DOCSLIB.ORG

Organic Chemistry III

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Organic Chemistry III Organic Chemistry III Mohammad Jafarzadeh Faculty of Chemistry, Razi University Organic Chemistry, Structure and Function (7th edition) By P. Vollhardt and N. Schore, Elsevier, 2014 1 950 CHAPTER 21 Amines and Their Derivatives Exercise 21-9 The cleavage of an N-alkyl-1,2-benzenedicarboximide (N-alkyl phthalimide) is frequently carried out with base or with hydrazine, H2NNH2. The respective products of these two treatments are the 1,2-benzenedicarboxylate A or the hydrazide B. Write mechanisms for these two transformations. (Hint: Review Section 20-6.) O O COOϪ ϪOH H NNH NH NR 2 2 A ϪRNH2 ϪRNH2 NH COOϪ O O AB Exercise 21-10 Show how you would apply the Gabriel method to the synthesis of each of the following amines: (a) 1-hexanamine; (b) 3-methylpentanamine; (c) cyclohexanamine; (d) H2NCH2CO2H, the amino acid glycine. (Caution: In the synthesis of glycine, you need to watch out for the carboxylic acid function. Can you see why?) For each of these four syntheses, would the azide displacement– reduction method be equally good, better, or worse? In Summary Amines can be made from ammonia or other amines by simple alkylation, but this method gives mixtures and poor yields. Primary amines are better made in stepwise fashion, employing nitrile and azide groups, or protected systems, such as 1,2-benzenedicarboxylic imide (phthalimide) in the Gabriel synthesis. 21-6 SYNTHESIS OF AMINES BY REDUCTIVE AMINATION 21-6 SYNTHESIS OF AMINES BY REDUCTIVE AMINATION Reductive amination of aldehydes and ketones, allows the construction of primary, secondary,A moreand generaltertiary methodamines of amine. synthesis, called reductive amination of aldehydes and ketones, allows the construction of primary, secondary, and tertiary amines. In this process, In thistheprocess, carbonylthe compoundcarbonyl iscompound exposed to isanexposed amine containingto an amine at leastcontaining one N–H atbondleast (NHone3, N–H primary, secondary amines) and a reducing agent to furnish a new alkylated amine directly bond (NH3, primary, secondary amines) and a reducing agent to furnish a new alkylated amine(adirectly primary,(a secondary,primary, secondary,or tertiary amine,or tertiary respectively).amine, Therespectively) new C–N bond. is formed to the carbonyl carbon of the aldehyde or ketone. The new C–N bond is formed to the carbonyl carbon of the aldehyde or ketone. General Reductive Amination R H ␦ϩ f i Reduction i f OPCCðNOH ~ ONð i f R ; i RЈ RЈ 2 The sequence begins by the initial condensation of the amine with the carbonyl com- ponent (Section 17-9) to produce the corresponding imine (for NH3 and primary amines) or iminium ion (secondary amines). Similar to the carbon–oxygen double bond in aldehydes and ketones, the carbon–nitrogen double bond in these intermediates is then reduced by simultaneous catalytic hydrogenation or by added special hydride reagents. The sequence begins by the initial condensation of the amine with the carbonyl component to produce the corresponding imine (for NH3 and primary amines) or iminium ion (secondary amines). Similar to the carbon–oxygen double bond in aldehydes and ketones, the carbon– nitrogen double bond in these intermediates21-6 Synthesisis ofthen Aminesreduced by Reductiveby simultaneous AminationcatalyticCHAPTER 21 951 hydrogenation or by added special hydride reagents. Reductive Amination of a Ketone with a Primary Amine R R RЉ G G D CPO ϩ H2NRЉ CPN ϩ H2O D Condensation D RЈ RЈ R RЉ R G D A Animation CPN RЈOOC NHRЉ D Reduction A ANIMATED MECHANISM: RЈ H Reductive amination This reaction succeeds because of the selectivity of the reducing agents: either 3 N hydrogen gas in the presence of a catalyst (Section 12-2) or sodium cyanoborohydride, c 12 ␦ϩ Electron Na BH3CN. Both react faster with the imine double bond than with the carbonyl group C withdrawing under