Synthesis of N-cycloalkenylazoles.

Article abstract of DOI:10.1021/jo020336m

N-(1-Cycloalkenyl)pyrroles 3a,b, -pyrazoles 6a,b, and -imidazoles 9a,b were synthesized via elimination of benzotriazole or 5-phenyltetrazole from the corresponding 1-[1-(heterocycyl)cycloalkyl]benzotriazoles 2, 5, and 8 or 1-[1-(heterocycyl)cyclohexyl]-5-phenyltetrazole (12 and 14). Intermediates 2, 5, 8, 12 and 14 were obtained by cyclizations of dihaloalkanes with N-(benzotriazol-1-ylmethyl)heterocycles, 1-imidazol-1-ylmethyl-5-phenyltetrazole (11), or 1-pyrazol-1-ylmethyl-5-phenyltetrazole (13) in the presence of n-BuLi.

Full text of DOI:10.1021/jo020336m

Syn th esis of N-Cycloa lk en yla zoles
Alan R. Katritzky,*,‡ Rexiat Maimait,‡ Yong-J iang Xu,‡ and Young Soo Gyoung§
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200, and Department of Chemistry, Kangnung National University,
Kangnung, Kangwondo 210-702, Korea
katritzky@chem.ufl.edu
Received May 15, 2002
N-(1-Cycloalkenyl)pyrroles 3a ,b, -pyrazoles 6a ,b, and -imidazoles 9a ,b were synthesized via
elimination of benzotriazole or 5-phenyltetrazole from the corresponding 1-[1-(heterocycyl)cycloalkyl]-
benzotriazoles 2, 5, and 8 or 1-[1-(heterocycyl)cyclohexyl]-5-phenyltetrazole (12 and 14). Intermedi-
ates 2, 5, 8, 12 and 14 were obtained by cyclizations of dihaloalkanes with N-(benzotriazol-1-
ylmethyl)heterocycles, 1-imidazol-1-ylmethyl-5-phenyltetrazole (11), or 1-pyrazol-1-ylmethyl-5-
phenyltetrazole (13) in the presence of n-BuLi.
In tr od u ction
Molecules containing N-(1-cycloalkenyl)heterocycles
have potential biological activity; thus, 1-[2-(methylsul-
fanyl)-1-cyclopentenyl]imidazole (I) and 1-[2-(2-thienyl)-
1-cyclopentenyl]imidazole (II) have been reported as
neuronal injury inhibitors1 (Figure 1); however, few
synthetic approaches to compounds of this type have been
reported. No literature was found for N-(1-cycloalkenyl)-
pyrroles 3a ,b. A single paper reported N-(1-cyclopent-1-
enyl)pyrazole (6a ) and N-(1-cyclohex-1-enyl)pyrazole (6b),
which were prepared in 73% and 78% yields, respectively,
from the corresponding 1,1-bispyrazolylcycloalkanes2
(Scheme 1, i). N-(1-Cyclohex-1-enyl)imidazole (9b) was
formed (9% yield) as a byproduct in the preparation of
1,1-bis(imidazol-1-yl)cyclohexane3 (Scheme 1, ii). Com-
pound II was obtained (64%) using 1-(2-bromocyclo-
penten-1-yl)imidazole, (Ph3P)4Pd, and 2-thienylboronic
acid with NaHCO3 in DME/H2O in a German patent1
(Scheme 1, iii), which also describes the synthesis of I.
N-Vinylpyrroles are extensively studied synthetic in-
termediates:4 General routes include (Scheme 2); (i)
cyclization of ketoximes and acetylenes in a strong
base-DMSO system;4 (ii) vinylation of pyrrole in super-
base media;5 (iii) reactions6,7 of potassium pyrrole with
epoxides in dry DMF. 1-Vinylimidazoles were also
made from the potassium imidazole and corresponding
epoxides.7,8 A recent paper reported the synthesis of
F IGURE 1.
SCHEME 1
‡ University of Florida.
§ Kangnung National University.
(1) Hoelscher, P.; Rehwinkel, H.; Burton, G.; Moewes, M.; Hillmann,
M. Ger. Offen. DE 19627310, 1998; Chem. Abstr. 1998, 128, 114949h.
(2) Trofimenko, S. J . Org. Chem. 1970, 35, 3459.
(3) Ogata, M.; Matsumoto, H.; Kida, S.; Shimizu, S. Tetrahedron
Lett. 1979, 5011.
