Efficient conversion of acids and esters to amides and transamidation of primary amides using OSU-6

doi:10.1016/j.tet.2015.10.016

Tetrahedron

Volume 71, Issue 48, 2 December 2015, Pages 9101-9111

https://doi.org/10.1016/j.tet.2015.10.016 Get rights and content

Abstract

OSU-6, an MCM-41 type hexagonal mesoporous silica with strong Bronsted acid properties, has been used to promote the high-yield conversion of carboxylic acids and esters to carboxamides as well as transamidations of primary amides in a one-pot solventless approach. A metal-free heterogeneous catalyst that promotes all of these processes has not been previously reported. OSU-6 enables these transformations to proceed in shorter times and at lower temperatures for a broad range of substrates. An added benefit is that the catalyst can be recycled and reused multiple times without significant loss of activity.

Graphical abstract

Introduction

Carboxamides are important functional motifs in both natural and unnatural products.¹ Due to their high polarity, stability, H-bond donating and accepting capability, and conformational diversity,1(a), 2 these groups are prevalent in many bioactive molecules.³ In chemical structures, amide linkages serve as important scaffolds for pharmaceuticals, agrochemicals, polymers, and materials.1(b), 3(b), 4 A recent report estimated that more than 25% of known drugs contain amide functional groups.⁵ Hence, improved methods for the synthesis of carboxamides involving a straightforward catalytic approach are in high demand.

Traditional methods for amide synthesis involve acylation of an amine by an acid chloride or anhydride, or a dehydrative coupling between an amine and a carboxylic acid.⁶ These procedures are often limited by harsh reagents, high temperatures, isolation problems or the generation of stoichiometric quantities of waste. Recently, organic chemists have shown a great deal of interest in catalyst-promoted syntheses of amides from acids and esters. For example, acids have been converted to amides with metal-based catalysts ZrCl₄ and Cp₂ZrCl₂,⁷ as well as non-metals B(OH)₃⁸ and related boron derivatives,⁹ silica,¹⁰ alumina,¹¹ and Starbons-400.¹² The ester-to-amide interconversion has been reported using Lewis acids such as InI₃¹³ and Zr(O-t-Bu)₄.¹⁴ These approaches permit reactions at lower temperatures and give cleaner products, but in most cases their use has been limited to amide formation from only one acyl derivative.

Among the non-metal catalysts for the acid-to-amide conversion, B(OH)₃⁸ and mesoporous silica SBA-15^10d appear to have the most promise. Boric acid is readily available, inexpensive, and promotes the reaction in refluxing toluene. However, reported procedures simply precipitate the amide product from the crude reaction mixture without specifying how residual B(OH)₃ is removed from the product. SBA-15 also promotes this process in refluxing toluene. It has acidic properties, a high surface area and good hydrothermal stability,¹⁵ but it has only been reported for this singular process and is not commercially available.

Transamidation is also an attractive route for the synthesis of amides. However, due to the intrinsic stability of the amide C–N bond and the acidic nature of the N–H bond, this is often a difficult process. Transamidations generally require high temperatures (180 °C) and long reaction times, and thus are restricted in their scope. Although various metal-based catalysts, including AlCl_3,¹⁶ polymer-bound HfCl₄,¹⁷ Eu(OTf)₃,¹⁸ ZrCl₄,¹⁹ Sc(OTf)₃,²⁰ Ti(NMe₂)₄,²¹ CeO₂,²² Cp₂ZrCl₂,²³ [Mn(Hbpoh) (OAc) (H₂O)]₂·6H₂O,²⁴ Fe(NO₃)₃·9H₂O²⁵ and Rh(II) NHC complexes²⁶ have been reported to promote this transformation, most of these metals require anhydrous and inert atmosphere conditions, long reaction times, or toxic solvents. In recent years, a number of researchers have focused on developing greener methods that use catalysts such as NH₂OH·HCl,²⁷ l-proline,²⁸ B(OH)₃,²⁹ chitosan³⁰ and heteroanion-based ionic liquids.³¹ Among the non-metal catalysts for this process, B(OH)₃ and chitosan appear to be the most versatile. Although these catalysts give the desired products, both suffer from application to a relatively narrow selection of substrates. Furthermore, chitosan also requires higher reaction temperatures.

