DOCSLIB.ORG

Intermolecular 2+2 Imine-Olefin Photocycloadditions Enabled by Cu(I)-Alkene MLCT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Intermolecular 2+2 Imine-Olefin Photocycloadditions Enabled by Cu(I)-Alkene MLCT Intermolecular 2+2 Imine-Olefin Photocycloadditions Enabled by Cu(I)-Alkene MLCT Daniel M. Flores, Michael L. Neville, and Valerie A. Schmidt* University of California San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Drive, La Jolla, CA, 92093, USA *Correspondence to: [email protected] Abstract: 2+2 Photocycloadditions are idealized, convergent approaches to the construction of 4- membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Ligand design allows this base metal-catalyzed method to achieve 2+2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway. Nitrogen heterocycles are prevalent motifs in small molecule pharmaceuticals and their rapid construction continues to drive new reaction development.1 While 3-, 5- and 6-membered N-heterocycles are exceptionally common, made possible by a variety of synthetically accessible routes for their construction, 4-membered heterocycles are scarce by comparison despite the promising biological activity displayed by many azetidine-containing compounds.2,3,4,5,6,7 The 2+2 photocycloaddition of two p-components is a prototypical approach to 4-membered ring construction. While limited in generality, the Paternò-Büchi reaction forms oxetanes through direct irradiation of a carbonyl C=O double bond followed by C=C double bond capture.8,9,10 Aza-Paternò-Büchi analogs using imines in place of aldehydes or ketones do not generally result in the formation of azetidines due to the low barrier E/Z isomerization available upon excitation of the imine C=N double bond.11 Maruoka reported a rare intermolecular azetidine-forming 2+2 photocycloaddition example using naphthyl derived N-sulfonyl aldimines and styrene or benzofuran (Figure 1A).12 However, this reactivity was exclusive to these substrate pairs and was enabled by a pi- stacking association of the substrates prior to excitation. Alternative strategies that overcome the challenge of imine isomerization have used cyclic imines which cannot undergo E/Z isomerization,13,14,15 via preferential excitation of a conjugated C=C double bond tethered to an imine,16,17 or both (Figure 1B). Despite these advances, catalyst-controlled approaches to 2+2 imine-olefin photocycloaddition (IOPC) remain limited as general strategies for azetidine construction. A. π-Stacking pre-organizationa TsN NTs 365 nm hv + 2-nap Ph 61% yield 2-nap Ph B. Intramolecular 2+2 photocycloadditionb R1 R1 O cat. xanthone N N O N N 350 nm hv 2 R2 R OR Ph RO Ph cat. [Ir] N N blue LEDs H H X X C. Cyclic glyoxylate iminec R1 N O Me R1 cat. [Ir] N O Me EtO Me + 427 nm hv 2 Me 2 3 R R R 3 O R CO2Et D. Intermolecular imine-olefin 2+2 (this work): H R3 R3 N cat. TpCu N + 100 W Hg lamp R1 R1 R2 R2 H R1 = H, alkyl, R2 = alkyl, R3 = alkyl, allyl, OMe Fig. 1. C=N Bond 2+2 photocycloadditions. aSee ref. 12. bSee refs. 13-14,16-17. cSee ref. 15. Transition metal compounds capable of photoexcitation via metal to ligand charge transfer (MLCT) to achieve intermolecular electron or energy transfer have recently gained significant recognition for their use in chemical synthesis.18,19,20,21 Meggers reported photochemical cyclobutane synthesis by in situ formation of the active chromophore as a chiral at metal, O-bound Rh-enone compound.22 Yoon achieved enantioselective 2+2 photocycloaddition of conjugated alkenes to form cyclobutanes via Dexter energy transfer through H-bonding and p-p interactions of substrate 3-alkoxyquinolones and Ir-based photocatalysts.23 We recently reported a Cu-catalyzed 2+2 carbonyl-olefin photocycloaddition approach for oxetane formation by inverting conventional Paternò-Büchi reactivity and achieved alkene activation via coordination followed by MLCT.24 We hypothesized that 2+2 imine-olefin photocycloadditions (IOPC) may be achieved to access azetidines by coordination and MLCT with either the alkene or imine p- component (Figure 1C). To assess this hypothesis, we irradiated a 1:3 mixture of N-butyl-2-methylpropan-1-imine (1) and norbornene with catalytic hydrotris(pyrazolyl)borate copper(I) (TpCu) in diethyl ether using a 100 W Hg lamp for 8 h which resulted in formation of the corresponding azetidine 1A in 31% yield with exclusive exo