substitution process

This is an acid-base reaction: a proton is

transferred from HCl, the acid, to hydroxide,
the base. The product is water and chloride
ion. You have undoubtedly seen this
reaction before in general chemistry.
Despite its simplicity, this reaction allows us
to consider for the first time many of the
fundamental ideas of organic chemistry that
we will be exploring in various contexts
throughout this text.

Substituted or unsubstituted
cyclopentadienyl are prepared by
reducing 4-ketocyclopentene to an
alcohol, replacing the hydroxyl
functionality with a leaving group and
deprotonating the resulting product
under base induced elimination
conditions.
The amino acid is transferred to a
special kind of RNA polymer called
transfer RNA, or tRNA for short. We
need not concern ourselves here with
the structure of tRNA molecules- all
we need to know for now is that the
nucleophile in this reaction is a
hydroxyl group on the terminal
adenosine of tRNA.





Substitution process

















Five-membered heterocycles having
biphenylsulfonyl substitution, process for their
preparation, their use as a medicament or
diagnostic, and medicament comprising them.
Compounds of the formula I in which the symbols
have the meanings indicated in the claims, have
outstanding antiarrhythmic properties and exhibit a
cardioprotective component. They can preventively
inhibit or greatly decrease the pathophysiological
processes in the formation of ischemically induced
damage, in particular in the elicitation of
ischemically induced cardiac arrhythmias. Moreover,
they have a potent inhibitory action on the
proliferation of cells.



Addition of nucleophiles to electron-deficient
arenes, even those containing leaving groups
X e.g. halogens, proceeds faster in positions
occupied by hydrogen than in those occupied
by halogens. Since spontaneous departure of
hydride anion from the initially formed H
adducts does not proceed and the addition is
a reversible process, nucleophilic substitution
of halogens (SNAr reaction), proceeding via
slower, but irreversible formation of the X
adducts is commonly observed process.
These relations are exemplified in scheme 1.

If aniline is treated with acetic
anhydride, it is converted to
acetanilide (Fig. 11-6). The
substituent on the ring is now
an acetamido group, and is still an
ortho, para director, but less strongly
activating, so that mono substitution
can be carried out easily. The acetyl
group can then be removed by
hydrolysis if desired ("Carboxylic
Acids").
The negative charge on the intermediate
is spread out into the benzene ring and
onto the ketone by resonance. The
resonance form with the charge on
oxygen looks very much like the
intermediate in carbonyl addition
elimination, except that there is a
benzene ring between the nucleophile
and the carbonyl.

Addition process
































a third mechanism for nucleophilic substitution has been
proposed. This two-step mechanism is characterized by initial
addition of the nucleophile (hydroxide ion or water) to the
aromatic ring, followed by loss of a halide anion from the
negatively charged intermediate as illustrated below. The sites
over which the negative charge is delocalized are colored
blue, and the ability of nitro, and other electron withdrawing,
groups to stabilize adjacent negative charge accounts for their
rate enhancing influence at the ortho and para locations.



Three additional examples of aryl halide nucleophilic
substitution are presented below. Only the 2- and 4-
chloropyridine isomers undergo rapid substitution, the 3-
chloro isomer is relatively unreactive. Nitrogen
nucleophiles will also react, as evidenced by the use of
Sanger's reagent for the derivatization of amino acids. The
resulting N-2,4-dinitrophenyl derivatives are bright yellow
crystalline compounds that facilitated analysis of peptides
and proteins.

The process comprises a step wherein a crude
solution of the pro-drug ester is subjected to an
evaporation which is controlled by the
evaporation rate of the organic solvent such that
a continuous operation is accomplished for the
crystallization of the desired purified pro-drug
ester or salt thereof. Said crystallization is
preferably preceded by an aqueous phase
extraction and/or an organic phase extraction,
both preferably also being performed
continuously.








Addition process















A process of preparing imatinib, either as the free base or
as an acid addition salt, which process comprises reacting
N-(2-methyl-5-aminophenyl-4-(3-pyridyl)-2-pyrimidine
amine of formula (II) with a 4-(4-methyl-piperazino
methyl)benzoyl halide of formula (III) in the presence of an
inert organic solvent, so as to yield a hydrohalide salt of
imatinib formula (I) where n represents 1, 2 or 3 and Hal
represents bromo, chloro, fluoro or iodo, either in
anhydrous or hydrated form, which can as desired
optionally be further converted either to the free base or a
further acid addition salt. The present invention is also
concerned with imatinib prepared according to the above
process.
'Aldol' is an abbreviation of aldehyde
and alcohol. When the enolate of an
aldehyde or a ketone reacts at the -
carbon with the carbonyl of another
molecule under basic or acidic
conditions to obtain -hydroxy
aldehyde or ketone, this reaction is
called Aldol Reaction.
This methodology is useful in the
synthesis of roxifiban, a drug in
development for a range of
cardiovascular disorders arising
from undesired platelet adhesion.