Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: A convenient, high-yield synthesis of substituted cinnolines and isoindazoles

Article abstract of DOI:10.1021/jo020229s

A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 °C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 °C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 °C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 °C.

Full text of DOI:10.1021/jo020229s

Cycliza tion of 1-(2-Alk yn ylp h en yl)-3,3-d ia lk yltr ia zen es: A
Con ven ien t, High -Yield Syn th esis of Su bstitu ted Cin n olin es a n d
Isoin d a zoles
David B. Kimball, Timothy J . R. Weakley, and Michael M. Haley*
Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253
haley@oregon.uoregon.edu
Received April 2, 2002
A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes
under neutral conditions is presented. The products that result from heating the starting triazenes
depend on both the type of alkyne ortho to the triazene functionality and the temperature used.
Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 °C
in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a
suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward
methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield
both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions.
Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-
ethynylphenyl)dialkyltriazenes. Heating to 170 °C results in a mixture of isoindazole and cinnoline
products, whereas the cinnolines are produced exclusively in high yield at 200 °C. Alternatively,
the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution
of the starting triazene with CuCl overnight at 50 °C.
In tr od u ction
(DBAs, e.g., 1), most of which would be difficult or
impossible using other methods.2c,d,6 The success of our
strategies has relied on the use of trimethylsilyl-protected
1-phenyl-1,3-butadiyne moieties (e.g., 2, Scheme 1),
which are synthesized in good overall yield from com-
mercially available anilines via triazene intermediates.
In cases where a strongly electron-withdrawing group
is para to the triazene, decomposition to the iodoarene
with iodomethane must be done at higher temperatures.
Since nitro or cyano substituents on the phenyl ring pull
electron density away from the distal dialkylamine,
nucleophilic attack on iodomethane, the first step in
decomposition, is less favored.7 In our experience, it has
been necessary to heat cyanophenyltriazenes to ca. 150
°C for the aryl iodide to form in high yield in less than
24 h. In most instances, the phenylacetylene/triazene
starting materials were stable at elevated temperatures
and the iodoarenes could be generated in nearly quan-
titative yield.
Aryltriazenes1 have been used extensively in the
preparation of a large variety of phenylacetylene-based
systems.2,3 Triazene preparation can be done efficiently
from commercially available anilines, and heating in
iodomethane at 100-150 °C produces the corresponding
iodoarenes in high yield.4 Combined with Pd-catalyzed
cross-coupling methodology,5 the ability to mask and
unmask a reactive iodoarene provides great control over
aromatic substitution patterns. The high-yielding conver-
sion to such a versatile synthon makes aryltriazenes
indispensable in the preparation of large phenylacetylene
oligomers and polymers requiring multiple synthetic
steps.2
Our group has used aryltriazenes with great success
in the synthesis of numerous dehydrobenzoannulenes
(1) Review of triazene chemistry: Kimball, D. B.; Haley, M. M.
Angew. Chem., Int. Ed. 2002, 41, in press.
(2) (a) Moore, J . S. Acc. Chem. Res. 1997, 30, 402-413. (b) Tour, J .
M. Acc. Chem. Res. 2000, 33, 791-804. (c) Haley, M. M.; Pak, J . J .;
Brand, S. C. In Topics in Current Chemistry (Carbon-Rich Compounds
II); de Meijere, A., Ed.; Springer-Verlag: Berlin, 1999; Vol. 201, pp
81-130. (d) Haley, M. M.; Wan, W. B. In Advances in Strained and
Interesting Organic Molecules, Volume 8; Halton, B., Ed.; J AI Press:
New York, 2000; pp 1-41.
Until recently, our research has focused on triazenes
that were ortho to monoacetylenes protected by SiMe3
or Sii-Pr3 groups that rarely contained electron-with-
(6) Inter alia: (a) Pak, J . J .; Weakley, T. J . R.; Haley, M. M. J . Am.
Chem. Soc. 1999, 121, 8182-8192. (b) Kehoe, J . M.; Kiley, J . H.;
English, J . J .; J ohnson, C. A.; Petersen, R. C.; Haley, M. M. Org. Lett.
2000, 2, 969-972. (c) Wan, W. B.; Brand, S. C.; Pak, J . J .; Haley, M.
M. Chem. Eur. J . 2000, 6, 2044-2052. (d) Bell, M. L.; Chiechi, R. C.;
J ohnson, C. A.; Kimball, D. B.; Matzger, A. J .; Wan, W. B.; Weakley,
T. J . R.; Haley, M. M. Tetrahedron 2001, 57, 3507-3520. (e) Wan, W.
B.; Haley, M. M. J . Org. Chem. 2001, 66, 3893-3901.
(7) For analogous decomposition using reagents other than io-
domethane, see: (a) Wu, Z.; Moore, J . S. Tetrahedron Lett. 1994, 35,
5539-5542. (b) Khalaj, A.; Beiki, D.; Rafiee, H.; Najafi, R. J . Label.
Comput. Radiopharm. 2001, 44, 235-240.
(3) Inter alia: (a) Mongin, O.; Papamicae¨l, C.; Hoyler, N.; Gossauer,
A. J . Org. Chem. 1998, 63, 5568-5580. (b) Fo¨rster, B.; Bertran, J .;
Teixidor, F.; Vin˜as, C. J . Organomet. Chem. 1999, 587, 67-73.
(4) (a) Moore, J . S.; Weinstein, E. J .; Wu, Z. Tetrahedron Lett. 1991,
32, 2465-2466. (b) Bhattacharya, S.; Majee, S.; Mukherjee, R.;
Sengupta, S. Synth. Commun. 1995, 25, 651-657. (c) Wautelet, P.;
Moroni, M.; Oswald, L.; Lemoigne, J .; Pham, A.; Bigot, J . Y.; Luzzati,
S. Macromolecules 1996, 29, 446-455.
(5) (a) Tsuji, J . Palladium Reagents and Catalysts; Wiley: New York,
1995. (b) Metal-Catalyzed Cross-Coupling Reactions; Stang, P. J .,
Diederich, F., Eds.; VCH: Weinheim, 1997.
10.1021/jo020229s CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/30/2002
J . Org. Chem. 2002, 67, 6395-6405
6395

Kimball et al.
SCHEME 1
and versatile methods for their synthesis could gain
increased importance. Since our initial report,11 we have
elucidated the complex mechanistic pathways for triazene
cyclization.12 The following report contains the full details
of this new synthesis and represents our efforts to
determine its scope.13
Resu lts a n d Discu ssion
Cycliza tion of Diyn e Tr ia zen es. Our first task was
to determine if this cyclization could be repeated with
similar starting materials. Thus, unfunctionalized phe-
nyltriazene 6 and 4-nitrophenyltriazene 7 (Scheme 2)
were synthesized for comparison with 3. The synthesis
of 3 provides a representative example. 4-Aminobenzoni-
trile was iodinated using BTEA‚ICl2 and CaCO3,14 the
product of which was first treated with HCl and aqueous
NaNO2 at -5 °C and then quenched with Et2NH and K2-
CO3 to generate triazene 8 in 89% yield. Triazene 9 was
obtained similarly starting from 2-iodoaniline.6b (Trim-
ethylsilyl)butadiyne was then cross-coupled to 8 and 9
under Sonogashira conditions15 to produce 3 and 6 in 94%
and 36% yield, respectively. Compound 7 followed simi-
larly from triazene 10, which had been synthesized
previously for the study of donor-acceptor annulenes and
was readily available.6a
Since the nitro functionality has electron-withdrawing
ability comparable to the cyano group, we expected 7 to
cyclize/dimerize in the same fashion as 3. This proved to
be the case as heating 7 in MeI at 145 °C for 48 h in a
sealed glass pressure tube gave dimer 11 in 36% yield
along with iodoarene 12 (27%, Scheme 2). In stark
contrast, transformation to iodoarene 13 was rapid above
120 °C when triazene 6 was used and occurred in nearly
quantitative yield.
Attempts to repeat these reactions at both lower and
higher temperatures revealed an interesting temperature
window. Using 3, 6, and 7, no reaction occurred below
110 °C. At 140-150 °C, 3 and 7 formed isoindazole
dimers 5 and 11, respectively, along with the correspond-
ing iodoarenes as a minor products. Cyclization/dimer-
ization of 6 could not be accomplished in MeI since
triazene decomposition occurred well below 145 °C. If 3
or 7 was heated above 160 °C, however, the iodoarenes
were obtained in excellent yield. These results indicate
that in order for cyclization/dimerization to occur in MeI,
suitably electron-withdrawing substituents must be
present to deactivate the dialkylamino nitrogen in the
triazene toward nucleophilic attack.
drawing substituents. An attempt to react a triazene
ortho to a 1,3-butadiyne moiety and para to a cyano group
(3, Scheme 2), however, gave the desired aryl iodide 4 in
very low yield (ca. 10%) along with an unexpected side
product in 33% yield. 1H NMR analysis of the new
compound revealed that although the aromatic reso-
nances had changed, the diethylamino signals were still
present but were upfield relative to the starting material.
Combining these results with evidence presented by the
13C NMR and mass spectra suggested that the chemical
nature of both the butadiyne unit and the triazene had
changed. An X-ray structure analysis (see the Supporting
Information) revealed that concurrent cyclization and
dimerization had produced a 2H-indazole (isoindazole)
dimer, compound 5. A review of the literature revealed
no examples of the formation of an isoindazole from a
triazene ortho to an acetylene under neutral conditions.
Although the majority of indazoles are synthesized using
a similar type of ring closure (i.e., ring closure with bond
formation between the 2-3 positions on the indazole),
acidic conditions or more reactive functional groups
(azides, electrophilic carbon functionalities) must be
employed.8 Recent examples of indazole synthesis have
utilized monoacetylenes,9 but the more reactive azide in
place of the triazene was necessary for cyclization.
Inspired by the surprising formation of 5, we decided
to explore the cyclization reactions of (2-alkynylphenyl)-
triazenes. Our interest in such systems is 3-fold: (1) our
extensive use of triazenes compels us to determine under
what conditions the aryl iodide will form in preference
to this new isoindazole dimer; (2) since this reaction is
done under neutral conditions, establishing the presence
of a novel cyclization mechanism could help develop new
synthetic methods using acetylenes; (3) 2H-indazoles
have received moderate attention in recent literature
regarding their medicinal properties,10 and finding new
Cycliza tion of Mon oyn e Tr ia zen es. To determine
whether monoalkynes could be used in place of butadiy-
nyl moieties, 14 and 15 (Scheme 3) were synthesized for
(10) (a) Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C. Tetrahedron
1992, 48, 325-334. (b) Rodgers, J . D.; J ohnson, B. L.; Wang, H.;
Greenberg, R. A.; Erickson-Viitanen, S.; Klabe, R. M.; Cordova, B. C.;
Rayner, M. M.; Lam, G. N.; Chang, C.-H. Bioorg. Med. Chem. Lett.
1996, 6, 2919-2924. (c) Sun, J .-H.; Teleha, C. A.; Yan, J .-S.; Rodgers,
J . D.; Nugiel, D. A. J . Org. Chem. 1997, 62, 5627-5629.
(11) Kimball, D. B.; Hayes, A. G.; Haley, M. M. Org. Lett. 2000, 2,
3825-3827.
(12) Kimball, D. B.; Herges, R.; Haley, M. M. J . Am. Chem. Soc.
2002, 124, 1572-1573.
(13) Complete mechanistic details of the triazene cyclizations will
be outlined in a forthcoming full paper.
(8) (a) Elderfield, R. C. In Heterocyclic Compounds; Elderfield, R.
C., Ed.; J ohn Wiley & Sons: New York, 1957; Vol. 5, pp 162-181. (b)
Behr, L. C.; Fusco, R.; J arobe, C. H. In Pyrazoles, Pyrazolines,
Pyrazolidines, Indazoles and Condensed Rings; Wiley, R. H., Ed.;
International Wiley Science: New York, 1967; pp 289-382.
(9) (a) Prikhodko, T. A.; Vasilevsky, S. F. Mendeleev Cummun. 1996,
98-99. (b) Prikhodko, T. A.; Vasilevsky, S. F. Mendeleev Commun.
1998, 149-150. (c) Prikhodko, T. A.; Vasilevsky, S. F. Russ. Chem.
Bull. Int. Ed. 2001, 50, 1268-1273.
(14) Kajigaeshi, S.; Kakinami, T.; Yamasaki, H.; Fujisaki, S.;
Okamoto, T. Bull. Chem. Soc. J pn. 1988, 61, 600-602.
(15) Sonogashira, K. In ref 5b, pp 203-229.
6396 J . Org. Chem., Vol. 67, No. 18, 2002

Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes
SCHEME 2a
a
Reagents and conditions: (a) BTEA‚ICl2, CaCO3, MeOH, THF; (b) (i) HCl, NaNO2, (ii) Et2NH or piperidine, K2CO3, H2O, MeCN; (c)
Me3SiCtCCtCH, PdCl2(PPh3)2, CuI, NEt3; (d) MeI, 145 °C.
