DOCSLIB.ORG

18.4 Nucleophilic Aromatic Substitution Reactions of Aryl Halides 829

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
18.4 Nucleophilic Aromatic Substitution Reactions of Aryl Halides 829 18_BRCLoudon_pgs4-3.qxd 11/26/08 9:09 AM Page 828 828 CHAPTER 18 • THE CHEMISTRY OF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION-METAL CATALYSIS Because an aryl cation is forced to assume a nonoptimal geometry and hybridization, it has a very high energy. The electron-withdrawing polar effect of the ring double bonds also desta- bilizes an aryl cation, just as a double bond destabilizes a vinylic cation. Thus, SN1 reactions of aryl halides do not occur because they would require the formation of carbocation interme- diates—aryl cations—with very high energy. Note that an aryl cation is quite different from the cation formed in electrophilic aromatic substitu- tion (Eq. 16.9a, p. 753), in which the carbocation intermediate is stabilized by resonance. In an aryl cation, the empty orbital is not part of the ring p-electron system but is orthogonal (at right angles) to it. Hence, this carbocation is not resonance-stabilized. The first direct observation of an aryl cation (the phenyl cation, Eq. 18.10) was reported in 2000 by chemists at the Ruhr-Universität in Bochum, Germany, who trapped the cation at 4 K and ob- served it spectroscopically. Thus, aryl cations are known species. However, they are far too unstable to form from aryl halides under typical SN1 conditions. PROBLEM 18.3 Within each series, arrange the compounds according to increasing rates of their reactions by the SN1–E1 mechanism. Explain your reasoning. (a) Br Br Br "C A CH2 "CH CH3 "CH CH3 cL 0L L cL L AB C (b) Cl Cl "CH CH3 Br kL L kL ACB NUCLEOPHILIC AROMATIC SUBSTITUTION 18.4 REACTIONS OF ARYL HALIDES Although aryl halides do not undergo nucleophilic substitution reactions by SN1 and SN2 mechanisms, aryl halides that have one or more nitro groups ortho or para to the halogen un- dergo nucleophilic substitution reactions under relatively mild conditions. 67 °C, 10 min O N F K CH O O N OCH K F (18.11) 2 | 3 _ CH OH 2 3 | _ LvL + 3 LvL + p-fluoronitrobenzene p-nitroanisole (93% yield) NO2 NO2 ) 170 °C, 6 h ) O N Cl NH O N NH HCl (18.12) 2 3 (pressure) 2 2 LvL ++32LvL 1-chloro-2,4-dinitrobenzene 2,4-dinitroaniline (70% yield) 18_BRCLoudon_pgs4-3.qxd 11/26/08 9:09 AM Page 829 18.4 NUCLEOPHILIC AROMATIC SUBSTITUTION REACTIONS OF ARYL HALIDES 829 These reactions are examples of nucleophilic aromatic substitution: substitution that occurs at a carbon of an aromatic ring by a nucleophilic mechanism. Let’s examine some of the characteristics of this mechanism. Like SN2 reactions, nucle- ophilic aromatic substitution reactions involve nucleophiles and leaving groups, and they also obey second-order rate laws. rate k[aryl halide][nucleophile] (18.13) = However, nucleophilic aromatic substitution reactions do not involve a concerted backside substitution for the reasons given in Sec. 18.1. Two clues about the reaction mechanism come from the reactivities of different aryl halides. First, the reaction is faster when there are more nitro groups ortho and para to the halogen leaving group: NO2 NO2 relative rate ) ) 5 6 (18.14a) O2N Cl_OCH3 O2N OCH3 Cl_ 10 –10 LvL + LvL + (18.14b) O2N Cl _OCH3 O2N OCH3 Cl_ 1 LvL + LLv + ≈0 (18.14c) Cl _OCH3 no reaction vL + Second, the effect of the halogen on the rate of this type of reaction is quite different from that in the SN1 or SN2 reaction of alkyl halides. In nucleophilic aromatic substitution reactions, aryl fluorides are most reactive. Reactivities of aryl halides: Ar F Ar Cl ' Ar Br ' Ar I (18.15) L >> L L L In SN2 and SN1 reactions of alkyl halides, the reactivity order is exactly the reverse: alkyl flu- orides are the least reactive alkyl halides (Secs. 9.4F and 9.6C). These data are consistent with a reaction mechanism in which the nucleophile reacts at the halide-bearing carbon below (or above) the plane of the aromatic ring to yield a resonance- stabilized anion called a Meisenheimer complex. In this anion, the negative charge is delocal- ized throughout the p-electron system of the ring. Formation of this anion is the rate-limiting step in many nucleophilic aromatic substitution reactions. _OCH3 