A pyrazole to furan rearrangement. Thermolysis of 5-Azido-4-formylpyrazoles

Article abstract of DOI:10.1021/jo9822075

5-Azido-3-benzyl-4-formyl-1-phenylpyrazoles 1a-c extrude dinitrogen upon heating in toluene to give the corresponding nitrenes, which immediately rearrange via a new ring-opening ring-closure reaction to produce an equimolar mixture of 4-cyano-2-phenyl-3-phenylazofurans 2a-c and 3-benzyl-4-cyano-1-phenylpyrazoles 3a-c. The formation of the 4-cyano-2-phenyl-3-phenylazofurans 2a-c is the first example in the pyrazole series of a nitrene rearrangement, in which the parent heterocyclic system of the product differs from that of the starting material. The isolation of equimolar amounts of the two products points to the fact that their formation occurs by two mechanistically interconnected pathways, between which the exchange of a redox equivalent takes place. Evidence for the existence of two mechanistically interlinked pathways is presented, and the insight into the stoechiometry of the reaction is taken advantage of to optimize the reaction with respect to either of the two products 2 or 3. Thus, it is demonstrated how one can bias the two pathways using external reagents, thereby changing the product distribution ratio 2:3 from 1:1 in the unbiased case, to 1:4 in one direction, and to better than 20:1 in the other direction.

Full text of DOI:10.1021/jo9822075

2814
J . Org. Chem. 1999, 64, 2814-2820
A P yr a zole to F u r a n Rea r r a n gem en t. Th er m olysis of
5-Azid o-4-for m ylp yr a zoles
Niels Svenstrup,† Klaus B. Simonsen,† Niels Thorup,‡ J ørgen Brodersen,† Wim Dehaen,§ and
J an Becher*,†
Department of Chemistry, Odense University, Campusvej 55, DK-5230 Odense, Denmark,
Department of Chemistry, The Technical University of Denmark, DK-2800 Lyngby, Denmark, and
Department of Chemistry, University of Leuven, B-3001 Heverlee, Belgium
Received November 3, 1998
5-Azido-3-benzyl-4-formyl-1-phenylpyrazoles 1a -c extrude dinitrogen upon heating in toluene to
give the corresponding nitrenes, which immediately rearrange via a new ring-opening ring-closure
reaction to produce an equimolar mixture of 4-cyano-2-phenyl-3-phenylazofurans 2a -c and 3-benzyl-
4-cyano-1-phenylpyrazoles 3a -c. The formation of the 4-cyano-2-phenyl-3-phenylazofurans 2a -c
is the first example in the pyrazole series of a nitrene rearrangement, in which the parent
heterocyclic system of the product differs from that of the starting material. The isolation of
equimolar amounts of the two products points to the fact that their formation occurs by two
mechanistically interconnected pathways, between which the exchange of a redox equivalent takes
place. Evidence for the existence of two mechanistically interlinked pathways is presented, and
the insight into the stoechiometry of the reaction is taken advantage of to optimize the reaction
with respect to either of the two products 2 or 3. Thus, it is demonstrated how one can bias the two
pathways using external reagents, thereby changing the product distribution ratio 2:3 from 1:1 in
the unbiased case, to 1:4 in one direction, and to better than 20:1 in the other direction.
In tr od u ction
cyanoformyl intermediate in the first step after genera-
tion of the nitrene (or nitrenoid species);7 the acyclic
cyanoformyl compound has never been isolated in the
5-azido-4-formylpyrazole thermolysis reaction, but simi-
lar intermediates have been isolated in the pyrolysis of
the 5-azido-4-formylpyrazole imines8,9 and 5-azido-4-
arylpyrazoles10,11 (Reaction 1).
The thermal or photochemical rearrangement of het-
erocyclic azides has attracted attention as a means of
constructing new heterocyclic compounds, which are
otherwise inaccessible by ring synthesis or by modifica-
tion of existing heterocycles.1 The synthetic utility of this
method owes itself to the characteristic ability of homo-
as well as heteroaromatic nitrenes to undergo rearrange-
ments,1,2 in contrast to carbenes, that are more inclined
to participate in addition chemistry.3 An especially at-
tractive variant of the heterocyclic nitrene rearrangement
reaction is the ring-opening ring-closure rearrangement
of heterocyclic azides,4 since it, depending on the nature
of the substituents, can provide access to new heterocyclic
compounds.5
We have previously studied the thermal rearrange-
ment of a variety of 5-azido-4-formyl heterocycles,4,5 in
particular the rearrangements of substituted pyrazoles.6
An important general feature of the mechanism of these
reactions is thought to be the formation of an acyclic
The acyclic cyanoformyl intermediate can potentially
cyclize by several different pathways, depending on the
reaction conditions, the atoms X, Y, and Z, the substit-
* To whom correspondence should be addressed. Tel: + 45 65 57
25 54. Fax: + 45 66 15 86 89.
† Odense University.
‡ The Technical University of Denmark.
§ University of Leuwen.
(7) For a detailed discussion of nitrene formation versus concerted
ring opening of azides, see: (a) Dyall, L. K.; Suffolk, P. M.; Dehaen,
W.; L’abbe´, G. J . Chem. Soc., Perkin Trans. 2 1994, 2115-2118. (b)
L’abbe´, G.; Dyall, L.; Meersman, K.; Dehaen, W. J . Chem. Soc., Perkin
Trans. 2 1994, 2401-2406. (c) L’abbe´, G.; Dyall, L.; Meersman, K.;
Dehaen, W. J . Chem. Soc., Perkin Trans. 2 1996, 2111-2118. (d)
L’abbe´, G.; Dyall, L. K.; Meersman, K.; Dehaen, W. J . Chem. Res.,
Miniprint 1997, 1631-1650.
(8) Dehaen, W.; Becher, J . Tetrahedron Lett. 1991, 32, 3565-3568.
(9) Becher, J .; Begtrup, M.; Gjerløv, A.; Larsen, S.; Dehaen, W.;
Christensen, L. K. Acta Chem. Scand. 1995, 49, 57-63.
(10) (a) Smith, P. A. S.; Breen, G. J . W.; Hajek, M. K.; Awang, D. V.
C. J . Org. Chem. 1970, 35, 2215-2221. (b) Smith, P. A. S.; Dounchis,
H. Ibid. 1973, 38, 2958-2963.
(11) Intermediates of this type have also been isolated in the 1,2,3-
triazole series: Smith, P. A. S.; Krbechek, L. O.; Resemann, W. J . Am.
