DOCSLIB.ORG

Regioselectivity of Aniline and Toluidine Nitration with HNO3 And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regioselectivity of Aniline and Toluidine Nitration with HNO3 And Regioselectivity of aniline and toluidine nitration with HNO 3 and H 2 SO 4 in acetic acid Ângelo F. Sousa, João P. Telo, Pedro P. Santos [email protected] Técnico Lisboa, Universidade de Lisboa, Av Rovisco Pais, s/n, 1049 - 001 Lisboa, Portugal ABSTRACT: The goal of this work is to study how the regioselectivity in aniline and toluidine nitration is affected by the resonance and induction effects of N - acetyl and N - succinimidil groups. Starting materi als were protected with acetic and succinic anh ydride, and nitration occured via S E Ar with a HNO 3 /H 2 SO 4 mixture in AcOH. Nitrated products were hydrolyzed and a sample of each experiment was analysed by HPLC. Aniline results show product distribution is controlled by both functional groups’ ortho/para directing and +R effects, yielding similar percentages of 2 - nitroaniline (23%) and 4 - nitroaniline (76%). For 4 - methylacetanilide, regioselectivity control is once again established by the +R effect, favoring the ortho - substituted product (97%). Since succi nimi de group is less activating than the acetamide group, reaction control is taken over by the methyl group, yielding 94% 4 - methyl - 3 - nitroaniline. 3 - methylacetanilide nitration yielded 91% 3 - methyl - 4 - nitroaniline, which is a product favored by both +R eff ect of the acetamide group and +I effect of the methyl group. For N - (3 - methylphenyl) - succinimide, the yield of 3 - methyl - 6 - nitroaniline increased to 62% since the succinimide group has a weaker activating effect due to the electronic pull of its two carbony l groups. For the N - (2 - methylphenyl) - succinimide, product distribution was controlled by the alkyl group, with the main products being ortho / meta substituted, yielding 29% 2 - methyl - 3 - nitroaniline and 55% 2 - methyl - 5 - nitroaniline. This is due to the non - plan ar position between the succinimide group and the aromatic ring, nullifying its +R effect. For the acetanilide derivative, regioselectivity is controlled by its +R effect (45% 2 - methyl - 4 - nitroaniline) and by the +I effect of the methyl group (33% 2 - methyl - 5 - nitroaniline). Overall it was shown that the +R effect of the acetamide groups is stronger than that of the succinimide group. This is due to the presence of one more carbonyl group in the latter, which pull s electrons away fro m the aromatic ring by indu ction ( - I effect) and by resonance ( - R effect) deactivating the starti ng material to an EAS reaction. Experiments with the N - acetyl derivative also showed that +R effect is more important to regioselectivity control than the +I of the alkyl group. This was an expected result, as the non - shared electron pair of the nitrogen atom has a greater importance to the stabilization of the aromatic ring than the e lectron - donating role of the CH 3 . Keywords: nitration, aniline, regioselectivity, Ele ctrophilic Aromatic Substitution 1. Introduction synthesis [3] , to dye [4] and pesticide [5] precursors 1.1 State of the art and many other uses. Given the large number of substracts used as starting mate rial in these Nitration of aromatic compounds has been heavily industries, and th e even larger number of isomers studied since the 19th century due to its importance that can be obtained during nitration, several in several chemical industries. Nitro aromatic synthetic routes have been developed with the species are present in a wide range of value chains objecti ve of maximizing overall conversion of the worth millions of E uros [1] , from the pharmaceutical reaction , as well as the selectivity of the desired industry [2] , us ed as intermediary in benzi midazole 1 isomer. The classical nitration method is the use of 1.2. Electrophilic Aromatic Substitution an HNO 3 /H 2 SO 4 mixture in acetic acid, chloroform EAS is an organic reaction where an atom or group or dichloroethane. Th is synthetic route originates a connected to the aromatic ring is subs tituted by great amount of acid effluents , hazardous to the ano ther. This reaction occurs by a nucleophilic environment. This generally leads to effluen t attack by the electron - rich aromatic ring o n an treatment, which results in an extra cost to the electron - depleted electrophile in a two - step company, reducing its profit. In order to keep up mechanism. The first step is the nucleophilic attack, with the always growing environmental issues, new connecting the aromatic ring to the electroph ile, ways to produce nitro aromatic compounds at an forming an arenium ion, stabilized by resonance. industrial scale are being studied with the main This is a slow step due to the momentary loss of concern b eing the necessity of synthesizing these aromaticity, and it determines the reaction’s overall compounds in mild conditions. The main processes rate. The second step is the loss of the proton include the use of transition - metal complexes as connected to the carbon atom where