Cyanohydrin hydration with [Ru(η6-p-cymene)Cl 2PR3] complexes

Article abstract of DOI:10.1021/om300047b

The catalytic hydration of cyanohydrins to their corresponding α-hydroxyamides provides a route to industrially useful α-hydroxy amides, α-hydroxy esters, α-hydroxy carboxylic acids, and their acrylic derivatives. However, until now, no homogeneous nitrile hydration catalyst has been capable of complete conversion of cyanohydrins to their corresponding amides because cyanohydrins degrade to produce cyanide, which poisons the catalyst. Because the cyanohydrin degradation is an equilibrium process, it was hypothesized that a faster nitrile hydration catalyst would be capable of hydrating the cyanohydrin before degradation occurs. Secondary coordination sphere effects were used to develop a faster catalyst based on the [Ru(η⁶-arene)Cl₂(PR₃)] scaffold. A series of [Ru(η⁶-p-cymene)Cl₂(PR₃)] complexes, where R = NMe₂, OMe, Et, was synthesized, and their activity toward cyanohydrin hydration was determined. The complex [Ru(η⁶-p- cymene)Cl₂(P(NMe₂)₃)] is an excellent catalyst, and the unprecedented complete conversion of a cyanohydrin to its corresponding amide using a homogeneous catalyst was achieved with glycolonitrile and lactonitrile.

Full text of DOI:10.1021/om300047b

Communication
pubs.acs.org/Organometallics
Cyanohydrin Hydration with [Ru(η6-p-cymene)Cl2PR3] Complexes
Spring Melody M. Knapp,† Tobias J. Sherbow,† J. Jerrick Juliette,‡ and David R. Tyler*,†
†Department of Chemistry, University of Oregon, Eugene, Oregon 97403, United States
‡Dow Advanced Materials-Performance Monomers, The Dow Chemical Company, Deer Park, Texas 77536, United States
S
* Supporting Information
ABSTRACT: The catalytic hydration of cyanohydrins to their
corresponding α-hydroxyamides provides a route to industri-
ally useful α-hydroxy amides, α-hydroxy esters, α-hydroxy
carboxylic acids, and their acrylic derivatives. However, until
now, no homogeneous nitrile hydration catalyst has been
capable of complete conversion of cyanohydrins to their
corresponding amides because cyanohydrins degrade to
produce cyanide, which poisons the catalyst. Because the
cyanohydrin degradation is an equilibrium process, it was
hypothesized that a faster nitrile hydration catalyst would be
capable of hydrating the cyanohydrin before degradation occurs. Secondary coordination sphere effects were used to develop a
faster catalyst based on the [Ru(η6-arene)Cl2(PR3)] scaffold. A series of [Ru(η6-p-cymene)Cl2(PR3)] complexes, where R =
NMe2, OMe, Et, was synthesized, and their activity toward cyanohydrin hydration was determined. The complex [Ru(η6-p-
cymene)Cl2(P(NMe2)3)] is an excellent catalyst, and the unprecedented complete conversion of a cyanohydrin to its
corresponding amide using a homogeneous catalyst was achieved with glycolonitrile and lactonitrile.
ethyl methacrylate and related derivatives of methacrylic
acid are important monomers used in the production of
Previously, we reported on a number of nitrile hydration
catalysts, but in all cases these catalysts displayed only nominal
hydration of acetone cyanohydrin and other cyanohydrins,
including glycolonitrile, lactonitrile, mandelonitrile, cyclohex-
anone cyanohydrin, and 2-hydroxybutyronitrile.7 In every case,
the poor activity of the catalyst toward cyanohydrins was
caused by cyanide poisoning of the catalyst. (The cyanide
comes from degradation of the cyanohydrin (Scheme 2).7)
Because of cyanide poisoning, no catalyst has ever hydrated
more than a minute quantity of acetone cyanohydrin in a
homogeneous reaction.
Cyanohydrin degradation is a slow equilibrium process, and
we reasoned that a faster catalyst would be less susceptible to
poisoning. Previous research showed that for most nitrile
hydration catalysts, the rate-limiting step in the catalytic cycle is
the nucleophilic attack by water on the coordinated nitrile.8 To
increase the rate of this step, we sought a way to simultaneously
activate both the coordinated nitrile and the external water
nucleophile. We hypothesized that a ligand with a better
hydrogen-bond accepting group in the secondary coordination
sphere should make a better nitrile hydration catalyst (Figure
1).