Chem. Soc. 1964, 86, 2025-2033.
(1) For recent reviews, see: (a) Dehaen, W.; Becher, J . Acta Chem.
Scand. 1993, 47, 244-254 (b) Funicello, M.; Spagnolo, P.; Zanirato, P.
Ibid. 1993, 47, 231-243.
(2) L’abbe´, G. Angew. Chem. 1975, 87, 831-838.
(3) Helquist, P. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.-in-chief; Fleming, I., Ed.; Oxford, 1991; Vol. 4, pp 951-997.
(4) (a) Becher, J .; Brøndum, K.; Krake, N.; Pluta, K.; Simonsen, O.;
Molina, P.; Begtrup, M. J . Chem. Soc., Chem. Commun. 1988, 541-
542. (b) Pluta, K.; Andersen, K. V.; J ensen, F.; Becher, J . J . Chem.
Soc., Chem. Commun. 1988, 1583-1584.
(5) Becher, J .; J ørgensen, P. L.; Pluta, K.; Krake, N. J .; Fa¨lt-Hansen,
B. J . Org. Chem. 1992, 57, 2127-2134.
(6) For
a comprehensive review of 1H-pyrazole chemistry, see:
Kirschke, K. In Methoden der Organischen Chemie (Houben-Weyl);
Schaumann, E., Ed.; Georg Thieme Verlag: Stuttgart, 1994; Vol. E8b,
Part 2, pp 399-763.
10.1021/jo9822075 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/19/1999

Thermolysis of 5-Azido-4-formylpyrazoles
J . Org. Chem., Vol. 64, No. 8, 1999 2815
Sch em e 1
uents, and external nucleophiles. Two main pathways
have been identified so far: self-contained cyclization
(pathway 1, reaction 2) and cyclization under the influ-
ence of an external nucleophile (pathway 2, reaction 3).
ing to methodology developed in this group.12 In the first
step, Meldrum’s acid 513 was acylated using 1 equiv of
the acid chlorides 4a -c in dichloromethane with 2.5
equiv of pyridine as the base and acylation catalyst.14 The
resulting acylated Meldrum’s acids 6a -c were not iso-
lated; instead they were subjected to an acidic aqueous
workup to remove the pyridine and immediately there-
after refluxed in absolute ethanol for 2.5 h to give the
â-ketoesters 7a -c in 51-81% yield after an aqueous
workup and vacuum distillation through a Claisen
column (Scheme 1).
This procedure, at least in our hands, proved vastly
superior to the conventional â-ketoester synthesis, in
which diethyl malonate is metalated using diethoxymag-
nesium and alkylated using an acid chloride, after which
the resulting acylmalonate is decarboxylated by heating
to 250 °C in the presence of naphthalene-2-sulfonic acid
monohydrate to give the desired â-ketoester.15
In the next step, the construction of the heterocyclic
rings, the required pyrazolones 8a -c were prepared by
condensing phenylhydrazine with the â-keto esters 7a -c
using standard chemistry differing in no significant way
However, none of these routes provide an entry into
other heterocyclic parent systems, since in all the known
examples pyrazoles are converted to differently substi-
tuted pyrazoles and so forth; in this paper, the develop-
ment of a new synthetic path for the synthesis of furans
as well as pyrazoles by thermal rearrangement of 5-azid-
oformyl pyrazoles 1a -c with benzylic subsitutents in the
3-position is described. In this case, two interconnected
pathways operate to produce an equimolar amount of the
furan 2 and the pyrazole 3 (reaction 4).
Additionally, this paper details our initial suggestion
for the mechanism of this reaction and how the insight
gained by this newly formulated mechanism enabled us
to optimize the reaction with respect to either the furan
or the pyrazole.
(12) Molina, P.; Arques, A.; Vinander, M. V.; Becher, J .; Brøndum,
K. J . Org. Chem. 1988, 53, 4654-4663.
(13) Davidson, D.; Bernhard, S. A. J . Am. Chem. Soc. 1948, 70,
3426-3428.
(14) The acid chlorides 4a ,b are commercially available, whereas
acid chloride 4c was prepared by the standard procedure using thionyl
chloride in toluene. See for example: Miller, W. H.; Dessert, A. M.;
Anderson, G. W. J . Am. Chem. Soc. 1948, 70, 500-502.
(15) Vogel, A. I. Textbook of Practical Organic Chemistry; Longman
Scientific and Technical: Essex, 1989; pp 742-743.
Resu lts a n d Discu ssion
Azid e Syn th esis. The requisite 3-substituted 5-azido-
4-formyl-1-phenylpyrazoles 1a -c were prepared accord-

2816 J . Org. Chem., Vol. 64, No. 8, 1999
Svenstrup et al.
Sch em e 2
from the procedures developed by Knorr16 in the late
nineteenth century (Scheme 2).17 The pyrazolones 8a -c
were then subjected to a Vilsmeier-Haack chloroformy-
lation18 using 3 equiv of N,N-dimethylformamide and an
excess of phosphoryl chloride.19 In some cases, the desired
5-chloro-4-formylpyrazoles crystallized directly from the
reaction mixture upon addition of water to hydrolyze the
intermediate and excess POCl3, while in other cases, the
reaction mixture had to be neutralized using solid sodium
carbonate following the addition of water (Scheme 2).
Finally, the 5-chloro-4-formylpyrazoles 9a -c were con-
verted to the corresponding azides 1a -c by reaction with
sodium azide in DMSO solution at 35 °C for 3 days in
the dark (Scheme 2). The azides 1a -c were obtained in
analytical purity after the crude reaction mixtures were
subjected to an aqueous workup followed by column
chromatography on silica gel.
This nucleophilic aromatic substitution, which would
be very difficult to carry out in the benzene series,
proceeds smoothly, thanks partly to the electronic nature
of the pyrazole ring and partly to the presence of the
electron-withdrawing formyl substituent in the 4-posi-
tion.20 However, it is essential that the temperature is
kept under 35 °C and all light must be excluded, as the
azides are quite prone to rearrangement under the
influence of both thermal and photochemical stimulation.
