DOCSLIB.ORG

Chemistry of Carbonyl Compounds

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemistry of Carbonyl Compounds Chemistry of Carbonyl Compounds •Nucleophilic addition (1,2-add) / substitution •Conjugate addition (1,4 add) •Robinson annulation (McM 23.12) Base δ- Electrophile •Alkylation of enolate anions O H •Enamines as enolate equivs. (McM 23.11) δ+ Nucleophile •Halogenation of enols / enolates •Related react. in nature Chemistry of Carbonyl Compounds Base δ- Electrophile O H δ+ Nucleophile Nucleophilic addition / substitution Aldehydes / Ketones Acid catalyzed Addition reactions H H H O O HO Nu HO Nu O H O Nu HO Nu R R' R R' R R' R R' _ H R R' R R' R R' Nu-H Nu Better electrophile Weaker nucleophile R, R': H, alkyl, aryl - Not good leaving groups Carboxylic acid derivatives Substitution O O Nu O R L R L R Nu May also be acid cat. Nu - L L - Good leaving groups -X > -OCOR > -OR > -NR2 X: Halogen, R: H, alkyl, aryl Aldehydes / Ketones The Cannizzarro reaction Addition reactions Hydride as leaving group! O O Nu H HO Nu R R' R R' R R' H Nu O O OH O R, R': H, alkyl, aryl - Not good leaving groups O OH R H + HO H R H R H R OH R H R: No acidic α-H ex -H, -Ph. -But 2 Aldehyde Carboxylic acid + prim. alcohol Nicotinamid adenine dinucleotide O H H O NH2 NH2 N N Alchohol dehydrogenase O O O O (NAD cont.) R-OH aldehyde / ketone OH OH O HO O HO P P HO HO prim or sec. NH2 NH2 O N N O N N N N N N O P O O P O O O O OH OH Aldehyde dehydrogenase OR OR O HO HO R OH R H NADH R=H NAD R=Phosphate: NADP+, NADPH Conjugate Addition δ- O O O O O δ- δ+ R R R R 1,2-addition R δ+ Nu 1,4-addition (conjugate addition / MIchael addition) Michael acceptor 1,2-addition, Ex: 1,4-addition, Ex: EWG •Alcohols •Amines •Organolithium •Organocuprates O O O O O N R N S Identity of Nu Termodyn. prod, R OR O O Sterical factors CN NO2 SO2R Michael reaction O O H O R'' O R'' O O O O O R'' Base R R' R R' R R H H H R O R O NB! resonance forms Well stabilized enolate anion HSAB theory (not in McM) HSAB : Hard and soft acids and bases Lewis bases / nucleophiles Lewis acids / electrophiles Donor atom - hard bases: Acceptor atom - hard acid •high electroneg. •small •low polarizability •high positive charge •hard to oxidize •no unchared e- pair in valence shell •high electroneg. •low polarizability Donor atom - soft bases: •low electroneg. Acceptor atom - soft acid •high polarizability •large •easy to oxidize •low positive charge •unchared e- pair in valence shell •low electroneg. Hardness •high polarizability F- > Cl- >Br- >I- Hard acids prefer to bind to hard bases F- > OH- > NH - > CH - 2 3 Soft acids prefer to bind to soft bases Hardest electrophilic site O R Softest nucleophilic site O O O HO Nu R R Nu Harder Nu 1,2 addition Softer Nu 1,4 addition But also •Kin. / termodyn. control •Steric shielding Robinson Annulation (McM 23.12) O O H H O O O O O O Base Base O R' R R' R R H H H R R O R O 1,5-diketone acidic α-H Michael react. O O R Ring forming react. O R annulus (lat.) = ring Aldol condensation O OH R O R - H2O O R O R Base δ- Electrophile O H δ+ Nucleophile Base O O O Enolate anion H Nucleophilic species E O (React with hard E+) E O E O E: - Alkyl halides E - Carbonyl compounds (Aldol, Claissen condens.) - Halides (React. with soft E+) Regioselectivity in enolate anion formation (not in McM) Acidic protons Kinetic control O O O sterically hidered base Low temp termodynamic control O O Electrophilic addition to conjugated dienes H sec, allylic cation H H Br Br 1,2-add. prod. H-Br kinetic prod. + H prim. cat. Br 1,4-add. prod. termodyn. prod. Termodyn prod: High activation barrier, most stable prod. Vigorous cond. (high temp), reversible Kinetic prod: Low activation barrier, less stable prod. Mils cond, (low temp,) irreversible EWG Michael acceptor O O O O O N R N O S H EWG Enolizable R OR O CN NO2 SO2R O O O H H H H CN H NO2 H SO2R R OR ca pKa: 17 19 25 25 10 30 Alkylation of enolate anions O O O Base: Strong, sterical hindrance Base