Synthesis of Titanium Complexes Supported by Carbinolamide- And Amide-Containing Ligands Derived from Ti(NMe2)4-Mediated Selective Amidations of Carbonyl Groups

Article abstract of DOI:10.1021/acs.inorgchem.0c01831

An efficient strategy for the syntheses of a series of titanium complexes has been developed. This protocol features the employment of Ti(NMe2)4 both as the metal center to trigger the deprotonation of the ligands and as an amine source to proceed the amidation reactions of carbonyl functionalities of the ligands. Treatment of Ti(NMe2)4 with a ligand HL1 (HL1 = 2,2′-(((2-hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) results in the formation of Ti(L1′)(NMe2) (1) (H3L1′ = N1-(2-((2-(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthalamide). One important feature regarding the synthesis of 1 is the occurrence of the in situ metal-ligand reaction between Ti(NMe2)4 and HL1, leading to the simultaneous formations of carbinolamide and amide scaffolds. Another prominent feature in terms of the preparation of 1 is the achievement of the selective ring-opening reaction of one of the two phthalimide units of the HL1 ligand, affording carbinolamide and amide functionalities within one ligand set. The developed methodology characterizes an ample substrate scope. The selective amidation reactions of the carbonyl groups have been realized for a series of analogous ligands HL2-HL7. Density functional theory calculations were employed to disclose the mechanisms for the formation of 1-7, and the details for the selective ring-opening reactions of the phthalimide unit were uncovered.

Full text of DOI:10.1021/acs.inorgchem.0c01831

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Article
Synthesis of Titanium Complexes Supported by Carbinolamide- and
Amide-Containing Ligands Derived from Ti(NMe2)4‑Mediated
Selective Amidations of Carbonyl Groups
Shengwang Xia, Zhilei Jiang, Yuan Huang, Dawei Li, Yanfeng Cui, Yahong Li,* and Yuanzhi Xia*
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ABSTRACT: An efficient strategy for the syntheses of a series of titanium complexes has been developed. This protocol features the
employment of Ti(NMe2)4 both as the metal center to trigger the deprotonation of the ligands and as an amine source to proceed
the amidation reactions of carbonyl functionalities of the ligands. Treatment of Ti(NMe2)4 with a ligand HL1 (HL1 = 2,2′-(((2-
hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) results in the formation of Ti(L1′)(NMe2) (1) (H3L1′ =
N1-(2-((2-(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthala-
mide). One important feature regarding the synthesis of 1 is the occurrence of the in situ metal−ligand reaction between Ti(NMe2)4
and HL1, leading to the simultaneous formations of carbinolamide and amide scaffolds. Another prominent feature in terms of the
preparation of 1 is the achievement of the selective ring-opening reaction of one of the two phthalimide units of the HL1 ligand,
affording carbinolamide and amide functionalities within one ligand set. The developed methodology characterizes an ample
substrate scope. The selective amidation reactions of the carbonyl groups have been realized for a series of analogous ligands HL2−
HL7. Density functional theory calculations were employed to disclose the mechanisms for the formation of 1−7, and the details for
the selective ring-opening reactions of the phthalimide unit were uncovered.
researches for exploring versatile synthetic protocols for N-
containing compounds continue to attract intense atten-
tion.29−34
Amide bond is a crucial functional group, which is
ubiquitous in many important compounds, such as proteins,
drugs, fertilizers, and plastics. Traditionally, amides are mainly
prepared by amidation reactions of a range of starting materials
including carboxylic acid derivatives,35−41 aldehydes,42−44 and
alcohols.45−50 Another two common methods for the synthesis
of amides involve the hydrolysis of nitriles51−54 and rearrange-
INTRODUCTION
■
Titanium complexes continue to attract enormous interest
from many groups around the world.1−9 Such complexes have
been employed as catalysts for a plethora of reactions including
olefin polymerization,10 Sharpless epoxidation,11 hydroami-
noalkylation,12−15 aldol and allylic additions to carbonyl
compounds,16,17 carbonate formation from CO2,18 and multi-
component couplings.19,20 Our recent studies revealed that
Ti(NMe2)4 could mediate the in situ metal−ligand reactions,21
affording the new nitrogen-containing compounds that could
not be accessible via intuitive approaches.
Nitrogen-containing molecules are among the most
important compounds possessing interesting physiological
and biological activity. Most of pharmaceuticals contain
nitrogen atoms.22−26 As indicated in the “Top 200
pharmaceutical products by prescriptions in 2019”,27,28 most
of pharmaceuticals are N-containing molecules. Thus, the
Received: June 21, 2020
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Scheme 1. Synthesis of Compound 1
ment of oxime.55−57 Because of the broad applications of
amides in both industrial and medicinal chemistry, the
development of versatile methods for preparing amides is
still an attractive research field.
Ti(NMe2)4 could mediate the C−N and C−C bond formation
reactions.21,81 Treatment of Ti(NMe2)4 with HL1 in toluene
afforded (dimethylamido)titanium complex Ti(L1′)(NMe2)
(1) (Scheme 1, H3L1′ = N1-(2-((2-(1-(dimethyl amino)-1-
hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)-
ethyl)-N2,N2-dimethylphthal-amide), which was isolated as a
pure red solid after recrystallization in toluene.
Description of Crystal Structure of 1. Single-crystal X-
ray diffraction studies reveal that complex 1 crystallizes in the
̅
triclinic P1 space group (Table S1). The ORTEP representa-
tion of the structure of 1 is shown in Figure 1. The crystal
structure of 1 exhibits several interesting features: (i) among
four carbonyl groups (C10, C17, C22, and C25), only two
carbonyl groups were involved in the reactions with −NMe2
moiety; (ii) the ring-opening process only occurred in one five-
Carbinolamide is the important structural motif present in
small molecule natural products,58−60 such as zampanolide52,61
and ansamitocin.62−64 Carbinolamide is conventionally pre-
pared by the reaction of amide and aldehyde.65−71 It plays vital
roles in the activity of bicymycin.72−75 Moreover, the unstable
nature of carbinolamide renders it to be precursor for the
preparation of more complicated N-containing compounds.76
Intrigued by the remarkable functionalities of amides and
carbinolamides in various fields, we are interested in
developing efficient protocols for preparing amides and
carbinolamides. In this work, we demonstrate a new strategy
that involving Ti(NMe2)4-mediated amidations of carbonyl
groups (Scheme 1), achieving both amide and carbinolamide
motifs in a one-pot reaction.
