Synthesis and characterisation of a mesocyclic tripodal triamine ligand

Article abstract of DOI:10.1039/c5ob01556a

Meso- and macrocyclic polydentate amine ligands have been widely explored in oxidation catalysis and for the stabilization of unstable metal-superoxide, -peroxide, and -oxo intermediates. Herein we report on the design and synthesis of a novel mesocyclic,

Full text of DOI:10.1039/c5ob01556a

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Synthesis and Characterisation of a Mesocyclic Tripodal Triamine
Ligand
Andrew D. Ure,a Isabel Abánades Lázaro,a Michelle Cotter,a and Aidan R. McDonalda*
Received 00th January 20xx,
Accepted 00th January 20xx
Abstract: Meso- and macrocyclic polydentate amine ligands have been widely explored in oxidation catalysis and for the
stabilization of unstable metal-superoxide, -peroxide, and -oxo intermediates. Herein we report on the design and
synthesis of a novel mesocyclic, tripodal, triamine ligand that we believe will be an excellent addition to this field. We
explored a number of synthetic procedures towards the mesocyclic asymmetric tetraalkylated ligand 1. We expect that 1
will bind metals in a facially capping manner, yielding complexes that display pseudo-tetrahedral geometry, potentially
providing access to unprecedented late transition metal-oxo complexes (metal = Co, Ni, Cu). We describe the preparation
of a library of mescocylcic polyamine synthons (8, 16, 17, 18, 19) that are precursors in the synthesis of 1. These synthons
will be used to tailor the electronic properties of metal complexes of 1 and derivatives thereof. The X-ray crystal structures
of 19 and mono- and di-protonated forms of 1b show that the triamine crystalises in a boat-chair conformation which is
undesirable for metal coordination. However, solution 1H NMR studies show that in solution both 19 and the
tetraalkylated derivative 1b are remarkably flexible. 1b reacted with [CuI(NCCH3)4](OTf) yielding a 1:1 copper(I) complex
[CuI(NCCH3)(1b)]+.
DOI: 10.1039/x0xx00000x
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A reason for the dearth in late transition metal-oxo complexes
is that in certain geometries, d-electrons destabilise the metal-
oxo interaction, preventing the isolation of metal-oxo’s of later
Introduction
Iron and copper containing metalloenzymes perform a variety
of oxidative conversions of inert hydrocarbon substrates.1-5
These enzymes are capable of performing otherwise difficult
oxidation reactions under ambient conditions. Terminal metal-
oxo intermediates are often postulated as the reactive
intermediates in these reactions. For example, in the
cytochromes P450, Compound I (an FeIV=O species) performs
hydrogen atom abstraction (HAA) of inert substrates.6 The di-
copper enzyme particulate methane monooxygenase (pMMO)
is capable of HAA from the strong C-H bond in methane (bond
dissociation energy (BDE) = 104 kcal mol-1(7)), ultimately
yielding methanol.8 The HAA reagent in pMMO is likely a bis-μ-
oxo dicopper(III) (CuIII–O–CuIII) or a terminal CuIII=O species.9
These impressive HAA reactivities have driven synthetic
chemists to develop bio-mimetic terminal metal-oxo
complexes that can replicate this chemistry. While a plethora
of well-characterised synthetic FeIV=O complexes has been
reported,10-13 there remains no examples of CuIII=O and other
terminal late transition metal-oxo (Co, Ni) complexes, although
our group and others are making progress towards such
species. 14-17
transition metals.15, 17-19 Nocera postulated that late transition
metal-oxo’s could be stabilised in complexes displaying low
coordination numbers.20-24 Based on this postulate, we believe
that late transition metal-oxo complexes could be accessible
using ancillary ligands that enforce a pseudo-tetrahedral
geometry. We therefore set out to design and synthesise
ligands and complexes that display such a pseudo-tetrahedral
geometry in order to prepare late transition metal-oxo
complexes (Figure 1).
In our ligand design considerations we decided that the ligand
must be tripodal and facially capping, so as to enforce a
pseudo-tetrahedral coordination environment. Furthermore,
the ligand should contain strong σ-donor atoms in order to
stabilise the high oxidation state of the metal centre in metal-
oxo complexes. Meso- and macro-cyclic, peralkylated amine
Figure 1 – Left: Target compound
oxo.
1, Right: a generic pseudo-tetrahedral metal-
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describe our efforts towards synthesizing the novel ligand
1
and derivatives thereof.
Results and Discussion
We identified triol 1,1,1-tris(hydroxymethyl)ethane (
2, Scheme
1), as a useful starting point for the preparation of
to prepare the asymmetric molecule , we attempted to
address single arm of the tri-substituted neo-pentyl
1. In order
1
a
framework, leaving the other two arms to be the basis of the
8-membered mesocycle. To this end we attempted to
Figure 2 – Chemdraw representations of the ligands related to 1b.
selectively address one of the hydroxyl groups of
protecting the other two hydroxyl groups. We prepared the
bis-protected triol (1,3-dioxane, ) according to a previously
published procedure.54 The remaining hydroxyl group in
was
2 while
ligands have been used to great success in stabilizing early
transition metal-oxo complexes (metal = Mn, Fe)11-13, 25-27 and
late transition metal-superoxide and -peroxide complexes.28-36
Meso- and macro-cyclic frameworks add further stability to
3
3
then activated through reaction with one equivalent of tosyl
chloride (tosyl (Ts) = 4-toluenesulphonyl) in pyridine to give
complexes bearing these ligands, because of the macrocyclic
38
Based on these considerations, we set-out to
the corresponding tosylate 4 55
The azide, 5, was then
.
effect.37,
prepared through nucleophilic substitution of the tosylate with
sodium azide according to the procedure reported by Liu.56 We
subsequently pursued two avenues towards the selective
prepare mesocyclic ligand
1 (Figure 1).
1
is a close analogue of the tripodal acyclic ligand 1,1,1-
derivitisation of azide
5 (Scheme 2), but neither provided us
tris(aminomethyl)ethane (TAME, Figure 2). Due to the lack of
steric bulk in TAME, 2:1 complexes are often formed.
Increasing the steric bulk via N-alkylation to give 1,1,1-tris(N,N-
dimethylamino)methylethane (Me6TAME, Figure 2) resulted in
the ligand switching from binding to metals in a tridentate
fashion, to a bidentate binding mode, with one of the
nitrogens remaining unbound.39 Similarly, the more bulky
guanidine derivative of TAME, 1,1,1-tris(2N-1,1,3,3-
with an efficient or facile route towards
1
.
