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SYNTHESIS, ISOLATION AND CHARACTERIZATION OF

SOME QUINOXALINE COMPOUNDS

Exploratory Project Report

(Semester-III)

Submitted by

D. INDU PRIYA

Under the supervision of

Dr. JEYAKUMAR KANDASAMY

ASSISTANT PROFESSOR

DEPARTMENT OF CHEMISTRY

INDIAN INSTITUTE OF TECHNOLOGY (B.H.U) VARANASI

UTTAR PRADESH - 221005

INDIA
SYNTHESIS, ISOLATION AND CHARACTERIZATION OF
SOME QUINOXALINE COMPOUNDS

INTRODUCTION

Quinoxaline and its derivatives are important nitrogen containing


heterocyclic compounds and they exhibit of various interesting biological
properties with several pharmaceutical applications. Quinoxaline
derivatives constitute the basis of many insecticides, fungicides,
herbicides, as well as being important in human health and as receptor
antagonists. Although rarely described in nature, synthetic quinoxaline
moiety is a part of number of antibiotics such as echinomycin, levomycin
and actinomycin which are known to inhibit the growth of Grampositive
bacteria and also active against various transplantable tumors (Figure 1).
In addition to antibacterial activities, quinoxalines also possess
antibacterial, anticancer and antiviral activities. Quinoxaline scaffold is
present in several anticancer agents such as chloroquinoxaline
sulfonamide (1), XK469 (2) and NCG555879-01 (3) and in some natural
products like izumiphenazine C (4) (Figure2). In addition, quinoxaline
derivatives are reported for their application in dyes, efficient
electroluminescent materials, organic semiconductors and DNA cleaving
agents. Substituted quinoxalines are an important class of
benzoheterocycles, which constitute the building blocks of wide range of
pharmacologically active compounds having antibacterial, antifungal,
anticancer, antitubercular, antileishmanial, antimalarial and
antidepressant activities. Also, some quinoxalin-2- ones and quinoxaline-
2,3-diones have been reported to show antimicrobial, novel, potent
antithrombotic, anti-pain and anti-inflammatory activities.
Figure 1.Sturucture of antibiotic Echinomycin

Figure 2. Structure of some anticancer agents

OBJECTIVES OF THE EXPLORATORY PROJECT

Synthesis, isolation and characterization of benzo[a]phenazine from 2-


Naphthol using MCPBA and ortho-phenylenediamine (Scheme 1)
Scheme 1. Synthesis of Benzo[a]phenazine

Experiment Section:

1) Procedure : To a solution of 2-naphthol (0.347 mmol, 50 mg) in 15 ml


of DCE (1,2-dichloroethane) was added m-CPBA (1.5 eq.,178 mg) as a
oxidant and covered round-bottom flask with aluminum foil and left the
reaction to stir for 30 mins. After the completion of the oxidation to
corresponding naphtha-1,2-quinone, as judged from TLC analysis
(explained below), we were added o-phenylenediamine in that reaction
mixture and stirred for 10 minutes and checked TLC. So the reaction
was found to be completed. The reaction mixture was extracted with
ethylacetate multiple times using NaHCO3 and brine solution as
aqueous Media. The combined organic extract was dried over
anhydrous Na2SO4 and concentrated in vacuum. The residue was
subjected to a short-pad silica gel column chromatography and isolated
the product in good yield (i.e.Benzo-[a]-phenazine,yield=75%) by
using 5% ethylacetate in hexane eluent.

2) TLC Monitoring:
Thin-layer chromatography (TLC) is a simple chromatography
technique used to separate non-volatile mixtures. Thin-layer
chromatography is performed on a sheet of glass, plastic, or aluminium
foil, which is coated with a thin layer of adsorbent material, usually
silica gel, aluminium oxide, or cellulose. This layer of adsorbent is
known as the stationary phase. After the sample has been applied on
the plate, a solvent or solvent mixture (known as the mobile phase) is
drawn up the plate via capillary action. Because
different analytes ascend the TLC plate at different rates, separation is
achieved.

Thin-layer chromatography can be used to monitor the progress of a


reaction, identify compounds present in a given mixture, and determine
the purity of a substance.

a.
b.

c.

Herein, TLCs run in 20% ethylacetate/n-hexane mixture, are showing


completion of the reaction. In fig. C first, second and third TLCs are after
5, 10 and 20 mins respectively with small amount of starting material left
over there. After 30 mins when we checked TLC, starting material was
completely consumed and naphtho-1,2-quinone spot was clearly shown.
Fifth and sixth TLCs are after 10 mins from the addition of o-
phenylenediamine insitu the reaction mixture, which is showing complete
conversion of starting material to corresponding product i.e. Benzo-[a]-
phenazine.

3) Column chromatography purification:

Column chromatography in chemistry is a method used to purify


individual chemical compounds from mixtures of compounds. It is often
used for preparative applications on scales from micrograms up to
kilograms. The main advantage of column chromatography is the
relatively low cost and disposability of the stationary phase used in the
process. The latter prevents cross-contamination and stationary phase
degradation due to recycling.
a) Stationary phase : The stationary phase or adsorbent in column
chromatography is a solid. The most common stationary phase for
column chromatography is silica gel, followed
by alumina. Cellulose powder has often been used in the past. Also
possible are ion exchange chromatography, reversed-phase
chromatography (RP), affinity chromatography or expanded bed
adsorption.

b) Mobile phase : The mobile phase or eluent is either a


pure solvent or a mixture of different solvents. It is chosen so that
the retention factor value of the compound of interest is roughly
around 0.2 - 0.3 in order to minimize the time and the amount of
eluent to run the chromatography. The eluent has also been chosen
so that the different compounds can be separated effectively. The
eluent is optimized in small scale pre-tests, often using thin layer
chromatography (TLC) with the same stationary phase.

Description for column chromatography:

The residue we have collected after extraction was placed in short


pad silica gel column chromatography and placed 5%
ethylacetate/n-hexane eluent into that.
The eluent was collected in test tubes and TLC was checked from
each test tube. Column was run until we have got the product.
Vessel containing isolated product was kept in vacuum for further
drying.

Characterization:

1. Melting point: 62oC (experimental)


2. Proton NMR

Conclusion:

In summary, we have developed a convenient procedure for the synthesis


of benzo-[a]-phenazine via cyclization of 1,2-naphthaquinone with o-
phenylenediamine. This protocol displays milder reaction condition and
excellent yield of corresponding product.

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