Reactions of substituted carbohydrazides with electron-poor olefins

Article abstract of DOI:10.1515/znb-2008-0813

Substituted carbohydrazides 1a-e reacted with ethenetetracarbonitrile (2) in dimethylformamide with formation of diacylhydrazines 4a-e and 5-amino-1-substiuted pyrazole-3,3,4-tricarbonitriles 5a-e. On the other hand, 1a-c reacted with diethyl (E)-2,3-dicy

Full text of DOI:10.1515/znb-2008-0813

Reactions of Substituted Carbohydrazides with Electron-poor Olefins
Alaa A. Hassan, Yusria R. Ibrahim, and Ahmed M. Shawky
Chemistry Department, Faculty of Science, El-Minia University, El-Minia, A. R. Egypt
Reprint requests to Prof. Dr. Alaa A. Hassan. E-mail: alaahassan2001@yahoo.com
Z. Naturforsch. 2008, 63b, 998 – 1004; received March 19, 2008
Substituted carbohydrazides 1a – e reacted with ethenetetracarbonitrile (2) in dimethylformamide
with formation of diacylhydrazines 4a – e and 5-amino-1-substiuted pyrazole-3,3,4-tricarbonitriles
5a – e. On the other hand, 1a–c reacted with diethyl (E)-2,3-dicyanobutenedioate (3) to give oxadi-
azinone and pyrazolone derivatives 12a – e and 13a – e, respectively.
Key words: Substituted Carbohydrazides, Electron-poor Olefins, Heterocyclization
Introduction
Hydrazide compounds, such as furoic hydrazide,
thiophenecarboxylic hydrazide and isonicotinic acid
hydrazide react with a series of 4-alkoxy-4-alkyl(aryl)-
1,1,1-trifluoro-3-alken-2-ones to give 3-alkyl(aryl)-5-
trifluoromethyl substituted pyrazoles [1]. One-pot re-
actions between carboxylic hydrazides and 2-isothio-
cyanatobenzonitrile afford pharmacologically relevant
1,2,4-triazolo[1,5-c]quinazoline-5-thiones [2]. Hydr-
azide compounds can also be converted to triaz-
ole-3-thiols [3], 1,3,4-oxadiazole [4], 1,3,4-oxadiaz-
ine [4], pyrazolotriazolopyrimidine [5, 6] and pyrazol-
otriazoloquinoline derivatives [7]. 1,2,4-Triazines are
formed via the condensation of 1,2-diketones with
acylhydrazides and ammonium acetate under tradi-
tional thermal and dry media microwave-assisted re-
action conditions [8, 9].
Ethenetetracarbonitrile (tetracyanoethylene) as well
as its derivatives containing the dicyano-vinylidene
moiety are electron-deficient substances, and it is
well known that their monoelectronic reduction usu-
ally results in the formation of fairly long-lived radi-
cal anions [10, 11]. This also applies to other species
containing cyano groups bound to a double bond
[12 – 15].
Scheme 1.
derivatives of 5-amino-3,4-dicyanopyrazole was iso-
lated [23].
As a part of our program aimed at the devel-
opment of new simple and efficient procedures for
the synthesis of some important heterocyclic systems
from hydrazinecarbothioamides, we have recently re-
ported different successful approaches for the synthe-
sis of thiazole, thiazine, thiadiazole, thiadiazine, thiadi-
azepine, indazole, and pyridazine derivatives [24 – 28].
As will be outlined in detail below, in this paper we
report several heterocyclizations of substituted carbo-
hydrazides 1a–e using ethenetetracarbonitrile (tetra-
cyanoethylene, 2) and diethyl (E)-2,3-dicyanobutene-
dioate (dicyanofumarate, 3) either as a reaction media-
tor or as a building block (Scheme 1).
Tetracyanoethylene shows a great affinity for elec-
trons, and is thus a fairly good dehydrogenating agent
towards dihydroaromatic and dihydroheteroaromatic
systems [16, 17]. It behaves as a strong electron accep-
tor towards suitable electron donors [16 – 20].
Results and Discussion
When carbohydrazides 1a – e were treated with two
The reaction of methylhydrazine with tetracyano- molar equivalents of tetracyanoethylene (2) in DMF
ethylene (2) has been studied in several laborato- as a solvent at r. t. with admission of air, the green
ries [21– 23]. A mixture of 1-N- and 2-N-methyl color of a transient charge-transfer complex is ob-
c
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A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
999
thus the presence of 2 is definitely required for the
transformations observed. Charge-transfer complexes
may (but not necessarily have to) play an intermedi-
ate role. The formation of 4a – e involves intermolec-
ular nucleophilic attack by a hydrazide-NH2 group on
the carbonyl group of the aldehyde formed from 7, fol-
lowed by dehydrogenation with another molecule of 2
(Scheme 3).