Azid e Rea r r a n gem en t. The azides 1a -c were sub-
jected to thermolysis by heating approximately 1 mmol
of the azides in toluene at 95 °C for 4 h. The initially
yellow reaction mixtures soon turned dark orange, and
formation of two individual products was evident in thin-
layer chromatography after about 30 min. Upon nearly
complete disappearance of the starting material, the
reactions mixtures were cooled to room temperature and
evaporated in vacuo, and the resulting residues were
subjected to column chromatography on silica gel to give
two products, which in the case of 1a were identified as
4-cyano-2-phenyl-3-phenylazofuran (2a ) and 3-benzyl-4-
cyano-1-phenylpyrazole (3a ), respectively, on the basis
of spectroscopic evidence (reaction 4).
phenylpyrazole (1a ), two orange compounds with Rf )
0.57 and 0.41, respectively, were formed, of which the
latter displayed an intense fluorescence on the TLC
plates.
The less polar compound was found to be 4-cyano-2-
phenyl-3-phenylazofuran (2a ) on the basis of the follow-
ing evidence: The isolated crystalline material gave an
elemental analysis consistent with the elemental com-
position C17H11N3O, corresponding to the loss of one
molecule of N2 and one molecule of H2 from the starting
material 1a . An EIMS molecular ion at m/z ) 273
confirmed this. In addition, the less polar compound 2a
1
displayed an H NMR spectrum, in which only aromatic
resonances could be seen: integration demonstrated the
spectrum to consist of signals from 11 hydrogen atoms
(two phenyl substituents and 1 furan proton). The 13C
NMR spectrum displayed 13 individual resonances, all
at δ >90, consistent with the presence two phenyl rings,
an unsymmetrical trisubstituted furan ring, and a nitrile.
In the IR spectrum, an intense band at 2232 cm-1
supported the evidence pointing to the presence of a
conjugated cyano group, and the presence of the azo
group was confirmed by Raman spectroscopy, in which
a band at 1429 cm-1 was prominent, indicative of the
presence of an asymmetric azo group (due to its unpolar
nature, the absorption from the phenylazo substituent
is absent or very weak in IR). All of these observations
in unison supported the hypothesis that 2a was the new
compound 4-cyano-2-phenyl-3-phenylazofuran. The struc-
ture of the furan product was unequivocally determined
by single-crystal X-ray structure analysis of the rather
more crystalline methoxy-substituted analogue 2b, which
could be crystallized from a mixture of 1,2-dichloroethane
and methanol.21 The X-ray data and ORTEP diagrams
for 2b are included as Supporting Information.
The more polar compound 3a was deduced to be
3-benzyl-4-cyano-1-phenylpyrazole on the basis of a
variety of spectroscopic and physical measurements. In
addition, compound 3a gave an elemental analysis sug-
gesting it to have the elemental composition C17H13N3,
and again this was supported by EIMS with a molecular
ion peak at m/z ) 293. In other words, 3a had been
formed from 1a by the formal extrusion of both a
molecule of N2 and an oxygen atom. The 1H NMR
spectrum of 3a displayed a singlet at 8.17 ppm (one
proton), a multiplet spanning from 7.70 to 7.20 ppm (10
protons), and a singlet at 4.17 ppm (two protons). The
13C NMR displayed 13 lines, one in the aliphatic and 12
in the aromatic region. Thus, the NMR data indicated
the presence of a phenyl and a benzyl substituent, as well
as the presence of a nitrile functionality and an unsym-
metrical trisubstituted pyrazole ring. The IR spectrum
Id en tifica tion of th e Th er m olysis P r od u cts. In the
case of the thermolysis of 5-azido-3-benzyl-4-formyl-1-
(16) Knorr, L. Chem. Ber. 1884, 17, 546-552.
(17) The preparation of compound 8a has been claimed in the
literature, but no spectroscopic or physical data were reported: Tietze,
L. F.; Steinmetz, A.; Balkenhohl, F. Bioorg. Med. Chem. Lett. 1997, 7,
1303-1306.
(18) Meth-Cohn, O.; Stanforth, S. P. In Comprehensive Organic
Synthesis; Trost, B. M., Ed-in-chief; Heathcock, C. H., Ed.; Pergamon
Press: Oxford, 1991; Vol. 2, pp 777-794.
(19) Becher, J .; Olesen, P. H.; Knudsen, N. A.; Toftlund, H. Sulfur
Lett. 1986, 4, 175-183.
(20) For a review of 3-chlorovinylaldehydes, see: Pulst, M.; Weis-
senfels, M. Z. Chem. 1976, 16, 337-348.

Thermolysis of 5-Azido-4-formylpyrazoles
J . Org. Chem., Vol. 64, No. 8, 1999 2817
Sch em e 3
displayed a prominent absorption at 2227 cm-1, indica-
tive of the presence of a conjugated cyano group, thus
supporting this hypothesis. In combination, these obser-
vations led us to conclude that 3a was the new hetero-
cyclic compound 3-benzyl-4-cyano-1-phenylpyrazole. The
structure of the pyrazole product was also successfully
determined by single-crystal X-ray structure analysis of
the more crystalline methoxy-substituted analogue 3b.21
This structure along with selected bond lengths and
angles can be found in the Supporting Information
section.
would allow the elimination of a molecule of water to give
the presumably highly reactive intermediate IV. Reaction
of IV with 1 equiv of H2 (in the form of the easily
oxidizable 1,2-disubstituted hydrazine VIII) or a similar
redox equivalent as shown in structure V then reduces
the betaine to the product 3-benzyl-4-cyano-1-phenylpyra-
zole (3a ) after loss of a proton.
In path B, the acyclic compound I first tautomerizes
to the vinylogous enol VI, the driving force presumably
being the highly extended conjugation of the system. The
highly electron-withdrawing effect of the phenylazo sub-
stituent causes VI to be quite electrophilic in the â-posi-
tion relative to this group, and it therefore presumably
undergoes a fast intramolecular Michael-type addition
to give the furan VII. Two prototopic shifts cause the
furan ring system to gain aromatic resonance stabiliza-
tion, thus forming the N,N′-disubstituted hydrazine VIII,
which can be assumed to have a very low oxidation
potential, since oxidation to an azo group confers com-
plete conjugation to the molecule. Transfer of one mol-
ecule of H2 to the pyrazole IV in the final step of the
reaction through transition state V completes path B, in
the process generating one molecule of 4-cyano-2-phenyl-
3-phenylazofuran (2a ).
P r op osed Rea ction Mech a n ism . To explain the
formation of equimolar amounts of the two products
2a -c and 3a -c, we formulated the following reaction
mechanism (Scheme 3):
In analogy with other known azide rearrangements of
pyrazoles,4-8 we assume the first step of the reaction to
be the extrusion of molecular dinitrogen from the azide,
thus generating a nitrene, which immediately rearranges
in what is presumed to be a concerted electrocyclic ring-
opening reaction to give the acyclic intermediate I. In
contrast to our previous systems, the benzylic CH2 group
of I enables it to undergo recyclization by two different
paths, namely path A leading to the formation of a new
pyrazole ring systems (in a way somewhat similar to most
of our already described azide rearrangements) and path
B leading to the formation of a furan ring in a reaction
which has no precedents.