3 12 rate-limiting O2N F LvL _ OCH3 OCH3 OCH3 12 12 12 O2N 2 % O2N _ % O2N % (18.16a) L/ Ll Ln ΄ "F 3 "F "F ΄ 1 a Meisenheimer complex _ 18_BRCLoudon_pgs4-3.qxd 11/26/08 9:09 AM Page 830 830 CHAPTER 18 • THE CHEMISTRY OF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION-METAL CATALYSIS The negative charge in this complex is also delocalized into the nitro group. M O OCH _O OCH 3 1 3 3 12 3 #N N A _ % % (18.16b) | Ll3 "F | l "F ΄_OM _OM ΄ 3 12 3 12 The Meisenheimer complex breaks down to products by loss of the halide ion. _ OCH 4 3 O N OCH F _ (18.16c) O2N % 2 3 L/ "F LvL + 3 12 3 12 3 Let’s see how this mechanism fits the experimental facts. Ortho and para nitro groups accelerate the reaction because the rate-limiting transition state resembles the Meisenheimer complex, and ortho and para nitro groups (but not meta nitro groups) stabilize this complex by resonance. Fluorine also stabilizes the negative charge by its electron-withdrawing polar ef- fect, which is greater than the polar effect of the other halogens. Because the loss of halide is not rate-limiting, the basicity of the halide, or equivalently, the strength of the carbon–halogen bond, is not important in determining the reaction rate. Although we have used aryl halides substituted with ortho- and para-nitro groups to illustrate nucleophilic aromatic substitution, it stands to reason that other substituents that can provide resonance stabilization to the Meisenheimer complex can also activate nucleophilic aromatic substitution. (See, for example, Problem 18.5a.) Notice how the nucleophilic aromatic substitution reaction differs from the SN2reactionof alkyl halides. First, there is an actual intermediate in the nucleophilic aromatic substitution re- action—the Meisenheimer complex. (In some cases, this is sufficiently stable that it can be di- rectly observed.) There is no evidence for an intermediate in any SN2reaction.Second,thenu- cleophilic aromatic substitution reaction is a frontside substitution; it requires no inversion of configuration. The SN2reactionofanalkylhalide,incontrast,isabacksidesubstitutionwith STUDY GUIDE LINK 18.1 inversion of configuration. Finally, the effect of the halogen on the reaction rate (Eq. 18.15) is Contrast of Aromatic Substitution different in the two reactions. Aryl fluorides react most rapidly in nucleophilic aromatic sub- Reactions stitution, whereas alkyl fluorides react most slowly in SN2 reactions. PROBLEMS 18.4 Complete the following reactions. (No reaction may be the correct response.) (a) heat O2N Cl C2H5NH2 LcL + 2 $NO2 (b) F CH (CH ) S 3 2 3 _ CH OH cL + 12 3 3 $NO2 (c) 25 C CH O F CH O ° 3 3 _ CH OH LcL + 21 3 3 18_BRCLoudon_pgs4-3.qxd 11/26/08 9:09 AM Page 831 18.5 INTRODUCTION TO TRANSITION-METAL CATALYZED REACTIONS 831 18.5 Which of the two compounds in each of the following sets should react more rapidly in a nu- cleophilic aromatic substitution reaction with CH3O_ in CH3OH? Explain your answers. (a) F F (b) F F NO NO " 2 " 2 " " M or M or r r r r %NO2 "C "NO2 O OCH ( % 3 INTRODUCTION TO TRANSITION-METAL 18.5 CATALYZED REACTIONS We’ve just learned that SN1 and SN2 reactions cannot be carried out on either aryl or vinylic halides. However, reactions that look very much like nucleophilic substitutions can be carried out using certain transition-metal catalysts. Here are some examples. H3C $ Pd P L Lc 34 CH3 (catalyst) CH3 (CH3CH2)3N % H2C A CH2 % HBr (18.17) CH C' N (solvent) i + 3 i + neutralized by Br 18 h, 125 °C CH A CH2 % % the (CH3CH2)3N o-bromotoluene o-methylstyrene (86% yield) This reaction, called the Heck reaction, has become very important in organic synthesis. We’ll revisit this reaction in Sec. 18.6A. Notice the formation of the carbon–carbon bond and the re- lease of bromide as HBr. Superficially, it looks as if the conjugate-base anion of ethylene dis- places bromide ion from the aromatic ring. However, this reaction occurs by a very different mechanism and does not happen without the palladium catalyst. (Only about 1 mole % of the catalyst is required.) In the following reaction, we see the substitution of a vinylic bromide by a thiolate anion. Ph Br Ph SCH2CH3 Pd(PPh3)4 (catalyst) CCA Li SCH CH CCA Li Br (18.18) $ ) | _ 2 3 benzene $ ) | _ + + HH) $ HH) $ (93% yield) This