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Synthesis and Characterization of Cu(II) and Pb(II)
Complexes of Trimethoxycarbonyl Thiourea Ligands
Jacquelyn Ak Taring (26485)
Bachelor of Science with Honours
(Resource Chemistry)
2013
Faculty of Resource Science and Technology
Synthesis and Characterization of Cu(II) and Pb(II) Complexes of
Trimethoxycarbonyl Thiourea Ligands
Jacquelyn Ak Taring (26485)
A final project report submitted in the fulfillment of the requirements for the degree of
Bachelor of Science with Honors
(Resource Chemistry)
Supervisor: Mdm Maya Asyikin
Co-Supervisor: Associate Professor Dr. Zainab Ngaini
Resource Chemistry
Department of Chemistry
Faculty of Resource Science and Technology
Universiti Malaysia Sarawak
2013
Declaration
I hereby declare this thesis submitted is my original research work in support of an
application for other degree of qualification or any university or private institution of
higher level. This thesis has not used sources without declaration in the text and any
quotation were inferred from literature review are clearly marked as such.
………………………………….
(Jacquelyn Ak Taring)
Resource Chemistry Programme
Department of Chemistry
Faculty science and Resource Technology
Universiti Malaysia Sarawak
I
Acknowledgement
I would like to take this opportunity to express my gratitude and appreciation to all those who
gave me the possibility to complete this report. A special thanks to my supervisor, Mdm.
Maya for her stimulating ideas, monitoring and constant encouragement throughout the
course of this Final Year Project (FYP).
Furthermore, I would like to express my special gratitude and thanks to our Assoc. Prof. Dr
Zainab Ngaini because of her talk on “Planning an effective and stimulating research
presentation” and workshop on ISISDRAW. Through this talk and workshop, it helps me to
plan my research presentation and learn to use ISISDRAW software in right way.
I would also like to acknowledge with much appreciation the crucial role of Mr. Wahab and
Mdm Nurhayati whose helps me to handle FTIR, UV and NMR spectroscopy. Furthermore, I
would like to thanks to all laboratory assistant, for their help to provide apparatus. I also
would like to express my gratitude to all master students, without them it is difficult for me to
conduct laboratory work and for the knowledge that they have shared with me during this
course.
Last but not least, thank almighty, my parents, brother, sisters and friends for their constant
encouragement and they are always willingly helped me out with their abilities.
II
Table of Content
Acknowledgement
I
Table of Content
II-III
List of Abbreviation
IV
List of Schemes, Figures & Tables
V-VII
Abstract
1
1.0 Introduction and Objectives
2-4
2.0 Literature Review
Research on thiourea compound
Research on thiourea metal complexes
Application of Thiourea Derivatives and Their Metal Complexes
5-8
8-11
11-12
3.0 Materials and Synthesis
Materials
13
Synthesis of 2-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid
(1) and 3-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid (2)
13-14
Synthesis of Cu(II) and Pb(II) Complexes of ligand (1)
15-16
Synthesis of Cu(II) and Pb(II) Complexes of ligand (2)
17-18
Characterization the complex compound
19
4.0 Results and discussions
Synthesis of Ligands (1) and (2)
Reaction of 3,4,5-trimethoxybenzoyl isothiocyanate with alpha-
alanine and beta-alanine
20
Percentage yield and melting point
20-21
FTIR Spectroscopy Analysis
21-23
NMR Spectroscopic Analysis
24-31
III
UV/Visible Spectroscopic Analysis
32-33
Synthesis of Transition Metal Complexes (3-6)
Reactions of Ligands (1) and (2) with Copper(II) and Lead(II)
Metals
34
