Photoredox-Catalyzed Branch-Selective Pyridylation of Alkenes for the Expedient Synthesis of Triprolidine

Total Page:16

File Type:pdf, Size:1020Kb

Photoredox-Catalyzed Branch-Selective Pyridylation of Alkenes for the Expedient Synthesis of Triprolidine ARTICLE https://doi.org/10.1038/s41467-019-08669-1 OPEN Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine Shengqing Zhu1, Jian Qin1, Fang Wang1, Huan Li1 & Lingling Chu 1 Alkenylpyridines are important pharmaceutical cores as well as versatile building blocks in organic synthesis. Heck reaction represents one of the most powerful platform for the 1234567890():,; construction of aryl-substituted alkenes, nevertheless, examples for Heck type coupling of alkenes with pyridines, particularly with branched selectivity, remain elusive. Here we report a catalytic, branch-selective pyridylation of alkenes via a sulfinate assisted photoredox catalysis. This reaction proceeds through a sequential radical addition/coupling/elimination, by utilizing readily available sodium sulfinates as reusable radical precursors as well as traceless elimination groups. This versatile protocol allows for the installation of important vinylpyridines with complete branched selectivity under mild conditions. Furthermore, this catalytic manifold is successfully applied to the expedient synthesis of Triprolidine. 1 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Center for Advanced Low-Dimension Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 201620 Shanghai, China. Correspondence and requests for materials should be addressed to L.C. (email: [email protected]) NATURE COMMUNICATIONS | (2019) 10:749 | https://doi.org/10.1038/s41467-019-08669-1 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-08669-1 red III IV = – 66 yridine is recognized as one of the most important het- *Ir(ppy)3 2 {E1/2 [*Ir /Ir ] 1.73 V vs. SCE } and cyano- red = – 67 erocycles in pharmaceuticals, agrochemicals, and bioactive pyridine 3 (E1/2 1.75 V vs. SCE in CH3CN) could be feasible P 1,2 natural products . Alkenylpyridines, an important subunit under specific conditions, generating pyridyl radical anion species 3 IV IV red IV of pyridines, also serve as versatile synthetic building blocks for and the oxidizing Ir 5.WehypothesizedthatIr 5 {E1/2 [Ir / complex pyridines3,4, as well as important ligand scaffolds in the IrIII] =+0.77 V vs. SCE}66,68 could affect the oxidation of sodium 5 fi fi red =+ area of catalysis (Fig. 1a) . As a result, the ef cient and selective methanesul nate 6 (E1/2 0.50 V vs. SCE) (see Supplementary assembly of alkenylpyridines from readily available starting Fig. 2) to form sulfonyl radical 7 and regenerate the ground-state IrIII materials has drawn intensive attentions of chemists6–10. catalyst 1. The electrophilic sulfonyl radical 7 would subsequently Alkenes are one of the most ubiquitous material in organic undergo facile radical addition to alkene to generate the nucleophilic synthesis. The cross-coupling of alkenes and aryl halides in the benzylic radical 9. At this stage, we envisioned that radical–radical presence of palladium catalyst, the Heck reaction11–13,isa coupling between the transient benzylic radical 9 and the persistent powerful protocol for the construction of aryl-substituted alkenes. pyridyl radical anion 4 would forge β-sulfonyl pyridine 1032–46.Due Nevertheless, there are few examples of Heck coupling of alkenes totheacidityofthebenzylicprotonandthegoodleavingabilityof with pyridines, probably due to the potential coordination sulfone, alkyl sulfone 10 would be expected to undergo E1 elimina- between the nitrogen atom and metal catalyst14–19. Alternatively, tion with the assistant of base, furnishing the final branched alke- several examples of Pd-catalyzed cross-coupling of alkenes with nylpyridine product 11,aswellassulfinate 6 that could be recycled. pyridine N-oxides have been reported, while only delivering vinylpyridine derivatives with linear selectivity20–23. To the best Optimization study. Our investigation into this photoredox of our knowledge, catalytic alkene–pyridine couplings with cascade protocol began with exposure of 1-(tert-butyl)-4-vinyl- branch selectivity, the control of which remains a big challenge in – benzene 12 and 4-cyanopyridine 3 to a 90 W blue light-emitting Heck couplings24 26, is unknown. diode (LED) in the presence of catalytic amounts of Ir(ppy) (5 Recently, radical-based chemistry provides an alternative platform 3 mol%) and readily