Synthesis and transformations of tetrazolylacroleins

Article abstract of DOI:10.1016/S0040-4020(03)01207-9

1-Methoxy-4-aryltetrazolyldienes have been subjected to oxidative degradation to yield tetrazolyl acroleins. These compounds when reacted with 1,1-dimethylhydrazine gave 1-dimethylamino-4-aryltetrazolyl-1-azadienes. Both the acroleins and the new 1-azadienes underwent ring transformation in reaction with fumaronitrile to afford pyrazolyl derivatives.

Full text of DOI:10.1016/S0040-4020(03)01207-9

Tetrahedron 59 (2003) 7485–7489
Synthesis and transformations of tetrazolylacroleins
†
a
,
a
a
a
b
´
´
´
´
´
´
Ildiko Nagy, Denes Konya, Zsuzsanna Riedl, Andras Kotschy, Geza Timari,
a
Andras Messmer and Gyorgy Hajos
a
,
*
´
´
¨
aChemical Research Center, Institute of Chemistry, Hungarian Academy of Sciences, P.O. Box 17, Pusztaszeri ut 59,
H-1025 Budapest, Hungary
¨ ¨
´ ´ ´ ´ ´ ´
Department of General and Inorganic Chemistry, Eotvos Lorand University, H-1117 Budapest, Pazmany P. setany 1, Hungary
b
Received 8 May 2003; revised 30 June 2003; accepted 30 July 2003
Abstract—1-Methoxy-4-aryltetrazolyldienes have been subjected to oxidative degradation to yield tetrazolyl acroleins. These compounds
when reacted with 1,1-dimethylhydrazine gave 1-dimethylamino-4-aryltetrazolyl-1-azadienes. Both the acroleins and the new 1-azadienes
underwent ring transformation in reaction with fumaronitrile to afford pyrazolyl derivatives.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
1-azadiene of type 10 in the area of tetrazolylazadienes.
The key to this new strategy was the observation that
1-methoxy-4-(2-aryltetrazolyl-5)butadienes (11) readily
obtainable by the reaction of 3-aryltetrazolopyridinium
salt (1a) with sodium methoxide7 (isolable as a mixture of
1-cis–3-trans and 1,3-cis–cis isomers) proved to be
unstable in crystalline state upon storage on air and, in
several days, underwent a spontaneous decomposition to
yield aryltetrazolyl-acroleins (12) (Scheme 3).
In the course of our extensive research1–4 on ring opening
of azolopyridinium salts (1) we found that reaction of these
compounds with nucleophiles can result in ring opening of
the pyridine moiety to afford azolyldienes (2) (Scheme 1).
We have also reported that related heteroaromatic triazo-
lium salts containing a diazine ring instead of the pyridine
moiety can also be transformed to the corresponding
azadienes. Thus, [1,2,3]triazolopyrimidinium salts (3 and
7) gave the 1- and 2-azadienes 4 and 8, respectively,5
whereas the pyrazine-fused azolium salt 5 afforded the
2-azadiene 6 (Scheme 2).2
Photodegradations analogous to this unexpected transform-
ation can be found in the literature and are mainly
interpreted by action of singlet oxygen to yield a dioxethane
intermediate and a subsequent decomposition. Thus,
transformation of olefins to two different oxo compounds
can be carried out8 and similar reaction of 1,4-bis-
alkoxydiene has also been reported9 to yield methyl formate
and 3-methoxypropenal.
Realization of a fourth variation of the position of the
nitrogen atom in the diene chain (i.e. the synthesis of 10)
seemed of further interest, but our synthetic strategy (i.e. the
nucleophilic attack on the azine ring) was obviously not
applicable for this desired synthesis as the appropriate
pyridazine-fused salt (9) contains a nitrogen atom at the
particular position.6
Because of the preparative importance of this finding a well
executable procedure convenient also for multigram scale
transformations seemed to be necessary. Furthermore, based
on the above mechanistic considerations (i.e. the supposi-
tion that singlet oxygen is the effective reagent) use of a
2. Discussion
Recently we have found that a different pathway seems
fairly straightforward in order to prepare the missing
Keywords: ring transformation; 1-azadiene; photooxidation; 1,3-dipolar
cycloaddition.
