Traube Purine Synthesis

ADVANCED ORGANIC CHEMISTRY- I
ASSIGNMENT - 03
TOPIC: Heterocyclic Chemistry: their respective

mechanism and Organic Name reactions with application
involved in synthesis of drugs containing five, six
membered and fused hetrocyclics such as: Traube purine
synthesis.
SUBMITTED BY: NURI FARZINA RAHMAN
M. PHARM 1ST SEMESTER
(PHARMACEUTICAL CHEMISTRY)
SUBMITTED TO: DR. LALZIKPUII
REGIONAL INSTITUTE OF PARAMEDICAL

AND NUSING SCIENCES
TRAUBE PURINE 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.
However, the use of impure starting materials can lead to unexpected product
formation, and even with pure pyrimidines, the reaction may only proceed to the
formylation stage. An alternative method involves cyclizing 4,5-diaminopyrimidines
with urea or potassium ethyl xanthate to form 8-oxo and 8-thioxo derivatives,
which can be further processed through desulfurization or oxidation.
Purines can also be synthesized through coupling with aldehydes in either a two-
step process with ferric chloride or copper acetate or a one-step
process via oxidative cyclization. It is important to avoid the 4-alkoxyamino group
as it is reduced during the reaction, preventing the preparation of 9-hydroxypurine
derivatives.
 Steps involved in the synthesis:
Here is a step-by-step overview of the Traube purine synthesis:
1. Nitrosation: 4-amino-6-hydroxypyrimidine or 4,6-diaminopyrimidine is first

nitrosated at the 5-position, resulting in the formation of a nitroso group.
2. Nitroso group conversion: The nitroso group is then further nitrosated to
form a nitro group.
3. Amino group introduction: The nitro groups are finally converted back to
amino groups, resulting in the introduction of an amino group at the 5-
position of the pyrimidine ring.
4. Purine formation: The 5-amino-4,6-diaminopyrimidine is then subjected to
formic acid, which leads to the formation of a purine derivative.
 The Traube purine synthesis is a multistep process that involves the

introduction of amino groups into the pyrimidine ring, followed by the
formation of a purine derivative. The reaction has been used in the synthesis
of various purine derivatives, including theophylline, a compound with
therapeutic uses in the treatment of chronic obstructive pulmonary disease
(COPD), asthma, and infant apnea.
 The reagents used in the Traube purine synthesis are:
i. Nitrosating agent: The first step of the reaction involves the nitrosation of
4-amino-6-hydroxypyrimidine or 4,6-diaminopyrimidine at the 5-position,
which is achieved using a nitrosating agent such as nitrous acid (HNO2) or
sodium nitrite (NaNO2).
ii. Nitrosation agent: The nitroso group formed in the first step is then
further nitrosated to form a nitro group. This is achieved using a nitrosation
agent such as nitric acid (HNO3) or a mixture of nitric and sulfuric acid
(HNO3/H2SO4).
iii. Reducing agent: The nitro groups are finally reduced back to amino groups,
resulting in the introduction of an amino group at the 5-position of the
pyrimidine ring. This is achieved using a reducing agent such as zinc dust (Zn)
or iron powder (Fe).
iv. Formic acid: The 5-amino-4,6-diaminopyrimidine is then subjected to formic
acid, which leads to the formation of a purine derivative.
In summary, the Traube purine synthesis involves the use of nitrosating agents,
nitrosation agents, reducing agents, and formic acid to synthesize purine
derivatives from 4-amino-6-hydroxypyrimidine or 4,6-diaminopyrimidine.
 Applications of traube purine synthesis:
The Traube purine synthesis has various applications in the synthesis of purine
derivatives, which are important in medicinal chemistry and drug development.
Some of the key applications of the Traube purine synthesis are:
Synthesis of theophylline: Theophylline, a compound with therapeutic uses in the

treatment of chronic obstructive pulmonary disease (COPD), asthma, and infant
apnea, can be synthesized using the Traube purine synthesis. Theophylline works by
blocking the action of adenosine, a molecule that can cause bronchoconstriction and
inflammation in the airways.
Synthesis of xanthine analogs: Xanthine derivatives, which are structurally

related to purines, have been identified as potential leads for the development of
new drugs. The Traube purine synthesis is one of the oldest and most widely used
methods for the synthesis of xanthine analogs.
Total synthesis of purines: The Traube purine synthesis has been used in the total
synthesis of purines, including adenine, hypoxanthine, xanthine, and isoguanine.
These compounds are essential building blocks in nucleic acids and have various
biological functions.
The Traube purine synthesis, with its ability to efficiently introduce amino groups
into pyrimidine rings and form purine derivatives, has been a valuable tool in the
synthesis of important compounds for medicinal and biological research.

Traube Purine Synthesis

Uploaded by

Copyright:

Available Formats

Traube Purine Synthesis

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Traube Purine Synthesis

Uploaded by

Copyright:

Available Formats

ADVANCED ORGANIC CHEMISTRY- I

TOPIC: Heterocyclic Chemistry: their respective

SUBMITTED BY: NURI FARZINA RAHMAN

M. PHARM 1ST SEMESTER

SUBMITTED TO: DR. LALZIKPUII

REGIONAL INSTITUTE OF PARAMEDICAL

 Steps involved in the synthesis:

Here is a step-by-step overview of the Traube purine synthesis:

1. Nitrosation: 4-amino-6-hydroxypyrimidine or 4,6-diaminopyrimidine is first

 The Traube purine synthesis is a multistep process that involves the

 The reagents used in the Traube purine synthesis are:

 Applications of traube purine synthesis:

Some of the key applications of the Traube purine synthesis are:

Synthesis of theophylline: Theophylline, a compound with therapeutic uses in the

Synthesis of xanthine analogs: Xanthine derivatives, which are structurally

You might also like