available MeSO Na (30 mol%) (Table 1). In to address this challenge. Particularly, the groups of MacMillan, Jui, 2 – the presence of a stoichiometric amount of 1,8-diazabicyclo[5.4.0] and others27 46 have successfully demonstrated that visible light undec-7-ene (DBU) as base; pleasingly, we found that the bran- photocatalyzed cross-couplings of pyridines to access to alkylated ched vinylpyridine product could be obtained in 69% yield (entry pyridines under mild conditions, by taking advantage of unique 1). The nature of sodium sulfinates was found to have an reactivity of open-shell pyridyl radical species (Fig. 1b). While sig- important effect to the reaction efficiency. Generally, electron- nificant advances, no examples of vinylation of pyridines via pyridyl poor aryl sulfinates, which are better leaving groups, afforded radical species has been reported. Herein, we demonstrate an alter- higher efficiency than electron-rich ones (entries 2–6). And, native protocol, through a sequential radical addition/radical cou- comparable yields were obtained when para-chlorophenyl sulfi- pling/elimination pathway, to access vinylpyridines from readily nate was employed as the co-catalyst (entry 4). Gratifyingly, available alkenes with complete branch selectivity (Fig. 1c). This increasing the photocatalyst loading to 5 mol% provided the reaction takes advantage of a synergistic combination of visible optimal yield of product (entry 7). Control experiments indicated light-induced photoredox catalysis and a catalytic radical precursor, that photocatalyst, sulfinate, and light were all essential to this providing an effective and selective strategy for the synthesis of transformation, as no desired products were observed in the α-vinylpyridines under mild conditions. absence of either photocatalyst, sulfinate, or light (entries 8–10). While conducting the reaction in the absence of DBU afforded Results the expected product in 18% yield, probably due to the basic condition in the presence of MeSO Na (entry 11). Interestingly, a Design plan. We hypothesized that sodium sulfinates would be the 2 trace amount of C2-substituted product 13′, which is assumed to ideal reusable radical precursors, due to the unique properties be formed by the S Ar reaction of cyanopyridine with alkyl of which: (i) sufinates have been recently employed as efficient sul- N radical, was observed under the reaction conditions69. fonyl coupling partners in photoredox catalysis47–62; (ii) it is well known that the alkyl sulfones would be prone to undergo desulfo- nylation under basic conditions63–65.AsdepictedinFig.2,we Substrate scope. With the optimal conditions in hand, we next envisioned that a single-electron reduction between photoexcited explored the generality of this transformation with respect to a Alkenylpyridine motifs b Photocatalyzed alkylation of pyridines via open-shell pyridyl species Privileged pharmaceutical cores N X CN Alkyl Radical e Versatile building blocks –radical coupling Important ligand scaffolds – N N N N Me N Challenging selective synthesis X = CN, Open-shell (MacMillan, Jui, Triprolidine halides pyridyl species and others) c This work: Branch-selective alkene-pyridine coupling via visible-light induced photoredox catalysis N Me CN SO2 CN Ir Base – N MeSO Na – – MeSo2 2 α N N -Vinylpyridines Alkene Pyridine SO2Me Branch selectivity Fig. 1 Design of catalytic and branch-selective alkene–pyridine coupling via photoredox catalysis. a Importance of alkenylpyridines. b Photocatalyzed alkylations of pyridines. c Design of branch-selective alkenylation of pyridines via photoredox catalysis 2 NATURE COMMUNICATIONS | (2019) 10:749 | https://doi.org/10.1038/s41467-019-08669-1 | www.nature.com/naturecommunications NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-08669-1 ARTICLE CN CN – N N 3 4 X N SET Vinylpyridine 11 IV *IrIII (2) Photoredox Ir (5) catalytic O cycle S – Me O 6 SET +Base Ir(ppy)3 (1) SO2Me O S Me O 7 X N 10 – CN– SO2Me X CN X – Alkene 8 9 N 4 Fig. 2 Proposed mechanism. Possible reaction pathway utilizing sulfinate as a promoter Table 1 Optimization of reaction conditionsa diminished yields (products 30–32,53–68% yields). Furthermore, this catalytic protocol was applicable to other aryl and heteroaryl alkenes, in the form of naphthalene, benzofuran, thiophene, and thiazole, furnishing the corresponding products in moderate CN Ir(ppy)3 (5 mol%) yields (products 33–36,56–78% yields). It should be noted that MeSO Na (30 mol%) 2 both cyclic (e.g., 1,2-dihydronaphthalene) and acyclic (e.g., trans- DBU, MeCN/EtOH, 40 °C N β-methylstyrenes and benzyl ether of cinnamyl alcohol) internal N 90 W Blue LED t Bu t Bu alkenes were found to be viable substrates, delivering the corre- Alkene 12 Pyridine 3 α-vinylpyridine 13 sponding alkenylpyridines with exclusive selectivity at the benzylic positions, respectively (products 37–40,69–75% yields). b Entry Ir(ppy)3 RSO2Na (30 mol%) Yield Finally, styrenes derived from drugs or natural products, including oxaprozin, nonivamide, hymecromone, estrone, and 1 1 mol% MeSO2Na 69% 2 1 mol% PhSO Na 52% indomethacin, could be successfully employed to furnish the 2 –