The structures of 4a – e are confirmed by charac-
teristic IR, NMR and mass spectral data, and com-
parison with authentic samples. Singh et al. [29] ear-
lier reported that iodobenzene diacetate (IBD) was
found to be an excellent reagent for the oxidation
of similar acid hydrazides [R = methyl(phenyl)pyraz-
olyl, methyl(4-methylquinolinyl)pyrazolyl, phenyl, 4-
Cl-C6H4, 4-MeO-C6H4 and PhCH2] to N,N1-diacyl-
hydrazines [29].
The dihydropyrazole structure of 5a – e has been as-
signed on the basis of elemental analyses and spec-
tral data. The 1H NMR spectrum of 5b, for exam-
ple clearly shows two broad signals with the ratio of
2 : 1 centered at δ = 6.92 and 11.52 ppm due to exo-
cyclic -NH2 and pyrazole -NH, in addition to thio-
phene protons. The 13C NMR spectrum shows sig-
nals at δ = 46.23 (C-3), 117.89, 118.96 (CN) and
169.86 (CO). Pyrazole C-4 and C-5 resonate at δ =
64.51 and 158.52, respectively, in accordance with
the observed trends in the δ values for C atoms in
push-pull alkenes [30, 31]. Further signals supporting
the assigned structure are given in the Experimental
Section.
Scheme 2.
served which quickly gives way to brown. After con-
centration of the mixture to dryness and subjecting the
residue to vacuum sublimation to remove any unre-
acted 2, chromatographic separation of the residue in
each case gave three zones, containing diacylhydraz-
ines 4a – e (12 – 17 %), 5-amino-1-substituted-1H-pyr-
azole-3,3,4(2H)-tricarbonitriles 5a – e (54– 59 %) and
1,1,2,2-tetracyanoethane (TCNE-H2) (6, 9 – 14 %). On
the other hand, an equimolar solution of 2 and 1a – e in
DMF, under the previous conditions, formed the previ-
ous products only in low yield in addition to unreacted
1a – e (Scheme 2).
Diacylhydrazine products 4a – e are not observed
when no 2 is added to the solution of 1a – e in DMF;
Scheme 3.
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A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
Scheme 4.
The analytical data of compound 5 would also ports the presence of intramolecular hydrogen bond-
match for the alternative structures 8 and 9, but these ing [34].
could be ruled out on the basis of 1H NMR, 13C NMR,
and IR data and the fragment ions in the mass spectrum
of 5b at m/z = 243, 215, 111, 83 and 66 (Scheme 3).
Furthermore, compound 5b was also identified on
the basis of an intramolecular hydrogen bond detected
by IR (in dilute CCl4) and 1H NMR spectroscopy (see
Experimental Section) as shown in Scheme 2.
The salient features of the 13C NMR spectra (in-
cluding 13C DEPT spectra) of 12d are the signals at
δ = 14.28 (CH3), 61.17 (CH2O), 69.89 (C-CN), 153.12
(C-5), 156.24 (C-2), 167.85 (ester-CO), and 171.36
(oxadiazinone-CO). The EI mass spectra of 12a – e are
characterized by molecular ions of low intensity and
the loss of 27 a. m. u. (representing HCN). The result-
Diethyl (E)-2,3-dicyanobutenedioate (dicyanofum- ing fragment ions undergo loss of 28 a. m. u. (N2 or
arate, 3) was chosen to compare its reactivity to- CO) followed by loss of EtO and RCO groups.
wards the substituted carbohydrazides 1a – e with 2
(Scheme 4). One might expect that 1a – e should re-
act with 3 similarly to 2, but the results were com-
pletely different (Scheme 4). Not only the struc-
ture of the acceptor is the reason for the instabil-
ity of the CT complexes and subsequent chemical
reaction, but also the electron affinity of the accep-
tors and the ease of undergoing the formation of an
adduct or a tricyanovinylation product are important
factors.
