Studies with 2-(arylhydrazono)aldehydes: Synthesis and chemical reactivity of mesoxalaldehyde 2-arylhydrazones and of ethyl 2-arylhydrazono-3- oxopropionates

Article abstract of DOI:10.1515/znb-2007-0407

The coupling reaction of 3-(dimethylamino)acrolein (2a) and ethyl 3-(dimethylamino)acrylate (2b) with arenediazonium chlorides afforded the 2-(arylhydrazono)aldehydes 1a-e. Compounds la, b reacted with hydroxylamine hydrochloride to yield the oximes 4a, b

Full text of DOI:10.1515/znb-2007-0407

Studies with 2-(Arylhydrazono)aldehydes: Synthesis and Chemical
Reactivity of Mesoxalaldehyde 2-Arylhydrazones and of
Ethyl 2-Arylhydrazono-3-oxopropionates
Saad Makhseeda, Huwaida M. E. Hassaneenb, and Mohamed H. Elnagdib
a Chemistry Department; Faculty of Science, University of Kuwait,
P. O. Box 5969, Safat; 13060-Kuwait
b Chemistry Department, Faculty of Science, Cairo University; Giza, A. R. Egypt
Reprint requests to Dr. Saad Makhseed. Fax: 009654816482.
E-mail: smakhseed@kuc01.kuniv.edu.kw
Z. Naturforsch. 2007, 62b, 529 – 536; received June 13, 2006
The coupling reaction of 3-(dimethylamino)acrolein (2a) and ethyl 3-(dimethylamino)acrylate
(2b) with arenediazonium chlorides afforded the 2-(arylhydrazono)aldehydes 1a – e. Com-
pounds 1a, b reacted with hydroxylamine hydrochloride to yield the oximes 4a, b. The dioxime 5
was obtained from reaction of 1a with an excess of hydroxylamine hydrochloride. This dioxime
afforded the 1,2,3-triazole carbonitrile 6 when treated with acetic anhydride, while α-hydrazono pro-
pionitrile 8 was obtained when 5 was treated with acetic acid. Compounds 1a – e could be utilized
for the synthesis of a variety of pyrazoles and arylazolopyrimidines via reaction with hydrazines,
haloketones and aminoazoles, respectively.
Key words: 2-Arylhydrazonopropane-1,3-dial, 2-Aryl-1,2,3-triazole-4-carbonitrile, Formazanes
Introduction
toward arenediazonium tetrafluoroborates where cy-
clization into cinnolines has been observed [9 – 11].
Compounds 1a – e were assigned the indicated hy-
drazone structure in preference to a potentially tau-
tomeric enolazo structure. This assignement is based
on 1H NMR and 13C NMR spectra which revealed sig-
nals for two formyl protons and carbons in 1a – d and
one such signal in the spectra of 1e. The appearance of
the hydrazone NH signal at δ ∼ 12 ppm in the 1H NMR
spectra of 1a – e can be assumed to result from the
existence of hydrogen bonding between the NH hy-
drogen and the formyl carbonyl group. Recent results
have established that 2-arylhydrazonoketones prefer
the anti form to fit stereoelectronic [15, 16] require-
ments. Thus, the low-field signals observed for hydra-
zone NH in 1a – e are most likely due to delocalization
of the lone pair at nitrogen over the adjacent imine and
carbonyl moieties. Compound 1e readily coupled fur-
ther with 4-chlorobenzenediazonium salts to yield for-
mazanes 3. These were also isolated as byproducts of
the reaction of 2a, b with arenediazonium salts. The
structure of 3 has been established by single crystal
X-ray structure determination (Scheme 1, Fig. 1).
In Table 1 selected bond lengths and bond angles
2-(Arylhydrazono)aldehydes are versatile reagents
and their chemistry is now receiving considerable
attention [1 – 6]. A general route to arylhydrazon-
als is the coupling of arenediazonium salts with
enamines [1 – 6]. However, recently it was reported
that some enaminonitriles couple with diazonium
tetrafluroborates to yield cyclic pyridazinones [7 – 11].
Anomalous behavior has also been reported for reac-
tions of cyclic enaminones and enamino esters with
arenediazonium salts [12, 13].
Results and Discussion
In conjunction with our interest in the chemistry
of arylhydrazoates we report here results of our work
aimed at exploring the potential utility of enaminals
and enaminoesters as precursors to arylhydrazonals
as well as some chemistry of the synthesized arylhy-
drazonals. Thus, the arylhydrazonals 1a – e could be
readily obtained upon coupling of the enaminoalde-
hyde 2a and the enaminoester 2b with arene diazo-
nium salts. The behavior of 2a, b toward arene dia-
zonium salts thus parallels the reported behavior of
enamines [14] and enaminones [1] toward the same are summarized. It is clear that all nitrogens are sp2
reagents but differs from the reported behavior of 2b hybridized which may point to extensive delocaliza-
0932–0776 / 07 / 0400–0529 $ 06.00 © 2007 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Unauthenticated
Download Date | 1/24/16 9:23 PM

530
S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
H
X
N=N-C6H4Cl-p
X
-
+
X
-
+
O
N
NCl
Ar
ArN NCl
N
H
N
NH
Me2N
N
Ar = p-ClC6H4
1a-e
X = CO2Et
Ar
C6H4Cl-p
2a: X = CHO
b: X = CO2Et
3
1a: X = CHO, Ar = p-ClC6H4;
b: X = CHO, Ar = C6H5
c: X = CHO, Ar = p-CH3OC6H4; d: X = CHO, Ar = m-ClC6H4
e: X = CO2Et, Ar = p-ClC6H4
Scheme 1.
