Green synthesis of dipyrromethanes in aqueous media catalyzed by SO3H-functionalized ionic liquid

Article abstract of DOI:10.1039/c5ob01953b

A mild, efficient and metal-free method was described for the green synthesis of dipyrromethanes from aldehydes and unsubstituted pyrrole catalyzed by SO₃H-functionalized ionic liquids (SO₃H-ILs) in aqueous media at room temperature. Notably, SO₃H-ILs, 1-butylsulfonic-3-methylimidazolium hydrogen sulfate ([bsmim][HSO₄]) was the most efficient catalyst for moderate to good yields of the corresponding desired products.

Full text of DOI:10.1039/c5ob01953b

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DOI: 10.1039/C5OB01953B
Organic & Biomolecular Chemistry
ARTICLE
Green synthesis of dipyrromethanes in water media catalyzed
by SO H-functionalized ionic liquid
3
W. Senapak, R. Saeeng, J. Jaratjaroonphong, T. Kasemsuk, U. Sirion*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A mild, efficient and metal-free method was described for the green synthesis of dipyrromethanes from aldehydes and
unsubstituted pyrrole catalyzed by SO
3
H-functionalized ionic liquids (SO
3
H-ILs) in water media at room temperature.
]) was the most efficient catalyst
Notably, SO H-ILs, 1-butylsulfonic-3-methylimidazolium hydrogen sulfate ([bsmim][HSO
3
4
for moderate to good yields of corresponding desired products.
R
R
-
Simple and Green synthesis
H
O H
H
10 mol% [bsmim][HSO
O, rt
4
]
- 100% Atom economic way
N
H
NH HN
-
Resuable catalyst
H
2
NH
15 examples
up to 89% yields
Introduction
O
Dipyrromethanes are important precursors for porphyrin
H
1
,2
R
syntheses,
particularly for the preparation of asymmetric
N
H
polyprrolic compounds, used in a wide range of applications for
aldehyde
1
ꢀ4
this work
material science, medicine
and optics.
Furthermore,
previous works (ref 1-7)
-
[bsmim][HSO
2.5-5.0 eq pyrrole
O, rt
- up to 89%
4
] catalyst
-
toxic or strong acid catalysts
dipyrromethanes are the structural skeletons of some critical
-
5
- excess pyrrole (10-200 eq)
biological compounds, especially prodigiosin and heme analogues
-
-
neat, CH
2
Cl
2
, heat or MW
- H
2
(
Figure 1). Recently, dipyrromethanes and their derivatives have
up to 85%
6
shown promising biological activity as antiꢀinflammatory agents.
Ts
H
R
N
OMe
R
O
R
N
N
4 eq.
H
4
0 eq.
-85%
ref 8)
H
OMe
R
NH
7
25-80%
(ref 9)
NH
N
O
R
R
MeO
(
Me
prodigiosin
CH
imine
1
,3-oxazinane
NH HN
NH
O
Me
N
Scheme 1. Strategies for Synthesis of dipyrromethane
Generally, dipyrromethanes are synthesized by condensation of
2
Me
CH
Me
CH
2
O
NH
HN
Me
Me
Me
2
N
N
N
N
FeII
OMe
1
aꢀf,2,7
aldehydes with pyrroles via double FriedelꢀCrafts reaction.
8
9
N
Imines and 1,3ꢀoxazinanes are used alternatively as carbonyl
equivalents to react with pyrroles. Most of the methods requires
metal catalysts as well as strong acid catalysts for stimulating the
Me
O
OH
verteporfin
(photodynamic therapy (PDT) drugs)
O
OH
1d
1e
OH
O
reactions such as TiCl
4
,
cation exchange resin, trifluoroacetic
ionic liquid, InCl
, Amberlyst 15, and metal triflates (Scheme 1).
heme B
1f,1j,2,4a,7eꢀf,9
7a,7h
7i
7j
7k
acid (TFA),
HCl/H
2
7m
O,
3
,
iodine,
7
l
8
H
2
SO
4
ꢀSiO
2
Figure 1. Examples of biologically active compound containing
diprromethane moiety
High yields of desirable products have been achieved with
conditions that include substituted pyrrole, excess pyrrole
7
iꢀj
1e,1j,7e
7
h,7k,7m
and/or harsh conditions.
Unsubstituted pyrrole reduces yield
due to instability of intermediates and desirable products and easily
generates oligomeric byꢀproducts. However, due to the versatile
applications of these dipyrromethane derivatives derived from
2
,3,4
unsubstituted pyrrole,
alternative more efficient syntheses
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DOI: 10.1039/C5OB01953B
ARTICLE
Journal Name
continue to be sought to provide high selectivity and yields. To date, Table 1 Optimization of FriedelꢀCrafts alkylation in water using
a
the synthetic processes under green context are increasing rapidly in various SO
response to biological applications. Furthermore, process reactions
that take place in water represent an interesting approach for the
3
HꢀIL catalysts
NO
2
O
H
10
green chemistry group. With these concerns and those for the
environment, our challenge was to synthesize dipyrromethanes using
metalꢀfree method under water media.
2
0 mol% SO
3
H-IL
N
H
H O, rt, 1.0 h
2
2
O N
11
6a
7
NH HN
Ionic liquids (ILs) are salts usually existing as a liquid at room
temperature. They have unique properties including; wide
temperature range of liquid state, nonꢀvolatile, nonꢀflammable, high
thermal stability, high solubility and recyclable. These qualities
confer them desirable as green solvents, reagents and catalysts in
many useful reactions. Since, ILs are widely utilized for
environmentally friendly benign processes, wellꢀdesigned ionic
liquids as taskꢀspecific ionic liquids (TSILs) have emerged as
activity enhancers. One of the TSILs, Brönsted acidic ionic liquids
8a
b
Entry
SO HꢀIL
3
Yield 8a (%)
1
2
3
4
5
6
7
8
3a, [bsdmim][OTf]
4a, [bsdmim][HSO
58
53
37
64
65
46
55
64
51
4
]
5a, [bsdmim][pTSA]
3b, [bsmim][OTf]
4
4b, [bsmim][HSO ]
5b, [bsmim][pTSA]
3c, [bspy][OTf]
12
(BAILs) has received attention as an efficient acidic catalysts due
to high performance under a wide range of reaction conditions.
Additionally, they are miscible in water, waterꢀtolerant and suitable
4c, [bspy][HSO
4
]
9
a
5c, [bspy][pTSA]
1
2l,m,n,o
for reactions that need to proceed in water
and can be reused
All reactions were conducted with 1.0 mmol of 6a and 5.0 mmol of 7
allowing products to be easily separated from water by simple
extraction. There are many reports on the use of BAILs as catalysts
b
using 20 mol% of SO
3
HꢀIL in 3.0 mL H
2
O at rt for 1.0 h. Isolated yield.
1
2a,b,d,e,t
in versatile organic reactions such as esterification,
mannich
The production of dipyrromethanes from 4ꢀnitrobenzaldehyde (6a)
with 5.0 equivalents of pyrroles (7) in the double FriedelꢀCrafts
reaction was initially investigated using 20 mol% of various
1
2c,f
12h,q
12j
reaction,
reaction,
nitration,
michael addition reaction
beckmann rearrangement, friedlander
1
2l
12r
and other oneꢀpot
In recently, Ishikawa group
12i,m,n,o,s
1g
multicomponent reactions.
synthesized SO
temperature for 1.0 h (Table 1). Yield of dipyrromethanes was
highest with [bsmim][OTf] (3b), [bsmim][ HSO (4b), and
bspy][HSO ] (4c) as catalysts (entries 4, 5 and 8, respectively).