For compounds 13a – e, the molecular ions in their
EI mass spectra confirm the molecular masses and the
gross compositions. Further, the following common
fragmentation patterns lend support to the assigned
structure: loss of N2 giving intense [M–28]+ ions and
loss of RCO giving rise to the ion with m/z = 180
common in the spectra of all the five compounds. The
IR spectra show characteristic absorptions for the NH
group in the range of 3325 to 3345, sharp bands in the
range 2215 – 2225 due to the cyano group, and three
bands around 1660, 1675 and 1715 cm−1 assigned to
carbonyl groups. The 1H NMR spectra show the pres-
ence of an NH group by broad signals for one proton
between δ = 12.43 and 12.55 ppm. For 13e, the ex-
pected signals for indole –CH (δ = 6.72) and indole
–NH (δ = 11.63) are observed. Signals around δ =
Mixing equimolar amounts of 1a – e and 3 in ethyl
acetate under reflux for 4 – 18 h led to the forma-
tion of oxadiazinone 12a – e and pyrazolone 13a – e
derivatives. The structural assignment of 12a – e and
13a – e was based on their spectral data. The oxadi-
azinone derivative 12d exhibited four IR absorption
bands at ν = 3315 (NH), 2225 cm−1 (CN), and two
bands at 1690 and 1730 cm−1 due to carbonyl ester
and oxadiazinone-CO groups, respectively. These ob-
servations indicate the presence of an intramolecular
hydrogen bond between oxadiazine-NH and the ester
group on the side chain of 12. The ester carbonyl band
of lower frequency was attributed to an intramolecu-
lar hydrogen-bonded α,β-unsaturated ester carbonyl
common to all related compounds as stated in the liter-
ature [32– 34]. The 1H NMR spectrum displayed one
broad signal at δ = 9.91 ppm for one proton due to oxa-
1) 3 CO
1) 2 CO
2) Oxadiazepine -NH
3) One CN
1) 3 CO
2) Pyrazole -NH
3) One CN
4) No cyclic -CH
2) No -NH
3) One CN
4) Cyclic -CH
4) No cyclic -CH
diazine –NH; the chemical shift of this proton also sup- Scheme 5.
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A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
1001
89.19 (C-4), 118.84 (CN), 155.98 (C-3), 165.34 (C-5), added dropwise, which caused a spontaneous change of color
168.49 (ester-CO), and 171.36 (CO) in the 13C NMR
from yellow to dark green and finally to brown. The mix-
ture was stirred for 4 h and left standing for 48 h at r. t. Af-
spectrum of 13e lend further support to the structures
ter ◦concentration to dryness, the residues were sublimed at
assigned to 13a – e. The analytical data of compounds
80 C and then subjected to plc using toluene/ethyl acetate
13 would also match for the isomeric products 14 and
(3 : 1) as eluent for the reaction of 1a – e with 2. On the other
15 (Scheme 5). These could be ruled out on the basis of
hand, toluene/ethyl acetate (2 : 1) was used as eluent for the
reaction of 1d,e with 2. Chromatographic separation of the
residue (after sublimation) gave numerous zones, three of
which (with high intensity) were removed and extracted. The
fastest moving zone contained the pyrazole derivatives 5a –
e (characterized with pale yellow color), the second mov-
ing zone contained the diacylhydrazines 4a – c, and finally
the slowest migrating zone contained TCNE-H2 as colorless
crystals after sublimation which decomposed at 165 – 170 ◦C
1
IR, H NMR, and 13C NMR spectra, and of the frag-
ment ions in the mass spectrum of 13b at m/z = 263,
246, 180, 111 and 83.
Experimental Section
Melting points have been determined using open glass
capillaries on a Gallenkamp melting point apparatus and are
uncorected. The IR spectra were recorded with Shimadzu
408 or Bruker Vector 22 FTIR instruments, using potas-
sium bromide pellets or CCl4. The 1H NMR (400.134 MHz)
and 13C NMR (100.6 MHz) spectra were measured in
[D6]DMSO using a Bruker AM400 with TMS as an inter-
nal standard; chemical shifts are expressed as δ (ppm), (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet and
b = broad).
Assignments of carbon resonances have been supported
by DEPT experiments. Moreover, the signals caused by qua-
ternary carbons were identified by the comparison between
13C NMR and DEPT spectra. Mass spectra have been ob-
tained with a Varian MAT 312 instrument using electron im-
pact ionization (70 eV). Elemental analyses have been de-
termined by the Microanalytical Center, Cairo University,
Egypt. Preparation layer chromatography (plc): Glass plates
(48 cm × 20 cm) were coated with silica gel Merck Pf254 (ap-
plied as aqueous slurry and air-dried affording a 1 mm layer).
Zones were detected by indicator fluorescence quenching
upon 254 nm illuminations, removed from plates and ex-
tracted with acetone.
◦
(lit. [41]: 165 – 170 C). Extraction of the other zones with
acetone and concentration gave residues, which were rechro-
matographed and recrystallized to give pure samples.
