Hetero Cyclic Compounds

Heterocyclic Compound
Introduction
Compounds classified as heterocyclic probably constitute the largest and most varied •
family of organic compounds. After all, every carbocyclic compound, regardless of
structure and functionality, may in principle be converted into a collection of heterocyclic
analogs by replacing one or more of the ring carbon atoms with a different element. Even
if we restrict our consideration to oxygen, nitrogen and sulfur (the most common
heterocyclic elements), the permutations and combinations of such a replacement are
numerous
Heterocyclic compounds are organic compounds that contain a ring structure•

containing atoms in addition to carbon, such as sulfur, oxygen or nitrogen, as part of the
ring.[1] They may be either simple aromatic rings or non-aromatic rings. Some examples
.(are pyridine (C5H5N), pyrimidine (C4H4N2) and dioxane (C4H8O2
Note that compounds such as cyclopropane, an anaesthetic with explosive properties, and•
cyclohexane, a solvent, are not heterocyclic; they are merely cycloalkanes. The prefix
'cyclic' implies a ring structure, whereas 'hetero' refers to an atom other than carbon, as
.above. Many heterocyclic compounds, including some amines, are carcinogenic
Heterocyclic chemistry is the chemistry branch dealing exclusively with synthesis, •

.properties, and applications of heterocyles
Nomenclature
Devising a systematic nomenclature system for heterocyclic compounds presented a formidable
challenge, which has not been uniformly concluded. Many heterocycles, especially amines, were
identified early on, and received trivial names which are still preferred. Some monocyclic
compounds of this kind are shown in the following chart, with the common (trivial) name in bold
and a systematic name based on the Hantzsch-Widman system given beneath it in blue. The rules
for using this system will be given later. For most students, learning these common names will
.provide an adequate nomenclature background
1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

An easy to remember, but limited, nomenclature system makes use of an elemental prefix for the
heteroatom followed by the appropriate carbocyclic name. A short list of some common prefixes
is given in the following table, priority order increasing from right to left. Examples of this
nomenclature are: ethylene oxide = oxacyclopropane, furan = oxacyclopenta-2,4-diene, pyridine
.= azabenzene, and morpholine = 1-oxa-4-azacyclohexane
Element oxygen sulfur selenium nitrogen phosphorous silicon boron
Valence II II II III III IV III
Prefix Oxa Thia Selena Aza Phospha Sila Bora
The Hantzsch-Widman system provides a more systematic method of naming heterocyclic

compounds that is not dependent on prior carbocyclic names. It makes use of the same hetero
atom prefix defined above (dropping the final "a"), followed by a suffix designating ring size and
saturation. As outlined in the following table, each suffix consists of a ring size root (blue) and an
ending intended to designate the degree of unsaturation in the ring. In this respect, it is important
to recognize that the saturated suffix applies only to completely saturated ring systems, and the
unsaturated suffix applies to rings incorporating the maximum number of non-cumulated double
bonds. Systems having a lesser degree of unsaturation require an appropriate prefix, such as
.""dihydro"or "tetrahydro
Ring Size 3 4 5 6 7 8 9 10

Suffix
ine ocine
Unsaturate irene ete ole epine onine ecine
inan ocan
d irane etane olane epane onane ecane
e e
Saturated
Despite the general systematic structure of the Hantzsch-Widman system, several exceptions and
modifications have been incorporated to accomodate conflicts with prior usage. Some examples
:are
.The terminal "e" in the suffix is optional though recommended•
Saturated 3, 4 & 5-membered nitrogen heterocycles should use respectively the•

.traditional "iridine", "etidine" & "olidine" suffix
.Unsaturated nitrogen 3-membered heterocycles may use the traditional "irine" suffix•
Consistent use of "etine" and "oline" as a suffix for 4 & 5-membered unsaturated•
.heterocycles is prevented by their former use for similar Sized nitrogen heterocycles
Established use of oxine, azine and silane for other compounds or functions prohibits•
.their use for pyran, pyridine and silacyclohexane respectively
Note that when a maximally unsaturated ring includes a saturated atom, its location may be
designated by a "#H " prefix to avoid ambiguity, as in pyran and pyrrole above and several
examples below. When numbering a ring with more than one heteroatom, the highest priority
.atom is #1 and continues in the direction that gives the next priority atom the lowest number

All the previous examples have been monocyclic compounds. Polycyclic compounds
incorporating one or more heterocyclic rings are well known. A few of these are shown in the
following diagram. As before, common names are in black and systematic names in blue. The
two quinolines illustrate another nuance of hetrocyclic nomenclature. Thus, the location of a
fused ring may be indicated by a lowercase letter which designates the edge of the heterocyclic
.ring involved in the fusion
Classification (1, 2
(
There are a lot of classification for heterocylic compounds but they are very complicated to
understand. The simplest way to classify heterocylic compounds is on the basis of their structural
.difference. These are classified according to number of members present in the ring structure
-: Simply the heterocylic compounds are classified as follows
Membered rings-3 .1
Membered rings-4 2.2
Membered rings-5.3
Membered rings-6.4
Heterocyclic amines and cancer.5
Membered rings-3•
Heterocycles with three atoms in the ring are more reactive because of ring strain. Those
containing one heteroatom are, in general, stable. Those with two heteroatoms are more likely to
:occur as reactive intermediates. Common 3-membered heterocycles are

Unsaturated Saturated Heteroatom
Aziridine Nitrogen
Oxirene Ethylene oxide (epoxides,

Oxygen
(oxiranes
(Thiirane (episulfides Sulfur
Membered rings-4•
Azetidine Nitrogen
Dithiete Oxetane Oxygen
Thietane, dithietane Sulfur

Membered rings-5•
With heterocycles containing five atoms, the unsaturated compounds are frequently more stable
.because of aromaticity

:With two heteroatoms
Diazines Piperazine Nitrogen
Oxazine Nitrogen / oxygen
Thiazine Nitrogen / sulfur
Dithiane Sulfur
Dioxane Oxygen
Heterocyclic amines and cancer•

