Diazoniapentaphenes. Synthesis from Pyridine-2-carboxaldehyde and Structural Verifications

Article abstract of DOI:10.1002/jhet.5570410224

Reactions of pyridine-2-carboxaldehyde (9) with α,α′ -dibromo-o- and p-xylenes led to the corresponding bis-pyridinium aldehydes 10 and 14. These aldehydes were quite reactive and the respective hydrates 11 and 15 were also formed. Cyclization of 10 or 11

Full text of DOI:10.1002/jhet.5570410224

Mar-Apr 2004
291
Diazoniapentaphenes. Synthesis from Pyridine-2-carboxaldehyde
and Structural Verifications
A. Paul Krapcho* and Sergio A. Cadamuro
Department of Chemistry, University of Vermont, Burlington, VT 05405
A.Paul.Krapcho@uvm.edu
Received November 7, 2003
Reactions of pyridine-2-carboxaldehyde (9) with α,α'-dibromo-o- and p-xylenes led to the corresponding
bis-pyridinium aldehydes 10 and 14. These aldehydes were quite reactive and the respective hydrates 11 and
15 were also formed. Cyclization of 10 or 11 with 48% HBr led to 12 while cyclization with PPA followed
by conversion to the bis tribromide and loss of bromine led to 1. Cyclization of 14 or 15 with 48% HBr led
to 3. Attempts to react α,α'-dibromo-m-xylene with pyridine-2-carboxaldehyde (9) were not successful for
the preparation of the bis-pyridinium aldehyde 13. The bis-pyridinium acetals 4, 5 and 6 were prepared and
cyclized to afford 1, 2 and 3, respectively, by the previously reported procedures. The structures of 1 and 2
1
13
were verified by H-NMR and C-NMR spectroscopy while that of 3 was confirmed by X-ray analysis.
J. Heterocyclic Chem., 41, 291 (2004).
Introduction.
In 1964 Bradsher and co-workers reported the synthesis
of 12a,14a- (1), 4a,12a- (2) and 4a,8a-diazoniapentaphene
salts (3)[1]. Subsequently a German group repeated these
procedures and studied their polarography [2]. Several
diazonia polycyclics were also described by an Eastman
Kodak (Rochester NY) group [3,4].
based solely on ultraviolet spectral considerations and
comparisons [1].
The acetal, 2-(1,3-dioxolan-2-yl) pyridine, was treated
with α,α'-dibromo-o-, m-, or p-xylene to afford the corre-
sponding bis-pyridinium salts 4, 5 and 6, respectively.
These bis-quaternary salts were cyclized on heating in
polyphosphoric acid (PPA) followed by precipitation with
HBr/Br2 to afford the insoluble bis-tribromide salts which
on standing or heating lost Br2 and led to the bromides 1, 2
and 3, respectively [1].
The initially formed acridizinium salt from the first
cyclization step derived from 4 can only undergo the
second cyclization step to afford a single product which
was formulated as 1. This structural formulation was
verified by chemical transformations. The cyclizations
of the bis-pyridinium salts 5 or 6 can either afford linear
products 7 and 8 or the angular products formulated as 2
or 3, respectively. These structural assignments were
The purpose of the present research was to clearly estab-
lish the proposed structures for 1, 2 and 3. In addition, we
wished to investigate the direct use of pyridine-2-carbox-
aldehyde (9), instead of the acetal in reactions involving
α,α'-dibromo-o-, m-, and p-xylenes to form the corre-
sponding bis-pyridinium salts. These latter compounds on
cyclization would lead to 1, 2 or 3, respectively. The ulti-
mate goal was the development of facile pathways to sub-
stituted analogues related to 1, 2 and 3, which were
required in another investigation.
Results and Discussion.
Following the procedure described in the earlier paper [1],
treatment of α,α'-dibromo-o-xylene with 2-(1,3-dioxolan-2-

292
A. P. Krapcho and S. A. Cadamuro
Vol. 41
yl) pyridine led to the bis-pyridinium salt 4 which on
cyclization in PPA and workup led to 1. Both 1 and 4 were
readily identifiable by their 1H a n d 13C NMRspectra.