reaction, too, looks superficially like a nucleophilic substitution reaction. But this reac- tion also proceeds by a different mechanism and does not take place without the catalyst, which is present in only 1 mole %. Notice also the retention of alkene stereochemistry, a very different result from that expected in an SN2 reaction. These are but two examples of thousands now known in which transition-metal catalysts bring about seemingly “impossible” reactions. The field of transition-metal catalysis has ex- ploded in the last four decades, and it has become very important in both laboratory and indus- trial chemistry, as well as in some areas of biology. This field is part of the larger field of.
Load more

Recommended publications
  • Solvent Effects on Structure and Reaction Mechanism: a Theoretical Study of [2 + 2] Polar Cycloaddition Between Ketene and Imine
    J. Phys. Chem. B 1998, 102, 7877-7881 7877 Solvent Effects on Structure and Reaction Mechanism: A Theoretical Study of [2 + 2] Polar Cycloaddition between Ketene and Imine Thanh N. Truong Henry Eyring Center for Theoretical Chemistry, Department of Chemistry, UniVersity of Utah, Salt Lake City, Utah 84112 ReceiVed: March 25, 1998; In Final Form: July 17, 1998 The effects of aqueous solvent on structures and mechanism of the [2 + 2] cycloaddition between ketene and imine were investigated by using correlated MP2 and MP4 levels of ab initio molecular orbital theory in conjunction with the dielectric continuum Generalized Conductor-like Screening Model (GCOSMO) for solvation. We found that reactions in the gas phase and in aqueous solution have very different topology on the free energy surfaces but have similar characteristic motion along the reaction coordinate. First, it involves formation of a planar trans-conformation zwitterionic complex, then a rotation of the two moieties to form the cycloaddition product. Aqueous solvent significantly stabilizes the zwitterionic complex, consequently changing the topology of the free energy surface from a gas-phase single barrier (one-step) process to a double barrier (two-step) one with a stable intermediate. Electrostatic solvent-solute interaction was found to be the dominant factor in lowering the activation energy by 4.5 kcal/mol. The present calculated results are consistent with previous experimental data. Introduction Lim and Jorgensen have also carried out free energy perturbation (FEP) theory simulations with accurate force field that includes + [2 2] cycloaddition reactions are useful synthetic routes to solute polarization effects and found even much larger solvent - formation of four-membered rings.
    [Show full text]
  • Reaction Mechanism
    Reaction Mechanism A detailed sequence of steps for a reaction Reasonable mechanism: 1. Elementary steps sum to the overall reaction 2. Elementary steps are physically reasonable 3. Mechanism is consistent with rate law and other experimental observations (generally found from rate limiting (slow) step(s) A mechanism can be supported but never proven NO2 + CO NO + CO2 2 Observed rate = k [NO2] Deduce a possible and reasonable mechanism NO2 + NO2 NO3 + NO slow NO3 + CO NO2 + CO2 fast Overall, NO2 + CO NO + CO2 Is the rate law for this sequence consistent with observation? Yes Does this prove that this must be what is actually happening? No! NO2 + CO NO + CO2 2 Observed rate = k [NO2] Deduce a possible and reasonable mechanism NO2 + NO2 NO3 + NO slow NO3 + CO NO2 + CO2 fast Overall, NO2 + CO NO + CO2 Is the rate law for this sequence consistent with observation? Yes Does this prove that this must be what is actually happening? No! Note the NO3 intermediate product! Arrhenius Equation Temperature dependence of k kAe E/RTa A = pre-exponential factor Ea= activation energy Now let’s look at the NO2 + CO reaction pathway* (1D). Just what IS a reaction coordinate? NO2 + CO NO + CO2 High barrier TS for step 1 Reactants: Lower barrier TS for step 2 NO2 +NO2 +CO Products Products Bottleneck NO +CO2 NO +CO2 Potential Energy Step 1 Step 2 Reaction Coordinate NO2 + CO NO + CO2 NO22 NO NO 3 NO NO CO NO CO 222In this two-step reaction, there are two barriers, one for each elementary step. The well between the two transition states holds a reactive intermediate.
