Rhodium/graphite-catalyzed hydrogenation of carbocyclic and heterocyclic aromatic compounds

Article abstract of DOI:10.1055/s-0029-1216852

Rhodium on graphite (Rh/Gr, C₂₄Rh) was prepared by reaction of anhydrous rhodium trichloride with potassium graphite (C₈K, 3 equivalents) and used as a heterogeneous catalyst for the hydrogenation of carbocyclic and heterocyclic aromatic compounds at room temperature and 1 atm of hydrogen pressure. The effect of substitution on the benzene ring was examined in a variety of derivatives, including those with alkyl, hydroxy, alkoxy, aryloxy, carboxy, amino, nitro, acyl, chloro, or functionalized alkyl groups. Reduction of carbonyl functions of aromatic aldehydes and ketones occurred with complete or partial cleavage of the benzylic C-O bond; this cleavage also occurred in the hydrogenation of benzylic alcohols and esters. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216852

2440
PAPER
Rhodium/Graphite-Catalyzed Hydrogenation of Carbocyclic and Heterocyclic
Aromatic Compounds
R
hodium/Graphite
i
-Cataly
u
zed
H
ydrog
s
Dipartimento di Chimica ‘G. Ciamician’, Università di Bologna, via Selmi 2, 40126 Bologna, Italy
Fax +39(051)2099456; E-mail: diego.savoia@unibo.it
Received 20 February 2009; revised 23 March 2009
the potassium are transferred to the p-system of graphite,
Abstract: Rhodium on graphite (Rh/Gr, C24Rh) was prepared by
reaction of anhydrous rhodium trichloride with potassium graphite
(C8K, 3 equivalents) and used as a heterogeneous catalyst for the
hydrogenation of carbocyclic and heterocyclic aromatic compounds
at room temperature and 1 atm of hydrogen pressure. The effect of
substitution on the benzene ring was examined in a variety of deriv-
atives, including those with alkyl, hydroxy, alkoxy, aryloxy, car-
boxy, amino, nitro, acyl, chloro, or functionalized alkyl groups.
Reduction of carbonyl functions of aromatic aldehydes and ketones
occurred with complete or partial cleavage of the benzylic C–O
bond; this cleavage also occurred in the hydrogenation of benzylic
alcohols and esters.
and a compound with negatively charged graphite layers
intercalated by layers of potassium cations is formed.2
Potassium graphite C8K has a very high reducing power
that can be exploited to reduce C=N, C=O, or activated
C=C double bonds or to cleave C–S or C–CN bonds.2
Most importantly, treatment of C8K with metal salts, in-
cluding titanium(III), titanium(IV), manganese(II), cop-
per(II), iron(III), cobalt(II), tin(II), or zinc(II) salts in
refluxing tetrahydrofuran or 1,2-dimethoxyethane gives
the corresponding zero-valent metal in a highly active
form.2 An alternative approach to the preparation of high-
ly reactive transition metals on graphite involves prelimi-
nary intercalation of metal salts in graphite followed by
reduction with an organolithium reagent at a low temper-
ature.3 Both protocols give highly dispersed metals on the
graphite surface, and almost no intercalated metal species
are formed.
Dispersions of platinum,4 palladium,5 rhodium,4c,6
nickel,7 or copper8 on graphite, prepared by reduction of
the intercalated metal salts with a 1% metal loading have
been commercially available for some time as Metal-
Graphimet®. Reduction of metal salts by C8K leads to
metal/graphite materials with a higher metal loading, e.g.
C16M or C24M, that depends on the oxidation state of the
metal cation. Examination by transmission electron mi-
croscopy (TEM) of samples of platinum/graphite pre-
pared by these two protocols has shown that both
materials consist of more- or less-dispersed metal on the
graphite surface, and no intercalated metal is present.9
Moreover, in the hydrogenation of 4-chloronitrobenzene,
the two platinum/graphite compounds showed compara-
ble activities that were superior to those of other support-
ed platinum species.4a In our opinion, however, the
procedure using C8K is simpler and more convenient.
