Reactions of 1,3-dipolar aldazines and ketazines with the dipolarophile dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1139/V02-169

The prepared aldazines (aldehyde azines) and ketazines (ketone azines) were allowed to react with 2 mol of the acetylene derivative. The first products formed were pentalene azine derivatives, which in some cases underwent skeletal rearrangment into acycl

Full text of DOI:10.1139/V02-169

1293
Reactions of 1,3-dipolar aldazines and ketazines
with the dipolarophile dimethyl
acetylenedicarboxylate
Abdullah El-Alali and Ahmed S. Al-Kamali
Abstract: The prepared aldazines (aldehyde azines) and ketazines (ketone azines) were allowed to react with 2 mol of
the acetylene derivative. The first products formed were pentalene azine derivatives, which in some cases underwent
skeletal rearrangment into acyclic tetraene azines. The latter underwent, in the case of some aldazine products, further
skeletal rearrangment into N-allyl pyrazoles. The occurence of these rearrangments is dependant on the nature of the
aldehydes or ketones used.
Key words: dimethyl acetylenedicarboxylate (DMAD), aldazines, ketazines, N-allyl pyrazoles.
Résumé : On a fait réagir des aldazines (azines d’aldéhydes) et des cétazines (azines de cétones) avec deux molécules
de dérivés acétyléniques. Les premiers produits formés sont des dérivés azines du pentalène qui, dans quelques cas,
subissent des réarrangements du squelette conduisant à des azines tétraènes acycliques. Dans certains cas, ces dernières
subissent d’autres réarrangements du squelette avec formation de N-allylpyrazoles. La formation de ces produits de
réarrangements dépend de la nature des aldéhydes ou des cétones utilisées.
Mots clés : acétylènedicarboxylate de diméthyle « DMAD », aldazines, cétazines, N-allylpyrazoles.
[Traduit par la Rédaction] El-Alali and Al-Kamali 1301
Introduction
Scheme 1.
The 1,3-dipolar aldazines or ketazines are actually 1,3-
heterodienes and have double 1,3-dipolar sites (Scheme 1).
These acyclic 1,3-heterodienes adopt the s-trans confor-
mation due to steric interactions of the alkyl or aryl substituents.
This conformation does not undergo the [4 + 2]-cyclo-
additions known as the Diels–Alder reactions (1, 2). The
above mentioned heterodienes 1 (Scheme 1), reacted with 2
equiv of dipolarophiles, such as dimethyl acetylenedicar-
boxylate 2, in [2 + 3]-cycloaddition (3–5) reactions and
gave, in this case, the pentalene azines 3 (Scheme 2).
Only two aldazines out of 10 and three ketazines out of
six stayed in the bicyclic azine 3 as the final products. The
formation of the acyclic teraene azines 4, as the final prod-
uct of three ketazines, after their conversion with the acety-
lene derivative 2, can only happen through skeletal
rearrangment (5) of the bicyclic form 3 as depicted in
Scheme 3. The N-allyl pyrazoles 7 as final products of the
eight aldazines are formed through further skeletal
rearrangment of the acyclic form 4, leading to a zwitterion 5
and then to the intermediates 6. The latter tautomerizes in
the final stage to the N-allyl pyrazoles 7, as shown in the
slightly modified mechanism in the literature (5) (Scheme 3).
Scheme 2.
Received 11 October 2001. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 7 October 2002.
Characterization of all products was achieved by using
1H NMR, 13C NMR, FT IR spectroscopy and elemental
analysis.
Investigation of the skeletal rearrangment taking place in
some cases is in progress. The observed reactions in the
A. El-Alali1 and A.S. Al-Kamali. Department of Chemistry,
Mutah University, P.O. Box 7. Al-Karak-H.K. of Jordan.
1Corresponding author (e-mail: elalali@mutah.edu.jo).
Can. J. Chem. 80: 1293–1301 (2002)
DOI: 10.1139/V02-169
© 2002 NRC Canada

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Can. J. Chem. Vol. 80, 2002
Table 1. The aldehydes and aldazines.
Scheme 3.
Table 2. Physical and analytical data.
