Silver-Catalyzed Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols

Article abstract of DOI:10.1002/chem.201702420

A simple silver-catalyzed protocol has been developed for the acceptorless dehydrogenation of primary alcohols into carboxylic acids and hydrogen gas. The procedure uses 2.5 % Ag₂CO₃ and 2.5–3 equiv of KOH in refluxing mesitylene to afford the potassium carboxylate which is then converted into the acid with HCl. The reaction can be applied to a variety of benzylic and aliphatic primary alcohols with alkyl and ether substituents, and in some cases halide, olefin, and ester functionalities are also compatible with the reaction conditions. The dehydrogenation is believed to be catalyzed by silver nanoparticles that are formed in situ under the reaction conditions.

Full text of DOI:10.1002/chem.201702420

A Journal of
Accepted Article
Title: Silver-Catalyzed Dehydrogenative Synthesis of Carboxylic Acids
from Primary Alcohols
Authors: Robert Madsen and Hajar Golshadi Ghalehshahi
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Silver-Catalyzed Dehydrogenative Synthesis of Carboxylic Acids
from Primary Alcohols
Hajar Golshadi Ghalehshahi[a,b] and Robert Madsen*[a]
Abstract: A simple silver-catalyzed protocol has been developed for
energetically more favored and prevents deactivation of the
catalyst by the carboxylic acid. We have developed the
the acceptorless dehydrogenation of primary alcohols into carboxylic
acids and hydrogen gas. The procedure uses 2.5% Ag
2
CO
3
and 2.5
2
ruthenium N-heterocyclic carbene complex [RuCl (IiPr)(p-
[5a]
–
3 equiv. of KOH in refluxing mesitylene to afford the potassium
cymene)] for the synthesis of carboxylic acids and have also
used the same complex for preparation of imines, amides and
esters from primary alcohols.[9]
carboxylate which is then converted into the acid with HCl. The
reaction can be applied to a variety of benzylic and aliphatic primary
alcohols with alkyl and ether substituents, and in some cases halide,
olefin and ester functionalities are also compatible with the reaction
conditions. The dehydrogenation is believed to be catalyzed by silver
nanoparticles that are formed in situ under the reaction conditions.
So far the acceptorless dehydrogenation of a primary alcohol
to the carboxylic acid has only been achieved with a metal
catalyst from the platinum group metals. However, there is a
significant interest in the field to develop cheaper catalysts for
these dehydrogenative transformations with alcohols. This has
been demonstrated in the synthesis of imines from alcohols and
amines where manganese, cobalt, iron, copper and silver
catalysts have been shown to perform the reaction in the
absence of an acceptor.[10] The silver-catalyzed imine synthesis
was performed with silver nanoparticles deposited on an
Introduction
Chemical reactions which are initiated by the dehydrogenation of
an alcohol have received much attention for more than a
decade.[1] In these transformations hydrogen gas is liberated
from the alcohol and no stoichiometric oxidant or hydrogen
acceptor is necessary. The most effective metal catalysts have
been a variety of ruthenium and iridium complexes which has
made it possible to prepare ketones, imines, amides and esters
directly from alcohols (and amines).[1]
alumina support.[10e] Ag/Al
2 3
O has also been shown to catalyze
the formation of amides from alcohols and amines, and the
dehydrogenation of alcohols into aldehydes and ketones.[11] In
addition, silver nanoparticles on either ZnO, silica-coated ferrite
or hydrotalcite have been shown to catalyze the production of
aldehydes and ketones from alcohols.[12] Thus, silver(0) catalysts
constitutes and interesting alternative to the platinum group
metals for dehydrogenative transformations with alcohols.
Herein, we describe the development of the first silver-
catalyzed acceptorless dehydrogenation of primary alcohols into
carboxylic acids.
In 2013 the conversion of a primary alcohol to the carboxylic
acid and hydrogen gas was presented for the first time catalyzed
by
a
ruthenium PNN pincer complex.[2] Since then the
transformation has also been achieved with a several other
ruthenium complexes containing PNP pincer,[3] NNN pincer, N-
heterocyclic carbene[5] and 2,2’-bipyridine type[6] ligands. In
addition, a binuclear rhodium complex with two terpyridine
ligands[7] and palladium on carbon[8] have been used to catalyze
the dehydrogenation to carboxylic acids where a reduced
pressure was necessary with the palladium catalyst to remove
the liberated hydrogen gas. In all cases, a catalyst loading
between 0.1% and 5% was employed and the reactions were
carried out at elevated temperature with water or toluene as the
solvent.2-8 In addition, a stoichiometric amount of a base was
[4]
Results and Discussion
The dehydrogenation was discovered by serendipity when
attempting to perform the same reaction with a manganese
catalyst. Manganese-catalyzed dehydrogenation of alcohols was
recently presented for the first time,[
10a]
but so far only
manganese(I) species stabilized by PNP pincer and carbon
monoxide ligands have been employed as catalysts.[13] We
decided to perform several experiments with more simple
systems and tested a variety of manganese sources and
additives as catalysts. Benzyl alcohol was selected as the
substrate and the reactions were performed by stirring the
catalyst with 2.5 equiv. of KOH powder in mesitylene solution for
10 min followed by addition of the alcohol and heating the
mixture to reflux. Interestingly, the best results were obtained in
the presence of a silver salt (Table 1, entries 1 – 7). Grey
particles were formed during the reactions, but the role of the
silver source was not immediately clear. However, the
transformation also proceeded in the absence of the manganese
salt (entries 8 – 12) which gave rise to speculations about silver
nanoparticles being responsible for the dehydrogenation.[
Silver nanoparticles are usually stabilized by a heterogeneous
2 3
added such as NaOH, KOH, CsOH or Cs CO giving rise to the
alkali metal salt of the carboxylic acid as the immediate product.