Percentage yield and melting point
34-35
FTIR Spectroscopy Analysis
36-40
UV/Visible Spectroscopic Analysis
41-44
5.0 Conclusion
45
6.0 References
46-47
IV
List of Abbreviations
FTIR Fourier Transform Infrared
NMR Nuclear Magnetic Resonance
UV/Visible Ultra-Violet/Visible
KSCN Potassium thiocyanate
DMSO Dimethylsulfoxide
DCM Dichloromethane
MIC Minimum Inhibitory Concentration
Cu(II) Copper(I)
Pb(II) Lead(II)
Cu(CH3COO)2.H2O Copper(II) acetate hydrate
Pb(CH3COO)2.3H2O Lead(II) acetate 3-hydrate
KOH Ethanol
V
List of Scheme
Title Page
Scheme 1: General reaction of synthesis benzoylthiourea ligand. 5
Scheme 2: Synthetic route of 1-(3-fluorophenyl)-3-(3,4,5-trimethoxybenzoyl)thiourea 6
Scheme 3: Synthesis of metal complexes 10
Scheme 4: Synthesis route of thiourea ligand (1) and (2) 14
Scheme 5: Synthesis of complexes (3) and (4) 16
Scheme 6: Synthesis of complexes (5) and (6) 18
VI
List of Tables
Table Page
Table 1: Percentage yield and melting points for Ligands (1) and (2) 21
Table 2: FTIR Stretching Vibration Values for Ligands (1) and (2) 22
Table 3: 1H NMR Chemical Shifts Values for Ligands (1) and (2) 25
Table 4: 13
C NMR Chemical Shifts Values for Ligands (1) and (2) 29
Table 5: The UV/Visible Maximum Absorption Values for Ligands (1) and (2) 32
Table 6: Percentage Yield and Melting Point Complexes (3-6) 35
Table 7: FTIR Stretching Vibration Values for Complexes (3-6) 37
Table 8: The UV/Visible Maximum Absorption Values for complexes (3-6) 42
VII
List Figures
Figure Page
Figure 1: Structure of N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea (1), 1,2-
Bis[N’-(2- methoxybenzoyl)thioureido]-4-nitrobenzene (2) and 1,2-Bis[N’-(2-
methoxybenzoyl)thioureido]-4- chlorobenzene (3)
7
Figure 2: Structure of 3-mercapto-N-(2-methylbenzoyl) thioureido)-N’-propanoic acid
(4), 3-mercapto-N-(3- methylbenzoyl)thioureido)-N’-propanoic acid (5) and 3-
mercapto-N-(4-methylbenzoyl)thioureido)-N’- propanoic acid (6)
8
Figure 3: Binding modes for thioureido functional groups towards transition group
metals (M)
9
Figure 4: Structure of Ni(etv)2 (7), Cu(mtv)2.H2O (8) and Pt(Hmtv)Cl2 (9) 11
Figure 5: The FTIR spectrum for Ligand (1) 23
Figure 6: The FTIR spectrum for Ligand (2) 23
Figure 7: The 1H NMR Spectrum for Ligand (1) 26
Figure 8: The 1H NMR Spectrum for Ligand (2) 27
Figure 9: The 13C NMR Spectrum for Ligand (1) 30
Figure 10: The 13C NMR Spectrum for Ligand (2) 31
Figure 11: The UV/Visible absorption spectrum of Ligand (1) 33
Figure 12: The UV/Visible absorption spectrum of Ligand (2) 33
Figure 13: The FTIR spectrum for Complex (3) 38
Figure 14: The UV/Visible absorption spectrum of Complex (4) 38
Figure 15: The UV/Visible absorption spectrum of Complex (5) 39
Figure 16: The UV/Visible absorption spectrum of Complex (6) 39
Figure 17: The structure of the complexes (3-6) 40
1
Synthesis and characterization of Cu(II) and Pb(II) Complexes of Trimethoxycarbonyl Thiourea
Ligands
Jacquelyn Ak Taring
Resource Chemistry Programme
Faculty of Resource Science and Technology
Universiti Malaysia Sarawak
ABSTRACT
The thiourea derivatives of 2-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid and
3-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid and their Cu(II) and Pb(II)
complexes have been successfully synthesized. The structures of the ligands were
determined using FTIR, UV, 1H NMR and
13C NMR spectroscopy. The FTIR spectra
showed significant stretching vibration of the ligands and complexes that supported the
structure. The n → π* transition were shown for ligands and π → π* transition were
observed for complexes. The structures for complexes were square planar and the ligands
were coordinated to the metal through the carboxylate group and amide.