selectivity (Table 1, entry 1). Removing either TpCu or any light source both resulted in no appreciable formation of 1A (entries 2 and 3). Using a small excess of imine relative to norbornene (1.1:1) improved reaction efficiency (entry 4), while using a 3-fold excess of 1, produced 1A in 79% yield (entry 5). Application of a 300 nm cut-on filter resulted in a significant decrease in the yield of 1A to 39% even after a prolonged 36 h reaction time suggesting that product forming irradiation occurred at wavelengths shorter than 300 nm (entry 6). Using CuCl or CuOTf in place of TpCu did not result in any detectable quantities of 1A (entries 7 and 8), underscoring the importance of the coordination environment of the Cu(I) source used. Reaction optimization: H nBu nBu N TpCu (20 mol %) + N 100 W Hg lamp C2 H iPr Et2O (0.15 M), 24 h H 1 iPr H 1 equiv 3 equiv standard conditions 1A Entry deviation from standard conditions Yield of 1Aa 1 none 31%b 2 no TpCu <5% 3 no light n.d. 4 1.1 equiv 1, 1 equiv norbornene 55% 5 3 equiv 1, 1 equiv norbornene 79% 6 entry 5 with 300 nm cut-on filter 39%c 7 CuCl (20 mol %) in place of TpCu n.d. 8 CuOTf (20 mol %) in place of TpCu n.d. Table 1. Summary of reaction optimization studies. a1A was detected as a >95:5 exo:endo mixture and 62:48 diastereomer mixture at C2 in all experiments; yields determined by 1H NMR analysis of crude reactions using durene as an internal standard. bReaction time 8 h due to consumption of 1. cReaction time 36 h. In exploration of imines that similarly undergo Cu-catalyzed 2+2 IOPC with norbornene, we found that aldimines from N-allyl amine and isobutyraldehyde, 3-(methylthio)propanal, and melonal all successfully were converted to their corresponding azetidines, 2, 3, and 4, respectively, in good to excellent yields (Figure 2). Imines bearing cyclopropyl groups participated in this 2+2 IOPC to produce azetidines exclusively without the detection of cyclopropyl ring-opened products (5 and 6).25,26 While imines derived from acetophenone, benzaldehyde, or aniline did not participate in this 2+2 IOPC, a phenethylamine derived isobutyraldimine, produced azetidine 7, suggesting that arene groups are tolerated when not conjugated to the imine. Heterocycles including tetrahydrofuran (8), thiophene (9), and morpholine (10) as well as an acyclic 3° amine (12) were all well tolerated in this process. Productive 2+2 IOPC was particularly notable in the presence of a g-lactam (11), showcasing the chemoselectivity of olefin activation even in the presence of other p-components capable of absorbing UV light. Imines derived from ketones also reacted efficiently to produce the corresponding azetidines even when the imine also contained Lewis-basic 3° amine (13), acetal (14), or ether (15) functionalities. H R3 R TpCu (20 mol %) R3 N 100 W Hg lamp N R + 1 R1 R2 R Et2O, 24-48 h R R R2 H Imine variation (R=norbornane): H H H H allyl R H nBu allyl allyl R N N R N R N N R Me R R R H R i R MeS i H Pr H H Pr H 2 92% yield 3 62% yield 4 71% yield 5 95% yielda 6 94% yielda 55:45 C2 dr 55:45 C2 dr 55:45 C2 dr 55:45 C2 dr 55:45 C2 dr H O H H O H Ph O R S R H N R N N N N N R N R R R R i i R i Pr Pr H R i Pr H H i Pr H Pr H 7 51% yield 8 71% yield 9 59% yield 10 51% yield 11 60% yield 51:49 C2 dr 58:42 C2 dr 67:32 C2 dr 64:34 C2 dr 59:41 C2 dr H H H H H H Et N R N R R N R MeO R 2 N R N N N R R R R R R H H iPr H O H H H MeN O n 12 37% yield O 14 n = 1, 16 95% yielda 54:46 C2 dr 13 91% yield 52% yield 15 66% yield n = 2, 17 78% yield 19 91% yield n = 3, 18 58% yielda Alkene variation: O H H H 23-HI salt H allyl allyl CN allyl N allyl N Me N N H H H H 20 95% yield 21 85% yield 22 47% yield 23 82% yield 65:35 rr 56:44 rr, 75:25 dr 50:50 rr, 60:40 dr 53:47 dr H O O allyl OTBS H O H H O H N allyl allyl allyl allyl N N N N O O O NMe H H iPr H H O MeN O H O O 24 91% yield 50:50 rr, 90:10 dr 25 98% yield (51%)b 26 68% yield (13%)b 27 96% yield (47%)b 28 49% yield (25%)b Fig. 2. 2+2 Imine-Olefin photocycloaddition reaction scope. All reactions carried out with 1 equiv norbornene, 1.1 equiv imine, 20 mol % TpCu, in diethyl ether (0.15 M) and irradiated with a 100 W Hg lamp; all yields are of isolated material following purification via basic alumina chromatography and diastereomeric ratios were determined via gas chromatography of crude reaction mixtures; all products detected as >95:5 exo:endo diastereomers.