Key words: aromatic compounds, graphite, heterogeneous cataly-
sis, hydrogenation, rhodium
Catalysis in all its forms (homogeneous catalysis, hetero-
geneous catalysis, biocatalysis, and organocatalysis) is
playing an ever-increasing role in modern organic synthe-
sis, as it can provide a convenient, economical, selective,
and efficient method for the construction of simple or
complex organic molecules. In particular, heterogeneous
catalysis has two main advantages: the ease of separation
of the insoluble catalyst from the organic materials merely
by filtration, and the possibility of re-using the recovered
catalyst without a significant loss of activity or selectivity.
Catalytic hydrogenation is a valuable tool for the synthetic
organic chemist.1 Noble metals anchored on a support that
is insoluble in the reaction medium have been most fre-
quently used as catalysts for heterogeneous hydrogena-
tion. A variety of materials can be used as catalyst
supports, e.g. metal salts, alumina, or carbon. Many met-
als highly dispersed on charcoal, including rhodium/char-
coal, are commercially available, but the different origins
of the charcoal can affect the properties of the catalyst.
Switching from activated carbon to graphite has several
advantages, including lower costs, easier manipulation,
greater thermal conductivity, and an ordered structure
(sheets). Graphite can accommodate alkali metals be-
tween the sheets. Intercalation compounds of graphite and
alkali metals of known stoichiometry, e.g. C8K or C24K,
can be prepared by melting potassium on graphite at the
appropriate molar ratios at 150 °C by stirring the mixture
under an inert atmosphere. In this way, the 4s electrons of
Hydrogenation of carbocyclic and heterocyclic aromatic
compounds is a straightforward route to the correspond-
ing saturated derivatives.10 Platinum,11 rhodium,12 and
ruthenium13 catalysts are most often used for this purpose.
In particular, the full hydrogenation of substituted pyr-
roles to the corresponding pyrrolidines has been accom-
plished by the use of such catalysts.14 We recently
completed a stereoselective synthesis of 8-aminopyrroliz-
idines by a route that involved hydrogenation of fused bi-
cyclic precursors containing the pyrrole ring.15 For this
purpose, we prepared a new heterogeneous catalyst com-
prising highly dispersed rhodium on graphite (Rh/Gr,
SYNTHESIS 2009, No. 14, pp 2440–2446
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x.
x
x
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0
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Advanced online publication: 02.06.2009
DOI: 10.1055/s-0029-1216852; Art ID: Z02609SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Rhodium/Graphite-Catalyzed Hydrogenation
2441
C24Rh), and found that it had a slightly superior activity to
other heterogeneous catalysts.
Rhodium on graphite (Rh/Gr, C24Rh, 26.3% Rh by
weight) was prepared by the same simple protocol used
for other previously described metal/graphites, and was
structurally characterized by means of TEM and powder
X-ray diffraction (PXRD).
H2 (1 atm), r.t.
Rh/Gr
Figure 1, part A shows a representative image of C24Rh
material. It can be seen that rhodium nanoparticles mea-
suring about 5 nm are present as aggregates that settle on
the graphite surface. These aggregates mainly form chains
and sponge-like structures. Their distribution on the
graphite surface, their size, and their degree of degree of
branching are not homogeneous. Single nanoparticles are
almost absent from the graphite surface. In the PXRD pat-
tern [Figure 1, part B], diffraction peaks for graphite (*)
and rhodium (#) are visible. The two theta positions of the
former are exactly those associated with the interplanar
spacings present in pure graphite, thus excluding the pres-
ence of any significant intercalation of particles in the
graphite structure, in agreement with the literature data.4a
The diffraction peaks associated with rhodium are very
broad; this observation is in agreement with the nanosized
nature of the particles, and also suggests that the material
has a low degree of crystallinity.
Scheme 1
Rh/Gr can be used effectively as a catalyst for the hetero-
geneous hydrogenation of carbocyclic or heterocyclic ar-
omatic compounds. Heptylbenzene was chosen as a
substrate to test the activity of the catalyst in the protic sol-
vents methanol, ethanol, and isopropanol and the apolar
solvent hexane (Scheme 1). All the reactions were carried
out at room temperature under 1 atm of hydrogen pressure
(balloon) using C24Rh as the catalyst (4% by weight, 1.8
mol%).