the conditions employed. With Na12BH CN, the conditions are relatively acidic A 3 ϪB (pH 5 2–3), activating the imine double bond by protonation on nitrogen and thus E ~ H & H facilitating hydride attack at carbon. As shown in the margin, the relative stability of H the modi! ed borohydride reagent at such low pH (at which NaBH4 hydrolyzes; Section Diminished ability of H to 8-6) is due to the presence of the electron-withdrawing cyano group, which renders the leave as :HϪ, hence reagent ϩ hydrogens less basic (hydridic). In a typical procedure, the carbonyl component and the is less sensitive to H amine are allowed to equilibrate with the imine and water in the presence of the reduc- ing agent. In this way, ammonia furnishes primary amines, and primary amines result in secondary amines. Amine Synthesis by Reductive Amination CH3 CH3 CH3 C ϪH2O C H2, Ni, CH3OH, 90°C, 100 atm C B ϩ NH3 B A A A ϩH2O H O N H NA H H Phenyl-2-propanone Not isolated Amphetamine (Industrial production) H O NCH3 H NCH3 NaBH3CN, ϪH2O CH3CH2OH, pH ϭ 2–3 ϩ CH3NH2 ϩH2O 78% Cyclohexanone Not isolated N-Methylcyclohexanamine Similarly, reductive aminations with secondary amines give tertiary amines. H O H3C H3C N(CH3)2 (CH3)2NH, NaBH3CN, CH3OH H3C CH3 H3C CH3 89% 760 CHAPTER 17 Aldehydes and Ketones OH Exercise 17-11 Try It Yourself O Show how the starting material for Exercise 17-10 may be converted into the alcohol in the O margin. Thioacetals are desulfurized to the corresponding hydrocarbon by treatment with Raney nickel (Section 12-2). Thioacetal generation followed by desulfurization is used to convert a carbonyl into a methylene group under neutral conditions. H H Raney Ni, H SS 2 65% Exercise 17-12 Suggest a possible synthesis of cyclodecane from . (Caution: Simple hydrogenation will not do. Hint: See Section 12-12.) In Summary Acetals and thioacetals are useful protecting groups for aldehydes and ketones. Acetals are21-6 formed Synthesis under acidic of conditions Amines andby areReductive stable toward Amination bases and nucleophiles.CHAPTER They 21 951 are hydrolyzed by aqueous acid. Thioacetals are usually prepared using Lewis acid catalysts 21-6and Synthesis are stable toof both Amines aqueous by baseReductive and acid. Amination Mercuric salts CHAPTERare required for 21 thioacetal 951 Reductivehydrolysis. Amination Thioacetals of a Ketonemay also with be desulfurizeda Primary Amineto hydrocarbons with Raney nickel. R R RЉ ReductiveG Amination of a Ketone with a Primary AmineG D CPO ϩ H2NRЉ CPN ϩ H2O R D 17-9 NUCLEOPHILICCondensationR RЉ ADDITIOND OF AMMONIA AND ITS G RЈ G D RЈ CPO ϩ H2NRЉ DERIVATIVESCPN ϩ H2O Condensation D R RЉ D R RЈ RЈ A Animation AmmoniaG andD the amines may be regarded as nitrogen analogs of water and alcohols. Do HHD R D H CPN RЈOOC NHRЉ G G ReductionR šN šN R theyRЉ D add to aldehydes and ketones? InA fact, they do, giving products correspondingAnimationANIMATED to MECHANISM: those A A G DjustRЈ studied. We shall seeA one importantH difference, however. The products of addition of H H CPN RЈOOC NHRЉ Reductive amination amines Reductionand their derivatives lose water, furnishing either of two new derivatives of the Ammonia Primary amineD A ANIMATED MECHANISM: RЈ original carbonyl compounds:H imines and enamines. Reductive amination This reaction succeeds because of the selectivity of the reducing agents: either N hydrogen gas in the presenceAmmonia of a andcatalyst primary (Section amines 12-2) or sodiumform iminescyanoborohydride, c 12 ␦ϩ Electron This reactionNa BH succeeds3CN. Both because reactUpon faster ofexposure the with selectivity to the an imineamine, of double aldehydes the reducing bond and than ketones agents: with initially theeither carbonyl form hemiaminals, group N the nitrogenC withdrawing ReactionR 12 A hydrogen gasunder in thethe presenceconditions of employed.a catalyst (SectionWith Na 12-2)BH or3CN, sodium the conditions cyanoborohydride, are relatively acidic c Ϫ 12 analogs of hemiacetals. In a subsequent, slower step, hemiaminals of primary␦ϩ aminesElectron loseB Na BH3CN.