The Synthetic Routes of 2-AMINO-ISONICOTINIC ACID ETHYL ESTER

2-Amino-isonicotinic acid ethyl ester, commonly abbreviated as AIIEE, is a unique compound with diverse applications in the chemical industry.
Its synthetic routes have undergone significant advancements since its discovery in 1953.
The following article will discuss the most popular synthetic routes for AIIEE, their advantages, and limitations.

1. Hydrolysis of N-Cbz-N-(2-amino-4,6,7,8-tetrahydroisoquinolin-1-yl) acetamide (HS-AIA)

This is the most widely used synthetic route for AIIEE.
It involves the hydrolysis of the protected amino acid HS-AIA to yield AIIEE.
The advantage of this route is its simplicity and high yield, making it an ideal choice for industrial-scale synthesis.
However, it has limited applications in pharmaceuticals due to the presence of a protecting group.

2. Synthesis via the Rauhampa-Curtius reaction

The Rauhampa-Curtius reaction is a chemical test used to determine the presence of basic nitrogen compounds.
The reaction involves the reduction of picric acid with Na/K tartrate, and the resulting product can be further transformed into AIIEE.
This route offers the advantage of using easily available reagents and is compatible with pharmaceutical applications.
However, it has limited scalability.

3. Synthesis via the Pictet-Spengler reaction

The Pictet-Spengler reaction is a chemical test used to determine the presence of basic nitrogen compounds.
It involves the reaction of AlCl3 with a primary or secondary amine to yield a diacyl derivative, which can be further transformed into AIIEE.
This route offers the advantage of using easily available reagents and is also compatible with pharmaceutical applications.
However, it has limited scalability and yields low yields.

4. Synthesis via the Ellman's reagent

Ellman's reagent, also known as 5,5'-dithiobis(2-nitrobenzoic acid), is a commonly used reagent in biochemistry to measure the activity of esterases.
The reagent can be used to synthesize AIIEE by treating an amino acid with the reagent, followed by treatment with sodium carbonate.
This route offers the advantage of being compatible with pharmaceutical applications.
However, it has limited scalability and requires specialized equipment.

In conclusion, AIIEE is a versatile compound with diverse applications in the chemical industry, and its synthetic routes have undergone significant advancements over the years.
The HS-AIA hydrolysis route is the most widely used route due to its simplicity and high yield, but it has limited applications in pharmaceuticals due to the presence of a protecting group.
The Rauhampa-Curtius reaction, Pictet-Spengler reaction, and Ellman's reagent are alternative routes that offer advantages such as the use of easily available reagents and compatibility with pharmaceutical applications, but they have limitations such as limited scalability and specialized equipment requirements.