Some heterocyclic amines (HCAs) found in cooked meat are known carcinogens. Research has
shown that cooking certain meats at high temperatures creates chemicals that are not present in
uncooked meats. For example, heterocyclic amines are the carcinogenic chemicals formed from
the cooking of muscle meats such as beef, pork, fowl, and fish. HCAs form when amino acids
and creatine (a chemical found in muscles) react at high cooking temperatures. Researchers have
identified 17 different HCAs resulting from the cooking of muscle meats that may pose human
cancer risk. NCI's Division of Cancer Epidemiology and Genetics found a link between
individuals with stomach cancer and the consumption of cooked meat, and other studies for
colorectal, pancreatic, and breast cancer is associated with high intakes of well-done, fried, or
.barbecued meats

PYRIDINE NUCLEUS
Pyridine is a chemical compound with the formula C5HYPERLINK

"http://en.wikipedia.org/wiki/Hydrogen"H5HYPERLINK
"http://en.wikipedia.org/wiki/Nitrogen"N. It is a liquid with a distinctively putrid, fish-like odour.
Pyridine is a simple and fundamentally important heterocyclic aromatic organic compound. It is
structurally related to benzene, wherein one CH group in the six-membered ring is replaced by a
nitrogen atom. The pyridine ring occurs in many important compounds, including the
nicotinamides. Pyridine is sometimes used as a ligand in coordination chemistry. As a ligand, it is
."usually abbreviated "py
PYRIDINE, also called azabenzene and azine, is a heterocyclic aromatic tertiary amine
characterized by a six-membered ring structure composed of five carbon atoms and a nitrogen
which replace one carbon-hydrogen unit in the benzene ring (C5H5N). The simplest member of
the pyridine family is pyridine itself. It is colorless, flammable, toxic liquid with a unpleasant
odor, miscible with water and with most organic solvents, boils at 115 C. Its aqueous solution is
slightly alkaline. Its conjugate acid is called pyridinium cation, C5H5NH+, used as a oxidation
..agent for organic synthesis
Pyridine and its derivatives are very important in industrial field as well as in bio chemistry.
Some pyridine system is active in the metabolism in the body. They can be the parent compound
.of many drugs, including the barbiturates
Pyridine and its derivatives are used as solvents and starting material for the synthesis of target
compounds such as insecticides, herbicides, medicines, vitamins, food flavorings, feed additives,
dyes, rubber chemicals, explosives, disinfectants, and adhesives. Pyridine is also used as a
denaturant for antifreeze mixtures, as a dyeing assistant in textiles and in fungicides. Compounds
not made from pyridine but containing its ring structure include niacin and pyridoxal; isoniazid,
.nicotine, and several other nitrogenous plant products

Basicity of Pyridine
The nitrogen atom on pyridine features a basic lone pair of electrons. Because this lone pair is •
not delocalized into the aromatic pi-system, pyridine is basic with chemical properties similar
to tertiary amines. The pKa of the conjugate acid is 5.21. Pyridine is protonated by reaction
with acids and forms a positively charged aromatic polyatomic ion called pyridinium cation.
The bond lengths and bond angles in pyridine and the pyridinium ion are almost identical[1]
because protonation does not disrupt the aromatic pi system. In addition, the pyridinium
.cation is isoelectronic with benzene
From heat of combustion measurements, the aromatic stabilization energy of pyridine is 21•
kcal/mole. The greater electronegativity of nitrogen (relative to carbon) suggests that such
canonical forms may contribute to a significant degree. Pyridine and its derivatives are weak
bases, reflecting the sp2 hybridization of the nitrogen. From the polar canonical forms shown
here, it should be apparent that electron donating substituents will increase the basicity of a
pyridine, and that substituents on the 2 and 4-positions will influence this basicity more than
an equivalent 3-substituent. The pKa values given in the table illustrate a few of these
substituent effects. Methyl substituted derivatives have the common names picoline (methyl
pyridines), lutidine (dimethyl pyridines) and collidine (trimethyl pyridines). The influence of
2-substituents is complex, consisting of steric hindrance and electrostatic components. 4-
Dimethylaminopyridine is a useful catalyst for acylation reactions carried out in pyridine as a
solvent
The diazines pyrazine, pyrimidine and pyridazine are all weaker bases than pyridine due to
the inductive effect of the second nitrogen. However, the order of base strength is
unexpected. A consideration of the polar contributors helps to explain the difference between
pyrazine and pyrimidine, but the basicity of pyridazine seems anomalous. It has been
suggested that electron pair repulsion involving the vicinal nitrogens destabilizes the neutral
.base relative to its conjugate acid
Pyridine as a solvent
Pyridine is a widely used and versatile solvent: it is polar but aprotic. It is miscible with a•

broad range of solvents including hexane and water. Deuterated pyridine, called pyridine-
.d5, is a common solvent for1H NMR spectroscopy
Role in Chemical Synthesis

Pyridine is important in industrial chemistry, both as a fundamental building block and as •
a solvent and reagent in organic synthesis.[2] It is used as a solvent in Knoevenagel
.condensations
It is also a starting material in the synthesis of compounds used as an intermediate in •

making insecticides, herbicides, pharmaceuticals, food flavorings, dyes, rubber
chemicals, adhesives, paints, explosives and disinfectants. Pyridine is also used as a
denaturant for antifreeze mixtures, for ethyl alcohol, for fungicides, and as a dyeing aid
.for textiles
Role in Chemical Analysis