The existence of of two interconnected reaction path-
ways is supported by the observation that approximately
equimolar amounts of the two products 2 and 3 are
isolated from the reaction. To gain further insight into
the progress of the reaction, it was decided to monitor
the reaction by 1H NMR: in a separate experiment,
5-azido-3-benzyl-4-formyl-1-phenylpyrazole was subjected
to thermolysis in toluene at 95 °C for 4 h, during which
time aliquots were taken from the reaction mixture every
In path A, the pyrazole ring is reformed by recycliza-
tion via a nucleophilic attack of N-1 onto the formyl group
as shown in structure II (attack onto the nitrile would
reform the intermediary nitrene), thereby giving rise to
a heterocyclic betaine III. Protonation of the betaine
1
15 min. H NMR of these aliquots confirmed our sup-
(21) The authors have deposited atomic coordinates and thermal
parameters for 2b and 3b with the Cambridge Crystallographic Data
Centre. The coordinates can be obtained on request from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, U.K.
position that the products 2 or 3 were being formed at
what appeared to be identical rates over the 4 h that we
monitored the reaction.

2818 J . Org. Chem., Vol. 64, No. 8, 1999
Svenstrup et al.
Ta ble 1
steps by thermolysis of 5-azidopyrazoles. The reaction
investigated appears to involve a disproportionation-like
transfer of redox equivalents from one reaction pathway
to another, thereby coupling the formation of the two
products. Evidence for the existence of such two inter-
linked pathways is as follows: In the unbiased reaction,
in which no external reagents are added, the two
products 2a -c and 3a -c are invariably formed in nearly
equimolar amounts. In addition, it is possible to influence
the course of the reaction by adding external redox
reagents: Addition of the oxidizing agent DDQ leads to
selective formation of the furan 2, while addition of the
reducing agent 1,2-diphenylhydrazine and a catalytic
amount of p-toluenesulfonic acid to the reaction signifi-
cantly favors the formation of the pyrazole 3. Thus, under
what is effectively the same conditions, it is possible to
produce two different heterocycles from the same starting
material by adding either an oxidizing or a reducing
agent.
yield of 2 yield of 3
azide
additive
(%)
(%)
1b
1b
1b
27
49
9
23
<1
41
2,3-dichloro-5,6-dicyanoquinone
1,2-diphenylhydrazine
To provide further evidence of the mechanism of this
chemical transformation, and to illuminate the scope of
the reaction, we decided to attempt to influence the
course of the reaction by adding external reagents. In the
proposed mechanism of formation of the furan 2 (Scheme
3), a transfer of a redox equivalent from the hydrazine
VIII is postulated, and we would therefore expect that
the addition of an oxidizing agent would promote the
formation of furan 2 on the expense of the pyrazole 3.
On the other hand, the mechanism of formation of the
pyrazole 3 calls for the acid-catalyzed loss of water from
the intermediate III, followed by addition of 1 equiv of
dihydrogen to intermediate IV and subsequent loss of a
proton to give the pyrazole 3; thus, we anticipated that
the addition of a suitable reducing agent, as well as a
small amount of p-toluenesulfonic acid to accelerate the
elimination of water from intermediate III would sig-
nificantly increase the yield of pyrazole 3, while at the
same time suppressing the formation of the furan 2.
Indeed, when the azide 1b was subjected to thermolysis
in dry toluene at 95 °C for 4 h in the presence of 1.5 equiv
of the well-known oxidizing agent 2,3-dichloro-5,6-dicy-
ano-1,4-quinone (DDQ), the furan 2b was formed in 49%
isolated yield while the formation of the pyrazole 3b was
at the same time completely suppressed (compare with
27% yield of the furan and 23% yield of the pyrazole in
the native experiment). These results are summarized
above (Table 1). Likewise, when the azide 1b was reacted
with the reducing agent 1,2-diphenylhydrazine (1.5 equiv)
in dry toluene at 95 °C for 4 h in the prescence of a
catalytic amount of p-toluenesulfonic acid, the pyrazole
3b was formed in 41% yield, while the formation of the
furan 2b was markedly inhibited: only 9% of 2b was
isolated after chromatography (Table 1).
It is an interesting fact that the combined yield of the
two products 2 and 3 rarely exceeds 50%, especially
because no other products were ever isolated from the
reaction mixture after chromatography. During the ther-
molysis of 1a -c, a maximum yield of product is achieved
under the conditions described in the Experimental
Section, and prolonged heating seems to lead only to
decomposition of the starting material; quite likely, the
polymerization of the very reactive intermediate I is a
competing reaction. An alternative explanation is that
the reaction slows down markedly when the effective
concentration of intermediate I drops (due to decreased
amounts of starting material) as the reaction pro-
gresses: in this situation a molecule of either of the
intermediates IV and VIII is less likely to encounter its
respective reaction partner for the formation of the
disproportionation-like transition state V (Scheme 3), and
competing reactions not leading to the desired products
2 and 3 therefore become more dominant.
Exp er im en ta l Section
Toluene for the thermolysis reactions was purified by
distillation from sodium benzophenone ketyl and stored over
4 Å molecular sieves, and ethanol was purified by distillation
from Mg under N2 and stored over 3 Å molecular sieves. DMF
and DMSO were dried by standing over 4 Å molecular sieves
for at least 24 h and were not distilled prior to use. Pyridine
was dried by standing over KOH overnight, after which it was
distilled in vacuo. Dichloromethane (HPLC grade) was used
without any prior purification. Water content of the purified
solvents was checked by Karl Fischer titration of 1 mL samples
of the solvents on a Metrohm Karl Fischer titration apparatus
based on a Metrohm 737 KF coulometer.
All reagents employed were of standard reagent grade and
purchased from Aldrich, except for Meldrum’s acid (5), which
was prepared from malonic acid and acetone following a
procedure published by Davidson,13 and 4-chlorophenylacetyl
chloride (4c), which was prepared from the commercially
available carboxylic acid by reaction with thionyl chloride in
toluene.14
Analytical thin layer chromatography (TLC) was performed
on Merck DC-Alufolien Kieselgel 60 F254 0.2 mm thickness
precoated TLC plates, while column chromatography was
performed using Merck Kieselgel 60 (0.040-0.063 mm, 230-
400 mesh). Developed TLC plates were visualized either by
quenching of UV fluorescence at 254 nm or by spraying with
1
iodine vapor. H NMR spectra were recorded at 250 MHz or
at 300 MHz using the deuterated solvent as lock and TMS or
the residual solvent as internal reference. 13C NMR spectra
were recorded at 63 or 75 MHz, respectively, using broad band
decoupling. Elemental analyses were performed at the Mi-
croanalytical Laboratory, University of Copenhagen, Denmark.
