Phase-transfer catalyzed mild synthesis of 1,5-diacyl thiocarbohydrazides and their solventless expeditious transformation to 1,5-diacyl carbohydrazides

Article abstract of DOI:10.1080/10426500600867240

1,5-diacyl thiocarbohydrazides were efficiently synthesized by the reactions of thiocarbohydrazide with a variety of aroyl chlorides at r.t. using PEG-400 as a phase-transfer catalyst. Meanwhile, 1,5-diacyl thiocarbohydrazides were be expeditiously transf

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Phosphorus, Sulfur, and Silicon
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Phase-Transfer Catalyzed
Mild Synthesis of 1,5-Diacyl
Thiocarbohydrazides and
Their Solventless Expeditious
Transformation to 1,5-Diacyl
Carbohydrazides
Zheng Li a , Yanlong Zhao a & Jingya Yang a
a Gansu Key Laboratory of Polymer Materials ,
Northwest Normal University , Lanzhou, Gansu,
People's Republic of China
Published online: 01 Feb 2007.
To cite this article: Zheng Li , Yanlong Zhao & Jingya Yang (2007) Phase-Transfer
Catalyzed Mild Synthesis of 1,5-Diacyl Thiocarbohydrazides and Their Solventless
Expeditious Transformation to 1,5-Diacyl Carbohydrazides, Phosphorus, Sulfur, and
Silicon and the Related Elements, 182:1, 79-84, DOI: 10.1080/10426500600867240
To link to this article: http://dx.doi.org/10.1080/10426500600867240
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Phosphorus, Sulfur, and Silicon, 182:79–84, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600867240
Phase-Transfer Catalyzed Mild Synthesis of 1,5-Diacyl
Thiocarbohydrazides and Their Solventless Expeditious
Transformation to 1,5-Diacyl Carbohydrazides
Zheng Li
Yanlong Zhao
Jingya Yang
Gansu Key Laboratory of Polymer Materials, Northwest Normal
University, Lanzhou, Gansu, People’s Republic of China
1,5-diacyl thiocarbohydrazides were efficiently synthesized by the reactions of thio-
carbohydrazide with a variety of aroyl chlorides at r.t. using PEG-400 as a phase-
transfer catalyst. Meanwhile, 1,5-diacyl thiocarbohydrazides were be expeditiously
transformed into corresponding 1,5-diacyl carbohydrazides with periodic acid by
r.t. grinding a under solventless condition. This protocol has advantages of a mild
condition, fast reaction rate, high yield, and simple work-up procedure.
Keywords 1,5-diacyl thiocarbohydrazide; 1,5-diacyl carbohydrazide; phase-transfer
catalysis; solventless
INTRODUCTION
Thiocarbohydrazide derivatives have attracted much attention in re-
cent years due to their applications in the synthesis of heterocyclic
compounds,1 synthesis of transition metal complexes,2 and pharma-
cological studies.3
Meanwhile, carbohydrazide derivatives are widely used as an oxygen
scavenger (metal passivator) for water treatment systems, particu-
larly for boiler-feed systems.4 They also are important intermediates
for metal complexes.5 Recently, Zhao et al.6 reported the self-assembly
properties of substituted carbohydrazides. Wang et al.7 reported the
Received March 22, 2006; accepted April 30, 2006.
The authors thank the “Chunhui Project” of Ministry of Education of China (Z2004-1-
62034) and Key Laboratory of Eco-Environment-Related Polymer Materials (Northwest
Normal University), Ministry of Education of China, for the financial support of this
work.
Address correspondence to Zheng Li, Gansu Key Labaratory of Polymer Materials,
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu, 730070 People’s Republic of China. E-mail: lizheng@nwnu.edu.cn
79