(4) J ones, R. A. The Chemistry of Heterocyclic Compounds: PYR-
ROLES Part II; Taylor, E. C., Ed; J ohn Wiley & Sons: New York, 1990;
p 143.
N-vinyl derivatives of nucleobases via direct vinyl ex-
change of the acetyl group of vinyl acetate with pyrimi-
dine and purine bases using TMSOTf as acid catalyst9
(Scheme 2, iv). Palladium-phosphine complexes cata-
lyzed vinylation of various azoles with vinyl bromides to
(5) Trofimov, B. A.; Tarasova, O. A.; Mikhaleva, A. I.; Kalinina, N.
A.; Sinegovskaya, L. M.; Henkelmann, J . Synthesis 2000, 1585.
(6) Irwin, W. J .; Wheeler, D. L. Tetrahedron 1972, 28, 1113.
(7) Cooper, G.; Irwin, W. J .; Weeler, D. L. Tetrahedron Lett. 1971,
4321.
(8) Cooper, G.; Irwin, W. J . J . Chem. Soc., Perkin Trans. 1. 1976,
545.
(9) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Procopio, A.; Romeo, R.;
Sindona, G. Synthesis 2002, 172.
10.1021/jo020336m CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/10/2002
8230
J . Org. Chem. 2002, 67, 8230-8233

Synthesis of N-Cycloalkenylazoles
SCHEME 2
SCHEME 3 a
give N-vinylazoles in 30-99% yields (Scheme 2, v).10
These routes, however, are not directly applicable for the
synthesis of N-(1-cycloalkenyl)pyrroles or -imidazoles. We
now report a new approach to N-(1-cycloalkenyl)het-
eroaromatics using benzotriazole methodology.
Resu lts a n d Discu ssion
a
Key: (a): yields obtained using method A; (b) yields obtained
using method B.
Syn th esis of Cyclic Com p ou n d s 2, 5, 8, 12 a n d 14.
N-(Benzotriazol-1-ylmethyl)heterocycles were previously
synthesized in our group.11 1-(Imidazol-1-yl)methyl-5-
phenyltetrazole (11) was synthesized by the reaction of
imidazole with 1-chloromethyl-5-phenyltetrazole in the
presence of sodium hydroxide in 77% yield, and com-
pound 13 was similarly made from pyrazole and 1-chlo-
romethyl-5-phenyltetrazole in 64% yield. Precursor mol-
ecule 1, 4, 7, 11, or 13 was treated with 2.3 equiv of
n-BuLi in THF at -78 °C for 1 h followed by the addition
of 1,4-dibromobutane or 1,5-dibromopentane to yield the
desired 5- or 6-membered cyclic ring systems in moderate
to good yields (Schemes 3 and 4). The structures of
products 2, 5, 8, 12, and 14 are clearly characterized by
1H and 13C NMR and microanalysis. The 1H NMR spectra
of the cyclization products showed the absence of any
singlet peak around 6.5 ppm that was ascribed to
BtCH2N in the precursor molecules. The expected four
separate groups of peaks (for a 6-membered ring) or three
groups of peaks (for a 5-membered ring) appear in the
aliphatic region.
SCHEME 4
B). Using the first approach, 6a and b were obtained in
73% and 85% yields by heating of compounds 5a and 5b,
respectively, with ZnBr2 in toluene at 80 °C for 30 min
(Scheme 3, ii). However, compounds 3a and 3b were
obtained in only 23% and 20% yields using the same
reaction system starting from compounds 2a and 2b
(Scheme 3, i). Moreover, no desired N-(1-cycloalkenyl)-
imidazoles were detected in ZnBr2/toluene, ZnBr2/THF,
or ZnBr2/CH2Cl2 reaction systems after exploring various
reaction conditions (varying time and temperature) start-
ing from compound 8 or from 12 in which the tetrazole
group was anticipated to be removed more easily than
benzotriazole.
Syn th esis of N-(1-Cycloa lk en yl)p yr r oles, -p yr a -
zoles, a n d -im id a zoles. Two methods have been used
in the present work for the removal of benzotriazole to
form the N-(1-cycloalkenyl)heterocycles: (i) Lewis acid
promoted removal of the benzotriazolyl group (method
A);12 (ii) base/DMSO effected removal of the benzotriazole
or tetrazole group based on their low pKa value (method
(10) Lebedev, A. Y.; Izmer, V. V.; Kazyul’kin, D. N.; Beletskaya, I.
