A modular synthesis of unsymmetrical tetraarylazadipyrromethenes

Article abstract of DOI:10.1021/jo050696k

A stepwise route to unsymmetrical tetraarylazadipyrromethenes by a condensation of 2,4-diaryl-5-nitroso-pyrroles with 2,4-diarylpyrroles is described. This modular building-block approach allows for the introduction of up to four different aryl substituents on the azadipyrromethene and is tolerant of a varied substituent set. An efficient synthesis of the 2,4-diarylpyrroles building blocks from 1,3-diaryl-4-nitro-butan-1-ones by nitro hydrolysis to a keto-aldehyde and subsequent ammonia condensation reaction has been achieved. The facile conversion of 2,4-diarylpyrroles into their α-nitroso analogues by their reaction with sodium nitrite generated the second building block required for the synthesis.

Full text of DOI:10.1021/jo050696k

A Modular Synthesis of Unsymmetrical
Tetraarylazadipyrromethenes
Michael J. Hall, Shane O. McDonnell, John Killoran, and Donal F. O’Shea*
Centre for Synthesis and Chemical Biology, Conway Institute, Department of Chemistry,
University College Dublin, Belfield, Dublin 4, Ireland
donal.f.oshea@ucd.ie
Received April 7, 2005
A stepwise route to unsymmetrical tetraarylazadipyrromethenes by a condensation of 2,4-diaryl-
5-nitroso-pyrroles with 2,4-diarylpyrroles is described. This modular building-block approach allows
for the introduction of up to four different aryl substituents on the azadipyrromethene and is tolerant
of a varied substituent set. An efficient synthesis of the 2,4-diarylpyrroles building blocks from
1,3-diaryl-4-nitro-butan-1-ones by nitro hydrolysis to a keto-aldehyde and subsequent ammonia
condensation reaction has been achieved. The facile conversion of 2,4-diarylpyrroles into their
R-nitroso analogues by their reaction with sodium nitrite generated the second building block
required for the synthesis.
Introduction
The dipyrrin class 1 was first described in the porphy-
rin synthesis work of Hans Fischer, and later in 1968
their boron difluoro analogues 2 were reported (Figure
1).1 Since that time derivatives of 2 have become widely
utilized fluorophores with many protein, nucleotide,
oligonucleotide, and enzyme conjugated analogues now
commercially available for use as fluorescent probes for
a range of biological processes.2 Other applications have
been explored including their use as inputs into molec-
ular wires,3 as laser dyes,4 as metal ion fluorescent
sensors,5 as probes for lipid membrane6 and protein
dynamics,7 and as labels for DNA sequencing.8 Their
value lies in their high fluorescent quantum yields and
FIGURE 1. Dipyrrins and azadipyrromethenes (azadipyrrin).
photostability with emission wavelength between 500
and 600 nm. We have recently described synthetic routes
to the bridging nitrogen analogues, the pyrrol-2-yl-pyrrol-
2-ylidene-amines 3 (azadipyrromethene or azadipyrrin)
and their BF2 analogues 4, which offer an optical
advantage of a bathochromic shift of approximately 150
nm in absorption and emission wavelength (Figure 1).9
We have shown how structural modification of the core
photosensitizer can give rise to control of the photophysi-
cal properties of this compound class for the development
of photodynamic therapeutic agents.9b,c
(1) (a) Fischer, H.; Eismayer, K. Ber. 1914, 47, 2019. (b) Fischer,
H.; Halbig, P.; Walach, B. Liebigs Ann. Chem. 1927, 452, 268. (c) Treibs,
A.; Kreuzer, F.-H. Liebigs Ann. Chem. 1968, 718, 208.
(2) Haugland, R. P. Handbook of Fluorescent Probes and Research
Products, 10th ed.; Molecular Probes: Eugene, OR.
(3) Wagner, R. W.; Lindsey, J. S. Pure Appl. Chem. 1996, 68, 1373.
(4) O’Neil M. P. Opt. Lett. 1993, 18, 37. (b) Guggenheimer, S. C.;
Boyer, J. H.; Thangaraj, K.; Shah, M.; Soong, M.-L. Pavlopoulos, T. G.
Appl. Opt. 1993, 32, 3942.
(5) (a)Rurack, K.; Kollmannsberger, M.; Resch-Genger, U.; Daub,
J. J. Am. Chem. Soc. 2000, 122, 968. (b) Rurack, K.; Kollmannsberger,
M.; Daub, J. Angew. Chem., Int. Ed. 2001, 40, 385. (c) Moon, S. Y.;
Cha, N. R.; Kim, Y. H.; Chang, S.-K. J. Org. Chem. 2004, 69, 181.
(6) Chen, J.; Burghart, A.; Derecskei-Kovacs, A.; Burgess, K. J. Org.
Chem. 2000, 65, 2900.
In addition, the tetra-aryl-BF2 analogues 4 have strong
absorptions and emissions profiles in the spectral region
(9) (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.;
O’Shea, D. F. Chem. Commun. 2002, 1862. (b) Gorman, A.; Killoran,
J.; O’Shea, C.; Kenna, T.; Gallagher, W. M.; O’Shea, D. F. J. Am. Chem.
Soc. 2004, 126, 10619. (c) Gallagher, W. M.; Allen, L. T.; O’Shea, C.;
Kenna, T.; Hall, M.; Killoran, J.; O’Shea D. F. Br. J. Cancer 2005, 92,
1702.
(7) Karolin, J.; Johansson, L. B.-A° .; Strandberg, L.; Ny, T. J. Am.
Chem. Soc. 1994, 116, 7801.
(8) Bergstro¨m, F.; Ha¨gglo¨f, P.; Karolin, J.; Ny, T.; Johansson, L. B.-A˙
Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 12477.
10.1021/jo050696k CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/15/2005
J. Org. Chem. 2005, 70, 5571-5578
5571

Hall et al.
SCHEME 1. Synthesis of Symmetrical
Tetraarylazadipyrromethenes
SCHEME 2. Proposed Route to Unsymmetrical
Tetraarylazadipyrromethenes
between 650 and 750 nm, which is a highly sought-after
region of the spectrum for optical applications. This
emerging class of chromophore offers an alternative to
the other compound classes with related near-infrared
spectral characteristics, such as the phthalocyanines,
azaporphyrins and cyanines dyes, with apparent poten-
tial for application in the areas of fluorescent biochemical
assaying and biomolecular probes. A key area of interest
is the application of near-infrared dyes for real time in
vivo fluorescence imaging for biomedical diagnostic ap-
plications, which is achievable as a result of efficient
penetration of light through body tissue and the low auto-
fluorescence of endogenous chromophores in this spectral
region.10
The chromophore class 3 was first reported over 60
years ago but remained unstudied until it attracted our
interest and we reported their spectral properties and
conversion into their corresponding BF2 chelated ana-
logues.11 We have detailed an optimized synthetic route
to the tetra-aryl C-2 symmetric derivatives 3 from the
reaction of 1,3-diaryl-4-nitro-butan-1-ones 5 with am-
monium acetate (Scheme 1).9b Although this approach is
synthetically very accessible, a limitation of this route
is that two molecules of 5 ultimately combine to yield 3
and consequently only symmetrical derivatives contain-
ing two pairs of aryl substituents can be generated.
As part of our ongoing work on tetraarylazadipyr-
romethenes and their chelated analogues we required a
stepwise synthesis of unsymmetrical systems, which
would facilitate the introduction of differing substituents
on each of the aryl rings. This type of synthetic control
would be required for fine-tuning of both spectroscopic
and solubility properties of the compounds and allow the
introduction of specific functional groups for both molec-
ular sensors and bioconjugated analogues. The modular
approach we chose to develop was to couple one-half of
the molecule with the other by the reaction of 2,4-
diarylpyrroles 6 with their corresponding R-nitroso ana-
logues 7 (Scheme 2).
of phenacyl azides,12 reaction of hexacarbonylmolybde-
num with 3-aryl-2H-azirines,13 and Grignard-mediated
dimerization of acetophenone oximes.14 Rhodium- and
zirconium-catalyzed reaction of alkynes, amines, and
carbon monoxide have been reported as procedures to
unsymmetrically substituted derivatives, but these meth-
ods require high-pressure CO conditions.15,16
Our approach was to exploit the 1-nitro-4-butanones
5 as our initial substrate as it would be a starting
material common to our previously reported symmetrical
synthesis.9b Our aim was to develop a direct transforma-
tion to the 2,4-diarylpyrroles 6 by a sequential Nef
transformation of 5 into a 1,4-keto-aldehyde that would
be converted to the desired pyrroles by an ammonia
condensation reaction.17 The starting point of the syn-
thesis was the diaryl R,â-unsaturated ketones (chalcones)
8 of which 8a,c,h were commercially available and the
remainder 8b,d,e,f,g,i,j were synthesized by an aldol/
dehydration reaction of the corresponding aldehyde and
acetophenone in high yield (see Supporting Information,
p S5). The two aldehydes (4-diethylaminomethyl-benzal-
dehyde and 4-morpholin-4-ylmethyl-benzaldehyde) re-
quired for the synthesis of 8e, 8f, and 8j were not
commercially available and were synthesized from the
reaction of 4-bromomethylbenzaldehyde18 with the cor-
responding amine (see SI p S3). 1,4-Addition of ni-
tromethane to 8a-j using diethylamine as base in
methanol at reflux provided us with a set of 1,3-diaryl-
4-nitro-butan-1-ones 5a-j in isolated yields of 68-93%
(Table 1).