In our previous report, we disclosed that the −NMe2 group
of Ti(NMe2)4 could activate C−O bond.21 We anticipate that
the CO bond and the C−N bond of an amide might be
activated by the −NMe2 group of Ti(NMe2)4 too. To examine
this hypothesis, we selected a ligand 2,2′-(((2-hydroxybenzyl)
azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione)
(HL1, Scheme 1) and conducted the reaction between
Ti(NMe2)4 and HL1. Gratifyingly, activations of the CO
bond and the C−N bond of the amide proceeded smoothly,
leading to the simultaneous formation of new amide and
carbinolamide scaffolds (Scheme 1). The concept for the
generation of the carbinolamide and the new amide scaffolds
via Ti(NMe2)4-mediated amidations of carbonyl groups opens
a new perspective for synthesizing bioactive molecules in a
simple, efficient, and selective manner.
RESULTS AND DISCUSSION
■
Synthesis of 1. The chemistry of titanium complexes
generated by the reactions between Ti(NMe2)4 and proto-
nated ligands has been well developed.2,77−80 It was found that
Figure 1. ORTEP representation of the structure of compound 1
(30% probability). Hydrogen atoms are omitted for clarity.
B
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Table 1. Selected Bond Lengths (Å) and Angles (deg) for Complexes 1−6
compound
1
2
3
4
5
6
Ti−O1
Ti−O2
Ti−O5
Ti−N1
Ti−N2
2.0736(11)
1.8571(11)
1.8844(11)
2.1152(13)
2.4052(13)
2.094(2)
1.836(2)
2.042(3)
2.108(3)
2.369(3)
2.108(3)
1.863(3)
1.879(3)
2.108(3)
2.368(3)
2.109(2)
1.855(2)
1.883(2)
2.119(3)
2.379(3)
2.1236(16)
1.8584(15)
1.8721(16)
2.1146(18)
2.3717(18)
2.089(4)
1.856(4)
1.880(4)
2.109(4)
2.377(4)
a
O2−Ti−O1
O2−Ti−O5
O5−Ti−O1
O2−Ti−N1
O1−Ti−N1
85.95(5)
97.64(5)
169.53(5)
160.22(5)
81.74(5)
92.03(5)
87.01(10)
96.39(11)
163.38(11)
160.32(12)
83.46(11)
88.20(12)
84.20(11)
102.09(11)
166.54(11)
158.33(12)
80.92(11)
89.56(12)
85.92(10)
100.29(11)
167.70(10)
159.38(12)
81.13(11)
89.81(11)
86.32(6)
99.90(7)
167.53(6)
159.53(7)
81.25(7)
89.60(7)
86.55(16)
99.39(18)
169.16(17)
158.98(19)
81.70(16)
89.83(18)
b
c
d
O5−Ti−N1
a
b
c
d
Ti−N7. O2−Ti−N7 N7−Ti−O1. N7−Ti−N1.
membered ring constructed by N1, C10, C11, C16, and C17,
with the other five-membered ring being unaffected; (iii) the
attack of one carbonyl (C17) group by −NMe2 group led to
the formation of a new amide, whereas the activation of
another carbonyl (C22) motif initiated by Ti(NMe2)4
produced a carbinolamide moiety. Thus, the formations of
two C−N bonds (C17−N5, C22−N4) and cleavage of a C−N
bond (C17−N1) generated a new ligand [L1′]3− as an
unsymmetrical molecule. The metal center of 1 is hexa-
coordinated by three oxygen atoms and two nitrogen atoms
from the [L1′]3− ligand and one nitrogen atom from −NMe2
group. The TiIV center displays distorted octahedron geometry.
The bond length of Ti−O1 is 2.0736 Å, which is apparently
longer than those of Ti−O2 (1.8571 Å) and Ti−O5 (1.8844
Å) bonds (Table 1).
Syntheses and Structures of 2−7. Motivated by the
successful preparation of 1 which possesses intriguing
structural features, we endeavored to expand the scope of
the reaction. We next investigated the reactions of Ti(NMe2)4
with a series of ligands (HL2−HL7), with the results being
summarized in Scheme 2. We introduced an electron-donating
methoxy group at the ortho-, meta-, and para-positions of the
hydroxyl group of phenol ring (HL3−HL5) and attached an
electron-withdrawing chloride substituent at the meta- and
para-positions (HL6 and HL7). It is interesting to find that the
electronic natures of the substituents could not influence the
ring-opening reactions and the formations of carbinolamides
and amides, as characterized by X-ray diffraction studies. X-ray
single-crystal diffraction analyses revealed that structures of 3,
4, 5, and 6 are similar to that of 1 (Tables S1−S6). We failed
to grow the crystal of 7, whereas the characterization of 7 by
NMR spectroscopy and elemental analysis indicated that it is
isomorphous to 6. To explore if the phenol moiety in the HL1
ligand could be replaced by other donors, 2,2′-(((1H-pyrrol-2-
yl)methyl)azanediyl)bis(ethane-2,1-diyl)bis(isoindoline-1,3-
dione (HL2) was synthesized. Transamination reaction
between Ti(NMe2)4 and pyrrolyl motif of HL2 resulted in
the formation of complex 2. It was found that the selective
activation of carbonyl groups and the ring-opening reaction
occurred for the HL2 ligand as well, as confirmed by the X-ray
crystal structure of 2 (Scheme 2).
Hydrolysis Reaction. Intrigued by the discovery that
carbinolamide and amide scaffolds were afforded in the
preparation of 1−7, we endeavored to isolate these in situ
formed compounds via hydrolysis. As can be seen in Scheme 3,
hydrolysis of 2 led to the production of compounds N1-(2-
(((1H-pyrrol-2-yl)methyl)(2-(1-(dimethylamino)-1-hydroxy-
3-oxoisoindolin-2-yl)ethyl)amino)ethyl)-N2,N2-dimethylph-
thalamide (C2) and N1-(2-(((1H-pyrrol-2-yl)methyl)(2-(1,3-
dioxoisoindolin-2-yl)ethyl)amino)ethyl)-N2,N2-dimethylph-
thalamide (C3). The existences of C2 and C3 were confirmed
by MS spectrometry and NMR spectroscopy of the mixture of
C2 and C3. However, they are hard to be separated by column
chromatography due to the similar polarity of these two
compounds.
