Ammonia N-H activation by a N,N′-diamidocarbene

Article abstract of DOI:10.1039/c0cc00638f

The synthesis and characterization of N,N′-dimesityl-4,6-diketo-5,5- dimethylpyrimidin-2-ylidene is reported; this crystalline N,N′- diamidocarbene was found to split ammonia and engage in other reactions not exhibited by typical N-heterocyclic carbenes.

Full text of DOI:10.1039/c0cc00638f

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Ammonia N–H activation by a N,N0-diamidocarbenew
Todd W. Hudnall, Jonathan P. Moerdyk and Christopher W. Bielawski*
Received 29th March 2010, Accepted 16th April 2010
First published as an Advance Article on the web 18th May 2010
DOI: 10.1039/c0cc00638f
The synthesis and characterization of N,N0-dimesityl-4,6-diketo-
5,5-dimethylpyrimidin-2-ylidene is reported; this crystalline
N,N0-diamidocarbene was found to split ammonia and engage
in other reactions not exhibited by typical N-heterocyclic
carbenes.
inhibit intramolecular C–H insertion and enable access to a
stable analogue.
While we were working toward the preparation of 2,
Lavigne and co-workers reported8 an elegant synthesis of this
compound, but encountered difficulties with its isolation. They
noted that 2 underwent rapid decomposition upon its generation
via deprotonation of 2ꢀHCl in THF and must be trapped with
S8 or (Rh(COD)Cl)2 (COD = 1,5-cyclooctadiene) at ꢁ40 1C.
Based on our previous studies with 1, which also proved to be
problematic when generated in THF,7 we reasoned that 2 may
be accessed by performing the deprotonation reaction in a
non-coordinating solvent.
The activation of industrially-important small molecules, such
as ammonia and dihydrogen, has garnered considerable attention
over the past two decades.1 Historically, transition metals have
been employed for such purposes,2 although main group
species capable of facilitating these transformations have been
reported more recently.3 Of the two aforementioned small
molecules, NH3 activation remains relatively challenging due
to the propensity to form stable Lewis acid–base adducts
rather than undergo bond scission.4 Recently, Bertrand and
co-workers revealed the potential of alkyl amino carbenes to
overcome many of these obstacles, resulting in the only
hitherto examples of metal-free NH3 activation.5
Herein we demonstrate that readily-accessible N,N0-diamido-
carbenes (DACs) split NH3. These efforts are part of a
burgeoning program aimed at expanding the reactivity exhibited
by nucleophilic N-heterocyclic carbenes (NHCs)6 to include
reactions typically displayed by traditional, electrophilic carbenes
(e.g., methylidene). For example, we recently reported7 that
DAC 1 (Fig. 1) exhibited substantial electrophilic character
and could effect C–H insertions into unactivated tertiary alkyl
groups, reversibly affix carbon monoxide (CO), and quantitatively
couple with organic isocyanides to afford diamidoketenimines.
To facilitate our studies into small molecule activation, we
sought an isolable DAC. Despite our best efforts, 1 was found
to undergo an intramolecular C–H insertion with a methine
group of its diisopropylphenyl N-substituents7 which complicated
subsequent reactivity studies. We envisioned that a derivative
featuring relatively less activated C–H bonds (i.e., 2) would
To test this hypothesis, 2ꢀHCl was first prepared using a
modified procedure reported8 by Lavigne et al. (Scheme 1). In
addition to various spectroscopic techniques,w the structure of
2ꢀHCl was elucidated by X-ray crystallography (see Fig. 2).
Close inspection of the solid state data revealed that the
C1–Cl1 distance (1.888(2) A) was relatively elongated
compared to the average sp3 C–Cl bond (ca. 1.76 A),9 suggesting
that the Cl atom was weakly bound to the diamidomethine
nucleus (see below for additional discussion).
Treatment of a suspension of 2ꢀHCl in benzene with sodium
hexamethyldisilazide (NaHMDS) followed by solvent removal
and washing with cold hexanes afforded the desired N,N0-
diamidocarbene (2) in 85% isolated yield.z A salient spectro-
scopic feature of 2 was a low-field 13C resonance observed
at d = 277.7 ppm (C6D6). This signal was assigned to the
carbene nucleus (C1) and determined to be consistent with the
Scheme 1 Conditions: (i) dimethylmalonyl dichloride, Et3N, CH2Cl2,
0 1C, 1 h; (ii) NaHMDS, C6H6, 25 1C, 30 min. Mes = 2,4,6-(CH3)3-C6H2.
Fig.
2,6-(iPr)2-C6H3, Mes = 2,4,6-(Me)3-C6H2.
1 =
Examples of N,N0-diamidocarbenes (DACs). Dipp
Department of Chemistry and Biochemistry, The University of Texas
at Austin, 1 University Station A5300, Austin, TX 78712, USA.