substitution catalyst s [6] [7] , nitration salts [8] [9] and ozone occurred , thus reestablishing aromaticity. mediated nitration [10] . Other nitro group sources have been investigated , such as VO(NO 3 ) 3 [11] . All these processes enable aromatic compound nitration in mild conditions that do not require the use of concentrated acids, extremely diminishing the environmental impact caused by the reaction. Other concern associated with the development of Scheme 1 - EAS mechanism these new ways of producing nitro aromatic Regioselectivity is mainly affected by the aromatic comp ounds is the desire to establish atom ring’s functional groups. These can either be economical reactions t hat substantially reduce , or activating or deactivating groups. Activating groups elim inate , the amount of effluents that have to be are electron donors by resonance (+R) or by treated before they can be discharged. induction (+I) and speed up the reaction by However, the use of more expensive reactants and increasing the aromatic ring’s electron density, catalysts increases the pro cess’ overall cost . making it more prone to attack an electrophile. Moreover , these new synthetic routes have a much Examples of these groups are NR 2 , NH 2 , OH and narrower range of application when compared to NHCOR . Activating groups are usually ortho / para the classic HNO 3 /H 2 SO 4 method, and are more directors due to the fact that ortho and para difficult to control, leading to unwanted and substituted species have one or more resonance hazardous multi - nitrated sub - products, as show n by contributors where all the atoms have a full octet. the process using VO(NO 3 ) 3 [11] . These problems are the reason why the classical nitration method which uses a mixture of concentrated nitric and sulfuric acid s is still used worldwide in a great number of nitro aromatic compound industries [12] even with the associated environmental issues it carries. 2 The fact tha t the NO 2 group is a deactiv ating group also explains why almost none multi nitrated byproducts were detected during every experimental procedure, since the presence of this group severely deactivates the aromatic ring for further nitration. Regioselectivi ty is also affected by the steric hindrance stablished by both the functional group Scheme 2 - Resonance contributors in an EAS mechanism with an activating group and the electrophile. Bulky groups tend to favor para substituted products, maximizing the distance These resonance contributors are very stable, between the functional group and the electrophile. which considerably decreases the activation energy necessary to form the intermediate complex. This significantly increases the reaction’s overall rate, as 1.3. Nitration via HNO 3 /H 2 SO 4 in acetic acid EAS is kinetically controlled . The exception to this Using a mixture of concentrated nitric and sulfuric are halogen atoms, which form more stable acids as nitrating agents is the ideal way of studying inter mediates in ortho and para substitution. the reaction’s regioselectivity since the reagents However, they act as deactivating groups, due to a used are cheaper than those needed for other more high electronegative property, attracting the complex processes. Furthermore, the reaction’s aromatic ring’s electron cloud, hence slowing the m echanism is well known, simple (EAS) and does reaction . not require a catalyst. The occurrence of multi - In contrast, deactivating groups are meta directors, nitrated byproducts was very limited in all of the sinc e ortho and para substituted products generate experiments, which means the isomeric distribution resonance contributors with a positively charged is more reliable. Since this experiment took place at carbon atom connect ed to the deactivating group, a labo ratory scale, the amount of effluents was not highly destabilizing the arenium ion. G roups such a major concern, as the reactions were prepared with small amounts of reagents which led to small as NO 2 , SO 3 H or CO OR are extremely electronegative and attract electrons from the quantities of acid effluents that were neutralized or aromatic ring, decreasing its e lectron density. This diluted in water prior to discharge. This synthetic resul ts in a less activated ring , consequently leading route is also a quite easy and quick nitration mean, to a much slower reaction. therefore allowing multiple experiments with the same starting material to ensure result repeatability. Given the main objective of this work was to understand how different functional groups affect the nitrat ion of aniline and toluidine, and also because the amine group is very sensitive to harsh acidic conditions, the starting materials were protected via acetylation in the presence of acetic and succinic anhydride prior to nitration to prevent amine oxidatio n. Scheme 3 - Resonance contributors in an EAS mechanism with a deactivating group 3 Scheme 4 – Experimental sequence Acetylation with acetic anhydride has been used in many research works, either with nitration being carried out by HNO 3 /H 2 SO 4 , as well as by the aforementioned processes.
