Synthesis of 1-aryloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-semicarbazides

Article abstract of DOI:10.1081/SCC-100104053

A simple and efficient route to 1,4-diacyl semicarbazides is described. 1-Aryloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-thiosemicarbazides (Ia-i) on treatment with potassium iodate in the aqueous solution afford 1-aryloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-semicarbazides (IIa-i) in excellent yields.

Full text of DOI:10.1081/SCC-100104053

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SYNTHESIS OF 1-
ARYLOXYACETYL-4- (5-(4-
CHLOROPHENYL)-2-FUROYL)-
SEMICARBAZIDES
Zheng Li a , Xicun Wang b , Yuxia Da a & Jichou
Chen a
a Department of Chemistry , Northwest Normal
University , Lanzhou, Gansu, 730070, P R China
b Department of Chemistry , Northwest Normal
University , Lanzhou, Gansu, 730070, P R China
Published online: 09 Nov 2006.
To cite this article: Zheng Li , Xicun Wang , Yuxia Da & Jichou Chen (2001)
SYNTHESIS OF 1-ARYLOXYACETYL-4- (5-(4-CHLOROPHENYL)-2-FUROYL)-
SEMICARBAZIDES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:9, 1433-1440, DOI: 10.1081/
SCC-100104053
To link to this article: http://dx.doi.org/10.1081/SCC-100104053
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SYNTHETIC COMMUNICATIONS, 31(9), 1433–1440 (2001)
SYNTHESIS OF 1-ARYLOXYACETYL-4-
(5-(4-CHLOROPHENYL)-2-FUROYL)-
SEMICARBAZIDES
Zheng Li, Xicun Wang,* Yuxia Da, and Jichou Chen
Department of Chemistry, Northwest Normal University,
Lanzhou, Gansu, 730070, P R China
ABSTRACT
Asimple and efficient route to 1,4-diacyl semicarbazides is
described. 1-Aryloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-
thiosemicarbazides (Ia–i) on treatment with potassium
iodate in the aqueous solution afford 1-aryloxyacetyl-4-(5-
(4-chlorophenyl)-2-furoyl)-semicarbazides (IIa–i) in excellent
yields.
1,4-Diacyl thiosemicarbazides have attracted much attention in recent
years because of their fungicidal1,2 and bactericidal3 activities. The synthetic
methods of these compounds have been established. They can be readily
prepared by the reactions of acyl chloride with ammonium thiocyanate
and acid hydrazides under the condition of phase transfer catalysis in
high yieids.4–13
However, the analogous species, 1,4-diacyl semicarbazides, cannot be
obtained using the similar methods because of the unstability of intermedi-
ates, acyl isocyanate. Therefore, there are no 1,4-diacyl semicarbazides
reported yet in the literature in terms of our knowledge. This led us to
investigate the efficient synthetic route and develop the application of them.
* Corresponding author.
1433
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1434
LI ET AL.
In this paper, we report an efficient and convenient method for
preparation of l,4-diacyl semicarbazides in the aqueous solution, which
uses easily made 1,4-diacyl thiosemicarbazides as starting materials and
commercially available potassium iodate as reagent.
Reaction of 5-(4-chlorophenyl)-2-furoyl chloride with ammonium
thiocyanate catalyzed by polyethylene glycol-400 (PEG-400) in the solution
of methylene chloride gives 5-(4-chlorophenyl)-2-furoyl isothiocyanate first,
which in situ treatment with aryloxyacetic acid hydrazides at room
temperature affords 1-aryloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl-thio-
semicarbazides (Ia–i). Compounds Ia–i on further treatment with potassium
iodate in the aqueous solution, result in the formation of 1-aryloxyacetyl-4-
(5-(4-chlorophenyl)-2-furoyl)-semicarbazides (IIa–i) in excellent yields
(Scheme).
It is observed that potassium iodate reacts spontaneously with 1,4-
diacyl thiosemicarbazides (Ia–i) leading to the 1,4-diacyl semicarbazides
(IIa–i) fairly rapidly in all cases studied. Moreover, these reactions can be
easily carried out in the aqueous slurry under gentle reflux. The color change
of aqueous solution from colorless to violet because of the release of iodine
can conveniently indicate the progress of the reaction. All reactions studied
can be finished within half an hour. The products can be obtained only by
filtration. All yields are between 87% and 93%.
Scheme.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on an Alpha Centauri
1
FTIR spectrophotometer and H NMR spectra on a FT-80Ainstrument
using (CD3)2SO as solvent and Me4Si as internal standard. Elemental
analyses were performed on a Carlo-Erba 1106 Elemental Analysis
instrument. Melting points were observed in an open capillary tube and
uncorrected. 5-(4-Chlorophenyl)-2-furoyl chloride14 and aryloxyacetic acid

