Formamide monomer and polymer synthesized therefrom

Abstract

Monomers containing formamide groups and polymers prepared by polymerization of the monomers are provided. Methods for polymerizing the monomers and methods for synthesizing functionalized polymers by pre-polymerization and / or post-polymerization functionalization are also provided. The monomers are non-toxic and can generate highly reactive isocyanate and isonitrile precursors in a one-pot synthesis, thereby enabling the addition of complex functional groups to the side chains of polymers synthesized from the monomers.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 818,188, filed on March 14, 2019, the entire contents of which are incorporated herein by reference.

[0003] About government rights

[0004] This invention was made with government support from the National Science Foundation under Award DMR1121288. The government has certain rights in this invention. Background Art

[0005] Recent advances in controlled polymerization methods have enabled unprecedented access to polymers with well-controlled architecture, molecular weight, and dispersity. Advances in living or controlled free radical polymerization (LFRP) and ring-opening metathesis polymerization (ROMP) and the development of related initiators and catalysts have rapidly expanded the diversity of polymers and their properties. These methods have produced new block copolymers (BCPs), bottle-brush copolymers, brush polymers, star polymers, and other complex structures. However, their further application requires the introduction of multiple functional groups, which is challenging.

[0006] There are numerous chemical transformations used to modify polymer side chain groups. While these transformations can be very effective for small molecules, it remains challenging to achieve these transformations efficiently and in high yields on polymer chains in a scalable fashion using relatively mild conditions to obtain a variety of mutually orthogonal functional groups. Isocyanate and isonitrile functional groups are commonly used to form urea, carbamate, thiourea, acyloxycarboxamide, lactam, and tetrazole linkages. However, the safety issues posed by these chemicals have not been universally addressed. The handling, manufacture, and transportation of these isocyanate and isonitrile chemicals are highly hazardous due to their toxicity. Therefore, despite incredible progress in the development of new polymer functionalization routes, newer, more efficient methods are still needed. Summary of the invention

[0007] The present invention provides a monomer containing a carboxamide group and a polymer prepared by polymerizing the monomer. Also provided are a method for polymerizing the monomer and a method for functionalizing a polymer prepared from the monomer.

[0008] One embodiment of the monomer containing a formamide group includes a formamide functional group attached to a polymerizable group, wherein the polymerizable group includes a styrene group, an acrylate group, a methacrylate group, or a cyclic olefin group. A variety of polymers can be formed by polymerizing one or more monomers containing a formamide group with optional one or more additional monomers.

[0009] Before or after the monomer polymerization, the formamide functional group can be converted into reactive isocyanate functional group and / or isonitrile functional group. The isocyanate and isonitrile groups can then be converted into a variety of useful chemical functional groups. These functional groups include carbamate groups, urea groups, carboxamide groups, beta-lactam derivatives, tetrazole derivatives, ATRP initiating groups and NMP initiating groups.

[0010] In some embodiments of converting formamide groups to isocyanate groups, the conversion of the formamide groups and the conversion of the isocyanate groups are carried out in a multi-component reaction.

[0011] Other principal features and advantages of the present invention will become apparent to those skilled in the art after reviewing the following drawings, detailed description and appended claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Exemplary embodiments of the present invention will be described below with reference to the accompanying drawings, wherein like reference numerals represent like elements.

[0013] Figure 1 The structure of formamide monomers and their polymerization are described, followed by their conversion into isocyanate and isocyanate intermediates using a one-pot multicomponent reaction (MCR) and subsequent functionalization into ureas, carbamates, and acyloxycarboxamide and amidocarboxamide derivatives.

[0014] Figure 2 The application of the one-pot MCR process to the conversion of carboxamide small molecules into isocyanate and isocyanate intermediates and their subsequent functionalization into urea, carbamate, acyloxycarboxamide and amidocarboxamide derivatives is described. These transformations can be applied to the carboxamide functionalized polymers described herein.

[0015] Figure 3 The synthetic scheme of vinylbenzylformamide (VBF) monomer and the proton NMR ( 1 H NMR) spectrum.