Load more

Recommended publications
  • Vapor Phase Nitration of Butane in a Fused Salt Reactor Frank Slates Adams Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1961 Vapor phase nitration of butane in a fused salt reactor Frank Slates Adams Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Chemical Engineering Commons Recommended Citation Adams, Frank Slates, "Vapor phase nitration of butane in a fused salt reactor " (1961). Retrospective Theses and Dissertations. 2472. https://lib.dr.iastate.edu/rtd/2472 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. This dissertation has been 61-6173 microfilmed exactly as received ADAMS, Jr., Frank Slates, 1931— VAPOR PHASE NITRATION OF BUTANE IN A FUSED SALT REACTOR. Iowa State University of Science and Technology Ph.D., 1961 Engineering, chemical University Microfilms, Inc., Ann Arbor, Michigan VAPOR PHASK NITRATION OF BUTANE IN A FUSED SALT REACTOR by Frank Slates Adams, Jr. A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHIDSOPHÏ Major Subject: Chemical Engineering Approved: Signature was redacted for privacy. In Charge of Major Work Signature was redacted for privacy. Head of Major Department Signature was
    [Show full text]
  • Preparation and Purification of Atmospherically Relevant Α
    Atmos. Chem. Phys., 20, 4241–4254, 2020 https://doi.org/10.5194/acp-20-4241-2020 © Author(s) 2020. This work is distributed under the Creative Commons Attribution 4.0 License. Technical note: Preparation and purification of atmospherically relevant α-hydroxynitrate esters of monoterpenes Elena Ali McKnight, Nicole P. Kretekos, Demi Owusu, and Rebecca Lyn LaLonde Chemistry Department, Reed College, Portland, OR 97202, USA Correspondence: Rebecca Lyn LaLonde ([email protected]) Received: 31 July 2019 – Discussion started: 6 August 2019 Revised: 8 December 2019 – Accepted: 20 January 2020 – Published: 9 April 2020 Abstract. Organic nitrate esters are key products of terpene oxidation in the atmosphere. We report here the preparation and purification of nine nitrate esters derived from (C)-3- carene, limonene, α-pinene, β-pinene and perillic alcohol. The availability of these compounds will enable detailed investigations into the structure–reactivity relationships of aerosol formation and processing and will allow individual investigations into aqueous-phase reactions of organic nitrate esters. Figure 1. Two hydroxynitrate esters with available spectral data. Relative stereochemistry is undefined. 1 Introduction derived ON is difficult, particularly due to partitioning into the aerosol phase in which hydrolysis and other reactivity Biogenic volatile organic compound (BVOC) emissions ac- can occur (Bleier and Elrod, 2013; Rindelaub et al., 2014, count for ∼ 88 % of non-methane VOC emissions. Of the to- 2015; Romonosky et al., 2015; Thomas et al., 2016). Hydrol- tal BVOC estimated by the Model of Emission of Gases and ysis reactions of nitrate esters of isoprene have been stud- Aerosols from Nature version 2.1 (MEGAN2.1), isoprene is ied directly (Jacobs et al., 2014) and the hydrolysis of ON estimated to comprise half, and methanol, ethanol, acetalde- has been studied in bulk (Baker and Easty, 1950).
