Synthesis, Reactions, and Medicinal Uses of Acridine

 

Synthesis, Reactions, and Medicinal Uses of Acridine

 



Acridine is a three-membered fused heterocyclic system containing Nitrogen as a heteroatom at the 10th position. Two benzene rings are fused to the "b" and "e" sides of pyridine. Other names for acridine are 2,3-Benzoquinoline and Dibenzo[b,e]pyridine.

Physical properties:

Colour: white
State: powder(solid)
Melting point: 106 - 110 oC
Boiling point: 344.86 oC
Solubility: Slightly soluble in hot water and soluble in organic solvents.

Structure and Aromaticity:



Acridine is a planar molecule, all atoms are sp2 hybridised. Unhybridised p-orbitals sidewise overlap to form pi bonds. Acridine contains seven double bonds and 14 delocalised pi electrons, following the huckles rule(4n+2)pi electrons (where n=3). Hence acridine is aromatic.

Synthesis of Acridine:

1. Ulmann synthesis: 


2-chlorobenzoic acid reacts with aniline in the presence of sodium hydroxide give diphenylamino-2-carboxylic acid(DPCA). 
(i) DPCA treated with strong acid give 9(10H)-acridinone, which upon reduced with Na in ethanol gives 9,10-dihydroacridine.
(ii) DPCA reacted with phosphorous oxychloride give 9-chloro-9,10-dihydroacridine, which upon reduced with hydrogen and nickel gives 9,10-dihydroacridine.
The formed 9,10-dihydroacridine upon oxidation give acridine.

2. Bernthsen acridine synthesis:


Diarylamine heated with a carboxylic acid or acid anhydride in the presence of Zinc chloride gives 9-substituted acridine.

3. From 2-benzyl aniline: 


2-benzyl aniline passed through a red hot tube gives acridine.

Electrophilic addition reactions to 'N' of Acridine.

1. Protonation:
 Acridine reacts with acids and gives acridinium salts.

2. N-alkylation: 
Acridine reacts with alkyl halides giving N-alkyl acridinium halides.

Electrophilic substitution reactions:


Electrophilic substitution reactions of acridine give a mixture of 2-substituted and 2,7-disubstituted derivatives.

1. Nitration: 
Acridine upon nitration gives a mixture of 2-nitro and 2,7-dinitro acridine.

2. Sulphonation:
Acridine upon sulphation gives acridine-2-sulphonic acid and acridine-2,7-sulphonic acid.

3. Halogenation: 
Acridine upon halogenation gives 2-halo and 2,7-dihalo acridine.

Nucleophilic substitution reactions:


Acridine readily reacts with nucleophiles. nucleophilic reactions take place at the 9th position.
Chichibabin reaction: Acridine reacts with Sodamide in liquid ammonia leading to 9-aminoacridine.



Oxidation reactions:


1. Acridine oxidized with sodium dichromate in acetic acid gives 9-(10H)-acridine.


2. Acridine is oxidised by potassium permanganate in an alkaline medium gives quionoline-2,3-dicarboxylic acid.



3. Acridine reacts with peroxy acids and gives acridine-N-oxides.


Reduction reactions:


1. Acridine reduced with hydrogen and pt as catalyst gives 1,2,3,4,5,6,7,8-octahydroacridine.



2. Acridine reduced with hydrogen and Ni as Catalyst or Zinc in Hcl gives 9,10-dihydroacridine.


3. Acridine reduced with Na in liquid ammonia gives 1,4,5,8-tetrahydroacridine.

Medicinal uses:

Drugs containing Acridine ring:

1. Tacrine: Anticholinesterase drug used in the treatment of Alzheimer's disease.


2. 9-Aminoacridine: Slow-acting germicide, used as an antiseptic and disinfectant. also used in the treatment of vaginal candidiasis.


3. Quinacrine: used in the treatment of malaria and tapeworm infections. also used in the treatment of cutaneous leishmaniasis and giardiasis.



4. Proflavine: A topical antiseptic agent used to prevent infections.



References (Latest editions):


Heterocyclic chemistry by Raj K. Bansal.
Heterocyclic chemistry by T.L. Gilchrist.
Organic chemistry by Morrison and Boyd.
A  textbook of organic chemistry - Arun Bahl. B.S. Bahl.