(pH Both 5 2–3), react fasteractivating with the imineimine doubledouble bond bond than by withprotonation the carbonyl on nitrogengroup and thus C withdrawingE ~ water to form12 a carbon–nitrogen double bond. This function is called an imine (an Holder & H under the conditions employed. With Na BH CN, the conditions are relatively acidic A facilitating hydride attackname isat Schiff*carbon. 3base As) shownand is thein thenitrogen margin, analog the of relative a carbonyl stability group. of ϪB H (pH 5 2–3), activating the imine double bond by protonation on nitrogen and thus E ~ the modi! ed borohydride reagent at such low pH (at which NaBH4 hydrolyzes; SectionH & HDiminished ability of H to facilitating8-6) hydride is due attack to the at presencecarbon. Asof theshown electron-withdrawing in the margin, the cyanorelative group, stability which of renders the H leave as :HϪ, hence reagent is less sensitive to Hϩ the modi! edhydrogens borohydride less reagentbasicImine (hydridic). at Formation such low In pHafrom typical (at Amines which procedure, andNaBH Aldehydes4 thehydrolyzes; carbonyl or Ketones Sectioncomponent and Diminishedthe ability of H to 8-6) is due to the presence of the electron-withdrawing cyano group, which renders the leave as :HϪ, hence reagent amine are allowed to equilibrate with the imine and water in the presence of theElimination reduc- ϩ hydrogens less basic (hydridic). In a HHtypical procedure, theDeprotonation carbonyl at N, componentH and the of water is less sensitive to H ing agent. In thisAddition way, ammonia furnishes primaryreprotonation amines, at O and Aprimary aminesϪ resultH O amine are allowed to equilibrate with theA ϩ imineA and water in the presence of the reduc- 2 ) š RONšH2 ϩin secondaryC š"O amines. N šOðϪ "N šOH N C E H " E H " ϩH2O R ing agent. In this way, ammonia furnishesR primaryC O amines, and primaryR aminesC resultO in secondary amines.
Load more

Recommended publications
  • Organic Chemistry
    Wisebridge Learning Systems Organic Chemistry Reaction Mechanisms Pocket-Book WLS www.wisebridgelearning.com © 2006 J S Wetzel LEARNING STRATEGIES CONTENTS ● The key to building intuition is to develop the habit ALKANES of asking how each particular mechanism reflects Thermal Cracking - Pyrolysis . 1 general principles. Look for the concepts behind Combustion . 1 the chemistry to make organic chemistry more co- Free Radical Halogenation. 2 herent and rewarding. ALKENES Electrophilic Addition of HX to Alkenes . 3 ● Acid Catalyzed Hydration of Alkenes . 4 Exothermic reactions tend to follow pathways Electrophilic Addition of Halogens to Alkenes . 5 where like charges can separate or where un- Halohydrin Formation . 6 like charges can come together. When reading Free Radical Addition of HX to Alkenes . 7 organic chemistry mechanisms, keep the elec- Catalytic Hydrogenation of Alkenes. 8 tronegativities of the elements and their valence Oxidation of Alkenes to Vicinal Diols. 9 electron configurations always in your mind. Try Oxidative Cleavage of Alkenes . 10 to nterpret electron movement in terms of energy Ozonolysis of Alkenes . 10 Allylic Halogenation . 11 to make the reactions easier to understand and Oxymercuration-Demercuration . 13 remember. Hydroboration of Alkenes . 14 ALKYNES ● For MCAT preparation, pay special attention to Electrophilic Addition of HX to Alkynes . 15 Hydration of Alkynes. 15 reactions where the product hinges on regio- Free Radical Addition of HX to Alkynes . 16 and stereo-selectivity and reactions involving Electrophilic Halogenation of Alkynes. 16 resonant intermediates, which are special favor- Hydroboration of Alkynes . 17 ites of the test-writers. Catalytic Hydrogenation of Alkynes. 17 Reduction of Alkynes with Alkali Metal/Ammonia . 18 Formation and Use of Acetylide Anion Nucleophiles .