[0016] Figure 4 The invention describes the conversion of VBF monomers to urethane monomers via an isocyanate intermediate via a one-pot chemical process. 1 The H NMR spectrum shows the disappearance of all expected peaks and the CHO peak. The top inset shows the polymerization of the functionalized monomer by reversible addition-fragmentation chain transfer (RAFT), with the resulting NMR and gas permeation chromatography (GPC) data showing well-controlled 100% functionalized polymer.

[0017] Figure 5A Describes the PVBF homopolymer 1H NMR spectra and GPC data. Figure 5B The molar ratio of P(VBF-rS) copolymer is 73:27. 1 H NMR and dispersity from GPC.

[0018] Figure 6 The structures of styrene, (meth)acrylate ((M)AF), and cyclic olefin carboxamide monomers are described.

[0019] Figure 7A-7C Synthetic protocols for three styrene formamide monomers are described. Fig.7D A synthetic protocol for (meth)acrylate formamide monomers is described. Figure 7E-7G A synthesis scheme for three cyclic olefin monomers, in this case norbornene carboxamide (NBF) monomer, is described. Figure 7H Norbornene derivatives that can be used in the synthesis of ROMP monomers are given.

[0020] Figure 8 Four reactions are described to form urea, carbamate, acyloxycarboxamide and β-lactam side chain functionalized monomers. M represents any monomer based on VBF, (M)AF or NBF. The resulting side chain functionalized homopolymers are given on the right (Method 1).

[0021] Fig. 9 A protocol for performing a 3-CR Passerini reaction on a formamide monomer to synthesize a Y-shaped initiator monomer is described. The Y-shaped initiator monomer can be polymerized using an orthogonal polymerization mechanism (nitroxide controlled radical, NMP and atom transfer radical polymerization, ATRP), and the polymer is used to synthesize bottle brush copolymers. The ROMP initiator monomer can be applied first to grow polymers A and B, and then the monomers are polymerized. Alternatively, the formamide monomer can be polymerized before the brush is grown.

[0022] Fig.10 Schematic representation of homopolymers and copolymers of formamide monomers and their subsequent conversion into functionalized polymers is depicted.

[0023] Fig.11 The proposed homopolymers and random copolymers are outlined. VBF (upper left scheme), (M)AF (lower left scheme), and VBF (upper and lower right schemes) are copolymerized with methyl methacrylate (MMA), methyl acrylate (MA), and norbornene (NB), respectively. The x:y ratios vary from 7:3, 1:1 to 2:8, respectively. DETAILED DESCRIPTION

[0024] The present invention provides monomers containing carboxamide groups (also referred to herein as carboxamide monomers) and polymers prepared by polymerizing the monomers. Also provided are methods for polymerizing the monomers and methods for synthesizing functionalized polymers by pre-polymerization and / or post-polymerization functionalization.

[0025] The monomer is nontoxic and can produce highly reactive isocyanates and isonitrile precursors in the one-pot synthesis, thereby complex functional groups can be added to the side chains of the polymer synthesized by the monomer. Therefore, the monomer and the polymer formed therefrom have greatly expanded the reaction chemistry based on isonitrile / isocyanate, thereby giving complex functional groups to polymers without the need to handle, apply or transport toxic isocyanates or isonitrile monomers. The polymer obtained can be used in biomedicine, medicine, electronics and coating applications and as a reactive polymer carrier. For example, polymers with reactive functional groups can be used for fixing industrially relevant enzymes on polymeric matrices to implement large-scale enzyme reactions, as templates for promoting organic conversions, as reactive resins and as surfaces for cell growth and expansion.

[0026] The carboxamide monomers include one or more carboxamide functional groups (-NH-C=O) attached to a polymerizable group. Examples of polymerizable groups include vinyl groups, styrene groups, acrylate groups, methacrylate groups, and cyclic olefin groups.