In the first of these routes, we utilised the azide moiety as a
masked amine. was refluxed with aqueous HCl in
tetrahydrofuran (THF) for 30 minutes to cleave the dioxane
protecting group.56 The resulting diol (
) was then immediately
reacted with 2.2 equivalents of tosyl chloride in the presence
of aqueous sodium hydroxide in THF to give the bis-tosylate
5
6
7
tetramethylguanidino)methylethane (guanTAME, Figure 2) has
41
We postulate
in a 64 % yield. Cyclic polyamines, including DACO, are readily
synthesised via the Richman-Atkins method of cyclisation.57, 58
In general, this involves the reaction of a di-tosylated diol (such
been shown to exhibit variable denticity.40,
that the mesocyclic nature of
putative metal-binding site will ensure
tridentate fashion yielding 1:1 complexes.38
1
and the steric bulk around the
1
would bind in a
as
cyclisation. In order to perform the cyclisation reaction of
ditosylates like , we prepared the activated diamine N,N'-
(propane-1,3-diyl)bis-tosylamide 12 by reacting 1,3-
diaminopropane (11) with tosyl chloride according to
reported procedure (Scheme 3a).52 12 was then deprotonated
7) with a deprotonated bis-tosylamide to facilitate
7
1
is also a close analogue of the 1,5-diazacyclooctane (DACO,
(
)
Figure 2) family of ligands.38, 42, 43 DACO ligands tend to bind to
the metal with the DACO framework displaying a boat-chair
configuration.44 These observations are important because we
a
using NaH and subsequently stirred with 7, without work-up,
require that
1 binds to metals yielding a chair-boat
configuration to ensure pseudo-tetrahedral geometry. Several
derivatives of DACO have been developed, exclusively through
N-alkylation (Figure 2).33-36, 45-53 In general, these ligands yield
square planar complexes. Overall, while many N-alkylated
derivatives of DACO exist, few tetrahedral complexes
employing DACO have been reported, and all are lacking the
high degree of steric bulk that we require. We envisioned that
introducing a third donor atom to DACO at the 3-position of
the DACO ring, rather than through N-alkylation, would
present several benefits. Firstly, introduction of ligating
functionalities at the 3-position would ensure a facially capping
ligand (and
a pseudo-tetrahedral complex), whereas N-
alkylated derivatives of DACO are mainly meridional binders.
Secondly, organic functionalities can be readily introduced
Scheme 1 – Synthesis of 1,3-dioxane protected azide 5.
through N-alkylation in 1, allowing us to easily modulate the
Scheme 2 – Unsuccessful synthetic routes towards target compound 1.
electronic and steric properties of the ligand. Herein, we
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at 145
°
the post-reaction mixture indicated none of the desired cycle
C in anhydrous dimethylformamide (DMF). Analysis of and dried over magnesium sulphate, gave an anhydrous
product.61 This anhydrous product was better suited to the
8
had formed. We attributed this to the organic azide being cyclisation step discussed below (Scheme 4), because it must
unstable under the high-temperature reaction conditions. The be performed under strictly anhydrous conditions.
azide group may act as a leaving group under such forcing
conditions.
Importantly, we found that the tris-tosylate 13 was easily
converted to the tris-bromide 14 in 76% yield by reaction
As a result of this negative outcome, we revisited the between 13 and NaBr in diethylene glycol heated to 145 °C.
protected azide, 5. Rather than cleaving the dioxane group we Using this method 14 can be used without further purification,
proceeded to reduce the azide moiety. This was achieved by unlike the previously reported reaction of the tris-
reacting
ammonium formate in methanol to give the primary amine
in a 50% yield. We then attempted to methylate the primary there are several reports detailing the synthesis of 14 directly
amine in using 2 equivalents of methyl iodide. However, ESI- from the reaction between
and PBr3,63 we have found them
5
with 10% wt of 5% Pd/C in the presence of benzenesulphonate analogue of 13 with NaBr,62 which we
found required the product be purified by distillation. While
9
9
2
MS revealed the formation of a statistical distribution of all of difficult to reproduce, and therefore prefer this two-step
the possible methylation products (secondary, tertiary and procedure for the preparation of 14. These two activated
quaternary), rather than a majority of the tertiary amine. tripodal neopentane precursors provide two useful synthons
These products were not separable using column towards the preparation of
chromatography. We then attempted the methylation of
under Eschweiler-Clarke conditions.59
was refluxed for 6
1.
9
9
hours in an excess of formic acid and formaldehyde. After
work up, the 1H NMR showed the disappearance of the two
characteristic dioxane methyl peaks at 1.41 and 1.45 ppm,
indicating that the dioxane protecting group had been cleaved
under these reaction conditions, giving no indication of the
formation of the desired product 10
.
Given these unexpected setbacks, we decided that rather than
selectively address individual arms of the triol precursor , we
would perform cyclisation reactions on activated derivatives of
triol , without protecting any of the hydroxyl functionalities.
1
2
We anticipated difficulties with this approach because of the
potential formation of oligomers and polymers in the Richman-
Atkins cyclisation reaction,58 however it was a necessary
approach.
2 was activated through its reaction with tosyl
chloride (4 equiv.) in pyridine (Scheme 3b) yielding the tris-
tosylate 13 in 83% yield. While 13 can be isolated simply by
precipitation after addition of ice-water followed by filtration60
we found that the work-up reported by Lindhorst and co-
workers, in which the product was extracted with ethyl acetate
Scheme 3 – a) Synthesis of the activated diamine 12; b) Synthesis of activated triols 13
and 14.
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Scheme 4 – Cyclisation reactions and derivatisation of cyclised products.
sodium azide to yield the azide
confirmed using NMR spectroscopy and Mass spectrometry. In
the Fourier transform infra-red (FT-IR) spectrum of , a strong
band at 2103 cm-1, which we assign as an N3 vibrational mode,
was observed. The azide group in was then reduced, using
8. Formation of 8 was
We reacted the bis-tosylamide, 12, with the activated triols 13
and 14 under conditions outlined by Richman and Atkins
(Scheme 4).57 The disodium salt of 12
(15) was generated in
8
8
situ by reacting 12 (0.1 M, 100 mL) with two equivalents of
sodium hydride in anhydrous DMF. After hydrogen evolution
had ceased (gas bubbles were no longer observed), the
reaction mixture was heated at 100 °C under argon for one
5% Pd/C and ammonium formate in methanol, to give the
amine 17 as confirmed by NMR and ESI-MS. The
disappearance of the FT-IR band at 2103 cm-1 and the
appearance of the characteristic amine symmetric and
asymmetric stretching frequencies at 3309 and 3151 cm-1 was
hour. A 0.2 M solution (50 mL) of an activated triol (13 or 14
in anhydrous DMF was then added dropwise. The resulting
reaction mixture was heated at 145 C under argon flow for at
least 24 h. This yielded the desired cyclised products 16a and
16b
16a and 16b were characterised using 1H and 13C NMR
spectroscopies and mass spectrometry. The 1H NMR spectra
displayed resonances typical of mesocyclic aliphatic
)
noted, confirming reduction of the azide moiety in
8 to an
°
amine in 17. The N-tosyl protecting groups in 17 were then
cleaved by heating 17 in 33% HBr/acetic acid (Scheme 4). No
1
aromatic peaks were observed in the H NMR of the triamine
.
product 19, which was purified as the tris-hydrogen bromide
salt, indicating complete N-tosyl deprotection and isolation of
the desired triamine product.
a
hydrocarbon, confirming cyclisation occurred. Additionally,
single crystals of 16b suitable for x-ray diffraction were grown
by slow evaporation of a solution of 16b in CHCl3 (Figure 3b,
Table S1). Heating at temperatures lower than 145 °C resulted
in no cyclised product formation. Such forcing reaction
conditions were required because of the neopentyl backbone,
in which the bulky vicinal substituents sterically shield the
carbon atom that the activated amine groups are attacking.64
Furthermore, the yield of the desired cyclised product was
significantly higher if tris-bromide 14 was used (16b obtained
in 48% yield). The yield of 16a from cyclisation using activated
triol 13 was 10%. Additionally, while Richman and Atkins
report that reaction solution concentrations for their
cyclisations must be finely tuned to prevent oligomer/polymer
formation,57 we have found that the poor kinetics of this
cyclisation reaction acts as an effective dilution.
