Synthesis and chemistry of 4,5-dimagnesioimidazole dianions

Article abstract of DOI:10.1021/jo0161680

An experimentally convenient procedure for the generation of 4,5-dimagnesioimidazoles is described. N-Protected 2-substituted 4,5-diiodoimidazoles were treated with i-PrMgC1 (2.4 equiv) in THF at 0-5 °C. The resulting vicinal dianions reacted with electro

Full text of DOI:10.1021/jo0161680

J . Org. Chem. 2002, 67, 2699-2701
2699
The starting materials 1-6 for the current work were
synthesized by adapting standard methodology as fol-
lows. Commercially available 2-phenyl- and 2-methylimi-
dazole were diiodinated with I2/KI/NaOH,11 and the
resulting 4,5-diiodides were deprotonated with NaH in
DMF11 and treated with MeI or EtOCH2Cl to give
compounds 1, 4, and 6. Triiodoimidazole12 was similarly
N-protected to give 1-methyl- and 1-ethoxymethyl-2,4,5-
triiodoimidazole. A regioselective palladium-catalyzed
coupling of 1-methyltriiodoimidazole with 4-chlorophenyl-
boronic acid13 then yielded the 2-aryl-4,5-diiodide 2.
Finally, treatment of the two N-protected triiodoimida-
zoles with n-Buli to effect metal halogen exchange at the
2-position,3 followed by addition of either dimethyl dis-
ulfide or hexachloroethane, afforded diiodides 3 and 5.
Syn th esis a n d Ch em istr y of
4,5-Dim a gn esioim id a zole Dia n ion s
Ralf H.-J . Butz and Stephen D. Lindell*
Aventis CropScience GmbH, Werk Ho¨chst, G 836,
D-65926 Frankfurt am Main, Germany
stephen.lindell@aventis.com
Received October 2, 2001
Abstr a ct: An experimentally convenient procedure for the
generation of 4,5-dimagnesioimidazoles is described. N-
Protected 2-substituted 4,5-diiodoimidazoles were treated
with i-PrMgCl (2.4 equiv) in THF at 0-5 °C. The resulting
vicinal dianions reacted with electrophiles to give 4,5-
disubstituted imidazoles in 27-71% yields.
The generation of imidazolyl carbanions, either by
metal-halogen exchange or by direct metalation, fol-
lowed by their reaction with electrophiles provides a
powerful method for the synthesis of functionalized
imidazoles.1 For example, fungicidally active cyanoimi-
dazoles,2 the antitumor agent carmethizole,3 the R2-
adrenergic agonist medetomidine,4 and the histamine H3
antagonist thioperamide5 have all been efficiently pre-
pared using imidazolyl anion chemistry. Most synthetic
examples have utilized imidazolyl monoanions, but di-
anions are also known. Thus, the synthesis and reactions
of 1,2-,6 1,4-,5,7 2,4-,8 and 2,5-dilithioimidazoles8-10 have
been reported. The preparation of a 2,4,5-trilithioimida-
zole has also been described.10 In this paper, as part of
our continuing interest in imidazolyl anion chemistry,11
we describe a facile procedure for the synthesis of 4,5-
dimagnesioimdiazoles by treatment of 4,5-diiodoimida-
zoles with i-PrMgCl (2.4 equiv) in THF at 0-5 °C. To
the best of our knowledge, such vicinal 4,5-dianions of
imidazole have not been previously described.