Recommended publications
  • Synthesis of Densely Substituted Pyridine Derivatives from Nitriles by a Non-Classical [4+2] Cycloaddition/1,5-Hydrogen Shift Strategy
    Synthesis of densely substituted pyridine derivatives from nitriles by a non-classical [4+2] cycloaddition/1,5-hydrogen shift strategy Wanqing Wu ( [email protected] ) South China University of Technology https://orcid.org/0000-0001-5151-7788 Dandan He South China University of Technology Kanghui Duan South China University of Technology Yang Zhou South China University of Technology Meng Li South China University of Technology Huanfeng Jiang South China University of Technology Article Keywords: pyridine derivatives, organic synthesis, medicinal chemistry. Posted Date: March 3rd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-258126/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/18 Abstract A novel strategy has been established to assemble an array of densely substituted pyridine derivatives from nitriles and o-substituted aryl alkynes or 1-methyl-1,3-enynes via a non-classical [4 + 2] cycloaddition along with 1,5-hydrogen shift process. The well-balanced anities of two different alkali metal salts enable the C(sp3)-H bond activation as well as the excellent chemo- and regioselectivities. This protocol offers a new guide to construct pyridine frameworks from nitriles with sp3-carbon pronucleophiles, and shows potential applications in organic synthesis and medicinal chemistry. Introduction Compounds containing pyridine core structures, not only widely exist in natural products, pharmaceuticals, and functional materials,1–7 but also serve as useful and valuable building blocks for metal ligands.8,9 For instance, pyridine derivative Actos I10 is a famous drug for the treatment of type 2 diabetes; Bi-(or tri-)pyridines II11–15 are often used as ligands in metal-catalyzed reactions; Kv1.5 antagonist III16 and alkaloid papaverine IV17 are two representative isoquinolines as a promising atrial- selective agent and a smooth muscle relaxant, respectively (Fig.
    [Show full text]
  • TR-470: Pyridine (CASRN 110-86-1) in F344/N Rats, Wistar Rats, And
    NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF PYRIDINE (CAS NO. 110-86-1) IN F344/N RATS, WISTAR RATS, AND B6C3F1 MICE (DRINKING WATER STUDIES) NATIONAL TOXICOLOGY PROGRAM P.O. Box 12233 Research Triangle Park, NC 27709 March 2000 NTP TR 470 NIH Publication No. 00-3960 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health FOREWORD The National Toxicology Program (NTP) is made up of four charter agencies of the U.S. Department of Health and Human Services (DHHS): the National Cancer Institute (NCI), National Institutes of Health; the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health; the National Center for Toxicological Research (NCTR), Food and Drug Administration; and the National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention. In July 1981, the Carcinogenesis Bioassay Testing Program, NCI, was transferred to the NIEHS. The NTP coordinates the relevant programs, staff, and resources from these Public Health Service agencies relating to basic and applied research and to biological assay development and validation. The NTP develops, evaluates, and disseminates scientific information about potentially toxic and hazardous chemicals. This knowledge is used for protecting the health of the American people and for the primary prevention of disease. The studies described in this Technical Report were performed under the direction of the NIEHS and were conducted in compliance with NTP laboratory health and safety requirements and must meet or exceed all applicable federal, state, and local health and safety regulations. Animal care and use were in accordance with the Public Health Service Policy on Humane Care and Use of Animals.
