Synthesis of tetraphosphine macrocycles using copper(i) templates

Article abstract of DOI:10.1039/c6dt00758a

The synthesis of phosphine macrocycles is a relatively underdeveloped area and no standard synthetic routes have emerged. Accordingly, two general synthetic routes to tetradentate phosphine macrocycles were investigated. Both routes use Cu(i) ions as temp

Full text of DOI:10.1039/c6dt00758a

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Synthesis of Tetraphosphine Macrocycles Using Copper(I) Templates†
Bryan P. Nell, Charles D. Swor, E. Adrian Henle, Lev N. Zakharov, N. Ian Rinehart, Aditya Nathan, and
David R. Tyler*
Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, 97403, USA
E-mail: dtyler@uoregon.edu
KEYWORDS: phosphines; macrocycles; Cu(I) template; tetradentate ligands; ambiphilic secondary
phosphines
Abstract
The synthesis of phosphine macrocycles is a relatively underdeveloped area and no standard
synthetic routes have emerged. Accordingly, two general synthetic routes to tetradentate
phosphine macrocycles were investigated. Both routes use Cu(I) ions as template ions because,
unlike other metals such as Pd(II) and Pt(II), the Cu(I) ions can be removed from the macrocyclic
complex without degrading the macrocycle ligand. The first route involves the coupling of two
bidentate secondary phosphines bonded to Cu(I) using 1,3-dibromopropane or 1,4-dibromobutane.
Using this route, tetradentate phosphine macrocycles with either −(CH2)3OCH3 or Ph groups
bonded to the P atoms were synthesized. Macrocycle phosphines containing the –(CH2)3OCH3
groups were investigated for their potential water-solubility, but experiments showed these
phosphines were not water soluble. The second synthetic route involved the alkylation of an open-
chain, mixed tertiary-secondary, tetradentate phosphine coordinated to Cu(I). Following formation
of the macrocyclic ligand, the Cu(I) template was removed by reaction with aqueous KCN to yield
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the free macrocyclic phosphine. This route was demonstrated for the preparation of the
macrocyclic phosphine ligand 1,5,9,13-tetraphenyl-1,5,9,13-tetraphosphacycloheptadecane.
Following demetallation, this macrocyclic ligand was coordinated to Fe(II) and Co(II) to form the
corresponding macrocyclic phosphine complexes.
2

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Introduction
Almost 15% of worldwide natural gas reserves are contaminated with high levels of
dinitrogen (N2).1–3 Dinitrogen acts as a diluent in natural gas, lowering the energy density and
limiting the gas’s use as a fuel. In general, levels less than 4% N2 are required for natural gas used
as fuel.4 N2 and methane are difficult to separate because N2 is chemically inert and also because
methane and dinitrogen have similar physical properties. Industrial nitrogen rejection (the process
of removing nitrogen from natural gas) uses cryogenic distillation to separate the gases, but this
technique is energy-intensive and requires large capital costs, making it economically feasible only
for large gas fields.3 Recent efforts have focused on membranes for the separation.5,6
In previous work, we showed that complexes of the type trans-Fe(P2)2X2 (where P2 is a
water-soluble bidentate phosphine) can act as absorbents in aqueous solution for separating N2
from methane in a pressure-swing scheme (Scheme 1).7 Unfortunately, in prolonged tests of the
water-soluble trans-Fe(DMeOPrPE)2Cl2 complex in a pressure swing process over a continuous six-
week period, the phosphine ligands slowly dissociated from the complex (Figure 1; DMeOPrPE =
1,2-bis[(dimethoxypropyl)phosphino]ethane). The eventual product was Fe(DMeOPrPE)32+ (Figure
1),7,8 which has no open coordination sites available for nitrogen coordination, and so the pressure-
swing system eventually failed. To achieve a longer lasting absorbent, we decided to replace the
two bidentate phosphine ligands with a tetradentate phosphine macrocycle ligand. The binding
constants of macrocyclic ligands are very large (the “macrocycle effect”9), and the resulting Fe-
macrocycle complex should be considerably more robust than complexes with two bidentate
phosphines such as trans-Fe(DMeOPrPE)2Cl2.
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Scheme 1. Solution phase pressure-swing process for separating N2 from methane.
Figure 1. Degradation of Fe(DMeOPrPE)2Cl2 in water (DMeOPrPE = 1,2-
bis[(dimethoxypropyl)phosphino]ethane).
The synthesis of phosphine macrocycles is a relatively underdeveloped area and no general
synthetic routes to these molecules have emerged.10 One approach to macrocyclic phosphines is a
template synthesis in which two secondary bidentate phosphines are coordinated to a common
metal center and then covalently linked (Scheme 2). This approach has been reported to yield
macrocyclic complexes, typically using d8 square planar metal centers (Ni(II), Pt(II), Pd(II)) as
4

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templates.10–14 Unfortunately, when using these metal ions as the template, it is generally not
possible to separate the metal ions from the macrocyclic ligands without degrading the macrocyclic
ligand in the process. There are, however, several reports of Cu(I)-based template systems where
the Cu metal center has been successfully removed using either H2S or CN-.15,16 In this paper, we
report the synthesis of tetradentate phosphine macrocycles with hydrophilic groups using this
synthetic approach.