˚
Table 1: Selected bond lengths (A) and angles (deg) of com-
ported earlier [17], failed. On the other hand, dioxime 5
afforded α-hydrazonopropionitrile8 when treated with
acetic acid (Scheme 2).
Treatment of 1c with hydroxylamine hydrochlo-
ride resulted in the formation of ethyl 1,2,3-triazole-
4-carboxylate 10. Intermediate oxime 9 could also be
isolated and readily cyclized to 10 on reflux in acetic
anhydride. Compounds 1a, c reacted with hydrazines
to yield the arylazopyrazoles 11a, b and 12a, b
(Scheme 3).
pound 3.
N3–N5
1.301(4)
1.332(4)
1.422(5)
1.326(5)
1.487(5)
1.438(5)
N5–N3–C11
N3–N5–C20
C8–N6–N17
N6–N17–C20
117.6(3)
119.4(3)
117.6(3)
120.3(4)
N5–C20
N6–C8
N6–N17
C9–C20
N17–C20
Compound 1a, e reacted with chloroacetone to yield
condensation products via elimination of one molecule
of hydrogen chloride and one molecule of water. These
were formulated as 14a, b and were assumed to be
formed via the intermediates 13a, b (Scheme 4). These
reactions parallel a recently reported pyrazole syn-
thesis from the reaction of 2-arylhydrazonals with
chloroacetone [18].
Compound 1e reacted with ethyl 4-chloroaceto-
acetate to yield the 3-oxoester 16, formed most likely
via intermediacy of the acyclic compound 15 in a man-
ner similar to that observed for the reaction of 1c with
chloroacetone. Although 16 may exist also in equilib-
1
rium with an enol form, the H NMR spectrum re-
vealed the absence of the latter as a signal for OH
was absent and a CH2 signal at δ = 4.54 ppm was
observed. Unexpectedly, the reaction of 1a with ethyl
4-chloroacetoacetate afforded a product of molecular
formula C15H12Cl2N2O3 corresponding to condensa-
tion of the ketoester with 1a via elimination of two
molecules of water. Structure 18 was concluded for this
product based on spectral data, and its formation is as-
sumed to proceed via intermediacy of 17 (Scheme 5).
Compounds 1a, c also reacted with aminoa-
Fig. 1. Molecular structure of 3 in the crystal.
tion of nitrogen lone pairs of N(3) and N(5). It is also
important to note that the trans relationship of the NH
and formyl substituents of the C=N function indicates
that stabilization by stereoelectronic effects supersedes
a possible fixation by hydrogen bonding.
Compounds 1a, b reacted with equimolar amounts
of hydroxylamine hydrochloride to yield the oximes
4a, b. When 1a was reacted with an excess of hy-
droxylamine hydrochloride in ethanolic sodium ac- zoles 19a, b to yield the azolopyrimidines 20a, b
etate, dioxime 5 was formed. Treatment of dioxime 5
with acetic anhydride afforded 1,2,3-trizazole-4-
and 21a, b (Scheme 6).
In conclusion we could show that the coupling reac-
carbonitrile 6. Experiments to isolate oxime 7, as re- tion of substituted enamines with arenediazonium salts
Unauthenticated
Download Date | 1/24/16 9:23 PM

S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
531
OH
N
NH2OH x HCl
CHO
1a,b
a: Ar = C6H4Cl-p
b: Ar = C6H5
H
NaOAc
N
NH
Ar
4a,b
Ar = C6H4Cl-p
OH
N
OH
CN
N
OH
N
N
H
Ac2O
N
N
N
N
N
NH
Ar
N
5
Ar
Ar
6
7
AcOH
OH
N
N
H
N
NH
8
Scheme 2.
Ar
O
O
OH
O
C H Cl-p-N=
C H Cl-p-NH-
N
6 4
N
N
EtO
6
4
EtO
N
N
N
N
N
N
NH
R
N
N
R
C6H4Cl-p
10
C6H4Cl-p
9
11
12
11a, 12a: R = H
11b, 12b: R = C6H5
Scheme 3.
spectrophotometer. 1H NMR and 13C NMR spectra were
recorded on a Varian EM-400 MHz spectrometer in
[D6]DMSO as a solvent and with TMS as internal stan-
dard; chemical shifts are reported in δ units (ppm). Mass
spectra were measured on MS 30 and MS 9 (AEI) instru-
ments at 70 eV. Microanalyses were performed with a LECO
CHClNS-932 instrument.