This facile two-step procedure provided the substrates
5 for the pyrrole generation. Deprotonation of 5 with
KOH in MeOH, with THF as a cosolvent to maintain a
homogeneous solution, generated a nitro-stabilized anion,
which upon hydrolysis with H2SO4 gave the 1-keto-4-
dimethylacetals intermediates 9. The intermediate ketal
9a (Ar1, Ar2 ) Ph) was isolated by silica gel chromatog-
raphy in 73% yield; however in subsequent examples this
was deemed unnecessary and the unpurified material
was converted directly to the pyrrole without isolation.
Results and Discussion
Synthesis of 2,4-Diaryl-1H-pyrroles. To pursue this
synthetic strategy we required a versatile synthesis of
2,4-diarylpyrroles. Despite their synthetic importance,
direct methods for making 2,4-diarylpyrroles 6 are
limited, especially if two different aryl substituents are
required. Routes to symmetrical substituted 2,4-diaryl-
pyrroles include SmI2-mediated reductive dimerization
(12) Fan, X.; Zhang, Y. Tetrahedron Lett. 2002, 43, 1863.
(13) Nitta, M.; Kobayashi, T. Chem. Lett. 1983, 1715.
(14) Deady, L. W. Tetrahedron 1967, 23, 3505.
(15) Campi, E. M.; Fallon, G. D.; Jackson, W. R.; Nilsson, Y. Aust.
J. Chem. 1992, 45, 1167.
(16) Buchwald, S. L.; Wannamaker, M. W.; Watson, B. T. J. Am.
Chem. Soc. 1989, 111, 776.
(17) Kikuchi, K.; Hibi, S.; Yoshimura, H.; Tokuhara, N.; Tai, K.;
Hida, T.; Yamauchi, T.; Nagai, M. J. Med. Chem. 2000, 43, 409.
(18) Wen, L.; Li, M.; Schlenoff, J. B. J. Am. Chem. Soc. 1997, 119,
7726.
(10) For some recent examples, see: (a) Ke, S.; Wen, X.; Gurfinkel,
M.; Charnsangavej, C.; Wallace, S.; Sevick-Muraca, E. M.; Li, C. Cancer
Res. 2003, 63, 7870. (b) Xu, C. X.; Ye, J.; Marks, D. L. Opt. Lett. 2004,
29, 1647. (c) Hawrysz, D. J.; Sevick-Muraca, E. M. Neoplasia 2000, 2,
388. (d) Tung, C.-H.; Mahmood, U.; Bredow, S.; Weissleder, R. Cancer
Res. 2000, 60, 4953.
(11) Rogers, M. A. T. J. Chem. Soc. 1943, 596.
5572 J. Org. Chem., Vol. 70, No. 14, 2005

Unsymmetrical Tetraarylazadipyrromethenes
TABLE 1. Synthesis of 1,3-Diaryl-4-nitro-butan-1-ones
TABLE 3. Generation of Nitroso-pyrrole Building
5a-ja
Blocks 7a-da
yield
nitroso-pyrrole (%)
sub-
yield
entry pyrrole
Ar1
Ar2
entry strate
Ar1
Ar2
C6H5
C6H5
C6H5
C6H5
C6H5
5
(%)
1
2
3
4
6a
6c
6h
6i
Ph
Ph
7a
7b
7c
7d
79
86
92
83
1
2
3
4
5
6
7
8
9
10
8a
8b
8c
8d
8e
8f
C6H5
5a
b
p-MeOC6H4 Ph
p-Me2NC6H4
p-MeOC6H4
p-BrC6H4
p-Et2NCH2C6H4
p-O(CH2CH2)2NCH2C6H4 C6H5
p-CH3CONHC6H4
C6H5
5b 87
Ph
Ph
p-MeOC6H4
p-FC6H4
5c
5d
b
b
a Conditions: NaNO2, EtOH, HCl (aq), rt, 30 min.
5e 92
5f 81
5g 68
8g
8h
8i
C6H5
p-MeOC6H4 5h
p-FC6H4 5i
p-MeOC6H4 5j
b
93
86
are stable solids, which can be obtained analytically pure
following alumina chromatography.
C6H5
8j
p-Et2NCH2C6H4
Synthesis of Unsymmetrical Tetraarylazadipyr-
romethenes. The cross-condensation of 7a-d with the
diarylpyrroles 6 was achieved by stirring the two com-
ponents in acetic anhydride/acetic acid mixture at 100
°C for 1 h during which time a deep blue color developed.
Reaction products were isolated by addition of ice to the
cooled reaction mixture and extraction with dichlo-
romethane with purification by recrystallization or chro-
matography. Encouragingly, the key condensation reac-
tion was tolerant of a range of both electronically
divergent and chemically sensitive functional groups,
with the unsymmetrical tetraarylazadipyrromethenes
10a-k isolated in excellent yields in all but one case
(Table 4). Our route allowed for the generation of
derivatives containing one to four differently substituted
aryl rings depending upon the pyrrole building blocks
used. The versatility of this approach is highlighted by
10j, which has the four different aryl group substitu-
ents: phenyl (Ph), an electron-withdrawing group (F), an
electron-donating group (OMe), and a basic amine group
(CH2N(Et)2) (entry 10). This ability to readily generate
poly-functionalized analogues of 10 will facilitate the
optimization of this chromophore class to a wide range
of applications.
a Conditions: MeNO2, Et2NH, MeOH, reflux, 16 h. b Previously
reported in ref 9b.
Subsequent acetal deprotection and condensation with
NH4OAc in acetic acid provided the 2,4-diaryl-1H-pyr-
roles 6a-j in good isolated yields (Table 2).
The pyrrole products were purified by recrystallization
or alumina column chromatography and could be stored
with no special precautions for prolonged periods of time.
Despite the relatively harsh conditions of the Nef reaction
we were pleased to find that the reaction sequence
tolerated a diverse set of aryl substituents, underlining
this approach as a new general route to diarylpyrrole
synthesis.
TABLE 2. Synthesis of 2,4-Diaryl-1H-pyrrole Building
Blocks 6a-ja
sub-
yield
entry strate
Ar1
Ar2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
pyrrole (%)
As the pyrrole rings of compounds 10 could be envis-
aged to exist with either an E or Z orientation about the
bridging nitrogen atom, solid-state evidence was sought
to determine the structural features of this compound
class. Compound 10b was crystallized by slow evapora-
tion of a chloroform solution at room temperature, in the
monoclinic space group P21/n. The X-ray structure analy-
sis of 10b proved that the aza-dipyrrole unit is essentially
planar, with both pyrrole units adopting the same
orientation in the solid state (see ORTEP diagram in SI
p S8). The comparable nitrogen-carbon bond lengths for
the bridging nitrogen to both pyrrole rings of N(1)-C(1)
) 1.340(6) Å and N(1)-C(18) ) 1.314(5) Å demonstrated
the conjugated nature of the chromophore (full details
in SI p S12). Notably, the tautomeric nature of the
pyrrole NH between both pyrrole units was established
as there was an unequal sharing of the pyrrole hydrogen
between both pyrrole rings, with two-thirds occupancy
on N2 and one-third on N3 (see SI p S20).