    [Show full text]
  • Recent Advances in the Direct Nucleophilic Substitution of Allylic
    SHORT REVIEW ▌25 Recentshort review Advances in the Direct Nucleophilic Substitution of Allylic Alcohols through SN1-Type Reactions AlejandroSN1 Reactions of Allylic Alcohols Baeza,* Carmen Nájera* Departamento de Química Orgánica and Instituto de Síntesis Orgánica, University of Alicante, Apdo.99, 03080 Alicante, Spain Fax +34(965)903549; E-mail: [email protected]; E-mail: [email protected] Received: 03.10.2013; Accepted after revision: 06.11.2013 Abstract: Direct nucleophilic substitution reactions of allylic alco- hols are environmentally friendly, since they generate only water as a byproduct, allowing access to new allylic compounds. This reac- tion has, thus, attracted the interest of the chemical community and several strategies have been developed for its successful accom- plishment. This review gathers the latest advances in this methodol- ogy involving SN1-type reactions. 1 Introduction 2SN1-Type Direct Nucleophilic Substitution Reactions of Allylic Alcohols 2.1 Lewis Acids as Catalysts Alejandro Baeza was born in Alicante (Spain) in 1979. He studied 2.2 Brønsted Acids as Catalysts chemistry at the University of Alicante and he received his M.Sc. (2003) and Ph. D. degrees (2006) from here under the supervision of 2.3 Other Promoters Prof. José Miguel Sansano and Prof. Carmen Nájera. He was a post- 3 Conclusions and Outlook doctoral researcher in Prof. Pfaltz’s research group (2007–2010). In 2010 he returned to Alicante and joined the research group of Prof. Key words: S 1 reaction, allylic substitution, carbocations, allylic N Carmen Nájera. His main research interests focus on the development alcohols, green chemistry of new environmentally friendly methodologies, especially in asym- metric synthesis.
    [Show full text]
  • Bsc Chemistry
    Subject Chemistry Paper No and Title 05, ORGANIC CHEMISTRY-II (REACTION MECHANISM-I) Module No and Title 15, The Neighbouring Mechanism, Neighbouring Group Participation by π and σ Bonds Module Tag CHE_P5_M15 CHEMISTRY PAPER :5, ORGANIC CHEMISTRY-II (REACTION MECHANISM-I) MODULE: 15 , The Neighbouring Mechanism, Neighbouring Group Participation by π and σ Bonds TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. NGP Participation 3.1 NGP by Heteroatom Lone Pairs 3.2 NGP by alkene 3.3 NGP by Cyclopropane, Cyclobutane or a Homoallyl group 3.4 NGP by an Aromatic Ring 4. Neighbouring Group Participation on SN2 Reactions 5. Neighbouring Group Participation on SN1 Reactions 6. Neighbouring Group and Rearrangement 7. Examples 8. Summary CHEMISTRY PAPER :5, ORGANIC CHEMISTRY-II (REACTION MECHANISM-I) MODULE: 15 , The Neighbouring Mechanism, Neighbouring Group Participation by π and σ Bonds 1. Learning Outcomes After studying this module, you shall be able to Know about NGP reaction Learn reaction mechanism of NGP reaction Identify stereochemistry of NGP reaction Evaluate the factors affecting the NGP reaction Analyse Phenonium ion, NGP by alkene, and NGP by heteroatom. 2. Introduction The reaction centre (carbenium centre) has direct interaction with a lone pair of electrons of an atom or with the electrons of s- or p-bond present within the parent molecule but these are not in conjugation with the reaction centre. A distinction is sometimes made between n, s and p- participation. An increase in rate due to Neighbouring Group Participation (NGP) is known as "anchimeric assistance". "Synartetic acceleration" happens to be the special case of anchimeric assistance and applies to participation by electrons binding a substituent to a carbon atom in a β- position relative to the leaving group attached to the α-carbon atom.