Pyridine, along with barbituric acid, is commonly used in colorimetric determinations of•
cyanide in aqueous matrices. Pyridine reacts with cyanogen chloride (formed in an earlier
step by reaction of the cyanide anion with chloramine-T) to form a conjugated species
that couples two molecules of barbituric acid together, forming a red-colored dye. Color
.intensity is directly proportional to cyanide concentration
Pyridine was originally used as the base in the Karl Fischer titration, but has since been•
largely replaced by imidazole, which is more basic than pyridine, allowing for a more
stable equivalence point and a faster reaction rate. Imidazole also has the advantage of
.being odorless
Preparation of Pyridine
Many methods exist in industry and in the laboratory (some of them named reactions) for•
the synthesis of pyridine and its derivatives: Pyridine was originally isolated industrially
from crude coal tar. It is currently synthesized from acetaldehyde, formaldehyde and
:ammonia, a process that involves the intermediacy of acrolein
CH2O + NH3 + 2 CH3CHO → C5H5N + 3 H2O

By substituting other aldehydes for acetaldehyde, one obtains alkyl and aryl substituted
.pyridines. 26,000 tons were produced worldwide in 1989
The Hantzsch pyridine synthesis is a multicomponent reaction involving formaldehyde, a•

.keto-ester and a nitrogen donor
Other examples of the pyridine class can be formed by the reaction of 1,5-diketones with•
ammonium acetate in acetic acid followed by oxidation. This reaction is called the
.Kröhnke pyridine synthesis
.Pyridinium salts can be obtained in the Zincke reaction•
The Ciamician-Dennstedt Rearrangement (1881) is the ring-expansion of pyrrole with•

dichlorocarbene to 3-chloropyridine and HCl
In the Chichibabin pyridine synthesis (Aleksei Chichibabin, 1906) the reactants are three•
equivalents of a linear aldehyde and ammonia
In the Gattermann-Skita synthesis (1916) a malonate ester salt reacts with•

dichloromethylamine
. Synthesis of pyridine derivatives using aza Diels–Alder methodology•
For example: - Hantzsch Dihydropyridine (Pyridine) Synthesis
This reaction allows the preparation of dihydropyridine derivatives by condensation of an

aldehyde with two equivalents of a β-ketoester in the presence of ammonia. Subsequent oxidation
(or dehydrogenation) gives pyridine-3,5-dicarboxylates, which may also be decarboxylated to
.yield the corresponding pyridines

Mechanism
The reaction can be visualized as proceeding through a Knoevenagel Condensation product as a

:key intermediate
A second key intermediate is an ester enamine, which is produced by condensation of the second
:equivalent of the β-ketoester with ammonia
:Further condensation between these two fragments gives the dihydropyridine derivative

.Synthesis of pyridine derivatives using aza Diels–Alder methodology
Amidrazone reacted with the unsymmetrical tricarbonyls giving triazines . These•

triazines were converted into their corresponding pyridine derivatives in aza Diels–Alder
reactions with 2,5-norbornadiene . Triazines gave the pyridolactones with 2,3-
dihydrofuran

Organic reactions of Pyridine

In organic reactions pyridine behaves both as a tertiary amine, undergoing protonation,
alkylation, acylation, and N-oxidation at nitrogen, and as an aromatic compound, undergoing
.Nucleophilic substitutions
Pyridine is a good nucleophile with a donor number of 33.1. It is easily attacked by•
.alkylating agents to give N-alkylpyridinium salts
Nucleophilic aromatic substitution occurs at C2/C4. For example in the Chichibabin•

reaction, pyridine reacts with sodium amide to give 2-aminopyridine. In the Emmert
reaction (Bruno Emmert, 1939) pyridine reacts with a ketone in presence of aluminium
.or magnesium and mercuric chloride to give the carbinol also at C2
Electrophilic Substitution of Pyridine
Pyridine is a modest base (pKa=5.2). Since the basic unshared electron pair is not part of the
aromatic sextet, as in pyrrole, pyridinium species produced by N-substitution retain the
aromaticity of pyridine. As shown below, N-alkylation and N-acylation products may be prepared
as stable crystalline solids in the absence of water or other reactive nucleophiles. The N-acyl salts
may serve as acyl transfer agents for the preparation of esters and amides. Because of the stability
of the pyridinium cation, it has been used as a moderating component in complexes with a
number of reactive inorganic compounds. Several examples of these stable and easily handled
reagents are shown at the bottom of the diagram. The poly(hydrogen fluoride) salt is a convenient
source of HF for addition to alkenes and conversion of alcohols to alkyl fluorides, pyridinium
chlorochromate (PCC) and its related dichromate analog are versatile oxidation agents and the
tribromide salt is a convenient source of bromine. Similarly, the reactive compounds sulfur
.trioxide and diborane are conveniently and safely handled as pyridine complexes
Amine oxide derivatives of 3º-amines and pyridine are readily prepared by oxidation with
peracids or peroxides, as shown by the upper right equation. Reduction back to the amine can
.usually be achieved by treatment with zinc (or other reactive metals) in dilute acid

From the previous resonance description of pyridine, we expect this aromatic amine to undergo
electrophilic substitution reactions far less easily than does benzene. Furthermore, as depicted
above the electrophilic reagents and catalysts employed in these reactions coordinate with the
nitrogen electron pair, exacerbating the positive charge at positions 2,4 & 6 of the pyridine ring.
Three examples of the extreme conditions required for electrophilic substitution are shown on the
left. Substituents that block electrophile coordination with nitrogen or reduce the basicity of the
nitrogen facilitate substitution, as demonstrated by the examples in the blue-shaded box at the
lower right, but substitution at C-3 remains dominant. Activating substituents at other locations
.also influence the ease and regioselectivity of substitution
The fused ring heterocycles quinoline and isoquinoline provide additional evidence for the
stability of the pyridine ring. Vigorous permanganate oxidation of quinoline results in
predominant attack on the benzene ring; isoquinoline yields products from cleavage of both rings.
Note that naphthalene is oxidized to phthalic acid in a similar manner. By contrast, the
heterocyclic ring in both compounds undergoes preferential catalytic hydrogenation to yield
tetrahydroproducts. Electrophilic nitration, halogenation and sulfonation generally take place at
C-5 and C-8 of the benzene ring, in agreement with the preceeding description of similar pyridine
.(reactions and the kinetically favored substitution of naphthalene at C-1 (α) rather than C-2 (β