SCHEME 3a
a
Reagents and conditions: (a) Me3SiCtCH, PdCl2(PPh3)2, CuI, NEt3; (b) K2CO3, MeOH, THF; (c) MeI, 145 °C.
comparison. Ethyne units are both readily available and
easier to work with compared to butadiynes. The corre-
sponding (2-iodophenyl)triazenes were first treated with
(trimethylsilyl)acetylene under Sonogashira conditions,
then cleavage of the trimethylsilyl group was accom-
plished with K2CO3 in MeOH/THF. Compounds 14 and
15 were stable under ambient conditions and could be
kept on the benchtop for weeks without apparent decom-
position.
Switching to a monoalkyne on the phenyltriazene
produced slightly different results upon heating in MeI.
When 14 was used in place of 3, the 2H-indazole dimer
was produced in 40% yield as a ca. 2:1 ratio of trans (16)
and cis isomers (17), respectively (Scheme 3). Similarly,
cyclization of 15 gave a ca. 1:1 ratio of dimers 18 and 19.
Recrystallization from EtOH of both sets of dimers
resulted in total conversion to the trans isomers, as
confirmed for 16 by X-ray analysis (see the Supporting
Information). Another unexpected side product, an isoin-
dazole aldehyde (20, 21), was also obtained in low yield
in both reactions. This result suggested that the reactive
intermediate, most likely a carbene,12 could also be
trapped by an oxygen atom source before dimerization
occurred.
Solven t Stu d ies. Since MeI as solvent severely lim-
ited the scope of this unusual transformation, we began
exploring different media. Heating cyanophenyltriazene
3 to 160-170 °C for 48 h in several common solvents
J . Org. Chem, Vol. 67, No. 18, 2002 6397

Kimball et al.
SCHEME 4
SCHEME 5a
a
Reagents and conditions: (a) BTEA‚ICl2, CaCO3, MeOH, THF;
(b) (i) HCl, NaNO2, (ii) Et2NH, K2CO3, H2O, MeCN; (c) Me3SiCtCH,
PdCl2(PPh3)2, CuI, NEt3; (d) K2CO3, MeOH, THF.
resulted either in no reaction (EtOAc, CHCl3, benzene,
toluene, MeCN) or a complex mixture of byproducts
(DMF, DMSO). Since the reaction consistently gave
isoindazole products close to 145 °C, we then focused on
solvents with boiling points above this temperature and
with polarity similar to MeI. We found that heating 3 in
o-dichlorobenzene (ODCB) successfully gave an isoinda-
zole product, but not the expected dimer. Instead, acyl-
2H-indazole 22 (Scheme 4) was produced in high yield.
Repeating this experiment with compound 6 gave the
corresponding indazole 23 along with the likely inter-
mediate in the acylindazole formation, propioloylindazole
24 (Scheme 4). NMR and mass spectral analysis cor-
roborated the structure of these acyl products. Although
inclusion of oxygen in these molecules was consistent
with the aldehydes obtained previously, loss of the SiMe3
protecting group as well as one methine unit from 22 and
23 was curious; a reasonable mechanism for this trans-
formation is not readily obvious.
SCHEME 6a
a
Reagents and conditions: (a) MeI, Cs2CO3, DMF; (b) (i) HCl,
Th er m olysis Stu d ies. The results using ODCB en-
couraged us to begin a systematic study of the thermal
cyclization of (2-ethynylphenyl)triazenes. This type of
system was used in preference to butadiynyl moieties as
(trimethylsilyl)acetylene is more readily available than
(trimethylsilyl)buta-1,3-diyne. Also, given the unusual
formation of 22 and 23, monoyne-containing systems
seemed to be the better choice. Compounds 25-32
(Scheme 5) were synthesized in four steps in moderate
to excellent overall yield from the corresponding 4-sub-
stituted anilines via iodotriazenes 33-39. The parent (2-
ethynylphenyl)triazene (R ) H) was prepared as previ-
ously described.6b The reaction sequence shown in Scheme
5 is a remarkably efficient process in that purification
needed after each step was minimal. The compounds
formed are stable to ambient conditions, and 6-8 g
quantities of 25-32 have been synthesized.
To study compounds with more electron-donating
substituents on the phenyl ring, methoxy- and acetox-
yphenyltriazenes 40 and 41, respectively, were prepared
from 4-amino-3-iodophenol16 (42, Scheme 6). After the
phenol was converted to the methyl ether or the acetyl
ester, the corresponding iodotriazenes 43 and 44 were
prepared by the usual method in good yield. Subsequent
cross-coupling with (trimethylsilyl)acetylene and desily-
NaNO2, (ii) Et2NH, K2CO3, H2O, MeCN; (c) Me3SiCtCH, PdCl2-
(PPh3)2, CuI, NEt3; (d) K2CO3, MeOH, THF; (e) Ac2O, pyr; (f)
Bu4NF, EtOH, THF.
lation with K2CO3 in MeOH or Bu4NF gave triazenes 40
and 41 in 84% and 36% overall yield, respectively.
Unlike their butadiynyl counterparts, the (2-ethy-
nylphenyl)triazenes typically gave a mixture of two
different heterocycles when heated to 170 °C in ODCB
for 24 h (Table 1). In most cases, both 5-substituted
3-formyl-2-diethyl-2H-indazoles (20, 45-53) and 6-sub-
stituted cinnolines (56-65) were isolated (Scheme 7).
Two notable exceptions are the (2-ethynylphenyl)triaz-
enes with electron-donating oxygen groups, i.e., 40 and
41. No cinnoline products were observed after heating
to 170 °C, and the isoindazole products were obtained in
surprisingly high yield (Table 1, entries k and l).
Interestingly, the above conditions are atypical of
traditional syntheses of cinnolines.17 Strong acids and
polar solvents are usually necessary to produce a diazo-
nium species susceptible to nucleophilic attack by an
activated ortho-carbon nucleophile. Diazonium salts are
either formed from anilines or regenerated from triaz-
enes. Acyl groups are common nucleophiles (through
enols), although the most prevalent syntheses involve an
acetylene. The latter is known as a Richter cyclization
and occurs by nucleophilic attack by an oxygen or halogen
(16) Kvalnes, D. E. J . Am. Chem. Soc. 1934, 56, 667-670.
6398 J . Org. Chem., Vol. 67, No. 18, 2002

Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes
TABLE 1. Yield s of Isoin d a zoles a n d Cin n olin es
TABLE 2. Cycliza tion of 26 in th e P r esen ce of Va r iou s
Meta l Sa ltsa
entry
R
isoindazolea,b
cinnolinea,c
metal salt
yield of 47a (%)
metal salt
yield of 47a (%)
a
b
c
d
e
f
g
h
i
H
Me
t-Bu
CtCH
Br
45, 55% [95%]
46, 20% [90%]
47, 22% [96%]
48, 36% [91%]
49, 15% [98%]
50, 14% [95%]
51, 25% [94%]
52, 63% [83%]
20, 50% [85%]d
53, 60% [78%]e
54, 85% [98%]
55, 89% [86%]
56, 35% (99%)
57, 51% (97%)
58, 61% (98%)
59, 39% (83%)
60, 70% (98%)
61, 58% (97%)
62, 35% (90%)
63, 28% (96%)
64, 45% (98%)
65, 25% (93%)
66, 0% (0%)f
CuI
CuCl
CuCl2
Cu(OAc)2
75
87
71
67
Cu2O
Rh2(OAc)4
ZnCl2
71
32
43
Cl
F
a
Conditions: 26 (1 equiv), metal salt (1 equiv), CH2Cl2 (25 mL),
48 h, rt.
CO2Me
CN
NO2
OMe
OAc
j
k
l
the cinnoline for entries a-j. Under these conditions, the
cinnolines were generated in excellent yield. Heating 40
or 41 (entries k and l) to 200 °C in ODCB, however, again
did not give the cinnoline products in observable amounts.
Interestingly, more than half of the 6-substituted cinno-
lines are new compounds despite their simple structures.
Aside from the parent heterocycle, which is commercially
available, our method permits much easier access to the
known cinnolines (60,19 61,20 6521) and in considerably
higher overall yields. Compounds 63 and 64 reflect the
versatility of this cyclization as their acid-sensitive
functionalities would not survive the harsh conditions
typical of previous cinnoline syntheses.17
67, 0% (0%)f
a
b
Yield at 170 °C. Yield of CuCl-promoted reaction in brackets.
c Yield at 200 °C in parentheses. Reaction run at rt; at 50 °C,
d
the yield of 20 dropped to 60% and was accompanied by 34% yield
of dimer 16. e Reaction run at rt; at 50 °C, the yield of 53 dropped
to 54% and was accompanied by 37% yield of dimer 18′ (Et2N in
place of piperidine). f Only isoindazole was generated under all
reaction conditions.
SCHEME 7
Op t im izin g Isoin d a zole F or m a t ion . The above
observations suggest that, of the two heterocycles that
result from the thermal cyclization of (2-ethynylphenyl)-
triazenes, the cinnoline is the thermodynamically favored
product. Encouraged by the high yields of 56-65, we
sought to find conditions suitable for the facile production
of the “kinetic” heterocycles 20 and 45-54. Several
factors pointed to a carbene mechanism for isoindazole
formation,11-13 such as neutral conditions, relatively high
temperatures, alkene dimers (e.g., 5, 18), and oxygen-
trapped products (e.g., 20, 24).
Copper salts have been known for some time to
stabilize carbene intermediates and allow their reactions
to be performed at lower temperatures.22 Thus, the
cyclization of 14 in the presence of CuI was examined as
a test case. Heating a solution of 14 in ODCB to 120-
130 °C in the presence of CuI did produce a slightly
higher yield of isoindazole 20; however, several new
products were also generated.23 Lowering the tempera-
ture further to 50 °C gave a higher yield of 20; more
importantly, cinnoline 64 was no longer detected. Stirring
26 in the presence of copper salts resulted in isoindazole
formation in good yield at room temperature (Table 2).
Rhodium and zinc salts resulted in some isoindazole
formation, but the material contained numerous other
products. Whereas the reaction mixture would eventually
become discolored as the isoindazole was generated over
16-30 h using copper salts, rhodium and zinc salts
caused immediate discoloration, with the starting mate-
rial consumed in less than 30 min (as monitored by NMR
spectroscopy). Optimization of the conditions led to the
source on the acetylene, inducing cyclization with the
nearby electron-deficient diazonium species similar to a
Michael addition.18 A similar mechanism is unlikely in
our system since no strong proton donor is available to
regenerate the diazonium salt. Also, the cinnolines
formed do not incorporate oxygen or nitrogen nucleo-
philes even when these are present in reaction mix-
tures.13
For all triazenes, the isoindazole dimers seen in
cyclizations performed in MeI were either not produced
or obtained only in trace amounts. Examination of the
ratio of cinnoline to isoindazole for each system showed
a difference in the yield of each heterocycle depending
on the electronic nature of the para substituent (Table
1). For most of the compounds, the cinnoline product was
generated in preference to or in equal quantities to the
isoindazole. The largest yields of isoindazole resulted
from the starting phenyltriazenes with either strongly
donating or strongly withdrawing groups on the benzene
ring. The product ratio could be controlled with temper-
ature. Heating the reaction to 195-205 °C furnished only
(17) (a) Simpson, J . C. E. In The Chemistry of Heterocyclic Com-
pounds. Condensed Pyridazine and Pyrazine Rings (Cinnolines, Ph-
thalazines, and Quinoxalines); Weisberger, A., Ed.; Interscience Pub-
lishers: New York, 1953; pp 3-65. (b) van der Plas, H. C.; Bourman,
D. J .; Vos, C. M. Recl. Trav. Chim. Pays-Bas 1978, 97, 50-51. (c)
Dowlatshahi, H. A. Synth. Commun. 1985, 15, 1095-1110. (d) Vasi-
levsky, S. F.; Tretyakov, E. V. Liebigs Ann. 1995, 775-779. (e)
Tretyakov, E. V.; Knight, D. W.; Vasilevsky, S. F. J . Chem. Soc., Perkin
Trans. 1 1999, 24, 3721-3726. (f) Bra¨se, S.; Dahmen, S.; Heuts, J .
Tetrahedron Lett. 1999, 40, 6201-6203.
(19) Schofield, K.; Swain, T. J . Chem. Soc. 1950, 392-395.
(20) Osborn, A. R.; Schofield, K. J . Chem. Soc. 1956, 4207-4213.
(21) Morley, J . S. J . Chem. Soc. 1951, 1971-1975.
(22) For use of copper as a carbene stabilizer, see: (a) Stechl, H.-H.