H
X
X
O
ClCH2COCH3
N
1a,e
COCH3
N
CH2COCH3
N
N
Ar
Ar
14a: X = CHO,
b: X = OCOEt, Ar = p-ClC6H4
Ar = p-ClC6H4
13a,b
Scheme 4.
Crystallographic analysis
is a general route to arylhydrazonals that are versatile
starting materials for the synthesis of polyfunctional
azoles and condensed azoles.
The crystal was mounted on a glass fiber. All measure-
ments were performed on an Enraf Nonius FR 590 diffrac-
tometer. The data were collected at a temperature of 20 1 ◦C
using the ω scanning technique to θmax = 26.02◦. The struc-
ture was solved by Direct Methods using SIR 92 and re-
Experimental Section
All melting points are uncorrected. IR spectra were fined by full-matrix least-squares [17]. Non-hydrogen atoms
recorded on KBr pellets with a Pye Unicam SP 1100 were refined anisotropically. Hydrogen atoms were located
Unauthenticated
Download Date | 1/24/16 9:23 PM

532
S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
O
O
CHO
EtO
EtO
ClCH2COCH2CO2Et
N
N
COCH2CO2Et
N
CO2Et
N
1e
O
Cl
Cl
15
16
OH
O
O
COOEt
Cl
Cl
OHC
ClCH2COCH2CO2Et
OEt
1a
N
N
N
p
NHC6H4Cl-
C6H4Cl-p
Scheme 5.
17
18
of charge from The Cambridge Crystallographic Data Centre
via http://www.ccdc.cam.ac.uk/data request/cif.
General procedure for the preparation of compounds 1a – e
and 3
A cold solution of the arenediazonium salt (10 mmol) was
prepared by adding a solution of sodium nitrite (10 mmol in
water) to a cold solution of the aromatic amine hydrochlo-
ride with stirring. The resulting solution of the diazonium salt
was added to a cold solution of 3-(dimethylamino)acrolein
(2a) (1.0 g, 10 mmol) in 30 mL of ethanol, ethyl 3-
(dimethylamino)acrylate (2b) (1.43 g, 10 mmol) or 1e
(2.54g, 10 mmol), containing sodium acetate. The reaction
mixture was stirred at r. t. for 30 min. The solid product
formed was washed with water and crystallized from the
proper solvent.
2-[(4-Chlorophenyl)hydrazono]malonaldehyde (1a)
M. p. 150 ◦C. – Yield: 1.47 g, 70 %. – IR (KBr): v = 1676
1
(C=O); 3435 (NH) cm−1. – H NMR (400 MHz): δ = 7.53
(d, J = 8.0 Hz, 2H, Ar-H); 7.74 (d, J = 8.0 Hz, 2H, Ar-H);
Scheme 6.
9.53 (s, 1H, formyl); 9.83 (s, 1H, formyl); 14.04 (s, 1H, NH).
–
13C NMR (100 MHz): δ = 112.6, 121.89, 131.08, 142.32,
geometrically and were refined isotropically. – Crystal data:
C16H15Cl2N4O2, Mr = 364.232, monoclinic space group
159.42, 189.88, 190.84. – MS (AEI, 70 eV): m/z (%) = 210
(90) [M]+. – C9H7ClN2O2 (210.62): calcd. C 51.32, H 3.35,
N 13.30; found C 51.30, H 3.34, N 13.29.
˚
P21/c, a = 7.9984(3), b = 10.6059(4), c = 20.4607(9) A,
β = 95.833(2)◦, Z = 4, Dx = 1.401 Mg m−3. 6153 reflec-
tions measured, wR = 0.126. Fig. 1 illustrates the molecular
structure.
2-[Phenylhydrazono]malonaldehyde (1b)
CCDC 611263 contains the supplementary crystallo-
M. p. 121 ◦C. – Yield: 1.16 g, 66 %. – IR (KBr): v = 1673
1
graphic data for this paper. These data can be obtained free (C=O); 3432 (NH) cm−1. – H NMR (400 MHz): δ = 7.29
Unauthenticated
Download Date | 1/24/16 9:23 PM

S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
533
(t, 1H, Ar-H); 7.48 (d, J = 8.0 Hz, 2H, Ar-H); 7.70 (d, J = for 30 min, and then poured onto water. The solid product
8.0 Hz, 2H, Ar-H); 9.54 (s, 1H, formyl); 9.84 (s, 1H, formyl); was collected by filtration and crystallized from ethanol.
14.15 (s, 1H, NH). – 13C NMR (100 MHz): δ = 116.89,
127.75, 130.69, 134.10, 142.12, 190.58, 190.84. – MS (AEI,
70 eV): m/z (%) = 176 (85) [M]+. – C9H8N2O2 (176.17):
calcd. C 61.36, H 4.58, N 15.90; found C 61.32, H 4.58,
N 15.88.