80
Z. Li et al.
SCHEME 1
application of carbohydrazides as an inhibitor. However, the general
synthetic method for carbohydrazide derivatives is to use extremely
toxic phosgene as a starting material, which makes the process unsafe
and environmentally unfriendly.8
In this article, we would like to report a mild, rapid, and high yielding
method to prepare both 1,5-diacyl thiocarbohydrazides and correspond-
ing 1,5-diacyl carbohydrazides in one route by using phase-transfer
catalysis and a solventless grinding method, respectively.
RESULTS AND DISCUSSION
Reactions of thiocarbohydrazide with two equivalents of aroyl chlo-
rides at r.t. using poly(ethylene glycol-400) (PEG-400) as a liquid–liquid
phase transfer catalyst and sodium hydroxide as a base afforded 1,5-
diacyl thiocarbohydrazides (1a–h) in a high yield (Scheme 1). In fact, all
the reactions were very efficient. Although water was used as a solvent
together with methylene chloride, no any hydrolysates were observed.
The different substituents on aryl rings had no obvious effect on the
reaction rate and yield. The reaction also was suitable to the furan het-
erocycle (compound 1h). All the products were easily separated from
the mixture by extraction.
Further, compounds 1a–h were ground with periodic acid in an agate
mortar with a pestle under solvent-free conditions to readily afford 1,5-
diacyl carbohydrazides (2a–h) in an excellent yield. It was found that
the periodic acid was quite an efficient reagent for the reactions. No
byproducts were observed. The 1:1 molar ratio for the two reactants
and about a 3–5 min reaction time were the optimized condition for
giving a high yield (Table I).
1
From the room-temperature H NMR spectrum of compound 1a in
DMSO-d6, an interesting result was observed. Although there were
two different kinds of NH protons in compound 1a, four significant

1,5-Diacyl Thiocarbohydrazides
81
TABLE I The Synthesis of Compounds 1a–h and 2a–h
Compound
R
Reaction time (min) M.P. (◦C) Yield (%)a
1a
1b
1c
1d
1e
1f
1g
1h
2a
2b
2c
2d
2e
2f
C6H5
30
25
30
30
25
20
20
25
3
4
4
4
3
190–192
184–185
184–186
156–158
184–186
188–190
224–225
130–132
206–207
203–205
218–219
180–182
219–220
241–243
246–248
204–205
95
93
89
90
89
91
91
95
96
94
90
91
89
88
90
95
4-CH3OC6H4
2-CH3C6H4
3-CH3C6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
Fur-2-yl
C6H5
4-CH3OC6H4
2-CH3C6H4
3-CH3C6H4
2-ClC6H4
4-ClC6H4
4-BrC6H4
Fur-2-yl
3
5
4
2g
2h
aYields refer to the isolated product.
NH single peaks at 10.59, 10.47, 10.22, and 9.80 ppm appeared. How-
1
ever, the high temperature H NMR spectrum at 60◦C for compound
1a showed that the four peaks for NH protons were changed into two
broad peaks at 9.91 and 9.06 ppm. The similar situations were also
observed for compounds 1b–h. IR spectra of compounds 1a–h showed
the characteristic absorptions at 3194–3254 cm−1 for N-H, 1676–1691
cm−1 for C O, and 1250–1259 for C S.
In addition, 1H NMR spectra of compounds 2a–h in DMSO-d6 showed
proton peaks at 10.10–10.23 and 8.32–8.53 ppm for NH groups. IR spec-
tra of compounds 2a–h showed the characteristic absorptions at 3196–
3288 cm−1 for N-H and 1661–1688 cm−1 for C O.
In summary, we have developed an efficient method to prepare both
1,5-diacyl thiocarbohydrazides and 1,5-diacyl carbohydrazides in one
route. This protocol has advantages of a mild reaction condition, short
reaction time, high yield, low cost of the catalyst, and simple handling
procedure. It is a good alternative to the synthesis of carbohydrazide
derivatives without using extremely toxic phosgene as a starting
material.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on a Digilab 300 FTIR
1
spectrophotometer and H NMR spectra on a Mercury-400BB instru-
ment using (CD3)2SO as a solvent and Me4Si as an internal standard.

