Dr. Solomon Derese...We will study the chemistry of heterocyclic compounds i.e. Cyclic organic compounds containing not just carbon atoms, but oxygen, nitrogen, sulfur etc. Dr. Solomon

Dr. Solomon Derese UPC 213 1

Dr. Solomon [email protected]

Chemistry Department; Room 118

mailto:[email protected]

UPC 213 (Pharmaceutical Chemistry II)

Heterocyclic Chemistry


n = 1,2,3, ……

Where Z is different (hetero) from carbon

Course outline

• Introduction to heterocyclic chemistry

• Nomenclature of Heterocycles

• Structure, reactions and synthesis ofaromatic heterocyclic compounds


www.facebook.com/kemiauon


Department of Chemistry facebook page

Like it Share it CommentPost


Study Nomenclature, Structure, Reaction andSynthesis of aromatic heterocyclic compounds.

Scope of the course

Aliphatic heterocycles


Aromatic heterocycles

We will study the chemistry of heterocycliccompounds i.e. Cyclic organic compoundscontaining not just carbon atoms, but oxygen,nitrogen, sulfur etc.

Dr. Solomon Derese 7UPC 213

It may seem strange that this rather narrowlydefined class of compounds deserves a wholeunit, but you will soon see that this is justifiedboth by the sheer number and variety ofheterocycles that exist and by their specialchemical features.


Why bother with heterocycles?

A recent analysis of the organic compoundsregistered in Chemical Abstracts revealed that as ofJune 2007, there were 24,282,284 compoundscontaining cyclic structures, with heterocyclicsystems making up many of these compounds –about two third of organic compounds areheterocyclic.

Most pharmaceuticals are based on heterocycles. Aninspection of the structures of the top-selling brand-name drugs in 2007 reveals that 8 of the top 10 and71 of the top 100 drugs contain heterocycles.


The history of medicine can be defined byheterocyclic compounds.

As early as 16th centuryhave been used to treatmalaria.

The first synthetic drug(1887) (used forreduction of fevers)


The first effectiveantibiotic (1938).

The first multi-millionpound drug (1970s),antiulcer drug.



Approved in 1997 fortreatment of male impotence.

Approved for treatment of Chronic MyelogenousLeukemia (CML) in 2001.


Nomenclature of Heterocyclic Compounds


The IUPAC rules allow three nomenclatures.

I. The Hantzsch-Widman Nomenclature.

II. Common Names

III. The Replacement Nomenclature


n = 1,2,3, ……

The Hantzsch-Widman nomenclature is based onthe type (Z) of the heteroatom; the ring size (n) andnature of the ring, whether it is saturated orunsaturated .

I. Hantzsch-Widman Nomenclature

This system of nomenclature applies to monocyclicthree-to-ten-membered ring heterocycles.


I. Type of the heteroatom

The type of heteroatom is indicated by aprefix as shown below for commonhetreroatoms:

O OxaN AzaS ThiaP Phospha

Hetreroatom Prefix


II. Ring size (n)The ring size is indicated by a suffix according toTable I below. Some of the syllables are derived fromLatin numerals, namely ir from tri, et from tetra, epfrom hepta, oc from octa, on from nona, ec fromdeca.

Ring size Suffix Ring size Suffix

3 ir 7 ep

4 et 8 oc

5 ol 9 on

6 in 10 ec

Table I: Stems to indicate the ring size ofheterocycles


Ring size Saturated Unsaturated Saturated (With Nitrogen)

3 -irane -irine -iridine

4 -etane -ete -etidine

5 -olane -ole -olidine

6 -inane -ine

7 -epane -epine

8 -ocane -ocine

9 -onane -onine

10 -ecane -ecine

Table II: Stems to indicate the ring size and degree ofunsaturation of heterocycles

The endings indicate the size and degree ofunsaturation of the ring.


Each suffix consists of a ring size root and anending intended to designate the degree ofunsaturation in the ring.

It is important to recognize that the saturatedsuffix applies only to completely saturated ringsystems, and the unsaturated suffix applies torings incorporating the maximum number of non-cumulated double bonds.

According to this system heterocyles are named bycombining appropriate prefix/prefixes with a stemfrom Table II. The letter “a” in the prefix is omittedwhere necessary.


Saturated 3, 4 & 5-membered nitrogenheterocycles should use respectively thetraditional "iridine", "etidine" & "olidine"suffix.

