Concetta Semeraro
email: csemeraro@sharjah.ac.ae

Mariateresa Caggiano
email: mariateresa.caggiano@iusspavia.it

Michele Dassisti
email: michele.dassisti@poliba.it

Sustainability Aspects and Impacts in Cyber-Physical Social Systems

Keywords: Cyber-Physical-Social system, Sustainable Development, Social System I

A Cyber-Physical-Social System (CPSS) is an emerging research trend that focuses on integrating the social dimension into Cyber-Physical System (CPS). The CPSS consists of social, physical, and cyberspaces. There is a lack of influential theories and design approaches to reach a unified structure of a CPSS. Furthermore, the impacts of a CPSS on the sustainability performance of systems and processes are still unexplored. The paper addresses this latter research issue by evaluating case studies on CPSSs discussed in the literature.

INTRODUCTION

A Cyber-physical system (CPS) aims at embedding computing, communication, and control capabilities (3C) into physical assets to empower and converge the physical space with the virtual space [START_REF] Kang | Smart manufacturing: Past research, present findings, and future directions[END_REF]. Cyber-Physical Systems (CPSs) give the possibility to sense the world through a network of connected devices. The combination of intelligent and sensing systems forms a large-scale distributed cyber-physical system with enormous potentialities to bring smartness into many application areas. Human operators in the future production scenarios will need advanced competencies to cope with the new challenges regarding technological and organizational developments. A Cyber-Physical Social System (CPSS) may help human operators by integrating human knowledge, mental capabilities, and sociocultural elements [START_REF] Kang | Smart manufacturing: Past research, present findings, and future directions[END_REF], [START_REF] Yilma | Systemic formalisation of Cyber-Physical-Social System (CPSS): A systematic literature review[END_REF], [START_REF] Semeraro | Digital twin paradigm for collaborative intelligent manufacturing[END_REF]. A CPSS combines cyber, physical, and social space, creating a sustainable network for sharing data and information about products, production practices, materials, and human skills. The design of a CPSS is still a challenging task due to the heterogeneity of subcomponents, software complexity, and hardware entities. There is a lack of methodologies and design approaches to guide the practical design of a CPSS. Additionally, the effects of a CPSS on sustainable development and performance are still unexplored topic to be faced. The paper explores new potentialities and applications of a CPSS analyzing case studies presented in literature with the aims of defining how a CPSS can impact and improve sustainability performances.

II. STATE OF ART OF CPSSS

A CPSS focuses on social behaviors and relationships, thus considering aspects related to human facilities interdependency may significantly improve the cooperation and collaboration opportunities between production systems. Indeed, capturing skills and human habits may bring relevant information to improve the production system, including the working life quality of operators. A CPSS, exploiting new Key Enabling Technologies (KETs), such as big data, cloud computing, Internet of Things), allows capturing the social environment (behaviors, habits), improving the decisionmaking. For example, the implementation of CPSS in the transport system reduces road congestion and, therefore, traffic intensity and pollution [START_REF] Zeng | A survey: Cyberphysical-social systems and their system-level design methodology[END_REF]. In production systems, a CPSS decreases the number of delayed orders [START_REF] Zhang | Cyber-Physical-Social Systems: The State of the Art and Perspectives[END_REF], improving productivity. It can also improve user satisfaction and social interaction. The development of a CPSS can facilitate the exchange of materials, best practices, skills, and human performances between different production systems. Despite the numerous potentialities of CPSS's, few complete implementations are present, and still, the design of CPSS is a complex task. In particular, incorporating human aspects in a Cyber-physical system (CPS) has several open research challenges [START_REF] Yilma | Systemic formalisation of Cyber-Physical-Social System (CPSS): A systematic literature review[END_REF]. First, CPSS are complex systems due to the heterogeneity of network, software, and hardware entities, and a practical design approach is still lacking. Second, there are no practical and widely accepted approaches to model cyber, physical, and social space uniformly. Finally, it is necessary to investigate sustainability aspects and performances related to CPSSs. The paper focuses on the relationships between the sustainability aspects and challenges with CPSS to foster convergence, methodologies, innovative tools, and applications.

III. OVERVIEW OF APPLICATION CASE STUDIES OF CPSSS

CPSSs finds application in different fields such as power grid, smart vehicles, energy, transport, agriculture [START_REF] Zeng | A survey: Cyberphysical-social systems and their system-level design methodology[END_REF], [START_REF] Zhang | Cyber-Physical-Social Systems: The State of the Art and Perspectives[END_REF]. This section reviews case studies found in the literature to speculate how a CPSS can improve sustainability performance.

[6] presents a CPSS for a transportation system to improve vehicular safety and energy efficiency to reduce pollution or road congestion using the ACP method. The ACP method is also proposed in [START_REF] Wang | Artificial societies, computational experiments, and parallel systems: a discussion on computational theory of complex social-economic systems[END_REF] to set artificial societies, computational experiments, and execution modules for cyber-physicalsocial systems. The ACP approach has been proven in [START_REF] Xiong | Cyber-physical-social system in intelligent transportation[END_REF] to be the practical framework for the management and control problems of CPSS. The theoretical research results of CPSS and ACP methodology are applied and verified in traffic areas such as plan optimization, large-scale evacuation, and public traffic scheduling. In [START_REF] Liu | Digital Quadruplets for Cyber-Physical-Social Systems based Parallel Driving: From Concept to Applications[END_REF], the authors present the development of digital quadruplets for a CPSS-based parallel driving with the enlightenment of ACP-based parallel driving. Digital quadruplets can improve road safety, traffic efficiency, and driving cooperation for future connected automated vehicles. In [START_REF] Ramadhan | Road traffic signal control using cyber physical social system[END_REF], the authors propose road traffic signal control analyzing the social media data combined with physical sensors data to provide information about the road.