E-mail: bielawski@cm.utexas.edu
w Electronic supplementary information (ESI) available: Additional
synthetic procedures, spectroscopic data and X-ray crystallographic
data. CCDC 770147–770151. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c0cc00638f
Fig. 2 ORTEP diagram of 2ꢀHCl with thermal ellipsoids drawn at
50% probability. H-atoms except for H1A have been omitted for
clarity.
ꢂc
This journal is The Royal Society of Chemistry 2010
4288 | Chem. Commun., 2010, 46, 4288–4290

View Article Online
Scheme 3 Synthesis of 5. Conditions: (i) NH3 (liq.), ꢁ78 1C - 25 1C,
12 h.
Next, our attention shifted toward exploring the ability of 2
to activate NH3. Condensing NH3 at ꢁ78 1C onto solid 2
followed by slowly warming to ambient temperature over 12 h
led to the formation of the desired product (5) in nearly
quantitative yield (Scheme 3). The 1H NMR (C6D6) spectrum
of 5 featured a diagnostic triplet at d = 5.22 ppm (CH) and a
broad doublet centered at 1.15 ppm (NH2), results similar to
those previously observed for the addition of NH3 across a
carbene nucleus.5 Additionally, the IR spectrum (KBr) featured
two peaks at n = 3415 and 3339 cmꢁ1, which were consistent
with N–H stretching modes of primary amines.z
Fig. 3 ORTEP diagram of 2 with thermal ellipsoids drawn at 50%
probability. H-atoms have been omitted for clarity.
analogous signal exhibited by 1 (278.4 ppm, C6D6).7 FT-IR
analysis revealed that the nCO displayed by 2 (1709 cmꢁ1; KBr)
was at an energy intermediate of those exhibited by typical
amides (ca. 1630–1695 cmꢁ1) and ketones (ca. 1710–1740 cmꢁ1).
To gain additional insight into the structure of 2, X-ray quality
crystals were obtained by slow vapor diffusion of hexanes into a
toluene solution saturated with this compound. As shown in
Fig. 3, the Ccarbene–N distances (avg. C1–N = 1.37 A) were
found to be significantly shorter than the N–Cacyl distances (avg.
N–Cacyl = 1.41 A). However, the C–O distances (avg. 1.21 A)
measured in the crystal structure of 2 were only slightly shorter
than the analogous C–O distances found in the solid state
structure of its amido precursor 2ꢀHCl (avg. 1.22 A). Collectively,
the X-ray crystallography results supported the IR spectro-
scopic data which characterized the NCO groups in 2 as
hybrids of canonical amides and ketones.y
Single crystals suitable for X-ray diffraction analysis
were obtained by cooling a hexanes : CH2Cl2 (2 : 1 v : v)
solution saturated with 5 to ꢁ30 1C. As shown in Fig. 4, the
C1 atom of the respective structure exhibited a high degree of
P
pyramidalization (
= 339.41) indicating that the
(N–C–N)
carbene nucleus rehybridized upon reaction with NH3.
Additionally, the C1–N3 distance (1.406(3) A) was in good
agreement with the analogous distance (1.428(7) A) observed
in the solid state structure of an adduct formed between an
alkyl amino carbene and NH3.5
To further explore the reactivities of DACs and their
precursors, NH3 was condensed into a toluene solution of 1
Upon the synthesis and characterization of 2, its reactivity
was explored. Similar to that observed with 1, DAC 2 engaged
in reactions typically exhibited by electrophilic carbenes
(Scheme 2). For example, bubbling CO through a toluene
solution of 2 resulted in the immediate formation of a purple
color (lmax = 543 nm) consistent with the formation of
N,N0-diamidoketene 3.7 The observation of 13C resonances
at d = 91.7 and 246.4 ppm (C7D8), corresponding to the
carbenoid CCO and ketenoid CCO nuclei, respectively,
and a nCO = 2091 cmꢁ1 (C7H8) confirmed the formation
of 3. Notably, this carbonylation reaction was determined
to be reversible with a Keq = 4.78 Mꢁ1 in C7D8 at 20 1C
(PCO = 15 psi). In contrast, a thermally-robust compound
(mp = 153–154 1C) was obtained in excellent yield when 2 was
treated with 2,6-dimethylphenylisocyanide. This product
displayed diagnostic7 13C chemical shifts at d = 106.3 and
202.7 ppm (C6D6) that were attributed to the CCN and CCN
resonances of diamidoketenimine 4, respectively, as well as a
characteristic IR stretching mode at nCCN = 1978 cmꢁ1 (KBr).
Fig. 4 ORTEP diagram of 5 with thermal ellipsoids drawn at 50%
probability. H-atoms except for H1A and H3A have been omitted for
clarity.