Yield
(%)
IR-KBr imine ꢀ
Time of
reflux
Aldazine
23
mp (°C) (Colour)
135–137, Yellow
(cm–1)
1H NMR ꢁ (ppm)
81
1617
2 h
7.3–8.2 (m, 8H, aromatic),
9.1 (s, 2H, imine)
literature (3–5) and in this work do not give a clear explana-
tion. Also the formation of N-allyl pyrazoles is highly inter-
esting. Similar compounds in the literature possess
biological activities such as antipyritic (6), antitumor (7),
herbicidal (8), and antibiotic (9, 10). The bioassay of these
compounds will be investigated later.
The aromatic ketazines 32–35 (Table 3), were also pre-
pared by modified procedures. Only the ketazine 35 is re-
ported (14). In the case of the ketazines, a few drops of
glacial acetic acid were added to the reaction mixture which
were not necessary for the preparation of aldazines, due to
their high reactivity.
The characterization of the ketazines 32–34 is shown in
Table 4.
Results and discussion
The two available alicyclic ketones 36 and 38 were al-
lowed to react with hydrazine monohydrate and gave the de-
sired ketazines 37 and 39 (Scheme 5).
Preparation of the aldazines and ketazines (Scheme 4
and Tables 1–4)
From Table 1, one can predict that only aromatic
aldazines were prepared (11–13) and the 2-chlorobenzalde-
hyde 23 was not reported. All other reported aldazines were
prepared in modified procedures. The characterization of the
aldazine 23 is depicted in Table 2.
Preparation of the bicyclic azines (Scheme 6)
As depicted in Scheme 6, only the two aldazines (2-
chlorobenzaldehyde azine 23 and 4-nitrobenzaldehyde azine
26) stayed in the final product as the bicyclic forms 40 and
© 2002 NRC Canada

El-Alali and Al-Kamali
1295
Scheme 4.
Table 3. The ketones and ketazines.
Table 4. Physical and analytical data.
No. of the
ketazine
R-KBr imine ꢀ
Time of
reflux
mp (°C) (Colour)
106–108, Orange
Yield (%)
87
(cm–1)
1H NMR ꢁ (ppm)
32
1601
20 h
1.25 (t, 6H, J = 1.0 Hz, CH3), 2.3 (s, 6H,
CH3-imine), 2.7 (9, 4H, J = 1.0 Hz, CH2),
7.2–7.9 (2d, 8H, J = 0.5 Hz, aromatic)
33
34
88–90, Orange
95–96, Orange
98
86
1605
1590
40 h
20 h
2.7 (s, 6H, CH3), 6.5–7.2 (m, 6H, aromatic)
2.35 (s, 6H, CH3), 7.1–7.5 (m, 6H, aromatic)
Scheme 5.
In the IR spectra, the imine stretching vibration is absent.
Moreover, the spiro compounds 43 and 44 represent a good
method for preparation of such spiro molecules.
Preparation of the acyclic tetraene azines (Scheme 7)
The acyclic tetraene azines 45–47 are symmetrical mole-
cules as in the case of the bicyclic azines, but the stretching
vibrations of the imine groups are present in the FT IR spec-
tra at 1612.61, 1636.14, and 1674 cm–1 (17, 18). The chemi-
cal shift of the carbon of this imine group at 158 ppm is
present, which is absent in the bicyclic spectra (Tables 8–
10).
As shown in Table 8, the aryl groups carry in the com-
pounds 45 and 47, ethyl and amino groups in the para posi-
tion, which are electron-donating groups. In compound 46,
the furan ring is an electron-rich molecule, and as a prelimi-
nary observation, these electron-donating groups could be
the reason behind the ring-opening of the bicyclic forms,
leading to the stable and highly conjugated acyclic forms.
The elemental analysis for compounds 46 and 47 was not
conducted, but mass spectrometric data are available (Ta-
bles 9 and 10).
41, respectively. The 2-acetylthiophene azine 33 is the only
aromatic ketone azine that formed the bicyclic diazine 42. It
could be, that from the above mentioned compounds, the
electron-withdrawing chloro- and nitro- groups, and in the
case of the thiophene moiety, the nature of the aromatic
ring, why they stayed in the bicyclic form. The two acyclic
ketone azines 37 and 39 were chosen because of this obser-
vation. These acyclic ketone azines gave the spiro bicyclic
azines 43 and 44 (Table 5).
