Controlled oxidation of organic sulfides to sulfoxides under ambient conditions by a series of titanium isopropoxide complexes using environmentally benign H2O2 as an oxidant

Article abstract of DOI:10.1039/b921720g

Controlled oxidation of organic sulfides to sulfoxides under ambient conditions has been achieved by a series of titanium isopropoxide complexes that use environmentally benign H₂O₂ as a primary oxidant. Specifically, the [N,N′-bis(2-oxo-3-R₁-5-R₂- phenylmethyl)-N,N′-bis(methylene-R₃)-ethylenediamine]Ti(O ⁱPr)₂ [R₁ = t-Bu, R₂ = Me, R ₃ = C₇H₅O₂ (1b); R₁ = R₂ = t-Bu, R₃ = C₇H₅O₂ (2b); R₁ = R₂ = Cl, R₃ = C₇H ₅O₂ (3b) and R₁ = R₂ = Cl, R ₃ = C₆H₅ (4b)] complexes efficiently catalyzed the sulfoxidation reactions of organic sulfides to sulfoxides at room temperature within 30 min of the reaction time using aqueous H₂O ₂ as an oxidant. A mechanistic pathway, modeled using density functional theory for a representative thioanisole substrate catalyzed by 4b, suggested that the reaction proceeds via a titanium peroxo intermediate 4c′, which displays an activation barrier of 22.5 kcal mol^-1 (ΔG^?) for the overall catalytic cycle in undergoing an attack by the S atom of the thioanisole substrate at its σ*-orbital of the peroxo moiety. The formation of the titanium peroxo intermediate was experimentally corroborated by a mild ionization atmospheric pressure chemical ionization (APCI) mass spectrometric technique. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b921720g

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Controlled oxidation of organic sulfides to sulfoxides under ambient
conditions by a series of titanium isopropoxide complexes using
environmentally benign H2O2 as an oxidant†
Manas K. Panda,a Mobin M. Shaikhb and Prasenjit Ghosh*a
Received 16th October 2009, Accepted 17th December 2009
First published as an Advance Article on the web 28th January 2010
DOI: 10.1039/b921720g
Controlled oxidation of organic sulfides to sulfoxides under ambient conditions has been achieved by a
series of titanium isopropoxide complexes that use environmentally benign H2O2 as a primary oxidant.
Specifically, the [N,N¢-bis(2-oxo-3-R1-5-R2-phenylmethyl)-N,N¢-bis(methylene-R3)-ethylenediamine]-
Ti(OiPr)2 [R1 = t-Bu, R2 = Me, R3 = C7H5O2 (1b); R1 = R2 = t-Bu, R3 = C7H5O2 (2b); R1 = R2 = Cl,
R3 = C7H5O2 (3b) and R1 = R2 = Cl, R3 = C6H5 (4b)] complexes efficiently catalyzed the sulfoxidation
reactions of organic sulfides to sulfoxides at room temperature within 30 min of the reaction time using
aqueous H2O2 as an oxidant. A mechanistic pathway, modeled using density functional theory for a
representative thioanisole substrate catalyzed by 4b, suggested that the reaction proceeds via a titanium
peroxo intermediate 4c¢, which displays an activation barrier of 22.5 kcal mol-1 (DG‡) for the overall
catalytic cycle in undergoing an attack by the S atom of the thioanisole substrate at its s*-orbital of the
peroxo moiety. The formation of the titanium peroxo intermediate was experimentally corroborated by
a mild ionization atmospheric pressure chemical ionization (APCI) mass spectrometric technique.
oxidizing agent like H2O2. Our choice of H2O2 rests on several
Introduction
advantages it naturally possesses right from being considered a
“green” oxidizing agent by virtue of eliminating H2O as a by-
product to being cheap and also atom efficient in carrying out the
oxidation reactions.9
The long standing interest in the sulfoxidation of organic sulfides is
primarily fuelled by its utility in diverse areas of chemistry originat-
ing from the constant use of sulfoxide derived chiral auxiliaries in
total synthesis,1 to its use in medicinal chemistry2 and biology,3 to
its application in industrially important desulfurization processes.4
Pioneering work in this area was done by Kagan10 and Modena11
who successfully employed a modified version of the “Katsuki
Sharpless reagent” consisting of Ti(OiPr)4/diethyltartarate/alkyl
hydroperoxide mixture for asymmetric oxidation of prochiral
sulfides. The system however suffered from many disadvan-
tages arising out of low activity requiring higher catalyst load-
ing of 4–6 mol% and thereby decreasing its cost effectivity.
Pasini12 employed a well characterized salen based titanium
precatalyst namely {2,2¢-[1,2-ethanediylbis-(nitrilomethylidene)]-
diphenoxy}TiO for the oxidation of thioanisole to the correspond-
ing sulfoxide albeit in low enantioselectivity (20% ee). The second
generation of salen based titanium precatalyst was reported by
Katsuki13 for enantioselective sulfoxidation. Apart from these
salen based complexes, the in situ formed titanium precatalysts
of the chiral diol ligands i.e. 1,2-bis-(methoxypheny1)ethane-1,2-
diol14 and (R) 1,1¢-binaphthyl-2,2¢-diol14 and Ti(OiPr)4 have also
been successfully employed in various sulfoxidation reactions.
Recently Licini15 reported a highly active well characterized
Ti(IV)-amine tris-phenolate complex namely, {phenoxy, 2,2¢,2¢¢-
[nitrilotris(methylene)]tris[6-(1,1-dimethylethyl)}Ti(OiPr) that ex-
hibited an increased turnover number (TON) of up to 8000 and
turnover frequency (TOF) of up to 1700 h-1 for sulfoxidation
of organic sulfides at 0.01 mol% of the catalyst loading using
H2O2 as an oxidant. Alongside the above mentioned development
in homogeneous catalysis significant research has also been
performed on heterogeneous systems.5a,5b,16 Besides these titanium
complexes various other metals like Mn,17 V,18 Mo,19 Fe20 etc. have
been reported for the sulfoxidation reaction.
5
The use of environmentally benign oxidizing agents like H2O2
or even molecular oxygen6 for achieving the sulfoxidation re-
action under amenable conditions, as opposed to some very
strong conditions like inorganic salts,7 thus, represent some of
the foremost objectives of research in this area. Furthermore,
achieving controlled oxidation of organic sulfides to sulfoxides
over the fully oxidized sulfones represents yet another notable
challenge of sulfoxidation. In this regard it is noteworthy that
sulfoxides are high value targets owing to their application as chiral
auxiliaries in organic synthesis as well as important functionalities
in many biologically active molecules8 and consequently, new
methods for the formation of sulfoxides, thus, remain always
in demand. Because of the aforementioned reasons we became
interested in looking into ways of devising highly efficient Lewis
acid catalyzed controlled oxidation of organic sulfides to sulfoxides
under amenable conditions employing an environmentally friendly
aDepartment of Chemistry, Indian Institute of Technology Bombay, Powai,
Mumbai 400 076. E-mail: pghosh@chem.iitb.ac.in; Fax: +91-22-2572-3480
bNational Single Crystal X-ray Diffraction Facility, Indian Institute of
Technology Bombay, Powai, Mumbai 400 076
† Electronic supplementary information (ESI) available: ORTEP plots of
2b–4b, geometry optimized structures of 1b¢–4b¢, 4c¢, 4e¢–4g¢ along with
the B3LYP coordinates of the optimized geometries for 1b¢–4b¢ and 4c¢–
4h¢, molecular orbital interaction table, X-ray crystallographic parameters
table, catalysis tables and natural charge analysis tables. CCDC reference
numbers 654513, 679212, 690057 and 711908. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b921720g
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In keeping with a key theme of our research on understanding
various oxidation processes of chemical and biological worlds, we
have recently reported several small molecule synthetic analogs
of the copper enzyme galactose oxidase21 and the iron enzyme
catechol dioxygenase22 that utilize molecular oxygen for the
oxidation reactions similar to the respective enzymes. Thus,
having successfully mimicked enzymes with these small molecule
synthetic analogs, we set out to design transition metal based
catalysts for a commercially important reaction particularly, the
controlled oxidation of organic sulfides to sulfoxides. In the back-
drop of a few prior reports of titanium isopropoxide complexes
for sulfoxidation reactions involving organic hydroperoxides as
oxidants,23 the Group (IV) elements being electron deficient and
non-toxic in nature, became our metal of choice for accomplishing
the controlled oxidation of organic sulfides to sulfoxide using
“green” H2O2 oxidant.24
Here in this contribution, we report a series of titanium(IV) iso-
propoxide complexes, [N,N¢-bis(2-oxo-3-R1-5-R2-phenylmethyl)-
N,N¢-bis(methylene-R3)-ethylenediamine]Ti(OiPr)2 [R1 = t-Bu,
R2 = Me, R3 = C7H5O2 (1b); R1 = R2 = t-Bu, R3 = C7H5O2
(2b); R1 = R2 = Cl, R3 = C7H5O2 (3b) and R1 = R2 = Cl, R3 =
C6H5 (4b)], that efficiently catalyzed the sulfoxidation reactions of
organic sulfides at ambient temperature using aqueous H2O2 as an
oxidant (Fig. 1). The catalytic cycle of the sulfoxidation reaction
as modeled using density functional theory studies revealed that
the rate-determining step involved an attack by the S atom of the
organic sulfide substrate at the s*-orbital of the peroxo moiety of
a titanium peroxo intermediate.