Treatment of the 4,5-diiodoimidazoles 1-6 with i-
PrMgCl (2.4 equiv) in dry THF at 0-5 °C led to formation
of the 4,5-dimagnesio species, which reacted with elec-
trophiles to give products 7-14 in 27-71% yield as
summarized in Table 1.14 The yield of dianion-derived
product isolated at the end of the reaction was dependent
upon the nature of the imidazole 2-substituent and on
the quenching electrophile. The best results were ob-
tained when the imidazole 2-position was blocked by a
stable nonreactive moiety and when reactive electrophiles
were employed. Accordingly, when the dianions gener-
ated from the 2-arylimidazoles 1, 2, and 4 were quenched
with benzaldehyde or water, products 7, 9, 10, and 12
were isolated in good yields (59-71%; Table 1, entries 1,
3, 4, and 6). In contrast, the imidazoles 5 and 6, which
contain the more reactive 2-chloro and 2-methyl substit-
uents, gave lower yields of the bis-carbinols 13 and 14
with benzaldehyde (43 and 27%, respectively; Table 1,
entries 7 and 8). In the latter case, the 5-monoanion-
derived product 15 was also isolated in 22% yield. Under
similar conditions, the analogous 2-unsubstituted imi-
dazole, 1-ethoxymethyl-4,5-diiodoimidazole, also yielded
a monoanion derived product 16 (40% yield) but in this
case no dianion derived product was isolated.
* To whom correspondence should be addressed. Fax: +49 (0)69
305 17768.
(1) Iddon, B.; Ngochindo, R. I. Heterocycles 1994, 38, 2487.
(2) Baker, G. P.; Bourne, I. I.; Ford, M. J .; Foster, R. W. G.; J ackson,
T. H.; Pannell, R. W.; Whitemore, M. W. Org. Process Res. Dev. 1999,
3, 104.
(3) Lipshutz, B. H.; Hagen, W. Tetrahedron Lett. 1992, 33, 5865.
(4) Kudzma, L. V.; Turnbull, S. P., J r. Synthesis 1991, 1021.
(5) Lange, J . H. M.; Wals, H. C.; van den Hoogenband, A.; van de
Kuilen, A.; en Hartog, J . A. J . Tetrahedron 1995, 51, 13447.
(6) Dirlam, U. P.; J ames, R. B.; Shoop, E. V. J . Org. Chem. 1982,
47, 2196. Iddon, B.; Khan, N. J . Chem. Soc., Perkin Trans. 1 1987,
1445.
(7) Katritzky, A. R.; Slawinski; J . J .; Brunner, F.; Gorun, S. J . Chem.
Soc., Perkin Trans. 1 1989, 1139.
(8) Effenberger, F.; Roos, M.; Ahmad, R.; Krebs, A. Chem. Ber. 1991,
124, 1639. These authors also report results consistent with the
formation of an imidazole 2,4,5-trianion. However, the quenching
electrophile (TMSCl) was present from the start so that sequential
monoanion formation and quenching cannot be ruled out.
(9) Carpenter, A. J .; Chadwick, D. J .; Ngochindo, R. I. J . Chem. Res.,
Synop. 1983, 196. Chadwick, D. J .; Ngochindo, R. I. J . Chem. Soc.,
Perkin Trans. 1 1984, 481. Ngochindo, R. I. J . Chem. Res., Synop. 1990,
58. Shapiro, G.; Marzi, M. Tetrahedron Lett. 1993, 34, 3401. Iddon,
B.; Petersen, A. K.; Becher, J .; Christensen, N. J ., J . Chem. Soc., Perkin
Trans. 1 1995, 1475.
(10) Iddon, B.; Khan, N. J . Chem. Soc., Perkin Trans. 1 1987, 1453.
(11) Turner, R. M.; Lindell, S. D.; Ley, S. V. J . Org. Chem. 1991,
56, 5739. Turner, R. M.; Ley, S. V.; Lindell, S. D. Synlett 1993, 748.
Carver, D. S.; Lindell, S. D.; Saville-Stones E. A. Tetrahedron 1997,
53, 14481.
(12) Brunings, K. J . J . Am. Chem. Soc. 1947, 69, 205.
(13) Kaswasaki, I.; Yamashita, M.; Ohta, S. J . Chem. Soc., Chem.
Commun. 1994, 2085; Chem. Pharm. Bull. 1996, 44, 1831.
(14) The reaction also proceeds but in much lower yield with
EtMgBr. For example, treatment of the diodide 2 with EtMgBr (2.4
equiv) followed by addition of benzaldehyde gave the 4,5-disubstituted
product 9 (12% yield) together with the monocarbinol 20 (47% yield).