Scheme 2. Generic synthetic approach to tetradentate phosphine macrocycles using
templated bidentate secondary phosphines.
A second approach to the preparation of tetraphosphine macrocycles involves linking the
free ends of an open-chain tetradentate phosphine ligand bonded to a metal template. This method
was demonstrated once with a Ni(II) template (Scheme 3),14 and in this paper we extend the
method to the use of a Cu(I) template. Both macrocycle synthetic routes developed in this paper
are, in principle, general and should be useful for the preparation of tetradentate macrocyclic
phosphines beyond the ones reported here.
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Scheme 3. Preparation of a tetraphosphine macrocycle with a Ni(II) template using an open-chain
tetradentate phosphine ligand.14
Results and Discussion
Synthesis of the bidentate and tetradentate ligands. Secondary phosphines 1
and 2 were prepared as previously described by us (Scheme 4).17 Both 1 and 2 are clear, colorless,
viscous oils. To our knowledge, these are the first examples of hydrophilic secondary phosphines.
Note the reactions in Scheme 4 are not stereospecific, and the three expected stereoisomers
(R,R(meso); S,R; and R,S) were not separated. The ambiphilic methoxypropyl functional group
causes these ligands to be miscible in a wide range of solvents, from water to hexanes. Over-
alkylation of the primary phosphines in Scheme 4 is a concern, but monitoring the reactions by 31
NMR spectroscopy revealed that over-alkylation can be prevented by keeping the reaction
temperature at -78 °C. Furthermore, because of the extra molecular mass of the methoxypropyl
group, the desired product can be separated from any under- or over-alkylated products by
fractional vacuum distillation.
P
6

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Scheme 4. Synthesis of the hydrophilic secondary phosphines 1 and 2.
To investigate synthetic routes like that in Scheme 3 involving a linear tetradentate
phosphine, ligand 4 (Scheme 5) was prepared according to literature methods as a mixture of
stereoisomers by reduction of the corresponding bis-phosphinate (3).18 The related new ligand
with –(CH2)3OCH3 groups (6; Scheme 6) was prepared by an analogous route. Both 4 and 6 were
isolated as colorless, extremely viscous liquids. Unfortunately, ligand 6 was not water-soluble, and
preliminary testing of the products that formed in its reactions with Cu(I) salts showed that it
formed complexes that were also water-insoluble (and also very viscous liquids). In contrast, the
reaction of ligand 4 with Cu(I) salts gave solid products (see the next section); for experimental
convenience it was therefore decided to pursue linear tetradentate macrocycle ligands with phenyl
groups rather than –(CH2)3OCH3 groups.
Scheme 5. Preparation of the tetradentate mixed tertiary/secondary phosphine ligand 4.
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Scheme 6. Preparation of the tetradentate mixed tertiary/secondary phosphine ligand 6.
O
AIBN
P
O
2
+
O
P
P
O
O
H
H
O
O
O
O
O
O
LAH
P
P
P
P
P
O
O
P
H H
P
P
O O
O
O
6
5
Synthesis and characterization of Cu(P2)2+ (P2 = a bidentate phosphine ligand). The
Cu(I) template complexes of ligands 1 and 2 were synthesized by reacting the ligands with
-
Cu(CH3CN)4X (X = OTf- or PF6 ) in CH3CN. The products were characterized as complexes 7 and 8 in
Scheme 7. Coordination of the phosphines was confirmed by 31P{1H} NMR spectroscopy, which
showed that the chemical shifts of the coordinated phosphines moved ~20 ppm downfield from
that of the free ligands (-41.1 ppm for 7 vs. -59.5 ppm for uncoordinated 1 and -50.5 ppm for 8 vs. -
8

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69.6 ppm for uncoordinated 2). The 31P NMR signals were significantly broadened because of
coupling with NMR-active, quadrupolar 63Cu and 65Cu nuclei (both spin 3/2, 69% and 31%
abundance, respectively).19,20 Note that Cu-P coupling is generally only observed for highly
symmetric Cu(PR3)4+ complexes.20–22 In some copper-phosphine complexes the broadening can be
minimized by obtaining the spectrum at high temperature,21–23 but the spectra of complexes 7 and
8 did not change between 25 °C and 90 °C. The [Cu(P2)2]+ formulas were supported by ESI-MS
analysis (7: m/z 539, calculated and observed; 8: m/z 567, calculated and observed; see the ESI).
The identity of these products was further confirmed by correct elemental analyses (see
Experimental Section).
Scheme 7. Synthesis of the Cu(P2)2+ templates.