    [Show full text]
  • Open PS Thesis - Clara Capparelli
    The Pennsylvania State University The Graduate School Department of Material Science and Engineering INFLUENCE OF CARBON SPACERS AND ALKYL PENDANT CHAINS ON THE STABILITY OF QUATERNARY AMMONIUM CATIONS FOR ANION EXCHANGE MEMBRANES A Thesis in Material Science and Engineering by Clara Capparelli 2015 Clara Capparelli Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science August 2015 The thesis of Clara Capparelli was reviewed and approved* by the following: Michael A. Hickner Associate Professor of Materials Science and Engineering Thesis Advisor James Runt Professor of Polymer Science T.C. Mike Chung Professor of Material Science and Engineering Suzanne Mohney Professor of Material Science and Engineering and Electrical Engineering Chair, Intercollege Graduate Degree Program in Material Science and Engineering *Signatures are on file in the Graduate School iii ABSTRACT Proton and anion exchange membranes are of great importance in the function of fuel cells, one of the most promising technologies for renewable energy conversion. Proton exchange membrane fuel cells (PEMFC) have been studied extensively in the past couple of decades, and there have been tremendous advances in the development of these systems, especially in industries such as automotive and portable power. Anion exchange membranes (AEM) have caught the attention of scientists because they would allow for the development of fuel cells without costly precious metal catalysts, among other advantages. Efforts are being made in developing long-lived and high performance AEMs for fuel cell applications. Primarily, the focus in AEM research has been membrane stability. It has been observed that AEMs are not as stable as the state-of-the-art NAFION® PEM and demonstrations of cell performance beyond 1000 hours is rare.
    [Show full text]
  • Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP‑TLC, RP‑HPLC and RP‑HPLC‑ESI‑MS Analysis
    http://dx.doi.org/10.21577/0103-5053.20160260 J. Braz. Chem. Soc., Vol. 28, No. 6, 1048-1062, 2017. Printed in Brazil - ©2017 Sociedade Brasileira de Química 0103 - 5053 $6.00+0.00 Article Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP-TLC, RP-HPLC and RP-HPLC-ESI-MS Analysis Aline Bernardes,a,b Caridad N. Pérez,a Mátyás Mayer,c Cameron C. da Silva,a Felipe T. Martinsa and Pál Perjési*,b aInstituto de Química, Universidade Federal de Goiás, 74690-900 Goiânia-GO, Brazil bInstitute of Pharmaceutical Chemistry and cDepartment of Forensic Medicine, University of Pécs, H-7624 Pécs, Hungary 4’-Hydroxychalcones have been reported to possess several beneficial biological effects. Several lines of evidence accumulated to demonstrate increased biological activities of the Mannich base derivatives of the parent 4’-hydroxychalcones. Bioactivities of chalcones and related α,β-unsaturated ketones are frequently associated with their reactivity with cellular thiols, such as GSH. For comparison of GSH reactivity, two bis Mannich bases of two 4’-hydroxychalcones were synthesized and reacted with GSH under non-cellular conditions. Reversed-phase thin layer chromatography (RP-TLC) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis showed formation of two polar products which structures were confirmed by RP-HPLC-ESI-MS (RP-HPLC-electrospray ionization mass spectrometry) as 1:1 chalcone-GSH adducts in each case. At pH values below 8.0, the two bis Mannich bases showed higher GSH reactivity than two 4’-hydroxychalcones. Influence of the nature of the amino groups, the ring-B substituents and pH of the medium on reactivity was also investigated.
