CHAPTER 1: INTRODUCTION
Carbonyl compounds are very useful starting materials for various transformations in
organic synthesis. Therefore, it becomes necessary to protect them and to deprotect
them as well, when required. One of the simplest potential routes is by converting
them to oximes. Oximes are the significant derivatives of carbonyl compounds with
C=N–OH functional group. Oximation represents a classical method for purification,
characterisation and protection of carbonyl compounds.
Many methods for the
regeneration of carbonyl compounds from oximes have been reported. These include
the hydrolytic method, oxidative cleavage or reductive cleavage.
Another, very
important reaction of ketoximes is their rearrangement into more stable amide isomers.
One of the most popular applications of this rearrangement is conversion of
cyclohexanone oxime into ε-caprolactam, an important industrial chemical which
yields Nylon-6 polymer.
Sulphuric acid is most commonly used acid for the
production of the lactam.
Some other reagents have also been reported for this
reaction. However, in view of the limited yields, corrosive and expensive catalysts,
longer reaction times and use of reflux conditions etc., there is still a need for
developing new eco-friendly methods for the above mentioned reactions of oximes.
PROGRAMME OF RESEARCH
RAPID DEOXIMATION OF ALDOXIMES AND KETOXIMES USING NEW
CATALYTIC SYSTEMS UNDER SOLVENT-FREE CONDITIONS
Since, previous methods for the deoximation reactions use harsh acid catalysts or
reflux conditions, so they suffer from usual limitations. Therefore, we aimed at
investigating rapid deoximation of aldoximes and ketoximes, under solvent-free
conditions in the presence of some new catalysts such as p-Chloroperbenzoic acid
(p-CPBA), Potassium Bromate [KBrO3],
Zirconyl Nitrate [ZrO(NO3)2.6H2O],
Zirconyl Oxychloride (ZrOCl2.8H2O), Samarium Nitrate [Sm(NO3)3.6H2O], Terbium
Nitrate [Tb(NO3)3.6H2O],
Copper Nitrate [Cu(NO3)2.3H2O], Aluminium nitrate
[Al(NO3)3.9H2O] etc.
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For this purpose, variously substituted aldoximes with electron withdrawing and
electron donating group would be deoximated: Oximes of 4-nitrobenzaldehyde,
2-nitrobenzaldehyde,
4-chlorobenzaldehyde,
3-nitrobenzaldehyde,
2,4-dimethoxybenzaldehyde,
2,4-dichlorobenzaldehyde,
4-bromobenzaldehyde,
4-hydroxybenzaldehyde etc. Variously substituted ketoximes would also be
deoximated: Oximes of benzophenone, 4-hydroxyacetophenone, acetophenone,
cyclohexanone, 4-nitroacetophenone, 4-chloroacetophenone, 4-methoxyacetophenone
etc. Oximes of some sterically hindered compounds such as, oximes of testosterone
propionate, androsterone, α-tetralone would also be deoximated.
RAPID SYNTHESIS OF AMIDES FROM KETOXIMES USING NEW
CATALYTIC SYSTEMS UNDER SOLVENT-FREE CONDITIONS
Since, synthesis of amides from ketoximes requires strongly acidic conditions, which
suffer from usual limitations such as harsh reaction conditions, hard to handle strong
acids, formation of by-products harmful to environment etc. Therefore, we aimed at
investigating mild, eco-friendly and easy to handle catalytic systems, which would
work efficiently to yield amides under solvent-free conditions. We envisaged
p-Toluenesulphonic acid monohydrate and Citric acid monohydrate over phase transfer
catalysts tetrabutylammonium bromide (TBAB), poly ethylene glycol (PEG) and
N-cetyl-N,N,N-trimethylammonium bromide (CTAB) to synthesize amides from
ketoximes. For this purpose, variously substituted ketones like benzophenone,
4-hydroxyacetophenone,
acetophenone,
cyclohexanone,
4-nitroacetophenone,
4-chloroacetophenone, 4-methoxyacetophenone would be investigated.
CHAPTER 2: RESULTS AND DISCUSSION
2.1
RAPID DEOXIMATION OF ALDOXIMES AND KETOXIMES USING
NEW
CATALYTIC
SYSTEMS
UNDER
SOLVENT-FREE
CONDITIONS
We tried to deoximate the oximes of variously substituted aldehydes and ketones,
using new catalytic systems, under solvent-free conditions upon microwave
irradiation.
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R1
R1
Catalyst
N
O
MW
R2
OH
R2
Aldehyde/Ketone
Oxime
R2=R/H
For this purpose, we explored the following catalytic systems:
 p-Chloroperbenzoic acid [Cl-C6H4COOOH].
 Zirconyl Nitrate [ZrO(NO3)2] in conjunction with Sodium Nitrite (NaNO2) and
tetrabutylammonium bromide (TBAB).
 Zirconyl Oxychloride [ZrOCl2.8H2O] in conjunction with Sodium Nitrite (NaNO2).
 Potassium Bromate [KBrO3] in conjunction with tetrabutylammonium bromide
(TBAB).
 Copper Nitrate [Cu(NO3)2.3H2O] in conjunction with tetrabutylammonium
bromide (TBAB).