M
acrylic plastics and in polymer dispersions for paints and
coatings.1,2 The importance of these monomers to the world’s
economy is reflected in their production figures: global
production of MMA in 2008 was an estimated 2.8 million
metric tons and is projected to increase at an average annual
rate of 3.3% during 2008−2013.3 The most widely used
method for the production of methacrylates is the acetone
cyanohydrin (ACH) process, shown in Scheme 1.4,5 The
byproducts of this process include ammonium hydrogen sulfate
(AHS) as well as acetone, acetone sulfonates, oligomers, and
polymers. The AHS byproduct is a major problem for
methacrylate producers. A typical ACH process generates
about 2.5 kg of AHS per kg of methacrylate product.
Consequently, disposing of the AHS (∼7 million metric
tons/year) or converting it requires considerable effort and
expense. A common procedure is to pyrolyze the AHS at
around 1000 °C, followed by other steps that eventually lead to
sulfuric acid. This process is highly energy intensive and
consumes large amounts of natural gas as fuel for the pyrolysis.6
In an alternative approach, the AHS is neutralized with
ammonia to form ammonium sulfate, which has some limited
use as a fertilizer. There is considerable expense and effort
associated with both of these methods, and therefore the
elimination of AHS would allow for considerable savings and
improvement in the production of methacrylates. Conse-
quently, there is a strong drive to find a replacement to the
ACH process that does not involve sulfuric acid.
This hypothesis is based on the work of Grotjahn and co-
workers, who showed that incorporation of hydrogen-bond
accepting groups into the secondary coordination sphere of
alkyne hydration catalysts can significantly enhance the rate of
anti-Markovnikov alkyne hydration.9−11 To probe this
hypothesis, we synthesized a series of [Ru(η6-p-cymene)-
One route to a non sulfuric acid method involves the
homogeneous catalytic hydration of acetone cyanohydrin.
Received: January 19, 2012
Published: April 4, 2012
© 2012 American Chemical Society
2941
dx.doi.org/10.1021/om300047b | Organometallics 2012, 31, 2941−2944

Organometallics
Communication
Scheme 1. ACH-Based Process for the Synthesis of Methacrylates
a
Scheme 2. Equilibrium between a Cyanohydrin and Its Corresponding Aldehyde/Ketone
a
The cyanide coordinates to the metal catalyst (M) irreversibly.
methods, NMR spectroscopy, and X-ray crystallography.
These techniques and their application to these catalysts are
discussed in more detail in the Supporting Information.)
Previous work showed that, in aqueous solutions, the
cyanohydrin decomposition equilibrium favors cyanohydrins
at low pH.16−18 Therefore, to limit cyanohydrin degradation
(and subsequent cyanide poisoning), the cyanohydrin hydra-
tion reactions should be run at low pH. Because many nitrile
hydration catalysts are only functional at high pH,8 the activity
of 1 toward acetonitrile was investigated over a range of pH
values (3.5−8.5). As the pH of the solution decreased, the rate
of hydration decreased slightly from a TOF of 41 h−1 at pH 8.5
to 25 h−1 at pH 3.5,19 indicating that the catalyst should still be
functional at pHs that are optimal for cyanohydrin hydration.
Hydration of Cyanohydrins. The cyanohydrin hydration
reactions of glycolonitrile (4), lactonitrile (5), and acetone
cyanohydrin (6) (Chart 1) were investigated under a variety of
reaction conditions using catalysts 1−3.
Figure 1. Simultaneous activation of a coordinated nitrile and a
noncoordinated hydrogen-bonding water molecule.
Cl2(PR3)] complexes, (R = NMe2 (1), OMe (2), Et (3)) and
examined their ability to hydrate cyanohydrins.12 The complex
[Ru(η6-p-cymene)Cl2(P(NMe2)3)] was previously examined by
Cadierno and co-workers, who found that the activity of the
catalyst exceeded the activity of other ruthenium arene nitrile
hydration complexes.13 A particular focus of our investigation
was on determining if there was a correlation between the
strength of the hydrogen bond accepting group in the
secondary coordination sphere and the rate of nitrile hydration.