Nꢀ-Benzoylbenzohydrazide (4a): lit. [29, 42]; Nꢀ-(thio-
phene-2-carbonyl)thiophene-2-carbohydrazide (4b): lit. [42,
43]; Nꢀ-(furan-2-carbonyl)furan-2-carbohydrazide (4c): lit.
[44]; Nꢀ-picolinoylpicolinohydrazide (4d): lit. [44]; Nꢀ(1H-
indole-2-carbonyl)-1H-indole-2-carbohydrazide (4e): lit.
[43].
5-Amino-1-benzoyl-1H-pyrazole-3,3,4(2H)-tricarbonitrile
(5a)
◦
M. p. 210 – 212 C. – IR (KBr): ν = 3380, 3300 – 3220
(NH2, NH), 2225, 2220 (CN), 1660 (CO), 1585 cm−1 (Ar-
C=C). – 1H NMR ([D6]DMSO): δ = 6.98 (br, 2H, NH2),
7.57 – 7.93 (m, 5H, Ar-H), 11.47 (pyrazole-NH). – 13C NMR
([D6]DMSO): δ = 48.48 (C-3), 64.14 (C-4), 117.94, 118.18,
119.26 (CN), 127.76, 128.93, 130.17 (Ar-CH), 134.36
(Ar-C), 158.64 (pyrazole-C-5), 170.19 (CO). – MS (EI,
70 eV): m/z (%) = 264 (33) [M]+, 237 (18), 171 (26),
105 (100), 66 (71). – C13H8N6O (264.08): calcd. C 59.09,
H 3.05, N 31.80; found C 58.87, H 2.92, N 32.04.
Starting materials
Substituted carboxylic hydrazides 1a – e were prepared
according to published procedures [4, 35 – 40], as were
thiophene-2-carboxylic hydrazide (1b, m. p. 135 – 137 ◦C,
lit. [35]: 134 – 136 ◦C), furan-2-carboxylic hydrazide (1c,
m. p. 77 – 79 ◦C, lit. [36]: 78 ◦C), pyridine-2-carboxylic
hydrazide (1d, m. p. 136 – 138 ◦C, lit. [37, 38]: 137 ◦C),
indole-2-carboxylic hydrazide (1e, m. p. 243 – 245 ◦C, lit.
5-Amino-1-(thiophene-2-carbonyl)-1H-pyrazole-3,3,4(2H)-
tricarbonitrile (5b)
◦
M. p. 224 – 226 C. – IR (KBr): ν = 3385, 3310, 3210
(NH2, NH), 2225, 2220 (CN), 1655 (CO), 1590 cm−1 (Ar-
C=C); ν (CCl4, 10−3 M, d = 3 cm) = 3370, 3195 (broad NH2
and OH assoc.), 1660 cm−1 (CO). – 1H NMR ([D6]DMSO):
δ = 6.92 (br, 2H, NH2), 7.21 – 7.87 (thiophene-CH), 11.52
(br, H, pyrazole-NH). – 13C NMR ([D6]DMSO): δ = 46.23
(C-3), 64.51 (C-4), 117.89, 118.08, 118.96 (CN), 129.23,
130.34, 131.67 (thiophene-CH), 137.69 (thiophene-C-2),
158.52 (C-5), 169.86 (CO). – MS (EI, 70 eV): m/z (%) = 270
(27) [M]+, 243 (31), 215 (23), 111 (100), 83 (69), 66 (49). –
◦
[4, 39, 40]: 246 C). Benzene carboxylic hydrazide (1a) and
diethyl (E)-2,3-dicyanobutenedioate (3) (Aldrich) were used
as received. Ethenetetracarbonitrile (2, Merck) was purified
by crystallization from chlorobenzene and sublimation.
Reaction of substituted carboxylic hydrazides 1a – e with
ethenetetracarbonitrile (2)
To a stirred solution of 256 mg (2.0 mmol) of 2 in 10 mL C11H6N6OS (270.27): calcd. C 48.88, H 2.24, N 31.09,
of dimethylformamide, a solution of 1.0 mmol of 1a – e was S 11.86; found C 49.08, H 2.31, N 30.88, S 12.05.
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A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
5-Amino-1-(furan-2-carbonyl)-1H-pyrazole-3,3,4(2H)-
tricarbonitrile (5c)
toluene/ethyl acetate (2 : 1) as eluent. Chromatographic sep-
aration of the residue gave numerous zones, two of which
(with high intensity) were collected and extracted. The fastest
moving zone contained the oxadiazinone derivatives 12a – e
with orange color, while the slowest moving zone contained
the pyrazolone derivatives 13a – e (which were characterized
by a brown color). Extraction of the zones with acetone and
recrystallization gave the pure compounds.