The addition of the base also makes the overall transformation
[
a]
b]
H. G. Ghalehshahi, Prof. Dr. R. Madsen
Department of Chemistry
Technical University of Denmark
2800 Kgs. Lyngby (Denmark)
E-mail: rm@kemi.dtu.dk
[
H. G. Ghalehshahi
Current address: Department of Chemistry
K. N. Toosi University of Technology
P. O. Box 15875, 4416 Tehran (Iran)
14]
Supporting information for this article is given via a link at the end of
the document.
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Chemistry - A European Journal
10.1002/chem.201702420
FULL PAPER
support, but can also be formed in solution under basic
conditions where the particles are stabilized by the absorption of
hydroxide at the surface.[15] In addition, alcohols are known to
serve as reducing agents for the formation of silver
(entry 15) although the result was not fully reproducible in some
cases. A small amount of a heterogeneous support was
therefore added and polyvinylpyrrolidone (PVP) is a well-known
dispersant for silver nanoparticles.[16] Under these conditions a
near quantitative GC yield of benzoic acid could now be
obtained consistently when repeating the reaction (entry 18).[
The base was also investigated again and the yield decreased
slightly with lower amounts of KOH (entries 16 and 17).
nanoparticles from silver salts.[16] The reaction with AgBF
was
4
17]
also tested in xylene, toluene, dioxane and tert-amyl alcohol at
reflux, but only 15 – 20% yield was obtained in these solvents
while no conversion occurred in water (results not shown). The
same result was observed when KOH was replaced with LiOH
We have previously established that the Cannizzaro reaction
may be operating in these dehydrogenations of benzylic
alcohols under basic conditions[ and this is also true for the
silver-catalyzed protocol. Subjecting benzaldehyde to the
optimized conditions in entry 18 led to rapid formation of a
mixture of potassium benzoate and benzyl alcohol where the
latter was slowly converted into the former over a period of 4 h
(
entry 13).
5a]
Table 1. Optimization of benzyl alcohol dehydrogenation.
(
Figure 1). Benzaldehyde, though, was not quantified in this
experiment due to co-elution with the solvent.
Entry
Catalyst
Yield [%][a]
1
2
3
4
5
6
7
8
9
2.5% MnBr
2
0
10% CpMn(CO)
10% MnCl , 10% Zn powder
10% Mn powder, 2.5% Ag CO
2.5% MnBr , 2.5% Ag
2.5% Mn (CO)10, 2.5% Ag
2.5% MnCl , 2.5% Ag CO
2.5% Ag CO
2.5% Ag
5% AgBF
3
19
10
32
47
67
74
81
78
73
66
48
0
2
2
3
2
2
O
2
2
CO
3
2
2
3
2
3
Figure 1. Dehydrogenation of benzaldehyde.
2
O
The evolution of hydrogen gas was measured under the
1
1
1
1
1
1
1
1
1
0
4
optimized conditions in entry 18 and a total of 7.3 mmol of H
was collected after 7 h from the reaction with 4 mmol of benzyl
alcohol and 0.1 mmol of Ag CO . The identity of the gas was
established through a subsequent hydrogenation of an olefin.
This proves that the transformation takes place by
2
1
5% AgNO
5% AgCl
3
2
3
2
a
3[b]
4
2.5% Ag
2.5% Ag CO , 2.5% MnCO
2 3
CO
dehydrogenation pathway where no stoichiometric oxidant is
involved. The experiment in entry 18 was also repeated four
times in the presence of 0.75 mmol of liquid mercury which was
added after 0, 2, 4 and 6 h, respectively. The four reactions gave
0%, 20%, 45% and 63% yield after 8 h and in all cases the
dehydrogenation stopped immediately after the addition of
mercury. This observation strongly indicates that silver
nanoparticles are responsible for the dehydrogenation where the
addition of mercury has led to the formation of an inactive
amalgam at the surface of the heterogeneous catalyst.[18]
2
3
3
81
98
86
73
99
5
2.5% Ag
2.5% Ag
2.5% Ag
2
2
2
CO
CO
CO
3
, 2.5% MnBr
, 2.5% MnBr
, 2.5% MnBr
2
6[c]
3
3
2
7[d]
8
2
2 3 2
2.5% Ag CO , 2.5% MnBr , PVP
[
a] GC yield. [b] With LiOH instead of KOH. [c] With 2 equiv. of KOH. [d] With
.6 equiv. of KOH.
A common procedure for preparation of silver nanoparticles
is the so-called polyol process where AgNO
ethylene glycol in the presence of PVP.[
1
3
is reacted with
Therefore, an
and PVP were
16a,c]
2 3
Ag CO gave the highest yield among the different silver
experiment was also performed where AgNO
3
sources. If nanoparticles are the reactive catalyst in the reaction,
the formation and stability of these species will influence the
yield. This made us test manganese sources again (entries 14 –
stirred in ethylene glycol solution at 120 °C for 1 h followed by
centrifugation and removal of the solvent.[16c] To the residue was
added KOH, mesitylene and benzyl alcohol and the mixture was
stirred at 165 °C for 8 h. This gave benzoic acid in 91% GC yield
1
7) since the manganese salt may affect the nanoparticle
formation. With MnBr an improvement in the yield was obtained
2
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which again points to silver nanoparticles as the responsible
dehydrogenation catalyst.