Load more

Recommended publications
  • Part I: Carbonyl-Olefin Metathesis of Norbornene
    Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2016 1 © 2016 Zara Maxine Seibel All Rights Reserved 2 ABSTRACT Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel This thesis details progress towards the development of an organocatalytic carbonyl- olefin metathesis of norbornene. This transformation has not previously been done catalytically and has not been done in practical manner with stepwise or stoichiometric processes. Building on the previous work of the Lambert lab on the metathesis of cyclopropene and an aldehyde using a hydrazine catalyst, this work discusses efforts to expand to the less stained norbornene. Computational and experimental studies on the catalytic cycle are discussed, including detailed experimental work on how various factors affect the difficult cycloreversion step. The second portion of this thesis details the use of chiral cyclopropenimine bases as catalysts for asymmetric Michael reactions. The Lambert lab has previously developed chiral cyclopropenimine bases for glycine imine nucleophiles. The scope of these catalysts was expanded to include glycine imine derivatives in which the nitrogen atom was replaced with a carbon atom, and to include imines derived from other amino acids. i Table of Contents List of Abbreviations…………………………………………………………………………..iv Part I: Carbonyl-Olefin Metathesis…………………………………………………………… 1 Chapter 1 – Metathesis Reactions of Double Bonds………………………………………….. 1 Introduction………………………………………………………………………………. 1 Olefin Metathesis………………………………………………………………………… 2 Wittig Reaction…………………………………………………………………………... 6 Tebbe Olefination………………………………………………………………………... 9 Carbonyl-Olefin Metathesis…………………………………………………………….
    [Show full text]
  • Amide Activation: an Emerging Tool for Chemoselective Synthesis
    Featuring work from the research group of Professor As featured in: Nuno Maulide, University of Vienna, Vienna, Austria Amide activation: an emerging tool for chemoselective synthesis Let them stand out of the crowd – Amide activation enables the chemoselective modification of a large variety of molecules while leaving many other functional groups untouched, making it attractive for the synthesis of sophisticated targets. This issue features a review on this emerging field and its application in total synthesis. See Nuno Maulide et al., Chem. Soc. Rev., 2018, 47, 7899. rsc.li/chem-soc-rev Registered charity number: 207890 Chem Soc Rev View Article Online REVIEW ARTICLE View Journal | View Issue Amide activation: an emerging tool for chemoselective synthesis Cite this: Chem. Soc. Rev., 2018, 47,7899 Daniel Kaiser, Adriano Bauer, Miran Lemmerer and Nuno Maulide * It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. Received 27th April 2018 However, a significant body of research on the selective activation of amides to achieve powerful DOI: 10.1039/c8cs00335a transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product rsc.li/chem-soc-rev synthesis, highlighting the synthetic applications and the potential of this approach. Creative Commons Attribution 3.0 Unported Licence.
