Angewandte Research Articles Chemie International Edition:DOI:10.1002/anie.201906008 Bioinspired Adhesives German Edition:DOI:10.1002/ange.201906008 Bioinspired Design Provides High-StrengthBenzoxazine Structural Adhesives Cody J. Higginson, Katerina G. Malollari, Yunqi Xu, Andrew V. Kelleghan, Nicole G. Ricapito, and Phillip B. Messersmith* Abstract: Asynthetic strategy to incorporate catechol func- Introduction tional groups into benzoxazine thermoset monomers was developed, leading to afamily of bioinspired small-molecule Thermoset polymers,cross-linked networks of repeating resins and main-chain polybenzoxazines derived from biolog- organic units,play avital role in the advanced materials arena ically available phenols.Lap-shear adhesive testing revealed due to their high durability and favorable mechanical, apolybenzoxazine derivative with greater than 5times chemical, and thermal properties.Among commonly em- improved shear strength on aluminum substrates compared ployed classes of these materials are phenolics,epoxies, to awidely studied commercial benzoxazine resin. Derivative polyurethanes,polyimides,acrylics,and cyanate esters.[1] In synthesis identified the catechol moiety as an important design recent years,polybenzoxazines have garnered much interest feature in the adhesive performance and curing behavior of this as apromising class of thermoset resins.[2] Conventionally bioinspired thermoset. Favorable mechanical properties com- prepared from phenol, formaldehyde,and primary amine parable to commercial resin were maintained, and glass precursors,1,3-benzoxazine monomers are cured by ather- transition temperature and char yield under nitrogen were mally-accelerated cationic ring-opening polymerization with- improved. Blending of monomers with bioinspired main-chain out the need for initiators or catalysts (Figure 1a).[3] Ther- polybenzoxazine derivatives provided formulations with en- mally cured polybenzoxazines possess asuite of desirable hanced shear adhesive strengths up to 16 MPa, while alloying properties,including low volatile formation and near-zero with commercial core–shell particle-toughened epoxy resins shrinkage during curing, good thermal stability,and high led to shear strengths exceeding 20 MPa. These results high- mechanical strength, making them particularly attractive light the utility of bioinspired design and the use of biomol- ecules in the preparation of high-performance thermoset resins and adhesives with potential utility in transportation and aerospace industries and applications in advanced composites synthesis. [*] Dr.C.J.Higginson, Y. Xu, A. V. Kelleghan, Prof. P. B. Messersmith DepartmentsofMaterialsScience and Engineering and Bioengi- neering, University of California, Berkeley Berkeley,CA94720-1760 (USA) E-mail:[email protected] K. G. Malollari Department of Mechanical Engineering, University of California, Berkeley (USA) Dr.N.G.Ricapito Zymergen,Inc. Emeryville, California (USA) Prof. P. B. Messersmith Materials Sciences Division, Lawrence Berkeley NationalLaboratory, Berkeley (USA) Figure 1. Benzoxazinechemistry and catechol-derived benzoxazine Supportinginformation and the ORCID identification number(s) for materials. A) Benzoxazinemonomers are readily prepared from phe- the author(s) of this article can be found under https://doi.org/10. nols, primary amines, and formaldehyde, and undergo thermally- 1002/anie.201906008. acceleratedring opening polymerization to yield polybenzoxazines. The 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. commercial benzoxazine resin, B-a,was used as abenchmark material KGaA. This is an open access article under the terms of the Creative in this work. B) Biologically occurring phenols were selected as starting Commons Attribution-NonCommercial-NoDerivs License, which materials to introduce novel functionality and properties into designed permitsuse and distribution in any medium, provided the original benzoxazine monomers. C) Bioinspired benzoxazines described in this work is properly cited, the use is non-commercial and no modifica- work contain deprotected catechols prior to curing and are prepared tions or adaptations are made. using asilyl ether protecting group strategy. Angew.Chem. Int.Ed. 2019, 58,12271 –12279 2019 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim 12271 Angewandte Research Articles Chemie materials in the transportation and aerospace industries,and bioinspired benzoxazine monomers,synthesized in part from for the preparation of high-performance composites.