[0027] The polymerizable styrene groups are polymerized through their vinyl double bonds to form a polymer backbone containing a carbon-carbon chain. The formamide functional group can be located in the para, ortho or meta position of the phenyl ring of the styrene group. The styrene group includes a styrene derivative group such as a tert-butyl styrene group, which includes other functional groups pendant from its phenyl ring except the formamide group. Various styrene derivative groups can be synthesized by Friedel-Craft reactions.

[0028] Acrylate and methacrylate groups (collectively referred to as (meth)acrylate groups) are connected by their vinyl and RC=C(CH 3 )H double chains are polymerized to form a polymer backbone containing carbon-carbon chains.

[0029] Cyclic olefins are polymerized through aromatic carbon-carbon double bonds via ROMP to form a polymer backbone comprising carbon-carbon double bonds. Depending on the cyclic olefin group used, the polymer backbone may also comprise a cyclic ring. Examples of cyclic olefin groups include norbornene groups. Norbornene groups include norbornene derivative groups that include other functional groups pendant to their norbornene rings in addition to the formamide group.

[0030] The carboxamide functional group is connected to the polymerizable group through a linker. In some carboxamide monomers, the linker is a single carbon atom. However, the length of the linker can be selected to provide desired properties, such as enhanced solubility in a given organic solvent. For example, the linker can contain a carbon chain of two or six carbon atoms, although longer carbon chains can also be used. However, the linker need not consist of only carbon atoms. Other groups including ether bonds, ester bonds and / or aromatic groups can also be part of the linker.

[0031] exist Figure 6 Examples of carboxamide monomers are given in . They include: styrene carboxamide monomers comprising a carboxamide functional group connected to a styrene group via a carbon linker containing 1, 2 or 3 carbon atoms (upper left); (meth)acrylate carboxamide monomers comprising a carboxamide functional group connected to a (meth)acrylate group via a carbon chain linker containing 2-6 carbon atoms (upper right); cyclic olefin carboxamide monomers comprising a carboxamide functional group connected to a norbornene group via a linker containing an ether bond and an aromatic group (lower left); cyclic olefin carboxamide monomers comprising two carboxamide functional groups each connected to a norbornene group via a linker containing a carbonyl group and a carbon chain having 2-6 carbon atoms (lower right); and cyclic olefin carboxamide monomers comprising a carboxamide functional group connected to a norbornene group via a linker containing an ester bond and a carbon chain having 2-6 carbon atoms (lower right).

[0032] A detailed description of a method for synthesizing formamide monomers is provided in Example 2. Typically, formamide monomers can be prepared by reacting a formamide precursor with a monomer comprising a polymerizable group. The formamide precursor can be a chemical comprising a formamide group, or a chemical that reacts with a monomer having a polymerizable group to form a formamide functional group.

[0033] Formamide monomers can be polymerized to form homopolymers, or polymerized with one or more additional monomers to form copolymers. The additional monomers can include other formamide monomers, non-formamide monomers or their compositions. Copolymers can be random copolymers or block copolymers. Examples of other monomers that can be polymerized with formamide monomers include vinyl monomers, styrene monomers, styrene derivative monomers such as tert-butylstyrene monomers, acrylate monomers, methacrylate monomers, monomers containing epoxy groups such as glycidyl methacrylate monomers, vinylpyridine monomers, 4,4-dimethyl-2-vinylazlactone monomers and cyclic olefin monomers. The molar ratio of various monomers in the polymer can be adjusted to provide desired polymer properties and solubility. Therefore, the number of formamide monomers in the polymer depends on the intended use of the polymer. As an illustration, in various embodiments of copolymers polymerized from formamide monomers, the formamide monomers will comprise at least 0.1 mol%, at least 1 mol%, at least 5 mol%, at least 10 mol%, at least 25 mol%, at least 50 mol%, at least 75 mol%, at least 90 mol%, at least 95 mol%, at least 99 mol%, and at least 99.9 mol% of the copolymer. As described in the examples, for ethylene, (meth)acrylate, and cyclic olefin monomers, known polymerization techniques may be used to polymerize the monomers. These techniques include free radical polymerization, RAFT polymerization, ATRP, and ROMP.