Complexes 7 and 8 were isolated as viscous liquids, and repeated attempts at obtaining
solid samples or single crystals for X-ray structural analysis were unsuccessful. In order to obtain
Cu(I) template complexes that were solids instead of viscous liquids for subsequent experiments,
complexes of the hydrophobic ligands MPPE (1,2-bis[(phenyl)phosphino]ethane) and MPPP (1,2-
bis[(phenyl)phosphino]propane) were also synthesized (complexes 9 and 10, respectively; Scheme
7). These complexes were isolated as crystalline solids and characterized by 31P NMR spectroscopy,
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ESI-MS, and elemental analysis. Although previous reports of related complexes state they are air-
stable, some oxidation was observed when these products were exposed to air, as evidenced by a
blue coloration when they were dissolved in solution. The complexes were therefore handled
under an inert atmosphere.
Synthesis and characterization of Cu(4)+ (11). Ligand 4 reacted with one equivalent of
[Cu(CH3CN)4]OTf in CH3CN to yield a solid product characterized as [Cu(4)]OTf (11) (Scheme 8).
The 31P{1H} NMR spectrum of the product exhibited two broad peaks centered at -15 and -40 ppm,
corresponding to the tertiary and secondary phosphorus atoms of the ligand, respectively. As
discussed above, the broadness is consistent with coordination of the phosphine to quadrupolar
63Cu/65Cu nuclei. As also noted above, Cu-P coupling is usually observed only for highly symmetric
Cu(PR3)4+ complexes.20–22 In complex 11, the tetrahedral geometry about Cu(I) is likely distorted by
the propylene bridges between the phosphorus atoms causing a less than ideal tetrahedral bite
angle, and consequently no Cu-P coupling is observed. Overall, the 31P NMR spectroscopy does not
reveal much structural information except for the types of coordinated phosphine present (tertiary
+
and secondary). The ESI-MS of the complex displayed the anticipated m/z at 623 (C33H40CuP4 )
with the expected isotope pattern (Figure S35). The complex also has the correct composition by
elemental analysis.
Scheme 8. Preparation of the Cu(I)-tetradentate phosphine complex (11).
10

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Macrocyclization of the Cu(P2)2+ complexes. Complexes 7 - 10 reacted with 2 equivalents
of 1,3-dibromopropane in the presence of K2CO3 in THF to form products characterized as the
macrocycle complexes 12-15, respectively (Scheme 9). Alkylation of the coordinated secondary
phosphines was suggested by the downfield shifts in the 31P NMR spectra (e.g., -2 ppm for 12 vs. -41
ppm for 7). The reactions to make 12 and 13 (from 7 and 8, respectively) took over two days to
reach completion, whereas complexes 14 and 15 (from 9 and 10, respectively) needed only four
hours. We hypothesize that complexes 9 and 10 reacted faster with base than complexes 7 and 8
because the electron-withdrawing phenyl groups in 9 and 10 make the P-H bond more acidic
relative to 7 and 8, which have electron-donating –(CH2)3OCH3 groups. ESI-MS of complexes 12-15
all showed molecular ion peaks consistent with the masses of the macrocyclic complexes (Table
S1), indicating complete alkylation with the 1,3-dibromopropane. In addition to the macrocycles
formed using 1,3-dibromopropane, the 16- and 18-membered macrocyclic complexes 16 and 17
were prepared from 9 and 10, respectively, using 1,4-dibromobutane.
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Scheme 9. Macrocyclization of Cu(P2)2+ templates with K2CO3.
Complex 15 was analyzed by single crystal X-ray diffraction, which shows the tetrahedral
coordination of the macrocyclic ligand (Figure 2). The four phosphorus atoms have alternating R
and S stereochemistry, giving the complex the relatively rare S4 symmetry; the complex is thus not
optically active.
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Figure 2. ORTEP drawing of the cation of 15 with thermal ellipsoids drawn at the 50% level. The
H-atoms are omitted for clarity.
The 65Cu NMR spectrum of complex 15 in DMSO-d6 (with a Cl- counterion in place of OTf-) is
shown in Figure 3. The spectrum shows a quintet centered at 293.8 ppm, consistent with coupling
of the Cu center to four nearly equivalent P atoms. (Modeling the spectrum gave the following Cu-P
coupling constants: J1Cu-P = 824.4, 824.4, 821.8, and 821.8 Hz.)
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Figure 3. 600 MHz 65Cu NMR spectrum of complex 15 in DMSO-d6. The counterion is Cl- rather
than OTf-.
Several experimental notes are of interest with regard to the preparation of complexes 12 -
17. If KOtBu is used as the base instead of K2CO3, the reaction is much faster and is done within
minutes instead of hours or days. The spectroscopic data of the products obtained from the
experiments with KOtBu matched those obtained when K2CO3 was used as the base. Mass
spectrometry showed that if a stoichiometric excess of the 1,3-dibromopropane or 1,4-
dibromopropane is added or if the reaction is too concentrated, multiple alkylations are possible.
For example, when complex 10 is alkylated with an excess of 1,3-dibromopropane or 1,4-
dibromobutane, the ESI mass spectrum of the products showed the formation of a coordinated
open-chain ligand with hanging propyl- or butyl-bromides (Figure 4; see the ESI for the ESI-MS).
Precise control of the stoichiometry and dilute reaction solutions eliminated these side-products
from forming, as indicated by mass spectrometry. Finally, it is noted that a potential problem with
the synthetic route in Scheme 9 is the possibility of forming double-chelate products (Scheme 10).