Figure 2 Hydrogenation of heptylbenzene with Rh/Gr (C24Rh, 4
wt%) at 20 °C and 1 atm of H2 pressure in various solvents
genation rate was only slightly affected by the substrate
concentration, although the highest rate was observed at a
1.4 M concentration.
Having determined the optimal reaction conditions, these
were used in the hydrogenation of representative carbocy-
clic and heterocyclic aromatic compounds. The results are
listed in Table 1, in which gives the time required to
achieve complete consumption of the starting compound
and, in some cases, the disappearance of the partially sat-
urated intermediates. The choice between methanol and
isopropanol as the solvent was dictated by the solubility of
the aromatic compound in the two solvents.
The results, graphically reported in Figure 2, show that
the nature of the solvent had only a slight effect on the re-
action rate, which decreased slightly in the order: MeOH
> i-PrOH > EtOH > hexane. In these cases, complete hy-
drogenation was achieved after 18–24 hours. By increas-
ing the amount of catalyst to 12% by weight (5.4 mol%),
complete conversion was achieved after only six hours in
MeOH (Figure 2). Moreover, we observed that the hydro-
Figure 1 (A) Transmission electron photomicrograph of a fragment of the C24Rh catalyst. (B) PXRD pattern of the same material; the dif-
fraction peaks of graphite and rhodium are indicated by the symbols * and #, respectively.
Synthesis 2009, No. 14, 2440–2446 © Thieme Stuttgart · New York

2442
G. Falini et al.
PAPER
Benzoic acid was converted into cyclohexanecarboxylic formed in an overall yield of 14% in the hydrogenation of
acid in 48 hours, whereas the reduction of the carbonyl 1-phenylethanol, which afforded 1-cyclohexylethanol in
group of acetophenone could not be avoided, and 1-cyclo- 86% yield after 34 hours. Similarly, the reaction of ethyl
hexylethanol was obtained in a 92% yield after 40 hours. rac-hydroxy(phenyl)acetate gave a mixture of two prod-
This was accompanied by small amounts of 1-cyclohexyl- ucts: the prevalent one being formed by hydrogenation of
ethanone (4%), ethylbenzene, and ethylcyclohexane, the the phenyl substituent (91%), and the byproduct (9%) be-
last two compounds being formed by cleavage of the ben- ing formed by concomitant hydrogenation and hydro-
zylic C–O bond. The same hydrocarbons were also genolysis steps.
Table 1 Hydrogenation of Aromatic and Heteroaromatic Compounds Catalyzed by Rhodium/Graphite (C24Rh) in 1.4 M Solutionsa
Substrate
toluene
Solvent
Rh
Time Product(s),
(mol%) (h)b
Yield (%)c
d
–
0.4
1.1
20
20
MeCy, quant
i-PrOH
i-PrOH
80
20
1.7
42
8
92
PhCºCH
BzOH
MeOH
MeOH
1.0
1.2
20
48
EtCy, quante
CyCO2H, quantf
O
OH
O
MeOH
MeOH
MeOH
1.2
1.2
1.8
40
34
20
4
92h
OH
86
OH
OH
11
3
OH
CO2Et
91
CO2Et
9
CO2Et
CHO
MeOH
MeOH
1.2
1.5
24
7
88
12
39
OAc
OAc
41
20
methyl L-phenylglycinate hydrochloride MeOH–37% aq HCl (9:1)
methyl L-phenylalaninate hydrochloride MeOH–37% aq HCl (9:1)
2.2
2.4
1.0
24h
32i
20
methyl L-cyclohexylglycinate hydrochloride, quant
methyl L-cyclohexylalaninate hydrochloride, quant
CyOH, quant
PhOH
MeOH–H2O (95:5)j,k
OH
OH
OH
MeOH
1.5
1.7
1.1
55
60
48
19l
81
O
O
O
i-PrOH
50
50
OMe
OMe
65
OMe
4
OMe
MeOH
31
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PAPER
Rhodium/Graphite-Catalyzed Hydrogenation
2443
Table 1 Hydrogenation of Aromatic and Heteroaromatic Compounds Catalyzed by Rhodium/Graphite (C24Rh) in 1.4 M Solutionsa
(continued)
Substrate
Solvent
Rh
Time Product(s),
(mol%) (h)b
Yield (%)c
pyridine
pyrrole
indole
MeOH
0.8
0.7
1.2
1.3
14
13
28
18
piperidine, quant
pyrrolidine, quant
octahydro-1H-indole, quant
PhNH2, quant
MeOH–AcOH (9:1)m
MeOH–AcOH (9:1)m
MeOH
PhNO2
a The reactions were performed in on 1–2 mmol scale of substrate in 1.4 M soln at r.t. and 1 atm H2 of pressure using Rh/Gr (C24K, 4% loading
by weight) as the catalyst.
