Synthesis and characterization of N-benzoyl-N′-carboxyalkyl substituted thiourea derivatives

Article abstract of DOI:10.1080/10426500307952

N-Benzoyl-N′-carboxyl substituted thiourea derivatives (I-X) have been synthesized by the reaction of benzoyl isothiocyanate with amino acids. Their structures are confirmed by IR, ¹HNMR, and elemental analysis. The reaction conditions are expe

Full text of DOI:10.1080/10426500307952

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Phosphorus, Sulfur, and Silicon and the Related
Elements
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Synthesis and Characterization of N-benzoyl-N′-
carboxyalkyl Substituted Thiourea Derivatives
Zhonghua Li a , Yan Zhang a & Yangang Wang a
a Central China Normal University , Wuhan, China
Published online: 27 Oct 2010.
To cite this article: Zhonghua Li , Yan Zhang & Yangang Wang (2003) Synthesis and Characterization of N-benzoyl-N′-
carboxyalkyl Substituted Thiourea Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:2, 293-297, DOI:
10.1080/10426500307952
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:293–297
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DOI: 10.1080/10426500390170534
SYNTHESIS AND CHARACTERIZATION
OF N-BENZOYL-N0-CARBOXYALKYL SUBSTITUTED
THIOUREA DERIVATIVES
Zhonghua Li, Yan Zhang, and Yangang Wang
Central China Normal University, Wuhan, China
(Received April 26, 2002; accepted June 3, 2002)
N-Benzoyl-N0-carboxyl substituted thiourea derivatives (I-X) have been
synthesized by the reaction of benzoyl isothiocyanate with amino acids.
Their structures are confirmed by IR, 1HNMR, and elemental analy-
sis. The reaction conditions are experimentally investigated, and the
preliminary biological tests show that some of the compounds have ex-
cellent plant growth promotion activities.
Keywords: Amino acid; N-benzoyl-N0-carboxyl substituted thiourea;
synthesis
Acyl substituted thiourea derivatives are not only important inter-
mediates in organic synthesis, but they also possess various biolog-
ical activities. It has been reported that phenylureas and thioureas
form the basis of many molecules possessing biological activity, some of
them are successfully used as insecticides,1 bactericides,2 and plant
growth regulators.3 In order to search for new compounds with ex-
cellent plant growth regulation, ten N-benzoyl-N0-carboxyl substi-
tuted thioureas derivatives (I-X) were synthesized by the reaction
Project 20072009 supported by NSFC.
Address correspondence to Z. Li, Department of Chemistry, Central China Normal
University, Wuhan, 430079, China. E-mail: zhongli@ccnu.edu.cn
293

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Z. Li et al.
of benzoyl isothiocyanate with amino acids. Their structures are con-
1
firmed by HNMR, IR, MS, and elemental analyses. The preliminary
biological tests show that the compounds have excellent plant growth
promotion activities for plant root and stalk growing.
RESULT AND DISCUSSIONS
Acylthiourea derivatives usually are synthesized from the appropri-
ate substituted anilines and acyl isothiocyanates, the reaction being
executed easily because aniline plays a role as both a nucleophile and
a base catalyst.4 The reaction with amino acids as nucleophiles, how-
ever, might seem hard to conduct. The reason might be due mainly to
characteristics of amino acids. Since amino acids are amphoteric com-
pounds, in solution a dipolar ion (+NH3CH(R)-COO ) is formed by a
proton transformation from the carboxyl group to the nitrogen atom of
amino group.5 It is the amphoteric nature of amino acids that largely
reduces the electron density on nitrogen. Thus the zwitterions amino
acids possess lower nucleophility than amines and are difficult to react
with acyl isothiocyanates. In order to facilitate the reaction, adding an
organic base such as pyridine might enhance the reaction rate.
Because addition and substitution always happened simultaneou-
sly in the reaction course, besides the expected addition products,
N-benzoyl-N0-carboxyl substituted thioureas and some substituted ben-
zoyl amide derivatives usually occurred.6 The competed reactions could
be indicated as the following.
It was found that the undesired by-product could be reduced to a cer-
tain extent if the reaction was carried out in anhydrous non-protonic
solvent such as acetone or acetonitrile. The amino acids did not im-
mediately dissolve in the solvent, but they did dissolve in acyl isothio-
cyanates. Thus a little excessive acyl isothiocyanate is needed actually.
In their IR spectra, N-benzoyl-N0-carboxyl-substituted thiourea
derivatives displayed a broad peak for N H and O H absorption be-
tween 3000–3300 cm 1. The frequencies of the two bonds were close
and overlapped with each other. The C O group (benzoyl) occurred at
1
1650 cm which was lower than the usual carbonyl group, owning to