(3JHH = 8 Hz) and 1.07–1.30 ppm (3JHH = 8 Hz) in the 1H NMR
spectrum while the corresponding carbon resonances appeared at
77.7–79.9 ppm, 26.1–26.9 ppm and 25.8–26.6 ppm respectively
1
in the 13C{ H} NMR spectrum. Quite interestingly, two of the
three methylene resonances of the 1b–4b complexes were found
to be diastereotopic in nature with each appearing as two sets of
doublets at 4.15–4.29 ppm (2JHH = 13 Hz) and 3.22–3.43 ppm
(2JHH = 13 Hz) and at 2.61–2.88 ppm (2JHH = 10 Hz) and 2.31–
2.44 ppm (2JHH = 11 Hz).
The molecular structures of 1b–4b as determined by X-ray
diffraction studies revealed the titanium center to be in a distorted
octahedral geometry in these complexes (Fig. 2 and Fig. S1–
S3, ESI†). The tetradentate [N2O2] ligand was seen chelated
to the metal center through two phenolate-O atoms and two
amine-N atoms, of which a pair of phenolate-O and amine-N
atoms occupied adjacent equatorial sites while the other pair
occupied adjacent equatorial and axial sites. The two Oi-Pr
moieties occupied the remaining equatorial and axial sites thereby
adopting a cis disposition to each other. Of particular interest
are the Ti–O distances in the 1b–4b complexes as the two Ti–
˚
O(phenolate) bonds [1.896(2)–1.919(3) A] are longer than the
˚
other two Ti–O(isopropoxide) bonds [1.775(4)–1.815(16) A]. For
comparison, the Ti–O single bond distance as obtained from the
25
˚
sum of the individual covalent radii is 1.984 A. The shorter
Ti–O(isopropoxide) distances in 1b–4b are a consequence of Ti–
O p-donation arising out of an interaction of an oxygen lone
pair with an empty d-orbital of the highly electron deficient
titanium(IV) d0 metal center in these complexes (Fig. 3). Further
support in favor of the Ti–O p-donation in these 1b–4b complexes
comes from density functional theory studies. In particular, the
electronic structures (1b¢–4b¢) of the 1b–4b complexes computed
at B3LYP/LANL2DZ, 6-31G(d) level of theory using atomic
coordinates adapted from X-ray analysis showed the presence of
such Ti–O p-back donation as depicted by the molecular orbitals
Fig. 1 Titanium isopropoxide 1b–4b complexes supported over [N2O2]
ligands 1a–4a.
Results and discussion
With the intent of stabilizing titanium(IV) isopropoxide complexes,
a series of tetradentate [N2O2] ligands namely N,N¢-bis(2-oxo-3-
R1-5-R2-phenylmethyl)-N,N¢-bis(methylene-R3)-ethylenediamine
[R1 = t-Bu, R2 = Me, R3 = C7H5O2 (1a); R1 = R2 = t-Bu, R3 =
C7H5O2 (2a); R1 = R2 = Cl, R3 = C7H5O2 (3a) and R1 = R2 =
Cl, R3 = C6H5 (4a)] were synthesized. Specifically, the 1a–4a
ligands were prepared by the Mannich condensation reaction
of the N,N¢-bis(methylene-R3)-ethylenediamine [R3 = C7H5O2,
C6H5] with the respective 2,4-disubstituted phenol and aqueous
formaldehyde (Scheme 1).
The titanium(IV) isopropoxide complexes, 1b–4b, were synthe-
sized by the direct reaction of the 1a–4a ligands with Ti(OiPr)4 in
65–90% yields. Consistent with the formations of the isopropoxide
derivative, the metal bound Oi-Pr moiety appeared as a septet at
4.90–5.19 ppm (3JHH = 8 Hz) and as two doublets at 1.12–1.32 ppm
Fig. 2 ORTEP of 1b. Hydrogen atoms on carbon are omitted for
◦
˚
clarity. Selected bond lengths (A) and angles ( ) are given: Ti1–O1
1.8961(16), Ti1–O2 1.8147(16), Ti1–O5 1.9036(16), Ti1–O6 1.8127(17),
Ti1–N1 2.430(2), Ti1–N2 2.3942(19), O1–Ti1–O6 90.58(7), O2–Ti1–O6
107.58(8), O1–Ti1–N2 92.55(7), O2–Ti1–N2 159.13(7), O5–Ti1–N2
78.97(6), O6–Ti1–N2 91.62(7).
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Scheme 1 General synthetic procedure of the 1b–4b complexes.
solvents28 and hence there exists a palpable need for improved
protocols.
(1)
Fig. 3 Ti–O p-interaction in 1b–4b.
The catalyst influence is very much evident when compared
to the blank runs carried out in the absence of these catalysts
which showed significantly subdued conversion to sulfoxides
under analogous conditions (Table 1 and Table S2, ESI†). It is
worth noting that control experiments performed with Ti(OiPr)4
showed a significantly higher buildup of sulfones in comparison to
the 1b–4b catalysts (Table 1 and Table S2, ESI†). Thus, the selective
and near quantitative formation of sulfoxides in the case of 1b–
4b highlights a key attribute of these catalysts. It is worth noting
that sulfoxides are important, high valued synthetic intermediates
of considerable commercial and biological interests29 and hence
the catalysts for selective oxidation of organic sulfides to the
corresponding sulfoxides are in great demand. Lastly, the attempts
to recover the catalyst after the catalysis runs proved to be
unsuccessful for a representative precatalyst 2b.
Another important attribute of these 1b–4b catalysts is the con-
venienceofthe use ofanenvironmentfriendlyoxidant likeaqueous
H2O2 instead of organic peroxides or other harsh inorganic
oxidants. For example, oxidation with an organic peroxide namely
m-chloroperbenzoic acid (m-CPBA) for a representative substrate
thioanisole by 1b yielded ca. 52% of sulfoxide as compared to 90%
with aqueous H2O2 under analogous conditions (Table S3, ESI†).
Quite interestingly, the use of t-butyl hydroperoxide (TBHP)
produced no sulfoxide product under analogous conditions.
Lastly, similar attempts with aerial oxidation as well as by bubbling
molecular oxygen showed no conversion even after 24 h.
MO 189 (1b¢), MO 212 (2b¢), MO 184 (3b¢) and MO 165 (4b¢) (Fig. 3
and Table S1, ESI†). Similar short Ti–O(isopropoxide) distances
have been observed in other structurally characterized titanium(IV)
complexes namely, [N,N-bis(2-oxy-3,5-dimethylbenzyl)-N¢,N¢-
i
26
˚
˚
˚
dimethylethanediamine]Ti(O Pr)2 [1.838(1) A and 1.808(1) A]
i
27
and [tris(3,5-di-t-butyl-2-oxybenzyl)amine]Ti(O Pr) [1.778(4) A]
˚
complexes. The Ti–N(amine) distances [2.331(3)–2.394(3) A] in
the 1b–4b complexes, on the other hand, display more of a single
bond character as these distances are longer than the sum of the
25
˚
individual covalent radii of Ti and N (2.024 A).
Quite significantly, the 1b–4b complexes effectively carried out
the sulfoxidation reaction of organic sulfides to sulfoxides at
ambient temperature using H2O2 as an oxidant (Table 1 and
eqn (1)). Specifically, when alkyl and aryl sulfides were treated
with H2O2 in the presence of 0.5 mol% of the 1b–4b catalysts,
excellent conversions to sulfoxides were obtained within 30 min of
the reaction time. In order to establish the practical efficacy of the
sulfoxidation reaction, isolated yields for the all the substrates used
in the catalysis were obtained for a representative 2b precatalyst
(Table S5, ESI†). Notably, the 1b–4b complexes were highly active
in a more competitive solvent like methanol using aqueous H2O2
as the primary oxidant (Table S6, ESI†). The better performance
of 1b–4b in methanol as a solvent assumes importance in the back
drop of the fact that many of the reported sulfoxidation procedures
use health and environmentally hazardous chlorohydrocarbons as
A concentration dependence study showed that an increase
in catalyst loading of 1b from 0.05 mol% to 0.5 mol% led
2430 | Dalton Trans., 2010, 39, 2428–2440
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Table 1 Selected results of oxidation of thioether by aqueous H2O2 catalyzed by 1b–4b
Conversiona% (SO : SO2)b
Entry
1.