    [Show full text]
  • Photoredox Catalysis Photoredox Catalysis: a Mild, Operationally Simple Approach to the Synthesis of A-Trifluoromethyl Carbonyl Compounds Phong V
    DOI: 10.1002/anie.201101861 Photoredox Catalysis Photoredox Catalysis: A Mild, Operationally Simple Approach to the Synthesis of a-Trifluoromethyl Carbonyl Compounds Phong V. Pham, David A. Nagib, and David W. C. MacMillan* The unique physical and chemical advantages conferred by the CÀF bond have led to the broad exploitation of this motif throughout the pharmaceutical,[1] materials,[2] and agrochem- ical[3] sectors. In drug design, for instance, incorporation of polyfluorinated alkyl groups, such as CF3 moieties, can profoundly impact the activity, metabolic stability, lipophilic- ity, and bioavailability of lead compounds.[1,4] Not surpris- ingly, the development of methods for the production of carbonyl-based synthons bearing a-CF3 substitution has emerged as a central objective in the field of chemical synthesis. Although important recent advances have been made toward this goal, there are currently few operationally simple methods for the conversion of enolates (or enolate equivalents) to a-trifluoromethylated carbonyl motifs. Stan- dard alkylation methods are generally not productive, due to the negative polarization of the trifluoromethyl moiety, thus specially tailored reagents have been developed to furnish an trifluoromethylation of a range of enolates or enolate [5] electrophilic CF3 equivalent. Alternatively, in recent years, a equivalents [Eq. (1)]. In this context, we elected to employ set of radical (Et3B/O2) and organometallic (Rh-catalyzed) enolsilanes and silylketene acetals as suitable enolic sub- approaches have been
    [Show full text]
  • Robert Burns Woodward
    The Life and Achievements of Robert Burns Woodward Long Literature Seminar July 13, 2009 Erika A. Crane “The structure known, but not yet accessible by synthesis, is to the chemist what the unclimbed mountain, the uncharted sea, the untilled field, the unreached planet, are to other men. The achievement of the objective in itself cannot but thrill all chemists, who even before they know the details of the journey can apprehend from their own experience the joys and elations, the disappointments and false hopes, the obstacles overcome, the frustrations subdued, which they experienced who traversed a road to the goal. The unique challenge which chemical synthesis provides for the creative imagination and the skilled hand ensures that it will endure as long as men write books, paint pictures, and fashion things which are beautiful, or practical, or both.” “Art and Science in the Synthesis of Organic Compounds: Retrospect and Prospect,” in Pointers and Pathways in Research (Bombay:CIBA of India, 1963). Robert Burns Woodward • Graduated from MIT with his Ph.D. in chemistry at the age of 20 Woodward taught by example and captivated • A tenured professor at Harvard by the age of 29 the young... “Woodward largely taught principles and values. He showed us by • Published 196 papers before his death at age example and precept that if anything is worth 62 doing, it should be done intelligently, intensely • Received 24 honorary degrees and passionately.” • Received 26 medals & awards including the -Daniel Kemp National Medal of Science in 1964, the Nobel Prize in 1965, and he was one of the first recipients of the Arthur C.