Sensors provide physical data such as the vehicle count of a specific road, while social data inform the road user's perception of the road. In [START_REF] Li | Multi-objective optimization for cyber-physical-social systems: a case study of electric vehicles charging and discharging[END_REF], the authors optimize the power load stability and the total cost of vehicle owners in the CPSS. Social aspects of traffic include driver's intention and driver's perception of road conditions.

[11] applies a CPSS in production networks. It allows the interaction between decision-makers making the networks more sustainable, responsible, and competitive. The authors introduce and review the social aspects, identifying three domains: individual, organizational, and contextual. A simulation study demonstrates how the management of social aspects can impact the production network competitiveness of CPSS. Traditional decision-making models do not consider human characteristics, such as age, gender, cultural background, and personality of operators. The authors [START_REF] Mladineo | Solving partner selection problem in cyber-physical production networks using the HUMANT algorithm[END_REF] develop an algorithm to solve partner selection problems in cyber-physical production networks. A hierarchical Petri netbased model and social flow are presented in [START_REF] Zeng | A system-level modeling and design for cyber-physical-social systems[END_REF] to extend the control flow and formally describe the social interactions of multiple users, respectively. In [START_REF] Kyzy | Integrating Cyber Physical Social Systems with Agricultural Supply Chain Systems: A New Paradigm for Social Fairness[END_REF], the authors apply a CPSS to Agriculture Supply Chain System (ASCS) management to improve the welfare of people in rural areas and increase the sales of products. Also, in [START_REF] Sisyanto | Hydroponic smart farming using cyber physical social system with telegram messenger[END_REF], the concept of CPSS for the agricultural sector has been developed by designing a prototype for hydroponic agriculture that can be monitored online via Telegram Messenger. The CPSS allows hydroponic farmers to know and monitor the condition of plants in real-time. [START_REF] Leng | Contextual self-organizing of manufacturing process for mass individualization: a cyberphysical-social system approach[END_REF] propose a cyber-physical-social-connected (SioT) model for mass individualization to narrow down the contextual computing complexity in a cyber-physical-social connected space.

In [START_REF] Yin | Understanding Data-Driven Cyber-Physical-Social System (D-CPSS) Using a 7C Framework in Social Manufacturing Context[END_REF], the authors propose a 7C framework for data-driven CPSS (D-CPSS) from a systematic perspective, including seven different levels: connection, conversion, communication, computation, cognition, configuration, and collective intelligence. Compared with the CPS configuration presented in [START_REF] Lee | A cyber-physical systems architecture for industry 4.0-based manufacturing systems[END_REF], the D-CPSS configuration emphasizes the importance of social factors and being data-driven. Level 1, level 3, level 5, and 7 in the 7C model are distributed in both the social space and physical space; level 2, level 4 and, level 6 in the 7C model belong to the cyber-space. The analysis of case studies allows understanding how some factors and performance can improve with CPSS, such as customer/user satisfaction, social interaction, process automation. In [START_REF] Xiong | Cyber-physical-social system in intelligent transportation[END_REF] - [START_REF] Li | Multi-objective optimization for cyber-physical-social systems: a case study of electric vehicles charging and discharging[END_REF], authors develop CPSSs for the transport sector, as already recalled, by endeavoring IoT and cloud computing technologies to connect drivers and vehicles, improving vehicular safety and energy efficiency, and reducing pollution or road congestion. The development of a CPSS can facilitate the exchange of materials, best practices, skills, and human habits between different production systems. Human characteristics and habits, such as age, gender, cultural background, and personal behaviors or needs, are evaluated and assessed in CPSSs solutions designed in [START_REF] Frazzon | Towards socio-cyber-physical systems in production networks[END_REF] - [START_REF] Yin | Understanding Data-Driven Cyber-Physical-Social System (D-CPSS) Using a 7C Framework in Social Manufacturing Context[END_REF].

IV. CPSS AND SUSTAINABILITY FRAMEWORK

This research intends to understand better the benefits that CPSSs can bring to sustainability performances to the system where the CPSS is applied. The paper investigates how the CPSSs functionalities and characteristics -available through various Key Enabling Technologies (KETs) -may be interconnected with the sustainability performances. For the scope of our study, we will focus in particular on the social sustainability dimension because it is still unclear how to include human rights, fair labor practices, living conditions, health, safety, wellness, diversity, equity, work-life balance, empowerment, community engagement into a virtual decisional tool. Fig. 1. Sustainability dimensions and related implications [START_REF] Pinzone | A framework for operative and social sustainability functionalities in Human-Centric Cyber-Physical Production Systems[END_REF].

The main CPSSs functionalities on social sustainability aspects are identified in [START_REF] Pinzone | A framework for operative and social sustainability functionalities in Human-Centric Cyber-Physical Production Systems[END_REF] and listed as follows: Safety management; Ergonomics and human factors; Learning and training; and Work-Life Balance. The authors in [START_REF] Pinzone | A framework for operative and social sustainability functionalities in Human-Centric Cyber-Physical Production Systems[END_REF] propose a framework (CyFL Matrix) composed of six functionalities that a CPSS must enable at three different levels of analysis, as shown in Figure 2. The framework allows understanding the impacts of a CPSS-oriented solution on social sustainability aspects but does not evaluate the Key Performance Indicators (KPIs) in each area.