Substrate
Product
1b
2b
3b
4b
74 (3 : 1)
80 (4 : 1)
90 (9 : 1)
82 (5 : 1)
2.
3.
90 (10 : 1)
62 (9 : 1)
82 (5 : 1)
96 (48 : 1)
82 (16 : 1)
66 (17 : 1)
93 (31 : 1)
55 (>99 : 1)
4.
5.
82 (5 : 1)
68 (8 : 1)
90 (9 : 1)
91 (10 : 1)
64 (21 : 1)
79 (4 : 1)
89 (22 : 1)
65 (13 : 1)
6.
7.
50 (7 : 1)
76 (25 : 1)
77 (6 : 1)
52 (>99 : 1)
63 (31 : 1)
66 (13 : 1)
90 (10 : 1)
84 (21 : 1)
8.
95 (>99 : 1)
65 (>99 : 1)
28 (>99 : 1)
95 (>99 : 1)
59 (>99 : 1)
16 (>99 : 1)
76 (4 : 1)
54 (18 : 1)
25 (>99 : 1)
7 (>99 : 1)
9.
32 (>99 : 1)
12 (>99 : 1)
10.
a Reaction conditions: 2.00 mmol of substituted thioether, 2.00 mmol of H2O2, 2.00 mmol of internal standard (1,2-dichlorobenzene) and 1.00 ¥ l0-2 mmol
Ti catalyst, in CH3OH (5 mL) at room temperature (30 min). Products were quantified by GC analysis with respect to internal standard and identified by
GCMS analysis. b Ratio of sulfoxide to sulfone is given in parenthesis under conversion.
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to an increase in sulfoxide formation from 26% to 90%, after
which a decrease to 73% was observed at 1 mol% along with
sulfone formation (15%) at this catalyst concentration (Table S4,
ESI†). A similar trend is reflected in the time dependence study,
carried out on thioanisole by 1b, which showed an increase in
sulfoxide formation along with a much reduced sulfone buildup
with increase in time (Fig. S24, ESI†).
under “Ligand Assisted Catalysis” (LAC) conditions employing
in situ generation of the catalyst,5b,10b,10d,24,31 in the reaction
mixture quite unlike the case of the well-defined precatalyst 1b–4b
employed in the present study.
Further insight into the mechanism of the sulfoxidation reaction
by the 1b–4b complexes came from density functional theory stud-
ies. Specifically, the sulfoxidation of thioanisole by a representative
complex 4b was modeled at B3LYP/LANL2DZ, 6-31G(d) level of
theory by applying suitable modifications to the starting geometry
optimized 4b¢ structure, computed using atomic coordinates ob-
tained from X-ray analysis data of 4b, to generate the catalytically
relevant species, and which were subjected to subsequent geometry
optimization followed by single-point calculation to obtain the
desired stationary and the transition states of the catalytic cycle.
In this regard, an oxygen transfer mechanism has been proposed
for the sulfoxidation reaction as opposed to an electron transfer
mechanism, the possibility of which was ruled out based on
UV-visible spectroscopy studies. UV-visible spectroscopy studies
showed the absence of any d–d transitions and thereby negating the
existence of a paramagnetic species that may possibly result in an
electron transfer pathway. It is worth noting that the electrophilic
oxygen transfer from a d0 titanium-peroxo complexes to an organic
sulfides has been reported earlier.23a,32
Important is the comparison of the efficiency of our catalyst
1b–4b with other reported examples particularly with those of
the well-defined titanium based ones. Quite interestingly, the
precatalyst 1b–4b exhibited superior activity in comparison to a
structurally characterized titanium binapthyl-bridged salen based
precatalyst namely [2,2¢-bis(3-t-Bu-2-hydroxybenzylideneimino)-
1,1¢-binaphthyl]TiCl2,30 which exhibited 60% conversion for the
p-tolylmethyl sulfide in 1200 min at 1 mol% of the precatalyst
loading using H2O2 as an oxidant while the precatalyst 1b–
4b exhibited 54–95% conversion for the same substrate at half
the precatalyst loading of 0.5 mol% in 30 min. The precatalyst
1b–4b were, however, found to be less active than that of
the another {phenoxy, 2,2¢,2¢¢-[nitrilotris(methylene)]tris[6-(1,1-
dimethylethyl)}Ti(OiPr) precatalyst,15a which exhibited conversion
of 92% in 30–60 min for the phenylmethyl sulfide substrate using
H2O2 as oxidant at 1 mol% precatalyst loading as compared to
the 1b–4b precatalyst displaying 66–90% conversions for the same
substrate at 0.5 mol% of the precatalyst loading in 30 min. In this
context it is worth noting that many of the other reported examples
of titanium mediated sulfoxidation reactions were performed
The initiation of the catalytic cycle is proposed to proceed with
the formation of a titanium peroxo intermediate 4c¢ from the
reaction of 4b¢ with H2O2 (Scheme 2 and Fig. S8, ESI†) as opposed
to an alternative higher energy hydroperxo pathway (see Fig. S9,
Scheme 2 Mechanism of the sulfoxidation reaction catalyzed by a representative precatalyst 4b.
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Fig. 4 Computed free energy (DG) profile (in red) and total energy (E) with zero-point energy (ZPE) correction (E + ZPE) profile (in blue) along reaction
coordinate of the catalytic cycle of oxidation of thioanisole.
ESI†). The peroxo intermediate 4c¢ displayed distorted octahedral
geometry at titanium similar to that in 4b¢. The Ti–O(peroxo)
˚
˚
distances of 1.833 A and 1.836 A are shorter than the sum of
25
˚
the individual covalent radii of Ti and O (1.984 A). The peroxo
˚
moiety is characterized by a O1–O4 distance of 1.444 A that is
25
˚
slightly longer than a O–O single bond distance (1.32 A).
Significantly enough, crucial evidence in favor of the proposed
Ti–peroxo species came from mass spectrometric studies. It is
worth noting that the mild ionization technique like atmospheric
pressure chemical ionization (APCI) has become an important
tool in detecting the reaction intermediates in various catalytic
processes.33 After rigorous mass spectrometric experiments we
found that the APCI method in both the positive and negative
ion modes are more suitable for the detection of our proposed
Ti–peroxo species involved in the catalytic cycle. Indeed, the
convincing evidence in favor of the formation of the proposed
Ti–peroxo species were observed in both the positive and negative
ion modes for two representative precatalysts, 1b and 2b, when
treated with H2O2 (50 equivalent) in a CHCl3–CH3CN (10 : 1)
mixed solvent (see Fig. S10–S17, ESI†).
˚
Fig. 5 Fully optimized transition state 4d¢. Selected bond lengths (A)
and angles (◦): Ti1–O1 1.872, Ti1–O2 1.898, Ti1–O3 1.906, Ti1–O4
1.730, O1–O4 1.802, O1–S1 2.214, O1–Ti1–O4 59.9, O2–Ti1–O3 146.8,
S1–O1–O4 174.6.
The intermediate 4c¢ undergoes a nucleophilic attack at the
peroxo-O atom by the S atom of the thioanisole to give a transition
state 4d¢ that is 22.5 kcal mol-1 higher in energy (DG value) (Fig. 4
the O1 and O4 atoms of the peroxo moiety in 4d¢ relative to 4c¢
along with the concomitant decrease in electron density on the S1
center of the thioanisole moiety in the 4d¢ relative to that of the free
thioanisole molecule (Tables S19 and S20, ESI†). Quite expectedly,
the thioanisole moiety as a whole too showed similar reduction of
electron density upon coordination to the metal center (see Fig.
S18 and S19, ESI†).
Quite interestingly, similar nucleophilic attack by the S atom
of organic sulfide at the peroxy-O of a metal bound peroxo
species resulting in a linear S ◊ ◊ ◊ O ◊ ◊ ◊ O transition state having
an activation barrier of ca. 25 kcal mol-1 has earlier been
predicted by Jøgersen.35 The experimental support in favor of the
nucleophilic attack by S atom of organic sulfide on the peroxy-
O of the metal bound peroxo species, however, comes from the
˚
and 5). Significant elongation of the O1 ◊ ◊ ◊ O4 distance (1.802 A)
˚
observed in the 4d¢ structure relative to that in 4c¢ (1.444 A) is
in concurrence with the nucleophilic attack by the S atom of the
thioanisole occurring at the s*-orbital of the peroxo (O1–O4)
bond resulting in a linear S1 ◊ ◊ ◊ O1 ◊ ◊ ◊ O4 orientation. A similar
linear S ◊ ◊ ◊ O ◊ ◊ ◊ O type transition state has been proposed for the
asymmetric sulfoxidation reaction of imidazole based prochiral
sulfides.34 Indeed, the natural charge analysis of intermediate
4c¢ and the transition state 4d¢, revealed that the thioanisole-
S mediated nucleophilic attack at the peroxo-O moiety in the
transition state 4d¢ led to the increase in the electron density on
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observation of negative Hammett r value for the oxidation of
organic sulfides to sulfoxides by a variety of oxidants like H2O2 or
organic hydroperoxides.32a,36
cycle. Quite interestingly, the transition state 4h¢ is more of a
product-like transition state with its structure closely resembling
the final peroxo intermediate 4c¢ as reflected in the Ti–O and O–O
˚
˚
The complete cleavage of the O1 ◊ ◊ ◊ O4 bond of the peroxo
moiety occurs subsequent to the transition state 4d¢ resulting
bond lengths in 4h¢ [Ti1–O1 1.852 A, Ti1–O4 2.062 A, and O1–O4
˚
˚
˚
1.447 A] and 4c¢ [Ti1–O1 1.836 A, Ti1–O4 1.833 A, and O1–O4
˚
=
in a lower energy intermediate 4e¢ containing a Ti O moiety
1.444 A].
and a weakly coordinated methyl phenyl sulfoxide moiety (Fig.