However, no example of this reactivity has ever been found,11–13 and it was not observed in this
study.
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Figure 4. Products formed in the macrocyclization reaction of 10 with 1,3-dibromopropane.
Double alkylation (shown on the right) is an observed side-product in ESI-MS.
Scheme 10. Possible side-reaction to form a double-chelate complex in the macrocyclization of a
bis-bidentate secondary phosphine.
R
R
R
R
R
R
R
R
PH
R
R
Br Br
K2CO3
2
HP
P
P
P
P
P
P
P
P
or
Cu
Cu
Cu
HP
R
PH
R
double-chelate
macrocycle
Macrocyclization of [Cu(4)]OTf (11). Complex 11 was converted to macrocyclic
+
complexes using the general route devised above for the Cu(P2)2 complexes. Deprotonation of
complex 11 with two equivalents of KOtBu in THF immediately gave a bright yellow solution,
presumably the diphosphide species. Reaction of this species with 1,2ꢀdibromoethane did not
give a clean reaction. However, with either 1,3ꢀdibromopropane, 1,4ꢀdibromobutane, or oꢀ
dibromoxylene, the macrocyclic complexes 15, 18, and 19, respectively, were obtained (Scheme
11). All of the complexes were isolated as yellow powders that displayed broad peaks in the
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region for coordinated tertiary phosphines in the 31P{1H} NMR spectra (Table 1), consistent with
alkylation of the two secondary phosphines to give an allꢀtertiary phosphine product. Because
no CuꢀP coupling was observed in the 31P NMR spectra, the complexes likely have a distorted
tetrahedral geometry about Cu.20–22,24–26 The identity of the products was confirmed by the
disappearance of the PꢀH stretch in the IR spectrum (2314 cmꢀ1), the correct m/z value in the
mass spectrum with the expected isotope patterns (see ESI and Experimental section), and by
accurate elemental analyses (Table 1). Unfortunately, repeated attempts to grow Xꢀray quality
crystals were unsuccessful, perhaps due to the lack of stereospecificity of the phosphine ligands.
Scheme 11. Macrocyclization of 11.
Table 1. Characterization data for complexes 11 and 15, 18, and 19.
ESI-MS: m/z
(expected)
Elemental Analysis
Actual (Calc’d)
Compound 31P{1H} NMR (ppm)
C
H
P
ꢀ15, ꢀ40
623 (623)
52.80 (52.82)
5.18 (5.21) 15.87 (16.02)
11
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ꢀ14.7, ꢀ20.9
ꢀ18.4
663 (663)
677 (677)
725 (725)
54.46 (54.60)
5.52 (5.45) 15.07 (15.23)
15
18
19
54.89 (55.17)
57.65 (57.63)
5.60 (5.63) 14.60 (14.98)
5.22 (5.30) 14.27 (14.15)
ꢀ14, ꢀ21
As in the reactions of the Cu(P2)2+ complexes, it is important to carefully control the
stoichiometry of the macrocyclization reactions with 11. For example, with a slight excess of 1,3-
dibromopropane, ESI-MS showed that, in addition to the expected macrocyclic complex, a side-
product resulting from alkylation by two separate molecules also formed, analogous to the over-
alkylated product in Figure 4.
Demetallation reactions. In order to examine the conditions of Cu(I) removal,
demetallation trials were first carried out with [Cu(MPPE)2]PF6 (9). Dissolving this complex in
dichloromethane or toluene and stirring with a saturated aqueous KCN solution overnight or
heating to 70 °C for 15 minutes yielded the free ligand in the organic layer, as indicated by 31P NMR
spectroscopy.12,16 The same procedure was then carried out with complexes 15, 18, and 19
(Scheme 12). The products obtained after removal of the solvent were colorless, oily residues (20)
or semi-solids (21, 22). Phosphines 20 - 22 displayed sharp peaks in their 31P{1H} NMR spectra
(Table 2). These peaks, indicative of tertiary phosphines, are much sharper than those in
complexes 15, 18, and 19, indicating the absence of Cu coordination. In the 1H NMR spectra, the
aromatic protons of the phenyl rings give rise to a group of signals at 7.3 ppm and the aliphatic
protons have broad signals from 1.2 to 2.1 ppm. In addition, the P-H signals present in ligand 4
were not in the 1H NMR spectrum of 20 - 22, a result consistent with full alkylation of the
phosphines.
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Scheme 12. Demetallation of complexes 15, 18, and 19 using KCN.
Table 2. NMR data for phosphines 20 - 22.
Compound
31P{1H} NMR
(ppm)
Integrals from 1H NMR: actual
(expected)
Aromatic
Aliphatic
ꢀ26.8
20 (20)
20 (20)
24 (24)
23.7 (24)
27.4 (26)
25.3 (22)
20
21
22
ꢀ26.3, ꢀ27.3
ꢀ23.2, ꢀ26.7
It is interesting to note that a singlet is observed for phosphine 20. Because the openꢀ
chain ligand precursor 4 can have many possible stereoisomers, a simple NMR spectrum of 20 is
not necessarily expected. Four isomers are possible for the macrocyclic phosphine ligand
(Figure 5), of which two isomers will have a singlet in the 31P NMR spectrum (Figure 5, A, D).
