Solvent- and catalyst-free synthesis of new unsymmetrical multidentate thio-bis-aminophenol ligands by mannich condensation

Article abstract of DOI:10.1080/00397910802654823

A one-pot, three-component, Mannich condensation of electron-rich aromatic compounds such as 5-methyl-2-hydroxyphenyl sulfide, 2-aminopyrimidine, and various aromatic aldehydes were used to prepare a series of new unsymmetrical multidentate aminophenol li

Full text of DOI:10.1080/00397910802654823

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Solvent- and Catalyst-
Free Synthesis of New
Unsymmetrical Multidentate
Thio-bis-aminophenol Ligands
by Mannich Condensation
Abbas Shockravi a , Mahdieh Sadeghpour a b
Abolfazl Olyaei c
&
a Faculty of Chemistry, Tarbiat Moallem University,
Tehran, Iran
b Department of Chemistry, Islamic Azad University,
Takestan Branch, Qazvin, Iran
c Department of Chemistry, Payame Noor University,
Qazvin, Iran
Published online: 01 Jun 2009.
To cite this article: Abbas Shockravi , Mahdieh Sadeghpour & Abolfazl Olyaei (2009)
Solvent- and Catalyst-Free Synthesis of New Unsymmetrical Multidentate Thio-
bis-aminophenol Ligands by Mannich Condensation, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:13,
2347-2359, DOI: 10.1080/00397910802654823
To link to this article: http://dx.doi.org/10.1080/00397910802654823
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Synthetic Communications1, 39: 2347–2359, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654823
Solvent- and Catalyst-Free Synthesis of New
Unsymmetrical Multidentate Thio-bis-
aminophenol Ligands by Mannich Condensation
Abbas Shockravi,1 Mahdieh Sadeghpour,1,2 and Abolfazl Olyaei3
1Faculty of Chemistry, Tarbiat Moallem University, Tehran, Iran
2Department of Chemistry, Islamic Azad University,
Takestan Branch, Qazvin, Iran
3Department of Chemistry, Payame Noor University, Qazvin, Iran
Abstract: A one-pot, three-component, Mannich condensation of electron-rich
aromatic compounds such as 5-methyl-2-hydroxyphenyl sulfide, 2-aminopyrimi-
dine, and various aromatic aldehydes were used to prepare a series of new unsym-
metrical multidentate aminophenol ligands. These compounds were synthesized
in solvent-free conditions as a fast, simple, convenient, and uncatalyzed method.
Details of the reaction conditions are discussed.
Keywords: Aminophenol, Mannich, multidentate, solvent-free, unsymmetrical
INTRODUCTION
Multicomponent reactions (MCRs) have attracted considerable attention
because of their convergence, easy execution, mechanism, and multiple
bond formation. Such a reaction may be employed for building structu-
rally diverse molecules.[1] They also deliver fewer by-products then classi-
cal stepwise synthetic routes. This reduces time and saves raw materials.[2]
The Mannich reaction (aminoalkylation) is an example of multicompo-
nent condensation of a nonenolizable aldehyde, an amine (1ꢀ or 2ꢀ),
Received September 13, 2008.
Address correspondence to Abbas Shockravi, Faculty of Chemistry, Tarbiat
Moallem University, Mofatteh Ave., No. 49, Postal Code 15614, Tehran, Iran.
E-mail: Shockravi@tmu.ac.ir
2347