Mechanistic Insights from DFT Calculations. Density
functional theory (DFT) calculations82 were carried out to
better understand the experimental outcomes with the results
given in Figures 2 and 3. It was proposed that the reaction
should be initiated by deprotonation of the phenolic hydroxyl
group in HL1 with Ti(NMe2)4. In this process, the first
formation of H-bonding complex IN1 is endergonic by 18.0
kcal/mol. In IN1 the proton is much closer to the N atom than
to the O atom (N−H = 1.11 and O−H = 1.46 Å). The ligand
displacement occurs via TS1 with activation barrier of 21.3
kcal/mol from the starting materials. Alternatively, the direct
addition of Ti-NMe2 moiety to the carbonyl group in HL1
would be much less favorable with a higher barrier of 26.8
kcal/mol (TS1′, given in the SI). From TS1, complex IN2 and
dimethylamine are formed exergonically by 10.6 kcal/mol
(Figure 2). From IN2, the insertion of one carbonyl group of
the phthalimide moiety into the Ti−N bond occurs via TS2
with an activation barrier of 22.1 kcal/mol, affording the
tetracoordinated complex IN3 slightly endergonic. IRC
calculations indicated that no pentacoordinated complex was
formed prior to the insertion. From IN3, the C−N bond
cleavage via TS3 is very easy with a small barrier of 5.9 kcal/
mol, opening the five-membered ring and forming hexacoordi-
nated intermediate IN4 exergonically. This could be trans-
formed into IN5 by an intramolecular ligand exchange prior to
the incorporation of the other phthalimide moiety.83 However,
the second carbonyl insertion reaction via TS4 would require a
very high barrier of 39.8 kcal/mol from IN4, indicating the
formation of a penta-coordinated intermediate IN6 is
impossible under the current conditions. Probably the high
energy for this step originates from the steric effects, as the
amino group has close interaction with both the phthalimide
Carbinolamides are important functionalities present in
many bioactive molecules.58−64 The broad scope of these
transformations demonstrates the synthetic novelty of this
work.
C
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Scheme 2. Syntheses of Compounds 2−7
and benzamide moieties in TS4. Key structural parameters to
show the steric effects in TS4 are given in the SI.
carbonyl insertion could occur prior to the ring-opening
process of the five-membered ring. As shown in Figure 3, from
the hexa-coordinated intermediate IN7, which is slightly less
stable than the tetra-coordinated IN3, the second carbonyl
insertion via TS5 is facile with a barrier of 10.1 kcal/mol from
IN3. After the formation of penta-coordinated complex IN8,
the ring-opening process of the five-membered ring via TS6
requires a barrier of only 1.5 kcal/mol, leading to a highly
According to the above energies, the transformation of IN3
to IN4 via TS3 is very facile (5.9 kcal/mol) and exergonic,
suggesting the complex IN4 is first formed as a kinetic product.
While further transformation of IN4 via TS4 is very difficult,
its reversion to IN3 via TS2 is much easier with a barrier of
10.9 kcal/mol. We proposed that from IN3, the second
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Scheme 3. Hydrolysis of 2
Figure 2. Possible formation of the penta-coordinated complex IN6 by sequential carbonyl insertion, ring-opening C−N bond cleavage, and a
second carbonyl insertion.82
Figure 3. Energy profile explaining for the exclusive formation of compound 1 (IN9).82
exergonic hexa-coordinated complex IN9. The possible
opening of the remaining five-membered ring in IN9 was
also evaluated, however, the energy for TS7 is 28.5 kcal/mol
above IN9, and the formed intermediate IN10 is relatively
unstable. While the high barrier for this process may result
from the hepta-coordination nature of the Ti center in TS7, it
is interesting to find that a slightly higher activation barrier is
required for opening of the second ring (29.0 kcal/mol via
TS7′, given in the SI) if dissociation of the carbonyl
coordination in IN9 occurs first. This could be attributed to
a much closer interaction between the breaking C−N bond
and Ti center in the latter case that causes more steric
hindrance between the ligands, as revealed by detailed analysis
of related geometries in the SI. Thus, the second carbinolamide
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filtered. The volatiles were removed under reduced pressure to yield
HL1 as a white solid.89 Yield: 6.92 g (82%).
moiety is retained in compound 1 (IN9 in Figure 3), being in
excellent agreement with the experimental observations.
2,2′-(((1H-Pyrrol-2-yl)methyl)azanediyl)bis(ethane-2,1-diyl)bis-
(isoindoline-1,3-dione) (HL2). To a solution of C1 (6.53 g, 18 mmol)
in 1,2-dichloroethane (200 mL) was added pyrrole-2-carboxaldehyde
(1.71 g, 18 mmol). The mixture was stirred for 10 min after which
time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly added. The
resulting mixture was further stirred at room temperature for 24 h and
was quenched by adding 80 mL of water. The organic components
and water layer were separated, and the organic fraction was
evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
pressure yielding HL2 as a yellow solid. Yield: 6.21 g (68%). 1H NMR
(400 MHz, CDCl3): δ 7.61 (d, 8H, Ar1-H, Ar2-H), 6.15 (s, 1H, 2-
C4H3N), 5.89 (s, 1H, 4-C4H3N), 5.85 (s, 1H, 3-C4H3N), 3.58 (t, 4H,
NCH2CH2NCH2CH2N), 3.52 (s, 2H, C4H3N−CH2), 2.67 (t, 4H,
NCH2CH2NCH2CH2N) ppm. 13C NMR (150 MHz, CDCl3): δ
168.48, 133.57, 132.26, 128.40, 122.96, 117.67, 107.99, 107.18, 52.64,
49.90, 35.96 ppm. Anal. calcd for C25H22N4O4: C, 67.86; H, 5.01; N,
12.66. Found: C, 67.48; H, 4.72; N, 12.56.
CONCLUSION
■
In summary, the reactions of Ti(NMe2)4 with a series of
monoanionic ligands HL1−HL7 bearing phthalimide scaffolds
afforded titanium complexes 1−7. The Ti(NMe2)4-mediated
amidation reactions of carbonyl groups of the ligands occurred
during the process for the formations of 1−7, giving the new
ligands [L1′]3−−[L7′]3−. The newly formed [L1′]3−−[L7′]3−
ligands bear the biologically active carbinolamide and amide
moieties. The opening of one of two phthalimide units of
HL1−HL7 is observed. The formation of 1 is ratified by DFT
calculations. It is found that upon the insertion of the carbonyl
group into the Ti−N bond, the ring-opening reaction of the
first carbinolamide moiety is very facile. However, the ring-
opening process for the second carbinolamide moiety is
unfavorable in both thermodynamic and kinetic aspects.
