BTMO

Cat Number

INS0004

CAS Number

920366-91-2

Price/Packaging

Inquiry

If you have any other questions, please contact our experts.

Product Detail Description Scientific Support Customer Q&A

CAS Number

920366-91-2

Storage

2-8℃

Molecular Formula

C12H12N2O2S2

Molecular Weight

280.37

Smiles

C(NCC1SC=CC=1)(=O)C(NCC1SC=CC=1)=O

Appearance

Powder

Relative Density

1.355±0.06

General Description

N,N′-Bis(thiophen-2-ylmethyl)oxalamide (BTMO) is an innovative oxalic-diamide ligand engineered to overcome the long-standing challenge of copper-catalyzed Goldberg amidation between unreactive (hetero)aryl chlorides and weakly nucleophilic amides. Its unique molecular structure incorporates thiophene rings with electron-rich sulfur atoms γ to the coordinating sites, enabling strong electron donation to Cu(I) while stabilizing the key Cu(III) intermediate.

Application

BTMO serves as a highly effective ligand for copper-catalyzed coupling reactions, specifically enabling the challenging amidation of (hetero)aryl chlorides with weakly nucleophilic amides. This ligand demonstrates exceptional versatility in facilitating C-N bond formation across a broad substrate scope, including electron-rich, electron-poor, and sterically hindered aryl chlorides, as well as various primary, cyclic, and lactam amides. With excellent functional group tolerance and scalability, BTMO provides a reliable, cost-efficient alternative to precious metal catalysts for industrial-scale coupling applications.

BTMO (N,N′-bis(thiophen-2-ylmethyl)oxalamide) is a potent and user-friendly ligand for copper-catalyzed Goldberg amidation of (hetero)aryl chlorides with amides. The transformation of amides with aryl chlorides remains an unreactive substrate because of the low reactivity of aryl chlorides, and even with activated chlorides or very reactive bromides the use of amides as nucleophiles is usually inefficient due to their weak nucleophilicity.
The team successfully addressed these issues by using BTMO to achieve a coupling with 10 mol % Cu2O and 10 mol % BTMO in t-BuOH at 130 ℃ with no need for excess aryl chloride or use of harsh additives. BTMO displayed excellent activity and stability in this coupling process among a series of oxalamide ligands, which was attributed to the electron-donating property of the thiophene sulfur to stabilize the Cu intermediate and facilitate reductive elimination. The system is also functional group- and substrate-tolerant, working with a broad scope of aromatic and aliphatic primary amides, lactams, and oxazolidinones.
The reaction scope is broad: Various (hetero)aryl chlorides, including sterically hindered and electron-rich chlorides, couple smoothly with amides to give the corresponding N-aryl amides in 74-92 % yields. The transformation is scalable and selective, providing a general and operationally simple way to access N-aryl amide building blocks useful for pharmaceutical and material sciences.

Fig. 1 BTMO for Cu-catalyzed Goldberg amidation of aryl chlorides with amides. (De S.; et al. 2017)

References

De S, et al. Copper-catalyzed coupling reaction of (hetero) aryl chlorides and amides. Organic Letters, 2017, 19(18): 4864-4867.

What is BTMO ligand used for?

BTMO enables efficient Cu-catalyzed amidation of (hetero)aryl chlorides with weakly nucleophilic amides.

What are the main advantages of BTMO?

High efficiency with aryl chloride, low cost, excellent functional group tolerance, and bench stability.

Can BTMO be used in pharmaceutical synthesis?

Yes, BTMO is ideal for synthesizing N-aryl amides and heterocycles prevalent in pharmaceuticals.

Is BTMO air-stable?

Yes, BTMO is a crystalline, bench-stable solid that requires no special storage.

What makes BTMO unique for Goldberg reactions?

BTMO's thiophene design provides superior electron donation and Cu(Ⅲ) stabilization.