H R-X Ketones, esters, nitriles N H + n-Bu-LI N Li + n-BuH (Aldehydes: condensation) O pKa ca 40 Litium Diisopropyl Amide R X Alkylation of 1,3-dicarbonyl compounds followed by decarboxylation O O H OH O O O O + O O Base R-X H /H2O O O C + R RO OR RO OR OH OH RO OR O OH O R R R Base R-X O O O R OH RO OR R R R H O O O O + H /H2O O O O R RO R' RO R' O R R' ´- CO2 R R Enamines as enolate equivalents (McM 23.11, Lab ex. 11) Synthesis of enamines prim. amine H H R R O R-NH2 N N O NH2-R HO NH-R - H ketone / aldehyde Iminium ion Imine sec. amine R R' R R R' O NH N Base N R' H H Enamine ketone / aldehyde Iminium ion Neutral imine Reactivity of enamines R R' R R' R N H O R H OH E N 2 HO N O H2O N R' E R' E E E E Enamine + RR'NH O E O E •Alkylation (alkyl halides) •Conjugate addition (Michael acceptors) •Acylation (acid halides) •Monoalkylation •No strong base Halogenation of enolate anions O O O H H OH R R R H H H H H X-BX O O O R X X R R X H X X OH H X X X Reacts further in the presence of base OH and halgen source O Fairly good leaving group CX + 3 HO R O HCX + 3 O R pKa X=I: 14 Halogenation of neutral enols mainly monohalogenated prod. H H O O H O O X-X X + HX H X X H H H H Aldehyde or ketone E2 (acid, ester, amide - not enolization) - HX O α-Bromination of acids Acid bromide generated in situ Enolize more easily than acid Br O P O Br O OH H Br H O Br P H Br2 Br OH O Br Br Br Br H + Br H2O cf McM 17.7 Br HO P R-OH + PBr3 R-Br Br O Br P-O bond Hell Volhart Zelinskii React. OH cf Wittig Intro of Cl also possible Carbonyl condensations in nature Acyl-CoA Acetyl-CoA (Acetyl co-enzyme A) NH2 N N Nature's Base N O OH O O O O N H H O N N P P O O O H3C S O O O or O O OH Cl O Nu PO3 Acetyl-CoA Choline OH N Synthesis of Acetylcholine O CoA (neurotransmittor) S Acetylcholine esterase O N O Acetylcholine Carbohydrates Hydrol. Citrate O O ≈ Aldol OH Degradation / oxidation Acyl-CoA cycle Energy CoA + CO H CO2H of fatty acids S HO C 2 HO2C 2 CO2 Oxaloacetic acid OH O Citric acid Metab. with little carbohydrates ≈ Claissen O O (Diabetes, starvation, diets) Degradation / oxidation condes. O O CoA CoA of fatty acids S S CoA Acetone S Acetoacetyl-CoA Biosynthesis Steroids, Lipids etc * +.
Load more

Recommended publications
  • Kimia Reaksi Anorganik
    12/22/2011 Kimia Reaksi Anorganik 2nd Mid-Semester Topics Yuniar Ponco Prananto • Frontier Orbitals (2 sks) • HSAB Application (5 sks) • Heterogeneous Acid Base Reaction (2 sks) • Reduction and Oxidation (12 sks): - Extraction of the Elements - Reduction Potential - Redox Stability in Water - Diagrammatic Presentation of Potential Data Frontier Orbitals …..summary Huheey, J.E., Keiter, E.A., and Keiter, R.L., 1993, Inorganic • Frontier orbitals, which are HOMO (highest occupied Chemistry, Principles of Structure and Reactivity , 4 th molecular orbital ) and LUMO (lowest unoccupied molecular ed., Harper Collins College Publisher, New York orbital ), has been focused nearly since the beginning of Miessler, D. L. and Tarr, D. A., 2004, Inorganic Chemistry , HSAB theory. 3rd ed., Prentice Hall International, USA • Koopman’s theorem , the energy of HOMO → the Atkins, P., Overton, T., Rourke, J., Shriver, D. F., Weller, M., ionization energy, while the energy of LUMO → the and Amstrong, F., 2009, Shriver and Atkins’ Inorganic electron affinity for a closed-shell spesies, in which both th Chemistry , 5 ed., Oxford University Press, UK orbitals are involved in the electronegativity and HSAB Gary Wulfsberg, 2000, Inorganic Chemistry , University relationships. Science Book, California, USA • Hard species → have a large HOMO – LUMO gap • Soft species → have a small HOMO – LUMO gap. [email protected] 1 12/22/2011 Frontier orbitals is the HOMO (filled or partly filled) and the LUMO (completely or partly vacant) of a MOLECULAR ENTITY. HOMO is the highest-energy molecular orbital of an atom or molecule containing an electron. Most likely the first orbital, from which an atom will lose an electron.