Fig. 2. CyFL matrix [19]

The rationale behind the performed analysis is by the technology transfer. On the one hand, we consider the Key Enabling Technologies (KETs) -such as IoT, Big Data, advanced simulation, and others) -used for designing CPSSs in the case studies discussed above. On the other hand, we consider the research on sustainability indicators and performances. The final objective is to link the Key Enabling Technologies (KETs) with social sustainability indicators to facilitate and clarify the impact of CPSS technologies on social sustainability performances. Following this, we develop a complete framework, as shown in Figure 3, to evaluate the relationships between technologies used for developing CPSSs and the social sustainability indicators. The development of a CPSS is made possible by the Key Enabling Technologies (KETs) below summarized [START_REF] Rüßmann | Industry 4.0: The future of productivity and growth in manufacturing industries[END_REF]:

• Sensors and actuators are the most basic technologies for collecting and controlling data in real time [START_REF] Bibby | Defining and assessing industry 4.0 maturity levels-case of the defence sector[END_REF]. • Big data analytics refers to a new generation of technologies and architectures that enable organizations to economically extract value through discovering, capturing, and analyzing vast volumes of a wide variety of data [START_REF] Wang | Big data in cyber-physical systems, digital manufacturing and industry 4.0[END_REF]. • Blockchain enables transparent, secure, trustworthy, and swift public or private solutions [START_REF] Wang | Survey on blockchain for Internet of Things[END_REF]. • Augmented reality (AR) is an up-and-coming technology that visualizes computer graphics placed in the physical environment [START_REF] Alcácer | Scanning the industry 4.0: A literature review on technologies for manufacturing systems[END_REF]. • Virtual Reality (VR) provides an immersive, interactive, computer-mediated experience in which a person perceives an artificial environment through humancomputer interaction equipment [START_REF] Yao | Towards a wisdom manufacturing vision[END_REF].

• Cloud Computing allows access to software and data storage in the cloud representation of the internet [START_REF] Zhang | Cloud computing: state-of-theart and research challenges[END_REF]. • Collaborative Robots perform specific tasks autonomously or using remote-control commands [START_REF] Kragic | Interactive, Collaborative Robots: Challenges and Opportunities[END_REF]. • Additive manufacturing or 3D printing denotes the manufacturing technique in which parts are built by melting thin layers of powder and adding one layer of material, either plastic or metal, on top of another, based on the geometry suggested by Computer-Aided Design (CAD) [START_REF] Alcácer | Scanning the industry 4.0: A literature review on technologies for manufacturing systems[END_REF]. • Digital Twin is a high-fidelity virtual model of the physical entities having the scope of replicating and simulating the states and behaviors of these latter's [START_REF] Rüßmann | Industry 4.0: The future of productivity and growth in manufacturing industries[END_REF]. In our framework, we relate the CPSS-KETs with social sustainability indicators [START_REF] Atanda | Developing a social sustainability assessment framework[END_REF] The case studies presented in section III are classified in the framework in Figure 3 to understand the above-referred link between technologies adopted and CPSS's impact on social sustainability.

We also adopted the 17 Sustainable Development Goals (SDGs) of the 2030 Agenda to classify the case studies for evaluating the CPSSs' impacts on sustainability. The 2030 Agenda comprises 17 Sustainable Development Goals deepened into 169 targets, as shown in Figure 4. The case studies are classified in the framework in Figure 3. This information is reported on the framework using the same color scale of the goals defined in [START_REF]THE 17 GOALS | Sustainable Development[END_REF]. For example, the application of a CPSS in the transport sector in [START_REF] Xiong | Cyber-physical-social system in intelligent transportation[END_REF] improves vehicular safety in line with goals 3, 7, and 11 targets 3.6, 7.3,11.2, and 11.6. [START_REF] Liu | Digital Quadruplets for Cyber-Physical-Social Systems based Parallel Driving: From Concept to Applications[END_REF], [START_REF] Ramadhan | Road traffic signal control using cyber physical social system[END_REF], [START_REF] Li | Multi-objective optimization for cyber-physical-social systems: a case study of electric vehicles charging and discharging[END_REF] are aligned with the targets 3.6 and 11.2, goals 3 and 11.

The resulting picture proves that sensors and actuators, cloud computing, big data analytics, and virtual reality technologies support the impacts of a CPSS on the sustainability performance of systems and processes.

The primary evidence from the picture is that CPSSs can be a solution with high potential on the following social sustainability categories: social equity, environmental education, participation and control, social cohesion, health, and safety. Considering the equity of process indicator set, CPSSs support and improve access to information and participation in decision-making processes. The presence of case studies in the environmental awareness and sensibility indicator sets demonstrates that CPSSs can improve the use of natural resources, material choices, energy sources, water, waste management, and pollution. Furthermore, the case studies in involvement, social interaction, and health and safety indicators reveal that CPSSs impact user participation and social interaction sustainability indicators. The overall framework allows evaluating the relationships between the social sustainability indicators, the key enabling technologies, and the Sustainable Development Goals (SDGs), assessing the global impacts of a CPSS on sustainability performances. According to the outcome of this analysis, it is possible to envision two research challenges to address in future works. In particular, we highlight two main questions:

Research Challenge #a.

(a) Which categories and indicators should be used to evaluate the impacts of CPSSs-KETs on sustainability in building assessment tools?

Our study focus is limited to social sustainability aspects. In the future, sustainability aspects related to external stakeholders, such as customers, suppliers, and the community, could also be addressed. Further, environmental and economic sustainability dimensions should be integrated to support a holistic view of the overall sustainability of a CPPS.

Research Challenge #b.

(b) How would they work in an assessment tool?