◦
M. p. 183 – 185 C. – IR (KBr): ν = 3375, 3315, 3320
(NH2, NH), 2220, 2215 (CN), 1655 (CO), 1590 (Ar-C=C),
1080 cm−1 (C–O–C). – 1H NMR ([D6]DMSO): δ = 6.89
(br, 2H, NH2), 6.87 – 8.10 (furan-CH), 11.62 (br, 1H, pyraz-
ole-NH). – 13C NMR ([D6]DMSO): δ = 46.41 (C-3), 64.48
(C-4), 117.95, 118.23, 119.12 (CN), 128.12, 142.81 (furan-
CH), 147.63 (furan-C-2), 158.38 (C-5), 169.94 (CO). – MS
(EI, 70 eV): m/z (%) = 254 (56) [M]+, 227 (16), 199 (9),
95 (100), 67 (55), 66 (63). – C11H6N6O2 (254.20): calcd.
C 51.97, H 2.38, N 33.06; found C 52.14, H 2.29, N 32.84.
Ethyl 2-cyano-2-(6-oxo-2-phenyl-4H-1,3,4-oxadiazin-
5(6H)-ylidene)acetate (12a)
◦
M. p. 192 – 194 C. – IR (KBr): ν = 3335 (NH), 2225
(CN), 1695, 1730 (CO), 1620 cm−1 (C=N). – 1H NMR
([D6]DMSO): δ = 1.20 (t, J = 7.12 Hz, 3H, CH3), 4.21 (q,
J = 7.12 Hz, 2H, CH2O), 7.07 – 7.64 (m, 5H, Ar-H), 9.89
(br, 1H, oxadiazine-NH). – 13C NMR ([D6]DMSO): δ =
14.43 (CH3), 61.12 (CH2O), 70.14 (C-CN), 118.36 (CN),
126.76, 128.93, 131.12 (Ar-CH), 132.77 (Ar-C), 152.84
(C-5), 156.18 (C-2), 167.83 (ester-CO), 171.18 (oxadiazine-
CO). – MS (EI, 70 eV): m/z (%) = 285 (39) [M]+, 258
(22), 230 (16), 185 (38), 105 (100), 77 (86), 45 (56). –
C14H11N3O4 (285.25): calcd. C 58.95, H 3.89, N 14.73;
found C 58.77, H 3.98, N 14.91.
5-Amino-1-picolinoyl-1H-pyrazole-3,3,4(2H)-tricarbo-
nitrile (5d)
◦
M. p. 215 – 217 C. – IR (KBr): ν = 3375, 3300, 3230
(NH2, NH), 2225, 2220 (CN), 1660 (CO), 1585 cm−1 (Ar-
C=C). – 1H NMR ([D6]DMSO): δ = 6.95 (br, 2H, NH2),
7.81 – 8.39 (pyridine-CH), 11.64 (pyrazole-NH). – 13C NMR
([D6]DMSO): δ = 45.96 (C-3), 64.22 (C-4), 118.02, 118.28,
119.14 (CN), 126.56, 128.77, 131.12, 142.66 (pyridine-CH),
150.34 (pyridine-C), 158.56 (C-5), 170.12 (CO). – MS (EI,
70 eV): m/z (%) = 265 (37) [M]+, 238 (22), 210 (11),
106 (100), 78 (57), 66 (42). – C12H7N7O (265.23): calcd.
C 54.34, H 2.66, N 36.97; found C 54.16, H 2.59, N 37.15.
Ethyl 2-cyano-2-(6-oxo-2-(thiophen-2-yl)-4H-1,3,4-oxadi-
azin-5(6H)-ylidene)acetate (12b)
◦
M. p. 207 – 209 C. – IR (KBr): ν = 3320 (NH), 2220
(CN), 1690, 1735 (CO), 1625 cm−1 (C=N). – 1H NMR
([D6]DMSO): δ = 1.22 (t, J = 7.10 Hz, 3H, CH3), 4.18 (q,
J = 7.10 Hz, 2H, CH2O), 7.19 – 7.18 (m, thiophene-H), 9.92
(br, 1H, oxadiazine-NH). – 13C NMR ([D6]DMSO): δ =
14.39 (CH3), 61.26 (CH2O), 70.26 (C-CN), 118.67 (CN),
126.84, 127.56, 127.83 (thiophene-CH), 129.35 (thiophene-
C), 153.12 (C-5), 156.26 (C-2), 167.64 (ester-CO), 171.36
(oxadiazine-CO). – MS (EI, 70 eV): m/z (%) = 291 (53)
[M]+, 264 (37), 236 (63), 191 (52), 111 (100), 45 (86). –
C12H9N3O4S (291.28): calcd. C 49.48, H 3.11, N 14.43,
S 11.01; found C 49.32, H 2.94, N 14.67, S 10.83.