Final confirmation was obtained by characterizing the
morphology of the prepared nanoparticles by transmission
electron microscopy (TEM). The reaction in Table 1, entry 18
2 3 2
suspension was obtained upon mixing Ag CO , MnBr , PVP and
KOH in mesitylene at room temperature and the mixture was
first stirred for 5 min at room temperature and then heated to
50 °C over an additional 5 min. At this temperature the alcohol
was added to give a black suspension which was heated to
165 °C at a rate of 5 °C/min. While the temperature increased
the mixture became colorless with some black particles visible.
After about 1 h at 165 °C the potassium salt of the carboxylic
acid precipitated as a light brown solid. Adding the alcohol at
80 °C or 100 °C, on the other hand, gave very little or no
conversion into the acid. A TEM micrograph was obtained after
4 h from the experiment where the alcohol was added at 100 °C.
The image showed particles with different shapes and sizes, and
where the diameter was larger than 500 nm (see supporting
information). This clearly shows the involvement of the alcohol in
the nanoparticle formation and the importance of adding the
alcohol at 50 °C in order to obtain the distribution shown in
Figure 2.
was stopped after
4 h and the solids were isolated by
centrifugation, washed with acetone/water, and then dispersed
in acetone. The TEM micrograph showed spherical and
monodispersed silver nanoparticles and revealed a narrow
particle size distribution with an average diameter of 15 nm
(
Figure 2).The crystalline nature of the nanoparticles was
confirmed by X-ray diffraction (XRD) (Figure 3). Four
characteristic peaks were observed at 38.3°, 44.5°, 64.7° and
77.7°, respectively, corresponding to the (111), (200), (220) and
(
311) planes of the face centered cubic crystal structure of
silver.[
16c]
An amorphous organic compound was also detected
at 16 – 23° which may correspond to PVP.
With the optimized protocol available, the substrate scope
and limitations could now be investigated in detail. First, a
number of benzylic alcohols were converted into the
corresponding acids using a reaction time of 8 h (Table 2). The
isolated yield of benzoic acid was 92% (entry 1) while p-toluic
acid was obtained in 85% yield (entry 2). With electron-
withdrawing substituents
dehydrogenation occurred
Trifluoromethyl)benzyl alcohol gave the acid in near quantitative
yield after only 2 h (entry 3). The shorter reaction time was also
necessary to avoid partial defluorination since p-
difluoromethyl)benzoic acid was observed as a byproduct after
in the
para
position the
more
rapidly. p-
(
(
8
h. In the same way p-chlorobenzyl alcohol afforded p-
chlorobenzoic acid after 1.5 h at 150 °C (entry 4) while refluxing
the mixture for 8 h gave complete dehalogenation to benzoic
acid (entry 5). Small amounts of benzoic acid and benzyl alcohol
were observed as byproducts under the milder conditions in
entry 4. p-Bromobenzyl alcohol yielded only benzoic acid
regardless of the reaction time (entry 6). Methyl p-
Figure 2. TEM micrograph of silver nanoparticles.
(
hydroxymethyl)benzoate
furnished
terephthalic
acid
monomethyl ester in 88% yield with the parent terephthalic acid
as the main byproduct (entry 7). The relatively little hydrolysis of
the ester was surprising since we observed complete ester
hydrolysis in our previous attempt to dehydrogenate the same
substrate with a ruthenium catalyst.[ The reason is most likely
the faster conversion of methyl p-(hydroxymethyl)benzoate with
the silver-catalyzed procedure leading to the insoluble
potassium salt of terephthalic acid monomethyl ester. Ether- and
phenyl-substituted benzyl alcohols gave the corresponding
benzoic acids in 71 – 76% yield (entries 8 – 10) while p-
5a]
(
methylthio)benzyl alcohol afforded the acid in a slightly lower
yield (entry 11). Notably, no hydrogenolysis of the benzyl ether
was observed in entry 9. Ortho-disubstituted 2,4,6-
trimethylbenzyl alcohol gave 58% yield of mesitoic acid due to
incomplete conversion of the hindered alcohol (entry 12). o-
Chlorobenzyl alcohol underwent complete dehalogenation (entry
Figure 3. XRD pattern of silver nanoparticles.
1
3) while 2-naphthylmethanol furnished 2-naphthoic acid in 73%
The exact protocol for mixing the reactants and heating the
mixture to reflux was important in order to achieve the near
quantitative conversion in Table 1, entry 18. A dark green
isolated yield (entry 14). p-Nitrobenzyl alcohol also underwent
dehydrogenation to the carboxylic acid, but the reaction was
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accompanied by reduction of the nitro group to afford p-
aminobenzoic acid.[19] No attempt was made to optimize the
reaction and to purify the product since the reduction requires 3
[a] Reaction conditions: Alcohol (4 mmol), KOH (10 mmol), Ag
2 3
CO (0.1 mmol),
MnBr (0.1 mmol), PVP (15 mg), mesitylene, reflux, 8 h, then aq. HCl. [b]
2
Reaction time 2 h. [c] Reaction time 1.5 h at 150 °C. [d] Reaction time 4 h.
equiv. of
H
2
and only 2 equiv. are released in the
dehydrogenation.