The carbinol 20 was the only product isolated when PhMgBr (2.4 equiv)
or t-BuMgCl (2.4 equiv) was employed (>85% yield). Similarly,
treatment of 4,5-dibromoimidazoles with i-PrMgCl (2.4 equiv) gave only
5-monoanion-derived products (>80% yield). Treatment of 4,5-di-
iodoimidazoles with a single equivalent of i-PrMgCl or EtMgBr gives
exclusively 5-monoanion-derived products (38-90%).11
10.1021/jo0161680 CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/19/2002

2700 J . Org. Chem., Vol. 67, No. 8, 2002
Ta ble 1. Rea ction of 4,5-Dim a gn esioim id a zoles w ith Electr op h iles
Notes
starting
material
isolated
yield (%)
entry no.
product
R1
R2
R3
electrophile
PhCHO
1
2
1
1
7
8
Me
Me
Ph
Ph
CH(OH)Ph
CHO
71a
30
3
4
5
2
2
3
9
10
11
Me
Me
Me
4-ClC6H4
4-ClC6H4
SMe
CH(OH)Ph
H
CHO
PhCHO
H2O
64a
61
37
6
7
8
4
5
6
12
13
14
CH2OEt
CH2OEt
CH2OEt
Ph
Cl
Me
CH(OH)Ph
CH(OH)Ph
CH(OH)Ph
PhCHO
PhCHO
PhCHO
59a
43a
27a,b
a
b
Ca. 10:9 mixture of diastereoisomers. Product 15 was also isolated (22%).
When N-methyl-N-(2-pyridyl)formamide was utilized
as the quenching electrophile, the 4,5-dicarboxaldehyde
products 8 and 11 were isolated in 30 and 37% yield,
respectively (Table 1, entries 2 and 5). Although these
yields are quite modest, the current methodology offers
a very direct route for synthesizing these useful inter-
mediates, which have been used to synthesize a variety
of fused ring systems.15 In addition, the 2-methylmer-
capto compound 11 is a precursor used in the synthesis
of the antitumor agent carmethizole.3
ing diiodo or dibromo heterocycles with n-Buli (2.0-2.5
equiv) at -95 to -50 °C.16 In several cases, however,
larger excesses of t-Buli (5-10 equiv) have been neces-
sary to achieve dianion formation.17 In our case, treat-
ment of the diiodomidazole 2 with n-Buli (2 equiv) at -78
°C followed by addition of benzaldehyde did not yield any
dianion-derived products. Instead, the iodo compound 20,
arising from 5-monoanion formation, was isolated in 76%
yield. A reaction performed with t-Buli (4.4 equiv) at -78
°C, followed by addition of benzaldehyde at ambient
temperature, did yield the desired 4,5-disubstituted
product 9 but only in 15% yield (5:3 ratio of diastereoi-
somers). These conditions were experimentally less con-
venient than those using i-PrMgCl, so this result was not
pursued further. However, it is interesting to note that
4,5-dimagnesioimidazoles appear to be more readily
formed than the corresponding dilithio compounds. A
possible explanation is that destabilizing electrostatic
interactions in the transition state leading from the
presumed 5-monomagnesio intermediate to the vicinal
diamagnesio compound are reduced (in comparison to the
dilithio species) due to the greater covalency of the C-Mg
bond.
The bis-carbinols 7, 9, 12, 13, and 14 were all formed
as ca. 10:9 mixtures of diastereoisomers (Table 1) indi-
cating that the reaction between the dimagnesioanions
and benzaldehyde was not diastereoselective. The ques-
tion remained, however, as to whether the 4- and
5-anions might react with electrophiles at different rates
in a regioselective manner. To answer this question,
benzaldehyde (1.0 equiv) was added to a solution of the
dianion derived from diiodide 1 at -78 °C. The reaction
was then allowed to warm to ambient temperature and
fully quenched with water to give products 7 (34%; 10:9
ratio of diastereoisomers), 17 (24%), 18 (10%), and 19
(17%). The regiochemistry of products 17 and 18 was
established by measuring 1H NMR NOE effects. Irradia-
In summary, a general method has been developed for
preparing 4,5-dimagnesioimidazoles by treating N-pro-
tected-2-substituted-4,5-diiodoimidazoles with i-PrMgCl
(2.4 equiv) in THF for 1 h at 0-5 °C. These previously
unknown vicinal dianions reacted with different electro-
philes to yield 4,5-disubstituted imidazoles in 27-71%
yield.