    [Show full text]
  • Detection of Phenethylamine, Amphetamine, and Tryptamine Imine By-Products from an Acetone Extraction
    Detection of Phenethylamine, Amphetamine, and Tryptamine Imine By-Products from an Acetone Extraction Mary A. Yohannan* and Arthur Berrier U.S. Department of Justice Drug Enforcement Administration Special Testing and Research Laboratory 22624 Dulles Summit Court Dulles, VA 20166 [email: mary.a.yohannan -at- usdoj.gov] ABSTRACT: The formation of imine by-products from phenethylamines, amphetamines, and tryptamines upon an acetone extraction is presented. These imine by-products were characterized using GC/MSD and exhibited preferential cleavage at the α-carbon of the alkyl chain. Further characterization of the imine by-products of phenethylamine and tryptamine was done using IR and NMR. KEYWORDS: phenethylamine, tryptamine, imine, acetone, schiff base, drug chemistry, forensic chemistry In most forensic laboratories, the solvents used to extract at the α-carbon on the alkyl chain. In addition to GC/MS, the drugs are chosen based upon their solubility properties and their imines formed from phenethylamine base and tryptamine base ability to not interact with the drug. In fact, there are very few were characterized by Fourier transform-infrared spectroscopy publications where a solvent used to extract a drug reacts with (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. the drug and forms by-products [1-3]. This laboratory recently discovered that an additional Experimental component was formed when acetone was used to extract a Solvents, Chemicals, and Materials sample containing a known tryptamine. Analysis by gas Acetone was ACS/HPLC grade from Burdick and Jackson chromatography/mass spectroscopy (GC/MS) of the acetone Laboratories (Muskegon, MI). Phenethylamine base and extract yielded an extra peak in the total ion chromatogram that tryptamine base were obtained from Sigma-Aldrich Chemicals was approximately half the abundance of the known tryptamine (Milwaukee, WI).
    [Show full text]
  • The Carcinogenicity of the O-Methoxy Derivatives of N-2-Fluorenylacetamide and of Related Compounds in the Rat
    [CANCER RESEARCH 28, 234-244, February 1968] The Carcinogenicity of the o-Methoxy Derivatives of N-2-Fluorenylacetamide and of Related Compounds in the Rat H. R. Gutmann, S. B. Galitski, and W. A. Foley Laboratory ]or Cancer Research, Veterans Administration Hospital, and Department o] Biochemistry, University o] Minnesota, Minneapolis, Minnesota 55417 SUMMARY acetamide by the sequential reactions of deacetylation and oxidation. In order to test the idea that the lack of carcinogenicity of the o-amidofluorenols, N- (1-hydroxy-2-fluorenyl) acetamide and INTRODUCTION N-(3-hydroxy-2-fluorenyl)acetamide, is due to the hydrophilic phenolic hydroxyl group, the methylated derivatives, N-(1- Several model studies from this laboratory have shown that methoxy-2-fluorenyl)acetamide and N-(3-methoxy-2-fluorenyl) the o-quinone imines, 2-imino-l,2-fluorenoquinone and 2-imino- acetamide as well as the hydrochlorides of 1-methoxy-2-fluo- 2,3-fluorenoquinone, which are derived from the carcinogen renamine and 3-methoxy-2-fiuorenamine, were prepared, and N-2-fluorenylacetamide by the sequential enzymatic reactions their carcinogenicity was evaluated in the rat. N-(1-Methoxy- of hydroxylation, deacetylation, and oxidation (6, 10, 12, 27, 2-fluorenyl)acetamide and 1-methoxy-2-fluorenamine hydro- 34, 35), form stable adducts with a variety of proteins (17, 18). chloride, when administered orally to male rats for 5 months, However, the relevance of the binding of these o-quinone imines gave a tumor incidence of 27 and 50%, respectively. Approxi- to chemical carcinogenesis has remained obscure largely be- mately one-half of the lesions produced by either com- cause the o-amidofluorenols, 1-OH-AAF 2 and 3-OH-AAF pound were adenocarcinomas of the small intestine.
    [Show full text]
  • Synthesis and Characterization of Novel Imine-Linked Covalent Organic Frameworks
    Synthesis and Characterization of Novel Imine-Linked Covalent Organic Frameworks THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Toni Beirl Graduate Program in Chemistry The Ohio State University 2015 Master's Examination Master's Examination Committee: Professor Psaras McGrier, Advisor Professor Jovica D. Badjic Copyrighted by Toni M.Beirl 2015 Abstract Covalent organic frameworks (COFs) are a class of porous crystalline materials composed of light elements (such as H, B, C, N, and O) that are linked by covalent bonds. The modular nature of COFs permits the integration of various π-conjugated molecular building blocks into highly ordered polymeric structures with low densities and high thermal stabilities making them suitable for applications related to energy storage and conversion, catalysis, and gas storage. Since a majority of the early examples of COFs contained boroxine or boronate esters linkages, many of these materials were often susceptible to hydrolysis when exposed to aqueous conditions resulting in decomposition of the framework. The recent discovery of imine-linked COFs has sparked the creation of COFs with superior chemical stability on account of an intramolecular hydrogen bond between the hydroxyl and imine functional groups, which enhances their stability in aqueous and acidic environments. Utilizing this feature, this thesis examines the synthesis and gas adsorption properties of novel imine-linked COFs that contain 1,3,5-tris(styryl)benzene and 1,3,5– tris(arylethynyl)benzene π-conjugated units. By creating analogs which were fluorescent in both solution and solid-state, studies were conducted to determine their ability to serve as chemical sensors for explosives.