P.; Voskoboynikov, A. Z. Org. Lett. 2002, 4, 623.
(11) Katritzky, A. R.; Drewniak-Deyrup, M.; Lan, X.; Brunner, F.
J . Heterocycl. Chem. 1989, 26, 829.
(12) Katritzky, A. R.; Lan, X.; Yang, J . Z.; Denisko, O. V. Chem.
Rev. 1998, 98, 409.
Fortunately, the desired compounds 9a ,b were ob-
tained in good yields by the reaction of 8a (Scheme 3,
iii) and 12 (Scheme 4) with KOH/DMSO mixture at 130
°C for 3 h. The expected pyrrole products 3a ,b were
J . Org. Chem, Vol. 67, No. 23, 2002 8231

Katritzky et al.
139.1, 146.8. Anal. Calcd for C14H15N5: C, 66.38; H, 5.97; N,
27.65. Found: C, 66.32; H, 6.10; N, 27.66.
obtained in 94% and 77% yields, respectively, as shown
in Scheme 3, i, in this KOH/DMSO mixture. The pyrazole
products 6a ,b were also formed under this reaction
mixture, but the yields were lower than that obtained in
the ZnBr2/toluene system (Scheme 3, ii). However, 6b was
obtained in 89% yield from 14 in KOH/DMSO mixture
(Scheme 4). The reasons for these variations in yields are
unknown.
1-[1-(1H -P yr a zol-1-yl)cycloh exyl]-1H -1,2,3-b en zot r i-
a zole (5b): white prisms (53%) (from ethyl acetate/hexanes);
mp 149-151 °C; 1H NMR δ 1.55-1.82 (m, 6H), 2.97-3.11 (m,
4H), 6.33 (t, J ) 1.8 Hz, 1H), 7.07-7.11 (m, 1H), 7.26-7.31
(m, 2H), 7.51 (d, J ) 2.4 Hz, 1H), 7.63 (br s, 1H), 7.98-8.03
(m, 1H); 13C NMR δ 22.2, 24.6, 36.2, 80.3, 107.5, 111.6, 119.9,
123.9, 127.4, 127.5, 131.6, 139.3, 146.5. Anal. Calcd for
C
15H17N5: C, 67.39; H, 6.41; N, 26.20. Found: C, 67.43; H,
The structures of products were fully supported by
their 1H and 13C NMR and microanalysis data. In the
proton NMR spectrum of 3a , a multiplet at 5.48-5.50
ppm was ascribed to the vinylic proton in the 5-membered
ring. For 6a and 9a , a multiplet at 5.85-5.89 ppm and
5.65-5.68 ppm also confirmed the formation of the N-(1-
cyclopentenyl)heterocycles. Similarly, a multiplet at 5.71-
6.30; N, 26.43.
1-[1-(1H -Im id a zol-1-yl)cyclop e n t yl]-1H -1,2,3-b e n zo-
tr ia zole (8a ): white prisms (52%) (from chloroform); mp 144-
148 °C; 1H NMR δ 1.94-2.04 (m, 4H), 2.78-2.90 (m, 2H),
3.19-3.28 (m, 2H), 7.00 (s, 1H), 7.04-7.14 (m, 2H), 7.32-7.40
(m, 2H), 7.81 (s, 1H), 8.02-8.10 (m, 1H); 13C NMR δ 22.0, 38.4,
83.9, 110.3, 117.4, 120.4, 124.4, 128.1, 130.5, 131.3, 135.1,
147.0. Anal. Calcd for C14H15N5: C, 66.38; H, 5.97; N, 27.65.
Found: C, 66.34; H, 6.35; N, 27.50.
1-[1-(1H -Im id a zol-1-yl)cycloh exyl]-1H -1,2,3-b en zot r i-
a zole (8b): white prisms (40%) (from chloroform); mp 165-
167 °C; 1H NMR δ 1.60-1.90 (m, 6H), 2.62-2.74 (m, 2H),
3.12-3.24 (m, 2H), 6.76-6.84 (m, 1H), 7.00 (s, 1H), 7.10 (s,
1H), 7.29-7.36 (m, 2H), 7.86 (s, 1H), 8.02-8.10 (m, 1H); 13C
NMR δ 22.2, 24.4, 37.0, 77.6, 110.5, 116.8, 120.4, 124.3, 128.0,
130.4, 131.2, 134.9, 146.6. Anal. Calcd for C15H17N5: C, 67.39;
H, 6.41; N, 26.20. Found: C, 67.67; H, 6.59; N, 26.52.