Other Reactions of Pyridine
Thanks to the nitrogen in the ring, pyridine compounds undergo nucleophilic substitution
reactions more easily than equivalent benzene derivatives. In the following diagram, reaction 1
illustrates displacement of a 2-chloro substituent by ethoxide anion. The addition-elimination
mechanism shown for this reaction is helped by nitrogen's ability to support a negative charge. A
similar intermediate may be written for substitution of a 4-halopyridine, but substitution at the 3-
position is prohibited by the the failure to create an intermediate of this kind. The two
Chichibabin aminations in reactions 2 and 3 are remarkable in that the leaving anion is hydride
(or an equivalent). Hydrogen is often evolved in the course of these reactions. In accord with this
.mechanism, quinoline is aminated at both C-2 and C-4
Addition of strong nucleophiles to N-oxide derivatives of pyridine proceed more rapidly than to
pyridine itself, as demonstrated by reactions 4 and 5. The dihydro-pyridine intermediate easily
.loses water or its equivalent by elimination of the –OM substituent on nitrogen

Derivatives of Pyridine
Pyridine-borane, C5H5NBH3 (m.p. 10–11 °C) is a mild reducing agent with improved•
stability relative to NaBH4 in protic solvents and improved solubility in aprotic organic
.solvents
Pyridine-sulfur trioxide, C5H5NSO3 (mp 175 °C) is a sulfonation agent used to convert•
alcohols to sulfonates, which in turn undergo C-O bond scission upon reduction with
.hydride agents
Related compounds
Structurally or chemically related compounds are
DMAP is short for 4-dimethylaminopyridine•
Bipyridine and viologen are simple polypyridine compounds consisting of two pyridine •
molecules joined by a single bond
.Terpyridine, a molecule of three pyridine rings connected together by two single bonds•
.Quinoline and Isoquinoline have pyridine and a benzene ring fused together•
Aniline is a benzene derivative with an attached NH2 group and NOT a pyridine•
Diazines are compounds with one more carbon replaced by nitrogen such as Pyrazine and•
Pyramidine
Triazines are compounds with two more carbons replaced by nitrogen and a tetrazine has•

four nitrogen atoms
.Lutidine is a trivial name for 2,6-dimethylpyridine-2,6•
.Collidine is the trivial name for 2,4,6-trimethylpyridine•
Pyridinium p-toluenesulfonate (PPTS) is a salt formed by proton exchange between•

pyridine and p-toluenesulfonic acid
Chloropyridine is a toxic environmentally significant component of the breakdown of -2•

.the pesticide imidacloprid
Microbial Metabolism of the Pyridine Ring

THE METABOLISM OF PYRIDINE-3,4-DIOL (3,4-DIHYDROXYPYRIDINE) BY
.AGROBACTERIUM SP
Pyridine-3,4-diol (3,4-dihydroxypyridine, 3-hydroxypyrid-4-one), an intermediate in 4-•

hydroxypyridine metabolism by an Agrobacterium sp (N.C.I.B. 10413), was converted
.by extracts into 1 mol of pyruvate, 2mol of formate and 1 mol ofNH3 at pH7.0
Formate, but not the alternative likely product formamide, was further oxidized fivefold•
faster by 4-hydroxypyridine-grown washed cells than by similar organisms grown on
.succinate
The oxidation of pyridine-3,4-diol by crude extracts at pH8.5 required 1 mol of 02/molof•

substrate, produced 1 mol of acid and led to the formation of formate and a new
compoundwith an extinction maximum of 285nm (Compound I). This step was believed
tobe mediated by a new labile dioxygenase (tQ = 4h at pH7.0, 4°C) cleaving the pyridine
.ringbetween C-2 and C-3
Many of the properties of this pyridine-3,4-diol dioxygenaseparalleled those of the•

extradiol ('meta') oxygenases of aromatic-ring cleavage. Theextreme lability of the
.enzyme has so far precluded extensive purification
Compound Ishowed changes in the u.v.-absorption spectrum with pH but after •

acidification it wasconverted into a new product, 3-formylpyruvate, with an extinction
.maximum now at279nm

Both Compound I and 3-formylpyruvate were metabolized by extracts but at very•

different rates. The slower rate of metabolism of Compound I was nevertheless consistent
.with that of pyridine-3,4-diol metabolism
On acidification Compound I released about 0.65mol of NH3 and has been identified as•
.3-formiminopyruvate
Formylpyruvate was hydrolysed to formate and pyruvate (K,, 2/CM) by an-3•

acylpyruvate hydrolase active against several other dioxo homologues. The activity of
.this enzyme was much lower in extracts of succinate-grown cells
Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine

:Introduction
Malaria affects 40% of global population and accounts annually for 300 to 500 million clinical
cases with 1.5 to 2.7 million deaths. The burden of malaria is increasing because of drug