Chem. Ber. 1964, 97, 2681-2688. (b) Nozaki, H.; Moriuti, S.; Takaya,
H.; Noyori, R. Tetrahedron Lett. 1966, 5239-5244.
(23) One of these products was isolated and a suitable crystal was
grown for X-ray analysis. The compound was a multi-ring trimeric
heterocycle that further implicated a carbene intermediate in isoin-
dazole formation. This compound will be published in the full mecha-
nistic paper.
(18) von Richter, V. Chem. Ber. 1883, 16, 677-683.
J . Org. Chem, Vol. 67, No. 18, 2002 6399

Kimball et al.
heated to 50 °C and stirred under N2 overnight. After cooling,
the solvent was evaporated and the crude product was redis-
solved in 10-50% CH2Cl2 in hexanes and vacuum filtered
through a pad of silica gel. The solvent was evaporated to yield
the product that was either purified by column chromatogra-
phy on silica gel (butadiynes) or immediately desilylated as
below (ethynes).
use of 5 equiv of CuCl as the carbene (carbenoid)
stabilizer, 1,2-dichloroethane as the solvent, and a reac-
tion temperature of 50 °C for complete conversion to the
isoindazole in 12-36 h. Excellent yields were obtained
in most instances (Table 1). The exceptions were with
strongly electron-withdrawing systems (20, 53), where
dimer formation (16, 18′) was a competitive side reaction
at 50 °C; however, if the cyclization was conducted for 3
d at room temperature, the yields of 20 and 53 increased
to 85 and 78%, respectively, along with trace amounts of
dimer. Although using 5 equiv of CuCl gives complete,
exclusive production of isoindazole, the reaction can be
done in the presence of catalytic amounts of CuCl using
longer reaction times. For example, stirring a mixture
of 28 and 10 mol % CuCl for 3 d resulted in nearly
quantitative formation of 49.
Gen er a l Desilyla tion P r oced u r e D. The [2-(trimethyl-
silyl)ethynylphenyl]triazene (1 equiv) and K2CO3 (10 equiv)
were dissolved in THF/MeOH (5:1 v/v, 0.1 M) and the mixture
was stirred at rt for 4 h. The reaction was diluted with Et2O
and washed with saturated NH4Cl solution. The organic layer
was dried (MgSO4), filtered, and concentrated. Column chro-
matography on silica gel gave the desired product.
Gen er a l Cin n olin e F or m a tion P r oced u r e E. To a seal-
able glass pressure tube was added the (2-ethynylphenyl)-
triazene in 1,2-dichlorobenzene (0.05 M). The tube was sealed
and heated to 200 °C with stirring overnight. After cooling,
the solvent was evaporated and the crude product was purified
by preparative TLC to yield the cinnoline.
Con clu sion s
Gen er a l Isoin d a zole F or m a tion P r oced u r e F . The (2-
ethynylphenyl)triazene (0.2 mmol) was dissolved in 1,2-
dichloroethane (30 mL), and CuCl (1 mmol) was added. The
mixture was heated to 50 °C for 12-36 h. After cooling, the
metal salts were removed by vacuum filtration through a pad
of silica gel, eluting with 1:1 hexanes/CH2Cl2. The solvent was
evaporated, and the crude product was purified by preparative
TLC to yield the isoindazole.
A novel route for the selective synthesis of 2H-indazoles
and cinnolines from (2-alkynylphenyl)triazenes has been
developed. Unlike previous methods, these cyclizations
are done under neutral conditions that allow for greater
versatility and functional group tolerance. The ability to
generate both the isoindazole and the cinnoline from the
same starting material under the same conditions is
unique to our system. This reaction is also temperature
sensitive, allowing for either heterocycle to be synthesized
in excellent yield by increasing the reaction temperature
or adding CuCl. We are currently working on extending
this new methodology for the construction of other
heterocyclic compounds.
1-(4-Cyan o-2-iodoph en yl)-3,3-dieth yl-1-tr iazen e (8). Ami-
nobenzonitrile (5 g, 42.3 mmol), BTEA‚ICl2 (30 g, 76.9 mmol),
and CaCO3 (8.5 g, 84.9 mmol) were reacted using general
procedure A (done at reflux). The product was immediately
combined with HCl (9 mL, 110 mmol), NaNO2 (1.78 g, 25.8
mmol), Et2NH (14 mL, 135 mmol), and K2CO3 (6.87 g, 52
mmol) using general procedure B. Concentration of the organic
layer furnished 8 (3.62 g, 89%) as a brown solid in sufficiently
pure form for further elaboration: mp 78.1-79.8 °C; 1H NMR
(CDCl3) δ 8.09 (d, J ) 1.8 Hz, 1H), 7.53 (dd, J ) 7.8, 1.8 Hz,
1H), 7.41 (d, J ) 7.8 Hz, 1H), 3.85 (q, J ) 7.2 Hz, 4H), 1.37 (t,
J ) 7.2 Hz, 3H), 1.32 (t, J ) 7.2 Hz, 3H); 13C NMR (CDCl3) δ
153.85, 142.62, 132.32, 118.07, 117.13, 108.91, 95.82, 49.87,
42.99, 14.38, 10.78; IR (KBr) 3083, 2224 cm-1; HRMS calcd
Exp er im en ta l Section
Gen er a l Meth od s. Reagents and instrumentation used
have been described previously.6d,e
Gen er a l Iod in a tion P r oced u r e A. The starting aniline
(1 equiv), BTEA‚ICl2 (1.15 equiv), and CaCO3 (1.5 equiv) were
dissolved in 5:1 CHCl3/MeOH (0.1 M) and either stirred at rt
or heated to reflux under N2 for 24 h. The resulting mixture
was filtered, and the solvent was evaporated. The crude
product was redissolved in Et2O and washed successively with
NaHSO3 (5% by weight) and water. The combined organics
were dried (MgSO4), filtered, and concentrated to afford the
desired product in sufficiently pure form for further use.
Gen er a l Tr ia zen e F or m a tion P r oced u r e B. The iodoa-
niline (1 equiv) was dissolved in a minimum amount of MeCN,
after which HCl (12 M, 8 equiv) and ice (∼2 g) were added.
The suspension was cooled to -5 °C, and a solution of NaNO2
(2.2 equiv) in 3:1 water/MeCN (2 M) was added slowly such
that the temperature remained between -5 and -2 °C. Once
the addition was complete, the solution was stirred at -5 °C
for 30 min, after which time it was transferred slowly via
cannula to a quench solution of Et2NH (10 equiv), K2CO3 (5
equiv), and 3:1 water/MeCN (0.1 M) cooled to 0 °C. Once the
transfer was complete, the mixture was allowed to gradually
warm to rt overnight. The mixture was diluted with water and
extracted with Et2O. The combined organics were dried
(MgSO4), filtered, and concentrated. Column chromatography
on silica gel gave the desired product.
for C11H13IN4 329.0263, found 329.0263. Anal. Calcd for C11H13
-
IN4 (328.15): C, 40.26; H, 3.99; N, 17.07. Found: C, 40.36; H,
3.83; N, 16.81.
1-[4-Cyan o-2-[(4-tr im eth ylsilyl)bu ta-1,3-diyn yl]ph en yl]-
3,3-d ieth yl-1-tr ia zen e (3). Iodide 8 (1.67 g, 5.10 mmol),
1-(trimethylsilyl)-1,3-butadiyne (810 mg, 6.63 mmol), PdCl2-
(PPh3)2 (215 mg, 0.31 mmol), and CuI (136 mg, 0.71 mmol)
were reacted using general procedure C. Chromatography on
silica gel (6:1 hexanes/EtOAc, Rf ) 0.21) gave 3 (1.54 g, 94%)
as a dark red oil: 1H NMR (CDCl3) δ 7.72 (t, J ) 0.9 Hz, 1H),
7.48 (d, J ) 1.2 Hz, 2H), 3.85 (q, J ) 7.2 Hz, 4H), 1.37 (t, J )
7.5 Hz, 3H), 1.30 (t, J ) 6.9 Hz, 3H), 0.23 (s, 9H); 13C NMR
(CDCl3) δ 157.17, 137.74, 132.74, 118.60, 117.68, 117.15,
107.41, 91.78, 87.80, 79.39, 73.22, 49.84, 42.75, 14.35, 10.63,
-0.42; IR (neat) 3069, 2226, 2201, 2101, 1593 cm-1; HRMS
calcd for C18H23N4Si 323.1692, found 323.1695.
3,3-Dieth yl-1-[2-[(4-tr im eth ylsilyl)bu ta -1,3-d iyn yl]p h e-
n yl]-1-tr ia zen e (6). Iodide 96b (1.02 g, 3.36 mmol), 1-(trim-
ethylsilyl)-1,3-butadiyne (523 mg, 4.28 mmol), PdCl2(PPh3)2
(144 mg, 0.21 mmol), and CuI (72 mg, 0.38 mmol) were reacted
using general procedure C. Chromatography on silica gel (5:1
hexanes/CH2Cl2, Rf ) 0.18) gave 6 (361 mg, 36%) as a tan oil:
1H NMR (CDCl3) δ 7.47 (dd, J ) 7.8, 1.2 Hz, 1H), 7.37 (dd, J
) 8.1, 0.9 Hz, 1H), 7.28 (td, J ) 7.2, 1.5 Hz, 1H), 7.03 (td, J )
7.8, 1.5 Hz, 1H), 3.80 (q, J ) 7.2 Hz, 4H), 1.32 (t, J ) 6.6 Hz,
6H), 0.22 (s, 9H); 13C NMR (CDCl3) δ 154.45, 133.85, 129.80,
124.55, 117.29, 116.02, 90.15, 88.59, 77.76, 75.91, 49.08, 41.88,
14.46, 10.78, -0.30; IR (neat) 3066, 2200, 2100 cm-1; HRMS
calcd for C17H24N3Si 298.1740, found 298.1740.
Gen er a l Acetylen e Cou p lin g P r oced u r e C. The (2-
iodophenyl)triazene (1 equiv), PdCl2(PPh3)2 (0.04 equiv), CuI
(0.07 equiv), and either (trimethylsilyl)-1,3-butadiyne or (tri-
methylsilyl)acetylene (TMSA, 1.5 equiv) were dissolved in NEt3
(0.1 M solution based on triazene). The mixture was im-
mediately degassed by three successive freeze-pump-thaw
cycles, and the flask was charged with N2. The mixture was
6400 J . Org. Chem., Vol. 67, No. 18, 2002

Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes
1-[4-Nitr o-2-[(4-tr im eth ylsilylbu ta -1,3-d iyn yl]p h en yl]-
a zop ip er id in e (7). Iodide 106a (200 mg, 0.56 mmol), 1-(tri-
methylsilyl)-1,3-butadiyne (85 mg, 0.69 mmol), PdCl2(PPh3)2
(23 mg, 0.03 mmol), and CuI (15 mg, 0.08 mmol) were reacted
using general procedure C. Chromatography on silica gel (3:1
hexanes/CH2Cl2, Rf ) 0.33) provided 7 (173 mg, 88%) as a
Rf ) 0.25) to give 12 (306 mg, 98%) as beige needles. The
spectral data were identical to those given above.
1-Iodo-2-[(4-tr im eth ylsilyl)bu ta-1,3-diyn yl]ben zen e (13).
To a sealable glass pressure tube were added 6 (400 mg, 1.34
mmol) and MeI (10 mL). The tube was sealed and heated to
125 °C overnight. After cooling, the solvent was evaporated
and the residue purified by chromatography on silica gel (9:1
hexanes/CH2Cl2, Rf ) 0.30) to give 13 (429 mg, 95%) as a
yellow oil: 1H NMR (CDCl3) δ 7.83 (d, J ) 7.9 Hz, 1H), 7.48
(d, J ) 7.6 Hz, 1H), 7.30 (t, J ) 7.6 Hz, 1H), 7.03 (t, J ) 7.9
Hz, 1H), 0.25 (s, 9H); 13C NMR (CDCl3) δ 138.81, 134.13,
130.26, 128.30, 127.80, 100.81, 92.56, 87.50, 77.79, 77.52,
1
bright yellow powder: mp 161.3-163.6 °C; H NMR (CDCl3)
δ 8.36 (d, J ) 2.7 Hz, 1H), 8.10 (dd, J ) 9.3, 2.4 Hz, 1H), 7.57
(d, J ) 9.0 Hz, 1H), 4.04 (br s, 2H), 3.90 (br s, 2H), 1.78 (br s,
6H), 0.24 (s, 9H); 13C NMR (CDCl3) δ 158.61, 144.20, 130.23,
125.15, 117.39, 116.88, 92.37, 80.06, 79.70, 73.46, 53.99, 44.66,
26.75, 24.84, 24.34, -0.14; IR (KBr) 3080, 2200, 2098, 1600,
1571, 1332, 1097 cm-1; HRMS calcd for C18H23N4O2Si 355.1590,
found 355.1589.