    [Show full text]
  • Generation of a Structurally Diverse Library Through Alkylation and Ring
    70 Acta Chim. Slov. 2013, 60, 70–80 Scientific paper Generation of a Structurally Diverse Library through Alkylation and Ring Closure Reactions Using 3-Dimethylamino-1-(thiophen-2-yl)propan-1-one Hydrochloride* Gheorghe Roman Petru Poni Institute of Macromolecular Chemistry, 41A Aleea Gr. Ghica Vodâ, Ias¸i 700487, Romania Corresponding author: E-mail: [email protected] Received: 01-06-2012 Abstract 3-Dimethylamino-1-(thiophen-2-yl)propan-1-one hydrochloride (2), a ketonic Mannich base derived from 2-acetyl- thiophene, was used as a starting material in different types of alkylation and ring closure reactions with a view to gene- rate a structurally diverse library of compounds. Compound 2 reacts with S-alkylated dithiocarbamic acid salts and aryl mercaptans to produce dithiocarbamates and thioethers, respectively. The dimethylamino moiety in compound 2 was exchanged with various aliphatic secondary and aromatic primary and secondary amines, whereas monocyclic NH-azoles such as pyrazole, imidazole, 1,2,4-triazole, and tetrazole were N-alkylated by compound 2. Ketones, pyrrole and in- doles have been the substrates subjected to C-alkylation reactions by compound 2. Ring closure reactions of compound 2 with a suitable bifunctional nucleophile yielded pyrazolines, pyridines, 2,3-dihydro-1,5-1H-benzodiazepines, 2,3- dihydro-1,5-1H-benzothiazepine, pyrimido[1,2-a]benzimidazole and 4-hydroxypiperidine derivatives. Keywords: Ketonic Mannich base, alkylation, amine exchange, cyclization. 1. Introduction through the replacement of the easily leaving dimethyla- mino group by various nucleophiles. Also, several cycliza- The chemistry of Mannich bases has drawn a great tions of the aforementioned Mannich base with bifunctio- deal of attention owing to the high synthetic potential and nal nucleophiles to 5-, 6- and 7-membered nitrogen-con- the outstanding applications of this class of compounds.2–4 taining heterocycles have been investigated.
    [Show full text]
  • Electrochemistry and Photoredox Catalysis: a Comparative Evaluation in Organic Synthesis
    molecules Review Electrochemistry and Photoredox Catalysis: A Comparative Evaluation in Organic Synthesis Rik H. Verschueren and Wim M. De Borggraeve * Department of Chemistry, Molecular Design and Synthesis, KU Leuven, Celestijnenlaan 200F, box 2404, 3001 Leuven, Belgium; [email protected] * Correspondence: [email protected]; Tel.: +32-16-32-7693 Received: 30 March 2019; Accepted: 23 May 2019; Published: 5 June 2019 Abstract: This review provides an overview of synthetic transformations that have been performed by both electro- and photoredox catalysis. Both toolboxes are evaluated and compared in their ability to enable said transformations. Analogies and distinctions are formulated to obtain a better understanding in both research areas. This knowledge can be used to conceptualize new methodological strategies for either of both approaches starting from the other. It was attempted to extract key components that can be used as guidelines to refine, complement and innovate these two disciplines of organic synthesis. Keywords: electrosynthesis; electrocatalysis; photocatalysis; photochemistry; electron transfer; redox catalysis; radical chemistry; organic synthesis; green chemistry 1. Introduction Both electrochemistry as well as photoredox catalysis have gone through a recent renaissance, bringing forth a whole range of both improved and new transformations previously thought impossible. In their growth, inspiration was found in older established radical chemistry, as well as from cross-pollination between the two toolboxes. In scientific discussion, photoredox catalysis and electrochemistry are often mentioned alongside each other. Nonetheless, no review has attempted a comparative evaluation of both fields in organic synthesis. Both research areas use electrons as reagents to generate open-shell radical intermediates. Because of the similar modes of action, many transformations have been translated from electrochemical to photoredox methodology and vice versa.