    [Show full text]
  • Modeling Nitrile-Terminated Polypropylene Imine Dendrimer Fragmentation with DFT
    Modeling Nitrile-Terminated Polypropylene Imine Dendrimer Fragmentation with DFT Eric W. Martin, Jacob T. Kilgore and William D. Price Marshall University Department of Chemistry Huntington, WV 25755 Abstract Dendrimers are regularly branched polymers with a treelike structure that can be tuned for size, shape, and functionality. This relatively new class of compound has shown potential for useful host-guest chemistries including site-specific drug delivery via molecular recognition, catalysis, and nonlinear optics. Gas-phase dissociation studies have been initiated to probe the structure and stability of the half and first generation polypropylene dendrimer complexes and to develop an analytical framework for their characterization. These dissociation studies result in fragmentation products of mass-to-charge ratios that can be assigned to multiple possible isomers formed by potentially competing mechanisms. Since these reactions are under kinetic control we will present density functional results for modeling the dissociation mechanisms for the most abundantly produced fragments from the protonated dendrimers. The BMK functional in conjunction with a moderately-sized basis has been chosen for its utility in determining transition state energies and kinetic parameters. Introduction Dendrimers have several promising and exciting possibilities ranging from use as chelating agents1 to site-specific host-guest chemistry and controlled gene2 and drug delivery systems3. Distinct properties of dendrimers, such as well-defined architecture and a high ratio of moieties to molecular volume, make these materials highly interesting for the development of nanomaterials and medicines4. The compact, nanometer- scale structure of the hyperbranched polymer results in high solubility and low solution viscosity5, while the dense arrangement of functional groups allows pharmaceutical agents and magnetic resonance imaging contrast dyes to be chemically grafted to the dendrimer in concentrated amounts6.
    [Show full text]
  • Chapter 19 the Chemistry of Aldehydes and Ketones. Addition Reactions
    Instructor Supplemental Solutions to Problems © 2010 Roberts and Company Publishers Chapter 19 The Chemistry of Aldehydes and Ketones. Addition Reactions Solutions to In-Text Problems 19.1 (b) (d) (e) (g) 19.2 (a) 2-Propanone (d) (E)-3-Ethoxy-2-propenal (f) 4,4-Dimethyl-2,5-cyclohexadienone 19.3 (b) 2-Cyclohexenone has a lower carbonyl stretching frequency because its two double bonds are conjugated. 19.4 (b) The compound is 2-butanone: (c) The high frequency of the carbonyl absorption suggests a strained ring. (See Eq. 19.4, text p. 897.) In fact, cyclobutanone matches the IR stretching frequency perfectly and the NMR fits as well: 19.6 The structure and CMR assignments of 2-ethylbutanal are shown below. The two methyl groups are chemically equivalent, and the two methylene groups are chemically equivalent; all carbons with different CMR chemical shifts are chemically nonequivalent. INSTRUCTOR SUPPLEMENTAL SOLUTIONS TO PROBLEMS • CHAPTER 19 2 19.7 (a) The double bonds in 2-cyclohexenone are conjugated, but the double bonds in 3-cyclohexenone are not. Consequently, 2-cyclohexenone has the UV spectrum with the greater lmax. 19.9 Compound A, vanillin, should have a p T p* absorption at a greater lmax when dissolved in NaOH solution because the resulting phenolate can delocalize into the carboxaldehyde group; the resulting phenolate from compound B, isovanillin, on the other hand, can only delocalize in the aromatic ring. 19.11 The mass spectrum of 2-heptanone should have major peaks at m/z = 43 (from a-cleavage), 71 (from inductive cleavage), and 58 (from McLafferty rearrangement).