The physical and analytical data are shown in Table 6. El-
emental analysis for the products 41, 42, and 44 was not
measured, instead, mass spectrometric data were measured
in addition to the spectroscopic data (Table 7).
Preparation of the N-allyl pyrazoles (Scheme 8)
The N-allyl pyrazoles 48–55 (Scheme 8) were formed by
the reaction of the aldazines 18, 19, 20, 21, 22, 24, 25, and
27 with 2 equiv of DMAD 2. The reactions with
phenylacetylene, diphenylacetylene, and methyl propiolate
were unsuccessful. This could be due to the electron-poor
LUMO of the DMAD 2, which can react with the electron-
rich HOMO of the 1,3-dipolar compounds. The nature of the
aryl groups, yield, and time of reflux are given (Table 11).
© 2002 NRC Canada

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Can. J. Chem. Vol. 80, 2002
Scheme 6.
Table 5. The bicyclic azines.
No. of the
azine
No. of the
bicyclic azine
Time of
reflux
R1
R2
Yield (%)
4 days
2 days
12 days
12 h
23
26
34
37
39
40
41
42
43
44
H
H
CH3
2-Chlorophenyl
4-Nitrophenyl
2-Thiophenyl
65
77
70
75
68
Spiro cyclobutane moiety
Spiro cyclohexane moiety
24 h
Table 6. Physical and analytical data.
No. of the
bicyclic azine
mp (°C)
(colour)
Molecular formula and
weight (g mol–1)
Elemental analysis calcd. and (or) found (%)
C
H
N
40
41
42
43
44
176 to 177
White
Yellow
Oil
Amber
Oil
Yellow
Oil
Yellow
Oil
C26H22N2O8Cl2
561.37
C26H22N4O12
582.47
C24H24N2O8S2
532.57
C20H24N2O8
420.41
55.62
55.48
Not measured
3.95
4.05
4.99
5.08
Not measured
57.13
58.01
Not measured
5.75
5.85
6.66
6.87
C24H32N2O8
476.52
Table 7. Spectroscopic and spectrometric data.
No. of the
product
IR (cm–1)
(carbonyl)
MS (M+) base-peak
and other fragments
1H NMR ꢁ (ppm)
13C NMR ꢁ (ppm)
40
1728.75
3.5–4.0 (4s, 12H, CH3-ester),
5.7 (s, 2H, allylic-H),
7.1–7.5 (m, 8H, aromatic)
3.6–3.8 (4s, 12H, CH3-ester),
6.4 (s, 2H, allylic-H),
51–53 (2 peaks, CH3-ester), 63 (allylic-C),
125–155 (8 peaks-sp2 carbons), 163–168
(2 peaks, CO-ester)
50–53 (2 peaks, CH3-ester), 62 (1 peak,
allylic-C), 124–135 (6 peaks, sp2-C),
162–168 (2 peaks, CO-ester)
—
41
1740.33
582, 260 (100%),
352, 323, 291, 202
8.3–8.5 (2d, 8H, J = 0.5 Hz,
aromatic)
42
1736.47
2.35 (s, 6H, CH3), 3.6–4.0 (4s,
12H, CH3-esters), 6.3–7.5
(3m, 6H, aromatic)
29 (1 peak, allylic-CH3), 52–53 (2 peaks,
CH3-ester), 63 (1 peak, allylic-C), 130–
156 (6 peaks, sp2-C), 165–168
532, 416 (100%),
472, 430, 408, 274
(2 peaks, CO-ester)
43
44
1736.57
1732.19
1.9–2.0 (m, 12H, cyclobutane
ring), 3.7–3.8 (2s, 12H,
CH3-ester)
1.9–2.0 (m, 20H, cyclohexane
ring), 3.7–3.9 (2s, 12H,
CH3-ester)
15–18 (3 peaks, cyclobutane), 51–52
(2 peaks, CH3-ester), 133–135 (2 peaks,
sp2-C), 162–168 (2 peaks, CO-ester)
16–19 (4 peaks, cyclohexane), 52–53
(2 peaks, CH3-ester), 133–135 (2 peaks,
sp2-C), 163–168 (2 peaks, CO-ester)
—
476, 153 (100%),
318, 205, 175
© 2002 NRC Canada

El-Alali and Al-Kamali
1297
Scheme 7.