N-Benzoyl-N 0-Carboxyalkyl Substituted Thiourea
295
the conjugation of it with benzene ring and the hydrogen bond formation
of it with NH,7 Another C O group (carboxyl) was at 1715 cm 1. It was
similar to that of the normal carboxylic acids. With a small force con-
1
stant, the C S bond appeared at 1250 cm with moderate intensity.
The 1HNMR characteristic of N-benzoyl-N0-carboxyl substituted
thiourea derivatives was the two imine protons labeled a and b. Proton
a was affected by the deshielding effect of C O and C S groups, and the
chemical shift was 5.5–7.0 ppm, which was downfield compared to that
of normal amides. Proton b was around 10 ppm. This was quite down-
field and a little affected by the R groups, because of the intramolecular
hydrogen bond interaction. A weak signal at 11.0 ppm for the proton
of the O H group appeared. It disappeared immediately when treated
with D2O.
The preliminary plant growth promotion activities of the title
compounds for the root and stalk growth of monocotyledon and
dicotyledonous plant were tested, the results showed that some of the
compounds have excellent growth promoting propensities. At the con-
centration of 10 ppm, for example, the promotive percentage of com-
pound I, V, VI, and VII for the root growth of rape was 39, 65, 48, and
51 respectively, Compounds I and V promoted the root growth of wheat
by 55% and 38%, and for barnyard grass 40% and 39%.
EXPERIMENTAL
All reagents were desiccated or redistilled. IR spectra were recorded on
1
a Perkin-Elmer Model 983 spectrophotometer (KBr pellets). HNMR
spectra were obtained using a Varian Associates XL-200 spectropho-
tometer using deuterated acetone as solvent and tetramethylsilane as
an internal standard (abbreviations used: b, broad; d, doublet; m, mul-
tiplet; s, singlet; t, triplet). MS were measured on a Hewlett Packard
5988 instrument. Elemental analyses were performed on a PE-2100
automatic meter. A X-4 numerical display meter determined melting
points, and the thermometer was uncorrected.
The general synthesis procedure of N-benzoyl-N0-carboxyalkyl-
substituted thioureas (I-X) is described as follows: A solution of 7.3 g
(75 mmol) of potassium isothiocyanate dissolved in 15 ml of anhydrous
acetone was treated slowly with 50 mmol of benzoyl chloride. The mix-
ture was stirred at 55–60 C for 1 h, and then 50 mmol of amino acid

