Organic Chemistry

Diploma in Pharmacy

Organic chemistry

• The branch of chemistry which deals with the study of hydrocarbon and their derivatives is known as organic chemistry.

Organic compounds

• Hydrocarbons and their derivatives are called organic compounds. Example: Methane, Paracetamol etc

Sources of organic compounds

• Plants
• Animals
• Coal tar
• Petroleum
• Synthetic compounds
• etc

Classification of Organic Compounds

Nomenclature of organic compounds

• The nomenclature of organic compounds can be
• Common name
• Special name for individual compound
• Such name has little or no structural information
• Systematic name
• Based upon the chemical structure
• Upon knowing the systematic name, chemical structure of substance can be deduced.
• Systematic names are often written according to IUPAC system.

# IUPAC refers to �International Union of Pure and Applied Chemistry (IUPAC)

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IUPAC System (Basic Rules)

• According to IUPAC, the name of organic compound in general consists of the following parts:
• Prefix(es) + word root + primary suffix + secondary suffix

Word root

• Looking for the parent chain or word root is the first step in naming organic compounds.
• The number of carbons in the longest chain is called parent chain.
• Depending upon the number of carbon atoms in the longest chain

Depending upon the number of carbon atoms in the longest chain, the compound is assigned a word root as follows.

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Primary suffix

• Primary suffix is used to represent the nature of carbon-carbon bonds or saturation/unsaturation in the carbon chain

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Secondary suffix

Secondary suffix is used to indicate the functional group in the organic compound.

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Prefix

• It is the part of the name which appears before the word root. These are of two types primary prefix, and secondary prefix.
• Primary prefix

It is used to distinguish aliphatic cyclic compounds from open chain compounds.

If the given compounds is an alicyclic compound, then a prefix cyclo is used just before the word root.

• Secondary Prefix

Functional groups are considered as substituents or side chains and are put before the word root prefixes.

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• When two or more functional groups are present, selection and naming of prefix or suffix is done using preferential series.

Preferential series (Priority order of functional groups)

Nomenclature of hydrocarbons without functional groups

• Selection of parent chain
• The longest possible chain of carbon atom is selected as parent chain.

• Numbering of parent chain

Lowest locant rule

Carbon bearing substituent gets

lowest possible number.

Lowest sum rule

When more than one substituents are present, numbering is done that yields lowest possible sum of number to substituents

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• Naming of the compound

Naming is done with regard to basic rule

Prefix + word root +primary suffix + secondary suffix

Alphabetical rule

• Names of substituents are written as per alphabetical order

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Complex alkyl substituent rule

• Separate numbering is done to the substituent. While numbering, lowest number is given to the carbon directly attached to the parent chain.

Nomenclature of compounds (with functional group/s)

• Selection of the parent chain
• The longest possible chain of carbon atom is selected as parent chain
• Numbering

Lowest number rule

• Position 1 is given if carbon atom contains in the functional group. Otherwise numbering is done such that functional group contain lowest possible number.

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• If a parent chain contains double or triple bond, numbering should done double or triple bond gets the lowest possible number.

• Lowest sum rule
• If a compound contain the same functional group in more than one position, the numbering should be done such that the sum of positions gets lower value.

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• Poly functional rule
• If more than one functional group is present, one functional group is chose according to priority order. Functional group with lower priority is indicated in prefix.

Preferential series (Priority order of functional groups)

Nomenclature of heterocyclic compounds

• Determination of prefix
• Prefix is selected on the basis of heteroatom present

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• Determination of suffix
• The suffix is selected on the basis of the saturated or unsaturated ring with or without nitrogen atom.

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• Numbering rules
• The heteroatom is counted as number one.

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• If more than one heteroatoms are present, priority sequence of heteroatoms shall be O>S>N

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• If a substituent is present in the heterocyclic ring, numbering is done such that the substituent should get the least possible number.

• If more than one substituent are present, numbering is done so the substituent get least set of number. The groups are arranged in alphabetical order.

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• In certain compounds, numbering is not done from heteroatoms.

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• There are large number of compounds which are name from their origin.

How to give chemical name of given structure/unknown compound?

• Choose the parent skeletal structure and give numbering according to rules.
• If substituents are complicated, then separate numbering should be given to them. The carbon atom attached to the parent structure should be given number 1.
• First write names of substituents prefixed with numbers in alphabetical order.
• Finally write the name of parent skeletal structure.