Table 8. The acyclic azines.
No. of the ketazine
No. of the acyclic azine
Ar
Yield (%)
Time of reflux
32
33
35
45
46
47
4-Ethylphenyl
4-Furfuryl
4-Aminophenyl
78
73
75
60 h
5 days
60 h
Table 9. Physical and analytical data.
No. of the
acyclic azine
mp (°C)
(colour)
Molecular formula and
Elemental analysis calcd. and (or) found
(%)
weight (g mol–1)
C
H
N
45
46
47
Amber
Oil
Amber
Oil
153–155
Yellow
C32H36N2O8
476.63
C24H24N2O10
500.45
C28H30N4O8
550.55
66.65
65.98
—
6.29
6.72
4.86
4.89
—
Table 10. Spectroscopic and spectrometric data.
No. of the IR (cm–1) (carbonyl
MS (M+), base-peak and
other fragments
product
and (or) imine)
1H NMR ꢁ (ppm)
13C NMR ꢁ (ppm)
45
1732.61
1612.99
1.6 (t, 6H, CH3-ethyl, J = 0.5Hz),
2.3 (s, 6H, CH3), 2.6 (q, 4H,
CH2, J = 0.5 Hz), 3.8–3.9 (2s,
12H, OCH3), 7.3–7.7 (2m, 8H)
15–20 (2 peaks, ethyl),
51–52 (2 peaks, OCH3),
115–145 (6 peaks, sp2-C),
157 (1 peak, C = N),
163–166 (2 peaks, CO-ester)
46
47
1721.03, 1636.14
1740.33, 1674.73
2.3 (s, 6H, CH3), 3.7–3.8
(s, 12H, OCH3), 6.5–7.5
(3m, 6H, aromatic)
29 (1 peaks, CH3), 51–52 (2 peaks, 500, 216 (100%), 366, 250,
OCH3), 100–144 (6 peaks,
sp2-C), 156 (1 peak, C = N),
162–165 (2 peaks, CO-ester)
15 (1 peak, CH3), 51–53 (2 peaks,
OCH3), 95–148 (6 peaks, sp2-C),
158 (1 peak, C = N), 164–169
(2 peaks, CO-ester)
203, 149, 123
2.3 (s, 6H, CH3), 3.7 (s,
12H, OCH3), 5.5 (s, 4H,
NH2), 6.8–7.9 (2d, 8H,
J = 0.5 Hz, aromatic)
550, 275 (100%), 260, 245,
216, 157, 149
Scheme 8.
© 2002 NRC Canada

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Can. J. Chem. Vol. 80, 2002
Table 11. The N-allyl pyrazoles.
Merck Co. Hydrazine hydrate (51%) was purchased from
Janssen-Chimica. The cyclohexanone was purchased from
May and Baker Ltd. 2-Acetyl thiophene (19) and 4-ethyl
acetophenone (20) were prepared following literature proce-
dures. The solvents acetonitrile, methanol, ethanol, toluene,
and n-hexane were dried and distilled over calcium hydride.
Diethyl ether and THF were dried over sodium and benzo-
phenone. All dried solvents were kept over activated molec-
ular sieves. The liquid aldehydes and ketones were distilled
prior to their use.
Analytical and preparative thin-layer chromatography
(TLC) were performed on silica gel plates precoated with
silica gel GF254 from theLaboratory Rasoyan Co.
Uncorrected melting points were obtained on an
electrothermal melting point apparatus. Infrared spectra were
recorded as KBr-disc or liquid films on a Matsson 5000 FT
1
IR spectrophotometer. H and 13C NMR spectra were re-
corded with a Bruker AC-200 MHz in a solution of CDCl3
and with TMS as an internal reference.
Electron impact (EI) mass spectra were recorded using a
Finnigan MAT731 spectrophotometer at 70 eV. Elemental
analyses were determined by M.H.W. Laboratories in Ari-
zona, U.S.A.
