Catalytic Conversion of Alcohols to Carboxylic Acid Salts and Hydrogen with Alkaline Water

Article abstract of DOI:10.1021/acscatal.6b03259

A [RuH(CO)(py-NP)(PPh₃)₂]Cl (1) catalyst is found to be effective for catalytic transformation of primary alcohols, including amino alcohols, to the corresponding carboxylic acid salts and two molecules of hydrogen with alkaline water. The reaction proceeds via acceptorless dehydrogenation of alcohol, followed by a fast hydroxide/water attack to the metal-bound aldehyde. A pyridyl-type nitrogen in the ligand architecture seems to accelerate the reaction.

Full text of DOI:10.1021/acscatal.6b03259

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Letter
Catalytic Conversion of Alcohols to Carboxylic
Acid Salts and Hydrogen with Alkaline Water
Abir Sarbajna, Indranil Dutta, Prosenjit Daw, Shrabani Dinda,
S. M. Wahidur Rahaman, Abheek Sarkar, and Jitendra K. Bera
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b03259 • Publication Date (Web): 16 Mar 2017
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ACS Catalysis
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Catalytic Conversion of Alcohols to Carboxylic Acid Salts and
Hydrogen with Alkaline Water
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Abir Sarbajna, Indranil Dutta, Prosenjit Daw, Shrabani Dinda, S. M. Wahidur Rahaman, Abheek
Sarkar and Jitendra K. Bera*
Department of Chemistry and Center for Environmental Science and Engineering, Indian Institute of Technology
Kanpur, Kanpur 208016.
ABSTRACT: A [RuH(CO)(py–NP)(PPh ) ]Cl (1) catalyst is found to be effective for catalytic transformation of primary
3
2
alcohols, including amino alcohols, to the corresponding carboxylic acid salts and two molecules of hydrogen with alka-
line water. The reaction proceeds via acceptorless dehydrogenation of alcohol, followed by a fast hydroxide/water attack
to the metal-bound aldehyde. A pyridyl-type nitrogen in the ligand architecture appears to accelerate the reaction.
KEYWORDS: water addition, aldehyde−water shift, acceptorless dehydrogenation, carboxylic acids, naphthyridine
Carboxylic acids are an important class of organic
compounds which serve as synthetic precursors for a wide
array of value–added chemicals. However, large–scale
assembling the necessary traits required to facilitate both
reactions. Ru−hydrides are widely documented as
intermediates in catalytic alcohol dehydrogenation.
1
9
syntheses of carboxylic acids are still being carried out by
oxidizing aldehydes with stoichiometric amount of
oxidants such as permanganate, chromate, chlorite
Hence, RuHCl(CO)(PPh ) − a commercially available and
stable Ru−hydride was used as the core unit of the
catalyst. Subsequently, we focused on the AWS reaction
3
3
2
generating copious waste. A few recent efforts are
that involves water reacting with a metal–bound
directed to realize an atom–economical, safe and
environmentally benign method for metal–catalyzed
transformation of alcohols to acids. Grützmacher
aldehyde. Several ligand systems have been devised for
heterolytic splitting of water and subsequent hydroxide
attack to the substrates. Heterolytic splitting of water
3
10
reported rhodium catalyzed dehydrogenative coupling of
primary alcohols and water to acids using sacrificial
ketones or alkenes as hydrogen acceptors. Another
caused aromatization of the ligand skeleton for Milstein’s
6a,11
catalyst (Scheme 2a).
Gas phase calculations by
4
Cundari, Goldberg and Heinekey revealed a simultaneous
water proton migration to the anionic ligand and
nucleophilic hydroxide attack to Ir–bound aldehyde
version of this reaction used atmospheric O2 as the
5
oxidant and DMSO as the oxygen acceptor. The real
8
c,d
impetus towards oxidation of alcohols to acids was
provided by Milstein’s elegant Ru−PNN pincer complex
which favored the reaction at low catalyst loadings and,
most importantly, without the aid of hydrogen
(Scheme 2b).
Grotjahn reported alkyne hydration
catalysts where pendant basic groups in the ligand
framework serve as an internal base to promote water
1
2
attack to electrophilic vinylidene carbon (Scheme 2c).
We recently reported water activating ability of 2–(2–
6a, 6b
acceptors.
Grützmacher and Beller independently
1
0a,13
studied dehydrogenation of methanol–water mixtures to
hydrogen and carbon dioxide through the intermediacy of
pyridyl)–1,8–naphthyridine
(py–NP).