 Aluminium Nitrate [Al(NO3)3.9H2O].
 Terbium Nitrate [Tb(NO3)3.6H2O].
 Samarium Nitrate [Sm(NO3)3.6H2O] in conjunction with tetrabutylammonium
bromide (TBAB).
Variously substituted aldoximes with electron withdrawing and electron donating
groups, were deoximated as given below:
Oximes of 4-nitrobenzaldehyde,
2,4-dimethoxybenzaldehyde,
2-nitrobenzaldehyde,
4-chlorobenzaldehyde,
3-nitrobenzaldehyde,
2,4-dichlorobenzaldehyde,
4-bromobenzaldehyde and 4-hydroxybenzaldehyde.
Variously
substituted
ketoximes
like
4-hydroxyacetophenone, acetophenone,
oximes
cyclohexanone,
of
benzophenone,
4-nitroacetophenone,
4-chloroacetophenone and 4-methoxyacetophenone were also deoximated.
After getting success in the regeneration of aldehydes and ketones from their oximes,
we also deoximated oximes of testosterone propionate, androsterone and α-tetralone.
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Yields obtained at different power levels varying from 90 W to 900 W, were compared
and the optimum power level was selected for every catalytic system. Therefore, all the
above listed substituted oximes were doximated at this optimum power level to yield
the corresponding carbonyl compounds. The yields were found to be 60-80 % in the
presence of p-CPBA, 85-95 % in the presence of KBrO3, 75-93 % in the presence of
ZrO(NO3)2, 75-90 % in the presence of ZrOCl2.8H2O, 71-95 % in the presence of
Cu(NO3)2.3H2O, 75-95 % in the presence of Al(NO3)3.9H2O, 75-95 % in the presence
of Tb(NO3)3.6H2O and 75-94 % in the presence of Sm(NO3)3.6H2O.
2.2
RAPID SYNTHESIS OF AMIDES FROM KETOXIMES USING NEW
CATALYTIC SYSTEMS UNDER SOLVENT-FREE CONDITIONS
We investigated the rapid synthesis of amides of variously substituted ketones, through
rearrangement reaction of their oximes using new catalytic systems, under solvent-free
conditions.
OH
O
N
NH2OH.H2O
O
H
R
R
MW
MW
R
Amide
Ketoxime
Ketone
N
H
We succeeded in finding p-toluenesulphonic acid monohydrate (TsOH.H2O) over
phase transfer catalysts, poly ethylene glycol (PEG)/ tetrabutylammonium bromide
(TBAB)/ N-cetyl-N,N,N-trimethylammonium bromide (CTAB)
and Citric acid
monohydrate (C6H8O7.H2O) over TBAB, as new catalytic systems, for the synthesis
of amides from ketoximes.
Amides of benzophenone, 4-hydroxyacetophenone, acetophenone, cyclohexanone,
4-nitroacetophenone,
4-chloroacetophenone
and
4-methoxyacetophenone
were
prepared.
Yields obtained at different power levels varying from 90 W to 900 W, were compared
and the optimum power level was selected for every catalytic system. Therefore, all the
above listed substituted ketones were converted into the amides at this optimum power
level. The yields were found to be 80-90 % in the presence of C6H8O7.H2O / TBAB,
60-80 % in the presence of TsOH.H2O / PEG, 65-85 % in the presence of
TsOH.H2O / TBAB and 60-82 % in the presence of TsOH.H2O / CTAB.
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CHAPTER 3: EXPERIMENTAL
3.1
RAPID DEOXIMATION OF ALDOXIMES AND KETOXIMES USING
NEW
CATALYTIC
SYSTEMS
UNDER
SOLVENT-FREE
CONDITIONS
Oxime of 4-nitrobenzaldehyde (1mmol) and specific amount of the catalyst
were mixed thoroughly in a 10 ml beaker and subjected to microwave irradiation until
the reaction was completed. TLC was used to monitor the progress of the reaction. An
optimum power level was decided by comparing the yields of benzophenone obtained
at different power levels. The product was extracted using diethyl ether.
Same
procedure was followed for the production of other carbonyl compounds from their
oximes at the identical reaction conditions. The products were identified on the basis
of comparison of their melting points/boiling points and spectroscopic data: 1H-NMR,
13
C-NMR and FT-IR with those of the authentic samples.
3.2
RAPID SYNTHESIS OF AMIDES FROM KETOXIMES USING NEW
CATALYTIC SYSTEMS UNDER SOLVENT-FREE CONDITIONS
Oxime of benzophenone (1mmol) and specific amount of the catalyst were
mixed thoroughly in the presence of distilled water (0.5 mL) in a 10ml Pyrex beaker
and and subjected to microwave irradiation until the reaction was completed. TLC was
used to monitor the progress of the reaction. An optimum power level was decided by
comparing the yields of amide obtained at different power levels. The product was
extracted using diethyl ether. Same procedure was followed for the production of
amides of other ketones at the identical reaction conditions.
The products were
identified on the basis of comparison of their melting points/boiling points and
spectroscopic data:
1
H-NMR,
13
C-NMR and FT-IR with those of the authentic
samples.
CHAPTER 4: REFERENCES
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