The aldazines (18–27)
General procedure A (modified):
The aldehyde (2.1 mol) was added slowly to the cooled
mixture of 1.0 mol hydrazine hydrate dissolved in ethanol or
methanol. The mixture was heated over a steam bath for
1.0 h, then refluxed for several hours. The time of reflux de-
pended on the nature of the aldehyde used. The reaction was
followed by TLC. The solvent was removed in vacuo and
the residue was recrystallized either from ethanol or metha-
nol.
The physical and analytical data are given (Table 12), and
the spectroscopic and spectrometric data are shown in Ta-
ble 13. The formation of these products was identified
mainly by NMR. The unsymmetrical shape was recognized
by the number of carbon peaks in the 13C NMR, where al-
most all carbon peaks were present. The four peaks of the
ester carbonyls were apparent between 162–169 ppm and the
peak of the allylic carbon atoms appeared between 58–
2,2>-Dimethoxybenzaldazine (18):
It was prepared following the modified procedure A. 2-
Methoxybenzaldehyde (5.0 g, 0.041 mol) and 0.64 g (0.02
mol) of hydrazine were used. The reaction time was 3.0 h,
mp 143 to 144°C, yellow needles, and 95% yield.
1
4,4>-Dimethoxybenzaldazine (19):
64 ppm. In the H NMR spectra, one observed four singlets
Procedure A was used; mp 167 to 168°C and with 91%
yield.
between 3.8 to 4.0 ppm for the methyl groups of the esters.
Moreover, the allylic protons in all compounds were ob-
served as singlets between 5.9 to 7.2 ppm, whereas the
vinylic protons appeared as singlets between 8.0 to 8.4 ppm.
In the FT IR spectroscopy, the carbon double bonds and
imine vibrations between 1600–1660 cm–1 were present as
broad peaks and could not be singly specified. Vibrations of
the carbonyl groups of the esters were present between
1724.89–1744.19 cm–1.
2,2>-Dimethylbenzaldazine (20):
Procedure A was used. The reaction time was only 10 min
at room temperature. The yellow solid was washed with ice
water, and crystallized from ethanol; mp 68–70°C and with
85% yield.
3,3>-Dimethylbenzaldazine (21):
Procedure A was used; mp 106–108°C and with 82%
yield.
Experimental
Materials and equipment
4,4>-Dimethylbenzaldazine (22):
o-, m-, and p-Toluylaldehydes and p-methoxybenzalde-
hyde were purchased from Fluka Co. Cinnamaldehyde was
purchased from the Gainland Chemical Co. Cyclobutanone
was purchased from the Aldrich Co. Dimethyl acetyl-
enedicarboxylate, 2-acetylfuran, 4-amino acetophenone, and
1-naphthalenecarboxaldehyde were purchased from the
It was prepared following known procedure (12); mp 157–
159°C and with 90% yield.
2,2>-Dichlorobenzaldazine (23):
Procedure A was used. Details are depicted in Table 2 in
the text.
© 2002 NRC Canada

El-Alali and Al-Kamali
1299
Table 12. Physical and analytical data of N-allyl pyrazoles.
No. of the
N-allyl pyrazoles
mp (°C)
(colour)
Molecular formula and
weight (g mol–1)
Elemental analysis calcd. and (or) found
(%)
C
H
N
48
49
50
51
52
53
54
55
168–170
Yellow
Yellow
Oil
Amber
Oil
138–140
White
134–136
White
Amber
Oil
C28H28N2O10
552.52
C28H28N2O10
552.52
C28H28N2O8
520.52
C28H28N2O8
520.52
C28H28N2O8
520.52
C30H32N2O8
548.58
C34H28N2O8
592.58
C30H28N2O8
544.54
60.86
61.08
60.86
60.66
64.61
64.40
64.61
64.80
64.61
64.72
68.91
67.81
55.93
56.75
—
5.11
4.89
5.11
5.13
5.42
5.53
5.42
5.51
5.42
5.51
4.76
5.47
4.27
4.74
—
5.07
5.09
5.07
4.87
5.38
5.26
5.38
5.54
5.38
5.39
4.73
4.24
5.93
4.52
—
Amber
Oil
Yellow
Oil
Table 13. Spectroscopic and spectrometric data.
