Tetrabutyldideazaporphyrin

Article abstract of DOI:10.1016/j.tetlet.2020.152619

McMurry coupling of a dibutylpyrrole diacrylaldehyde afforded an unstable tetrabutyldideazaporphyrin. Although this porphyrin analogue was highly unstable, proton NMR spectroscopy demonstrated that it retained a high degree of diatropic character.

Full text of DOI:10.1016/j.tetlet.2020.152619

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Tetrabutyldideazaporphyrin
Jonathan T. Laxner, Timothy D. Lash
PII:
S0040-4039(20)31122-9
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152619
TETL 152619
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Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
18 September 2020
26 October 2020
28 October 2020
Please cite this article as: Laxner, J.T., Lash, T.D., Tetrabutyldideazaporphyrin, Tetrahedron Letters (2020), doi:
https://doi.org/10.1016/j.tetlet.2020.152619
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Tetrabutyldideazaporphyrin
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Jonathan T. Laxner and Timothy D. Lash
n-Bu
n-Bu
n-Bu
CHO
1.TiCl4/Zn(Cu)
n-Bu
N
N
H
H
H
N
2. DDQ
3. HBr
n-Bu
n-Bu
OHC

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Tetrabutyldideazaporphyrin
Jonathan T. Laxnera and Timothy D. Lasha, 
aDepartment of Chemistry, Campus Box 4160, Illinois State University, Normal, Illinois 61790-4160, USA
———
ARTICLE INFO
ABSTRACT
 Corresponding author. Tel.: +1-309-438-8554; fax: +1-309-438-5538; e-mail: tdlash@ilstu.edu
Article history:
Received
McMurry coupling of a dibutylpyrrole diacrylaldehyde afforded an unstable
tetrabutyldideazaporphyrin. Although this porphyrin analogue was highly unstable,
Received in revised form
Accepted
Available online
proton NMR spectroscopy demonstrated that it retained a high degree of diatropic
character.
2020 Elsevier Ltd. All rights reserved.
Keywords:
Aromaticity
Porphyrins
Macrocycles
McMurry condensation
Diatropicity
lacks one of the nitrogens found in porphyrin structures.8
Furthermore, carbaporphyrinoid systems have been described
where one or two of the nitrogen atoms have been replaced with
carbon atoms.9 In order to further probe the aromatic
Introduction
Ph
characteristics of porphyrinoids, a dideazaporphyrin 4a was
synthesized by McMurry coupling of pyrrole diacrylaldehyde 5a
(Scheme 1).10 Although a potentially antiaromatic intermediate 6
may be formed, this spontaneously oxidizes to give the aromatic
N
N
N
N
N
N
N
H
H
Ph
Ph
H
H
H
product. Tetraphenyldideazaporphyrin 4a exhibited porphyrin-
like properties, and the UV-vis spectrum afforded a Soret band at
401 nm and a weaker absorption at 565 nm.10 The proton NMR
spectrum for 4a showed the presence of a strong diamagnetic
ring current and the internal CH protons were shifted upfield to -
2.52 ppm, while the external macrocyclic protons appeared
downfield between 9.8 and 10.0 ppm. Addition of trifluoroacetic
N
N
N
N
Ph
3
2
1
vacataporphyrin
2+
acid (TFA) generated a dicationic species 4aH2 that exhibited
Porphyrins 1 are macrocyclic systems that have been widely
studied due to their importance as natural products (hemes,
chlorophylls, etc.),1 photosensitizers,2 catalysts,3 sensors4 and so
on. These structures are built up from four pyrrolic subunits and
all twenty-four atoms within the porphyrin framework are sp2
hybridized. Porphyrins are examples of nonbenzenoid aromatic
enhanced diatropicity. In this species, the interior protons
appeared further upfield at -5.45 ppm while the exterior protons
shifted further downfield to give resonances at 11.07 and 11.11
ppm. The UV-vis spectrum for the dication also showed a
stronger Soret band at 422 nm and a series of Q bands between
600 and 750 nm. Subsequently, a second example of a
dideazaporphyrin 7 was reported by Latos-Grazynski and this
“divacataporphyrin” also exhibited aromatic characteristics.11
Interestingly, the proton NMR spectrum of 7 showed the
presence of a minor conformation 7’ that was in equilibrium with
the principal species (Scheme 2).11
compounds and have
a high degree of thermodynamic
stabilization. Proton NMR spectroscopy provides a convenient
method for assessing the diatropic characteristic of this system
and commonly shows the external meso-protons downfield near
+10 ppm while the internal NH protons often appear upfield at -4
ppm.5 The origin of aromaticity in porphyrin-type structures has
been widely debated.6 Many synthetic porphyrin chemists
consider porphyrins to be examples of bridged [18]annulenes due
to the presence of an 18 electron delocalization pathway (shown
in bold for structure 1).6 Other models have been proposed,
including a 22 electron version that incorporates two of the
pyrrole lone pair electrons (structure 2).7 However,
a
deazaporphyrin 3 named vacataporphyrin was reported that
retained porphyrin-like aromaticity even though the structure