2348
A. Shockravi, M. Sadeghpour, and A. Olyaei
and an enolizable carbonyl compound.[3] Direct aminoalkylation has
great interest in synthetic organic chemistry and considerable importance
for the synthesis of drugs, pesticides, and natural products.[4]
Many methods of aminoalkylation of electron-rich aromatic
compounds have been studied to date. Katritzky and Risch reported
an improved aminoalkylation of 2-naphthol and phenol derivatives with
preformed iminium salts derived from aromatic aldehydes in a two-step
sequence with 26–92% yields.[5] In recent years, aminoalkylation of
electron-rich aromatic compounds in the presence of LiClO4, Sc(OTf)3,
Yb(OTf)3, La(OTf)3, YbCl3, TiCl4, and Me3SiCl has been reported.[6–8]
Also, a series of larger molecules such as diaminodinaphthols, diamino-
diphenols, and diaminotetraphenols have been prepared from ethylene-
diamine, various amounts of paraformaldehyde, and 2,4-disubstituted
phenols by controlling the stoichiometry and reaction conditions.
By using 2,4-disubstituted phenols and varying those substituents,
researchers modulate the electronic and steric properties of the alcohol
moieties, affecting both how many phenol groups can bind to a transi-
tion metal and how strongly those phenols will bind.[9–13] Moreover,
optically active aminophenol and aminonaphthol ligands have been
used as ligands complexed to dialkyl zinc for enantioselective
addition to aryl aldehydes. These ligands show highly efficient asym-
metric induction to give the corresponding alcohols up to 99% ee
yields.[14–16]
Wenowdescribethesynthesisofnewmultidentatethio-diaminodiphenol
derivatives via a facial three-component and one-pot method for
aminoalkylation of electron-rich aromatic compounds such as
5-methyl-2-hydroxyphenyl sulfide, using aromatic aldehydes and
2-aminopyrimidine in the absence of catalyst with short reaction time
and solvent-free conditions. As such, utilization of environmentally
friendly conditions (absence of organic solvent) provides the product
not only in an easy workup procedure but also in accord with green
sustainable chemistry principles.
RESULTS AND DISCUSSION
As part of a continuous effort to develop new N,O,S-ligand derivatives
relevant to the Mannich reaction, we report a fast, simple, and conveni-
ent method for the synthesis of new thio-diaminodiphenol with hetero-
aryl amine and aromatic aldehydes in solvent-free conditions in
moderate to good yields. The promising advantages, such as removal
of organic solvent, lack of catalyst, easy workup, and short reaction time,
are discussed. Our literature survey showed that thio-diaminodiphenol

Thio-bis-aminophenol Ligands
2349
has not previously been used for the synthesis of diaminodiphenol ligand
derivatives.
As the model reaction, we initially examined the one-pot, three-
component Mannich reaction of 5-methyl-2-hydroxyphenyl sulfide (1),[17]
2-aminopyrimidine, and benzaldehyde in CH3CN, EtOH, and MeOH in
the presence of formic acid as catalyst at room temperature. We found that
at least 24 h was needed for the reaction of 2-aminopyrimidine with benzal-
dehyde to afford the corresponding Schiff base. We then examined the same
reaction under reflux conditions in the same solvents, in which the desired
product was not observed and only the corresponding Schiff base was
formed. When this reaction was performed in solvent-free conditions at
70–100ꢀC in the absence of acid catalyst, the corresponding Schiff base
was obtained. Our investigation demonstrated that the best result was
obtained when temperature was fixed at 125ꢀC, at which the reaction com-
pleted in 10 min. Therefore, we decided to examine the other reactions in
solventless conditions at 125ꢀC in the absence of acid catalyst.
2-Aminopyrimidine was used in all Mannich condensations toward
the synthesis of series of multidentate aminophenol ligands (3a–i).
Thio-bis-aminophenols (3a–i) were prepared by combining 1 equivalent
of thio-bis-phenol 1 with 2 equivalents aromatic aldehydes (2a–i) and 2
equivalents of 2-aminopyrimidine in solventless conditions during
10–30 min at 125ꢀC (Scheme 1). Each compound was isolated by addition
of ethanol to a cooled reaction mixture and filtration of the resulting
precipitate in moderate to good yields.
To get insight into the reaction mechanism, we initially studied the
reaction of compound 1 with aldehyde. No reaction progress was
observed during several hours. Our studies confirmed that formation of
Schiff bases play an important rule in the Mannich codensation toward
the final products. When we isolated the Schiff bases and then allowed
their reactions with bis-phenol 1, we obtained the same products from
a one-pot reaction of these compounds (Scheme 2).
Scheme 1. Synthesis of thio-bis-aminophenols (3a–i) by solvent-free Mannich
reaction. Ar ¼ a: ph, b: 4-Me-ph, c: 4-MeO-ph, d: 4-Br-ph, e: 3-Br-ph, f:
4-Cl-3-NO2-ph, g: 4-NO2-ph, h: 3-NO2-ph, and i: 4-Cl-ph.