Wa r n in g! Although no problems were experienced in this
study, heterocyclic azido compounds are potentially explosive,
and care should be taken in their handling and storage.
Eth yl P h en yla cetoa ceta te 7a . Gen er a l P r oced u r e for
7a -c. To a solution of Meldrum’s acid 5 (21.8 g, 0.151 mol) in
CH2Cl2 (60 mL) in a 250 mL round-bottomed flask, equipped
with an addition funnel and nitrogen inlet and cooled to 0 °C,
was added pyridine (30 mL) over a period of 10 min. To this
solution was then added a solution of freshly distilled pheny-
lacetyl chloride 4a (22.8 g, 0.147 mol) in CH2Cl2 (45 mL), which
resulted in an orange solution. After the addition was complete
(approximately 2 h), the resulting dark orange solution was
stirred for 1 h at 0 °C, allowed to warm to room temperature,
and stirred for an additional hour. The solution was diluted
with CH2Cl2 (50 mL) and poured onto 2 M HCl and ice. The
phases were separated, and the aqueous phase was extracted
with CH2Cl2 (2 × 50 mL). The combined organic phases were
washed with 2 M HCl (2 × 50 mL) and brine (100 mL), dried
over Na2SO4, and evaporated. The resulting orange crystals,
Con clu sion
In this paper, we have demonstrated that highly
substituted furans and pyrazoles can be formed from
readily available starting materials in a few synthetic

Thermolysis of 5-Azido-4-formylpyrazoles
J . Org. Chem., Vol. 64, No. 8, 1999 2819
which mainly consisted of the acetylated Meldrum’s acid, were
suspended in EtOH (300 mL) in a 500 mL round-bottomed
flask and refluxed for 2.5 h. The solvent was removed in vacuo,
leading to a dark oil. Distillation under reduced pressure gave
24.5 g (81%) of 7a as a clear oil: bp 88 °C (0.07 mbar); 1H
NMR (CDCl3) δ 7.4-7.1 (m, 5H), 4.17 (q, J ) 7.1 Hz, 2H), 3.82
(s, 2H), 3.44 (s, 2H), 1.26 (t, J ) 7.2 Hz, 3H).22
Eth yl 4-Meth oxyp h en yla cetoa ceta te (7b). Compound 7b
was prepared as described for 7a using Meldrum’s acid 5 (15.0
g, 0.104 mol) and 4-methoxyphenylacetyl chloride (4b) (18.28
g, 0.099 mol). Distillation under reduced pressure gave 11.90
g (51%) of 7b as a clear oil: bp 95-98 °C (0.07 mbar); 1H NMR
(CDCl3) δ 7.21 (d, J ) 8.5 Hz, 2H), 6.86 (d, J ) 8.5 Hz, 2H),
4.14 (q, J ) 7.2 Hz, 2H), 3.79 (s, 3H), 3.55 (s, 2H), 1.26 (t, J )
7.2 Hz, 3H).
Eth yl 4-Ch lor op h en yla cetoa ceta te 7c. Compound 7c
was prepared as described for 7a using Meldrum’s acid 5 (11.0
g, 0.076 mol) and 4-methoxyphenylacetyl chloride 4c (14.0 g,
0.081 mol). Distillation under reduced pressure gave 11.2 g
(57%) of 7c as a clear oil: bp 115 °C (0.07 mbar); 1H NMR
(CDCl3) δ 7.30 (d, J ) 8.2 Hz, 2H), 7.13 (d, J ) 8.3 Hz, 2H),
4.17 (q, J ) 7.1 Hz, 2H), 3.80 (s, 2H), 3.45 (s, 2H), 1.26 (t, J )
7.2 Hz, 3H).
3-Ben zyl-1-p h en yl-5-p yr a zolon e (8a ). To a well-stirred
solution of ethyl phenylacetoacetate 7a (26.7 g, 0.115 mol) in
60% EtOH (12 mL) was added dropwise phenylhydrazine (12.1
g, 0.112 mol) at such a rate that the temperature was kept
below 50 °C (approximately 30 min). The yellow reaction
mixture was stirred at room temperature for 2 h, refluxed for
4 h, and finally allowed to cool to room temperature and poured
into a mixture of H2O/ice (100 mL) containing two drops of
concentrated HCl. The resulting yellow solid was filtered,
washed with H2O (3 × 100 mL), and dried. Recrystallization
from 96% EtOH gave 23.5 g (82%) of 8a as white crystals: mp
134-135 °C; 1H NMR (CDCl3) δ 7.88 (d, J ) 7.7 Hz, 2H), 7.4-
7.1 (m, 8H), 3.82 (s, 2H), 3.33 (s, 2H); 13C NMR (CDCl3) δ 170.6,
158.7, 138.1, 135.6, 129.1, 128.9, 128.8, 127.5, 125.2, 119.0,
41.0, 37.9; MS (EI) m/z 250 (M+, 100); IR (KBr) ν 1714, 1690
cm-1. Anal. Calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19.
Found: C, 76.75; H, 5.61; N, 11.36.
this step to prevent the reaction mixture from becoming solid
midway through the addition, thus causing the temperature
to rise out of control). Then 3-benzyl-1-phenyl-5-pyrazolone
(8a ) (12.5 g, 0.05 mol) was added in small portions, and the
resulting solution was stirred at room temperature for 30 min
and at 100 °C for 1 h. The dark reaction mixture was cooled
to room temperature and poured slowly onto ice/H2O (75 mL)
and neutralized to pH 6-7 by adding Na2CO3 in small
portions. The resulting brown solid was filtered and washed
with H2O. Recrystallization from EtOH gave 9.94 g (67%) of
9a as yellow plates: mp 107-108 °C; 1H NMR (CDCl3) δ 9.95
(s, 1H), 7.6-7.1 (m, 10H), 4.31 (s, 2H); 13C NMR (CDCl3) δ
183.5, 154.1, 129.3, 129.2, 129.1, 128.4, 126.5, 125.3, 116.9,
33.8; MS (EI) m/z 296 (M+, 100); IR (KBr) ν 1679, 1523 cm-1
.