2,2′-(((2-Hydroxy-3-methoxybenzyl)azanediyl))bis(ethane-2,1-
diyl)bis(isoindoline-1,3-dione) (HL3). To a solution of C1 (6.53 g, 18
mmol) in 1,2-dichloroethane (200 mL) was added 2-hydroxy-3-
methoxybenzaldehyde (2.74 g, 18 mmol). The mixture was stirred for
10 min after which time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly
added. The resulting mixture was further stirred at room temperature
for 24 h and was quenched by adding 80 mL of water. The organic
components and water layer were separated, and the organic fraction
was evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
EXPERIMENTAL SECTION
■
General Methods. All air- and moisture-sensitive reactions were
carried out in an MBraun drybox under a dry nitrogen atmosphere.
All solvents were dried over purple sodium benzophenone ketyl.
Ti(NMe2)4 was purchased from Acros chemical and used as received.
Elemental analyses for C, H, and N were carried out on a PerkinElmer
2400 analyzer. 1H NMR spectra were recorded at the ambient
temperature on Bruker Avance-III 400 and 600 MHz NMR
spectrometer. 13C NMR spectra were recorded at the ambient
temperature on Bruker Avance-III 600 MHz NMR spectrometer.
Crystallographic Studies. The data collections of 1−6 were
performed from a Bruker D8-Quest diffractometer equipped with a
graphite monochromator utilizing Mo Kα radiation (λ = 0.7107 Å). A
single crystal of suitable size was quickly wrapped with Paratone oil to
prevent decomposition and was mounted on a glass fiber. The data
were processed and reduced utilizing Bruker Apex III.84 The crystal
structures of 1−6 were solved by using the charge-flipping algorithm
(program SUPERFLIP85) method and refined on F02 using full-matrix
least-squares method. All operations were done using the OLEX2
interface.86 For complex 2, the crystals are very small, and the
qualities of the crystals are not good. Thus, we cannot get satisfactory
R(int) value for this compound. A small amount of spatially
delocalized electron density could be found in the crystal lattice of
compound 2, but acceptable refinement results could not be obtained
for this electron density. The SQUEEZE routine of PLATON87 was
used in the treatment of the solvent contribution, but the R(int) value
is still high. Despite the difficulty in generating a lower R(int) value,
the structure of complex 2 is unambiguous. All structures were
examined using the Addsym subroutine of PLATON88 to ensure that
no additional symmetry could be applied to the models.
Syntheses of Ligands. 2,2′-(Azanediylbis(ethane-2,1-diyl))bis-
(isoindoline-1,3-dione) (C1). To a solution of phthalic anhydride
(14.8 g, 0.1 mol) in acetic acid (80 mL) was added diethylenetriamine
(5.2 g, 0.05 mol). The reaction mixture was heated to 135 °C for 2 h
and then concentrated up to 10 mL. The concentrated solution was
diluted by adding ethyl alcohol, and the resulting mixture was refluxed
for 1.5 h to produce white precipitate. The white precipitate was
collected by filtration and dried under vacuum.89 Yield: 12.0 g (67%).
2,2′-(((2-Hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis-
(isoindoline-1,3-dione) (HL1). To a solution of C1 (6.53 g, 18 mmol)
in 1,2-dichloroethane (200 mL) was added salicylaldehyde (2.20 g, 18
mmol). The mixture was stirred for 10 min after which time
NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly added. The resulting
mixture was further stirred at room temperature for 24 h and was
quenched by adding 80 mL of water. The organic components and
water layer were separated, and the organic fraction was evaporated to
afford a yellow oily product. The oil was extracted into methanol and
1
pressure yielding HL3 as a white solid. Yield: 7.2 g (80%). H NMR
(400 MHz, CDCl3): δ 7.77 (dd, 4H, Ar1-H, Ar2-H), 7.69 (dd, 4H,
Ar1-H, Ar2-H), 6.64 (d, 2H, 4,6-C6H3(OCH3)(OH)), 6.57 (s, 1H, 5-
C6H3(OCH3)(OH)), 3.86 (d, 6H, NCH2CH2NCH2CH2N,
C6H3(OCH3)(OH)-CH2), 3.60 (s, 3H, C6H3(OCH3)(OH)), 2.93
(t, 4H, NCH2CH2NCH2CH2N) ppm. 13C NMR (150 MHz, CDCl3):
δ 168.13, 147.57, 146.00, 133.74, 132.13, 123.17, 122.12, 121.36,
119.11, 56.58, 55.76, 51.27, 34.90 ppm. Anal. calcd for C28H25N3O6:
C, 67.33; H, 5.04; N, 8.41. Found: C, 66.89; H, 4.68; N, 8.36.
2,2′-(((2-Hydroxy-4-methoxybenzyl)azanediyl))bis(ethane-2,1-
diyl)bis(isoindoline-1,3-dione) (HL4). To a solution of C1 (6.53 g, 18
mmol) in 1,2-dichloroethane (200 mL) was added 2-hydroxy-4-
methoxybenzaldehyde (2.74 g, 18 mmol). The mixture was stirred for
10 min after which time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly
added. The resulting mixture was further stirred at room temperature
for 24 h and was quenched by adding 80 mL of water. The organic
components and water layer were separated, and the organic fraction
was evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
pressure yielding HL4 as a white solid. Yield: 6.54 g (73%). 1H NMR
(400 MHz, CDCl3): δ 7.81−7.75 (m, 4H, Ar1-H, Ar2-H), 7.71 (dd,
4H, Ar1-H, Ar2-H), 6.81 (d, 1H, 5-C6H3(OCH3)(OH)), 6.29 (s, 1H,
3-C6H3(OCH3)(OH)), 5.79 (s, 1H, 6-C6H3(OCH3)(OH)), 3.87 (t,
4H, NCH2CH2NCH2CH2N), 3.80 (s, 2H, C6H3(OCH3)(OH)-CH2),
3.64 (d, 3H, C6 H3 (OCH3 ) (OH)), 2.93 (t, 4H,
NCH2CH2NCH2CH2N) ppm. 13C NMR (150 MHz, CDCl3): δ
168.17, 160.49, 157.82, 133.78, 132.17, 129.56, 123.14, 113.66,
105.25, 101.67, 57.54, 55.05, 51.33, 34.82 ppm. Anal. calcd for
C28H25N3O6: C, 67.33; H, 5.04; N 8.41. Found: C, 66.92; H, 4.73; N
8.40.