b Time required for the complete consumption of the starting aromatic compound and the disappearance of partially hydrogenated derivatives,
unless otherwise stated.
c The yields and diastereomeric ratios were determined by GC/MS analysis in the presence of an internal standard.
d The reaction was performed in toluene using a 1.9% loading of Rh/Gr.
e The formation of EtPh was observed at intermediate times (EtPh/EtCy 24:76 after 8 h).
f The reaction was monitored by 1H NMR analysis.
g EtPh and EtCy were also formed (<4%); PhCH(Me)OH was detected at intermediate reaction times and was the major product (56%) after
20 h.
h Complete hydrogenation in MeOH required 36 h under the same conditions.
i Complete hydrogenation in MeOH required 42 h.
j Cyclohexanone was detected in the reaction mixture after 5 h.
k The reaction in MeOH gave a 91:9 mixture of CyOH and 1,1-dimethoxycyclohexane after 20 h.
l Ratio cis/trans = 91:9.
m The product of partial hydrogenation of the pyrrole ring (indoline) was observed at intermediate reaction times; complete hydrogenation in
MeOH required 26 h.
Reduction of the carbonyl group and subsequent hydro- tained. Similarly, the hydrogenation of methoxybenzene
genolysis of the benzylic alcohol was the main pathway in was largely incomplete after 48 hours, at which time
the hydrogenation of 4-methylbenzaldehyde in methanol, methoxycyclohexane and 1-methoxycyclohexene were
which after 24 hours gave p-xylene as the main product formed in yields of 31% and 4%, respectively.
accompanied by a small amount of 1,4-dimethylcyclohex-
We then examined the reduction of aromatic azaheterocy-
ane. The reaction of benzyl acetate was not selective; after
cles. Pyridine was smoothly converted into piperidine in
seven hours, a mixture of three compounds was produced:
methanol in 14 hours. On the other hand, electron-rich
cyclohexyl acetate (41%), toluene (39%), and methylcy-
pyrrole required 26 hours for complete hydrogenation to
clohexane (20%). Both the starting material and the hy-
pyrrolidine; however the reaction time could be shortened
drocarbons were observed in the reaction mixture at
to 13 hours in the presence of acetic acid.
intermediate reaction times.
Pyrrole was smoothly hydrogenated to pyrrolidine. Simi-
The hydrogenation of methyl L-phenylglycinate and
larly, indole was fully hydrogenated in 9:1 methanol–ace-
methyl L-phenylalaninate as their hydrochlorides in meth-
tic acid to give its octahydro derivative in 28 hours,
anol was complete after 36 and 42 hours, respectively.
whereas in methanol solution, less than 5% conversion to
The reaction rate increased slightly in a 9:1 mixture of
the same product was observed. Under the former condi-
methanol and 37% hydrochloric acid; for example, the hy-
tions, the partially hydrogenated compound, indoline, was
drogenation of methyl L-phenylglycinate hydrochloride
observed at intermediate reaction times. We have previ-
was complete in 24 hours. Conversely, no reaction oc-
ously reported that rhodium/graphite is slightly more ef-
curred on the free-base forms of these esters.