1
tion of the N-Me signal in the H NMR spectra of 17 and
18 resulted in a positive NOE signal for the benzylic
methine of 17 and for the imidazole C(5)H of 18. Overall,
the results do not indicate any synthetically useful
differences in reactivity between the two carbanions.
Exp er im en ta l Section
Melting points are uncorrected. IR spectra were recorded on
the pure substances using a Golden Gate detector. 1H NMR
spectra were recorded in solution at 300 MHz using TMS as
internal reference. Dry column chromatography18 was perfomed
on prepacked “Isolute” silica gel cartridges purchased from IST.
HPLC separations were performed on a LiChrosphor Si 60
column (50 × 250 mm). Experiments involving organometallic
reagents were conducted in oven dried glassware using solvents
dried over 0.4 nm molecular sieves prior to use. Other solvents
and reagents were used as purchased.
Vicinal dilithiated derivatives of other heterocyclic
systems have been prepared by treating the correspond-
(16) Zaluski, M.-C.; Robba, M.; Bonhomme, M. Bull. Soc. Chim. Fr.
1970, 1838. J anda, M.; Srogl, J .; Stibor, I.; Nemec, M.; Vopatrna, P.
Synthesis 1972, 545. Earle, M. J .; Massey, A. G.; Al-Soudani, A.-R.;
Zaidi, T. Polyhedron 1989, 8, 2817. Bevierre, M. O.; Mercier, F.; Ricard,
L.; Mathey, F. Bull. Soc. Chim. Fr. 1992, 129, 1.
(17) Cugnon de Sevricourt, M.; Robba, M. Bull. Soc. Chim. Fr. 1977,
142. Christopfel, W. C.; Miller, L. L. J . Org. Chem. 1986, 51, 4169.
Liu, Y.; Gribble, G. W. Tetrahedron Lett. 2001, 42, 2949.
(15) Schubert, H.; Rudorf, W. D. Z. Chem. 1971, 11, 175. El Borai,
M.; Hassanein, M. Org. Prep. Proced. Int. 1982, 14, 409. El Borai, M.;
Hassan, M. A.; Mohamed, M. M. Egypt. J . Chem. 1985, 28, 139. Bovy,
P. R.; O’Neal, J .; Collings, J . T.; Olins, G. M.; Corpus, V. M.; Burrows,
S. D.; McMahon, E. G.; Palomo, M.; Koehler, K. Med. Chem. Res. 1991,
1, 86.
(18) Harwood, L. M. Aldrichim. Acta 1985, 18, 25.

Notes
4,5-Bis(r-h ydr oxyben zyl)-1-m eth yl-2-ph en ylim idazole (7).
J . Org. Chem., Vol. 67, No. 8, 2002 2701
1422 (w), 1262 (s), 749 (s) cm-1; 1H NMR (CDCl3) δ 2.77 (s. 3H),
3.87 (s, 3H), 10.06 (s, 1H), 10.28 (s, 1H); MS (EI) m/z 184 (M+,
35), 156 (74), 141 (29), 109 (100), 83 (87). Anal. Calcd for C7H8N2-
SO2: C, 45.64; H, 4.38; N, 15.21. Found: C, 46.00; H, 4.48; N,
15.05.
A 2 M solution of i-PrMgCl in THF (1.46 mL, 2.92 mmol) was
instilled into a cooled (0-5 °C; ice/water) solution of the diiodide
1 (500 mg, 1.22 mmol) in dry THF (20 mL) under an argon
atmosphere over a period of ca. 10 min. The resulting solution
was allowed to warm to rt and stirred for 1 h, and then neat
benzaldehyde (0.30 mL, 2.95 mmol) was slowly added at such a
rate that the internal temperature did not exceed 30 °C. After
being stirred for a further 2 h, saturated aqueous NH4Cl solution
(0.3 mL) was added, and the mixture was diluted with CH2Cl2
(100 mL), dried over MgSO4, and evaporated in vacuo at 40 °C.