2,2′-(((2-Hydroxy-5-methoxybenzyl)azanediyl))bis(ethane-2,1-
diyl)bis(isoindoline-1,3-dione) (HL5). To a solution of C1 (6.53 g, 18
mmol) in 1,2-dichloroethane (200 mL) was added 2-hydroxy-5-
methoxybenzaldehyde (2.74 g, 18 mmol). The mixture was stirred for
10 min after which time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly
added. The resulting mixture was further stirred at room temperature
for 24 h and was quenched by adding 80 mL of water. The organic
components and water layer were separated, and the organic fraction
was evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
F
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Article
pressure yielding HL5 as a white solid. Yield: 6.82 g (76%). 1H NMR
(400 MHz, CDCl3): δ 7.79 (dd, 4H, Ar1-H, Ar2-H), 7.71 (dd, 4H,
Ar1-H, Ar2-H), 6.59 (s, 1H, 4-C6H3(OCH3)(OH)), 6.51 (s, 1H, 6-
C6H3(OCH3)(OH)), 6.18 (s, 1H, 3-C6H3(OCH3)(OH)), 3.88 (t,
4H, NCH2CH2NCH2CH2N), 3.83 (s, 2H, C6H3(OCH3)(OH)-CH2),
3.70 (s, 3H, C6 H3 (OCH3 ) (OH)), 2. 93 (t, 4H,
NCH2CH2NCH2CH2N) ppm. 13C NMR (150 MHz, CDCl3): δ
168.17, 152.63, 150.51, 133.78, 132.16, 123.15, 121.97, 116.47,
114.73, 113.99, 58.15, 55.64, 51.45, 34.79 ppm. Anal. calcd for
C28H25N3O6: C, 67.33; H, 5.04; N, 8.41. Found: C, 66.97; H, 4.69; N,
8.38.
2,2′-(((5-Chloro-2-hydroxybenzyl)azanediyl))bis(ethane-2,1-
diyl)bis(isoindoline-1,3-dione) (HL6). To a solution of C1 (6.53 g, 18
mmol) in 1,2-dichloroethane (200 mL) was added 5-chloro-2-
hydroxybenzaldehyde (2.82 g, 18 mmol). The mixture was stirred for
10 min after which time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly
added. The resulting mixture was further stirred at room temperature
for 24 h and was quenched by adding 80 mL of water. The organic
components and water layer were separated, and the organic fraction
was evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
pressure yielding HL6 as a white solid. Yield: 7.02 g (77%). 1H NMR
(400 MHz, CDCl3): δ 7.86−7.63 (m, 8H, Ar1-H, Ar2-H), 6.98 (d, 1H,
6-C6H3(OH)Cl), 6.90 (s, 1H, 4-C6H3(OH)Cl), 6.19 (d, 1H, 3-
C6H3(OH)Cl), 3.87 (dd, 6H, NCH2CH2NCH2CH2N, C6H3(OH)
Cl−CH2), 2.94 (t, 4H, NCH2CH2NCH2CH2N) ppm. 13C NMR (150
MHz, CDCl3): δ 168.16, 155.44, 133.84, 132.10, 128.79, 128.66,
123.88, 123.17, 122.72, 117.26, 57.59, 51.47, 34.66 ppm. Anal. calcd
for C27H22ClN3O5: C, 64.35; H, 4.40; N, 8.34. Found: C, 66.15; H,
4.06; N, 8.40.
2,2′-(((4-Chloro-2-hydroxybenzyl)azanediyl))bis(ethane-2,1-
diyl)bis(isoindoline-1,3-dione) (HL7). To a solution of C1 (6.53 g, 18
mmol) in 1,2-dichloroethane (200 mL) was added 4-chloro-2-
hydroxybenzaldehyde (2.82 g, 18 mmol). The mixture was stirred for
10 min after which time NaBH(OAc)3 (7.06 g, 0.032 mol) was slowly
added. The resulting mixture was further stirred at room temperature
for 24 h and was quenched by adding 80 mL of water. The organic
components and water layer were separated, and the organic fraction
was evaporated to afford a yellow oily product. The oil was extracted
into methanol and filtered. The volatiles were removed under reduced
pressure yielding HL7 as a white solid. Yield: 6.91 g (78%). 1H NMR
(400 MHz, CDCl3): δ 7.81−7.71 (m, 8H, Ar1-H, Ar2-H), 6.71−6.63
(m, 2H, 3,5-C6H3(OH)Cl), 6.48 (dd, 1H, 6-C6H3(OH)Cl), 3.88 (dd,
6H, NCH2CH2NCH2CH2N, C6H3(OH)Cl-CH2), 2.94 (t, 4H,
NCH2CH2NCH2CH2N) ppm. 13C NMR (150 MHz, CDCl3): δ
168.16, 157.52, 133.86, 132.10, 129.80, 123.18, 119.94, 119.57,
116.38, 57.50, 51.53, 34.74 ppm. Anal. calcd for C27H22ClN3O5: C,
64.35; H, 4.40; N, 8.34. Found: C, 66.11; H, 4.06; N, 8.38.
106.00, 64.87, 62.35, 60.47, 50.12, 49.00, 47.94, 45.00, 41.25, 37.66,
37.01, 33.59 ppm. Anal. calcd for C33H40N6O5Ti: C, 61.11; H, 6.22;
N, 12.96. Found: C, 60.77; H, 6.41; N 12.47.