fective than other rhodium or platinum catalysts for the
Phenol was quantitatively hydrogenated to cyclohexanol hydrogenation of substituted pyrrole rings.15 Mild experi-
in a 95:5 methanol–water mixture, whereas in methanol, mental conditions were required to hydrogenate the pyr-
the partial formation of 1,1-dimethoxycyclohexane (9%) role nucleus, which was highly activated by N- or C-acyl
was observed. 2-Naphthol underwent slow hydrogenation groups.11
and was completely consumed after 55 hours; at this time,
Nitrobenzene was selectively converted into aniline under
1,2,3,4-tetrahydronaphthalene-2-ol was the prevalent
routine conditions, and the product resisted ring hydroge-
product, although the fully hydrogenated compound was
nation even after prolonged reaction times. In a separate
also obtained in 19% yield (dr = 91:9, GC/MS analysis).
experiment, aniline was resistant to hydrogenation, and
Diphenyl ether underwent slow hydrogenation in isopro- afforded a mixture of products in low yields.
panol, and the saturation of both phenyl groups was not
As the catalyst could be recovered from the reaction mix-
achieved even after 60 hours, at which time a 1:1 mixture
tures merely by filtration, we wished to check the possi-
of cyclohexyl phenyl ether and dicyclohexyl ether was ob-
Synthesis 2009, No. 14, 2440–2446 © Thieme Stuttgart · New York

2444
G. Falini et al.
PAPER
bility of re-using the same catalyst in a number of
consecutive reactions. We therefore carried out four runs
of the hydrogenation reaction of heptylbenzene, each time
using the catalyst recovered from the previous run. The re-
actions were monitored by GC analysis at constant times
for each run to determine the corresponding yields of 1-
cyclohexylheptane. The reaction rate decreased only
slightly after each run (Figure 3). Note that in the first two
runs, the conversion of heptylbenzene into heptylcyclo-
hexane may have been complete in less than 20 hours.
Figure 3 Progress in the formation of heptylcyclohexane in four
consecutive hydrogenation reactions of heptylbenzene (1.4 M in
MeOH, r.t., 1 atm H2) using the catalyst Rh/Gr (C24K, 4% by weight)
recovered each time from the previous run
Figure 4 Progress in the formation of heptylcyclohexane from
heptylbenzene (A) and of methoxycyclohexane from methoxybenzene
(B) in hydrogenation reactions performed in MeOH using 1.8 mol%
of catalyst
Finally, the lack of reactivity of the following aromatic
compounds is worthy of note: naphthalene, 2-naphthalde-
hyde, chlorobenzene, 2-phenylpropanal, methyl benzoate,
and 2-methylpyrazine. At the moment, we cannot offer a
plausible explanation for all the observed failures.
satisfactory rate was observed at 100 atm. In the latter
case, complete hydrogenation was achieved after 26 hours
with either C8K or rhodium/alumina, although the reac-
tion rate was higher with the latter catalyst. Hence, similar
forcing conditions should be used to hydrogenate less re-
active aromatic compounds.
A more thorough comparative investigation of the behav-
ior of rhodium/graphite and 5% rhodium/alumina in hy-
drogenation reactions was carried out, taking
heptylbenzene and methoxybenzene as the substrates. In
all cases, the hydrogenation reactions were conducted un-
der the same typical experimental conditions using the
identical loading of the catalyst (1.8 mol%), and the
progress of the reactions with time was monitored
(Figure 4). With heptylbenzene and 5% rhodium/alumina,
the reaction rate was very high at the beginning of the re-
action, but decreased continuously with time so that the
formation of heptylcyclohexane was incomplete (74%
yield) after 18 hours. On the other hand, in the same reac-
tion with rhodium/graphite, the rate was lower but re-
mained almost constant with time and complete
conversion of the substrate to the product was observed
after 18 hours. Note that the reaction with rhodium/graph-
ite was complete after 10 hours at 30 atm.