2350
A. Shockravi, M. Sadeghpour, and A. Olyaei
Scheme 2. Mechanism for the formation of compounds 3a–i.
The thio-bis-phenol 1 was already synthesized and characterized by
different means including x-ray spectroscopy.[17] The hydroxyl groups
have been used to synthesize different multidentate macrocycles[18,19]
and polymers[20] and studied for different applications in metal-ion
complexation.[21] These previous synthetic studies indicated that the
presence of a sulfur atom in the bis-phenol (1) not only plays an impor-
tant role in the complexation behavior but also in the physical properties
of polymers and dynamic behavior of macrocyclic compounds.
In the compound 5-methyl-2-hydroxyphenyl sulfide (1), hydroxyl
and sulfide groups can direct electrophilic substitutions on the para posi-
tion with respect to the sulfur and on the ortho position with respect to
1
the hydroxyl group. Based on the coupling constant (J) observed in H
NMR spectra, we can conclude that hydroxyl group dominates in elec-
tronic direction for electrophilic substitution. The coupling constant
was about 1.5 Hz for all final products (3a–i), as the structures show in
Scheme 1 based on this evidence.
Identification of 3a–i was carried out on the basis of spectroscopic
1
data. The H NMR spectra of these compounds show a sharp singlet
for two methyl groups at about d 2.1 ppm. Hydroxyl groups appear as
broad signal at about d 9.0 ppm. The mixed NH, methine, and pyrimidine
H-5 protons were observed at about d 6.5–6.7 ppm. As a result of the
addition of D2O into the sample solution of 3a, the hydroxyl and amine
1
proton signals disappeared in H NMR spectrum. The pyrimidine H-4,6
moieties in all of the products were exhibited in the region of d 8.3 ppm as

Thio-bis-aminophenol Ligands
2351
two doublets, indicating that two types of pyrimidine ring are in the
products. Moreover, in compound 3a, two types of NH signal appear
as two well-resolved doublets at about d 6.35 and 6.37. In addition,
two types of CH signals showed at the positions 4,40 on the phenolic rings
as two well-resolved doublets. These spectroscopic data indicated that the
obtained products have unsymmetric structures and that the hydrogen
nuclei are diastrotopic. Also the number of carbons revealed in the 13C
NMR spectra of compounds 3a–i was in agreement with unsymmetrical
products. Details of 1H NMR and 13C NMR are presented in the
experimental section. The OH and NH absorptions are observed at
3410–3250 cmꢁ1 in IR spectra. Compounds 3a–i exhibit the expected
parent ions with low intensity in mass spectra. Table 1 illustrates reaction
times and yields of the synthesized new aminophenol derivatives (3a–i).
In conclusion, this method could be considered as a convenient and
environmentally friendly approach for the synthesis of new thio-bis-
aminophenol ligands via one-pot, three Component Mannich condensation
of 5-methyl-2-hydroxyphenyl sulfide (1), 2-aminopyrimidine, and aromatic
aldehydes using solvent-free conditions. The present method has advantages
such as no organic solvent, generality and simplicity of the procedure, less
reaction time, elimination of acid catalyst, and moderate to good yields.
To the best of our knowledge, this is the first report on the synthesis of
compounds of type 3, and these multidentate compounds may provide a
valuable source of new potentially chelating agents for metal ions.
EXPERIMENTAL
All commercially available chemicals and reagents were used without
further purification. Melting points were determined with an Electro-
thermal model 9100 apparatus and are uncorrected. IR spectra were
recorded on a Shimadzu 4300 spectrophotometer. The 1H and 13C NMR
spectra were recorded in CDCl3 on Bruker DRX-500 Avance spectrometers.
Chemical shifts (d) are reported in parts per million (ppm) and are referenced
to the NMR solvent. Mass spectra of the products were obtained with a HP
(Agilent technologies) 5937 mass selective detector. Elemental analyses
were carried out by a CHN-O-Rapid Heraeus elemental analyzer
(Wellesley, MA).
General Procedure for the Synthesis of Thio-bis-[5-methyl-3-
(aryl(2-pyrimidinylamino)methyl]-2-phenol
An aromatic aldehyde (4 mmol) was added to a mixture of compound 1
(2 mmol) and 2-aminopyrimidine (4 mmol). The reaction mixture was

2352
A. Shockravi, M. Sadeghpour, and A. Olyaei
Table 1. One-pot reactions of thio-bis-phenol 1,2-aminopyrimidine and aromatic
aldehydes
Time Yield Mp
(ꢀC)
Entry Aldehyde
1
Product 3
(min) (%)
10
80 138–139
2
3
25
75 147–149
30
20
82 146–147
4
5
76 144–146
12
78 144–145
6
15
85 148–150
(Continued )

