Research Proposal

1) Topic of project:
Synthesis and characterization of copper (II) complexes with carbocyclic carbenes as ligands and their application in
decarboxylative coupling reactions and CH bond activation reactions.
2) Objectives:
N-heterocyclic carbenes (NHCs) have proved to be efficient control ligands in organometallic homogeneous
catalysis and they are attracting more and more attention, since N-heterocyclic carbene ligands exhibit unique
advantages such as a) their stronger -donating character b) the strength of carbene-metal bond c) the presence of
sterically encumbering groups bound to the N atoms favors reductive elimination of the product from metals 1.
Among the class of N-heterocylic carbene ligands, carbocyclic carbene ligands have emerged as versatile
phosphine-free ligands for homogeneous catalysis 2-3. Most of the Carbocyclic carbenes derived from aromatic
nitrones, particularly to its strong sigma-donor ability and anionic nature of the carbene ligand.
(i) To design and synthesis of different types of carbocyclic carbenes with various donor atoms and their
corresponding Cu(II) complexes.
(ii) Characterization of these complexes using elemental analysis, single crystal X-ray diffraction technique and
spectroscopic methods.
(iii) Examination of electron transfer properties.
(iv) Investigation of the catalytic efficiencies of the new Cu(II) complexes in decarboxylative coupling reactions and
CH bond activation reactions.
3) Methodology:
3. 1. Synthesis of carbocyclic carbene ligands and their Cu(II) complexes:
Synthesis and characterization of different carbocyclic carbenes ligands with various donor atoms and the synthesis
of their corresponding Cu(II) complexes will be carried out. The ligands and the complexes thus obtained will be
recrystallized from suitable solvents; the compounds separated using column chromatography.
3.1.1. Synthesis of N-(3-(1-methoxy-3-methyl-1-oxobutan-2-ylcarbamoyl)benzylidene)-2-methylpropan-2amine oxide ligand
Compound 1 will be synthesized by the formation of amide bond between 3-formylbenzoic acid and L-valine ester
using widely available 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) as coupling reagent and
Hydroxybenzotriazole(HOBT), N,N-diisopropylethaylamine(DIPEA) in dichloromethane at 0 C to room
temperature for 6h. After evaporating the solvent the resulting solid obtained will be subjected to further
purification. The carboxyamido/carbocylic carbene ligand 2 can be prepared by the imine bond formation between

the above obtained compound 1 and N-tert-butylhydroxylamine acetic acid using trietylamine as base and
dichloromethane as solvent at 0C to room temperature for 10 h (scheme 1).3
O

HOBT, EDCI
OH
NH2

DIPEA, DCM
COOMe RT, 6h

CHO

NH

tBUNHOH. ACOH
COOMe
Et3N, DCM
N 2 atm, RT, 10h

CHO

COOMe

NH
2
N

Scheme 1
3.1.2. Synthesis of N-(3-(pyridin-2-ylcarbamoyl)benzylidene)propan-2-amine oxide ligand
Compound 1 can be synthesized by the formation of amide bond between 3-formylbenzoic acid and 2aminopyridine using widely available 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) as coupling reagent
and Hydroxybenzotriazole(HOBT), N,N-diisopropylethaylamine(DIPEA) in dichloromethane at 0 C to room
temperature for 3h. The semi-solid obtained by evaporating the solvent will be subjected to further purification. The
carboxyamido/carbocylic carbene ligand 2 can be prepared by the imine bond formation between the above obtained
compound 1 and N-tert-butylhydroxylamine acetic acid using trietylamine as base and dichloromethane as solvent at
0 C to room temperature for 6 h (Scheme 2).
O
O

O
HOBT, EDCI

OH H 2 N
N

tBUNHOH. ACOH
NH

DIPEA, DCM
RT, 3h

Et3N, DCM
N 2 atm, RT, 6h

CHO

CHO

NH

N O

Scheme 2
3.1.3. Synthesis of 2-methyl-N-(3-(pyridin-2-ylamino)benzylidene)propan-2-amine oxide ligand
The above ligand can be prepared by the imine bond formation between 3-(pyridin-2-ylamino)benzaldehyde and Ntert-butylhydroxylamine acetic acid using trietylamine as base and dichloromethane as solvent at 0 0C to room
temperature for 4 h (Scheme 3).
NH