Lowest yield was found in case of pTSA anion (entries 3, 6 and 9).
3
HꢀILs in water under air atmosphere at room
reported the use of BAILs for the synthesis of symmetric porphyrins
from aldehydes and pyrrole in oneꢀpot process using CH Cl2 as a
2
4
]
solvent. Herein, we first report on the use of reusable BAIL as a
catalyst for the green synthesis of dipyrromethanes from aldehydes
and pyrrole in water via double FriedelꢀCrafts reaction.
[
4
7
i
Byꢀproducts were observed same as earlier study to include
tripyrranes and other oligomeric compounds, likely due to the
presence of oxygen.
When this reaction was performed in degas water and under
nitrogen atmosphere with 20 mol% of each of the three most
efficient SO HꢀILs (3b, 4b, and 4c) for 1.0 h (Table 2, entries 5ꢀ7),
3
yields increased to 72 and 73% for catalysts (4b) and (4c),
respectively and remained unchanged for catalyst (3b). These
Results and discussion
A series of SO Hꢀfunctionalized ionic liquids (SO HꢀILs) bearing
3
3
imidazolium and pyridinium cations with three different anions was
1
2a
investigated. According to a previous report, the preparation of
these SO HꢀILs was achieved in twoꢀstep synthesis using
a
3
inexpensive materials. Reactions were completely converted to
disclosed that the activity of SO
3
HꢀILs depends on counterꢀanion,
and HSO anion exhibited better catalytic activity for double Friedelꢀ
Crafts process than OTf and pTSA anions under oxygenꢀfree
SO HꢀILs (3a-c, 4a-c and 5a-c) providing in excellent yields
3
4
(
Scheme 2).
O
O
O
condition. The order of catalytic activity for this protocol is
S
N
N
or
N
N
or
N
+
13
[
4
bsmim][HSO ]>[bsmim][OTf]>[bsmim][pTSA].
The reaction with no catalyst was also performed (Table 2, entry
). We found no reaction within 1.0 h, while 25% yield of desired
1
a
1b
1c
2
1
X
product (8a) was produced with a longer reaction period (24 h). In
addition, general acids such as CF SO H, H SO , and pTsOH, were
N
N
1
2
) CH
) HX, anh. toluene, 80 oC, 24 h
HX = CF SO H, H SO , pTsOH)
3
CN, 80 oC, 24 h
3
SO H
3
3
2
4
employed, and resulted in lower yields of desired product (8a) than
3
4
5
a, [bsdmim][OTf] (92%)
a, [bsdmim][HSO ] (99%)
a, [bsdmim][pTSA] (92%)
(
3
3
2
4
our synthesized SO HꢀILs (Table 2, entries 2ꢀ4). Surprisingly, the
4
3
reaction generated a higher yield after 1.0 h when amount of SO Hꢀ
3
X
X
N
IL catalysts (4b and 4c) was reduced to 10 mol% (Table 2, entries 8
N
N
SO
3
H
SO
3
H
and 9). This was especially the case for SO HꢀIL (4b) with 84%
3
increase in yield of desired product (8a) (90% conversion yield).
However, the highest yield of desired product (8a), 89%, occurred
when reaction time was slightly increased to 1.5 h under the same
conditions (Table 2, entry 10).
3
4
5
b, [bsmim][OTf] (99%)
b, [bsmim][HSO ] (>99%)
b, [bsmim][pTSA] (>99%)
3c, [bspy][OTf] (99%)
4c, [bspy][HSO ] (>99%)
5c, [bspy][pTSA] (98%)
4
4
3
Scheme 2 Preparations of SO Hꢀfunctionalized Ionic Liquids
2
| Org. Biomol. Chem., 201x, xx, x-x
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Orga Pn l ieca s&e Bd oi o nmo to al ed cj uu sl ta mr Ca rhg ei nms istry
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DOI: 10.1039/C5OB01953B
Journal Name
Table 2 Optimization of FriedelꢀCrafts reaction in water using
ARTICLE
a
Table 3 Synthesis of dipyrrolemethanes with various substances
a
SO
3
HꢀIL catalyst under nitrogen atmosphere
R
NO2
O
4b
O
R
H
N
H
H
2
O, rt, N
2
gas
NH HN
catalyst
H
6
a-o
7
8a-o
b
N
H
H
2 2
O, rt, N gas
2
O N
NO
2
F
6
a
7
NH HN
8a
Entry
Catalyst
Catalyst Pyrrole 7 Time
Yield
b
(
equiv.)
(h)
(%)
(
mol%)
ꢀ
c
NH HN
NH HN
NH HN
1
2
3
4
5
6
7
8
9
ꢀ
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.5
2.5
2.5
5.0
2.5
5.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
1.5
1.5
3.0
1.5
3.0
3.0
0.5
0(25)
62
8a (89%)
8b (76%)
8c (67%)
CF
SO
pTsOH
3
SO
3
H
20
20
20
20
20
20
10
10
10
10
10
10
10
5
Cl
NMe2
H
2
4
66
OH
49
3b, [bsmim][OTf]
4b, [bsmim][HSO
65
4
]
73
NH HN
d (80%)
NH HN
NH HN
4c, [bspy][HSO
4b, [bsmim][HSO
4c, [bspy][HSO
4
]
72
8
8e (12%)
8f (52%)
d
4
]
84(90)
78
OH
4
]
OMe
OMe
OH
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4b, [bsmim][HSO
4
]
4
]
4
]
4
]
4
]
4
]
4
]
4
]
89
e
OH
31
31
NH HN
g (31%)
NH HN
NH HN
59
8
8h (59%)
8i (53%)
f
f
f
73
MeO
81
O
HN
5
65
OMe
1
50
53
a
NH HN
j (49%)
NH HN
NH HN
All reactions were conducted with 1.0 mmol of 6a and 5.0 mmol of 7
8
8k (76%)
8l (53%)
using 0ꢀ50 mol% of acidꢀIL in 3.0 mL H
b
2
O at rt for 1.0ꢀ3.0 h
c
d
e
Isolated yield. Performed for 24 h. Conversion yield. Performed at
Ph
o
f
1
2
0 C. Performed with 1.5 mL of H O.
The other effects of the most efficient catalyst (4b) (10 mol%) in
concert with reaction temperature and amount of pyrrole (7) on yield
of desired product (8a) were explored (Table 2, entries 11ꢀ17). At 10
NH HN
m (60%)
NH HN
NH HN
8
8n (38%)
8o (40%)
o
a
C, some of the remaining initial aldehyde was observed on the TLC,
All reactions were conducted with 1.0 mmol of aldehyde 6 and 5.0 mmol of
pyrrole 7 using 10 mol% of 4b, [bsmim][HSO ] in 3.0 mL H O at rt for 1.5 h.