-0.43; IR (KBr) 3062, 2205, 2102 cm-1
.
1-(4-Cya n o-2-eth yn ylp h en yl)-3,3-d ieth yltr ia zen e (14).
Iodide 8 (250 mg, 0.76 mmol), TMSA (0.14 mL, 0.95 mmol),
PdCl2(PPh3)2 (43 mg, 0.06 mmol), and CuI (20 mg, 0.11 mmol)
were reacted using general procedure C. The crude product
was immediately treated with K2CO3 (1.3 g, 9.8 mmol) using
general procedure D. Chromatography on silica gel (9:1 hex-
anes/EtOAc, Rf ) 0.35) gave 14 (152 mg, 88%) as a yellow
powder: mp 47.1-48.5 °C; 1H NMR (CDCl3) δ 7.76 (s, 1H),
7.51-7.49 (m, 2H), 3.84 (q, J ) 7.0 Hz, 4H), 3.32 (s, 1H), 1.36
(t, J ) 7.0 Hz, 3H), 1.28 (t, J ) 7.0 Hz, 3H); 13C NMR (CDCl3)
δ 156.02, 137.52, 132.53, 118.76, 117.95, 117.49, 107.40, 82.62,
79.91, 49.72, 42.53, 14.36, 10.67; IR (neat) 3292, 3070, 2226,
2108 cm-1; HRMS calcd for C13H15N4 227.1297, found 227.1298.
Anal. Calcd for C13H14N4 (226.28): C, 69.00; H, 6.24; N, 24.76.
Found: C, 68.77; H, 6.07; N, 24.50.
Cya n o Dim er 5. To a sealable glass pressure tube were
added 3 (1.10 g, 3.41 mmol) and MeI (40 mL). The tube was
sealed and heated overnight at 145 °C. After cooling, the
solvent was evaporated, and the crude product was puri-
fied by chromatography on silica gel (5:1 hexanes/EtOAc, Rf
) 0.31) to give 5 (363 mg, 33%) as a light yellow solid: mp
239.8-241.5 °C; 1H NMR (CDCl3) δ 8.22 (br s, 2H), 7.80 (d, J
) 9.0 Hz, 2H), 7.48 (dd, J ) 9.0, 1.5 Hz, 2H), 3.38 (q, J ) 6.9
Hz, 8H), 1.02 (t, J ) 6.6 Hz, 12H), -0.23 (s, 18H); 13C NMR
(CDCl3) δ 146.16, 132.96, 129.49, 126.77, 123.13, 119.87,
119.39, 117.39, 108.88, 105.25, 101.23, 51.97, 12.21, -1.16; IR
(KBr) 3068, 2226, 2155, 1629 cm-1; HRMS calcd for C36H45N8-
Si2 645.3306, found 645.3308. Anal. Calcd for C36H44N8Si2
(644.96): C, 67.04; H, 6.88; N, 17.37. Found: C, 66.79; H, 6.86;
N, 17.45. Isolation of an earlier band afforded iodide 4 (11 mg,
1-(2-Eth yn yl-4-n itr op h en yl)a zop ip er id in e (15). Iodide
10 (300 mg, 0.83 mmol), TMSA (0.15 mL, 1.08 mmol), PdCl2-
(PPh3)2 (35 mg, 0.05 mmol), and CuI (19 mg, 0.10 mmol) were
reacted using general procedure C. The crude product was
vacuum filtered through a pad of silica gel eluting with CH2-
Cl2. The solvent was evaporated, and the residue was im-
mediately treated with K2CO3 (1.65 g, 12.5 mmol) using
general procedure D. Chromatography on silica gel (3:2 hex-
anes/CH2Cl2, Rf ) 0.24) furnished 15 (154 mg, 72%) as a yellow
solid: mp 96-98.5 °C; 1H NMR (CDCl3) δ 8.35 (d, J ) 2.7
Hz, 1H), 8.09 (dd, J ) 9.3, 2.4 Hz, 1H), 7.57 (d, J ) 9.0 Hz,
1H), 4.01 (br s, 2H), 3.87 (br s, 2H), 3.36 (s, 1H), 1.74 (s,
6H); 13C NMR (CDCl3) δ 157.53, 144.16, 129.69, 124.85,
117.63, 117.07, 83.21, 80.07, 53.90, 44.51, 26.69, 24.76, 24.33;
IR (KBr) 3300, 3111, 2109, 1599, 1324 cm-1; HRMS calcd
for C13H15N4O2 259.1195, found 259.1201. Anal. Calcd for
1
10%) as a white solid: mp 109.2-110.9 °C; H NMR (CDCl3)
δ 7.89 (d, J ) 8.2 Hz, 1H), 7.69 (d, J ) 2.1 Hz, 1H), 7.26 (dd,
J ) 8.2, 2.1 Hz, 1H), 0.26 (s, 9H); 13C NMR (CDCl3) δ 139.94,
136.48, 132.17, 130.23, 117.27, 112.46, 106.90, 94.72, 86.76,
79.86, 75.46, -0.54; IR (KBr) 3060, 2232, 2099 cm-1; HRMS
calcd for C14H13INSi 349.9862, found 349.9869. Anal. Calcd
for C14H12INSi (349.24): C, 48.15; H, 3.46; N, 4.01. Found: C,
48.32; H, 3.51; N, 3.82.
4-Iod o-3-[(4-t r im et h ylsilyl)b u t a -1,3-d iyn yl]b en zon i-
tr ile (4). A solution of 3 (250 mg, 0.78 mmol) in MeI (10 mL)
was heated at 160 °C overnight in a sealed glass pressure tube.
After cooling, the solvent was evaporated and the residue
purified by chromatography on silica gel (3:2 hexanes/CH2Cl2,
Rf ) 0.36) to give 4 (268 mg, 98%) as a white solid. The spectral
data were identical to those given above.
Nitr o Dim er 11. To a sealable glass pressure tube were
added 7 (50 mg, 0.14 mmol) and MeI (5 mL). The tube was
sealed and heated at 145 °C with stirring for 48 h. After
cooling, the solvent was evaporated, and the crude product was
purified by chromatography on silica gel (1:1 hexanes/CH2Cl2,
Rf ) 0.05) to give 11 (18 mg, 36%) as a pale yellow solid: mp
C13H14N4O2 (258.28): C, 60.45; H, 5.46; N, 21.69. Found: C,
60.27; H, 5.65; N, 21.78.
Cya n o Dim er 16. To a sealable glass pressure tube were
added 14 (50 mg, 0.22 mmol) and MeI (8 mL). The tube was
sealed and stirred at 125 °C for 48 h. After cooling, the solvent
was evaporated and the crude product was purified by
preparative TLC (7:3 hexanes/EtOAc) to give a 2:1 mixture of
16 and 17 (20 mg, 40%) as a light yellow solid. Recrystalliza-
tion of the mixture from EtOH yielded trans dimer 16
exclusively: mp 224.6-226.4 °C; 1H NMR (CDCl3) δ 8.41-
8.40 (m, 2H), 7.93 (s, 2H), 7.82 (dd, J ) 8.7, 0.9 Hz, 2H), 7.53
(dd, J ) 8.7, 1.5 Hz, 2H), 3.48 (s, 2H), 3.36 (s, 2H), 0.90 (t, J
) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 146.66, 135.41, 128.08,
127.41, 120.02, 119.58, 118.16, 116.66, 106.03, 52.68, 12.15;
IR (KBr) 3071, 2220, 1620 cm-1; HRMS calcd for C26H28N8
452.2437, found 452.2437. Anal. Calcd for C26H28N8 (452.55):
C, 69.00; H, 6.24; N, 24.67. Found: C, 68.95; H, 6.16; N, 24.49.
Isolation of a second band furnished aldehyde 20 (5 mg, 9%)
1
247-249 °C dec; H NMR (CDCl3) δ 8.93 (d, J ) 2.1 Hz, 2H),
8.18 (dd, J ) 9.6, 2.1 Hz, 2H), 7.81 (d, J ) 9.3 Hz, 2H), 3.40
(br s, 8H), 1.97 (br s, 8H), 1.70 (br s, 4H), -0.22 (s, 18H); 13C
NMR (CDCl3) δ 147.05, 143.03, 132.94, 121.95, 120.68, 120.37,
118.98, 116.88, 108.09, 100.44, 56.42, 26.01, 23.36, -1.07; IR
(KBr) 3103, 2155, 1326 cm-1; HRMS calcd for C36H45N8O4Si2
709.3102, found 709.3097. Anal. Calcd for C36H44N8O4Si2
(708.97): C, 60.99; H, 6.26; N, 15.81. Found: C, 60.88; H, 6.16;
N, 15.97. Isolation of an earlier band afforded iodide 12 (14
mg, 27%) as a beige solid: mp 185.1-186.4 °C; 1H NMR
(CDCl3) δ 8.27 (d, J ) 2.6 Hz, 1H), 8.04 (d, J ) 8.8 Hz, 1H),
7.84 (dd, J ) 8.8, 2.6 Hz, 1H), 0.26 (s, 9H); 13C NMR (CDCl3)
δ 147.74, 139.97, 130.31, 128.16, 124.08, 109.11, 94.91, 86.71,
79.97, 75.54, -0.55; IR (KBr) 3095, 2100, 1348 cm-1. Anal.
Calcd for C13H12INO2Si (369.24): C, 42.29; H, 3.28; N, 3.79.
Found: C, 42.34; H, 3.25; N, 3.68.
1
as a yellow powder: mp 165.8-167.2 °C; H NMR (CDCl3) δ
10.41 (s, 1H), 8.66 (t, J ) 1.1 Hz, 1H), 7.88 (dd, J ) 8.7, 0.9
Hz, 1H), 7.56 (dd, J ) 8.7, 1.5 Hz, 1H), 3.46-3.34 (m, 4H),
0.90 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 180.99, 146.03,
133.62, 128.67, 128.22, 119.70, 118.75, 109.68, 52.81, 11.98;
IR (KBr) 3077, 3026, 2227, 1670, 1627 cm-1; HRMS calcd for
C13H15N4O 243.1246, found 243.1245. Anal. Calcd for C13H14N4O
(242.28): C, 64.18; H, 6.21; N, 23.03. Found: C, 64.20; H, 5.94;
N, 22.91.
1-Iod o-4-n itr o-2-[(4-tr im eth ylsilyl)bu ta -1,3-d iyn yl]ben -
zen e (12). A solution of 7 (300 mg, 0.85 mmol) in MeI (10 mL)
was heated to 160 °C overnight in a sealed glass pressure tube.
After cooling, the solvent was evaporated and the residue
purified by chromatography on silica gel (3:2 hexanes/CH2Cl2,
J . Org. Chem, Vol. 67, No. 18, 2002 6401

Kimball et al.
Nitr o Dim er 18. To a sealable glass pressure tube were
added 15 (52 mg, 0.20 mmol) and MeI (5 mL). The tube was
sealed and stirred overnight at 150 °C. After cooling, the
solvent was evaporated and the crude product was purified
by preparative TLC (1:1 hexanes/CH2Cl2) to give a 1:1 mixture
of 18 and 19 (26 mg, 52%) as an orange solid. Recrystallization
of the mixture from EtOH yielded trans dimer 18 exclusively:
1-(4-ter t-Bu tyl-2-iodoph en yl)-3,3-dieth yl-1-tr iazen e (34).
4-tert-Butylaniline (0.96 mL, 6.0 mmol) was reacted using
general procedure A (rt) and general procedure B using the
same quantities of reagents described for 33. After workup,
34 (1.93 g, 89%) was obtained as a yellow oil in sufficiently
pure form for further elaboration: 1H NMR (CDCl3) δ 7.81 (d,
J ) 1.7 Hz,1H), 7.29 (dd, J ) 8.4, 1.7, 2H), 7.25 (d, J ) 8.4
Hz, 1H), 3.76 (q, J ) 7.2 Hz, 4H), 1.29 (t, J ) 7.2 Hz, 6H),
1.28 (s, 9H); 13C NMR (CDCl3) δ 149.80, 136.82, 135.86, 125.91,
116.91, 96.62, 49.15 (br), 41.96 (br), 34.29, 31.32, 14.54 (br),
11.22 (br); IR (neat) 3067 cm-1; HRMS calcd for C14H23N3I
360.0937, found 360.0938.