According to the research question, the first aspect of addressing is the state-of-art on design methodology for CPSSs defining the critical concept, perspective, applications, and techniques of CPSS. Further, the design methodologies of CPSS discussed in literature should be analyzed in detail, evaluating layer-based design, component-based design, model-based design, virtual integration, and human-based design in order to design, formalize and develop a new widely accepted systematic design methodology to guide the practical design of a CPSS. The design methodology is the basis for developing an assessment tool for evaluating social characteristics and social business opportunities.

  -[30]. [28] -[30] define eight social sustainability indicator categories explained as follow: • The social equity category has two indicator sets: equity of process and fair distribution measuring the access to information, participation in decision making, formation of governance structure, planning of space, use of natural resources. • The environmental education category includes environmental awareness and sensibility and ecological literacy as indicators sets. • The participation and control category measures the involvement through the following indicators: user participation, willingness to act and improve the environment, creative place-making opportunities. • The social cohesion category involves social programs and social interaction • The health and safety category includes five indicators: health impacts of materials, energy sources, the health impact of water consumption, health impacts of Indoor Environmental Quality (IEQ), feeling of safety. • The accessibility and satisfaction category involves two indicator sets: the ease of accessibility set and the satisfaction level set. • Cultural value local identity category assesses the design of spaces indicator set through indigenous environmental management practices and intercultural dialogue indicators. • The physical resilience category has disaster resilience and mitigation set indicators.

Fig. 3 .

 3 Fig. 3. CPSSs-Sustainability Framework proposed and the Mapping case studies accordingly (The number on the map refers to the literature references belonging to different case studies)

Fig. 4 .

 4 Fig. 4. Sustainability Goals [29]V. CONCLUSIONS AND FUTURE WORKS

Acknowledgments

The Italian Ministry of Education supported this work, University and Research under the Programme "Department of Excellence" Legge 232/2016 (Grant No. CUP -D94I18000260001)


Jie Zhang
email: jiezhang@sdu.edu.cn

Tong Zhao

Ju Xie
email: xieju@yzu.edu.cn

Zedong He

William W Yu

H-Bond Catalytic Mechanism of Aromatic Electrophilic Substitution between Phenol and Formaldehyde

Keywords: H-Bond Catalytic Mechanism, Aromatic Electrophilic Substitution, Computational chemistry

Phenolic resins are widely used as moulding plastics, coatings, industrial bondings and ablative materials. An essential reaction step for preparing phenolic resins is aromatic electrophilic substitution. However, the current understanding of this reaction mechanism is kind of too general, making them not able to explain some phenomena such as highly exothermic characteristic of the early reaction stage between phenol and aldehyde under acid catalysis, and how attacking species form when the reaction begins. We studied the detailed catalytic mechanism by quantum mechanics. A new hydrogen-bond (H-bond) catalytic mechanism is suggested. It reveals that the essence of the acid catalytic mechanism is electrophile activation through hydrogen-bonding, and the substrate-catalyst complex formed through an H-bond is the attacking species. Besides, the study discloses that oxalate anion takes part in the reaction through bonding with arenium ion.The thermodynamic and kinetic characters based on this mechanism are quite different from the current theories.

Introduction

Phenolic resins have broad applications such as moulding plastics, coatings, industrial bondings and ablative materials. [START_REF] Zhang | The effect of titanium incorporation on the thermal stability of phenol-formaldehyde resin and its carbonization microstructure[END_REF][START_REF] Chen | The effects of zirconium diboride particles on the ablation performance of carbon-phenolic composites under an oxyacetylene flame[END_REF] Thermoplastic phenolic resins are synthesized by the reaction of phenol with formaldehyde in an acidic medium. It is a strong exothermic reaction at the beginning of the process. [START_REF] Knop | Phenolic Resins: Chemistry, Applications and Performance[END_REF] The large amount of heat is thought to result from the aromatic electrophilic substitution, which is usually called addition-elimination process as shown in Figure 1. However, there is no reasonable explanation for the strong exothermic phenomenon based on the mostly accepted mechanism. According to this mechanism, an arenium ion firstly forms in an endothermic step, which is thought to be the rate determining step. Next is deprotonation, and it is faster than the first one. [START_REF] Peter | Organic Chemistry: Structure and Function[END_REF] There is no sign that a lot of heat is released in this step. In spite of its broad acceptance, the essential reaction to produce phenolic resin has not been sufficiently studied. Some experimental studies on phenolic resin preparation focused on the kinetics of substitution (namely addition) and condensation reactions in alkaline medium, including reaction rate constant and reaction order. [START_REF] Astarloa-Alerbe | Kinetics of phenolic resol resin formation by HPLC[END_REF][START_REF] Grenier-Loustalot | Pheno lic resins: 1. Mechanisms and kinetics of phenol and of the first polycondensates tow ards formaldehyde in solution[END_REF][START_REF] Grenier-Loustalot | Influence of Catalyst Type on Reaction-Mechanisms and Kinetics[END_REF] However, the details for every step cannot be obtained by experimental methods.