[0034] RAFT is a form of living free radical polymerisation that is capable of polymerising polymers with complex architectures, including block, graft, comb and star structures. The RAFT process involves conventional free radical polymerisation of substituted monomers in the presence of a suitable chain transfer agent.

[0035] ATRP can be used to polymerize a wide variety of monomers under highly controlled conditions. The control in ATRP comes from the reversible redox activation of dormant polymer chain termini (halide functionalization) by halogen transfer to a transition metal complex.

[0036] ROMP is a living polymerization form characterized by ease of polymerization, tolerance to functional groups, and the ability to build complex structures from bicyclic and oligomeric cyclic olefins. ROMP uses a catalyst that generates a metal carbene species that is able to initiate the polymerization of cyclic olefins to form polymers with double bonds in the backbone. This feature allows the construction of complex densely substituted structures.

[0037] The known formamide reaction chemistry can be used to convert the formamide functional group of the monomer or the polymer formed therefrom into reactive isocyanates or reactive isonitrile intermediates, which can then be converted into a large number of useful functional groups. For example, the formamide functional group can be converted into an isocyanate functional group by reacting with an oxidant, or converted into an isonitrile functional group by utilizing a dehydrating agent for dehydration. The conversion of the formamide functional group into an isocyanate or isonitrile group can be implemented before or after the polymerization of the formamide monomer. However, the prepolymerization conversion usually requires the separation of the intermediate before further functionalization, which may be a disadvantage because the intermediate is toxic. In contrast, the conversion of the formamide group into an isocyanate or isonitrile group after polymerization is likely to implement the further functionalization of the polymer in a multicomponent reaction (MCR; also referred to as one-pot synthesis) without the need to separate the toxic intermediate. The conversion reactions for isocyanates and isonitriles are well known, and these chemical reactions can be applied in one-pot synthesis. MCRs based on these intermediates can include two, three, four, or even more components in the reaction, thereby exploiting the ability to functionalize polymers with a variety of complex orthogonal functional groups.

[0038] Isocyanate groups are a class of highly reactive functional groups known for a variety of organic transformations, including reaction with diols to form polyurethanes. The formation of carbamate or urethane chains is also common in polymers in post-functionalization reactions. Isonitriles are also an important class of reactive functional groups. Their reactivity derives from a carbon center that is divalent and therefore reactive with electrophiles and nucleophiles. They have been used in multicomponent reactions to form highly functional molecules. They are added as one of the 3-components (3-CR) in the Passerini reaction or as one of the 4-components (4-CR) in the Ugi reaction.

[0039] application Figure 1 The simple case of carbamate conversion in Figure 1 describes the conversion of formamide groups to different functional groups via isocyanate intermediates. In the first step, formamide monomers are polymerized to formamide-functionalized polymers. As shown in the reaction scheme on the left, in the presence of an oxidant, formamide groups can be converted to intermediate isocyanate groups, which are then converted to carbamate functional groups in a one-pot synthesis by reaction with an alcohol. This conversion is discussed in more detail in Example 1. Alternatively, isocyanates can be converted to carbamate groups by reaction with primary amines. By using oligomeric primary amines, isocyanate groups can be converted to urea groups.

[0040] exist Figure 1The right side has provided more complicated conversion.Here, the formamide group is first converted into the isonitrile intermediate, which is converted into the acyloxy carboxamide functional group by reacting with aldehyde and acid using Passerini-3CR reaction in the one-pot synthesis.Other isonitrile conversions that can be applied include using Ugi-β-lactam-3CR reaction to be converted into β-lactam group by reacting with aldehyde and amino acid, using Ugi-4-CR reaction to be converted into amido carboxamide by reacting with aldehyde, acid and primary amine, and using Ugi tetrazolium reaction to be converted into tetrazolium derivative by reacting with aldehyde, primary amine and ammonia.These reactions are discussed in more detail in Example 3.