Systems having a lesser degree ofunsaturation require an appropriate prefix,such as "dihydro"or "tetrahydro".


Examples

Oxa+irane= Oxirane Aza+iridine= Aziridine

Oxa+etane=Oxetane Aza+etidine=Azetidine

Oxa+olane= Oxolane Aza+olidine= Azolidine

Thia+irane= Thiirane

Thia+etane=Thietane

Thia+olane= Thiolane


Azinane Azine

Pyridine


In case of substituents, the heteroatom isdesignated number 1, and the substituents aroundthe chain are numbered so as to have the lowestnumber for the substituents.


The compound with the maximum number ofnoncumulative double bonds is regarded asthe parent compound of the monocyclicsystems of a given ring size.


Partial Unsaturation

Use fully unsaturated name with dihydro, tetrahydro,etc

Azepine 2,3-Dihydroazepine

4,5-Dihydroazepine 2,5-Dihydroazepine

12

3


1-Ethyl-4-methyl-4,5-dihydroazepine

1-Ethyl-5-methyl-2,3,4,5-tetrahydroazepine

When numbering give priority to saturated atoms.


O OxaN AzaS ThiaP Phospha

Hetreroatom Prefix

Ring size Saturated Unsaturated Saturated (With Nitrogen)

3 -irane -irine -iridine

4 -etane -ete -etidine

5 -olane -ole -olidine

6 -inane -ine

7 -epane -epine

8 -ocane -ocine

9 -onane -onine

10 -ecane -ecine

Type (Z) - PrefixSize (n) - SuffixNature of ring - Ending

Revision


Rings With More Than One Heteroatom


Two or more similar atoms contained in a ring areindicated by the prefixes ‘di-’, ‘tri’, etc.

1,3,5-Triazine

If more than one hetero atom occur in the ring,then the heterocycle is named by combining theappropriate prefixes with the ending in Table I inorder of their preference, O > S > N.


Oxaziridine1,3-Thiazole (Thiazole)

1,4-Oxazine 3-chloro-5-methyl-1,2,4-oxadiazole


O

S

Se

NB

P

C

Priority of heteroatoms for numbering purposes:

Highest

Lowest


The ring is numbered from the atom ofpreference in such a way so as to give thesmallest possible number to the other heteroatoms in the ring. As a result the position ofthe substituent plays no part in determininghow the ring is numbered in suchcompounds.

4-Methyl-1,3-thiazole


There are a large number of important ringsystems which are named widely known withtheir non-systematic or common names.

II. Common Names



1,4-Dihydropyridine 2,3-Dihydropyridine


Identical systems connected by a single bond

Such compounds are defined by the prefixes bi-, tert-, quater-, etc., according to the number of systems,and the bonding is indicated as follows:

1

22’

1’

1

2 3’’ 1’’

1’

2’

2’’

4’

2,2' - Bipyridine 2,2': 4',3'' - Terthiophene


Naming Hetrocycles with fused rings

When naming such compounds the side of theheterocyclic ring is labeled by the letters a, b, c, etc.,starting from the atom numbered 1. Therefore side‘a’ being between atoms 1 and 2, side ‘b’ betweenatoms 2 and 3, and so on as shown below forpyridine.

a

b

c d

e

f


The name of the heterocyclic ring is chosen asthe parent compound and the name of thefused ring is attached as a prefix. The prefix insuch names has the ending ‘o’, i.e., benzo,naphtho and so on.

Benzo [b] furan

Benzo [b] pyridine

Benzo [c] thiophene

a

b c

a

b

ab


ca

b

d Benzo [d] thiepine


In a heterocyclic ring, other things being equal,numbering preferably commences at a saturatedrather than at an unsaturated hetero atom.

3-Ethyl-5-methylpyrazole 1-Methylindazole

1 12

2


Handling the “Extra Hydrogen”


Heterocycles with maximum number of double bondswhich can be arranged in more than one way.

Examples

Pyrans

Pyrroles

Double bonds @ 2 and 4





Therefore, should have different names.


This is a special problem resulting from isomerism in theposition of the double bonds which is sometimes referredto as “extra-hydrogen” and this can be addressed bysimply adding a prefix that indicates the number of thering atom that possesses the hydrogen using italic capital‘1H’ ‘2H’ ‘3H’, etc. The numerals indicate the position ofthese atoms having the extra hydrogen atom.

1

2

1 2

3

4

2H-Pyran4H-Pyran

The saturated position takes priority in numbering.