We sought an alternative synthetic route to 19, because the
azide reduction described above gave inconsistent yields. To
this end, we reacted 16b with sodium tosylamide at 145 °C in
anhydrous DMF to give the tosylamide 18 (Scheme 4). The
formation of 18 was confirmed by 1H NMR and 13C NMR
spectroscopy, which showed the aromatic and aliphatic
Figure 3 – a) ORTEP plot of the X-ray crystal structure of 19ꢀ3HBr at 50% probability.
Bromine and hydrogen atoms have been omitted for clarity. b) ORTEP plot of the X-ray
After preparing the 1,5-diazacycloctane mesocycles 16a and
16b, we then sought to introduce an amine functionality onto
the remaining arm. We have adopted two approaches to
aminating 16a and 16b (Scheme 4). In the first approach, we
reacted the 1,5-diazacyclooctane mesocycles 16a and 16b with
crystal structure of 16b at 50% probability. N-Tosyl groups and hydrogen atoms have
been omitted for clarity.
Figure 4 – a) 1H NOE Spectrum of the 19 irradiated at 1.72 ppm; b) 1H Spectrum of the
19; c) 1H Spectrum of 1b; d) ROESY Spectrum of 1b irradiated at 1.63 ppm.
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bind the metal in a pseudo-tetrahedral fashion. We therefore
probed the solution behaviour of 19 further. 1H NOE NMR
studies on 19 (Figure 4, prepared by deprotonation of 19ꢀ3HBr
with KOH) were performed. The NOE spectra, with irradiation
of the multiplet at 1.70 ppm (corresponding to the central CH2
of the propylene linker (CH2-CH2-CH2)), showed that this -CH2-
displayed through space coupling to all other protons in the
molecule. Of note is the through-space coupling to both the
CH3 group and CH2NH2 of the primary amine, indicating that
the central CH2 of the propylene linker can ‘see’ both faces of
the mesocycle. This demonstrated that 19 retains a high
degree of flexibility in solution and indicated that
sufficiently flexible to bind metals in the desired manner.
1 would be
We attempted to methylate 19
tetramethylated triamine product 1a under Eschweiler-Clarke
conditions.59 19
3HBr was refluxed in formic acid in the
ꢀ3HBr to give the
resonances expected after the inclusion of the third
tosylamide functionality. ESI-MS also confirmed the formation
of 18 (m/z = 620.1931 for C29H37N3O6S3; expected m/z =
620.1923). All N-tosyl groups were then cleaved by treatment
ꢀ
presence of an excess of formaldehyde. From this reaction we
1
identified a mixture of products (at least 4) by H NMR, none
with 33% HBr/acetic acid to give the triamonium salt 19ꢀ3HBr
of which could be attributed to the desired peralkylated
product, while suggesting that all of the starting material
in a 10% yield. The yield of the deprotection step when conc.
H2SO4 was used instead of HBr/acetic acid was significantly
higher at 50%. This corresponds to an overall yield of 20%,
much improved on the overall yield of 4% when HBr/acetic
acid was used for deprotection.
19
intermediate imine that formed upon initial reaction between
the amine groups in 19 3HBr and formaldehyde, was not fully
reduced prior to a secondary reaction between the imine and
one of the other adjacent amine groups of the triamine 19
ꢀ3HBr had been consumed. We postulated that an
ꢀ
Single crystals of 19ꢀ3HBr suitable for X-ray diffraction were
obtained by diffusing ethanol into a solution of 19ꢀ3HBr in
water.
.
This resulted in the formation of aminal containing cyclic
amines rather than the desired permethylated product 1a. To
overcome this we attempted several reductive aminations
This was an important achievement as we wanted to
understand the structure and structural flexibility of our
mesocyclic ligands. Crystal data and refinement parameters
are shown in Table S1. Analysis of the crystal structure of
utilising more powerful reducing agents. 19ꢀ3HBr was refluxed
with an excess of formaldehyde and acetic acid in the presence
of stronger reductants (NaBH4, KBH4, or zinc). Unfortunately
1
similar H NMR spectra, indicative of aminal formation, were
19ꢀ3HBr (Figure 3a) showed that the DACO ring in 19ꢀ3HBr
displayed a boat-chair conformation. All bond lengths were in
agreement with those previously reported for diprotonated
DACO rings.65 Unusually, when compared to the other crystal
structures we obtained (vide infra) and those previously
reported in the literature for a diprotonated DACO moiety,65
obtained in all cases. Unfortunately, permethylation of
19ꢀ3HBr was also not possible using methyl tosylate or
iodomethane as we consistently obtained over-alkylated
products, in the presence of the desired product 1a (according
to ESI-MS and 1H NMR), that were not separable by column
chromatography.
the nitrogen lone pairs in 19ꢀ3HBr are located on opposite
faces of the ring. This arrangement would disfavour complex
formation. We reason that this occurs as it allows for the
maximum separation of the two positively charged nitrogen
atoms.
Fortunately, however, we found that we were able to alkylate
19ꢀ3HBr using benzyl bromide. The reaction of 19ꢀ3HBr with
19ꢀ3HBr
1.531
1.506
1.495
-
16b
[1bꢀH]PF6
1.531
[1bꢀ2H](OTf)2
1.535
Mean Cyclic C-C / Å
Mean C-N1 / Å
1.532
1.480
1.477
-
1.484
1.475
Mean C-N2 / Å
1.514
1.519
Mean C-N3 / Å
1.477
1.534
N4-N8 Distance / Å
C3-N1-C5 Fold Angle / °
C7-N2-C9 Fold Angle / °
3.6325(2)
N/A
2.8572(1)
115.369(2)
116.590(2)
2.6906(1)
111.408(2)
111.466(2)
2.8003(1)
113.050(3)
113.569(3)
N/A
Table 1 – Selected bond lengths and angles for the reported crystal structures.
Scheme 5 - Preparation of 1b and [CuI(NCCH3)(1b)](OTf).
In order to promote the formation of pseudo-tetrahedral
complexes, we required that
1 displayed the ability to form an
alternative boat-chair conformation analogous to that shown
exactly four equivalents of benzyl bromide in the presence of
by 16b (Figure 3b), where the nitrogen atoms are primed to
excess base (Na2CO3) gave the tetra-alkylated product 1b
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Similarly, single crystals of [1b
ꢀ
2H](OTf)2 (Figure 5b) were
obtained after layering of a wet CH3CN solution of 1b and
Zn(OTf)2 with Et2O. The crystal structures shown in Figure 5
unambiguously demonstrate that the cyclic amine was
protonated before the acyclic amine, as would be expected
based on their reported higher basicity.66 Selected bond
lengths and angles for these structures, as well as those in
Figure 3, are shown in Table 1.