    [Show full text]
  • Chapter 14 Chemical Kinetics
    Chapter 14 Chemical Kinetics Learning goals and key skills: Understand the factors that affect the rate of chemical reactions Determine the rate of reaction given time and concentration Relate the rate of formation of products and the rate of disappearance of reactants given the balanced chemical equation for the reaction. Understand the form and meaning of a rate law including the ideas of reaction order and rate constant. Determine the rate law and rate constant for a reaction from a series of experiments given the measured rates for various concentrations of reactants. Use the integrated form of a rate law to determine the concentration of a reactant at a given time. Explain how the activation energy affects a rate and be able to use the Arrhenius Equation. Predict a rate law for a reaction having multistep mechanism given the individual steps in the mechanism. Explain how a catalyst works. C (diamond) → C (graphite) DG°rxn = -2.84 kJ spontaneous! C (graphite) + O2 (g) → CO2 (g) DG°rxn = -394.4 kJ spontaneous! 1 Chemical kinetics is the study of how fast chemical reactions occur. Factors that affect rates of reactions: 1) physical state of the reactants. 2) concentration of the reactants. 3) temperature of the reaction. 4) presence or absence of a catalyst. 1) Physical State of the Reactants • The more readily the reactants collide, the more rapidly they react. – Homogeneous reactions are often faster. – Heterogeneous reactions that involve solids are faster if the surface area is increased; i.e., a fine powder reacts faster than a pellet. 2) Concentration • Increasing reactant concentration generally increases reaction rate since there are more molecules/vol., more collisions occur.
    [Show full text]
  • Reaction Kinetics in Organic Reactions
    Autumn 2004 Reaction Kinetics in Organic Reactions Why are kinetic analyses important? • Consider two classic examples in asymmetric catalysis: geraniol epoxidation 5-10% Ti(O-i-C3H7)4 O DET OH * * OH + TBHP CH2Cl2 3A mol sieve OH COOH5C2 L-(+)-DET = OH COOH5C2 * OH geraniol hydrogenation OH 0.1% Ru(II)-BINAP + H2 CH3OH P(C6H5)2 (S)-BINAP = P(C6 H5)2 • In both cases, high enantioselectivities may be achieved. However, there are fundamental differences between these two reactions which kinetics can inform us about. 1 Autumn 2004 Kinetics of Asymmetric Catalytic Reactions geraniol epoxidation: • enantioselectivity is controlled primarily by the preferred mode of initial binding of the prochiral substrate and, therefore, the relative stability of intermediate species. The transition state resembles the intermediate species. Finn and Sharpless in Asymmetric Synthesis, Morrison, J.D., ed., Academic Press: New York, 1986, v. 5, p. 247. geraniol hydrogenation: • enantioselectivity may be dictated by the relative reactivity rather than the stability of the intermediate species. The transition state may not resemble the intermediate species. for example, hydrogenation of enamides using Rh+(dipamp) studied by Landis and Halpern (JACS, 1987, 109,1746) 2 Autumn 2004 Kinetics of Asymmetric Catalytic Reactions “Asymmetric catalysis is four-dimensional chemistry. Simple stereochemical scrutiny of the substrate or reagent is not enough. The high efficiency that these reactions provide can only be achieved through a combination of both an ideal three-dimensional structure (x,y,z) and suitable kinetics (t).” R. Noyori, Asymmetric Catalysis in Organic Synthesis,Wiley-Interscience: New York, 1994, p.3. “Studying the photograph of a racehorse cannot tell you how fast it can run.” J.