1
mp 351-352 °C dec; H NMR (CDCl3) δ 9.12 (d, J ) 2.4 Hz,
2H), 8.23 (dd, J ) 9.6, 2.1 Hz, 2H), 8.11 (s, 2H), 7.82 (d, J )
9.3 Hz, 2H), 3.39-3.35 (m, 8H), 2.06-1.98 (m, 8H), 1.72 (s,
4H); 13C NMR (CDCl3) δ 147.65, 143.80, 134.05, 121.07, 119.67,
119.28, 118.03, 116.55, 56.90, 26.39, 23.57; IR (KBr) 3099,
3080, 1616, 1327 cm-1; HRMS calcd for C26H28N8O4 516.2234,
found 516.2235. Anal. Calcd for C26H28N8O4 (516.55): C, 60.45;
H, 5.46; N, 21.69. Found: C, 60.34; H, 5.38; N, 21.88. Isolation
of a second band furnished aldehyde 21 (7 mg, 13% yield) as
a dark orange powder: mp 172.9-173.7 °C; 1H NMR (CDCl3)
δ 10.44 (s, 1H), 9.11 (d, J ) 1.5 Hz, 1H), 8.19 (dd, J ) 9.3, 2.1
Hz, 1H), 7.86 (d, J ) 9.3 Hz, 1H), 3.39 (t, J ) 5.7 Hz, 4H),
1.95-1.87 (m, 4H), 1.69-1.65 (m, 2H); 13C NMR (CDCl3) δ
180.30, 146.53, 146.00, 131.45, 121.27, 119.44, 119.36, 118.49,
57.50, 25.70, 23.02; IR (KBr) 3099, 3084, 1668, 1624, 1339
cm-1; HRMS calcd for C13H15N4O3 275.1144, found 275.1143.
Anal. Calcd for C13H14N4O3 (274.28): C, 56.93; H, 5.14; N,
21.69. Found: C, 56.48; H, 5.10; N, 21.88.
1-(4-Br om o-2-iod op h en yl)-3,3-d ieth yl-1-tr ia zen e (35).
4-Bromoaniline (1.01 g, 5.88 mmol) was reacted using general
procedure A (rt) and general procedure B using the same
quantities of reagents described for 33. After workup, 35 (2.06
g, 92%) was obtained as a red oil in sufficiently pure form for
further elaboration: 1H NMR (CDCl3) δ 7.96 (d, J ) 2.1 Hz,
1H), 7.38 (dd, J ) 8.7, 2.1 Hz, 1H), 7.23 (d, J ) 8.4 Hz, 1H),
3.79 (q, J ) 7.2 Hz, 4H), 1.31 (br s, 6H); 13C NMR (CDCl3) δ
149.52, 140.68, 131.54, 118.19, 118.13, 96.86, 49.29, 42.32,
14.49, 10.87; IR (neat) 3061 cm-1; HRMS calcd for C10H13N3
BrI 380.9338, found 380.9337.
-
79
1-(4-Ch lor o-2-iod op h en yl)-3,3-d ieth yl-1-tr ia zen e (36).
4-Chloroaniline (0.75 g, 5.88 mmol) was reacted using general
procedure A (rt) and general procedure B using the same
quantities of reagents described for 33. After workup, 36 (1.61
g, 81%) was obtained as a red oil in sufficiently pure form for
further elaboration: 1H NMR (CDCl3) δ 7.81 (d, J ) 2.1 Hz,
1H), 7.29 (d, J ) 8.4 Hz, 1H), 7.24 (dd, J ) 8.4, 1.2 Hz, 1H),
3.79 (q, J ) 7.5 Hz, 4H), 1.32 (s, 6H); 13C NMR (CDCl3) δ
3-Acyl-5-cya n o-2-d ieth yla m in o-2H-in d a zole (22). To a
sealable glass pressure tube were added 3 (50 mg, 0.16 mmol)
and ODCB (5 mL). The tube was sealed and stirred at 165 °C
overnight. After cooling, the solvent was evaporated and the
crude product was purified by preparative TLC (4:1 hexanes/
EtOAc, Rf ) 0.25) to give 22 (26 mg, 96%) as a tan oil: 1H
NMR (CDCl3) δ 8.70-8.69 (m, 1H), 7.79 (dd, J ) 8.7, 0.9 Hz,
1H), 7.50 (dd, J ) 8.7, 1.5 Hz, 1H), 3.39 (br d, 4H), 2.86 (s,
3H), 0.93 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 189.35,
145.71, 134.24, 130.33, 127.76, 120.30, 119.42, 119.16, 108.93,
52.77, 30.78, 11.79; IR (neat) 3104, 3080, 2253, 2225, 1661,
1625 cm-1; HRMS calcd for C14H17N4O 257.1402, found
257.1403.
3-Acyl-2-d ieth yla m in o-2H-in d a zole (23) a n d 2-Dieth y-
la m in o-3-(3-t r im et h ylsilyl-2-p r op yn -1-oyl)-2H -in d a zole
(24). To a sealable glass pressure tube were added 6 (63 mg,
0.21 mmol) and ODCB (5 mL). The tube was sealed and stirred
at 155 °C for 48 h. After cooling, the solvent was evaporated
and the crude product was purified by chromatography on
silica gel (1:1 hexanes/CH2Cl2) to give 23 (15 mg, 31% yield,
Rf ) 0.1) as a yellow oil: 1H NMR (CDCl3) δ 8.25 (d, J ) 8.7
Hz, 1H), 7.75 (d, J ) 8.4 Hz, 1H), 7.42-7.30 (m, 2H), 3.47 (br
s, 2H), 3.31 (br s, 2H), 2.86 (s, 3H), 0.94 (t, J ) 6.9 Hz, 6H);
13C NMR (CDCl3) δ 189.68, 145.63, 133.22, 126.89, 125.72,
122.43, 121.39, 117.74, 52.63, 30.83, 11.86; IR (neat) 3072,
3056, 1659, 1625 cm-1; HRMS calcd for C13H18N3O 232.1450,
found 232.1452. Isolation of an earlier band (Rf ) 0.18)
furnished 24 (12 mg, 18% yield) as an unstable tan oil: 1H
NMR (CDCl3) δ 8.30 (d, J ) 7.5 Hz, 1H), 7.79 (d, J ) 7.8 Hz,
1H), 7.45-7.33 (m, 2H), 3.44 (br s, 2H), 3.28 (br s, 2H), 0.95
(t, J ) 7.2 Hz, 6H), 0.32 (s, 9H); IR (neat) 3058, 2153, 1737,
1599, 846 cm-1; HRMS calcd for C17H24N3OSi 314.1689, found
314.1694.
149.12, 138.03, 130.45, 128.68, 117.69, 96.28, 49.25, 42.25,
14.49, 10.88; IR (neat) 3062 cm-1; HRMS calcd for C10H13N3
ClI 336.9843, found 336.9838.
-
35
3,3-Dieth yl-1-(4-flu or o-2-iod op h en yl)-1-tr ia zen e (37).
4-Fluoroaniline (0.56 mL, 5.88 mmol) was reacted using
general procedure A (rt) and general procedure B using the
same quantities of reagents described for 33. After workup,
37 (1.12 g, 59%) was obtained as a red oil: 1H NMR (CDCl3)
δ 7.56 (dd, J ) 7.9, 2.6 Hz, 1H), 7.31 (dd, J ) 9.1, 5.9 Hz, 1H),
7.01 (ddd, J ) 9.1, 7.9, 3.0 Hz, 1H), 3.79 (q, J ) 7.1 Hz, 4H),
1.32 (t, J ) 7.1 Hz, 6H); 13C NMR (CDCl3) δ 159.90 (d, J )
248.8 Hz), 147.03, 125.34 (d, J ) 24.1 Hz), 117.57 (d, J ) 8.3
Hz), 115.62 (d, J ) 22.2 Hz), 95.55 (d, J ) 8.3 Hz), 49.11, 42.17,
14.53, 10.98; IR (neat) 3068 cm-1; HRMS calcd for C10H14N3-
FI 322.0217, found 322.0226.
1-(4-Ca r bom eth oxy-2-iod op h en yl)-3,3-d ieth yl-1-tr ia z-
en e (38). Methyl 4-aminobenzoate (5.00 g, 33.1 mmol), BTEA‚
ICl2 (22.1 g, 56.2 mol), CaCO3 (5.00 g, 49.6 mmol), and CH2Cl2/
MeOH (300 mL, 2:1 v:v) were combined using general procedure
A. The solvent volume was reduced in half by rotary evapora-
tion, and the solution was washed with saturated Na2S2O3
solution and dried (MgSO4). Removal of the solvent yielded
9.16 g (∼99% yield) of product as a brown powder. The crude
product (1.52 g, 5.5 mmol) was immediately dissolved in MeCN
(5.0 mL) and treated with concd HCl (1.35 mL, 44.0 mmol),
NaNO2 (759 mg, 11.0 mmol), Et2NH (5.7 mL, 55.0 mmol), and
K2CO3 (4.60 g, 33.0 mmol) using general procedure B. This
mixture was diluted with CH2Cl2, washed with saturated
NaHCO3 solution, dried (MgSO4), and filtered. Concentration
of the solution furnished 38 (1.67 g, 84%) as a yellow oil: 1H
NMR (CDCl3) δ 8.52 (d, J ) 1.8 Hz, 1H), 7.94 (dd, J ) 8.7, 1.8
Hz, 1H), 7.39 (d, J ) 8.7 Hz, 1H), 3.90 (s, 3H), 3.84 (q, J ) 7.2
3,3-Dieth yl-1-(2-iod o-4-m eth ylp h en yl)-1-tr ia zen e (33).
p-Toluidine (0.63 g, 5.88 mmol), BTEA‚ICl2 (2.63 g, 6.75 mol),
and CaCO3 (0.84 g, 8.41 mmol) were reacted using general
procedure A (rt). The crude product was immediately treated
with HCl (4 mL, 48 mmol), NaNO2 (0.93 g, 13.4 mmol), Et2-
NH (6.21 mL, 60 mmol), and K2CO3 (4 g, 30 mmol) using
general procedure B. Chromatography on silica gel (9:1 hex-
anes/CH2Cl2, Rf ) 0.2) gave 33 (1.48 g, 79%) as a pale yellow
liquid: 1H NMR (CDCl3) δ 7.68 (d, J ) 1.3 Hz, 1H), 7.25 (d, J
) 8.2 Hz, 1H), 7.08 (dd, J ) 8.2, 1.3, 1H), 3.78 (q, J ) 7.0 Hz,
4H), 2.29 (s, 3H), 1.32 (t, J ) 7.0 Hz, 6H); 13C NMR (CDCl3) δ
148.14, 139.22, 136.34, 129.46, 117.02, 96.45, 49.00 (br), 42.06
Hz, 4H), 1.37 (t, J ) 7.5 Hz, 3H), 1.33 (t, J ) 6.9 Hz, 3H); 13
C
NMR (CDCl3) δ 165.88, 153.87, 140.70, 140.67, 130.08, 127.54,
116.64, 95.75, 52.07, 49.60, 42.65, 14.43, 10.88; IR (neat) 3067,
1708 cm-1; HRMS calcd for C12H16N3O2I 361.0287, found
361.0289.
3,3-Dieth yl-1-(2-iodo-4-n itr oph en yl)-1-tr iazen e (39). 4-Ni-
troaniline (0.94 g, 6.79 mmol), BTEA‚ICl2 (3.04 g, 7.79 mmol),
and CaCO3 (0.97 g, 9.71 mmol) were reacted using general
procedure A (reflux). Chromatography on silica gel (2:1 hex-
(br), 20.34, 14.10 (br), 11.09 (br); IR (neat) 3057, 3023 cm-1
HRMS calcd for C11H17N3I 318.0467, found 318.0470.
;
6402 J . Org. Chem., Vol. 67, No. 18, 2002

Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes
anes/EtOAc, Rf ) 0.4) gave the iodinated product (0.94 g). This
compound was treated with HCl (2.4 mL, 29 mmol), NaNO2
(0.56 g, 8.12 mmol), Et2NH (3.5 mL, 34 mmol), and K2CO3 (2.4
g, 20 mmol) using general procedure B. Chromatography on
silica gel (1:1 hexanes/CH2Cl2, Rf ) 0.4) provided 39 (875 mg,
product was immediately treated with K2CO3 (12.6 g, 95 mmol)
using general procedure D. Chromatography on silica gel (4:1
hexanes/CH2Cl2, Rf ) 0.21) gave 29 (650 mg, 58%) as a yellow
liquid: 1H NMR (CDCl3) δ 7.45 (d, J ) 2.4 Hz, 1H), 7.35 (d, J
) 9.0 Hz, 1H), 7.22 (dd, J ) 8.7, 2.4 Hz, 1H), 3.79 (q, J ) 7.2
Hz, 4H), 3.28 (s, 1H), 1.30 (s, 6H); 13C NMR (CDCl3) δ 151.65,
132.78, 129.48, 129.39, 118.21, 118.12, 81.81, 80.73, 49.14,
41.82, 14.42, 10.79; IR (neat) 3300, 3067, 2108 cm-1; HRMS
calcd for C12H14N335Cl 235.0876, found 235.0874.
3,3-Dieth yl-1-(2-eth yn yl-4-flu or oph en yl)-1-tr iazen e (30).
