Large scale, efficient synthesis of 9-unsubstituted dipyrrinone

Article abstract of DOI:10.1081/SCC-120003151

9-Unsubstituted dipyrrinone 8, the useful precursor for the synthesis of biliverdins, bilirubins, and other bile pigments, was synthesized in large scale and high yield starting from acetaldehyde and nitroethane in eight steps with overall yield 10%. The key intermediate 3,4-dimethyl-2-ethoxycarbonylpyrrole 3 was synthesized via Zard-Barton's method in high yield.

Full text of DOI:10.1081/SCC-120003151

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LARGE SCALE, EFFICIENT SYNTHESIS OF 9-
UNSUBSTITUTED DIPYRRINONE
b
a
b
b
c
Qingqi Chen , Tianyu Wang , Yi Zhang , Qiuan Wang & Jinshi Ma
a
Department of Chemistry , University of British Columbia , 2036 Main Mall, Vancouver, BC,
V6T 1Z1, Canada
b
Center for Molecular Science , Institute of Chemistry , Chinese Academy of Sciences ,
Beijing, 100080, China
c
College of Chemistry and Chemical Engineering , Hunan University , Changsha, 410082,
China
Published online: 21 Aug 2006.
To cite this article: Qingqi Chen , Tianyu Wang , Yi Zhang , Qiuan Wang & Jinshi Ma (2002) LARGE SCALE, EFFICIENT
SYNTHESIS OF 9-UNSUBSTITUTED DIPYRRINONE, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 32:7, 1031-1040, DOI: 10.1081/SCC-120003151
To link to this article: http://dx.doi.org/10.1081/SCC-120003151
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SYNTHETIC COMMUNICATIONS, 32(7), 1031–1040 (2002)
LARGE SCALE, EFFICIENT SYNTHESIS
OF 9-UNSUBSTITUTED DIPYRRINONE
1
,
2
2
Qingqi Chen, * TianyuWang, Yi Zhang,
3
2,
Qiuan Wang, and Jinshi Ma *
1
Department of Chemistry, University of British
Columbia, 2036 Main Mall,
Vancouver, BC, V6T1Z1, Canada
2
Center for Molecular Science, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, China
3
College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, China
ABSTRACT
9-Unsubstituted dipyrrinone 8, the useful precursor for the
synthesis of biliverdins, bilirubins, and other bile pigments,
was synthesized in large scale and high yield starting from
acetaldehyde and nitroethane in eight steps with overall
yield 10%. The key intermediate 3,4-dimethyl-2-ethoxycarbo-
nylpyrrole 3 was synthesized via Zard–Barton’s method in
high yield.
Key Words: Dipyrrinone; Barton-Zard’s method; pyrrole
*Corresponding authors. Current address: Synapse Technologies, Inc., 6660 NW
Marine Drive, Vancouver, BC, Canada, V6T1Z4; E-mail: qchen@synapse-tech.com
1
031
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1
032
CHEN ET AL.
9-Unsubstituted dipyrrinone I, the yellow and fully conjugated com-
pound, is the structural moiety of bilirubin II, biliverdins, phycoerythrobi-
1
lin, and many other bile pigments. It is also an important precursor for the
2
synthesis of symmetric 10-substituted bilirubin, b-homorubin, biliverdin,
3
2
2
,4
5
6
7
b-homoverdin, hemirubin, semirubin, and
10-substituted biliverdin,
1
many other bile pigments. Since it is structurally one half of bilirubins,
it was also used as a model compound to investigate and to understand
the solution properties, and stereochemistry, as well as in vivo metabolic
8
properties of bilirubins.
1
Although dipyrrinone 8 has been known for many years and a
2
a,6b,8c,9,10
number of synthetic procedures have been reported,
larger scale,
convenient synthetic methods are still not available. In this paper we wish to
report a larger scale, efficient synthesis of the 9-unsubstituted dipyrrinone 8.