Hydrogen
bonding interaction of a free naphthyridine nitrogen with
a metal–bound water promotes water addition to the
metal leading to oxygenation of the Ir–bound 1,5–
7
formic acid.
AD
13
cyclooctadiene (Scheme 2d). Ligand–assisted water
O
O
OH
OH
catalyst
-H2
catalyst
H2
H2O
dissociation was computed to be a favorable process than
direct water oxidative addition to the metal center.
R
OH
R
OH
-
R
H
R
H
AWS
H
H
PtBu2
O
R
H
PtBu2
O
R
Scheme 1. Alcohol Dehydrogenation (AD) followed by
Aldehyde–Water Shift (AWS) Reaction
H2O
N
H
Ru
N
CO
N
H
Ru
N
CO OH
(a)
We took the following approach to design catalyst for
dehydrogenative coupling of primary alcohols and water
to acids. Direct conversion of alcohols to carboxylic acids
can be considered as two consecutive reactions: 1.
acceptorless dehydrogenation (AD) of alcohol to
Ph2
P
Ru
N
OH
N
O
O
H
H
C
N
Ir
N
PPh
2
N
O
N
H
N
tBu
H
R
O
N
Ir
O
H
N
H
H
tBu
8
(b)
(c)
(d)
aldehyde, 2. subsequent ‘aldehyde−water shift’ (AWS)
reaction (Scheme 1). An ‘ideal catalyst’ can be designed by
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Scheme 2. Ligand–Assisted Water Reaction
mechanism was not operative here. Under identical con-
1
2
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
ditions, aliphatic alcohols showed lower conversions. So
small amounts (0.1 mL) of 1,4 dioxane as a co–solvent
were added to promote homogeneity for better efficiency.
We obtained satisfactory results when the duration of the
reaction was increased to 24 h (entries 10–12). When a diol
was used, dicarboxylic acid was obtained as a major prod-
uct (58%) with small quantities of lactone (12%) (entry
With this background in mind, we sought to examine
the efficacy of a catalytic system, arising out of the
combination of py–NP and RuHCl(CO)(PPh ) , for alcohol
3
3
conversion to carboxylic acid with water. Herein, a non-
pincer catalyst [RuH(CO)(py–NP)(PPh ) ]Cl (1) is
3
2
reported that is efficient towards dehydrogenative
coupling of alcohols to the corresponding carboxylic acid
salts and hydrogen with alkaline water. A pyridyl–type
nitrogen in the ligand architecture polarizes the water
molecule through hydrogen-bond interaction thus
promoting AWS reaction.
1
3). For terephthalic acid, dicarboxylic acid product was
obtained exclusively (entry 14). Interestingly, when cin-
namyl alcohol was used as a substrate (entry 15), apart
from the expected acid product, reduced forms of the
substrate and the acid were also obtained attributed to
0
1
2
3
4
5
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7
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9
0
1
2
3
4
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7
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6a
the generated H gas (vide infra). Conventional synthesis
2
Reaction of py–NP with RuHCl(CO)(PPh ) in THF gave
3
3
of amino acids from amino alcohols usually require pro-
1
in 88% yield after 4 h at room temperature. The py–NP
14
tection and deprotection steps of amine groups. We at-
binds in a chelating mode with the pyridine nitrogen and
one of the NP nitrogens (Figure 1). Ru1−H1A distance is
tempted a direct, atom–economic and safe synthesis of
6b
amino acids using this dehydrogenation protocol. When
1
.429(19) Å. Two trans PPh ligands (Ru–P = 2.3497(6) Å)
3
2–aminobenzyl alcohol was employed as starting material,
corresponding anthranilic acid was obtained quantitative-
ly (entry 16). 2–Phenylglycinol showed appreciable yields
of amino acid (78%, entry 17). Aliphatic amino alcohols
were considerably less reactive as seen for valinol (35%,
entry 18). However, for 4–amino–1–butanol, cyclic γ–
butyrolactam was obtained in 86% yield (entry 19).
and a carbonyl (Ru1−C14 = 1.845(4) Å) complete the
coordination sphere of the central ruthenium.
A
1
characteristic triplet at δ −9.01 ppm in H NMR confirms
the presence of a metal–hydride (See, Figure S1). The
chemical equivalency of two phosphines is expressed as a
3
1
single peak at δ 46.1 ppm in P NMR (See, Figure S3).