No. of the IR (cm–1) (carbonyl
MS (M+), base-peak
and other fragments
product
and (or) imine)
1H NMR ꢁ (ppm)
13C NMR ꢁ (ppm)
52–53 (6 peaks, OCH3), 61
(1 peak, allylic-C), 111–158 (17
peaks, sp2-C), 163–168 (4 peaks,
CO-ester)
51–58 (6 peaks, OCH3), 61
(1 peak, allylic), 115–160 (13
peaks, sp2-C), 163–169 (4 peaks,
CO-ester)
48
1724.89
3.6 (s, 6H, OCH3-rings), 3.6–3.9 (4s,
12H, OCH3-esters), 6.0 (s, 1H,
allylic-H), 6.7–7.5 (m, 8H,
aromatic), 8.05 (s, 1H, vinylic-H)
3.5–3.7 (2s, 6H, OCH3-rings), 3.6–3.9
(4s, 12H, OCH3-ester), 6.0 (s, 1H,
allylic), 6.8–7.4 (m, 8H, aromatic),
8.0 (s, 1H, vinylic)
2.2–2.3 (2s, 6H, CH3-rings), 3.5–4.0
(4s, 12H, OCH3-ester), 5.9 (s, 1H,
allylic), 6.8–7.3 (m, 8H, aromatic),
8.0 (s, 1H, vinylic)
2.1–2.2 (2s, 6H, CH3-rings), 3.5–4.0
(4s, 12H, OCH3-ester), 6.1 (s, 1H,
allylic), 6.8–7.5 (m, 8H, aromatic),
8.1 (s, 1H, vinylic)
552, 289 (100%),
263, 230, 204,
171, 145
49
50
51
52
1725.40
1728.75
1732.19
1728.75
—
22–23 (2 peaks, CH3-rings), 51–54 550, 273 (100%),
(4 peaks, OCH3), 58 (1 peak,
allylic), 114–158 (17 peaks, sp2-
C), 162–168 (4 peaks, CO-ester)
22–23 (2 peaks, CH3-rings), 50–53
(4 peaks, OCH3), 59 (1 peak,
allylic), 114–159 (17 peaks, sp2-
C), 163–169 (4 peaks, CO-ester)
22–23 (2 peaks, CH3-ring),
51–54 (4 peaks, OCH3), 59
(1 peak, allylic), 114–148 (13
peaks, sp2-C), 162–168 (4 peaks,
CO-ester)
247, 214, 188,
129
—
—
2.1–2.3 (2s, 6H, CH3-rings), 3.5–3.9
(4s, 12H, OCH3-ester), 5.9 (s, 1H,
allylic), 6.9–7.2 (m, 8H, aromatic),
8.0 (s, 1H, vinylic)
53
1726.73
3.5–4.0 (4s, 12H, OCH3-ester), 5.7
(s, 1H, allylic), 6.8–8.0 (m, 14H,
aromatic), 8.4 (s, 1H, vinylic)
51–53 (4 peaks, OCH3), 63
(1 peak, allylic-C), 115–162 (25
peaks, sp2-C), 166–168 (4 peaks,
CO-ester)
51–53 (4 peaks, OCH3), 63 (1 peak,
allylic), 130–158 (13 peaks, sp2-C),
164–168 (4 peaks, CO-ester)
51–54 (4 peaks, OCH3), 62
(1 peak, allylic-C), 114–159
(17 peaks, sp2-C), 162–167 (4
peaks, CO-ester)
—
—
54
55
1734.12
1744.19
3.7–3.9 (4s, 12H, OCH3-ester), 6.0 (s,
1H, allylic), 6.5–7.7 (m, 6H, aro-
matic), 8.0 (s, 1H, vinylic)
3.9–4.0 (4s, 12H, OCH3-ester), 7.2 (S,
1H, allylic), 7.5–8.1 (m, 14H, vinyl
benzene), 8.3 (s, 1H, vinylic)
544, 259 (100%),
417, 402, 232,
183.