[0041] Conversion of the formamide functional group may form side chain groups with complex branching structures, including bottle brush structures. For example, the formamide group can be converted to an isonitrile group, which in turn can be converted to branched side chains containing ATRP initiators and NMP initiators. NMP is a controlled free radical polymerization in which the polymerization is initiated by heat in the absence of an external free radical source or metal catalyst. In NMP, an alkoxyamine initiator can be used as a unimolecular reagent to provide a reactive initiating group and a stable regulating nitroxide radical. ATRP initiators include alkyl halide groups, including secondary and tertiary alkyl halides. The two different initiators can then react with two different monomers to grow two different polymer chains from the main brush backbone. This chemistry is discussed in more detail in Example 3.

[0042] Polymerization and side chain group functionalization can be implemented in a variety of organic solvents. The specific solvent for a given polymerization / functionalization reaction depends on the monomer and reactant used. For example, for functionalization by an isocyanate intermediate, a variety of solvents can be used, including mesitylene, diglyme, m-xylene, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile (MeCN) and chlorinated solvents. Under the oxidation conditions of converting formamide to carbamate, chlorinated solvents can be used. For functionalization by an isonitrile intermediate, the solvent used depends on a dehydrating agent. For the conversion of using triphosgene, chlorinated solvents can be used.

[0043] Example

[0044] The following examples describe the design and synthesis of polymerized or polymerizable carboxamide monomers. The carboxamide side chain groups of the monomers can then be efficiently functionalized to a variety of functional groups via an isonitrile or isocyanate intermediate in a one-pot reaction.

[0045] Example 1 : This example describes the synthesis and polymerization of vinylbenzylformamide (VBF) monomer.

[0046] Monomer design and synthesis: VBF monomer was synthesized in over 75% yield. Para-substituted styrenes were synthesized using the procedure described in Robertson, J. et al., Org. Biomol. Chem. 2005, 3 (23), 4246-4251. Starting from commercially available vinylbenzyl chloride, a one-step conversion to VBF was performed using sodium iodide in DMF. Sodium dicarboximide was added as a source of carboxamide groups. A typical procedure is as follows: Sodium dicarboximide (5.91 g, 62.24 mmol) was added to a stirred solution of vinylbenzyl chloride (5.0 g, 32.76 mmol) and sodium iodide (NaI) (10.80 g, 72.07 mmol) in DMF (40 mL), and the mixture was heated at 100° C. for 48 h. The hot reaction mixture was poured into water. The mixture was extracted with dichloromethane (DCM) (200 mL), and the combined organic phases were concentrated in vacuo. The product was further dissolved in DCM (50 mL) and KOH (0.1 g, 1.79 mmol) was added. The mixture was stirred at room temperature for 1 h and the organic layer was concentrated in vacuo to give a pale yellow solid as the product (3.94 g, 75.5%). The product was further purified by column chromatography (silica 1:2 hexane: ethyl acetate). 1 H NMR confirmed its chemical structure ( Figure 3 ). The monomer itself is soluble in various solvents such as DCM, chloroform, tetrahydrofuran (THF), DMF, DMSO and methanol, and partially soluble in acetonitrile and hexane.

[0047] Conversion to carbamate chains via isocyanate intermediate formamide: To confirm the reactivity of formamide in VBF monomer, a simple carbamate conversion was performed using ethanol. 0.16 g of VBF and a small amount of MS (molecular sieves)-4A° were placed in a 50 mL round bottom (RB) flask filled with 5 mL of DCM. The reaction mixture was purged with Ar for 15 min. 0.430 g of the oxidant [PhI(COOCF 3 ) 2 ], and continue stirring for 10min. Monitor the complete conversion of formamide into isocyanate by thin layer chromatography (TLC), then add 0.43g 2-methylbutanol to the solution. Continue the reaction for 3h. Remove the molecular weight by filtration, and evaporate the solvent. Purify the crude product by flash chromatography. 1 H NMR confirmed the complete disappearance of the formamide protons and the formation of the product in quantitative yield via the isocyanate intermediate ( Figure 4 ). The styrene double bonds are not affected by this reaction and are available for polymerization. This monomer is further polymerized by RAFT to form a well-defined polymer ( Figure 4 , above).

