ChemCatChem
10.1002/cctc.201700878
COMMUNICATION
7[d]
22 [e,f,g]
temperature for 18 h, before the heating bath was removed and the system
was cooled to room temperature. After depressurization, the crude mixture
was diluted with brine (ca. 10 mL) and the resulting biphasic mixture was
extracted with EtOAc (3 × 30 mL). The combined organic layers were
washed with brine, dried over Na SO , and concentrated in vacuo. The
48[h]
2
4
8
crude material obtained was then purified by flash column chromatography
on silica gel providing the desired primary alcohol.
[
a] Reaction conditions: nitrile (3.0 mmol), RuHCl(CO)(PPh
)
3 3
(1.0 mmol%),
1
1
,4-dioxane, and water were heated in a glass autoclave at 120 °C under
0 bar H pressure for 18 h. [b] Reaction was carried out at 140 °C and run
Acknowledgements
2
for 69 h. [c] Starting material was recovered in 88%. [d] Reaction was carried
out at 140 °C. [e] Formation of Ru black. [f] Starting material was recovered
in 7%. [g] 4-Aminobenzonitrile and 4-nitrobenzamide (10p) were isolated as
major side products in 14 and 41% yields, respectively. [h] Isonicotinamide
CaRLa (Catalysis Research Laboratory) is co-financed by the
Ruprecht-Karls-Universität Heidelberg (Heidelberg University)
and BASF SE.
10q was isolated as major side product in 47% yield.
Keywords: Nitriles • Deamination • Hydrogenation • Alcohols •
Our
deaminative
hydrogenation
methodology
was
Ruthenium
successfully applied to aromatic nitriles (1j-1q) as well (Table 3).
In this case, considerable amounts of the corresponding amides
[
[
[
[
1]
2]
3]
4]
P. Pollak, G. Romeder, F. Hagedorn, H.-P. Gelbke, in Ullmann's
Encyclopedia of Industrial Chemistry, Wiley-VCH Verlag GmbH & Co.
KGaA, 2000.
(
10) were detected in the crude mixtures suggesting that the rate
of the competing hydrolysis is faster. To suppress this undesired
side reaction, the reaction temperature was decreased to 120 °C.
Under these modified reaction conditions benzonitriles featuring
a methyl group either in the para (1j) or in the ortho position (1k)
were converted to the corresponding benzyl alcohols 4j and 4k in
high yields (Table 3, entries 1 and 2). In contrast, substrate 1l with
two ortho substituents was more problematic and provided only
a) P. Roose, K. Eller, E. Henkes, R. Rossbacher, H. Höke, in Ullmann's
Encyclopedia of Industrial Chemistry, Wiley-VCH Verlag GmbH & Co.
KGaA, 2000.
For selected reviews on nitrile reduction, see: a) D. B. Bagal, B. M.
Bhanage, Adv. Synth. Catal. 2015, 357, 883-900; b) S. Werkmeister, K.
Junge, M. Beller, Org. Process Res. Dev. 2014, 18, 289-302.
For recent examples on nitrile reduction with Ru-complexes, see: a) A.
Mukherjee, D. Srimani, Y. Ben-David, D. Milstein, ChemCatChem 2017,
9, 559-563; b) R. Adam, C. B. Bheeter, R. Jackstell, M. Beller,
ChemCatChem 2016, 8, 1329-1334; c) R. Adam, E. Alberico, W.
Baumann, H.-J. Drexler, R. Jackstell, H. Junge, M. Beller, Chem. Eur. J.
low conversion and yield even under more forcing conditions
15]
(
entry 3).[
While p-thiomethyl (1m) and p-chloro (1n)
substituents were well tolerated by the reaction, the presence of
strongly electron withdrawing groups, such as the
methoxycarbonyl group (1o) or the nitro (1p), proved to be
disadvantageous for achieving high levels of yield and selectivity
2016, 22, 4991-5002; d) S. Saha, M. Kaur, K. Singh, J. K. Bera, J.
Organomet. Chem. 2016, 812, 87-94; e) J.-H. Choi, M. H. G. Prechtl,
ChemCatChem 2015, 7, 1023-1028; f) J. Neumann, C. Bornschein, H.
Jiao, K. Junge, M. Beller, Eur. J. Org. Chem. 2015, 5944-5948; g) S.