2-[(4-Chlorophenyl)hydrazono]malonaldehyde monooxime
(4a)
M. p. 130 ◦C. – Yield: 1.66 g, 65 %. – IR (KBr): v =
1660 (C=O); 3110 (NH); 3426 (OH) cm−1. – 1H NMR
(400 MHz): δ = 7.39 (d, J = 8.0 Hz, 2H, J = 8.0 Hz,
Ar-H); 7.51 (d, J = 8.0 Hz, 2H, Ar-H); 8.16 (s, 1H); 9.40
(s, 1H); 12.27 (s, 1H, NH); 12.61 (s, 1H, OH). – 13C NMR
(100 MHz): δ = 116.11, 126.43, 129.10, 129.98, 141.84,
143.75, 190.09. – MS (AEI, 70 eV): m/z (%) = 225 (30)
[M]+. – C9H8ClN2O2 (225.63): calcd. C 47.91, H 3.57,
N 18.62; found C 47.89, H 3.55, N 18.60.
2-[(4-Methoxyphenyl)hydrazono]malonaldehyde (1c)
M. p. 173 ◦C. – Yield: 1.23 g, 60 %. – IR (KBr): v = 1663
(C=O); 3435 (NH) cm−1. – 1H NMR (400 MHz): δ = 3.79
(s, 3H, OCH3); 7.04 (m, 2H, Ar-H); 7.73 (m, 2H, Ar-H); 8.32
(s, 1H, formyl); 9.14 (br., 1H, formyl); 12.78 (br., 1H, NH). –
MS (AEI, 70 eV): m/z (%) = 206 (86) [M]+. – C10H10N2O3
(206.20): calcd. C 58.25, H 4.89, N 13.59. found C 58.11,
H 4.88, N 13.57.
2-[Phenylhydrazono]malonaldehyde monooxime (4b)
2-[(3-Chlorophenyl)hydrazono]malonaldehyde (1d)
M. p. 146 ◦C. – Yield: 1.22 g, 64 %. – 1H NMR
(400 MHz): δ = 7.16 (t, 1H, Ar-H); 7.33 – 7.46 (m, 4H,
Ar-H); 8.18 (s, 1H); 9.43 (s, 1H); 12.23 (br., 1H, NH); 12.66
M. p. 139 ◦C. – Yield: 1.45 g, 69 %. – IR (KBr): v = 1683
(C=O); 3436 (NH) cm−1. – 1H NMR (400 MHz): δ = 7.32
(d, J = 7.8 Hz, 1H, Ar-H); 7.48 (t, J = 7.8 Hz, 1H, Ar-H); (br., 1H, OH). – 13C NMR (100 MHz): δ = 116.28, 125.57,
7.68 (d, J = 8.0 Hz, 1H, Ar-H); 7.81 (s, 1H, Ar-H); 9.55
131.07, 132.88, 142.81, 149.05, 190.114. – MS (AEI, 70 eV):
m/z (%) = 191 (66) [M]+. – C9H9N3O2 (191.19): calcd.
(s, 1H, formyl); 9.84 (s, 1H, formyl); 13.94 (s, 1H, NH). –
13C NMR (100 MHz): δ = 116.9, 117.2, 127.0, 132.3, 134.5, C 56.54, H 4.74, N 21.98; found C 56.56, H 4.70, N 21.90.
135.1, 143.9, 186.8, 191.0. – MS (AEI, 70 eV): m/z (%) =
210 (90) [M]+. – C9H7ClN2O2 (210.62): calcd. C 51.32,
2-[(4-Chlorophenyl)hydrazono]malonaldehyde dioxime (5)
H 3.35, N 13.30; found C 51.31, H 3.33, N 13.30.
A mixture of 1a (2.10 g, 10 mmol); hydroxylamine hy-
drochloride (1.38 g, 20 mmol) and sodium acetate (3 g) in
ethanol (20 mL) was heated under reflux for 30 min, then
poured onto water. The solid product was collected by filtra-
tion and crystallized from ethanol.
2-[(4-Chlorophenyl)hydrazono]-3-oxopropionic acid ethyl
ester (1e)
M. p. 88 ◦C. – Yield: 1.57 g, 62 %. – IR (KBr): v = 1655,
1692 (2CO); 3446 (NH) cm−1. – 1H NMR (400 MHz): δ =
1.30 (t, J = 7.2 Hz, 3H); 4.30 (q, J = 7.2 Hz, 2H); 7.49 (d,
J = 8.0 Hz, 2H, Ar-H); 7.62 (d, J = 8.0 Hz, 2H, Ar-H); 9.64
(s, 1H, formyl); 13.94 (s, 1H, NH). – 13C NMR (100 MHz):
δ = 14.86, 61.829, 119.20, 128.46, 130.02, 130.50, 141.69,
164.29, 187.89. – MS (AEI, 70 eV): m/z (%) = 254 (100)
[M]+. – C11H11ClN2O3 (254.67): calcd. C 51.88, H 4.35,
N 11.00; found C 51.84, H 4.37, N 10.95.
M. p. 140 ◦C. – Yield: 1.61 g, 67 %. – 1H NMR
(400 MHz): δ = 7.20 (d, J = 8.0 Hz, 2H, Ar-H); 7.34 (d,
J = 8.0 Hz, 2H, Ar-H); 7.76 (s, 1H); 8.24 (s, 1H); 12.13 (s,
1H, NH); 12.65 (s, 1H, OH); 12.68 (s, 1H, OH). – 13C NMR
(100 MHz): δ = 116.13, 126.31, 129.27, 129.49, 140.39,
142.15, 148.98. – MS (AEI, 70 eV): m/z (%) = 240 (45)
[M]+. – C9H9ClN4O2 (240.65): calcd. C 44.92, H 3.77,
N 23.28; found C 44.90, H 3.72, N 23.22.
