Formamide-1-d1

• CAS: 35692-88-7
• Catalog Number: ACM35692887
• Category: Main Products
• Molecular Weight: 46.05
• Molecular Formula: DCONH2
• Boiling Point: 210 °C
• Melting Point: 2 - 3 °C
• Density: 1.134 g/cm³
• Appearance: Liquid

Case Study

Study on the Application of Formamide-1-d1 in Palladium-Catalyzed Amidation for Heterocycle Synthesis

Rosenberg, Adam J. Development of Pd Catalyzed Amidations & Applications to the Synthesis of Heterocycles. Dissertation, Syracuse University, 2013.

This study explored the use of Formamide-1-d1 as a deuterated amide coupling partner in palladium-catalyzed amidation reactions for the synthesis of imidazo[4,5-b]pyridines and related heterocycles. Formamide-1-d1, with deuterium substitution at the amide N-H position, was employed to investigate reaction mechanism and improve product selectivity. The reactions were carried out using 2-chloro-3-amino-heterocycles as substrates, palladium catalysts (Pd₂(dba)₃·CHCl₃), ligands (e.g., P(t-Bu)₃, Xantphos), and bases (Cs₂CO₃) in solvents such as 1,4-dioxane or toluene at 100-110°C. Results showed that Formamide-1-d1 successfully participated in regioselective amidation, forming C-N bonds with 2-chloro-3-aminopyridines to yield deuterium-labeled imidazo[4,5-b]pyridine derivatives. The deuterium label remained intact during the reaction, confirming the stability of Formamide-1-d1 under palladium-catalyzed conditions. This method provided access to deuterated heterocycles with substitution at N1 and C2, and was compatible with functionalized primary and secondary amide derivatives. These studies demonstrate that Formamide-1-d1 is a viable tool for palladium-catalyzed amidation, offering utility in mechanistic studies and the synthesis of deuterium-labeled heterocyclic compounds.
The in vitro application of Formamide-1-d1 was verified through optimized palladium-catalyzed amidation experiments. Substrates (2-chloro-3-aminopyridines, 0.5 mmol), Formamide-1-d1 (1.0 mmol), Pd₂(dba)₃·CHCl₃ (2 mol%), ligand (8 mol%), and Cs₂CO₃ (1.5 mmol) were mixed in 1,4-dioxane (5 mL) and heated at 100°C for 12-24 hours under an inert atmosphere. Reaction progress was monitored by TLC, and products were purified by column chromatography. Deuterium incorporation and product identity were confirmed by ¹H NMR, ²H NMR, and HRMS. Control experiments with non-deuterated formamide were conducted to compare reaction efficiency, showing comparable yields (65-87%) for both formamide and Formamide-1-d1. The method was extended to the synthesis of deuterated pentosidine precursors, demonstrating compatibility with multi-step heterocycle synthesis.

Custom Q&A

What is the molecular formula of formamide?

The molecular formula of formamide is CH3NOHCONH2.

What is the molecular weight of formamide?

The molecular weight of formamide is 45.041 g/mol.

What is the freezing point of formamide?

The freezing point of formamide is 36 °F.

What is the IUPAC name of formamide?

The IUPAC name of formamide is formamide.

What is the InChIKey of formamide?

The InChIKey of formamide is ZHNUHDYFZUAESO-UHFFFAOYSA-N.

What is the CAS number of formamide?

The CAS number of formamide is 75-12-7.

What are the synonyms of formamide?

The synonyms of formamide are Methanamide, carbamaldehyde, and Formimidic acid.

What is the role of formamide?

Formamide has a role as a solvent.

What is the EC number of formamide?

The EC number of formamide is 200-842-0.

What is the Wikipedia page for formamide?

The Wikipedia page for formamide is "Formamide".