    [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]
  • Predicting Metal Interactions with a Novel Quantitative Ion Character -Activity Relationship (QICAR) Approach
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 2002 Predicting metal interactions with a novel quantitative ion character -activity relationship (QICAR) approach David R. Ownby College of William and Mary - Virginia Institute of Marine Science Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Environmental Sciences Commons, and the Toxicology Commons Recommended Citation Ownby, David R., "Predicting metal interactions with a novel quantitative ion character -activity relationship (QICAR) approach" (2002). Dissertations, Theses, and Masters Projects. Paper 1539616800. https://dx.doi.org/doi:10.25773/v5-w1nf-pb08 This Dissertation is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Reproduced with with permission permission of the of copyright the copyright owner. owner.Further reproductionFurther reproduction prohibited without prohibited permission. without permission. PREDICTING METAL INTERACTIONS WITH A NOVEL QUANTITATIVE ION CHARACTER-ACTIVITY RELATIONSHIP (QICAR) APPROACH A Dissertation Presented to The Faculty of the School of Marine Science The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Doctor of Philosophy by David R. Ownby 2002 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. APPROVAL SHEET This dissertation is submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy David R. Ownby^' Approved, May 2002 / r , V v t ( n i t Michael C.
    [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]
  • The Hard-Soft Acid-Base Principle in Enzymatic Catalysis: Dual Reactivity of Phosphoenolpyruvate YAN LI and JEREMY N
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 4612-4616, May 1996 Biochemistry The hard-soft acid-base principle in enzymatic catalysis: Dual reactivity of phosphoenolpyruvate YAN LI AND JEREMY N. S. EVANSt Department of Biochemistry and Biophysics, Washington State University, Pullman, WA 99164-4660 Communicated by R. G. Pearson, University of California, Santa Barbara, CA, January 11, 1996 (received for review October 9, 1995) ABSTRACT In this paper, the chemical reactivity of C3 of Fukui function f(r) (9) is one such quantity that is related to phosphoenolpyruvate (PEP) has been analyzed in terms of the electronic density in the frontier molecular orbitals and density functional theory quantified through quantum chem- thus determines the chemical selectivity (10). For a chemical istry calculations. PEP is involved in a number of important reaction, a Taylor series expansion can be performed up to enzymatic reactions, in which its C3 atom behaves like a base. second order by energy perturbation methods within the In three different enzymatic reactions analyzed here, C3 framework of density functional theory (11). The energy sometimes behaves like a soft base and sometimes behaves like change for a molecule will be, to second order in the changes a hard base in terms ofthe hard-soft acid-base principle. This AN and Av(r): dual nature of C3 of PEP was found to be related to the conformational change of the molecule. This leads to a ( aE\- aE testable hypothesis: that PEP adopts particular conforma- AE = AN + tions in the enzyme-substrate complexes of different PEP- aN\ vN,(r) a v (r) N Av (r)dr using enzymes, and that the enzymes control the reactivity through controlling the dihedral angle between the carboxy- _E - l( d2E late and the C=C double bond of PEP.
    [Show full text]
  • 19.1 Ketones and Aldehydes
    19.1 Ketones and Aldehydes • Both functional groups possess the carbonyl group • Important in both biology and industry Simplest aldehyde Simplest ketone used as a used mainly as preservative a solvent Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 19-1 Klein, Organic Chemistry 3e 19.1 Ketones And Aldehydes Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 19-2 Klein, Organic Chemistry 3e 19.2 Nomenclature • Four discrete steps to naming an aldehyde or ketone • Same procedure as with alkanes, alcohols, etc… 1. Identify and name the parent chain 2. Identify the name of the substituents (side groups) 3. Assign a locant (number) to each substituents 4. Assemble the name alphabetically Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 19-3 Klein, Organic Chemistry 3e 19.2 Nomenclature 1. Identify and name the parent chain – For aldehydes, replace the “-e” ending with an “-al” – the parent chain must include the carbonyl carbon Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 19-4 Klein, Organic Chemistry 3e 19.2 Nomenclature 1. Identify and name the parent chain – The aldehydic carbon is assigned number 1: Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 19-5 Klein, Organic Chemistry 3e 19.2 Nomenclature 1. Identify and name the parent chain – For ketones, replace the “-e” ending with an “-one” – The parent chain must include the C=O group – the C=O carbon is given the lowest #, and can be expressed before the parent name or before the suffix Copyright © 2017 John Wiley & Sons, Inc. All rights reserved.