Anal. Calcd for C17H13ClN2O: C, 68.81; H, 4.42; N, 9.44.
Found: C, 68.76; H, 4.39; N, 9.42.
5-Ch lor o-4-for m yl-3-(4-m eth oxyben zyl)-1-p h en ylp yr a -
zole (9b). Compound 9b was prepared as for 9a above
employing 3-(4-methoxybenzyl)-1-phenyl-5-pyrazolone (8b) (8.72
g, 0.031 mol). The product crystallized immediately upon being
poured into water, thus allowing it to be isolated by filtration.
After the product was washed thoroughly on the filter with
water and air dried, the crude product was recrystallized from
EtOH to give 8.54 g (84%) of 9b as yellow plates: mp 90-91
1
°C; H NMR (CDCl3) δ 9.94 (s, 1H), 7.65-7.55 (m, 5H), 7.33
(d, J ) 8.6 Hz, 2 H), 6.83 (d, J ) 8.6 Hz, 2 H), 4.23 (s, 2H),
3.77 (s, 3H); 13C NMR (CDCl3) δ 183.4, 158.2, 154.5, 136.9,
133.6, 130.1, 130.0, 129.2 (2C), 125.2, 116.7, 113.8, 55.1, 32.8;
MS (EI) m/z 326 (M+, 100); IR (KBr) ν 1675, 1524 cm-1. Anal.
Calcd for C18H15ClN2O2: C, 66.16; H, 4.63; N, 8.57. Found: C,
66.00; H, 4.67; N, 8.54.
5-Ch lor o-3-(4-ch lor ob en zyl)-4-for m yl-1-p h en ylp yr a -
zole (9c). Compound 9c was prepared as for 9a above
employing 3-(4-chlorobenzyl)-1-phenyl-5-pyrazolone (8c) (5.7
g, 0.020 mol). The pale brown solid isolated was pure by NMR
and TLC for further reaction: yield 5.8 g (88%); mp 87-88 °C
1
(EtOH); H NMR (CDCl3) δ 9.92 (s, 1H), 7.60-7.45 (m, 5H),
7.33 (d, J ) 8.5 Hz, 2 H), 7.24 (d, J ) 8.5 Hz, 2 H), 4.25 (s,
2H); 13C NMR (CDCl3) δ 183.4, 153.5, 136.8, 136.4, 133.9,
132.3, 130.4, 129.2 (2C), 128.4, 125.1, 116.7, 33.1; MS (EI) m/z
330 (M+, 100); IR (KBr) ν 1681, 1524 cm-1. Anal. Calcd for
3-(4-Meth oxyben zyl)-1-p h en yl-5-p yr a zolon e (8b). Com-
pound 8b was prepared as reported for 8a using ethyl
4-methoxyphenylacetoacetate (7b) (9.69 g, 0.041 mol) and
phenylhydrazine (4.43 g, 0.041 mol). Recrystallization from
96% EtOH gave 9.58 g (84%) of 8b as white crystals: mp 131-
132 °C; 1H NMR (CDCl3) δ 7.91 (d, J ) 7.6 Hz, 2H), 7.28 (d, J
) 8.6 Hz, 2H), 7.25 (m, 3H), 6.88 (d, J ) 8.6 Hz, 2H), 3.77 (s,
3H), 3.70 (s, 2H), 3.32 (s, 2H); 13C NMR (CDCl3) δ 170.3, 158.7,
147.2, 137.6, 128.5, 127.9, 127.2, 126.2, 123.4, 114.5, 55.1, 40.9,
C
17H12Cl2N2O: C, 61.56; H, 3.65; N, 8.46. Found: C, 61.83; H,
3.74; N, 8.36.
5-Azid o-3-ben zyl-4-for m yl-1-p h en ylp yr a zole (1a ). The
appropriate 3-benzyl-5-chloro-4-formyl-1-phenylpyrazole (9a )
(1.48 g, 5 mmol) was dissolved in DMSO (25 mL) in a 100 mL
round-bottomed flask, and sodium azide (0.975 g, 15 mmol)
was added. The reaction mixture was stirred for 3 d at 35 °C
in the absence of light, after which it was diluted with H2O
(200 mL) and extracted with Et2O (150 mL). The organic phase
was washed with brine (3 × 100 mL) and H2O (150 mL), after
which it was dried (Na2SO4). Removal of the solvent left a solid
residue, which was purified by column chromatography (silica
gel, CH2Cl2, Rf ) 0.46) to give 0.70 g (46%) of 1a as a green
crystalline solid: mp 98-99 °C; 1H NMR (CDCl3) δ 9.86 (s,
1H), 7.80-7.2 (m, 10H), 4.25 (s, 2H); 13C NMR (CDCl3) δ 183.6,
154.4, 140.7, 138.0, 137.0, 129.0, 128.7, 128.5, 126.7, 124.3,
111.8, 33.7; MS (EI) m/z 303 (M+, 1), 275 (M+ - N2, 15); IR
(KBr) ν 2145, 1669, 1523 cm-1. Anal. Calcd for C17H13N5O: C,
67.32; H, 4.32; N, 23.09. Found: C, 67.23; H, 4.28; N, 23.15.
5-Azid o-4-for m yl-3-(4-m et h oxyb en zyl)-1-p h en ylp yr a -
zole (1b). Compound 1b was prepared as for 1a described
above and purified by chromatography (silica gel, CH2Cl2, Rf
) 0.34) to give 1.47 g (88%) of 1b as greenish needles: mp
60-61 °C; 1H NMR (CDCl3) δ 9.86 (s, 1H), 7.62 (d br, J ) 7.1
Hz, 2H), 7.55-7.4 (m, 3H), 7.24 (d, J ) 8.7 Hz, 2H), 6.86 (d, J
) 8.7 Hz, 2H), 4.18 (s, 2H), 3.78 (s, 3H); 13C NMR (CDCl3) δ
183.6, 158.4, 154.8, 140.6, 137.0, 130.0, 129.5, 129.0, 128.4,
124.2, 114.1, 111.7, 55.2, 32.8; MS (EI) m/z 333 (M+, 2), 305
(M+ - N2, 7); IR (KBr) ν 2147, 1672, 1512 cm-1. Anal. Calcd
for C18H15N5O2: C, 64.86; H, 4.54; N, 21.01. Found: C, 64.41;
H, 4.46; N, 20.84.
36.9; MS (EI) m/z 280 (M+, 100); IR (KBr) ν 1714, 1693 cm-1
.