Fluoride 37 (1.12 g, 3.49 mmol), TMSA (0.641 mL, 4.53 mmol),
PdCl2(PPh3)2 (147 mg, 0.21 mmol), and CuI (80 mg, 0.42 mmol)
were reacted using general procedure C. The crude product
was immediately treated with K2CO3 (5.0 g, 37.8 mmol) using
general procedure D. After workup, chromatography on silica
gel (4:1 hexanes/CH2Cl2, Rf ) 0.32) gave 30 (0.64 g, 83%) as a
dark red oil: 1H NMR (CDCl3) δ 7.36 (dd, J ) 8.7, 5.6 Hz,
1H), 7.17 (dd, J ) 9.1, 2.9 Hz, 1H), 6.99 (ddd, J ) 9.0, 8.2, 3.0
Hz, 1H), 3.78 (q, J ) 7.5 Hz, 4H), 3.27 (s, 1H), 1.30 (t, J ) 7.2
Hz, 6H); 13C NMR (CDCl3) δ 159.59 (d, J ) 243.2 Hz), 149.68,
119.35 (d, J ) 24.1 Hz), 118.31 (d, J ) 9.3 Hz), 117.96 (d, J )
9.3 Hz), 116.72 (d, J ) 22.2 Hz), 81.66, 80.91, 48.96 (br), 41.68
(br), 14.74 (br), 10.72 (br); IR (neat) 3302, 3074, 2108, 1602,
1578 cm-1; HRMS calcd for C12H15N3F 220.1250, found
220.1247.
1
37%) as an orange solid: mp 71.8-73.4 °C; H NMR (CDCl3)
δ 8.71 (d, J ) 2.3 Hz, 1H), 8.14 (dd, J ) 8.8, 2.3 Hz, 1H), 7.44
(d, J ) 8.8 Hz, 1H), 3.88 (q, J ) 7.0 Hz, 4H), 1.39 (t, J ) 7.3
Hz, 3H), 1.33 (t, J ) 7.3 Hz, 3H); 13C NMR (CDCl3) δ 155.31,
144.50, 134.81, 124.17, 116.26, 95.02, 50.06, 43.20, 14.34,
10.73; IR (KBr) 3088, 3069, 1320 cm-1; HRMS calcd for C10H14
IN4O2 349.0162, found 349.0167.
-
3,3-Dieth yl-1-(2-eth yn yl-4-m eth ylph en yl)-1-tr iazen e (25).
Iodide 33 (1.40 g, 4.41 mmol), TMSA (0.91 mL, 6.42 mmol),
PdCl2(PPh3)2 (235 mg, 0.34 mmol), and CuI (128 mg, 0.67
mmol) were reacted using general procedure C. The crude
product was immediately treated with K2CO3 (10 g, 76 mmol)
using general procedure D. Chromatography on silica gel (4:1
hexanes/CH2Cl2, Rf ) 0.15) gave 25 (730 mg, 77%) as a deep
red oil: 1H NMR (CDCl3) δ 7.31 (d, J ) 2.3 Hz, 1H), 7.29 (d,
J ) 8.4 Hz, 1H), 7.09 (dd, J ) 8.5, 2.1 Hz, 1H), 3.78 (q, J )
7.0 Hz, 4H), 3.23 (s, 1H), 2.30 (s, 3H), 1.30 (t, J ) 7.0 Hz, 6H);
13C NMR (CDCl3) δ 150.88, 134.15, 133.69, 130.29, 116.85,
116.61, 82.22, 80.35, 48.52 (br), 41.65 (br), 20.67, 14.03 (br),
10.78 (br); IR (neat) 3292, 3062, 3024, 2103 cm-1; HRMS calcd
for C13H18N3 216.1501, found 216.1500.
1-(4-ter t-Bu t yl-2-et h yn ylp h en yl)-3,3-d iet h yl-1-t r ia z-
en e (26). Iodide 34 (1.93 g, 5.37 mmol), TMSA (1.9 mL, 13.6
mmol), PdCl2(PPh3)2 (252 mg, 0.36 mmol), and CuI (137 mg,
0.72 mmol) were reacted using general procedure C. The crude
product was immediately treated with K2CO3 (14 g, 100 mmol)
using general procedure D. Chromatography on silica gel (4:1
hexanes/CH2Cl2, Rf ) 0.13) gave 26 (720 mg, 52%) as a yellow
oil: 1H NMR (CDCl3) δ 7.51 (br s, 1H), 7.32 (br s, 2H), 3.78 (q,
J ) 7.0 Hz, 4H), 3.23 (s, 1H), 1.31 (s, 9H), 1.30 (m, 6H); 13C
NMR (CDCl3) δ 150.79, 147.51, 130.17, 126.73, 116.68, 116.21,
82.69, 80.00, 48.66 (br), 41.71 (br), 34.29, 31.23, 14.09, 10.95;
IR (neat) 3314, 3293, 3097, 3067, 3032, 2106 cm-1; HRMS calcd
for C16H24N3 258.1970, found 258.1977.
3,3-Dieth yl-1-(2,4-dieth yn ylph en yl)-1-tr iazen e (27). Bro-
mide 35 (500 mg, 1.3 mmol), TMSA (0.47 mL, 2.9 mmol), PdCl2-
(PPh3)2 (36 mg, 0.05 mmol), and CuI (35 mg, 0.18 mmol) were
reacted using general procedure C. The crude product was
immediately treated with K2CO3 (2.9 g, 22 mmol) using general
procedure D. Chromatography on silica gel (3:1 hexanes/CH2-
Cl2, Rf ) 0.21) gave 27 (270 mg, 92%) as a yellow solid: mp
93.7-96.4 °C; 1H NMR (CDCl3) δ 7.64 (d, J ) 1.2 Hz, 1H),
7.39-7.37 (m, 2H), 3.78 (q, J ) 7.2 Hz, 4H), 3.26 (s, 1H), 3.07
(s, 1H), 1.29 (br s, 6H); 13C NMR (CDCl3) δ 153.02, 137.21,
132.91, 117.92, 117.07, 116.85, 83.15, 81.26, 81.01, 77.12, 49.20
(br), 41.99 (br), 14.44 (br), 10.78 (br); IR (KBr) 3286, 3261,
3065, 3031, 2104 cm-1; HRMS calcd for C12H16N3 202.1344,
found 202.1341. Anal. Calcd for C14H15N3 (225.29): C, 74.64;
H, 6.71; N, 18.65. Found: C, 74.52; H, 6.47; N, 18.67.
1-(4-Ca r bom eth oxy-2-eth yn ylp h en yl)-3,3-d ieth yl-1-tr i-
a zen e (31). Ester 38 (600 mg, 1.66 mmol), TMSA (0.33 mL,
2.33 mmol), PdCl2(PPh3)2 (70 mg, 0.10 mmol), and CuI (38 mg,
0.20 mmol) were reacted using general procedure C. The crude
product was purified by chromatography on silica gel (1:1
hexanes/CH2Cl2, Rf ) 0.3) and subsequently treated with K2-
CO3 (6.02 g, 46 mmol) using general procedure D. Chroma-
tography on silica gel (1:1 hexanes/CH2Cl2, Rf ) 0.13) gave 31
(170 mg, 40%) as a yellow oil: 1H NMR (CDCl3) δ 8.17 (d, J )
2.1 Hz, 1H), 7.91 (dd, J ) 8.8, 2.1 Hz, 1H), 7.44 (d, J ) 8.8 Hz,
1H), 3.87 (s, 3H), 3.79 (q, J ) 6.9 Hz, 4H), 3.27 (s, 1H), 1.36-
1.22 (m, 6H); 13C NMR (CDCl3) δ 166.30, 156.22, 135.23,
130.42, 125.77, 116.84, 116.56, 81.30, 81.06, 51.89, 49.37,
42.12, 14.31, 10.63; IR (neat) 3294, 3073, 2107, 1718 cm-1
HRMS calcd for C14H18N3O2 260.1399, found 260.1399.
;
3,3-Dieth yl-1-(2-eth yn yl-4-n itr op h en yl)-1-tr ia zen e (32).
Nitro 39 (800 mg, 2.30 mmol), TMSA (0.49 mL, 3.45 mmol),
PdCl2(PPh3)2 (65 mg, 0.09 mmol), and CuI (39 mg, 0.21 mmol)
were reacted using general procedure C. The crude product
was immediately treated with K2CO3 (4.56 g, 35 mmol) using
general procedure D. Chromatography on silica gel (1:1 hex-
anes/CH2Cl2, Rf ) 0.35) gave 32 (540 mg, 95%) as a yellow
1
powder: mp 106.5-108.7 °C; H NMR (CDCl3) δ 8.36 (d, J )
2.6 Hz, 1H), 8.10 (dd, J ) 9.1, 2.6 Hz, 1H), 7.53 (d, J ) 9.1 Hz,
1H), 3.87 (q, J ) 7.3 Hz, 4H), 3.33 (s, 1H), 1.38 (t, J ) 7.3 Hz,
3H), 1.30 (t, J ) 7.0 Hz, 3H); 13C NMR (CDCl3) δ 157.61,
143.72, 129.31, 124.56, 117.39, 116.85, 82.64, 79.89, 49.90,
42.75, 14.33, 10.64; IR (neat) 3295, 3101, 3082, 2111, 1603,
1326 cm-1; HRMS calcd for C12H15N4O2 247.1195, found
247.1194. Anal. Calcd for C12H14N4O2 (246.27): C, 58.53; H,
5.73; N, 22.75. Found: C, 58.41; H, 5.50; N, 22.58.
1-(4-Br om o-2-eth yn ylph en yl)-3,3-dieth yl-1-tr iazen e (28).
Bromide 35 (2.13 g, 5.58 mmol), TMSA (0.91 mL, 6.42 mmol),
PdCl2(PPh3)2 (186 mg, 0.26 mmol), and CuI (101 mg, 0.53
mmol) were reacted using general procedure C (stirred at rt
after degassing). The crude product was immediately treated
with K2CO3 (10 g, 76 mmol) using general procedure D.
Chromatography on silica gel (4:1 hexanes/CH2Cl2, Rf ) 0.15)
gave 28 (780 mg, 50%) as a pale yellow oil: 1H NMR (CDCl3)
δ 7.61 (d, J ) 2.3 Hz, 1H), 7.37 (dd, J ) 9.7, 2.2 Hz, 1H), 7.28
(d, J ) 9.8 Hz, 1H), 3.78 (q, J ) 7.5 Hz, 4H), 3.28 (s, 1H), 1.30
(br s, 6H); 13C NMR (CDCl3) δ 152.07, 135.69, 132.33, 118.65,
118.41, 116.97, 81.90, 80.59, 49.16 (br), 41.85 (br), 14.47 (br),
10.77 (br); IR (neat) 3298, 3064, 2107 cm-1; HRMS calcd for
3,3-Dieth yl-1-(2-iodo-4-m eth oxyph en yl)-1-tr iazen e (43).
To a mixture of 4-amino-3-iodophenol12 (1.8 g, 7.7 mmol) and
Cs2CO3 (6.2 g, 19 mmol) in DMF (50 mL) was added MeI (0.45
mL, 7.2 mmol) in ca. 75 µL portions over 6 h. The mixture
was stirred at ambient temperature for 48 h, diluted with
water, and extracted with Et2O. The combined organics were
washed with water, dried (MgSO4), filtered, and concentrated
to give a light brown oil: 1H NMR (CDCl3) δ 7.21 (d, J ) 2.6
Hz, 1H), 6.77 (dd, J ) 8.8, 2.6 Hz, 1H), 6.70 (d, J ) 8.8 Hz,
1H), 3.72 (s, 3H); 13C NMR (CDCl3) δ 152.67, 140.77, 123.45,
116.09, 115.37, 84.24, 55.91.
The above methyl ether (1.72 g, 6.9 mmol) was immediately
reacted with HCl (0.88 mL, 10.5 mmol), NaNO2 (230 mg, 3.3
mmol), Et2NH (1.57 mL, 15 mmol), and K2CO3 (992 mg, 7.5
mmol) using general procedure B. After workup, column
chromatography on silica gel (3:1 hexanes/CH2Cl2, Rf ) 0.4)
C
12H15N379Br 280.0449, found 280.0444.
1-(4-Ch lor o-2-eth yn ylph en yl)-3,3-dieth yl-1-tr iazen e (29).