4-Methyl-2H-oxete

1

23

4

1 2

34

2-Methyl-2H-oxete

1H-Pyrrole(Pyrrole)

3H-Pyrrole 2H-Pyrrole



In replacement nomenclature, theheterocycle's name is composed of thecarbocycle's name and a prefix that denotesthe heteroatom.

III. The Replacement Nomenclature

Thus, "aza", "oxa", and "thia" are prefixes for anitrogen ring atom, an oxygen ring atom, and asulfur ring atom, respectively.

Notice that heterocyclic rings are numbered sothat the heteroatom has the lowest possiblenumber.



UPC 213

Dr. Solomon Derese

REACTIONS AND PROPERTIES OF AROMATIC HETEROCYLCES

50

N..

Pyridine

Pyridine is aromatic asthere are six delocalizedelectrons in the ring.

Six-membered heterocycles are more closelyrelated to benzene as they are aromatic on thebasis of their p-electron systems without the needfor delocalization of heteroatom lone pairs. Theempirical resonance energy for pyridine is about 28Kcal/mol, only slightly lower than that for benzene.

SIX MEMBERED AROMATIC HETEROCYCLES

51

Pyridine has divalent negatively charged N, which isa stable condition for N. The positive charge isdispersed to carbons around the ring, specifically toC-2 and C-4.

Structure of Pyridine

The net effect is to reduce the p-electron density inthe ring relative to benzene, and as result pyridineis electron deficient compared to benzene.

As a result, unlike benzene pyridine is polarmolecule due to the electronegative nitrogen.

53

Six membered heterocycleswith an electronegativeheteroatom are generallyelectron deficient comparedto benzene. Such compoundsare classified as p-deficient.

Electron-withdrawing heteroatoms decreasethe p-electron density at the carbon atomsand are thus p-deficient relative to benzene.

54

Structure of five membered heterocycles

The five-membered aromaticheterocycle ring has a p-electronexcess (six on five atoms), while inbenzene, the p-electron density isone on each ring atom.

Five membered heterocycles with an electronegativeheteroatom are generally electron rich compared tobenzene (six electrons for five carbons). Suchcompounds are classified as p-excessive.

55

36 kcal/mol

29 kcal/mol

22 kcal/mol

16 kcal/mol

The ease with which the lone pairelectron is released is directlyrelated to the electronegativity ofthe heteroatom. Thus the lowerthe electronegativity of theheteroatom, the higher thearomaticity.

The degree of aromatic characterin a five membered ring isdetermined by the ease withwhich the lone pair may bereleased into the delocalizedsystem.

56

57

Aromatic Heterocycles

p- Excessive p- Deficient

This classification is not trivial; there is a vastdifference between the properties of the two typesof aromatic compounds.

58

Reactions of p-deficient heterocyclic aromatic compounds

A hallmark of p-deficient heterocyclic systemsis their low reactivity with electrophilicagents, slower than benzene. For example,pyridine is less reactive than benzene by afactor of 106 when subjected to conditions ofnitration. The reactivity is on the order of thatof nitrobenzene, which is well known torequire much more drastic conditions thanthose for benzene itself.

59

For example, 3-bromopyridine is formed whenpyridine is reacted with bromine in the presence ofoleum (sulfur trioxide in conc. sulfuric acid) at 130°C.

Conversely pyridines are susceptible to nucleophilicattack.

60

The reactivity is greater than that of benzeneand is in roughly the same range as found forbenzenes bearing electron releasing groupssuch as in aniline. The greater electron densityin these rings accounts for this higherreactivity.

A significant feature of the p-excessive ringsystems is that they undergo electrophilicaromatic reactions faster than benzene.

Reactions of p-excessive heterocyclic aromatic compounds

These heterocycles undergo electrophilic aromaticsubstitution reactions much faster than benzeneunder similar conditions. The reasons for this are:

I. The resonance energy of the heterocycles is lessthan that of benzene, i.e. less aromatic thanbenzene.

II. The five-membered aromatic heterocycle ring hasa p-electron excess (six on five atoms), while inbenzene, the p-electron density is one on eachring atom.

61

62

Reaction with bromine requires no Lewis acid andleads to substitution at all four free positions.

no Lewis acid

63

FIVE MEMBEREDAROMATIC

HETEROCYCLES

64

a-substitution b-substitutionThe Substitution is regioselective to the a position; whenthese positions are occupied, the b-position is substituted.