(Scheme 5). Analysis of the 1H NMR of 1b showed the
appearance of two new peaks at 3.64 ppm compared to 19
,
corresponding to the benzyl CH2 groups on the aliphatic
amine.
The structure of [1b
ꢀ
H]PF6 consists of a discrete 1b
ꢀ
H+ cation
boat/chair
Furthermore, a multiplet at 7.4 ppm was observed, which
corresponds to the phenyl groups of the benzylic
functionalities. A peak in the ESI-MS was observed at m/z =
518.3534 (expected m/z = 518.3535 for C36H44N3), confirming
and a PF6 anion. The DACO ring adopts
a
conformation, and has a C-N-C fold angle of 111°. The average
cyclic C-C bond length remains similar to those found for
19ꢀ3HBr and 16b, (~1.5 Å). Protonation of N2 results in a
longer mean C-N2 bond length (1.514 Å) when compared to
the mean C-N1 bond length (1.484 Å), which is in agreement
the identity of 1b. The reaction between 19
bromide did not yield over-alkylated quaternised amine
products, whereas the reaction between 19 3HBr and
ꢀ3HBr and benzyl
ꢀ
with the C-N bond lengths discussed above for 19
16b. The N1-N2 distance for [1b H]PF6 is 2.69 Å, comparable to
that measured for 16b and significantly shorter than that
measured for 19 3HBr suggesting that monoprotonation of
the DACO ring allows for the nitrogen atoms to be in closer
proximity. The structure of [1b 2H](OTf)2 consists of a discrete
1b
2H+ cation and two triflate anions. After protonation of N2
and N3 (rather than N1), the structure retains the same
boat/chair conformation as in [1b H]PF6. In the structures of
both [1b H]PF6 and [1b 2H](OTf)2 the C-N-C fold angle is
ꢀ3HBr and
iodomethane did. We ascribe this difference in reactivity to
the steric bulk of the benzyl functionality retarding the rate of
the quaternisation reaction compared to methyl
functionalities. This provides a strong indication that the
benzyl functionalised ligand 1b will have a sterically protected
metal binding pocket.
ꢀ
ꢀ
ꢀ
ꢀ
Similar to 19ꢀ3HBr we assessed the solution flexibility of 1b
ꢀ
(Figure 4) with 1H Rotating-frame Overhauser Effect
Spectroscopy (ROESY) NMR. Irradiation of the central CH2 of
the propylene linker CH2 of the mesocycle at 1.63 ppm showed
through-space coupling to all of the other protons within the
DACO ring, as well as the benzyl CH2 groups and, importantly,
the exo-cyclic CH3 and CH2 groups. This demonstrated that
although we have alkylated all amine groups in 1b, the
molecule retains is structural flexibility, and should bind metals
in the desired pseudo-tetrahedral geometry.
ꢀ
ꢀ
comparable to both previously reported protonated DACO
moieties58, 65, 67, 68 as well as metal complexes containing the
DACO moiety.35 Furthermore, the bond lengths and angles
were found to be in the region of those previously reported.
This suggests that alkylation of the DACO ring at the C2, N1
and N2 positions should not hinder complex formation.
The 1H NMR of the crystals of [1b
ꢀH]PF6 and [1bꢀ2H](OTf)2 are
shown in Figure 6 and were assigned in conjunction with the
corresponding heteronuclear single quantum coherence
(HSQC) and heteronuclear multiple bond correlation HMBC
spectra (See supporting information, Figures S30-35). The 1H
Figure 5 – a) X-ray crystal structure of [1bꢀH]PF6. Ellipsoids are shown at the 50%
probability level. Only refined hydrogen atoms are shown. Counter ions have been
omitted for clarity. b) X-ray crystal structure of [1bꢀ2H](OTf)2. Ellipsoids are shown at
the 50% probability level. Only refined hydrogen atoms are shown. Counter ions have
been omitted for clarity.
NMR of the freebase 1b and of [1bꢀH]PF6 are shown in Figure
6a and 6b respectively. The spectra show that upon
protonation at N2 (Figure 6b), the apparent singlet at 3.59
ppm arising from H6/6’ in 1b resolves into the pair of doublets,
at 3.84 and 3.65 ppm in [1bꢀH]PF6. The coupling constant (~13
Hz) indicates that these doublets are a result of geminal
coupling and no 3J N-H coupling is observed. The difference
between these chemical shifts (~0.2 ppm) is a result of the
relative axial/equatorial arrangement of these diastereotopic
protons, arising from a change in local magnetic anisotropy
brought about by protonation. An equivalent resolution of
signals is observed after protonation at N3 (Figure 6c), H7/7’ are
resolved into a pair of signals at 4.60 and 4.32 ppm. The
Figure 6 – a) 1H NMR spectrum of 1b, 400 MHz, CD3CN; b) 1H NMR spectrum of
[1bꢀH]PF6, 600 MHz, CD3CN; c) 1H NMR spectrum of [1bꢀ2H](OTf)2, 600 MHz, CD3CN.
Crystal Structures of both the monoprotonated and
diprotonated congeners of 1b were obtained (Figure 5, Table
S1). Serendipitously, single crystals of [1bꢀH]PF6 (Figure 5a)
precipitated after layering a reaction mixture of 1b, CuCl2 and
doublet at 4.60 has a coupling constant (~14 Hz) indicative of
geminal coupling only, whereas the multiplet at 4.32 is split
KPF6 in wet acetonitrile (CH3CN) with diethylether (Et2O).
6 | J. Name., 2012, 00, 1-3
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Encouragingly, no 2:1 (ligand:metal) species were observed in
the ESI-MS spectra. These observations suggest that 1b binds
the metal centre as a tripod yielding a four-coordinate
complex. Unfortunately, work-up of this reaction mixture did
not yield the desired complex. Consequently, the same
reaction was repeated utilising dichloromethane (DCM) as the
reaction solvent (CH3CN was eliminated from the reaction as
we suspect the complex is unstable in CH3CN). Figure 8 shows
1
the H NMR spectrum of the yellow solid obtained from the
DCM reaction mixture. The signal assignments shown in Figure
8 were made in combination with HSQC spectra (Figure S38).
The splitting of the diastereotopic signals resembles that
observed after protonation of 1b, however, the new material
displayed resonances distinct from those of 1b, [1b
ꢀH]PF6, and
[
1b
ꢀ
2H](OTf)2, indicating complexation of CuI by 1b had
3
further, possibly by J HNCH coupling. The overlapping signals
for H3/3’ (2.46 - 2.39 ppm) and H4/4’ (1.54 ppm) in 1b are
resolved into pairs of multiplets for H3/3’ (3.10 and 2.74 ppm)
occurred. Notably, a resonance at 2.42 (corresponding to 3
protons) was observed. We assigned this to a coordinated CH3-
CN ligand (uncoordinated CH3CN = 2.01 ppm). This assignment
was confirmed by the presence of a high-field signal at 2.9
ppm in the 13C NMR, typical of a nitrile methyl group.
