The Synthetic Routes of 5H-PYRROLO[3,2-C]PYRIDAZINE

The synthesis of 5H-PYRROLO[3,2-C]PYRIDAZINE is a well-studied topic in the field of organic chemistry, and there are many synthetic routes available to synthesize this compound.
In this article, we will discuss some of the most commonly used synthetic routes for the preparation of 5H-PYRROLO[3,2-C]PYRIDAZINE, which are widely used in the chemical industry.

Route 1: via Nitration of Aniline

One of the most commonly used methods for the synthesis of 5H-PYRROLO[3,2-C]PYRIDAZINE involves the nitration of aniline with nitric acid.
The reaction proceeds through several steps, including the formation of aniline nitrate, which then undergoes aromatization and hydrodehalogenation to form the final product.

Step 1: Nitration of Aniline
Aniline is dissolved in nitric acid, and the mixture is heated to a temperature of around 80-90°C.
The reaction proceeds via the following mechanism:

C6H7N H+ + NO3- + H2O → C6H7N(NO3)H

Step 2: Aromatization
The aniline nitrate formed in the first step is then treated with a base, such as sodium hydroxide, to convert it into the aromatic compound.

Step 3: Hydrodehalogenation
The aromatic compound obtained in step 2 is then treated with a reducing agent, such as lithium aluminum hydride (LiAlH4), to remove the nitrate group and form the final product.

Route 2: via Coupling of Benzaldehyde and Ammonia

Another common method for the synthesis of 5H-PYRROLO[3,2-C]PYRIDAZINE involves the coupling of benzaldehyde and ammonia.
The reaction proceeds through several steps, including the formation of aza-aldehyde, which then undergoes electrophilic substitution to form the final product.

Step 1: Formation of Aza-aldehyde
Benzaldehyde and ammonia are reacted in the presence of an acid catalyst, such as sulfuric acid, to form the aza-aldehyde.

Step 2: Electrophilic Substitution
The aza-aldehyde formed in step 1 is then treated with a nucleophile, such as hydroxylamine, to form the final product.

Route 3: via Sonogashira Coupling

The Sonogashira coupling reaction is a commonly used method for the synthesis of 5H-PYRROLO[3,2-C]PYRIDAZINE.
In this method, an aryl iodide and a pyrrole derivative are reacted in the presence of a catalyst, such as iron(II) chloride, to form the final product.

Step 1: Formation of aryl-pyrrole intermediate
The aryl iodide and pyrrole derivative are reacted under conditions that promote the coupling reaction, forming an aryl-pyrrole intermediate.

Step 2: Hydrogenation
The aryl-pyrrole intermediate formed in step 1 is then treated with hydrogen gas in the presence of a catalyst, such as palladium on barium sulfate, to reduce the carbon-carbon double bond and form the final product.

Conclusion
There are several synthetic routes available for the synthesis of 5H-PYRROLO[3,2-C]PYRIDAZINE, each with its own advantages and disadvantages.
The choice of route depends on various factors, such as the availability of starting materials, the desired yield