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
C6H5
6a
6b
6c
6d
6e
6f
70
52
68
63
70
71
p-Me2NC6H4
p-MeOC6H4
p-BrC6H4
p-Et2NCH2C6H4
p-O(CH2CH2)2N-
CH2C6H4
7
5g
5h
5i
p-CH3CONHC6H4 C6H5
6g
6h
6i
52
72
65
59
8
C6H5
C6H5
p-MeOC6H4
9
p-FC6H4
10
5j
p-Et2NCH2C6H4
p-MeOC6H4
6j
a Conditions: (i) KOH, MeOH/THF, rt, 1 h; (ii) H2SO4, MeOH,
0 °C to rt; 1 h; (iii) NH4OAc, AcOH, 100 °C, 1 h.
The penultimate step was the transformation of the
diarylpyrroles 6a,c,h,i into their corresponding R-nitroso
derivatives 7a-d, which was readily achieved by their
reaction with sodium nitrite in ethanol/aqueous HCl
(Table 3). This reaction was very efficient for selective
nitrosation at the unsubstituted R-pyrrole position, with
the products isolated by direct precipitation from the
reaction mixture in high yields. The nitroso-pyrroles 7
1H and 13C NMR confirmed the unsymmetrical nature
of 10 with two â-pyrrole signals observed in the proton
spectrum and a doubling of the signal numbers in the
J. Org. Chem, Vol. 70, No. 14, 2005 5573

Hall et al.
TABLE 4. Synthesis of Unsymmetrical Tetraarylazadipyrromethenesa
entry
7
Ar1
Ar2
6
Ar3
p-Me2NC6H5
p-MeOC6H4
p-BrC6H4
p-Et2NCH2C6H4
p-O(CH2CH2)2NCH2C6H4
p-CH3CONHC6H4
Ph
p-Et2NCH2C6H4
Ph
Ar4
product
yield (%)
1
7a
7a
7a
7a
7a
7a
7a
7b
7c
7d
7d
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
6b
6c
6d
6e
6f
6g
6i
6j
Ph
Ph
Ph
Ph
Ph
Ph
10a
10b
10c
10d
10e
10f
10g
10h
10i
35
86
92
94
90
78
88
94
72
88
94
2
3
4
5
6
7
p-FC6H4
8
p-MeOC6H4
Ph
p-FC6H4
p-FC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
9
p-MeOC6H4
6c
6j
6c
10
11
Ph
Ph
p-Et2NCH2C6H4
Ph
10j
10k
a Conditions: acetic anhydride, acetic acid, 100 °C, 1 h.
new routes to unsymmetrical tetraarylazadipyrromethenes
together with our previously reported methods for the
synthesis of symmetrical derivatives should open the way
to exploitation of this compound class for a diverse range
of applications. Work in our group is currently focused
on examining the spectroscopic properties of the BF2
chelated analogues and their application as biomolecular
sensors and labels and as targeted PDT agents.
Experimental Section
General Procedure for Synthesis of 1,3-Diaryl-4-nitro-
butan-1-ones, 5a-j. A solution of 1,3-diarylpropenone 8a-j
(5 mmol) in MeOH (50 mL) was treated with diethylamine (2.6
mL, 25 mmol) and nitromethane (1.4 mL, 25 mmol) and heated
under reflux for 16 h.
5b,g,i: The solution was cooled, partitioned between CH2-
Cl2 (100 mL) and water (100 mL), and acidified with 1 M HCl.
The aqueous layer was extracted with a further portion of CH2-
Cl2 (100 mL), and the combined organics were washed with
water (100 mL) and brine (100 mL) and dried over Na2SO4.
The solvent was removed under reduced pressure, and the
resulting oil was purified by column chromatography on silica
gel (Et2O/cyclohexane) or by crystallization from methanol or
ethanol.
5e,f,j: The solution was cooled, partitioned between CH2-
Cl2 (100 mL) and water (100 mL) and extracted with CH2Cl2
(100 mL). The combined organics were extracted with 1 M HCl
(200 mL), and the aqueous layer was then neutralized with 2
M NaOH and extracted with CH2Cl2 (2 × 100 mL). The
combined organics were washed with water (100 mL) and brine
(100 mL) and dried over Na2SO4. The solvent was removed
under reduced pressure, and the resulting oil was purified by
column chromatography on alumina (Et2O/cyclohexane) or by
crystallization from methanol or ethanol.
FIGURE 2. UV-vis spectra of 10b (black), 10c (green), 10e
(red), and 10i (yellow) in CHCl3 at 4 × 10-6 M concentration.
carbon spectrum when compared to the previously re-
ported symmetrical examples. As expected the UV-vis
spectra of 10a-k all displayed a strong absorbance with
high extinction coefficients in the region of 600 nm with
wavelength of maximum absorbance being dependent
upon aryl substituents (Figure 2 and SI p S24).
As previously shown for symmetrical analogues it
would be anticipated that the conversion of 10a-k into
their BF2 chelated analogues would result in a batho-
chromic shift of absorbance maximum in the range of 50-
70 nm, an increase in extinction coefficient, and the
provision of a high fluorescence quantum yield.9b
3-(4-Dimethylamino-phenyl)-4-nitro-1-phenyl-butan-1-
one (5b). Colorless solid (1.36 g, 87%), mp 114-115 °C
1
(MeOH). H NMR (CDCl3) δ: 7.88-7.92 (m, 2H), 7.51-7.57
Conclusions
(m, 1H), 7.40-7.46 (m, 2H), 7.13 (d, J ) 8.7 Hz, 2H), 6.67 (d,
J ) 8.7 Hz, 2H), 4.76 (dd, J ) 12.3, 6.8 Hz, 1H), 4.61 (dd, J )
12.3, 7.9 Hz, 1H), 4.06-4.15 (m, 1H), 3.31-3.47 (m, 2H), 2.89
(s, 6H). 13C NMR (CDCl3) δ: 197.5, 150.3, 136.8, 133.6, 128.9,
We have demonstrated a straightforward three-step
route from readily available starting materials to a
valuable class of diarylpyrroles with a range of aromatic
substituents. We have subsequently used these com-
pounds as building blocks to access a number of unsym-
metrical tetraarylazadipyrromethenes carrying varying
aryl substituents. Both the pyrrole synthesis and the
coupling of pyrrole with R-nitroso-pyrrole is tolerant of
a wide range of functional groups. The described robust
128.3, 128.3, 126.6, 113.0, 80.2, 42.0, 40.6, 38.8. IR (KBr) cm-1
:
1680. ES-MS: m/z 313 [M + H]+. HRMS calcd for C18H21N2O3
[M + H]+ 313.1552, found 313.1557. Anal. Calcd for C18H20-
N2O3: C, 69.21; H, 6.45; N, 8.97. Found: C, 69.40; H, 6.39; N,
8.83.
3-(4-Diethylaminomethyl-phenyl)-4-nitro-1-phenyl-bu-
tan-1-one (5e). Colorless solid (1.63 g, 92%), mp 92-93 °C
5574 J. Org. Chem., Vol. 70, No. 14, 2005

Unsymmetrical Tetraarylazadipyrromethenes
1
(MeOH). H NMR (CDCl3) δ: 7.91 (d, J ) 7.3 Hz, 2H), 7.55-
removed under reduced pressure to provide 9 as an oil, which
was carried into the next stage without further purification.
The oil was treated with acetic acid (10 mL) and NH4OAc (0.77
g, 10 mmol), and the resulting solution was heated at 100 °C
for 1 h. The reaction mixture was cooled to room temperature,
ice (50 mL) was added, and the mixture carefully neutralized
with aqueous 4 M NaOH. The solution extracted with dichlo-
romethane (2 × 50 mL), the combined extracts were washed
with water (50 mL) and brine (50 mL) and dried over Na2-
SO4, and the solvent removed under reduced pressure. Puri-
fication by column chromatography on alumina (Et2O, cyclo-
hexane) or by recrystallization from EtOH.
7.60 (m, 1H), 7.43-7.48 (t, m 2H), 7.30 (d, J ) 8.1 Hz, 2H),
7.21 (d, J ) 8.1 Hz, 2H), 4.80-4.85 (m, 1H), 4.64-4.71 (m,
1H), 4.19-4.26 (m, 1H), 3.52 (s, 2H), 3.37-3.50 (m, 2H), 2.50
(q, J ) 7.1 Hz, 4H), 1.02 (t, J ) 7.1 Hz, 6H). 13C NMR (CDCl3)
δ: 197.0, 139.8, 137.5, 136.5, 133.6, 129.5, 128.8, 128.1, 127.3,
79.7, 57.1, 46.7, 41.7, 39.1, 11.7. IR (KBr disk) cm-1: 1689.
