Stabilization of a Strained Heteroradialene by Peripheral Electron Delocalization

Article abstract of DOI:10.1021/acs.orglett.6b00577

Dimethylamine and 2,4,6-triformylphloroglucinol react to form a product with a highly contorted nonplanar geometry due to favorable electron delocalization. This new heteroradialene compound has been studied by X-ray diffraction, variable-temperature multinuclear NMR spectroscopy, IR spectroscopy, UV-vis spectroscopy, and ab initio calculations. Electron delocalization throughout the periphery of the central ring leads to a structure that retains very little of the aromatic characteristics of the starting material.

Full text of DOI:10.1021/acs.orglett.6b00577

Letter
pubs.acs.org/OrgLett
Stabilization of a Strained Heteroradialene by Peripheral Electron
Delocalization
S. Hessam M. Mehr, Brian O. Patrick, and Mark J. MacLachlan*
Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
*
S Supporting Information
ABSTRACT: Dimethylamine and 2,4,6-triformylphlorogluci-
nol react to form a product with a highly contorted nonplanar
geometry due to favorable electron delocalization. This new
heteroradialene compound has been studied by X-ray
diffraction, variable-temperature multinuclear NMR spectros-
copy, IR spectroscopy, UV−vis spectroscopy, and ab initio
calculations. Electron delocalization throughout the periphery
of the central ring leads to a structure that retains very little of
the aromatic characteristics of the starting material.
lectron delocalization within conjugated molecules is a
challenge our notions of aromaticity and beg the following
questions: What stabilizes the TSANs to compensate for the loss
of aromaticity in 2k vs 2e? Does the additional stabilization arise
exclusively from improved hydrogen-bonding interactions, or is
there another explanation?
E
versatile chemical concept that is at the root of fundamental
phenomena including the aromaticity of benzene, the acidity of
carboxylic acids, and the properties of biologically relevant
1
molecules such as vitamin A (retinal), vitamin B6 (pyridoxal
2
3
phosphate), and chlorophyll. Controlled delocalization of
To investigate these questions, we prepared compound 3 by
reacting 1 with a secondary amine. Using a secondary amine
allows us to evaluate the propensity of the electronic structure to
favor the keto-enamine form in the absence of changes in the σ
4
electrons is central to the design of modern electronic devices
and, in the case of π electrons, has given rise to the exciting
5
,6
properties of graphene and its derivatives.
17
In 2003, we reported a new family of heteroradialenes that are
skeleton or the influence of hydrogen bonding. We expected 3
to have an aromatic zwitterionic structure, but our experiments
show that the push−pull interaction of the charged side chains
undermines aromaticity and introduces a new mode of electron
delocalization. Here, we describe our detailed structural,
spectroscopic, and computational studies of compound 3.
These findings illustrate the promise of alternative electron
delocalization motifs and contribute to a better structural
understanding of TSANs.
prepared from the Schiff base condensation of 2,4,6-triformyl-
7
phloroglucinol 1 and primary amines (Scheme 1a). Surprisingly,
Scheme 1. Reactions of 1 with a Primary Amine (a) and
Dimethylamine (b)
Compound 3 was prepared in 99% yield by bubbling an excess
of gaseous dimethylamine into a suspension of 1 in chloroform
(
Scheme 1b). The reaction is complete in 1 h at room
temperature (rt), and evaporation of solvent gives the product
as a bright yellow-orange solid that is stable in the absence of
oxygen and water. Compared to TSANs 2k/2e, 3 replaces the
labile NH/OH hydrogen atoms with methyl groups, preventing
intramolecular hydrogen bonding or tautomerizationthe
zwitterionic and keto-enamine forms of 3 are resonance
structures rather than tautomers.
Slow evaporation of a solution of 3 in a mixture of hexanes and
dichloromethane yielded orange crystals suitable for single-
crystal X-ray diffraction (SCXRD). The solid-state molecular
structure of 3 reveals a highly distorted, asymmetric structure
these new tris(salicylaldimine) molecules 2 (TSANs) exist
exclusively as the keto-enamine tautomer 2k rather than the
expected enol-imine tautomer 2e. While the keto-enamine motif
has been exploited in a variety of discrete and extended
(
Figure 1a). Compared to the planar core observed for TSANs
7
−16
structures,
little work has been done to explain its dominance
Received: February 29, 2016
over the canonical enol-imine structure. These new molecules
©
XXXX American Chemical Society
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DOI: 10.1021/acs.orglett.6b00577
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Organic Letters
Letter
prepared from reacting 1 with a primary amine (i.e., 2k, Figure
1
2
1
b), oxygen atoms O and O in 3 have surprisingly large
deviations from the mean plane of the molecule (31 and 18°,
respectively).