The results of our study are reported herein.
Hydration of Acetonitrile. Initial nitrile hydration studies
using 1−3 were conducted on acetonitrile at 100 °C and 5%
catalyst loading. All three catalysts converted acetonitrile to
acetamide, although 1 displayed considerably faster reactivity
(TOF = 35 h−1 (1), 0.41 h−1 (2), and 0.18 h−1 (3)). As detailed
in a footnote, the faster reactivity of 1 cannot be attributed to
either steric or electronic effects,14 and the enhanced rate with
1 can likely be attributed to the hydrogen bond accepting
ability of the tris(dimethylamino)phosphine ligand. To explore
the role of H bonding in determining the relative rates of the
hydration reactions, the ability of the catalysts to H bond to
water was examined. To do this, the IR spectra of 1−3 were
examined in wet KBr. The ν(OH) of water was observed at
3424, 3431, and 3441 cm−1 for 1−3, respectively. Prior studies
showed an excellent correlation between ν(OH) and the O−O
bond distance in compounds containing O−H- - -O bonds;
specifically, as the O−O bond distance decreased (indicating a
stronger hydrogen bond), the ν(OH) frequency also
decreased.15 On the basis of this analysis, the ν(OH) trend
above indicates that the H bond strength to water follows the
order 1 > 2 > 3. In addition to these solid-state studies,
solution-phase IR studies were done with the complexes
dissolved in THF using phenol as a H bond donor. The same
general trend in ν(OH) was observed: i.e., 1 > 2 ≅ 3. (the
solution-phase IR data are given in the Supporting
Information). Thus, the hydration reactivity of the catalysts
correlates with their ability to hydrogen bond to water: i.e., the
best H bonding catalyst is the fastest catalyst. (Note that other
methods have been developed to determine the relative
strengths of hydrogen bond acceptors, including UV−vis
Chart 1. Structures of Glycolonitrile (4), Lactonitrile (5),
and Acetone Cyanohydrin (6)
As shown in Table 1, the only catalyst to hydrate
glycolonitrile at any temperature was 1. For example, note in
entry 3 that, at 25 °C and pH 8.5, glycolonitrile was completely
hydrated within 43 h.20 In comparison, the catalyst PtCl-
(PMe2OH){PMe2O)2H} only hydrated glycolonitrile to
glycolamide with a 4% yield,7 making the hydration of
glycolonitrile with 1 the first example of the complete
conversion of a cyanohydrin to its corresponding amide using
a homogeneous catalyst. To explore the effect of temperature,
the hydration reactions were also carried out at 85 and 100 °C.
At 85 °C (entry 2), the yield of glycolamide was 93% within 0.7
h; no further conversion was observed after that time.
Increasing the temperature to 100 °C (entry 1) resulted in a
lower net conversion (67%) but in only 0.2 h. No further
reaction occurred after this time. In all cases, no formation of
glycolic acid was observed. Needless to say, the decomposition
of glycolonitrile to form equilibrium cyanide concentrations will
be faster as the temperature is increased, and it is proposed that,
at these higher temperatures, the complete cessation of activity
is due to cyanide poisoning.
Reactions using either catalyst 2 or 3 did not show any
conversion of glycolonitrile to glycolamide at any temperature.
2942
dx.doi.org/10.1021/om300047b | Organometallics 2012, 31, 2941−2944

Organometallics
Communication
Table 1. Glycolonitrile Hydration Results Using [Ru(η6-p-
cymene)Cl2(P(NMe2)3)], [Ru(η6-p-cymene)Cl2(P(OMe)3)],
at pH 3.0, the yields were 14% (25 °C) and 15% (70 °C) in a
10.6 M acetone solution. Although not a complete conversion,
this is the best yield that has been observed for the hydration of
acetone cyanohydrin with any homogeneous nitrile hydration
catalyst. As expected, these conversions decreased as the pH
increased. Thus, at pH 8.5 and 25 °C, no conversion of acetone
cyanohydrin to α-hydroxyisobutyramide was observed, even
after several weeks. The absence of reactivity is attributed to
cyanide poisoning of the catalyst. To drive the equilbrium back,
acetone was added to the reaction mixture at pH 8.5, but still
no hydration was observed.
a
and [Ru(η6-p-cymene)Cl2(PEt3)]
reacn temp
hydration reacn time
b
entry
1
cat.