    [Show full text]
  • Subject Index
    455 Subject Index Aminohydroxylation, 364 a-Aminoketone, 281 4-Aminophenol, 18 A Aminothiophene, 158 Abnormal Claisen rearrangement, 1 a-Aminothiophenols, 184 Acrolein, 378 Ammonium ylide, 383 2-(Acylamino)-toluenes, 245 Angeli-Rimini hydroxamic acid Acylation, 100, 145, 200 synthesis, 9 Acyl azides, 98 ~-Anomer, 225 Acylium ion, 145, 149, 175, 177 Anomeric center, 211 a-Acyloxycarboxamides, 298 Anomeric effect, 135 a-Acyloxyketones, 17 ANRORC mechanism, 10 a-Acyloxythioethers, 327 Anthracenes, 51 Acyl transfer, 17, 42, 228, 298, 305, Anti-Markovnikov addition, 219 327,345 Amdt-Eistert homologation, 11 AIBN, 22, 23, 415 Aryl-acetylene, 66 Alder ene reaction, 2 Arylation, 253 Alder's endo rule, Ill 0-Aryliminoethers, 67 Aldol condensation, 3, 14, 26, 34, 2-Arylindoles, 38 69, 130, 147, 172, 305, Aryl migration, 31 340,396,412 Autoxidation, 69, 115, 118 Aldosylamine, 8 Auwers reaction, 13 Alkyl migration, 16, 132, 315, 443 Axial, 347 Alkylation, 144, 145 Azalactone, I 00 N-Aikylation, 162 Azides, 125, 330 Alkylidene carbene, 151 Azirine, 6, 7, 281 Allan-Robinson reaction, 4, 228 Azulene, 310 Allene, 119 1t-Allyl complex, 414 B Allylation, 213, 414 Baeyer-Drewson Allylstannane, 213 indigo synthesis, 14 Allylsilanes, 349 Baeyer-Villiger oxidation, 16, 53 Alper carbonylation, 6 Baker-Venkataraman Alpine-borane®, 262 rearrangement, 17 Aluminum phenolate, 149 Balz-Schiemann reaction, 354 Amadori rearrangement, 8 Bamberger rearrangement, 18 Amide acetal, 74 Bamford-Stevens reaction, 19 Amides, 28, 67,276,339, 356 Bargellini reaction, 20 Amidine,
    [Show full text]
  • Solvating Alkylamine Hofmann Elimination in Zeolites Through Cooperative Adsorption Han Chen† and Omar A
    Solvating Alkylamine Hofmann Elimination in Zeolites Through Cooperative Adsorption Han Chen† and Omar A. Abdelrahman †,‡* † Department of Chemical Engineering, University of Massachusetts Amherst, 686 N. Pleasant Street, Amherst, MA 01003, USA ‡ Catalysis Center for Energy Innovation, University of Delaware, 150 Academy Street, Newark, DE 19716, USA *Corresponding Author: [email protected] Abstract. A kinetic investigation of the vapor phase Hofmann elimination of tert-butylamine over H- ZSM-5 reveals a carbocation mediated E1-like mechanism, where isobutene and ammonia are exclusively produced over Brønsted acid sites. Hofmann elimination kinetics are found to be insensitive to Al content or siting, varying only with alkylamine carbocation stability (rtertiary > rsecondary > rprimary). Under conditions of complete tert-butylamine surface coverage, experimentally measurable apparent kinetics are directly equivalent to the intrinsic kinetics of the rate determining unimolecular surface elimination. The direct measurement of elementary step kinetics served as a water-free reactive probe, providing a direct measurement of the impact of water on solid Brønsted acid catalyzed chemistries at a microscopic level. Over a range of temperatures (453‒513 K) and tert-butylamine partial pressures (6.8×10-2‒6.8 kPa), water reversibly inhibits the rate of Hofmann elimination. Despite expected changes in aluminosilicate hydrophobicity, the water-induced inhibition is found to be insensitive to Al content, demonstrated to be due to one water molecule per Brønsted acid site. Regardless of the significant reduction in the rate of Hofmann elimination, kinetic interrogations and operando spectroscopic measurements reveal that the coverage of TBA adsorbed on H-ZSM-5 is unaltered in the presence of water.