Keywords: thiourea derivatives, metal complexes, synthesized.
ABSTRAK
Terbitan asid tiourea 2-(3-(3,4,5-trimetoksibenzoil)tioureido propanoik dan 3-(3-(3,4,5-
trimetoksibenzoil)tioureido propanoik dan kompleks Cu(II) dan Pb(II) telah berjaya
disintesis. Struktur bagi ligan telah ditentukan dengan menggunakan spektroskopi Fourier
Transformasi Infra-Merah (FTIR) dan Ultralembayung (UV) dan Resonans Magnetik
Nuclear (RMN). Spectrum FTIR menunjukkan regangan penting dalam ligan dan kompleks
yang menyokong struktur. Peralihan n → π* dan π → π* telah ditunjukkan oleh ligan dan
kompleks logam. Struktur bagi kompleks adalah planar persegi dan ligan terkoordinat
kepada logam melalui kumpulan kaboksilat dan (C=Oamida).
Kata kunci: terbitan tiourea, kompleks logam, sintesis.
2
1.0 Introduction
Thiourea is also known as 2-thiourea, thiocarbamide and sulfourea with molecular formula
CS(NH2)2 (Skylakakis, 2003). Thiourea is very important for the structural modifications to
synthesize new derivatives because it is basically occurs in two tautomeric forms and has
three functional groups (Ibrahim et al., 2009).
Thiourea and its derivatives molecule are known to be the part of complexes as polydentate
ligands. This is because they contain several nucleophilic electron-donor centers, their
geometry of arrangement and the electronic configuration of complex metal can be used to
determine the possibility of yielding various structure complexes (Orysyk et al., 2011).
According to Mohamad Halim et al. (2011), thiourea derivatives have various biological
properties such as antibacterial, anticancer, antimicrobial, antifungal, antimalarial and
antituberculosis that make them widely used in many field especially pharmaceutical
industries. This is because oxygen, nitrogen and sulfur donor atoms in thiourea derivatives
provide a various binding possibilities (Arslan et al., 2009). Besides that, the protonation
of sulphur atom that can occur in acidic solution causes thiourea derivatives to be known
as interesting organic inhibitors in corrosion activity (Mohamad Halim et al., 2011).
The hybrid nitrogen/soft sulphur donor atom in the thiourea structure set generating a
magnitude of possibilities for coordination both hard and soft metal centres and therefore
the thioureas are very versatile (Henderson et al., 1996). Thioureas so far are being the
most extensively observed binding mode, thus they are able to coordinate as neutral
ligands, monoanions or as dianions (Henderson et al., 1996). According to Ibrahim et al.
3
(2009), there are numbers of heterocyclic compounds containing nitrogen and sulphur
showed a wide variety of biological activity that already been explored.
Thiourea derivatives yield a variety of complexes of different symmetries with various
metal ions. Metal such as Fe, Co, Cu, Ni, Zn, Cd and Pb function as essential elements for
biological system. In addition, these metal ions also play an important part in bioinorganic
chemistry. In order to understand the function of these metal ions in biological system, the
structure of biological compounds and their metal complexes are important to be studied
(Al-Assadi, 2011).
Compounds that contain carbonyl and thio carbonyl group play an important role as a
potential donor ligand for transition metal ions. Thus, this type of thiourea derivatives will
be a very versatile ligand which able to coordinate to range of metal centres. Besides that,
they also readily form supramolecular structures via hydrogen bonds (Al-Assadi, 2011).