1-[1-(1H-Im id a zol-1-yl)cycloh exyl]-5-p h en yl-1H-1,2,3,4-
tetr a zole (12): white needles (56%) (from chloroform); mp
105-106 °C; 1H NMR δ 1.40-1.90 (m, 6H), 2.62-2.76 (m, 2H),
3.20-3.54 (m, 2H), 7.04 (s, 1H), 7.19 (s, 1H), 7.44-7.54 (m,
3H), 7.88 (s, 1H), 8.08-8.18 (m, 2H); 13C NMR δ 21.9, 24.1,
35.6, 78.1, 116.0, 126.9, 127.0, 128.9, 130.0, 130.6, 134.4, 165.1.
Anal. Calcd for C16H18N6: C, 65.29; H, 6.16; N, 28.55. Found:
C, 65.14; H, 6.38; N, 28.43.
1-[1-(1H-P yr a zol-1-yl)cycloh exyl]-5-p h en yl-1H-1,2,3,4-
tetr a zole (14): white prisms (54%) (ethyl acetate/hexanes);
mp 111-113 °C; 1H NMR δ 1.50-1.80 (m, 6H), 2.90-3.20 (m,
4H), 6.31 (br s, 1H), 7.40-7.48 (m, 3H), 7.56 (br s, 1H), 7.74
(d, J ) 2.4 Hz, 1H), 8.10-8.18 (m, 2H); 13C NMR δ 22.0, 24.3,
35.1, 81.3, 106.9, 127.0, 127.2, 127.3, 128.8, 130.3, 140.2, 164.7.
Anal. Calcd for C16H18N6: C, 65.29; H, 6.16; N, 28.55. Found:
C, 65.67; H, 6.03; N, 28.71.
Typ ica l P r oced u r e for th e Syn th esis of N-Cycloa l-
k en yla zoles. Meth od A. Compound 2a (0.25 g, 1 mmol) and
ZnBr2 (0.45 g, 2 mmol) were placed in a dry flask under argon,
5 mL of toluene was added, and the mixture was heated at 80
°C for 45 min. The reaction mixture was then cooled to room
temperature, extracted with ethyl ether, dried (MgSO4), and
concentrated to give a white solid that was purified by column
chromatography with hexane as eluent to give 30 mg of white
powder.
1
5.74 ppm in the H NMR of 3b was due to the vinylic
proton in the 6-membered ring. For 6b and 9b, a multi-
plet at 6.10-6.13 ppm and 5.82-5.85 ppm also charac-
terized the structures of N-(1-cyclohexenyl)heterocycles.
In summary, 1-[1-(heterocycyl)cycloalkyl]benzotri-
azoles and 1-[1-(heterocycyl)cyclohexyl]-5-phenyltetra-
zoles were easily obtained via cyclization of the corre-
sponding starting materials in good yields. The benzotri-
azolyl or 5-phenyltetrazolyl groups in these compounds
can be eliminated to give N-(1-cycloalkenyl)azoles, a
compound class previously rarely reported.
Exp er im en ta l Section
Gen er a l Com m en ts. Tetrahydrofuran was distilled under
nitrogen from sodium-benzophenone immediately before use.
All reactions with moisture-sensitive compounds were carried
out under a dry argon atmosphere.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
2, 5, 8, 12, a n d 14. The corresponding starting material (10.0
mmol) was dissolved in THF (180 mL) at -78 °C, and n-BuLi
(23.0 mmol, 14.4 mL, 1.6 M in hexane) was added dropwise.
The resulting solution was stirred for 45-60 min. An ap-
propriate dibromoalkane (1.2 equiv, 12.0 mmol) was then
added dropwise. The mixture was stirred overnight and
allowed to come to 20 °C. The reaction was quenched with 20
mL of water, and the layers were separated. The aqueous layer
was extracted with diethyl ether (3 × 20 mL). The combined
organic layer was dried over MgSO4 and concentrated to give
a brown oil. The product was purified by column chromatog-
raphy on silica gel.