    [Show full text]
  • Chapter 23: Substituted Hydrocarbons and Their Reactions
    736-773_Ch23-866418 5/9/06 3:37 PM Page 736 CHAPTER 23 Substituted Hydrocarbons and Their Reactions Chemistry 2.b, 2.d, 2.h, 3.a, 3.g, 8.c, 10.a, 10.b, 10.e I&E 1.b, 1.c, 1.j What You’ll Learn ▲ You will recognize the names and structures of several important organic functional groups. ▲ You will classify reactions of organic substances as sub- stitution, addition, elimina- tion, oxidation-reduction, or condensation and predict products of these reactions. ▲ You will relate the struc- tures of synthetic polymers to their properties. Why It’s Important Whether you are removing a sandwich from plastic wrap, taking an aspirin, or shooting baskets, you’re using organic materials made of substituted hydrocarbons. These com- pounds are in turn made of molecules whose atoms include carbon, hydrogen, and other elements. Visit the Chemistry Web site at chemistrymc.com to find links about substituted hydrocarbons and their reactions. The spooled threads shown in the photo are made from large organ- ic molecules called polymers. 736 Chapter 23 736-773_Ch23-866418 5/9/06 3:37 PM Page 737 DISCOVERY LAB Making Slime Chemistry 10.b n addition to carbon and hydrogen, most organic substances con- Itain other elements that give the substances unique properties. In this lab, you will work with an organic substance consisting of long carbon chains to which many ϪOH groups are bonded. How will the properties of this substance change when these groups react to form bonds called crosslinks between the chains? Safety Precautions Do not allow solutions or product to contact eyes or exposed skin.
    [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]
  • AROMATIC NUCLEOPHILIC SUBSTITUTION-PART -2 Electrophilic Substitution
    Dr. Tripti Gangwar AROMATIC NUCLEOPHILIC SUBSTITUTION-PART -2 Electrophilic substitution ◦ The aromatic ring acts as a nucleophile, and attacks an added electrophile E+ ◦ An electron-deficient carbocation intermediate is formed (the rate- determining step) which is then deprotonated to restore aromaticity ◦ electron-donating groups on the aromatic ring (such as -OH, -OCH3, and alkyl) make the reaction faster, since they help to stabilize the electron-poor carbocation intermediate ◦ Lewis acids can make electrophiles even more electron-poor (reactive), increasing the reaction rate. For example FeBr3 / Br2 allows bromination to occur at a useful rate on benzene, whereas Br2 by itself is slow). In fact, a substitution reaction does occur! (But, as you may suspect, this isn’t an electrophilic aromatic substitution reaction.) In this substitution reaction the C-Cl bond breaks, and a C-O bond forms on the same carbon. The species that attacks the ring is a nucleophile, not an electrophile The aromatic ring is electron-poor (electrophilic), not electron rich (nucleophilic) The “leaving group” is chlorine, not H+ The position where the nucleophile attacks is determined by where the leaving group is, not by electronic and steric factors (i.e. no mix of ortho– and para- products as with electrophilic aromatic substitution). In short, the roles of the aromatic ring and attacking species are reversed! The attacking species (CH3O–) is the nucleophile, and the ring is the electrophile. Since the nucleophile is the attacking species, this type of reaction has come to be known as nucleophilic aromatic substitution. n nucleophilic aromatic substitution (NAS), all the trends you learned in electrophilic aromatic substitution operate, but in reverse.
    [Show full text]
  • Ketenes 25/01/2014 Part 1
    Baran Group Meeting Hai Dao Ketenes 25/01/2014 Part 1. Introduction Ph Ph n H Pr3N C A brief history Cl C Ph + nPr NHCl Ph O 3 1828: Synthesis of urea = the starting point of modern organic chemistry. O 1901: Wedekind's proposal for the formation of ketene equivalent (confirmed by Staudinger 1911) Wedekind's proposal (1901) 1902: Wolff rearrangement, Wolff, L. Liebigs Ann. Chem. 1902, 325, 129. 2 Wolff adopt a ketene structure in 1912. R 2 hν R R2 1905: First synthesis and characterization of a ketene: in an efford to synthesize radical 2, 1 ROH R C Staudinger has synthesized diphenylketene 3, Staudinger, H. et al., Chem. Ber. 1905, 1735. N2 1 RO CH or Δ C R C R1 1907-8: synthesis and dicussion about structure of the parent ketene, Wilsmore, O O J. Am. Chem. Soc. 1907, 1938; Wilsmore and Stewart Chem. Ber. 1908, 1025; Staudinger and Wolff rearrangement (1902) O Klever Chem. Ber. 1908, 1516. Ph Ph Cl Zn Ph O hot Pt wire Zn Br Cl Cl CH CH2 Ph C C vs. C Br C Ph Ph HO O O O O O O O 1 3 (isolated) 2 Wilsmore's synthesis and proposal (1907-8) Staudinger's synthesis and proposal (1908) wanted to make Staudinger's discovery (1905) Latest books: ketene (Tidwell, 1995), ketene II (Tidwell, 2006), Science of Synthesis, Vol. 23 (2006); Latest review: new direactions in ketene chemistry: the land of opportunity (Tidwell et al., Eur. J. Org. Chem. 2012, 1081). Search for ketenes, Google gave 406,000 (vs.
