2918
T. Dohi et al.
PRACTICAL SYNTHETIC PROCEDURES
lytical data of all new compounds are listed; some of the bipyrrole
products are already known.9
above. These compounds were separable by purification on neutral
silica gel (n-hexane–EtOAc). Typically, the H-T dimers 4 were ob-
tained in the more polar fractions.
In general, the melting points were measured using a Büchi B 545
apparatus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded at 300 MHz using a JEOL JMN-300 spectrometer in
CDCl3 at 25 °C with TMS as the internal standard. IR spectra were
obtained using a Hitachi 270-50 spectrophotometer. MS spectra
were obtained using a Shimadzu GCMS-QP 5000 instrument with
ionization voltages of 70 eV. HRMS were performed by the Ele-
mental Analysis Section of Osaka University. Column chromatog-
raphy and TLC were carried out on Merck Silica gel 60 (230–400
mesh) and Merck Silica gel F254 plates (0.25 mm), respectively. The
spots and bands were detected by UV irradiation (254, 365 nm).
3,4¢-Dimethyl-1H,1¢H-2,2¢-bipyrrole (4a)
Light yellow oil; Rf = 0.31 (hexane–EtOAc, 4:1).
IR (KBr): 3377 (m), 3096 (w), 2924 (m), 2866 (m), 1562 (m), 1504
(m), 1435 (m), 1381 (m), 1261 (m), 1207 (w), 1173 (m), 1097 (s),
1063 (m), 1030 (m), 972 (m), 912 (s), 889 (s), 793 (s), 741 (s), 689
(m) cm–1.
1H NMR (300 MHz, CDCl3): d = 2.14 (s, 3 H), 2.20 (s, 3 H), 6.00–
6.04 (m, 1 H), 6.07 (t, J = 2.4 Hz, 1 H), 6.49–6.53 (m, 1 H), 6.59 (t,
J = 2.4 Hz, 1 H), 7.93 (br s, 2 H).
PIFA was prepared from commercially available phenyliodine(III)
diacetate (PIDA) and TFA.14 The pyrroles 1b, 1ba, 1bb, 1bc, 1be,
1bf, 1bg, and 3b, TMSBr and abs CH2Cl2 are commercially avail-
able and used as received. The other 1H-pyrroles were prepared ac-
cording to a previous report.15 All reaction were usually finished
within 1 h unless otherwise noted in the text.
13C NMR (300 MHz, CDCl3): d = 11.8, 12.0, 106.7, 111.3, 114.5,
115.4, 116.5, 119.6, 122.1, 125.6.
MS (EI, 70 eV): m/z = 160 (M+).
3,3¢-Dimethyl-1H,1¢H-2,2¢-bipyrrole (5a)
Light yellow oil; Rf = 0.35 (hexane–EtOAc 4:1).
1H NMR (300 MHz, CD2Cl2): d = 2.16 (s, 6 H), 6.14 (t, J = 2.4 Hz,
2 H), 6.72 (t, J = 2.4 Hz, 2 H), 7.95 (br s, 2 H).
MS (EI, 70 eV): m/z = 160 (M+).
Note: 1H,1¢H-2,2¢-Bipyrroles 2 and 4–6 and 2,3¢-bipyrrole 7 are not
air-stable and decompose within 1 month at r.t., thus they should be
stored in a refrigerator under N2.
Procedure 1
3,3¢,4,4¢-Tetraethyl-1H,1¢H-2,2¢-bipyrrole (2a); Typical Proce-
Procedure 2
dure
1,1¢-Dibenzyl-2,3¢-bipyrrole (7bb); Typical Procedure for
Gram-Scale Preparation
In a flame-dried 2-necked round-bottomed flask, under N2, to a
stirred soln of 1H-pyrrole 1a (111 mg, 0.9 mmol) in CH2Cl2 (15
mL) were quickly added PIFA (129 mg, 0.3 mmol) and TMSBr (79
mL, 0.6 mmol) at –78 °C. The mixture was then stirred for 1 h, while
the temperature was maintained below –40 °C. When the reaction
was complete, sat. aq NaHCO3 (ca. 20 mL) was added to the mix-
ture at –40 °C, and the mixture was stirred for an additional 10 min
at r.t. The organic layer was separated, and the aqueous phase was
extracted with CH2Cl2. The combined extract was dried (Na2SO4)
and evaporated to dryness. The residue was purified by column
chromatography (neutral silica gel, hexane–EtOAc) to give pure
2,2¢-bipyrrole 2a (56 mg, 75%) as a white powder; mp 90–92 °C;
Rf = 0.35 (hexane–EtOAc, 4:1). The less polar fractions included
unreacted 1a in a pure form (31 mg).