A comparison of the effectiveness and selectivity of our
new catalyst with the outcomes of previously described
hydrogenation reactions of arenes using other heteroge-
neous rhodium catalyst showed some analogies, but also
a few discrepancies. For example, the hydrogenation rate
of typical aromatic compounds catalyzed by silica-sup-
ported rhodium hydride (500 psi H2, 22 °C) decreased in
the order: benzene > anisole > naphthalene> aniline.16 In
hydrogenation reactions catalyzed by rhodium powder
prepared by reduction of a rhodium complex by hydrogen
in dichloromethane, the presence of any substituent on the
benzene ring decreased the reaction rate with respect to
benzene, and benzoic acid was not hydrogenated at all;
moreover, hydrogenolysis of the hydroxy group of phenol
as well as those of benzylic alcohols occurred along with
the hydrogenation of the aromatic ring.17
A similar trend was observed in the hydrogenation reac-
tions of methoxybenzene, a less reactive substrate. A sat-
isfactory reaction rate was observed with rhodium/
graphite at 30 atm of hydrogen pressure, and an even more
Synthesis 2009, No. 14, 2440–2446 © Thieme Stuttgart · New York

PAPER
Rhodium/Graphite-Catalyzed Hydrogenation
2445
Catalytic reductions of phenylglycine and phenylalanine Optical rotations were measured on a digital polarimeter (Perkin
25
Elmer 343) in a 1-dm cell, and [a]D values are given in degrees
derivatives were previously performed with 5% rhodium/
cm3 g–1. MS spectra were recorded at an ionizing voltage of 70 eV
charcoal or rhodium/alumina to give excellent yields of
on an Agilent Technologies 5975 spectrometer with GLC injection.
the corresponding cyclohexyl derivatives under typical
Analytical gas chromatography (GC) was performed on an HP6890
conditions of aqueous phosphoric, hydrochloric, or sulfu-
(HP-5 column, 30 m, ID 0.25 mm) instrument equipped with a
ric acid, 60 °C, 50 psi hydrogen, and 24 hours reaction
time.18 Similarly, aromatic-ring hydrogenations of (R)-3-
phenyllactic acid and (R)-3-phenylalanine were accom-
plished by using either 5% or 10% rhodium/charcoal in
protic solvents at 4–15 bar hydrogen pressure.19 10%
Rhodium/charcoal was more active than analogous palla-
dium, iridium, platinum, or ruthenium catalysts in the hy-
drogenation of arenes in water at 80 °C and 3–5 atm of
hydrogen pressure,20 as well as in the hydrogenation of 1-
phenylethanol13b or benzoic acid21 in supercritical carbon
dioxide at 50 °C and 3–10 mPa of hydrogen pressure.
flame-ionization detector and a split-mode capillary-injection sys-
tem. Rhodium chloride hydrate (99.98% purity) was purchased
from Aldrich and dried by heating at 50 °C under reduced pressure
for 3 h before use. Graphite (< 500 ppm) was obtained from Roth.
All the products are known compounds; their spectra matched those
reported in the corresponding references.
Rhodium/Graphite (C24Rh)
Graphite powder (0.690 g) was poured into a three-necked flask
equipped with a condenser, a dropping funnel, an argon inlet, and a
magnetic stirrer bar, and the contents of the flask were heated under
argon at 150 °C for 10 min. Freshly cut potassium (0.280 g, 7.19
mmol) was slowly added to the graphite at 150 °C with stirring. Af-
ter all the potassium pieces had melted and bronze-colored C8K
powder was formed, the flask was allowed to cool to r.t. and the C8K
was covered with anhyd THF (15 mL) without stirring. A suspen-
sion of anhyd RhCl3 (0.50 g, 2.40 mmol) in THF (50 mL) was slow-
ly added with stirring. The mixture was then refluxed for 3 h, cooled
to 0 °C, and H2O (10 mL) was slowly added. The mixture was
stirred for 30 min and then filtered. The solid was washed succes-
sively with H2O, MeOH, and Et2O (30 mL each), then dried at r.t.
under vacuum for 6 h to give C24Rh as a dark grey powder; yield:
0.901 g (96%).
Rhodium nanoparticles stabilized or supported on poly-
meric matrices,22 zeolites,23or nanofibers,24 and homoge-
neous rhodium catalysts25 often display excellent
performances in hydrogenation reactions of arenes; these
performances, especially those of the homogeneous cata-
lysts, are far superior to those of more common heteroge-
neous rhodium catalysts.