    [Show full text]
  • Nitroso and Nitro Compounds 11/22/2014 Part 1
    Hai Dao Baran Group Meeting Nitroso and Nitro Compounds 11/22/2014 Part 1. Introduction Nitro Compounds O D(Kcal/mol) d (Å) NO NO+ Ph NO Ph N cellular signaling 2 N O N O OH CH3−NO 40 1.48 molecule in mammals a nitro compound a nitronic acid nitric oxide b.p = 100 oC (8 mm) o CH3−NO2 57 1.47 nitrosonium m.p = 84 C ion (pKa = 2−6) CH3−NH2 79 1.47 IR: υ(N=O): 1621-1539 cm-1 CH3−I 56 Nitro group is an EWG (both −I and −M) Reaction Modes Nitro group is a "sink" of electron Nitroso vs. olefin: e Diels-Alder reaction: as dienophiles Nu O NO − NO Ene reaction 3 2 2 NO + N R h 2 O e Cope rearrangement υ O O Nu R2 N N N R1 N Nitroso vs. carbonyl R1 O O O O O N O O hυ Nucleophilic addition [O] N R2 R O O R3 Other reaction modes nitrite Radical addition high temp low temp nitrolium EWG [H] ion brown color less ion Redox reaction Photochemical reaction Nitroso Compounds (C-Nitroso Compounds) R2 R1 O R3 R1 Synthesis of C-Nitroso Compounds 2 O R1 R 2 N R3 3 R 3 N R N R N 3 + R2 2 R N O With NO sources: NaNO2/HCl, NOBF4, NOCl, NOSbF6, RONO... 1 R O R R1 O Substitution trans-dimer monomer: blue color cis-dimer colorless colorless R R NOBF OH 4 - R = OH, OMe, Me, NR2, NHR N R2 R3 = H or NaNO /HCl - para-selectivity ΔG = 10 Kcal mol-1 Me 2 Me R1 NO oxime R rate determining step Blue color: n π∗ absorption band 630-790 nm IR: υ(N=O): 1621-1539 cm-1, dimer υ(N−O): 1300 (cis), 1200 (trans) cm-1 + 1 Me H NMR (α-C-H) δ = 4 ppm: nitroso is an EWG ON H 3 Kochi et al.
    [Show full text]
  • Mdi), 1,6 Hexamethylene Diisocyanate (Hdi
    4.03.11. PRODUCTION OF ISOCYANATES FOR POLYURETHANE PRO- DUCTION CHEMICALS AND ALLIED APPLICATION NOTE 4.03.11 PRODUCTION OF ISOCYANATES FOR POLYURETHANE PRODUCTION METHYLENE DIPHENYL DIISOCYANATE (MDI), 1,6 HEXAMETHYLENE DIISOCYANATE (HDI) Typical end products Polyurethane foam for different applications, for example, bedding, of materials can be produced to meet the needs for furniture, packaging, coatings and elastomers. specific applications. Chemical curve: R.I. for MDI at Ref. Temp. of 25˚C Application The most commonly used isocyanates for the production of PU are methylene diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI). If color and transparency are important, an aliphatic diisocyanate such as hexamethylene diisocyanate (HDI) is used. The first step in the production of polyurethane is the synthesis of the raw materials. The diisocyanate is typically produced from basic raw materials via nitration, hydrogenation and phosgenation. The feedstock and initial processing steps depend on the Introduction desired isocyanate, but all go through a phosgenation step. Polyurethanes (PUs) are a class of versatile materials with great potential for use in different applications. For instance, for the production of MDI, benzene and They are used in the manufacture of many different nitric acid are reacted to produce nitrobenzene. After items, such as paints, liquid coatings, elastomers, a hydrogeneration step, the nitrobenzene is converted insulators, elastics, foams and integral skins. to aniline. It is then condensed with formaldehyde to produce methylene diphenyl diamine (MDA), the Polyurethanes are produced by polymerization of precursor for MDI. The MDA is fed to a phosgenation a diisocyanate with a polyol. Because a variety of reactor where it reacts with phosgene to produce the diisocyanates and a wide range of polyols can be end-product MDI.