X = O, S or NH

Electrophilic aromatic substitution reaction of fivemembered aromatic heterocycles

65

WHY?The +ve charge is better resonance stabilized whenthe substitution is at the a-position than at b-position.

A more stable intermediate carbocation having 3resonance forms.

only 2 resonance forms

66

Common reactions of pyrrole, furan, and thiophene

Electrophilic aromatic substitution reaction is easyand is preferred at a-position; also easy at b-position.

The following reaction are common to the three fivemembered aromatic heterocycles.

A. Electrophilic Aromatic Substitution

Z = O, S, NH

67

C. Vilsmeier-Haack reaction

B. Substitution at a-position via a-lithiated Intermediates

Z = O, S, NR

Vilsmeier reaction (Vilsmeier‐Haack reaction) allowsthe formylation (addition of -CHO) of heterocyclicmolecules. The formylating agent, chloroiminiumion, is formed in situ from N,N‐dimethylamide andPOCl3.

68

Z = O, S, NH

Example

Vilsmeier-Haack reaction

69

Mechanism

Chloroiminium ion

70

The reaction of electron rich heterocycles withformaldehyde and primary/secondary amineforming an amino alkylated heterocylcic compoundis called the Mannich reaction.

D. Mannich reaction

Z = O, S, NH

71

Mechanism

72

Furans are volatile, fairly stable compounds withpleasant odours. Furan itself is slightly soluble inwater. It is readily available, and its commercialimportance is mainly due to its role as the precursorof the very widely used solvent tetrahydrofuran(THF).

73

By analogy with benzene, furanundergoes reactions with electrophilicreagents, often with substitution.However, it can also react by additionand/or ring-opening depending onreagent and reaction conditions.

Reactions of Furans

74

Electrophilic Aromatic Substitution Reaction

75

Halogenation

Furan can be halogenated at a-position. Bromination andiodination are easy to control as only one halogen atomsadds to furan. In the case of chlorination, di-substitution hasbeen known to occur.

76

AcylationAcetyl groups in the presence of phosphoric acid (or a Lewisacid) add at a-position of furans.

In general, position 2 (a-position) is more reactive thanposition 3. When position 2 is blocked, b-acylation canproceed smoothly.

77

n-Butyllithium in hexane metalates furan inthe 2-position, while excess of reagent athigher temperature produces 2,5-dilithiofuran.

Metalation

78

Addition reactions

Furans yield the corresponding tetrahydrofurans bycatalytic hydrogenation.

In some addition reactions, furans behave as 1,3-dienes. For example, furan reacts with bromine inmethanol in the presence of potassium acetate togive 2,5-dimethoxy-2,5-dihydrofuran by a 1,4-addition:

79

Ring-opening reactions

Furans are protonated in the 2-position, and not onthe O-atom, by BRÖNSTED acids:

Concentrated acid

Dilute acid

80

Thiophene prefers reactionswith electrophilic reagents.Additions and ring-openingreactions are less importantthan with furan, andsubstitution reactions aredominant.

Some additional reactions, such as oxidationand desulfurization, are due to the presenceof sulfur and are thus confined to thiophenes.

81

Electrophilic substitutions

Thiophene reacts more slowly than furan but fasterthan benzene. Substitution is regioselective in the 2-or in the 2,5-position.

82

Reactions with nucleophilic reagents

83

Thiophenes are oxidized by peroxy acids to givethiophene 1,1 –dioxides:

Oxidation

84

Pyrrole reacts with sodium, sodium hydride or potassium ininert solvents, and with sodium amide in liquid ammonia, togive salt-like compounds:

85

Electrophilic substitution reactions on carbon

Nitration

86

Halogenation

87

6-Membered Aromatic Heterocycles

Containing one

Heteroatom

88

Pyridines

Pyridine is the simplest heterocycle of theazine type. It is derived from benzene byreplacement of a CH group by a N-atom.

89

The structure of pyridine is completely analogous to that ofbenzene, being related by replacement of CH by N.

The key differences are:

I. The departure from perfectly regular hexagonalgeometry caused by the presence of the hetero atom, inparticular the shorter carbon-nitrogen bonds,

II. The replacement of a hydrogen in the plane of the ringwith an unshaired electron pair, likewise in the plane ofthe ring, located in an sp2 hybrid orbital, and not at allinvolved in the aromatic p-electron sextet; it is thisnitrogen lone pair which is responsible for the basicproperties of pyridines, and

90

III.A strong permanent dipole, traceable to thegreater electronegativity of the nitrogencompared with carbon.