Thio-bis-aminophenol Ligands
2353
Table 1. Continued
Time Yield Mp
(min) (%)
(ꢀC)
Entry Aldehyde
7
Product 3
12
90 154–155
8
15
87 133–135
9
18
84 143–145
magnetically stirred on a preheated oil bath at 125ꢀC for the appropriate
time as indicated in Table 1. The progress of the reaction was monitored
by thin-layer chromatography (TLC). After completion, the reaction
mixture was cooled to rt, and ethanol (10 mL) was added. The precipitate
was filtered, washed with cold ethanol, dried, and purified by recrystalli-
zation from EtOH to give the thio-bis aminophenol 3 as color crystals.
Data
Thio-bis-[5-methyl-3-(phenyl(2-pyrimidinyl amino)methyl)-
2-phenol (3a)
Pale yellow crystal; IR (KBr): 3410, 3247, 3028, 2922, 1588, 1515, 1447,
1234, 800 cmꢁ1; 1H NMR (500 MHz, CDCl3): d ¼ 2.15 (s, 6H, CH3), 6.35
(d, 1H, J ¼ 3.2 Hz, NH), 6.37 (d, 1H, J ¼ 3.2 Hz, NH), 6.55 (d, 2H,
J ¼ 3.2 Hz, methine-H), 6.56–6.59 (m, 2H, pyrimidine H-5,50), 6.91 (s,
1H, phenolic H-4), 6.92 (s, 1H, phenolic H-40), 7.01 (s, 2H, phenolic
H-6,60), 7.29–7.38 (m, 10H, ph-H), 8.30 (d, 2H, J ¼ 4.8 Hz, pyrimidine

2354
A. Shockravi, M. Sadeghpour, and A. Olyaei
H-4,6), 8.32 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.34 (broad, 2H, OH)
1
ppm; H NMR (500 MHz, CDCl3 þ D2O): d ¼ 2.15 (s, 6H, CH3), 6.54
(s, 2H, methine-H), 6.55–6.58 (m, 2H, pyrimidine H-5,50), 6.91 (s,1H,
phenolic H-4), 6.92 (s,1H, phenolic H-40), 7.01 (s, 2H, phenolic H-6,60),
7.29–7.38 (m, 10H, ph-H), 8.29 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-4,6),
8.31 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60) ppm; 13C NMR (125 MHz,
CDCl3): d ¼ 20.98, 54.28, 111.52, 111.53, 121.71, 127.20, 127.22, 127.54,
128.85, 129.76, 130.67, 130.68, 130.73, 130.74, 133.60, 141.53, 141.55,
152.54, 158.54, 161.78 ppm; MS: m=z (%) ¼ 612 [M]þ, 611 [Mꢁ1]þ,
583, 527, 489, 377, 333, 262, 195, 183, 95. Anal. calcd. for C36H32N6O2S:
C, 70.58; H, 5.22, N, 13.72. Found: C, 70.52; H, 5.28; N, 13.77.
Thio-bis-[5-methyl-3-(4-methylphenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3b)
Pale yellow crystal; IR (KBr): 3410, 3275, 3022, 2920, 1588, 1513, 1448,
1234, 801 cmꢁ1; 1H NMR (500 MHz, CDCl3): d ¼ 2.15 (s, 6H, CH3), 2.36
(s, 6H, CH3), 6.53–6.55 (m, 6H, NH, methine-H, pyrimidine H-5,50), 6.92
(s, 1H, phenolic H-4), 6.93 (s, 1H, phenolic H-40), 7.00 (s, 2H, phenolic
H-6,60), 7.15–7.30 (m, 8H, tolyl-H), 8.25 (d, 2H, J ¼ 4.8 Hz, pyrimidine
H-4,6), 8.27 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.35 (broad, 2H,
OH) ppm; 13C NMR (125 MHz, CDCl3): d ¼ 20.99, 21.74, 54.01,
111.35, 111.37, 121.70, 121.72, 127.18, 127.19, 129.55, 129.96, 130.53,
130.57, 130.65, 130.67, 133.43, 133.46, 137.13, 138.56, 138.58, 152.52,
152.56, 158.51, 161.78 ppm; MS: m=z (%) ¼ 640 [M]þ, 554, 454, 350,
244, 212, 197, 152, 120, 105, 91. Anal. calcd. for C38H36N6O2S: C,
71.25; H, 5.62; N, 13.12. Found: C, 71.30; H, 5.55; N, 13.10.
Thio-bis-[5-methyl-3-(4-methoxyphenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3c)
Pale yellow crystal; IR (KBr): 3410, 3278, 3002, 2931, 1587, 1512, 1454,
1248, 1177, 801 cmꢁ1
;
1H NMR (500 MHz, CDCl3): d ¼ 2.16 (s, 6H,
CH3), 3.82 (s, 6H, OCH3), 6.43–6.57 (m, 6H, NH, methine-H, pyrimidine
H-5,50), 6.84–7.30 (m, 12H, phenolic H-4,40,6,60, OMe-ph-H), 8.25 (d, 2H,
J ¼ 4.8 Hz, pyrimidine H-4,6), 8.28 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60),
9.34 (broad, 2H, OH) ppm; 13C NMR (125 MHz, CDCl3): d ¼ 21.00, 53.76,
55.67, 111.40, 111.42, 114.22, 114.29, 121.70, 121.72, 128.39, 128.41,
129.98, 130.52, 130.54, 130.65, 130.67, 133.50, 133.61, 133.63, 152.50,
152.53, 158.51, 159.04, 161.74 ppm; MS: m=z (%) ¼ 672 [M]þ, 615, 602,
574, 500, 486, 366, 260, 213, 152, 135, 95. Anal. calcd. for C38H36N6O4S:
C, 67.85; H, 5.35; N, 12.50. Found: C, 67.90; H, 5.26; N, 12.59.