Acetazolamide

• 1,3,4 thiadiazole is the parent structure
• Numbering starts from sulfur
• Substituents are 2- acetamido and 5-sulphamoyl
• Final structure name is 2-acetamiod, 5-sulphamoyl, 1,3,4-thiadiazole

Chlorpromazine

• Phenothiazine is parent ring
• Numbering from side. S gets position 5.
• Substituent numbering is done. Position 1 is given to carbon atom joining to the phenothiazine ring. The name of the substituent is 3-dimethyl amino propyl. This substituent is present in position 10.
• Chloro group at position 2 of the phenothiazine ring
• 2-chloro, 10-(3-dimethyl amino propyl), phenolthiazine

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Chorpheniramine

• Pyridine is the parent nucleus
• [1-( p-chlorophenyl),3-dimethylamino propyl] group is present in position 2.
• So the final name of the structure is
• 2-[1-( p-chlorophenyl),3-dimethylamino propyl] pyridine

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Pethidine

• It is ester. So chemical name starts with alklyl group.
• Groups present in the piperidine ring are methyl group at postion 1 and phenyl group at position 4
• Hence chemical name written as:

Ethyl 1-methyl 4-phenyl piperidine -4-carboxylate

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Drawing chemical structures from chemical name

• Draw the parent structure
• Give numbering according to rules
• Write groups at specified positions

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Example:

Draw the structure of

• 2,4-diamino 5-(3,4,5 trimethoxy benzyl) pyrimidine

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Example

Draw the structure of

• 2,4-diamino 5-(3,4,5 trimethoxy benzyl) pyrimidine

Cyclic compounds

• These are the compounds having closed end. Example : cyclopropane, benzene, pyridine etc.

Cyclic compounds may be heterocylic or homocyclic.

Heterocyclic compounds

• The cyclic compound having one or more heteroatom such as O, S, N etc are called heterocylic compounds.
• Examples: Pyrrole, Pyridine, Furan, Thiophene etc

Homocyclic compounds

• These are the cyclic compounds having a single type of atom in the ring structure. Example: Cyclopropane, Benzene etc

Difference between homocyclic and heterocyclic compounds

Aromatic compounds

• These are the compounds that consist of conjugated planar ring system accompanied by pi-electron clouds in place of individual alternating double and single bonds.
• In simple terms, aromatic compounds are those which can join one or more benzene ring in their molecular structure.
• Aromatic compounds need to follow the Huckel’s rule.
• Examples of aromatic compounds include Benzene, Naphthalene, Anthracene etc

Huckel’s rule

• In simple terms,
• If the compound is cyclic, planar, conjugated and possess 4n+2 pi elctrons, then the compound is aromatic. (n = 0,1,2,…..)

Properties of aromatic compounds

• Aromatic compounds are cyclic and have flat structure.
• These are unsaturated but are resistant to addition reaction, instead they give electrophilic substitution reaction.
• These are usually stable.
• These compounds have high carbon percentage hence they burn with sooty flame.
• Aromatic compounds contain delocalized system of (4n+2) pi electrons where n= 0,1,2,3…. called as Huckel’s rule.

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Benzene

• Benzene is the simplest hydrocarbon belonging to the family of aromatic compounds.
• Michael Faraday discovered benzene in 1825.

Structure of benzene

Monosubstituted benzene derivatives

• Methyl benzene (Toluene)
• Ethyl benzene
• Benzoic acid
• Chlorobenzene
• Nitrobenzene

Disubstituted benzene derivatives

• Consists of two substituents
• The second substituent can enter into any one of the five positions of the ring.

Ortho, Meta, Para positions

Ortho position

The position of two adjacent carbon atoms of benzene nucleus (ie 1,6 or 1,2) is known as ortho position which is denoted by ‘o’

Meta position

The position of two alternate carbon atoms of benzene nucleus ie 1,3 or 1,5 is known meta position which is denoted by ‘m’

Para position

The position of two diagonal carbon atoms of benzene nucleus ie 1,4 is known as para position which is denoted by ‘p’

Trisubstituted benzene derivatives

Trisubstituted benzene derivative having same substituent can be viccinal (vic-), asymmetrical(-as) and symmetrical(s)

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vic-tribromobenzene

as-tribromobenzene

s -tribromobenzene

Isomerism

Isomerism is the phenomenon in which more than one compounds have the same chemical formula but different chemical structures.

The molecules involved in this phenomenon are called isomers.