    [Show full text]
  • Reactions of Benzene & Its Derivatives
    Organic Lecture Series ReactionsReactions ofof BenzeneBenzene && ItsIts DerivativesDerivatives Chapter 22 1 Organic Lecture Series Reactions of Benzene The most characteristic reaction of aromatic compounds is substitution at a ring carbon: Halogenation: FeCl3 H + Cl2 Cl + HCl Chlorobenzene Nitration: H2 SO4 HNO+ HNO3 2 + H2 O Nitrobenzene 2 Organic Lecture Series Reactions of Benzene Sulfonation: H 2 SO4 HSO+ SO3 3 H Benzenesulfonic acid Alkylation: AlX3 H + RX R + HX An alkylbenzene Acylation: O O AlX H + RCX 3 CR + HX An acylbenzene 3 Organic Lecture Series Carbon-Carbon Bond Formations: R RCl AlCl3 Arenes Alkylbenzenes 4 Organic Lecture Series Electrophilic Aromatic Substitution • Electrophilic aromatic substitution: a reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile H E + + + E + H • In this section: – several common types of electrophiles – how each is generated – the mechanism by which each replaces hydrogen 5 Organic Lecture Series EAS: General Mechanism • A general mechanism slow, rate + determining H Step 1: H + E+ E El e ctro - Resonance-stabilized phile cation intermediate + H fast Step 2: E + H+ E • Key question: What is the electrophile and how is it generated? 6 Organic Lecture Series + + 7 Organic Lecture Series Chlorination Step 1: formation of a chloronium ion Cl Cl + + - - Cl Cl+ Fe Cl Cl Cl Fe Cl Cl Fe Cl4 Cl Cl Chlorine Ferric chloride A molecular complex An ion pair (a Lewis (a Lewis with a positive charge containing a base) acid) on ch lorine ch loronium ion Step 2: attack of
    [Show full text]
  • Oligomerization and Nitration of the Grass Pollen Allergen Phlp5
    International Journal of Molecular Sciences Article Oligomerization and Nitration of the Grass Pollen Allergen Phl p 5 by Ozone, Nitrogen Dioxide, and Peroxynitrite: Reaction Products, Kinetics, and Health Effects Anna T. Backes 1,* , Kathrin Reinmuth-Selzle 1 , Anna Lena Leifke 1, Kira Ziegler 1 , Carola S. Krevert 1,† , Georg Tscheuschner 2 , Kurt Lucas 1 , Michael G. Weller 2 , Thomas Berkemeier 1 , Ulrich Pöschl 1 and Janine Fröhlich-Nowoisky 1,* 1 Multiphase Chemistry Department, Max Planck Institute for Chemistry, 55128 Mainz, Germany; [email protected] (K.R.-S.); [email protected] (A.L.L.); [email protected] (K.Z.); [email protected] (C.S.K.); [email protected] (K.L.); [email protected] (T.B.); [email protected] (U.P.) 2 Division 1.5 Protein Analysis, Federal Institute for Materials Research and Testing (BAM), 12489 Berlin, Germany; [email protected] (G.T.); [email protected] (M.G.W.) * Correspondence: [email protected] (A.T.B.); [email protected] (J.F.-N.) † Current address: Department of Molecular Spectroscopy, Max Planck Institute for Polymer Research, 55128 Mainz, Germany. Citation: Backes, A.T.; Reinmuth-Selzle, K.; Leifke, A.L.; Abstract: The allergenic and inflammatory potential of proteins can be enhanced by chemical Ziegler, K.; Krevert, C.S.; modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms Tscheuschner, G.; Lucas, K.; Weller, and kinetics of such modifications, however, have not yet been fully resolved. We investigated the M.G.; Berkemeier, T.; Pöschl, U.; oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O3), nitrogen dioxide Fröhlich-Nowoisky, J.
