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ChemComm
In a second experiment, a small amount of H/D exchange was
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observed when acetamide-d3 was converted into the secondary
amide. It is unlikely that a ketene mechanism plays any
significant role in the reaction, as this would be expected to lead
to a greater level of H/D exchange (D/H ~ 67/33).
5
50
55
60
Analysis of the 1H NMR spectra of Cp2ZrCl2 in the presence of
varying concentrations of either benzamide or benzylamine
revealed that the cyclopentadienyl ligands were not displaced and
that both substrates bound fairly weakly (Ka = 0.4 M-1 for
5. (a) C. Gunanathan, Y. Ben-David and D. Milstein, Science, 2007, 317,
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10 benzylamine and 1.5 M-1 for benzamide).
A kinetic analysis of the reaction established that the reaction
was first order in both Cp2ZrCl2 and benzamide. However, the
reaction was found to be second order in benzylamine. One
explanation for this might be that the amine is used as a base as
15 well as a nucleophile in the reaction, but the reaction rate was
found to be zero order with respect to tertiary amine when
iPr2NEt was added (in fact the rate decreased slightly).
6. For recent examples see; (a) C. L. Allen, R. Lawrence, L. Emmett and
J. M. J. Williams, Adv. Synth. Catal., 2011, 353, 3262-3268;
(b).Gnanamgari and R. H. Crabtree, Organometallics., 2009, 28, 922-
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352, 288-292; (d a n Bosson e - on le
Marion and S. P. Nolan, J. Org. Chem., 2010, 75, 1197-1202;
One possible mechanism which is consistent with the data is
presented in Scheme 2. Reaction of the zirconium catalyst with
20 the amine leads to formation of a zirconium amide (i.e. Zr-NHR). 65 7. (a) A. Galat and G. Elion, J. Am. Chem. Soc., 1943, 65, 1566-1567.
Complexation of the carboxamide to the catalyst would be
followed by addition of the amine to the carboxamide as shown
in Scheme 2, intermediate 4. We speculate that this addition may
be assisted by the zirconium amide (Zr-NHR), which would
25 rationalize why the reaction is second order in amine. After loss
of ammonia from intermediate 6, secondary amide would be
exchanged from intermediate 7 to complete the catalytic cycle.
For an example of a reactive amide, see; (b) M. Hutchby, C. E.
Houlden, M. F. Haddow, S. N. G. Tyler, G. C. Lloyd-Jones and K. I.
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70
9. C. L. Allen, B. N. Atkinson and J. M. J. Williams, Angew. Chem. Int.
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10. T. B. Nguyen, J. Sorres, M. Q. Tran, L. Ermolenko and A. Al-
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75 11. (a) P. Starkov and T. D. Sheppard, Org. Biomol. Chem., 2011, 9,
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80
85
90
95
3364; (e) J. Lasri, M. E. González-Rosende and J. Sepúlveda-Arques,
Org. Lett., 2003, 5, 3851-3853.
12. (a) S. E. Eldred, D. A. Stone, S. H. Gellman and S. S. Stahl, J. Am.
Chem. Soc., 2003, 125, 3422-3423; (b) D. A. Kissounko, I. A. Guzei,
S. H. Gellman and S. S. Stahl, Organometallics, 2005, 24, 5208-5210;
(c) D. A. Kissounko, J. M. Hoerter, I. A. Guzei, Q. Cui, S. H. Gellman
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Scheme 2 Possible mechanism for transamidation
30
In summary, we have identified zirconocene dichloride as an
effective catalyst for transamidation reactions of primary amides
under milder conditions than previously reported.
We thank the EPSRC (BNA) and the Doctoral Training Centre
in Sustainable Chemical Technology (HVL) for funding. We
14. (a) J. M. Hoerter, K. M. cui, S. H. Gellman, Q. Cui and S. S. Stahl, J.
Am. Chem. Soc., 2007, 130, 647-654; (b) J. M. Hoerter, K. M. Otte, S.
H. Gellman and S. S. Stahl, J. Am. Chem. Soc., 2006, 128, 5177-5183.
See also; (c) E. Bon, D. C. H. Bigg and G. Bertrand, J. Org. Chem.,
1994, 59, 4035-4036.
35 thank the University of Bath for further support.
Notes and references
15.M. Tamura, T. Tonomura, K.-I. Shimizu and A. Satsuma, Green
Chem., 2012, 14, 717-724.
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16. Zhangꢀ I Bähn L eubert H eu ann and Beller
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