Thin-layer studies on surface functionalization of polyetherimide: Hydrolysis versus amidation

Among the high-performance and engineering polymers, polyimides and the closely related polyetherimide (PEI) stand out by their capability to react with nucleophiles under relatively mild conditions. By targeting the phthalimide groups in the chain backbone, post-functionalization offers a pathway to adjust surface properties such as hydrophilicity, solvent resistance, and porosity. Here, we use ultrathin PEI films on a Langmuir trough as a model system to investigate the surface functionalization with ethylene diamine and tetrakis(4-aminophenyl)porphyrin as multivalent nucleophiles. By means of AFM, Raman spectroscopy, and interfacial rheology, we show that hydrolysis enhances the chemical and mechanical stability of ultrathin films and allows for the formation of EDC/NHS-activated esters. Direct amidation of PEI was achieved in the presence of a Lewis acid catalyst, resulting in free amine groups rather than cross-linking. When comparing amidation with hydrolysis, we find a greater influence of the latter on material properties. Graphic abstract

Direct Amidation to Access 3-Amido-1,8-Naphthalimides Including Fluorescent Scriptaid Analogues as HDAC Inhibitors

Methodology to access fluorescent 3-amido-1,8-naphthalimides using direct Buchwald–Hartwig amidation is described. The protocol was successfully used to couple a number of substrates (including an alkylamide, an arylamide, a lactam and a carbamate) to 3-bromo-1,8-naphthalimide in good yield. To further exemplify the approach, a set of scriptaid analogues with amide substituents at the 3-position were prepared. The new compounds were more potent than scriptaid at a number of histone deacetylase (HDAC) isoforms including HDAC6. Activity was further confirmed in a whole cell tubulin deacetylation assay where the inhibitors were more active than the established HDAC6 selective inhibitor Tubastatin. The optical properties of these new, highly active, compounds make them amenable to cellular imaging studies and theranostic applications.

Direct Amidation of Esters via Ball Milling

<p><i>The direct mechanochemical amidation of esters – enabled by ball-milling – is herein described. The operationally simple procedure requires inputs of ester, amine, and sub-stoichiometric KOtBu and is applicable to a preparation of a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of API’s, agrochemicals, and its ability to deliver gram-scale synthesis of active pharmaceuticals and building blocks is demonstrated, all in the absence of a reaction solvent.</i></p>

Direct Amidation of Esters via Ball Milling

<p><i>The direct mechanochemical amidation of esters – enabled by ball-milling – is herein described. The operationally simple procedure requires inputs of ester, amine, and sub-stoichiometric KOtBu and is applicable to a preparation of a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of API’s, agrochemicals, and its ability to deliver gram-scale synthesis of active pharmaceuticals and building blocks is demonstrated, all in the absence of a reaction solvent.</i></p>

Direct Amidation of Esters via Ball Milling

<p><i>The direct mechanochemical amidation of esters – enabled by ball-milling – is herein described. The operationally simple procedure requires inputs of ester, amine, and sub-stoichiometric KOtBu and is applicable to a preparation of a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of API’s, agrochemicals, and its ability to deliver gram-scale synthesis of active pharmaceuticals and building blocks is demonstrated, all in the absence of a reaction solvent.</i></p>