The preparation of dicompartmental multifunctional group ligands

Article abstract of DOI:10.1080/10426500600864890

A convenient method for the preparation of the phenol-based ligands 1,6-bis(2-thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-methylbenzyl)-2, 5-diazahexane and 1,6-bis(5-methyl-2-thiophenyl)-2,5-bis(2-hydroxy-3- hydroxymethyl-5-methyl-benzyl)-2,5-diazahexane possessing two dissimilar compartments having multifunctional groups is reported. To synthesize these ligands, an equivalent of 1,6-bis(2-thiophene)-2,5-diazahexane or 1,6-bis(5-methyl-2-thiophene)-2,5-diazahexane and two equivalents of 2,2-dimethyl-6-methyl-8-(chloromethyl)benzo-1,3-dioxin were reacted in the presence of Na₂CO₃ in 1,4-dioxane, followed by acid hydrolysis of an acetonide-protecting group. Characterization data for the new compounds is reported. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500600864890

Phosphorus, Sulfur, and Silicon, 181:2817–2823, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600864890
The Preparation of Dicompartmental Multifunctional
Group Ligands
Yeganeh Khaniani
Hamid Golchoubian
Department of Chemistry, University of Mazandaran, Babolsar, Iran
A convenient method for the preparation of the phenol-based ligands 1,6-bis(2-
thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-methylbenzyl)-2,5-diazahexane
and 1,6-bis(5-methyl-2-thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-methyl-
benzyl)-2,5-diazahexane possessing two dissimilar compartments having multi-
functional groups is reported. To synthesize these ligands, an equivalent of 1,6-bis(2-
thiophene)-2,5-diazahexane or 1,6-bis(5-methyl-2-thiophene)-2,5-diazahexane and
two equivalents of 2,2-dimethyl-6-methyl-8-(chloromethyl)benzo-1,3-dioxin were
reacted in the presence of Na CO in 1,4-dioxane, followed by acid hydrolysis of
2
3
an acetonide-protecting group. Characterization data for the new compounds is
reported.
Keywords Acyclic ligand; compartmental ligand; multifunctional ligand; phenol-based
ligand; synthesis
INTRODUCTION
Phenol-based binucleating ligands containing two different compart-
ments have received attention because of their capability to bind two
1−8
different metal centers in close proximity.
Since unsymmetrical di-
compartmental ligands are of importance for providing discrete het-
erodinuclear core complexes, various types of compartmental ligands
including the end-off, side-off, and their macrocyclic type have been
9
−11
developed.
They have a basic structure of type 1 (Figure 1) where
“B” is an electron-pair donating atom. The introduction of donor aux-
iliary “A” residues to the two amino nitrogen atoms in 1 provides new
unsymmetrical compartmental ligands of type 2. A synthetic method
Received ; accepted .
Please send reprint requests to Dr. H. Golchoubian, E-mail: h.golchobian@umz.ac.ir
We appreciate financial support of the University of Mazandaran of the Islamic
Republic of Iran.
Address correspondence to Hamid Golchoubian, University of Mazandaran,
Department of Chemistry, P.O. Box 453, Babolsar, Iran. E-mail: h.golchobian@umz.ac.ir
2817

2
818
Y. Khaniani and H. Golchoubian
FIGURE 1 (I) and (II) examples of dicompartmental ligands reported in the
literature. (III) the dicompartmental ligands reported in this paper.
for the preparation of compounds 2 with pyridyl groups “A” and two
6
dialdehyde groups “B” was reported by Fraser et al. and is based upon
nine consecutive steps. In this report we describe a successful four-step
reaction leading to the new ligands 3a and 3b. This route has the po-
tential of facilitating the synthesis of other analogues of compound 3.
RESULTS AND DISCUSSION
The acyclic dialcohols 3a and 3b were prepared by the sequence steps
outlined in Scheme 1. First, the diamine moiety of the desired com-
pound was prepared by the condensation of ethylenediamine with two
equivalents of 2-thiophenealdehyde or 5-methyl 2-thiophenealdehyde
at r.t. under aerated conditions, which resulted in the formation of the
crystalline diimine compounds 4a and 4b in a 92–96% yield. These
1
compounds are sufficiently pure (95% based on H NMR) for further
treatment. Subsequently, these diimine compounds were converted to
their diamine counterparts 5a and 5b quantitatively by NaBH4 as a re-
ducing agent. The infrared spectra of the imine and amine compounds
are generally similar. The main spectral differences between the imines
−
1
and amines are the emergence of a sharp but weak band at 3268 cm
,
which is attributed to the N-H stretch of the quaternized amine and the
−
1
disappearance of the strong band at 1643 cm , which corresponds to
the C N stretch of the imine groups.12 A band near 1550 cm for com-
−1
pounds 4a and 5a is assigned to the skeletal vibration of the aromatic