*
Corresponding author. Tel.: þ36-1-3257550; fax: þ36-1-3257863;
e-mail: ghajos@chemres.hu
Present address: CHINOIN Pharmaceutical Works Co. Ltd, H-1325
Budapest, P.O. Box 110, Hungary.
†
Scheme 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01207-9

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I. Nagy et al. / Tetrahedron 59 (2003) 7485–7489
Scheme 4.
the exceptions in this respect, and simultaneous formation
of two compounds (14 and 15 in a ratio of 4:1, respectively)
was experienced under fairly forced conditions (Scheme 5).
Although this finding provided a synthetically valuable
approach to a new type of (i.e. to pyrazole-substituted)
dieneamines (14), it has also shown that the new
1-azadienes (13) do not participate in a common Diels–
Alder reaction as expected. Instead, the tetrazole ring
undergoes nitrogen elimination under the forced conditions
applied to yield a nitrilimine (a reactive 1,3-dipole), and this
reactive intermediate can undergo further transformations as
well documented in the literature.10–12 Either this inter-
mediate reacts with the dipolarophile via the well known
[1,3] dipolar cyclization route (i.e. to give a dihydropyrazole
intermediate followed by hydrogen cyanide elimination) to
the pyrazole 14 or, more interestingly, an intramolecular
ring closure involving the azadiene chain takes place and a
[1,5] dipolar cyclization yields 15.
Scheme 2.
photosensitiser was studied. For this purpose, a solution of
the starting methoxydiene (11) in dichloromethane was
irradiated by a common lamp in the presence of tetra-
phenylporphyrin and a continuous introduction of air at
room temperature for a prolonged period. As expected, the
acrolein product 12 was obtained in medium to good yield.
Structure elucidation revealed that the crude product was
still a mixture of cis and trans isomers, but after
recrystallization from isopropanol the isomerization to the
trans product (12) seemed to be complete (Scheme 4).
Similar to the reactivity of 13, the acrolein compound 12
also underwent ring transformation in the presence of
fumaronitrile to yield pyrazolyl-acroleins (16). It is inter-
esting to note that in both cases (i.e. with formation of both
14 and 16) the elimination was totally selective as supported
by the 1H NMR (HMBC and HetCor) experiments of these
products.
Besides fumaronitrile, fumaric ester was also successfully
applied in 1,3-dipolar cycloaddition reaction with 13. In this
case, the starting compound 13a afforded a dihydropyrazole
product 17 which, unlike the previous case, could be
isolated in this dihydro form and no spontaneous aromatiza-
tion took place. Work up of the reaction mixture revealed
We have found that the new acrolein derivatives (12) readily
participated in a condensation reaction with 1,1-disubsti-
tuted hydrazines to give hydrazones. Thus, a smooth
reaction of 12 with 1,1-dimethylhydrazine gave the desired
1-dimethylamino-1-azadiene (13) in good yield.
Although some of the earlier synthesized tetrazolyldien-
amines as well as some azadieneamines proved to be
reactive towards dienophiles in Diels–Alder type trans-
formations, our efforts to observe such a reactivity of 13
failed in the most cases (e.g. no reaction could be detected
with N-phenylmaleinimide, dimethyl acetylene dicarbox-
ylate, etc.).
Fumaronitrile, interestingly however, proved to be one of
Scheme 3.
Scheme 5.

I. Nagy et al. / Tetrahedron 59 (2003) 7485–7489
7487
(150 mL), catalytic amount of tetraphenylporphyrin (30 mg,
approximately) was added, the reaction mixture was
illuminated by a 60 W electric bulb, and air was bubbled
through the reaction mixture at room temperature. The
progress of the reaction was monitored by TLC. After
completion of the reaction (4–7 days) the solvent was
removed in vacuo, the residue was purified by column
chromatography (Kieselgel 60H, dichloromethane/hexane
(1:1) as an eluent), and the main fraction was recrystallized
from isopropanol.
Scheme 6.