To a dry, N2-purged, 2-necked round-bottomed flask was added
1bb (1.55 g, 10 mmol) and CH2Cl2 (50 mL). The soln was cooled to
–78 °C with stirring and then PIFA (2.15 g, 5 mmol) and TMSBr
(1.32 mL, 10 mmol) were rapidly added; the mixture was then
stirred for 3 h. TLC analysis of the mixture indicated that all the
starting pyrrole had been consumed. Sat. aq NaHCO3 was added to
the mixture, which was then stirred at r.t. for an additional 10 min.
The organic layer was separated, and then dried (anhyd Na2SO4).
After evaporation, the residue was purified by column chromatog-
raphy (silica gel, n-hexane–EtOAc) to give the 2,3¢-bipyrrole 7bb
(1.31 g, 85%) as a colorless oil.
IR (KBr): 3063 (w), 3028 (m), 2922 (mw), 1604 (w), 1497 (s), 1452
(s), 1358 (s), 1338 (s), 1283 (m), 1155 (m), 1078 (m), 918 (m), 707
(s), 671 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 4.98 (s, 2 H), 5.18 (s, 2 H), 6.14
(dd, J = 3.0, 2.1 Hz, 1 H), 6.18–6.21 (m, 2 H), 6.55 (t, J = 2.1 Hz, 1
H), 6.60 (t, J = 3.0 Hz, 1 H), 6.67 (dd, J = 3.0, 2.1 Hz, 1 H), 6.98–
7.07 (m, 4 H), 7.21–7.31 (m, 6 H).
13C NMR (300 MHz, CDCl3): d = 50.6, 53.4, 106.9, 107.9, 109.1,
116.2, 119.4, 121.2, 121.4, 126.2, 126.9, 127.6, 128.5, 128.6, 129.7,
137.7, 139.2.
IR (KBr): 3373 (m), 2963 (s), 2867 (m), 1553 (w), 1435 (m), 1371
(m), 1327 (w), 1259 (w), 1190 (w), 1086 (m), 1063 (m), 1038 (m),
947 (m), 912 (s), 742 (s), 650 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.05 (t, J = 7.8 Hz, 6 H), 1.25 (t,
J = 7.8 Hz, 6 H), 2.42 (q, J = 7.8 Hz, 4 H), 2.52 (q, J = 7.8 Hz, 4 H),
6.53 (br s, 2 H), 7.58 (br s, 2 H).
13C NMR (300 MHz, CDCl3): d = 14.3, 16.0, 17.9, 18.6, 113.8,
121.1, 122.9, 125.2.
MS (EI, 70 eV): m/z = 244 (M+).
HRMS (FAB): m/z [M + Na]+ calcd for C22H20N2Na: 335.1532;
found: 335.1528.
1H,1¢H-2,2¢-Bipyrrole (2b)
White powder; mp 187–189 °C; Rf = 0.32 (hexane–EtOAc, 4:1).
Acknowledgment
IR (KBr): 3366 (m), 3123 (w), 3103 (w), 1574 (w), 1518 (w), 1454
(w), 1425 (w), 1404 (w), 1261 (w), 1097 (m), 1032 (m), 912 (s), 891
(w), 775 (m), 743 (s), 658 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 6.05–6.19 (m, 4 H), 6.70–6.72 (m,
2 H), 8.23 (br s, 2 H).
13C NMR (300 MHz, CDCl3): d = 103.5, 109.4, 117.6, 125.9.
MS (ES, 70 eV): m/z = 132 (M+).
This work was supported by a Grant-in-Aid for Scientific Research
(A) and for Encouragement of Young Scientists, and by a Grant-in-
Aid for Scientific Research on Priority Area ‘Advanced Molecular
Transformations of Carbon Resources’ from the Ministry of Educa-
tion Culture, Sports, Science, and Technology, Japan. T.D. also
thanks the Industrial Technology Research Grant Program from the
New Energy and Industrial Technology Development Organization
(NEDO) of Japan.
Bipyrroles 4 and 5
The bipyrrole products of the 3-substituted pyrroles were formed as
a mixture of two regioisomers 4 and 5 using the procedure described
Synthesis 2007, No. 18, 2913–2919 © Thieme Stuttgart · New York