1,4-DIACYL SEMICARBAZIDES
1435
hydrazides15 were prepared according to literature procedures. Ammonium
thiocyanate, potassium iodate and PEG-400 were commercially available
and used as received.
General Procedure for the Preparation of Compounds Ia–i
To a solution of 5-(4-chlorophenyl)-2-furoyl chloride (0.72 g, 3 mmol)
in methylene chloride (20 mL), ammonium thiocyanate (0.34 g, 4.5 mmol)
and polyethylene glycol-400 (0.04 g, 0.1 mmol) were added. The mixture was
stirred for 1 h at room temperature. Then an aryloxyacetic acid hydrazide
(2.95 mmol) was added and the reaction mixture was stirred for another
0.5 h at room temperature. To the resulting mixture, water (10 mL) was
added so that the inorganic salts were dissolved, then the slurry was filtered,
the solid was washed with water (3ꢀ5 mL), and recrystallized from DMF-
EtOH-H2O, and the product was given. The physical and spectral data of
compounds Ia–i are shown below.
1-Phenyloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-
thiosemicarbazide (Ia)
Yield: 94%. m.p.: 212ꢁ-213ꢁC. H NMR (DMSO-d6) ꢀ 12.55 (s, 1H,
1
NH), 11.74 (s, lH, NH), 10.92 (s, 1H, NH), 7.04–8.31 (m, 11H, Ar-H,
Fu-H), 4.66 (s, 2H, CH2) IR(KBr, ꢁ, cmꢂ1): 3272, 3150(N-H), 1689, 1669
(C ¼ O), 1169(C ¼ S). Anal. calc. for C20H16N3O4SCl: C, 55.88; H, 3.75; N,
9.77. Found: C, 55.64; H, 3.61; N, 9.60.
1-(2-Methylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-
thiosemicarbazide (Ib)
Yield: 90%. m.p.: 193ꢁ–194ꢁC. 1H NMR (DMSO-d6) ꢀ 12.53
(s, 1H, NH), 11.86 (s, 1H, NH), 10.98 (s, 1H, NH), 6.95–8.51 (m, 10H,
Ar-H, Fu-H), 4.67 (s, 2H, CH2), 2.31 (s, 3H, CH3). IR(KBr, ꢁ, cmꢂ1):
3225, 3119 (N-H), 1698, 1657(C ¼ O), 1197(C ¼ S). Anal. calc. for
C21H18N3O4SCl: C, 56.82; H, 4.09; N, 9.47. Found: C, 57.12; H, 4.13; N, 9.20.
1-(4-Methylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)
thiosemicarbazide (Ic)
Yield: 96%. m.p.: 199ꢁ–200ꢁC. H NMR (DMSO-d6) ꢀ 12.62 (s, 1H,
1
NH), 11.78 (s, 1H, NH), 11.03 (s, 1H, NH), 6.84–8.61 (m, 10H, Ar-H,

1436
LI ET AL.
Fu-H), 4.62 (s, 2H, CH2), 2.24 (s, 3H, CH3). IR(KBr, ꢁ, cmꢂ1): 3218, 3186
(N-H), 1687, 1668 (C ¼ O), 1189 (C ¼ S). Anal. calc. for C21H18N3O4SCl: C,
56.82; H, 4.09; N, 9.47. Found: C, 56.93; H, 4.06; N, 9.53.
1-(4-methoxylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiose-
micarbazide (Id)
Yield: 88%. m.p.: 171ꢁ–172ꢁC. H NMR (DMSO-d6) ꢀ 12.60 (s, 1H,
1
NH), 11.84 (s, 1H, NH), 11.04 (s, 1H, NH), 7.08–8.02 (m, 10H, Ar-H,
Fu-H), 4.68 (s, 2H, CH2), 3.45 (s, 3H, CH3) IR(KBr, ꢁ, cmꢂ1): 3276, 3169
(N-H), 1691, 1672 (C ¼ O), 1168(C ¼ S). Anal. calc. for C21H18N3O5SCl: C,
54.84; H, 3.94; N, 9.14. Found: C, 55.01; H, 4.03; N, 9.01.
1-(2-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiosemi-
carbazide (Ie)
Yield: 86%. m.p.: 220ꢁ–221ꢁC. H NMR (DMSO-d6) ꢀ 12.80 (s, 1H,
1
NH), 11.88 (s, 1H, NH), 11.09 (s, 1H, NH), 7.14–8.16 (m, 10H, Ar-H,
Fu-H), 4.86 (s, 2H, CH2). IR(KBr, ꢁ, cmꢂ1): 3270, 3239 (N-H), 1705,
1667 (C ¼ O). 1167 (C ¼ S). Anal. calc. for C20H15N4O6SCl: C, 50.59; H,
3.18; N, 11.80. Found: C, 50.34; H, 2.93; N, 11.63.
1-(3-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiosemi-
carbazide (If)
Yield: 89% m.p.: 226ꢁ–227ꢁC. H NMR (DMSO-d6) ꢀ 12.74 (s, 1H,
1
NH), 11.84 (s, 1H, NH), 11.13 (s, 1H, NH), 7.11–8.12 (m, 10H, Ar-H,
Fu-H), 4.89 (s, 2H, CH2). IR(KBr, ꢁ, cmꢂ1): 3278, 3176 (N-H), 1703,
1671 (C ¼ O). 1172 (C ¼ S). Anal. calc. for C20H15N4O6SCl: C, 50.59; H,
3.18; N, 11.80. Found: C, 50.73; H, 3.30; N, 11.80.
1-(4-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiosemi-
carbazide (Ig)
Yield: 87%. m.p.: 208ꢁ–209ꢁC. H NMR (DMSO-d6) ꢀ 12.71 (s, 1H,
1
NH), 11.86 (s, 1H, NH), 11.14 (s, 1H, NH), 7.19–8.04 (m, 10H, Ar-H,
Fu-H), 4.87 (s, 2H, CH2). IR(KBr, ꢁ, cmꢂ1): 3321, 3210 (N-H), 1699,
1668 (C ¼ O), 1169 (C ¼ S). Anal. calc. for C20H15N4O6SCl: C, 50.59; H,
3.18; N, 11.80. Found: C, 50.43; H, 3.12; N, 11.73.