resistance, and there is an urgent need for new antimalarial drugs. Intra-erythrocytic stages of
malaria parasites consume and degrade huge quantities of hemoglobin in the food vacuole and
release large quantities of redox active free heme as a by-product . Free heme (ferriprotoporphyrin
IX) is very toxic , and parasites detoxify free heme by forming hemozoin, mainly through the
biocrystallization or biomineralization process . Molecules that inhibit parasite growth through
binding to heme are potential antimalarials, and the inhibition of hemozoin formation is
considered a valid target for developing new antimalarials. Again, the inhibition of hemozoin
formation may develop oxidative stress due to the accumulation of free heme, which can generate
highly reactive hydroxyl radical (·OH), and the malaria parasite is susceptible to oxidative stress.
Therefore, the enhancement of oxidative stress to the parasite by any means is a promising
.strategy in developing new antimalarial agents
Triarylmethanes represent an important class of medicinally important molecules and are known
to possess a wide variety of biological activities such as antitubercular, anti-implantation , and
antiproliferative activities and activity against breast cancer . The potent antimycotic drug
clotrimazole, a member of the triarylmethanes, inhibits the in vitro parasite growth of different
strains of chloroquine-sensitive and -resistant Plasmodium falciparum . Very recently,
antimalarial agents based on the clotrimazole scaffold have been synthesized . Again,
trisubstituted methanes (TRSMs) containing sulfide, sulfoxide, or sulfone spacers have also been
reported to show various biological activities. A small set of 9-(lupinylthio)xanthenes, 9-
(lupinylthio)thioxanthenes, and a-(lupinylthio)diphenylmethanes was found to exhibit diverse
biological activities . Arylsulfanyl and arylsulfonyl moities are integral parts of many antimalarial
agents. For example, the antimalarial activity of several arylacridinyl sulfones has been reported
recently . Furoxan derivatives bearing a sulfone moiety were reported to have antimalarial activity
. A series of imidazole-dioxolane compounds bind to the heme and showed promising anti-
Plasmodium activity . These results prompted us to synthesize and evaluate a new series of
TRSMs for antimalarial efficacy. Here we report the antimalarial activity of a series of
[(aryl)arylsufanylmethyl]pyridines (AASMPs) that represents a new class of TRSMs. Our work
focused on the evaluation of the antimalarial activity of these compounds, including the
mechanistic details on the effect of heme interaction, hemozoin formation, and in vitro and in
.vivo antimalarial effect
:Chemistry
Our method for the synthesis of AASMPs involved S alkylation of different aryl or heteroaryl
thiols using carbinols 3a and 3b as the alkylating agents . The formation of a sulfur link between a
diarylmethane and an aryl or a heteroaryl ring can be achieved either by the nucleophilic attack of

an aryl or heteroarylthiolate anion on diarylmethyl halides and diarylmethyl-p-tolylsulfonates or

by protic or Lewis acid-catalyzed condensation of diarylcarbinols with different aryl or
heteroarylthiols . Carbinols 3a and 3b were obtained by the Grignard reaction of 4-
methoxyphenylmagnesium bromide 1 with pyridine-3-carbaldehyde and pyridine-2-aldehyde,
respectively. The S alkylation reactions on carbinols 3a and 3b were achieved in the presence of
anhydrous AlCl3 (1.1 eq) in dry benzene at room temperature. However, in the case of S
alkylation of 2-mercaptobenzothiazole on carbinol 3a the reaction was performed at reflux
condition since 2-mercaptobenzothiazole is insoluble in benzene at room temperature. Although
in every case the reaction condition was like that of a typical Friedel-Crafts alkylation reaction
due to the higher nucleophilicity of sulfur than that of aromatic ring carbon atoms, nucleophilic
.attack occurred through sulfur
:Discussion
AASMP has antiplasmodial activity. The mechanistic studies reveal that it effectively inhibits
hemozoin formation and induces oxidative stress in the malaria parasite to inhibit P. falciparum
growth. The data indicate that this novel class of antimalarial shows selective activity against the
malaria parasite with a selectivity index of greater than 100 and offers antimalarial activity in vivo
in the rodent model
Compounds that inhibit hemozoin formation usually interact with heme. The addition of AASMP
clearly perturbed the heme spectrum, a finding indicative of an interaction between the AASMP
and the heme units. The spectral changes of heme-AASMP mixtures were similar to those
observed for molecular complex formation between metalloporphyrines and other aromatic
molecules involving a cofacial - interaction
The possible mechanism by which AASMP develops oxidative stress and parasite death is
mediated through its inhibitory effect on hemozoin formation. The inhibition of hemozoin
formation causes death of the parasite due to the accumulation of toxic free heme . Free heme can
damage cellular metabolism of the malaria parasite by inhibiting enzymes, promoting the
peroxidation of membranes and the production of reactive oxygen species in the acidic
environment of the food vacuole . It also well known that the malaria parasite is very much
susceptible to oxidative stress . Inhibition of heme detoxification function is known to kill the
.parasite through membrane lysis and the interference of other vital function

SOME COMPOUNDS CONTAINING PYRIDINE NUCLEUS
Amlodipine besylate
Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-
aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-
pyridinedicarboxylate, monobenzenesulphonate . Its empirical formula is
:C20H25CIN2O5•C6H6O3S, and its structural formula is
.Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1
:Therapeutic use
Hypertension•
(Coronary Artery Disease (CAD•
Chronic Stable Angina•
(Vasospastic Angina (Prinzmetal's or Variant Angina•
Angiographically Documented CAD•
Note : NORVASC has been safely administered with thiazides, ACE inhibitors, beta-blockers,
.long-acting nitrates, and/or sublingual nitroglycerin

Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel
blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and
cardiac muscle. The contractile processes of cardiac muscle and vascular smooth muscle are
dependent upon the movement of extracellular calcium ions into these cells through specific ion
channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a
.greater effect on vascular smooth muscle cells than on cardiac muscle cells
Side Effects
Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation),
bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural
.dizziness, postural hypotension, vasculitis
:Other side effects are
Edema•
Dizziness•
Flushing•
Palpitation•
Headache•
Fatigue•
Nausea•
Abdominal pain•

Clopidogrel bisulfate
Chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-
acetate sulfate (1:1). The empirical formula of clopidogrel bisulfate is C16H16ClNO2S•H2SO4 and
.its molecular weight is 419.9
:The structural formula is as follows
Clopidogrel bisulfate is a white to off-white powder. It is practically insoluble in water at neutral

pH but freely soluble at pH 1. It also dissolves freely in methanol, dissolves sparingly in
.methylene chloride, and is practically insoluble in ethyl ether
: Therapeutic use
Recent MI, Recent Stroke, or Established Peripheral Arterial Disease•
Acute Coronary Syndrome•
:Mechanism of action
Clopidogrel is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function
have been shown to decrease morbid events in people with established cardiovascular
atherosclerotic disease as evidenced by stroke or transient ischemic attacks, myocardial
.infarction, unstable angina or the need for vascular bypass or angioplasty

Side Effect
Chest Pain•
Fatigue•
Edema•
Hypertension•
Dizziness•
Dyspepsia•
Nausea•
Epistaxis•
Rhinitis•
Dyspnea•

Isoniazid
Isoniazid is an antibacterial available as 100 mg or 300 mg tablets for oral administration.