Computational chemistry is especially important for elucidating mechanisms of chemical reactions. [START_REF] Xi | Mechanistic Studies of Copper-Catalyzed Asymmetric Hydroboration of Alkenes[END_REF][START_REF] Okumura | Palladium-Catalyzed Intermolecular Exchange between C-C and C-Si σ-Bonds[END_REF][START_REF] Hu | Substrate-Dependent Two-State Reactivity in Iron-Catalyzed Alkene [2+2] Cycloaddition Reactions[END_REF][START_REF] Ramos | Computational Enzymatic Catalysis[END_REF][START_REF] Cheng | Computational organic chemistry: bridging theory and experiment in establishing the mechanisms of chemical reactions[END_REF] Aromatic electrophilic substitution is also one of the objects of computational chemistry. [START_REF] Tomberg | A predictive tool for electrophilic aromatic substitutions using machine learning[END_REF][START_REF] Oliveira | Thoughts about the electrophilic aromatic substitution mechanism: the Friedel-crafts alkylation and acylation of benzene with acetyl and t-butyl catyions in the gas phase[END_REF][START_REF] Liljenberg | Mechanism and regioselectivity of electrophilic aromatic nitration in solution: the validity of the transition state approach[END_REF] As a research mothod, it gives new thoughts on it. [START_REF] Galabov | Electrophilic aromatic substitution: new insights into an old calss of reactions[END_REF][START_REF] Liljenberg | Theoretical investigation into rate-determining factors in electrophilic aromatic halogenation[END_REF][START_REF] Stuyver | Electrophilic aromatic substitution reactions: mechanistic landscape, electrostatic and electric-field control of reaction rates, and mechanistic crossovers[END_REF] Hill and Conner studied the reactivity of phenolic compounds with formaldehyde under basic conditions. [START_REF] Conner | Predicting the reactivity of phenolic compounds with formaldehyde under basic conditions: An Ab Initio Study[END_REF][START_REF] Mitsunaga | Reaction of formaldehyde with phenols: A computational chemistry study[END_REF] But computational studies on the reaction under acidic condition are very few. [START_REF] Xu | Addition Mechanisms of Phenol toward Formaldehyde under Acidic Condition: a Theoretical Investigation[END_REF][START_REF] Li | Theoretical Confirmation of the Quinone Methide Hypothesis for the Condensation Reactions in Phenol-Formaldehyde Resin Synthesis[END_REF] It is generally accepted that in the arenium ion mechanism the attacking species may form in various ways, but what happens on the aromatic ring is basically the same in all cases. For this reason, most mechanism studies mainly focus on the identity of the attacking entities and how they are formed. The acid-catalyzed mechanism has been investigated at the PW91/DNP level with COSMO (conductor-like screening model) solvent model. [START_REF] Xu | Addition Mechanisms of Phenol toward Formaldehyde under Acidic Condition: a Theoretical Investigation[END_REF] However, the data cannot explain the highly exothermic characteristic of the reaction, because protonated methanediol or protonated formaldehyde is treated as the attacking entities. Besides, the effect of the counterion of proton (i.e., the catalyst anion, or the conjugated base) has not been revealed in the acid catalyzed mechanism. A more detailed mechanism is needed to help us further understand the reaction.

From the beginning of this century, small-molecule chiral hydrogen-bond (H-bond) donors have been used to catalyze an array of C-C and C-heteroatom bond-forming reactions with high enantioselectivity and broad scope of substrates. [START_REF] Doyle | Small-Molecule H-Bond Donors in Asymmetric Catalysis[END_REF] The derivatives of thiourea [START_REF] Vachal | Structure-based analysis and optimization of a highly enantioselective catalyst for the strecker reaction[END_REF][START_REF] Etter | Encoding and decoding hydrogen-bond patterns of organic compounds[END_REF] and phosphoric acid [START_REF] Akiyama | Enantioselective Mannich-Type Reaction Catalyzed by a Chiral Brønsted Acid[END_REF][START_REF] Uraguchi | Chiral Brønsted Acid-Catalyzed Direct Mannich Reactions via Electrophilic Activation[END_REF][START_REF] Connon | Chiral phosphoric acids: Powerful organocatalysts for asymmetric addition reactions to imines[END_REF] are the most representative catalysts employed in H-bond catalyses.

Experimental and theoretical studies of catalytic reactions reveal that H-bonding interaction between catalysts and substrates is the key activation mechanism. For example, Jacobsen testified the formation of an imine-catalyst complex through an H-bond between the imine nitrogen and an acidic proton of the urea catalyst in Strecker reaction. [START_REF] Vachal | Structure-based analysis and optimization of a highly enantioselective catalyst for the strecker reaction[END_REF] In their review article on small-molecule chiral H-bond donors, Doyle and Jacobsen pointed out that elucidation of fundamentally distinct modes of activation of Brønsted-acid catalysts would likely inspire the design of new H-bond acid catalysts and bring in new reactions and reaction partners for enantioselective catalysis. [START_REF] Doyle | Small-Molecule H-Bond Donors in Asymmetric Catalysis[END_REF] In this paper, an H-bond catalytic mechanism for aromatic electrophilic substitution between phenol and formaldehyde in a Brønsted-acidic medium is presented. It discloses that the essence of the catalysis is electrophile activation through H-bonding. Besides, the effect of the conjugate Brønsted base is also proposed. This mechanism illustrates that the aromatic electrophilic substitution is a highly exothermic reaction, which is well consistent with the experimental observation. [START_REF] Knop | Phenolic Resins: Chemistry, Applications and Performance[END_REF]