ES-MS: m/z 355 [M + H]+. HRMS calcd for C21H27N2O3
[M + H]+ 355.2022, found 355.2029. Anal. Calcd for C21H26-
N2O3: C, 71.16; H, 7.39; N, 7.90. Found: C, 71.21; H, 7.44; N,
7.77.
3-(4-Morpholin-4-ylmethyl-phenyl)-4-nitro-1-phenyl-
butan-1-one (5f). Colorless solid (1.49 g, 81%), mp 109-110
°C (MeOH). 1H NMR (CDCl3) δ: 7.91 (d, J ) 7.8 Hz, 2H), 7.55-
7.60 (m, 1H), 7.43-7.48 (m, 2H), 7.29 (d, J ) 8.1 Hz, 2H), 7.23
(d, J ) 8.1 Hz, 2H), 4.82 (dd, J ) 12.4, 6.6 Hz, 1H), 4.68 (dd,
J ) 12.4, 8.1 Hz, 1H), 4.17-4.27 (m, 1H), 3.69 (t, J ) 4.5 Hz,
4H), 3.47 (s, 2H), 3.39-3.50 (m, 2H), 2.41 (t, J ) 4.5 Hz, 4H).
13C NMR (CDCl3) δ: 196.9, 138.0, 137.4, 136.4, 133.6, 129.9,
128.8, 128.0, 127.4, 79.6, 79.6, 63.0, 53.6, 41.6, 39.0. IR (KBr
disk) cm-1: 1690. ES-MS: m/z 369 [M + H]+. HRMS calcd for
C21H25N2O4 [M + H]+ 369.1814, found 369.1831. Anal. Calcd
for C21H24N2O4: C, 68.46; H, 6.57; N, 7.60. Found: C, 68.85;
H, 6.55; N, 7.36.
2,4-Diphenyl-1H-pyrrole (6a). Light pink solid (0.31 g,
1
70%), mp 178-180 °C (EtOH). H NMR (CDCl3) δ: 8.45 (bs,
1H), 7.50-7.58 (m, 4H), 7.34-7.42 (m, 4H), 7.17-7.27 (m, 2H),
7.15 (d, J ) 3.8 Hz, 1H), 6.83 (d, J ) 3.8 Hz, 1H). 13C NMR
(DMSO-d6) δ: 136.2, 133.2, 132.8, 129.2, 129.0, 126.2, 125.5,
125.2, 124.9, 123.9, 117.1, 103.7. IR (KBr disk) cm-1: 3439.
ES-MS: m/z 220 [M + H]+. HRMS calcd for C16H14N [M +
H]+ 220.1126, found 220.1133. Anal. Calcd for C16H13N: C,
87.64; H, 5.98; N, 6.39. Found: C, 87.46; H, 6.03; N, 6.40.
4-(4-Dimethylamino-phenyl)-2-phenyl-1H-pyrrole (6b).
1
Light brown solid (0.34 g, 52%), mp 201-204 °C (EtOH). H
NMR (DMSO-d6) δ: 11.29 (bs, 1H), 7.71 (d, J ) 7.2 Hz, 2H),
7.47 (d, J ) 8.8 Hz, 2H), 7.38-7.41 (m, 2H), 7.17-7.22 (m,
2H), 6.87 (s, 1H), 6.77 (d, J ) 8.8 Hz, 2H), 2.93 (s, 6H). 13C
NMR (DMSO-d6) δ: 148.8, 133.3, 132.2, 129.1, 125.9, 125.7,
125.6, 124.9, 123.7, 115.5, 113.4, 103.3, 40.9. IR (KBr disk)
N-[4-(1-Nitromethyl-3-oxo-3-phenyl-propyl)-phenyl]-
acetamide (5g). Colorless solid (1.11 g, 68%), mp 82-84 °C
1
(EtOH). H NMR (DMSO-d6) δ: 9.88 (s, 1H), 7.90 (d, J ) 7.2
Hz, 2H), 7.58-7.63 (m, 1H), 7.44-7.51 (m, 4H), 7.26 (d, J )
8.5 Hz, 2H), 4.93 (dd, J ) 12.7, 5.7, 1H), 4.78 (dd, J ) 12.7,
9.8, 1H), 3.94-3.99 (m, 1H), 3.40-3.57 (m, 2H), 1.98 (s, 3H).13C
NMR (DMSO-d6) δ: 197.9, 168.7, 138.8, 136.8, 134.8, 133.8,
129.2, 128.5, 128.4, 119.5, 80.2, 41.6, 39.1, 24.4. IR (KBr disk)
cm-1
:
3422. ES-MS: m/z 263 [M + H]+. HRMS calcd for
C18H19N2 [M + H]+ 263.1548, found 263.1556. Anal. Calcd for
C18H18N2: C, 82.41; H, 6.92; N, 10.68. Found: C, 82.11; H,
6.90; N, 10.66.
cm-1
:
1687. ES-MS: m/z 327 [M + H]+. HRMS calcd for
4-(4-Methoxy-phenyl)-2-phenyl-1H-pyrrole (6c). Light
C18H19N2O4 [M + H]+ 327.1345, found 327.1361. Anal. Calcd
for C18H18N2O4: C, 66.25; H, 5.56; N, 8.58. Found: C, 65.96;
H, 5.69; N, 8.29.
1
brown solid (0.34 g, 68%), mp 190-191 °C (EtOH). H NMR
(DMSO-d6) δ: 11.34 (s, 1H), 7.61 (d, J ) 7.5 Hz, 2H), 7.50 (d,
J ) 8.6 Hz, 2H), 7.31-7.36 (m, 2H), 7.21 (s, 1H), 7.11-7.16
(m, 1H), 6.88 (d, J ) 8.6 Hz, 2H), 6.86 (s, 1H), 3.72 (s, 3H). 13
C
1-(4-Fluoro-phenyl)-4-nitro-3-phenyl-butan-1-one (5i).
Colorless solid (1.34 g, 93%), mp 70-71 °C (EtOH). H NMR
1
NMR (DMSO-d6) δ: 153.5, 129.1, 128.4, 125.0, 124.8, 121.9,
120.9, 119.7, 112.0, 110.3, 99.4, 51.3. IR (KBr disk) cm-1: 3427.
ES-MS: m/z 250 [M + H]+. HRMS calcd for C17H16NO [M +
H]+ 250.1223, found 250.1232. Anal. Calcd for C17H15NO: C,
81.90; H, 6.06; N, 5.62. Found: C, 81.61; H, 6.12; N, 5.60.
(CDCl3) δ: 7.90-7.95 (m, 2H), 7.19-7.34 (m, 5H), 7.06-7.12
(m, 2H), 4.81 (dd, J ) 12.5, 6.6 Hz, 1H), 4.67 (dd, J ) 12.5,
8.0 Hz, 1H), 4.16-4.25 (m, 1H), 3.44 (dd, J ) 17.7, 6.6 Hz,
1H), 3.37 (dd, J ) 17.7, 7.4 Hz, 1H). 13C NMR (CDCl3) δ: 195.3,
165.9 (d, J ) 255.2 Hz), 139.1, 132.8, 130.7 (d, J ) 9.4 Hz),
129.1, 127.9, 127.5, 115.9 (d, J ) 21.7 Hz), 79.5, 41.4, 39.3. IR
(KBr disk) cm-1: 1686. ES-MS: m/z 286 [M - H]-. HRMS
calcd for C16H13NO3F [M - H]- 286.0879, found 286.0872.
Anal. Calcd for C16H14FNO3: C, 66.86; H, 4.91; N, 4.88.
Found: C, 66.81; H, 4.94; N, 4.90.
4-(4-Bromo-phenyl)-2-phenyl-1H-pyrrole (6d). Light blue
solid (0.38 g, 63%), mp 215-218 °C (EtOH). 1H NMR (DMSO-
d6) δ: 11.50 (s, 1H), 7.66 (d, J ) 7.3 Hz, 2H), 7.56 (d, J ) 8.5
Hz, 2H), 7.46 (d, J ) 8.5 Hz, 2H), 7.32-7.38 (m, 3H), 7.13-
7.18 (m, 1H), 6.95 (s, 1H). 13C NMR (DMSO-d6) δ: 135.5, 132.9,
132.8, 131.8, 129.2, 126.8, 126.3, 123.9, 123.8, 118.0, 117.6,
103.6. IR (KBr disk) cm-1: 3435. ES-MS: m/z 298 [M + H]+.
HRMS calcd for C16H13BrN [M + H]+ 298.0231, found 298.0233.
Anal. Calcd for C16H12BrN: C, 64.45; H, 4.06; N, 4.70. Found:
C, 64.30; H, 4.13; N, 4.61.
