734
D. Sánchez-García, S. Borrós, S. Nonell, J. I. Borrell, C. Colominas, J. Teixidó
Vol. 39
On the other hand, treatment of 2a and 2b with 4 equivalents
of NBS at reflux in CH CN and CCl , respectively, yielded the
corresponding tetrabromo substituted biimidazoles 4a and 4b
in 46% and 51% yield. Due to the ALP (Adjacent Lone Pair)
effect [15] that presents the C4 position of each imidazole ring,
the 4,4'-dibromo substituted biimidazole 5a was obtained in
water, dried (MgSO ) and concentrated in vacuo. The resulting
solid was digested in hexane/acetone to yield 3.8g (12.1 mmol,
4
3
4
8
1%) of 2a as a white solid: mp 147-148 °C (EtOH); ir (film):
-1 1
3
109, 3029, 2992, 1605, 1495, 1438, 1283, 726 cm ; H nmr
(deuteriochloroform): δ 7.24 (m, 3H, ArH), 7.13-7.12 (m, 1H,
H4), 7.05-7.01 (m, 2H, ArH), 6.93-6.92 (m, 1H, H5), 5.70 (s, 2H,
1
3
CH2); C nmr (deuteriochloroform) δ:138.3, 137.3, 128.6 128.4,
27.6, 127.5, 121.4, 50.8; ms: (70eV, electron impact) m/z
78% yield when 4a was treated with BuLi at -78 °C followed
1
by quenching with isopropanol [15]. Similarly, the SEM pro-
tected 4,4'-dibromobiimidazole 5b (98%) was obtained upon
treatment of 4b in the same reaction conditions. The structural
assignments of 3a, 5a, and 5b were carried out on the basis of
NOE and NOESY experiments. Thus, irradiating the N-CH2
protons of 5a and 5b there was an enhancement in the intensity
of H5-H5' signals of 7.5% and 6.1% respectively.
314(100), 237(22), 223(64), 91(33).
Anal. Calcd for C20H18 N : C, 76.41; H, 5.77; N, 17.82.
4
Found: C, 76.39; H, 5.75; N, 17.82.
1,1'-Dibenzyl-5,5'-dibromo-2,2'-biimidazole (3a).
NBS (1.4 g, 7.9 mmol) were added portionwise to a solution of
1
g (3.2 mmol) of the benzyl protected biimidazole 2a in 200 mL
of CH CN cooled to 0 °C. The mixture was stirred for 30 minutes
3
at 0 °C, concentrated in vacuo and the residue obtained was dis-
solved in CH Cl . The resulting solution was washed with water
2
2
(
4 x 25 mL), dried (MgSO ) and concentrated in vacuo to afford
4
0.8 g (1.7 mmol, 53%) of 3a as a white solid: mp 171-172 °C
(
9
3
EtOH); ir (potassium bromide): 3031, 1487, 1454, 1389, 1262,
13, 727 cm ; H nmr (deuteriochloroform): δ 7.17-7.16 (m,
-1 1
H, ArH), 7.12 (s, 1H, H4), 6.88-6.85 (m, 2H, ArH), 5.80 (s, 1H,
Figure 2. NOE Irradiations.
13
CH2); C nmr (deuteriochloroform): δ 138.7, 136.3, 129.1,
1
4
28.6, 127.4, 126.8, 106.4, 48.9; ms: (70eV, electron impact) m/z
72 (85), 391(17), 381(55), 91(100).
The results obtained, which are in agreement with those
described in the literature for imidazoles, open the door to
the symmetrical functionalization of the biimidazole ring
either in positions C4-C4' or C5-C5'[16]. Moreover, the
fact of having two different protecting groups in the case
of structure 5 should allow the use of a wide range of reac-
tion conditions for such functionalization.
In conclusion, we have developed a synthetic method
that allows obtaining all the possible symmetrically substi-
tuted dibromo 2,2'-biimidazoles in a straightforward man-
ner from a common precursor. The uses of these symmetri-
cally halogenated protected 2,2'-biimidazoles as starting
materials for the synthesis of macrocyclic compounds will
be object of a series of forthcoming papers.