2
prepare a symmetrically substituted pyrrole to avoid the
R
R
formation of isomers and, given this restriction, dibutylpyrrole 5c
CHO
R
R
was selected for this investigation.
N
N
TiCl4
H
H
H
Zn(Cu)
N
5
O
OHC
R
CH3NO2
CH3(CH2)4NO2
C
R
CH3(CH2)2
H
O
C
1. Et3N
a. R = Ph, b. R = Et, c. R = n-Bu
8
6
2. H2SO4, Ac2O
3. NaBH4
[O]
(CH2)3CH3
H
Et3N
R
R
R
R
n-Bu
n-Bu
N
N
TFA
CH3(CH2)3
H
(CH2)3CH3
CH
CH
OX
H
CO2Et
N
N
N
O2N
a. X = H
9
R
CNCH2CO2Et
DBU
R
H
10
R
R
21,23-Dideazaporphyrins
Ac2O
H2SO4
4
NaOH
2+
4
H2
(CH2OH)2
b. X = OAc

Scheme 1. Synthesis of dideazaporphyrins.
n-Bu
n-Bu
n-Bu
n-Bu
Me2N-CH=CH-CHO
Ph
Ph
N
POCl3
N
H

N
OHC
CHO
H
11
5c
N
Ph
Scheme 3. Synthesis of a dibutylpyrrole diacrylaldehyde.
Ph
Ph
N
Ph
N
Ph
The alkyl substituents were introduced using the Barton-Zard
methodology.15,16 Initially, 1-nitropentane (8) was required and
this was prepared by reacting butyraldehyde with nitromethane
(Henry reaction) in the presence of triethylamine, followed by
acetylation with acetic anhydride-H2SO4 and reduction with
sodium borohydride (Scheme 3).17 Triethylamine-catalyzed
7
Ph
7’
Scheme 2. Isomerization of a dideazaporphyrin.
Henry reaction of
8
with valeraldehyde generated
Results and Discussion
hydroxynitrodecane 9a and subsequent acetylation afforded the
related acetate 9b as a mixture of diastereomers. Condensation of
9b with ethyl isocyanoacetate in the presence of two equivalents
of DBU gave dibutylpyrrole ethyl ester 10 in 40% yield. This
was subjected to base catalyzed hydrolysis and decarboxylation
with sodium hydroxide in ethylene glycol at 200 C to produce
3,4-dibutylpyrrole (11) in virtually quantitative yield. This
In the initial publication, we concluded that the spectroscopic
results confirmed that porphyrins have [18]annulene-like
characteristics.10 This inspired further computational studies by
others that considered the merits of this assertion.12.13 It had been
our intention to stimulate discussion in this area and the
[18]annulene model for porphyrinoid aromaticity must be
considered to be an oversimplification. Schleyer and coworkers
concluded that the aromatic characteristics for macrocyclic
systems of this type are multifaceted and “energetic and magnetic
aromaticity measures” may not always be in agreement.12 The
results indicated that the spectroscopic properties of porphyrins
derive from the macrocyclic  conjugation pathways but may not
necessarily play an important role in determining the
thermodynamic stability of these structures.12 In order to further
investigate these issues, the synthesis of dideazaporphyrins that
do not bear aryl substituents was investigated. The phenyl
substituents in 4a may be involved in a degree of -conjugation
and the properties of alkyl substituted structures could provide a
useful contrast.
o
doubly -unsubstituted pyrrole underwent
a
vinylogous
Vilsmeier-Haack reaction with phosphorus oxychloride and 3-
dimethylaminoacrolein in refluxing 1,2-dichloroethane and,
following hydrolysis with aqueous sodium acetate, gave the
required stretched dialdehyde 5c. The proton NMR spectrum for
5c gave a doublet of doublets at 6.90 ppm (J = 7.8, 15.6 Hz), a
doublet at 7.34 ppm (J = 15.7 Hz) and a doublet at 9.64 ppm
(CHO, J = 7.8 Hz) for the two acrylaldehyde side chains,
confirming that the alkene units have a trans-configuration.
McMurry coupling of 5c with titanium(IV) chloride and a
zinc-copper couple in THF was investigated. In reactions of
diphenylpyrrole diacrylaldehyde 5a with TiCl4-Zn/Cu, no
oxidation of the intermediates was required. However, the
formation of 4c from 5c was only evident after an oxidation step.
This was accomplished by brief exposure to 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ). The resulting product proved to be
rather unstable, particularly in the free base form. Protonation
Initially, the synthesis of tetraethyldideazaporphyrin 4b was
investigated. McMurry coupling of the known dialdehyde 5b14
was conducted under the same conditions used to prepare 4a.
However, while the targeted species could be detected by UV-vis
spectroscopy, the macrocycle could not be isolated. The
problems encountered were two-fold: 1) the dideazaporphyrin
appeared to be somewhat unstable; and 2) the product was
virtually insoluble in organic solvents such as chloroform. In
order to overcome the latter issue, longer chain substituents were
introduced onto the pyrrolic precursor. It was necessary to
2+
gave a dicationic species 4cH2 that could be isolated, but even
so decomposition readily occurred. The product was isolated as
either the dihydrobromide or the trifluoroacetate salt. The UV-vis
2+
spectrum for the dicationic species 4cH2 gave a strong Soret
band at 413 nm and Q bands at 585, 660 and 735 nm (Figure 1).

