The Synthetic Routes of 5-Isothiocyanato-3-(trifluoromethyl)picolinonitrile

The Synthetic Routes of 5-Isothiocyanato-3-(trifluoromethyl)picolinonitrile: A Comprehensive Overview in the Chemical Industry

Are you a researcher in the chemical industry looking for a reliable and efficient way to synthesize 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile? Look no further, because we have you covered with this comprehensive guide on the synthetic routes of this important compound.

Introduction

5-Isothiocyanato-3-(trifluoromethyl)picolinonitrile, also known as FC-108 or 1,5-bis(5-isothiocyanato-1,2,4-thiadiazol-2-yl)-3-(trifluoromethyl)picolinonitrile, is a versatile compound with applications in a wide range of industries, from pharmaceuticals to material science.
Due to its unique properties, it has become an essential building block in the synthesis of various materials and drugs.

The synthesis of 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile can be achieved through several different methods, each with its advantages and limitations.
In this article, we will explore the various synthetic routes available for this compound and discuss their efficacy, ease of use, and cost-effectiveness.

Synthetic Route 1: Via 5-Isothiocyanato-1,2,4-thiadiazole-2-thiol

One of the most commonly used synthetic routes for 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile involves the synthesis of 5-isothiocyanato-1,2,4-thiadiazole-2-thiol, which is then converted into the desired nitrile using a series of chemical reactions.

The synthesis of 5-isothiocyanato-1,2,4-thiadiazole-2-thiol starts with the reaction of 2-mercapto-1,3-dithiolane-4-thiol and 2-chloromethyl-1,3-dithiolane-4-thiol in the presence of a reducing agent, such as hydride.
The resulting product is then reacted with 2,2'-dithiopyrrole-1,1'-disulfide in the presence of a sulfurizing agent, such as dithiothreitol, to form the 5-isothiocyanato-1,2,4-thiadiazole-2-thiol.

The synthesis of 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile from the 5-isothiocyanato-1,2,4-thiadiazole-2-thiol can be achieved using a variety of methods, including the C-C bond formation reaction with potassium carbonate in DMF, followed by treatment with sodium nitrite and hydrochloric acid.

Synthetic Route 2: Via 3-Amino-N-(5-isothiocyanato-1,2,4-thiadiazol-2-yl)acetamide

Another synthetic route for 5-isothiocyanato-3-(trifluoromethyl)picolinonitrile involves the synthesis of 3-amino-N-(5-isothiocyanato-1,2,4-thiadiazol-2-yl)acetamide, which can then be converted into the desired nitrile using a series of chemical reactions.

The synthesis of 3-amino-N-(5-isothiocyanato-1,2,4-thiadiazol-2-yl)acetamide involves the reaction of 3-nitro-N-(1,2,4-thiadiazol-2-yl)acetamide with sodium hydroxide in the presence of a carboxylic acid, such as acetic acid, to form the amide.
The amide is then treated with 2,2'-d