Switch in Catalyst State: Single Bifunctional Bi-state Catalyst for Two Different Reactions

Article abstract of DOI:10.1002/anie.201702142

Disclosed here is a molecular switch which responds to acid-base stimuli and serves as a bi-state catalyst for two different reactions. The two states of the switch serve as a highly active and poorly active catalyst for two catalytic reactions (namely a hydrogenation and a dehydrogenative coupling) but in a complementary manner. The system was used in an assisted tandem catalysis set-up involving dehydrogenative coupling of an amine and then hydrogenation of the resulting imine product by switching between the respective states of the catalyst.

Full text of DOI:10.1002/anie.201702142

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201702142
German Edition: DOI: 10.1002/ange.201702142
Hydrogenation
Switch in Catalyst State: Single Bifunctional Bi-State Catalyst for Two
Different Reactions
Shrivats Semwal and Joyanta Choudhury*
Abstract: Disclosed here is a molecular switch which responds
to acid-base stimuli and serves as a bi-state catalyst for two
different reactions. The two states of the switch serve as a highly
active and poorly active catalyst for two catalytic reactions
(namely a hydrogenation and a dehydrogenative coupling) but
in a complementary manner. The system was used in an
assisted tandem catalysis set-up involving dehydrogenative
coupling of an amine and then hydrogenation of the resulting
imine product by switching between the respective states of the
catalyst.
Simplification of complexity in chemical systems is a difficult
task, yet entertained by chemists. For example, enzymes,
a class of smart catalysts gifted by nature, regulate a myriad of
highly sophisticated and extremely complex catalytic pro-
cesses with the required level of precision over the desirable
outcome.[1] Mimicking such smart activity by artificial man-
made molecules is an incessant quest for modern chemists.
Recently, artificial switchable catalysts have been constructed
through judicious incorporation of reversibly responsive,
function-regulatory feature(s) controlled by various external
stimuli.[2] However, almost all of the developed switchable
catalysts show an activity-switching or stereo/chemoselectiv-
ity-switching behavior for only one catalytic reaction (S!P,
Figure 1A).[2,3] The next generation of smart catalysts is
intended to be more sophisticated by featuring switching
activity and facilitating two different reactions (S1!P1 and
S2!P2, Figure 1B).[4] Such a bifunctional bistate catalyst
having single active site to regulate two state-specific catalytic
reactions is rare, even in biology. A system close to having the
above-described sophistication has been recently uncovered
by Fushinobu et al. They discovered that the enzyme fructose-
1,6-biphosphate aldolase/phosphatase (FBPA/P) catalyzes
two chemically distinct reactions (a reversible aldol conden-
sation and a dephosphorylation reaction) within a single
catalytic domain by substrate-induced active-site metamor-
phosis.[5] The concept of this orthogonal catalytic behavior has
recently found application in electro-splitting of water, albeit
with nanoparticulate material, thus catalyzing a hydrogen
evolution reaction (HER) and oxygen evolution reaction
Figure 1. Design of stimuli-active switchable catalysis: A) Present gen-
eration bi-state, unifunctional catalyst. B) Target design of next-gener-
ation bi-state, bifunctional switchable catalyst. C) The design adopted
in this work based on acid-base triggered molecular coordination
switch.
(OER) through a switch in the catalyst state.[6] Only two such
systems, involving a synthetic catalyst having a single active
site, have been reported. That is, a redox-switchable and
photoswitchable catalyst as reported by the groups of Byers[7a]
and Bielawski,[7b] respectively. The rarity of examples empha-
sizes the challenge in devising a simple yet ideal switchable,
bifunctional bi-state catalyst which fulfills the following
prerequisites: a) ability to catalyze two different synthetically
important reactions through tiny structural/electronic
changes; b) sustainable, robust, selective, and recyclable;
and c) at least two orders of magnitude rate difference
between the reactions catalyzed by either catalyst form and
still remain switchable. Toward this end, herein, we present
a successful design of a bi-state molecule which catalyzes two
contrasting reactions by switching between its two states. The
working principle of this new switchable catalyst is different
from that of either the natural or artificial systems described
earlier. The design works on an acid/base-controlled molec-
ular switch involving two interconvertible metal coordination
modes (state I and state II), each of which shows fast and slow
catalysis in two contrasting reactions, namely, a catalytic
imine hydrogenation and a dehydrogenative coupling of an
amine (Figure 1C). The system exhibits excellent switching
between outputs for the catalytic activity during the actual
[*] S. Semwal, Dr. J. Choudhury
Organometallics & Smart Materials Laboratory
Department of Chemistry
Indian Institute of Science Education and Research Bhopal
Bhopal 462066 (India)
E-mail: joyanta@iiserb.ac.in
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.201702142.