Comments

Post a Comment

Popular posts from this blog

Synthesis, Reactions, and Medicinal Uses of Pyrazole

Image
  Synthesis, Reactions, and Medicinal Uses of Pyrazole Pyrazole is a five-membered heterocyclic aromatic compound containing two adjacent nitrogen atoms at 1 and 2 positions.  Physical properties: Colour                :  colorless State                   :   solid Boiling point     : 186 - 188  o C Melting point    :    66 - 70  o C Solubility           :    soluble in hot water, soluble in organic solvents. Structure & Aromaticity: All atoms in the pyrrole ring are  sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the four hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma bonds lie in one pla...
Read more

Relative aromaticity and reactivity of Pyrrole, Furan, and Thiophene

Image
Relative aromaticity and reactivity of Pyrrole, Furan, and Thiophene Relative aromaticity of Pyrrole, Furan, and Thiophene: Aromatic compounds are cyclic hydrocarbon compounds contains alternate double and single bonds.pi electrons are delocalised inside the ring enhance the stability of the compound. Pyrrole, thiophene and furan are the heterocyclic aromatic compounds contain nitrogen, sulfur and oxygen as heteroatom respectively. the lone pair of electrons on heteroatom get involved and participate in aromaticity. In order to know the order of aromaticity in pyrrole, furan and thiophene we need to about electronegativity of nitrogen, sulfur and oxygen. Electronegativity is the tendency of an atom which drags the shared pair of electrons towards it. Electronegative values of nitrogen, oxygen and sulfur are given below. High electronegative means it tightly holds the electrons, especially lone pair of electrons present on an atom and hinders the delocalisation of pi electrons ...
Read more

Synthesis, Reactions and Medicinal Uses of Oxazole

Image
  Synthesis, Reactions, and Medicinal Uses of Oxazole    O xazole is a five-membered heterocyclic compound having one oxygen and one nitrogen atom as a heteroatoms at 1 and 3 positions respectively. Physical properties: Colour                :  clear to pale yellow State                   :   liquid Boiling point     :  69 to 70 o C Melting point    :    -84 o C Solubility              :   partially soluble in water, soluble in organic solvents Structure & Aromaticity: C, N and O atoms in the oxazole ring are  sp 2   hybridised, so the oxazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the three hydrogens forming C-C, C-N, C-H, and...
Read more

Synthesis, Reactions and Medicinal Uses of Pyrrole

Image
Synthesis, Reactions, and Medicinal Uses of Pyrrole                 P yrrole is a five-membered heterocyclic compound having one nitrogen atom as a heteroatom. Physical properties: Colour                :  colorless State                   :    liquid Boiling point     : 131 o C Melting point    :    -23 o C Solubility           :    Insoluble in water, soluble in organic solvents Structure & Aromaticity: All atoms in the pyrrole ring are sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the five hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma ...
Read more

Synthesis, Reactions, and Medicinal Uses of Imidazole

Image
  Synthesis, Reactions, and Medicinal Uses of Imidazole I midazole is a five-membered unsaturated heterocyclic compound having two nitrogen atoms as heteroatoms at 1 and 3 positions. Physical properties: Colour                : White or colourless State                   :  Solid Boiling point     : 256 o C Melting point    :   89 to 91 o C Solubility           :   Soluble in water, soluble in organic solvents Structure & Aromaticity: All atoms in the Imidazole ring are  sp 2   hybridised, so the imidazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with "s" atomic orbital of the four hydrogens forming C-C, C-N, C-H, and N-H sigma bonds. all these sigma bonds lie in one plane. Imidazole also h...
Read more