4.2.1. 2-(4-Chlorophenyl)-5-[(1E)-3-oxoprop-1-en-1-yl]-
2H-tetrazole (12a). 1.64 g, 70%. Pale yellow crystals; mp
998C; nmax (KBr) 1686, 1493, 1418, 1113, 1100, 1003, 987,
833 cm21; dH (200 MHz, CDCl3) 9.85 (1H, d, J¼7.7 Hz,
CHO), 8.10–8.14 (AA0), 7.48–7.67 (3H, m, BB0, 10-H),
7.29 (1H, dd, J¼7.7, 16.2 Hz, 20-H); dC (100 MHz, CDCl3)
192.7, 162.4, 136.6, 135.7, 135.3, 135.2, 130.4, 121.5. Anal.
calcd for C10H7ClN4O (234.64), C: 51.19, H: 3.01, N:
23.88; found C: 51.44, H: 2.81, N: 23.73.
that the intramolecular cyclization also took place to form
the same byproduct as above (15) in traces (Scheme 6).
3. Conclusion
These findings reveal that our new approach provides a
relatively facile access to new hetarylazadienes and
hetarylacroleines. Elaboration of further synthetic tools
exploiting the reactivity of the aldehyde function of
tetrazolylacroleines is in progress and will be published
elsewhere.
4.2.2. 2-(4-Fluorophenyl)-5-[(1E)-3-oxoprop-1-en-1-yl]-
2H-tetrazole (12b). 1.00 g, 46%. Colorless crystals; mp
97–998C; nmax (KBr) 1687, 1507, 1233, 1113, 1002,
839 cm21; dH (200 MHz, CDCl3) 9.85 (1H, d, J¼7.7 Hz,
CHO), 8.13–8.20 (AA0), 7.64 (1H, d, J¼16.2 Hz, 10-H),
7.22–7.34 (3H, m, AA0, 20-H); dC (100 MHz, CDCl3) 192.4,
165.8, 161.9, 160.8, 134.8, 121.8 (JC,F¼8.7 Hz), 117.1,
116.7 (JC,F¼23.5 Hz). Anal. calcd for C10H7FN4O (218.19),
C: 55.05, H: 3.23, N: 25.68; found C: 54.82, H: 3.17, N:
25.67.
4. Experimental
Melting points were determined by a Bu¨chi apparatus and
are uncorrected. The IR spectra were recorded with a
Nicolet Magna 750 FT-IR, spectrophotometer; the NMR
spectra were recorded with Varian UNITY INOVA
1
spectrometer (200 and 400 MHz for H and 100 MHz for
13C).
4.2.3. 2-(4-Isopropyl)-5-[(1E)-3-oxoprop-1-en-1-yl]-2H-
tetrazole (12c). 1.11 g, 46%. Pale yellow crystals; mp
78–808C (iPrOH); nmax (KBr) 2964, 1687, 1515, 1106,
1004, 983, 838 cm21; dH (200 MHz, CDCl3) 9.85 (1H, d,
J¼7.7 Hz, CHO), 8.03–8.07 (AA0), 7.65 (1H, d, J¼16.1 Hz,
10-H), 7.41–7.45 (BB0), 7.28 (1H, dd, J¼16.1, 7.7 Hz, 20-H),
3.01 (1H, m, CH), 1.32 (6H, d, J¼6.8 Hz, CH3); dC
(100 MHz, CDCl3) 192.8, 162.0, 151.9, 135.7, 134.9, 134.7,
128.1, 120.3, 34.3, 24.1. Anal. calcd for C13H14N4O
(242.28), C: 64.45, H: 5.82, N: 23.13; found C: 64.67, H:
5.71, N: 22.96.
4.1. Synthesis of 1-tetrazolyl-4-methoxybutadienes (11)
The synthetic procedure for 2-(4-chlorophenyl)-5-(4-meth-
oxy-buta-1,3-dienyl)-2H-tetrazole (11a) was reported ear-
lier.7 The p-fluoro and p-isopropyl substituted derivatives
(11b and 11c, respectively) were also prepared according to
this literature procedure.
4.1.1. 2-(4-Fluorophenyl)-5-(4-methoxybuta-1,3-dienyl)-
2H-tetrazole (a mixture of 1Z,3E and 1Z,3Z isomers,
11b). Starting from 3-(4-fluorophenyl)tetrazolo[1,5-a]pyr-
idinium fluoroborate (1, Ar¼4-fluorophenyl, 0.95 g,
3 mmol) colorless crystals were obtained: 0.34 g, 46%;
mp 60–688C (iPrOH). Anal. calcd for C12H11FN4O
(246.24), C: 58.53, H: 4.50, N: 22.75; found C: 58.44, H:
4.67, N: 22.53.