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

Angewandte
Communications
Chemie
both reactions, which are triggered by simple acid/base inputs.
Finally, the switch was effectively utilized to construct an
assisted tandem catalysis[8] involving the dehydrogenative
coupling of an amine followed by hydrogenation of the
resulting imine, in one pot, and it was achieved by alter-
natively triggering a change in the catalyst state.
A hybrid pyridylidene-benzimidazole ligand (L), bound
to a catalytic [RuII(para-cymene)] center, was utilized to
exploit the acid/base control switch of the coordination (states
I and II) through the benzimidazole functionality, and to
provide a robust metal-ligand platform. The Ru–C(pyridyli-
dene) bonding seemed to be crucial for the success of the
system as this covalent binding of the ligand to the metal
center assured that the ligand would not dissociate from the
metal center, not even at high reaction temperatures. The
complex switches between an acid-stimulated RuII–benzimid-
azole coordination mode featuring a neutral imino-type s-
donating N!Ru coordination (state I) and a base-stimulated
RuII–benzimidazolate coordination mode consisting of
anionic s- and p-donating amido-type N–Ru covalent bond-
ing (state II). The complexes 1 and 2, that is, states I and II,
respectively, were synthesized according to the reactions as
shown in Figure 2A, and characterized fully by several
spectroscopic and single-crystal X-ray diffraction techniques
(Figure 2B and the Supporting Information).
After successfully verifying the smooth interconversion
between 1 and 2 in solution with acid-base inputs (Figure 2C),
the two complexes were used for the catalytic hydrogenation
of imines with molecular hydrogen under ambient conditions
(1 atm H2 at 408C) in 2,2,2-trifluoroethanol (TFE; Figure 3).
TFE is a highly polar and coordinating solvent which
facilitates removal of the iodide ligand from the metal
coordination sphere of the catalysts, as required for subse-
quent activation of H2. It was observed that 2 was highly
active (product yield 69 to 88%), whereas 1 was almost
inactive (product yield 1% to 5%) in this reaction, as it was
tested for a range of substrates.
Next, the catalyst switch was utilized for a complementary
reaction. The activity of 1 and 2 was reversed for the
dehydrogenative coupling of a series of benzylic amines to
the corresponding imines performed in the presence of NaBF4
in acetonitrile/toluene at 1008C under open-flask conditions
(Figure 3). In this reaction, NaBF4 was used for removal of the
iodide ligand to facilitate substrate binding. Herein, 1 was
more efficient (product yield 78 to 94%) than 2 (product yield
2% to 25%).
This type of orthogonal catalytic response of the 1$2-
based switch for the two reactions was further explored for
online temporal control of the switch during the progress of
the reactions. Thus, when a model hydrogenation reaction was
started with the less effective catalyst 1, no product formation
was observed in the first 2 hours of catalysis. Addition of NEt3
(1 equiv with respect to catalyst) generated the active catalyst
2, which afforded fast reaction and 26% yield of the product
in the next 2 hours. The activity of 2 was drastically slowed
down by adding 1 equivalent of CF3COOH, and it was
restored again with addition of NEt3. Three representative
cycles were performed without any loss of activity of the
catalyst, thus showing 0–2% of product yield in the slow state
Figure 2. A) Synthesis (A) and ORTEP[9] representation (B) of solid-
state molecular structures of 1 and 2. The thermal ellipsoids are
shown at 30% probability. C) Acid-base triggered 1$2 interconversion
monitored by UV/Vis spectroscopic method in solution.