Our improved procedure starting with acetaldehyde and nitroethane
with a total of eight steps is outlined in Scheme 1.
Thus, the important 5-substituted pyrrole 3 was prepared in 53% yield
1
via Barton–Zard’s method using 2-acetoxy-3-nitrobutane 2, which was
1
prepared in high yield by condensation of nitroethane with acetaldehyde
1
in two steps. Although 3 was synthesized in 24% yield starting from
2
1
3
-butanone in two steps, in our hand the yield was only about 10%.
2
It would be also prepared in low yield starting from 3,4,5-trimethyl-2-
1
4
benzoxycarbonylpyrrole via multiple steps including steps such as oxida-
tion with surfuryl chloride, hydrolysis, iodination, and reduction.
Upon treating with sodium hydroxide in ethanol, pyrrole 3 was hydro-
lyzed to afford quantitatively pyrrole acid 4, which was further converted to
2,5-unsubstituted pyrrole 5 in 90% yield by dry distillation (compound 4
was distilled under vacuum without solvent). 3,4-Dimethylpyrrole (5) could
1
5
also be prepared in 30–40% yield from 2,3-dimethylbutanediene-1,3 and
urethane (Scheme 2). However, we found that this reaction produced inter-
mediates with a terrible smell. The yield was only ꢀ25% in our hand with
tedious purification procedure (see experimental section).

9
-UNSUBSTITUTED DIPYRRINONE
1033
Scheme 1.
Reagents and Conditions: KF/i-PrOH, r.t., 54%. Ac
a
b
2
O/CH Cl
2
2
/DMAP, r.t., 96%.
c
d
Ethyl isocyanoacetate/tetramethylguanidine/THF/i-PrOH, r.t., 53%. NaOH/
e
EtOH, reflux, 95%. Dry distillation, 90%. POCl /DMF, then NaOH, 73%.
f
3
g
ꢁ
h
, 50 C, 80%. KOH/EtOH, reflux, 75%.
Pyridine/H
2
O
2
Scheme 2.
By standard Vilsmeier formylation methods, 5 was smoothly trans-
formed to 2-formylpyrrole 6 in 73%. Oxidation of 5 with hydrogen peroxide
in pyridine gave 3,4-dimethyl-2-pyrrolinone 7 in 80%. Condensation of 6
and 7 under a strong base condition afforded the expected dipyrrinone 8 in
7
1
5% yield at 50 mmol scale. The reaction could be scaled up to 100 mmol, or
5 g of dipyrrinone 8 in good yield.
In summary, we described in this paper an improved and highly
efficient procedure for the synthesis of 2,3,7,8-tetramethyldipyrinone (8)
on large scale with overall yield 10%. The key intermediate 3 was directly
1
1
synthesized in high yield via Zard-Barton’s method.

1
034
CHEN ET AL.
EXPERIMENTAL SECTION
Melting points were determined on a Yanaco MP-500 micro-
melting point apparatus and uncorrected. IR spectra were recorded on a
BIO-RAD FT-165 IR spectrometer. NMR spectra were recorded on a
Varian Gemini-200 MHz instrument using tetramethylsilane as internal
standard. UV-VIS spectra were obtained on a Hitachi U-2001 spectro-
photometer. Mass spectra were obtained on a VG TR10-200 spectro-
meter. Elemental analyses were performed on a Carlo Erba-120 elemental
1
6
17
analyzer. Ethyl isocycanaocetate,
2,3-dimethylbutanediene-1,3,
3
and
1
sodium salt of 2-methyl-3-oxobutyraldehyde were prepared according to
literatures.