Figure 2. Space-filling diagram derived from the SCXRD structure of 3.
Table 1. Bond Lengths of Compound 3 and Comparable
Molecules
a
Representative keto-enamine shown in Figure 1b (R = CH-
1
8 b
(CH OH)CH CH ).
Representative enol-imine from the liter-
2
2
3
1
9
ature.
bond lengths of N,N-dimethylformamide are very close, as well.
Thus, 3 might be described as an amide in which the electronic
coupling between the CO and NRR′ groups is mediated by the
central ring, with this mode of delocalization replacing classic
aromaticity.
Given the unusual solid-state structure of 3, we undertook a
study of its solution dynamics using variable-temperature (VT)
1
NMR spectroscopy. At rt, the H NMR spectrum of 3 in
toluene‑d shows broad CH signals around 3 ppm, with only one
8
3
broad resonance at 8.15 ppm for the CCHN groups. This is
consistent with rapid rotation about the C−CH bonds, which we
next attempted to impede at low temperature. Thus, at −89 °C,
eight peaks are seen near 3 ppm and four near 8 ppm, due to the
discrete symmetric (3s) and asymmetric (3a) forms of 3 (Figure
Figure 1. (a) Solid-state molecular structure of 3 with methyl hydrogen
atoms omitted for clarity. (b) Representative keto-enamine tautomer
2
k, with yellow atoms showing truncated (CH(CH OH)CH CH )
2 2 3
18
groups.
3
). The symmetric form contributes two distinct peaks for CH3
1
2
The large displacements of O and O can be understood by
examining their proximity to the methyl groups, where two
groups and one CH resonance; the asymmetric form produces
six distinct peaks for CH groups and three distinct CH
resonances. Heating the sample above 60 °C causes coalescence
of the peaks assigned to the methyl protons, indicating facile
rotation about both the CH−N and C−CH bonds.
3
1
2
methyl groups push O out of the plane and one pushes O out of
the plane (Figure 2). Partial coplanarity of the side chains with
the central ring allows electron delocalization between the formal
phenoxide and iminium units, hence the close oxygen−methyl
contacts. Ab initio geometry optimization of this structure in
isolation relaxes the strain negligibly, suggesting that the
observed molecular shape is not merely due to interactions in
the crystalline phase. Another notable feature is that the
compound crystallized reproducibly as the asymmetric form
rather than the C3h symmetric form generally observed in the
crystal structures of keto-enamines 2k.
The same general behavior is observed in other solvents. Table
2 shows the coalescence temperatures (T ) and free energies of
c
⧧
activation for rotation (ΔG ) about the C−CH and CH−N
rot
⧧
bonds calculated using the Eyring model. These ΔG values
rot
are in good agreement with those previously reported for γ-keto-
2
0
⧧
enamines. The remarkably low ΔG
(C−CH) and high
rot
⧧
ΔG
(CH−N) in CD OD could be indicative of larger
rot
3
zwitterionic characteristics in CD OD, likely due to better
3
Bond lengths in 3 (Table 1) resemble those of keto-enamine
rather than enol-imine TSANs. In fact, the departure from
aromaticity and toward the keto-enamine structure in 3 is
stronger than that of typical keto-enamines 2k. Corresponding
stabilization of the negative charge on the oxygen atoms through
hydrogen bonding.
At low temperature, the relative areas of the peaks on the H
1
NMR spectrum of 3 can be used to calculate the 3s/3a ratio. This
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Organic Letters
Letter
15N NMR study of isotopically labeled 3 to gauge the relative
contributions of keto-enamine and zwitterionic characteristics.
The 15N-labeled analogue of 3, 3- N , was synthesized by
15
3
15
15
reacting 1 with excess NH(CH ) . In CD OD (at rt), the N
3
2
3
NMR spectrum of this compound gives a single sharp resonance
at 130.2 ppm, between the reported enamine and imine chemical
1
5
shift ranges. Next, the temperature dependence of the N signal
1
15
was examined via indirect measurement using H− N HSQC
15
(
J
= 12 Hz). In CD Cl , a very broad N signal results at rt that
NH 2 2
resolves to three distinct resonances upon cooling below −20 °C.