Dicompartmental Multifunctional Group Ligands
2819
SCHEME 1
rings.13 Also, the H NMR spectrum of diimines 4 shows a singlet at
1
8.21 ppm corresponding to the proton attached to the imine moiety.
However, the amine shows a singlet for the CH2 moiety attached to the
1
nitrogen in the H NMR spectrum at 2.36 ppm. On the other hand,
the triol 7 and its protected derivative 8 were made by a method de-
14
scribed by Fraser et al. In the next step, 8 was chlorinated efficiently
by the Corey procedure.15 Finally, the coupling of benzyl chloride 9 with
diamine 5 under mild conditions followed by acid hydrolysis of the ace-
tonide protecting group afforded dialcohol ligands 3a or 3b in yields of
54–94%.
The IR spectra of both 3a and 3b were similar and showed a weak
−1
band at around 3300 cm , which is probably attributed to the OH
stretch of the alcoholic groups. The total yields of the final products 3a
and 3b are typically lower than 20% and 35%, respectively. These yields
are limited mainly by the preparation of triol 7 (yield 51%) and by the
condensation reaction of 5a with 9 (yield 54%). The major reason for
the low yield in the formation of 3a is the polymerization of compound
5
b under the applied reaction condition. It has been proven that the un-
1
6
substituted α–position in thiophene is susceptible for polymerization.
In fact, using compound 5b, in which the α-position is substituted by
a methyl group, resulted in a significant increase in the yield of the

2
820
Y. Khaniani and H. Golchoubian
1
condensation reaction (95%). In the H NMR spectra of compounds 3a
and 3b, the signals belonging to the protons of the phenolic hydroxy
groups were broad. This indicates that the protons are acidic and sug-
gests the formation of O-H N hydrogen bonds. This phenomenon has
17
been observed in similar systems and was also confirmed by single
crystal X-ray diffraction.18
It can be concluded that the dissimilar two compartmental ligands
3
were prepared in satisfactory yields by a simple and convenient mul-
tistep method.
EXPERIMENTAL
All elemental analyses were performed on a LECO CHN-600 elemental
1
analyzer. H NMR spectra were recorded on a Bruker 300 fourier trans-
form spectrometer. Infrared spectra were recorded in KBr pellets with a
single beam Bruker VECTOR22 FTIR instrument. Mass spectra were
obtained on a VG 70E double-focusing high-resolution spectrometer.
All samples were dried to constant weight under high vacuum prior
1
4
to analysis. Compounds 2,6-bis(hydroxymethyl)-4-methylphenol,
1
4
2
,2-dimethyl-6-methyl-8-(hydroxymethyl)benzo-1,3-dioxin, and 1,6-
19
bis(2-thiophene)-2,5-diazahexane were prepared by standard meth-
ods. All reagents were commercial materials. Solvents used were
dried over CaH2 (CH2Cl2), LiAlH4 (ether and dioxane), and K
(
THF).
N,N’-Bis(5-methyl-2-thiophenemethyl)-1,2-ethanediamine
4b) and 1,6-Bis(5-methyl-2-thiophenyl)-2,5-diazahexane (5b)
(
The diimine compound 4b and its diamine counterpart 5b were pre-
1
9
pared by procedures similar to those described by Patra and Goldberg
using 5-methyl-2-thiophenealdehyde instead of 2-thiophenealdehyde
as a starting material. The desired diimine was obtained as a brown
solid (96%), and the diamine was obtained as a light-brown liquid with
◦
−1
a quantitative yield. 4b: m.p.: 44–45 C. IR: strong band at 1643 cm
.
1
H NMR (300.13 MHz, CDCl3) δ: 2.54 (s, 6H, Thiophene-CH3), 3.83 (s,
4
2
6
H, N CH2), 6.67 (d, J= 4.6 Hz, 2H, thiophene-H), 7.03 (d, J= 4.6 Hz,
H, thiophene-H), 8.21 (s, 2H, N CH). Anal. calcd. for C14H16N2S2: C,
0.83; H, 5.83; N, 10.13%. Found: C, 60.54; H, 5.50; N 10.33%. 5b: IR:
−1 1
medium band at 3268 cm . H NMR (300.13 MHz, CDCl3) δ:1.56 (br.
s, 2H, N-H), 2.36 (s, 4H, -CH2-thiophene), 2.69 (s, 6H, thiophene-CH3),
3.81 (s, 4H, -CH2-CH2-), 6.49 (d, J=3.8 Hz, 2H, thiophene-H), 6.60