and incremental yields of 19–22% in the fast state for every
2 hour period (Figure 4A). Similarly, switchability of the
system was successfully verified for the dehydrogenative
catalysis starting with the less active catalyst 2, which
furnished only 4% of the product within the initial 3 hour
period. After addition of CF3COOH (1 equiv with respect to
catalyst) the more active catalyst 1 was generated and
accelerated the reaction to provide 17% yield of the product
in the next 3 hours. Addition of NEt3 stopped the catalysis and
to restore it acid was added. Three representative cycles were
tested and exhibited 4–8% yield in the slow state and 17–24%
yield in the fast state for alternating 3 hour periods (Fig-
ure 4B).
After successful demonstration of the switchable catalysis,
the power of the method was further tested for an assisted
tandem catalysis[8] (such as A!B!C) by switching on the
correct catalyst state (I or II) for each step by using the
appropriate stimulus. Finding common but compatible reac-
tion conditions (solvent, temperature etc.) for both of the
catalyses in a single pot was challenging. To demonstrate
proof-of-concept, however, we compromised the activity to
some extent and chose a preliminary reaction set-up as
described below. At first, the dehydrogenative coupling of 4-
methylbenzylamine (5 f) was started with the less active
2
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!

Angewandte
Communications
Chemie
Figure 5. Design of an assisted tandem catalysis set-up (5 f!6 f!4i)
based on the 1$2 switch: A) Reaction conditions applied for dehydro-
genative coupling of 5 f to 6 f, followed by hydrogenation of 6 f to 4i.
B) Time versus yield profile of the assisted tandem catalysis involving
consecutive 5 f!6 f and 6 f!4i conversions by the respective active
and dormant states of the catalyst.
hydrogenation reaction was applied in the same pot as shown
in Figure 5A, and the reaction was again left to continue. As
1 was less active in the hydrogenation reaction, the corre-
sponding amine product 4i was formed in only 8% yield after
12 hours (step iii; Figure 5B). At this stage, the required
stimulus, that is, base (1 equiv of NEt3 with respect to
catalyst), was added to switch 1 into 2, which was supposed
to be highly active in hydrogenation. After 12 hours of further
reaction under the same reaction conditions, 55% yield of the
desired amine product was recorded (step iv; Figure 5B), thus
demonstrating successful and fast hydrogenation catalysis, by
2, for 6 f, which was formed in the first reaction. An overall
70% yield of 4i was achieved after 24 hours of total reaction
time (step v; Figure 5B). Notably, the activity of 2 under these
modified but somewhat compromised reaction conditions
involving a one-pot multicomponent set-up was comparable
to the original activity as shown in Figure 3. This assisted
tandem catalysis was further performed successfully for
a large-scale set-up as well (see the Supporting Information).
Next we sought an acceptable explanation of our hypoth-
esis on the above bifunctional, bi-state catalyst. We believe
that the difference in activity of 1 and 2 in the hydrogenative
catalysis is due to the nature of the ligand sphere and its
influence on the activation of H2, in line with our previous
investigation involving similar iridium-based complexes (see
Scheme S5).[10] The basic amido ligand in 2 is highly efficient
in metal–ligand cooperative activation of H2 to generate Ru-
H species and facilitate hydride insertion and subsequent
hydrogenation. In contrast, the imino ligand in 1 is unable to
play any such cooperative role to activate H2 and the catalysis
is promoted via a coordinated dihydrogen species from which
the hydride delivery is extremely poor.[11] To gain insight into
the differential activity of 1 and 2 in the dehydrogenative
catalysis, mechanistic investigations, including evaluation of
rate law by initial-rate kinetics, kinetic deuterium isotope
Figure 3. Examples of hydrogenative (A) and dehydrogenative (B)
catalysis performed by 1 and 2. C) Yields [%] of the products depicted
in (A and B).