    [Show full text]
  • Organic Seminar Abstracts
    L I B RA R.Y OF THE UN IVE.R.SITY Of ILLI NOIS 547 l£6s \ 954/55 PV Return this book on or before the Latest Date stamped below. University of Illinois Library Llf.1—H41 Digitized by the Internet Archive in 2012 with funding from University of Illinois Urbana-Champaign http://archive.org/details/organicsemi195455univ \7^ — SEMINAR TOPICS CHEMISTRY 435 I Semester 1954-55 The Quinolizinium Ion and Some of its Derivatives Harvey M. Loux, September 24 1 The Stereochemistry of Atropine and Cocaine Ho E . Knipmeyer, September 24 4 Recent Developments in the Chemistry of Cinnoline Derivatives Roger H. Kottke , October 1 8 Interpretation of Electrophiiic Aromatic Substitution and Solvolysis of Allylic and Benzhydryl Chlorides in Terms of Hyperconjugation Robert D. Stolow, October 1 11 The Decahydronaphtholic Acids and Their Relationship to the Decalols and the Decalylamines Robert J. Harder, October 8 14 Bis-Cyclopentadienyl Metal Compounds Edwin L. DeYoung, October 8 17 Ion-Pairs as Intermediates in Solvolysis Reactions Arthur H. Goldkamp, October 15 21 Synthesis of Morphine Mohan D. Nair, October 15 24 Structural and Geometrical Isomerism in the Oxidation of Azo Compounds D. F. Morrow, October 22 27 Stereochemical Aspects of Thermochromism John W. Johnson, Jr., October 22 30 A New Method for the Preparation of Olefins --The Pyrolysis of Sulfites F. M. Scheidt, October 29 33 Recent Studies of Macrocyclic Ring Systems: Cyclophanes Fred P. Hauck, Jr., October 29 36 Mechanism of the Para-Claisen Rearrangement Hugh H . Gibbs , November 5 40 A Proposed Mechanism for Basic c is -Dehydrohalogenat ion Robert M.
    [Show full text]
  • Mannich Reaction
    1. Introduction 1.1- Mannich Reaction The Mannich reaction is three component condensation in which a compound containing an active hydrogen atom is allowed to react with formaldehyde and an NH-amine derivative . Secondary amines rather than primary amines and ammonia are employed , the resulting product (Mannich Base ) is an amine compound having the N atom linked to the R substrate through a methylene group 1,2. The aminoalkylation of CH-acidic compounds was described by several authors as early as the 19th. century. However, it was Carl Mannich who was the first to recognize the enormous significance of this reaction , and it was he who extended the chemistry into a broad based synthetic methodology through systematic research. Since then this reaction that now carries his name has developed into one of the most important C-C bond-forming reactions in organic chemistry3,4. The Mannich reaction is a classical method for the preparation of β -aminoketones and aldehydes (Mannich bases) and, as such, is one of the most important basic reaction types in organic chemistry. It is the key step in the synthesis of numerous pharmaceuticals and natural products3,4. 1 The Mannich reaction can be presented by the following equation: The essential feature of the reaction is the replacement of the active hydrogen atom by an aminomethyl or substituted aminomethyl group. The symbolizes the active hydrogen component which includes ketones, aldehydes, acids, esters, phenols, acetylenes, picolines, nitroalkanes and quinolines1,2. 1.2- Mechanism of the Mannich reaction The mechanism of the Mannich reaction has been well investigated, the condensation reaction occurs in two steps: first, the amine reacts with formaldehyde to give condensation product (5 ), (6), ( 7) (step I) which then attacks the substrate R-H (step II) .The reaction does not normally follow the other possible route (step III and IV) ; however, some successful reaction between hydroxymethyl derivatives (8) and alkylamines to give Mannich bases (9) should be mentioned .