15
1
As Figure 4 shows, each N peak is coupled to two methyl H
1
15
15
Figure 4. H− N HSQC spectrum of 3- N at −84 °C (CD Cl , 400
3
2
2
MHz).
signals. An additional weak 15N resonance (seen on the 15
N
projection) appears to be due to the symmetric form. The
measured 15N chemical shifts are in the 115−130 ppm range
throughout the temperature range studied. These values are in
good agreement with those reported for cyclic γ-keto-enamines
2
4
(
110−150 ppm) and suggest that the electron distribution in 3
is keto-enamine-like regardless of temperature.
In general, N chemical shift values moved downfield by ∼15
ppm when methanol-d was used as solvent. Other researchers
have reported that N signals move upfield in polar solvents or
when hydrogen bonding is present. We suspect that this
1
Figure 3. VT H NMR spectrum of 3 in toluene-d and the two distinct
15
8
structures seen at −89 °C.
4
15
Table 2. Coalescence Temperatures (T ) and Activation
c
25
⧧
Energies for Bond Rotation (ΔG rot) for 3 from VT NMR
exceptional behavior can be attributed to the amplified
zwitterionic characteristics of 3 in methanol, consistent with
C−CH rotation
CH−N rotation
1
⧧
⧧
our VT H NMR experiments.
Comparing the infrared spectra of 3 and 3- N gives further
Tc
°C)
Δν
ΔG
rot
Tc
Δν
ΔG
rot
a
a
15
(
(Hz) (kJ/mol)
(°C) (Hz) (kJ/mol)
3
toluene-d8
DMF-d7
7
122
75
57
54
60
45
250
188
138
64
62
information about bonding in 3. The intense absorption at
1582 cm− in 3 experiences a small red shift of ∼9 cm (0.6%) to
1
−1
−3
<−89
−
1
15
14
methanol-d4
47
<37
>58
>65
1573 cm in 3- N , and values closer to the expected C N/
3
15
a
⧧
C N isotope shift of 1.5% are only seen for the weak resonances
ΔG values are ±2 kJ/mol.
−1
around 1200 cm . Ab initio analysis of the vibrational modes in
3
indicates that the normal modes around 1600 cm− correspond
1
ratio is solvent-dependent and can be as large as 1:5 in toluene-d8.
Ab initio calculations show that the geometry obtained in the
solid state (Figure 1a), when energy-optimized, is slightly more
stable than other possible asymmetric isomers. We therefore
suspect that the dominant form of 3 in solution at low
temperature (3a) corresponds to that observed in SCXRD. 1
A number of studies have demonstrated the utility of 5N
NMR as a sensitive probe in the study of tautomeric species.
to strongly coupled C−O/CH−N stretches. In this light, the
intermediate isotope shift obtained is not surprising given the
mixed nature of these vibrational modes. On the other hand, the
peaks around 1200 cm− arise due to relatively pure N−CH3
stretches and undergo the expected isotope shift.
In the presence of air, compound 3 is transformed into an
intractable sticky red mass over a period of days at rt. The yellow-
orange color of 3 in crystalline and solution form, however,
seems to originate from 3 and not any contaminants. In fact,
time-dependent density functional theory calculation of the
electronic excited states of 3 closely matched the UV−vis
absorption peaks at 363 and 308 nm (calcd 350 and 325 nm).
1
15
Changes in the tautomeric state have been shown to alter the N
2
1−23
chemical shift by more than 100 ppm.
Simple enamines
24
have chemical shifts in the 50−80 ppm range, whereas imines
have chemical shifts above 200 ppm. We therefore undertook a
C
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Organic Letters
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Our calculations show that the former excitation is principally
from HOMO (mostly radialene CCH π) to LUMO (CO
and CHN π*) and the latter from HOMO−1 (O lone pairs
and ring σ*) to LUMO.
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(
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(
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(
(
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Supporting Information
The Supporting Information is available free of charge on the
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Improved synthesis of 1, synthesis and characterization of
15
3
, 3- N , and 4, expanded ab initio section, and energy-
3
optimized atomic coordinates for all species used in the
calculations (PDF)
Crystal structure of 3 (CIF)
AUTHOR INFORMATION
■
*
Corresponding Author
E-mail: mmaclach@chem.ubc.ca.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank NSERC for funding this research (Discovery Grant).
S.H.M.M. thanks Jeff Therrien (UBC Chemistry) for assistance
with cyclic voltammetry.
D
DOI: 10.1021/acs.orglett.6b00577
Org. Lett. XXXX, XXX, XXX−XXX