Thio-bis-aminophenol Ligands
2355
Thio-bis-[5-methyl-3-(4-bromophenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3d)
Pale yellow crystal; IR (KBr): 3410, 3251, 3025, 2921, 1587, 1568, 1514, 1488,
1448, 1235, 1180, 1010, 800 cmꢁ1; 1H NMR (500MHz, CDCl3): d ¼ 2.16 (s,
6H, CH3), 6.45–6.50 (m, 4H, NH, methine-H,), 6.57 (t, 1H, J ¼ 4.8Hz, pyr-
imidine H-5), 6.59 (t, 1H, J ¼ 4.8 Hz, pyrimidine H-50), 6.87 (d, 1H,
J¼ 1.3 Hz, phenolic H-4), 6.88 (d, 1H, J ¼ 1.3 Hz, phenolic H-40), 7.03 (d,
2H, 1.3, phenolic H-6,60), 7.24 (d, 2H, J ¼ 2.9Hz, 4-Br-ph-H), 7.26 (d, 2H,
J¼ 2.9 Hz, 4-Br-ph-H), 7.45 (d, 2H, J ¼ 1.9 Hz, 4-Br-ph-H0), 7.46 (d, 2H,
J¼ 1.9 Hz, 4-Br-ph-H0), 8.27 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-4,6), 8.29 (d,
2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.26 (broad, 2H, OH) ppm; 13C NMR
(125 MHz, CDCl3): d ¼ 20.96, 53.98, 111.72, 111.74, 121.46, 121.77, 121.79,
129.00, 129.02, 129.29, 130.71, 130.76, 130.94, 131.89, 133.92, 133.98,
140.70, 152.52, 158.55, 161.67ppm; MS: m=z (%) ¼ 772 [M]þ, 770 [M]þ,
768 [M]þ, 750, 584, 414, 276, 183, 120, 95. Anal. calcd. for C36H30Br2N6O2S:
C, 56.10; H, 3.89; N, 10.90. Found: C, 56.01; H, 3.95; N, 10.95.
Thio-bis-[5-methyl-3-(3-bromophenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3e)
Pale yellow crystal; IR (KBr): 3411, 3251, 3020, 2920, 1586, 1569, 1512,
1448, 1234, 1185, 783 cmꢁ1; 1H NMR (500 MHz, CDCl3): d ¼ 2.15 (s, 6H,
CH3), 6.53–6.67 (m, 6H, NH, methine-H, pyrimidine H-5,50), 6.86 (s, 1H,
phenolic H-4), 6.88 (s, 1H, phenolic H-40), 7.03 (s, 2H, phenolic H-6,60),
7.17–7.56 (m, 8H, 3-Br-ph-H), 8.24 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-4,6),
8.27 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.22 (broad, 2H, OH)
ppm;13C NMR (125 MHz, CDCl3): d ¼ 21.00, 53.93, 111.71, 111.73,
121.77, 121.79, 123.07, 126.04, 126.08, 129.22, 130.28, 130.30, 130.35,
130.65, 130.68, 130.72, 130.98, 131.00, 133.93, 133.99, 144.07, 144.09,
152.46, 152.51, 158.54, 161.67 ppm; MS: m=z (%) ¼ 772 [M]þ, 770
[M]þ, 768 [M]þ, 584, 414, 308, 278, 227, 197, 152, 120, 95. Anal. calcd.
for C36H30Br2N6O2S: C, 56.10; H, 3.89; N, 10.90. Found: C, 56.07; H,
3.93; N, 10.85.
Thio-bis-[5-methyl-3-(4-chloro-3-nitro phenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3f)
Yellow crystal; IR (KBr): 3412, 3250, 3033, 2924, 1586, 1537, 1448, 1349,
1235, 1048, 800 cmꢁ1
;
1H NMR (500 MHz, CDCl3): d ¼ 2.18 (s, 6H,
CH3), 6.54–6.68 (m, 6H, NH, methine-H, pyrimidine H-5,50), 6.88 (d,