    [Show full text]
  • Effect of Some Electron Donor and Electron Acceptor Groups on Stability of Complexes According to the Principle of HSAB
    ISSN: 1304-7981 Number: 4 , Year: 2014, Pages: 82-89 http://jnrs.gop.edu.tr Received: 31.01.2014 Editors-in-Chief: Naim Çağman Accepted: 19.03.2014 Area Editor: Yakup Budak Effect of Some Electron Donor and Electron Acceptor Groups on Stability of Complexes According to the Principle of HSAB Savaş Kayaa,1 ([email protected]) Sultan Erkan Karipera ([email protected]) Ayhan Ungördüa ([email protected]) Cemal Kayaa ([email protected]) aChemistry Department, Faculty of Science, Cumhuriyet University, 58100, Sivas, TURKEY Abstract – Chemical hardness is an important feature of substances. Lewis acids and bases have been classified to considering the chemical hardness concept and HSAB (Hard and Soft Acid- base) Principle has been demonstrated by Pearson. HSAB principle is an extremely useful qualitative theory that enables predictions of what adducts will form in a complex mixture of potential Lewis acids and bases. Furthermore, Keywords – HSAB, Pyrithione, chemical hardness is associated with chemical reactivity of molecules. In DFT, Chemical hardness, this study, effect of the chemical hardness in complexes formation was Coordination complexes investigated. For this purpose, complexes with Ca2+, Zn2+, Mg2+, Cu2+ ions of pyrithione (PT) ligand and its derivatives were studied. All calculations were made using the Gaussian 09, Revision B.01 program. The obtained geometries were further optimized at the b3lyp/ 6-31g (d,p) level using Gaussian package. In complex formation reactions, reaction energy (ΔE) has been calculated. 1. Introduction Chemical hardness fundamentally signifies the resistance toward the deformation or polarization of electron cloud of the atoms, ions, or molecules [1]. Chemical hardness is one of extremely useful conceptual constructs of chemistry and physics.
    [Show full text]
  • Hard and Soft Acids and Bases 1965- Ralph Pearson Introduced the Hard-Soft-Acid-Base (HSAB) Principle
    380 Hard and Soft Acids and Bases 1965- Ralph Pearson introduced the hard-soft-acid-base (HSAB) principle. “Hard acids prefer to coordinate the hard bases and soft acids to soft bases” This very simple concept was used by Pearson to rationalize a variety of chemical information. 1983 – the qualitative definition of HSAB was converted to a quantitative one by using the idea of polarizability. A less polarizable atom or ion is “hard” and a more easily polarized atom or ion is “soft” 381 The Quantitative Definition of hardness: The average of ionization N = (I.P. – E.A.) /2 potential and electron affinity Actually, the electronegativity, X, of a neutral species is the same X = (I.P. – E.A.) /2 One can relate n (hardness) to the gap between the HOMO and LUMO: E (energy) 2n = (ELUMO - EHOMO) HOMO and LUMO orbitals (molecules) or simply highest occupied and lowest unoccupied orbitals in atoms participate in the bonding more than any other levels. (The lower the energy of the HOMO and the higher the energy of the LUMO, the more stable the species is thermodynamically) The greater the n value - the more hard the species is. 382 Basically, HSAB theory endeavors to help one decide if AB + A’B’ AB’ + A’B goes to the left or the right A= and Acid B = Base Hard and Soft Acids and Bases Hard acid: High positive charge Small size Not easily polarizable Hard base: Low polarizability High electronegativity Not easily oxidized Soft acid: Low positive charge Large size; easily oxidized Highly polarizable Soft base: High polarizability Diffuse donor orbital Low electronegativity Easily oxidized 383 Hard acids prefer to bind to hard bases and soft acids prefer to bind to soft bases.
