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silane may undergo activation by siloxide followed by a hydride
transfer to the imidazolium salt with release of a hydrogen
molecule leading to the formation of the siloxane byproduct
(see the ESI,† Fig. S6) and regenerates the free aNHC catalyst.
In the present study, we have developed the first metal-free
catalytic silylative dehydration of primary amides to nitriles at
room temperature. We demonstrated that aNHC can act as an
efficient metal-free catalyst for this dehydration process. This
catalytic transformation enables dehydration of 30 different
aromatic, heteroaromatic, and aliphatic amides using one
equivalent of silane. Characterization of reaction intermediates
supported by various experimental evidence and high-level DFT
calculations helped us to delineate the mechanistic picture for
this conversion.
We thank the SERB (DST), India (Grant No. EMR/2017/
000772). P. K. H. and J. A. thank IISER Kolkata for a research
Scheme 2 Proposed mechanism for the aNHC catalyzed silylative dehy-
fellowship. S. M. thanks CSIR, Delhi (09/921(0233)/2019-EMR-I)
and N. M. R. thanks SERB-NPDF (PDF/2017/001767), Delhi
for the research fellowship. The authors also thank the NMR
dration of primary amides.
DMMS, rt, 80%; 5 mol% [Fe], DEMS, 100 1C, 23%; 5 mol% [Fe], facility of IISER Kolkata.
DEMS, rt, o5%; POCl , Et N, rt, 27%; T P, 100 1C, 48%; 5 mol%
TBAF, PhSiH , 100 1C, 8%; and 5% TBAF, PhSiH
3
3
3
3
3
, rt, o5%).
Conflicts of interest
Finally, we have synthesized 4-methoxybenzonitrile 2f in a gram-
scale from 4-methoxybenzamide using 1 equivalent of silane at
There are no conflicts to declare.
25 1C. From the results presented in Scheme 1, it appears that the
electronic influence of the substituents attached to the substrate Notes and references
plays a key role in the catalytic activity. Therefore, we attempted to
correlate the structure–reactivity relationships for the catalytic
dehydration of primary amides using Density Functional Theory
1
L. R. Subramanian, Nitriles, in Science of Synthesis, ed. B. M. Trost
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(DFT) study (B3LYP method). Assuming the catalytic dehydration
3
4
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of amides is initiated by the nucleophilic attack of amide nitrogen
to the electrophilic silicon centre, we looked at the atomic charges
on the nitrogen atom of the corresponding amide. The electronic
properties of the amides were calculated using the Natural Bond
Orbital (NBO) model (see the ESI,† Fig. S65). For amides with
electron-donating groups (EDGs), the negative charge on the
nitrogen atom was expected to be high and the nucleophilic
attack will be favourable to afford the higher yield. On the other
hand, for amides with electron withdrawing groups (EWGs), a low
anionic charge on the nitrogen was calculated (see the ESI,†
5
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39
Fig. S65) leading to low reactivity.
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A plausible catalytic cycle is proposed in Scheme 2. Each of
the proposed steps is supported by DFT calculations and key
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4
0
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In the presence of an amide, it undergoes dehydrogenation
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1
1
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À1
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(
see the ESI,† Fig. S62). The N-silyl and O-silyl imidates readily
1
1
8 J. A. Krynitsky and H. W. Carhart, Org. Synth., 1963, IV, 436.
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‡
À1 30,31
t
equilibrate, according to the DFT study (DG = 15.7 kcal mol ).
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À1
2008, 4097–4100.
of aNHC (287.0 kcal mol ) was significantly higher than that of
2
1 S. Zhou, D. Addis, S. Das, K. Junge and M. Beller, Chem. Commun.,
À1 38
normal NHC (229.9 kcal mol ). Because of aNHC’s strong
2009, 4883–4885.
proton affinity, it takes a proton from O-silyl imidate and rapidly 22 S. Elangovan, S. Quintero-Duque, V. Dorcet, T. Roisnel, L. Norel,
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eliminates the siloxide, which directly forms the desired nitrile
product via TS2 (DG = 6.6 kcal mol ; C–N, 1.25 Å; C–O, 1.40 Å
where in Int3 C–N, 1.27 Å; C–O, 1.36 Å). Next, another molecule of
4521–4528.
‡
À1
2
3 W. Yao, H. Fang, Q. He, D. Peng, G. Liu and Z. Huang, J. Org. Chem.,
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