Diethyl-[4-(5-phenyl-1H-pyrrol-3-yl)-benzyl]-amine (6e).
Light pink solid (0.43 g, 70%), mp 116-117 °C (EtOH). 1H
NMR (DMSO-d6) δ: 11.40 (s, 1H), 7.66 (d, J ) 7.3 Hz, 2H),
7.52 (d, J ) 8.1 Hz, 2H), 7.32-7.36 (m, 2H), 7.28 (s, 1H), 7.22
(d, J ) 8.1 Hz, 2H), 7.12-7.16 (m, 1H), 6.91 (s, 1H), 3.47 (s,
2H), 2.43 (q, J ) 7.1 Hz, 4H), 0.94 (t, J ) 7.1 Hz, 6H). 13C
NMR (DMSO-d6) δ: 133.0, 130.7, 129.2, 128.6, 125.4, 125.2,
122.3, 121.2, 120.7, 119.9, 112.9, 99.7, 53.2, 42.6, 8.2. IR (KBr
disk) cm-1: 3383, 1604. ES-MS: m/z 305 [M + H]+. HRMS
calcd for C21H25N2 [M + H]+ 305.2018, found 305.2018. Anal.
Calcd for C21H24N2: C, 82.85; H, 7.95; N, 9.20. Found: C, 82.57;
H, 7.90; N 8.93.
3-(4-Diethylaminomethyl-phenyl)-1-(4-methoxy-phen-
yl)-4-nitro-butan-1-one (5j). Yellow oil (1.65 g, 86%). 1H
NMR (CDCl3) δ: 7.90 (d, J ) 8.8 Hz, 2H), 7.29 (d, J ) 8.2 Hz,
2H), 7.21 (d, J ) 8.2 Hz, 2H), 6.92 (d, J ) 8.8 Hz, 2H), 4.82
(dd, J ) 12.4, 6.4 Hz, 1H), 4.67 (dd, J ) 12.4, 8.1 Hz, 1H),
4.14-4.24 (m, 1H), 3.86 (s, 3H), 3.52 (s, 2H), 3.30-3.45 (m,
2H), 2.50 (q, J ) 7.1 Hz, 4H), 1.03 (t, J ) 7.1 Hz, 6H). 13C
NMR (CDCl3) δ: 199.5, 170.0, 167.8, 143.7, 141.6, 134.4, 133.5,
131.3, 117.9, 83.7, 61.1, 59.6, 50.7, 45.3, 43.2, 15.7. IR (neat)
cm-1
:
1679. ES-MS: m/z 385 [M + H]+. HRMS calcd for
C22H29N2O4 [M + H]+ 385.2127, found 385.2142. Anal. Calcd
for C22H28N2O4: C, 68.73; H, 7.34; N, 7.29. Found: C, 68.43;
H, 7.30; N, 6.99.
General Procedure for Synthesis of 2,4-Diaryl-1H-
pyrroles, 6a-j. A stirred solution of 5a-j (2 mmol) in MeOH
(20 mL) and THF (40 mL) at room temperature was treated
with KOH (0.56 g, 10 mmol). After 1 h the mixture was added
dropwise to a solution of H2SO4 (4 mL) in MeOH (20 mL) at 0
°C, following which the solution was allowed to warm to room
temperature and stirred for a further 1 h. Water (50 mL) and
ice (50 mL) were added, and the mixture was neutralized with
aqueous 4 M NaOH and extracted with dichloromethane (2 ×
50 mL). The combined extracts were washed with water (50
mL) and brine (50 mL) and dried over Na2SO4.The solvent was
4-[4-(5-Phenyl-1H-pyrrol-3-yl)-benzyl]-morpholine (6f).
Light pink solid (0.45 g, 71%), mp 166-167 °C (EtOH). 1H
NMR (CDCl3) δ: 8.48 (bs, 1H), 7.51-7.53 (m, 4H), 7.35-7.40
(m, 1H), 7.28-7.33 (m, 2H), 7.21-7.24 (m, 2H), 7.13 (s, 1H),
6.81 (s, 1H), 3.72 (t, J ) 4.5 Hz, 4H), 3.50 (s, 2H), 2.48 (t, J )
4.5 Hz, 4H). 13C NMR (CDCl3) δ: 135.0, 134.5, 133.1, 132.5,
129.6, 129.0, 126.5, 125.0, 123.9, 115.5, 104.0, 67.1, 63.3, 53.7.
IR (KBr disk) cm-1: 3420. ES-MS: m/z 317 [M - H]-. HRMS
J. Org. Chem, Vol. 70, No. 14, 2005 5575

Hall et al.
calcd for C21H23N2O [M + H]+ 319.1810, found 319.1798. Anal.
Calcd for C21H22N2O: C, 79.21; H, 6.96; N, 8.80. Found: C,
79.03; H, 6.97; N, 8.64.
131.0, 129.4, 126.8, 124.5, 114.4, 111.8, 131.3, 55.4. IR (KBr
disk) cm-1: 3303. EI-MS: m/z 279 [M + H]+. HRMS calcd for
C17H15N2O2 [M + H]+ 279.1134, found 279.1145.
5-(4-Methoxy-phenyl)-2-nitroso-3-phenyl-1H-pyrrole
(7c). Yellow solid (0.26 g, 92%), mp 171-173 °C. 1H NMR
(CDCl3) δ: 8.11-8.13 (m, 2H), 7.87 (d, J ) 8.4 Hz, 2H), 7.45-
7.50 (m, 3H), 7.13 (s, 1H), 6.99 (d, J ) 8.4 Hz, 2H), 3.86 (s,
3H), (NH not observed). 13C NMR (CDCl3) δ: 163.4, 162.6,
152.6, 143.1, 131.8, 129.5, 129.5, 129.2, 128.7, 121.9, 114.9,
114.5, 55.5. IR (KBr disk) cm-1: 3452. ES-MS: m/z 279.1 [M
+ H]+. HRMS calcd for C17H15N2O2 [M + H]+ 279.1134, found
279.1131.
N-[4-(5-Phenyl-1H-pyrrol-3-yl)-phenyl]-acetamide (6g).
Light tan solid (0.29 g, 52%), mp 214-216 °C (EtOH). 1H NMR
(DMSO-d6) δ: 11.38 (s, 1H), 9.87 (s, 1H), 7.67 (d, J ) 7.2 Hz,
2H), 7.51-7.56 (m, 4H), 7.37 (t, J ) 7.8 Hz, 2H), 7.27 (d, J )
4.1 Hz, 1H), 7.14-7.17 (m, 1H), 6.90 (d, 4.1 Hz, 1H), 2.04
(s, 3H). 13C NMR (DMSO-d6) δ: 168.4, 137.1, 133.1, 132.5,
131.1, 129.1, 126.1, 125.0, 123.8, 119.7, 116.5, 103.5, 24.4.
IR (KBr) cm-1
:
3412, 1657, 1601. ES-MS: m/z 277
[M + H]+. HRMS calcd for C18H17N2O [M + H]+ 277.1341,
found 277.1345.
5-(4-Fluoro-phenyl)-2-nitroso-3-phenyl-1H-pyrrole (7d).
1
Yellow solid (0.22 g, 83%), mp 176-178 °C. H NMR (CDCl3)
2-(4-Methoxy-phenyl)-4-phenyl-1H-pyrrole (6h). Light
pink solid (0.36 g, 72%), mp 206-208 °C (EtOH). 1H NMR
(DMSO-d6) δ: 11.28 (bs, 1H), 7.45-7.56 (m, 4H), 7.25-7.30
(m, 3H), 7.06-7.09 (m, 1H), 6.89-6.92 (m, 2H), 6.78 (s, 1H),
3.73 (s, 3H). 13C NMR (DMSO-d6) δ: 154.2, 132.5, 129.0, 125.2,
122.3, 121.6, 121.4, 121.2, 121.0, 122.4, 110.8, 98.6, 51.7. IR
(KBr disk) cm-1: 3387. ES-MS: m/z 250 [M + H]+. HRMS
calcd for C17H16NO [M + H]+ 250.1232, found 250.1237.
δ: 8.10-8.13 (m, 2H), 7.89-7.94 (m, 2H), 7.45-7.48 (m, 3H),
7.15-7.20 (m, 2H), 7.12 (s, 1H), (NH not observed). 13C NMR
(CDCl3) δ: 164.6 (d, J ) 254.7 Hz), 163.2, 150.2, 142.9, 131.7,
129.7, 129.6, 129.4 (d, J ) 8.9 Hz), 128.8, 125.8 (d, J ) 3.2
Hz), 116.7 (d, J ) 22.0 Hz), 114.0. IR (KBr disk) cm-1: 3451.