1-[1-(1H -P yr r ol-1-yl)cyclop en t yl]-1H -1,2,3-b en zot r i-
a zole (2a ): white prisms (78%) (from ethyl acetate/hexanes);
mp 120-123 °C; 1H NMR δ 1.93-1.98 (m, 4H), 2.73-2.82 (m,
2H), 3.11-3.20 (m, 2H), 6.20 (t, J ) 2.1 Hz, 2H), 6.87 (t, J )
2.1 Hz, 2H), 6.90 (d, J ) 5.4 Hz, 1H), 7.26-7.33 (m, 2H), 8.00-
8.04 (m, 1H); 13C NMR δ 22.2, 38.6, 85.3, 109.6, 110.8, 119.0,
119.9, 124.0, 127.5, 131.7, 146.8. Anal. Calcd for C15H16N4: C,
71.40; H, 6.39; N, 22.20. Found: C, 71.12; H, 6.82; N, 22.23.
1-[1-(1H -P yr r ol-1-yl)cycloh e xyl]-1H -1,2,3-b e n zot r i-
a zole (2b): white crystals (68%) (from ethyl acetate/hexanes);
mp 120-122 °C; 1H NMR δ 1.56-174 (m, 4H), 1.78-1.90 (m,
2H), 2.60-2.75 (m, 2H), 2.98-3.06 (m, 2H), 6.28 (br s, 2H),
6.32 (d, J ) 8.1 Hz, 1H), 6.95 (br s, 2H), 7.18-7.29 (m. 2H),
8.00 (d, J ) 7.8 Hz, 1H); 13C NMR δ 22.4, 24.6, 37.4, 78.5,
109.8, 111.0, 118.8, 119.7, 123.8, 127.5, 131.6, 146.2. Anal.
Calcd for C16H18N4: C, 72.15; H, 6.81; N, 21.04. Found: C,
71.77; H, 6.81; N, 20.77.
Meth od B. Compound 2a (0.10 g, 0.4 mmol) was dissolved
in 5 mL of dry DMSO, and KOH powder (0.10 g, 1.6 mmol,
86%) was added. The resulting mixture was heated at 110 °C
for 3 h under nitrogen atmosphere with stirring. The reaction
mixture was cooled to room temperature and extracted with
CH2Cl2, the organic layer was washed with water (5 × 5 mL)
and dried (Na2SO4). The solvent was evaporated under reduced
pressure in an ice-water bath. The product was purified by
column chromatography on silica gel using 5% ethyl ether in
pentane.
N-(1-Cyclopen ten -1-yl)-1H-pyr r ole (3a): white solid (from
pentane); mp 32-34 °C; 1H NMR δ 1.99-2.10 (m, 2H), 2.46-
2.51 (m, 2H), 2.73-2.79 (m, 2H), 5.48-5.50 (m, 1H), 6.21 (t, J
) 2.1 Hz, 2H), 6.91 (t, J ) 2.1 Hz, 2H); 13C NMR δ 22.0, 30.5,
31.8, 109.2, 109.3, 118.7, 140.1. Anal. Calcd for C9H11N: C,
81.16; H, 8.32; N, 10.52. Found: C, 80.98; H, 8.63; N, 10.39.
1-[1-(1H -P yr a zol-1-yl)cyclop en t yl]-1H -1,2,3-b en zot r i-
a zole (5a ): white prisms (52%) (from ethyl acetate/hexanes);
mp 119-121 °C; 1H NMR δ 1.92-1.97 (m, 4H), 3.12-3.28 (m,
4H), 6.27 (t, J ) 2.1 Hz, 1H), 7.30-7.38 (m, 2H), 7.40-7.48
(m, 2H), 7.52-7.58 (m, 1H), 7.98-8.03 (m, 1H); 13C NMR δ
22.2, 37.8, 86.9, 107.6, 111.6, 119.9, 124.1, 127.5, 127.7, 131.8,
1
N-(1-Cycloh exen -1-yl)-1H-p yr r ole (3b): colorless oil; H
NMR δ 1.61-1.69 (m, 2H), 1.77-1.85 (m, 2H), 2.14-2.21 (m,
2H), 2.42-2.47 (m, 2H), 5.71-5.74 (m, 1H), 6.18-6.20 (m, 2H),
6.88-6.90 (m, 2H); 13C NMR δ 22.0, 22.6, 24.2, 27.1, 108.6,
8232 J . Org. Chem., Vol. 67, No. 23, 2002

Synthesis of N-Cycloalkenylazoles
112.8, 117.9, 136.2; HRMS calcd for C13H13N (M) 147.1048,
found 147.1087.
powder (1.6 g, 40 mmol) were dissolved in DMSO (20 mL, dried
over molecular sieves) and heated at 60 °C for 30 min. Then,
1-chloromethyl-5-phenyltetrazole (3.8 g, 20 mmol) was added
in one portion and the mixture heated at 60 °C for 1 h. The
reaction mixture was cooled to room temperature and poured
over 100 g of ice in a beaker with rapid stirring. After 10 min,
the precipitate was filtered off and washed with cold water
(100 mL). The product was purified via recrystallization.