1,4-DIACYL SEMICARBAZIDES
1437
1-(1-Naphthyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiosemi-
carbazide (Ih)
Yield: 93%. m.p.: 196ꢁ–197ꢁC. H NMR (DMSO-d6) ꢀ 12.46 (s, 1H,
NH), 11.70 (s, 1H, NH), 11.13 (s, 1H, NH), 7.28–8.31 (m, 13H, Ar-H,
Fu-H), 4.81 (s, 2H, CH2). IR(KBr, ꢁ, cmꢂ1): 3277, 3210 (N-H), 1698,
1658 (C ¼ O), 1178 (C ¼ S). Anal. calc. for C24H18N3O4SCl: C, 60.06; H,
3.78; N, 8.76. Found: C, 60.37; H, 3.97; N, 8.91.
1
1-(4-Chlorophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-thiose-
micarbazide (Ii)
Yield: 92%. m.p.: 203ꢁ–204ꢁC. H NMR (DMSO-d6) ꢀ 12.51 (s, 1H,
1
NH), 11.73 (s, 1H, NH), 10.99 (s, 1H, NH), 6.94–8.15 (m, 10H, Ar-H,
Fu-H), 4.86 (s, 2H, CH2). IR(KBr, ꢁ, cmꢂ1): 3267, 3129 (N-H), 1701,
1668 (C ¼ O), 1170 (C ¼ S). Anal. calc. for C20H15N3O4SCl2: C, 51.73; H,
3.26; N, 9.05. Found: C, 51.92; H, 3.11; N, 10.10.
General Procedure for the Preparation of Compounds IIa–i
Asuspension of compound I (0.5 mmol) and KIO3 (0.75 mmol) in
H2O (30 mL) was refluxed for 0.5 h. The resulting mixture was filtered, the
solid was washed with H2O(3 ꢀ 5 mL), and recrystallized from DMF-EtOH-
H2O, then the product was given. The physical and spectral data of
compounds IIa–i are reported below.
1-Phenyloxyacetyl-4-(5-(4-chlorophenyl)-2-furoyl)-semicarbazide (IIa)
Yield: 91%. m.p.: 183ꢁ–184ꢁC. H NMR (DMSO-d6) ꢀ 11.87 (s, 1H,
1
NH), 11.01 (s, 2H, NH), 7.01–8.23 (m, 11H, Ar-H, Fu-H), 4.65 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3351 (N-H), 1701, 1663 (C ¼ O). Anal. calc. for
C20H16N3O5Cl: C, 58.05; H, 3.90; N, 10.15. Found: C, 58.32; H, 4.11; N, 10.37.
1-(2-Methylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIb)
Yield: 92%. m.p.: 203ꢁ–204ꢁC. H NMR (DMSO-d6) ꢀ 11.85 (s, 1H,
1
NH), 10.98 (s, 2H, NH), 6.93–8.63 (m, 10H, Ar-H, Fu-H), 4.68 (s, 2H,
CH2), 2.29 (s, 3H, CH3). IR(KBr, ꢁ, cmꢂ1): 3347 (N-H), 1708, 1665