] = 1ꢀbutylsulfonicꢀ3ꢀmethylimidazolium bisulfate
.
indicating the reaction was incompleted and isolated yield of desired
product (8a) was only 31% (Table 2, entry 11). With decreasing
pyrrole (7) to 2.5 equivalents, the desired product (8a) were obtained
4
2
b
Isolated yield. [bsmim][HSO
4
in lower yields, 31 and 59 % (8a) after 1.5 and 3.0 h, respectively yield was lowest, 53%, when catalyst was increased to 50 mol%
Table 2, entries 12 and 13, respectively). High concentrated reaction (Table 2, entry 17). This is likely due to too strong acidic conditions
(
volume could improve yield of desired product (8a) to 73% after 1.5 created by the large amount of acid catalyst causing the production
h (Table 2, entry 14). However this result indicated that a reduction of oligomers as complex mixtures.
in amount of pyrrole (7) to 2.5 equivalents resulted in lower yield of
The recycling performance of the catalyst (4b) was also
desired product (8a) than that when pyrrole (7) was present at 5.0 investigated using 4ꢀnitrobenzadehyde substrate. After completion of
equivalents. It is obvious that 2.5 equivalent of pyrrole (7) was not the reaction (Table 2, entry 10), the product (8a) was isolated from
sufficient to produce the desired product (8a) in highest yield using catalytic system by simple extraction, and then 4ꢀnitrobenzaldehyde
this protocol. Nonetheless, yield was higher than that in previous (6a) and pyrrole (7) were directly added into the catalytic system
6
,7j,7l
studies with a similar amount of pyrrole (7).
The catalyst (4b) (water layer containing catalyst) for next runs. The results showed
was tested with 5 mol% under high concentration condition with that the catalyst could be reused without significant loss of activity;
both 5.0 and 2.5 equivalents of pyrrole (7), the desired product (8a) the yields remained unchanged even after four cycles (89, 89, 88 and
was obtained in acceptable yields after 3.0 h with 81 and 65% yields, 87%, respectively) and the used catalyst retained its structure as
respectively (Table 2, entries 15 and 16). In addition, desired product confirmed by NMR.
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The chemical suitability of the substrate for the green synthesis General procedure for synthesis of 1-butylsulfonic-2,3-
of diprromethane derivatives via SO HꢀIL catalyzed FriedelꢀCrafts dimethylimidazolium salts (3a, 4a and 5a)
reaction was investigated under this optimized reaction condition
Table 2, entry 10). A variety of either aromatic or aliphatic
3
To a solution of 1,2ꢀdimethylimidazole 1a (5.00 g, 52.0 mmol) in
CH CN (25.0 mL) was added 1,4ꢀbutanesultone 2 (7.79 g, 57.2
(
3
aldehydes were tested with respect to moderate and good product
yields (Table 3). Corresponding desirable products were yielded
depending on electronic and steric effects of aldehyde substrates.
However, this new protocol is tolerant of various functional groups
of aldehydes including both electron donating and electron
withdrawing groups. Aldehyde substrates with electron withdrawing
group (6a, 6c, and 6d) including benzadehyde (6b) produced good
yield of products (8a-8d; 67ꢀ89% yields). While aldehyde substrates
with electron donating group (6f-6j) provided the products (8i-8j) in
moderate yields (31ꢀ59% yields). In contrast high electronꢀrich 4ꢀ
mmol) in portion at room temperature. The reaction mixture was
o
heated to 80 C with stirring for 24 h, and then cooled to room
temperature resulting precipitate white solid. The white solid was
filtered and washed with ethanol (3×5 mL) to remove any unreacted
starting materials, and then the solid was dried in vacuum to give the
zwitterion compound as white solid in 81% yield (9.7403 g). mp.
o
1
1
7
2
97ꢀ200 C; HꢀNMR (400 MHz, CD
.5 Hz, CH ), 2.01 (quint, 2H, J = 7.5 Hz, CH
.87 (t, 2H, J = 7.5 Hz, CH ), 3.84 (s, 3H, CH
), 7.50 (d, 1H, J = 2.0 Hz, CH), 7.57 (d, 1H, J = 2.0 Hz,
3
OD): δ 1.83 (quint, 2H, J =
), 2.67 (s, 3H, CH ),
), 4.23 (t, 2H, J = 7.5
2
2
3
2
3
Hz, CH
2
(
N,Nꢀdimethylamino)benzaldehyde (6e) produced very low product
13
CH); CꢀNMR (100 MHz, CD
1.39, 122.26, 123.63, 146.01. A mixture of zwitterion compound
1.50 g, 6.46 mmol) in anhydrous toluene (3.00 mL) was added
3
OD): δ 9.48, 22.83, 29.44, 35.35,
yield, 12%, (8e) for the same time due to incomplete reaction.
Moreover, heteroaromatic aldehydes such as furanꢀ2ꢀcarbaldehyde
5
(
(
6k) and pyrroleꢀ2ꢀcarbaldehyde (6l) also produced the product (8k)
in good yields (76% yield) and the product (8l) in moderate yield
53% yield), respectively. Interestingly, this protocol also works well
stoichiometric amount of acid HX (1 eq.) in portion at room
o
temperature. The reaction mixture was then stirred at 80 C for 24 h.
(
After white solid was all soluble, the reaction mixture was cooled to
room temperature, removed toluene layer and extracted with ethyl
acetate (3×10 mL) to remove remaining organic compounds. The
insoluble residue was dried under high vacuum to give the products
in 92ꢀ99% yields.
with aliphatic aldehydes (6m, 6n, and 6o) and gave the desired
products (8m, 8n, and 8o) in moderate yields (38ꢀ60%).
Conclusions
In summary, we have demonstrated a green method for synthesis of
dipyrromethanes under mild and metalꢀfree condition in water
media. The reaction was performed by using catalytic amount of
1
-Butylsulfonic-2,3-dimethylimidazolium
trifluoromethanesulfonate (3a). 92% yield (2.4253 g) as a brown
1
color oil; HꢀNMR (400 MHz, CD
Hz, CH ), 2.02 (quint, 2H, J = 7.5 Hz, CH
t, 2H, J = 7.5 Hz, CH ), 3.85 (s, 3H, CH
), 7.50 (d, 1H, J = 2.0 Hz, CH), 7.56 (d, 1H, J = 2.0 Hz, CH);
OD): δ 9.49, 22.76, 29.40, 35.37, 48.97,
3
OD): δ 1.84 (quint, 2H, J = 7.5
), 2.67 (s, 3H, CH ), 2.90
), 4.23 (t, 2H, J = 7.5 Hz,
SO
3
HꢀIL, which consisted of imidazolium cation and HSO
4
anion,
2
2
3
named as [bsmim][HSO
4
]. The desired products were successfully
(
2
3
obtained in moderate to good yields with a wide range of aldehyde
substrates. Corresponding products are easily separated from
reaction system by simple extraction and catalyst recycling was
possible for subsequent reactions. This protocol may offer the green
chemistry from the aspect of avoiding toxic catalysts and solvents.
CH
2
13
CꢀNMR (100 MHz, CD
3
5
1.43, 122.20, 123.63, 145.98.