The energy landscape of the catalytic cycle was modeled in
free energy (DG) as well as in total energy (DE) with zero-point
energy (ZPE) correction (DE + ZPE) surfaces (Fig. 4). Both the
free energy (DG) and the total energy with zero-point energy
correction (DE + ZPE) profiles showed the rate-determining step
of the catalytic cycle to be the nucleophilic attack of the S atom
of thioanisole on the s*-molecular orbital of the peroxo moiety
as represented by the transition state 4d¢ which displayed an
activation barrier of 22.5 kcal mol-1 on the free energy (DG) surface
and of 10.1 kcal mol-1 on the (DE + ZPE) surface. In this regard it
is worth noting that the free energy activation barrier for similar
sulfoxidation of imidazole based sulfide has been estimated to vary
in the range 14.7–24.5 kcal mol-1 depending upon the proposed
reaction pathways.34 Furthermore, the difference in energy at both
ends of the free energy profile show an overall negative free energy
(-36.3 kcal mol-1) for the oxidation of thioanisole with H2O2 to
methyl phenyl sulfoxide, thereby indicating its exergonic nature
and at the same time also pointing towards the irreversibility of
the sulfoxidation processes.
˚
S20, ESI†). The observed Ti–O4(oxo) distance [1.646 A], being
double bonded in character is significantly shorter than the other
Ti–O1(methyl phenyl sulfoxide) distance [2.079 A] of the weakly
bound methyl phenyl sulfoxide moiety in the 4e¢ intermediate.
Quite expectedly, the S1–O1 distance [1.564 A] falls between S–
O single (1.70 A) and double (1.56 A) bond distances. Our
attempt to detect the formation of the titanium coordinated
sulfoxide species by 1H NMR experiments, performed both at low
and ambient temperatures, proved to be unsuccessful suggesting
either a rapid exchange of the coordinated sulfoxide moiety or
the formation of the same in minute amounts occurring in the
catalytic cycle. Similar fast exchange of the coordinated sulfoxide
moiety had earlier been observed in the literature.37 Specifically,
˚
˚
25
˚
˚
1
the H NMR spectrum of a representative precatalyst, 1b, when
treated with H2O2 in the presence of thioanisole in CDCl3 at
room temperature, showed the formation of the partially oxidized
sulfoxide, as evidenced by a peak at 2.73 ppm and the fully oxidized
sulfone as observed by a peak at 3.05 ppm, in 3 : 1 ratio within
the first 5 min of the reaction time. It is worth noting that very
little shift was observed of the sulfoxide methyl resonances in the
reaction mixture with respect to its free form, thereby suggesting
either a rapid exchange in the NMR time-scale or the formation
in minute amounts in the catalytic cycle. However, complete
conversion to the fully oxidized sulfone product was seen in 15 min
of the reaction time. The analogous experiment performed at
low temperature of -40 ◦C showed much slower conversion with
similar formation of sulfone and sulfoxide products along with
unreacted sulfide in a 1 : 1 : 6 ratio within 5 min of the reaction
time. However, very little progress of the reaction was observed
even after 15 min of the reaction time as the ratio of sulfoxide,
sulfone and the unreacted sulfide slightly increased to be 1.6 : 1 : 5.3
in favor of the oxidized products.
Conclusions
In summary,
a series of titanium(IV) isopropoxide com-
plexes namely, [N,N¢-bis(2-oxo-3-R1-5-R2-phenylmethyl)-N,N¢-
bis(methylene-R3)-ethylenediamine]Ti(OiPr)2 [R1 = t-Bu, R2
=
Me, R3 = C7H5O2 (1b); R1 = R2 = t-Bu, R3 = C7H5O2 (2b);
R1 = R2 = Cl, R3 = C7H5O2 (3b) and R1 = R2 = Cl, R3 = C6H5
(4b)] that efficiently carry out sulfoxidation reactions of organic
sulfides at ambient temperature using environmentally friendly
aqueous H2O2 as an oxidant, have been designed. The catalytic
cycle modeled using density functional theory studies for the
reaction of thioanisole with H2O2 catalyzed by a representative
complex 4b suggests that the catalysis proceeds via a titanium
peroxo intermediate 4c¢ that undergoes nucleophilic attack by the
S atom of thioanisole at the s*-orbital of the peroxo moiety and
which also represents the rate-determining step of the catalytic
cycle displaying an activation barrier of 22.5 kcal mol-1. The APCI
mass spectrometry studies corroborate the formation a peroxo
intermediate in the catalysis cycle.
Further reaction of the titanium oxo intermediate 4e¢ with
another molecule of H2O2 results in the formation of a transition
state 4f¢ in which a proton transfer is seen to occur from the H2O2
molecule to the Ti1–O4 moiety (Fig. S21, ESI†). Consequently,
a much elongated Ti–O4 distance [1.729 A] was observed in the
transition state 4f¢ as compared to the same in the immediately
˚
˚
=
preceding 4e¢ species, [Ti1–O4(oxo) = 1.646 A], containing a Ti O
moiety.
Experimental
The transition state 4f¢ subsequently leads to a lower en-
ergy titanium–(hydroxo)(hydroperoxo) intermediate 4g¢ (Fig. S22,
ESI†). The Ti1–O4(hydroxo) [1.843 A] and the Ti1–
General procedures
˚
˚
O5(hydroperoxo) [1.896 A] distances are more consistent with a
single bond character.