    [Show full text]
  • Toxicological Profile for Pyridine
    TOXICOLOGICAL PROFILE FOR PYRIDINE Agency for Toxic Substances and Disease Registry U.S. Public Health Service September 1992 ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. 1 1. PUBLIC HEALTH STATEMENT This Statement was prepared to give you information about pyridine and to emphasize the human health effects that may result from exposure to it. The Environmental Protection Agency (EPA) has identified 1,177 sites on its National Priorities List (NPL). Pyridine has been found at 4 of these sites. However, we do not know how many of the 1,177 NPL sites have been evaluated for pyridine. As EPA evaluates more sites, the number of sites at which pyridine is found may change. This information is important for you to know because pyridine may cause harmful health effects and because these sites are potential or actual sources of human exposure to pyridine. When a chemical is released from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment as a chemical emission. This emission, which is also called a release, does not always lead to exposure. You can be exposed to a chemical only when you come into contact with the chemical. You may be exposed to it in the environment by breathing, eating, or drinking substances containing the chemical or from skin contact with it. If you are exposed to a hazardous chemical such as pyridine, several factors will determine whether harmful health effects will occur and what the type and severity of those health effects will be.
    [Show full text]
  • Enantioselective Alkylation of Aldehydes
    Angewandte Chemie International Edition: DOI: 10.1002/anie.201503789 Synthetic Methods Hot Paper German Edition: DOI: 10.1002/ange.201503789 Enantioselective a-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from b- Cyanoaldehydes** Eric R. Welin, Alexander A. Warkentin, Jay C. Conrad, and David W. C. MacMillan* Abstract: The combination of photoredox catalysis and Recently, we questioned whether this dual photoredox- enamine catalysis has enabled the development of an enantio- organocatalysis platform could be translated to the asym- selective a-cyanoalkylation of aldehydes. This synergistic metric catalytic alkylation of aldehydes using a-bromo catalysis protocol allows for the coupling of two highly cyanoalkyls, a protocol that would generate b-cyanoalde- versatile yet orthogonal functionalities, allowing rapid diversi- hydes in one step. As a critical design element, we recognized fication of the oxonitrile products to a wide array of that a-bromo cyanoalkylating reagents would not be suitable medicinally relevant derivatives and heterocycles. This meth- electrophiles for most catalytic enolate addition pathways; odology has also been applied to the total synthesis of the however, the corresponding open-shell radicals, derived by lignan natural product (À)-bursehernin. one-electron reduction of a-bromonitriles, should readily undergo coupling with transiently generated chiral enamines. The enantioselective a-alkylation of carbonyl compounds In addition, the nitrile functional group offers
    [Show full text]
  • Electrochemistry and Photoredox Catalysis: a Comparative Evaluation in Organic Synthesis
    molecules Review Electrochemistry and Photoredox Catalysis: A Comparative Evaluation in Organic Synthesis Rik H. Verschueren and Wim M. De Borggraeve * Department of Chemistry, Molecular Design and Synthesis, KU Leuven, Celestijnenlaan 200F, box 2404, 3001 Leuven, Belgium; [email protected] * Correspondence: [email protected]; Tel.: +32-16-32-7693 Received: 30 March 2019; Accepted: 23 May 2019; Published: 5 June 2019 Abstract: This review provides an overview of synthetic transformations that have been performed by both electro- and photoredox catalysis. Both toolboxes are evaluated and compared in their ability to enable said transformations. Analogies and distinctions are formulated to obtain a better understanding in both research areas. This knowledge can be used to conceptualize new methodological strategies for either of both approaches starting from the other. It was attempted to extract key components that can be used as guidelines to refine, complement and innovate these two disciplines of organic synthesis. Keywords: electrosynthesis; electrocatalysis; photocatalysis; photochemistry; electron transfer; redox catalysis; radical chemistry; organic synthesis; green chemistry 1. Introduction Both electrochemistry as well as photoredox catalysis have gone through a recent renaissance, bringing forth a whole range of both improved and new transformations previously thought impossible. In their growth, inspiration was found in older established radical chemistry, as well as from cross-pollination between the two toolboxes. In scientific discussion, photoredox catalysis and electrochemistry are often mentioned alongside each other. Nonetheless, no review has attempted a comparative evaluation of both fields in organic synthesis. Both research areas use electrons as reagents to generate open-shell radical intermediates. Because of the similar modes of action, many transformations have been translated from electrochemical to photoredox methodology and vice versa.