Curiously, other phosphine macrocycles, both coordinated and free, have been prepared where a
singlet has been observed for isomers B and C.27,11,12 (For this to occur, however, all the P
resonances must be coincident with no PꢀP coupling.) Alternatively, the symmetric A4 spinꢀ
18

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system could be a result of stereoselective inversion of the coordinated phosphide anions, formed
as an intermediate in Scheme11, to yield a preferred geometry.28,29 i ii
Figure 5. Possible stereoisomers of tetraphosphine 20.
Because the exceptionally oily nature of 20 ꢀ 22 prevented their more detailed
characterization, metal complexes containing the ligands were synthesized as a way to help
confirm the identities of the ligands. The coordination complexes of 21 with Co(II) and Fe(II)
are described in the following section.
The demetallations of macrocycle ligands derived from complexes 12 – 17 were carried
out using the same procedure as described above for complexes 15, 18, and 19, e.g., Scheme 13.
The free ligands obtained in these reactions were also viscous liquids. Details are found in the
Experimental section.
i Phosphine 21 displays two equally intense singlets at -25.6 ppm and -26.8 ppm. Two peaks are
expected because there are two different phosphorus environments but the two peaks could also
arise from two isomers of 21. Because 21 is less symmetric than 20, there are 7 possible
diastereomeric pairs (two meso forms and five pair of enantiomers; see the ESI).
ii Phosphine 22 displayed sharp peaks in the expected region in the 31P NMR spectrum, but the
number of peaks indicated some degradation of the phosphine during demetallation.
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Scheme 13. Demetallation of complex 16 using KCN.
Coordination chemistry of ligands 21 and 23. Reaction of 21 with anhydrous CoCl2 in
CH2Cl2 gave an emerald green solution from which a green solid was isolated (Scheme 14). The
product showed an m/z 708 in the ESI-MS, corresponding to the calculated value for [Co(21)Cl]+,
and the expected isotope pattern for this formula was also observed (see the ESI). The green
product had broad NMR signals, consistent with a paramagnetic species, which is expected for a
Co(II) complex. The complex has a μeff of 1.54 B.M., consistent with 1 unpaired electron30 and also
consistent with the magnetic moments found with other Co(II) tetraphosphorus complexes.24–26,31
The electronic spectrum has two peaks in the visible region, similar in appearance to other five-
coordinate [Co(P)4Cl]+-type complexes (P = a phosphine) (Table 3).24,27,25,26,31–33 (It is also noted
that similar five-coordinate complexes form when CoX2 is reacted with phosphines. For example,
1,3-bis(dimethylphosphino)propane (dmpp) reacts with CoI2 to form [Co(dmpp)2I]I.32) Finally, the
elemental analysis of the green powder gave a formula of [Co(21)]Cl2•4H2O, consistent with the
proposed formula. (The elemental analysis is also consistent with the formula [Co(21)2][CoCl4],
which has been found for selected phosphorus-containing macrocycle ligands.27)
20

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Scheme 14. Reactions of 21 with CoCl2 and FeCl2·4H2O.
21

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Table 3. Electronic spectra of [Co(P)4Cl]X-type complexes.
Complex
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λmax (ε)
[Co(21)Cl]Cl
611(397), 660(372)
[Co(23)Cl]Cl
589 (78), 681 (117)
588 (570), 630 (490)
610 (419), 690 (319)
575 (240), 675 (400)
600 (600), 680 (730)
24
[Co(PPh(OEt)2)4Cl]BPh4
32
[Co(dmpp)2Cl]BPh4
[Co(MC)2][CoCl4]27
[Co(dppp)2Cl]Cl33
QP = tris-(o-diphenylphosphinophenyl) phosphine
dmpp = 1,3-bis(dimethylphosphino)propane
MC = Macrocycles with two phosphorus atoms, acting
as a bidentate ligand
Reaction of ligand 23 with anhydrous CoCl2 in CH2Cl2 also gave an emerald green solution
from which a solid green product, characterized as [Co(23)Cl]Cl, was isolated. The green product
had broad 1H NMR signals and a broad 31P NMR signal, consistent with a paramagnetic species. The
product showed a single peak in the ESI-MS at an m/z of 694 amu, in agreement with [Co(23)Cl]+;
the isotope pattern of the peak at 694 is also consistent with [[Co(23)Cl]+ (see the ESI).
Reaction of 21 with simple FeX2 salts did not yield any identifiable products. However,
reaction of 21 with FeCl2•4H2O and two equivalents of NaBPh4 in CH3CN, gave an orange solid
identified as [Fe(21)(CH3CN)2](BPh4)2 (Scheme 14). (The same product was also obtained using
[Fe(CH3CN)2](OTf)2 as the starting material.) The ESI-MS showed peaks at 670 and 335 m/z,
22

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corresponding to [m-2(BPh4)]+ and [m-2(BPh4)]2+, respectively (see the ESI). Elemental analysis of
the orange product indicated a formula of [Fe(21)(CH3CN)2](BPh4)2·2CH3CN·3.5CH2Cl2. Repeated
attempts to remove the solvent molecules by prolonged heating in vacuo were unsuccessful.