Ti(L2′)(NMe2) (2) (H3L2′ = N1-(2-(((1H-Pyrrol-2-yl)methyl)(2-(1-
(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)amino)-
ethyl)-N2,N2-dimethylphthalamide). To a solution of HL2 (0.442 g,
1 mmol) in toluene was added a solution of Ti(NMe2)4 (0.224 g, 1
mmol) in toluene (10 mL). After the solution was stirred for 24 h, the
volatiles were removed under vacuum to give a red solid. Yield: 0.603
g (93%). Crystals suitable for X-ray crystallography were grown from
a saturated THF solution left standing at −35° in a vibration-free
environment. 1H NMR (600 MHz, CDCl3): δ 7.84 (dd, 2H, 4-Ar1-H,
2-Ar2-H), 7.50 (s, 2H, 5-Ar1-H, 5-Ar2-H), 7.39 (d, 1H, 3-Ar1-H), 7.20
(t, 1H, 2-Ar1-H), 7.01 (s, 1H, 3-Ar2-H), 6.86 (d, 1H, 4-Ar2-H), 6.02
(s, 1H, 2-C4H3N), 5.80 (s, 1H, 4-C4H3N), 5.32 (d, 1H, 3-C4H3N),
4.26 (d, 1H, NCH2 CH2 NCH2 CH2 N), 4.13 (d, 1H,
NCH2CH2NCH2CH2N), 3.85 (t, 1H, NCH2CH2NCH2 CH2N),
3.37 (t, 1H, NCH2 CH2 NCH2 CH2 N), 3.26 (d, 1H,
NCH2CH2NCH2CH2N), 3.08 (s, 2H, C4H3N−CH2), 2.88 (s, 6H,
CONMe2), 2.76−2.67 (m, 6H, CONMe2), 2.51 (t, 1H,
NCH2CH2NCH2 CH2N), 2.39 (t, 2H, NCH2CH2NCH2CH2N),
2.01 (s, 6H, NMe2). 13C NMR (150 MHz, CDCl3): δ 173.53, 170.26,
166.95, 144.71, 142.10, 137.08, 131.58, 131.41, 131.17, 130.10,
128.82, 127.70, 127.10, 124.95, 124.59, 123.05, 122.29, 106.51,
106.10, 100.07, 66.76, 61.90, 55.87, 50.27, 45.54, 41.24, 37.31, 37.08,
34.28 ppm. Anal. calcd for C31H39N7O4Ti: C, 59.95; H, 6.32; N,
15.77. Found: C, 59.80; H, 5.81; N, 15.44.
Ti(L3′)(NMe2) (3) (H3L3′ = N1-(2-((2-(1-(Dimethylamino)-1-
hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxy-3-methoxybenzyl)-
amino)ethyl)-N2,N2-dimethylphthalamide). To a solution of HL3
(0.500 g, 1 mmol) in toluene was added a solution of Ti(NMe2)4
(0.224 g, 1 mmol) in toluene (10 mL). After the solution was stirred
for 24 h, the volatiles were removed under vacuum to give a red solid.
Yield: 0.529 g (78%). Crystals suitable for X-ray crystallography were
grown from a saturated THF solution left standing at −35° in a
vibration-free environment. 1H NMR (600 MHz, CDCl3): δ 7.81 (dd,
1H, 4-Ar1-H), 7.75 (d, 1H, 2-Ar2-H), 7.50−7.48 (m, 1H, 5-Ar1-H),
7.34 (t, 1H, 3-Ar1-H), 7.24 (d, 1H, 2-Ar1-H), 7.18−7.12 (m, 3H, 3, 4,
5-Ar2-H), 6.85−6.82 (m, 1H, 6-C6H3(OCH3)O), 6.79 (d, 1H, 5-
C6H3(OCH3)O), 6.70 (t, 1H, 4-C6H3(OCH3)O), 4.06 (d, 1H,
NCH2CH2NCH2CH2N), 3.98 (dd, 1H, NCH2CH2NCH2CH2N),
3.88 (s, 1H, NCH2CH2NCH2CH2N), 3.81−3.76 (m, 3H,
C6H3(OCH3)O), 3.49 (t, 1H, NCH2CH2N CH2CH2N), 3.12 (s,
6H, NMe2), 2.96−2.89 (m, 6H, CONMe2), 2.78 (s, 6H, CONMe2),
2.35 (s, 2H, C6 H3 (OCH3 )O−CH2 ), 2.13 (s, 2H,
NCH2CH2NCH2CH2N), 1.86−1.84 (m, 1H, NCH2CH2
NCH2CH2N), 1.80 (s, 1H, NCH2CH2NCH2CH2N) ppm. 13C
NMR (150 MHz, CDCl3): δ 174.09, 170.22, 166.89, 154.28,
146.97, 145.64, 141.34, 131.68, 131.14, 129.95, 128.48, 126.70,
125.34, 125.23, 122.68, 121.78, 121.01, 120.12, 118.42, 113.10,
112.04, 106.05, 64.93, 62.23, 60.54, 60.12, 56.30, 55.93, 49.47, 48.69,
48.14, 44.94, 41.26, 37.78, 37.03, 33.62, 31.54, 22.60, 14.08 ppm.
Anal. calcd for C34H42N6O6Ti: C, 60.18; H, 6.24; N, 12.38. Found: C,
60.82; H, 6.34; N, 12.09.
Synthesis of Compounds. Ti(L1′)(NMe2) (1) (H3L1′ = N1-(2-((2-
(1-(Dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-
hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthalamide). To a
solution of HL1 (0.469 g, 1 mmol) in toluene was added a solution
of Ti(NMe2)4 (0.224 g, 1 mmol) in toluene (10 mL). After the
solution was stirred for 24 h, the volatiles were removed under
vacuum to give a red solid. Yield: 0.510 g (82%). Crystals suitable for
X-ray crystallography were grown from a saturated toluene solution
Ti(L4′)(NMe2) (4) (H3L4′ = N1-(2-((2-(1-(Dimethylamino)-1-
hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxy-4-methoxybenzyl)-
amino)ethyl)-N2,N2-dimethylphthalamide). To a solution of HL4
(0.500 g, 1 mmol) in toluene was added a solution of Ti(NMe2)4
(0.224 g, 1 mmol) in toluene (10 mL). After the solution was stirred
for 24 h, the volatiles were removed under vacuum to give a red solid.