4.3. General procedure for the synthesis of
N,N-dimethyl-hydrazones (13)
A mixture of the appropriate tetrazolylacrolein 12 (1 mmol),
sodium sulfate (0.3 g) and 1,1-dimethyl-hydrazine (0.61 g,
1.1 mmol, 0.78 mL) and dichloromethane (5 mL) was
allowed to stand at room temperature for 3 h. After
completion of the reaction the sodium sulfate was filtered
off, washed several times with dichloromethane, and the
solvent was removed in vacuo. The residue was purified by
recrystallisation from acetonitrile.
4.1.2. 2-(4-Isopropylphenyl)-5-(4-methoxybuta-1,3-di-
enyl)-2H-tetrazole (a mixture of 1Z,3E and 1Z,3Z
isomers, 11c). This compound was obtained from 3-(4-
isopropylphenyl)tetrazolo[1,5-a]pyridinium fluoroborate (1,
Ar¼4-isopropylphenyl, 0.98 g, 3 mmol). Yellow oil, 0.48 g,
59%; HRMS (EI): Mþ, found 269.1456. C15H17N4O
requires 269.1402.
4.3.1. 2-(4-Chlorophenyl)-5[(1E,3E)-5-(dimethylhydra-
zono)-prop-1-en-1-yl]-2H-tetrazole (13a). 0.25 g, 90%.
Yellow crystals; mp 161–1638C (CH3CN); nmax (KBr)
1630, 1549, 1492, 1417, 1350, 1203, 1092, 1059, 995,
830 cm21; dH (200 MHz, CDCl3) 8.03–8.09 (AA0), 7.49–
7.64 (3H, m, BB0, 20-H), 7.06 (1H, d, J¼9.2 Hz, 30-H), 6.63
(1H, d, J¼16.1 Hz, 10-H), 3.03 (6H, s, N–CH3); dC
4.2. Synthesis of tetrazolylacroleins (12)
The appropriate 2-aryl-5-(4-methoxy-buta-1,3-dienyl)-2H-
tetrazole (11, 10 mmol) was dissolved in dichloromethane

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I. Nagy et al. / Tetrahedron 59 (2003) 7485–7489
(100 MHz, CDCl3) 164.8, 136.2, 135.3, 135.1, 130.9, 129.8,
120.8, 113.4, 42.4 (N–CH3). Anal. calcd for C12H13ClN6
(276.72), C: 52.08, H: 4.74, N: 30.37; found C: 52.11, H:
4.67, N: 30.33.
4.4.2. 1-(4-Fluorophenyl)-3-[(1E,3E)-3-(dimethyl-hydra-
zono)prop-1-en-1-yl]-1H-pyrazole-4-carbonitrile (14b).
98 mg, 69%. Yellow crystals (1308C, 30 h); mp 150–
1538C (CH3CN); nmax (KBr) 2222, 1624, 1537, 1516, 1420,
1347, 1218, 1062, 965. 836 cm21; dH (200 MHz, CDCl3)
8.17 (1H, s, 5-H), 7.62–7.68 (AA0), 7.430 (1H, dd, J¼16.1,
9.2 Hz, 20-H),0 7.02–7.22 (3H, m, BB0, 3 -H), 6.58 (1H, d,
J¼16.1 Hz, 1 -H), 3.00 (6H, s, N–CH3); dC (100 MHz,
CDCl3) 164.3, 153.1, 135.0, 133.4, 132.5, 131.9, 121.3
(JC,F¼8.3 Hz), 117.4, 116.4 (JC,F¼23.2 Hz), 113.5 (CuN),
92.1, 42.5 (N–CH3). Anal. calcd for C15H14FN5 (283.30),
C: 63.59, H: 4.98, N: 24.72; found C: 63.29, H: 4.78, N:
24.90.
4.3.2. 2-(4-Fluorophenyl)-5[(1E,3E)-5-(dimethylhydra-
zono)-prop-1-en-1-yl]-2H-tetrazole (13b). 0.19 g, 76%.