The IR spectrum of the orange powder has weak C≡N stretches at 2251 and 2284 cm-1
(unbonded and bonded acetonitrile, respectively),34 and a very strong stretch at 2091 cm-1, which is
tentatively assigned to ν(N≡N).35,36 To check this assignment, the complex was prepared in an
argon-filled glovebox. An IR spectrum (ATR method) of the resulting product showed a 64%
reduction in the intensity of the stretch at 2091 cm-1 relative to other peaks in the spectrum. When
the complex was exposed again to N2 for three minutes in CDCl3 solution, there was a 12% increase
in the intensity of the 2091 cm-1 band (relative to the other bands in the spectrum, which were
assumed not to change in intensity). These preliminary experiments suggest that the complex
binds N2 strongly enough to displace an acetonitrile ligand.
Computational Results. To gain better insights into the relative stabilities of the four
stereoisomers depicted in Figure 5, the four stereoisomers of complex 15 were optimized and their
single-point energies computed by DFT (B3LYP/6-31G(d)) in Gaussian 09.37 The calculated
energies (Table 4) indicate that the most stable isomer has an anti-syn-anti conformation (structure
D in Figure 5). Note this structure is the one obtained in the X-ray crystal structure of complex 15.
The higher energies of the other stereoisomers appear to come from distortions in the Cu(I)
coordination geometries. For example, isomer C has a nearly square planar geometry around the
Cu center. The complete computational results will be presented in a subsequent paper.
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Table 4. Relative energies of the four stereoisomers depicted in Figure 5.
Geometry
ΔE (kJ/mol)
A
B
C
61.2
7.9
93.9
0
D
Key points and conclusions. Two methods were investigated for the preparation of
tetradentate phosphine ligands. The first method is shown in Scheme 9 and involves the coupling
of two bidentate secondary phosphines bonded to Cu(I). The second method is shown in Scheme
11 and involves the coupling of secondary phosphorus atoms in a linear tetradentate phosphine,
again bonded to Cu(I). The Cu(I) ion was chosen as the template because prior work showed that it
was generally difficult, if not impossible, to remove Pd(II) and Pt(II) templates without also
degrading the macrocycle ligand. This study showed that Cu(I) can be straightforwardly removed
by stirring with KCN. Fe(II) would be the perfect template ion for these reactions because then it
would not be necessary to remove the template and replace it with Fe(II) for use in the pressure-
swing process (Scheme 1). However, our prior work showed that Fe(II) is not a satisfactory
template for the synthesis of macrocycles via Schemes 9 and 11.17
The macrocycle ligands isolated in this study (20 - 23) were viscous oils. Characterization
by X-ray crystallography was, therefore, not possible. However, the Co and Fe complexes of these
ligands were powders in some cases, and this trait permitted the characterization of the complexes.
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The pressure-swing nitrogen separation process outlined in Scheme 1 uses N2-binding Fe
complexes that are water-soluble by virtue of having water-soluble phosphine ligands. The
bidentate phosphine ligand DMeOPrPE (containing –(CH2)3OCH3 groups; Figure 1) is water soluble,
and we expected macrocycle ligands with this R group to also be soluble. Unfortunately, neither the
macrocycles with this R group nor their complexes are water-soluble so new phosphines are
currently being synthesized with alternative water-solubilizing R groups. Note that conventional
-
water-solubilizing groups such as –SO3 and –OH are not viable because our prior work showed that
these groups can coordinate to metal centers and block N2 binding.7 As noted above, preliminary
work shows that the Fe(21)(CH3CN)22+ complex binds N2, and work is continuing on this reaction
and its use in a pressure-swing natural gas purification scheme.
EXPERIMENTAL SECTION
Materials and Reagents. Unless otherwise noted, all experimental procedures were
performed under an N2 atmosphere using standard Schlenk and glovebox techniques.
Commercially available reagents were used as received. HPLC-grade THF was dried and
deoxygenated by passing it through commercial columns of CuO then alumina under an argon
atmosphere. Deuterated solvents were obtained from Cambridge Isotope Laboratories and
degassed using three freeze-pump-thaw cycles. [Fe(CH3CN)2](OTf)2,38 and 1415 were synthesized
according to literature methods. [Cu(CH3CN)4]OTf was prepared from a modified procedure.39
Ligands 1 and 2 were prepared as previously described.17 The ligands MPPP40 and 418 were
synthesized according to literature methods.
Instrumentation. Airꢀsensitive NMR samples were sealed in N2ꢀfilled JꢀYoung tubes.