ES-MS: m/z 267 [M + H]+. HRMS calcd for C16H10FN2O [M
- H]- 265.0777, found 265.0784. Anal. Calcd for C16H11FN2O:
C, 72.17; H, 4.16; N, 10.52. Found: C, 71.81; H, 4.19; N, 10.18.
2-(4-Fluoro-phenyl)-4-phenyl-1H-pyrrole (6i). Light pink
solid (0.31 g, 65%), mp 176-178 °C, (EtOH). 1H NMR (DMSO-
d6) δ: 11.47 (bs, 1H), 7.71-7.75 (m, 2H), 7.63 (d, J ) 7.4 Hz,
2H), 7.30-7.36 (m, 3H), 7.13-7.22 (m, 3H), 6.94 (s, 1H). 13C
NMR (DMSO-d6) δ: 158.7, 155.4, 132.2, 127.9, 125.8, 125.0,
4,4-Dimethoxy-1,3-diphenyl-butan-1-one (9a). A stirred
solution of 5a (1.35 g, 5 mmol) in MeOH (50 mL) and THF
(100 mL) at room temperature was treated with KOH (1.4 g,
25 mmol). After 1 h the mixture was added dropwise to a
solution of H2SO4 (10 mL) in MeOH (50 mL) at 0 °C, following
which the solution was allowed to warm to room temperature
and stirred for a further 1 h. Half of the solvent was removed
under reduced pressure, and the remainder was added to
water (100 mL) and ice (50 mL). The mixture was neutralized
with aqueous 4 M NaOH and extracted with dichloromethane
(2 × 200 mL). The combined extracts were dried over Na2-
SO4, and the solvent was removed under reduced pressure to
provide an oil that was purified by column chromatography
on silica gel (EtOAc/cycloheaxne) to give 9a as a colorless solid
(1.04 g, 73%), mp 80-82 °C, (MeOH). 1H NMR (CDCl3) δ: 7.93
(d, J ) 7.0 Hz, 2H), 7.50-7.55 (m, 1H), 7.42 (t, J ) 7.4 Hz,
2H), 7.25-7.34 (m, 4H), 7.16-7.22 (m, 1H), 4.49 (d, J ) 5.4
Hz, 1H), 3.72-3.79 (m, 1H), 3.55 (dd, J ) 17.2, 5.1 Hz, 1H),
3.36 (s, 3H), 3.30-3.39 (m, 1H), 3.31 (s, 3H). 13C NMR (CDCl3)
δ: 198.6, 140.6, 137.3, 132.8, 128.6, 128.4, 128.3, 128.0, 126.7,
107.9, 55.3, 54.8, 44.1, 39.6. IR (KBr disk) cm-1: 1680. ES-
MS: m/z 307 [M + Na]+; HRMS calcd for C18H20O3Na [M +
Na]+ 307.1310, found 307.1313. Anal. Calcd for C18H20O3: C,
76.03; H, 7.09. Found: C, 75.77; H, 7.29.
General Procedure for Synthesis of Unsymmetrical
Tetraarylazadipyrromethenes (10a-k). 1-Nitroso-2,4-di-
arylpyrrole 7 (0.5 mmol) and 2,4-diarylpyrrole 6 (0.5 mmol)
were dissolved in AcOH (2.5 mL) and acetic anhydride (0.5
mL) and heated to 100 °C for 1 h. During the course of the
reaction an intense blue color formed. Ice (20 mL) and 2 M
NaOH (20 mL) was added, and the mixture was stirred for 30
min, extracted with CH2Cl2 (2 × 100 mL), and washed aqueous
NaHCO3 (100 mL), water (100 mL), and brine (100 mL). The
combined organics were dried over Na2SO4, and the solvent
was removed under reduced pressure to provide the product
as a dark blue solid. Purification was by silica gel or alumina
column chromatography.
121.7, 120.9, 113.0, 112.2, 111.9, 99.6. IR (KBr disk) cm-1
:
3429. ES-MS: m/z 236 [M - H]-. HRMS calcd for C16H11FN
[M - H]- 236.0874, found 236.0864. Anal. Calcd for C16H12-
FN: C, 80.99; H, 5.10; N, 5.90. Found: C, 80.79; H, 5.14; N
5.79.
Diethyl-{4-[5-(4-methoxy-phenyl)-1H-pyrrol-3-yl]-ben-
zyl}-amine (6j). Light pink solid (0.46 g, 59%), mp 182-184
°C (EtOH). 1H NMR (DMSO-d6) δ: 11.38 (s, 1H), 7.59 (d, J )
8.3 Hz, 2H), 7.49 (d, J ) 7.6 Hz, 2H), 7.19-7.24 (m, 3H), 6.92
(d, J ) 8.3 Hz, 2H), 6.75 (s, 1H), 3.73 (s, 3H), 3.45 (s, 2H),
2.42 (q, J ) 7.0 Hz, 4H), 0.95 (t, J ) 7.0 Hz, 6H). 13C NMR
(DMSO-d6) δ: 154.3, 133.1, 131.1, 129.0, 125.5, 122.5, 121.5,
121.2, 120.9, 112.3, 110.9, 98.6, 53.5, 51.8, 42.8, 8.4. IR (KBr
disk) cm-1: 3445. ES-MS: m/z 335 [M + H]+; HRMS calcd for
C22H27N2O [M + H]+ 335.2123, found 335.2122. Anal. Calcd
for C22H26N2O: C, 79.00; H, 7.84; N, 8.38. Found: C, 78.89;
H, 7.83; N, 8.40.
General Procedure for Synthesis 2,4-Diaryl-5-nitroso-
pyrroles (7a-d). To a stirred solution of 6 (1 mmol) in EtOH
(10 mL) was added concentrated HCl (0.2 mL), followed by a
dropwise addition of aqueous NaNO2 (80 mg, 1.15 mmol, in 2
mL of H2O). The solution was stirred for 30 min and cooled to
0 °C, and another portion of concentrated HCl (1 mL) was
added. The solution was allowed to stir for 1 h, and the
resulting red solid was collect by filtration and washed with
Et2O. The solid was dissolved in minimal EtOH, an excess of
aqueous NaOAc and ice was added, and the solution was
stirred for 1 h. The resulting solid was collected by filtration
dried and purified by chromatography on alumina (EtOAc/
cyclohexane).
2-Nitroso-3,5-diphenyl-1H-pyrrole (7a). Green solid (0.20
1
g, 79%), mp 138-140 °C. H NMR (CDCl3) δ: 8.16-8.19 (m,
(3,5-Diphenyl-1H-pyrrol-2-yl)-[3-(4-dimethylamino-
phenyl)-5-phenylpyrrol-2-ylidene]-amine (10a). Dark blue
metallic solid (0.086 g, 35%), mp 238-240 °C (silica; CH2Cl2/
pentane 3:2). 1H NMR (300 MHz, CDCl3) δ: 7.98-8.09 (m, 6H),
7.85-7.89 (m, 2H), 7.31-7.55 (m, 9H), 7.10 (s, 2H), 6.73-6.78
(m, 2H), 3.05 (s, 6H), (NH not observed). 13C NMR (75 MHz,
CDCl3) δ: 160.9, 153.8, 150.8, 149.3, 146.3, 146.0, 139.7, 134.5,
133.0, 132.4, 130.5, 129.3, 129.3, 129.2, 129.2, 128.4, 127.7,
127.2, 126.1, 122.2, 113.8, 112.5, 112.1, 40.5. IR (KBr disk)
cm-1: 1606. HRMS calcd for C34H29N4 [M + H]+ 493.2392,
found 493.2402. Anal. Calcd for C34H28N4: C, 82.90; H, 5.73;
N, 11.37. Found: C, 82.70; H, 5.71; N, 11.26. λ max (CHCl3):
2H), 7.80-7.83 (m, 2H), 7.47-7.51 (m, 6H), 7.14 (s, 1H), (NH
not observed). 13C NMR (CDCl3) δ: 162.7, 147.6, 141.8, 132.1,
131.2, 129.8, 129.5, 129.3, 129.0, 128.8, 127.1, 112.4. IR (KBr
disk) cm-1: 3287. ES-MS: m/z 249 [M + H]+. HRMS calcd for
C16H13N2O [M + H]+ 249.1028, found 249.1028. Anal. Calcd
for C16H12N2O: C, 77.40; H, 4.87; N, 11.28. Found: C, 77.35;
H, 4.97; N, 11.23.