    [Show full text]
  • Enamine-Based Organocatalysis with Proline And
    Acc. Chem. Res. 2004, 37, 580-591 carbon bond in a stereospecific fashion. These same Enamine-Based Organocatalysis features are typically absent in traditional synthetic asym- with Proline and Diamines: The metric aldol methodologies.2,3 Our ideal synthetic catalyst would be one that could Development of Direct Catalytic generate enamines from any number of aldehydes or ketones and then direct bond-forming reactions with a Asymmetric Aldol, Mannich, wide variety of electrophiles beyond the carbonyl elec- Michael, and Diels-Alder trophiles of the aldol reaction. Further, since these cata- lysts also generate imines as part of their reaction mech- Reactions anism, electrophilic catalysis might facilitate diverse WOLFGANG NOTZ, FUJIE TANAKA, AND reactions with nucleophiles. Such an antibody might be termed an ªopen-active siteº catalytic antibody. Indeed, CARLOS F. BARBAS, III* The Skaggs Institute for Chemical Biology and the we were able to demonstrate that our aldolase antibodies Departments of Chemistry and Molecular Biology, The could catalyze not only a wide range of intra- and Scripps Research Institute, 10550 North Torrey Pines Road, intermolecular aldol reactions but also decarboxylation La Jolla, California 92037 reactions via imine catalysis and certain Michael reactions Received February 2, 2004 as well.2 Significantly for what would become our studies in organocatalysis, in our search for ªopen-active siteº ABSTRACT antibody catalysis, we studied the potential of aldolase Enamines and imines have long been recognized as key intermedi- antibodies to catalyze the addition of ketones to nitrosty- ates in enzyme catalysis, particularly within a class of enzymes renes in Michael reactions, the addition of ketones to organic chemists would very much like to emulate, the aldolases.
    [Show full text]
  • Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry
    Journal of Visualized Experiments www.jove.com Video Article Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry Maha A. Aljuhani1, Jérémie D.A. Pelletier1, Jean-Marie Basset1 1 KAUST Catalysis Center, Division of Physical Sciences and Engineering, King Abdullah University of Science and Technology (KAUST) Correspondence to: Jérémie D.A. Pelletier at [email protected] URL: https://www.jove.com/video/59409 DOI: doi:10.3791/59409 Keywords: Chemistry, Issue 152, surface organometallic chemistry (SOMC), metal-nitrogen fragments, catalysis by design, heterogeneous catalysis, dehydroxylated silica, imine metathesis, well-defined single-site catalysts Date Published: 10/18/2019 Citation: Aljuhani, M.A., Pelletier, J.D., Basset, J.M. Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry. J. Vis. Exp. (152), e59409, doi:10.3791/59409 (2019). Abstract 1 With this protocol, a well-defined singlesite silica-supported heterogeneous catalyst [(≡Si-O-)Hf(=NMe)(η -NMe2)] is designed and prepared according to the methodology developed by surface organometallic chemistry (SOMC). In this framework, catalytic cycles can be determined by isolating crucial intermediates. All air-sensitive materials are handled under inert atmosphere (using gloveboxes or a Schlenk line) or high -5 vacuum lines (HVLs, <10 mbar). The preparation of SiO2-700 (silica dehydroxylated at 700 °C) and subsequent applications (the grafting of complexes and catalytic runs) requires the use of HVLs and double-Schlenk techniques. Several well-known characterization methods are used, such as Fourier-transform infrared spectroscopy (FTIR), elemental microanalysis, solid-state nuclear magnetic resonance spectroscopy (SSNMR), and state-of-the-art dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP-SENS).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,686,507 B2 Watson Et Al
    US006686,507B2 (12) United States Patent (10) Patent No.: US 6,686,507 B2 Watson et al. (45) Date of Patent: Feb. 3, 2004 (54) PURIFICATION OF 2-METHOXY-5- 5,294,744 A 3/1994 Godek et al. ............... 568/442 TRFLUOROMETHOXYBENZALDEHYDE 5,773,450 A 6/1998 Lowe et al. ................ 514/329 5,807,867 A 9/1998 Ito et al. ..................... 514/305 (75) Inventors: Timothy J. N. Watson, Waterford, CT (US); Patrice Arpin, Sorel-Tracy (CA); OTHER PUBLICATIONS Michael G. Vetelino, North Stonington, CT (US) W. E. Smith, Journal of Organic Chemistry, vol. 37, No. 24, (73) Assignee: Pfizer Inc, New York, NY (US) p. 3972 (1972). (*) Notice: Subject to any disclaimer,- the term of this Chemical Abstracts, 99(15), 1983, No. 122032. patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. Primary Examiner James O. Wilson Assistant Examiner Sikarl A. Witherspoon (21) Appl. No.: 10/314,598 (74) Attorney, Agent, or Firm-Peter C. Richardson; Paul (22) Filed: Dec. 9, 2002 H. Ginsburg; Jolene W. Appleman (65) Prior Publication Data (57) ABSTRACT US 2003/0176741 A1 Sep. 18, 2003 A process for the purification of 2-methoxy-5-trifluoro Related U.S. Application Dat methoxybenzaldehyde oil in which the oil is converted to (60) Provisionalelated application U.S. ApplicationNo. 60/361.931, Uata filed on Mar. 6, amine by reaction of a nitroaniline- with the oil;1. the imine- - is- 2002. isolated as a Solid; and the Solid imine is converted back to (51) Int. Cl. ................................................ C07C 45/90 the 2-methoxy-5-trifluoromethoxy benzaldehyde oil.