Integration of the resonances in Figure 8 showed a 1:1 ratio of
1b to CH3CN, and thus a coordination number of four. This is
further corroborated by our ESI-MS data that indicated the
formation of [CuI(NCCH3)(1b)]+. Complexes containing the
DACO moiety tend to form four or five coordinate complexes
(vide supra)33-36, 38, 42, 43, 45-52 and six coordinate complexes are
unprecedented. Furthermore, Cu(I) complexes prefer to sit in
tetrahedral geometry. We are therefore confident in our
assignment of this spectrum as a pseudo-tetrahedral species
[CuI(NCCH3)(1b)]+.
and H4/4’ (2.07 and 1.74 ppm) in [1bꢀH]PF6. As above, the
difference in chemical shift (~0.4 ppm) for these pairs of
diastereotopic protons is a result of their relative axial/
equatorial arrangement. Protonation at N3 (Figure 6c)
maintains the splitting patterns observed for protons
associated with the ring, although their chemical shifts differ
1
slightly. Notably, a H Nuclear Overhauser Effect Spectroscopy
(NOESY) experiment (See supporting information, Figures S33)
indicates no through space coupling between H1 and H3/3’, in
contrast to analogous experiments conducted on 19 and 1b
(Figure 4). Furthermore, only through space coupling is
observed to one of the diastereotopic pair H2/2’ whereas
coupling to both can be observed in a selective 1H-NOSEY of 1b
(See supporting information Figure S29). We postulate that
this is most likely due to
a slight reduction in the
conformational flexibility of the DACO ring upon protonation.
Figure 7 – ESI-MS spectrum of [CuI(NCCH3)(1b)]+. Inset shows the predicted isotopic
pattern.
The alkylated triamine 1b was reacted with [CuI(NCCH3)4](OTf)
in anhydrous CH3CN. Upon addition of a solution of 1b to the
copper salt an immediate colour change from colourless to
Figure 8 – 1H NMR spectrum of [CuI(NCCH3)(1b)]+, CDCl3, 400 MHz.
Conclusion
We have outlined several synthetic routes towards our target
ligand 1, a novel, mesocyclic, tripodal, triamine ligand. Our
yellow was observed. ESI-MS analysis of an aliquot of this
reaction mixture indicated a peak at m/z = 621.2963 with an
isotopic pattern typical of copper, which we assign as
modular approach to the synthesis of
library of synthons that will allow us to tune the reactivity of
metal complexes of . Importantly, we have developed and
optimised the synthesis of the mesocyclic fragment in
1 has provided us with a
1
[CuI(NCCH3)(1b)]+ (expected m/z
= 621.3018, Figure 7).
1,
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utilizing a Richman-Atkins cyclisation to form 16. We have layer was washed with brine (3 x 100 mL) then dried over
outlined multiple routes to the further derivatisation of 16 to MgSO4. The solvent was removed in vacuo to give a colourless
ultimately give the triamine skeleton 19, which we have shown oil. The crude product was purified by column chromatography
can be alkylated to give our target ligand 1b. We have probed (Hexane: EtOAc, 4:1) to give
the conformational flexibility of both 19 and 1b using a solid.
7 (7.2 g, 64%) as an off-white
combination of NMR and x-ray crystallography studies. While 1H NMR (400 MHz, CDCl3) δ = 0.93 (s, 3H), 2.47 (s, 6H), 3.26 (s,
the x-ray crystal structure obtained for 19 displayed an 2H), 3.78 (s, 4H), 7.38 (d, J=8.1, 4H), 7.76 (d, J=8.1, 4H).
unusual configuration, we have shown that it maintains a high 13C NMR (101 MHz, CDCl3) δ = 17.0, 21.8, 39.7, 53.6, 70.7,
degree of flexibility in solution. Additionally, we have 128.0, 130.1, 132.1, 145.4.
ν
max /cm-1: 3068, 2981, 2951, 2927, 2895, 2530, 2220, 2111, 1980,
structural flexibility in solution, protonation at the N1 position 1925, 1809, 1654, 1597, 1495, 1471, 1451, 1410, 1399, 1368, 1289,
demonstrated that while 1b maintains a high degree of
results in a loss of conformational flexibility. We have also
been able to prepare [CuI(NCCH3)(1b)]+ demonstrating the
potential of 1b to form pseudo-tetrahedral metal complexes.
Present work in our lab is focussed on preparing further
1211, 1191, 1175, 1121, 1098, 1034, 1017, 964, 934, 917, 893, 866,
840, 831, 814, 804, 794, 706, 664, 629, 603, 568, 553.
HRMS (m/z -ESI): Found: 476.0961 (M+ + Na predicted mass:
476.0926 C19H23N3O6S2Na )
derivatives of ligand
1, and preparing metal-oxo species
derived from low-valent copper and nickel complexes of 1b
.
Synthesis
of
3-(azidomethyl)-3-methyl-1,5-ditosyl-1,5-
diazocane (8)
Experimental Details
16a (800 mg, 1.3 mmol) was dissolved in diethylene glycol (25
mL). Sodium azide (252 mg, 3.9 mmol) was added and the
reaction mixture was stirred at 135 °C for 5 days. The reaction
mixture was cooled and diluted with water (25 mL). The
resulting emulsion was extracted with DCM (3 x 25 mL). The
organic layer was collected and dried over MgSO4 and the
solvent removed in vacuo. The crude product was purified by
column chromatography (EtOAc: Hexane: Triethylamine,
All reagents and solvents were purchased from commercial
sources and used as received, unless otherwise stated. All
reactions with air-sensitive materials were conducted under an
inert atmosphere using either standard Schlenk techniques or
a nitrogen atmosphere glove box. Anhydrous DMF and CH3CN
were purchased and used without further purification.
Anhydrous THF and Et2O were dispensed through an
Innovative Technology PureSolv EN solvent purification system
and deoxygenated by purging with argon. Ammonium formate
was recrystalised from ethanol before use. CDCl3 was dried
and de-acidified by stirring and subsequently storing over 4 Å
molecular sieves and basic alumina. 1H and 13C NMR were
recorded on either a Bruker DPX 400 MHz or Bruker Avance II
600 MHx spectrometer. ESI mass spectra were acquired using
a Micromass time of flight spectrometer (tof), interfaced to a
Waters 2690 HPLC. Fourier-Transform Infrared spectra were
recorded using a Perkin-Elmer Spectrum 1 FT-IR spectrometer.
Thin-layer chromatography (TLC) was performed with
Analytical Chromatography alumina sheets coated with silica
gel (0.25mm). Spots were visualised under UV light. Flash
column chromatography was conducted with Fluka Silica Gel
45:45:10) to give azide 8 (280 mg, 44%) as a white powder.
1H NMR (400 MHz, CDCl3) δ = 1.15 (s, 3H), 1.82 - 2.02 (m, 2H),
2.46 (s, 6H), 2.96 - 3.29 (m, 8H), 3.54 (s, 2H), 7.36 (d, J=8.1,
4H), 7.68 (d, J=8.1, 4H).