    [Show full text]
  • A Synergistic LUMO Lowering Strategy Using Lewis Acid Catalysis in Water to Enable Photoredox Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue A synergistic LUMO lowering strategy using Lewis acid catalysis in water to enable photoredox Cite this: Chem. Sci.,2018,9,7096 – All publication charges for this article catalytic, functionalizing C C cross-coupling of have been paid for by the Royal Society † of Chemistry styrenes Elisabeth Speckmeier, Patrick J. W. Fuchs and Kirsten Zeitler * Easily available a-carbonyl acetates serve as convenient alkyl radical source for an efficient, photocatalytic cross-coupling with a great variety of styrenes. Activation of electronically different a-acetylated acetophenone derivatives could be effected via LUMO lowering catalysis using a superior, synergistic combination of water and (water-compatible) Lewis acids. Deliberate application of fac-Ir(ppy)3 as photocatalyst to enforce an oxidative quenching cycle is crucial to the success of this (umpolung type) transformation. Mechanistic particulars of this dual catalytic coupling reaction have been studied in detail using both Stern–Volmer and cyclic voltammetry Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Received 12th May 2018 experiments. As demonstrated in more than 30 examples, our water-assisted LA/photoredox Accepted 17th July 2018 catalytic activation strategy allows for excess-free, equimolar radical cross-coupling and subsequent DOI: 10.1039/c8sc02106f formal Markovnikov hydroxylation to versatile 1,4-difunctionalized products in good to excellent rsc.li/chemical-science yields. redox properties: with an oxidation potential of only 0.66 V vs. Introduction À SCE (Eox(Brc/Br ) ¼ 0.66 V) mesolytically cleaved bromide Visible light photocatalysis as a powerful tool for the selective anions can easily get oxidized to the corresponding bromine This article is licensed under a generation of radicals has given rise to numerous unprece- radicals and hence potentially may also form elemental Br2 by 8–10 dented C–C-coupling reactions in recent years.1 Especially alkyl most common photocatalysts.
    [Show full text]
  • Thiocyanate Pyridine Complexes
    W&M ScholarWorks Undergraduate Honors Theses Theses, Dissertations, & Master Projects 5-2017 Structural Comparison of Copper(II) Thiocyanate Pyridine Complexes Joseph V. Handy College of WIlliam & Mary Follow this and additional works at: https://scholarworks.wm.edu/honorstheses Part of the Inorganic Chemistry Commons Recommended Citation Handy, Joseph V., "Structural Comparison of Copper(II) Thiocyanate Pyridine Complexes" (2017). Undergraduate Honors Theses. Paper 1100. https://scholarworks.wm.edu/honorstheses/1100 This Honors Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Undergraduate Honors Theses by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Structural Comparison of Copper(II) Thiocyanate Pyridine Complexes A thesis submitted in partial fulfillment of the requirement for the degree of Bachelor of Science in Chemistry from The College of William & Mary by Joseph Viau Handy Accepted for ____________________________ ________________________________ Professor Robert D. Pike ________________________________ Professor Deborah C. Bebout ________________________________ Professor David F. Grandis ________________________________ Professor William R. McNamara Williamsburg, VA May 3, 2017 1 Table of Contents Table of Contents…………………………………………………...……………………………2 List of Figures, Tables, and Charts………………………………………...…………………...4 Acknowledgements….…………………...………………………………………………………6
    [Show full text]
  • Efficient Synthesis of Novel Pyridine-Based Derivatives Via
    molecules Article Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities Gulraiz Ahmad 1, Nasir Rasool 1,*, Hafiz Mansoor Ikram 1, Samreen Gul Khan 1, Tariq Mahmood 2, Khurshid Ayub 2, Muhammad Zubair 1, Eman Al-Zahrani 3, Usman Ali Rana 4, Muhammad Nadeem Akhtar 5 and Noorjahan Banu Alitheen 6,* 1 Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan; [email protected] (G.A.); [email protected] (H.M.I.); [email protected] (S.G.K.); [email protected] (M.Z.) 2 Department of Chemistry, COMSATS Institute of Information Technology, University Road, Tobe Camp, 22060 Abbottabad, Pakistan; [email protected] (T.M.); [email protected] (K.A.) 3 Chemistry Department, Faculty of Science, Taif University, 888-Taif, Saudi Arabia; [email protected] 4 Sustainable Energy Technologies Center, College of Engineering, P.O. Box 800, King Saud University, Riyadh 11421, Saudi Arabia; [email protected] 5 Faculty of Industrial Sciences & Technology, University Malaysia Pahang, Lebuhraya Tun, Razak 26300, Kuantan Pahang, Malaysia; [email protected] 6 Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, Serdang, Selangor Darul Ehsan 43400, Malaysia * Correspondence: [email protected] (N.R.); [email protected] (N.B.A.); Tel.: +92-332-7491790 (N.R.); +60-3-8946-7471 (N.B.A.); Fax: +92-41-9201032 (N.R.); +60-3-8946-7510 (N.B.A.) Academic Editor: Diego Muñoz-Torrero Received: 20 November 2016; Accepted: 6 January 2017; Published: 27 January 2017 Abstract: The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i.