5-Amino-1-(1H-indole-2-carbonyl)-1H-pyrazole-3,3,4(2H)-
tricarbonitrile (5e)
◦
M. p. 276 – 278 C. – IR (KBr): ν = 3410, 3350 – 3230
(NH2, NH), 2225, 2220 (CN), 1650 (CO), 1595 cm−1
(Ar-C=C). – 1H NMR ([D6]DMSO): δ = 6.87 (br, 2H,
NH2), 7.11 – 7.67 (m, 5H, Ar-H), 11.41 (br, 1H, pyrazole-
NH), 11.76 (br, 1H, indole-NH). – 13C NMR ([D6]DMSO):
δ = 46.18 (C-3), 64.42 (C-4), 115.18 (indole-CH), 117.93,
118.17, 119.12 (CN), 126.71, 127.16, 128.57, 129.63
(Ar-CH), 131.84, 138.66, 139.94 (Ar-C and indole-C-2),
158.45 (C-5), 170.72 (CO). – MS (EI, 70 eV): m/z (%) =
303 (41) [M]+, 276 (17), 248 (21), 144 (100), 116 (64), 66
(54). – C15H9N7O (303.28): calcd. C 59.40, H 2.99, N 32.33;
found C 59.23, H 3.11, N 32.19.
Ethyl 2-cyano-2-(2-(furan-2-yl)-6-oxo-4H-1,3,4-oxadiazin-
5(6H)-ylidene)acetate (12c)
◦
M. p. 169 – 171 C. – IR (KBr): ν = 3330 (NH), 2225
(CN), 1695, 1725 (CO), 1630 cm−1 (C=N). – 1H NMR
([D6]DMSO): δ = 1.25 (t, J = 6.97 Hz, 3H, CH3), 4.21 (q,
J = 6.97 Hz, 2H, CH2O), 7.16 – 7.74 (m, 3H, furan-H), 9.86
Reaction of substituted carboxylic hydrazides 1a – e with di-
ethyl (E)-2,3-dicyanobutenedioate (3)
A solution of 222 mg (1.0 mmol) of 3 in 30 mL of dry (br, 1H, oxadiazine-NH). – 13C NMR ([D6]DMSO): δ =
ethyl acetate was heated with a) 136 mg (1.0 mmol) of 1a, 14.35 (CH3), 61.19 (CH2O), 69.82 (C-CN), 118.44 (CN),
b) 142 mg (1.0 mmol) of 1b, c) 126 mg (1.0 mmol) of 1c, 126.18, 141.83 (furan-CH), 144.12 (furan-C), 152.88 (C-5),
d) 137 mg (1.0 mmol of 1d, e) 175 mg (1.0 mmol) of 1e 156.27 (C-2), 167.90 (ester-CO), 171.28 (oxadiazine-CO). –
and stirred under reflux for 4 h (a), 8 h (b, c) and 18 h (d, MS (EI, 70 eV): m/z (%) = 275 (24) [M]+, 248 (33), 220
e), respectively. The color of the solution changed from col- (6), 175 (34), 140 (27), 95 (100), 45 (31). – C12H9N3O5
orless to reddish orange. After concentration of the reaction (275.22): calcd. C 52.37, H 3.30, N 15.27; found C 52.16,
mixture to dryness, the residue was subjected to plc using H 3.42, N 15.48.
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A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
1003
Ethyl
2-cyano-2-(6-oxo-2-(pyridin-2-yl)-4H-1,3,4-oxadi- (Ar-C=C). – 1H NMR ([D6]DMSO): δ = 1.24 (t, J =
azin-5(6H)-ylidene)acetate (12d)
7.06 Hz, 3H, CH3), 4.25 (q, J = 7.06 Hz, 2H, CH2O),
7.19 – 7.82 (m, 3H, thiophene-H), 12.46 (br, 1H, pyraz-
ole-NH). – 13C NMR ([D6]DMSO): δ = 14.28 (CH3),
61.36 (CH2O), 88.38 (C-4), 118.76 (CN), 127.83, 128.24
and 128.55 (thiophene-CH), 130.12 (thiophene-C-2), 155.89
(C-3), 165.94 (C-5), 168.97 (ester-CO), 170.92 (CO). – MS
(EI, 70 eV): m/z (%) = 291 (39) [M]+, 263 (11), 246 (54),
180 (36), 111 (100), 83 (56). – C12H9N3O4S (291.28): calcd.
