Transcript Document

Dr. Kristoffer Rem Labing-isa
Massachusetts Institute of Technology
Nitro Group Structure
N double bonded to O
and also single bonded
to O and to an R.
Background
Often highly explosive, especially when the
compound contains more than one nitro group.
one of the most common explosophores
(functional group that makes a compound
explosive) used globally.
Background
The NO2 group is called as nitro group. It is
electron withdrawing group due to its Inductive effect as well as -Resonance effect.
The structure of NO2 group is given below.
Background
Trinitrotoluene,
best known as a
useful explosive
material with
convenient handling
properties
Nomenclature
Name the longest and continuous carbon chain
Name the –NO2 compound as a –nitro substituent
Aliphatic Nitro
Nitromethane
Aromatic Nitro
Nitrobenzene
Nomenclature
Nitro butane
2-methyl-3-nitrobutane
1-nitronaphthalene
Physical Properties
Aliphatic Nitro
colorless liquids with pleasant smell, sparingly
soluble in water, have high boiling points. Most
of nitro alkanes are quite stable and can be
distilled without decomposition, and they are
polar due to the presence of nitro group
Physical Properties
Aromatic Nitro
yellow color liquids which intensified to brown
by time color with characteristic odor, steam
volatile and can be purified by steam
distillation and they are polar due to the
presence of nitro group
Chemical Properties
Aliphatic Nitro
Nitro compounds undergo tautomerism in
solution to azinitro form, which is acidic in
nature. Hence, all the nitro compounds are
weakly acidic in nature.
Chemical Properties
Aromatic Nitro
Nitro benzene is electron withdrawing group by
both inductive effect and resonance effect.
Hence it deactivates the benzene ring and it is
meta directing group.
Preparation
By direct nitration of alkanes
CH3-CH3 + HNO3/H2SO4 → CH3-CH2-NO2
ethane
benzene
nitroethane
nitrobenzene
Preparation
By treating amines with alkaline KMnO4
aminomethane
nitromethane
Nitro Journal
α-Fluoro-α-nitro(phenylsulfonyl)methane
as a fluoromethyl pronucleophile:
Efficient stereoselective
Michael addition to chalcones
G. K. Surya Prakash1, Fang Wang, Timothy Stewart,
Thomas Mathew, and George A. Olah1
Introduction
Enantioselective preparation of
fluoromethylated organics is one of the major
areas of interest today because fluoromethyl
substituted compounds carry great
importance in pharmaceutical chemistry,
material science and healthcare
Introduction
One of the major recent developments in this
area involves the efficient, and highly
enantioselective monofluoralkylation of
alcohols using the Mitsunobu reaction
Introduction
Our recent investigations showed that fluorine
containing (phenylsulfonyl)methane derivatives
such as -nitro, cyano, ester, or acetyl-substituted
fluoro(phenylsulfonyl)methane can be effectively
used under mild conditions for the synthesis of a
variety of functionalized monofluoromethylated
compounds, which are crucial synthons for many
valuable compounds in the pharmaceutical arena
Introduction
Introduction
Very recently, Shibata and colleagues have
achieved a catalytic enantioselective Michael
addition of FBSM to chalcones using cinchona-based
phase transfer catalysts.
Michael addition between nitromethane
and chalcone with high ee and chemical yields
using cinchona alkaloid-derived chiral bifunctional
thiourea asan effective organocatalyst.
Introduction
Preliminary
screening of the
catalysts was
carried out using
dichloromethane or
toluene as solvent.
Introduction
We have screened a series of
catalysts for the enantioselective addition of fluoro--nitro- (phenylsulfonyl)methane (FNSM)
to chalocones systematically and we found
that catalysts enable this reaction to occur
successfully in the absence of any base
to provide exclusive 1,4-addition products
Discussion
Introduction
FNSM has been added to a
series of chalcone
derivatives to obtain the
corresponding adducts in
high yields with high
diastereomeric ratios and
excellent enantiomeric
excesses
Discussion
The bifunctional catalysts
themselves are capable of
deprotonating the FNSM into
the corresponding carbanion,
which can attack the Michael
acceptors in an appropriate
configuration by undergoing
an inversion
Discussion
The absolute configuration of the product was unequivocally
established by X-ray crystallographic analysis
Methods
Typical Procedure for Catalytic 1,4-Addition of
-Fluoro--nitro(phenylsulfonyl) methane to ,-Unsaturated Ketones.
To a solution of -fluoro--nitro(phenylsulfonyl) methane (21.9 mg, 0.1
mmol, 1 equivalent) and ketone (0.2 mmol, 2 equivalent) in CH2Cl2, Et3N
(10.0 L of 0.1 mmol, 0.7 equivalent) was added. The reaction mixture was
stirred for 12 h at room temperature and the conversion was monitored
by 19F NMR before purification (diastereomeric ratios were 1:1 in all of
the cases). The reaction mixture was loaded on to a preparative TLC
plate. In most cases, the diastereomers can be separated with
hexane/ethyl acetate (4/1– 6/1) to produce the title product in good to
excellent yield.
Methods
Typical Procedure for Catalytic Enantioselective 1,4-Addition of
-Fluoro--nitro- (phenylsulfonyl)methane to Chalcones.
To a solution of -fluoro--nitro(phenylsulfonyl) methane (21.9 mg, 0.1 mmol, 1
equivalent) and ketone (0.2 mmol, 2 equivalent) in precooled toluene (20 °C,
0.5 mL), catalystQNI was added (6.0 mg, 0.01 mmol, 10 mol%) in one load. The
reaction mixture was stirred for 1 min and placed in freezer (20 °C) for 2
days without stirring. The reaction mixture was monitored by 19F NMR for
conversion and diastereoselectivity, and loaded on to preparative TLC plate. In
most cases, the diastereomers can be separated with hexane/ethyl acetate
(4/1– 6/1) to produce the title product in good to excellent yield. Products
were characterized by spectral analysis (1H NMR, 13C NMR, 19F NMR, and
HRMS), and the ee values were determined by chiral HPLC.
Conclusion
In conclusion, we have achieved an
enantioselective and diastereoselective
1,4-conjugate addition of FNSM, an effective
fluoromethyl pronucleophile to chalcones using
cinchona alkaloid based bifunctional catalysts
with highest efficacy observed for QN I.