Anal. Calcd for C16H14N2O: C, 72.84; H, 5.75; N, 9.99. Found:
C, 76.75; H, 5.61; N, 11.36.
3-(4-Ch lor oben zyl)-1-p h en yl-5-p yr a zolon e (8c). Com-
pound 8c was prepared as reported for 8a using ethyl
4-chlorophenylacetoacetate (7c) (11.17 g, 0.046 mol) and
phenylhydrazine (5.02 g, 0.046 mol). Recrystallization from
96% EtOH gave 11.40 g (87%) of 8c as white crystals: mp
131-132 °C; 1H NMR (CDCl3) δ 7.86 (d, J ) 7.6 Hz, 2H), 7.5-
7.1 (m, 7H), 3.79 (s, 2H), 3.32 (s, 2H); 13C NMR (DMSO-d6) δ
165.5, 151.5, 138.1, 137.9, 130.8, 130.3, 128.8, 128.1, 125.6,
120.9, 87.6, 33.5; MS (EI) m/z 284 (M+, 100); IR (KBr) ν 1714,
1690 cm-1. Anal. Calcd for C16H13ClN2O: C, 67.49; H, 4.60;
N, 9.84. Found: C, 67.48; H, 4.56; N, 9.84.
3-Ben zyl-5-ch lor o-4-for m yl-1-ph en ylpyr azole (9a). DMF
(11.0 g, 0.15 mol) was poured into a 250 mL three-necked
round-bottomed flask equipped with a mechanical stirrer,
addition funnel, and thermometer and cooled to 0 °C on an
ice bath. To the reaction flask was slowly added POCl3 (32
mL, 0.35 mol) at such a rate that the temperature was
maintained below 10 °C (mechanical stirring is essential in
(22) Interestingly, this procedure appears to produce the keto form
exclusively, as opposed to a similar procedure that produces a mixture
of the keto an enol forms: Capozzi, G.; Roelens, S.; Talami, S. J . Org.
Chem. 1993, 58, 7932-7936.
5-Azid o-4-for m yl-3-(4-ch lor ob e n zyl)-1-p h e n ylp yr a -
zole (1c). Compound 1c was prepared as above for 1a and
purified by chromatography (silica gel, CH2Cl2, Rf ) 0.56) to

2820 J . Org. Chem., Vol. 64, No. 8, 1999
Svenstrup et al.
give 1.07 g (63%) of 1c as an orange crystalline solid: mp 93-
(s, 2H), 3.78 (s, 3H); 13C NMR (CDCl3) δ 158.4, 156.4, 138.8,
132.3, 129.8, 129.6, 129.4, 127.8, 119.6, 114.0, 113.2, 93.5, 55.2,
32.8; MS (EI) m/z 289 (M+, 100); IR (KBr) ν 2230 cm-1; HRMS
found 289.1217, calcd 289.1210. Anal. Calcd for C18H15N3O:
C, 74.72; H, 5.23; N, 14.52. Found: C, 75.01; H, 5.22; N, 14.67.
Single crystals for X-ray diffraction were prepared by slow
evaporation of a solution of 3b in 10% methanolic HCl.
1
94 °C; H NMR (CDCl3) δ 9.86 (s, 1H), 7.7-7.2 (m, 9H), 4.20
(s, 2H); 13C NMR (CDCl3) δ 183.1, 153.8, 140.8, 136.9, 136.4,
132.6, 129.9, 129.1, 128.8, 128.6, 124.2, 111.7, 33.0; MS (EI)
m/z 337 (M+, 4), 309 (M+ - N2, 15); IR (KBr) ν 2146, 1672,
1525 cm-1. Anal. Calcd for C17H12ClN5O: C, 60.45; H, 3.58;
N, 20.73. Found: C, 60.53; H, 3.62; N, 20.64.
Th er m olyses of 5-Azid o-4-for m ylp yr a zoles. The ap-
propriate azidopyrazole (1 mmol) was dissolved in toluene (40
mL) in an atmosphere of dry N2 and stirred at 95 °C while
continuously being monitored by TLC (eluent CH2Cl2) to reveal
two major products. After 4 h, the starting material had been
consumed, the reaction mixture was cooled to room temper-
ature, and the toluene was removed in vacuo. The resulting
orange solid was chromatographed to give two major fractions;
thus, 1a gave 2a and 3a , 1b gave 2b and 3b, and 1c gave 2c
and 3c.
3-(4-Ch lor oph en yl)-4-cyan o-1-ph en ylpyr azole (3c): yield
80 mg (25%); Rf ) 0.47 (CH2Cl2), chromatographed on SiO2
(CH2Cl2/cyclohexane 2:1); mp 92-93 °C; 1H NMR (CDCl3) δ
8.17 (s, 1H), 7.64 (dt, J ) 1.4, 8.0 Hz, 2H), 7.48 (t, J ) 7.2 Hz,
2H), 7.44-7.27 (m, 5H), 4.13 (s, 2H), 3.78 (s, 3H); 13C NMR
(CDCl3) δ 155.5, 138.7, 135.8, 132.7, 132.4, 130.2, 129.7, 128.7,
128.0, 119.6, 113.0, 93.6, 32.9; MS (EI) m/z 293 (M+, 100); IR
(KBr) ν 2228 cm-1; HRMS found 293.0728, calcd 293.0720.
Anal. Calcd for C17H12ClN3: C, 69.51; H, 4.12; N, 14.30.
Found: C, 69.43; H, 4.16; N, 14.20.
4-Cya n o-2-p h en yl-3-p h en yla zofu r a n (2a ): yield 77 mg
(28%); Rf ) 0.57 (CH2Cl2), chromatographed on SiO2 (CH2Cl2/
cyclohexane 1:1); mp 152-153 °C; 1H NMR (CDCl3) δ 8.15 (dd,
J ) 1.7, 8.2 Hz, 2H), 7.95 (s, 1H), 7.95 (dd, J ) 1.6, 8.1 Hz,
2H), 7.6-7.4 (m, 6H); 13C NMR (CDCl3) δ 154.1, 152.3, 150.4,
136.4, 131.6, 130.0, 129.1, 128.8, 128.2, 127.3, 123.0, 112.5,
92.4; MS (EI) m/z 273 (M+, 98); IR (KBr) ν 2232 cm-1. Anal.
Calcd for C17H11N3O: C, 74.71; H, 4.06; N, 15.38. Found: C,
74.45; H, 4.09; N, 15.18.