Scheme 2 Synthesis of diamidoketene 3 and diamidoketenimine 4.
Conditions: (i) CO, 25 1C, C7D8; (ii) CN-(2,6-(Me)2-C6H3), 25 1C,
C7H8, 1 h. Ar = 2,6-(CH3)2-C6H3.
Scheme 4 Synthesis of 5 and 6. Conditions: (i) NH3 (liq.), ꢁ78 1C -
25 1C, 12 h.
ꢂc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 4288–4290 | 4289

View Article Online
Notes and references
z Using a similar protocol, 1ꢀHCl was prepared in 96% yield from
N,N0-bis(2,6-di-isopropylphenyl)formamidine. DAC
1
was also
generated via deprotonation of 1ꢀHCl with NaHMDS in aromatic
hydrocarbons.
y Under an inert atmosphere, 2 was found to be indefinitely stable in
the solid state (mp = 166–168 1C; dec.) and for several days in
solution (C6D6, C7D8 and 1,4-dioxane).
z A triazolylidene was reported to insert into the NH bond of
morpholine, see: D. Enders, K. Breuer, G. Raabe, J. Runsink, J. H.
Teles, J.-P. Melder, K. Ebel and S. Brode, Angew. Chem., Int. Ed.
Engl., 1995, 34, 1021.
8 If the pKas of the conjugate acids of the DACs described herein are
significantly lower than those of typical NHCs (16–24),12 carbene
generation via NH3-facilitated deprotonation (followed by NH3
activation) may be possible. However, Et3N was found to be
insufficiently basic to generate 2 from 2ꢀHCl or 1 from [1H][OTf].
** At temperatures greater than 200 1C, DAC decomposition was
observed and independently confirmed by performing analogous
high temperature experiments under an inert atmosphere in sealed
vessels.
Scheme 5 Proposed mechanism for the formation of NH3 adducts 5
and 6 from their respective protonated precursors.
(generated in situ from 1ꢀHCl and NaHMDS) at ꢁ78 1C,
which resulted in the formation of the expected product (6) in
high yield (Scheme 4). Similarly, condensing NH3 onto solid 2ꢀ
HCl, 1ꢀHCl or [1H][OTf] (OTf = triflate) followed by warming
to ambient temperature also resulted in the formation of 5 and
6, respectively, in excellent yields. The results of the reactions
involving the HCl adducts or [1H][OTf] were in accord with
previous observations7,8 that [1H][OTf] and 2ꢀHCl readily
react with alcohols and water to form the corresponding
alkoxy or hydroxy adducts, respectively.w As such, we suspect
that NH3 added directly to the C1 position of [1H][OTf]
(Scheme 5) or displaced the chloride atoms in the afore-
mentioned HCl adducts via a nucleophilic type substitution
reaction.8 The latter is supported by the relatively long C–Cl
bond length observed in the solid state structure of 2ꢀHCl
(Fig. 2), an indicator of a weakened chloride bond.
1 D. M. Heinekey, A. Lledos and J. M. Lluch, Chem. Soc. Rev.,
2004, 33, 175; R. H. Crabtree, Acc. Chem. Res., 1990, 23, 95;
G. J. Kubas, Acc. Chem. Res., 1988, 21, 120; G. S. McGrady and
G. Guilera, Chem. Soc. Rev., 2003, 32, 383.
2 G. L. Hillhouse and J. E. Bercaw, J. Am. Chem. Soc., 1984, 106,
5472; Y. Nakajima, H. Kameo and H. Suzuki, Angew. Chem., Int.