2356
A. Shockravi, M. Sadeghpour, and A. Olyaei
1H, J ¼ 1.5 Hz, phenolic H-4), 6.90 (d, 1H, J ¼ 1.5 Hz, phenolic H-40),
7.06 (d, 2H, J ¼ 1.5 Hz, phenolic H-6,60), 7.45 (m, 6H, 4-Cl-3-NO2-
ph-H), 8.26 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-4,6), 8.28 (d, 2H, J ¼ 4.8 Hz,
pyrimidine H-40,60), 8.92 (broad, 2H, OH) ppm; 13C NMR (125 MHz,
CDCl3): d ¼ 20.90, 54.03, 112.21, 112.23, 121.92, 124.19, 124.21, 125.91,
128.23, 130.92, 130.95, 131.51, 131.53, 132.10, 132.16, 132.20, 134.62,
134.65, 142.73, 148.18, 152.35, 152.38, 158.60, 161.51 ppm; MS: m=z
(%) ¼ 771 [M]þ, 578, 552, 523, 368, 313, 236, 185, 95. Anal. calcd. for
C36H28Cl2N8O6S: C, 56.03; H, 3.63; N, 14.53. Found: C, 56.10; H,
3.68; N, 14.47.
Thio-bis-[5-methyl-3-(4-nitrophenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3g)
Yellow crystal; IR (KBr): 3412, 3254, 3038, 2924, 1586, 1519, 1505, 1463,
1
1448, 1407, 1346, 1238, 1181, 851 cmꢁ1; H NMR (500 MHz, CDCl3):
d ¼ 2.17 (s, 6H, CH3), 6.57–6.64 (m, 6H, NH, methine-H, pyrimidine
H-5,50), 6.87 (d, 1H, J ¼ 1.5 Hz, phenolic H-4), 6.89 (d, 1H, J ¼ 1.5 Hz,
phenolic H-40), 7.04 (d, 2H, J ¼ 1.5 Hz, phenolic H-6) 7.06 (d, 2H,
J ¼ 1.5 Hz, phenolic H-60), 7.53 (d, 2H, J ¼ 2.1 Hz, 4-NO2-ph-H), 7.55
(d, 2H, J ¼ 2.1 Hz, 4-NO2-ph-H), 8.16 (d, 2H, J ¼ 1.5 Hz, 4-NO2-ph-H0),
8.18 (d, 2H, J ¼ 1.5 Hz, 4-NO2-ph-H0), 8.28 (d, 2H, J ¼ 4.8 Hz, pyrimidine
H-4,6), 8.30 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.09 (broad, 2H, OH)
ppm; 13C NMR (125 MHz, CDCl3): d ¼ 20.93, 54.58, 112.07, 112.10,
121.86, 121.91, 124.01, 128.06, 128.08, 128.67, 130.95, 131.04, 131.35,
134.29, 134.42, 147.42, 147.44, 149.28, 152.36, 152.40, 158.60,
161.58 ppm; MS: m=z (%) ¼ 702 [M]þ, 578, 552, 524, 433, 368, 313,
285, 228, 201, 181, 151, 129, 95. Anal. calcd. for C36H30N8O6S: C,
61.54; H, 4.27; N, 15.95. Found: C, 61.50; H, 4.30; N, 16.00.
Thio-bis-[5-methyl-3-(3-nitrophenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3h)
Pale yellow crystal; IR (KBr): 3409, 3252, 3034, 2925, 1587, 1529,
1
1449, 1412, 1349, 1235, 1130, 801 cmꢁ1; H NMR (500 MHz, CDCl3):
d ¼ 2.16 (s, 6H, CH3), 6.59–6.67 (m, 6H, NH, methine-H, pyrimidine
H-5,50), 6.87 (d, 1H, J ¼ 1.5 Hz, phenolic H-4), 6.89 (d, 1H, J ¼ 1.5 Hz,
phenolic H-40), 7.06 (d, 2H, J ¼ 1.5 Hz, phenolic H-6), 7.47–8.14 (m,
8H, 3-NO2-ph-H), 8.28 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-4,6), 8.30
(d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.05 (broad, 2H, OH) ppm;
13C NMR (125 MHz, CDCl3): d ¼ 20.92, 54.23, 112.05, 112.09,