In this project, we reported the synthesis and characterization of thiourea compound
namely 2-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid and 3-(3-(3,4,5-
trimethoxybenzoyl)thioureido)propanoic acid and their metallic complexes with Cu(II) and
Pb(II). The complexes structures of the synthesised compounds were confirmed using
melting point, FTIR, UV/Visible and 1H and
13C NMR spectroscopy.
4
1.1 Objectives
The objectives of this project are:
1. To synthesis trimethoxycarbonyl thiourea ligands and their Copper (II) and Lead
(II) complexes.
2. To characterise the synthesised compounds using various chemical instrumentation
techniques such as FTIR, UV-visible and 1H and
13C NMR spectroscopy.
5
2.0 Literature Review
2.1 Research on thiourea compound
There are many researchers that synthesize thiourea compounds through various
modification methods to yield their desired compounds. However, the common procedure
to synthesize benzoylthiourea ligands is by reaction of benzoyl chloride with amine group
using dry acetone as a solvent (Arslan & Külcui, 2003; Mohamad Halim et al., 2011;
Saeed et al., 2009). The general reaction involves is shown in Scheme 1. Benzoyl chloride
are reacted with potassium thiocyanate to give intermediate that is subsequently reacted
with different type of amines.
Intermediate
Scheme 1: General reaction of synthesis benzoylthiourea ligand.
6
However, in the synthetic route of 1-(3-fluorophenyl)-3-(3,4,5-trimethoxybenzoyl)thiourea
as shown in Scheme 2 by Saeed et al., (2011) dry acetonitrile has been used as a solvent.
The reaction was also conducted with an equimolar quantity of 3-fluoroaniline in dry
acetonitrile to obtain the title thiourea in a greater yield.
In previous study by Mohamad Halim et al. (2011), benzoyl isothiocyanate was used an
intermediate to yield N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea (1),
1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-nitrobenzene (2) and 1,2-Bis[N’-(2-
methoxybenzoyl)thioureido]-4-chlorobenzene (3) as shown in Figure 1.
Scheme 2: Synthetic route of 1-(3-fluorophenyl)-3-(3,4,5-trimethoxybenzoyl)thiourea (Saeed et
al., 2011)
7
Benzoylisothiocyanate were prepared by stirring the solution mixtures of benzoyl chloride
and ammonium thiocyanate in acetone solution at 50°C for 20 minutes (Mohamad Halim
et al., 2011). On the other hand, Roslan et al. (2009), reported that the intermediate of N-
methylbenzoyl isothiocyanate were prepared by refluxing the mixture of N-methylbenzoyl
chloride and ammonium thiocyanate for 1 hour. The intermediate then reacted with
cysteine to yield three novel compounds of N-methylbenzoyl thiourea derivatives, namely
3-mercapto-N-(2-methylbenzoyl) thioureido)-N’-propanoic acid (4), 3-mercapto-N-(3-
methylbenzoyl)thioureido)-N’-propanoic acid (5) and 3-mercapto-N-(4-
methylbenzoyl)thioureido)-N’-propanoic acid (6) (Figure 2).
O
HN
HN
O S
NH
O
O
HNNH
NH
NH
O
O2N
S
OS
O
O
HNNH
NH
NH
O
Cl
S
OS
Figure 1: Structure of N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea (1), 1,2-Bis[N’-(2-
methoxybenzoyl)thioureido]-4-nitrobenzene (2) and 1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-
chlorobenzene (3) (Mohamad Halim et al., 2011)
(1) (2)
(3)
8
Most of the researchers reported different solvent used to recrystallized thiourea
derivatives. Ethanol is a well-known solvent that had been used by many researchers to
recrystallize thiourea compounds (Kabbani et al., 2005; Roslan et al., 2009; Mohamad
Halim et al., 2011). According to Arslan and Külcü (2003), a mixture of ethanol/DCM
solvent was used for the recrystallization of thiourea compounds in their study.