Treatment of pyridine 2-carboxaldehyde (9) with α,α'-
dibromo-o-xylene (7.2:1 molar equivalents) in DMF at 45
°C for 48 hours led to the bis-pyridinium salt 10 along with
dihydrate 11 (78%).
as a bis-tribromide salt. This salt on standing lost Br2, and
afforded 1. This product was identical in all aspects to the
product obtained following the original procedure [1] pre-
viously described for cyclization of the bis-acetal 1.
Attempts to prepare 13 (or the corresponding dihydrate)
by treatment of pyridine 2-carboxaldehyde (9) with α,α'-
dibromo-m-xylene (7.2:1 molar equivalents) in DMF led
to a small amount of an orange solid, which readily turned
to a dark intractable gum in air. No identifiable products
could be isolated from this reaction although the crude
proton nmr indicated some of the desired product.
The synthesis of 5 was performed following the litera-
ture procedure [1] and 5 was cyclized in 48% HBr (PPA
was used in literature) to afford 2. The structural assign-
1
ment for 2 can be established by H nmr since fourteen
proton resonances are exhibited in its spectrum. Structure
7 is excluded on this basis alone since because of symme-
try only seven (two H each) proton resonances should be
observed. In the 13C nmr spectrum of 2 only eighteen car-
bons were detected (two missing). Structure 7 would
exhibit ten carbon resonances.
Treatment of pyridine 2-carboxaldehyde (9) with α,α'-
dibromo-p-xylene in DMF led to 14 along with dihydrate
15. As in the case of 10, 14 readily undergoes hydration
and this product dominated when workup was performed
under humid conditions. Of particular diagnostic value are
the proton resonances at δ 6.3 and 6.0 for the methylene
bridges in 14 and 15, respectively. If the dialdehyde stands
in air, it undergoes a facile hydration to form the stable
dihydrate. The dialdehyde or mixture readily cyclized on
treatment with 48% HBr to afford 3 (68%).
The bis-pyridinium salt 1 0, as expected, was quite sus-
ceptible to hydration and, indeed if the product was isolated
by filtration on a humid day, the dihydrate of the bis-pyri-
dinium salt 11 was obtained.Addition of D2O to the
DMSO-d6 solutions led to an nmr spectrum consistent with
the dihydrate. Of obvious diagnostic values were the bridge
methylene resonances at δ 6.6 and 6.2 for the bis-pyri-
dinium aldehyde 1 0 and the hydrated form 11, respectively,
and the presence or absence of the CHO resonance at δ 10.3
in the proton nmr spectrum. If the crude product was dis-
solved in a methanol- ethyl acetate mixture, followed by
evaporation of the solvent, the dihydrate 11 was the major
product. On standing, the initially obtained product, which
was predominantly 1 0, was transformed into a mixture of
bis-aldehyde 10 (60%) and the hydrated form 11 (40%, nmr
analysis of the singlets at δ 6.6 and 6.2, respectively).
It is of interest to note that treatment of the dialdehyde
10 and dihydrate 11 mixture with 48% HBr led to the bro-
momethyl analogue of the mono cyclized product 12, the
apparent product of displacement of formally pyridine 2-
carboxaldehyde by the bromide anion in the initial cycliza-
tion product.
The bis-pyridinium salt 6 was prepared from the acetal
as described previously and cyclized to afford 3. The
exclusion of structure 8 based on 1H or 13C nmr analysis is
On the other hand, the product which was obtained upon
heating the mixture of 10 and 11 in PPA could be isolated

Mar-Apr 2004
Diazoniapentaphenes. Synthesis from Pyridine-2-carboxaldehyde
293
13
8.40 (s, 2H), 8.31 (t, J = 7.1 Hz, 2H). C NMR (DMSO-d ): δ
142.11, 137.40, 137.33, 137.07, 135.34, 132.96, 128.32, 126.66,
125.30, 123.08.
quite difficult since both 3 and 8 would exhibit seven dis-
tinct protons and ten distinct carbons.
This sample readily crystallized from water.An X-ray
analysis indicated the correct formulation of the double
cyclodehydration of 6 as 3 [5]. The ORTEP view of 3,
which is planar, is shown in Figure 1.
6
Method B.
The conversion of 4 to 1 (33%) was performed following the
1
literature procedure [1]. The sample was identical in its H nmr
13
and C nmr spectra to the product that was obtained in method A
from 10 and 11.