All manipulations were carried out using a combination of
standard schlenk techniques and glove box. Solvents were purified
and degassed by standard procedures. The 2,4-di-t-butylphenol,
2-t-butyl-4-methylphenol, 2,4-di-chlorophenol, piperonal and
Ti(OiPr)4 were purchased from Sigma Aldrich, Germany and used
without any further purification. The N,N¢-bis(2-hydroxo-3,5-
di-chlorophenylmethyl)-N,N¢-dibenzylethylenediamine (4a) was
prepared by following a modified literature procedure.38 1H and
Finally, the last step involves a proton transfer between a
titanium bound hydroperoxo moiety to an adjacent titanium
bound hydroxo moiety via a transition state 4h¢ along with the
elimination of the much desired methyl phenyl sulfoxide product
(Fig. S23, ESI†). Additionally, the transition state 4h¢ eliminates a
molecule of H2O to regenerate back the starting titanium peroxo
intermediate 4c¢, whereby marking the completion of the catalytic
1
13C{ H} NMR spectra were recorded on a Varian 400 MHz NMR
2434 | Dalton Trans., 2010, 39, 2428–2440
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Table 2 X-Ray crystallographic parameters for 1b–4b
Compound
1b
2b
3b
4b
Lattice
Formula
Formula weight
Triclinic
Monoclinic
C61H84N2O8Ti
1021.20
Trigonal
Orthorhombic
C36H40Cl4N2O4Ti
754.40
C62H80N2O8Ti
1029.18
¯
P1
C19H20Cl2NO4Ti0.50
421.21
¯
Space group
P-21/c
R3c
P212121
˚
a/A
11.8560(3)
16.7553(6)
16.9088(6)
62.844(4)
86.881(3)
70.612(3)
2800.27(16)
2
19.743(4)
18.552(4)
16.993 (4)
90.000(17)
113.19(2)
90.000(17)
5721(2)
25.514(4)
25.514(2)
30.429(2)
90.00
90.00
120.00
11.1277(4)
15.5670(7)
21.1098(7)
90.00
90.00
90.00
˚
b/A
˚
c/A
a/◦
b/◦
g /◦
V/A
Z
3
˚
17 154(3)
36
3656.7(2)
4
4
T/K
150(2)
0.71073
1.221
0.209
25.00
25 227/9773
0.0389
150(2)
0.71073
1.186
0.204
25.00
28 748/9986
0.0997
150(2)
0.71073
1.468
0.560
25.00
150(2)
0.71073
1.370
0.567
25.00
21 722/6330
0.0864
˚
Radiation (l/A)
r(calcd.)/g cm-3
m(Mo Ka)/mm-1
q max/◦
Reflection collected/unique
R(int)
44 655/3359
0.2281
Data/restraints/parameters
R indices (all data)
9733/0/672
R1 = 0.0822
wR2 = 0.1307
R1 = 0.0488
wR2 = 0.1188
0.945
9986/0/666
R1 = 0.1315
wR2 = 0.1324
R1 = 0.0567
wR2 = 0.1112
0.885
3359/0/242
R1 = 0.1029
wR2 = 0.2152
R1 = 0.0853
wR2 = 0.2020
1.127
6330/0/428
R1 = 0.0913
wR2 = 0.0836
R1 = 0.0507
wR2 = 0.0711
0.962
Final R indices I > 2s(I)
GOF
Flack x parameter
—
—
—
0.0340 (0.0387)
1
1
spectrometer. H NMR peaks are labeled as singlet (s), doublet
(d), triplet (t) and septet (sept). Infrared spectra were recorded
on a Perkin Elmer Spectrum One FT-IR spectrometer. Mass
spectrometry measurements were done on a Micromass Q-Tof
spectrometer. X-Ray diffraction data were collected on a Bruker
P4 difractometer equipped with a SMART CCD detector. The
crystal data collection and refinement parameters are summarized
in Table 2. The structures were solved using direct methods and
standard difference map techniques, and were refined by full-
matrix least-squares procedures on F2 with SHELXTL (version
6.10).39 GC spectra were obtained on a PerkinElmer Clarus
600 equipped with a FID. GCMS spectra were obtained on a
PerkinElmer Clarus 600 T equipped with an EI source. APCI/MS
experiments were performed with a Varian Proctar 500-LCMS
instrument, with upper mass limit of m/z 2000, through direct
infusion via a syringe pump. Standard experimental conditions in
the LCMS was at the given capillary voltage 80 V, syringe pressure
as a white solid (0.718 g, 58%). H NMR (CDCl3, 400 MHz,
25 ◦C): d 10.4 (s, 2H, OH), 6.98 (s, 2H, C6H2{2-OH,3-C(CH3)3,5-
CH3}), 6.68 (s, 2H, C6H2{2-OH,3-C(CH3)3,5-CH3}), 6.67 (s, 2H,
C7H5O2), 6.60–6.57 (m, 4H, C7H5O2), 5.89 (s, 4H, C7H5O2),
3.60 (s, 4H, CH2), 3.38 (s, 4H, CH2), 2.62 (s, 4H, CH2), 2.22
(s, 6H, CH3), 1.40 (s, 18H, C(CH3)3). 13C{ H} NMR (CDCl3,
1
100 MHz, 25 ◦C): d 154.0 (C6H2{2-OH,3-C(CH3)3,5-CH3}),
147.9 (C7H5O2), 147.2 (C7H5O2), 136.6 (C6H2{2-OH,3-C(CH3)3,5-
CH3}), 130.6 (C7H5O2), 127.5 (C6H2{2-OH,3-C(CH3)3,5-
CH3}), 127.4 (C6H2{2-OH,3-C(CH3)3,5-CH3}), 126.9 (C6H2{2-
OH,3-C(CH3)3,5-CH3}), 122.9 (C7H5O2), 121.9 (C6H2{2-OH,3-
C(CH3)3,5-CH3}), 109.8 (C7H5O2), 108.1 (C7H5O2), 101.1
(C7H5O2), 58.9 (CH2), 58.2 (CH2), 50.1 (CH2), 34.7 (C(CH3)3),
29.7 (C(CH3)3), 20.9 (CH3). Melting point: 115–116 ◦C. IR (KBr
pellet cm-1): 3430 (m), 2913 (w), 2833 (s), 1608 (m), 1493 (s), 1444
(s), 1400 (w), 1365 (w), 1351 (w), 1249 (s), 1232 (s), 1103 (w), 1035
(s), 971 (w), 825 (w), 810 (w), 765 (s), 644 (w), 600 (w). HRMS
(ES): m/z 681.3911 [(ligand + H)]+, Calcd. 681.3904.
◦
10 Psi, temperature 320 C, flow rate 10 mL min-1, RF loading
80%, nebulizing gas, helium. Elemental analysis was carried out
on Thermo Quest FLASH 1112 SERIES (CHNS) Elemental
Analyzer. Melting points of the compounds were recorded on
a Buchi Melting Points B-545 instrument.
Synthesis of [N,N¢-bis(2-oxo-3-t-butyl-5-methylphenylmethyl)-
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine]Ti(OiPr)2
(1b)
To a solution of N,N¢-bis(2-hydroxo-3-t-butyl-5-methylphenyl-
methyl)-N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine
1a (0.204 g, 0.299 mmol) in toluene (ca. 10 mL), a solution
of Ti(OiPr)4 (0.169 g, 0.595 mmol) in toluene (ca. 1 mL) was
added. The resulting solution was stirred at 50 ◦C for 4 h after
which the volatiles were removed under reduced pressure. The
residue was washed with hexane (ca. 2 mL) and dried under
vacuum to obtain product 1b as a yellow solid (0.203 g, 80%).
1H NMR (CDCl3, 400 MHz, 25 ◦C): d 6.98 (d, 2H, 4JHH = 2 Hz,
Synthesis of N,N¢-bis(2-hydroxo-3-t-butyl-5-methylphenylmethyl)-
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine (1a)
A solution of N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenedi-
amine (0.603 g, 1.84 mmol), 2-t-butyl-4-methylphenol (0.602 g,
3.67 mmol) and aqueous formaldehyde (39% w/v, 0.605 g,
7.34 mmol) in methanol (ca. 30 mL) was refluxed for 24 h. The
white precipitate formed was filtered, washed with methanol (ca.
4 ¥ 20 mL) and then dried in vacuum to obtain product 1a
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 2428–2440 | 2435
©

View Article Online
C6H2O{3-C(CH3)3,5-CH3}), 6.76 (d, 2H, 3JHH = 7 Hz, C7H5O2),
(0.261 g, 0.341 mmol) in toluene (ca. 10 mL), a solution of
Ti(OiPr)4 (0.184 g, 0.648 mmol) was added. The resulting solution
was stirred at 50 ◦C for 4 h after which the volatiles were removed
under reduced pressure. The residue was washed with hexane
(ca. 2 mL) and dried under vacuum to obtain product 2b as
a yellow solid (0.283 g, 89%). 1H NMR (CDCl3, 400 MHz,
4
6.54 (d, 2H, JHH = 2 Hz, C6H2O{3-C(CH3)3,5-CH3}), 6.50 (d,
3
2H, JHH = 7 Hz, C7H5O2), 6.48 (s, 2H, C7H5O2), 5.96 (m,
3
4H, C7H5O2), 4.90 (sept, 2H, JHH = 7 Hz, OCH(CH3)2), 4.24
2
(d, 2H, JHH = 13 Hz, CH2), 4.12 (s, 4H, CH2), 3.31 (d, 2H,
2
2JHH = 13 Hz, CH2), 2.88 (d, 2H, JHH = 10 Hz, CH2), 2.35
25 ◦C): d 7.08 (d, 2H, JHH = 2 Hz, C6H2O2{3,5-C(CH3)3}),
4
2
(d, 2H, JHH = 10 Hz, CH2), 2.20 (s, 6H, CH3), 1.48 (s, 18H,
3
4
3
6.65 (d, 2H, JHH = 8 Hz, C7H5O2), 6.52 (d, 2H, JHH = 2 Hz,
C(CH3)3), 1.26 (d, 6H, JHH = 7 Hz, OCH(CH3)2), 1.13 (d, 6H,
C6H2O2{3,5-C(CH3)3}), 6.41 (d, 2H, 3JHH = 8 Hz, C7H5O2), 6.37
1
3JHH = 7 Hz, OCH(CH3)2). 13C{ H} NMR (CDCl3, 100 MHz,
25 ◦C): d 159.6 (C6H2O{3-C(CH3)3,5-CH3}), 147.7 (C7H5O2),
147.6 (C7H5O2), 136.8 (C7H5O2), 128.5 (C6H2O{3-C(CH3)3,5-
CH3}), 127.4 (C6H2O{3-C(CH3)3,5-CH3}), 126.3 (C7H5O2),
126.1 (C6H2O{3-C(CH3)3,5-CH3}), 125.4 (C6H2O{3-C(CH3)3,5-
CH3}), 124.0 (C6H2O{3-C(CH3)3,5-CH3}), 112.6 (C7H5O2), 108.1
(C7H5O2), 101.3 (C7H5O2), 77.7 (OCH(CH3)2), 59.7 (CH2),
58.9 (CH2), 44.9 (CH2), 35.0 (C(CH3)3), 30.6 (C(CH3)3), 26.9
(OCH(CH3)2), 26.6 (OCH(CH3)2), 20.9 (CH3). Melting point:
3
(s, 2H, C7H5O2), 5.87 (m, 4H, C7H5O2), 4.85 (sept, 2H, JHH
=
2
7 Hz, OCH(CH3)2), 4.15 (d, 2H, JHH = 13 Hz, CH2), 4.03 (s,
4H, CH2), 3.22 (d, 2H, 2JHH = 13 Hz, CH2), 2.74 (d, 2H, 2JHH
=
2
10 Hz, CH2), 2.31 (d, 2H, JHH = 10 Hz, CH2), 1.42 (s, 18H,
3
C(CH3)3), 1.20 (s, 18H, C(CH3)3), 1.12 (d, 6H, JHH = 7 Hz,
OCH(CH3)2), 1.07 (d, 6H, JHH = 7 Hz, OCH(CH3)2). 13C{ H}
NMR (CDCl3, 100 MHz, 25 ◦C): d 159.7 (C6H2O{3,5-C(CH3)3}),
147.6 (C7H5O2), 147.5 (C7H5O2), 138.9 (C6H2O{3,5-C(CH3)3}),
135.8 (C6H2O{3,5-C(CH3)3}), 129.2 (C7H5O2), 126.6 (C7H5O2),
126.0 (C6H2O{3,5-C(CH3)3}), 124.4 (C6H2O{3,5-C(CH3)3}),
123.6 (C6H2O{3,5-C(CH3)3}), 112.5 (C7H5O2), 108.1 (C7H5O2),
101.3 (C7H5O2), 77.7 (OCH(CH3)2), 60.0 (CH2), 59.4 (CH2),
46.2 (CH2), 35.3 (C(CH3)3), 34.3 (C(CH3)3), 31.9 (C(CH3)3), 30.6
(C(CH3)3), 26.9 (OC(CH3)2), 26.5 (OCH(CH3)2). Melting point:
3
1
◦
270–272 C dec. IR (KBr pellet cm-1): 3431 (m), 2964 (w), 2612
(w), 1608 (w), 1490 (s), 1467 (s), 1442 (s), 1360 (s), 1249 (s), 1125
(s), 1041 (m), 930 (m), 841 (m), 608 (m), 564 (m). Anal. Calcd.