In conclusion, we have described the easy preparation of
a new heterogeneous catalyst, rhodium/graphite. In this
catalyst, rhodium nanoparticles are assembled in sponge-
like clusters on the graphite surface, and no intercalation
appears to be present. This catalyst was highly effective in
the hydrogenation of carbocyclic and heterocyclic aro-
matic rings under mild conditions of room temperature
and atmospheric pressure. Unsaturated functionalities,
such as alkyne, alkene, nitro, formyl, and acetyl groups di-
rectly linked to the benzene ring were concomitantly re-
duced. On the other hand, ester, chloro, and amino
substituents inhibited the hydrogenation of the benzene
ring. Moreover, benzylic C–O bonds underwent partial or
complete hydrogenolysis. However, a number of func-
tionalities were tolerated, allowing the selective hydroge-
nation of carboxylic acids, phenols, and aryl ethers.
Optically active phenyl-substituted a-amino acids could
be easily hydrogenated without loss of optical activity.
More forcing conditions could be used for the hydrogena-
tion of more resistant substrates, such as diphenylmethane
or aryl ethers.
Structural Characterization of Rhodium/Graphite (C24Rh)
PXRD patterns were collected using a PanAnalytical X’Pert Pro
equipped with X’Celerator detector powder diffractometer using Cu
Ka radiation (l = 1.5418 Å) generated at 40 kV and 40 mA. The in-
strument was configured with a 1/4° divergence and 1/4° antiscat-
tering slits. A standard quartz sample holder 1-mm deep, 20-mm
high, and 15-mm wide was used. The diffraction patterns were col-
lected within the 2Q range from 10° to 85° with a step size (D 2Q)
of 0.02° and a counting time of 10 s.
TEM observations were carried out by using a Philips CM 100 in-
strument (80 kV). The powdered samples were dispersed in H2O
and then few droplets of the slurry were deposited on porous carbon
foils supported on conventional copper microgrids. The images
were recorded by using a charge-coupled device digital camera.
Methyl L-Cyclohexylglycinate Hydrochloride; Typical Proce-
dure for Hydrogenation
Rh/Gr (C24Rh, 0.010 g, 4% by weight) was added to a soln of
methyl L-phenylglycinate hydrochloride (0.250 g, 1.2 mmol) in an-
hyd MeOH (1.2 mL) containing 37% aq HCl (0.1 mL), and the mix-
ture was magnetically stirred under H2 (1 atm, balloon). The
progress of the reaction was monitored by GC/MS, after treatment
of the sample with 2 M aq NaOH and extraction with EtOAc. The
starting material disappeared within 24 h. The solid was filtered off
through a pad of Celite, and the organic phase was concentrated at
reduced pressure to give methyl L-cyclohexylglycinate hydrochlo-
ride as a white powder; yield: 0.241 g (97%, 1.16 mmol).
Among the advantages of the new catalyst are its two-step
preparation, the ready availability of the starting reagents,
and the possibility of recovering and reusing the catalyst.
Although the precursor C8K is pyrophoric, it is immedi-
ately transformed into rhodium/graphite, which has been
safely stored for months under air without loss of activity.
Therefore, despite the mildness of experimental condi-
tions and excellent selectivity and stereospecificity of-
fered by other heterogeneous and homogeneous rhodium
catalysts, extended applications of rhodium/graphite in
organic synthesis are expected.
The free amine was obtained by treatment with base: [a]D25 +32.8 (c
0.5, MeOH) [Lit.26 +33.4 (c 0.52, MeOH)].
Methyl L-Cyclohexylalaninate hydrochloride was similarly ob-
tained from methyl L-phenylalaninate hydrochloride (0.250 g, 1.16
mmol); yield: 0.246 g (96%); free base [a]D25 +24.3 (c 1.0, MeOH)
[Lit.27 +23.4 (c 1.0, MeOH)].
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G. Falini et al.
PAPER
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Acknowledgment
This work was carried out as part of the Prin Project: ‘Sintesi e ste-
reocontrollo di molecole organiche per lo sviluppo di metodologie
innovative’. The hydrogenation reactions at high pressures were
conducted using apparatus in the laboratory of Prof. Reinhard Neier
at the University of Neuchâtel (Switzerland). We also thank the
University of Bologna for financial support.
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Synthesis 2009, No. 14, 2440–2446 © Thieme Stuttgart · New York