The silver-catalyzed protocol could also be applied for
dehydrogenation of aliphatic alcohols although a longer reaction
time of 20 h was necessary in this case (Table 3). In addition,
Table 2. Silver-catalyzed dehydrogenation of benzylic alcohols.[a]
[20]
the amount of base was changed to 3 equiv. which gave a
higher yield than 2.5 equiv. Decan-1-ol gave rise to decanoic
acid in 71% yield (entry 1) while cyclopentylmethanol and 2-
cyclohexylethanol afforded the acid in 79% and 59% yield,
respectively (entries 2 and 3). 3-Phenylpropan-1-ol furnished 3-
phenylpropanoic acid in 91% yield (entry 4) and the same
product was obtained from cinnamyl alcohol (entry 5). In the
latter case, a small amount of 3-phenylpropan-1-ol was detected
after the reaction indicating that the reduction of the olefin is
faster than the dehydrogenation of the alcohol. Cyclohex-3-
enylmethanol, on the other hand, yielded only the unsaturated
carboxylic acid as the product (entry 6) which may show that
coordination to the alcohol is involved in the reduction of the
olefin in entry 5. Dec-9-en-1-ol could also be converted into the
corresponding acid, but it contained about 20% of the isomer
from olefin migration, i.e. dec-8-enoic acid, which could not be
separated (result not shown). (‒)-Cis-myrtanol gave the
thermodynamically more stable (+)-trans-dihydromyrtenic acid
where the basic conditions had caused complete inversion of
stereochemistry (entry 7). 2-Phenylethanol led to complete
elimination to styrene and no dehydrogenation was observed in
this case. Aliphatic diols such as octane-1,8-diol and 2-
phenylpropane-1,3-diol gave less than 50% conversion after 20
h. Most likely, the nanoparticle formation was influenced by the
diols and no attempt was made to develop an optimized
procedure for diols. 1-Adamantanemethanol also reacted slowly
and only afforded about 50% yield of the acid after 20 h which
again illustrates the influence of steric hindrance.
Entry
Substrate
Product
Isolated yield
%]
[
1
92
2
85
98
86
93
94
3[b]
4[c]
5
6
7[d]
88
8
9
75
71
76
65
Table 3. Silver-catalyzed dehydrogenation of aliphatic alcohols.[a]
Entry
Substrate
Product
Isolated yield
%]
[
1
0
1
1
2
3
71
1
79
59
12
58
4
5
91
89
1
3
4
88
73
1
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the tube was evacuated and refilled three times with nitrogen. Mesitylene
(
3 mL) was added and the mixture stirred at room temperature for 5 min.
The tube was then placed in an oil bath and heated with a rate of
°C/min. At 50 °C the primary alcohol (4 mmol) was added and heating
6
7
78
5
the mixture with a rate of 5 °C/min continued until 165 °C. The reaction
was monitored by GC until completion (8 h for benzylic alcohols; 20 h for
aliphatic alcohols) and the Schlenk tube was then removed from the oil
bath and cooled to room temperature. Water (2 mL) was added to
dissolve the salts followed by 19% aqueous HCl (~1 mL for benzylic
alcohols; ~2 mL for aliphatic alcohols) until pH 5 – 6. The solution was
washed with EtOAc (5 mL). The aqueous layer was acidified with 19%
aqueous HCl to pH 1 and then extracted with EtOAc (3 × 8 mL). The
78
[
a] Reaction conditions: Alcohol (4 mmol), KOH (12 mmol), Ag
2
CO
3
(0.1 mmol),
MnBr
2
(0.1 mmol), PVP (15 mg), mesitylene, reflux, 20 h, then aq. HCl.
Only two studies have previously investigated the
2 4
combined organic layers were dried over Na SO and concentrated in
mechanism in detail for the silver-catalyzed dehydrogenation of
alcohols.[11c,21] In both cases, FTIR spectroscopy and labelling
vacuo to give the corresponding acid which may be further purified by
recrystallization.
Dehydrogenation of Benzyl Alcohol with Preformed Silver
Nanoparticles: Following a literature protocol[16c] PVP (100 mg) was
dissolved in ethylene glycol (2 mL) in a Schlenk tube under nitrogen.
experiments were employed and silver was deposited on a
heterogeneous support (alumina[11c] or silica ). The studies
revealed a catalytic pathway where the alcohol is absorbed on
the surface of the support, which is also responsible for
abstracting the proton from the hydroxy group.[11c,21] Silver then
cleaves hydride from the alkoxide to form the carbonyl
[21]
3
AgNO (68 mg, 0.4 mmol) was added and the mixture was heated at a
rate of 5 °C/min to 120 °C in an oil bath. After heating for 1 h at 120 °C
the tube was cooled to room temperature and acetone (10 mL) was
added. Centrifugation and removal of the solvent left a black sticky
precipitate which was washed with acetone (2 mL). The residue was
transferred to another Schlenk tube and dried under vacuum. The tube
was filled with nitrogen, and KOH (560 mg, 10.0 mmol) and mesitylene (3
mL) were added. The mixture was heated as described above and
benzyl alcohol (0.41 mL, 4 mmol) was added at 50 °C. Nonane (0.2 mL)
was added as an internal reference after heating at 165 °C for 8 h and
the mixture was quenched with 19% aqueous HCl. The GC yield of
benzoic acid was determined to be 91%.
compound and silver hydride where the latter reacts with the
abstracted proton to release hydrogen gas.[11c,21] A similar
pathway can be envisioned in the present case where hydroxide
at the surface of the silver nanoparticles is responsible for
deprotonating the primary alcohol.