Yield: 0.536 g (79%). Crystals suitable for X-ray crystallography were
grown from a saturated THF solution left standing at −35° in a
vibration-free environment. 1H NMR (600 MHz, CDCl3): δ 7.81 (dd,
1H, 4-Ar1-H), 7.74 (d, 1H, 2-Ar2-H), 7.51−7.48 (m, 1H, 5-Ar1-H),
7.33−7.31 (m, 1H, 3-Ar1-H), 7.13−7.10 (m, 2H, 4, 5-Ar2-H), 7.01 (d,
1H, 3-Ar2-H), 6.93 (d, 1H, 2-Ar1-H), 6.82 (d, 1H, 6-C6H3(OCH3)O),
6.39−6.36 (m, 1H, 3-C6H3(OCH3)O), 6.30−6.27 (m, 1H, 5-
C6H3(OCH3)O), 4.05 (d, 1H, NCH2CH2NCH2CH2N), 4.00−3.97
( d d , 1 H , N C H 2 C H 2 N C H 2 C H 2 N ) , 3 . 8 2 ( s , 1 H ,
NCH2CH2NCH2CH2N), 3.76 (s, 3H, C6H3(OCH3)O), 3.46 (t,
1
left standing at −35° in a vibration-free environment. H NMR (600
MHz, CDCl3): δ 7.81 (dd, 1H, 4-Ar1-H), 7.73 (d, 1H, 2-Ar2-H),
7.50−7.47 (m, 1H, 5-Ar1-H), 7.31 (t, 1H, 3-Ar1-H), 7.15 (t, 1H, 2-
Ar1-H), 7.12−7.07 (m, 3H, 3, 4, 5-Ar2-H), 7.04 (d, 1H, 6-C6H4O),
6.80 (dd, 2H, 3,5-C6H4O), 6.70−6.67 (m, 1H, 4-C6H4O), 4.05 (d,
1 H , N C H 2 C H 2 N C H 2 C H 2 N ) , 3 . 9 8 ( d d , 1 H ,
NCH2CH2NCH2CH2N), 3.75 (t, 1H, NCH2CH2N CH2CH2N),
3.46 (t, 1H, NCH2CH2NCH2CH2N), 3.08 (s, 6H, NMe2), 2.89−2.83
(m, 6H, CONMe2), 2.75 (s, 2H, C6H4O−CH2), 2.65−2.57 (m, 6H,
CONMe2), 2.21−2.19 (m, 1H, NCH2CH2NCH2CH2N), 2.13 (s, 2H,
NCH2CH2NCH2CH2N), 1.80 (s, 1H, NCH2CH2NCH2CH2N) ppm.
13C NMR (150 MHz, CDCl3): δ 174.13, 170.35, 166.88, 164.18,
163.19, 145.53, 141.33, 131.69, 131.14, 130.00, 129.82, 129.66,
129.50, 128.91, 128.52, 126.75, 125.09, 122.69, 120.42, 118.76,
G
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1H, NCH2CH2NCH2CH2N), 3.08 (m, 6H, NMe2), 2.92−2.87 (m,
6H, CONMe2), 2.76 (s, 2H, C6H3(OCH3)O−CH2), 2.63−2.57 (m,
6H, CONMe2), 2.40−2.38 (m, 1H, NCH2CH2NCH2CH2N), 2.15 (s,
2H, NCH2CH2NCH2CH2N), 1.81 (s, 1H, NCH2CH2NCH2CH2N)
ppm. 13C NMR (150 MHz, CDCl3): δ 174.15, 170.36, 166.88,
164.97, 163.96, 161.16, 145.50, 141.29, 131.70, 131.14, 130.00,
129.90, 129.68, 129.11, 128.98, 128.54, 128.44, 128.17, 126.79,
125.16, 122.70, 117.33, 105.97, 104.80, 101.60, 64.84, 62.25, 60.04,
55.25, 45.00, 41.26, 37.65, 37.03, 33.58, 31.54, 22.61, 14.08 ppm.
Anal. calcd for C34H42N6O6Ti: C, 60.18; H, 6.24; N, 12.38. Found: C,
60.77; H, 5.92; N, 11.86.
4.06 (d, 1H, NCH2CH2NCH2CH2N), 4.00 (dd, 1H,
NCH2CH2NCH2CH2N), 3.72 (t, 1H, NCH2CH2NCH2CH2N),
3.45 (t, 1H, NCH2CH2NCH2CH2N), 3.08 (s, 6H, NMe2), 2.90−
2.84 (m, 6H, CONMe2), 2.76 (s, 2H, C6H3OCl-CH2), 2.64−2.56 (m,
6H, CONMe2), 2.38 (t, 1H, NCH2CH2NCH2CH2N), 2.12 (s, 2H,
NCH2CH2NCH2CH2N), 1.81 (s, 1H, NCH2CH2N CH2CH2N) ppm.
13C NMR (150 MHz, CDCl3): δ 174.17, 170.47, 166.85, 164.53,
145.31, 141.22, 134.61, 131.23, 130.13−129.82 (m), 128.63, 126.88,
125.15, 123.59, 122.71, 118.33, 116.66, 106.02, 64.89, 62.30, 60.06,
59.61, 47.98, 45.13, 41.29, 37.59, 37.04, 33.56, 31.53, 22.60, 14.08
ppm. Anal. calcd for C33H39ClN6O5Ti: C, 58.03; H, 5.76; N, 12.30.
Found: C, 58.60; H, 5.99; N 11.95.
Ti(L5′)(NMe2) (5) (H3L5′ = N1-(2-((2-(1-(Dimethylamino)-1-
hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxy-5-methoxybenzyl)-
amino)ethyl)-N2,N2-dimethylphthalamide). To a solution of HL5
(0.500 g, 1 mmol) in toluene was added a solution of Ti(NMe2)4
(0.224 g, 1 mmol) in toluene (10 mL). After the solution was stirred
for 24 h, the volatiles were removed under vacuum to give a red solid.
Yield: 0.489 g (72%). Crystals suitable for X-ray crystallography were
grown from a saturated THF solution left standing at −35° in a
vibration-free environment. 1H NMR (600 MHz, CDCl3): δ 7.79 (dd,
1H, 4-Ar1-H), 7.73 (d, 1H, 2-Ar2-H), 7.47 (t, 1H, 5-Ar1-H), 7.31 (t,
1H, 3-Ar1-H), 7.13−7.08 (m, 3H, 3, 4, 5-Ar2-H), 6.77−6.75 (m, 1H,
2-Ar1-H), 6.73−6.70 (d, 2H, 3, 4-C6H3(OCH3)O), 6.63−6.60 (m,
1H, 6-C6H3(OCH3)O), 4.05 (d, 1H, NCH2CH2NCH2CH2N), 4.00−
3.97 (m, 1H, NCH2CH2NCH2CH2N), 3.75 (s, 3H, C6H3(OCH3)O),
3.73−3.70 (m, 1H, NCH2CH2NCH2CH2N), 3.46 (t, 1H,
NCH2CH2NCH2CH2N), 3.09 (s, 6H, NMe2), 2.93−2.89 (m, 6H,
CONMe2), 2.75 (t, 2H, C6H3(OCH3)O−CH2), 2.63−2.57 (m, 6H,
CONMe2), 2.32 (d, 1H, NCH2CH2NCH2CH2N), 2.13 (s, 2H,
NCH2CH2NCH2CH2N), 1.79 (s, 1H, NCH2CH2NCH2CH2N) ppm.