Ethyl 2-[2-(4-chlorophenyl)-1-diazenyl]-2-[2-(4-chloro-
phenyl)hydrazono]acetate (3)
2-(4-Chlorophenyl)-2H-[1,2,3]triazole-4-carbonitrile (6)
M. p. 175 ◦C. – Yield: 2.99 g, 82 %. – 1H NMR
(400 MHz): δ = 1.31 (t, J = 7.2 Hz, 3H); 4.27 (q, J =
7.2 Hz, 2H); 7.45 – 8.54 (m, 8H, Ar-H); 14.68 (s, 1H, NH). –
C16H14Cl2N4O2 (365.21): calcd. C 52.62, H 3.86, N 15.34;
found C 52.58, H 3.80, N 15.29.
A mixture of 5 (2.4 g, 10 mmol) and acetic anhydride
(20 mL) was refluxed for 2 h, then poured into water. The
solid formed was collected by filtration and crystallized from
ethanol.
M. p. 130 ◦C. – Yield: 1.43 g, 70 %. – IR (KBr): v = 2253
(CN) cm−1. – 1H NMR (400 MHz): δ = 7.69 (d, J = 8.0 Hz,
2H, Ar-H); 8.08 (d, J = 8.0 Hz, 2H, Ar-H); 8.90 (s, 1H). –
13C NMR (100 MHz): δ = 112.66, 121.94, 123.38, 131.07,
General procedure for the preparation of compounds 4a, b
and 9
A mixture of 1a, b (10 mmol) or 1e (2.54 g, 10 mmol); 135.02, 138.07, 142.32. – MS (AEI, 70 eV): m/z (%) = 204
hydroxylamine hydrochloride (0.69 g, 10 mmol) and sodium (100) [M]+. – C9H5ClN4 (204.62): calcd. C 52.83, H 2.46,
acetate (3 g) in ethanol (20 mL) was heated under reflux N 27.38; found C 52.85, H 2.40, N 27.33.
Unauthenticated
Download Date | 1/24/16 9:23 PM

534
S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
2-[(4-Chlorophenyl)hydrazono]-3-hydroxyimino-propio-
nitrile (8)
12.60 (s, 1H, NH). – 13C NMR (100 MHz): δ = 124.48,
126.14, 130.47, 135.64, 141.91, 151.96, 154.80. – MS (AEI,
70 eV): m/z (%) = 206 (60) [M]+. – C9H7ClN4 (206.63):
calcd. C 52.31, H 3.41, N 27.11; found C 52.30, H 3.43,
N 27.15.
A mixture of 5 (2.49 g, 10 mmol) and acetic acid (20 mL)
was refluxed for 2 h, and then poured into water. The solid
formed was collected by filtration and crystallized from
ethanol.
4-(4-Chlorophenylazo)-1-phenyl-1H-pyrazole (11b)
M. p. 264 ◦C. – Yield: 1.46 g, 66 %. – IR (KBr): v = 2212
(CN); 3349 (NH); 3498 (OH) cm−1. – 1H NMR (400 MHz):
δ = 7.39 (d, J = 8.0 Hz, 2H, Ar-H); 7.50 (s, 1H, CH); 7.68 (d,
J = 8.0 Hz, 2H, Ar-H); 7.88 (s, 1H, NH); 11.78 (s, 1H, OH). –
MS (AEI, 70 eV): m/z (%) = 222 (100) [M]+. – C9H7ClN4O
(222.63): calcd. C 48.55, H 3.17, N 25.17; found C 48.53,
H 3.12, N 25.05.
M. p. 196 ◦C. – Yield: 1.98 g, 70 %. – 1H NMR
(400 MHz): δ = 7.40 (t, 1H, Ar-H); 7.57 (d, J = 8.0 Hz,
2H, Ar-H); 7.64 (d, J = 8.0 Hz, 2H, Ar-H); 7.83 (d, J =
8.0 Hz, 2H, Ar-H); 7.98 (d, J = 8.0 Hz, 2H, Ar-H); 8.29
(s, 1H); 9.40 (s, 1H). – 13C NMR (100 MHz): δ = 119.86,
124.67, 127.65, 128.33, 130.61, 131.40, 143.39, 136.21,
140.06, 143.36, 151.91. – MS (AEI, 70 eV): m/z (%) = 282
(80) [M]+. – C15H11ClN4 (282.73): calcd. C 63.72, H 3.92,
N 19.82; found C 63.70, H 3.90, N 19.80.