Benzoic acid:[4a] Table 1, entry 1. Isolated as white crystals after
recrystallization from water in 92% yield (450 mg). 1H NMR (400 MHz,
Conclusions
DMSO-d ):  = 7.50 (t, J = 7.1 Hz, 2H), 7.62 (t, J = 7.3 Hz, 1H), 7.95 (d, J
6
In summary, we have described
a new protocol for the
13
=
8.0 Hz, 2H), 12.94 (s, OH) ppm. C NMR (100 MHz, DMSO-d
6
):  =
dehydrogenation of primary alcohols into carboxylic acids where
a platinum group metal or a specially prepared metal complex is
not required. A variety of benzylic and aliphatic alcohols undergo
+
128.4, 129.1, 130.6, 132.7, 167.1 ppm. MS (EI): m/z = 122.05 [M] .
[5a]
p-Methylbenzoic acid: Table 1, entry 2. Isolated as a white solid after
recrystallization from water/ethanol in 85% yield (463 mg). 1H NMR (400
the transformation in the presence of 2.5% of Ag
2
CO
3
and 2.5 –
MHz, DMSO-d
6
):  = 2.35 (s, 3H), 7.28 (d, J = 8.0 Hz, 2H), 7.83 (d, J =
13
3
equiv. of KOH in refluxing mesitylene. The reaction is believed
8.2 Hz, 2H), 12.77 (s, OH) ppm. C NMR (100 MHz, DMSO-d
6
):  = 21.4,
+
128.3, 129.4, 129.6, 143.3, 167.6 ppm. MS (EI): m/z = 136.05 [M] .
to proceed through the in situ formation of silver nanoparticles
as the active catalyst responsible for the release of hydrogen
gas.
[
22]
p-(Trifluoromethyl)benzoic acid: Table 1, entry 3. Isolated as a white
1
solid in 98% yield (745 mg). H NMR (400 MHz, DMSO-d
6
):  = 7.74 (d, J
=
8.2 Hz, 2H), 8.09 (d, J = 8.1 Hz, 2H), 13.41 (s, 1H) ppm. 13C NMR (100
MHz, DMSO-d
6
):  = 123.6 (q, J = 272 Hz), 125.3 (q, J = 4 Hz), 130.0,
+
1
32.6 (q, J = 32 Hz), 134.6, 166.2 ppm. MS (EI): m/z = 189.90 [M] .
p-Chlorobenzoic acid:[ Table 1, entry 4. Isolated as a white solid after
7]
Experimental Section
recrystallization from water/ethanol in 86% yield (539 mg). 1H NMR (400
General Information: Mesitylene was dried by distillation from sodium.
All solvents were of HPLC grade and were not further purified. Gas
6
MHz, DMSO-d ):  = 7.56 (d, J = 8.2 Hz, 2H), 7.94 (d, J = 8.2 Hz, 2H)
ppm. 13C NMR (100 MHz, DMSO-d
):  = 129.0, 129.9, 131.4, 138.1,
6
166.8 ppm. MS (EI): m/z = 155.95 [M]+.
chromatography was performed on
a Shimadzu GCMS-QP2010S
p-(Methoxycarbonyl)benzoic acid:[ Table 1, entry 7. Isolated as a
23]
instrument fitted with an Equity 5, 30 m × 0.25 mm × 0.25 m column.
The TEM image was obtained on a Zeiss EM10C transmission electron
microscope operating at 100 kV. The XRD measurement was carried out
on a Philips X’pert 1710 diffractometer (CuK radiation,  = 0.154056 nm)
operating at 40 kV/30 mA over the 2 range of 5° – 80° at a scan rate of
white solid after recrystallization from water/ethanol in 88% yield (634
1
mg). H NMR (400 MHz, DMSO-d
6
):  = 3.86 (s, 3H), 8.00–8.10 (m, 4H),
):  = 52.7, 129.6,
13.33 (s, 1H) ppm. 13C NMR (100 MHz, DMSO-d
6
129.8, 133.4, 135.1, 165.9, 166.8 ppm. MS (EI): m/z = 179.95 [M]+.
p-Methoxybenzoic acid:[4a] Table 1, entry 8. Isolated as a white solid
after recrystallization from water/ethanol in 75% yield (454 mg). 1H NMR
0
.02°/s. NMR spectra were recorded on
spectrometer. Chemical shifts were measured relative to the signals of
residual DMSO-d ( = 2.50 ppm) and DMSO-d ( = 39.5 ppm). The
a Bruker Ascend 400
(400 MHz, DMSO-d
J = 8.8 Hz, 2H), 12.61 (s, OH) ppm. C NMR (100 MHz, DMSO-d ):  =
6
):  = 3.82 (s, 3H), 7.01 (d, J = 8.9 Hz, 2H), 7.90 (d,
5
H
6
C
13
evolution of hydrogen gas was measured in the same way as described
previously.[5a]
6
+
55.2, 113.6, 122.8, 131.2, 162.7, 166.8 ppm. MS (EI): m/z = 152.05 [M] .
p-(Benzyloxy)benzoic acid:[24] Table 1, entry 9. Isolated as a white solid
General Procedure: A three neck Schlenk tube (50 mL) was charged
with PVP (15 mg), MnBr (21.5 mg, 0.1 mmol), Ag CO (27.6 mg, 0.1
2 2 3
after recrystallization from water/ethanol in 71% yield (649 mg). 1H NMR
mmol), KOH (560 mg, 10.0 mmol for benzylic alcohols; 672 mg, 12.0
mmol for aliphatic alcohols) and a stir bar. A coldfinger was attached and
(400 MHz, DMSO-d
= 7.1 Hz, 1H), 7.39 (t, J = 7.3 Hz, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.90 (d, J
8.8 Hz, 2H), 12.64 (s, OH) ppm. 13C NMR (100 MHz, DMSO-d
):  =
6
):  = 5.17 (s, 2H), 7.09 (d, J = 8.8 Hz, 2H), 7.33 (t, J
=
6
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10.1002/chem.201702420
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6
9.7, 114.8, 123.4, 128.0, 128.2, 128.7, 131.6, 136.7, 162.2, 167.2 ppm.