[4] phenol and catechol metabolites (Figure 1b), with enhanced One of the most attractive features of benzoxazine resins adhesive performance compared to awidely studied and is their rich molecular design flexibility,which enables commercially available benzoxazine resin, B-a (Huntsman tailoring of the monomer functionality and the thermoset Advanced Materials,Figure 1a). properties for their end use.Introduction of various func- While mussel-inspired catechol chemistry has been high- tional groups at the amine or phenol fragment in many cases lighted in awide range of synthetic materials,only one recent has imbued benzoxazines with interesting and useful proper- report describes its application in the context of polybenzox- ties,including enhanced reactivity,reduced polymerization azines,inwhich amono-benzoxazine resin was prepared from temperature,additional chemical cross-linking mechanisms, pyrocatechol as the phenol reactant.[8f] Thermally-accelerated flame-retardant characteristics,modified mechanical proper- ring-opening polymerization unmasked the catechol func- ties,shape memory and self-healing behaviors,among oth- tionality to provide athermoset polymer with improved ers.[2a,5] Many favorable properties of polybenzoxazines have adhesion strength on stainless steel compared to derivatives been attributed to complex intermolecular and intramolecu- prepared from the corresponding 1,3- or 1,4-benzenediols. lar hydrogen bonding within the thermoset network.[4,6] Earlier studies reported using pyrocatechol or the 3-substi- However,asix-membered intramolecular hydrogen bond tuted catechol natural product urushiol to prepare benzox- between the phenol hydrogen and amine nitrogen in the azine resins which also unveil catechols upon curing, but the polybenzoxazine backbone may be of particular relevance to adhesive performance of these resins was unexplored.[17] In adhesion in that it reduces the material surface energy, this work, phenol and catechol metabolites were transformed weakening interfacial interactions with other materials.[7] Few into benzoxazine monomers and polymers with the intention studies have concentrated on enhancing the adhesive perfor- of preparing high-performance thermoset adhesives.Incon- mance of polybenzoxazines,and many of these studies trast to previous work, we set out to synthesize benzoxazine emphasize formulation and alloying rather than benzoxazine monomers with free catechol groups (Figure 1c), reasoning monomer design to improve adhesion.[8] that in mussel adhesion the catechols in adhesive proteins are An important recent trend in polymer chemistry research unprotected during processing, secretion and solidification of is the preparation of monomers and polymers from bio-based the byssal plaque.Hypothesizing that this would lead to precursors.[9] This interest is driven by both agrowing demand improved adhesive performance,aprotecting group strategy for sustainable materials and the rich chemical functionality was applied to access afamily of bioinspired benzoxazines 2 of biologically-derived molecules compared to conventional from the corresponding silyl ether protected derivatives 1. petroleum-derived building blocks.[9a] Through advanced microbial engineering,natural and bioengineered metabolic pathways can provide access to an array of monomers and Results and Discussion synthetic precursors with diverse structures and properties that are challenging to obtain through synthetic methods Catechol-Modified Benzoxazine Synthesis alone.[10] Furthermore,the development of high throughput genomic engineering tools that integrate automation, ma- Phenols and catechols both participate in the Mannich chine learning, and molecular biology may enable cost- reaction commonly employed to prepare 1,3-benzoxazine effective and industrial-scale access to the molecular diversity monomers,complicating the use of unprotected catechol- present in living systems.[11] This unique pool of potential containing precursors in the traditional monomer synthesis. starting materials includes arange of phenolic molecules that Indeed, catechol derivatives are viable starting materials for are just beginning to be explored as building blocks for 1,3- the synthesis of monofunctional and bifunctional benzoxazine benzoxazine monomers.[12] resins.[8f, 17] To access catechol-modified benzoxazine mono- Nature not only provides access to constituents with mers,aprotecting group strategy was developed. Informed by useful chemical handles for materials synthesis,but also stability studies carried out with amodel benzoxazine delivers inspiration for synthetic polymers and engineering monomer (C-m)prepared from para-cresol and 2-methox- materials with extraordinary properties and behaviors.[13] In yethylamine,silyl ethers were identified among common our material design, we take inspiration from marine mussels, catechol protecting groups,such as cyclic borate,acetals, which have the ability to adhere strongly to awide range of acetate