Isoniazid is chemically known as isonicotinyl hydrazine or isonicotinic acid hydrazide. Isoniazid
is odorless, and occurs as a colorless or white crystalline powder or as white crystals. It is freely
soluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform and in ether.
.Isoniazid is slowly affected by exposure to air and light
Therapeutic use
Mainly ISONIAZID is used for the treatment of Tuberculosis. Isoniazid is used in conjunction
with other anti-tuberculosis agents. Drug susceptibility testing should be performed on the
organisms initially isolated fro all patients with newl diagnosed tuberculosis. If the bacilli
.becomes resistant, therapy must be changed to agents to which the bacilli are susceptible
Mechanism of Action
Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell
wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and
extracellular Mycobacterium tuberculosis organisms lsoniazid resistant Mycobacterium
.tuberculosis bacilli develop rapidly when lsoniazid monotherapy is administered
Side Effects
.The most frequent reactions are those affecting the nervous system and the liver

Nervous System Reactions : The most common toxic effect are neuritis, convulsions,•
toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic
.psychosis
Hepatic Reactions : Elevated serum transaminase (SGOT SGPT), bilirubinemia,•

.bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis
.Gastrointestinal Reactions : Nausea, vomiting, and epigastric distress•

Niacin
Niacin (nicotinic acid, or 3-pyridinecarboxylic acid) is a white, crystalline powder, very soluble
:in water, with the following structural formula
Therapeutic use
Niacine is used in the treatment of hyperlipidemia because it reduces very low density
.lipoprotein(VLDL) , a precursor of low density lipoprotein or bad cholesterol
Mechanism of Action
The mechanism by which niacin alters lipid profiles has not been well defined. It may involve
several actions including partial inhibition of release of free fatty acid from adipose tissue, and
increased lipoprotein lipase activity, which may increase the rate of chylomicron triglyceride
from plasma. Niacin decreases the rate of hepatic synthesis of VLDL and LDL, and does not
.appear to affect fecal excretion of fats,sterol or bile acids
: Side effects
Dizziness•
Tachycardia•
Palpitations•
Shortness of breath•
Sweating•
Chills•
Edema•
Cardiac arrhythmias•
Tachycardia•
Ulceration•
Jaundice•
Eructation•

Dyspnea•

:Nicotine
:Structural Formula
Chemical Name: S-3-(1-methyl-2-pyrrolidinyl) pyridine•
Molecular Formula: C10H14N2•
Molecular Weight: 162.23•
Ionization Constants: pKa1 = 7.84, pKa2 = 3.04 at 15° C•
Octanol-Water Partition Coefficient: 15:1 at pH 7•
Nicotine is a tertiary amine composed of a pyridine and a pyrrolidine ring. It is a colorless to pale
yellow, freely water-soluble, strongly alkaline, oily, volatile, hygroscopic liquid obtained from
the tobacco plant. Nicotine has a characteristic pungent odor and turns brown on exposure to air
.or light. Of its two stereoisomers, S(-) nicotine is the more active
Pharmacologic Action
Nicotine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotinic-cholinergic
receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the
brain. Two types of central nervous system effects are believed to be the basis of nicotines
positively reinforcing properties. A stimulating effect is exerted mainly in the cortex via the locus
ceruleus and a reward effect is exerted in the limbic system. At low doses the stimulant effects
predominate while at high doses the reward effects predominate. Intermittent intravenous
administration of nicotine activates neurohormonal pathways, releasing acetylcholine,
.norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH
Side Effects
:The main side effect is drug dependence. And the other adverse events are

Local Irritation•
Dizziness•
Anxiety•
Sleep disorder•
Depression•
Fatigue•
Nausea•
-:Nifedipine
Nifedipine is an antianginal drug belonging to a class of pharmacological agents, the calcium

channel blockers. Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2, 6-dimethyl-4-(2-
:nitrophenyl)-, dimethyl ester, C17H18N2O6, and has the structural formula
Nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol.
.It has a molecular weight of 346.3
:Therapeutic use
Vasospastic Angina•
Chronic Stable Angina•
: Mechanism of action

The precise means by which this inhibition relieves angina has not been fully determined, but
:includes at least the following two mechanisms
Relaxation and Prevention of Coronary Artery Spasm•
Reduction of Oxygen Utilization•
: Side iffects
Dizziness, lightheadedness, giddiness•
Flushing, heat sensation•
Headache•
Weakness•
Nausea, heartburn•
Muscle cramps, tremor•
Nervousness, mood changes•
Palpitation•
Dyspnea, cough, wheezing•
Nasal congestion, sore throat•
Pirbuterol
Pirbuterol acetate is a white, crystalline racemic mixture of two optically active isomers. It is a
.powder, freely soluble in water, with a molecular weight of 300.3
: Pharmacological actions

Pirbuterol is indicated for the prevention and reversal of bronchospasm in patients 12 years of age
and older with reversible bronchospasm including asthma . It may be used with or without
.concurrent theophylline and/or corticosteroid therapy
Pirbuterol is a beta adrenergic agonist which stimulates intracellular adenyl cyclase, which
catalyzes the conversion of adenosine triphosphate to cyclic adenosine monophosphate (c-AMP).
.Increased c-AMP levels are associated with relaxation of bronchial smooth muscle
: Side effects
Seizures•
angina•
hypertension•
arrhythmias•
nervousness•
headache•
dry mouth•
palpitation•
nausea•
dizziness•
fatigue•