Ed., 2006, 45, 950; J. Zhao, A. S. Goldman and J. F. Hartwig,
Science, 2005, 307, 1080; A. L. Casalnuovo, J. C. Calabrese and
D. Milstein, Inorg. Chem., 1987, 26, 971; M. M. B. Holl,
P. T. Wolczanski and G. D. Van Duyne, J. Am. Chem. Soc.,
1990, 112, 7989; E. G. Bryan, B. F. G. Johnson and J. Lewis,
J. Chem. Soc., Dalton Trans., 1977, 1328; P. Sabatier and
J.-B. Senderens, Ann. Chim. Phys., 1905, 4, 319; Y. Peng,
B. D. Ellis, X. Wang and P. P. Power, J. Am. Chem. Soc., 2008,
130, 12268; Y. Peng, J.-D. Guo, B. D. Ellis, Z. Zhu, J. C. Fettinger,
S. Nagase and P. P. Power, J. Am. Chem. Soc., 2008, 131, 16272.
3 P. A. Chase and D. W. Stephan, Angew. Chem., Int. Ed., 2008, 47,
7433; G. C. Welch, R. R. San Jaun, J. D. Masuda and
D. W. Stephan, Science, 2006, 314, 1124; G. C. Welch and
D. W. Stephan, J. Am. Chem. Soc., 2007, 129, 1880; Y. Xiong,
While it is tempting to surmise that the free DACs 1 and 2
reacted with NH3 in a similar fashion as their protonated
adducts (i.e., via the formation of a Werner-type complex4),
this requires the buildup of negative charge on the carbene
nucleus. Alternatively, these DACs may be activating the N–H
bond of NH3 in a concerted fashion and in a manner
analogous to that proposed for the CAACs.5 For example, 5
was observed to form rapidly upon bubbling NH3 through a
dilute solution of 2 in C6D6 ([2]0 = 8.9 ꢃ 10ꢁ2 M, 25 1C).
Unfortunately, no reaction was observed between 2 and H2,
even under forcing conditions (1000 psi H2, 200 1C) in C6H6 or
1,4-dioxane.** This lack of reactivity was surprising considering
the similar bond-dissociation energies of NH3 and H2 (107 and
104 kcal molꢁ1, respectively)10,11 and given that Bertrand’s
alkyl amino carbenes, a class of substrates that shares many
similar reactivities as the DACs, were reported to activate both
NH3 and H2.5 Further investigation is underway.
S. Yao, R. Muller, M. Kaupp and M. Driess, J. Am. Chem. Soc.,
¨
2010, DOI: 10.1021/ja1031024.
4 A. Werner, Z. Anorg. Chem., 1893, 3, 267; R. E. Tapscott,
J. D. Mather and T. F. Them, Coord. Chem. Rev., 1979, 29, 87;
Z. Wang and C. Kutal, Inorg. Chim. Acta, 1994, 226, 285;
J. D. Davies, W. H. Daly, Z. Wang and C. Kutal, Chem. Mater.,
1996, 8, 850.
5 G. D. Frey, V. Lavallo, B. Donnadieu, W. W. Schoeller and
G. Bertrand, Science, 2007, 316, 439; V. Lavallo, Y. Canac,
B. Donnadieu, W. W. Schoeller and G. Bertrand, Angew. Chem.,
Int. Ed., 2006, 45, 3488; X. Zeng, G. D. Frey, R. Kinjo,
B. Donnadieu and G. Bertrand, J. Am. Chem. Soc., 2009, 131,
8690.
In conclusion, we report the synthesis and first solid state
characterization of a free DAC, and demonstrate the ability of
this carbene to split ammonia. These results expand the few
known organic5 systems capable of activating an industrially
important small molecule. An attractive feature of the substrates
reported herein is that they can be obtained in high-yield over
two steps starting from inexpensive, commercially-available
materials and are readily-amenable to further modification.
As a result, we believe that DACs offer promise in the
development of new synthetic strategies for transforming NH3
into structurally- and functionally-diverse nitrogen-containing
compounds.
6 For reviews on NHCs and related compounds, see: D. Bourissou,
O. Guerret, F. P. Gabbaı and G. Bertrand, Chem. Rev., 2000, 100,
¨
¨
39; K. Ofele, E. Tosh, C. Taubmann and W. A. Herrmann, Chem.
Rev., 2009, 109, 3408; S. Dıez-Gonzalez, N. Marion and
S. P. Nolan, Chem. Rev., 2009, 109, 3612.
´
´
7 T. W. Hudnall and C. W. Bielawski, J. Am. Chem. Soc., 2009, 131,
16039; T. W. Hudnall, E. J. Moorhead, D. G. Gusev and
C. W. Bielawski, J. Org. Chem., 2010, 75, 2763.
8 V. Cesar, N. Lugan and G. Lavigne, Eur. J. Inorg. Chem., 2010,
´
361.
9 S. S. Batsanov, Inorg. Mater. (Transl. of Neorg. Mater.), 2001, 37,
871.
10 S. J. Blanksby and G. B. Ellison, Acc. Chem. Res., 2003, 36,
255.
11 V. I. Bakhmutov, Dihydrogen Bonds. Principles, Experiments and
Applications, Wiley, Hoboken, NJ, 2008.
12 R. W. Alder, P. R. Allen and S. J. Williams, J. Chem. Soc., Chem.
Commun., 1995, 1267; T. L. Amyes, S. T. Diver, J. P. Richard,
F. M. Rivas and K. Toth, J. Am. Chem. Soc., 2004, 126, 4366.
We are grateful to the National Science Foundation
(CHE-0645563 and 0741973), the Robert A. Welch Foundation
(F-1621), the Alfred P. Sloan Foundation, and the Arnold and
Mabel Beckman Foundation for their generous financial
support.
ꢂc
This journal is The Royal Society of Chemistry 2010
4290 | Chem. Commun., 2010, 46, 4288–4290