[0048] Polymerization of VBF: The polymerizability of the purified VBF monomer was tested using a variety of methods. First, conventional free radical polymerization was performed using azobisisobutyronitrile (AIBN) in DMF at 75°C for 12 h to obtain the polymer (M n :14.2K, (M w / M n )=1.66). The feasibility of controlled free radical polymerization was also explored. Among the available methods, RAFT has the best effect. VBA (1.0 g, 6.2 mmol), 4-cyano-4-[(dodecylsulfonylthiocarbonyl)sulfonyl]pentanoic acid (24.9 mg, 0.05 mmol) and AIBN (2.5 mg, 0.0015 mmol) were added to a 10 mL Schlenk flask together with 2.5 mL DMF. The reaction mixture was degassed by purging with Ar for 30 min, followed by three freeze-pump-thaw cycles for 15 min, and then heated at 75 °C for 12 h with stirring. The reaction mixture was cooled and deposited into a large amount of methanol. The resulting polymer was further purified by redeposition. A light yellow polymer powder was collected. Yield: 0.66 g. By 1 H NMR and GPC analysis confirmed the structure [Mn: 5.5K, M w / M n =1.14]( Figure 5A ). Thus, controlled molecular weight and dispersity can be achieved with these monomers. The polymer is soluble in methanol, DMF, and DMSO, and partially soluble in DCM, THF, and chloroform. VBF can also be copolymerized with styrene via RAFT to form a polymer that is more soluble in DCM ( Figure 5B ). This copolymer can be further used to implement Figure 4 The same carbamate conversion in 20% yielded over 60%.

[0049] The monomers can be further homopolymerized or copolymerized by conventional and controlled radical methods with good control over molecular weight and dispersibility. Copolymerization improves solubility in organic solvents such as DCM. Conversion of these carboxamide side chain groups to carbamate bonds is also feasible at the monomer and polymer stage via reactive isocyanate intermediates. These results demonstrate that the use of non-toxic, scalable monomers and their polymers constitutes a highly versatile platform for all post-functionalization reactions that are currently not synthesized via one-pot methods.

[0050] Example 2 (Prophetic): This example describes various synthetic schemes for styrenic carboxamide monomers, (meth)acrylate carboxamide monomers, and cyclic olefin carboxamide monomers.

[0051] Monomers and homopolymers and copolymers prepared from the monomers can be designed to have a wide range of solubility in organic solvents. For example, one can synthesize Figure 6 The synthetic route is shown in Fig. 7A – Figure 7G The synthetic scheme shown is described in the figure. For styrene monomers ( Fig. 7A – Figure 7C ), since the precursors (chlorine, cyanide or amine) are readily available, the linker length (n) can be varied fairly easily from 1 to 3. However, monomers can also be formed using longer linkers. For monomers based on acrylate (AF) or methacrylate (MF) ( Fig.7D ), a two-step synthesis was performed using commercially available ethanolamine converted to a formamide derivative followed by esterification with commercially available acryloyl chloride or methacryloyl chloride.

[0052] When it is a cyclic olefin monomer, aryl formamide ( Fig. 7E ) and alkylformamide functionalized norbornene monomers ( Figure 7F , Figure 7G ). The proposed synthesis of these monomers is as follows Fig. 7A – Figure 7G As shown. Using ROMP monomers, bifunctional monomers can also be prepared to add functional groups to the polymer. Alternative norbornene derivatives that can be used to synthesize ROMP monomers are Figure 7H shown.