    [Show full text]
  • Dynamic Imine Chemistry at Complex Double Emulsion Interfaces
    Dynamic Imine Chemistry at Complex Double Emulsion Interfaces The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Zentner, Cassandra A. et al. "Dynamic Imine Chemistry at Complex Double Emulsion Interfaces." Journal of the American Chemical Society 141, 45 (November 2019): 18048–18055 © 2019 American Chemical Society As Published http://dx.doi.org/10.1021/jacs.9b06852 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/128146 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. Page 1 of 10 Journal of the American Chemical Society 1 2 3 4 5 6 7 Dynamic Imine Chemistry at Complex Double Emulsion Interfaces. 8 † ‡ ‡ † 9 Cassandra A. Zentner, Francesca Anson, S. Thayumanavan,* and Timothy M. Swager* 10 †Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States 11 12 ‡Department of Chemistry, University of Massachusetts – Amherst, Amherst, Massachusetts 01003, United states 13 14 ABSTRACT: Interfacial chemistry provides an opportunity to control dynamic materials. By harnessing the dynamic 15 covalent nature of imine bonds, emulsions are generated in situ, predictably manipulated, and ultimately destroyed along 16 liquid-liquid and emulsion-solid interfaces through simply perturbing imine equilibria. We report the rapid production of 17 surfactants and double emulsions through spontaneous in situ imine formation at the liquid-liquid interface of oil/water. 18 Complex double emulsions with imine surfactants are stable to neutral and basic conditions and display dynamic behavior 19 with acid catalyzed hydrolysis and imine exchange.
    [Show full text]
  • CHEM 341 Problem Set 25 Key Acyl-Transfer Reactions: Back To
    CHEM 341 Problem Set 25 Key Acyl-Transfer Reactions: Back to the Basics The acyl transfer reaction is a very common reaction pathway for carboxylic acid derivatives. It is the reason aspirin works. It is how proteins are made. It is how nylon and Kevlar are synthesized. To understand how it works, we need to look at the reaction itself. acylating agent O nucleophile O Y X R X R Y Acyl group being transferred The reaction consists of two reactants: an acylating agent and a nucleophile. The rate of the reaction (and its mechanism) is dependent on the acylating agent and the nucleophile. For the most part, the reactivity of the acylating agent can be predicted by the stability of the leaving group X:-. The more stable the X:- the more reactive the acylating agent. Think basicity. 1.) Rank the following in terms of reactivity with 1 being the most reactive: O O O O O O Ph O Cl N O H O 4 1 5 3 2 amide anhydride ester acid chloride phenyl ester The more basic the nucleophile, the more reactive it is in acyl transfer chemistry. 2.) Rank the following nucleophiles with 1 being the most reactive: NH OH O 2 Cl 3 1 2 4 3.) O R" cat. O O O + OH H3O O O HO OH R OH R' OH "R OH H2O O R' glycerol fatty acids R O (glycerine) O 4.) O R" O O O OH O 3 NaOH O HO OH R ONa R' ONa "R ONa O R' glycerol surfactants R O (glycerine) O Chem 341 Reaction Sheets: Transesterification O O NaOEt OMe O EtOH Mechanism: O NaOEt OMe EtOH Summary (Key words): The entire reaction is reversible.
    [Show full text]