2-Nitro-butanol-3 [1, C H NO ]: A 1-l three-necked round-bottomed
4 9 3
flask equipped with a magnetic stirrer was charged with acetaldehyde
260 ml, 4.6 mol), 2-propanol (170 ml), and potassium fluoride (13.48 g,
.23 mol, 0.05 mol equiv.). The stirrer was started and the flask was chilled
(
0
in an ice-salt bath. To the mixture, nitroethane (334 ml, 4.6 mol, 1.0 mol
ꢁ
equiv.) was added dropwise at 0 over a period of 1 h. Then the mixture
was slowly warmed up to room temperature and kept for 10 h under con-
tinuously stirring before removing all solvent under vacuum. The resulting
oily crude product was filtered to remove solid inorganic waste and washed
with dichloromethane. After removing all solvent under vacuum, colorless
oily product 1 was obtained (300 g, 54%) which was immediately used for
the next step synthesis. Note: we observed a small scale explosion during
vacuum distillation. Therefore, purifying this product by distillation is not
recommended. IR (KBr, film): n ¼ 3471, 2954, 2860, 1743, 1555, 1455,
À1
1
1
3
0
372, 1226, 1026, 973, 861, 732, 632, 602 cm
.
H NMR (CDCl ,
3
00 MHz); d 1.0–1.1 (m, 3H, CH ), 1.3–1.4 (m, 3H, CH ), 3.9–4.0 (m,
.5H), 4.1–4.2 (m, 0.5H), 4.3–4.4 (m, 1H) ppm (it is a mixture of two iso-
1
mers). C NMR (CDCl ): d (12.4, 15.6), (18.5, 18.8), (68.2, 69.0), (87.1,
3
3
3
3
8
8.90) ppm (it is a mixture of two isomers).
2-Nitro-3-acetoxyl-butane [2, C H NO ]: 2-Nitro-butanol-3 (1, 150 g,
.26 mole) was dropwise added over 10 min to a solution of dichloro-
6
11
4
1
methane (100 ml), acetic anhydride (193 g, 1.89 mol, 1.5 mol equiv.), and
4
-dimethylaminopyrridine (DMAP, 2 g). Due to the exothermic reaction,
ꢁ
the temperature of the solution could reach to 40 C. The mixture was
allowed to stir at room temperature for 4 h. Methanol (300 ml) was added
to destroy the excess acetic anhydride. After stirring for a further 30 min, the
solution was poured into dilute sodium bicarbonate (90 g in 500 ml water)
and extracted with dichloromethane (3 Â 200 ml). The organic layer was
dried over sodium sulfate and filtered through a short column of silica.
Evaporation of the solvent gave the desire product 2 as a clear liquid

9
-UNSUBSTITUTED DIPYRRINONE
1035
(195 g, 96%), which was directly used in the next step. Note: vacuum
distillation to purify this product was not recommended due to the possibility
of explosion. We observed a small scale explosion during vacuum distillation.
IR (KBr, film): n ¼ 3468, 2995, 1746, 1558, 1449, 1384, 1234, 1093, 1039,
À1
9
(
(
51, 857, 643, 607, 539 cm . GC-MS (T : 4.6 and 4.9 min, two isomers) m/z
r
1
%) ¼ 146 (5), 114 (13), 101 (2), 87 (10), 75 (12), 73 (100), 55 (10). H NMR
CDCl , 300 MHz); d 1.2–1.3 (m, 3H, CH ), 1.4 (m, 3H, CH ), 1.90 (ss,
3
3
3
3
H, COCH ), 4.5–4.6 (m, 1H, CH), 5.1–5.2 (m, 1H, CH) ppm (it is a
3
3
1
mixture of two isomers). C NMR (CDCl ): d (13.2, 15.2), (15.5, 15.7),
3
(
20.4, 20.5), (69.7, 70.4), (84.3, 85.4), (169.3, 169.5) ppm (it is a mixture of
two isomers).