1-Butylsulfonic-2,3-dimethylimidazoluium hydrogen sulfate
1
(
4a). 99% yield (2.1152 g) as a brown color oil; HꢀNMR (400 MHz,
CD OD): δ 1.84 (quint, 2H, J = 7.5 Hz, CH ), 2.02 (quint, 2H, J =
.5 Hz, CH ), 2.68 (s, 3H, CH ), 2.91 (t, 2H, J = 7.5 Hz, CH ), 3.86
s, 3H, CH ), 4.23 (t, 2H, J = 7.5 Hz, CH ), 7.51 (d, 1H, J = 2.0 Hz,
3
2
Experimental section
7
(
2
3
2
General methods
3
2
13
All chemicals were purchased from commercial sources and used CH), 7.57 (d, 1H, J = 2.0 Hz, CH); CꢀNMR (100 MHz, CD OD): δ
3
without further purification. Proton NMR spectra were recorded on a 9.52, 22.72, 29.38, 35.40, 48.93, 51.47, 122.17, 123.63, 145.96.
BRUKER AVANC (400 MHz). All spectra were measured in CDCl
or CD OD solvent and chemical shifts are reported as δ values in
parts per million (ppm) relative to tetramethylsilane (δ 0.00), CDCl
δ 7.26) or CD
spectra were recorded on a BRUKER AVANC (100 MHz). All J = 7.5 Hz, CH ), 2.40 (s, 3H, CH ), 2.64 (s, 3H, CH ), 2.90 (t, 2H, J
3
3
1-Butylsulfonic-2,3-dimethylimidazolium p-toluenesulfonate
(5a). 92% yield (2.4195 g) as a yellow color oil; HꢀNMR (400
1
3
(
3
3 2
OD (δ 3.34) as internal standard. Carbon NMR MHz, CD OD): δ 1.83 (quint, 2H, J = 7.5 Hz, CH ), 2.00 (quint, 2H,
2
3
3
spectra were measured in CDCl
3 3
2 3 2
or CD OD solvent and chemical = 7.5 Hz, CH ), 3.82 (s, 3H, CH ), 4.20 (t, 2H, J = 7.5 Hz, CH ),
shifts are reported as δ values in parts per million (ppm) relative to 7.28 (d, 2H, J = 8.0 Hz, H ), 7.48 (d, 1H, J = 2.0 Hz, CH), 7.54 (d,
Ar
1
3
3 3
CDCl (δ 77.0) or CD OD (δ 49.0) as internal standard. Highꢀ 1H, J = 2.0 Hz, CH), 7.72 (d, 2H, J = 8.0 Hz, HAr); CꢀNMR (100
resolution mass spectra (HRMS) data were obtained with a Bruker MHz, CD OD): δ 9.49, 21.29, 22.71, 29.37, 35.37, 48.92, 51.45,
3
Daltonics ꢀ micrOTOFꢀQ. Infrared spectra were determined on a 122.16, 123.61, 126.93 (2C), 129.90 (2C), 142.01, 143.08, 145.92.
PERKIN ELMER FT/IRꢀ2000S spectrophotometer and are reported
ꢀ
1
in wave number (cm ). Openꢀcolumn chromatography was carried General procedure for synthesis of 1-butylsulfonic-3-
out using silica gel 60 PF254 [E. Merck, Darmstadt, Germany]. methylimidazolium salts (3b, 4b and 5b)
Melting points were measured using a Melting point apparatus To a solution of 1ꢀmethylimidazole 1b (5.00 g, 60.9 mmol) in
(
Griffin) and are uncorrected.
CH CN (25.0 mL) was added 1,4ꢀbutanesultone 2 (9.12 g, 67.0
3
4
| Org. Biomol. Chem., 201x, xx, x-x
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Page 5 of 8
Orga Pn l iec a s&e Bd oi o nmo to al ed cj uu sl ta mr Ca rhg ei nms istry
View Article Online
DOI: 10.1039/C5OB01953B
Journal Name
ARTICLE
mmol) in portion at room temperature. The reaction mixture was zwitterion compound as white solid in in 57% yield (7.7744 g). Mp.
o
o
1
heated to 80 C with stirring for 24 h, and then cooled to room 193ꢀ196 C; HꢀNMR (400 MHz, CD
temperature resulting precipitate white solid. The white solid was 7.5 Hz, CH ), 2.24 (quint, 2H, J = 7.5 Hz, CH
filtered and washed with ethanol (3×5 mL) to remove any unreacted Hz, CH ), 4.73 (t, 2H, J = 7.5 Hz, CH ), 8.16 (bst, 2H, J = 7.0 Hz,
Ar), 8.63 (t, 1H, J = 8.0 Hz, HAr), 9.07 (bsd, 2H, J = 6.0 Hz, HAr);
3
OD): δ 1.88 (quint, 2H, J =
2
2
), 2.92 (t, 2H, J = 7.5
2
2
starting materials, and then the solid was dried in vacuum to give the
zwitterion compound as white solid in 71% yield (9.4700 g). mp.
H
1
3
3
CꢀNMR (100 MHz, CD OD): δ 22.70, 31.16, 51.28, 62.52, 129.52
o
1
1
93ꢀ196 C; HꢀNMR (400 MHz, CD
3
OD): δ 1.81 (quint, 2H, J = (3C), 146.06, 146.85. A mixture of zwitterion compound (1.50 g,
), 2.08 (quint, 2H, J = 7.5 Hz, CH ), 2.88 (t, 2H, J = 7.5 6.97 mmol) in anhydrous toluene (3.00 mL) was added
), 4.30 (t, 2H, J = 7.5 Hz, CH ), 7.61 (brs, stoichiometric amount of acid HX (1 eq.) in portion at room
7.5 Hz, CH
2
2
Hz, CH
1
2
), 3.97 (s, 3H, CH
3
2
1
3
o
H, CH), 7.70 (brs, 1H, CH), 9.00 (s, 1H, CH); CꢀNMR (100 temperature. The reaction mixture was then stirred at 80 C for 24 h.
MHz, CD OD): δ 22.72, 29.83, 36.47, 50.31, 51.41, 123.72, 124.99, After white solid was all soluble, the reaction mixture was cooled to
38.05. A mixture of zwitterion compound (1.50 g, 6.87 mmol) in room temperature, removed toluene layer and extracted with ethyl
3
1
anhydrous toluene (3.00 mL) was added stoichiometric amount of acetate (3×10 mL) to remove remaining organic compounds. The
acid HX (1 eq.) in portion at room temperature. The reaction mixture insoluble residue was dried under high vacuum to give products in
o
was then stirred at 80 C for 24 h. After white solid was all soluble, 98% to quantitative yields.
the reaction mixture was cooled to room temperature, removed
toluene layer and extracted with ethyl acetate (3×10 mL) to remove
remaining organic compounds. The insoluble residue was dried 94% yield (2.3853 g) as an orange color oil; HꢀNMR (400 MHz,
under high vacuum to give the products in mostꢀquantitative yields. CD OD): δ 1.88 (quint, 2H, J = 7.5 Hz, CH ), 2.23 (quint, 2H, J =
.5 Hz, CH ), 2.93 (t, 2H, J = 7.5 Hz, CH ), 4.72 (t, 2H, J = 7.5 Hz,
CH ), 8.16 (brt, 2H, J = 6.5 Hz, HAr), 8.63 (t, 1H, J = 7.5 Hz, HAr),
.05 (brd, 2H, J = 6.0 Hz, HAr); CꢀNMR (100 MHz, CD
22.63, 31.09, 51.27, 62.53, 129.53 (3C), 146.00, 146.88.
1-Butylsulfonic pyridinium trifluoromethanesulfonate (3c).