−
1
Solid state IR spectrum shows ν
at 2005 cm and νCO
Ru–H
−
1
Conversion of primary alcohol to carboxylic acid is
accompanied by the concomitant release of two
molecules of hydrogen. A volumetric analysis using gas
buret revealed near–quantitative formation of two
equivalents of hydrogen (See, Figure S17). The generated
hydrogen gas was identified by GC (thermal detector)
techniques (See, Figures S18–19). In another experiment,
the catalytic reaction was conducted in a flask that was
connected to a second flask in which equimolar styrene
and a catalytic amount of RhCl(PPh ) in benzene were
at 1915 cm . The ESI–MS exhibits signal at m/z 862.169 (z
+
=
1) attributed to [1–Cl] (See, Figure S6).
py-NP
3 3
RuHCl(CO)(PPh )
+
N
N
N
THF, rt
Cl
N
N
Ph P
3
N
3 3
Ru
CO
15
H
placed. Ethylbenzene was detected in the second flask
after the completion of the reaction demonstrating that
hydrogen gas is generated in the reaction (See, Scheme
S1). Evidently, the reaction is more efficient in an ‘open
system’ where evolved hydrogen escapes from the
reaction mixture and drives the reaction forward (See,
entry 10, Table S2).
PPh3
1
Figure 1. Synthesis of 1. Molecular structure of the
cationic unit in 1 is depicted inset.
Complex 1 was evaluated as a catalyst for the conversion
of primary alcohols to carboxylic acids with 5% catalyst
loading at 110°C in presence of alkaline water under strict
nitrogen atmosphere. The corresponding acid salts
produced were neutralized with HCl and then extracted
with EtOAc for further analyses. Lowering the
temperature to 80°C had a detrimental effect on the acid
conversion (See, entry 2, Table S2). Benzyl alcohol
showed quantitative conversion to benzoic acid (Table 1,
entry 1). The reaction was extended to electron rich aro-
matic alcohols and they showed excellent yields (entries
The homogeneous nature of the catalytic system was
1
6
confirmed by mercury addition experiments. Since a
high pH was maintained throughout the reaction, other
possible but less likely scenarios were also considered. A
reaction with benzyl alcohol in absence of the catalyst
was ineffective (See, entry 4, Table S2). When non–
enolizable benzaldehyde was used under similar
condition, only trace amount (<3%) of benzoic acid was
obtained (See, entry 5, Table S2).
A Cannizzaro
disproportionation pathway is thus less likely to be the
main route. Related Tischenko reaction would render
ester as an intermediate susceptible to hydrolysis in
alkaline media. However, no ester was detected under any
circumstances when catalytic reactions were performed
either in water or in organic solvents, and in presence and
absence of base (See, entries 6–7, Table S2). These results
discount the intermediacy of ester during acid synthesis.
2, 3 and 6). The reaction was considerably slow for elec-
tron deficient aromatic alcohols (entries 4, 5). Both sub-
strates, however, showed >95% yield when the reaction
time was extended to 24 h. 2–Phenylethanol and 3–
phenyl–1–propanol gave corresponding acids in high
yields (entries 7, 8). The benzylic position was not com-
promised suggesting that a radical or rearrangement
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1
8
16
OH (99%) mixed with known amounts of Na OH and
2
Table 1. Conversion of Primary Alcohols to Carboxylic
Acids with Alkaline Water Catalyzed by 1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
benzyl alcohol was stirred to give a mixture that was
18
calculated to be ~60% O labeled. Subsequent catalysis
1
6
18
with 5 mol% 1 produced both O and O incorporated
1
8
benzoic acids after 4h in the ratio 5:6 (~55% O labeling)
as revealed in GC–HRMS spectrum (See, Figure S20). A
b
Entry
–5
R=H,
Me,
Substrate
Product
Time
(h)
Yield (%)
100, 93,
1
8
close agreement between the calculated and observed O
product shows that the source of incorporated oxygen
atom in acid is water and not dioxygen.
1
Kinetic studies reveal that the reaction is 1.4±0.02 times
slower for benzyl alcohol in D O than in H O indicating
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
OMe,
100, 70, 62
2
2
NO2,
that O–H bond cleavage is not necessarily involved in the
rate determining step (RDS) (See, Figure S21).
F
A
competition reaction between benzyl alcohol and benzyl
6
7
8
6
6
6
100
100
98
alcohol–α,α–d2 (PhCD OH) showed high KIE value of
2
5.2±0.04, suggesting that aldehyde generation might be
one of the slower steps of the reaction (See, SI). This is
also reflected in the long induction periods for the
reaction followed by an enhancement in the rate of prod-
uct formation (See, Table S3).
