Synthesis and Application of Heterogeneous Zinc Catalysts for the Decarboxylative Coupling

1. Synthesis and Application of Heterogeneous
Zinc Catalysts for the Decarboxylative
Coupling
BY
Jagdish Chandra Jat
Registration No: 17mscchm01
Supervisor
Dr. Rakesh Kumar
Central University of Punjab, Bathinda

2. Heterogeneous catalyst
Reactant and catalyst have different phase
Herein we are utilizing biopolymer supported catalyst ie. Chitosan-supported
zinc catalyst
Advantages includes-
i. Easily and effectively catalyst separation
ii. The reaction can occur at milder reaction condition
iii. Environmentally friendly
iv. High possibility of reusing and regenerating catalyst
v. Prevents metal leaching
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3. Review of Literature
 Coupling between Phenylglyoxylic acid, Morpholine, and Phenylacetylene
 Cu-catalyzed coupling of glyoxylic acid, amine, and alkyne forming propargylamine
 While AuBr3-catalyzed coupling of glyoxylic acid, amine, and alkyne forming
butenolides
Pereshivko, O. P. P., Vsevolod A Van der Eycken, Erik V. (2011).
Unprecedented Cu(I)-catalyzed microwave-assisted three-
component coupling of a oxoacetic acid, an alkyne, and an
amine. Organic Letters, 12: 2638-2641.
Zhang, Q., Cheng, M., Hu, X., Li, B. G., & Ji, J. X. (2010).
Gold-catalyzed three-component tandem process: An
efficient and facile assembly of complex butenolides
from alkynes, amines, and glyoxylic acid. Journal of the
American Chemical Society, 132: 7256-7257.
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4. Importance of propargylamine
Important building block for the several nitrogen-containing heterocyclic
compounds (such as pyrrole, pyridine, and oxazoles, etc.)
 Several biologically active compounds (such as β-lactams, peptides, isosteres,
fungicides, herbicides, etc.)
 Natural products (such as paragyline, rasagyline, etc.)
 Parkinson’s disease
 Alzheimer’s disease
1. Chen, J. J., Swope, D. M., & Dashtipour, K. (20017). A comprehensive review of rasagiline, a
second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease.
Clinical Therapeutics, 29: 1825-1849.
2. Weinreb, O., Amit, T., Bar-Am, O., & BH Youdim, M. (2016). Ladostigil: a novel multimodal
neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory
activities for Alzheimer's disease treatment. Current Drug Targets, 13: 483-494.
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5. Objectives
 To synthesize various chitosan-supported zinc catalysts (Heterogeneous
catalyst)
 To study the effect of various chitosan-supported zinc catalysts towards
decarboxylative A3-coupling
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6. Results and discussion
Catalyst Preparation:
 Chitosan-supported Zinc nitrate [Zn(NO3)2] catalyst
 Chitosan-supported Zinc chloride [ZnCl2] catalyst
Catalyst Characterization:
 FT-IR
 UV-Visible
 FE-SEM
 FE-SEM-EDS
 ICPMS (Zinc content in the Chit@Zn(NO3)2 and Chit@ZnCl2 is 2.94 wt%
and 4.41 wt% respectively)
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7. FT-IR UV-Visible
FE-SEM FE-SEM-EDS
Chitosan Chit@Zn(NO3)2 Chit@ZnCl2 Chit@Zn(NO3)2 Chit@ZnCl2
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8. Screening of catalytic activity
 Comparison of catalytic activity of Chit@Zn(NO3)2 and Chit@ZnCl2 catalysts
for the synthesis of propargylamine through decarboxylative A3-coupling
reaction
 Here Chit@Zn(NO3)2 shows better reactivity than that of Chit@ZnCl2, so
we further optimized Chit@Zn(NO3)2 catalyst
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9. Screening of reaction at various temperature
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10. Screening of various catalysts
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11. Screening of various solvents
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12. Mechanism for decarboxylative A3-coupling
Yadav, J. S., Reddy, B. V. S., Naveenkumar, V., Rao, R. S., & Nagaiah, K. (2004). [bmim] PF6/CuBr: a novel and
recyclable catalytic system for the synthesis of propargyl amines. New Journal of Chemistry, 28: 335-337.12

13. 1H-NMR and 13C-NMR of Propargylamine
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14. Conclusions
 By above-optimized results, it is noted that our best optimization condition
involves phenylglyoxylic acid (1.1 mmol), morpholine (1.0 mmol), and
phenylacetylene (1.5 mmol) catalyzed by Chit@Zn(NO3)2 (10 mg) under the
solvent-free condition for 4 h
 To investigate the decarboxylative pathway, we designed a controlled
experiment between phenylglyoxylic acid (1.1 mmol) and morpholine (1.0 mmol)
and observed that it formed benzaldehyde and no Phenylglyoxylic acid was
detected
 The propargylamine synthesis via decarboxylative A3-coupling of phenylglyoxylic
acid, amine, and alkyne is an efficient and atom-economical strategy
 In this work, we have explored various chitosan-supported zinc catalysts, ionic
liquid, and solvents for the decarboxylative three-component coupling reaction
 The reaction could be successfully achieved under the solvent-less condition
with Chit@Zn(NO3)2 catalyst
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