[0053] Example 3 (prediction): This example describes various polymerization schemes of formamide monomers

[0054] Formamide monomers are a versatile platform that can be exploited in two ways to generate functionalized polymers. The first approach is to convert the monomers into new functionalized monomers via isocyanate / isonitrile intermediates and then polymerize the functionalized monomers ( Figure 8 ) to form a polymer. The second method is to polymerize the formamide monomer itself and then functionalize the polymer. The first method is essentially small molecule chemistry and can be almost quantitative. The subsequent polymerization of the functionalized monomer can be implemented by RAFT, ATRP or ROMP. This method also allows various functionalized monomers to be mixed in a predetermined feed ratio to synthesize copolymers with a selected composition. The first method is a multi-step method and may require the synthesis and purification of functionalized monomers before polymerization. The second method is more user-friendly and can provide a blank template that can be used for further functionalization at the user end. This blank template can be used for further functionalization of solid supports, microcarriers, etc. These methods, which are described in more detail below, emphasize the versatility of this platform and provide guidance for the large-scale expansion of the functionalization toolkit available to polymer chemists.

[0055] Method 1: Polymerization of functionalized monomers: A set of transformations illustrating the polymerization of formamide monomers and pre- and post-polymerization functionalization is described here. These transformations include the conversion of formamide monomers to: (a) carbamate monomers using simple alcohols (2-methylbutanol) via isocyanate intermediates, (b) oligomeric primary amines [aminopolyethylene glycol monomethyl ether (PEG-NH 2 ), 2000 g / mol, purchased from Sigma Aldrich] via an isocyanate intermediate to a urea monomer, (c) using Passerini-3CR via an isonitrile intermediate to an acyloxycarboxamide monomer by reaction with an aldehyde (2-methylbutyraldehyde) and an acid (benzoic acid), and (d) using Ugi-β-lactam-3CR via an isonitrile intermediate to a β-lactam monomer by reaction with an aldehyde (2,5-dimethoxybenzaldehyde) and an amino acid (β-alanine). Reaction schemes that can be used for these conversions are as follows: Figure 2 and Figure 8 as shown. These transformations form important linkages in polymer chemistry for conjugating a variety of oligomers, small molecules, and peptides. The side-chain PEG-functionalized polymers produced by the above transformation (b) are an important class of polymers for use in biomaterials, coatings, and other responsive surfaces. The β-lactam functionality from the Ugi-lactam reaction is very relevant and valuable for the generation of nylon-3 polymers. These nylon-3 polymers are similar to proteins and peptides derived from α-amino acids; therefore, they have been explored for a range of biological properties, including toxicity to bacteria and cell growth and proliferation. Having a β-lactam functionality in the side chain can produce different structures, such as comb-like or bottle-brush-like copolymers.

[0056] Synthesis of Dual-Head Initiator Monomers and Bottlebrush Copolymers: The following description is provided to verify the structure of the functionalized polymer, in which a dual-head orthogonal initiator, which is also a monomer, is synthesized using a multicomponent reaction. The combination of monomer and initiator is called an "initiator monomer". These initiator monomers contain an ATRP initiator and an NMP initiator in a Y-shaped structure attached to a formamide monomer. When polymerized, the proposed Y-shaped initiator monomer has two such initiation sites on each repeating unit.

[0057] This type of structure is very useful for the synthesis of bottle brush copolymers. Bottle brush copolymers are themselves a class of comb polymers where the main chain is longer than the side chains. In this structure, steric repulsion between the side chains results in an extended chain conformation of the main chain. Thus, high aspect ratio cylindrical bottle brushes can be synthesized. Using orthogonal chemistry, Y-shaped initiating monomers can form bottle brush copolymers with a 1:1 ratio of polymer A to polymer B "grafted" from the monomers. The choice of polymer A and polymer B grafted onto the main chain is very wide and is only limited by the polymerization method, i.e. NMP or ATRP. This method can be applied to Figure 6 Based on VBF monomer, Fig. 9 One such example is given in . Even among sterically hindered monomers, NBF monomers ( Fig. 9 , below) are also particularly effective. Aromatic VBF and NBF monomers can be used to form 1:1 bottle brush copolymers using polystyrene (PS) and polymethyl methacrylate (PMMA) as polymers A and B, respectively.