(°C)
(%)
(h)
[Ru(η6-p-cymene)
100
85
25
85
25
85
25
25
67
0.2
Cl2(P(NMe2)3)]
2
3
4
5
6
7
8
[Ru(η6-p-cymene)
93
>99
0
0.7
43
1
Cl2(P(NMe2)3)]
[Ru(η6-p-cymene)
Cl2(P(NMe2)3)]
[Ru(η6-p-cymene)
Catalyst Degradation. Previous investigations done by
Cadierno and co-workers showed that, under aqueous
conditions, the [Ru(η6-arene)Cl2(P(NMe2)3)] complexes
completely degraded within 48 h at room temperature to
form [Ru(η6-arene)Cl2(HNMe2)], as evidenced by the
formation of several peaks in the 31P NMR spectra, as well as
Cl2(P(OMe)3)]
[Ru(η6-p-cymene)
0
43
1
Cl2(P(OMe)3)]
[Ru(η6-p-cymene)
0
Cl2(PEt3)]
[Ru(η6-p-cymene)
0
43
52.6
Cl2(PEt3)]
1
the formation of a broad singlet around 2.6 ppm in the H
PtCl(PMe2OH)
{(PMe2O)2H}
4
NMR spectra.13 Additionally, when [Ru(η6-p-cymene)-
Cl2(HNMe2)] and [Ru(η6-p-cymene)Cl2(P(NMe2)3)] were
used to hydrate benzonitrile at 100 °C and 5% catalyst loading,
the activity of [Ru(η6-p-cymene)Cl2(HNMe2)] was much lower
than [Ru(η6-p-cymene)Cl2(P(NMe2)3)], with TOFs of <1 and
4 h−1, respectively.13 The stability of 1 was also investigated
during cyanohydrin hydration, not only because the catalyst
was previously shown to degrade but also because cyanide can
react with the catalyst to poison it. Over the course of hydration
of acetonitrile, glycolonitrile, lactonitrile, and acetone cyanohy-
drin, several unidentified peaks were observed in the 31P NMR
spectrum. These spectra are given in the Supporting
Information. Arene loss was only observed when catalyst
activity ceased during the hydration of cyanohydrins. No arene
loss was observed in the hydration of acetonitrile.21
c
a
Reactions performed under an N2 atmosphere in D2O with 0.15 M
glycolonitrile, pH 8.5, and 7.5 mM catalyst (5% catalyst loading).
Yields determined by H NMR. No formation of glycolic acid was
b
1
observed for any glycolonitrile hydration trial. No evidence of H−D
c
exchange of the α-nitrile protons was observed. See ref 7.
Because these catalysts are slower, it is proposed that catalyst
poisoning occurs before hydration.
The hydration reactions of lactonitrile and acetone
cyanohydrin, cyanohydrins both sterically bulkier than
glycolonitrile, with catalyst 1 were investigated (Table 2). At
25 °C, pH 3.5, and 5% catalyst loading, lactonitrile was
completely converted to lactamide in approximately 110 h.
Consistent with the prior observation that cyanohydrin
decomposition increases at higher pH, at pH 8.5 the yield
was only 13% in 61 h with no further conversion after that time
(Table 2, entry 4).