© 2002 NRC Canada

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Can. J. Chem. Vol. 80, 2002
1,1>-Naphthaldazine (24):
procedure (16) as follows: a mixture of 16.5 g (0.17 mmol)
of cyclohexanone, 4.0 g (0.08 mmol) of hydrazine hydrate,
and 25 g (0.3 mole) of sodium acetate were dissolved in
100 mL of H2O and 100 mL of ethanol. The reaction mix-
ture was heated for 4 h over a water bath. Five times its
weight of ZnCl2 (82.5 g) was added to the reaction mixture
and heated at 130°C. A complex compound precipitated
(C12H20N2.HCl·ZnCl2). The melting point was 271 to 272°C
and it decomposed with ammonia gas and gave the oily
product 39 in 75% yield.
Procedure A was used. The reaction time was 10 min at
room temperature. The solid product was crystallized from
ethanol with a few drops of hydrochloric acid; mp 155–
157°C and with 86% yield.
2,2>-Furfuralazine (25):
Procedure A was used. The reaction time took 20 h under
reflux. The residue was extracted with ether, dried over
MgSO4, and after removal of ether, a brown solid was ob-
tained; mp 111 to 112°C and with 88% yield.
4,4>-Dinitrobenzaldazine (26):
The preparation of the products:
Precedure A was used. The reaction time was 10 min at
room temperature. The solid residue was crystallized in
pyridine; m., 296 to 297°C and with 89% yield.
General procedure C (modified)
A mixture of 1.0 mol azine and 3.0 mol of DMAD was
dissolved in dry acetonitrile and heated under reflux for a
period of time (see Tables 5–13). After removal of the sol-
vent in vacuo, the excess DMAD was removed under re-
duced pressure (0.5 mmHg (1 mmHg = 133.322 Pa), 50°C).
The residual amber oil was redissolved in methanol, and
scratched with a glass rod for a few hours. The formed solid
was crystallized from methanol, and the liquid products
were purified by TLC plates or column chromatography.
Cinnamaldazine (27):
Preparation and crystallization carried out as for com-
pound 24; mp 173 to 174°C and with 86% yield.
The acyclic ketazines (32–35)
General procedure B (modified procedure):
2.1 mol of ketone was added slowly to 1.0 mol of
hydrazine hydrate with a few drops of glacial acetic acid dis-
solved in methanol or ethanol. The reaction mixture was
then refluxed for 20–40 h depending on the nature of the
ketone. The solid residue was extracted with ether and
washed successfully with 10% NaHCO3. The ether layer
was dried over MgSO4 and the solvent was removed in
vacuo. The solid products were crystallized from ethanol.
The bicycle azines (40ꢂ44):
1,5-Bis(2>-chlorophenyl)-2,3,6,7-tetrakis(carbomethoxy)-1,5-
dihydro-pyrazolo[1,2-a]pyrazole (40):
Procedure C was used. Details in Tables 5–7.
1,5-Bis(4>-nitrophenyl)-2,3,6,7-tetrakis(carbomethoxy)-1,5-
dihydropyrazolo[1,2-a]pyrazole (41):
4.4>-Diethylacetophenone azine (32):
Procedure B was used. Details in Table 4. Recry-
stallization was achieved from petroleum ether.
Procedure C was used The oily product was separated on
TLC plates (50% EtOAc in hexane). See details in Tables 5–7.
2,2>-Diacetylfuran azine (33):
Procedure B was used. Details in Table 4.
1,5-Bis(2>-thiophenyl)-2,3,6,7-tetrakis(carbomethoxy)-1,5-
dimethylpyrazolo[1,2-a]pyrazole (42):
Procedure C was used. The oily product was separated on
TLC plates (30% EtOAc in hexane). See Tables 5, 6, and 7.
2,2>-Diacetylthiophene azine (34):
Precedure B was used. For details, see Table 4.
Recrystallization as for compound 32.
1,5-Bis(spirocyclobutane)-2,3,6,7-tetrakis(carbomethoxy)
dihydropy-razolo[1,2-a]pyrazole (43):
4,4>-Diaminoacetophenone azine (35):
Procedure B was used. Details in Table 4.
Procedure C was used. The oily product was separated on
TLC plates (30% EtOAc in hexane). See details in Tables 5–7.
The alicyclic ketazines 37 and 39
1,5-Bis(spirocyclohexane)-2,3,6,7-tetrakis(carbomethoxy)di-
hydropy-razolo[1,2-a]pyrazole (44):
Procedure C was used. Separation on TLC (30% MeOH
in hexane). Details in Tables 5–7.