[0058] Method 2: Polymerization and copolymerization of formamide monomers: All styrenics and (meth)acrylate monomers proposed were first homopolymerized by RAFT or ATRP. Both methods offer sufficient options in terms of solvent, ligand, temperature and catalyst system to ensure that the polymerization conditions are optimized ( Fig.10 ). Fig.11 Given by Figure 6 The structures of polymers prepared from monomers of the invention are shown in Figure 2. For cyclic olefin monomers, efficient polymerization can be achieved using the standard Grubbs (G3) ruthenium catalyst, which is known for its excellent functional group tolerance, rapid initiation and propagation, and essentially living polymerization. In general, solvents such as DCM are very effective for ROMP at room temperature. To further adjust the solubility of the resulting polymer, a series of copolymers containing 30, 50, and 80 mol% of formamide monomer can be synthesized using MMA or NB monomers. Preliminary studies have shown that copolymerization of VBF monomer with MMA (data not shown) can improve solubility in DCM more than copolymerization with styrene. Therefore, copolymers of MMA monomer and VBF, AF, and / or MF monomers can be prepared. Block copolymers (BCPs) can be formed using formamide monomers. BCPs with a 1:1 volume ratio of formamide monomers can be synthesized using a second monomer, namely PVBF-b-PMMA, PNBF-b-PNB, and PMAF-b-PMMA.

[0059] The term "exemplary" as used herein is used to illustrate, exemplify, or describe. Any aspect or design described herein as "exemplary" is not necessarily to be understood as being preferred or advantageous over other aspects or designs. In addition, for the purposes of the present invention and unless otherwise specified, the "indefinite article" means "one or more".

[0060] The above descriptions of exemplary embodiments of the present invention are provided for the purpose of illustration and description. They are not intended to be exhaustive or to limit the present invention to the precise form disclosed, and adjustments and changes may be made based on the above teachings and may also be made by implementing the present invention. The embodiments are selected and described to explain the principles of the present invention and as a practical application of the present invention, to enable those skilled in the art to utilize the present invention in various embodiments and to make various adjustments as contemplated for practical use. It is expected that the scope of the present invention is limited by the appended claims and their equivalents.

Claims

1. A formamide monomer having the following structure: Where n is 1-10.

2. A method of forming a polymer, the method comprising polymerizing the formamide monomer of claim 1 and optionally one or more additional monomers to form a polymer having a backbone and formamide side chain groups extending from the backbone.

3. The method of claim 2 further comprising converting at least some of the pendant carboxamide groups to isocyanate groups.

4. The method of claim 3, further comprising converting at least some of the isocyanate groups to urethane groups or urea groups.

5. The method of claim 2 further comprising converting at least some of the carboxamide side chain groups to isonitrile groups.

6. The process of claim 5 further comprising converting at least some of the isonitrile groups to carboxamide groups.

7. The method of claim 5, further comprising converting at least some of the isonitrile groups to beta-lactam derivatives.

8. The method of claim 5, further comprising converting at least some of the isonitrile groups to tetrazole derivatives.

9. The method of claim 5, further comprising converting at least some of the isonitrile groups into ATRP initiating groups, NMP initiating groups, or a combination thereof.

10. The process of claim 4, wherein the formamide side chain groups are converted into isocyanate groups after polymerization of the monomers, and wherein the conversion of the formamide groups and the conversion of the isocyanate groups are carried out in a multicomponent reaction.

11. The process of claim 6, wherein the formamide side chain groups are converted into isonitrile groups after polymerization of the monomers, and wherein the conversion of the formamide groups and the conversion of the isonitrile groups are carried out in a multicomponent reaction.

12. The process of claim 7, wherein the formamide side chain groups are converted into isonitrile groups after polymerization of the monomers, and wherein the conversion of the formamide groups and the conversion of the isonitrile groups are carried out in a multicomponent reaction.

13. The process of claim 8, wherein the formamide side chain groups are converted to isonitrile groups after polymerization of the monomers, and wherein the conversion of the formamide groups and the conversion of the isonitrile groups are carried out in a multicomponent reaction.

14. The process of claim 9, wherein the formamide side chain groups are converted to isonitrile groups after polymerization of the monomers, and wherein the conversion of the formamide groups and the conversion of the isonitrile groups are carried out in a multicomponent reaction.

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