C 49.48, H 3.11, N 14.43, S 11.01; found C 49.61, H 3.39,
N 14.51, S 10.87.
◦
M. p. 202 – 204 C. – IR (KBr): ν = 3315 (NH), 2225
(CN), 1690, 1725 (CO), 1630 cm−1 (C=N). – 1H NMR
([D6]DMSO): δ = 1.18 (t, J = 7.05 Hz, 3H, CH3), 4.21 (q,
J = 7.05 Hz, 2H, CH2O), 7.58 – 8.42 (m, 4H, pyridyl-H),
9.91 (br, 1H, oxadiazine-NH). – 13C NMR ([D6]DMSO):
δ = 14.28 (CH3), 61.17 (CH2O), 69.89 (C-CN), 118.72
(CN), 126.18, 127.83, 130.12, 144.11 (pyridyl-CH), 147.82
(pyridyl-C), 153.12 (C-5), 156.24 (C-2), 167.85 (ester-CO),
171.36 (oxadiazine-CO). – MS (EI, 70 eV): m/z (%) = 286
(51) [M]+, 259 (28), 231 (11), 186 (44), 106 (93), 78 (100),
45 (32). – C13H10N4O4 (286.24): calcd. C 54.55, H 3.52,
N 19.57; found C 54.37, H 3.66, N 19.41.
Ethyl 1-(furan-2-carbonyl)-4-cyano-5-oxo-2,5-dihydro-1H-
pyrazole-3-carboxylate (13c)
◦
M. p. 199 – 201 C. – IR (KBr): ν = 3340 (NH), 2220
(CN), 1720, 1685 and 1660 (CO), 1625 (C=N), 1590 (Ar-
C=C), 1083 cm−1 (C–O–C). – 1H NMR ([D6]DMSO): δ =
1.22 (t, J = 7.11 Hz, 3H, CH3), 4.27 (q, J = 7.11 Hz, 2H,
CH2O), 7.24 – 7.77 (m, 3H, furan-H), 12.62 (br, 1H, pyr-
azole-NH). – 13C NMR ([D6]DMSO): δ = 14.26 (CH3),
61.34 (CH2O), 89.11 (C-4), 118.81 (CN), 125.66, 140.18
(furan-CH), 143.36 (furan-C-2), 155.66 (C-3), 165.48 (C-5),
169.24 (ester-CO), 171.35 (CO). – MS (EI, 70 eV): m/z (%) =
275 (26) [M]+, 247 (16), 180 (25), 95 (100), 67 (74). –
C12H9N3O5 (275.05): calcd. C 52.37, H 3.30, N 15.27;
found C 52.49, H 3.14, N 15.46.
Ethyl 2-cyano-2-(2-1H-indole-2-yl)-6-oxo-4H-1,3,4-oxadi-
azin-5(6H)-ylidene)acetate (12e)
◦
M. p. 259 – 261 C. – IR (KBr): ν = 3340 – 3305 (NH),
2220 (CN), 1695, 1730 (CO), 1620 cm−1 (C=N). – 1H NMR
([D6]DMSO): δ = 1.21 (t, J = 6.90 Hz, 3H, CH3), 4.16
(q, J = 6.90 Hz, 2H, CH2O), 6.98 – 7.55 (m, 5H, Ar-H),
9.85 (br, 1H, oxadiazine-NH), 11.71 (br, 1H, indole-NH). –
13C NMR ([D6]DMSO): δ = 14.31 (CH3), 61.33 (CH2O),
70.12 (C-CN), 111.23 (indole-CH), 118.65 (CN), 126.26,
126.76, 128.75, 129.24 (Ar-CH), 130.61, 131.55, 1232.25
(Ar-C and indole-C-2), 152.81 (C-5), 155.93 (C-2), 167.91
(ester-CO), 171.42 (oxadiazine-CO). – MS (EI, 70 eV): m/z
(%) = 324 (26) [M]+, 297 (16), 269 (28), 224 (51), 140
(33), 144 (100), 116 (76), 92 (67), 77 (54). – C16H12N4O4
(324.29): calcd. C 59.26, H 3.73, N 17.28; found C 59.41,
H 3.64, N 17.46.