Figure 4. Switches of reactivity throughout hydrogenation of N-benzyli-
deneaniline (A) and dehydrogenative coupling of benzylamine (B).
catalyst 2 (1.5 mol%) under the reaction conditions as
applied previously (Figure 5A). As expected, yield of the
imine product (6 f) was low (18%) after 22 hours of reaction
(step i; Figure 5B). In the next step, the acid stimulus (1 equiv
of CF3COOH with respect to catalyst) was added to the
reaction to generate the more active catalyst 1, and the
reaction was continued. A high yield (96%) of 6 f was
obtained after 22 hours (step ii; Figure 5B). Then, a modified
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
effects (KDIEs), and substrate (amine) coordination/de-
Conflict of interest
coordination equilibrium constants for both 1 and 2 were
conducted (see the Supporting Information). Based on the
experimental results, two different catalytic cycles were
proposed (see Schemes S6 and S7) and provide an explan-
ation for the observed fast and slow dehydrogenative catalysis
with 1 and 2, respectively. Most importantly, efficient
substrate (amine) coordination to the electron-poor ruthe-
nium center in 1[12] [Kasso = 875.09mꢀ1 for 1 was much higher
compared to that for 2 (2.06 ꢀ 10ꢀ3 mꢀ1)], and amine-assisted
The authors declare no conflict of interest.
Keywords: hydrogenation · imines · ligand effects · ruthenium ·
synthetic methods
ꢀ
rate-determining substrate N H bond cleavage (kH/kD = 3.44
[1] a) T. Traut, Allosteric Regulatory Enzymes, Springer, New York,
2008; b) D. Ringe, G. A. Petsko, Science 2008, 320, 1428.
[2] For recent reviews on switchable catalysis, see: a) V. Blanco, D.
Leigh, V. Marcos, Chem. Soc. Rev. 2015, 44, 5341; b) A. J. Teator,
D. N. Lastovickova, C. W. Bielawski, Chem. Rev. 2016, 116, 1969;
c) Z. Yu, S. Hecht, Chem. Commun. 2016, 52, 6639; d) S. M.
Guillaume, E. Kirillov, Y. Sarazin, J.-F. Carpentier, Chem. Eur. J.
2015, 21, 7988; e) F. Wang, X. Liu, I. Willner, Angew. Chem. Int.
Ed. 2015, 54, 1098; Angew. Chem. 2015, 127, 1112; f) M.
Schmittel, Chem. Commun. 2015, 51, 14956; g) A. M. Lifschitz,
M. S. Rosen, C. M. McGuirk, C. A. Mirkin, J. Am. Chem. Soc.
2015, 137, 7252; h) R. Gçstl, A. Senf, S. Hecht, Chem. Soc. Rev.
2014, 43, 1982; i) F. A. Leibfarth, K. M. Mattson, B. P. Fors, H. A.
Collins, C. J. Hawker, Angew. Chem. Int. Ed. 2013, 52, 199;
Angew. Chem. 2013, 125, 210; j) B. M. Neilson, C. W. Bielawski,
ACS Catal. 2013, 3, 1874; k) R. S. Stoll, S. Hecht, Angew. Chem.
Int. Ed. 2010, 49, 5054; Angew. Chem. 2010, 122, 5176; l) U.
Lꢁning, Angew. Chem. Int. Ed. 2012, 51, 8163; Angew. Chem.
2012, 124, 8285.
[3] For selected representative articles, see: a) S. Neri, S. G. Martin,
C. Pezzato, L. J. Prins, J. Am. Chem. Soc. 2017, 139, 1794; b) J.
Wei, M. N. Riffel, P. L. Diaconescu, Macromolecules 2017, 50,
1847; c) K. E. Ruhl, T. Rovis, J. Am. Chem. Soc. 2016, 138, 15527;
d) S. Yuan, L. Zou, H. Li, Y.-P. Chen, J. Qin, Q. Zhang, W. Lu,
M. B. Hall, H.-C. Zhou, Angew. Chem. Int. Ed. 2016, 55, 10776;
Angew. Chem. 2016, 128, 10934; e) F. della Sala, J. L.-Y. Chen, S.