Werkmeister, K. Junge, B. Wendt, A. Spannenberg, H. Jiao, C.
Bornschein, M. Beller, Chem. Eur. J. 2014, 20, 4227-4231; h) R. Reguillo,
M. Grellier, N. Vautravers, L. Vendier, S. Sabo-Etienne, J. Am. Chem.
Soc. 2010, 132, 7854-7855. i) S. Werkmeister, C. Bornschein, K. Junge,
M. Beller, Eur. J. Org. Chem. 2013, 3671-3674; j) S. Werkmeister, C.
Bornschein, K. Junge, M. Beller, Chem. Eur. J. 2013, 19, 4437-4440; k)
M. Vilches-Herrera, S. Werkmeister, K. Junge, A. Börner, M. Beller, Catal.
Sci. Technol. 2014, 4, 629-632; l) S.-H. Lee, G.I. Nikonov,
ChemCatChem 2015, 7, 107-113; m) B. Paul, K. Chakrabarti, S. Kundu,
Dalton. Trans. 2016, 45, 11162-11171; n) V.H. Mai, G.I. Nikonov,
Organometallics 2016, 35, 943-949.
(
entries 4 and 5 cf. entries 6 and 7). Compound 1q featuring a
heteroaromatic ring could also be converted to the desired alcohol
q, albeit with moderate yield due to the formation of
4
isonicotinamide (10q) as side product (entry 8).
In conclusion, we developed an operationally simple and
highly selective transformation for the direct conversion nitriles to
primary alcohols, using the commercially available and
3 3
inexpensive RuHCl(CO)(PPh ) as catalyst. As the reaction
requires the use of relatively low pressures of hydrogen, it can be
conducted in Fischer-Porter-type glass autoclaves that are easier
to handle and more cost-efficient than high pressure steel
autoclaves. Moreover, our methodology was found to be suitable
for the conversion of not only aromatic but also aliphatic nitriles
and also features a relatively broad functional group tolerance.
[5]
a) Y. P. Xie, J. Men, Y. Z. Li, H. Chen, P. M. Cheng, X. J. Li, Catal.
Commun. 2004, 5, 237-238; b) G. D. Han, S. K. Chung, Chin. Chem. Lett.
1996, 7, 1079-1080; c) A. Chatterjee, R. A. Shaikh, A. Raj, A. P. Singh,
Catal. Lett. 1995, 31 301-305. d) K. Takahashi, M. Shibagaki, H.
Matsushita, Chem. Lett. 1990, 311-314; e) R. P. Beatty, Process for
reductive hydrolysis of nitriles. US5741955 A (1998). f) A. Gauvreau, A.
Lattes, J. Perie, Bull. Soc. Chim. Fr. 1969, 126-127; g) S. Takenaka, C.
Shinmakawa, N. Tatayama, Production of Aldehydes and Alcohols. JP
4036250 (1992).
Experimental Section
General procedure for Tables 2 and 3:
[
6]
For reports on catalytic hydrogenation of nitriles to amines in aqueous
media: H. Cheng. X. Meng, C. Wu, X. Shan, Y. Yu, F. Zhao, J. Mol. Catal.
A: Chem. 2013, 379, 72-79; C. Bianchini, V. D. Santo, A. Meli, W.
Oberhauser, R. Psaro, F. Vizza, Organometallics 2000, 19, 2433-2444.
S. Gomez, J. A. Peters, T. Maschmeyer, Adv. Synth. Catal. 2002, 344,
A ca. 80 mL Fischer-Porter-type glass autoclave was charged with
RuHCl(CO)(PPh ) (0.03 mmol, 28.6 mg), the specified nitrile (3.0 mmol),
3 3
degassed 1,4-dioxane (3.0 mL) and degassed water (3.0 mL) under air.
After closing the reaction vessel, the system was purged first with nitrogen
[
[
7]
8]
1037-1057.
(
3-5×) and then with hydrogen (3-5×). Finally, the autoclave was
pressurized with hydrogen (10 bar) and placed into a preheated oil bath
120 or 140 °C). The reaction mixture was then stirred at the specified
V. Theodorou, G. Paraskevopoulos, K. Skobridis, Arkivoc 2015, 101-112
and references cited therein.
(
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