Dicompartmental Multifunctional Group Ligands
2821
(
d, J = 3.8 Hz, 2H, thiophene-H). Anal. calcd. for C14H20 N2S2: C, 59.96;
H, 7.19; N, 9.99%. Found: C, 60.21; H, 7.50; N, 9.77%.
2,2-Dimethyl-6-methyl-8-(chloromethyl)benzo-1,3-dioxine (9)
A stirred solution of N-chlorosuccinimide (7.61 g, 57.0 mmol) in dry dis-
◦
tilled CH2Cl2 (200 mL) in a fume hood was cooled to 0 C, and dimethyl-
sulfide (37.0 g, 600 mmol) was added dropwise. The resulting colorless
◦
reaction mixture was further cooled to −25 C, and 2,2-dimethyl-6-
methyl-8-(hydroxymethyl)benzo-1,3-dioxine 8 (11.30 g, 50.0 mmol) in
dry distilled CH2Cl2 (10 mL) was added slowly dropwise. After stirring
◦
at 0 C for 2 h, the resulting reaction mixture was poured into cold brine
(
∼200 mL), the aqueous layer was extracted with Et2O (2 × 50 mL), and
the combined organic layers were dried over anhydrous Na2SO4. The fil-
tration and concentration under reduced pressure gave a crude product
as yellow oil. The crude compound was dissolved in a minimal amount
of Et2O: n-hexane (1:1) mixture, loaded onto a short column (1 inch
diameter) containing silicagel (20 g), and eluted with Et2O: n-hexane
(
1:1). The desired compound came out with the first fraction. The con-
centration of the eluent under reduced pressure gave pure compound 9
1
as yellow oil, 10.3 g (85%). H NMR (300.13 MHz, CDCl3) δ: 1.54 (s,
6
H, C-CH ), 2.26 (s, 3H, Ar-CH ), 4.57 (s, 2H, ArCH -Cl), 4.80 (s, 2H,
3 3 2
ArCH -O), 6.76 (s, 1H, Ar-H), 7.04 (s, 1H, Ar-H). The high-resolution
2
mass spectrum showed the main peak at m/z 226.0756 corresponding to
−
1
the molecular formula of C12H15O2Cl. FT-IR (KBr): 1445 cm (aromatic
skeleton).
1
,6-Bis(2-thiophenyl)-2,5-bis(2-hydroxy-3-hydroxymethyl-5-
methylbenzyl)-2,5-diazahexane(3a)
1,6-bis(2-thiophenyl)-2,5-diazahexane 5a (0.512 g, 2.0 mmol) and
2,2-dimethyl-6-methyl-8-(chloromethyl)benzo-1,3-dioxine 9 (1.00 g,
4.1 mmol) were dissolved under argon in dry distilled 1,4-dioxane
(
30 mL), and anhydrous Na2CO3 (1.900 g, 17.9 mmol) was added. The
◦
reaction mixture was stirred at 100 C for 2 days, allowed to cool to
r.t., and then filtered through Celite. Dioxane was removed in vacuo to
give a viscous orange-brown oil, which was treated with aqueous HCl
(
1.16 M, 50 mL) and heated on a steam bath for 10 min. After cooling, the
yellow suspension was extracted with Et2O (4 × 20 mL). The aqueous
layer was adjusted to pH ≈ 7.0 with aqueous NaOH (1 M) and then to
pH ≈ 8.4 by an addition of saturated aqueous NaHCO3. The oily mixture
was extracted with CH2Cl2(8 × 10 mL), and the combined organic ex-
tracts were dried over Na2SO4. The filtration and concentration under