1
3
2
7
2
2
2
1
-Butylsulfonic-3-methylimidazolium
1
3
9
3
OD): δ
trifluoromethanesulfonate (3b). 98% yield (2.5211 g), as an orange
1
color oil; HꢀNMR (400 MHz, CD
Hz, CH ), 2.08 (quint, 2H, J = 7.5 Hz, CH
CH ), 3.96 (s, 3H, CH ), 4.29 (t, 2H, J = 7.5 Hz, CH
CH), 7.68 (brs, 1H, CH), 8.97 (s, 1H, CH); CꢀNMR (100 MHz,
CD OD): δ 22.67, 29.79, 36.48, 50.32, 51.40, 123.69, 124.99,
37.98.
3
OD): δ 1.82 (quint, 2H, J = 7.5
), 2.90 (t, 2H, J = 7.5 Hz,
), 7.60 (brs, 1H,
2
2
1
-Butylsulfonic pyridinium hydrogen sulfate (4c). quantitative
2
3
2
1
1
3
yield (2.3695 g) as an orange color oil; HꢀNMR (400 MHz,
CD OD): δ 1.88 (quint, 2H, J = 7.5 Hz, CH ), 2.24 (quint, 2H, J =
.5 Hz, CH ), 2.94 (t, 2H, J = 7.5 Hz, CH ), 4.73 (t, 2H, J = 7.5 Hz,
CH ), 8.16 (brt, 2H, J = 6.5 Hz, HAr), 8.64 (t, 1H, J = 7.5 Hz, HAr),
.06 (brd, 2H, J = 6.0 Hz, HAr): CꢀNMR (100 MHz, CD
22.64, 31.11, 51.29, 62.52, 129.54 (3C), 146.03, 146.88.
3
2
3
7
2
2
1
2
1
3
9
3
OD): δ
1-Butylsulfonic-3-methylimidazolium hydrogen sulfate (4b).
1
quantitative yield (2.3228 g) as an orange color oil; HꢀNMR (400
MHz, CD OD): δ 1.82 (quint, 2H, J = 7.5 Hz, CH ), 2.08 (quint, 2H,
J = 7.5 Hz, CH ), 2.90 (t, 2H, J = 7.5 Hz, CH ), 3.97 (s, 3H, CH ),
.30 (t, 2H, J = 7.5 Hz, CH ), 7.61 (brs, 1H, CH), 7.69 (brs, 1H,
CH), 8.99 (s, 1H, CH); CꢀNMR (100 MHz, CD OD): δ 22.68,
9.80, 36.51, 50.32, 51.43, 123.68, 124.99, 137.96.
3
2
1
-Butylsulfonic pyridinium toluenesulfonate (5c). 98% yield
2
2
3
1
(
2.6732 g) as a yellow color oil; HꢀNMR (400 MHz, CD
1.87 (quint, 2H, J = 7.5 Hz, CH ), 2.22 (quint, 2H, J = 7.5 Hz, CH
.41 (s, 3H, CH ), 2.92 (t, 2H, J = 7.5 Hz, CH ), 4.71 (t, 2H, J = 7.5
Hz, CH ), 7.28 (d, 2H, J = 8.0 Hz, HAr), 7.73 (d, 2H, J = 8.0 Hz,
Ar), 8.14 (brt, 2H, J = 6.5 Hz, HAr), 8.62 (t, 1H, J = 8.0 Hz, HAr),
9.05 (brd, 2H, J = 6.0 Hz, HAr); CꢀNMR (100 MHz, CD
1.28, 22.63, 31.08, 51.25, 62.53, 126.92 (2C), 129.52 (3C), 129.83
2C), 141.78, 143.43, 145.97, 146.85.
3
OD): δ
4
2
1
3
2
2
),
3
2
3
2
2
2
H
1-Butylsulfonic-3-methylimidazolium p-toluenesulfonate (5b).
1
3
1
3
OD): δ
quantitative yield (2.6970 g) as a brown color oil; HꢀNMR (400
MHz, CD OD): δ 1.81 (quint, 2H, J = 7.5 Hz, CH ), 2.06 (quint, 2H,
J = 7.5 Hz, CH ), 2.41 (s, 3H, CH ), 2.89 (t, 2H, J = 7.5 Hz, CH ),
.95 (s, 3H, CH ), 4.28 (t, 2H, J = 7.5 Hz, CH ), 7.28 (d, 2H, J = 8.0
Hz, HAr), 7.59 (brs, 1H, CH), 7.67 (brs, 1H, CH), 7.73 (d, 2H, J =
2
(
3
2
2
3
2
3
3
2
General procedure for the synthesis of dipyrromethanes
OD): δ To a suspension of [bsmim][HSO ] (4b)* (10 mol%) in degas water
1.29, 22.38, 29.59, 36.41, 49.92, 51.45, 123.33, 124.66, 126.64, (3.0 mL) was added aldehyde (1.0 mmol) and pyrrole (5.0 mmol) at
13
8
2
1
.0 Hz, HAr), 8.97 (s, 1H, CH); CꢀNMR (100 MHz, CD
3
4
26.69, 129.92, 129.97, 137.66, 142.01, 142.78.
room temperature under nitrogen gas. The mixture suspension was
stirred at room temperature for 1.5 h. Then, the mixture was
General procedure for synthesis of 1-butylsulfonic pyridinium extracted with ethyl acetate (3×2 mL). The combined organic layer
salts (3c, 4c and 5c)
was washed with brine (20 mL) and dried over sodium sulfate
anhydrous. The solvent was removed by rotary and concentrated
under reduced pressure. The residue was purified by column
chromatography to give the desired products (8).
*Recycling experiment. After completion of the reaction, the
remaining catalyst in aqueous solution could be reused directly by
adding aldehyde and pyrrole substrates in the next run without
purification.
To a solution of 1ꢀmethylimidazole 1c (5.00 g, 63.3 mmol) in
CH CN (25.0 mL) was added 1,4ꢀbutanesultone 2 (9.47 g, 69.6
3
mmol) in portion at room temperature. The reaction mixture was
o
heated to 80 C with stirring for 24 h, and then cooled to room
temperature resulting precipitate white solid. The white solid was
filtered and washed with ethanol (3×5 mL) to remove any unreacted
starting materials, and then the solid was dried in vacuum to give the
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Organic & Biomolecular Chemistry
Page 6 of 8
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DOI: 10.1039/C5OB01953B
ARTICLE
meso-(4-Nitrophenyl)dipyrromethane (8a).