-Ethoxycarbonyl-3,4-dimethyl-1H-pyrrole [3, C H NO ] Method A:
2
9
13
2
1
1
Via Zard–Barton’s Method. In a 2-l round-bottomed flask equipped with
a magnetic stirrer was charged ethyl isocycanoacetate (148 g, 1.3 mol,
1.05 mol equiv.), and tetramethylguanidine (300 g, 2.54 mol, 2.05 mol
equiv.). The stirrer was started and the flask was cooled in an ice-water
bath. To the mixture, a solution of 3-acetoxy-2-nitro-butane (2, 200 g,
ꢁ
1.24 mol) in dry THF (200 ml) and isopropanol (200 ml) was added to 0 C
dropwise over a period of 30 min. The mixture was allowed to stir at room
temperature for another 20 h after the addition was complete. The resulting
mixture was concentrated under vacuum to dryness. The oily residue was
taken up by dichloromethane (2500 ml) and washed successively with water
(
3 Â 400 ml), 5% aqueous hydrochloric acid (3 Â 400 ml), water (400 ml),
aqueous saturated sodium bicarbonate (400 ml), and brine (400 ml). After
drying over anhydrous sodium sulfate and removing all solvent under
vacuum, the residue oil was crystallized from dichloromethane-hexane.
The expected product 3 was obtained 110 g (53%).
1
3
Method B: From 2-Butanone. A 3-l three-necked round-bottomed
flask, equipped with mechanic stirrer and a reflux condenser, was charged
with glacial acetic acid (400 ml). Sodium hydroxide (50 g, 1.25 mol, 0.80 mol
equiv.) was added slowly under stirring. While sodium hydroxide was
dissolving the mixture was warmed up to reflux by exothermic reaction.
A solution of diethyl malonate (321 g, 2.0 mol) in glacial acetic acid
(
cooled by an ice–water bath. Then a solution of sodium nitrite (280 g,
500 ml) was then added to the hot solution. The reaction flask was then
ꢁ
4
.04 mol, 2.0 mol equiv.) in water (380 ml) was added dropwise under 5 C
by adjusting the dropping speed. The addition was completed in approxi-
mately 5 h. The homogeneous mixture was allowed to cool and stand over-
ꢁ
night at 5 C. A solution of sodium hydroxide (126 g, 3.11 mol) in ice–water
(
350 ml) was dropwise added to the stirred mixture in a steady stream under
ꢁ
10 C (ice–salt bath was required); the mixture was then extracted with ether
(
4 Â 500 ml). The combined extracts were washed with aqueous saturated

1
036
CHEN ET AL.
sodium bicarbonate (2 Â 500 ml) and water (500 ml). The solvent was
removed under vacuum to give a bright yellow oil product, diethyl oximi-
nomalonate, which was used directly for the next step synthesis.
In a 5-l four-necked round-bottomed flask, equipped with a mechan-
ical stirrer, a drop funnel, a thermometer, and a condenser, were charged
with glacial acetic acid (2500 ml) and anhydrous sodium acetate (600 g). The
ꢁ
mixture was stirred and heated to 85 C. Then, sodium salt 2-methyl-3-oxo
butyraldehyde (244 g, 2.0 mol, prepared from the condensation of 2-buta-
1
3
none with ethyl formate in the presence of sodium ), crude diethyl oximi-
nomalonate (prepared from above ꢀ2.0 mol) and a solution of glacial acetic
acid (400 ml) in water (200 ml) were consecutively introduced, and the mix-
ꢁ
ture was heated to 95 C. Zinc dust (390 g, 6.0 mol, 3.0 mol equiv.) was then
ꢁ
slowly added to maintain the temperature between 90 and 100 , after which
the reaction mixture was heated and stirred for another 30 min. Pouring the
reaction mixture to 10 l ice–water mixture caused the separation of yellow
oil, which solidified on standing in a cold room. The product was collected
by suction filtration, and dissolved in dichloromethane (500 ml), and fil-
trated to remove any insoluble waste. The filtrate was washed with water
(
2 Â 100 ml), then aqueous sodium bicarbonate (2 Â 100 ml). After drying
over anhydrous sodium sulfate, the solvent was removed under vacuum.
