University Institute of Pharmaceutical Sciences

Panjab University Chandigarh

B. Pharmacy Second Year Fourth Sem

Pharmaceutical Organic Chemistry III

PURINES
Presented By Shruti Goyal and Ojaswi
Quick Revision
 What is Purine?

- Aromatic Heterocycle Composed of Carbon and Nitrogen.

- Have 9 atoms in its structure
- Purine has two cycles - Six membered Pyrimidine Ring and a five
membered imidazole ring fused together.
-Four nitrogen atoms are
present at the 1, 3, 7, and 9
positions.

-The numbering of purine starts

with the first nitrogen of the six-
membered ring and then
proceeds in an anticlockwise
direction. The imidazole ring is
numbered clockwise.
 General Method of

Preparation of Purine
 (1) Fischer Method

Uric acid 2,6,8- 2,6- Purine

Trichloropurine Diiodopurine

Oldest Method for Synthesis of Purine like adenine

and guanine.
(2) Traube Synthesis

The Traube reaction, also

known as the Traube purine
synthesis, is a method for
synthesizing purine
derivatives from 4-amino-6-
hydroxypyrimidine or 4,6-
diaminopyrimidine.
The reaction involves introducing the amino group into the 5-position
of the pyrimidines through nitrosation and reduction with ammonium
sulfide (NH4)2S. Ring closure is achieved using either formic acid
HCOOH or chlorocarbonic ester.
(3) Synthesis of substituted Purine
 Chemical Reactions of Purines

The purine ring system can be viewed as a pyrimidine

fused to an imidazole . The electrons of the purine ring are
extensively delocalised. The principle contributing
structure of purine suggest that positions 2,6 and are
susceptible to attack by nucleophiles, and position 3 and 7
are electron rich and are susceptible to attack by
electrophiles.
 1. NUCLEOPHILIC DISPLACEMENT REACTION

The nucleophilic displacement reaction of halide is useful procedure

as compared to electrophilic substitution reaction. chlorine is more
easily displaced at C-6 than at C-2: for example 2,6-dichloropurine
gives 6-Amino-2-chloropurine with methanolic ammonia at 100°C.
with 2,6,8-Trichloropurine, the chloride at C-8 is the least easily
displaced in alkaline media because the proton at the adjacent
nitrogen atom is removed by the base. If this nitrogen atom is
alkylated, however, the order of displacement of halide in purine is
8>6>2.
2. ELECTROPHILIC SUBSTITUTION REACTION
Adenine, guanine and several other purine can be brominated
at C-8, but otherwise the electrophilic substitution is of limited
value.
3. OXIDATION REACTION

8-Oxoguanine

2-Oxoadenine
Adenine is oxidised by per acid to
give 1-Oxopurine and guanine is
converted to 3-Oxopurine by
action of pertrifluoroacetic acid
 4. - N ALKYLATION OF PURINES

Purines can be N-Alkylated but the site of reaction is dependent upon the
substituents present, and the reagent used. For eg Adenine can be
alkylated at N-9, N-3, and N-1 under different conditions. In general, the
purines are alkylated into 9-Methylpurine by reaction with dimethyl sulfate
in aqueous solution.
 5. MUREOXIDE REACTION
The murexide reaction of caffeine was investigated to clarify the pathway of the
coloration. From the reaction mixture of caffeine with nitric acid, 1, 3-
dimethylalloxan (II) and 1, 3, 7-trimethyl-2, 6-dioxo-8-nitro-1H, 3H, 7H-xanthine
(IV) were isolated. Compound II was found to be the key intermediate, since it was
converted to a purple-red-colored substance, murexoin (III), by treatment with
conc. ammonia. It was found that 1-hydroxy-5, 7-dimethyl-2, 4, 6-trioxo-1H, 5H,
7H-oxazolo [4, 5-d] pyrimidine (I), previously obtained by the oxidation of caffeine
with hydrogen peroxide and hydrochloric acid, was also transformed to III with conc.
ammonia. Consequently, the murexide reaction of caffeine was shown to have two
pathways of coloration depending on the oxidizing agent employed.
 1-hydroxy-5, 7-dimethyl-2, 4, 6-
trioxo-1H, 5H, 7H-oxazolo [4, 5-d]
pyrimidine
 MEDICINAL USES OF PURINES

1. Nucleoside antimetabolite: Acyclovir, Valacylovir,

Ganciclovir, Vidarabine act as antiviral agent.
2. Antimetabolites such as 6-Mercaptopurine,
Thioguanine, Azathiopurine used as anticancer
drug.
3. Caffine, Theobromine, Theophylline - they act as
CNS stimulant and are used in bronchial asthma.
VIDABRINE 6-Mercaptopurine

Antiviral Anticancer
Thank

you!