We thank the Villum Fonden for financial support (grant 12380).
+
MS (EI): m/z = 227.00 [M] .
[
1,1’]-Biphenyl-4-carboxylic acid:[22] Table 1, entry 10. Isolated as a
white solid after recrystallization from water/ethanol in 76% yield (600
Keywords: alcohols • carboxylic acids • dehydrogenation •
nanoparticles • silver
1
mg). H NMR (400 MHz, DMSO-d
6
):  = 7.41 (t, J = 7.3 Hz, 1H), 7.49 (t, J
7.5 Hz, 2H), 7.72 (d, J = 7.3 Hz, 2H), 7.79 (d, J = 8.3 Hz, 2H), 8.03 (d, J
8.3 Hz, 2H), 13.03 (s, OH) ppm. 13C NMR (100 MHz, DMSO-d
):  =
26.6, 126.8, 128.1, 128.9, 129.5, 129.8, 138.9, 144.1, 167.0 ppm. MS
=
=
1
6
[1]
[2]
[3]
(a) C. Gunanathan, D. Milstein, Science 2013, 341, 1229712. (b) G. E.
Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681–703.
E. Balaraman, E. Khaskin, G. Leitus, D. Milstein, Nat. Chem. 2013, 5,
122‒125.
(
EI): m/z = 197.95 [M]+.
p-(Methylthio)benzoic acid:[5a] Table 1, entry 11. Isolated as a white
solid after recrystallization from water/ethanol in 65% yield (435 mg). 1
NMR (400 MHz, DMSO-d ):  = 2.57 (s, 3H), 7.38 (d, J = 8.5 Hz, 2H),
.91 (d, J = 8.5 Hz, 2H), 12.90 (s, OH) ppm. 13C NMR (100 MHz, DMSO-
H
(a) L. Zhang, D. H. Nguyen, G. Raffa, X. Trivelli, F. Capet, S. Desset, S.
Paul, F. Dumeignil, R. M. Grauvin, ChemSusChem 2016, 9, 1413‒1423.
(b) J.-H. Choi, L. E. Heim, M. Ahrens, M. H. G. Prechtl, Dalton Trans.
2014, 43, 17248‒17254. (c) P. Sponholz, D. Mellmann, C. Cordes, P. G.
Alsabeh, B. Li, Y. Li, M. Nielsen, H. Junge, P. Dixneuf, M. Beller,
ChemSusChem 2014, 7, 2419‒2422.
6
7
d
1
2
6
):  = 13.6, 124.5, 126.3, 129.3, 144.4, 166.7 ppm. MS (EI): m/z =
+
67.95 [M] .
,4,6-Trimethylbenzoic acid:[ Table 1, entry 12. Isolated as a white
22]
solid after recrystallization from water/ethanol in 58% yield (374 mg). 1H
[4]
[5]
(a) E. W. Dahl, T. Louis-Goff, N. K. Szymczak, Chem. Commun. 2017,
53, 2287‒2289. (b) Z. Dai, Q. Luo, X. Meng, R. Li, J. Zhang, T. Peng, J.
Organomet. Chem. 2017, 830, 11‒18.
NMR (400 MHz, DMSO-d ):  = 2.52 (s, 3H), 2.57 (s, 6H), 7.15 (s, 2H),
6
1
1
2
3.27 (s, 1H) ppm. 13C NMR (100 MHz, DMSO-d
):  = 19.3, 20.6, 128.0,
6
32.6, 133.7, 138.0, 170.9 ppm. MS (EI): m/z = 164.00 [M]+.
(a) C. Santilli, I. S. Makarov, P. Fristrup, R. Madsen, J. Org. Chem.
2016, 81, 9931‒9938. (b) D. Ventura-Espinosa, C. Vicent, M. Baya, J.
A. Mata, Catal. Sci. Technol. 2016, 6, 8024‒8035. (c) J. Malineni, H.
Keul, M. Möller, Dalton Trans. 2015, 44, 17409‒17414.
-Naphthoic acid:[22] Table 1, entry 14. Isolated as a light brownish solid
after recrystallization from water/ethanol in 73% yield (500 mg). 1H NMR
(
7
400 MHz, DMSO-d
.98‒8.00 (m, 3H), 8.11 (d, J = 8.1 Hz, 1H), 8.61 (s, 1H), 13.03 (s, OH)
ppm. 13C NMR (100 MHz, DMSO-d
):  = 124.8, 126.4, 127.2, 127.7,
27.8, 127.9, 128.9, 130.1, 131.7, 134.5, 167.0 ppm. MS (EI): m/z =
71.95 [M]+.