The residue was then crystallized from dichloromethane-hexane to afford
ꢁ
the expected compound 3 as yellow solid (31.7 g, 9.5%). m.p. 92–94 C
ꢁ
ꢁ
1
(
lit [13] 90–92 C, lit [14a] 94–95 C). H NMR (300 MHz, CDCl ,); d 1.3
3
(
4
t, 3H, J ¼ 7.2 Hz, CH CH ), 2.0 (s, 3H, pyrr-CH ), 2.3 (s, 3H, pyrr-CH ),
2
3
3
3
.3 (q, 2H, J ¼ 7.2 Hz, CH CH ), 6.7 (d, 1H, J ¼ 2.7 Hz, pyrr-H), 8.9 (br
2
3
1
3
s, 1H, NH) ppm. C NMR (300 MHz, CDCl ); d 9.8 (OCH CH ), 10.2
3 2 3
(
pyrr-CH ), 14.5 (pyrr-CH ), 59.7 (OCH CH ), 120.5, 120.9, 121.0, 126.9,
3
3
2
3
1
61.7 (COOEt) ppm.
2-Carboxy-3,4-dimethyl-1H-pyrrole [4, C H NO ]: 2-Ethoxycarbonyl-
,4-dimethyl-1H-pyrrole (3, 60 g, 0.36 mol) was suspended in 95% ethanol
7 9 2
3
(
200 ml), then 30% potassium hydroxide (280 ml, 1.12 mol, 3.1 mol equiv.)
was added at once. The mixture was heated at reflux for two hours, with the
resulting brown solution cooled down to room temperature and chilled by a
salt-ice bath. Concentrated hydrochloric acid was added dropwise to the
cold brown solution to give white precipitate. The fine white solid was
collected by filtration and washed with water. The solid was dried under
ꢁ
vacuum to give the expected compound 4 (48 g, 96%). m.p. 200 (dec.)
ꢁ
1
(
lit [13] 205 dec.). H NMR (300 MHz acetone-d ): d 1.93 (s, 3H, pyrr-
6
CH ), 2.20 (s, 3H, pyrr-CH ), 6.72 (d, 1H, J ¼ 2.7 Hz, pyrr-H), 9.34 (br s,
3
3
1
3
1
H, NH), 10.23 (s, 1H, COOH) ppm. C NMR (75 MHz, acetone-d ): d
6
9
.05 (pyrr-CH ), 9.43 (pyrr-CH ), 118.50, 119.91, 120.66, 125.89, 161.72
3
3
(
COOEt) ppm.

9
-UNSUBSTITUTED DIPYRRINONE
1037
3,4-Dimethyl-1H-pyrrole [5, C H N] Method A: Dry distillation from 4.
-Carboxy-3,4-dimethyl-1H-pyrrole (26 g, 0.21 mol) was added to a 100 ml
6
9
2
round bottomed flask and heated over an oil bath. The acid was distilled at a
ꢁ
temperature of oil bath 180–190 C under vacuum (water aspirator pump).
The pure decarboxylated product was obtained by using a short distillation
apparatus with ice-cooled received flask. During the distillation the com-
pounds solidified in the receiving flask. Pure product 5, which smells like
ꢁ
benzene, was obtained (17.8 g, 90%) as colorless needle crystals at 0 C,
which was stable for one year without noticeable decomposition under
ꢁ
nitrogen and À5 C.
Method B: From the reaction of 2,3-dimethylbutadiene-1,3. In a 2-l
four-necked round-bottomed flask, equipped with a mechanical stirrer, a
reflux condenser closed at the top with an anhydrous calcium chloride
drying tube, and two 100 ml dropping funnels, were placed in ethyl carba-
mate (urethane, 48 g, 0.53 mole, 1.10 mole equiv.) and dry benzene (350 ml).