    [Show full text]
  • Aromatic Nucleophilic Substitution Reaction
    Aromatic Nucleophilic Substitution Reaction DR. RAJENDRA R TAYADE ASSISTANT PROFESSOR DEPARTMENT OF CHEMISTRY INSTITUTE OF SCIENCE, NAGPUR Principles There are four principal mechanisms for aromatic nucleophilic substitution which are similar to that of aliphatic nucleophilic substitution. (SN1, SN2, SNi, SET Mechanism) 1. SNAr Mechanism- addition / elimination CF3, CN, CHO, COR, COOH, Br, Cl, I Common Activating Groups for NAS Step [1] Addition of the nucleophile (:Nu–) to form a carbanion Addition of the nucleophile (:Nu–) forms a resonance-stabilized carbanion with a new C – Nu bond— three resonance structures can be drawn. • Step is rate-determining • Aromaticity of the benzene ring is lost Step [2] loss of the leaving group re-forms the aromatic ring. • This step is fast because the aromaticity of the benzene ring is restored. ? Explain why a methoxy group (CH3O) increases the rate of electrophilic aromatic substitution, but decreases the rate of nucleophilic aromatic substitution. 2.ArSN1 Mechanism- elimination /addition • This mechanism operates in the reaction of diazonium salts with nucleophiles. •The driving force resides in the strength of the bonding in the nitrogen molecule that makes it a particularly good leaving group. 3.Benzyne Mechanism- elimination /addition Step [1] Elimination of HX to form benzyne Elimination of H and X from two adjacent carbons forms a reactive benzyne intermediate Step [2] Nucleophilic addition to form the substitution product Addition of the nucleophile (–OH in this case) and protonation form the substitution product Evidence for the Benzyne Mechanism Trapping in Diels/Alder Reaction O O B E N Z Y N E C C O O O D i e l s / A l d e r O N H 3 N N Dienophile Diene A d d u c t Substrate Modification – absence of a hydrogens LG Substituent Substituent No Reaction Base Isotopic Labeling LG Nu H Nu Structure of Benzyne • The σ bond is formed by overlap of two sp2 hybrid orbitals.
    [Show full text]
  • A Marcus-Theory-Based Approach to Ambident Reactivity
    Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München A Marcus-Theory-Based Approach to Ambident Reactivity Robert Martin Breugst aus München 2010 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 (in der Fassung der vierten Änderungssatzung vom 26. November 2004) von Herrn Professor Dr. Herbert Mayr betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet. München, 28.10.2010 _________________________ Dissertation eingereicht am: 28.10.2010 1. Gutachter: Prof. Dr. Herbert Mayr 2. Gutachter: Prof. Dr. Hendrik Zipse Mündliche Prüfung am: 21.12.2010 II Acknowledgements Acknowledgements First of all, I would like to express my cordial gratitude to Professor Dr. Herbert Mayr for the opportunity to compose this thesis in his group. I have cherished all the valuable discussions with him, his endless support, and his inspiring confidence very much and I have always appreciated working under these excellent conditions. From the very first day in his group Professor Mayr made me feel welcome, has always been willing to discuss my ideas, and encouraged me to pursue a scientific career. Furthermore, I would like to thank Professor Dr. Hendrik Zipse for numerous discussions and helpful comments on quantum chemical calculations, and of course also for reviewing my thesis. Additionally, I am very indebted to Professor J. Peter Guthrie, Ph.D., for giving me the opportunity to spend almost 4 months in his group at the University of Western Ontario. During this time, I have learned so many new things and I am grateful for the reams of discussions in his office.
    [Show full text]
  • Effect of Nucleophile on Reaction
    1 Effect of nucleophile on reaction H H H H H H H RDS H H RDS + Nuc R H Nuc X R X R Nuc R X Nuc R X • Nucleophile not involved in RDS of SN1 so does not effect the reaction (well obviously it controls the formula of the product!) • Nucleophile has a big effect on SN2 • Large nucleophiles are poor in SN2 reactions due to steric hindrance Large nucleophile (t-BuOH) suffers steric interactions Small nucleophile (MeOH) can easily approach 2 Nucleophile strength • The stronger the nucleophile the faster / more efficient the SN2 reaction • Nucleophilic strength (nucleophilicity) relates to how easily a compound can donate an electron pair • The more electronegative an atom the less nucleophilic as the electrons are held closer nucleophilic strength Anion more nucleophilic H O than its neutral analogue (basicity) HO > 2 nucleophilic strength R C (basicity) 3 > R2N > RO > F As we move along a row the electronegativity electronegativity C < N < O < F increases and nucleophilic strength nucleophilicity decreases (basicity) R NH2 > R OH > R F As we go down a group both anions and neutral atoms get more nucleophilic strength H2S > H2O (basicity) nucleophilic - electrons I > Br > Cl > F not held as tightly as size increases 3 Solvent effects SN1 • Intermediate - the carbocation - is stabilised by polar solvents • Leaving group stabilised by protic solvents (encourages dissociation) • Water, alcohols & carboxylic acids good solvents for SN1 Br H O H O H H Br O H O H O cation hydrogen stabilised O bonds SN2 • Prefer less polar, aprotic solvents • Less
    [Show full text]