Ethyl 2-[(4-chlorophenyl)hydrazono]-3-hydroxyimino-
propionionate (9)
4-[(4-Chlorophenyl)hydrazono]-2,4-dihydropyrazol-3-one
(12a)
M. p. 182 ◦C. – Yield: 1.94 g, 72 %. – IR (KBr): v =
1699 (C=O); 3230 (NH); 3402 (OH) cm−1. – 1H NMR
(400 MHz): δ = 1.29 (t, J = 7.2 Hz, 3H); 4.25 (q, J =
7.2 Hz, 2H); 7.29 (d, J = 8.0 Hz, 2H, Ar-H); 7.45 (d, J =
8.0 Hz, 2H, Ar-H); 8.29 (s, 1H); 12.23 (s, 1H, NH); 12.62 (s,
1H, OH). – MS (AEI, 70 eV): m/z (%) = 269 (85) [M]+. –
C11H12ClN3O3 (269.68): calcd. C 48.99, H 4.48, N 15.58;
found C 48.95, H 4.43, N 15.35.
M. p. 156 ◦C. – Yield: 1.65 g, 74 %. – IR (KBr): v = 1667
(C=O); 3232, 3451 (2NH) cm−1. – 1H NMR (400 MHz):
δ = 7.46 – 7.48 (m, 4H, Ar-H); 7.55 (s, 1H, NH); 7.95 (s,
1H); 11.95 (s, 1H, NH). – 13C NMR (100 MHz): δ = 118.43,
119.15, 126.32, 129.60, 130.15, 130.79, 138.88, 141.29,
157.04, 165.74, 165.85. – MS (AEI, 70 eV): m/z (%) = 222
(100) [M]+. – C9H7ClN4O (222.63): calcd. C 48.55, H 3.17,
N 25.17; found C 48.54, H 3.15, N 25.14.
Ethyl 2-(4-chlorophenyl)-1,2,3-triazole-4-carboxylate (10)
A mixture of 9 (2.69 g, 10 mmol) and acetic anhydride
(20 mL) was refluxed for 2 h, and then poured into water.
The solid formed was collected by filtration and crystallized
from ethanol.
4-[(4-Chlorophenyl)hydrazono]-2-phenyl-2,4-dihydropyr-
azol-3-one (12b)
M. p. 190 ◦C. – Yield: 2.15 g, 72 %. – IR (KBr): v =
1654 (C=O); 3432 (NH) cm−1. – 1H NMR (400 MHz):
δ = 7.26 (t, 1H, Ar-H); 7.47 – 7.52 (m, 4H, Ar-H); 7.65 (d,
J = 8.0 Hz, 2H, Ar-H); 7.91 (d, J = 8.0 Hz, 2H, Ar-H);
8.17 (s, 1H); 12.98 (s, 1H, NH). – 13C NMR (100 MHz):
δ = 118.44, 119.04, 119.15, 126.32, 129.60, 129.99, 130.58,
138.88, 141.29, 141.84, 157.04. – MS (AEI, 70 eV): m/z
(%) = 298 (100) [M]+. – C15H11ClN4O (298.73): calcd.
C 60.31, H 3.71, N 18.76; found C 60.28, H 3.73, N 18.72.
M. p. 183 ◦C. – Yield: 1.83 g, 73 %. – IR (KBr): v = 1728
(C=O) cm−1. – 1H NMR (400 MHz): δ = 1.34 (t, J = 7.2 Hz,
3H); 3.38 (q, J = 7.2 Hz, 2H); 7.68 (d, J = 8.0 Hz, 2H,
Ar-H); 8.09 (d, J = 8.0 Hz, 2H, Ar-H); 8.63 (s, 1H). – MS
(AEI, 70 eV): m/z (%) = 251 (100) [M]+. – C11H10ClN3O2
(251.67): calcd. C 52.50, H 4.01, N 16.70; found C 52.51,
H 4.00, N 16.72.
General procedure for the preparation of compounds 11a, b
and 12a, b
General procedure for the preparation of compounds 14a, b
A mixture of 1a (2.1 g, 10 mmol) or 1e (2.54 g, 10 mmol)
with hydrazine hydrate (0.5 g, 10 mmol) or phenylhydrazine
A mixture of 1a, e (2.10 g, 10 mmol) or 1e, g (2.54 g,
10 mmol) and chloroacetone (10 mmol) in ethanol (30 mL)
(1.08 g, 10 mmol) was refluxed in ethanol for 1 h. The solid containing triethylamine (10 mmol) was refluxed for 30 min,
product obtained was collected by filtration and crystallized then left to cool. The solid products were collected by filtra-
tion and crystallized from dimethylformamide.
from the proper solvent.
4-(4-Chlorophenylazo)-1H-pyrazole (11a)
5-Acetyl-1-(4-chlorophenyl)-1H-pyrazole-3-carbaldehyde
(14a)
M. p. 170 ◦C. – Yield: 1.50 g, 73 %. – IR (KBr): v = 3172
(NH) cm−1. – 1H NMR (400 MHz): δ = 7.60 (d, J = 8.0 Hz,
M. p. 180 ◦C. – Yield: 1.64 g, 66 %. – IR (KBr): v = 1654
2H, Ar-H); 7.77 (d, J = 8.0 Hz, 2H, Ar-H); 8.30 (s, 2H); (C=O); 3432 (NH) cm−1. – 1H NMR (400 MHz): δ = 2.58 (s,
Unauthenticated
Download Date | 1/24/16 9:23 PM

S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
535
3H); 7.57 – 7.61 (m, 4H, Ar-H); 7.86 (s, 1H); 10.00 (s, 1H). – to cool to r. t. The solid product was collected by filtration
MS (AEI, 70 eV): m/z (%) = 248 (80) [M]+. – C12H9ClN2O2 and crystallized from ethanol.