HPLC chromatography (4:1 EtOAc/heptane) yielded the two
diastereoisomers of the title compound 7:
1-Eth oxym eth yl-4,5-bis(r-h yd r oxyben zyl)-2-p h en ylim i-
d a zole (12). Diastereoisomer A (144 mg from 500 mg of diiodide
4, 0.35 mmol, 31%): mp 80-83 °C; IR νmax 3650 (w), 3061 (w),
2976 (w), 1602 (w), 1492 (m), 1449 (m), 1378 (m), 1023 (m), 696
(s) cm-1; H NMR (CDCl3) δ 1.08 (t, J ) 8 Hz, 3H), 3.16-3.33
1
(m, 2H), 4.79 (d, J ) 8 Hz, 1H), 5.05 (d, J ) 8 Hz, 1H), 5.85 (s,
1H), 6.08 (s, 1H), 7.16-7.63 (m, 15H); MS (EI) m/z 414 (M+, 4),
396 (17), 337 (55), 105 (72), 77 (100). Anal. Calcd for C26H26N2O3‚
0.5H2O: C, 73.74; H, 6.43; N, 6.61. Found: C, 73.91; H, 6.57; N,
6.47.
Diastereoisomer A (154 mg, 0.42 mmol, 34%); mp 142-145
°C dec; IR νmax 3400 (w), 3026 (w), 1602 (w), 1473 (m), 1449 (m),
1394 (m), 1024 (m), 696 (s) cm-1
;
1H NMR (CDCl3) δ 2.3-3.4
Diastereoisomer B (130 mg from 500 mg of diiodide 4, 0.31
mmol, 28%): mp 70-73 °C; IR νmax 3650 (w), 3061 (w), 2976
(w), 1602 (w), 1492 (m), 1449 (m), 1378 (m), 1023 (m), 696 (s)
(bs, 2H, exch. with D2O), 3.32 (s, 3H), 5.85 (s, 1H), 6.07 (s, 1H),
7.13-7.53 (m, 15H); MS (EI) m/z 370 (M+, 4), 352 (76), 275 (50),
247 (22), 77 (100). Anal. Calcd for C24H22N2O2‚1.0H2O: C, 74.21;
H, 6.23; N, 7.21. Found: C, 74.10; H, 6.33; N, 7.18.
cm-1; H NMR (CDCl3) δ 1.07 (t, J ) 8 Hz, 3H), 3.16-3.27 (m,
1
2H), 4.75 (d, J ) 8 Hz, 1H), 5.00 (d, J ) 8 Hz, 1H), 5.99 (s, 1H),
6.15 (s, 1H), 7.20-7.59 (m, 15H); MS (EI) m/z 414 (M+, 2), 396
(13), 337 (28), 105 (63), 77 (100). Anal. Calcd for C26H26N2O3‚
0.2H2O: C, 74.69; H, 6.36; N, 6.70. Found: C, 74.72; H, 6.49; N,
6.69.
Diastereoisomer B (168 mg, 0.45 mmol, 37%): mp 142-145
°C dec; IR νmax 3600 (w), 3030 (w), 1601 (w), 1471 (m), 1450 (m),
1396 (m), 1023 (m), 696 (s) cm-1 1H NMR (CDCl3) δ 3.28 (s,
;
3H), 5.99 (s, 1H), 6.06 (s, 1H), 7.13-7.51 (m, 15H); MS (EI) m/z
370 (M+, 4), 352 (37), 275 (27), 247 (19), 77 (100). Anal. Calcd
for C24H22N2O2‚1.5H2O: C, 72.52; H, 6.34; N, 7.05. Found: C,
72.31; H, 6.05; N, 6.95.