for C48H64N2O8Ti: C, 68.23; H, 7.64, N, 3.32. Found: C, 68.53; H,
8.15, N, 3.37.
◦
279–282 C dec. IR (KBr pellet cm-1): 3446 (m), 3356 (m), 3118
Synthesis of N,N¢-bis(2-hydroxo-3,5-di-t-butylphenylmethyl)-
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine (2a)
(m), 2963 (s), 2865 (m), 2544 (s), 1658 (w), 1598 (w), 1503 (w),
1491 (m), 1441 (m), 1411 (w), 1392 (w), 1361 (w), 1270 (s), 1243
(s), 1203 (w), 1168 (w), 1124 (m), 1041 (m), 992 (w), 930 (m), 914
(w), 878 (w), 846 (s), 811 (w), 776 (w), 748 (w), 697 (w), 650 (w),
610 (m), 553 (m), 470 (m). Anal. Calcd. for C54H76N2O8Ti: C,
69.81; H, 8.25, N, 3.02. Found: C, 69.49; H, 8.37, N, 3.10.
A
solution of N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylene-
diamine (1.00 g, 3.08 mmol), 2,4-di-t-butylphenol (1.27 g,
6.15 mmol) and aqueous formaldehyde (39% w/v, 1.08 g,
13.1 mmol) in methanol (ca. 30 mL) was refluxed for 24 h. The
white precipitate obtained was filtered, washed with methanol
(ca. 4 ¥ 20 mL) and then dried in vacuum to obtain product
1
Synthesis of N,N¢-bis(2-hydroxo-3,5-di-chlorophenylmethyl)-
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine (3a)
2a as white solid (1.14 g, 49%). H NMR (CDCl3, 400 MHz,
25 ◦C): d 10.3 (s, 2H, OH), 7.13 (s, 2H, C6H2{2-OH,3,5-
C(CH3)3}), 6.73 (s, 2H, C6H2{2-OH,3,5-C(CH3)3}), 6.66-6.64 (m,
4H, C7H5O2), 6.57 (m, 2H, C7H5O2), 5.92 (s, 4H, C7H5O2),
3.62 (s, 4H, CH2), 3.40 (s, 4H, CH2), 2.65 (s, 4H, CH2),
A
solution of N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylene-
diamine (1.00 g, 3.05 mmol), 2,4-di-chlorophenol (0.998 g,
6.12 mmol) and aqueous formaldehyde (39% w/v, 1.01 g,
12.2 mmol) in methanol (ca. 30 mL) was refluxed for 24 h. The
white precipitate formed was filtered, washed with cold methanol
(ca. 4 ¥ 20 mL) and then dried in vacuum to obtain product 3a as
a white solid (1.20 g, 58%). 1H NMR (CDCl3, 400 MHz, 25 ◦C):
1.39 (s, 18H, C(CH3)3), 1.25 (s, 18H, C(CH3)3). 13C{ H}
1
NMR (CDCl3, 100 MHz, 25 ◦C): d 153.9 (C6H2{2-OH,3,5-
C(CH3)3}), 147.9 (C7H5O2), 147.2 (C7H5O2), 140.9 (C6H2{2-
OH,3,5-C(CH3)3}), 135.9 (C6H2{2-OH,3,5-C(CH3)3}), 130.6
(C7H5O2), 123.8 (C6H2{2-OH,3,5-C(CH3)3}), 123.2 (C6H2{2-
OH,3,5-C(CH3)3}), 123.1 (C7H5O2), 121.2 (C6H2{2-OH,3,5-
C(CH3)3}), 109.9 (C7H5O2), 108.2 (C7H5O2), 101.2 (C7H5O2), 59.3
(CH2), 58.1 (CH2), 50.2 (CH2), 35.0 (C(CH3)3), 34.3 (C(CH3)3),
31.9 (C(CH3)3), 29.8 (C(CH3)3). Melting point: 141–143 ◦C. IR
(KBr pellet cm-1): 3396 (m), 2956 (s), 2902 (s), 2864 (s), 1600 (m),
1501 (m), 1489 (m), 1441 (s), 1388 (w), 1363 (w), 1352 (w), 1242
(s), 1208 (w), 1164 (w), 1124 (w), 1096 (w), 1072 (w), 1036 (s),
994 (w), 928 (m), 881 (w), 845 (w), 805 (w), 774 (w), 761 (w), 723
(w), 684 (w), 649 (w). HRMS (ES): m/z 765.4857 [(ligand + H)]+,
Calcd. 765.4843.
4
d 11.4 (s, 2H, OH), 7.25 (d, 2H, JHH = 2 Hz, C6H2{2-OH,3,5-
4
Cl2}), 6.81 (d, 2H, JHH = 2 Hz, C6H2{2-OH,3,5-Cl2}), 6.73 (d,
3
2H, JHH = 8 Hz, C7H5O2), 6.65 (s, 2H, C7H5O2), 6.58 (d, 2H,
3JHH = 8 Hz, C7H5O2), 5.96 (s, 4H, C7H5O2), 3.64 (s, 4H, CH2),
1
3.44 (s, 4H, CH2), 2.63 (s, 4H, CH2). 13C{ H} NMR (CDCl3,
100 MHz, 25 ◦C): d 152.2 (C6H2{2-OH,3,5-Cl2}), 148.2 (C7H5O2),
147.7 (C7H5O2), 129.1 (C6H2{2-OH,3,5-Cl2}), 129.0 (C7H5O2),
126.9 (C6H2{2-OH,3,5-Cl2}), 123.9 (C6H2{2-OH,3,5-Cl2}), 123.8
(C6H2{2-OH,3,5-Cl2}), 123.0 (C7H5O2), 121.7 (C6H2{2-OH,3,5-
Cl2}), 109.6 (C7H5O2), 108.5 (C7H5O2), 101.4 (C7H5O2), 58.9
(CH2), 57.9 (CH2), 50.2 (CH2). Melting point: 175–176 ◦C. IR
(KBr pellet cm-1): 3459 (w), 3070 (w), 2896 (w), 2842 (w), 2597
(w), 1670 (w), 1599 (m), 1501 (s), 1452 (s), 1391 (m), 1378 (m),
1283 (m), 1250 (s), 1232 (m), 1170 (m), 1103 (m), 1044 (s), 933
(m), 884 (m), 865 (m), 849 (m), 806 (m), 725 (s), 661 (w), 547
(w), 494 (w). HRMS (ES): m/z 677.0806 [(ligand + H)]+, Calcd.
677.0780.