(248.67): calcd. C 57.96, H 3.65, N 11.27; found C 57.65,
H 3.63, N 11.23.
(4-Chlorophenyl)-pyrazolo[1,5-a]pyrimidin-6-yl-diazene
(20a)
Ethyl 5-acetyl-1-(4-chlorophenyl)-1H-pyrazole-3-carboxyl-
M. p. 269 ◦C. – Yield: 1.80 g, 70 %. – 1H NMR
(400 MHz): δ = 7.22 (d, 1H); 7.68 (d, J = 8.0 Hz, 2H, Ar-H);
M. p. 170 C. – Yield: 2.0 g, 69 %. – IR (KBr): v = 1691 7.94 (d, J = 8.0 Hz, 2H, Ar-H); 8.37 (d, 1H); 8.70 (d, 1H);
(C=O); 3446 (NH) cm−1. – 1H NMR (400 MHz): δ = 1.31 (t, 9.14 (d, 1H). – MS (AEI, 70 eV): m/z (%) = 257 (70) [M]+. –
J = 7.2 Hz, 3H); 2.57 (s, 3H,); 4.34 (q, J = 7.2 Hz, 2H); 7.51 C12H8ClN5 (257.68): calcd. C 55.93, H 3.13, N 27.18; found
(d, J = 8.0 Hz, 2H, Ar-H); 7.57 (d, J = 8.0 Hz, 2H, Ar-H); C 55.85, H 3.06, N 27.11.
ate (14b)
◦
7.81 (s, 1H); 10.08 (s, 1H). – MS (AEI, 70 eV): m/z (%) =
292 (85) [M]+. – C14H13ClN2O3 (292.72): calcd. C 57.44,
H 4.42, N 9.57; found C 57.40, H 4.42, N 9.52.
(4-Chlorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl-
diazene (20b)
M. p. 246 ◦C. – Yield: 1.76 g, 68 %. – 1H NMR
(400 MHz): δ = 7.75 (d, J = 8.0 Hz, 2H, Ar-H); 7.98 (d, J =
8.0 Hz, 2H, Ar-H); 8.86 (s, 1H); 9.42 (s, 1H); 10.16 (s, 1H). –
A mixture of 1a (2.10 g, 10 mmol) or 1e (2.54 g, MS (AEI, 70 eV): m/z (%) = 258 (100) [M]+. – C11H7ClN6
10 mmol); ethyl 4-chloroacetoacetate (10 mmol); and tri- (258.67): calcd. C 51.08, H 2.73, N 32.49; found C 51.01,
General procedure for the preparation of compounds 16 and
18
ethylamine (10 mmol) in ethanol (30 mL) was refluxed
for 30 min, then left to cool. The solid product was collected
by filtration and crystallized from a suitable solvent.
H 2.75, N 32.49.
6-[(4-Chlorophenyl)hydrazono]-6H-pyrazolo[1,5-a]pyr-
imidin-7-one (21a)
Ethyl 1-(4-chlorophenyl)-5-(2-ethoxycarbonyl-acetyl)-1H-
pyrazole-3-carboxylate (16)
M. p. 191 ◦C. – Yield: 1.97 g, 72 %. – IR (KBr): v = 1643
(C=O); 3132 (NH) cm−1. – H NMR (400 MHz): δ = 6.59
1
M. p. 186 ◦C. – Yield: 2.62 g, 72 %. – IR (KBr): v = 1674, (d, 1H); 7.52 (d, J = 8.0 Hz, 2H, Ar-H); 7.57 (d, J = 8.0 Hz,
1710, 1719 (3CO) cm−1. – 1H NMR (400 MHz): δ = 1.29 –
1.39 (m, 6H, 2CH3); 4.30 – 4.44 (m, 4H, 2CH2); 4.54 (s, 2H,
2H, Ar-H); 7.78 (d, 1H); 8.83 (s, 1H); 14.91 (s, 1H, NH). –
13C NMR (100 MHz): δ = 98.35, 119.62, 124.77, 130.57,
CH2); 7.35 (d, J = 8.0 Hz, 2H, Ar-H); 7.74 (s, 1H); 8.15 131.81, 139.95, 144.70, 148.62, 154.97, 193.95. – MS (AEI,
70 eV): m/z (%) = 273 (100) [M]+. – C12H8ClN5O (273.68):
(d, J = 8.0 Hz, 2H, Ar-H); 9.04 (s, 1H, pyrrole H-4). – MS
(AEI, 70 eV): m/z (%) = 364 (60) [M]+. – C17H17ClN2O5
calcd. C 52.66, H 2.95, N 25.59; found C 52.66, H 2.95,
(364.78): calcd. C 55.97, H 4.70, N 7.68; found C 55.93, N 25.59.