Chloride 36 (1.61 g, 4.77 mmol), TMSA (0.94 mL, 6.68 mmol),
PdCl2(PPh3)2 (201 mg, 0.29 mmol), and CuI (109 mg, 0.57
mmol) were reacted using general procedure C. The crude
J . Org. Chem, Vol. 67, No. 18, 2002 6403

Kimball et al.
gave 43 (2.22 g, 87% from 4-amino-3-iodophenol) as a tan oil:
1H NMR (CDCl3) δ 7.38 (d, J ) 2.6 Hz, 1H), 7.30 (d, J ) 8.8
Hz, 1H), 6.87 (dd, J ) 8.8, 2.6 Hz, 1H), 3.78 (s, 3H), 3.76 (q, J
) 7.0 Hz, 4H), 1.31 (t, J ) 7.0 Hz, 6H); 13C NMR (CDCl3) δ
157.50, 144.38, 123.14, 117.53, 115.29, 96.65, 55.66, 48.00 (br),
42.22 (br), 12.00 (br); IR (neat) 3067, 1104, 1037 cm-1; MS
(ESI) m/z 334.0 (20, M+ + H), 261.0 (10, M+ - C4H10N).
3,3-Die t h yl-1-(2-e t h yn yl-4-m e t h oxyp h e n yl)-1-t r ia z-
en e (40). Iodoether 43 (430 mg, 1.3 mmol), TMSA (0.26 mL,
1.8 mmol), PdCl2(PPh3)2 (36 mg, 0.05 mmol), and CuI (27 mg,
0.14 mmol) were reacted using general procedure C. The crude
product was immediately treated with K2CO3 (859 mg, 6.5
mmol) using general procedure D. After workup, 40 (290 mg,
97%) was obtained as a dark oil: 1H NMR (CDCl3) δ 7.35 (d,
J ) 9.1 Hz, 1H), 7.01 (d, J ) 2.9 Hz, 1H), 6.87 (dd, J ) 9.1,
2.9 Hz, 1H), 3.79 (s, 3H), 3.76 (q, J ) 7.3 Hz, 4H), 3.25 (s,
1H), 1.29 (t, J ) 7.3 Hz, 6H); 13C NMR (CDCl3) δ 156.56,
147.23, 118.05, 117.45, 116.77, 116.69, 81.97, 80.71, 55.51,
48.00 (br s), 43.00 (br s), 13.00 (br s); IR (neat) 3287, 2104,
1037 cm-1; MS (ESI) m/z 232.1 (100, M+ + H), 161.1 (70, M+
- C4H10N).
1-(4-Acetoxy-2-iod op h en yl)-3,3-d ieth yl-1-tr ia zen e (44).
4-Amino-3-iodophenol12 (705 mg, 3.0 mmol) was treated with
Ac2O (3.0 mL, 3.0 mmol) in pyridine (50 mL) according to the
method of Theobold.24 Evaporation of the solvent and purifica-
tion by chromatography on silica gel (3:2 hexanes/EtOAc) gave
the corresponding ester (650 mg, 73%) as an off-white solid:
1H NMR (CDCl3) δ 7.37 (d, J ) 2.6 Hz, 1H), 6.89 (dd, J ) 8.5,
2.6 Hz, 1H), 6.71 (d, J ) 8.5 Hz, 1H), 4.05 (br s, 2H), 2.25 (s,
3H); 13C NMR (CDCl3) δ 169.80, 144.84, 142.29, 131.34, 122.51,
114.26, 82.76, 20.92.
27-28.5 °C; 1H NMR (CDCl3) δ 10.38 (s, 1H), 8.01 (s, 1H), 7.70
(d, J ) 8.8 Hz, 1H), 7.27 (d, J ) 8.8 Hz, 1H), 3.43 (br s, 2H),
3.30 (br s, 2H), 2.49 (s, 3H), 0.88 (t, J ) 4.5 Hz, 6H); 13C NMR
(CDCl3) δ 181.46, 144.63, 136.67, 132.28, 129.94, 120.24,
119.63, 117.90, 52.64, 21.98, 12.02; IR (KBr) 3061, 3028, 1671,
1631 cm-1; HRMS calcd for C13H18N3O 232.1450, found
232.1448. Anal. Calcd for C13H17N3O (231.29): C, 67.51; H,
7.41; N, 18.17. Found: C, 67.58; H, 7.37; N, 17.94.
5-ter t-Bu tyl-2-d ieth yla m in o-3-for m yl-2H-in d a zole (47).
Obtained from 26 using general procedure F (colorless oil that
solidifies on standing, 96%): mp 79-81.5 °C; 1H NMR (CDCl3)
δ 10.40 (s, 1H), 8.15 (d, J ) 1.2 Hz, 1H), 7.74 (d, J ) 9.1 Hz,
1H), 7.55 (dd, J ) 9.1, 1.7 Hz, 1H), 3.37 (br s br, 4H), 1.40 (s,
9H), 0.88 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 181.52,
149.77, 144.51, 132.79, 126.76, 119.97, 117.76, 115.71, 52.64,
35.27, 31.22, 12.02; IR (neat) 3071, 3034, 1669 cm-1; HRMS
calcd for C16H24N3O 274.1919, found 274.1916.
2-Diet h yla m in o-5-et h yn yl-3-for m yl-2H -in d a zole (48).
Obtained from 27 using general procedure F (orange solid,
1
91%): mp 97-98.2 °C; H NMR (CDCl3) δ 10.39 (s, 1H), 8.42
(s, 1H), 7.73 (d, J ) 8.8 Hz, 1H), 7.48 (d, J ) 8.9 Hz, 1H), 3.36
(br s, 4H), 3.15 (s, 1H), 0.89 (t, J ) 7.0 Hz, 6H); 13C NMR
(CDCl3) δ 181.17, 145.13, 132.85, 130.47, 125.94, 120.12,
119.40, 118.38, 83.82, 77.89, 52.69, 12.00; IR (KBr) 3253, 3074,
2983, 2938, 2855, 2103, 1672, 1620; HRMS calcd for C14H16N3O
242.1293, found 242.1295.
5-Br om o-2-dieth ylam in o-3-for m yl-2H-in dazole (49). Ob-
tained from 28 using general procedure F (tan oil, 98%): 1H
NMR (CDCl3) δ 10.37 (s, 1H), 8.42 (d, J ) 1.8 Hz, 1H), 7.68
(d, J ) 9.2 Hz, 1H), 7.51 (dd, J ) 9.2, 2.0 Hz, 1H), 3.39 (br s,
4H), 0.88 (t, J ) 7.5 Hz, 6H); 13C NMR (CDCl3) δ 181.09,
144.27, 132.30, 131.08, 123.62, 120.89, 120.55, 119.88, 52.72,
11.99; IR (KBr) 3073, 1667, 1620 cm-1; HRMS calcd for
The above ester (370 mg, 1.3 mmol), HCl (0.55 mL, 6.6
mmol), NaNO2 (138 mg, 2.0 mmol), Et2NH (1.4 mL, 13.3
mmol), and K2CO3 (1.4 g, 10.6 mmol) were reacted using
general procedure B. After workup, product 44 (330 mg, 69%)
was obtained as a light yellow oil in sufficiently pure form for
further elaboration: 1H NMR (CDCl3) δ 7.58 (d, J ) 2.3 Hz,
1H), 7.35 (d, J ) 8.8 Hz, 1H), 7.04 (dd, J ) 8.8, 2.3 Hz, 1H),
3.79 (q, J ) 7.0 Hz, 4H), 2.27 (s, 3H), 1.31 (t, J ) 7.0 Hz, 6H);
13C NMR (CDCl3) δ 169.30, 148.29, 147.82, 131.53, 121.89,
117.15, 95.59, 49.14 (br), 42.21 (br), 21.02, 14.53 (br), 10.99
(br); IR (neat) 3065, 1761, 1108 cm-1; MS (ESI) MS m/z 362.0
C
12H15N3O79Br 296.0399, found 296.0394.
5-Ch lor o-2-dieth ylam in o-3-for m yl-2H-in dazole (50). Ob-
tained from 29 using general procedure F (tan oil that solidifies
slowly on standing, 95%): mp 92-93.5 °C; 1H NMR (CDCl3) δ
10.37 (s, 1H), 8.23 (d, J ) 2.1 Hz, 1H), 7.73 (d, J ) 9.2 Hz,
1H), 7.37 (dd, J ) 9.2, 2.1 Hz, 1H), 3.39 (br s, 4H), 0.88 (t, J
) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 181.10, 144.15, 132.53,
128.72, 120.27, 119.73, 52.72, 12.00; IR (neat) 3086, 1671, 1624
cm-1; HRMS calcd for C12H15N3O35Cl 252.0904, found 252.0898.
2-Dieth yla m in o-5-flu or o-3-for m yl-2H-in da zole (51). Ob-
tained from 30 using general procedure F (light green oil,
94%): 1H NMR (CDCl3) δ 10.37 (s, 1H), 7.83 (dd, J ) 8.5, 2,4
Hz, 1H), 7.78 (dd, J ) 9.1, 4.4 Hz, 1H), 7.22 (dt, J ) 8.9, 2.6
Hz, 1H), 3.42 (br s, 4H), 0.89 (t, J ) 6.9 Hz, 6H); 13C NMR
(CDCl3) δ 181.13, 161.46 (d, J ) 246 Hz), 143.01, 133.35 (d, J
) 8.3 Hz), 120.50 (d, J ) 9.3 Hz), 120.00 (d, J ) 12 Hz), 118.54
(d, J ) 27.8 Hz), 104.67 (d, J ) 25 Hz), 52.70, 12.01; IR (neat)
3082, 1726, 1670, 1634 cm-1; HRMS calcd for C12H15N3OF
236.1199, found 236.1203.
(100, M+ + H), 320.0 (20, M+ - C2H2O), 246.9 (90, M+ - C6H12
NO).
-
1-(4-Acet oxy-2-et h yn ylp h en yl)-3,3-d iet h yl-1-t r ia zen e
(41). Iodoester 44 (315 mg, 0.87 mmol), TMSA (0.17 mL, 1.2
mmol), PdCl2(PPh3)2 (24 mg, 0.035 mmol), and CuI (18 mg,
0.096 mmol) were reacted using general procedure C. The
crude product was immediately treated with Bu4NF (1.0 mL,
1.0 M in THF) and EtOH (0.5 mL) in THF. After the mixture
was stirred for 24 h under N2, the solvent was evaporated and
the crude product was purified by chromatography (5:1 hex-
anes/EtOAc) to give 38 (160 mg, 71%) as a colorless oil: 1H
NMR (CDCl3) δ 7.40 (d, J ) 8.8 Hz, 1H), 7.22 (d, J ) 2.6 Hz,
1H), 7.01 (dd, J ) 8.8, 2.6 Hz, 1H), 3.77 (q, J ) 7.3 Hz, 4H),
3.26 (s, 1H), 2.27 (s, 3H), 1.29 (t, J ) 7.3 Hz, 6H); 13C NMR
(CDCl3) δ 169.32, 150.89, 147.11, 125.81, 122.79, 117.69,
117.59, 81.46, 81.09, 49.02 (br), 41.68 (br), 21.02, 14.38 (br),
10.76 (br); IR (neat) 3289, 2580, 2106, 1764 cm-1; MS (ESI)
m/z 260.1 (100, M+ + H), 218.1 (40, M+ - C2H2O), 145.0 (90,
M+ - C6H12NO).
5-Ca r b om e t h oxy-2-d ie t h yla m in o-3-for m yl-2H -in d a -
zole (52). Obtained from 31 using general procedure F (yellow
solid, 83%): mp 90.1-90.8 °C; 1H NMR (CDCl3) δ 10.43 (s,
1H), 8.97 (t, J ) 1.2 Hz 1H), 8.05 (dd, J ) 9.1, 1.5 Hz, 1H),
7.80 (dd, J ) 9.1, 0.9 Hz, 1H), 3.95 (s, 3H), 3.39 (br s, 4H),
0.89 (t, J ) 7.2 Hz, 6H); 13C NMR (CDCl3) δ 181.17, 166.94,
147.22, 134.16, 128.05, 127.28, 125.07, 118.99, 118.20, 52.72,
52.25, 12.00; IR (KBr) 3067, 3036, 1719, 1665, 1629 cm-1
;
HRMS calcd for C14H18N3O3 276.1348, found 276.1352; Anal.
Calcd for C14H17N3O3 (275.30): C, 61.08; H, 6.22; N, 15.26.
Found: C, 60.82; H, 6.23; N, 15.38.
5-Cya n o-2-d ieth yla m in o-3-for m yl-2H-in da zole (20). Ob-
tained from 14 using general procedure F (60%) along with
isoindazole dimer 16 (34%). The spectral data were identical
to those given above. The yield of 20 could be improved to 85%
using general procedure F for 3 d at rt.
2-Diet h yla m in o-3-for m yl-2H-in d a zole (45). Obtained
from 3,3-diethyl-1-(2-ethynylphenyl)-1-triazene6b using general
procedure F (yellow oil, 95%): 1H NMR (CDCl3) δ 10.42 (s,
1H), 8.22 (d, J ) 7.6 Hz, 1H), 7.80 (d, J ) 8.2 Hz, 1H), 7.53-
7.36 (m, 2H), 3.39 (br s, 4H), 0.89 (t, J ) 7.2 Hz, 6H); 13C NMR
(CDCl3) δ 181.42, 145.84, 132.81, 127.22, 126.40, 121.24,
119.85, 118.24, 52.68, 12.02; IR (neat) 3068, 1669, 1627 cm-1
HRMS calcd for C12H16N3O 218.1293, found 218.1294.