Synthesis of [N,N¢-bis(2-oxo-3,5-di-t-butylphenylmethyl)-N,N¢-
bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine]Ti(OiPr)2 (2b)
To a solution of N,N¢-bis(2-hydroxo-3,5-di-t-butylphenylmethyl)-
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine
2a
2436 | Dalton Trans., 2010, 39, 2428–2440
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Synthesis of [N,N¢-bis(2-oxo-3,5-di-chlorophenylmethyl)-N,N¢-
Synthesis of [N,N¢-bis(2-oxo-3,5-di-chlorophenylmethyl)-N,N¢-
bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine]Ti(OiPr)2 (3b)
dibenzylethylenediamine]Ti(OiPr)2 (4b)
To a solution of N,N¢-bis(2-hydroxo-3,5-di-chlorophenylmethyl)-
To a solution of N,N¢-bis(2-hydroxo-3,5-di-chlorophenylmethyl)-
N,N¢-dibenzylethylenediamine 4a (0.205 g, 0.347 mmol) in toluene
(ca. 5 mL), a solution of Ti(OiPr)4 (0.196 g, 0.614 mmol) in
toluene (ca. 1 mL) was added. The resulting solution was stirred
at 50 ◦C for 4 h after which the volatiles were removed under
reduced pressure. The residue was washed with hexane (ca. 2 mL)
and dried under vacuum to obtain product 4b as a yellow solid
(0.208 g, 80%). 1H NMR (CDCl3, 400 MHz, 25 ◦C): d 7.33-7.31
(m, 6H, C6H5), 7.28 (d, 2H, 4JHH = 2 Hz, C6H2O{3,5-Cl2}), 7.08
(m, 4H, C6H5), 6.79 (d, 2H, 4JHH = 2 Hz, C6H2O{3,5-Cl2}), 5.18
(sept, 2H, 3JHH = 6 Hz, OCH(CH3)2), 4.29 (d, 2H, 2JHH = 13 Hz,
N,N¢-bis(1,3-benzodioxol-5-ylmethyl)ethylenediamine
3a
(0.302 g, 0.445 mmol) in toluene (ca. 10 mL), a solution of
Ti(OiPr)4 (0.251 g, 0.883 mmol) in toluene (ca. 1 mL) was added.
The resulting solution was stirred at 50 ◦C for 4 h after which the
volatiles were removed under reduced pressure. The residue was
washed with hexane (ca. 3 mL) and dried under vacuum to obtain
1
product 3b as a yellow solid (0.242 g, 65%). H NMR (CDCl3,
400 MHz, 25 ◦C): d 7.29 (d, 2H, 4JHH = 3 Hz, C6H2O{3,5-Cl2}),
6.84 (d, 2H, 4JHH = 3 Hz, C6H2O{3,5-Cl2}), 6.79 (d, 2H, 3JHH
=
8 Hz, C7H5O2), 6.57 (s, 2H, C7H5O2), 6.55 (s, 2H, C7H5O2), 5.99
3
3
(m, 4H, C7H5O2), 5.19 (sept, 2H, JHH = 6 Hz, OCH(CH3)2),
CH2), 4.19 (s, 4H, CH2), 3.41 (d, 4H, JHH = 13 Hz, CH2), 2.62
2
2
2
4.25 (d, 2H, JHH = 14 Hz, CH2), 4.13 (s, 4H, CH2), 3.43 (d,
(d, 2H, JHH = 11 Hz, CH2), 2.44 (d, 2H, JHH = 11 Hz, CH2),
3 3
2
2
2H, JHH = 14 Hz, CH2), 2.61 (d, 2H, JHH = 11 Hz, CH2),
1.33 (d, 6 H, JHH = 6 Hz, OCH(CH3)2), 1.30 (d, 6H, JHH
=
◦
2
3
1
2.42 (d, 2H, JHH = 11 Hz, CH2), 1.32 (d, 2H, JHH = 6 Hz,
6 Hz, OCH(CH3)2). 13C{ H} NMR (CDCl3, 100 MHz, 25 C): d
157.9 (C6H2O{3,5-Cl2}), 132.5 (C6H2O{3,5-Cl2}), 132.4 (C6H5),
129.5 (C6H5), 128.6 (C6H5), 128.5 (C6H5), 128.3 (C6H2O{3,5-
Cl2}), 126.8 (C6H2O{3,5-Cl2}), 122.7 (C6H2O{3,5-Cl2}), 121.3
(C6H2O{3,5-Cl2}), 79.9 (OCH(CH3)2), 59.3 (CH2), 57.3 (CH2),
47.9 (CH◦2), 26.2 (OCH(CH3)2), 25.9 (OCH(CH3)2). Melting point:
229–230 C dec. IR (KBr pellet cm-1): 3436 (m), 3063 (w), 3028
(w), 2966 (w), 2924 (w), 2860 (w), 2377 (w), 1583 (w), 1462 (s), 1441
(s), 1374 (w), 1312 (m), 1217 (w), 1178 (w), 1125 (m), 1070 (w),
1016 (m), 987 (m), 869 (m), 785 (w), 769 (m), 732 (w), 704 (m), 623
(w), 613 (w), 570 (w), 485 (m). Anal. Calcd. for C36H40Cl4N2O4Ti:
C, 57.32; H, 5.34, N, 3.71. Found: C, 56.98; H, 5.27,
N, 3.82.
3
1
OCH(CH3)2), 1.28 (d, 2H, JHH = 6 Hz, OCH(CH3)2). 13C{ H}
NMR (CDCl3, 100 MHz, 25 ◦C): d 157.8 (C6H2O{3,5-Cl2}),
147.9 (C7H5O2), 147.8 (C7H5O2), 129.4 (C6H2O{3,5-Cl2}),
128.2 (C6H2O{3,5-Cl2}), 126.7 (C7H5O2), 125.9 (C6H2O{3,5-
Cl2}), 125.8 (C6H2O{3,5-Cl2}), 122.6 (C6H2O{3,5-Cl2}), 121.3
(C7H5O2), 112.3 (C7H5O2), 108.3 (C7H5O2), 101.4 (C7H5O2),
79.8 (OCH(CH3)2), 58.9 (CH2), 57.2 (CH2), 47.7 (CH2), 26.1
(OCH(CH3)2), 25.8 (OCH(CH3)2). Melting point: 261–262 ◦C
dec. IR (KBr pellet cm-1): 3437 (m), 2967 (m), 2901 (w), 1503
(m), 1490 (s), 1461 (s), 1443 (s), 1376 (w), 1362 (m), 1319 (m),
1300 (m), 1240 (m), 1217 (w), 1177 (w), 1127 (m), 1040 (m),
1022 (m), 928 (w), 864 (s), 779 (s), 755 (m), 592 (w), 572 (w), 534
(w), 503 (w), 482 (w). Anal. Calcd. for C38H40Cl4N2O8Ti:
C, 54.18; H, 4.79, N, 3.33. Found: C, 53.77; H, 5.69,
N, 3.06.
Computational methods
Density functional theory (DFT) calculations were performed
using GAUSSIAN 0340 suite of quantum chemical programs
on the 1b–4b complexes, with respective computed structures
designated by 1b¢–4b¢ (Fig. S4–S7, ESI†) and on the various
derived intermediates and transition states namely, 4c¢–4h¢, per-
taining to a proposed mechanistic pathway. The Becke three
parameter exchange functional in conjunction with Lee–Yang–
Parr correlation functional (B3LYP) has been employed in this
study.41 The LANL2DZ basis set was used for the Ti atom while all
other atoms are treated with 6-31G(d) basis set.37,42 The geometry
of the transition state structures were optimized in the first order
saddle point using Gaussian 03 program suite. Stationary points
were characterized as minima by evaluating Hessian indices on the
respective potential energy surfaces using tight SCF convergence
(10-8 a.u). Fully optimized transition state structures have been
characterized by a single imaginary frequency, while rest of
the optimized structures possesses only real frequency. Natural
bond orbital (NBO) analysis43 was performed using the NBO 3.1
programs implemented in the Gaussian 03 package (Tables S7–
S16, ESI†).