2-Ch lor o-1-eth oxym eth yl-4,5-bis(r-h yd r oxyben zyl)im i-
d a zole (13). Diastereoisomer A (79 mg from 400 mg of diiodide
5, 0.27 mmol, 22%): IR νmax 3350 (w), 3031 (w), 2980 (w), 1602
(w), 1491 (m), 1472 (m), 1174 (m), 1105 (s), 696 (s) cm-1; 1H NMR
(CDCl3) δ 1.12 (t, J ) 8 Hz, 3H), 3.43 (m, 3H, 1H exch. with
D2O), 4.00 (bs, 1H, exch. with D2O), 4.83 (d, J ) 12 Hz, 1H),
5.08 (d, J ) 12 Hz, 1H), 5.79 (s, 1H), 6.08 (s, 1H), 7.16-7.44 (m,
10H); MS (CI) m/z 373 (M+ + H, 100), 355 (23). Anal. Calcd for
C20H21N2O3Cl‚2.0H2O: C, 58.75; H, 6.16; N, 6.85. Found: C,
58.64; H, 5.86; N, 6.64.
All other dianion reactions were performed using essentially
identical conditions (2.4 equiv of both i-PrMgCl and quenching
agent, etc.) with the following exceptions. After addition of the
electrophile N-methyl-N-(2-pyridyl)formamide, the reaction mix-
tures were stirred for 3.5 h before addition of aqueous NH4Cl.
Dry column chromatography18 was used to purify the dicarbox-
aldehydes 8 and 11 (1:4 EtOAc/heptane) and product 10 (4:1
EtOAc/heptane).
1-Met h yl-2-p h en ylim id a zole-4,5-d ica r b oxa ld eh yd e (8)
(157 mg from 1.0 g of diiodide 1, 0.73 mmol, 30%): IR υmax 3056
(w), 2960 (w), 1695 (m), 1668 (m), 1470 (m), 1299 (m), 749 (s)
cm-1; 1H NMR (CDCl3) δ 4.02 (s, 3H), 7.53-7.70 (m, 4H), 10.15
(s, 1H), 10.48 (s, 1H); MS (EI) m/z 214 (M+, 12), 186 (58), 116
(33), 83 (100). Anal. Calcd for C12H10N2O2‚0.1H2O: C, 66.72; H,
4.76; N, 12.97. Found: C, 66.78; H, 4.79; N, 12.76.
Diastereoisomer B (73 mg from 400 mg of diiodide 5, 0.24
mmol, 21%): IR νmax 3350 (w), 3040 (w), 2980 (w), 1602 (w), 1493
(m), 1473 (m), 1174 (m), 1105 (s), 696 (s) cm-1; 1H NMR (CDCl3)
δ 1.13 (t, J ) 8 Hz, 3H), 3.28 (bs, 1H), 3.41 (m, 2H), 4.03 (bs,
1H), 4.80 (d, J ) 12 Hz, 1H), 5.05 (d, J ) 12 Hz, 1H), 5.88 (s,
1H), 6.13 (s, 1H), 7.27-7.47 (m, 10H); MS (CI) m/z 373 (M+
+
H, 100), 355 (25); HRMS (EI) calcd for C20H21N2O3Cl 372.1241,
found 372.1229.
2-(4′-Ch lor op h en yl)-4,5-b is(r-h yd r oxyb en zyl)-1-m et h -
ylim id a zole (9). Diastereoisomer A (132 mg from 500 mg of
diiodide 2, 0.33 mmol, 29%): mp 147-149 °C dec; IR νmax 3460
1-Eth oxym eth yl-4,5-bis(r-h yd r oxyben zyl)-2-m eth ylim i-
d a zole (14). Diastereoisomer A (64 mg from 500 mg of diiodide
6, 0.18 mmol, 14%): IR νmax 3350 (w), 3060 (w), 2977 (w), 1586
(w), 3030 (w), 1603 (w), 1466 (m), 1092 (m), 722 (s) cm-1
;
1H
(w), 1493 (m), 1449 (m), 1185 (m), 1097 (m), 697 (s) cm-1 1H
;
NMR (CDCl3) δ 3.31 (s, 3H), 3.35-4.0 (bs, 2H, exch. with D2O),
5.83 (s, 1H), 6.07 (s, 1H), 7.11-7.47 (m, 14H); MS (EI) m/z 404
(M+, 7), 386 (92), 309 (61), 105 (45), 77 (100). Anal. Calcd for
NMR (CDCl3) δ 0.99 (t, J ) 8 Hz, 3H), 2.27 (s, 3H), 3.15 (q, J )
8 Hz, 2H), 4.81 (bs, 2H), 4.97 (q, J ) 12 Hz, 2H), 5.99 (s, 1H),
6.20 (s, 1H), 7.17-7.47 (m, 10H); MS (EI) m/z 352 (M+, 2), 334
(10), 288 (20), 275 (13), 77 (77), 59 (100); HRMS (Auto CI) calcd
for C21H24N2O3 353.1865, found 353.1885.