13C NMR (101 MHz, CDCl3) δ = 17.0, 21.8, 25.7, 39.7, 53.6, 68.0,
70.7, 128.0, 130.1, 132.1, 132.1, 145.4
ν
max /cm-1: 1156, 1335, 2103.
HRMS (m/z -ESI): Found: 492.1730 (M+ + H. C22H30N5O4S2
predicted mass: 492.1695).
Synthesis of (2,2,5-trimethyl-1,3-dioxan-5-yl)methanamine
(9)
60 Å (230-400mesh). Compounds 3 54 4 55 5 56 6 56 1252 and
, , ,
,
1361 were synthesised according to literature procedures.
Compounds 969 and 1462 were prepared by modified literature
procedures as described below. X-ray diffraction refinement
details and refinement parameters along with all NMR spectra
are provided in the supporting information.
Azide
5 (3.52 g, 19 mmol) and ammonium formate (4.87 g, 76
mmol) were added to degassed methanol (100 mL) and stirred
until the ammonium formate completely dissolved. 5% Pd/C
(365 mg, 10% wt) was then added and the reaction mixture
stirred for 3 hours at room temperature. The reaction mixture
was then filtered through a pad of Celite and the methanol
removed in vacuo. The residue was taken up into distilled
water (10 mL) and washed with Et2O (3 x 20 mL). The aqueous
layer was then basified with KOH (10 g) and extracted with CH-
3CN (5 x 10 mL). The organic layer was collected and dried over
Synthesis of 2-(azidomethyl)-2-methylpropane-1,3-diyl bis-
tosylate (7)
6
(3.53 g, 24 mmol) was dissolved in THF (50 mL) and added to
a solution of NaOH (9 g) in water (9 mL). Tosyl chloride (11.6 g,
61 mmol) in THF (10 mL) was added dropwise with vigorous
stirring. The reaction mixture was stirred for a further 16 h at
room temperature. The mixture was diluted with water (100
mL) and then extracted with CHCl3 (3 x 50 mL). The organic
MgSO4. The solvent was removed in vacuo to give
9 (1.50 g,
50%) as a colourless oil.
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1H NMR (600 MHz, CDCl3) δ = 0.80 (s, 3H), 0.99 (s, 2H), 1.38 (s, and the solution stirred until the evolution of hydrogen gas
3H), 1.42 (s, 3H), 2.78 (s, 2H), 3.57 (d, J= 11.7, 2H), 3.62 (d, J= ceased. The reaction vessel was transferred to a Schlenk line
11.7, 2H).
13C NMR (151 MHz, CDCl3) δ = 17.9, 21.0, 26.5, 34.2, 46.3, 67.2, (bromomethyl)-2-methylpropane 14 (3.8 g, 12.3 mmol) in
97.8. anhydrous DMF (50 mL) was then added dropwise by cannula.
HRMS (m/z -ESI): Found: 160.1342 (M+ + H. C8H17NO2 The reaction mixture was heated at 145 °C for a further 24
and heated at 145 °C for 1 hour. A solution of 1,3-dibromo-2-
predicted mass: 160.1338).
hours. The DMF was removed by distillation and the residue
was taken up into Et2O (150 mL). The Et2O solution was
Synthesis of 1,3-dibromo-2-(bromomethyl)-2-methylpropane washed with water (3 x 50 ml) and brine (3 x 50 ml) and dried
(14)
over MgSO4. The solvent was removed in vacuo. The crude
product was purified by recrystalisation in the minimum
13 (46 g, 79 mmol) and NaBr (83 g, 790 mmol) were heated in amount of boiling methanol. The product was collected by
diethylene glycol (250 mL) at 145 °C for 18 hours. After vacuum filtration and washed with cold methanol (3 x 10 mL)
cooling, the reaction mixture was diluted with deionised water to give 16b as an off white solid (3.1 g, 48%).
(250 mL), mixed vigorously, then transferred to a separating 1H NMR (400 MHz, CDCl3) δ = 1.28 (s, 3H), 1.96 (m, 2H), 2.46 (s,
funnel. The more dense oil (14) was collected. The aqueous 6H), 3.09 - 3.28 (m, 8H), 3.64 (s, 2H), 7.35 (d, J=7.9, 4H), 7.69
layer was washed with Et2O (3 x 50 mL). The organic extracts (d, J=8.0, 4H),
were combined with the oil and dried over MgSO4. The solvent 13C NMR (101 MHz, CDCl3) δ = 21.1, 23.1, 28.1, 39.1, 43.4, 49.1,
was removed in vacuo to give 14 (18.5 g, 76%) as a pale yellow 53.8, 127.0, 129.4, 134.3, 143.4.
oil.
1H NMR (400 MHz, CDCl3) δ = 1.29 (s, 3H), 3.50 (s, 6H).
νmax /cm-1: 547, 572, 653, 706, 755, 800, 845, 1018, 1089,
1156, 1260, 1306, 1335, 1383, 1457, 1494, 1598, 2860, 2870,
2924, 2963.
Synthesis of (3-methyl-1,5-ditosyl-1,5-diazocan-3-yl)methyl HRMS (m/z -ESI): Found: 551.0652 (M+ + Na. C22H29N2O4S2Br
tosylate (16a)
predicted mass: 551.0650).
Melting point: 140-143°C
In a glove box, N,N'-(propane-1,3-diyl)bis-tosylate 12 (3.80 g,
9.93 mmol) was dissolved in anhydrous DMF (100 mL). NaH, as Synthesis
of
(3-methyl-1,5-ditosyl-1,5-diazocan-3-
a 60% dispersion in mineral oil (1.0 g, 20 mmol) was added and yl)methanamine (17)
the solution stirred until the evolution of hydrogen gas ceased.
The reaction vessel was transferred to a Schlenk line and
8 (0.280 g, 0.57 mmol) and ammonium formate (0.144 g, 2.28
heated at 145 °C for 1 hour. A solution of 13 (5.786 g, 9.9 mmol) were added to degassed methanol (100 mL) and stirred
mmol) in anhydrous DMF (60 mL) was then added dropwise by until the ammonium formate completely dissolved. 5% Pd/ C
cannula. The reaction mixture was then heated at 145 °C for a (0.056 g, 20% wt) was then added and the reaction mixture
further 24 hours. The DMF was removed by distillation and the stirred for 18 h at room temperature. The reaction mixture
residue was taken up into CHCl3. The organic layer was washed was filtered through a pad of celite and the methanol removed
with water (3 x 50 mL) and brine (3 x 50 mL) then dried over in vacuo. The residue was taken up into distilled water (10 mL)
MgSO4. The solvent was removed in vacuo. The crude product and washed with Et2O (3 x 20 mL). The aqueous layer was
was purified by column chromatography (EtOAc: Hexane: basified with KOH (10 g) and extracted with CH3CN (5 x 10 mL).
Triethylamine, 35:60:5) to give 16a (591 mg, 10%) as an off- The organic layer was collected and dried over MgSO4. The
white crystalline solid.
solvent was removed in vacuo to give 17 (0.140 g, 53%).