Pale yellow crystals; mp 127–1288C (CH3CN); 1627, 1552,
1510, 1050, 998, 836 cm21; dH (200 MHz, CDCl3) 8.08–
8.15 (AA0),07.56 (1H, dd, J¼15.9, 9.1 Hz, 20-H), 7.20–7.30
(3H, m, BB , 30-H), 6.70 (1H, d, J¼15.9 Hz, 10-H), 3.04 (6H,
s, N–CH3); dC (100 MHz, CDCl3) 165.3, 160.3, 135.5,
121.6, 121.5 (JC,F¼8.6 Hz), 116.8, 116.4 (JC,F¼23.1 Hz),
114.7, 42.7 (N–CH3). Anal. calcd for C12H13FN6 (260.27),
C: 55.38, H: 5.03, N: 32.29; found C: 55.38, H: 4.95, N:
32.11.
4.4.3. 1-(4-Isopropylphenyl)-3-[(1E,3E)-3-(dimethyl-
hydrazono)prop-1-en-1-yl]-1H-pyrazole-4-carbonitrile
(14c). 65 mg, 42%. Yellow crystals (1408C, 40 h); mp 101–
1028C (diisopropylether); nmax (KBr) 3137, 2959, 2228,
4.3.3. 2-(4-Isopropylphenyl)-5[(1E,3E)-5-(dimethylhy-
drazono)-prop-1-en-1-yl]-2H-tetrazole (13c). 0.17 g,
61%. Beige crystals; mp 105–1068C (CH3CN); nmax
(KBr) 2967, 1630, 1552, 1513, 1471, 1420, 1350, 1197,
1056, 998, 974, 833 cm21; dH (200 MHz, CDCl3) 7.99–
8.04 (AA0), 7.59 (1H, dd, J¼9.2, 16.1 0Hz, 20-H), 7.36–7.40
(BB0), 7.09 (1H, d, J¼9.2 Hz, 3 -H), 6.68 (1H, d,
J¼16.1 Hz, 10H), 3.02 (7H, m, N–CH3, CH), 1.30 (6H, d,
J¼7.0 Hz, CH3); dC (100 MHz, CDCl3) 164.5, 150.5, 135.6,
134.8, 131.3, 127.5, 119.6, 119.0, 42.4 (N–CH3), 33.8
(CH), 23.8 (CH3). Anal. calcd for C15H20N6 (284.36),
C: 63.36, H: 7.09, N: 29.55; found C: 63.45, H: 7.18, N:
29.49.
1626, 1533, 1517, 1422, 1346, 1046, 970, 957, 839 cm21
;
dH (200 MHz, CDCl3) 8.18 (1H, s), 7.55–7.59 (AA0), 7.44
(1H, dd, J¼16.1, 9.0 Hz), 7.30–7.37 (BB0), 7.06 (1H, d,
J¼9.0 Hz), 6.61 (1H, d, J¼16.1 Hz), 2.99 (6H, s, N–CH3),
2.93 (1H, m, CH), 1.27 (6H, d, J¼6.5 Hz, CH3); dC
(100 MHz, CDCl3) 152.8, 149.0, 133.0, 132.3, 132.2, 127.6,
119.6, 117.8, 91.7, 42.4, 33.7, 23.8. Anal. calcd for
C18H21N5 (307.39), C: 70.33, H: 6.89, N: 22.78; found C:
70.29, H: 6.91, N: 22.89.
4.4.4. [2-(4-Isopropylphenylazo)-pyrrol-1-yl]-dimethyl-
amine (15c). Yellow oil, yield: 10% (1408C, 40 h); dH
(200 MHz, CDCl3) 7.72–7.77 (AA0), 7.30–7.34 (BB0),
7.05 (1H, dd, J¼3.1, 2.5 Hz, pyrrol b-H), 6.58 (1H, dd,
J¼4.0, 2.5 Hz, pyrrol d-H), 6.12 (1H, dd, J¼4.0, 3.1 Hz,
pyrrol g-H), 3.15 (6H, s, N–CH3), 2.97 (1H, m, CH),
1.28 (6H, d, J¼7.0 Hz, CH3); dC (100 MHz, CDCl3)
150.2, 146.8, 133.2, 127.0, 124.8, 122.1, 107.1, 97.9,
48.1, 34.0, 23.9; HRMS (EI): Mþ, found 256.3466.
