1. One Pot Copper Catalyzed Conversion of
Oximes to Thioamides
Paulami Bose, Dr. Niranjan Panda*
Objective
To develop a facile and environmentally friendly synthetic method towards the
preparation of thioamides.
Paulami Bose
Roll. 412CY2006
A Presentation on:

2. Introduction
 Thioamides are important structural motifs found in many biologically
active molecules (figure 1).
 Few thioamides show antitumor activity and even act as anti-thyroid
drug.1
 Also act as important precursors for various fine chemicals, heterocycles.
Figure 1. Examples of biologically active thioamide derivatives
Methamazole
Polythiouracil
Carbimazole
Structures of Chalcogenopyrylium Compounds
NH
N
CH3
S
N
H
NH
O
S
N
N
O S
N
S
R2
R1
S
Cl R1= tBu, R2=
R1=R2=
R1=R2= tBu
NMe2

3. Reported Protocols From Different Precursors
 General procedure
 Classical method
 Willgerodt–Kindler Method
 Jiang’s Method
R1
O
NH2
R1
S
NH2
P2S5
R1
SH
NH
R Z
O
R1
N
O
R3
R2
HNR1
R2
Lawesson's Reagent
or P4S10
R1
N
S
R3
R2
O
S8
O
H
N N
O
S
130 o
C, 3h
TsOH
R1
X HN
R3
R2
Na2S.9H2O N
S
R3
R2
R180-110 o
C, 8h
DMF

4. Reported Protocols from Oximes
 Key Reaction: Beckmann Rearrangement
 Other methods:
R N
OH TiCl3OTf-[bmim]Br
(NH4)2S, 80 o
C
R NH2
S
N
OH
R2
R1
PSCl3, H2O,Et3N
R1
N
S
H
R2
R2
R1
O (i) HO-NH2 .HCl/AcONa, 80-90 o
C
EtO
P
EtO
S
SH
(ii) N
H
R1
R2
S
, dioxane
N
OH
R2
R1
P2S5 (0.5 eq)
R1
N
S
H
R2
Benzene
Reflux

5. Beckmann Rearrangement
 Acid catalyzed direct conversion of Oximes to N- substituted amides.
 For aldoximes, it is observed that 2
 Limitations : 1. High reaction temperature required
2. use of large amount of strong Brønsted acids
3. huge amount of byproduct generated.
R NOH
Beckmann
Rearrangent
Metal-catalyzed
Rearrangement
R NH2
O
H N
O
H
R
N Conc. H2SO4
R2
N
O
H
R1
HeatR2
R1 OH

6. Background of Project
 Importance of Copper catalyst
 Reduction of catalyst cost
 Needs lower catalyst loading
 Requires milder reaction condition
 Tolerates various functional groups
 Recently, Panda et al. reported that 3
 Concept: Oxime is a useful precursor for synthesis of its amide, hence it
can be presumed that in the presence of a thionating agent it can lead to
its corresponding thioamide.
Ph I Ar NOH
DMEDA
K2CO3
o-xylene, 130 o
C, 12 h
CuSO4.5H2O
Ar N
H
O
Ph

7. Results and Discussions
 The optimized scheme:
Entry Aldoxime Thioamide Yield [%]
1 80
2 40
3 79
4 20
5 75
N
OH
Cl
NH2
S
Cl
NH2
S
N
OH
MeO
NH2
S
MeO
N
OH
O2N
NH2
S
O2N
O
N OH
O
NH2
S
N
OH
N
OH
NH2
S
CuI (10 mol-%)
Et3N (2.5 equiv.)
P2S5 (1equiv.)
DMF (3 mL),140 o
C,12h

8. Conclusion
 One step protocol for direct conversion of aldoximes to
thioamides in the presence of copper catalyst.
 Plausible mechanism:
N
OH
NH2
S
CuI
Et3N, P2S5
DMF ,140 o
C,12 h
R
N
OH
[Cu]
R
N
OH
H
Cu
H2O
R
N
Cu
R
N
Cu
SH
R
NH2
S
H2O
S

9. NMR Data of Benzothioamide
1H NMR (400 MHz, CDCl3) δ 7.90-7.87 (m, 2H, J=8 Hz), 7.55-7.51 (m, 1H, J=1.2
Hz), 7.45-7.41 (m, 2H, J=2 Hz);
13C NMR (100 MHz, CDCl3) δ 202.9, 139.2, 132.0, 130.1, 128.5, 126.9, 77.3,
77.0, 76.7.
References
1. Bitton, A. Inflamm. Bowel Dis. 2005, 11, 513.
2. J. Clayden, N. Greeves, S. Warren, P. Wothers, Organic Chemistry, 1st ed., Oxford University Press, Oxford,
UK, UK, 2001, p. 997;
3. N. Panda, R. Mothkuri, and D. K. Nayak, Eur. J. Org. Chem. 2014, 1602.
NH2
S