Ranallo, D. Badocco, P. Pastore, F. Ricci, L. J. Prins, Angew.
Chem. Int. Ed. 2016, 55, 10737; Angew. Chem. 2016, 128, 10895;
f) B. Liu, D. Cui, T. Tang, Angew. Chem. Int. Ed. 2016, 55, 11975;
Angew. Chem. 2016, 128, 12154; g) C. Romain, Y. Zhu, P.
Dingwall, S. Paul, H. S. Rzepa, A. Buchard, C. K. Williams, J.
Am. Chem. Soc. 2016, 138, 4120; h) S. M. Quan, X. Wang, R.
Zhang, P. L. Diaconescu, Macromolecules 2016, 49, 6768;
i) A. C. H. Jans, A. Gꢂmez-Suꢃrez, S. P. Nolan, J. N. H. Reek,
Chem. Eur. J. 2016, 22, 14836; j) S. IbꢃÇez, M. Poyatos, E. Peris,
ChemCatChem 2016, 8, 3790; k) X. Mao, W. Tian, J. Wu, G. C.
Rutledge, T. A. Hatton, J. Am. Chem. Soc. 2015, 137, 1348;
l) J. B. Geri, N. K. Szymczak, J. Am. Chem. Soc. 2015, 137, 12808;
m) A. M. Lifschitz, R. M. Young, J. Mendez-Arroyo, C. L. Stern,
C. M. McGuirk, M. R. Wasielewski, C. A. Mirkin, Nat.
Commun. 2015, 6, 6541; n) D. Zhao, T. M. Neubauer, B. L.
Feringa, Nat. Commun. 2015, 6, 6652; o) M. Galli, J. E. M. Lewis,
S. M. Goldup, Angew. Chem. Int. Ed. 2015, 54, 13545; Angew.
Chem. 2015, 127, 13749; p) G.-H. Ouyang, Y.-M. He, Y. Li, J.-F.
Xiang, Q.-H. Fan, Angew. Chem. Int. Ed. 2015, 54, 4334; Angew.
Chem. 2015, 127, 4408; q) P. Neumann, H. Dib, A.-M. Caminade,
E. Hey-Hawkins, Angew. Chem. Int. Ed. 2015, 54, 311; Angew.
Chem. 2015, 127, 316; r) Y. Zhu, C. Romain, C. K. Williams, J.
Am. Chem. Soc. 2015, 137, 12179; s) C. Romain, C. K. Williams,
Angew. Chem. Int. Ed. 2014, 53, 1607; Angew. Chem. 2014, 126,
1633; t) X. Wang, A. Thevenon, J. L. Brosmer, I. Yu, S. I. Khan,
P. Mehrkhodavandi, P. L. Diaconescu, J. Am. Chem. Soc. 2014,
136, 11264.
for 1) suggested higher activity in the 1-catalyzed reaction.[13]
In contrast, poor substrate (amine) coordination to the p-
donating amido-ligand-bound electron-rich ruthenium center
in 2[12] (Kasso = 2.06 ꢀ 10ꢀ3 m for 2, and kH/kD = 0.89 for 2) in the
rate-limiting amine association step resulted in sluggish
dehydrogenative catalysis with 2. A detailed study, including
DFT calculations, will be undertaken in future to either
validate the above or to discover other possibilities.