C15H20N4 requires 256.3461.
4.4. General procedure for the ring transformation of
the 4-tetrazolyl-1-dimethylamino-1-azadienes to
pyrazolyl derivatives 14 and 16
A mixture of the appropriate tetrazolylazadiene or tetra-
zolylacrolein (13 or 12, respectively, 0.5 mmol), fumaroni-
trile (0.23 g, 2.93 mmol) in xylene (10 mL) was stirred
under an argon atmosphere at 140 or 1308C, and the reaction
was monitored by TLC. After completion of the reaction,
the solvent was removed in vacuo, and the residue was
purified by preparative layer chromatography, (hexane/ethyl
acetate (2:1) as an eluent). The separation allowed also the
detection of the pyrrol derivative 15 in traces (higher Rf
value), and in case of transformation of 13c, [2-(4-
isopropyl-phenylazo)-pyrrol-1-yl]-dimethyl-amine (15c)
was also isolated by chromatography, and identified by
1H- and 13C NMR spectroscopy.
4.4.5. 1-(4-Chlorophenyl)-3-[(1E)-3-oxoprop-1-en-1-yl]-
1H-pyrazole-4-carbonitrile (16a). 69.6 mg, 54%. Beige
crystals (1408C, 22 h); mp 146–1498C (CH3CN); nmax
(KBr) 2235, 1691, 1534, 1499, 1215, 1113, 1058, 977, 958,
827 cm21; dH (200 MHz, CDCl3) 9.78 (1H, d, J¼7.6 Hz,
CHO), 08.36 (1H, s, 5-H), 7.65–7.69 (AA0), 7.48–70.56 (3H,
m, BB , 10-H), 7.16 (1H, dd, J¼16.3, 7.6 Hz, 2 -H); dC
(100 MHz, CDCl3) 192.9 (CvO), 149.8, 138.6, 136.8,
134.7, 133.4, 132.4, 130.1, 121.0, 112.1 (CuN), 94.6. Anal.
calcd for C13H8ClN3O (257.68), C: 60.60, H: 3.13, N:
16.31; found C: 60.50, H: 3.19, N: 16.45.
4.4.1. 1-(4-Chlorophenyl)-3-[(1E,3E)-3-(dimethyl-hydra-
zono)prop-1-en-1-yl]-1H-pyrazole-4-carbonitrile (14a).
94.4 mg, 63%. Pale yellow crystals (1308C, 72 h); mp
162–1638C (iPrOH); nmax (KBr) 3129, 2225, 1626, 1533,
1499, 1421, 1352, 1288, 1221, 1054, 955, 822 cm21; dH
(400 MHz, CDCl3) 8.22 (1H, s, 3-H), 7.64 (AA0), 7.46
(BB0), 7.44 0(1H, dd, J¼16.0, 9.0 Hz, 20-H), 7.05 (1H, d,
J¼9.0 Hz, 3 -H), 6.58 (1H, d, J¼16.0 Hz, 10-H), 3.00 (6H, s,
N–CH3); dC (100 MHz, CDCl3) 153.2 (5-C), 137.3 (10-C),
133.6 (40-C), 133.7 (20-C), 132.3 (3-C), 131.7 (30-C), 129.8
(30, 50-C), 120.6 (20, 60-C), 117.2 (10-C), 113.3 (CuN), 92.4
(4-C), 42.4 (N–CH3). Anal. calcd for C15H14ClN5 (299.76),
C: 60.10, H: 4.71, N: 23.36; found C: 60.12, H: 4.64, N:
23.36.