Thio-bis-aminophenol Ligands
2357
121.88, 121.91, 122.02, 122.04, 122.62, 128.67, 129.71, 130.84, 130.92,
131.31, 131.34, 133.63, 133.65, 134.38, 134.47, 144.15, 144.17, 148.78,
152.41, 152.48, 158.59, 161.62ppm; MS: m=z (%) ¼ 702 [M]þ, 552, 538,
523, 379, 368, 313, 246, 228, 151, 129, 95. Anal. calcd. for C36H30N8O6S:
C, 61.54; H, 4.27; N, 15.95. Found: C, 61.57; H, 4.32; N, 15.90.
Thio-bis-[5-methyl-3-(4-chlorophenyl(2-pyrimidinyl
amino)methyl)-2-phenol (3i)
Pale yellow crystal; IR (KBr): 3412, 3257, 3028, 2922, 1587, 1513, 1449,
1235, 1091, 800 cmꢁ1
;
1H NMR (500 MHz, CDCl3): d ¼ 2.15 (s, 6H,
CH3), 6.51–6.67 (m, 6H, NH, methine-H, pyrimidine H-5,50), 6.87
(s,1H, phenolic H-4), 6.88 (s,1H, phenolic H-40), 7.02 (s, 2H, phenolic
H-6,60), 7.30 (m, 8H, 4-Cl-ph-H), 8.23 (d, 2H, J ¼ 4.8 Hz, pyrimidine
H-4,6), 8.26 (d, 2H, J ¼ 4.8 Hz, pyrimidine H-40,60), 9.27 (broad, 2H,
OH) ppm; 13C NMR (125 MHz, CDCl3): d ¼ 20.96, 53.90, 111.65,
111.67, 121.77, 121.78, 128.68, 128.70, 128.93, 129.40, 129.42, 130.66,
130.70, 130.90, 133.32, 133.34, 133.87, 133.89, 140.17, 140.18, 152.51,
158.52, 161.68 ppm; MS: m=z (%) ¼ 681 [M]þ, 494, 370, 264, 232, 139,
120, 95. Anal. calcd. for C36H30Cl2N6O2S: C, 63.44; H, 4.40; N, 12.33.
Found: C, 63.38; H, 4.36; N, 12.39.
ACKNOWLEDGMENT
We thank the Research Council of the Tarbiat Moallem University for
financial support.
REFERENCES
1. (a) Domling, A.; Ugi, I. Multicomponent reactions with isocyanides. Angew.
Chem. Int. Ed. 2000, 39, 3168–3210; (b) Thmson, L. A.; Ellman, J. A.
Synthesis and application of small molecule libraries. Chem. Rev. 1996, 96,
555–600.
2. (a) Chetia, A.; Saikia, C. J.; Lekhok, K. C.; Boruah, R. C. Facile synthesis of
1,7-dicarbonyl compounds via three-component Michael addition reactions.
Tetrahedron Lett. 2004, 45, 2649–2651, (b) Wang, L. M.; Xia, J.; Qin, F.;
Qian, C.; Sun, J. Yb(OTf)3-catalyzed one-pot synthesis of quinazolin-4
(3H)-ones from anthranilic acid, amines, and ortho esters (or formic acid)
in solvent-free conditions. Synthesis 2003, 1241–1247.
3. Arend, M.; Westermann, B.; Risch, N. Modern variants of the Mannich
reaction. Angew. Chem. Int. Ed. 1998, 37, 1044–1077.