2
822
Y. Khaniani and H. Golchoubian
1
reduced pressure gave 3a as pale-brown oil (ca. 85% by H NMR) that
1
slowly solidified, 0.64 g, (54%). H NMR (300.13 MHz, CDCl3) δ:1.73
(
t, J = 5.7 Hz, 2H, Ar-CH2-OH), 2.60 (s, 6H, Ar-CH3), 2.79 (s, 4H, N-
CH2-thiophene), 3.75 (s, 4H, N-CH2-Ph), 3.88 (s, 4H, N-CH2-CH2-N),
4
.54 (d, J= 5.7 Hz, 4H, Ar-CH2-OH), 6.97 (s, 2H, Ar-H), 6.98 (s, 2H,
Ar-H), 6.97–7.46 (m, 6H, thiophene-H), 11.00 (br. s, 2H, Ar-OH). When
one drop of D2O was added to the H NMR sample, the signals at 11.00
1
and 1.73 ppm disappeared, and the doublet at 4.54 ppm sharpened
into a singlet at 4.53 ppm. The high-resolution mass spectrum showed
the main peak at m/z= 552.2132 corresponding to a monopositively
charged compound. Anal. calcd. for C30H36N2O4S2: C, 65.19; H, 6.56; N,
5.07. Found: C, 65.01; H, 6.78; N, 5.21.
1
,6-Bis(5-methyl-2-thiophenyl)-2,5-bis(2-hydroxy-3-
hydroxymethyl-5-methylbenzyl)-2,5-diazahexane
3b)
(
Compound 3b was prepared in the manner as previously described
for the preparation of 3a using 1,6-bis(5-methyl-2-thiophene)-2,5-
diazahexane instead of 1,6-bis(2-thiophenyl)-2,6-diazahexane. Com-
1
pound 3b was obtained as a pale-brown solid (94%). H NMR
(
300.13 MHz, CDCl3) δ: 1.70 (t, J= 5.5 Hz, 2H, Ar-CH2-OH), 2.60
(
s, 6H, Ar-CH3), 2.68 (s, 6H, thiophene-CH3), 2.81 (s, 4H, N-CH2-
thiophene), 3.80 (s, 4H, N-CH2-Ph), 3.88 (s, 4H, N-CH2-CH2-N), 4.50 (d,
J= 5.5 Hz, 4H, Ar-CH2-OH), 7.01 (s, 2H, Ar-H), 7.05 (s, 2H, Ar-H), 7.45
(
1
d, J= 3.8 Hz, 2H, thiophene-H), 7.62 (d, J= 3.8 Hz, 2H, thiophene-H),
1
0.11 (br. s, 2H, Ar-OH). When one drop of D2O was added to the H
NMR sample, the signals at 10.11 and 1.70 ppm disappeared, and the
doublet at 4.50 ppm sharpened into a singlet at 4.49 ppm. The high-
resolution mass spectrum showed the main peak at m/z = 580.2435
corresponding to the monopositively charged compound. Anal. calcd.
for C32H40N2O4S2: C, 66.17; H, 6.94; N, 4.82. Found: C, 66.48; H, 6.66;
N, 4.51.
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