Anal. Calcd for C20H16N Br : C, 50.87; H, 3.41; N, 11.86.
4
2
Found: C, 50.83; H, 3.05; N, 11.60.
1,1'-Dibenzyl-4,4',5,5'-tetrabromo-2,2'-biimidazole (4a).
The procedure was the same as stated above for 3a but using
6.1 g (19.4 mmol) of 2a and 16.9 g (94 mmol) of NBS in 800
mL of CH3CN cooled at 0 °C. The mixture was stirred for 30
minutes at 0 °C and then was heated at reflux until complete
conversion (tlc analysis, circa 2 hours). The yield was 5.6 g
(
°
8.9 mmol, 46%) of 4a as a slightly yellow solid: mp 204-205
C (EtOH); ir (film): 2985, 1484, 1435, 1370, 1240, 979, 721
-
1 1
cm ; H nmr (deuteriochloroform): δ 7.21-6.87 (m, 5H, Ph),
5
1
13
.79 (s, 2H, CH2); C nmr (deuteriochloroform): δ 137.3,
35.5, 128.7, 127.6, 126.9, 116.9, 107.6, 50.5; ms: (70eV, elec-
tron impact) m/z 630(10), 539(4), 91(100).
Anal. Calcd for C20H14N Br : C, 38.13; H, 2.24; N, 8.89.
Found: C, 38.27; H, 1.82; N, 8.63.
4
4
EXPERIMENTAL
2
,2'-Biimidazole (1).
1,1'-Bis(trimethylsilylethoxymethyl)-4,4',5,5'-tetrabromo-2,2'-
biimidazole (4b).
Ammonia was bubbled into 300mL of 20% aqueous glyoxal.
The temperature was maintained at 30-40 °C. After 10 hours, the
dark suspension is filtered and the solid was dissolved in 10%
hydrochloric acid, the solution was refluxed for 15 minutes with
Darco. The yellow solution is carefully neutralised with saturated
potassium carbonate to yield 8.7g (64.9 mmol, 15%) of 1 as a
white solid, ir (potassium bromide): 3174, 3074, 3002, 2897,
The procedure was the same as stated above for 4a but using
1 g (2.5 mmol) of 2b in 30 mL of CCl4. The yield was 0.91 g (1.3
mmol, 51%) of 4b as colourless oil which crystallizes on stand-
ing: ir (potassium bromide) 2953, 2925, 1486, 1375, 1249, 1103,
-1 1
836 cm ; H nmr (deuteriochloroform): δ 5.93 (s, 2H, NCH2),
3.60-3.54 (t, J=9 Hz, 2H,CH2), 0.93-0.87 (t, J=9 Hz, 2H, CH2),
-1
1
-0.04 (s, 9H, CH ); 13C nmr (deuteriochloroform): δ 137.5,
2
806, 1545, 1480, 1405, 1104, 939, 884, 747, 689 cm ; H nmr
3
(
DMSO-d ): δ 7.06 (s, Ar-H).
117.4, 107.8, 75.0, 66.7, 17.8, -1.5; ms: (70eV, electron impact)
m/z 710(17), 609(28), 579(100), 577(70).
6
1
,1'-Dibenzyl-2,2'-biimidazole (2a).
Anal. Calcd for C18H30N O Br Si : C, 30.44; H, 4.26; N,
4
2
4
2
Benzyl chloride (3.8 g, 30.0 mmol) were added to a solution of
g (14.9 mmol) of 2,2'-biimidazole in 6 mL of 12.5 M NaOH and
mL of DMSO. The mixture is refluxed for 30 minutes, cooled,
7.89. Found: C, 30.53; H, 4.52; N, 7.57.
2
5
1,1'-Dibenzyl-4,4'-dibromo-2,2'-biimidazole (5a).
and diluted with water. The resulting solution was extracted with
CH Cl , and the combined organic extracts were washed with
A 1.6 M solution of BuLi (13 mL, 20 mmol) in hexane were
added dropwise to a solution of 5.6 g (8.9 mmol) of the tetra-
2
2