Methods

Optimized geometries of all species and the stationary points on the potential surface were obtained at the MP2(fc)/6-31+G(d,p) level of theory. [START_REF] Møller | Note on an Approximation Treatment for Many-Electron Systems[END_REF][START_REF] Gordon | Analytic MP2 frequencies without fifth-order storage. Theory and application to bifurcated hydrogen bonds in the water hexamer[END_REF][START_REF] Freeman | An ab initio molecular orbital theory study of the conformational free energies of 2-methyl-, 3-methyl-, and 4-methyltetrahydro-2 H-pyran[END_REF][START_REF] Kestutis | On the Accuracy of Density Functional Theory to Predict Shifts in Nuclear Magnetic Resonance Shielding Constants due to Hydrogen Bonding[END_REF][START_REF] Curtiss | Gaussian-3 theory using reduced Møller-Plesset order[END_REF] The single point energies of all optimized structures were obtained at the level of MP2(fc)/6-311++G(3df,2p) to increase the accuracy of the energy values. The solvent effect in water was modeled using the self-consistent reaction field (SCRF) method with the Tomasi's polarized continuum model (PCM). [START_REF] Miertus | Approximate evaluations of the electrostatic free energy and internal energy changes in solution processes[END_REF][START_REF] Tomasi | Molecular Interactions in Solution: An Overview of Methods Based on Continuous Distributions of the Solvent[END_REF] The corresponding harmonic frequencies were calculated based on the MP2(fc)/6-31+G(d,p) optimized geometries to obtain zero-point energies (ZPEs) and to determine all stationary points as either minima (no imaginary frequencies) or transition states (only one imaginary frequency). The reaction paths were examined by intrinsic coordinate reaction (IRC) calculations at the MP2(fc)/6-31+G(d,p) level. The IRC results are reported in the Supporting Information. Based on the MP2(fc)/6-31+G(d,p) optimized geometries, natural bond orbital (NBO) analyses at the same level were then used. [START_REF] Glendening | NBO Version 3.1, TC1[END_REF] The Gaussian 09 series of programs were employed in all calculations. 37

Results and discussion

Formation of Attacking Specie: H-bonded complex

For the aromatic electrophilic substitution, the most important thing is to determine the attacking species. Formaldehyde is usually used in aqueous solution. So in a previous computational study, methylene glycol was thought to be the existence form of formaldehyde in aqueous solution, then protonated methylene glycol and protonated formaldehyde were treated as the attacking entities considering an acid environment. [START_REF] Xu | Addition Mechanisms of Phenol toward Formaldehyde under Acidic Condition: a Theoretical Investigation[END_REF] But this leaves a few things not well explained. First, according to our calculations, the process from formaldehyde to methylene glycol has a barrier of 153.1 kJ/mol though it is exothermic of 21.6 kJ/mol (Figure S1). Second, it is well known that methylene glycol is thermodynamically unstable and is liable to revert to formaldehyde through dehydration under acidic conditions. [START_REF] Peter | Organic Chemistry: Structure and Function[END_REF] Our calculations show that this dehydration reaction proceeds without a barrier (Scheme S1), which testifies that protonated methylene glycol is difficult to exist in an acidic system. If protonated formaldehyde is considered as the attacking entity, it should be formed first.

However, the calculated results show that the formation of protonated formaldehyde is endothermic (Scheme S2). So, in terms of energy, both protonated methylene glycol and protonated formaldehyde are not the dominant attacking entities. The charge distributions can help to predict the initial state of reaction system and to judge the reactive site. Natural bond orbital (NBO) analysis was carried out and the NBO charges are shown in Figure 2. It can be seen that phenolic hydroxyl changes the charge distribution of the aromatic ring. The carbon atoms on ortho or para positions carry more negative charges than meta ones. Therefore, the ortho-and para-carbon atoms are more likely to be attacked by electrophilic reagents. 38 Considering the high dissociation constant of oxalic acid (pKa1 = 1.27) in aqueous, hydrated proton instead of oxalic acid molecule is involved in the reaction. The oxygen atoms of phenolic hydroxyl and carbonyl of formaldehyde as well as aromatic ring are all possible hydrated proton acceptors. Thus, three types of substrate-catalyst complexes through an H-bond have been optimized as shown in Scheme 1 as well as their binding energies. Scheme 1. The formation of H-bonded complexes, regarding proton only (left) and regarding hydrated proton (right).

It can be seen in Scheme 1 (right) that when H-bonded complexes are formed, H2O molecule disassociates from the hydrated proton and forms an H-bond with phenolic hydroxyl. This is the same in all five complexes. This type of H-bonding stabilizes the initial state of the reaction system. However, it is not the reactive site for electrophilic substitution. Therefore, H2O does not affect the acid catalytic mechanism much, but proton plays the major role. Proton can bridge phenol and formaldehyde to form another type of H-bond, which not only stabilizes the initial state of the reaction system, but also decides the next reaction.

With this consideration, we also optimized a simplified model of H-bonded complex regarding proton only (Scheme 1, left). It can be seen that the ways of formation of H-bond in reactive site are not affected by H2O molecule. The involvement of H2O molecule only influences the absolute values of the binding energy of the five H-bonded complexes, but it does not affect the relative magnitude of their stability.

Since there is no barrier to form H-bonded complexes, it can be confirmed that their formation is not the rate determining step for the multi-step aromatic electrophilic substitution.

