25306-15-4 | 5-(DIFLUOROMETHYL)-2-AMINO-1,3,4-THIADIAZOL

CAS:25306-15-4 | 5-(DIFLUOROMETHYL)-2-AMINO-1,3,4-THIADIAZOL,Description

The compound 5-(Difluoromethyl)-1,3,4-thiadiazol-2-amine is a derivative of 1,3,4-thiadiazole, which is a heterocyclic compound containing both sulfur and nitrogen within a five-membered ring. This particular derivative is characterized by the presence of a difluoromethyl group attached to the thiadiazole ring. The 1,3,4-thiadiazole moiety is a common scaffold in medicinal chemistry due to its diverse biological activities.

Synthesis Analysis

The synthesis of 1,3,4-thiadiazol-2-amine derivatives can be achieved through various methods. For instance, the ibuprofen derivative of 1,3,4-thiadiazol-2-amine hydrochloride was prepared via cyclization of ibuprofen with thiosemicarbazide in the presence of POCl3. Similarly, 5-amino-1,3,4-thiadiazole-2-thiol and its derivatives were synthesized using ultrasound-assisted methods, which proved to be more efficient than conventional methods. These methods highlight the versatility in synthesizing thiadiazole derivatives, which could be applied to the synthesis of 5-(Difluoromethyl)-1,3,4-thiadiazol-2-amine.

Molecular Structure Analysis

The molecular structure of 1,3,4-thiadiazol-2-amine derivatives has been extensively studied using various spectroscopic techniques and X-ray crystallography. For example, the crystal and molecular structure of a chlorophenyl derivative was characterized and showed that the compound crystallized in the orthorhombic space group with specific unit cell parameters. Quantum chemical calculations, such as density functional theory (DFT), have been used to predict the geometry and electronic properties of these compounds, which are in good agreement with experimental data.

Chemical Reactions Analysis

1,3,4-thiadiazol-2-amine derivatives participate in a variety of chemical reactions. Reactions with primary and secondary amines have been shown to yield thiadiazole-thiones and thiadiazol-ones, among other products. The reactivity of these compounds can be influenced by the nature of substituents on the thiadiazole ring, as seen in the formation of cocrystals and salts with carboxylic acids. These reactions are indicative of the potential transformations that 5-(Difluoromethyl)-1,3,4-thiadiazol-2-amine could undergo.

Physical and Chemical Properties Analysis

The physical and chemical properties of 1,3,4-thiadiazol-2-amine derivatives are closely related to their molecular structure. The presence of different substituents can significantly affect these properties. For instance, the adamantane-1,3,4-thiadiazole hybrids showed different orientations of the amino group depending on the presence of halogen substituents, which influenced the non-covalent interactions within the crystal structures. The vibrational analysis of these compounds provides insights into their bond character and potential applications, such as in nonlinear optical materials.

Scientific Research Applications

• Late-stage Difluoromethylation 
  • Field : Chemistry Research
  • Summary : This research focuses on the advances made in difluoromethylation processes based on X–CF 2 H bond formation. The last decade has witnessed an upsurge of metal-based methods that can transfer CF 2 H to C (sp 2) sites both in stoichiometric and catalytic mode.
  • Methods : The formation of X–CF 2 H bond where X is oxygen, nitrogen or sulfur is conventionally achieved upon reaction with ClCF 2 H. More recently, numerous protocols have achieved X–H insertion with novel non-ozone depleting difluorocarbene reagents.
  • Results : These advances have streamlined access to molecules of pharmaceutical relevance, and generated interest for process chemistry.
• Photocatalytic Difluoromethylation 
  • Field : Organic Chemistry
  • Summary : This research discusses the role of late-stage difluoromethylation reactions in positively impacting the physical properties of organic compounds including solubility, metabolic stability, and lipophilicity. These properties are of considerable importance in pharmaceutical, agrochemical, and materials science.
  • Methods : Visible-light-photocatalyzed difluoromethylation reactions are accomplished on (hetero)aromatic and carbon–carbon unsaturated aliphatic substrates under mild and environmentally benign conditions.
  • Results : The introduction of difluoromethyl groups in the last stages of synthetic protocols has played relevant roles as the CF2X group substitutions exert positive impacts on the physical properties of organic compounds.
• Difluoromethylation of Heterocycles via a Radical Process 
  • Field : Organic Chemistry
  • Summary : This research highlights the importance of difluoromethylation in functionalizing diverse fluorine-containing heterocycles, which are the core moieties of various biologically and pharmacologically active ingredients. The construction of difluoromethyl substituted scaffolds has been a highly intriguing research topic.
  • Methods : The review summarizes the state-of-the-art advances in difluoromethylation of heterocycles via a radical process over the past few years (2018 to early 2022). The focus is on the design and catalytic mechanism as well as on the representative outcomes and applications.
  • Results : The introduction of difluoromethyl groups has significantly impacted the physical properties of organic compounds, making it a prime area of research.
• Fragmentation of the 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole Radical Anion 
  • Field : Chemistry Research
  • Summary : This research involves the fragmentation of the 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole radical anion.
  • Methods : The fragmentation of the radical anion yields the difluoromethyl radical which adds to [LnNi n+1 Ar]. The resulting [Ar–Ni n+2 –CF2H] complex undergoes reductive elimination to release the difluoromethylarene with regeneration of LnNi n X.
  • Results : The research provides a novel method for the generation of difluoromethyl radicals.
• Late-stage Difluoromethylation: Concepts, Developments and Perspective 
  • Field : Chemistry Research
  • Summary : This review describes the recent advances made in difluoromethylation processes based on X–CF 2 H bond formation where X is C (sp), C (sp 2 ), C (sp 3 ), O, N or S. This field of research has benefited from the invention of multiple difluoromethylation reagents.
  • Methods : The formation of X–CF 2 H bond where X is oxygen, nitrogen or sulfur is conventionally achieved upon reaction with ClCF 2 H. More recently, numerous protocols have achieved X–H insertion with novel non-ozone depleting difluorocarbene reagents.
  • Results : These advances have streamlined access to molecules of pharmaceutical relevance, and generated interest for process chemistry.
• Difluoromethylation of Heterocycles via a Radical Process 
  • Field : Organic Chemistry
  • Summary : Difluoromethylation is of prime importance due to its applicability in functionalizing diverse fluorine-containing heterocycles, which are the core moieties of various biologically and pharmacologically active ingredients.
  • Methods : In this review, the state-of-the-art advances in difluoromethylation of heterocycles via a radical process over the past few years (2018 to early 2022) are summarized.
  • Results : The construction of difluoromethyl substituted scaffolds has been a highly intriguing research topic, and substantial progress has been made in the past decades.

Safety And Hazards

The safety and hazards of a specific compound depend on its physical and chemical properties. It’s important to refer to the Safety Data Sheet (SDS) of the specific compound for detailed information.

Future Directions

The field of difluoromethylation has seen significant advances in recent years. The development of new synthetic methods and the exploration of novel applications in pharmaceutical, agrochemical, and materials science are areas of ongoing research.

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