H 4.65, N 7.61.
6-[(4-Chlorophenyl)hydrazono]-6H-[1,2,4]triazolo-
Ethyl 3-chloro-5-[2-(4-chlorophenyl)-1-diazenyl]-2-hydr-
oxobenzoate (18)
[1,5-a]pyrimidin-7-one (21b)
M. p. 202 ◦C. – Yield: 1.92 g, 70 %. – IR (KBr): v = 1645
M. p. 146 ◦C. – Yield: 2.54 g, 75 %. – IR (KBr): v = 1681
(C=O); 3432 (OH) cm−1. – 1H NMR (400 MHz): δ = 1.38 (t,
J = 7.2 Hz, 3H); 4.45 (q, J = 7.2 Hz, 2H); 7.66 (d, J = 8.0 Hz,
2H, Ar-H); 790 (d, J = 8.0 Hz, 2H, Ar-H); 8.19 (d, 1H); 8.29
(d, 1H); 11.60 (br., 1H, OH). – MS (AEI, 70 eV): m/z (%) =
338 (20) [M]+. – C15H12Cl2N2O3 (339.17): calcd. C 53.12,
H 3.57, N 8.26; found C 53.05, H 3.48, N 8.17.
1
(C=O); 3110 (NH) cm−1. – H NMR (400 MHz): δ = 7.52
(d, J = 8.0 Hz, 2H, Ar-H); 7.57 (d, J = 8.0 Hz, 2H, Ar-H);
8.33 (s, 1H); 8.78 (s, 1H); 15.11 (s, 1H, NH). – MS (AEI,
70 eV): m/z (%) = 274 (100) [M]+. – C11H7ClN6O (274.67):
calcd. C 48.10, H 2.57, N 30.60; found C 48.06, H 2.55,
N 30.55.
Acknowledgements
The support of the University of Kuwait received through
research grant No. SC06/03 and the facilities used from
ANALAB and SAF (GS 01/01, GS 02/01) are gratefully ac-
General procedure for the preparation of compounds 20a, b
and 21a, b
Compound 1a (2.10 g, 10 mmol) or 1e (2.54 g, 10 mmol) knowledged. The authors are grateful to Dr. B. Al-Saleh for
in ethanol (30 mL) was heated with one of the heterocyclic her keen interest in following this work and providing labo-
amines 19a, b (10 mmol) under reflux for 4 – 6 h and allowed ratory facilities.
Unauthenticated
Download Date | 1/24/16 9:23 PM

536
S. Makhseed et al. · Mesoxalaldehyde 2-Arylhydrazones and Ethyl 2-Arylhydrazono-3-oxopropionates
[1] F. Al-Omran, M. M. Abdel-Khalik, A. Abuel-Khair,
M. H. Elnagdi, Synthesis 1997, 91.
[2] H. Bahbehani, M. M. Abdel-Khalik, M. H. Elnagdi,
OPPI 1999, 31, 551.
[10] M. S. Manhas, J. W. Brown, U. K. Pandit, Tetrahedron
1975, 31, 1325.
[11] A. R. Katritzky, L. Urogdi, R. C. Patel, J. Chem. Soc.,
Perkin Trans 1 1982, 1349.
[3] M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez,
M. H. Elnagdi, J. Chem. Res. (S) 2004, 174.
[4] M. M. Abdel-Khalik, S. M. Agamy, M. H. Elnagdi,
Z. Naturforsch. 2000, 55b, 1211.
[5] M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez,
M. H. Elnagdi, J. Heterocycl. Chem. 2004, 41, 647.
[6] M. M. Abdel-Khalik, S. M. Agamy, M. H. Elnagdi,
Synthesis 2001, 1861.
[7] P. Simunek, M. Peskova, V. Bertolasi, A. Lyeka,
V. Machacek, Eur. J. Org. Chem. 2004, 5055.
[8] P. Simunek, M. Peskova, V. Bertolasi, V. Machacek,
A. Lyeka, Tetrahedron 2005, 61, 8130.
[12] S. Al-Mousawi, M. M. Abdel-Kalik, E. John, M. H. El-
nagdi, J. Heterocycl. Chem. 2003, 40, 689.
[13] P. Simunek, A. Lycka, V. Machacek, Eur. J. Org. Chem.
2002, 2764.
[14] H. Buff and U. Kucklander, Tetrahedron 2000, 56,
5137.
[15] O. Eldesoky. N. Al-Awadi, M. A. AbdelKhalik, M. H.
Elnagdi, J. Chem. Res. (S) 2006, 291.
[16] I. Kenawy, M. H. Elnagdi, Spectrochim. Acta 2006,
A65, 801.
[17] M. S. Manha, J. W. Brown, U. K. Bandit, T. Houde-
wind, Tetrahedron 1975, 31, 1325.
[9] C. B. Kanner, U. K. Pandit, Tetrahedron 1985, 37,
3513.
[18] B. Al-Saleh, M. A. El-Apasery, M. H. Elnagdi,
J. Chem. Res. (S) 2004, 578.
Unauthenticated
Download Date | 1/24/16 9:23 PM