As can be seen in Scheme 1, 3 is the most stable complex, which is formed by oxygen atom of phenolic hydroxyl, proton, and formaldehyde. The bridging interaction stabilizes 3 by 43.9 kJ/mol, which is stronger than the classical O-H…O H-bond. [START_REF] Vachal | Structure-based analysis and optimization of a highly enantioselective catalyst for the strecker reaction[END_REF] The complexes 4, 5, 6, and 7 use π electrons on aromatic ring as electron donor at ortho or para positions. The O -H…π H-bond leads to 21-25 kJ/mol stabilization energy to the complexes, because O-H…π is a relatively weak H-bond. 37 There are experimental evidences that a class of uncertain structure intermediates, named encounter complexes, are present before arenium ion is formed. 38 They are called as π complexes. However, experimental results on π complexes contradict each other. Some suggested that π complex formation might be the rate determining step, [START_REF] Condon | Relationship Between Rates of Halogenation and Basicities of Methylbenzenes[END_REF][START_REF] Olah | Aromatic Substitution. VII. Friedel-Crafts Type Nitration of Aromatics 2[END_REF][START_REF] Olah | Aromatic Substitution. XIV. Ferric Chloride Catalyzed Bromination of Benzene and Alkylbenzenes wth Bromine in Nitromethane Solution[END_REF] while some suggested that arenium ion was formed in the rate determining step. [START_REF] Brown | Solubility of Hydrogen Chloride at Low Temperatures. A Measure of the Basic Properties of Aromatic Nuclei; π-and σ-Complexes and Their Role in Aromatic Substitution1,2[END_REF][START_REF] Brown | Relative Rates of Bromination of Benzene and the Methylbenzenes. Partial Rate Factors for the Bromination Reaction1-3[END_REF][START_REF] Olah | Aromatic Substitution. XXII: Acetylation of Benzene, Alkylbenzenes, and Halobenzenes with Methyloxocarbonium (Acetylium) Hexafluoro-and Hexachloroantimonate[END_REF][START_REF] El-Dusouqui | ChemInform Abstract: π-Complex Formation and Collapse in Electrophilic Halogenation of Aromatic Substrates[END_REF][START_REF] Sedaghat-Herati | Substituent effects in aromatic substitution of aryltriethyltin compounds by mercuric halides[END_REF] Based on the above results, we supposed that the encounter complexes are attacking species, and are substrate-catalyst complexes through an H-bond. Their formation hence leads to a new mechanism for the aromatic electrophilic substitution.

H-bond catalysis mechanism

As mentioned above, H-bonded complex is formed between catalyst and substrates. The distribution of the frontier molecular orbitals (FMOs) on the reaction system can help to predict the reactivity in the next step. The FMOs of reactants (formaldehyde and phenol) and H-bonded complexes (3~7, 3 ' ~7' ,) are shown in Figure 3. In order to further investigate the acid catalytic mechanism, FMOs of the two models of H-bonded complex were considered. From Fig. 3 (right), it can be seen that there are no distributions of FMOs on H2O molecule which is released from hydrated proton.

In other words, H2O molecule does not take part in the catalytic reaction. By now, it is reasonable to say that it is proton which plays the major role in catalytic action of oxalic acid.

Therefore the simplified model of H-bonded complexes regarding proton only will be used as the attacking species and also for the sake of brevity, H2O molecule is not considered in the following sections.

It can be seen that in complex 3 the HOMO is located on the phenol fragment, while the LUMO is located on formaldehyde fragment. O-H…O H-bond exists in this complex. In complexes 4, 5, 6, and 7, the HOMO formed by using π electrons on aromatic ring as electron donor mostly distributes on phenol, and a small part is situated on formaldehyde (on formaldehyde oxygen, specifically). The O-H…π H-bond is formed with formaldehyde oxygen, proton, and benzene ring in these complexes. In addition, the HOMO distribution on formaldehyde of the para-complexes 6 and 7 is slightly larger than that on the formaldehyde of ortho-complexes 4 and 5. It is worth mentioning that the formation of the H-bonded complexes significantly decreases the LUMO energy of the electrophilic formaldehyde and reduces the energy gap between the LUMO of formaldehyde and the HOMO of phenol. The energy gap between HOMO of phenol and LUMO of formaldehyde is 10.569 eV, while the energy gaps of the complexes are somewhat lower. For example, complex 5 has a decreased energy gap of 8.939 eV. This means the bridging H-bond interaction reduces the LUMO energy of the electrophile and enhances its electrophilic ability, thereby reduces the barrier of electrophilic substitution and catalyzes the reaction. This is consistent well with the typical LUMO activation mechanism of H-bond catalysis. [START_REF] Vachal | Structure-based analysis and optimization of a highly enantioselective catalyst for the strecker reaction[END_REF][START_REF] Walvoord | Quantification of Electrophilic Activation by Hydrogen-Bonding Organocatalysts[END_REF] The energy gap between LUMO and HOMO can be employed to predict the reactivity. A smaller energy gap represents a higher reactivity. Complexes 4, 5, 6, and 7 possess similar energy gap. The complex 3 formed by proton, formaldehyde and phenolic hydroxyl group has the highest energy gap. It can be predicted that the reaction starting with complex 3 has higher barrier than those of the reactions starting from other four complexes.

From H-Bonded Complex to Arenium Ions 1. Ortho Arenium Ion 3 is the most stable complex. Starting from it, the ortho-arenium ion 10 is formed through three steps, as shown in Figure 4. The first step is the rate determining step with a barrier of 28.6 kJ/mol. Considering 43.9 kJ/mol of heat that is released in the last step, the barrier is overcome easily. In this step, H-bond breaks and proton transfers to formaldehyde in transition state TS1, leading to the formation of intermediate 8. In the following two steps phenol and protonated formaldehyde get to close each other by adjusting their relative position via transition states TS2 and TS3 till ortho arenium ion 10 forms, in which C (phenol)-C (formaldehyde) bond is formed. There is almost no heat effect in the two steps, just endothermic by 0.8 kJ/mol. It can be seen that the ortho arenium ion 10 is more stable than reactants by 43.1 kJ/mol, although its aromaticity is destroyed. The covalent bonding and the delocalization of lone pair electrons of oxygen atom of phenolic hydroxyl to benzene ring contribute to its stability. Starting from complexes 6 and 7, ortho arenium ion 10 and 11 are formed after overcoming barriers of 8.6 and 9.2 kJ/mol, via transition states TS4 and TS5, respectively (Figure 5). In these two paths, para H-bonded complex with phenol, proton and formaldehyde first turns to ortho complex between phenol and protonated formaldehyde in transition state, and then C (phenol)-C (formaldehyde) bond is formed. The two paths are exothermic by 17.7 kJ/mol and 14.0 kJ/mol, respectively. Overcoming a barrier of 18.8 kJ/mol, ortho arenium ion 11 turns to para arenium ion 12 via transition state TS6. Consider the reaction barriers, ortho arenium ion 10 is mainly formed from complex 6 rather than complex 3. Arenium ions 10, 11 and 12 are more stable than the corresponding reactants. The reason is given above.