Ethyl 1-picolinoyl-4-cyano-5-oxo-2,5-dihydro-1H-pyrazole-
3-carboxylate (13d)
◦
M. p. 231 – 233 C. – IR (KBr): ν = 3325 (NH), 2215
(CN), 1710, 1680 and 1665 (CO), 1625 (C=N), 1600 cm−1
(Ar-C=C). – 1H NMR ([D6]DMSO): δ = 1.29 (t, J =
7.05 Hz, 3H, CH3), 4.28 (q, J = 7.05 Hz, 2H, CH2O), 7.61 –
8.44 (pyridyl-H), 12.45 (br, 1H, pyrazole-NH). – 13C NMR
([D6]DMSO): δ = 14.29 (CH3), 61.41 (CH2O), 89.35 (C-4),
119.16 (CN), 126.83, 127.22, 130.14, 143.22 (pyridyl-CH),
147.12 (pyridyl-C-2), 156.24 (C-3), 165.54 (C-5), 168.84
(ester-CO), 171.38 (CO). – MS (EI, 70 eV): m/z (%) =
286 (46) [M]+, 258 (6), 180 (19), 106 (100), 78 (87). –
C13H10N4O4 (286.24): calcd. C 54.55, H 3.52, N 19.57;
found C 54.76, H 3.36, N 19.69.
Ethyl 1-benzoyl-4-cyano-5-oxo-2,5-dihydro-1H-pyrazole-3-
carboxylate (13a)
◦
M. p. 227 – 229 C. – IR (KBr): ν = 3345 (NH), 2220
(CN), 1710, 1680 and 1655 (CO), 1620 (C=N), 1590 cm−1
(Ar-C=C). – 1H NMR ([D6]DMSO): δ = 1.27 (t, J =
7.10 Hz, 3H, CH3), 4.28 (q, J = 7.10 Hz, 2H, CH2O),
7.36 – 7.87 (m, 5H, Ar-H), 12.51 (br, 1H, pyrazole-NH). –
13C NMR ([D6]DMSO): δ = 14.28 (CH3), 61.49 (CH2O),
88.12 (C-4), 118.62 (CN), 128.22, 128.93 and 129.84
(Ar-CH), 131.55 (Ar-C), 156.11 (C-3), 166.53 (C-5), 169.23
(CO-ester), 171.12 (CO). – MS (EI, 70 eV): m/z (%) = 285
(51) [M]+, 257 (27), 240 (29), 180 (64), 105 (82), 77 (100),
65 (66). – C14H11N3O4 (285.25): calcd. C 58.95, H 3.89,
N 14.73; found C 59.19, H 4.12, N 14.51.
Ethyl 1-(1H-indole-2-carbonyl)-4-cyano-5-oxo-2,5-dihydro-
1H-pyrazole-3-carboxylate (13e)
◦
M. p. 287 – 289 C. – IR (KBr): ν = 3335, 3270 (NH),
2220 (CN), 1715, 1675 and 1660 (CO), 1625 (C=N),
1
1595 cm−1 (Ar-C=C). – H NMR ([D6]DMSO): δ = 1.23
(t, J = 7.12 Hz, 3H, CH3), 4.25 (q, J = 7.12 Hz, 2H, CH2O),
6.72 (indole-CH), 7.22 – 7.65 (m, 4H, Ar-H), 11.63 (br,
1H, indole-NH), 12.55 (br, 1H, pyrazole-NH). – 13C NMR
([D6]DMSO): δ = 14.22 (CH3), 61.72 (CH2O), 89.19
Ethyl 1-(thiophene-2-carbonyl)-4-cyano-5-oxo-2,5-dihydro-
1H-pyrazole-3-carboxylate (13b)
◦
M. p. 237 – 239 C. – IR (KBr): ν = 3330 (NH), 2225 (C-4), 111.22 (indole-CH), 118.89 (CN), 126.74, 128.12,
(CN), 1725, 1675 and 1660 (CO), 1625 (C=N), 1585 cm−1 128.81, 129.17 (Ar-CH), 130.55, 131.67 (Ar-C), 155.98
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1004
A. A. Hassan et al. · Reactions of Substituted Carbohydrazides with Electron-poor Olefins
(C-3), 165.34 (C-5), 168.49 (ester-CO), 171.36 (CO). – MS Acknowledgement
(EI, 70 eV): m/z (%) = 324 (35) [M]+, 296 (24), 180 (52),
144 (86), 116 (43), 92 (91), 77 (100), 65 (86). – C16H12N4O4
(324.29): calcd. C 59.26, H 3.73, N 17.28; found C 59.02,
H 3.92, N 17.45.
A. A. Hassan is indebted to the Alexander von Humboldt-
Foundation, Bonn, for the donation of the Shimadzu 408 IR
spectrophotometer.
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