N-(1-Cyclop en ten -1-yl)-1H-p yr a zole (6a ):2 colorless oil;
1H NMR δ 2.04-2.14 (m, 2H), 2.50-2.58 (m, 2H), 2.83-2.91
(m, 2H), 5.85-5.89 (m, 1H), 6.32-6.33 (m, 1H), 7.59 (br d, J
) 2.7 Hz, 1H), 7.60 (d, J ) 1.8 Hz, 1H); 13C NMR δ 22.1, 30.7,
31.4, 106.3, 112.3, 127.2, 140.3, 140.4.
N-(1-Cycloh exen -1-yl)-1H-p yr a zole (6b):2 colorless oil; 1H
NMR δ 1.63-1.71 (m, 2H), 1.80-1.88 (m, 2H), 2.19-2.26 (m,
2H), 2.55-2.61 (m, 2H), 6.10-6.13 (m, 1H), 6.30-6.31 (m, 1H),
1-(1H-Im id a zol-1-ylm eth yl)-5-p h en yl-1H-1,2,3,4-tetr a -
zole (11): brown prisms (ethyl acetate/hexanes); mp 123-126
7.58 (br d, J ) 1.8 Hz, 1H), 7.61 (dd, J ) 2.4, 0.6 Hz, 1H); 13
C
1
°C; H NMR δ 6.65 (s, 2H), 7.11 (s, 1H), 7.24 (s, 1H), 7.45-
7.54 (m, 3H), 7.87 (s, 1H), 8.12-8.18 (m, 2H); 13C NMR δ 60.3,
118.9, 126.4, 127.0, 128.9, 130.9, 131.0, 137.4, 166.2. Anal.
Calcd for C11H10N6: C, 58.40; H, 4.46; N, 37.15. Found: C,
58.69; H, 4.66; N, 37.03.
NMR δ 21.9, 22.4, 24.0, 26.0, 105.8, 113.9, 125.8, 136.5, 139.6.
N-(1-Cyclop en t en -1-yl)-1H -im id a zole (9a ): off-white
prisms (ethyl acetate/hexanes); mp 40-42 °C; 1H NMR δ 2.04-
2.14 (m, 2H), 2.48-2.55 (m, 2H), 2.74-2.81 (m, 2H), 5.65-
5.68 (m, 1H), 7.08 (br s, 1H), 7.14-7.16 (m, 1H), 7.67 (br s,
1H); 13C NMR δ 21.8, 30.4, 31.7, 113.3, 116.9, 129.7, 135.1,
136.9; HRMS calcd for C8H10N2 (M) 134.0844, found 134.0856.
N-(1-Cycloh exen -1-yl)-1H-im id a zole (9b):3 brown oil; 1H
NMR δ 1.65-1.71 (m, 2H), 1.78-1.86 (m, 2H), 2.18-2.22 (m,
2H), 2.40-2.44 (m, 2H), 5.82-5.85 (m, 1H), 7.08 (s, 1H), 7.09
(s, 1H), 7.67 (s, 1H); 13C NMR δ 21.4, 22.1, 23.8, 27.1, 116.2,
116.4, 129.0, 133.5, 134.2.
1-(1H -P yr a zol-1-ylm et h yl)-5-p h en yl-1H -1,2,3,4-t et r a -
zole (13): white needles (ethyl acetate/hexanes); mp 115-116
°C; 1H NMR δ 6.37 (t, J ) 2.1 1H), 6.82 (s, 2H), 7.46-7.48 (m,
3H), 7.62 (d, J ) 1.5 Hz, 1H), 7.80 (d, J ) 2.4 Hz, 1H), 8.15-
8.18 (m, 2H); 13C NMR δ 64.9, 108.0, 126.6, 126.9, 128,8, 130.3,
130.6, 141.8, 165.8. Anal. Calcd for C11H10N6: C, 58.40; H, 4.46;
N, 37.15. Found: C, 58.60; H, 4.40; N, 37.02.
Gen er a l P r oced u r e for th e Syn th esis of Com p ou n d s
11 a n d 13.11 Imidazole or pyrazole (20 mmol) and NaOH
J O020336M
J . Org. Chem, Vol. 67, No. 23, 2002 8233