Example:

Ethyl alcohol and dimethyl ether are isomers of each other as both the compounds have the same molecular formula – C2H6O

Isomers of benzene derivative (ethyl benzene)

Isomerism in benzene derivatives

Positional isomerism (ortho meta para)

Occurs due to position in different groups

Eg o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene

Chain isomerism

Occurs when the alkyl chain attached differs in structure Eg n-butyl benzene, sec-butyl benzene, isobutyl benzene, tert. butyl benzene

Functional isomerism

Occurs when compounds have same molecular formula but different functional groups Eg Benzyl alcohol, Cresol

Resonance structure of benzene

Orientation effects substituted benzenes

Substituted rings are divided into two groups based on the type of the substituent that the ring carries:

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Activating groups: the substituents on the ring are groups that donate electrons.

Deactivating groups: the substituents on the ring are groups that withdraw electrons.

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Examples of activating groups in the relative order from the most activating group to the least activating:

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-NH2, -NR2 > -OH> -OR> -NHCOR> -CH3 and other alkyl groups

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Examples of deactivating groups in the relative order from the most deactivating to the least deactivating:

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-NO2 >-CF3> -COR> -CN> -CO2R> -SO3H > Halogens

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Types of orientation effects

Ortho -para directing groups

These groups increase electron density at ortho and para positions making substitutions more likely there

Eg -OH, -NH2, -OR, NHCOR (Activating) Halogens(Deactivating)

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Meta directing groups

These groups withdraw electrons strongly reducing electron density at ortho and para positions

Examples -NO2, -CN, -SO3H, -CHO (Deactivating)

Summary

Physical properties of benzene

• Benzene is colorless liquid having boiling point 80.4 degree celsius.
• It has a characteristic odor
• It is not soluble in water but soluble in other organic solvents.
• The vapor of benzene is highly inflammable, toxic and carcinogenic.
• It is a good solvent of fats, resins, sulphur, iodine an a large number of organic compounds.

Chemical properties

• The ring of benzene containing six carbon atom is highly stable. However it shows two types of reactions.
• Substitution Reaction
• Addition reaction
• Combustion reaction

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Uses

• As a starting material in the various synthesis of drugs, plastics, perfumes, explosives et
• It is used as solvent for the extraction of oils and fats from seeds.
• As a motor fuel under the name “Benzol”
• As a dry cleaning agent for woolen clothes.
• For the preparation of maleic acid.

Common heterocyclic rings with example of drugs

Common heterocyclic rings with example of drugs

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Azine,Azepine, Hydantoin, Pyridine, Piperidine, Quinoline, isoquinoline, coumarine, Purine,

Tropine, Pyrazine, Pyrimidine, Pyrrole, Imidazoline, Uracil, Thiazole, Thiazolidine,

furan, pyrrolidine, indole, penam and cepham.

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(Pyridine) Azine

Pyridxoine, Pyridostigmine, Chlorpheniramine, Nicotinamide

Azepine

Example: Carbamazepine

Hydantoin

Example: Phenytoin, Nitrofurantoin

Piperidine

Example: Pethidine, Haloperidol, Cyproheptadine

Quinoline

Example: Quinine, Chloroquine, Primaquine etc

Isouinoline

Example: Berberine , Emetine etc

Coumarin

Example: Warfarin

Purine

Example: 6-mercaptopurine

Tropane

Example: Atropine, Hyoscine

Tropine

Example: Atropine, Hyoscine

Pyrazine

Example: Pyrazinamide

Pyrimidine

Example: Trimethoprim, Thiamine, Silver sulfadiazine

Pyrole

Example: Atorvastatin

Pyrroline

Example: Glimepiride

Imidazole

Example: Metronidazole, Secnidazole, Tinidazole

Imidazoline

Example: Oxymetazoline, Carbimazole

Uracil

Example: 5-Fluorouracil, Zidovudine

Thiazole

Example: Cefotaxime

Thiazolidine

Example: Rosiglitazone, Benzyl penicillin

Furan

Example: Nitrofurantoin, Diloxanide

Pyrrolidine

Example: Glycopyrronium, Levetiracetam

Pyrrolidine

Example: Glycopyrronium, Levetiracetam

Indole

Example: Indomethacin, Ergotamine

Penam

Example: Penicillins

Cephem

Examples: Cephalosporins

Aziridine

Eg Mitomycin

indole, penam and cepham.