9
n=2,
, 6, 15
–12
c
78, 76 ,
24
c
c
61 , 59
4
D–labeling experiments were carried out to examine the
contribution of alcohol and water in the catalytic cycle.
Use of either D-labeled alcohol, or water, or both would
generate H , HD or D gases during the reaction. The
c
5
8 (+ 12%
1
3
24
24
lactone)
2
2
14
95
relative ratios of these evolved gases were estimated by
monitoring the D-content in ethylbenzene while adding
15
1
7
styrene in the reaction. We performed three sets of
reactions with PhCH OH–D O, PhCD OH–H O and
24
75 (3:4:8)
2
2
2
2
PhCD OH–D O. D–ethylbenzene was observed as the
2
2
major product for the first two reactions (H : HD: D = 1.5:
2
2
2
.5: 1 and 3.1: 5.4: 1 respectively). However, for PhCD OH–
2
16
17
18
24
24
24
24
99
78
35
D O, D –ethylbenzene was obtained as the major product
2
2
NH2
(
H : HD: D ratio 1: 1.6: 2.5). D-labeling of both alcohol and
2 2
COOH
water clearly affects the evolved gas composition from
HD major to D major signifying their contribution in the
2
catalytic cycle (See, Figures S23, S24, Scheme S2).
Although protic–hydridic exchange in alkaline media is
substantial, the observed results clearly suggest the
involvement of water in the reaction.
d
19
86
a
Reaction conditions: 1 mmol alcohol, 1 (5 mol%), degassed,
deionized alkaline water (18.5 mmol NaOH in 3 mL water),
Control experiments were performed to investigate the
influence of ligands towards the efficacy of the catalyst.
RuHCl(CO)(PPh ) , in absence of a ligand was ineffective
b
1
10°C. Carboxylic acids were obtained by acid treatment of the
salts and determined by GC–MS using dodecane (1 mmol) as
3
3
c
d
internal standard. 0.1 mL dioxane added. Yield determined by
H NMR.
under identical reaction conditions (Table 2, entry 2a).
Several ligands were added to RuHCl(CO)(PPh3)3 and
1
screened
for
the
reaction.
Ligands
bpy,
1
,10−phenanthroline, TMEDA which do not offer a
Despite alkaline pH, no traces of aldol products were
obtained for enolizable aldehydes. This suggests that the
nitrogen in the vicinity of the metal center, showed poor
activity (<25% yield, entries 2b–2d). However, employing
6a,7b
generated aldehyde is only a transient intermediate.
2
−substituted NP derivatives led to significantly higher
yields of carboxylic acid products (82–99%, entries 2e–g).
–((2–phenylhydrazono)methyl)–1,8–naphthyridine
phm–NP) was, however, less effective as a ligand (entry
h) (vide infra). Molecular structures of complexes con-
For an efficient AWS reaction, the generated aldehyde
needs to be metal–bound when water adds to the
carbonyl carbon. Introduction of one equivalent of
pyridine as an additive impedes the product formation
2
(
2
(
See, entry 9, Table S2). A plausible rationalization is that
taining bpy (2) and phm–NP (3) ligands were also deter-
mined. (See, Figures S15, S16). Interestingly, doubling the
NaOH amount under otherwise identical conditions led
to an increase in yield to 65% for 2. The positive role of
the ligand is masked under increased hydroxide concen-
tration.
pyridine binds to the metal and thus prohibits aldehyde
coordination. Regardless, the only species detected
throughout the catalysis were the acid products and the
unreacted starting material.
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N
H
N
N
N
N
N
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
N
- PPh3
RCH OH
- H
N
β-H elimination
H
N
Table 2. Ligand Screening
Ru
Ru
CO
Ru
CO
+
2
O
Ph
3
P
PPh
3
PPh
3
O
PPh
3
CO
2
H
R
A
H
B
No ligand
1
H
R
+
2
RCH OH
OH
-H
2
-H
2
2
OH / H O
RCOO
- RCOOH
2
a, 0%
2b, 25%
2f, 85%
2c, 20%
2g, 82%
2d, <10%
2h, 38%
N
H
N
N
N
N
N
=
N
N
N
N
β-H elimination
N
PPh
N
Ru
Ru
CO
O
O
PPh
3
3
H
2e, 99%
CO
HO
R
D
R
C
HO
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
Reaction conditions:
1
mmol benzyl alcohol,
Scheme 3. Proposed Catalytic Cycle for Alcohol to
Acid Conversion in Alkaline Water
RuHCl(CO)(PPh ) (5 mol%), ligand (5 mol%), degassed,
deionized alkaline water (18.5 mmol NaOH in 3mL water),
3 3
1
(
10°C. Yields were determined by GC–MS using dodecane
1 mmol) as internal standard after 6 h.