Journal Name
1
e,1j,6,7b,7e,7h,7k,7l,8a,9a
o
meso-(3-Hydroxyphenyl)dipyrromethane (8f). 52% yield
o
89% yield (0.2388 g) as a yellow solid; m.p. 135ꢀ138 C; R
f
= 0.17 (0.1229 g) as a brown solid; m.p. 105ꢀ107 C; R
f
= 0.23 (20%
(
10% EtOAc/nꢀhexane); IR (Neat): 3391, 1594, 1515, 1346, 1028, EtOAc/nꢀhexane); IR (Neat): 3383, 1599, 1456, 1265, 1092, 1027,
ꢀ
1
1
ꢀ1
1
7
5
2
8
4
28, 556 cm ; HꢀNMR (400 MHz, CDCl
.85ꢀ5.89 (m, 2H, 2×H ), 6.16ꢀ6.20 (m, 2H, 2×H
H, 2×H ), 7.37 (2H, d, J = 8.5 Hz, 2×HAr), 8.00 (brs, 2H, 2×H
.17 (d, 2H, J = 8.5 Hz, 2×HAr); CꢀNMR (100 MHz, CDCl
3.78, 107.80 (2C), 108.77 (2C), 117.95 (2C), 123.77 (2C), 129.22 2H, 2×H
108.30 (2C), 113.97, 115.25, 117.33, 117.35, 120.94, 129.84, 132.32
3
): δ 5.58 (s, 1H, H1'), 723, 549 cm ; HꢀNMR (400 MHz, CDCl
), 6.73ꢀ6.77 (m, 5.91ꢀ5.95 (m, 2H, 2×H ), 6.14ꢀ6.18 (m, 2H, 2×H
), Ar), 6.67ꢀ6.70 (m, 2H, 2×H ), 6.72 (dd, 1H, J = 7.5, 2.0 Hz, HAr),
): δ 6.81 (d, 1H, J = 7.5 Hz, HAr), 7.19 (t, 1H, J = 7.5 Hz, HAr), 7.94 (brs,
3
): δ 5.41 (s, 1H, H1'),
3
4
3
4
), 6.58 (brs, 1H,
5
1
H
5
13
3
1
3
1 3
); CꢀNMR (100 MHz, CDCl ); δ 43.64, 107.21 (2C),
(2C), 130.79 (2C), 146.89, 149.64; HRMS (ESI) m/z C15
H
13
N
3
O
2
+
+
[
M+Na] calcd 290.0905, found 290.0907.
(2C), 143.84, 155.64; HRMS (ESI) m/z C15
61.1004, found 261.1003.
H
14
N
2
O [M+Na] calcd
2
1
b,1e,1j,1f,6,7b,7e,7g,7h,7k,7l,7m,8a,9a
meso-(Phenyl)dipyrromethane (8b).
o
7l,8a
7
6% yield (0.1682 g) as a white solid; m.p. 91ꢀ101 C; R
f
= 0.32
meso-(2-Hydroxyphenyl)dipyrromethane (8g).
31% yield
= 0.18 (20%
o
(10% EtOAc/nꢀhexane); IR (Neat): 3379, 3100, 1559, 1495, 1451, (0.0749 g) as a brown solid; m.p. 103ꢀ105 C; R
f
ꢀ
1 1
1
1
6
090, 1027, 722, 550 cm ; HꢀNMR (400 MHz, CDCl
H, H1'), 5.89ꢀ5.93 (m, 2H, 2×H ), 6.14ꢀ6.17 (m, 2H, 2×H
.70 (m, 2H, 2×H ), 7.19ꢀ7.34 (m, 5H, 5×HAr), 7.19 (brs, 2H, 2×H
CꢀNMR (100 MHz, CDCl ): δ 43.92, 107.20 (2C), 108.38 (2C), 2×H
17.20 (2C), 126.94, 128.36 (2C), 128.61 (2C), 132.47 (2C), 142.03; (t, 1H, J = 7.5 Hz, HAr), 7.08 (dd, 1H, J = 7.5, 1.5 Hz, HAr), 7.19 (td,
3
): δ 5.47 (s, EtOAc/nꢀhexane); IR (Neat): 3407, 1594, 1599, 1456, 1276, 1087,
ꢀ
1 1
3
4
), 6.67ꢀ 1027, 722, 534 cm ; HꢀNMR (400 MHz, CDCl
); OH), 5.54 (s, 1H, H1'), 5.99ꢀ6.02 (m, 2H, 2×H ), 6.15ꢀ6.18 (m, 2H,
), 6.70ꢀ6.73 (m, 2H, 2×H ), 6.86 (d, 1H, J = 7.5 Hz, HAr), 6.91
3
): δ 5.22 (brs, 1H,
5
1
3
13
3
4
5
1
+
13
HRMS (ESI) m/z C15
2
H
14
N
2
[M+Na] calcd 245.1055, found 1H, J = 7.5, 1.5 Hz, HAr), 8.18 (brs, 2H, 2×H
MHz, CDCl ): δ 40.01, 106.97 (2C), 108.44 (2C), 117.33, 117.87
2C), 121.42, 128.34, 128.62, 130.02, 130.98 (2C), 153.54; HRMS
1
); CꢀNMR (100
45.1050.
3
(
1
e,7e,8a
+
meso-(4-Fluorophenyl)dipyrromethane (8c).
67% yield (ESI) m/z C15
= 0.30 (20% EtOAc/nꢀ
hexane); IR (Neat): 3378, 1603, 1561, 1506, 1222, 1158, 1092,
14 2
H N O [M+Na] calcd 261.1004, found 261.1008.
o
(0.1606 g) as a brown solid; m.p. 96 C; R
f
meso-(3-Methoxy-4-hydroxyphenyl)dipyrromethane
): δ 5.46 (s, 1H, 59% yield (0.1583 g) as a brown solid; m.p. 113ꢀ115 C; R
(8h).
= 0.23
ꢀ
1
1
o
1
028, 720, 541 cm ; HꢀNMR (400 MHz, CDCl
3
f
H
1'), 5.87ꢀ5.90 (m, 2H, 2×H
3
), 6.14ꢀ6.18 (m, 2H, 2×H
4
), 6.69ꢀ6.72 (20% EtOAc/nꢀhexane); IR (Neat): 3380, 1603, 1512, 1463, 1431,
ꢀ
1
1
(
m, 2H, 2×H
5
), 6.96ꢀ7.04 (m, 2H, 2×HAr), 7.14ꢀ7.20 (m, 2H, 2×HAr), 1273, 1230, 1028, 721, 550 cm ; HꢀNMR (400 MHz, CDCl
3
): δ
): δ 43.16, 107.29 3.80 (s, 3H, OMe), 5.40 (brs, 1H, OH), 5.56 (s, 1H, H1'), 5.92 (brs,
), 6.16 (dd, 2H, J = 5.5, 2.5 Hz, H ), 6.66ꢀ6.72 (m, 4H, H
Ar), 6.85 (d, 1H, J = 8.0 Hz, HAr), 7.94 (brs, 2H, 2×H
[M+H] calcd 241.1141, found (100 MHz, CDCl ): δ 43.53, 55.82, 106.99 (2C), 108.28 (2C),
111.02, 114.25, 117.09 (2C), 120.97, 132.73 (2C), 133.97, 144.42,
13
1 3
7.92 (brs, 2H, 2×H ); CꢀNMR (100 MHz, CDCl
(
(
2C), 108.46 (2C), 115.35 (2C, J = 21.0 Hz), 117.38 (2C), 129.83 2H, H
2C, J = 8.0 Hz), 132.31 (2C), 137.80, 161.75 (J = 244.0 Hz);
3
4
5
,
1
3
H
1
); CꢀNMR
+
HRMS (ESI) m/z C15
41.1143.