NMR spectra were obtained on either a Varian Unity/Inova 300 spectrometer at an operating
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frequency of 299.94 MHz (1H) or 121.42 MHz (31P), a Varian Unity/Inova 500 spectrometer
operating at a frequency of 500.62 MHz (1H) or 202.45 MHz (31P), or a Bruker 600 spectrometer
at an operating frequency of 600.15 MHz (1H), 242.94 MHz (31P), or 170.46 MHz (65Cu). The
1H and 13C NMR spectra were referenced to residual solvent peaks, and the 31P NMR spectra
were referenced to external 1% H3PO4 in D2O. ESI mass spectra were obtained using a Thermo
Finnigan LCQ Deca XP Plus ESI Mass Spectrometer using THF or CH3CN as the solvent.
Infrared spectra were recorded using a ThermoꢀScientific Nicolet 6700 FTꢀIR spectrometer.
UVꢀvis spectra were collected on an Agilent 8453 spectrophotometer. Elemental analyses were
performed by Complete Analysis Laboratories, Inc., Parsippany, NJ.
X-ray Crystallography. Diffraction intensities for complex 15 were collected at 150 K on a
Bruker Apex2 CCD diffractometer using MoKα radiation, λ= 0.71073 Å. The space group was
determined based on systematic absences. Absorption corrections were applied by SADABS.41 The
structures was solved by direct methods and Fourier techniques and refined on F2 using full matrix
least-squares procedures. All non-H atoms were refined with anisotropic thermal parameters. All H
-
atoms were refined in calculated positions in a rigid group model. The anion CF3SO3 in the
structure is highly disordered and was treated by SQUEEZE.42 Corrections of the X-ray data by
-
SQUEEZE (146 electron/cell) is close to the required value of 134 electron/cell for two CF3SO3
anions in the full unit cell. Diffraction data were collected up to 2θmax = 56.0°, but only data up to
2θmax = 50.0° have been used in the final refinement. Diffraction intensities at high angles were weak and
as a result there is a relatively high peak, 2.147 eÅ-3, on the residual density. The structure was refined
as a racemic twin. The Flack parameter, 0.48(7), is close to 0.5, indicating a possible centro-
symmetrical space group, but we think that the crystal is a racemic twin consisting of two domains
with opposite configuration of the Cu-cations. All calculations were performed by the Bruker
SHELXL-2013 package.43
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Synthesis of isopropyl allyl(phenyl)phosphinate. Allyl bromide (6.01 g, 49.7 mmol, 2.40
eq.) was added to a 50 mL Schlenk flask containing diisopropyl phenylphosphonite (5.02 g, 20.7
mmol, 1.00 eq) and the mixture was heated to 70 °C for 12 hr. After heating, the product was
distilled under reduced pressure (85-90 °C @ 250 mTorr) to yield a clear oil. Yield: 4.91 g (96.7 %).
1
31P{1H} NMR (CDCl3): δ -38.8 (s). H NMR (CDCl3): δ 7.77 (m, 2H), 7.47 (m, 3H), 5.72 (ddtd, JHH
=
17.4, 10.6, 7.5 Hz, JPH = 5.7 Hz, -CH2CH=CH2, 1H), 5.06 (m, 2H), 4.61 (d of sept, JHH = 6.2 Hz, JPH = 8.6
Hz, -CH(CH3)2, 1H), 2.73 (dd, JHH = 7.5 Hz, JPH = 18.4 Hz, -CH2CH=CH2, 2H), 1.36 (dd, JHH = 6.2 Hz, -
CH(CH3)2, 3H), 1.19 (dd, JHH = 6.2 Hz, -CH(CH3)2, 3H). 13C{1H} NMR (CDCl3): 132.2, 131.9, 128.4,
127.5, 120.3, 69.9, 36.6 (d, JPC = 97 Hz), 24.6, 24.1.
[Cu(MeOPrPE)2]PF6 (7). A CH3CN solution of 1 (0.019 g, 0.080 mmol) was added to
Cu(CH3CN)4PF6 (0.015 g, 0.040 mmol). The reaction mixture was stirred for 1 hour at room
temperature after which the solvent was removed under reduced pressure. Yield: 0.025 g (93.0%)
of an off-white viscous oil. 31P NMR (THF): δ -41 (br, ꢀν1/2 (linewidth at half maximum) = 2350 Hz).
ESI-MS: 539 amu (m+). Anal. Calcd for C20H48F6CuO4P5: C, 35.07; H, 7.06; P, 22.61. Found: C, 34.98;
H, 7.13; P, 22.49.
[Cu(MeOPrPP)2]OTf (8). A CH3CN solution of 2 (0.0698 g, 0.277 mmol, 1.92 equiv) was
added to a CH3CN solution of Cu(CH3CN)4OTf (0.0542 g, 0.144 mmol, 1 equiv) and stirred for 1
hour. The solvent was removed under reduced pressure to yield an off-white viscous oil. 31P NMR
(THF): δ -50.5 (br). ESI-MS: 567 amu (m+). Anal. Calcd for C23H52F3CuO7P4S: C, 38.52; H, 7.31; P,
-
17.28. Found: C, 38.46; H, 7.28; P, 17.04. The complex was also synthesized as the PF6 salt: 31P
NMR (THF): δ -30.5 (br, ꢀν1/2 = 2150 Hz).