Piroxicam
Piroxicam is a member of the oxicam group of nonsteroidal anti-inflammatory drugs
(NSAIDs). The chemical name for piroxicam is 4-hydroxyl-2-methyl-N-2-pyridinyl-2H-
1,2,-benzothiazine-3-carboxamide 1,1-dioxide. Piroxicam occurs as a white crystalline
solid, sparingly soluble in water, dilute acid and most organic solvents. It is slightly
soluble in alcohol and in aqueous solutions. It exhibits a weakly acidic 4-hydroxy proton
(pKa 5.1) and a weakly basic pyridyl nitrogen (pKa 1.8). The molecular weight of
piroxicam is 331.35. Its molecular formula is C15H13N3O4S and it has the following
:structural formula
:Therapeutic use
.For relief of the signs and symptoms of osteoarthritis•
For relief of the signs and symptoms of rheumatoid arthritis•
The mechanism of action of pirbuterol like that of other NSAIDs, is not completely
.understood but may be related to prostaglandin synthetase inhibition
.: Side effects
Anorexia•
Abdominal pain•
Constipation•
Diarrhea•

.Vomiting•
Dizziness•
Headache•
.Fever•
Congestive heart failure•
Hypertension•
.Tachycardia•
Dry mouth•
Anxiety•
Drowsiness•
.Blurred vision•

Pralidoxime Chloride
Chemical name: 2-formyl-1-methylpyridinium chloride oxime. Available in the United States as

Protopam Chloride, pralidoxime chloride is frequently referred to as 2-PAM Chloride.
Pralidoxime chloride occurs as an odorless, white, nonhygroscopic, crystalline powder which is
soluble in water to the extent of 1 g in less than 1 mL. Stable in air, it melts between 215° and
225°C, with decomposition. The chloride is preferred because of physiologic compatibility,
excellent water solubility at all temperatures
: Therapeutic use
Mainly pralidoxime is used to reactivate cholinesterase (i.e. it is used in organophosphate
.poisoning
ORGANOPHOSPHATE POISONING•
ANTICHOLINESTERASE OVERDOSAGE•
: Side effects
Forty to 60 minutes after intramuscular injection, mild to moderate pain may be experienced at
.the site of injection
When given parenterally to normal volunteers who have not been exposed to
anticholinesterase poisons Pralidoxime may cause
Blurred vision•
Diplopia•
Dizziness•
Headache•

Drowsiness•
Nausea•
Tachycardia•
Increased systolic and diastolic pressure•
Hyperventilation•
Muscle weakness•

Pyridostigmine Bromide
Pyridostigmine is an orally active cholinesterase inhibitor. Chemically, pyridostigmine bromide is
:3-hydroxy-1-methylpyridinium bromide dimethylcarbamate. Its structural formula is
:Therapeutic use
Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis and to•
.combat the effects of curariform drug toxicity
Pyridostigmine bromide has been FDA approved for military use during combat •
situations as an agent to be given prior to exposure to the nerve agent Soman in order to
.(increase survival (it has been used in particular during the first Gulf War
.Pyridostigmine is now also used to treat orthostatic hypotension•
Pyridostigmine bromide is available under the trade names Mestinon (Valeant•

.Pharmaceuticals) and Regonol
Mechanism of action
In order to understand the mode of action, a quick outline of a synapse is given below. For more
information, look up synapse. Action potentials are conducted along motor nerves to their
terminals where they initiate a Ca2+ influx and the release of acetylcholine (ACh). The ACh
diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing
an influx of Na+ and K+ ions, resulting in depolarisation. If large enough, this depolarisation
results in an action potential. In order to prevent constant stimulation once the ACh is released, an
enzyme called acetylcholinesterase is present in the endplate membrane close to the receptors on
.the post synaptic membrane, and quickly hydrolizes ACh
Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the
.hydrolysis of acetylcholine

:Side effects
The side effects of pyridostigmine are most commonly related to overdosage and generally are of
:two varieties, muscarinic and nicotinic. Side effects are
,nausea•
,vomiting•
,diarrhea•
,abdominal cramps•
,increased peristalsis, salivation, and bronchial secretions•
.miosis and diaphoresis•
Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and•
.weakness

Quinidine
Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class la activity; it is

the d-isomer of quinine, and its molecular weight is 324.43. Quinidine sulfate is the sulfate salt of
.quinidine; its chemical name is cinchonan-9-ol, 6'-methoxy-, (9S)-, sulfate(2:1) dihydrate
:Therapeutic uses
: By slowing conduction and prolonging the effective refractory period, quinidine can be used in
.Atrial fibrillation or flutter•
.Paroxysmal supraventricular tachycardia•
.Maintenance of sinus rhythm following electroconversion•
Mechanisms of Action
In patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, with little
.effect upon sporozites or upon pre-erythrocytic parasites
In cardiac muscle and in Purkinje fibers, quinidine depresses the rapid inward depolarizing
sodium current, thereby slowing phase-0 depolarization and reducing the amplitude of the action
potential without affecting the resting potential. . The result is slowed conduction and reduced
.automaticity in all parts of the heart, with increase of the effective refractory period
Quinidine is gametocidal to Plasmodium vivax and P. malariae, but not to P. falciparum. So it is

.also used in malaria

:Side effects
Diarrhea•
Nausea•
Vomiting•
Heart burn•
Deafness•
Blurred vision•
Diplopia•
Vertigo•
Delirium•
Mydriasis•
Night blindness•

Torsemide
Torsemide is a diuretic of the pyridine-sulfonylurea class. Its chemical name is 1-isopropyl-3-[(4-
:m-toluidino-3-pyridyl) sulfonylurea and its structural formula is
Its empirical formula is C16H20N4O3S, its pKa is 7.1, and its molecular weight is
.348.43.Torsemide is a white to off-white crystalline powder
: Therapeutic use
Congestive Heart Failure•
Chronic Renal Failure•
Hepatic Cirrhosis•
Hypertension•
: Side effects
Dizziness•
Headache•
Nausea•
Weakness•
Vomiting•
Hyperglycemia•
Excessive urination•
Hyperuricemia•
Hypokalemia•

Excessive thirst•
Hypovolemia•
Impotence•
Oesophageal hemorrhage•
.Dyspepsia•

AZATADINE
(C20H22N2 (290.41
CHEMICAL NAME(S): 6,11-Dihydro-11-(-methyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta [1,2-