In the case of acetone cyanohydrin, many different
conditions were employed in an attempt to effect complete
hydration (Table 2). However, no conditions were found that
resulted in complete conversion. For example, at pH 3.5, a 9%
conversion to α-hydroxyisobutyramide was obtained after 5
days. This conversion increased slightly as the pH was lowered:
Conclusions. Catalytic cyanohydrin hydration is challeng-
ing, because cyanohydrins degrade to produce HCN (and
cyanide), which poisons homogeneous nitrile hydration
catalysts. Because cyanohydrins are always going to be in
equilibrium, faster nitrile hydration catalysts need to be
developed. Following the hypothesis that a catalyst that
contains ligands with hydrogen bond accepting groups will be
faster, the nitrile hydration catalyst [Ru(η6-p-cymene)Cl2(P-
(NMe2)3)] was investigated. This catalyst was an excellent
a
Table 2. Selected Cyanohydrin Hydration Results Using [Ru(η6-p-cymene)Cl2(P(NMe2)3)]
[cosolvent] [cyanohydrin]
[catalyst]
(mM)
reacn temp
calcd [HCN] @
hydration reacn time
b
c
d
entry cyanohydrin
cosolvent
(M)
(M)
pH
(°C)
equilibrium (mM)
(%)
(h)
0.2
49
0.2
1
glycolonitrile
glycolontrile
lactonitrile
lactonitrile
lactonitrile
lactonitrile
ACH
0.15
0.15
0.16
0.15
0.15
0.15
0.16
0.15
0.15
0.15
0.15
0.15
7.6
7.6
7.8
7.6
7.6
7.5
8.8
8.7
7.5
7.5
7.5
7.5
8.5
8.5
8.5
8.5
3.5
3.5
8.5
8.5
3.5
3.0
3.0
3.0
100
25
100
25
25
25
25
25
25
95
70
25
0.07
0.07
26.3
25.4
2.01
0.00
160
67
>99
10
13
>99
>99
0
2
3
4
61
112
109
478
478
118
22
5
6
acetaldehyde
0.3
7
8
ACH
acetone
acetone
acetone
acetone
acetone
12.1
11.2
10.6
10.6
10.6
127
0
9
ACH
0.95
1.01
1.01
1.01
9
10
11
12
ACH
6
ACH
15
14
22
ACH
149
a
b
Reactions performed under an N2 atmosphere in water (H2O or D2O) with 5% catalyst loading. Cosolvent is any solvent not including water. No
deuterated cosolvents were used. Concentration of cyanide at equilibrium was calculated using published equilibrium constants.16 Yields
determined by H NMR. No formation of carboxylic acid byproduct was observed in any cyanohydrin hydration trial. No evidence of H−D
exchange of the α-nitrile protons was observed.
c
d
1
2943
dx.doi.org/10.1021/om300047b | Organometallics 2012, 31, 2941−2944

Organometallics
Communication
3965. (c) Fung, W. K.; Huang, X.; Man, M. L.; Ng, S. M.; Hung, M. Y.;
Lin, Z.; Lau, C. P. J. Am. Chem. Soc. 2003, 125, 11539−11544.
(d) Oshiki, T.; Yamashita, H.; Sawada, K.; Utsunomiya, M.; Takahashi,
nitrile hydration catalyst and completely hydrated glycolonitrile
and lactonitrile. This catalyst also hydrated acetone cyanohy-
drin (15% conversion to the amide product). These are the
highest conversions of cyanohydrin to amide product with a
homogeneous catalyst and, in the case of glycolonitrile and
lactonitrile, are the first examples of complete conversion of
cyanohydrins to their corresponding amides using a homoge-
neous nitrile hydration catalyst. Further mechanistic work,
including investigation of other complexes containing hydrogen
bond accepting groups and DFT calculations of the hydrogen
bonding interactions, is currently underway.
̌
K.; Takai, K. Organometallics 2005, 24, 6287−6290. (e) Smejkal, T.;
Breit, B. Organometallics 2007, 26, 2461−2464. (f) Cadierno, V.;
Francos, J.; Gimeno, J. Chem. Eur. J. 2008, 14, 6601−6605.
́
́
(13) Garcıa-Alvarez, R.; Díez, J.; Crochet, P.; Cadierno, V.
Organometallics 2011, 30, 5442−5451.
(14) Tolman’s parameters indicate that 1 and 3 are almost identical
electronically. Additionally, 1 is the bulkiest sterically, which typically
decreases the rate of nitrile hydration. See: Tolman, C. A. Chem. Rev.
1977, 77, 313−348.
(15) Novak, A. In Structure and Bonding; Springer: Berlin,
Heidelberg, 1974; Vol. 18, pp 177−216.
ASSOCIATED CONTENT
* Supporting Information
■
(16) Stewart, T. D.; Fontana, B. J. J. Am. Chem. Soc. 1940, 62, 3281−
S
3285.
Text, a table, and figures giving experimental procedures, a
discussion of techniques for determining H bond acceptor
strength, solution-phase IR data, and 31P NMR spectra and
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
(17) Schlesinger, G.; Miller, S. L. J. Am. Chem. Soc. 1973, 95, 3729−
3735.