From an environmental viewpoint, developing a clean method to promote both the conversion of acids and esters to amides and transamidations of primary amides has been a challenge. Though various methods are reported for these reactions, most involve metal-based catalysts that are often hazardous and require remediation prior to disposal. Other potential drawbacks of metal-based catalysts are that they can be deactivated by coordination with heterocyclic substrates³² or contaminate the final products.

Our recent endeavors have demonstrated the potency of OSU-6 as a catalyst for the formation of 3-oxoisoindoline-1-carbonitriles and carboxamides³³ as well as 2-alkyl- and 2-aryl-(3-oxoisoindolin-1-yl)phosphonates.³⁴ OSU-6 is an MCM-41 type, hexagonal, mesoporous silica developed by Al Othman and Apblett.³⁵ It has acidic properties (due to aging with 2 M HCl during its preparation) and robust characteristics similar to SBA-15 but is more readily available. Based on our earlier work, we envisioned a platform by, which various methods for amide formation could be achieved by reaction of acids or esters with amines or by exchanging the amine portion of a primary amide using OSU-6 as a catalyst. To the best of our knowledge, a metal-free heterogeneous catalyst that promotes all three of these transformations has not been previously reported.

Section snippets

Synthesis of amides from acids

Our study first sought to establish the feasibility of this process by reacting benzoic acid (1a) with 4-methoxybenzylamine (2a) to prepare amide 3aa in various solvents using 10 wt % (relative to 1a) of OSU-6. Initially, the reaction was attempted in polar aprotic media such as DMF, DMSO or NMP at 140 °C, but these solvents gave unacceptably low yields (Table 1). We then evaluated non-polar media such as toluene and xylene. In these solvents, the reaction proceeded cleanly within 24 h at 120 °C

Conclusions

We have developed an efficient strategy for the synthesis of amides by reaction of acyl compounds with amines using OSU-6 as a common catalyst. The method has wide application, including conversion of acids and esters to amides as well as transamidations of primary amides. It also offers several advantages, including (1) high yields, (2) lower temperatures, (3) minimal formation of by-products, and (4) catalyst recyclability. A broad scope of amine substrates is reported, including benzylic,

General experimental details

The OSU-6 catalyst can be purchased from XploSafe LLC (website: www.xplosafe.com) as Product No 9001. All reactions were run under N₂. Reactions were monitored by thin layer chromatography on silica gel GF plates (Analtech No. 21521). Column chromatography, when necessary, was performed using silica gel (Davisil^® grade 62, 60–200 mesh) mixed with UV-active phosphor (Sorbent Technologies, No. UV-05); band elution was monitored using a hand held UV lamp. The saturated NaCl, saturated NH₄Cl, 5%

Acknowledgements

The authors wish to thank Dr. Rajasekar Pitchimani (XploSafe, LLC) for a generous gift of OSU-6. The authors are also grateful to the OSU College of Arts and Sciences for funds to purchase a new 400 MHz NMR for our Statewide NMR facility. This facility was established with support from the National Science Foundation (NSF) (BIR-9512269), the Oklahoma State Regents for Higher Education, the W.M. Keck Foundation, and ConocoPhillips, Inc.

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Efficient conversion of acids and esters to amides and transamidation of primary amides using OSU-6

Abstract

Graphical abstract

Introduction

Section snippets

Synthesis of amides from acids

Conclusions

General experimental details

Acknowledgements

Chem. Rev.

Chem. Rev.

Curr. Opin. Drug Discov. Dev.

Eur. J. Org. Chem.

Chem. Rev.

Angew. Chem., Int. Ed.

J. Org. Chem.

Green Chem.

J. Org. Chem.

The Amide Linkage: Structural Significance in Chemistry, Biochemistry and Material Science

Chem. Soc. Rev.

Trends Biochem. Sci.

Curr. Opin. Struct. Biol.

J. Comb. Chem.

Advanced Organic Chemistry, Part B: Reactions and Synthesis

Chem. Commun.

Org. Process Res. Dev.

Synthesis

Chem. Commun.

Org. Synth.

J. Org. Chem.

Angew. Chem., Int. Ed.

J. Org. Chem.

Chem. Commun.

Green Chem.

Green Chem.

Synthesis

Green Chem.

Synth. Commun.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

J. Org. Chem.

Synth. Commun.

J. Org. Chem.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

J. Am. Chem. Soc.