1438
LI ET AL.
(C ¼ O). Anal. calc. for C21H18N3O5Cl: C, 58.95; H, 4.24; N, 9.82. Found:
C, 58.71; H, 4.12; N, 9.60.
1-(4-Methylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIc)
Yield: 89%. m.p.: 190ꢁ–191ꢁC. H NMR (DMSO-d6) ꢀ 11.91 (s, 1H,
1
NH), 10.83 (s, 2H, NH), 6.98–8.69 (m, 10H, Ar-H, Fu-H), 4.63 (s, 2H,
CH2), 2.25 (s, 3H, CH3). IR(KBr, ꢁ, cmꢂ1): 3353 (N-H), 1697, 1661
(C ¼ O). Anal. calc. for C21H18N3O5Cl: C, 58.95; H, 4.24; N, 9.82. Found:
C, 59.17; H, 4.31; N, 10.02.
1-(4-Methylphenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IId)
Yield: 93%. m.p.: 178ꢁ–179ꢁC. H NMR (DMSO-d6) ꢀ 11.93 (s, 1H,
1
NH), 10.91 (s, 2H, NH), 7.07–8.21 (m, 10H, Ar-H, Fu-H), 4.67 (s, 2H,
CH2), 3.43 (s, 3H, CH3). IR(KBr, ꢁ, cmꢂ1): 3349 (N-H), 1701, 1659
(C ¼ O). Anal. calc. for C21H18N3O6Cl: C, 56.83; H, 4.09; N, 9.47. Found:
C, 56.62; H, 4.01; N, 9.29.
1-(2-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIe)
Yield: 91%. m.p.: 193ꢁ–194ꢁC. H NMR (DMSO-d6) ꢀ 11.97 (s, 1H,
1
NH), 11.01 (s, 2H, NH), 7.11–8.17 (m, 10H, Ar-H, Fu-H), 4.84 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3362 (N-H), 1712, 1664 (C ¼ O). Anal. calc.
for C20H15N4O7Cl: C, 52.36; H, 3.30; N, 12.21. Found: C, 52.57; H, 3.41;
N, 12.50.
1-(3-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIf)
Yield: 88%. m.p.: 200ꢁ–201ꢁC. H NMR (DMSO-d6) ꢀ 11.89 (s, 1H,
1
NH), 10.93 (s, 2H, NH), 7.09–8.15 (m, 10H, Ar-H, Fu-H), 4.87 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3358 (N-H), 1691, 1659 (C ¼ O). Anal. calc.
for C20H15N4O7Cl: C, 52.36; H, 3.30; N, 12.21. Found: C, 52.49; H, 3.28;
N, 12.11.

1,4-DIACYL SEMICARBAZIDES
1439
1-(4-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIg)
Yield: 87%. m.p.: 181ꢁ–182ꢁC. H NMR (DMSO-d6) ꢀ 11.93 (s, 1H,
NH), 10.88 (s, 2H, NH), 7.21–8.11 (m, 10H, Ar-H, Fu-H), 4.88 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3347 (N-H), 1690, 1657 (C ¼ O). Anal. calc. for
C20H15N4O7Cl: C, 52.36; H, 3.30; N, 12.21. Found: C, 52.14; H, 3.24; N, 12.08.
1
1-(1-Naphthyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIh)
Yield: 90%. m.p.: 192ꢁ–193ꢁC. H NMR (DMSO-d6) ꢀ 11.84 (s, 1H,
1
NH), 10.86 (s, 2H, NH), 7.19–8.40 (m, 13H, Ar-H, Fu-H), 4.79 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3364 (N-H), 1683, 1664 (C ¼ O). Anal. calc. for
C24H18N3O5Cl: C, 62.14; H, 3.91; N, 9.06. Found: C, 62.26; H, 4.07; N, 9.18.
1-(2-Nitrophenyloxyacetyl)-4-(5-(4-chlorophenyl)-2-furoyl)-semi-
carbazide (IIi)
Yield: 92%. m.p.: 196ꢁ–197ꢁC. H NMR (DMSO-d6) ꢀ 11.86 (s, 1H,
1
NH), 10.83 (s, 2H, NH), 6.97–8.21 (m, 10H, Ar-H, Fu-H), 4.84 (s, 2H,
CH2). IR(KBr, ꢁ, cmꢂ1): 3349 (N-H), 1708, 1659 (C ¼ O). Anal. calc. for
C20H15N3O5Cl: C, 53.59; H, 3.37; N, 9.37. Found: C, 53.72; H, 3.42; N, 9.50.
ACKNOWLEDGMENTS
The authors thank the Natural Science Foundation of Gansu Province
for the financial support of this work.
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Received in the August 9, 2000