Cyclobutanone azine (37):
It was prepared using a modified procedure to that re-
ported in the literature (15).
A mixture of 1.17 g (17 mmol) of the cyclobutanone and
0.54 g (8 mmol) of the hydrazine hydrate in 40 mL of tolu-
ene and 10 mL of ethanol was refluxed for 4 h, then strirred
at room temperature overnight. After removal of the sol-
vents, the residue was extracted with 100 mL of ether and
dried over MgSO4. The ether layer was cooled in a dry ice
bath. After a few hours, white crystals precipitated and were
separated by suction filteration; mp 68 to 69°C and with
83% yield.
The acyclic azines (45ꢂ47):
All these compounds were prepared following procedure
C, and their data are depicted in Tables 8–10.
Methyl-2-oxo-3-carbomethoxy-4-methyl-4-(4>-ethylphenyl)-
but-3-enoate azine (45):
Separation on a TLC plate (30% EtOAc in hexane).
Methyl-2-oxo-3-carbomethoxy-4-methyl-4-(2>-furfuryl)-but-
3-enoate azine (46):
Cyclohexanone azine (39):
Procedure B was used without an acid catalyst. Another
preparation was also elaborated following the reported
Separation on a TLC plate (20% EtOAc in hexane).
© 2002 NRC Canada

El-Alali and Al-Kamali
1301
Methyl-2-oxo-3-carbomethoxy-4-methyl-4-(4>-aminophenyl)-
but-3-enoate azine (47):
Separation was achieved by recrystallization from metha-
nol.
the N-allyl pyrazoles. Investigation of the rearrangements is
now going on in our research laboratory to develop an ex-
planation. Furthermore, the bicyclic azines (the pentalene
derivatives) are compounds of interest to many researchers.
The acyclic tetraene azines could undergo thermal or photo-
chemical cyclization to become interesting compounds. As
mentioned before, the N-allyl pyrazoles are promising com-
pounds and could possess biological activities.
The N-allylphyrazoles (48–55):
All these products were prepared following procedure C.
The data are depicted in Tables 11–13.
Methyl-2-[3>,4>-dicarbomethoxy-5-(2>>-methoxylphenyl)-1>-
pyrazolyl]-3-carbo-methoxy-4-(2>>-methoxyphenyl)but-3-
enoate (48):
References
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Methyl-2-[3>,4>-dicarbomethoxy-5>-(4>>-methoxyphenyl)-1>-
pyrazoly-l]-3-carbo-methoxy-4-(4>>-methoxyphenyl)-but-3-
enoate (49):
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1125 (1975).
Methyl-2-[3>,4>-dicarbomethoxy-5>-(2>>-methylphenyl)-1>-py-
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(50):
Separation procedure used was the same as in compound
49.
Methyl-2-[3>,4>-dicarbomethoxy-5>-(4>>-methylphenyl)-1>-
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Methyl-2-[3>,4>-dicarbomethoxy-5>-(4>>-methylphenyl)-1>-
pyrazolyl]-3-carbo-methoxy-4-(4>>-methylphenyl)-but-3-
enoate (52):
Separated by crystallization from methanol.
Methyl-2-[3>,4>-dicarbomethoxy-5>-(1>>naphthalyl)-1>-pyra-
zolyl]-3-carbo-methoxy-4-(1>>-naphthalyl)-but-3-enoate (53):
Separated on TLC plates using (ether:dichloromethane,
0.5:9.5).
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Methyl-2-[3>,4>-dicarbomethoxy-5>-(2>>-furyl)-1>-pyrazolyl]-
3-carbom-ethoxy-4-(2>>-furyl)-but-3-enoate (54):
Separation procedure used was the same as in compound
49.
17. V.M. Kolb, A.C. Kuffel, H.O. Spiwek, and T.E. Janota. J. Org.
Chem. 54, 2771 (1989).
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Methyl-2-[3>,4>-dicarbomethoxy-5>-styryl-1>-pyrazolyl]-3-
carbometh-oxy-4-styryl-but-3-enoate (55):
Separated on TLC plates (30% EtOAc in hexane).
Conclusion
The transformations in this work delivered three types of
products namely, the bicyclic azines, the acyclic azines, and
© 2002 NRC Canada