H13FN
2
3
2
+
1
46.54; HRMS (ESI) m/z C16
80% found 269.1290.
f
= 0.30
16 2 2
H N O [M+H] calcd 269.1290,
1
e,7b,7m,8a
o
meso-(4-Chlorophenyl)dipyrromethane (8d).
yield (0.2061 g) as a bark brown solid; m.p. 96ꢀ98 C; R
(
10% EtOAc/nꢀhexane):IR (Neat): 3378, 1560, 1489, 1255, 1089,
meso-(2-Hydroxy-3-Methoxy)dipyrromethane (8i). 53% yield
): δ 5.45 (s, 1H, (0.1434 g) as brown solid; R = 0.22 (20% EtOAc/nꢀhexane):IR
), 6.14ꢀ6.19 (m, 2H, 2×H ), 6.69ꢀ6.73 (Neat): 3402, 2938, 1478, 1441, 1274, 1223, 1067, 1026, 721, 550
), 7.15 (d, 2H, J = 8.0 Hz, 2×HAr), 7.29 (d, 2H, J = 8.0 cm ; HꢀNMR (400 MHz, CDCl
ꢀ
1 1
1
027, 723, 511 cm ; HꢀNMR (400 MHz, CDCl
1'), 5.87ꢀ5.91 (m, 2H, 2×H
m, 2H, 2×H
Hz, 2×HAr), 7.94 (brs, 2H, 2×H
3.23, 107.36 (2C), 108.44 (2C), 117.44 (2C), 128.61 (2C), 129.65 2×H
3
f
H
(
3
4
ꢀ
1 1
5
3
): 3.88 (s, 3H, OMe), 5.71 (s, 1H,
1'), 5.91 (brs, 1H, OH), 5.94ꢀ5.98 (m, 2H, 2×H ), 6.13ꢀ6.16 (m, 2H,
), 6.67ꢀ6.70 (m, 2H, 2×H ), 6.75ꢀ6.85 (m, 3H, 3×HAr), 8.27
CꢀNMR (100 MHz, CDCl ); δ 38.80, 55.99,
106.58 (2C), 108.10 (2C), 109.32, 116.80 (2C), 119.90, 121.91,
13
1
); CꢀNMR (100 MHz, CDCl
3
); δ
H
3
4
4
5
13
(2C), 131.94 (2C), 132.61, 140.59; HRMS (ESI) m/z C15
H
13ClN
2
(brs, 2H, 2×H
1
);
3
+
[
M+Na] calcd 279.0665, found 279.0669.
1
27.96, 132.05 (2C), 142.78, 146.59; HRMS (ESI) m/z C16
H
16
2
N O
2
7
b,7l
+
meso-(4-(N,N-dimethylamino)phenyl)dipyrromethane (8e).
[M+H] calcd 269.1290, found 269.1294.
o
1
f
2% yield (0.0306 g) as a brown solid; m.p. 111ꢀ117 C; R = 0.44
7
m
(
10% EtOAc/nꢀhexane): IR (Neat): 3397, 1611, 1519, 1349, 1026,
meso-(2,5-Dimethoxyphenyl)dipyrromethane (8j).
49%
ꢀ
1
1
o
7
5
6
2
17, 534 cm ; HꢀNMR (400 MHz, CDCl
.40 (s, 1H, H1'), 5.91ꢀ5.96 (m, 2H, 2×H ), 6.13ꢀ6.18 (m, 2H, 2×H
.66ꢀ6.69 (m, 2H, 2×H
H, J = 8.0 Hz, 2×HAr), 7.93 (brs, 2H, 2×H
); δ 40. 63(2C), 43.18, 106. 90(2C), 108. 44(2C), 112. 91(2C), 6.15 (m, 2H, 2×H
16.8 0(2C), 129.0 9(2C), 130.10, 133. 37(2C), 149.81; HRMS Hz, HAr), 6.75 (dd, 1H, J = 8.0, 3.0 Hz, HAr), 6.85 (d, 1H, J = 9.0 Hz,
3
): δ 2.94 (s, 6H, 2×CH
3
), yield (0.1374 g) as a brown solid; m.p. 117ꢀ127 C; R
f
= 0.19 (10%
3
4
), EtOAc/nꢀhexane): IR (Neat): 3381, 1559, 1497, 1428, 1223, 1026,
ꢀ
1 1
5
), 6.71 (d, 2H, J = 8.0 Hz, 2×HAr), 7.09 (d, 271, 566 cm ; HꢀNMR (400 MHz, CDCl
3
): δ 3.70 (s, 3H, OMe),
); CꢀNMR (100 MHz, 3.71 (s, 3H, OMe), 5.74 (s, 1H, H1'), 5.89ꢀ5.93 (m, 2H, 2×H ), 6.11ꢀ
), 6.64ꢀ6.68 (m, 2H, 2×H ), 6.70 (d, 1H, J = 3.0
1
3
1
3
CDCl
1
(
3
4
5
+
13
ESI) m/z C17
H
19
N
3
[M+H] calcd 266.1657, found 0266.1650.
1 3
HAr), 8.14 (brs, 2H, 2×H ); CꢀNMR (100 MHz, CDCl ); δ 38.07,
5
5.53, 56.56, 106.69 (2C), 108.13 (2C), 112.13, 112.73, 115.91,
6
| Org. Biomol. Chem., 201x, xx, x-x
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Orga Pn l iec a s&e Bd oi o nmo to al ed cj uu sl ta mr Ca rhg ei nms istry
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DOI: 10.1039/C5OB01953B
Journal Name
16.75 (2C), 132.27 (3C), 150.96, 153.82; HRMS (ESI) m/z Acknowledgements
ARTICLE
1
+
17 18 2 2
C H N O [M+H] calcd 283.1447, found 283.1446.
This work was financial supported by a Research Grant from
Burapha University through a National Research Council of
Thailand grant (No. 29/2555 and 17/2556) and a Thailand Research
Fund grant (No. TRG5780298). Special thanks to Prof. Dr. Frederick
W.H. Beamish, Faculty of Science, Burapha University, for his
comments and English correction and Dr. Byoung Se Lee
7
d,7l,7m,8b
meso-(Furan-2-yl)dipyrromethane (8k).
76% yield
= 0.52 (20%
o
(
0.1602 g) as a pale gray solid; m.p. 73ꢀ77 C; R
f
EtOAc/nꢀhexane); IR (Neat): 3383, 3117, 1727, 1558, 1505, 1466,
ꢀ
1 1
1
(
6
2
(
427, 1403, 1250, 1090, 1028, 1010, 768, 721, 553 cm ; HꢀNMR
400 MHz, CDCl ): δ 5.52 (s, 1H, H1'), 5.97ꢀ6.01 (m, 2H, 2×H ),
.13ꢀ6.18 (m, 3H, 2×H , H3'), 6.32ꢀ6.35 (m, 1H, H4'), 6.68ꢀ6.72 (m,
H, 2×H ), 7.37ꢀ7.41 (m, 1H, H5'), 8.10 (brs, 2H, 2×H
3
3
(
FutureChem Co. Ltd., Korea) for helpful discussion.
4
13
5
1
); CꢀNMR
): δ 37.67, 106.72 (2C), 106.90, 108.33 (2C), Notes and references
100 MHz, CDCl
3
1
10.24, 117.51 (2C), 129.92 (2C), 142.02, 154.26; HRMS (ESI) m/z
1
(a) C.ꢀH. Lee, J. H. Lindesey, Tetrahedron, 1994, 50, 11427ꢀ
1440; (b) T. Mizutani, T. Ema, T. Tomita, Y. Kuroda, H.
+
C
13 12 2
H N O [M+Na] calcd 235.0847, found 235.0845.