    [Show full text]
  • Elimination Reactions Are Described
    Introduction In this module, different types of elimination reactions are described. From a practical standpoint, elimination reactions widely used for the generation of double and triple bonds in compounds from a saturated precursor molecule. The presence of a good leaving group is a prerequisite in most elimination reactions. Traditional classification of elimination reactions, in terms of the molecularity of the reaction is employed. How the changes in the nature of the substrate as well as reaction conditions affect the mechanism of elimination are subsequently discussed. The stereochemical requirements for elimination in a given substrate and its consequence in the product stereochemistry is emphasized. ELIMINATION REACTIONS Objective and Outline beta-eliminations E1, E2 and E1cB mechanisms Stereochemical considerations of these reactions Examples of E1, E2 and E1cB reactions Alpha eliminations and generation of carbene I. Basics Elimination reactions involve the loss of fragments or groups from a molecule to generate multiple bonds. A generalized equation is shown below for 1,2-elimination wherein the X and Y from two adjacent carbon atoms are removed, elimination C C C C -XY X Y Three major types of elimination reactions are: α-elimination: two atoms or groups are removed from the same atom. It is also known as 1,1-elimination. H R R C X C + HX R Both H and X are removed from carbon atom here R Carbene β-elimination: loss of atoms or groups on adjacent atoms. It is also H H known as 1,2- elimination. R C C R R HC CH R X H γ-elimination: loss of atoms or groups from the 1st and 3rd positions as shown below.
    [Show full text]
  • Review: Synthetic Methods for Amphetamine
    Review: Synthetic Methods for Amphetamine A. Allen1 and R. Ely2 1Array BioPharma Inc., Boulder, Colorado 80503 2Drug Enforcement Administration, San Francisco, CA Abstract: This review focuses on synthesis of amphetamine. The chemistry of these methods will be discussed, referenced and precursors highlighted. This review covers the period 1985 to 2009 with emphasis on stereoselective synthesis, classical non-chiral synthesis and bio-enzymatic reactions. The review is directed to the Forensic Community and thus highlights precursors, reagents, stereochemistry, type and name reactions. The article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 -2009. Although this is the same fundamental ground as the recent publication by K. Norman; “Clandestine Laboratory Investigating Chemist Association” 19, 3(2009)2-39, this current review offers another perspective. Keywords: Review, Stereoselective, Amphetamine, Syntheses, references, Introduction: It has been 20 years since our last review of the synthetic literature for the manufacture of amphetamine and methamphetamine. Much has changed in the world of organic transformation in this time period. Chiral (stereoselective) synthetic reactions have moved to the forefront of organic transformations and these stereoselective reactions, as well as regio-reactions and biotransformations will be the focus of this review. Within the synthesis of amphetamine, these stereoselective transformations have taken the form of organometallic reactions, enzymatic reactions, ring openings, - aminooxylations, alkylations and amination reactions. The earlier review (J. Forensic Sci. Int. 42(1989)183-189) addressed for the most part, the ―reductive‖ synthetic methods leading to this drug of abuse. It could be said that the earlier review dealt with ―classical organic transformations,‖ roughly covering the period from 1900-1985.
    [Show full text]
  • Rearrangement Reactions
    Rearrangement Reactions A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. 1, 2-Rearrangements A 1, 2-rearrangement is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1, 2 shift the movement involves two adjacent atoms but moves over larger distances are possible. In general straight-chain alkanes, are converted to branched isomers by heating in the presence of a catalyst. Examples include isomerisation of n-butane to isobutane and pentane to isopentane. Highly branched alkanes have favorable combustion characteristics for internal combustion engines. Further examples are the Wagner-Meerwein rearrangement: and the Beckmann rearrangement, which is relevant to the production of certain nylons: Pericyclic reactions A pericyclic reaction is a type of reaction with multiple carbon-carbon bonds making and breaking wherein the transition state of the molecule has a cyclic geometry and the reaction progresses in a concerted fashion. Examples are hydride shifts [email protected] and the Claisen rearrangement: Olefin metathesis Olefin metathesis is a formal exchange of the alkylidene fragments in two alkenes. It is a catalytic reaction with carbene, or more accurately, transition metal carbene complexintermediates. In this example (ethenolysis, a pair of vinyl compounds form a new symmetrical alkene with expulsion of ethylene. Pinacol rearrangement The pinacol–pinacolone rearrangement is a method for converting a 1,2-diol to a carbonyl compound in organic chemistry. The 1,2-rearrangement takes place under acidic conditions.
    [Show full text]