4a,12a-Diazoniapentaphene Bromide (2).
The 1,3-Bis(1-methylene-2-[1,3-dioxolan-2-yl]pyridinium
bromide)-benzene (5, 250 mg, 0.39 mmol) in concd HBr (1 mL)
was refluxed 16 hours and then the cooled solution was poured
into THF (10 mL). The product was collected by filtration and
dried under vacuum to afford 2 (98 mg, 48%) as a yellow pow-
1
der; mp above 300 °C; lit. [1] >400 °C. H-NMR (DMSO-d ): δ
6
11.72 (s, 1H), 10.47 (s, 1H), 10.41 (s, 1H), 9.61-9.59 (m, 2H),
9.25 (s, 1H), 8.79 (d, J = 8.4 Hz, 1H), 8.72 (d, J = 8.3 Hz, 1H),
8.55-8.47 (m, 2H), 8.39 (d, J = 9.1 Hz, 1H), 8.29-8.26 (m, 3H).
13
C-NMR (DMSO-d ): δ 142.58, 141.32, 138.24, 138.11,
6
137.62, 137.23, 136.89, 133.96, 131.84, 130.27, 128.79, 128.26,
127.28, 126.30, 125.75, 125.15, 123.19, 123.10.
4a,8a-Diazoniapentaphene (3).
Figure 1. ORTEP view of 3.
Method A.
A solution of the bis quaternary salts (14 and 15, 200 mg, 0.42
mmol) in 48% aqueous HBr (2 mL) were refluxed for 16 hours.
To the cooled solution was added THF (20 mL). The product 3
was collected by filtration as a yellow powder (184 mg, 68 %):
The structural assignments previously proposed for 1,2
and 3 have been verified. The pyridinium salts (and
hydrates) obtained from pyridine 2-carboxaldehyde and o-
and p-α,α'-dibromoxylene have been isolated and charac-
terized. These compounds readily undergo double
cyclodehydration under acidic conditions and workup to
afford 1 and 3, respectively.
1
mp: above 300 °C: lit. [1] >400°C. H-NMR (DMSO-d ): δ
6
10.28 (s, 2H), 10.27 (s, 2H), 9.56 (d, J = 6.7 Hz, 2H), 8.78 (d, J =
8.5 Hz, 2H), 8.54 (t, J = 7.7 Hz, 2H), 8.32 (dd, J = 7.0 Hz, 1.3 Hz,
13
2H), 8.26 (s, 2H). C-NMR (DMSO-d ): δ 140.16, 137.53,
6
136.44, 136.24, 132.27, 127.86, 127.78, 126.32, 124.94, 123.91.
Method B.
EXPERIMENTAL
Cyclization of 6 following the literature procedure led to 3
(84%) [1] which was identical in its nmr spectra to the sample
obtained by method A.
The pyridine 2-carboxaldehyde and the α,α'-dibromo-o-, m-
and p-xylenes were purchased from Acros. Melting points were
1
taken on a Fisher-Johns apparatus and are uncorrected. The H
13
and C NMR spectra were obtained on a Bruker ARX-500
1,2-Bis(1-methylene-2-[1,3-dioxolan-2-yl]pyridinium bromide)
benzene (4).
pulsed spectrometer with tetramethylsilane as an internal stan-
dard.
This compound was prepared via the literature procedure in
1
78% yield [1]. H NMR (DMSO-d ): δ 8.94 (d, J = 6.2 Hz, 2H),
6
8.02 (t, J = 7.8 Hz, 2H), 8.39 (d, J = 7.0 Hz, 2H), 8.26 (t, J = 6.8
Hz, 2H), 7.43 (m, 2H), 6.82 (m, 2H), 6.48 (s, 2H), 6.15 (s, 4H),
12a,14a-Diazoniapentaphene Bromide (1).
Method A.
13
4.38 (s, 8H). C NMR (DMSO-d ): δ 153.26, 148.72, 147.85,
6
131.89, 131.26, 129.75, 129.21, 127.55, 98.20, 66.73, 58.77.