1H NMR (600 MHz, CDCl3) δ = 1.14 (s, 3H), 1.92 (m, 2H), 2.44 (s, 1H NMR (600 MHz, CDCl3) δ = 1.06 (s, 3H), 1.87 (m, 2H), 2.43 (s,
6H), 2.45 (s, 3H), 3.11- 3.21 (m, 8H), 4.05 (s, 2H), 7.32 (d, J=8.0, 6H), 2.70 (s, 2H), 2.93 (d, J=15.1, 2H), 3.08-3.25 (m, 4H), 7.31
4H), 7.36 (d, J=8.1, 2H), 7.62 (d, J=8.2, 4H), 7.84 (d, J=8.3, 2H).
(d, J=8.2, 4H), 7.66 (d, J=8.2, 4H).
13C NMR (151 MHz, CDCl3) δ = 21.6, 21.7, 21.8, 28.8, 39.8, 49.7, 13C NMR (151 MHz, CDCl3) δ = 21.5, 28.1, 40.4, 47.8, 49.8, 53.5,
53.2, 76.4, 127.5, 128.2, 130.0, 130.0, 132.7, 134.9, 143.9, 127.4, 129.8, 135.1, 143.6,
145.0.
max /cm-1: 1156, 1174, 1307, 1336
ν
max /cm-1: 1151, 1327, 3151, 3310,
HRMS (m/z -ESI): Found: 466.1833 (M+ + H. C22H32N3O4S2
ν
HRMS (m/z -ESI): Found: 643.1580 (M+ + Na. C29H36N2O7S3Na predicted mass: 466.1790).
predicted mass: 643.1582).
Melting point: 86-88°C
Synthesis
of
N-((3-methyl-1,5-ditosyl-1,5-diazocan-3-
yl)methyl)tosylamide (18)
Synthesis
of
3-(bromomethyl)-3-methyl-1,5-ditosyl-1,5- 16b (9.0 g, 17 mmol) and sodium tosylamide (9.85 g, 51 mmol)
were heated at 145°C in anhydrous DMF (200 mL) for 4 days.
diazocane (16b)
Once the reaction mixture had cooled, the solvent was
In a glove box, N,N'-(propane-1,3-diyl)bis-tosylate 12 (4.7 g, removed in vacuo. The crude reaction mixture was
12.3 mmol) was dissolved in anhydrous DMF (200 mL). NaH, as recrystalised in the minimum amount of boiling methanol. The
a 60% dispersion in mineral oil (0.985 g, 24.6 mmol) was added resulting white precipitate was collected by filtration and
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washed with cold methanol to give 18 (8.0 g, 76%). The crude
product was then recrystalised from acetone.
General procedure for the generation of the Freebase 19.
1H NMR (400 MHz, CDCl3) δ = 1.09 (s, 3H), 1.85 (m, 2H), 2.41 (s,
3H), 2.43 (s, 6H), 2.7 - 3.5 (m, 8H), 3.48 (d, J=5.0, 2H), 7.27 – 19
7.37 (m, 4H), 7.63 (d, J=8.0, 2H), 7.77 (d, J=8.0, 2H).
ꢀ
3HBr was dissolved in the minimum amount of deionised
water. NaOH (10 e.q) and toluene (~20 mL) were then added.
13C NMR (151 MHz, CDCl3) δ = 21.7, 22.1, 28.5, 39.8, 48.1, 50.7, The toluene solution was then heated under reflux with a
127.0, 127.6, 129.9, 130.0, 134.4, 137.5, 143.2, 144.1.
Dean-Stark trap for 24 hours. After cooling, the any insoluble
νmax /cm-1: 3290, 2925, 2286, 2050, 1980, 1598, 1494, 1458, material was removed by filtration and the solvent removed
1382, 1328, 1305, 1216, 1153, 1089, 1017, 967, 847, 811, 752, under vacuum to give 19 as a colourless oil.
739, 705, 653, 567.
HRMS (m/z -ESI): Found: 620.1931 (M+ + H. C29H37N3O6S3 2.58 (s, 2H), 2.58 (d, J=14.1, 2H), 2.80 (d, J=14.1, 2H), 2.84 -
1H NMR (600 MHz, CDCl3) δ = 0.76 (s, 3H), 1.65 - 1.77 (m, 2H),
predicted mass: 620.1931).
Melting point: 110-114°C
3.02 (m, 4H),
13C NMR (151 MHz, CDCl3) δ = 20.98, 28.49, 38.59, 49.08,
49.2053.79.
General Procedure for the Deprotection of N-Tosyl Protected νmax /cm-1: 3295, 2903, 2862, 1595, 1459, 1393, 1365, 1293,
Amines to give 19
ꢀ
3HBr Using 33% HBr in Acetic Acid and 1230, 1146, 1069, 880, 845, 810, 769, 747, 692, 639, 623, 616,
Phenol
609, 601, 593, 585, 578, 570, 563, 555.
HRMS (m/z -ESI): Found: 158.1674 (M+ + H. C8H20N3 predicted
A solution of 33% HBr in acetic acid (1 mL) was added to the mass: 158.1652).
protected amine (0.25 mmol,) and phenol (1 g). The reaction
mixture was heated at 90 °C for 16 hours. The temperature Synthesis of N,N-dibenzyl-1-(N’,N’’-1,5-dibenzyl-3-methyl-1,5-
was lowered to 60 °C and 33% HBr in acetic acid (1 mL) was diazocan-3-yl)methanamine (1b)
added and the reaction mixture heated for a further 5 hours.
The reaction mixture was cooled in the freezer at -40°C 19
overnight. The resulting white precipitate was collected by Benzyl bromide (1.88 g, 1.3 mL, 11.0 mmol) and K2CO3 (7.6 g,
filtration and washed with Et2O (5 mL) To give 19 3HBr as an 55 mmol) were added. The reaction mixture was heated at
off white solid (~10%). Crystals of 19 3HBr suitable for X-ray reflux for 16 hours. After this the insoluble material was
diffraction were grown by slow diffusion of ethanol into a removed by filtration and the solvent was removed in vacuo.
ꢀ3HBr (1.1 g, 2.7 mmol) was suspended in CH3CN (30 mL).
ꢀ
ꢀ
solution of 19
ꢀ
3HBr in water.
The resulting yellow oil was dissolved in H2O (5 mL) and added
to a suspension of sodium hydroxide (5 g) in toluene (50 mL).
1
3HBr: H NMR (400 MHz, D2O) δ = 1.24 (s, 3H), 2.23 (m, The toluene solution was then heated under reflux with a
19ꢀ
2H), 3.14 (s, 2H), 3.46 – 3.24 (m, 8H).
Dean-Stark trap for 24 hours. After cooling, the insoluble
material was removed by filtration and the solvent removed
under vacuum to give 1b (0.988 g, 70%) as a white solid.
13C NMR (151 MHz, D2O) δ = 18.8, 19.2, 42.6, 43.8, 45.5, 47.5.