    [Show full text]
  • S.T.E.T.Women's College, Mannargudi Semester Iii Ii M
    S.T.E.T.WOMEN’S COLLEGE, MANNARGUDI SEMESTER III II M.Sc., CHEMISTRY ORGANIC CHEMISTRY - II – P16CH31 UNIT I Aliphatic nucleophilic substitution – mechanisms – SN1, SN2, SNi – ion-pair in SN1 mechanisms – neighbouring group participation, non-classical carbocations – substitutions at allylic and vinylic carbons. Reactivity – effect of structure, nucleophile, leaving group and stereochemical factors – correlation of structure with reactivity – solvent effects – rearrangements involving carbocations – Wagner-Meerwein and dienone-phenol rearrangements. Aromatic nucleophilic substitutions – SN1, SNAr, Benzyne mechanism – reactivity orientation – Ullmann, Sandmeyer and Chichibabin reaction – rearrangements involving nucleophilic substitution – Stevens – Sommelet Hauser and von-Richter rearrangements. NUCLEOPHILIC SUBSTITUTION Mechanism of Aliphatic Nucleophilic Substitution. Aliphatic nucleophilic substitution clearly involves the donation of a lone pair from the nucleophile to the tetrahedral, electrophilic carbon bonded to a halogen. For that reason, it attracts to nucleophile In organic chemistry and inorganic chemistry, nucleophilic substitution is a fundamental class of reactions in which a leaving group(nucleophile) is replaced by an electron rich compound(nucleophile). The whole molecular entity of which the electrophile and the leaving group are part is usually called the substrate. The nucleophile essentially attempts to replace the leaving group as the primary substituent in the reaction itself, as a part of another molecule. The most general form of the reaction may be given as the following: Nuc: + R-LG → R-Nuc + LG: The electron pair (:) from the nucleophile(Nuc) attacks the substrate (R-LG) forming a new 1 bond, while the leaving group (LG) departs with an electron pair. The principal product in this case is R-Nuc. The nucleophile may be electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.
    [Show full text]
  • Nucleophilic Substitution and Elimination Reactions
    8 NUCLEOPHILIC SUBSTITUTION AND ELIMINATION REACTIONS substitution reactions involve the replacement of one atom or group (X) by another (Y): We already have described one very important type of substitution reaction, the halogenation of alkanes (Section 4-4), in which a hydrogen atom is re- placed by a halogen atom (X = H, Y = halogen). The chlorination of 2,2- dimethylpropane is an example: CH3 CH3 I I CH3-C-CH3 + C12 light > CH3-C-CH2Cl + HCI I I Reactions of this type proceed by radical-chain mechanisms in which the bonds are broken and formed by atoms or radicals as reactive intermediates. This 8-1 Classification of Reagents as Electrophiles and Nucleophiles. Acids and Bases mode of bond-breaking, in which one electron goes with R and the other with X, is called homolytic bond cleavage: R 'i: X + Y. - X . + R : Y a homolytic substitution reaction There are a large number of reactions, usually occurring in solution, that do not involve atoms or radicals but rather involve ions. They occur by heterolytic cleavage as opposed to homolytic cleavage of el~ctron-pairbonds. In heterolytic bond cleavage, the electron pair can be considered to go with one or the other of the groups R and X when the bond is broken. As one ex- ample, Y is a group such that it has an unshared electron pair and also is a negative ion. A heterolytic substitution reaction in which the R:X bonding pair goes with X would lead to RY and :X? R~:X+ :YO --' :x@+ R :Y a heterolytic substitution reaction A specific substitution reaction of this type is that of chloromethane with hydroxide ion to form methanol: In this chapter, we shall discuss substitution reactions that proceed by ionic or polar mechanisms' in which the bonds cleave heterolytically.
    [Show full text]