3
Although the spectrum resembles the one reported for 4aH22+, the
absorptions are hypsochromically shifted by 9-16 nm.
Nevertheless, the spectrum retains a remarkably porphyrin-like
appearance, indicating that this species has similar electronic
features. Addition of triethylamine afforded the free base form 4c
and this gave a diminished Soret band at 384 nm and a weaker
absorption at 536 nm (Figure 1). This spectrum is still similar to
a porphyrin-type system, but also closely resembles the
electronic spectrum for [18]annulene.18 The UV-vis spectrum for
4c is blue shifted compared to its tetraphenyl counterpart 4a by
17-29 nm. These results indicate that the porphyrinoid core in 4a
has a significant conjugation interaction with the phenyl
substituents.
Conclusions
In conclusion, the formation of a tetraalkyl dideazaporphyrin
by McMurry coupling of a pyrrole diacrylaldehyde has been
investigated. The product exhibits porphyrin-like spectroscopic
properties, including strongly diatropic NMR spectra, but is
nevertheless highly unstable. The results concur with recent
computational analyses.
Acknowledgments
This work was supported by the National Science Foundation
(CHE-1855240).
1.4
1.2
1
Declaration of Competing Interest
The authors declare that they have no competing financial
interests or personal relationships that could have appeared to
influence the work reported in this paper.
0.8
A
0.6
0.4
0.2
0
Electronic Supplementary Information
1
1
Experimental procedures and selected H NMR, H-1H COSY,
HSQC, DEPT-135, 13C NMR, and UV-Vis spectra are provided.
References and notes
350
450
550
650
750
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(d) Gopalaiah, K. Chem. Rev. 2013, 113, 3248-3296.
Wavelength (nm)
Figure 1. UV-vis spectra of 4c.2HBr in chloroform (red line) and
1% Et3N-chloroform (blue line).
2+
The proton NMR spectrum of 4cH2 demonstrated that this
species is highly diatropic. The internal CH protons were
strongly shielded, giving a multiplet at -5 ppm, and the NHs
afforded a resonance at -1.1 ppm (Figure 2). In addition, the
external protons were strongly deshielded and produced a
multiplet at 10.9 ppm, confirming the presence of a strong
aromatic ring current. The NMR spectrum for the free base form
could only be obtained by adding a small amount of NaOD in
D2O to the NMR tube. The resulting NMR spectrum, while of
poor quality, showed the internal CH protons upfield at -2.4 ppm
and the external protons downfield near 9.7 ppm. The results
show that the free base has decreased diatropicity but still has a