3-(4-Methoxy-phenyl)-2-nitroso-5-phenyl-1H-pyrrole
(7b). Green solid (0.24 g, 86%), mp 173-174 C. 1H NMR
(CDCl3) δ: 8.17 (d, J ) 8.9 Hz, 2H), 7.78-7.82 (m, 2H), 7.48-
7.52 (m, 3H), 7.07 (s, 1H), 7.02 (d, J ) 8.9, 2H), 3.89 (s, 3H),
(NH not observed). 13C NMR (CDCl3) δ: 163.1, 161.2, 141.4,
593 nm. ꢀ ) 37,000 L mol-1 cm-1
.
5576 J. Org. Chem., Vol. 70, No. 14, 2005

Unsymmetrical Tetraarylazadipyrromethenes
(3,5-Diphenyl-1H-pyrrol-2-yl)-[3-(4-methoxy-phenyl)-5-
phenyl-pyrrol-2-ylidene]-amine (10b). Dark blue metallic
solid (0.21 g, 86%), mp 267-269 °C (silica; CH2Cl2/EtOAc 3:1).
1H NMR (CDCl3) δ: 8.01-8.05 (m, 4H), 7.88-7.93 (m, 4H),
7.33-7.54 (m, 9H), 7.14 (s, 1H), 7.12 (s, 1H), 6.94 (d, J ) 8.9
Hz, 2H), 3.88 (s, 3H), (NH not observed). 13C NMR (CDCl3) δ:
159.8, 157.7, 152.2, 151.3, 147.8, 134.5, 141.2, 133.9, 132.3,
132.0, 130.4, 130.2, 129.7, 129.1, 129.1, 128.2, 127.8, 126.8,
126.4, 126.2, 114.5, 113.7, 55.4. IR (KBr disk) cm-1: 3457. ES-
MS: m/z 480 [M + H]+. HRMS calcd for C33H26N3O [M + H]+
480.2076, found 480.2077. Anal. Calcd for C33H25N3O: C,
82.65; H, 5.25; N, 8.76. Found: C, 82.45; H, 5.27; N, 8.70. λ
(CDCl3) δ: 165.3, 163.3, 158.0, 152.3, 151.4, 147.0, 144.7, 141.2,
133.9, 133.9, 133.6, 131.9, 129.9, 129.3, 129.3, 129.2, 129.0,
128.4, 128.0, 126.3, 116.5, 116.3, 113.4. IR (KBr disk) cm-1
:
3424. ES-MS: m/z 468 [M + H]+. HRMS calcd for C32H23N3F
[M + H]+ 468.1876, found 468.1897. λ max (CHCl3): 597 nm.
ꢀ ) 44,000 L mol-1cm-1
.
[3-(4-Diethylamino-methyl-phenyl)-5-(4-methoxy-phen-
yl)-pyrrol-2-ylidene]-[5-(4-methoxy-phenyl)-3-phenyl-1H-
pyrrol-2-yl]-amine (10h). Dark blue metallic solid (0.28 g,
94%), mp 165-168 °C, (alumina; CH2Cl2/EtOAc 9:1). 1H NMR
(CDCl3) δ: 8.01 (d, J ) 8.1 Hz, 2H), 7.96 (d, J ) 8.2 Hz, 2H),
7.76-7.81 (m, 4H), 7.31-7.41 (m, 5H), 7.04 (s, 1H), 7.02 (s,
1H), 6.95 (d, J ) 8.8 Hz, 2H), 6.94 (d, J ) 8.8 Hz, 2H), 3.83 (s,
3H), 3.82 (s, 3H), 3.63 (s, 2H), 2.58 (q, J ) 7.1 Hz, 4H), 1.09 (t,
J ) 7.1 Hz, 6H), (NH not observed). 13C NMR (CDCl3) δ: 161.1,
161.0, 154.8, 153.3, 149.9, 148.8, 142.3, 141.5, 139.5, 134.0,
132.4, 129.0, 128.7, 128.1, 128.1, 127.9, 127.6, 125.0, 124.9,
max (CHCl3): 601 nm. ꢀ ) 47,000 L mol-1 cm-1
.
[3-(4-Bromo-phenyl)-5-phenyl-pyrrol-2-ylidene]-(3,5-
diphenyl-1H-pyrrol-2-yl)-amine (10c). Dark blue metallic
solid (0.24 g, 92%), mp 282-285 °C (silica; CH2Cl2/EtOAc 3:1).
1H NMR (10% TFA/CDCl3) δ: 11.77 (s, 2H), 7.89-7.95 (m, 4H),
7.22-7.58 (m, 17H). 13C NMR (10% TFA/CDCl3) δ: 156.3,
155.3, 149.1, 146.9, 136.3, 135.9, 133.7, 133.4, 131.9, 131.6,
131.3, 130.6, 130.4, 130.2, 129.7, 128.7, 127.8, 127.6, 126.9,
125.2, 116.2, 115.2. (KBr disk) cm-1: 3420. ES-MS: m/z 528
[M + H]+. HRMS calcd for C32H23N3Br [M + H]+ 528.1075,
found 528.1091. λ max (CHCl3): 601 nm. ꢀ ) 45,000 L mol-1
114.5, 114.1, 113.8, 57.5, 55.4, 46.8, 11.8. IR (KBr disk) cm-1
:
3457. ES-MS: m/z 595 [M + H]+. HRMS calcd for C39H39N4O2
[M + H]+ 595.3073, found 595.3079. Anal. Calcd for C39H38-
N4O2: C, 78.76; H, 6.44; N, 9.42. Found: C, 78.56; H, 6.49; N,
9.21. λ max (CHCl3): 621 nm. ꢀ ) 41,000 L mol-1cm-1
.
[5-(4-Methoxy-phenyl)-3-phenyl]-1H-pyrrol-2-yl)-[3-(4-
methoxy-phenyl)-5-phenyl-pyrrol-2-ylidene]-amine (10i).
Dark blue metallic solid (0.18 g, 72%), mp 294-296 °C, (silica;
cm-1
.
[3-(4-Diethylamino-methyl-phenyl)-5-phenyl-pyrrol-2-
ylidene]-(3,5-diphenyl-1H-pyrrol-2-yl)-amine (10d). Dark
blue metallic solid (0.25 g, 94%), mp 162-165 °C (alumina;
1
CH2Cl2/EtOAc 3:1). H NMR (1%TFA/CDCl3) δ: 8.01 (d, J )
8.4 Hz, 2H), 7.93-7.95 (m, 2H), 7.51-7.56 (m, 4H), 7.44-7.47
(m, 4H), 7.24-7.29 (m, 2H), 7.20 (s, 1H), 7.11 (s, 1H), 6.98 (d,
J ) 8.4 Hz, 2H), 6.71 (d, J ) 8.4 Hz, 2H), 3.89 (s, 3H), 3.87 (s,
3H), (NH not observed). 13C NMR (1%TFA/CDCl3) δ: 164.1,
161.1, 155.1, 153.5, 135.8, 135.5, 132.4, 132.1, 131.6, 130.4,
130.3, 129.9, 129.4, 128.5, 127.4, 124.7, 119.5, 116.5, 115.7,
115.3, 114.1, 113.2, 112.7, 55.7, 55.5. IR (KBr disk) cm-1: 3425.
ES-MS: m/z 510 [M + H]+. HRMS calcd for C34H28N3O2 [M +
H]+ 510.2182, found 510.2203. Anal. Calcd for C34H27N3O2: C,
80.13; H, 5.34; N, 8.25. Found: C, 79.85; H, 5.32; N, 8.11. λ
1
CH2Cl2/EtOAc 9:1). H NMR (CDCl3) δ: 8.01 (d, J ) 6.7 Hz,
2H), 7.96 (d, J ) 8.1 Hz, 2H), 7.84-7.88 (m, 4H), 7.34-7.48
(m, 11H), 7.11 (s, 1H), 7.10 (s, 1H), 3.63 (s, 2H), 2.58 (q, J )
7.1 Hz, 4H), 1.09 (t, J ) 7.1 Hz, 6H), (NH not observed). 13C
NMR (CDCl3) δ: 155.7, 154.1, 150.1, 149.1, 142.8, 142.1, 139.8,
133.8, 132.2, 132.1, 130.0, 129.8, 129.3, 129.0, 128.8, 128.2,
127.8, 126.6, 126.4, 114.8, 114.4, 57.4, 46.8, 11.8. IR (KBr disk)
cm-1
:
3440. ES-MS: m/z 535 [M + H]+. HRMS calcd for
C37H35N4 [M + H]+ 535.2862, found 535.2880. Anal. Calcd for
C37H34-
max (CHCl3): 615 nm. ꢀ ) 53,000 L mol-1cm-1
.