C
24H21N2O2Cl‚1.8H2O: C, 65.92; H, 5.67; N, 6.41. Found: C,
66.00; H, 5.36; N, 6.18.
Diastereoisomer B (158 mg from 500 mg of diiodide 2, 0.395
mmol, 35%): mp 110-115 °C dec; IR νmax 3350 (w), 3060 (w),
Diastereoisomer B (59 mg from 500 mg of diiodide 6, 0.17
mmol, 13%): IR νmax 3350 (w), 3070 (w), 2970 (w), 1601 (w), 1493
(m), 1449 (m), 1185 (m), 1095 (m), 696 (s) cm-1; 1H NMR (CDCl3)
δ 1.04 (t, J ) 8 Hz, 3H), 2.25 (s, 3H), 3.19 (m, 2H), 3.96 (bs, 2H),
4.88 (q, J ) 8 Hz, 2H), 5.88 (s, 1H), 6.09 (s, 1H), 7.16-7.43 (m,
10H); MS (EI) m/z 352 (M+, 11), 334 (13), 288 (75), 275 (100),
77 (83), 59 (73). Anal. Calcd for C21H24N2O3‚2.5 H2O: C, 63.46;
H, 7.35; N, 7.05. Found: C, 63.59; H, 6.92; N, 7.18.
1
1601 (w), 1466 (m), 1092 (m), 697 (s) cm-1; H NMR (CDCl3) δ
2.80-3.40 (bs, 2H, exch. with D2O), 3.27 (s, 3H), 5.97 (s, 1H),
6.08 (s, 1H), 7.07-7.49 (m, 14H); MS (EI) m/z 404 (M+, 7), 386
(75), 309 (47), 105 (57), 77 (100). Anal. Calcd for C24H21N2O2Cl‚
0.5H2O: C, 69.65; H, 5.36; N, 6.77. Found: C, 69,65; H, 5.48; N,
6.92.
(4′-Ch lor op h en yl)-1-m eth ylim id a zole (10) (132 mg from
500 mg of diiodide 2, 0.69 mmol, 61%): IR νmax 3106 (w), 2953
(w), 1602 (w), 1469 (s), 1092 (s), 1010 (s), 725 (s) cm-1; 1H NMR
(CDCl3) δ 3.73 (s, 3H),6,96 (s, 1H), 7.11 (s, 1H), 7.43 (d, J ) 8.8
Hz, 2H), 7.57 (d, J ) 8.8 Hz, 2H); MS (EI) m/z 192 (M+, 87), 191
(100), 157 (11), 156 (32). Anal. Calcd for C10H9N2Cl‚0.4H2O: C,
60.10; H, 4.94; N, 14.02. Found: C, 60.58; H, 5.35; N, 13.52.
1-Meth yl-2-m eth ylm er ca p toim id a zole-4,5-d ica r boxa ld e-
h yd e (11) (260 mg from 1.47 g of diiodide 3, 1.4 mmol, 37%):
mp 100-103 °C; IR νmax 3054 (w), 2987 (w), 1698 (m), 1672 (m),
Ack n ow led gm en t. We wish to thank Professor S.
H. Hu¨ttenhain of the Fachhochschule Darmstadt, for
useful discussions during the course of this work.
Su p p or tin g In for m a tion Ava ila ble: Copies of 300 MHz
1H NMR spectra for compounds 7-14. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0161680