HRMS (m/z -ESI): Found: 158.1695 (M+ + H. C8H20N3 predicted 1H NMR (600 MHz, CDCl3) δ = 0.95 (s, 3H), 1.55 - 1.70 (m, 2H),
mass: 158.1652).
2.31 - 2.56 (m, 6H), 2.58 (s, 2H), 2.71 (d, J=14.1, 2H), 3.64 (s,
4H), 3.74 (m, 4H), 6.57 - 7.93 (m, 20H),
13C NMR (151 MHz, CDCl3) δ = 22.2, 28.3, 42.5, 54.5, 60.7, 61.6,
Melting Point: Decomposes at ~255°C
General Procedure for the Deprotection of N-Tosyl Protected 62.1, 65.0, 126.4, 126.6, 127.9, 127.9, 128.4, 129.1, 139.9,
Amines to give 19
ꢀ
3HBr Using Concentrated H2SO4
141.9.
νmax /cm-1: 3084, 3063, 3025, 2965, 2949, 2939, 2922, 2888,
Concentrated H2SO4 (1 mL) was added to the protected amine 2814, 2780, 2711, 2049, 1940, 1870, 1803, 1602, 1585, 1493,
(~1 mmol). The reaction mixture was heated under argon at 1468, 1451, 1357, 1332, 1302, 1283, 1243, 1212, 1192, 1176,
160 °C for 1 hour. The reaction mixture was cooled to 0°C in an 1145, 1115, 1090, 1071, 1062, 1045, 1027, 984, 972, 935, 922,
ice-bath and ethanol (10 mL) followed by Et2O (8 mL) was 906, 888, 861, 838, 821, 760, 744, 731, 695, 632, 613, 583,
added dropwise. The reaction mixture was cooled in the 569, 555.
fridge at 2 °C for 16 hours. The resulting brown precipitate was HRMS (m/z -ESI): Found: 518.3530 (M+ + H. C36H44N3 predicted
collected by filtration onto a pad of celite. The precipitate and mass: 518.3535).
the celite were then transferred to a round-bottomed flask to Melting point: 88-90°C
which water (10 mL) and activated carbon were added. The
mixture was refluxed for 1.5 hours. The insoluble materials NMR Data for [1bꢀH]PF6
1H NMR (600 MHz, CD3CN), δ =0.23 (s, 3H), 1.69-1.77 (m, 2H) 2.03-
were removed by filtration and the solvent was removed
under reduced pressure. The resulting brown residue was
taken up into 48% hydrobromic acid (1 mL) and to this solution
2.10 (m, 2H), 2.34 (s, 2H), 2.52 (d, J = 14.2 Hz, 1H), 2.74-2.66 ( m,
4H), 2.99-3.13 (m, 2H), 3.84 (d, J = 13.3 Hz, 2H), 3.65 (d, J = 14.7 Hz,
ethanol (20 mL) was added dropwise. The resulting white 2H), 7.27-7.45 (m, 20H).
precipitate, 19
3HBr (~50%) was collected by filtration and 13C NMR (151 MHz, CDCl3) = 21.2, 21.4, 37.2, 56.7, 60.9, 61.7,
ꢀ
washed with cold Et2O (5 mL).
63.7, 129.4, 130.0, 130.0, 130.3, 131.7, 134.3, 140.4.
10 | J. Name., 2012, 00, 1-3
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M. Costas, K. Chen and L. Que Jr, Coord. Chem. Rev., 2000,
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NMR Data for [1bꢀ2H](OTf)2
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1H NMR (600 MHz, CDCl3) δ = 0.15 (s, 3H), 1.68-1.71 (m, 2H), 1.95-
1.98 (m, 2H), 2.52 (d, J = 14.5 Hz, 2H), 2.42 (d, J = 14.5 Hz, 2H), 2.65-
2.75 (m, 2H), 2.98-3.13 (m, 4H), 3.76 (d, J = 13.0 Hz, 2H), 3.82 (d, J =
13.1 Hz, 2H), 4.27-4.35 (m, 2H), 4.61 (d, J = 12.6 Hz, 2H), 7.23-7.69
(m, 20H).
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13C NMR (151 MHz, CDCl3) = 18.9, 20.8, 35.4, 55.7, 56.1, 59.1,
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133.7.
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Synthesis of [CuI(NCCH3)(1b)](OTf) (21)
In a glovebox, 1b (0.079 g, 0.15 mmol) and [CuI(NCCH3)4](OTf)
(0.063 g, 0.17 mmol) were stirred in anhydrous CH3CN (~5 mL)
for 10 minutes. The reaction mixture was then concentrated
under vacuum. Anhydrous CH3CN (1 mL) was added followed
by anhydrous Et2O (20 mL) giving an off-white precipitate. The
precipitate was collected by vacuum filtration and washed
with anhydrous Et2O (2 x 5 mL) to give [CuI(NCCH3)(1b)](OTf)
(0.045 g, 49%) as pale yellow solid.
10.
11.
12.
13.
14.
ESI-MS (m/z -ESI): Found: 619.0834 (M+ + K. C36H43N3Cu0K
predicted mass: 619.2390).
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Air sensitive compound, no melting point determined.
Synthesis of [CuI(NCCH3)(1b)](PF6) (22)
16.
17.
In a glovebox, 1b (0.050 g, 0.09 mmol) and [CuI(NCCH3)4](PF6)
(0.040 g, 0.1 mmol) were stirred in anhydrous DCM (2 mL) for
10 minutes. Anhydrous Et2O (15 mL) was added resulting in
the formation of a pale yellow precipitate. The supernatant
was decanted and the precipitate dissolved in the minimum
amount of DCM. The resulting solution was layered with
anhydrous Et2O and the product recrystalised to give 1b as
pale yellow needles (0.048 g, 65 %).
1H NMR (400 MHz, CDCl3) δ = 0.17 (s, 3H), 1.84-1.98 (m, 2H),
2.04-2.11 (m, 4H), 2.33 (d, J= 14.5 Hz, 2H), 2.42 (s, 3H), 2.55-
2.63 (m, 2H), 3.19 (d, J = 12.3 Hz, 2H), 3.43 (s, 4H), 3.50-3.63
(m, 2H), 3.96 (d, J = 12.3 Hz, 2H).
18.
19.
20.
21.
T. A. Betley, Q. Wu, T. Van Voorhis and D. G. Nocera,
Inorg. Chem., 2008, 47, 1849-1861.
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13C NMR (151 MHz, CDCl3) = 2.9, 23.8, 24.4, 30.9, 38.4, 59.2,
59.4, 61.7, 62.2, 67.1, 127.5, 128.4, 128.6, 129.3, 130.9, 131.6,
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Acknowledgements
This publication has emanated from research supported in part
by the European Union (FP7-333948) and a research grant
from Science Foundation Ireland (SFI/12/RC/2278). We thank
Dr. John O’Brien (NMR) and Dr. Brendan Twamley (XRD) for
technical support. Dr. Brendan Twamley acknowledges PRTLI
and ERDF for funding.
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L. Que, Acc. Chem. Res., 2007, 40, 493-500.
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J. Cho, H. Y. Kang, L. V. Liu, R. Sarangi, E. I. Solomon and
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