6
):  = 7.61 (t, J = 7.0 Hz, 1H), 7.66 (t, J = 6.8 Hz, 1H),
[6]
A. Sarbajna, I. Dutta, P. Daw, S. Dinda, S. M. W. Rahaman, A. Sarkar,
J. K. Bera, ACS Catal. 2017, 7, 2786‒2790.
6
1
1
[7]
[8]
X. Wang, C. Wang, Y. Liu, J. Xiao, Green Chem. 2016, 18, 4605‒4610.
Y. Sawama, K. Morita, S. Asai, M. Kozawa, S. Tadokoro, J. Nakajima,
Y. Monguchi, H. Sajiki, Adv. Synth. Catal. 2015, 357, 1205‒1210.
(a) I. S. Makarov, R. Madsen, J. Org. Chem. 2013, 78, 6593‒6598. (b) I.
S. Makarov, P. Fristrup, R. Madsen, Chem. Eur. J. 2012, 18,
15683‒15692. (c) A. Maggi, R. Madsen, Organometallics 2012, 31,
451‒455.
[
5a]
Decanoic acid: Table 2, entry 1. Isolated as a white solid in 71% yield
492 mg). 1H NMR (400 MHz, DMSO-d
):  = 0.85 (t, J = 6.7 Hz, 3H),
.20‒1.30 (m, 12H), 1.48 (t, J = 7.1 Hz, 2H), 2.18 (t, J = 7.4 Hz, 2H),
1.95 (s, OH) ppm. 13C NMR (100 MHz, DMSO-d
):  = 13.9, 22.1, 24.5,
8.6, 28.7, 28.8, 28.9, 31.3, 33.7, 174.4 ppm. MS (EI): m/z = 172.00 [M]+.
(
6
[9]
1
1
2
6
Cyclopentanecarboxylic acid:[5a] Table 2, entry 2. Isolated as a yellow
oil in 79% yield (361 mg). 1H NMR (400 MHz, DMSO-d
):  = 1.21‒2.07
[10] (a) A. Mukherjee, A. Nerush, G. Leitus, L. J. W. Shimon, Y. Ben David,
N. A. E. Jalapa, D. Milstein, J. Am. Chem. Soc. 2016, 138, 4298‒4301.
(b) G. Jaiswal, V. G. Landge, D. Jagadeesan, E. Balaraman, Green
Chem. 2016, 18, 3232‒3238. (c) G. Zhang, S. K. Hanson, Org. Lett.
2013, 15, 650‒653. (d) J. M. Pérez, R. Cano, M. Yus, D. J. Ramón, Eur.
J. Org. Chem. 2012, 4548‒4554. (e) H. Liu, G.-K. Chuah, S. Jaenicke,
J. Catal. 2012, 292, 130‒137.
6
13
(m, 8H), 2.60 (td, J = 7.9, 3.2 Hz, 1H), 11.87 (s, OH) ppm. C NMR (100
MHz, DMSO-d ):  = 25.9, 30.0, 43.7, 177.8 ppm. MS (EI): m/z = 114.00
6
[
M]+.
Cyclohexylacetic acid:[25] Table 2, entry 3. Isolated as a white solid in
5
2
1
3
3
9
9% yield (334 mg). 1H NMR (400 MHz, DMSO-d
H), 1.01–1.31 (m, 3H), 1.38–1.74 (m, 6H), 2.07 (d, J = 6.7 Hz, 2H),
1.96 (s, 1H) ppm. 13C NMR (100 MHz, DMSO-d
):  = 25.6, 25.7, 32.4,
4.2, 41.6, 173.7 ppm. MS (EI): m/z = 141.95 [M]+.
-Phenylpropanoic acid:[5c] Table 2, entry 4. Isolated as a yellow oil in
1% yield (548 mg). 1H NMR (400 MHz, DMSO-d
):  = 2.54 (t, J = 7.7
6
):  = 0.69–0.99 (m,
[11] (a) K. Shimizu, K. Ohshima, A. Satsuma, Chem. Eur. J. 2009, 15,
9977‒9980; (b) K. Shimizu, R. Sato, A. Satsuma, Angew. Chem. Int. Ed.
2009, 48, 3982‒3986; Angew. Chem. 2009, 121, 4042‒4046. (c) K.
Shimizu, K. Sugino, K. Sawabe, A. Satsuma, Chem. Eur. J. 2009, 15,
2341‒2351.
6
6
Hz, 2H), 2.83 (t, J = 7.6 Hz, 2H), 7.19‒7.29 (m, 5H), 12.16 (s, OH) ppm.
13C NMR (100 MHz, DMSO-d
):  = 30.4, 35.3, 126.0, 128.3, 128.3,
41.0, 173.9 ppm. MS (EI): m/z = 150.05 [M]+.
Cyclohex-3-enecarboxylic acid:[26] Table 2, entry 6. Isolated as a
yellow oil in 78% yield (393 mg). 1H NMR (400 MHz, DMSO-d
):  =
.37–1.61 (m, 1H), 1.88 (dt, J = 12.7, 4.2 Hz, 1H), 1.94–2.19 (m, 4H),
.40 (ddt, J = 12.0, 5.9, 3.3 Hz, 1H), 5.61 (d, J = 11.1 Hz, 2H), 12.09 (s,
):  = 24.1, 24.8, 27.2, 38.5,
25.5, 126.6, 176.5 ppm. MS (EI): m/z = 126.00 [M]+.
1S,2S,5S)-6,6-Dimethylbicyclo[3.1.1]heptane-2-carboxylic
Table 2, entry 7. Isolated as a yellow-brown oil in 78% yield (525 mg). []
[12] (a) M. Hosseini-Sarvari, T. Ataee-Kachouei, F. Moeini, Mater. Res. Bull.