In summary, a ruthenium(II)-based bi-state molecular
switch, which is responsive to acid/base stimuli, was designed
and exhibits highly reversible metal–ligand coordination
modes. The modes are either a neutral imino-type s-donating
N!Ru coordinate bonding state or an anionic s/p-donating
amido-type N-Ru covalent bonding state. The switch between
modes presents a bifunctional bi-state catalyst for two
different reactions. The “Ru-amido state” is highly active in
catalytic hydrogenation of various imine substrates while the
“Ru-imino state” remains poorly active in this reaction. On
the contrary, for the catalytic dehydrogenative coupling of
amines, the “Ru-imino state” was much more efficient
compared to the “Ru-amido state”. Furthermore, modulation
of rates by switching between fast/slow catalysis of during the
hydrogenative and dehydrogenative reactions was also ach-
ieved by simply applying acid/base inputs into the system. In
both the applications, the system featured a large difference in
reaction rates, and demonstrated high switchability and
robustness. Extending the concept further, the switch was
also utilized effectively to demonstrate an assisted tandem
catalysis involving the dehydrogenative coupling of an amine
followed by hydrogenation of the resulting imine, in one pot,
all triggered by acid and base stimuli in an alternating
manner. The work may be considered a step forward to
develop more sophisticated next-generation multifunctional
switchable catalysts. Efforts are ongoing to upgrade the
present system in this direction.
Acknowledgments
J.C. thanks DST-SERB (grant no. EMR/2016/003002) and
IISER Bhopal for generous financial support. S.S. is recipient
of UGC doctoral fellowship. We thank the reviewers for their
insightful comments.
[4] Recently Schmittel and co-workers designed a sophisticated
toggle nanoswitch which confined two distinct catalysts to
regulate two different catalytic reactions: S. De, S. Pramanik,
4
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!

Angewandte
Communications
Chemie
M. Schmittel, Angew. Chem. Int. Ed. 2014, 53, 14255; Angew.
free of charge from The Cambridge Crystallographic Data
Chem. 2014, 126, 14480.
Centre.
[10] S. Semwal, J. Choudhury, ACS Catal. 2016, 6, 2424.
[11] To correlate with the previous investigations (Ref. [9]), kinetic
studies and NMR analyses were performed. See the Supporting
[5] S. Fushinobu, H. Nishimasu, D. Hattori, H.-J. Song, T. Wakagi,
Nature 2011, 478, 538.
[6] a) S. Cobo, J. Heidkamp, P.-A. Jacques, H. Fize, V. Fourmond, L.
Guetaz, B. Jousselme, V. Ivanova, H. Dau, S. Palacin, M.
Fontecave, V. Artero, Nat. Mater. 2012, 11, 802; for a similar
nanoparticulate catalyst, see: b) C. He, X. Wu, Z. He, J. Phys.
Chem. C 2014, 118, 4578.
[7] a) A. B. Biernesser, K. R. D. Chiaie, J. B. Curley, J. A. Byers,
Angew. Chem. Int. Ed. 2016, 55, 5251; Angew. Chem. 2016, 128,
5337; b) A. J. Teator, H. Shao, G. Lu, P. Liu, C. W. Bielawski,
Organometallics 2017, 36, 490.
[8] a) D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248,
2365; b) J.-C. Wasilke, S. J. Obrey, R. T. Baker, G. C. Bazan,
Chem. Rev. 2005, 105, 1001; c) T. L. Lohr, T. J. Marks, Nat. Chem.
2015, 7, 477.
[9] CCDC 1534311 (1) and 1534312 (2) contain the supplementary
crystallographic data for this paper. These data can be obtained
Information for details.
3+
[12] The Ru2+
/
redox potential in 1 was found to be 72 mV higher
than that in 2 (for 1: 1020 mV; for 2: 948 mV vs. saturated
calomel electrode). See the Supporting Information for details.
[13] When a control catalysis experiment was performed using
a model complex in which the N-H group in 1 was replaced
with N-CH3 group, no product formation was observed, thus
suggesting the key role of the N-H group in 1 during substrate
activation and/or other steps. See the Supporting Information for
details.
Manuscript received: February 27, 2017
Revised: March 22, 2017
Final Article published: && &&, &&&&
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Hydrogenation
In a state: An acid-base responsive bi-
state catalyst controls the rates of two
different catalytic processes in a comple-
mentary manner. This concept was used
in an assisted tandem catalysis by
S. Semwal,
J. Choudhury*
&&&& — &&&&
Switch in Catalyst State: Single
Bifunctional Bi-State Catalyst for Two
Different Reactions
switching between catalyst states to ach-
ieve the desired reaction sequence.
6
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!