The bis-pyridinium bromides 10 and 11 (478 mg, 0.93 mmol)
were dissolved in polyphosphoric acid (3.5 mL) at 100 °C over a
period of 2 hours. The solution was stirred at 150 °C for 16 hours
and then was cooled to room temperature. Water (9 mL) was
added and the mixture was refluxed for 2 hours. To the cooled
1,3-Bis(1-methylene-2-[1,3-dioxolan-2-yl]pyridinium Bromide
(5).
The 2-(1,3-dioxolan-2-yl)pyridine (0.62 g, 0.0041 mmol) and
α,α'-dibromo-m-xylene (0.41 g, 0.0015 mmol) [ 2.7 molar
equivalents] were placed in DMF (0.5 mL). The solution was
stirred at 30 °C for 20 h and then kept without stirring for 96 h at
rt. After this period a rock-like colorless solid coated the bottom
of the flask. The solid was collected by filtration and washed
with ether. This material was recrystallized from MeOH-EtOAc
(soluble in MeOH, insoluble in EtOAc) to afford gorgeous white
solution HBr/Br (3:1) was added to precipitate the tribromide
2
salt, which was collected by filtration to afford a yellow powder.
This product on standing at room temperature for 1 day to
remove Br yielded 1 (146 mg, 35%) as a yellow powder: mp >
2
300 °C; lit. [1] >400 °C (dec 300 °C).
1
H NMR (DMSO-d ): δ 11.47 (s, 2H), 9.46 (d, J = 6.7Hz, 2H),
6
9.27 (s, 2H), 8.81 (d, J = 8.5 Hz, 2H), 8.50 (t, J = 7.8 Hz, 2H),

294
A. P. Krapcho and S. A. Cadamuro
Vol. 41
13
1H), 8.19-8.12 (m, 2H), 8.10-8.02 (m, 2H), 5.41 (s, 2H). C-
NMR (DMSO-d ): δ 137.75, 137.19, 135.93, 135.61, 132.47,
rhombic crystals (0.55 g, 89%); mp 160-165 °C: lit. [1] 95.5-97
1
°C. H-NMR (DMSO-d ): δ 9.08 (d, J=5.8, 2H), 8.74 (t, J= 7.7,
6
6
131.81, 128.18, 125.71, 123.81, 122.95, 29.75.
Anal. Calcd. for C H Br N: C, 47.63; H, 3.14; N, 3.97.
2H), 8.32 (d, J = 8.0 Hz, 2H), 8.26-8.19 (m, 2H), 7.51 (t, J = 7.4
Hz,1H), 7.38 (dd, J = 7.6, 1.3 Hz, 2H), 7.27 (s, 1H), 6.45 (s, 2H),
14 11
Found: C, 47.40; H, 2.98; N, 3.80.
2
13
6.01 (s, 4H), 4.09 (s, 8H). C-NMR (DMSO-d ): δ 152.00,
6
147.30, 147.23, 134.50, 129.78, 128.61, 128.54, 127.86, 126.06,
96.98, 65.57, 59.51.
1,4-Bis(1-methylene-2-[carboxaldehyde]pyridinium bromide)-
benzene 14 and Dihydrate 15.
1,4-Bis(1-methylene-2-[1,3-dioxolan-2-yl]pyridinium Bromide (6).
Pyridine-2-carboxaldehyde (1.37 g, 0.012 mol) and α,α' -
dibromo-p-xylene (0.53 g, 0.002 mol) were dissolved in DMF (3
mL). The solution was placed in an oil bath at 42 °C and a yellow
solid was visible after 17 hours at this temperature. The mixture
was heated for a total of 64 hours. The solid was collected by fil-
tration and washed with ether to afford a pale yellow solid (0.37 g,
50%) which in the nmr showed trace amounts of the solvent DMF
This compound was prepared using the literature procedure in
1
a 74% yield [1]. H NMR (DMSO-d ): δ 9.06 (d, J = 6.2 Hz,
6
2H), 8.73 (t, J = 7.9 Hz, 2H), 8.32 (d, J = 7.9 Hz, 2H), 8.22 (t, J =
13
7.5 Hz, 2H), 7.39 (s, 4H), 6.46 (s, 2H), 6.02 (s, 8H). C NMR
(DMSO-d + D O): δ 153.14, 148.44, 148.00, 135.20, 129.89,
6
129.66, 127.49, 98.14, 66.85, 61.03.