4.4.6. 1-(4-Fluorophenyl)-3-[(1E)-3-oxoprop-1-en-1-yl]-
1H-pyrazole-4-carbonitrile (16b). 39.8 mg, 33%. Color-
less crystals (1408C, 22 h); mp 126–1298C (CH3CN); nmax
(KBr) 3123, 2234, 1678, 1513, 1374, 1248, 1224, 1161,
1128, 1065, 980, 833 cm21; dH (200 MHz, CDCl3) 9.79
(1H,0 d, J¼7.3 Hz, CHO), 8.31 (1H, s, 5-H), 7.66–7.73
(AA ), 07.54 (1H, d, J¼16.5 Hz, 10-H), 7.10–7.28 (3H, m,
BB0, 2 -H); dC (100 MHz, CDCl3) 193.2, 150.1, 139.0,
135.0, 133.9, 132.7, 122.2 (JC,F¼8.3 Hz), 117.1
(JC,F¼23.5 Hz), 112.5 (CuN), 94.8. Anal. calcd for
C13H8FN3O (241.22), C: 64.73, H: 3.34, N: 17.42; found
C: 64.56, H: 3.23, N: 17.15.

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4.4.7. 1-(4-Isopropylphenyl)-3-[(1E)-3-oxoprop-1-en-1-
Acknowledgements
yl]-1H-pyrazole-4-carbonitrile (16c). 49.1 mg, 37%. Pale
yellow crystals (1408C, 25.5 h); mp 125–1268C (CH3CN);
nmax (KBr) 2925, 2240, 1678, 1534, 1507, 1368, 1125,
1050, 980, 836 cm21; dH (200 MHz, CDCl3) 9.77 (1H, d,
J¼7.7 Hz, CHO), 8.33 (1H, s, 5-H), 7.49–7.63 (3H, m, AA0,
10-H), 7.36–7.40 (BB0), 7.16 (1H, dd, J¼7.7, 16.1 Hz, 20-H),
2.99 (1H, m, CH), 1.29 (6H, d, J¼7.0 Hz, CH3); dC
(100 MHz, CDCl3) 192.9, 150.1, 149.4, 139.0, 136.3, 133.4,
132.1, 127.8, 119.9, 112.4, 94.0, 33.8, 23.8. Anal. calcd for
C16H15N3O (265.31), C: 72.43, H: 5.70, N: 15.84; found C:
72.36, H: 5.71, N: 15.86.
National research funds OTKA 35176 and 1/047 NKFP
MediChem as well as EU fund QLK2-CT-2002-90436 are
gratefully acknowledged.
References
´
1. Kotschy, A.; Hajos, Gy.; Messmer, A.; Jones, G. Tetrahedron
1995, 52, 1399.
´ ´ ´
2. Beres, M.; Hajos, Gy.; Riedl, Zs.; Timari, G.; Messmer, A.;
Holly, S.; Schantl, J. G. Tetrahedron 1997, 53, 9393–9400.
´
4.4.8. Dimethyl (4S,5R)-rel-1-(4-chlorophenyl)-
3[(1E,3E)-3-dimethylhydrazono)prop-1-en-1-yl]-4,5-
dihydro-1H-pyrazole 4,5-dicarboxylate (17). A mixture
of tetrazolylazadiene 13a (0.140 g, 0.5 mmol), dimethylfu-
marate (0.28 g, 2 mmol) and xylene (12 mL) was stirred
under an argon atmosphere at 1308C for 46 h. The solvent
was removed in vacuo, and the residue was purified by
column chromatography (silica, hexane/ethyl acetate (2:1)
as an eluent). The product was recrystallized from a mixture
of diethyl ether–hexane to give the title compound (0.080 g,
41%); mp 131–1328C; nmax (KBr) 2953, 1741, 1596, 1497,
1396, 1296, 1225 cm21; dH (200 MHz, CDCl3) 7.10–7.30
(AA0), 6.8–7.0 (3H, m, BB0, 10-H), 6.74 0(1H, dd, J¼16.0,
8.3 Hz, 20-H), 6.54 (1H, d, J¼16.0 Hz, 3 -H), 4.79 (1H, d,
J¼4.4 Hz, 5-H), 4.02 (1H, d, J¼4.4 Hz, 4-H), 3.49 (6H, s,
COOCH3), 2.69 (6H, s, N–CH3); dC (100 MHz, CDCl3)
169.6, 168.9, 145.5, 141.9, 133.2, 132.6, 129.0, 125.1,
120.8, 114.4, 65.3, 54.7, 53.1, 53.0, 42.5. Anal. calcd for
C18H21ClN4O4 (392.84), C: 55.03, H: 5.39, N: 14.26; found
C: 55.10, H: 5.37, N: 14.23.
´ ´ ´
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