2015, 72, 98‒105. (b) A. Bayat, M. Shakourian-Fard, N. Ehyaei, M. M.
Hashemi, RSC Adv. 2015, 5, 22503‒22509. (c) T. Mitsudome, Y.
Mikami, H. Funai, T. Mizugaki, K. Jitsukawa, K. Kaneda, Angew. Chem.
Int. Ed. 2008, 47, 138‒141; Angew. Chem. 2008, 120, 144‒147.
[13] (a) S. Chakraborty, U. Gellrich, Y. Diskin-Posner, G. Leitus, L. Avram,
D. Milstein, Angew. Chem. Int. Ed. 2017, 56, 4229‒4233; Angew.
Chem. 2017, 129, 4293‒4297. (b) N. Deibl, R. Kempe, Angew. Chem.
Int. Ed. 2017, 56, 1663‒1666; Angew. Chem. 2017, 129, 1685‒1688.
(c) M. Mastalir, M. Glatz, N. Gorgas, B. Stöger, E. Pittenauer, G.
Allmaier, L. F. Veiros, K. Kirchner, Chem. Eur. J. 2016, 22,
12316‒12320. (d) S. Elangovan, J. Neumann, J.-P. Sortais, K. Junge,
C. Darcel, M. Beller, Nat. Commun. 2016, 7: 12641.
6
1
6
1
2
OH) ppm. 13C NMR (100 MHz, DMSO-d
6
1
(
acid:[5a]
20
1
D
= +1.9 (c = 1.0, EtOAc). H NMR (400 MHz, DMSO-d ):  = 0.82 (s, 3H),
6
1
1
2
.18 (s, 3H), 1.39 (d, J = 9.5 Hz, 1H), 1.62 (ddt, J = 14.4, 6.5, 4.5 Hz, 1H),
.76 (ddd, J = 9.3, 6.4, 2.6 Hz, 2H), 1.82 (tt, J = 5.4, 2.5 Hz, 1H), 1.92–
.02 (m, 1H), 2.06 (dt, J = 5.6, 1.5 Hz, 2H), 2.74 (t, J = 8.7 Hz, 1H), 8.44
[14] X.-Y. Dong, Z.-W. Gao, K.-F. Yang, W.-Q. Zhang, L.-W. Xu, Catal. Sci.
Technol. 2015, 5, 2554‒2574.
(
s, OH) ppm. 13C NMR (100 MHz, DMSO-d
6
):  = 16.3, 20.1, 23.6, 23.9,
[15] G. Merga, R. Wilson, G. Lynn, B. H. Milosavljevic, D. Meisel, J. Phys.
Chem. C 2007, 111, 12220‒12226.
2
6.3, 38.7, 39.7, 40.6, 43.4, 177.1 ppm. MS (EI): m/z = 168.00 [M]+.
[
16] (a) A. Slistan-Grijalva, R. Herrera-Urbina, J. F. Rivas-Silva, M. Ávalos-
Borja, F. F. Castillón-Barraza, A. Posada-Amarillas, Physica E 2005, 25,
438‒448, (b) M. Zheng, M. Gu, Y. Jin, G. Jin, Mater. Res. Bull. 2001,
Acknowledgements
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3
6, 853‒859. (c) P.-Y.Silvert, R. Herrera-Urbina, N. Duvauchelle, V.
[20] A longer reaction time for aliphatic alcohols as compared to benzylic
alcohols was also employed in the previous dehydrogenations
Vijayakrishnan, K. T. Elhsissen, J. Mater. Chem. 1996, 6, 573‒577.
[
17] Other additives were also investigated for stabilizing the nanoparticles.
2
catalyzed by [RuCl (IiPr)(p-cymene)] and Pd/C; see refs 5a and 8.
However, only 20
–
44% yield were obtained when using 2-
[21] V. L. Sushkevich, I. I. Ivanova, E. Taarning, ChemSusChem 2013, 5,
2367‒2373.
hydroxypyridine, 2,2’-dipyridine-6,6’-diol, N,N’-dimethylethylenediamine,
triethylenetetramine, 2-pyridinemethanamine or di(2-picolyl)amine
instead of PVP.
[22] R. Zheng, Q. Zhou, H. Gu, H. Jiang, J. Wu, Z. Jin, D. Han, G. Dai, R.
Chen, Tetrahedron Lett. 2014, 55, 5671‒5675.
[
18] (a) G. M. Whitesides, M. Hackett, R. L. Brainard, J.-P. P. M. Lavalleye,
A. F. Sowinski, A. N. Izumi, S. S. Moore, D. W. Brown, E. M. Staudt,
Organometallics 1985, 4, 1819‒1830. (b) D. R. Anton, R. H. Crabtree,
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1098‒1106.
2 3
[19] For Ag/Al O -catalyzed reduction of nitrobenzenes in the presence of
alcohols, see: K. Shimizu, K. Shimura, M. Nishimura, A. Satsuma,
ChemCatChem 2011, 3, 1755‒1758.
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Silver-Catalyzed Dehydrogenative
Synthesis of Carboxylic Acids from
Primary Alcohols
No platinum group metals: The acceptorless dehydrogenation of primary alcohols
into carboxylic acids is achieved with silver carbonate as the precatalyst. The
reaction can be applied to a variety of alcohols and is believed to be mediated by in
situ formed silver nanoparticles.
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