91

I. The heteroatom make pyridines very unreactiveto normal electrophilic aromatic substitutionreactions. Conversely pyridines are susceptible tonucleophilic attack. Pyridines undergoelectrophilic substitution reactions (SEAr) morereluctantly but nucleophilic substitution (SNAr)more readily than benzene.

II. Electrophilic reagents attack preferably at the N-atom and at the b-C-atoms, while nucleophilicreagents prefer the a- and c-C-atoms.

The following reactions can be predicted forpyridines on the basis of their electronic structure:

92

In reactions which involve bond formation using thelone pair of electrons on the ring nitrogen, such asprotonation and quaternisation, pyridines behave justlike tertiary aliphatic or aromatic amines.

Electrophilic Addition at Nitrogen

Reactions of Pyridine

When a pyridine reacts as abase or a nucleophile itforms a pyridinium cation inwhich the aromatic sextet isretained and the nitrogenacquires a formal positivecharge.

93

Protonation at Nitrogen

Nitration at Nitrogen

Pyridines form crystalline,frequently hygroscopic,salts with most protic acids.

This occurs readily byreaction of pyridineswith nitronium salts,such as nitroniumtetrafluoroborate.

Protic nitrating agents such as nitric acid of courselead exclusively to N-protonation.

94

Acid chlorides and arylsulfonic acids react rapidlywith pyridines generating 1-acyl- and 1-arylsulfonylpyridinium salts in solution.

Acylation at nitrogen

95

Alkylation at nitrogen

Alkyl halides and sulfates react readily with pyridinesgiving quaternary pyridinium salts.

96

Electrophilic substitution at Carbon atoms of the pyridine ring

Electrophilic substitution of pyridines at a carbon isvery difficult. Two factors seem to be responsible forthis unreactivity:

I. Pyridine ring is less nucleophilic than the benzenering; nitrogen ring atom is more electronegativethan carbon atoms and therefore it pulls electronsaway from the carbon atoms inductively leaving apartial plus on the carbon atoms.

97

II. When pyridine compound is exposed to an acidicmedium, it forms pyridinium salt. This increasesresistance to electrophilic attack since the reactionwill lead to doubly positive charged species.

Less reactive than pyridine

98

When an electrophile attacks the pyridine ring, onlyposition 3 is attacked.

Hint: draw resonance structures that result fromelectrophilic attack at various positions. The positivecharge residing on an electronegative element withsextet configuration is unfavoured.

Why?

99

For example, 3-bromopyridine is formed whenpyridine is reacted with bromine in the presence ofoleum (sulfur trioxide in conc. sulfuric acid) at 130°C.

100

Mechanism of bromination of pyridine

101

Pyridine can be activated to electrophilicsubstitution by conversion to pyridine-N-oxides.

A series of preparatively interesting reactions onpyridine can be carried out by means of pyridine N-oxides such as the introduction of certain functionsinto the ring and side-chain which cannot beachieved in the parent system by direct methods.

102

The activating oxygen atom can be removed byreacting the pyridine N-oxide withphosphorous trichloride.

103

In such reactions there is a balance between electronwithdrawal, caused by the inductive effect of the oxygenatom, and electron release through resonance from thesame atom in the opposite direction. Here, the resonanceeffect is more important, and electrophiles react at C-2(6)and C-4.

104

Thionyl chloride, for example, gives a mixture of 2-and 4-chloropyridine N-oxides in which the 4-isomeris predominant.

105

However, pyridine N-oxide reacts with aceticanhydride first to give 1-acetoxypyridinium acetateand then, on heating, to yield 2-acetoxypyridinethrough an addition-elimination process.

106

When a similar reaction is carried out upon the 2,3-dimethyl analogue, the acetoxy group rearrangesfrom N-1 to the C-2 methyl group, at 1800C, to form2-acetoxymethyl-3-methylpyridine.

107

108

109

Resonance stabilized

Anion Chemistry of Pyridine

Works for 2(6)- and 4-alkylpyridines not for 3(5)-alkylpyridines, why?

The negative chargegenerated on thecarbon goes to theelectronegativenitrogen, which canbetter accommodateit.

