),[6b,c,d] does not interfere with subsequent reactions.
Considerable control of the selectivity toward HMF/FMF
versus LA is possible by varying the temperature, reaction
time, and strong acid additives (Table 1). For example, HMF
formed in 95% yield when the dehydration was conducted in
DMSO.
Solutions of FMF and HMF in FA were found to undergo
hydrogenation and hydrogenolysis into DMF upon addition
of a THF slurry of the Pd/C catalyst. The conversion is
proposed to proceed through the intermediacy of 2-hydroxy-
methyl-5-methylfuran (HMMF) and its monoformate ester
(FMMF; Scheme 3). LA was unreactive under these condi-
tions and thus remained in the solution at the end of the
reaction. Pd/C and formic acid were recovered by filtration
and distillation. Control experiments confirmed that a
solution of FMF in formic acid (2.46 mLgꢀ1) and H2SO4
(0.13 equiv) and subsequent addition of THF with Pd/C
yielded DMF quantitatively upon heating to reflux.
acetic acid is ineffective for the dehydration of fructose into
HMF. The diacetate ester of BHMF is unreactive toward Pd/C
except in the presence of H2 wherein we observe formation of
significant amounts of 2,5-dimethyltetrahydrofuran. The use
of formic acid completely avoids ring hydrogenation.
In summary, formic acid, a potentially renewable carrier
of hydrogen, enables an efficient one-pot synthesis of the
promising liquid fuel 2,5-dimethylfuran from fructose. Formic
acid serves three distinct functions: as an acid catalyst for
dehydration of fructose to HMF, a hydrogen source for one
hydrogenation (HMF to BHMF), and as a reagent for the
deoxygenation of furanylmethanols. Additional flexibility in
the transformation is possible if the initially produced HMF is
isolated; the HMF can then be subjected to palladium-
catalyzed decarbonylation[18] (CO is a precursor to formic
acid[14]), and the resulting furfuryl alcohol then undergoes
hydrogenolysis with formic acid to give 2-methylfuran.
Experimental Section
Synthesis of DMF from HMF: A suspension of HMF (0.25 g,
2 mmol), FA (0.78 mL, 20 mmol), H2SO4 (14 mL, 0.26 mmol), THF
(10 mL), and Pd/C (0.4 g) was stirred at reflux for 15 h. 1H and
Use of acetic acid in the above processes highlights a
number of advantages for formic acid. Being a weaker acid,
Angew. Chem. Int. Ed. 2010, 49, 6616 –6618
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6617