    [Show full text]
  • Heterocyclic Chemistrychemistry
    HeterocyclicHeterocyclic ChemistryChemistry Professor J. Stephen Clark Room C4-04 Email: [email protected] 2011 –2012 1 http://www.chem.gla.ac.uk/staff/stephenc/UndergraduateTeaching.html Recommended Reading • Heterocyclic Chemistry – J. A. Joule, K. Mills and G. F. Smith • Heterocyclic Chemistry (Oxford Primer Series) – T. Gilchrist • Aromatic Heterocyclic Chemistry – D. T. Davies 2 Course Summary Introduction • Definition of terms and classification of heterocycles • Functional group chemistry: imines, enamines, acetals, enols, and sulfur-containing groups Intermediates used for the construction of aromatic heterocycles • Synthesis of aromatic heterocycles • Carbon–heteroatom bond formation and choice of oxidation state • Examples of commonly used strategies for heterocycle synthesis Pyridines • General properties, electronic structure • Synthesis of pyridines • Electrophilic substitution of pyridines • Nucleophilic substitution of pyridines • Metallation of pyridines Pyridine derivatives • Structure and reactivity of oxy-pyridines, alkyl pyridines, pyridinium salts, and pyridine N-oxides Quinolines and isoquinolines • General properties and reactivity compared to pyridine • Electrophilic and nucleophilic substitution quinolines and isoquinolines 3 • General methods used for the synthesis of quinolines and isoquinolines Course Summary (cont) Five-membered aromatic heterocycles • General properties, structure and reactivity of pyrroles, furans and thiophenes • Methods and strategies for the synthesis of five-membered heteroaromatics
    [Show full text]
  • The Mechanism of Pyridine Hydrogenolysis on Molybdenum-Containing Catalysts III
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Universiteit Twente Repository JOURNAL OF CATALYSIS 34, 215-229 (1974) The Mechanism of Pyridine Hydrogenolysis on Molybdenum-Containing Catalysts III. Cracking, Hydrocracking, Dehydrogenation and Disproportionation of Pentylamine J. SONNEMANS” AND P. MARS l’wente University of Technology, Enschede, The Netherlands Received October 30, 1973 The conversion of pentylamine on a MoOrA1203 catalyst was studied between 250 and 350°C at various hydrogen pressures. The reactions observed were cracking to pentene and ammonia, hydrocracking to pentane and ammonia, dehydrogenation to pentanimine and butylcarbonitrile, and disproportionation to ammonia and dipentylamine. The equilibrium between pentylamine, dipentylamine and ammonia appeared to be established under most of the experimental conditions. The equilibrium constant is about 9 at 250°C and about 5 at 320°C. The disproportionation reaction is zero order in hydrogen and of -1 order in the initial pentylamine pressure. Dehydrogenation was observed at low hydrogen pressures, and especially at higher temperatures; the reaction is first order in pentylamine. Both cracking and hydrocracking take place, mainly above 300°C. Hydrocracking appears to be half order in hydrogen; the rate of cracking is almost independent of the hydrogen pressure. The hydrocarbon formation is of zero order in pentyl- amine or dipentylamine. The same type of reactions (except hydrocracking) take place on alumina, but with a far lower reaction rate. INTRODUCTION catalysts at hydrogen pressures of about One of the intermediates formed in the 60 atm (Z-4). They reported a high rate hydrogenolysis of pyridine is pentylamine of ammonia formation from the primary (1).
    [Show full text]