Synthesis of N,N¢-bis(2-hydroxo-3,5-di-chlorophenylmethyl)-
N,N¢-dibenzylethylenediamine (4a)
A
solution of N,N¢-dibenzylethane-1,2-diamine (1.00 g,
4.16 mmol), 2,4-dichlorophenol (1.36 g, 8.34 mmol) and formalde-
hyde (39% w/v, 1.36 g, 16.4 mmol) in methanol (ca. 20 mL)
was refluxed for 24 h. A white precipitate was formed which
was filtered and washed with methanol (ca. 4 ¥ 20 mL) and
then dried over vacuum to obtain product 4a as a white powder
(2.03 g, 83%). H NMR (CDCl3, 400 MHz, 25 ◦C): d 11.5 (S,
1
3
2H, OH), 7.32–7.30 (m, 6H, C6H5), 7.25 (d, 4H, JHH = 8 Hz,
4
C6H5), 7.14 (d, 2H, JHH = 2 Hz, C6H2{2-OH,3,5-Cl2}), 6.80
4
(d, 2H, JHH = 2 Hz, C6H2{2-OH,3,5-Cl2}), 3.64 (s, 4H, CH2),
1
3.54 (s, 4H, CH2), 2.63 (s, 4H, CH2). 13C{ H} NMR (CDCl3,
◦
100 MHz, 25 C): d 152.3 (C6H2{2-OH,3,5-Cl2}), 135.4 (C6H5),
129.5 (C6H5), 129.2 (C6H5), 129.1 (C6H5), 128.4 (C6H2{2-OH,3,5-
Cl2}), 127.0 (C6H2{2-OH,3,5-Cl2}), 124.0 (C6H2{2-OH,3,5-Cl2}),
123.9 (C6H2{2-OH,3,5-Cl2}), 121.8 (C6H2{2-OH,3,5-Cl2}), 59.2
(CH2), 58.2 (CH2), 50.3 (CH2). Melting point: 169–171 ◦C. IR
Data (KBr pellet cm-1): 3429 (m), 3079 (w), 3028 (w), 2925
(w), 2856 (w), 2542 (w), 1600 (w), 1452 (s), 1392 (w), 1362 (w),
1272 (w), 1249 (w), 1211 (w), 1169 (m), 1065 (w), 1019 (w), 966
(w), 864 (m), 846 (m), 749 (s), 728 (s), 705 (m), 672 (w), 612
(w), 483 (w). HRMS (ES): m/z 589.0973 [(ligand + H)]+, Calcd.
589.0983.
General procedure for sulfoxidation catalysis
In a typical run, to a solution of thioether (2.00 mmol), catalyst
1b–4b (0.01 mmol) and internal standard 1,2-dichlorobenzene
(2.00 mmol) in dry degassed methanol (5 mL), 50% aq. H2O2
(2.00 mmol) was added and the reaction mixture was allowed
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to stirred at room temperature under nitrogen atmosphere for
30 min. The products in the solution were quantified by gas
chromatography (PerkinElmer Clarus 600) and subsequently
identified by GC-MS (PerkinElmer Clarus 600 T) analysis.
CHCl3–CH3CN (10 : 1) mixture was injected in the LCMS(APCI)
instrument and the spectrum was collected in both positive and
negative ion modes. Specifically, the positive ion mode spectrum
of 1b and H2O2 showed a peak at m/z 759 (10% of the base peak)
corresponding to the desired Ti-peroxo species (see Fig. S10–S11,
ESI†). Additionally, a peak at m/z 680 (100%) of ligand 1a, a
cleaved product, and a peak at m/z 785 (25%) corresponding to
the cationic species derived from 1b by loss of one OiPr moiety were
observed. Similarly, the spectrum of 1b and H2O2 in the negative
ion mode showed the Ti-peroxo species at m/z 758 (20%) along
with a more intense peak at m/z 793 (35%) that corresponded to
its Cl- adduct (Fig. S12–S13, ESI†). In this regard it should be
mentioned that similar Cl- adducts have been reported previously
in the literature.44
The APCI/MS in positive ion mode spectrum of 2b and
H2O2 showed a small peak at m/z 842 (2% of the base peak)
corresponding to the desired Ti-peroxo species. Additionally, a
peak at m/z 765 (100%) of the ligand 2a, a cleaved product, and
a peak at m/z 870 (2.5%) corresponding to the cationic species
derived from 2b by loss of one OiPr moiety were observed (see
Fig. S14–S15, ESI†). As observed earlier, the spectrum of 2b and
H2O2 in the negative ion mode showed the Ti-peroxo species at
m/z 842 (10%) along with an intense peak at m/z 877 (25%) that
corresponded to its Cl- adduct (see Fig. S16–S17, ESI†).
Control catalysis experiment performed in absence of H2O2
A solution of thioether (2 mmol), catalyst 1b (0.01 mmol) and
internal standard 1,2-dichlorobenzene (2 mmol) in dry degassed
methanol (5 mL) was allowed to stirred at room temperature
under nitrogen atmosphere for 30 min in the absence of any added
H2O2. The reaction mixture was analyzed by gas chromatography
(PerkinElmer Clarus 600) which showed no formation of the
sulfoxide product. The same blank experiment when carried out in
presence of air also showed no formation of the desired sulfoxide
product.
Control catalysis experiment performed using molecular oxygen as
oxidant
To a solution of thioether (2 mmol), catalyst 1b (0.01 mmol) and
internal standard 1,2-dichlorobenzene (2 mmol) in dry degassed
methanol (5 mL), oxygen gas was bubbled through and the
reaction mixture was allowed to stir at room temperature for
30 min. The reaction mixture was analyzed by gas chromatography
and which showed no formation of the desired sulfoxide product.
1H NMR experiment for detecting coordinated sulfoxide species at
room temperature
Catalyst recovery experiment
To a solution of thioether (6.00 mmol), catalyst 2b (0.03 mmol)
in dry degassed methanol (5 mL), 50% aq. H2O2 (6.00 mmol)
was added and the reaction mixture was allowed to stir at room
temperature under nitrogen atmosphere for 30 min. The volatiles
were removed under reduced pressure and the product mixture was
analyzed by 1H NMR spectra which showed no peak characteristic
of the precatalyst 2b.
H2O2 (12 mL, 0.212 mmol) was added to a mixture of 1b (0.029 g,
0.035 mmol) and thioanisole (0.013 g, 0.106 mmol) in CDCl3
(0.7 mL) in an NMR tube and the reaction was monitored by 1H
NMR spectroscopy at room temperature. Within the first 5 min,
the formation of sulfoxide, characterized by a peak at 2.73 ppm
and the sulfone characterized by a peak at 3.05 ppm, in 3 : 1 ratio
was observed and complete conversion to sulfone was seen in
15 min. The fact that no significant shift of the sulfoxide methyl
proton, between its coordinated and free forms, was observed in
UV-Vis experiment
1
the H NMR spectrum suggested the rapid exchange between
In order to investigate the possibility of the sulfoxidation reaction
proceeding via an electron transfer process the following UV-
visible experiment was performed. To a 1 ¥ 10-2 M solution of
1b in CHCl3 (1 mL) was added 1 mL of 2 ¥ 10-2 M methanolic
solution of H2O2 and 1 mL methanol and the UV-visible spectrum
was recorded at room temperature. In a subsequent experiment, to
a mixture of 1 ¥ 10-2 M solution of 1b in a CHCl3 (1 mL) and 1 mL
of 2 ¥ 10-2 M methanolic solution of H2O2, was added 1 mL of 2 ¥
10-2 M methanolic solution of thioanisole and the reaction was
monitored by UV-visible spectroscopy in different time intervals
up to 35 min. No additional bands corresponding to any redox
intermediate or any radical species were observed upon addition
of thioanisole, thereby ruling out the possibility of an electron
transfer mechanism occurring in the sulfoxidation reaction.32b
the coordinated and the free sulfoxide at room temperature or
the formation of the coordinated sulfoxide species in trace
amounts.
1H NMR experiment for detecting coordinated sulfoxide species at
-40 ◦C
H2O2 (12 mL, 0.212 mmol) was added to a mixture of 1b (0.030 g,
0.035 mmol) and thioanisole (0.013 g, 0.106 mmol) in CDCl3
(0.7 mL) in an NMR tube and the reaction was monitored by 1H
NMR spectroscopy at -40 ◦C. The formation of both sulfoxide
and sulfone was observed in the reaction mixture as their methyl
resonances appeared at 2.79 ppm and 3.29 ppm respectively along
with the unreacted sulfide in 1 : 1 : 6 ratios after 5 min of the
reaction time. However, the observation of no significant shift
of the sulfoxide methyl proton may be ascribed to the rapid
exchange between the coordinated and the free sulfoxide even at
low temperature (-40 ◦C). Concentration of sulfide, sulfoxide and
sulfone were determined by the integration of the methyl group
signals in the recorded spectra.
APCI/MS experiment for detection of the proposed peroxo species
The APCI/MS experiments were performed in both positive and
negative ion modes to detect the proposed Ti(IV)-peroxo species of
the sulfoxidation catalytic cycle by 1b–4b. In a typical experiment,
a solution of the precatalyst 1b or 2b, and H2O2 (50 equivalent) in
2438 | Dalton Trans., 2010, 39, 2428–2440
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Acknowledgements
We thank DST, New Delhi, for financial support of this research.
We are grateful to the National Single Crystal X-ray Diffraction
Facility and Sophisticated Analytical Instrument Facility (SAIF)
at IIT Bombay, India, for the crystallographic and other char-
acterization data. Computational facilities from the IIT Bombay
Computer Center are gratefully acknowledged. MP thanks CSIR,
New Delhi, for research fellowship.
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