;beta]pyridine
BROMPHENIRAMINE
(C16H19BrN2 (319.24
CHEMICAL NAME(S): R-(4-bromophenyl)N, N-dimethyl-2-Pyridinepropanamine

CARBINOXAMINE
(C16H19ClN2O (290.79
DEXCHLORPHENIRAMINE
(C16H19ClN2 (274.7

DOXYLAMINE
(C17H22N2O (270.37
alpha-[2-(Dimethylamino)ethoxy]-alpha-methylbenzyl]-Pyridine]-2
LORATADINE
(C22H23ClN2O2 (382.89
:(CHEMICAL NAME(S
Ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6] cyclohepta[1,2-b] pyridin-11- ylidene)-1-piperidine
carboxylate; Claratyne
PYRILAMINE
(C17H23N3O (285.39
:(CHEMICAL NAME(S
N-[(4-methoxyphenyl)methyl]-N',N'-dimethyl-N-2-pyridinyl-1,2-Ethanediamine

TRIPELENNAMINE
(C16H21N3 (255.36
:(CHEMICAL NAME(S
N,N-dimethyl-N'-(phenylmethyl)-N'-2-pyridinyl-1,2-Ethanediamine; 2-[benzyl[2-
(dimethylamino)ethyl]amino]-Pyridine
TRIPROLIDINE
(C19H22N2 (278.40

CONCLUSION
Pyridine is a six-membered heterocyclic aromatic organic compound. Pyridine is an aromatic

.tertiary amine
.Pyridine and its derivatives are very important in industrial field as well as in bio chemistry
,Pyridine and its derivatives are used as solvents and starting material for the synthesis of target
,dyes, rubber chemicals, explosives, disinfectants, and adhesives.compounds such as insecticides
.herbicides, medicines, vitamins, food flavorings, feed additive
Many drugs containing pyridine ring are used in various pharmaceutical preparation but these can
not be categorized into a single group (i.e. they are used for the treatment of various
:abnormalities). For example
Amlodipine is used as an anti hypertensive agent; Clopidogrel is an inhibitor of platelet

aggregation ; Isoniazid is an antibacterial agent; niacin is used in the treatment of hyperlipidemia;
Nifedipine is an antianginal drug; Pirbuterol is a beta adrenergic agonist; pralidoxime is used to
reactivate cholinesterase (i.e. it is used in organophosphate poisoning); Pyridostigmine is used as
.a cholinergic agent; Quinidine is an antimalarial agent; Torsemide is a diuretic etc

BIBLIOGRAPHY
Eicher, T.; Hauptmann, S, (2003), “ The Chemistry of Heterocycles: Structure, .1
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Heterocyclic Amines in Cooked Meats"; National Cancer Institute (15 Sep 2004). ".2
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Gattermann-Skita @ Institute of Chemistry, Skopje, Macedonia.3
Sherman, A. R. “Pyridine in e-EROS (Encyclopedia of Reagents for Organic .4
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Mulder G etal,(1986) “Sex differences in drug conjugation and their consequences.5
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.edition

Hetero Cyclic Compounds

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Hetero Cyclic Compounds

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Heterocyclic Compound

Heterocyclic compounds are organic compounds that contain a ring structure•

Heterocyclic chemistry is the chemistry branch dealing exclusively with synthesis, •

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Element oxygen sulfur selenium nitrogen phosphorous silicon boron

Valence II II II III III IV III

Prefix Oxa Thia Selena Aza Phospha Sila Bora

The Hantzsch-Widman system provides a more systematic method of naming heterocyclic

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

.The terminal "e" in the suffix is optional though recommended•

Saturated 3, 4 & 5-membered nitrogen heterocycles should use respectively the•

2 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

-: Simply the heterocylic compounds are classified as follows

Membered rings-4 2.2

Heterocyclic amines and cancer.5

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Unsaturated Saturated Heteroatom

Oxirene Ethylene oxide (epoxides,

(Thiirane (episulfides Sulfur

Unsaturated Saturated Heteroatom

Dithiete Oxetane Oxygen

Thietane, dithietane Sulfur

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

:With two heteroatoms

Unsaturated Saturated Heteroatom

Diazines Piperazine Nitrogen

Oxazine Nitrogen / oxygen

Thiazine Nitrogen / sulfur

Heterocyclic amines and cancer•

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Pyridine is a chemical compound with the formula C5HYPERLINK

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

2 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Role in Chemical Synthesis

It is also a starting material in the synthesis of compounds used as an intermediate in •

Role in Chemical Analysis

CH2O + NH3 + 2 CH3CHO → C5H5N + 3 H2O

2 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

The Hantzsch pyridine synthesis is a multicomponent reaction involving formaldehyde, a•

.Pyridinium salts can be obtained in the Zincke reaction•

The Ciamician-Dennstedt Rearrangement (1881) is the ring-expansion of pyrrole with•

In the Gattermann-Skita synthesis (1916) a malonate ester salt reacts with•

. Synthesis of pyridine derivatives using aza Diels–Alder methodology•

For example: - Hantzsch Dihydropyridine (Pyridine) Synthesis

This reaction allows the preparation of dihydropyridine derivatives by condensation of an

2 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

The reaction can be visualized as proceeding through a Knoevenagel Condensation product as a

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

.Synthesis of pyridine derivatives using aza Diels–Alder methodology

Amidrazone reacted with the unsymmetrical tricarbonyls giving triazines . These•

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Organic reactions of Pyridine

Nucleophilic aromatic substitution occurs at C2/C4. For example in the Chichibabin•

Electrophilic Substitution of Pyridine

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

Other Reactions of Pyridine

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

DMAP is short for 4-dimethylaminopyridine•

1 G.V.S.P JAIPUR B. PHARMA FINAL YEAR

four nitrogen atoms

.Lutidine is a trivial name for 2,6-dimethylpyridine-2,6•