substantial ring current that is comparable to [18]annulene and
many porphyrinoid systems. Hence, the high degree of aromatic
character evident in these proton NMR spectra does not appear to
have any bearing on the stability of the structures.
4. Paolesse, R.; Nardis, S.; Monti, D.; Stefanelli, M.; Natale, C. D. Chem
Rev. 2017, 117, 2517-2583.
5. Medforth, C. J. In The Porphyrin Handbook, Kadish K. M.; Smith, K.
M.; Guilard, R., Eds.; Academic Press: San Diego, 2000; Vol. 5, pp 1–80.
6. (a) Lash T. D. J. Porphyrins Phthalocyanines 2011, 15, 1093-1115. (b)
Lash T. D. J. Porphyrins Phthalocyanines 2012, 16, 1093
7. Cyranski, M. K.; Krygowski, T. M.; Wisiorowski, M.; Hommes, N. J. R.
v. E.; Schleyer, P. v. R. Angew. Chem. Int. Ed. 1998, 37, 177-180.ꢀ
8. Pacholska, E.; Latos-Grazynski, L.; Ciunik, Z. Chem. Eur. J. 2002, 8,
5403-5406.ꢀ
9. (a) Lash T. D. Chem. Rev. 2017, 117, 2313-2446. (b) AbuSalim, D. I.;
Lash, T. D. J. Org. Chem. 2013, 78, 11535-11548.
10. Lash, T. D.; Jones, S. A.; Ferrence, G. M. J. Am. Chem. Soc. 2010, 132,
12786-12787.
11. Pacholska-Dudziak, E.; Szterenberg, L.; Latos-Grazynski, L. Chem. Eur.
J. 2011, 17, 3500-3511. ꢀ
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315-321.
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Chem. 2014, 12, 6145-6150.
14. Xu, L.; Ferrence, G. M.; Lash, T. D. Org. Lett. 2006, 8, 5113-5116.
15. (a) Barton, D. H. R.; Zard, S. Z. J. Chem. Soc., Chem. Commun. 1985,
21, 1098-1100. (b) Barton, D. H. R.; Kervagoret, J.; Zard, S. Z. Tetrahedron
1990, 46, 7587-7598. (c) Lash, T. D.; Bellettini, J. R.; Bastian, J. A.; Couch,
K. B. Synthesis 1994, 170-172.
16. Gribble, G. W. In Name Reactions in Heterocyclic Chemistry; Li, J. J.,
Ed.; Wiley: Hoboken, NJ, 2005, pp 70-78. ꢀ
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4710-4713.
Figure 2. Partial proton NMR spectrum of 4c.2HBr in CDCl3
showing the downfield and upfield regions.

4
Declaration of Competing Interest
Highlights
The authors declare that they have no competing financial
interests or personal relationships that could have appeared to
influence the work reported in this paper.
 Analysis of aromatic character in
2.
porphyrinoid systems
 Relationship between porphyrins and
[18]annulene
 McMurry synthesis of conjugated
macrocycles
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 Magnetic aromaticity (diatropicity) is not a
measure of stability
1.
3.
Tetrabutyldideazaporphyrin
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Jonathan T. Laxner and Timothy D. Lash
n-Bu
n-Bu
n-Bu
CHO
n-Bu
N
H
H
N
1.TiCl4/Zn(Cu)
H
N
2. DDQ
3. HBr
n-Bu
n-Bu
OHC