Synthesis, Reactions and Medicinal Uses of Pyridine

Image
  Synthesis, Reactions, and Medicinal Uses of Pyridine          Pyridine is a six-membered heterocyclic compound that contains one Nitrogen as heteroatom. Physical properties: Colour: colourless State: liquid Melting point: -41.6  o C Boiling point: 115.2  o C Solubility: Soluble in water Structure and Aromaticity: Pyridine contains five carbon atoms and one nitrogen atom, all are  sp 2  hybridized. Pyridine is a planar molecule that contains unhybridised p orbitals perpendicular to the ring. these p orbitals sidewise overlap to form pi bonds. Pyridine contains a total of six delocalised pi electrons, following the Huckls rule hence pyridine is aromatic.    Resonance structures: Basicity Of Pyridine: Pyridine is more basic than pyrrole and less basic than Aliphatic amine. In pyridine, lone pair of electrons on nitrogen is easily available for protonation and participate in acid-base reactions. whereas in pyrrole, lone pair...
Read more

Synthesis, Reactions and Medicinal Uses of Thiazole

Image
  Synthesis, Reactions, and Medicinal Uses of Thiazole  Thiazole is a five-membered heterocyclic compound having one Sulphur and one Nitrogen atom as heteroatoms at 1 and 3 positions respectively. Physical properties: Colour                :  Colourless or pale yellow State                   :   liquid Boiling point     :  116 - 118  o C Melting point    :   -33  o C Solubility               :  slightly soluble in water, soluble in organic solvents Structure & Aromaticity: C, N and S atoms in the thiazole ring are  sp 2   hybridised, so the thiazole contains a planar ring structure. the  sp 2  hybrid orbitals overlap with each other and with the "s" atomic orbital of the three hydrogens forming C-C, C-N...
Read more

Synthesis, Reactions, and Medicinal Uses of Isoquinoline

Image
  Synthesis, Reactions, and Medicinal Uses of Isoquinoline  Isoquinoline is a bicyclic hetero-aromatic compound having nitrogen at the second position as heteroatom. It is also called benzo[c]pyridine, the benzene is fused with the "c" side of pyridine. another name for isoquinoline is 2-azanaphthalene. Physical properties: Colour: colourless State: liquid Melting point: 26 - 28  o C Boiling point: 242  o C Solubility: Slightly soluble in water and soluble in organic liquids and dilute acids. Structure and Aromaticity: All atoms in Isoquinoline are  sp 2  hybridised and have a planar structure. Unhybridised p-orbitals sidewise overlap to form five pi bonds. Isoquinoline contains a total of ten delocalised pi electrons, following the huckles rule hence quinoline is an Aromatic. Resonance structures: Synthesis of Isoquinoline: 1. Bischler-Napieralski synthesis:  2-aryl ethanamines react with acyl chloride to give an amide, which upon treated with phospho...
Read more

Synthesis, Reactions, and Medicinal Uses of Furan

Image
Synthesis, Reactions, and Medicinal Uses of Furan Furan is a five-membered heterocyclic compound having one Oxygen atom as a heteroatom. Physical properties: Colour                :   colorless State                   :    liquid Boiling point     :    31.3  o C Melting point    :    -85.6  o C Solubility           :   soluble in organic solvents(ethanol, ether, and acetone, etc.,)                                        slightly soluble in water. Structure & Aromaticity: All atoms in the Furan ring are  sp 2   hybridised, so the pyrrole contains a planar ring structure. the  sp 2  hybrid orbita...
Read more

Synthesis, Reactions and Medicinal Uses of Quinoline

Image
  Synthesis, Reactions, and Medicinal Uses of Quinoline          Quinoline is a bicyclic hetero-aromatic compound having nitrogen at the first position as heteroatom. Physical properties: Colour: colourless State: liquid Melting point: -15  o C Boiling point: 237  o C Solubility: Slightly soluble in water and soluble in organic liquids. Structure and Aromaticity: Quinoline is a fused ring system of pyridine and benzene. All atoms in quinoline are  sp 2  hybridised and have a planar structure. Unhybridised p-orbitals sidewise overlap to form five pi bonds. Quinoline contains a total of ten delocalised pi electrons, follows the huckles rule hence quinoline is an Aromatic. Resonance structures: Synthesis of Quinoline: 1. Friedlander Synthesis: O-amino benzaldehyde reacts with carbonyl compound with active methylene compound in presence of alcoholic NaOH give Quinoline. 2. Knorr quinoline Synthesis:  Condensation of aniline with ke...
Read more