2.2 Research on thiourea metal complexes
According to Adam (2000), classical coordination and organometallic chemistry are the
two broad areas that involve transition elements can be occurred in the synthesis of metal
complexes. Classical coordination is when metals are in their higher oxidation states which
greater than positive two bonded to organic, inorganic ions or molecules, while
organometallic compounds are formed when metals directly bonded to the carbon bond
producing low formal oxidation states (Adam, 2000).
NH
N OH
OSH
O
S NH
N OH
OSH
O
S NH
N OH
OSH
O
S
(4) (5) (6)
Figure 2: Structure of 3-mercapto-N-(2-methylbenzoyl) thioureido)-N’-propanoic acid (4), 3-mercapto-N-(3-
methylbenzoyl)thioureido)-N’-propanoic acid (5) and 3-mercapto-N-(4-methylbenzoyl)thioureido)-N’-
propanoic acid (6) (Roslan et al., 2009)
9
There are four common types of binding modes that has been observed for thioureido
functional groups towards transition group metals as shown in Figure 3 where most of the
metals are bonded through sulphur atom (Lenthall, 2007).
Ethanol is the common solvent used to synthesize thiourea metal complexes (Criado et al.,
1997; Arslan et al., 2009; Jadhao & Rathord, 2012). But there are other researchers that
used methanol as a solvent to synthesize thiourea metal complexes (Téllez et al., 2004;
Campo et al., 2004). According to Jadhao and Rathord (2012), H2O2 also can be used to
recrystallize heavy metal ion complexes. In their study, Arslan et al., (2009) used 1:2 ratio
of metal with a small excess of thiourea ligand to yield thiourea metal complexes as shown
in Scheme 3.
NH
NH
S
M
NH
NH
S
MM
NH
N
S M
N N
S M
(b) (a) (c) (d)
Figure 3: Binding modes for thioureido functional groups towards transition group metals
(M) (Lenthall, 2007).
10
The structure of the ligands can determine the reactivity and toxicity of metal complexes
(Beyer et al., 1996; Criado et al., 1997). Criado et al., (1997) introduce thiourea
derivatives of L-valine methylester (Hetv and Hmtv) to Cu(II), Ni(II) and Pt(II) producing
metallic complexes (Figure 4). The presences of an ester group in these thiourea ligands
allow the modification of the chelating capacity of metallic cations as well as the
hydrophobic or hydrophilic character of the ligands and their complexes.
Cl
O
KSCN NCS
O
NH
O
NR2
S
O
S
R2N
Cu
S
O
NR2
HNR2
Cu+2
HNR2 : HN(C2H5)2
HN(C3H7)2
HN(C4H9)2
HN(C6H5)2
HN(C4H8)2
Scheme 3: Synthesis of metal complexes (Arslan et al., 2009)
11
2.3 Application of Thiourea Derivatives and Their Metal Complexes.
Thiourea ligands show remarkable of biological properties such as anticancer,
antimicrobial, antibacterial, antifungal, antimalarial and antituberculosis (Mohamad Halim
et al., 2011). According to Arslan et al. (2009), thiourea metal complexes also display
variety of bioactivities. There are quite a number of heterocyclic compounds containing
nitrogen and sulphur were found to show a wide variety of biological activity (Ibrahim et
al., 2009).
Some acyl thioureas are found as a superior pesticidal, fungicidal and antiviral while for 1-
acyl-3-(2’- aminophenyl) thioureas, it shown as anti-Intestinal Nematode Prodrug (Saeed
et al., 2011). Apart from that, according to Beyer et al. (1996), N-benzoyI-N'-
alkylthioureides has become an interesting ligand that can be studied in several research
because they are categorized as selective ligands that are very useful in the separation of
metal cations of Pt group.