82
Z. Li et al.
Elemental analyses were performed on a Vario E1 Elemental Analysis
instrument. Mass spectra were recorded on a QP-1000A GC-MS us-
ing the impact mode (70 eV). Melting-points were observed in an elec-
trothermal melting-point apparatus. Aroyl chlorides were prepared by
the reactions of corresponding substituted benzoic acids with thionyl
chloride. Thiocarbohydrazide was prepared according to the literature
procedure.9
General Procedure for the Preparation of Compounds 1a–h
To a solution of sodium hydroxide (10 mmol), thiocarbohydrazide
(5 mmol), and PEG-400 (0.15 mmol) in 10 mL of water, aroyl chlorides
(12 mmol) in 10 mL of CH2Cl2 were added dropwise. Then the mixture
was stirred for an appropriate time indicated in Table I. The completion
of the reaction was monitored by TLC using petroleum ether, acetone,
and chloroform (5:2:2) as an eluent. Then the organic layer was sepa-
rated, and the aqueous layer was extracted with CH2Cl2 (2X5 mL). The
combined organic solution was dried by anhydrous Na2SO4. The solvent
was evaporated off, and the residue was crystallized from EtOH-DMF-
H2O (6:3:1) to give a product. The analytic data for compounds 1a–h
follow:
1
1a: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.59 (s, 1H,
NH), 10.47 (s, 1H, NH), 10.22 (s, 1H, NH), δ 9.80 (s, 1H, NH), 7.47–7.95
(m, 10H, Ar-H). IR: (KBr, ν, cm−1): 3254 (N-H), 1676(C O), 1254(C S).
MS: m/z, 314 (M+). Anal. calcd. for C15H14N4O2S: C, 57.31; H, 4.49; N,
17.82. Found: C, 57.19; H, 4.56; N, 17.73.
1
1b: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.39 (s, 1H,
NH), 10.28 (s, 1H, NH), 10.10 (s, 1H, NH), 9.67 (s, 1H, NH), 7.01–7.91
(m, 8H, Ar-H), 3.82 (s, 6H, CH3). IR: (KBr, ν, cm−1): 3212 (N-H), 1687
(C O), 1254 (C S). MS: m/z, 374 (M+). Anal. calcd. for C17H18N4O4S:C,
54.53; H, 4.85; N, 14.96. Found: C, 54.42; H, 4.93; N, 14.88.
1
1c: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.35 (s, 1H,
NH), 10.23 (s, 1H, NH), 10.05 (s, 1H, NH), 9.61 (s, 1H, NH), 6.91–7.87
(m, 8H, Ar-H), 2.40 (s, 6H, CH3). IR: (KBr, ν, cm−1): 3199 (N-H), 1681
(C O), 1253 (C S). MS: m/z, 342 (M+). Anal. calcd. for C17H18N4O2S:C,
59.63; H, 5.30; N, 16.36. Found: C, 59.52; H, 5.25; N, 16.47.
1
1d: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.33 (s, 1H,
NH), 10.22 (s, 1H, NH), 10.03 (s, 1H, NH), 9.58 (s, 1H, NH), 6.90–7.88
(m, 8H, Ar-H), 2.39 (s, 6H, CH3). IR: (KBr, ν, cm−1): 3194 (N-H), 1680
(C O), 1252 (C S). MS: m/z, 342 (M+). Anal. calcd. for C17H18N4O2S:C,
59.63; H, 5.30; N, 16.36. Found: C, 59.71; H, 5.37; N, 16.41.
1
1e: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.63 (s, 1H,
NH), 10.51 (s, 1H, NH), 10.26 (s, 1H, NH), δ 9.82 (s, 1H, NH), 7.51–8.01