;
2-Dieth yla m in o-3-for m yl-5-n itr o-2H-in d a zole (53). Ob-
tained from 32 using general procedure F (yellow solid, 54%).
The yield of 53 could be improved to 78% using general
procedure F for 3 d at rt: mp 175.7-177.3 °C; 1H NMR (CDCl3)
2-Dieth ylam in o-3-for m yl-5-m eth yl-2H-in dazole (46). Ob-
tained from 25 using general procedure F (tan solid, 90%): mp
(24) Theobold, D. W. Tetrahedron 1983, 39, 1605-1607.
6404 J . Org. Chem., Vol. 67, No. 18, 2002

Cyclization of 1-(2-Alkynylphenyl)-3,3-dialkyltriazenes
δ_10.44 (s, 1H), 9.20 (d, J ) 2.1 Hz, 1H), 8.25 (dd, J ) 9.4,
2.3 Hz, 1H), 7.89 (d, J ) 9.4 Hz, 1H), 3.46-3.37 (m, 4H), 0.91
(t, J ) 7.0 Hz, 6H); 13C NMR (CDCl3) δ_180.85, 147.03,
146.14, 135.39, 121.58, 119.74, 119.44, 118.17, 52.81, 11.96;
IR (KBr) 3432, 3325, 3106, 1668, 1343 cm-1; HRMS calcd
for C12H15N4O3 263.1144, found 263.1149. Anal. Calcd for
6-Br om ocin n olin e (60). Obtained from 28 using general
procedure E (yellow solid, 98%): mp 127-128.1 °C (lit.19 mp
129-130 °C); 1H NMR (CDCl3) δ 9.31 (d, J ) 5.9 Hz, 1H), 8.40
(d, J ) 9.1 Hz, 1H), 8.02 (d, J ) 2.1 Hz, 1H), 7.90 (dd, J ) 9.1,
2.1 Hz, 1H), 7.77 (d, J ) 6.4 Hz, 1H); 13C NMR (CDCl3) δ
149.33, 145.51, 134.49, 131.60, 128.71, 126.95, 126.13, 121.25;
C
12H14N4O3 (262.26): C, 54.96; H, 5.38; N, 21.36. Found: C,
IR (KBr) 3071, 3057, 3028, 1606 cm-1
.
55.08; H, 5.34; N, 21.06. Isolation of a second band provided
isoindazole dimer 18′ (37%) as an orange solid: mp 271-272.4
°C; 1H NMR (CDCl3) δ 9.07 (d, J ) 1.8 Hz, 2H), 8.22 (dd, J )
9.9, 2.1 Hz, 2H), 8.06 (s, 2H), 7.81 (d, J ) 9.3 Hz, 2H), 3.42 (br
s, 8H), 0.96 (t, J ) 6.9 Hz, 12H); 13C NMR (CDCl3) δ 147.77,
143.65, 137.59, 120.98, 119.56, 119.05, 118.53, 115.94, 52.61,
12.15; IR (KBr) 3076, 1618, 1327 cm-1; MS (ESI) m/z 493.2
(100, M+ + H), 391.3.1 (30, M+ - C4H11N3). Anal. Calcd for
6-Ch lor ocin n olin e (61). Obtained from 29 using general
procedure E (yellow solid, 97%): mp 128.8-129.9 °C (lit.20 mp
1
131-131.5 °C); H NMR (CDCl3) δ 9.30 (d, J ) 6.2 Hz, 1H),
8.47 (dd, J ) 9.1, 0.6 Hz, 1H), 7.82 (d, J ) 2.1 Hz, 1H), 7.77
(d, J ) 6.2 Hz, 1H), 7.76 (dd, J ) 9.1, 2.1 Hz, 1H); 13C NMR
(CDCl3) δ 149.16, 145.50, 137.45, 131.97, 131.66, 126.59,
125.21, 121.44; IR (KBr) 3061, 3034 cm-1
.
6-F lu or ocin n olin e (62). Obtained from 30 using general
procedure E (dark semisolid oil, 90%): 1H NMR (CDCl3) δ 9.29
(d, J ) 5.9 Hz, 1H), 8.59 (q, J ) 9.4, 5.3 Hz, 1H), 7.84 (d, J )
5.9 Hz, 1H), 7.64 (td, J ) 8.6, 2.7 Hz, 1H), 7.44 (dd, J ) 8.3,
2.6 Hz, 1H); 13C NMR (CDCl3) δ 162.90 (d, J ) 255.5 Hz),
148.59, 145.16, 133.41 (d, J ) 9.3 Hz), 122.11 (d, J ) 5.6 Hz),
121.89 (d, J ) 26.8 Hz), 109.31 (d, J ) 22.2 Hz); IR (neat)
3044, 1626 cm-1; HRMS calcd for C8H6N2F 149.0515, found
149.0516.
6-Ca r bom eth oxycin n olin e (63). Obtained from 31 using
general procedure E (dark solid, 96%): mp 130.4-131.2 °C;
1H NMR (CDCl3) δ 9.41 (d, J ) 5.9 Hz, 1H), 8.60 (d, J ) 2.1
Hz, 1H), 8.59 (d, J ) 9.1 Hz, 1H), 8.40 (dd, J ) 9.1, 1.8 Hz,
1H), 7.96 (d, J ) 5.9 Hz, 1H), 4.01 (s, 3H); 13C NMR (CDCl3)
δ 165.64, 151.29, 145.73, 132.16, 130.32, 129.99, 129.94,
125.15, 123.41, 52.84; IR (KBr) 3063, 1716 cm-1; HRMS calcd
for C10H9N2O2 189.0664, found 189.0667.
C
24H28N8O4 (492.53): C, 58.53; H, 5.73; N, 22.75. Found: C,
58.35; H, 5.77; N, 22.55.
2-Dieth yla m in o-3-for m yl-5-m eth oxy-2H-in d a zole (54).
Obtained from 40 using general procedure F (yellow oil,
98%): 1H NMR (CDCl3) δ 10.36 (s, 1H), 7.68 (d, J ) 9.1 Hz,
1H), 7.48 (d, J ) 2.3 Hz, 1H), 7.10 (dd, J ) 9.1, 2.3 Hz, 1H),
3.90 (s, 3H), 3.40 (br s, 2H), 3.25 (br s, 2H), 0.88 (t, J ) 6.9
Hz, 6H); 13C NMR (CDCl3) δ 181.48, 159.04, 142.05, 132.54,
121.79, 120.86, 119.70, 97.87, 55.66, 52.60, 12.04; IR (neat)
3087, 1662, 1627, 1217 cm-1; MS (ESI) m/z 270.1 (80, M+
+
Na + H), 248.1 (100, M+ + H).
5-Acetoxy-2-d ieth yla m in o-3-for m yl-2H-in d a zole (55).
Obtained from 41 using general procedure F (clear oil, 86%):
1H NMR (CDCl3) δ 10.37 (s, 1H), 7.91 (d, J ) 2.1 Hz, 1H),
7.80 (d, J ) 9.1 Hz, 1H), 7.16 (dd, J ) 9.1, 2.1 Hz, 1H), 3.36
(br s, 4H), 2.34 (s, 3H), 0.88 (t, J ) 7.0 Hz, 6H); 13C NMR
(CDCl3) δ 181.11, 169.75, 149.10, 143.88, 133.32, 123.37,
119.84, 119.66, 112.51, 52.69, 21.04, 11.96; IR (neat) 3079,
6-Cya n ocin n olin e (64). Obtained from 14 using general
procedure E (light orange oil that solidifies on standing,
98%): mp 129-131 °C; 1H NMR (CDCl3) δ 9.50 (d, J ) 5.9
Hz, 1H), 8.70 (d, J ) 8.8 Hz, 1H), 8.30 (d, J ) 1.5 Hz, 1H),
7.99 (dd, J ) 8.8, 1.8 Hz, 1H), 7.94 (dd, J ) 5.9, 0.7 Hz, 1H);
13C NMR (CDCl3) δ 149.98, 146.29, 133.52, 131.70, 130.95,
125.05, 122.20, 117.40, 115.11; IR (neat) 3449, 3070, 3040,
2224 cm-1; HRMS calcd for C9H6N3 156.0562, found 156.0563.
6-Nitr ocin n olin e (65). Obtained from 32 using general
procedure E (light tan powder, 95%): mp 194-195 °C (lit.21
mp 205-206 °C); 1H NMR (CDCl3) δ 9.54 (d, J ) 6.2 Hz, 1H),
8.84 (d, J ) 2.3 Hz, 1H), 8.77 (d, J ) 9.1 Hz, 1H), 8.60 (dd, J
) 9.4, 2.3 Hz, 1H), 8.09 (d, J ) 5.9 Hz, 1H); 13C NMR (CDCl3)
δ 150.69, 146.29, 132.49, 124.96, 124.02, 123.93, 123.72; IR
1761, 1669, 1632, 1211 cm-1; MS (ESI) m/z 322.2 (100, M+
+
2Na), 276.1 (18, M+ + H).
Cin n olin e (56). Obtained from 3,3-diethyl-1-(2-ethynylphen-
yl)-1-triazene6b using general procedure E (dark oil, 99%): 1H
NMR (CDCl3) δ 9.33 (d, J ) 5.9 Hz, 1H), 8.56 (dd, J ) 8.5, 0.9
Hz, 1H), 7.92-7.83 (m, 3H), 7.80-7.74 (m, 1H); 13C NMR
(CDCl3) δ 150.91, 145.05, 131.18, 130.67, 129.93, 126.61,
126.06, 122.54. NMR data matched those of commercially
available samples.
6-Meth ylcin n olin e (57). Obtained from 25 using general
procedure E (dark oil, 97%): 1H NMR (CDCl3) δ 9.23 (d, J )
5.9 Hz, 1H), 8.41 (d, J ) 8.8 Hz, 1H), 7.75 (d, J ) 5.9 Hz, 1H),
7.67 (dd, J ) 8.8, 1.7 Hz, 1H), 7.57 (s, 1H), 2.58 (s, 3H); 13C
NMR (CDCl3) δ 149.98, 145.04, 141.92, 133.22, 129.51, 126.32,
124.93, 121.99, 22.08; IR (KBr) 3053, 1627 cm-1; HRMS calcd
for C9H9N2 145.0766, found 145.0768.
6-ter t-Bu tylcin n olin e (58). Obtained from 26 using gen-
eral procedure E (dark oil, 98%): 1H NMR (CDCl3) δ 9.25 (d,
J ) 5.9 Hz, 1H), 8.45 (d, J ) 9.1 Hz, 1H), 7.94 (dd, J ) 9.1,
2.1 Hz, 1H), 7.82 (d, J ) 5.6 Hz, 1H), 7.70 (d, J ) 1.8 Hz, 1H),
1.43 (s, 9H); 13C NMR (CDCl3) δ 154.53, 149.91, 145.10, 130.05,
129.28, 126.13, 122.70, 121.10, 35.48, 30.79; IR (neat) 3062,
1623 cm-1; HRMS calcd for C12H15N2 187.1235, found 187.1233.
6-Eth yn ylcin n olin e (59). Obtained from 27 using general
procedure E (tan solid, 83%): mp 145-146 °C; 1H NMR
(CDCl3) δ 9.34 (d, J ) 5.6 Hz, 1H), 8.50 (d, J ) 9.1 Hz, 1H),
7.99 (d, J ) 1.5 Hz, 1H), 7.87 (dd, J ) 8.8, 1.8 Hz, 1H), 7.81
(d, J ) 5.5 Hz, 1H), 3.34 (s, 1H); 13C NMR (CDCl3) δ 149.82,
145.66, 133.36, 130.68, 130.05, 125.65, 125.27, 121.94, 82.30,
81.17; IR (neat) 3453, 3152, 3040, 2095, 1618 cm-1; HRMS
calcd for C10H7N2 155.0609, found 155.0610.
(KBr) 3447, 3101, 3035, 1526, 1347 cm-1
.
Ack n ow led gm en t. We thank the National Science
Foundation, the Petroleum Research Fund, adminis-
tered by the American Chemical Society, and The
Camille and Henry Dreyfus Foundation (Teacher-
Scholar Award 1998-2003 to M.M.H.) for financial
support.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra for
compounds 5, 11, 14, 16, 18, 20, 25-32, 40, 41, 45-55, and
57-65; X-ray structures of 5 and 16, structure refinement
details, tables of atomic coordinates, thermal parameters, bond
lengths, bond angles, torsion angles, and mean planes. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O020229S
J . Org. Chem, Vol. 67, No. 18, 2002 6405