COOCH3
N
N
S
C6H5
(Et)2N H3COOC
N
CH(CH3)2
N
S
C6H5
N(Et)2
Ni
(H3C)2H2C
O
N N
S N COOCH3
CH(CH3)2
O
NN
SNH3COOC
(H3C)2HC Cu
H2O
H2ONH3
O
N N
S NH COOCH3
CH(CH3)2Pt
Cl Cl
(7) (8) (9)
Figure 4: Structure of Ni(etv)2 (7), Cu(mtv)2.H2O (8) and Pt(Hmtv)Cl2 (9) (Criado et al., 1997)
12
Most of the researchers reported that thiourea compounds with metal such as copper can
enhance antibacterial activities (Mohamad Halim et al., 2011). From the previous study
that has been carried out by Saeed et al. (2010), nickel and copper metal complexes of N-
(R-carbamothioyl)-4-nitrobenzamide (R= diphenyl and ethylbutyl) were screened for their
in vitro antibacterial activities and it was found that the complexes showed greater
antibacterial efficacy than thiourea ligands. The metal complexes compound with MIC
value ranging between 30-200μg/cm3 indicates that they inhibited the growth of the
bacterial.
According to Parmar et al. (2010), the chelation tends to cause ligand to act more as a mere
powerful and potent bactericidal agent. This is because the metal chelates increase the
lipophilic character that favors its permeation through the lipid layer of the bacterial
membrane. There are six novel amino acid-thiourea derivatives that have been synthesized
for the anti-amoebic activity investigation (Ibrahim et al., 2011). In this study, the result
shows that they have potent anti-amoebic activities. From six novel of amino acid-thiourea
derivatives, there were two compounds which are 2-(3-benzoylthioureido)-3-
mercaptopropanoic acid and 2-(3-benzoylthioureido)-4-(methylthio)butanoic acid are
found to have higher activity compared to the rest.
13
3.0 Materials and Synthesis
3.1 Materials
3,4,5-trimethoxybenzoyl chloride, alpha-alanine, beta-alanine, distilled acetone, KSCN,
KOH pellet, distilled ethanol, distilled water, DCM, Cu(CH3COO)2.H2O powder and
Pb(CH3COO)2.3H2O powder.
3.2 Synthesis
3.2.1 Synthesis of 2-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid (1) and
3-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid (2)
Ligand (1) was prepared by dissolving 3mmole (0.69g) trimethoxycarbonyl in 15ml
distilled acetone and 3mmole (0.291g) KSCN in 15ml distilled acetone was added
dropwise to the suspension. Then, the reaction mixture was stirred at room temperature for
1 hour. KCl that was formed was filtered and removed. A solution of 3mmole (0.267g) of
alpha-alanine in 15ml distilled acetone was added to the filtrate solution. The mixture was
refluxed for 24 hours at temperature ranged from 60-75ºC. After the mixtures had been
refluxed, the solution was filtered and the filtrate was left to evaporate at room temperature
for four days. The precipitate formed was recrystallized from ethanol/dichloromethane (1:1
ratio) to give out pure compound (1). The same procedure was repeated for ligand (2), but
the amine that was used is 3mmole (0.69) of beta-alanine. Ligand (2) was recrystallized
using distilled ethanol to obtained pure compound (2). The synthesis route of ligands (1)
and (2) is shown in Scheme 4.
14
O
ClO
O
O
3,4,5-trimethoxybenzoyl chloride
+ KSCNO
NCSO
O
O
3,4,5-trimethoxybenzoyl isothiocyanate
H2N
O
OH
alpha-alanine, reflux 24hours
NH2 O
OH
beta-alanine, reflux 24 hours
stirr, 1 hour
O
HNO
O
O
HN
SO
OH
2-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid (1)
O
HNO
O
O
HN
S
O
OH
3-(3-(3,4,5-trimethoxybenzoyl)thioureido)propanoic acid (2)
Scheme 4: Synthesis route of thiourea ligand (1) and (2)