    [Show full text]
  • MDI Process Update Process Economics Program Review 2016-13
    ` IHS CHEMICAL MDI Process Update Process Economics Program Review 2016-13 March 2017 ihs.com PEP Review 2016-13 MDI Process Update Ron Smith Senior Principal Analyst Downloaded 20 March 2017 08:28 AM UTC by Anandpadman Vijayakumar, IHS ([email protected]) IHS Chemical | PEP Review 2016-13 MDI Process Update PEP Review 2016-13 MDI Process Update Ron Smith, Senior Principal Analyst Abstract Isocyanates are a major ingredient for the production of polyurethane products that are formed by the reactive polymerization of isocyanates with polyols. A long and difficult search for a reasonable economic pathway to produce isocyanates by vapor-phase phosgenation of diphenylmethane diamine (MDA) in place of liquid-phase phosgenation of MDA has been developed and commercialized since our last report on isocyanates (PEP Report 1E) was published in August 1992. In this review, we investigate large-scale, single-train integrated technology and economics for the production of methylene diphenyl diisocyanate (MDI), including condensation of aniline with formaldehyde to produce MDA, production of phosgene from carbon monoxide and chlorine, gas-phase phosgenation of MDA to produce crude MDI, and separation/recovery of MDI products. The key gas-phase phosgenation step produces isocyanates from MDA at high pressure and temperature, enabling a significant shortening of residence time in the reactor. The rate determining step is the dissociation of the polymeric MDA–carbonyl chloride intermediate into polymeric MDI and HCl followed by HCl removal. A summary of the process economics for the production of 373 million lbs/yr of crude MDI and 336 million lbs/yr of polymeric MDI (PMDI) and 37 million lbs/yr of pure MDI for continuous vapor-phase isocyanate production shows that on a US Gulf Coast basis, the world-scale, single-train, integrated vapor-phase technology–based plant will meet plant gate costs.
    [Show full text]
  • Nitration of Aromatic Compounds: Preparation of Methyl-M-Nitrobenzene
    EXPERIMENT 3 (Organic Chemistry II) Pahlavan/Cherif Nitration of Aromatic Compounds: Preparation of methyl-m-nitrobenzoate Purpose a) Study electrophilic aromatic substitution reaction (EAS) b) Study regioselectivity for EAS reactions Chemicals Materials 150 – mL beaker Methyl benzoate 400-mL beaker Sulfuric acid (conc.) 125-mL flask Nitric acid (conc.) Stirring rod Ice Mel-temp Methanol Suction filtration funnel Introduction Unlike nucleophilic substitutions, which proceed via several different mechanisms, electrophilic aromatic substitutions (EAS) generally occur via the same process. Because of the high electron density of the aromatic ring, during EAS reactions electrophiles are attracted to the ring's π system and protons serve as the leaving groups. Equation 1. During SN1 reactions, however, nucleophiles attack an aliphatic carbon and weak Lewis bases serve as leaving groups. Ar - H + E+ Ar - E +H+ Eq. 1 arene electrophile substituted arene 1 Generally, EAS reactions occur in three steps, Scheme I. During Step I, the electrophile is produced, Scheme I Usually, by the interaction of a compound containing the potential electrophile and a catalyst. During Step II, the aromatic π system donates an electron pair to the electrophile, forming a σ bond ( an arenium cation) followed by - deprotonation in step III in the present of a base ( HSO4 ) affording the substituted arene. EAS reactions are generally second-order processes, i.e., first order in electrophile and first order in arene. Thus, Step II. is the rate- determining step (rds); rate = k2 [arene][electrophile]. 2 Electrophilic Aromatic Substitution: Nitration of Methyl Benzoate Benzene rings are components of many important natural products and other useful organic compounds.
    [Show full text]
  • Reactions of Aromatic Compounds Just Like an Alkene, Benzene Has Clouds of  Electrons Above and Below Its Sigma Bond Framework
    Reactions of Aromatic Compounds Just like an alkene, benzene has clouds of electrons above and below its sigma bond framework. Although the electrons are in a stable aromatic system, they are still available for reaction with strong electrophiles. This generates a carbocation which is resonance stabilized (but not aromatic). This cation is called a sigma complex because the electrophile is joined to the benzene ring through a new sigma bond. The sigma complex (also called an arenium ion) is not aromatic since it contains an sp3 carbon (which disrupts the required loop of p orbitals). Ch17 Reactions of Aromatic Compounds (landscape).docx Page1 The loss of aromaticity required to form the sigma complex explains the highly endothermic nature of the first step. (That is why we require strong electrophiles for reaction). The sigma complex wishes to regain its aromaticity, and it may do so by either a reversal of the first step (i.e. regenerate the starting material) or by loss of the proton on the sp3 carbon (leading to a substitution product). When a reaction proceeds this way, it is electrophilic aromatic substitution. There are a wide variety of electrophiles that can be introduced into a benzene ring in this way, and so electrophilic aromatic substitution is a very important method for the synthesis of substituted aromatic compounds. Ch17 Reactions of Aromatic Compounds (landscape).docx Page2 Bromination of Benzene Bromination follows the same general mechanism for the electrophilic aromatic substitution (EAS). Bromine itself is not electrophilic enough to react with benzene. But the addition of a strong Lewis acid (electron pair acceptor), such as FeBr3, catalyses the reaction, and leads to the substitution product.