Azid e Th er m olysis Op tim ized for th e P r od u ction of
4-Cya n o-2-(4-m eth oxyp h en yl)-3-(p h en yla zo)fu r a n (2b). A
solution of a mixture of 5-azido-4-formyl-3-(4-methoxybenzyl)-
1-phenylpyrazole (1b) (300 mg, 0.90 mmol) and 2,3-dichloro-
5,6-dicyano-1,4-quinone (10) (306 mg, 1.35 mmol, 1.5 molar
equiv) in dry toluene (20 mL) was heated at 95 °C in an
atmosphere of dry N2. During this time, the progress of the
reaction was monitored by TLC, revealing the gradual ap-
pearance of the spot corresponding to the presence of furan
2b, and at the same time confirming the formation of only
trace amounts of the pyrazole 3b. After 4 h of heating, the
reaction was cooled to room temperature, and the solvent was
removed in vacuo, leaving a solid residue, which was purified
by column chromatography on silica gel (eluent DCM) to give
134 mg of 4-cyano-2-(4-methoxyphenyl)-3-phenylazofuran (2b)
(0.44 mmol, 49%). This material was identical to the material
isolated in the unbiased reaction as described above.
4-Cya n o-2-(4-m eth oxyp h en yl)-3-(p h en yla zo)fu r a n (2b):
yield 82 mg (27%); Rf ) 0.49 (CH2Cl2), chromatographed on
SiO2 (CH2Cl2/cyclohexane 1:1); mp 179-180 °C; 1H NMR
(CDCl3) δ 8.07 (d, J ) 8.9 Hz, 2H), 7.91 (dd, J ) 1.6 and 8.0
Hz, 2H), 7.88 (s, 1H), 7.55-7.45 (m, 3H), 7.00 (d, J ) 8.9 Hz,
2H), 3.86 (s, 3H); 13C NMR (CDCl3) δ 161.1, 154.4, 152.3, 149.9,
135.1, 131.3, 129.1, 128.9, 122.9, 120.9, 114.4, 112.7, 92.3, 55.3;
MS (EI) m/z 303 (M+, 75); IR (KBr) ν 2236 cm-1. Anal. Calcd
for C18H13N3O2: C, 71.28; H, 4.32; N, 13.85. Found: C, 70.89;
H, 4.43; N, 13.75. Single crystals for X-ray diffraction were
prepared by recrystallization from 1,2-dichloroethane/MeOH.
2-(4-Ch lor op h en yl)-4-cya n o-3-(p h en yla zo)fu r a n (2c):
yield 80 mg (25%); Rf ) 0.56 (CH2Cl2), chromatographed on
SiO2 (CH2Cl2/cyclohexane 2:1); mp 174-176 °C; 1H NMR
(CDCl3) δ 8.07 (dt, J ) 2.1, 8.8 Hz, 2H), 7.95 (s, 1H), 7.94-
7.88 (m, 2H), 7.57-7.49 (m, 3H), 7.47 (dt, J ) 2.1 and 8.8 Hz,
2H); 13C NMR (CDCl3) δ 152.9, 152.1, 150.4, 136.5, 136.3,
131.9, 129.2 (2C), 128.3, 126.6, 123.0, 112.3, 92.6; MS (EI) m/z
Azid e Th er m olysis Op tim ized for th e P r od u ction of
4-Cya n o-3-(4-m eth oxyp h en yl)-1-p h en ylp yr a zole (3b). 5-
Azido-4-formyl-3-(4-methoxybenzyl)-1-phenylpyrazole (1b) (150
mg, 0.45 mmol) was dissolved in dry toluene (20 mL) under a
blanket of N2, and a mixture of 1,2-diphenylhydrazine (0.68
mmol) and p-toluenesulfonic acid (4 mg) was added. The
resulting yellow mixture was heated at 95 °C for 4 h while
being constantly monitored by TLC as described in the
procedure above, after which the solvent was removed in
vacuo. The red residue was subjected to column chromatog-
raphy on silica gel to give, in order of elution, 12 mg of 4-cyano-
2-(4-methoxyphenyl)-3-phenylazofuran (2b) (0.04 mmol, 9%)
and 53 mg of 4-cyano-3-(4-methoxyphenyl)-1-phenylpyrazole
(3b) (0.183 mmol, 41%). The compound isolated in this
experiment were indistinguishable from the products isolated
from the thermolysis of 5-azido-4-formyl-3-(4-methoxybenzyl)-
1-phenylpyrazole (1b).
307 (M+, 19); IR (KBr) ν 2239 cm-1. Anal. Calcd for C17H10
-
ClN3O: C, 66.35; H, 3.28; N, 13.65. Found: C, 66.05; H, 3.27;
N, 13.71.
3-Ben zyl-4-cya n o-1-p h en ylp yr a zole (3a ): yield 77 mg
(30%); Rf ) 0.41 (CH2Cl2), chromatographed on SiO2 (CH2Cl2/
1
cyclohexane 1:1); mp 95 °C; H NMR (CDCl3) δ 8.17 (s, 1H),
7.70-7.20 (m, 10H), 4.17 (s, 2H); 13C NMR (CDCl3) δ 156.0,
138.7, 137.4, 132.3, 129.6, 128.8, 128.6, 127.9, 126.8, 119.6,
113.2, 93.7, 33.6; MS (EI) m/z 259 (M+, 100); IR (KBr) ν 2227
cm-1; HRMS found 259.1104, calcd 259.1110. Anal. Calcd for
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
C
17H13N3: C, 78.74; H, 5.05; N, 16.20. Found: C, 78.35; H,
and 13C NMR spectra for compounds 1a -c, 2a -c, and 3a -c;
crystal data, data collection details and refinement param-
eters, as well as ORTEP representations of the X-ray crystal
structures of 2b and 3b. This material is available free of
charge via the Internet at http://pubs.acs.org.
5.15; N, 16.06.
4-Cya n o-3-(4-m eth oxyp h en yl)-1-p h en ylp yr a zole (3b):
yield 66 mg (23%): Rf ) 0.23 (CH2Cl2), chromatographed on
SiO2 (CH2Cl2); mp 75 °C; 1H NMR (CDCl3) δ 8.17 (s, 1H), 7.64
(d, J ) 8.0 Hz, 2H), 7.48 (t, J ) 7.7 Hz, 2H), 7.44 (t, J ) 7.3
Hz, 1H), 7.31 (d, J ) 8.6 Hz, 2H), 6.86 (dt, 2.0, 8.7, 2H), 4.10
J O9822075