tBUNHOH. ACOH
N

CHO

NH
N

Et3N, DCM
N 2 atm, RT, 10h

N O

Scheme 3
3. 2. Preparation of Cu(II) precursors:
Cu(II) precursors such as CuX2 (where X = Cl or Br) and Cu(OAc)24H2O will be effectively used as starting
materials for the synthesis of Cu(II) complexes. All the Cu(II) starting precursors will be prepared from the literature
methods.4-7
3. 3. Synthesis of Cu(II) complexes:
A number of tetra coordinated Cu(II) complexes will be synthesized from the reaction of carbocyclic carbene
ligands with Cu(II) precursors under various experimental conditions.
3.4. Characterization of Cu(II) complexes:
All the complexes will be characterized by elemental analysis (C, H and N) and various spectroscopic (FT-IR, UVVis and EPR) methods. Attempts will be made to grow single crystals of all the newly synthesized ligands bearing
Cu(II) complexes from suitable solvents. The molecular structures of the complexes can be investigated by single
crystal X-ray diffraction technique.
3.5. Catalytic transformations:
3.5.1. Decarboxylative coupling reactions:
Deacarboxylative cross coupling reaction will be carried out in the presence of variety of arene carboxylic acids and
aryl, heteroaryl halides and triflates8-14. The yield obtained from the conversion will be determined by GC or NMR
techniques by comparison with authentic samples.
X

COOH

Catalyst

R
or

Ar

R1

X= I, Br, Cl, OTf

OK

3.5.1. C-H bond activation:

Cu/O2 catalytic system can be used to couple aromatic C-H with amide N-H with the aid of directing group or
directly. Based on literature investigations 15-17, it is believed that the intermediate (amide compound) can be further
coupled intra-molecularly to construct C-O bond, this protocol will provide the synthesis of structurally diverse
benzoxazole derivatives in tandem pathway.
R[DG]
R1

O
+

H 2N

R2

Cu/O2
o

t C/z h

R1

R[DG]

R[DG]
H
N

R1

O
intermediate

N
H

R[DG]

R2
OH

R1

N
O

R2

4) Significant outcome from proposed work:

It is believed that the results of the project will be much useful in developing a new family of organometallic
complexes. This project will be helpful in understanding the reactivity and stability of different carbocylic carbene
ligands and with Cu(II) ions. Further, the synthesized Cu(II) coordination complexes will be generated as promising
catalysts for the decarboxylative coupling reactions and C-H bond activation reactions.
5) Year wise work plan:
The project work is planned in steps as given below.
1st Year:

Design and synthesis of various carbocylic carbene ligands and their Cu(II) complxes.
Designed catalyst should have high activity, selectivity and more importantly high stability and long lifetime.
The complete structural characterization of the new complexes will be done based on analytical, spectral,
electrochemical and X-ray diffraction methods.

nd

2 Year:

Evaluating the efficiency of catalyst towards the decarboxylative cross coupling reaction and CH bond

activation reactions.
Utilization of the catalyst to generate a diverse range of products in good to excellent yields.
Characterization of the resulting compounds by using different spectroscopic techniques.

3rd Year:

Preparation of final technical report.

Publishing the results in peer reviewed journals.

Filing the patents.

6. References:
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2002, 21, 2866.
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3. Q. Yao, M. Zabawa, J. Woo, C. Zheng, J. Am. Chem. Soc., 2007, 129, 3088.
4. S. Maloth, S. Pal, Inorg. Chim. Acta, 2011, 372, 407.
5. T. Ghosh, S. Das, S. Pal, Polyhedron, 2010, 29, 3074.
6. T. Ghosh, S. Pal, Inorg. Chim. Acta, 2010, 363, 3632.
7. S. Das, S. Pal, Inorg. Chim. Acta, 2010, 363, 3028.
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12. L. J. Goossen, N. Rodriguez, P. P. Lange, C. Linder, Angew. Chem. Ent. Ed., 2010, 122, 1129.
13. L. J. Goossen, B. Zimmermann, C. Linder, N. Rodriguez, P. P. Lange, J. Hartunga, Adv. Synth. Catal., 2009,
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14. L. J. Goossen, B. Zimmermann, T. Knauber, Angew. Chem. Int. Ed., 2008, 47, 7103.
15. L. Zhang, G. Y. Ang, S. Chiba, Org. Lett., 2010, 12, 3682-3685.
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