    [Show full text]
  • Nitration of Toluene (Electrophilic Aromatic Substitution)
    Nitration of Toluene (Electrophilic Aromatic Substitution) Electrophilic aromatic substitution represents an important class of reactions in organic synthesis. In "aromatic nitration," aromatic organic compounds are nitrated via an electrophilic aromatic substitution mechanism involving the attack of the electron-rich benzene ring on the nitronium ion. The formation of a nitronium ion (the electrophile) from nitric acid and sulfuric acid is shown below. The sulfuric acid is regenerated and hence acts as a catalyst. It also absorbs water to drive the reaction forward. Figure 1: The mechanism for the formation of a nitronium ion. The methyl group of toluene makes it around 25 times more reactive than benzene in electrophilic aromatic substitution reactions. Toluene undergoes nitration to give ortho and para nitrotoluene isomers, but if heated it can give dinitrotoluene and ultimately the explosive trinitrotoluene (TNT). Figure 2: Reaction of nitric acid and sulfuric acid with toluene. Procedure: 1. Place a 5 mL conical vial, equipped with a spin vane, in a crystallizing dish filled with ice-water placed on a stirrer. 2. Pour 1.0 mL of concentrated nitric acid into the vial. While stirring, slowly add 1.0 mL of concentrated sulfuric acid. 3. After the addition of sulfuric acid is complete, add 1.0 mL of toluene dropwise and slowly over a period of 5 minutes (slow down if you see boiling. Reaction produces a lot of heat). 4. While Stirring, allow the contents of the flask to reach the room temperature. Stir at room temperature for another 5 minutes. 5. Add 10 mL of water into a small separatory funnel.
    [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]
  • NITROGYLCERIN and ETHYLENE GLYCOL DINITRATE Criteria for a Recommended Standard OCCUPATIONAL EXPOSURE to NITROGLYCERIN and ETHYLENE GLYCOL DINITRATE
    CRITERIA FOR A RECOMMENDED STANDARD OCCUPATIONAL EXPOSURE TO NITROGYLCERIN and ETHYLENE GLYCOL DINITRATE criteria for a recommended standard OCCUPATIONAL EXPOSURE TO NITROGLYCERIN and ETHYLENE GLYCOL DINITRATE U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control National Institute for Occupational Safety and Health June 1978 For »ale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 DISCLAIMER Mention of company name or products does not constitute endorsement by the National Institute for Occupational Safety and Health. DHEW (NIOSH) Publication No. 78-167 PREFACE The Occupational Safety and Health Act of 1970 emphasizes the need for standards to protect the health and provide for the safety of workers occupationally exposed to an ever-increasing number of potential hazards. The National Institute for Occupational Safety and Health (NIOSH) evaluates all available research data and criteria and recommends standards for occupational exposure. The Secretary of Labor will weigh these recommendations along with other considerations, such as feasibility and means of implementation, in promulgating regulatory standards. NIOSH will periodically review the recommended standards to ensure continuing protection of workers and will make successive reports as new research and epidemiologic studies are completed and as sampling and analytical methods are developed. The contributions to this document on nitroglycerin (NG) and ethylene glycol dinitrate (EGDN) by NIOSH staff, other Federal agencies or departments, the review consultants, the reviewers selected by the American Industrial Hygiene Association, and by Robert B. O ’Connor, M.D., NIOSH consultant in occupational medicine, are gratefully acknowledged. The views and conclusions expressed in this document, together with the recommendations for a standard, are those of NIOSH.
    [Show full text]