2358
A. Shockravi, M. Sadeghpour, and A. Olyaei
4. (a) Paqett, L. O. (Ed.). Encyclopedia of Reagents for Organic Synthesis; Wiley:
London, 1995; vol. 4, p. 2582; (b) Tramontini, M.; Angionili, L. Further
advances in the chemistry of Mannich bases. Tetrahedron 1990, 46,
1791–1837.
5. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Tymoshenko, D. O.; Belyakov, S.
A.; Ghiviriga, I.; Steel, P. J. Amino(hetero)arylmethylation of phenols with
N-[a-amino(hetero)arylmethyl]benzotriazoles. J. Org. Chem. 1999, 64,
6071–6075.
6. Mojtahedi, M. M.; Sharifi, A.; Mohsenzadeh, F.; Saidi, M. R. Microwave-
assisted aminomethylation of electron-rich compounds under solvent-free
condition. Synth. Commun. 2000, 30, 69–72.
7. Saidi, M. R.; Azizi, N.; Naimi-jamal, M. R. Lithium perchlorate–assisted
one-pot three-component aminoalkylation of electron-rich aromatic
compounds. Tetrahedron Lett. 2001, 42, 8111–8113.
8. Huang, T.; Li, C. J. Synthesis of amino acids via a three-component reaction
of phenols, glyoxylates, and amines. Tetrahedron Lett. 2000, 41, 6715–6719.
9. Subramanian, P.; Spence, J. T.; Ortega, R.; Enemark, J. H. Molybde-
num(VI)–dioxo complexes with sterically bulky ligands. Inorg. Chem. 1984,
23, 2564–2572.
10. Amudha, P.; Thirumavalavan, M.; Kandaswamy, M. Synthesis, spectral,
electrochemical, and magnetic properties of new phenoxo-bridged dicopper
(II) complexes derived from unsymmetrical binucleating ligands. Polyhedron
1999, 18, 1363–1369.
11. Tshuva, E. Y.; Gendeziuk, N.; Kol, M. Single-step synthesis of salans and
substituted salans by Mannich condensation. Tetrahedron Lett. 2001, 42,
6405–6407.
12. Higham, C. S.; Dowling, D. P.; Shaw, J. L.; Cetin, A.; Ziegler, C. J.; Farrell,
J. R. Multidentate aminophenol ligands prepared with Mannich condensa-
tions. Tetrahedron Lett. 2006, 47, 4419–4423.
13. D’Hardemare, A. du M.; Jarjayes, O.; Mortini, F. Solvent- and catalyst-free
selective Mannich reaction on catechols and para-substituted phenols: A
convenient route to catechol- and phenol-iminodiacetic acid ligands. Synth.
Commun. 2004, 34, 3975–3988.
14. Palmieri, G. A practical o-hydroxybenzylamines promoted enantioselective
addition of dialkylzincs to aldehydes with asymmetric amplification. Tetrahe-
dron: Asymmetry 2000, 11, 3361–3373.
15. Cardellicchio, C.; Ciccarella, G.; Naso, F.; Perna, F.; Tortorella, P. Use of
readily available chiral compounds related to the Betti base in the enantiose-
lective addition of diethylzinc to aryl aldehydes. Tetrahedron 1999, 55,
14685–14692.
16. Lu, J.; Xu, X.; Wang, C.; He, J.; Hu, Y.; Hu, H. Synthsis of chiral
ligands derived from the Betti base and their use in the enantioselective
addition of diethylzinc to aromatic aldehydes. Tetrahedron Lett. 2002, 43,
8367–8369.
17. Shockravi, A.; Alizadeh, R.; Aghabozorg, H.; Moghimi, A.; Rostami, E.;
Bavili, S. Synthesis and crystal structure determination of 2,20-sulfinyl-bis

Thio-bis-aminophenol Ligands
2359
(4-methyl phenol) and 2,20-thio-bis(4-methyl phenol). Phosphorus, Sulfur,
Silicon Relat. Elem. 2003, 178, 2519–2527.
18. Shockravi, A.; Bavili, S.; Rostami, E.; Yousefi, A.; Dehjurian, A.; Tohidi, R.
Synthesis of new dibenzosulfid and dibenzosulfoxide macrocyclic compounds.
J. Incl. Phenom. Macrocycl. Chem. 2004, 49, 163–166.
19. Shockravi, A.; Bavili, S. Synthesis of new dibenzosulfid macrocyclic diamide.
J. Incl. Phenom. Macrocycl. Chem. 2005, 52, 223–227.
20. Shockravi, A.; Mehdipour-Ataei, S.; Abouzari-Lotf, E.; Yousefi, A. Eur.
Polym. J. 2006, 42, 133–134.
21. Shockravi, A.; Shamsipur, M.; Fattahi, H.; Taghdiri, M.; Heidarian, D.;
Alizadeh, K.; Rostami, E.; Abbaszadeh, M.; Yousefi, A. J. Incl. Phenom.
Macrocycl. Chem. 2008, 61, 153–160.