296
Z. Li et al.
and a few drops of pyridine were added. The mixture was refluxed for
6 h. The solution was treated with cooled ice-water. When standing, a
precipitate appeared which was filtrated, washed with water, and re-
crystallized (ethanol) to provide the product.
N-Benzoyl-N0-carboxyl methylene thiourea (I): Yellow solid, m.p.
199–200 C, yield 73%. IR (cm 1): 3000–3300 (N H, O H), 1655, 1700
(C O), 1245 (C S): 1HNMR ( ppm): 5.86–6.75 (b, 1H, NH), 7.35–8.10
(m, 5H, ArH), 10.28 (s, 1H, NH), 11.10 (s, 1H, COOH): m/e: 238 (M+):
Anal. calcd. for C10H10N2O3S: C, 50.42; H, 4.20; N, 11.77: Found: C, 51.
10; H, 3.77; N, 12.01.
N-Benzoyl-N0-carboxyl ethylidene thiourea (II): Yellow solid, m.p.
187–189 C, yield 69%. IR (cm 1): 3100–3400 (N H, O H), 1670, 1720
(C O), 1265 (C S); 1HNMR ( ppm): 5.75–6.85 (b, 1H, NH), 7.53–8.25
(m, 5H, ArH), 10.25 (s, 1H, NH), 11.25 (s, 1H, COOH); Anal. calcd. for
C11H12N2O3S: C, 52.38; H, 4.76; N, 11.11; Found: C, 52.01: H, 4.93; N,
10.95.
N-Benzoyl-N0-carboxyl propylidene thiourea (III): White solid, m.p.
189–190 C, yield 63%. IR (cm 1): 3015–3200 (N H, O H), 1670, 1725
(C O), 1265 (C S); 1HNMR ( ppm): 5.70–6.80 (b, 1H, NH), 7.45–8.20
(m, 5H, ArH), 10.15 (s, 1H, NH), 11.15 (s, 1H, COOH): Anal. calcd. for
C12H14N2O3S: C, 54. 14; H, 5.26; N, 10.53; Found: C, 53.96: H, 5.02: N,
10.11.
N-Benzoyl-N0-carboxyl butylidene thiourea (IV): White solid, m.p.
185–186 C, yield 65%. IR (cm 1): 3025–3150 (N H, O H), 1675, 1725
(C O), 1260 (C S); 1HNMR ( ppm): 5.72–6.85 (b, 1H, NH), 7.40–8.25
(m, 5H, ArH), 10.30 (s, 1H, NH), 11.20 (s, 1H, COOH).
N-Benzoyl-N0-carboxyl isobutylidene thiourea (V): Yellow solid, m.p.
131–132 C, yield 58%. IR (cm 1): 3100–3250 (N H, O H), 1670, 1700
(C O), 1250 (C S); 1HNMR ( ppm): 5.90–6.80 (b, 1H, NH), 7.40–8.15
(m, 5H, ArH), 10.25 (s, 1H, NH), 10.15 (s, 1H, COOH): m/e: 294 (M+):
Anal. calcd. for C14H18N2O3S: C, 57.14; H, 6.12; N, 9.52; Found: C, 57.32;
H, 5.87; N, 9.13.
N-Benzoyl-N0-carboxyl isopentylidene thiourea (VI): Yellow solid,
m.p. 149–151 C, yield 53%. IR (cm 1): 3005–3200 (N H, O H), 1660,
1720 (C O), 1240 (C S); 1HNMR ( ppm): 5.86–6.90 (b, 1H, NH), 7.25–
8.20 (m, 5H, ArH), 10.20 (s, 1H, NH), 11.20 (s, 1H, COOH); Anal. calcd.
for C14H13N2O3S: C, 57.14: H, 6.12; N, 9.52; Found: C, 57.32; H, 5.87;
N, 9.13.
N-Benzoyl-N0-carboxyl methylthiopropylidene thiourea (VII): White
solid, m.p. 150–152 C, yield 48%. IR (cm 1): 3100–3250 (N H, O H),
1670, 1700 (C O), 1250 (C S); 1HNMR ( ppm): 5.90–6.80 (b, 1H, NH),
7.40–8.15 (m, 5H, ArH), 10.25 (s, 1H, NH), 10.15 (s, 1H, COOH).

N-Benzoyl-N 0-Carboxyalkyl Substituted Thiourea
297
N-Benzoyl-N0-carboxyl 2-hydrovyl propylidene thiourea (VIII):
White solid, m.p. 131–132 C, yield 58%. IR (cm 1): 3100–3250 (N H,
O H), 1670, 1700 (C O), 1250 (C S); 1HNMR ( ppm): 5.90–6.80 (b, 1H,
NH), 7.40–8.15 (m, 5H, ArH), 10.25 (s, 1H, NH), 10.15 (s, 1H, COOH).
N-Benzoyl-N0-carboxyl phenylmethylidene thiourea (IX): White
solid, m.p. 161–162 C, yield 60%. IR (cm 1): 3125–3250 (N H, O H),
1670, 1720 (C O), 1245 (C S); 1HNMR ( ppm): 5.85–6.75 (b, 1H, NH),
7.40–8.15 (m, 5H, ArH), 10.25 (s, 1H, NH), 10.15 (s, 1H, COOH).
N-Benzoyl-N0-carboxyl phenylethylidene thiourea (X): White solid,
m.p. 172–173 C, yield 58%. IR (cm 1): 3100–3250 (N H, O H), 1670,
1700 (C O), 1250 (C S); 1HNMR ( ppm): 5.90–6.80 (b, 1H, NH), 7.40–
8.15 (m, 5H, ArH). 10.25 (s, 1H, NH), 10.15 (s, 1H, COOH).
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