N. Mizuno et al.
grade) and were used as received.
TiO2 (anatase, JRC-TIO-1, BET sur-
face area: 73 m2 gÀ1) and Al2O3 (KHS-
24, 160 m2 gÀ1) were obtained from the
Catalysis Society of Japan and Sumito-
mo Chemical, respectively. Ru/HAP
(ruthenium chloride species supported
on hydroxyapatite; 9.1 wt%) and Ru/
C (Ru(0) species supported on activat-
Conclusion
ed carbon; 5 wt%) were purchased from Wako Pure Chemical Industries
and NE Chemcat Corp., respectively. Compound 2i’ (>99% ee;
>99% D at the a-position) was synthesized according a reported proce-
dure.[12i] Supported metal hydroxide catalysts were prepared according a
reported procedure (see the Supporting Information).[12]
Ru(OH)x/TiO2 could act as an efficient heterogeneous cata-
lyst for the N-alkylation of ammonia (or its surrogates) and
amines with alcohols as alkylating reagents. Various kinds of
symmetrically and unsymmetrically substituted amines could
be synthesized in high yield. In addition, Ru(OH)x/TiO2
could be applied to the oxidative synthesis of nitriles direct-
ly from alcohols and ammonia surrogates with molecular
oxygen (air) as an oxidant. The catalyst/product separation
could be easily carried out by simple filtration (or centrifu-
gation) and Ru(OH)x/TiO2 was recyclable. The transforma-
tion proceeded through sequential N-alkylation reactions, in
which a ruthenium dihydride species plays a key role. The
present Ru(OH)x/TiO2-catalyzed system has the following
significant advantages: 1) applicability to various nitrogen
sources (i.e., ammonia, including its surrogates, and amines)
and alkylating reagents (various kinds of structurally diverse
primary and secondary alcohols); 2) high catalytic activity
and selectivity; 3) no use of cocatalysts and additives; 4) a
simple workup procedure, namely, catalyst/product separa-
tion; and 5) reusability of the catalyst. The results demon-
strated herein will open up a new avenue for the green
amine synthesis, which can completely avoid the use of con-
ventional hazardous reagents, such as organic halides and
the formation of inorganic byproducts.
Procedure for the synthesis of amines: All the operations for the synthe-
sis of amines were carried out in a glovebox under argon. Ru(OH)x/TiO2,
an alcohol, nitrogen source, and mesitylene were successively placed into
a pyrex-glass screw-cap vial (volume: ca. 20 mL). A teflon-coated mag-
netic stirring bar was added, and the reaction mixture was vigorously
stirred (800 rpm) under argon (1 atm; see Tables 1–6 for the detailed re-
action conditions). The yields of the products were periodically deter-
mined by GC analyses. After the reaction was completed, the spent
Ru(OH)x/TiO2 catalyst was separated by filtration (or centrifugation),
washed with mesitylene and 2-propanol, and dried in vacuo prior to
being recycled. The products were isolated by column chromatography
on silica gel (eluent: n-hexane until elution of mesitylene, then ethyl ace-
tate or diethyl ether). The products were confirmed by 1H and 13C NMR
spectroscopic and/or GCMS analyses.[5,9,28] For nitrile synthesis, the reac-
tions were carried out under air (6 atm) with a teflon-coated autoclave
(volume: ca. 15 mL).
Dehydrative condensation of benzaldehyde and aniline: Benzaldehyde
(1 mmol), aniline (1 mmol), toluene (3 mL), and Ru(OH)x/TiO2 (50 mg,
or without the catalyst) were successively placed into a glass vial. The re-
action mixture was stirred at 258C under air (1 atm). The conversion and
yield were periodically determined by GC analysis. The reaction rates
were determined from the slopes of the reaction profiles (plots of [ben-
zaldehyde]0À[benzaldehyde]t vs. time) at low conversions of benzalde-
hyde (<10%; the initial-rate method).
Acknowledgements
Experimental Section
This work was supported in part by the Core Research for Evolutional
Science and Technology (CREST) program of the Japan Science and
Technology Agency (JST), the Global COE Program (Chemistry Innova-
tion through Cooperation of Science and Engineering), and Grants-in-
Aid for Scientific Researches from Ministry of Education, Culture,
Sports, Science and Technology.
General: The GC analyses were performed on a Shimadzu GC-2014 ma-
chine using a flame ionization detector (FID) equipped with a DB-WAX
ETR capillary column (internal diameter: 0.25 mm, length: 30 m), a TC-
WAX capillary column (internal diameter: 0.25 mm, length: 30 m), a TC-
1 capillary column (internal diameter: 0.25 mm, length: 30 m), or a TC-5
capillary column (internal diameter: 0.25 mm, length: 60 m). The mass
spectra were recorded on a Shimadzu GCMS-QP2010 machine equipped
with a TC-5HT capillary column (internal diameter: 0.25 mm, length:
30 m). The NMR spectra were recorded on a JEOL JNM-EX-270 spec-
trometer. The 1H and 13C NMR spectra were measured at 270 and
67.8 MHz, respectively, in CDCl3 with trimethylsilane (TMS) as an inter-
nal standard. The 2H NMR spectra were measured at 41.25 MHz with
[D6]benzene as an external standard. The ICP-AES analyses were per-
formed on a Shimadzu ICPS-8100 machine. The ESR measurements (X-
band) were performed on a JEOL JES-RE-1X spectrometer at À1508C
in an argon atmosphere.
[1] a) B. R. Brown, The Organic Chemistry of Aliphatic Nitrogen Com-
pounds, Oxford University Press, New York, 1994; b) R. N. Salva-
Smith, J. March, Marchꢀs Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 6th ed., Wiley, New York, 2007.
[2] a) P. T. Anastas, J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, London, 1998; b) R. A. Sheldon, Green
Reagents: Substrates (alcohols and amines) and solvents were commer-
cially obtained from Tokyo Kasei, Aldrich, and Fluka (reagent grade)
and were purified before use.[27] Compound 2a’ (98% D at the a-posi-
tion) was obtained from Isotec and used as received. Ammonium salts
and urea were commercially obtained from Nacalai Tesque, Aldrich, and
Wako Pure Chemical Industries (reagent grade) and were used as re-
ceived. Ruthenium salts and complexes were obtained from Wako Pure
Chemical Industries, Kanto Chemical Co., and Tokyo Kasei (reagent
[3] M. H. S. A. Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth.
[4] a) R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit, T. Tongpenyai, J.
[5] a) F. Valotl, F. Fachel, R. Jacquot, M. Spagnol, M. Lemairel, Tetrahe-
7206
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Chem. Eur. J. 2010, 16, 7199 – 7207