Green Chemistry
Page 4 of 6
with and activation of the strong ligating CN group analogous to
Discipline of New Materials and Process Engineering
the cases in TM-catalyzed reactions,8,12 and consequently
enhance the reactivity of the CN group in hydration steps.
50 (20110949), and Undergraduate Training Program for
DOI: 10.1039/C3GC42310G
A possible mechanism was then proposed (Scheme 1). Thus,
CsOH readily reacts with DMSO to give dimethylsulfinyl
anion I and Cs+;17 meanwhile, coordination of Cs+ with
nitriles may form Cs-activated complex III.8,12,16 To avoid
existence of free OH- that can lead to over hydrolysis of
nitriles to byproduct acids, more DMSO than CsOH must be
(JWDC2012064) for financial support.
5
Notes and references
a
College of Chemistry and Materials Engineering, Wenzhou University,
55 Wenzhou, Zhejiang 325035, China. Fax: (+)-86-577-86689302; Tel: (+)-
86-13857745327; E-mail: qing-xu@wzu.edu.cn
10 added to ensure complete consumption of OH-. Then, O-
addition of I at the carbon of CN moiety of III may take place
to give II’, a more reactive intermediate than free II (eq. 5)
due to activation by coordinating with Cs+.16 Next, H2O may
attack the S centre of DMSO moiety to afford amides and
15 regenerate I and Cs+ via an old S-O bond cleavage and a new
S-O bond formation (path a), which can be described as a
DMSO-participated indirect hydration process involving O-
transfer from DMSO onto nitriles to give O-transferred
amides; otherwise, H2O may also directly attack the carbon of
20 CN moiety of II’ via path b to afford amides and regenerate
Cs+ and I. Although direct hydration of nitirles by free OH-
can not be excluded completely, it should be a less possible
process, because the preceding contrastive results have clearly
showed that I is a much more active catalyst than free OH-
25 (Table 1, runs 9-11), even not to mention that free OH- has
already been controlled in very low levels by using much
more amounts of DMSO than CsOH.
b
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang
310027, China. E-mail: panyuanjiang@zju.edu.cn
c School of Chemistry and Chemical Engineering, Yangzhou University,
60 Yangzhou, Jiangsu 225002, China.
† Dedicated to the memory of Professor Xian Huang on the occasion of his 80th
birthday.
‡ Electronic Supplementary Information (ESI) available: experimental
details, condition screening tables, product characterization, secondary
65 mass analysis, and 1H and 13C NMR copies of all products. See
DOI: 10.1039/b000000x/
1
2
B. A. Trofimov, Sulfur Rep., 1992, 11, 207 and references therein.
Selected examples: (a) L. Rout, T. K. Sen and T. Punniyamurthy,
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70
75
3
Selected examples: (a) Y. Yuan, I. Thomé, S. H. Kim, D. Chen, A.
Beyer, J. Bonnamour, E. Zuidema, S. Chang and C. Bolm, Adv.
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CsOH + DMSO
O
80
Cs
N
(DMSO >> CsOH)
CH2
S
R
NH2
H
O
O
R
O
CH3
path a
Cs
CN
+
S
H
H2C
R
CH3
I
R
(indirect hydration
with O-transfer)
85
Cs :N
III
C
4
5
D. Tzalis and P. Knochel, Angew. Chem. Int. Ed., 1999, 38, 1463.
However, mechanism of the CsOH/THF/DMSO system was not
discussed and remains unknown.
Cs
N
CH2
S
Cs
N
H
H2O
CH2
S
CH3
O
O
(a) We found nitrile hydration easily took place at heating when
CsOH was used in condensation of (substituted)acetonitriles with
aldehydes, affording unexpected amides in good yields; (b) Q. Xu, J.
Chen, H. Tian, X. Yuan, S. Li, C. Zhou and J. Liu, Angewan. Chem.
Int. Ed., DOI: 10.1002/anie.201308642; (c) L. Yu, Y. Wu, H. Cao,
X. Zhang, X. Shi, J. Luan, T. Chen, Y. Pan and Q. Xu, Green Chem.,
2013, DOI: 10.1039/C3GC41562G; (d) Q. Xu, Q. Li, X. Zhu and J.
Chen, Adv. Synth. Catal., 2013, 355, 73; (e) Q. Xu, J. Chen and Q.
Liu, Adv. Synth. Catal., 2013, 355, 697.
R
H
path b
(direct hydration)
90
R
O
CH3
II'
30 Scheme 1. Proposed mechanism for Cs-activated
dimethylsulfinyl anion-catalyzed controllable and selective
nitrile hydration reaction in water
95
In summary, we developed a mild and efficient, general and
35 practical, green and scalable method for selective synthesis of
the versatile amides from the readily available nitriles in
water by using a simple, water soluble, and recoverable
CsOH/DMSO catalyst system. Mechanistic studies showed
that the reaction may proceed via novel and unexpected Cs-
40 activated processes including a DMSO-participated indirect
hydration reaction involving O-transfer from DMSO onto
nitriles to give O-transferred amides or a dimethylsulfinyl
anion-catalyzed direct hydration reaction of the nitriles with
water.20 Further extensions of the hydration method and
45 deeper mechanistic insights are underway.
6
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Acknowledgements
We thank NNSFC (20902070, 21025207), ZJNSF (Y4100579),
ZJQJTP (QJD0902004), Zhejiang Provincial Top Key
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