The reaction flask was cooled by a water bath. Pyridine (85 ml, 1.05 mol,
2.2 mol equiv.) and thionyl chloride (38.6 ml, 0.53 mole, 1.1 mole equiv.)
were respectively placed in two dropping funnels, and were added dropwise
over 30 min at the same rate with vigorous stirring. The black mixture was
then stirred at room temperature for 1.5 h, then 2,3-dimethylbutandiene-1,3
(
39.5 g, 0.48 mole) was added in one portion. The mixture was heated at
gentle reflux for 5 h, then cooled down to room temperature, and allowed to
stand overnight. Insoluble materials were then removed by suction filtration.
The filtrate cake was washed with dry benzene (4 Â 100 ml). Caution: very
bad smell, all reaction and work-up job should be done inside fume-hood. T he
combined filtrates and washings were concentrated under vacuum to afford
a dark oily residue of the crude intermediate 2-ethoxycarbonyl-3,6-dihydro-
4,5-dimethyl-1.2-thiazine-1-oxide. To the residue a solution of potassium
hydroxide (213 g, 3.8 mole, 8 mole equiv.) in methanol (550 ml) was then
added at once. The mixture was then heated at reflux for 2 h. Solvent was
distilled, and the dark residue was steam-distilled until no oily materials
were received, which required 14–16 h. The distillates were combined and
extracted with dichloromethane (3 Â 150 ml). The extracts were dried over
anhydrous potassium carbonate and the solvent was removed under
vacuum. The residue was distilled under vacuum to give a colorless oil
ꢁ
at room temperature and solidified to crystalline at 0 C (11.4 g, 25%
based on the theoretical amount of 2,3-dimethylbutandiene used).
1
H NMR (300 MHz chloroform-d): d 2.1 (s, 6H, 2 pyrr-CH ), 6.5 (d, 2H,
3
1
3
J ¼ 2.0 Hz, 2 pyrr-H), 7.8 (br s, 1H, NH) ppm. C NMR (chloroform-d):
d 9.9 (pyrr-CH ), 118.5, 115.5, 118.2 ppm.
3
2-Formyl-3,4-dimethyl-1H-pyrrole [6, C H NO]: In a 500 ml three-
necked round-bottomed flask, equipped with a magnetic stirrer, a condenser
7 9

1
038
CHEN ET AL.
closed at top with an anhydrous CaCl tube, and a nitrogen inlet, was
2
charged with phosphyl oxochloride (24.6 g, 160 mmole, 1.1 mol equiv.).
The stirrer was started and the flask was chilled by an ice-salt bath while
nitrogen was introduced. Then a mixture of 3,4-dimethyl-1H-pyrrole
(
5, 13.86 g, 146 mmol) in dry dichloromethane (200 ml) containing dry
N,N-dimethylformamide (13 g, 198 mmol, 1.3 mol equiv.) was added. The
reaction mixture was stirred at room temperature overnight. After removing
all solvent under vacuum, the residue was mixed with water (120 ml). To the
stirred mixture sodium hydroxide (36.8 g, 920 mmol) was added slowly.
Next, the mixture was allowed to stir 1 h at room temperature, the yellow
precipitate was collected, washed with water, and dried to afford the
ꢁ
ꢁ
expected product 6 (13 g, 73%). m.p. 132–134 C (lit [13] 133–134 C).
1
H NMR (300 MHz chloroform-d): d 2.0 (s, 3H, pyrr-CH ), 2.3 (s, 3H,
3
pyrr-CH ), 6.8 (s, 1H, pyrr-H), 9.2 (br s, 1H, NH), 9.6 (s, 1H, CHO)
1
3
3
ppm. C NMR (chloroform-d): d 9.8 (pyrr-CH ), 10.0 (pyrr-CH ), 121.1,
3
3
122.1, 124.2, 127.8, 178.2 ppm.