Para Arenium Ion

Figure 6 shows that para arenium ion 12 is formed from complex 4 or complex 5. The two paths are exothermic by 32.9 kJ/mol and 33.5 kJ/mol, respectively. Para arenium ion is also more stable than reactants, just like the ortho arenium ion. In summary, the formation of arenium ion is an H-bond catalysis process. Oxalic acid decreases the reaction barrier through LUMO activation mechanism. Complexes 4, 5, 6 and 7 lead to paths with barriers not more than 10 kJ/mol, especially the paths from complexes 4 and 5 to para arenium ion 12, only 4.7 or 5.7 kJ/mol. This means that the rate constants to form arenium ions are quite high. Once the four complexes are formed, they turn to arenium ions quickly. The path starting from complex 3 has a barrier of 28.6 kJ/mol, higher than those of other paths. The results testify our prediction on the reaction barriers based on the energy gaps between LUMO and HOMO of the complexes. The smaller the energy gap is, the lower the reaction barrier will be.

The departure of Proton

Following the formation of arenium ion is the loss of proton, and then a neutral substitution product is produced. It is certain that the proton departs with the help of a negative group.

The ready negative group in reaction system is oxalate anion. We found that oxalate anion first combines with arenium ion through bonding the carbon adjacent to the site of electrophilic attack, because that carbon is electron-deficient, as natural charges shows in Figure 7 (numbers in blue). In addition, the adjacent position is favorable for the following hydrogen abstraction of oxalate anion. Para arenium ion 20 has two carbons adjacent to the site of electrophilic attack. So, there are two paths for the proton to leave. As Figure 10 shows, the reaction heats of two paths are 174.3 and 174.0 kJ/mol, respectively. Figure 11 gives a summary of the whole reaction. It can be seen that every step, including the formation of H-bond complexes, the neutralization reaction between arenium ion and oxalate anion and the departure of proton, is exothermic. This means that the aromatic electrophilic substitution is a violent exothermal reaction, which is consistent with the experimental observation at the beginning stage to prepare phenolic resins in an acidic medium. [START_REF] Knop | Phenolic Resins: Chemistry, Applications and Performance[END_REF] The departure of proton contributes the most to the violent exothermal process. The energy barriers are from 60 to 80 kJ/mol, higher than the barriers of the formation of arenium ions. In other words, proton departure is the rate determining step, rather than the arenium ion formation. Besides, arenium ion is more stable than reactants. This means the kinetic and thermodynamic characteristics of this mechanism are quite different from the general mechanism of aromatic electrophilic substitution.

Conclusions

Computational studies on aromatic electrophilic substitution between phenol and formaldehyde catalyzed by oxalic acid suggests an H-bond catalysis process. The calculation results of frontier orbitals show that the H-bond bridging interaction of substrate-catalyst complexes reduce the LUMO energy of formaldehyde and thus reduce the reaction barrier, thereby catalyze the reaction. Both the thermodynamic and kinetic characteristics based on this mechanism are different from those based on the generally accepted mechanism.

H-bonded complexes are the attacking species of the substitution. The departure of proton, rather than the formation of arenium ion, is the rate determining step. Arenium ions are more stable than reactants. The whole reaction is highly exothermic, especially the step of departure of proton. The counterion of proton, oxalate anion, takes part in the reaction by bonding with arenium ion first, and then abstracting the proton to release the catalyst, oxalic acid. The H-bond catalytic mechanism perfectly explains the highly exothermic characteristic of the early stage reaction between phenol and aldehyde under acid catalysis. The essence of H-bond catalysis is to lower the LUMO of the H-bond complexes of substrate-catalyst; as a result, the reaction barrier of the formation of arenium ion is very low.

Figure 1 .

 1 Figure 1. Potential energy diagram of the classical mechanism of aromatic electrophilic substitution.

Figure 2 .

 2 Figure 2. NBO charge distribution of benzene, phenol and formaldehyde at MP2(fc)/6-31+G(d,p) level.

Figure 3 .

 3 Figure 3. Frontier molecular orbitals of reactants and two models of H-bonded complex.

Figure 4 .

 4 Figure 4. Energy profile of the formation of ortho arenium ion 10.

Figure 5 .

 5 Figure 5. Energy profile of the formation of ortho arenium ions 10 and 11.

Figure 6 .

 6 Figure 6. Energy profiles of the formations of para arenium ion 12.

Figure 7 .

 7 Figure 7. Natural charges (in parentheses) of arenium ions.

Figure 8 .

 8 Figure 8. Energy profile of the formation of ortho substitute 15.

Figure 9 .

 9 Figure 9. Energy profile of the formation of ortho substitute 19.

Figure 10 .

 10 Figure 10. Energy profile of the formation of para substitute 21.

Figure 11 .

 11 Figure 11. Energy profile of aromatic electrophilic substitution between phenol and formaldehyde with oxalic acid as catalyst.