(18) Yates, W. F.; Heider, R. L. J. Am. Chem. Soc. 1952, 74, 4153−
4155.
(19) The pH of the solution was decreased using hydrochloric acid. A
control reaction done with NaCl shows that the addition of excess
chloride has no effect on the rate of hydration.
AUTHOR INFORMATION
Corresponding Author
*E-mail: dtyler@uoregon.edu.
■
(20) A control reaction showed that the rate of acetonitrile hydration
with 3 is 2 orders of magnitude faster at pH 8.5 than at pH 5.0,
presumably because of the higher concentration of hydroxide, which is
more nucleophilic than water. Additionally, the equilibrium constants
Notes
for glycolonitrile degradation are KpH9.0 = 3.29 × 10−8 and KpH4.0
=
The authors declare no competing financial interest.
1.09 × 10−9. Because there is little difference in the position of the
glycolonitrile equilibrium at high pH, all glycolonitrile hydration trials
were conducted at pH 8.5.
ACKNOWLEDGMENTS
■
Acknowledgment is made to Rohm and Hass Chemical Co. and
the NSF (No. CHE-0719171) for the support of research
carried out in the authors’ laboratory. S.M.M.K. also wishes to
acknowledge the U.S. Department of Education (No.
P200A070436) and the NSF Graduate STEM Fellows in K-
12 Education (GK-12) program (No. DGE-0742540) for
additional support.
(21) Cadierno and co-workers found that addition of 200 equiv of
free arene ligand led to a decrease in the rate of benzonitrile hydration
with [Ru(η6-arene)Cl2(P(NMe2)3)] when arene = C6H6, toluene, p-
cymene, mesitylene. However, in these cases, the arene could
potentially competitively coordinate to the catalyst by η2-arene
coordination, decreasing the rate of nitrile hydration.
REFERENCES
■
(1) Richardson, T. L.; Lokensgard, E. Industrial Plastics Theory and
Application, 3rd ed.; Delmar: Boston, MA, 1997.
(2) Odian, G. G. Principles of Polymerization, 4th ed.; Wiley:
Hoboken, NJ, 2004.
(3) Bizzari, S. In Chemical Economics Handbook; SRI Consulting:
Englewood, CO, 2009.
(4) Green, M. M.; Wittcoff, H. A. In Organic Chemistry Principles and
Industrial Practice; Wiley-VCH: Weinheim, Germany, 2003; pp 137−
156.
(5) Anonymous Product Focus. Chemical Week Online 2006, http://
www.chemweek.com/inc/articles/t/2006/08/02/040.html.
(6) Ammonia is also formed but is not recovered, because under
these conditions it reacts with oxygen to form N2.
(7) Ahmed, T. J.; Fox, B. R.; Knapp, S. M. M.; Yelle, R. B.; Juliette, J.
J.; Tyler, D. R. Inorg. Chem. 2009, 48, 7828−7837.
(8) Ahmed, T. J.; Knapp, S. M. M.; Tyler, D. R. Coord. Chem. Rev.
2011, 255, 949−974.
(9) Grotjahn, D. B. Chem. Eur. J. 2005, 11, 7146−7153.
(10) Grotjahn, D. B.; Kragulj, E. J.; Zeinalipour-Yazdi, C. D.;
Miranda-Soto, V.; Lev, D. A.; Cooksy, A. L. J. Am. Chem. Soc. 2008,
130, 10860−10861.
(11) Grotjahn, D. B.; Miranda-Soto, V.; Kragulj, E. J.; Lev, D. A.;
Erdogan, G.; Zeng, X.; Cooksy, A. L. J. Am. Chem. Soc. 2008, 130, 20−
21.
(12) Several studies suggest that nitrile hydration catalysts containing
hydrogen bond accepting ligands have enhanced activity. See the
following references: (a) Muranaka, M.; Hyodo, I.; Okumura, W.;
́
́
Oshiki, T. Catal. Today 2011, 164, 552−555. (b) Garcıa-Alvarez, R.;
́
Dıez, J.; Crochet, P.; Cadierno, V. Organometallics 2010, 29, 3955−
2944
dx.doi.org/10.1021/om300047b | Organometallics 2012, 31, 2941−2944