3,4-Dimethyl-3-pyrrolin-2-one [7, C H NO]: 3,4-Dimethyl-1H-pyrrole
5, 17.0 g, 0.18 mol) was dissolved in pyridine (30 ml) under nitrogen pro-
6
9
(
tection. Then 30% hydrogen peroxide (27 ml, 0.45 mol) was added at once.
ꢁ
The mixture was stirred at 50 C for 2 h. Solvent was removed under vacuum
to give a light orange oil which solidified on drying under vacuum overnight.
The crude product was crystallized from dichloromethane-hexane to give
ꢁ
ꢁ
the desired product 7 (15.9 g, 80%). m.p. 114–116 C (lit [13] 116–118 C) IR
KBr, film): n ¼ 3320, 3100, 2945, 1601, 1545, 1480, 1449, 1320, 1155, 1080,
(
8
À1
þ
1
10, 750, 699 cm . GC-MS: m/z ¼ 111 (M ). H NMR (300 MHz CDCl ): d
3
1
.8 (s, 3H, pyrr-CH ), 2.0 (s, 3H, pyrr–CH ), 3.8 (s, 2H, CH ), 7.3 (br s, 1H,
3
3
2
NH) ppm. C NMR (50 MHz, CDCl ), d 7.8, 9.3, 47.3, 126.5, 154.5,
3
176.3 ppm.
2
,3,7,8-Tetramethyldipyrrinone [8, C H N O]: In a 250-ml three-
1
3
16
2
necked round-bottomed flask, equipped with a nitrogen inlet, a condenser,
and a magnetic stirrer, were charged with 2-formyl-3,4-dimethyl-1H-pyrrole
(
6, 6.0 g, 48 mmol), 3,4-dimethyl-3-pyrrolin-2-one (7, 5.8 g, 52 mmol,
1
1
.09 mol equiv.), aqueous potassium hydroxide (4 M, 150 ml, 0.60 mol,
2.5 mol equiv.) and methanol (125 ml). The suspension was stirred at
reflux for 10 h under nitrogen (a yellow precipitate was formed during
reflux). Solvents were evaporated, the yellow precipitate was collected by
filtration, washed with water and dried to give the expected title compound 8
ꢁ
as yellow powder (7.8 g, 75%). m.p. 268–270 C (dec.) (lit [9b] m.p.
ꢁ
2
1
(
71–273 C). IR (KBr, film): n ¼ 3350, 3200, 3151, 2932, 1596, 1501, 1436,
À1
þ
236, 1175, 1103, 945, 800 cm . MS (FAB): m/z ¼ 216 (M ). UV–Vis
1
Chloroform): lmax(e) ¼ 394 (25 300) nm. H NMR (300 MHz, chloroform-
d): d 1.5 (s, 3H, pyrr–CH ), 1.9 (s, 3H, pyrr–CH ), 2.0 (s, 3H, pyrr-CH ), 2.1
3
3
3

9
-UNSUBSTITUTED DIPYRRINONE
1039
(
s, 3H, pyrr-CH ), 6.2 (s, 1H, ¼CH), 6.9 (s, 1H, pyrr-H), 10.2 (br s, 1H,
3
1
3
NH), 10.9 (br s, 1H, NH) ppm. C NMR (chloroform-d): d 8.4 (pyrr-CH ),
3
9
.5 (pyrr-CH ), 10.0 (pyrr-CH ), 10.2 (pyrr-CH ), 101.1, 119.5, 120.9, 121.1,
3 3 3
124.0, 124.4, 129.8, 142.4, 174.3 (C¼O) ppm.
ACKNOWLEDGMENTS
Q. C. thanks Professor David A. Lightner (University of Nevada) and
Professor David Dolphin (University of British Columbia), in whose labora-
tories part of this work was done. J. M. thanks The Major State Basic
Research Development Program (G2000078100) NFSC (20172055).
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Received in the USA March 28, 2001