2
and an absorption peak at δ 5.4 indicative of protons of a–CH Br
1
2
moiety (half-reacted analogue): H-NMR (DMSO-d ): δ 10.30 (s,
1,2-Bis(1-methylene-2-[carboxaldehyde]pyridinium bromide)-
benzene 10 and Dihydrate 11.
6
2H), 9.28 (t, J=6.0, 2H), 8.90 (t, J=7.9, 2H), 8.65-8.60 (m, 2H),
1
8.46-8.39 (m, 2H), 7.42 (s, 4H), 6.30 (s, 4H). H-NMR (DMSO-
d + D O): δ 8.89 (d, J = 6.1 Hz, 2H), 8.65 (t, J = 7.8 Hz, 2H), 8.34
Pyridine-2-carboxaldehyde (1.41 g, 0.013 mole) and α,α'-
dibromo-o-xylene (0.49 g, 0.0018 mole) were dissolved in DMF
(3 mL). The solution was placed in an oil bath pre-heated to 48
°C. After 18 h a yellow solid appeared and the mixture was
heated for a period of 48 h. The mixture was removed from the
bath and the solid (0.54 g, 78%), was collected by filtration and
washed with ether. A trace of DMF and about 10% hydrate was
6
(d, J = 7.6 Hz, 2H), 8.06 (t, J = 6.7 Hz, 2H), 7.32 (s, 4H), 6.17 (s,
2
13
2H), 6.00 (s, 4H). C NMR (DMSO-d + D O): δ 156.84,
6
2
147.46, 146.86, 135.08, 128.93, 128.02, 126.37, 85.57, 59.40.
Acknowledgement.
1
detectable in the nmr spectrum. H NMR (DMSO-d ): δ 10.29 (s,
We wish to thank Novuspharma SpA (Bresso, Italy) for pro-
viding financial support for Sergio Cadamuro (Universita di
Padova) as a visiting graduate student at the University of
Vermont. We also express our gratitude to Professor William
Watson of Texas Christian University for obtaining the X-ray
structure.
6
2H), 9.12 (d, J = 6.0 Hz, 2H), 9.01-8.95 (m, 2H), 8.77-8.72 (m,
2H), 8.50-8.44 (m, 2H), 7.46-7.40 (m, 2H), 6.95-6.91 (m, 2H),
1
6.54 (s, 4H). H NMR (DMSO-d + D O): δ 8.95 (d, J = 5.7 Hz,
6
2
2H), 8.78 (t, J = 7.6 Hz, 2H), 8.45 (d, J = 7.5 Hz, 2H), 8.13 (t, J =
6.9 Hz, 2H), 7.41-7.36 (m, 4H), 6.69-6.66 (m, 4H), 6.25 (s, 4H),
13
6.20 (s, 2H) ( trace CHO resonance at _ 10.33). C NMR
(DMSO-d + D O): δ 157.14, 147.47, 146.36, 132.33, 129.43,
6
127.73, 127.20, 126.16, 85.40, 56.88.
2
REFERENCES AND NOTES
7-Bromomethylacridizinium Bromide (12).
[1] C. K. Bradsher and J. C. Parham, J. Org. Chem., 29, 856
(1964).
A solution of bis-quaternary salts 10 and 11 (460 mg, 0.75
mmol) in 48% aqueous HBr (1.1 mL) was refluxed for 16 hours.
The cooled solution was poured into THF (20 mL) on which a
brown oily material formed. On trituration, a yellow powder
formed along with a brown paste. The yellow powder was col-
lected by filtration (71 mg, 48%); mp 230 °C (darkens) still solid
[2] S. Hunig, J. Gross, E. F. Lier and H. Quast, Liebigs Ann.
Chem., 339 (1973).
[3] D. L. Fields, J. B. Miller and D. D. Reynolds, J. Org. Chem.,
30, 252 (1965).
[4] D. L. Fields, T. H. Regan and J. C. Dignan, J. Org. Chem.,
33, 390 (1968).
[5] Crystallographic data will be presented in an appropriate
Journal.
1
> 300 °C. H-NMR (DMSO-d ): δ 10.68 (s, 1H), 9.48 (d, J = 6.9
6
Hz, 1H), 9.32 (s, 1H), 8.6 (d, J = 8.9 Hz, 1H), 8.38 (d, J = 8.6 Hz,