13C NMR (150 MHz, CDCl3): δ 174.12, 170.29, 166.88, 158.76,
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c01831.
■
sı
Text, tables, figure, and CIF files giving X-ray crystallo-
graphic details data, 1H NMR spectrum, 13C NMR
spectrum for all and entry compounds and computa-
tional details and results (PDF)
(XYZ)
Accession Codes
CCDC 1978110−1978113, 1978116, and 2009683 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
157.72, 153.38, 131.67, 131.12, 129.97, 129.81, 128.97, 128.48,
128.16, 126.71, 125.68, 125.18, 122.67, 116.05, 115.84, 115.20,
113.41, 64.82, 62.41, 60.76, 60.32, 55.76, 50.04, 47.92, 44.91, 41.23,
37.66, 36.99, 33.58 ppm. Anal. calcd for C34H42N6O6Ti: C, 60.18; H,
6.24; N 12.38. Found: C, 59.88; H, 6.44; N, 11.85.
AUTHOR INFORMATION
Corresponding Authors
■
Ti(L6′)(NMe2) (6) (H3L6′ = N1-(2-((5-Chloro-2-hydroxybenzyl)(2-
(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)amino)-
ethyl)-N2,N2-dimethylphthalamide). To a solution of HL6 (0.504 g,
1 mmol) in toluene was added a solution of Ti(NMe2)4 (0.224 g, 1
mmol) in toluene (10 mL). After the solution was stirred for 24 h, the
volatiles were removed under vacuum to give a red solid. Yield: 0.560
g (69%). Crystals suitable for X-ray crystallography were grown from
a saturated THF solution left standing at −35° in a vibration-free
Yahong Li − College of Chemistry, Chemical Engineering, and
Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China; orcid.org/0000-0002-6467-
0607; Email: liyahong@suda.edu.cn
Yuanzhi Xia − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, People’s Republic of
China; orcid.org/0000-0003-2459-3296; Email: xyz@
wzu.edu.cn
1
environment. H NMR (600 MHz, CDCl3): δ 7.81 (dd, 1H, 4-Ar1-
H), 7.50−7.47 (m, 2H, 2-Ar2-H, 5-Ar1-H), 7.33 (t, 1H, 3-Ar1-H), 7.21
(d, 1H, 2-Ar1-H), 7.15−7.10 (m, 3H, 3, 4, 5-Ar2-H), 7.03 (s, 1H, 6-
C6H3ClO), 6.83 (d, 1H, 5-C6H3ClO), 6.59 (d, 1H, 3-C6H3ClO), 4.08
(d, 1H, NCH2 CH2 NCH2 CH2 N), 4. 04 (dd, 1H,
NCH2CH2NCH2CH2N), 3.71 (t, 1H, NCH2CH2NCH2CH2N),
3.47 (t, 1H, NCH2CH2NCH2CH2N), 3.09 (s, 6H, NMe2), 2.94−
2.87 (m, 6H, CONMe2), 2.77 (s, 2H, C6H3OCl-CH2), 2.60−2.56 (m,
6H, CONMe2), 2.33 (s, 1H, NCH2CH2 NCH2CH2N), 2.13 (s, 2H,
NCH2CH2NCH2CH2N), 1.82 (s, 1H, NCH2CH2NCH2CH2N) ppm.
13C NMR (150 MHz, CDCl3): δ 174.14, 170.41, 166.87, 162.75,
Authors
Shengwang Xia − College of Chemistry, Chemical Engineering,
and Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China
Zhilei Jiang − College of Chemistry, Chemical Engineering, and
Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China
Yuan Huang − College of Chemistry, Chemical Engineering, and
Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China
Dawei Li − College of Chemistry, Chemical Engineering, and
Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China
145.37, 141.27, 131.63, 131.23, 130.09, 129.92, 129.57, 129.38,
129.21, 128.98, 128.62, 128.31, 128.17, 126.85, 126.51, 125.19,
122.79, 122.64, 117.38, 64.82, 62.33, 60.22, 47.94, 45.12, 41.30, 37.61,
37.06, 33.59, 21.42 ppm. Anal. calcd for C33H39ClN6O5Ti: C, 58.03;
H, 5.76; N, 12.30. Found: C, 58.18; H, 5.78; N, 12.19.
Ti(L7′)(NMe2) (7) (H3L7′ = N1-(2-((4-Chloro-2-hydroxybenzyl)(2-
(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)amino)-
ethyl)-N2,N2-dimethylphthalamide). To a solution of HL7 (0.504 g,
1 mmol) in toluene was added a solution of Ti(NMe2)4 (0.224 g, 1
mmol) in toluene (10 mL). After the solution was stirred for 24 h, the
volatiles were removed under vacuum to give a red solid. Yield: 0.622
Yanfeng Cui − College of Chemistry, Chemical Engineering, and
Materials Science, Soochow University, Suzhou 215123,
People’s Republic of China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.0c01831
1
g (81%). H NMR (600 MHz, CDCl3): δ 7.82 (dd, 1H, 4-Ar1-H),
7.50−7.45 (m, 2H, 2-Ar2-H, 5-Ar1-H), 7.33 (t, 1H, 3-Ar1-H), 7.13−
7.09 (m, 2H, 4, 5-Ar2-H), 7.03 (d, 1H, 3-Ar2-H), 6.95 (d, 1H, 2-Ar1-
H), 6.82 (dd, 2H, 3, 4-C6H3ClO), 6.70−6.68 (m, 1H, 6-C6H3ClO),
Notes
The authors declare no competing financial interest.
H
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ACKNOWLEDGMENTS
■
The authors appreciate the financial support from Natural
Science Foundation of China (21772140 and 21873074),
Natural Science Foundation of Jiangsu Province of China
(BK20171213), a Project Funded by the Priority Academic
Program Development of Jiangsu Higher Education Institu-
tion, and the project of scientific and technologic infrastructure
of Suzhou (SZS201708).
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