[Cu(MPPE)2]PF6 (9). This complex was prepared in a manner similar to 7 using MPPE
(0.0211 g, 0.0860 mmol) and Cu(CH3CN)4PF6 (0.0170 g, 0.0460 mmol). Yield: 0.281 g (97.3 %) of a
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white granular solid. 31P NMR (THF): δ -31 (br, ꢀν1/2 = 2140 Hz). ESI-MS: 555 amu (m+). Anal. Calcd
for C28H32CuF6P5: C, 47.98; H, 4.60; P, 22.09. Found: C, 47.95; H, 4.67; P, 22.01. The analogous
triflate complex was also prepared, using Cu(CH3CN)4OTf instead of Cu(CH3CN)4PF6. The
spectroscopic data were identical.
[Cu(MPPP)2]OTf (10). This complex was prepared in a manner similar to 8, using MPPP
(0.383 g, 1.47 mmol) and Cu(CH3CN)4OTf (0.278 g, 0.740 mmol). Yield: 0.5177 g (95.9%) of a white
granular solid. 31P NMR (THF): δ -43 (br, ꢀν1/2 = 2220 Hz). ESI-MS: 583 amu (m+). Anal. Calcd for
C31H36F3CuO3P4S: C, 50.79; H, 4.95; P, 16.90. Found: C, 50.76; H, 4.81; P, 16.77.
General method for macrocyclization with K2CO3. Cu(P2)2X (X = OTf or PF6) was
dissolved in THF and excess K2CO3 was added in one portion. The solution immediately turned
bright yellow and was stirred at room temperature for 10 minutes. The desired dihalide (two
equivalents) was diluted with THF and then added dropwise. The reaction mixture was stirred
overnight, during which time the reaction became lighter yellow with a white precipitate. The
reaction was filtered over celite and the solvent removed in vacuo. The remaining yellow residue
was redissolved in dichloromethane and filtered again over celite. Removal of the solvent yielded
the product as a yellow powder.
Synthesis of 12. This complex was prepared following the general method above, using
[Cu(MeOPrPE)2]PF6 (0.155 g, 0.227 mmol) and 1,3-dibromopropane (0.990 g, 0.490 mmol). Yield:
0.973 g (56 %) 31P{1H} NMR (CDCl3): δ -2 ppm (br, ꢀν1/2 = 2150 Hz). ESI-MS: 619 amu (m+).
Synthesis of 13. This complex was prepared following the general method above, using
[Cu(MeOPrPP)2]PF6 (0.251 g, 0.352 mmol) and 1,3-dibromopropane (0.149 g, 0.738 mmol). Yield:
0.1661 g (56 %). ESI-MS: 647 amu (m+).
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Synthesis of 15. This complex was prepared following the general method above, using
[Cu(MPPP)2]OTf (0.301 g, 0.334 mmol) and 1,3-dibromopropane (0.139 g, 0.688 mmol). Yield:
0.214 g (65 %) 31P{1H} NMR (CDCl3): δ -15 (br, ꢀν1/2 = 2550 Hz), -21(br, ꢀν1/2 = 2340 Hz) ppm. ESI-
MS: 663 amu (m+).
Synthesis of 16. This complex was prepared following the general method above, using
[Cu(MPPE)2]OTf (0.304 g, 0.432 mmol) and 1,4-dibromobutane (0.104 mL, 0.871 mmol). Yield:
0.275 g (95.8 %) 31P{1H} NMR (CDCl3): δ 6 (br, ꢀν1/2 = 2450 Hz). ESI-MS: 663 amu (m+). Anal. Calcd
for C37H44CuF3O3P4S: C, 54.6; H, 5.45. Found: C, 48.86; H, 4.92. This rather poor elemental analysis
is likely due to residual KBr left over from the reaction. Anal. Calcd for C37H44CuF3O3P4S•0.8 KBr: C,
48.92; H, 4.88.
General method for macrocyclization with KOtBu. Cu(P2)2X (X = OTf or PF6) was
dissolved in THF and 4 equivalents of KOtBu were added in one portion. The solution immediately
turned bright yellow and was stirred at room temperature for 10 minutes. The desired dihalide
(two equivalents) was diluted in THF and added dropwise. The reaction mixture was stirred and
became cloudy and lighter yellow after a few minutes. The reaction was stirred for at least four
hours. The reaction was filtered over celite and the solvent removed in vacuo. The remaining
yellow residue was redissolved in dichloromethane and filtered again over celite. Removal of the
solvent yielded the product as a yellow powder.
Synthesis of 17. This complex was prepared following the general method above with
KOtBu, using [Cu(MPPP)2]OTf (0.0535 g, 0.0730 mmol), KOtBu (0.0319 g, 0.284 mmol) and 1,4-
dibromobutane (0.0160 mL, 0.134 mmol). 31P{1H} NMR (CDCl3): δ -13 (br, ꢀν1/2 = 2800 Hz), -45 (br,
ꢀν1/2 = 3050 Hz). ESI-MS: 691 amu (m+). This complex can also be prepared using the general
route using K2CO3. The spectroscopic evidence is identical.
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