In conclusion, we report an efficient non-pincer catalyst
for the dehydrogenative coupling of alcohols to the
corresponding carboxylic acid salts using alkaline water.
Mechanistic studies point to an initial acceptorless
alcohol dehydrogenation followed by the fast attack of
hydroxide/water to the metal-coordinated aldehyde. The
precise role of 2−substituted naphthyridine ligands in
accelerating the reaction is currently being investigated.
A
tentative mechanism is proposed based on
experimental findings (Scheme 3). Dissociation of one of
the phosphine ligands from 1 is followed by alcohol
coordination and the release of a hydrogen molecule in
unison forming a Ru–alkoxide intermediate A. An
alkoxide attack to the central metal ion is a possibility in
strong alkaline medium; however, in that case the solvent
18
AUTHOR INFORMATION
Corresponding Author
cage would be involved in the first hydrogen release (See,
7b
Scheme S3).
The Ru–alkoxide intermediate then
jbera@iitk.ac.in
Notes
The authors declare no competing financial interests.
undergoes a β–H elimination to yield an aldehyde–bound
Ru−hydride intermediate B. Because the free aldehyde is
barely detected in solution, it is proposed that the
aldehyde undergoes a series of fast reactions while still
being coordinated to the metal. Since the reaction is
carried out in alkaline medium, a direct attack of aqueous
hydroxide to the aldehyde carbon is considered. Here
again, solvent cage would facilitate the release of the
second molecule of hydrogen. This assertion is in line
ASSOCIATED CONTENT
Details of synthesis, X-ray data, catalytic experiments, cross-
over experiments are provided in the SI. This material is
available free of charge via the Internet at
http://pubs.acs.org.
ACKNOWLEDGMENT
with
Beller’s
dehydrogenation
methanol/water mixture in alkaline medium.
mechanism
of
The
7b
This work is financially supported by the DST, DAE and
CSIR, India. A.S. thanks UGC, India, I.D. thanks CSIR, India
for fellowships. Authors thank the reviewers for insightful
comments on the reaction mechanism.
Ru−gem−diolate intermediate C then undergoes a second
β–H elimination to form D where acid is coordinated to
the metal. The base present favors detachment of the acid
species from the metal and thus drives the equilibrium
towards acid salt formation.
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York, 2007.
3) Selected Examples: (a) Iwahama, T.; Yoshino, Y.; Keitoku, T.;
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428–3431. (d) Jiang, X.; Zhang, J.; Ma, S. J. Am. Chem. Soc. 2016, 138,
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The reaction does not proceed in non-aqueous medium.
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OH2 and D-labeling studies suggest the direct
involvement of water in the acid formation. Further,
−substituted naphthyridine ligands, which offer a free
nitrogen atom, display superior activity (Table 2). A
plausible rationale is that the pyridyl–type nitrogen from
naphthyridine unit enhances the nuleophilicity of a water
molecule through hydrogen bonding interactions favoring
2
(
2
3
13
aldehyde hydroxylation (See, Scheme S4a). The unbound
nitrogen can also promote a solvated hydroxide attack
through hydrogen bonding with water molecule of the
solvent cage (See, Scheme S4b). Alternatively, the
unbound nitrogen may facilitate a hydroxide attack by
coordination with Na . Although the role of the
naphthyridine based ligands in accelerating the reaction
is evident, the exact mechanism of action is not clear.
(
g) Zhang, L.; Nguyen, D. H.; Raffa, G.; Trivelli, X.; Capet, F.; Desset,
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(17) Catalyst 1 hydrogenates styrene quantitatively (See, SI). There-
fore, styrene was directly added in the reaction mixture and
ethylbenzene was observed albeit in lower yields.
(
18) Drastic reduction in benzoic acid yield was observed when the
reaction was carried out in presence of excess PPh , suggesting PPh
dissociation from 1 in the initial step (See, Figure S22).
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(19) Siek, S.; Burks, D. B.; Gerlach, D. L.; Liang, G.; Tesh, J. M.;
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Organometallics 2017, DOI: 10.1021/acs.organomet.6b00806.
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