1
Ogoshi, J. Am. Chem. Soc., 1994, 116, 4240ꢀ4250; (c) C.ꢀH.
Lee, F. Li, K. Iwamoto, J. Dadok, A. A. BothnerꢀBy, J. S.
Lindsey, Tetrahedron, 1995, 51, 11645ꢀ11672; (d) Jꢀi. Setsune,
M. Hashimoto, K. Shiozawa, Jꢀy. Hayakawa, T. Ochi and R.
Masuda, Tetrahedron, 1998, 54, 1407ꢀ1424; (e) R. Naik, P.
Joshi, S. P. Kaiwar, R. K. Deshpande, Tetrahedron, 2003, 59,
7
m,8b
Tripyrromethane (8l).
53% yield (0.1128 g) as a brownꢀ
o
yellow solid; m.p. 113ꢀ117 C; R = 0.22 (10% EtOAc/nꢀhexane); IR
f
ꢀ
1
1
(
Neat): 3366, 1554, 1401, 1113, 1091, 1026, 722, 537 cm ; Hꢀ
NMR (400 MHz, CDCl
3
): δ 5.53 (s, 1H, H1'), 6.02ꢀ6.06 (m, 3H,
), 6.65ꢀ6.69 (m, 3H, 3×H ), 7.93 (brs,
); CꢀNMR (100 MHz, CDCl ): δ 37.16, 106.74 (3C),
08.39 (3C), 117.34 (3C), 131.14 (3C); HRMS (ESI) m/z C13
3
3
1
×H
H, 3×H
3
), 6.15ꢀ6.19 (m, 3H, 3×H
4
5
13
1
3
2
6
207ꢀ2213; (f) G. R. Geier, J. S. Lindsey, Tetrahedron, 2004,
0, 11435ꢀ11444; (g) S. Kitaoka, K. Nobuoka, Y. Ishikawa,
13 3
H N
+
[
M+Na] calcd 234.1007, found 234.1008.
Chem. Commun., 2004, 1902ꢀ1903; (h) S.ꢀJ. Hong, M.ꢀH. Lee,
C.ꢀH. Lee, Bull. Korean Chem. Soc., 2004, 25, 1545ꢀ1550; (i)
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Nietzold, H.ꢀU. Reissig, Adv. Synth. Catal., 2013, 355, 1409ꢀ
meso-(Cyclopentyl)dipyrromethane (8m). 60% yield (0.1289
g) as a pale orange solid; m.p. 65ꢀ69 C; R
hexane); IR (Neat): 3378, 3078, 3002, 2868, 1558, 1429, 1090,
026, 718, 563 cm ; HꢀNMR (400 MHz, CDCl
H, Hcꢀpentyl), 1.49ꢀ1.62 (m, 4H, Hcꢀpentyl), 1.73ꢀ1.82 (m, 2H, Hcꢀ
pentyl), 2.38ꢀ2.50 (m, 1H, Hcꢀpentyl), 3.79 (d, 1H, J = 9.5 Hz, H1'),
o
f
= 0.38 (10% EtOAc/nꢀ
ꢀ
1 1
1
2
3
): δ 1.25ꢀ1.35 (m,
1
422; (l) Y. Terazono, E. J. North, A. L. Moore, T. A. Moore,
6
2
2
1
2
.06ꢀ6.09 (m, 2H, 2×H
H, 2×H ), 7.74 (brs, 2H, 2×H
5.23 (2C), 29.67, 31.77 (2C), 43.42, 105.71 (2C), 107.85 (2C),
3
), 6.12ꢀ6.15 (m, 2H, 2×H
4
), 6.58ꢀ6.62 (m,
D. Gust, Org. Lett., 2012, 14, 1776ꢀ1779; (m) H. R. A. Golf,
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R. A. Golf, H.ꢀU. Reissig, A. Wiehe, A. J. Org. Chem., 2015,
1
3
5
1
); CꢀNMR (100 MHz, CDCl ): δ
3
+
18 2
16.75 (2C), 133.47 (2C); HRMS (ESI) m/z C14H N [M+H] calcd
8
0, 5133ꢀ5143. (o) K. Singh, S. Sharma, P. Kaur, C.ꢀH. Lee,
15.1548, found 215.1543.
Tetrahedron, 2015, 71, 8373ꢀ8390.
2
3
M. Ak, V. Gancheva, L. Terlemezyan, C. Tanyeli, L. Toppare,
Eur. Polym. J., 2008, 44, 2567ꢀ2573.
meso-(3-Phenylpropyl)dipyrromethane (8n). 38% yield
0.0948 g) as a yellow oil; R = 0.58 (20% EtOAc/nꢀhexane); IR
Neat): 3378, 2926, 2861, 1559, 1496, 1545, 1092, 1026, 720, 566
(
(
f
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1 1
cm ; HꢀNMR (400 MHz, CDCl
.63 (t, 2H, J = 7.5 Hz, H3'), 3.98 (t, 1H, J = 7.5 Hz, H1'), 6.09ꢀ6.13
m, 2H, 2×H ), 6.14ꢀ6.19 (m, 2H, 2×H ), 6.62ꢀ6.66 (m, 2H, 2×H ),
.10ꢀ7.22 (m, 3H, HAr), 7.26ꢀ7.32 (m, 2H, HAr), 7.78 (brs, 2H,
3
): δ 2.28 (q, 2H, J = 7.5 Hz, H2'),
2
(
3
4
5
7
2
13
1 3
×H ); CꢀNMR (100 MHz, CDCl ): δ 33.42, 35.88, 36.79, 105.57
(
1
2C), 107.94 (2C), 117.16 (2C), 125.81, 128.31 (2C), 128.46 (2C),
33.11 (2C), 141.78; HRMS (ESI) m/z C17H N [M+H] calcd
18 2
+
251.1548, found 251.1545.
meso-(Butyl)dipyrromethane (8o). 40% yield (0.0810 g) as a
o
pale orange solid; m.p. 58 C; R
f
= 0.61 (20% EtOAc/nꢀhexane); IR
(
Neat): 3377, 2956, 2931, 2860, 1559, 1467, 1087, 1026, 721, 565
4
9, 2236ꢀ2239; (j) D. Gust, T. A. Moore, A. L. Moore, Acc.
ꢀ
1 1
cm ; HꢀNMR (400 MHz, CDCl
.23ꢀ1.40 (m, 4H, H3', H4'), 1.94 (q, 2H, J = 7.5 Hz, H2'), 3.95 (t, 1H,
J = 7.5 Hz, H1'), 6.06ꢀ6.10 (m, 2H, 2×H ), 6.14ꢀ6.17 (m, 2H, 2×H ),
); CꢀNMR (100 MHz,
): δ 14.00, 22.54, 29.72, 34.14, 37.51, 105.42 (2C), 107.87
3
): δ 0.89 (t, 3H, J = 7.0 Hz, H5'),
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R. Diers, C. Kirmaier, D. F. Bocian, J. S. Lindsey, D. Holten, J.
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3
4
13
6
5 1
.59ꢀ6.62 (m, 2H, 2×H ), 7.68 (brs, 2H, 2×H
CDCl
3
+
18 2
(2C), 117.03 (2C), 133.66 (2C); HRMS (ESI) C13H N [M+Na]
calcd 225.1368, found 225.1365.
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C5OB01953B
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