1,5-Diacyl Thiocarbohydrazides
83
(m, 8H, Ar-H). IR: (KBr, ν, cm−1): 3215 (N-H), 1688 (C O), 1255 (C S).
MS: m/z, 382 (M+). Anal. calcd. for C15H12Cl2N4O2S:C, 47.01; H, 3.16;
N, 14.62. Found: C, 46.91; H, 3.22; N, 14.70.
1
1f: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.64 (s, 1H,
NH), 10.50 (s, 1H, NH), 10.28 (s, 1H, NH), δ 9.83 (s, 1H, NH), 7.53–8.00
(m, 8H, Ar-H). IR: (KBr, ν, cm−1): 3216 (N-H), 1688 (C O), 1256 (C S).
MS: m/z, 382 (M+). Anal. calcd. for C15H12Cl2N4O2S:C, 47.01; H, 3.16;
N, 14.62. Found: C, 47.12; H, 3.08; N, 14.56.
1
1g: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.69 (s, 1H,
NH), 10.56 (s, 1H, NH), 10.31 (s, 1H, NH), δ 9.86 (s, 1H, NH), 7.58–8.08
(m, 8H, Ar-H). IR: (KBr, ν, cm−1): 3217 (N-H), 1689 (C O), 1258 (C S).
MS: m/z, 470 (M+). Anal. calcd. for C15H12Br2N4O2S:C, 38.16; H, 2.56;
N, 11.87. Found: C, 38.07; H, 2.66; N, 11.96.
1
1h: White crystal. H NMR: (DMSO-d6, 400 MHz): δ 10.58 (s, 1H,
NH), 10.47 (s, 1H, NH), 10.23 (s, 1H, NH), 9.74 (s, 1H, NH), 7.46–7.95
(m, 6H, Fu-H). IR: (KBr, ν, cm−1): 3204 (N-H), 1679 (C O), 1250 (C S).
MS: m/z, 294 (M+). Anal. calcd. for C11H10N4O4S:C, 44.89; H, 3.43; N,
19.04. Found: C, 44.94; H, 3.51; N, 19.14.
General Procedure for the Preparation of Compounds 2a–h
Compounds 1a–h (0.5 mmol) and HIO4.2H2O (0.5 mmol) were added
to an agate mortar (6 cm in diameter). Then the mixture was ground
with a pestle at r.t. for the appropriate time indicated in Table I. The
completion of the reaction was monitored by TLC using petroleum
ether, acetone, and chloroform (2:3:3) as an eluent. The resulting solid
was washed with H2O (3X5 mL) and recrystallized from EtOH-DMF-
H2O (6:3:1) to give the product. The analytic data for compounds 2a–h
follows:
2a: White crystal. 1H NMR (DMSO-d6): δ 10.17 (s, 2H, NH), 8.34 (bs,
2H, NH), 7.36–7.75 (m, 9H, Ar-H). IR (KBr, ν, cm−1): 3272 (N-H), 1668
(C O). MS: m/z, 298 (M+). Anal. calcd. for C15H14N4O3: C, 60.40; H,
4.73; N, 18.78. Found: C, 60.29; H, 4.88; N, 18.84.
1
2b: White crystal. H NMR (DMSO-d6): δ 10.19 (s, 2H, NH), 8.36
(bs, 2H, NH), 7.38–7.77 (m, 8H, Ar-H), 3.85 (s, 6H, CH3). IR (KBr, ν,
cm−1): 3212 (N-H), 1664 (C O). MS: m/z, 358 (M+). Anal. calcd. for
C17H18N4O5: C, 56.96; H, 5.10; N, 15.63. Found: C, 57.03; H, 5.02; N,
15.51.
1
2c: White crystal. H NMR (DMSO-d6): δ 10.16 (s, 2H, NH), 8.33
(bs, 2H, NH), 7.34–7.74 (m, 8H, Ar-H), 2.35 (s, 6H, CH3). IR (KBr,
ν, cm−1): 3196 (N-H), 1662 (C O). MS: m/z, 326 (M+). Anal. calcd. for
C17H18N4O3: C, 62.54; H, 5.60; N, 17.16. Found: C, 62.66; H, 5.68; N,
17.21.

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Z. Li et al.
1
2d: White crystal. H NMR (DMSO-d6): δ 10.15 (s, 2H, NH), 8.32
(bs, 2H, NH), 7.34–7.73 (m, 8H, Ar-H), 2.34 (s, 6H, CH3). IR (KBr, ν,
cm−1): 3271 (N-H), 1661 (C O). MS: m/z, 326 (M+). Anal. calcd. for
C17H18N4O3: C, 62.54; H, 5.60; N, 17.16. Found: C, 62.47; H, 5.51; N,
17.09.
2e: White crystal. 1H NMR (DMSO-d6): δ 10.20 (s, 2H, NH), 8.37 (bs,
2H, NH), 7.35–7.80 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3264 (N-H), 1668
(C O). MS: m/z, 366 (M+). Anal. calcd. for C15H12Cl2N4O3: C, 49.07; H,
3.29; N, 15.26. Found: C, 49.14; H, 3.35; N, 15.19.
2f: White crystal. 1H NMR (DMSO-d6): δ 10.21 (s, 2H, NH), 8.38 (bs,
2H, NH), 7.37–7.83 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3264 (N-H), 1668
(C O). MS: m/z, 366 (M+). Anal. calcd. for C15H12Cl2N4O3: C, 49.07; H,
3.29; N, 15.26. Found: C, 48.99; H, 3.21; N, 15.32.
2g: White crystal. 1H NMR (DMSO-d6): δ 10.22 (s, 2H, NH), 8.39 (bs,
2H, NH), 7.36–7.81 (m, 8H, Ar-H). IR (KBr, ν, cm−1): 3265 (N-H), 1670
(C O). MS: m/z, 454 (M+). Anal. calcd. for C15H12Br2N4O3: C, 39.50; H,
2.65; N, 12.28. Found: C, 39.61; H, 2.70; N, 12.30.
2h: White crystal. 1H NMR (DMSO-d6): δ 10.10 (s, 2H, NH), 8.53 (bs,
2H, NH), 6.65–7.88 (m, 6H, Fu-H). IR (KBr, ν, cm−1): 3263 (N-H), 1669
(C O). MS: m/z, 278 (M+). Anal. calcd. for C11H10N4O5: C, 47.49; H,
3.62; N, 20.14. Found: C, 47.56; H, 3.54; N, 20.20.
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