110

111

112

115

Nucleophilic substituition of pyridine

a) X=Hb) X=Good leaving group

X=H, Substitution with “hydride” transfer

Nu: NaNH2 - aminationNu: BuLi, PhLi etc - alkylation / arylationNu: NaOH - “hydroxylation”

116

At high temperature the intermediate anion canaromatize by loss of a hydride ion, eventhough, it is apoor leaving group.

117

b) X=LG, The nucleophilic substitution is much morefacile when good leaving group such as X:Halogen (F>>Cl,>Br,>I), -OSO2R, -NO2, -OR, areemployed.

118

119

-H: is a bad leaving group

120

121

Halogenopyridines can undergo metal-halogenexchange when treated with butyllithium. Thelithium derivatives then behave in a similar mannerto arylithiums and Grignard reagents and react withelectrophiles such as aldehydes, ketones and nitriles.

UPC 213

Dr. Solomon Derese

Synthesis of Heterocycles Compounds

122

:Nu

UPC 213

Dr. Solomon Derese 123

Synthesis of Furan,

Pyrrole

and

Thiophene

UPC 213


:Nud+ d+

Furans, pyrroles and thiophenes from 1,4-dicarbonyl compounds: Paal Knorr synthesis

:Nu = RNH2, H2S

UPC 213


UPC 213


UPC 213


Furans, pyrroles and thiophenes from 1,3-dicarbonyl (b-ketocarbonyl) compounds

acidic hydrogens React with

electrophiles

UPC 213


Feist–Benary synthesis of furans

The Feist-Benary synthesis is an organicreaction between a-haloketones and b-dicarbonyl compounds to give substituted furans inthe presence of base.

a-haloketones

X = Cl, Br, I

UPC 213


130

UPC 213


Knorr-pyrrole synthesis

This involves the condensation of a-amino ketoneswith a b-diketone or a b-ketoester to give asubstituted pyrrole in the presence of a base likepyridine.

a-amino ketones

UPC 213


UPC 213


Fiesselmann synthesis

1,3-Dicarbonyl compounds or b-chlorovinylaldehydes react with thioglycolates or other thiolspossessing a reactive methylene group to givethiophenes in the presence of pyridine.

UPC 213


UPC 213


Synthesis of Pyridine

:Nu = RNH2

136

I. Reaction between a 1,5-diketone and ammonia

Ammonia reacts with 1,5-diketones to give unstable1,4-dihydropyridine, which can be easilydehydrogenated (using nitrobenzene or nitric acid)to give pyridine.

1,4-dihydropyridine

137

II. The Guareschi synthesis

Unsymmetrical pyridines can be synthesised from areaction between a b-dicarbonyl compound and a b-enaminocarbonyl compound or nitrile.

138

139

140

III. The Hantzsch synthesis

Symmetrical 1,4-dihydropyridines, which can beeasily dehydrogenated (to form pyridines), areproduced from the condensation of an aldehyde,ammonia, and two equivalents of a 1,3-dicarbonylcompounds (commonly a β-ketoester) which musthave a central methylene.

The product from the classical Hantzsch synthesis isnecessarily a symmetrically substituted 1,4-dihydropyridine. Subsequent oxidation (ordehydrogenation) gives a symmetrical pyridinecompound.

141

STEP I

The reaction is believed to proceed via KnoevenagelCondensation.

STEP II

A second key intermediate is an ester enamine,which is produced by condensation of the secondequivalent of the β-ketoester with ammonia:

142

STEP III

Further condensation between these two fragmentsgives the dihydropyridine derivative:

143

144

MECHANISM

145

146

Nifedipineis in a group of drugscalled calcium channelblockers. It works byrelaxing the muscles ofyour heart and bloodvessels. Nifedipine is usedto treat hypertension (highblood pressure) andangina (chest pain).

147

148

OXAZOLE

149

IMIDAZOLES

THIAZOLES

150

Diazepam (Valium) used for the treatment ofanxiety disorders. Diazepamalso is used for thetreatment ofagitation, tremors, delirium,seizures, and hallucinationsresulting from alcoholwithdrawal. It is used for thetreatment of seizures andrelief of muscle spasms insome neurological diseases

151

152

Antifungal drug

153

154

155

ClopiracNonsteroidal Antiinflammatory Drug)

156

Documents

Dr. Solomon Derese...We will study the chemistry of heterocyclic compounds i.e. Cyclic organic compounds containing not just carbon atoms, but oxygen, nitrogen, sulfur etc. Dr. Solomon