[3-(4-Diethylamino-methyl-phenyl)-5-(4-methoxy-phen-
yl)-pyrrol-2-ylidene]-[5-(4-flouro-phenyl)-3-phenyl-1H-
pyrrol-2-yl]-amine (10j). Dark blue metallic solid (0.26 g,
88%), mp 202-203 °C, (alumina; CH2Cl2/EtOAc 9:1). 1H NMR
(CDCl3) δ: 8.01 (d, J ) 7.0 Hz, 2H), 7.96 (d, J ) 8.2 Hz, 2H),
7.88 (d, J ) 8.8 Hz, 2H), 7.74-7.80 (m, 2H), 7.32-7.41 (m,
5H), 7.12-7.18 (m, 2H), 7.13 (s, 1H), 6.98-7.01 (m, 2H), 6.98
(s, 1H), 3.88 (s, 3H), 3.63 (s, 2H), 2.58 (q, J ) 7.1 Hz, 4H),
1.09 (t, J ) 7.1 Hz, 6H). 13C NMR (CDCl3) δ: 161.8, 159.6,
152.9, 148.2, 148.1, 144.7, 140.1, 139.5, 134.0, 131.9, 128.9,
128.7, 128.2, 125.0, 116.4, 116.3, 114.6, 112.1, 57.5, 55.5, 46.8,
11.9. IR (KBr disk) cm-1: 3459. ES-MS: m/z 583 [M + H]+.
HRMS calcd for C38H36FN4O [M + H]+ 583.2873, found
583.2884. Anal. Calcd for C38H35FN4O: C, 78.32; H, 6.05; N,
9.61. Found: C, 78.47; H, 6.13; N, 9.57. λ max (CHCl3): 607
N4: C, 83.11; H, 6.41; N, 10.48. Found: C, 82.72; H, 6.39; N,
10.25. λ max (CHCl3): 600 nm. ꢀ ) 45,000 L mol-1 cm-1
.
(3,5-Diphenyl-1H-pyrrol-2-yl)-[3-(4-morpholin-4-ylmeth-
yl-phenyl)-5-phenyl-pyrrol-2-ylidene]-amine (10e). Dark
blue metallic solid (0.25 g, 90%), mp 238-241 °C, (alumina;
CH2Cl2/EtOAc 9:1). 1H NMR (CDCl3) δ: 8.02-8.07 (m, 4H),
7.95 (d, J ) 7.2 Hz, 4H), 7.37-7.57 (m, 11H), 7.20 (s, 1H),
7.19 (s, 1H), 3.74-3.80 (m, 4H), 3.57 (s, 2H), 2.49-2.53 (m,
4H), (NH not observed). 13C NMR (CDCl3) δ: 155.6, 155.1,
150.0, 149.7, 142.8, 138.0, 134.0, 132.9, 132.4, 132.4, 129.3,
129.3, 129.3, 129.2, 128.4, 128.2, 126.8, 126.7, 115.0, 115.0,
67.3, 63.5, 53.9. IR (KBr disk) cm-1: 3465. ES-MS: m/z 549
[M + H]+. HRMS calcd for C37H33N4O [M + H]+ 549.2654,
found 549.2672. Anal. Calcd for C37H32N4O: C, 80.99; H, 5.88;
N, 10.21. Found: C, 81.30; H, 6.09; N, 9.95. λ max (CHCl3):
nm. ꢀ ) 42,000 L mol-1cm-1
.
600 nm. ꢀ ) 47,000 L mol-1cm-1
.
[5-(4-Fluoro-phenyl)-3-phenyl-1H-pyrrol-2-yl]-[5-(4-
methoxy-phenyl)-3-phenyl-pyrrol-2-ylidene]-amine (10k).
Dark blue metallic solid (0.23 g, 94%), mp 265-268 °C, (silica;
CH2Cl2/EtOAc 3:1). 1H NMR (CDCl3) δ: 7.98-8.01 (m, 4H),
7.85 (d, J ) 8.0 Hz, 2H), 7.74-7.79 (m, 2H), 7.32-7.42 (m,
6H), 7.09-7.18 (m, 2H), 7.12 (s, 1H), 6.96-7.01 (m, 2H), 6.99
(s, 1H), 3.88 (s, 3H), (NH not observed). 13C NMR (CDCl3) δ:
161.8, 159.0, 152.4, 149.0, 146.5, 144.5, 134.0, 134.0, 133.5,
129.1, 128.9, 128.7, 128.2, 128.1, 127.8, 127.7, 127.7, 125.0,
N-{4-[2-(3,5-Diphenyl-1H-pyrrol-2-ylimino)-5-phenyl-
2H-pyrrol-3-yl]-phenyl}-acetamide (10f). Dark blue metal-
lic solid (0.20 g, 78%), mp 343-345 °C, (silica; CH2Cl2/EtOAc
1
3:1). H NMR (10%TFA/CDCl3) δ: 11.84 (bs, 1H), 11.64 (bs,
1H), 8.85 (bs, 1H), 7.67 (d, J ) 7.5 Hz, 2H), 7.61 (d, J ) 7.0
Hz, 2H), 7.23-7.42 (m, 10H), 7.11-7.16 (m, 5H), 7.09 (s, 1H),
7.00 (s, 1H), 3.35 (s, 3H). 13C NMR (10%TFA/CDCl3) δ: 173.6,
155.1, 155.0, 148.6, 146.9, 138.1, 135.6, 133.4, 133.3, 131.1,
131.0, 130.5, 130.3, 129.5, 128.7, 128.2, 127.6, 127.4, 126.5,
126.4, 121.0, 115.4, 144.5, 22.9. IR (KBr disk) cm-1: 3451,
3282, 1658. ES-MS: m/z 507 [M + H]+. HRMS calcd for C36H27-
NO2 [M + H]+ 507.2185, found 507.2192. λ max (CHCl3): 604
116.5, 116.4, 116.1, 114.6, 112.4, 55.5. IR (KBr disk) cm-1
:
3463. ES-MS: m/z 498 [M + H]+. HRMS calcd for C33H25FN3O
[M + H]+ 498.1982, found 498.1993. Anal. Calcd for C33H24-
FN3O: C, 79.66; H, 4.86; N, 8.45. Found: C 79.23; H, 4.94; N,
nm. ꢀ ) 41,000 L mol-1cm-1
.
7.90. λ max (CHCl3): nm 606. ꢀ ) 46,000 L mol-1cm-1
.
(3,5-Diphenyl-1H-pyrrol-2-yl)-[5-(4-fluoro-phenyl)-3-
phenyl-pyrrol-2-ylidene]-amine (10g). Dark blue metallic
solid (0.21 g, 88%), mp 288-291 °C, (silica; CH2Cl2/EtOAc 3:1).
1H NMR (CDCl3) δ: 8.04-8.08 (m, 4H), 7.97-8.02 (m, 2H),
7.89 (d, J ) 7.2 Hz, 2H), 7.36-7.57 (m, 9H), 7.24-7.26 (m,
2H), 7.21 (s, 1H), 7.16 (s, 1H), (NH not observed). 13C NMR
Acknowledgment. This work was supported by the
Program for Research in Third-Level Institutions ad-
ministered by the HEA. S.McD. thanks IRCSET for
studentship funding. We thank Dr. D. Rai of the CSCB
J. Org. Chem, Vol. 70, No. 14, 2005 5577

Hall et al.
4-ylmethyl-benzaldehyde, and 4-diethylaminomethyl-benzal-
dehyde. 1H and 13C NMR spectra for 6a-j, 7a-d, 9a, and
10a-k. UV-vis spectra of 10a-k. X-ray crystallographic data
of 10b as a CIF file with ORTEP drawing. This material is
available free of charge via the Internet at http://pubs.acs.org.
Mass Spectroscopy Centre, Dr. H. Mueller-Bunz of the
UCD Crystallographic Centre, and G. Fitzpatrick of the
UCD NMR Centre for analyses.
Supporting Information Available: Experimental pro-
cedures and characterization data for 8b,e,f,g,i,j, 4-morpholin-
JO050696K
5578 J. Org. Chem., Vol. 70, No. 14, 2005